Stroke

Section 1: Epidemiology and aetiology

 Stroke is defined as a rapid onset of focal neurological deficit lasting more than 24
hours, with no apparent cause other than disruption of blood supply to the brain.
 A transient ischaemic attack (TIA) refers to a similar presentation that resolves within
24 hours, although the majority of TIAs resolve within one hour.
 Stroke is a common condition affecting around 150,000 people every year in the UK
and, at any given time, there are about 2,500 stroke patients in an average health
district.

Risk factors

 While the incidence of stroke increases with age, 25 per cent of all strokes occur in
people below the age of 65. Risk factors for stroke include hypertension, diabetes
mellitus, dyslipidaemia, cardiac disease, African-Caribbean ethnicity, obesity,
smoking and recreational drug and alcohol misuse.
 Approximately 15 per cent of strokes are haemorrhagic and the remainder are
ischaemic. Ischaemic strokes may be classified in terms of their aetiology of large
vessel atherothromboembolism, cardioembolism, small vessel occlusion, or other
determined or undetermined causes.

Stroke subtypes

 The proportions of the major stroke subtypes depend on ethnicity. In Caucasians,

approximately 15 per cent are due to large vessel disease, 30 per cent are due to
cardioembolism and 15 per cent are due to small vessel disease.
 In African-Caribbean people, approximately 8 per cent are due to large vessel disease,
15 per cent are due to cardioembolism and 30 per cent are due to small vessel disease.
 Epidemiological studies have shown the exact aetiopathogenesis of stroke may be
unknown in up to 20 per cent of cases and around 5 per cent of strokes are found to be
due to a rare or unusual cause.
 Less common causes of stroke include arterial dissection, autoimmune or connective
tissue disorders, such as systemic lupus erythematosus, and haematological disorders,
such as thrombophilic states and sickle cell disease.

Section 2: Making the diagnosis

Clinical features

 The symptoms and signs of stroke depend on the brain structures that are affected
which are, in turn, dependent on the vascular territory involved.
 For example, stroke affecting the anterior cerebral artery territory may result in
emotional changes, dysphasia and contralateral weakness.
 Stroke affecting the middle cerebral artery territory may result in dysphasia and
contralateral weakness, sensory loss, visual field loss and neglect.
 Stroke affecting the posterior cerebral artery territory may result in contralateral
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visual field loss, neglect, weakness and sensory loss.

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  Strokes affecting the posterior brain structures supplied by the vertebrobasilar arterial
system may cause nausea, vomiting, vertigo, visual disturbance, nystagmus,
dysarthria, ataxia, weakness or sensory disturbance.

Recognising stroke

 Strokes involving only a small blood vessel (<400(mu)m in diameter) supplying deep
brain structures lack cortical features (dysphasia, visual field loss, neglect, perceptual
abnormalities) and present as pure hemiparesis, hemisensory loss, sensorimotor stroke
or ataxic hemiparesis.
 A detailed history is crucial to exclude other possible diagnoses. Key features pertain
to the symptoms being focal rather than non-focal, negative (something not working)
rather than positive, of sudden onset and maximal at onset rather than progressing
over a period.
 Rapid recognition of stroke is critical to acute care pathways. Structured assessment
tools, such as face arm speech test (FAST) and recognition of stroke in the emergency
room (ROSIER) tests, have been demonstrated to be effective pre-hospital and in
emergency departments respectively.
 Clinical evaluation should assess for conscious level, temperature, heart rate and
rhythm, BP, cardiac murmurs, carotid bruits and evidence of aspiration, in addition to
a detailed neurological examination.

Investigation

 Basic blood tests to assess for derangement of serum haematological or biochemical

parameters should be undertaken in all suspected stroke patients in addition to brain
imaging.
 Without brain imaging it is impossible to determine whether a stroke is ischaemic or
haemorrhagic. The most commonly used modality of brain imaging in the acute
assessment of stroke patients is CT scanning due to its ease of use and availability.
 MRI has higher sensitivity to tissue oedema and ischaemia but is less available, more
expensive, potentially claustrophobic for patients and contraindicated for patients with
fragments of metal, cardiac pacemakers or any other electrical or magnetic implanted
device.

Section 3: Managing the condition

 Stroke used not to be considered an emergency and hospitalisation was thought to be

necessary only for nursing or social care needs.
 This nihilistic perception has been changed by evidence demonstrating the
effectiveness of acute stroke care and that for every minute a stroke goes untreated,
1.9 million brain neurons die.
 RCTs have demonstrated reductions in mortality, institutionalisation and dependency
for patients managed on a stroke unit compared with conventional care, with 19 per
cent more patients alive and independent at one year.
 A stroke unit is a discrete area within a hospital, staffed by a specialist
multidisciplinary team with access to monitoring and rehabilitation equipment.
 Stroke unit guidelines advocate interventions to maintain physiological homeostasis
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in terms of oxygenation, hydration, nutrition and BP and glucose control, in addition

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 to strategies to prevent and treat complications, such as urinary incontinence, pressure
sores and venous thrombosis.

IV thrombolysis

 In addition to control of classical vascular risk factors, such as hypertension and

hyperlipidaemia, certain specific treatment strategies exist.
 RCTs have demonstrated that treatment with IV thrombolysis, which breaks down
blood clots, improves the outcome of one in three ischaemic stroke patients treated
within three hours of symptom onset and of one in six patients treated in the three to
4.5 hours window.
 More specifically, trial data has shown that thrombolysis within three hours provides
a 14 per cent increase in the chance of being alive and independent three months after
stroke and thrombolysis at three to 4.5 hours provides a 7 per cent increase.
 Perfusion imaging allows direct visualisation of brain tissue that is potentially
salvageable with thrombolysis.

Intra-arterial thrombolysis

 Administering thrombolytic agents directly to the area of clot may increase efficacy
and reduce the risk of bleeding.
 Intra-arterial thrombolysis is recommended as an option for treatment of selected
patients who have a major stroke of less than six hours duration due to occlusion of
the middle cerebral artery and who are not otherwise candidates for IV thrombolysis.
 However, clinical benefit may be counterbalanced by delays initiating treatment as
treatment requires the patient to be at the stroke centre with immediate access to
cerebral angiography.
 The concept of combining the advantages of IV thrombolysis (speed and certainty of
initiation of therapy as well as widespread availability) and intra-arterial
recanalisation therapy when possible (titrated dosing, mechanical aids to
recanalisation, and possibly superior and earlier recanalisation) has been evaluated
and suggested as a future treatment for patients with large vessel occlusion.

Aspirin

 Large RCTs have demonstrated the beneficial effect of aspirin treatment in the
secondary prevention of ischaemic stroke, with benefit being greater in patients
receiving aspirin within the first three hours of stroke.
 Giving aspirin in doses above 75mg daily to patients who have had an ischaemic
stroke reduces the risk of a further stroke by about 13 per cent and the stroke risk per
year from 7 per cent to 6 per cent. This equates to one stroke being prevented for
every 100 patients prescribed aspirin.
 Where patients are aspirin intolerant, alternatives, such as clopidogrel or
dipyridamole, may be used and the combination of aspirin with these has been shown
to be beneficial in certain circumstances.
 Once 14 days have passed from symptom onset, guidelines advocate anticoagulation
rather than antiplatelet therapy to prevent ischaemic stroke of cardioembolic origin.
 In patients with stroke associated with 70-99 per cent internal carotid artery stenosis,
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carotid endarterectomy provides a 16 per cent five-year absolute risk reduction of

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 stroke, with the benefit decreasing substantially if surgery is delayed for more than
two weeks.
 Regarding treatment for haemorrhagic stroke, there is consensus opinion that surgical
evacuation of infratentorial intracerebral haemorrhage or supratentorial haematoma
smaller than 1cm from the cortical surface is favourable compared with conservative
medical treatment.
 However, for all other supratentorial haemorrhagic stroke, surgery does not improve
outcome compared with conservative medical treatment.

Section 4: Prognosis

 In addition to specific medical treatments for stroke, guidelines recommend goal-

oriented multidisciplinary rehabilitation (involving physiotherapists, occupational
therapists, speech and language therapists, dieticians, psychologists, nurses and
physicians) to minimise the functional consequences of the stroke and the impact of
the stroke on the life of the patient and their carers, and to maximise the patient's
autonomy.
 For those patients who can return home because they can care for themselves or have
the help of family or professional care, 'early supported discharge' schemes with
rehabilitation that can be provided at home reduces death and dependency and is cost-
effective.
 Approximately 20-30 per cent of stroke patients die within a month. Stroke is the
second leading cause of death and single largest cause of adult physical disability in
the world. It costs the NHS about £2.8 billion per year but with the additional societal
costs, it is estimated the national cost is approximately £7 billion per year.

Long-term disability

 Very few stroke survivors make a complete recovery; nearly 12-18 per cent are left
with speech problems, 25 per cent are unable to walk, 50 per cent have residual
weakness and 24-53 per cent remain dependent on carers for day-to-day activities.
 The risk of recurrent stroke is greatest soon after the first stroke: about 2-3 per cent of
survivors of a first stroke have a recurrent stroke within the first 30 days, about 9 per
cent in the first six months and 10-16 per cent within one year, which is about 15
times greater than the risk in the general population of the same age and sex.
 After the first year, the average annual risk of recurrent stroke for the next four years
falls to about 5 per cent.
 This risk is about nine times the risk of stroke in the general population of the same
age and sex.
 These data emphasise the importance of preventing further strokes and the need for
preventive measures to be instituted as soon as possible.
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 Transient ischaemic attack

Section 1: Epidemiology and aetiology

 The assumption when the definition was written was that this meant there was no
permanent structural brain damage. The analogy would have been angina pectoris and
MI.
 However, with increasingly sensitive brain imaging, it has been realised that many
patients with TIA, even when the symptoms last just a few minutes, have ischaemic
damage, so the justification for having a separate diagnosis of TIA and stroke ceases
to have much coherence.
 Many stroke physicians would prefer to drop the diagnosis and call all such attacks
stroke.
 Every year in England, approximately 20,000 people will experience their first
TIA,1 with an incidence rate of 0.5 in 1,000.
 A large proportion of TIAs go unrecognised, with about half never coming to medical
attention.2
 Unfortunately, many major strokes are preceded by TIAs that have either not been
recognised in time, or not been effectively treated.
 The care of patients with TIA has improved dramatically in the past decade, with
work focusing on early recognition and prevention of more disabling events. An
understanding of the different mechanisms is crucial for treatment and prevention.

Classification

 The aetiology and epidemiology of stroke and TIA are identical. Most TIAs are due to
ischaemia, but it is important to remember that a small primary intracerebral
haemorrhage can occasionally present with transient symptoms.
 Large-artery events are caused by lesions in the internal carotid artery, anterior or
middle cerebral arteries, or in the posterior circulation in the vertebral or basilar
territories. Any obstruction at these sites can cause
 TIA symptoms, especially if collateral circulation is inadequate. Embolic events
usually arise from a process starting from an extracranial large artery or from the
heart, and occasionally from smaller vessels within the brain. Cardiac causes are most
commonly secondary to AF or left ventricular disease.
 Lacunar or small-vessel events are due to stenosis of one of the intracranial vessels,
anteriorly from the middle cerebral artery or its branches and posteriorly from the
vertebrobasilar system. The process involved is usually atherosclerosis driven by risk
factors, such as hypertension and hypercholesterolaemia.
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 Section 2. Making the diagnosis

 A diagnosis of TIA warrants urgent specialist assessment. The assumption should be

that if there are persisting symptoms or signs, the diagnosis is stroke, not TIA, and the
patient should be taken to hospital.
TIA symptoms result from a sudden change in vascular dynamics, so are of sudden
onset. Four questions (see box 1) will determine whether the diagnosis is likely to be
TIA.
 Symptoms lasting a few seconds, or recurrent, frequent, stereotypical events, are
unlikely to be due to TIA.
 Conditions that mimic TIA include seizures, sepsis, delirium, hypo- and
hyperglycaemia, migraine, space-occupying lesions and functional disorders.

Symptoms and signs

 Carotid artery territory TIA symptoms include unilateral weakness or numbness,

speech disturbance and visual defects, such as hemianopia or amaurosis fugax.
 Vertebrobasilar territory symptoms include ataxia, articulation difficulty, diplopia,
bilateral visual loss and hemianopic visual defects.
 Isolated vertigo, syncope or amnesia are rarely thought to be caused by TIA, although
a paper from the Oxford Vascular Study reporting on a consecutive series of patients
with definite vertebrobasilar territory stroke found many with non-focal brainstem
symptoms, such as vertigo and transient generalised weakness, in the preceding
weeks.3
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 Investigations
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Patients with suspected TIA should receive aspirin immediately unless strongly

MRCGP THEORY
 contraindicated, and have initial basic investigations, most importantly blood glucose
and ECG.
 If the patient is in AF, an urgent brain scan is needed to exclude haemorrhage. They
should be started on an immediate-acting anticoagulant.
 The ABCD2 score (see table 1) offers guidance on stroke risk – many stroke services
stratify TIA management into high risk (ABCD2 >4; see, investigate and assess in
under 24 hours) or low risk (ABCD2 <4; see, investigate and assess within one
week).4
 Further investigations are based on risk stratification and exclusion of differential
diagnoses. This includes a full blood work-up and possible brain imaging. Diffusion-
weighted MRI is the modality of choice.
 If MRI is not possible, CT can be especially useful in identifying haemorrhage and
space-occupying lesions. Not all TIA referrals need brain imaging – it is only needed
if the diagnosis is in doubt and the findings will influence management.
 There is no need to image the carotid arteries unless surgery would be considered if
significant stenosis were to be identified.

Section 3 Managing the condition

 It is essential for all patients to have aggressive risk factor management (see box 2).
Lifestyle advice should target as many of the risk factors as possible.

 Patients in whom TIA is suspected must be advised not to drive for one month or until
further discussion in a TIA clinic.
 Treatment with antiplatelets, antihypertensives and statins has been shown to reduce
the stroke rate if introduced early.

Antiplatelets

 Aspirin in patients with previous TIA or stroke has been shown to reduce the risk of
vascular events by 13%.6
 Aspirin 300mg once daily should be started while investigations are pending. TIA can
occasionally be due to a small intracerebral haemorrhage, but this is uncommon and it
is reasonable to start an antiplatelet without brain imaging.
 The NICE recommendations for antiplatelet therapy after stroke are long-term
combination of aspirin 75mg once daily (or clopidogrel if aspirin is not tolerated) and
dipyridamole modified release 200mg
twice daily.
 However, most stroke physicians see no reason to adopt a different approach to
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antiplatelet therapy in TIA from that for stroke. The National clinical guideline for
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 stroke 2012 supports the use of clopidogrel first-line after TIA, only using the aspirin
and dipyridamole combination if the patient cannot tolerate clopidogrel.
 The CHANCE trial7 tested whether dual treatment with aspirin and clopidogrel started
at day one after symptoms and continued for 90 days was superior to aspirin alone in
minor stroke. It showed a significant reduction, from 11.7% to 8.2%, in progression to
stroke, with no increase in haemorrhage rate.
 This strategy is being adopted in neurovascular clinics, particularly in patients at very
high risk, such as those with crescendo angina.

Antihypertensives

 Antihypertensive treatment is recommended for the prevention of recurrent stroke and

other vascular events following TIA.
 The absolute BP target should be individualised (more rigorous control in patients
with diabetes). Observational studies and clinical trials support BP reduction for
secondary prevention, regardless of initial BP.
 Although the optimal regimen remains uncertain, data from trials such as PROGRESS
support the use of diuretics and the combination of diuretics and ACE inhibitors.8
However, it seems reasonable to follow
the latest NICE hypertension management guidelines.

Statins, diabetes, smoking

 Cholesterol-lowering drugs have been shown to be beneficial for primary and

secondary prevention.10 This should be addressed by dietary modification and use of
a statin if total cholesterol is >3.5mmol/L.
 Tight glucose control is important in patients with diabetes with TIA or ischaemic
stroke, to reduce micro- and macrovascular complications. HbA1c should be
optimised to <53mmol/mol. Smoking raises the risk of stroke by about 50%. All TIA
and ischaemic stroke patients should be supported to stop smoking.

Carotid endarterectomy

 Carotid endarterectomy is indicated in patients with TIA or stroke with a symptomatic

carotid stenosis
of 70% to 99%. Surgery needs to be performed as soon as possible after the TIA;
evidence suggests that by 12 weeks, drug treatment is as effective as surgery in
preventing recurrence.

Anticoagulation

 AF contributes to about 20% of ischaemic strokes and TIA. Anticoagulation with

warfarin has been the mainstay for patients with a CHADS-VASc score of >1, but for
many, non-vitamin K antagonist oral anticoagulants (NOACs) offer easier, more
reliable anticoagulation.
 Patients should be given the choice between warfarin and a NOAC. Aspirin has no
role in preventing stroke in patients with AF.
 If an anticoagulant is not used, nothing useful can be achieved by treating with an
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antiplatelet.
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 Section 4 Prognosis

 More than 20% of strokes are preceded by a TIA, although this is often not noticed
and reported by the patient.13
 The prognosis for TIA and stroke is related to a timely diagnosis, referral to a
specialist service and initiation of treatment, including secondary prevention.
 The effect of urgent treatment of TIA and minor stroke on early recurrent stroke
(EXPRESS) study suggested that rapid assessment and treatment, with the patient
being seen the same day in clinic and having medication initiated there, reduced the
risk of recurrence or development of stroke by up to 80%.5
 Although a TIA should not have any long-term impact on patients’ daily activities,
they must stop driving for a month.

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 Multiple sclerosis
Section 1: Epidemiology and aetiology

 Multiple sclerosis (MS) is the most common cause of progressive neurological

disability affecting young people, with an estimated 100,000 patients in the UK and at
least 2.5m worldwide.
 Women are affected approximately three times as frequently as men, with a median
age of onset around 30 years, although it may also affect children and middle-aged
adults.
 The cause remains unknown, but is thought to be multifactorial, with genetic and
environmental factors contributing to the risk of disease.

Genetics

 The overall incidence of MS is about one in 800. The concordance rate is about 30%
for identical twins and 5% for non-identical twins.
 Having a first-degree relative with MS increases an individual's risk to two to three
per 100.
 The strongest genetic risk of MS is conferred by the HLA DRB1 1501 allele, which
increases the risk of MS three fold, and more in homozygous carriers.
 Large international consortia have been established to investigate the genetic
determinants of MS. They have identified a growing number of loci associated with
increased risk of MS.
 Most of the genetic loci associated with susceptibility to MS are implicated with
immune function and a shared with a number of autoimmune diseases.1 These
findings confirm the widely held view that MS is primarily an autoimmune rather
than neurodegenerative illness.
 The incidence of MS is lowest near the equator and increases with increasing latitude
in both hemispheres (a phenomenon known as the north-south gradient). It has been
demonstrated that people who migrate between areas of high and low risk for MS are
more likely to adopt the level of risk for their new country if they move before their
early teens.2 This has suggested that environmental factors acting in early life may
also be involved.
 Environmental agents attracting research at present are low levels of vitamin D,
exposure to the Epstein-Barr virus, cigarette smoking and obesity.

Classification

 Disease course classifications in MS have recently been updated.1 MS is classified as

being either relapsing or progressive:

Relapsing remitting MS (RRMS)

 RRMS is the most common presenting form, affecting about 85-90% of people. It is
characterised by attacks of new or worsening neurological signs and symptoms
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(relapses), followed by improvement and periods of stability (remission), without

progression of disability between attacks.
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  Common presentations of MS include acute optic neuritis, double vision and sensory
symptoms.2 A first episode of CNS demyelination in a person without previous
neurological symptoms is referred to as a clinically isolated syndrome (CIS).

Secondary progressive MS (SPMS)

 Over time many people with RRMS transition to SPMS with gradual progression of
disability over time with or without relapses.

Primary progressive MS (PPMS)

 In PPMS, level of disability slowly worsens from the outset. PPMS affects men and
women equally and often presents at an older age than RRMS (mean age at onset is
40 years), usually with a progressive myelopathy.
 With the use of MRI to investigate unrelated problems (e.g. headache, sinus disease)
people are now increasingly recognised with subclinical or pre-clinical MS with
evidence of MRI abnormalities suggestive of demyelination but no symptoms. This
situation is referred to as the radiologically isolated syndrome (RIS).

Section 2: Making the diagnosis

 There is no one diagnostic test for MS. However, the diagnosis is dependent on
demonstrating dissemination of CNS lesions in time and space.
 Historically this was on the basis of clinical symptoms and signs alone (requiring two
or more attacks) with paraclinical evidence such as MRI scans, CSF examination and
evoked responses supporting the diagnosis.
 The diagnostic criteria for MS were revised in 2010, allowing the use of MRI to
provide evidence for dissemination in space and time, including in patients with a
single attack (the clinically isolated syndrome).4
 Use of the revised McDonald criteria (see table 1) has resulted in earlier diagnosis of
MS, which potentially allows for the earlier initiation of counselling and treatment for
patients.

Clinical features of MS

 Patients with MS can present in a wide variety of ways, depending on which parts of
the brain and spine are affected by the condition (see box 1).
 It is also recognised that for every clinical presentation, five to 10 areas of
demyelination may have occurred without causing any symptoms.
 Relapses are likened to the tip of the iceberg, with many CNS lesions occurring
without clinical symptoms.
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 Presentations of MS
 Loss of vision in one eye (optic neuritis)
 Diplopia
 Ataxia
 Ascending bilateral sensory loss with or without bladder and bowel involvement
(transverse myelitis)
 Bladder or bowel symptoms
 Limb weakness or spasticity
 Pain or sensory abnormalities
 Cognitive changes
 Tremor
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 Section 3: Managing the condition

 Treatment can be complicated because of variable symptoms, unpredictable relapses

and the differing disease course. Access to a multidisciplinary team with expertise in
the management of MS is crucial.
 National guidelines in the UK5,6 stress the importance of early referral to MS nurses
and the provision of appropriate information and support, such as that provided by
the MS Society and the MS Trust.

Disease-modifying drugs

 Treatment of MS began to change in the 1990s with the introduction of beta-

interferons and glatiramer acetate. Injectables reduced relapse rates by about 30% and
reduced MRI brain lesions by up to 70%.9
 Since then, there has been significant development in drugs to treat RRMS with
increasing efficacy in reducing relapses, new MRI lesions and rates of brain atrophy.
 There are currently more than 10 treatments licensed for RRMS, with several
awaiting regulatory approval and others in late-stage development.
 Neurologists treating MS are becoming increasingly aggressive in their approach,
with the aim being to customise disease-modifying treatment for each patient. The
aim is to stop all disease activity, not just clinical relapse, but also MRI measures of
lesion load and atrophy. This is known as treating to no evidence of disease activity or
NEDA.10
 When choosing treatment for a patient, there are many considerations to address.
These include the level of MS activity - frequency and severity of relapses, MRI
lesion load and location, preferred method and frequency of administration,
monitoring requirements, the desire for pregnancy, the patient's lifestyle and levels of
compliance and adherence, and tolerability and safety.
 Resources are available for patients to aid decision making through discussions with
specialist nurses.
 Disease-modifying treatments (see box 2) are increasingly effective in reducing
relapses and possibly delaying progression if started early. But, for those patients
whose MS is in an established progressive course, there are as yet no effective
treatments (treatments for progressive MS are in late-stage development).

Disease-modifying treatments
 Interferon beta-1a
 Interferon beta-1b
 Glatiramer acetate
 Teriflunomide
 Dimethylfumarate
 Fingolimod
 Natalizumab
 Alemtuzumab (active RRMS)
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 In all patients, symptomatic treatment for ambulatory problems, bladder and bowel
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disturbance, pain and fatigue is important to improve quality of life.

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 Section 4: Prognosis

 A number of studies have investigated the effect of MS on life expectancy.12 Overall,

they suggest it is shortened by five to 10 years. Many of these studies, however, were
performed before disease-modifying treatments became available.
 It is hoped that with more widespread use of these treatments and other advances in
management, this difference will decrease.

Relapse management

 Although disease-modifying treatments can significantly reduce relapses, when these

do occur, they can cause significant disability and distress, so urgent assessment and
treatment are required.
 Many centres provide a relapse clinic, with rapid assessment by a multidisciplinary
team.
 If causes of deterioration or new symptoms can be excluded (intercurrent infection is
a common cause), treatment with steroids may be considered.
 One trial has shown no difference in efficacy between oral or IV methylprednisolone.
A common regimen is methylprednisolone 500mg for five days. Longer courses, or
use of more than two courses per year, are not advised, due to the risk of side-effects
such as osteoporosis.

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 Epilepsy
Section 1: Epidemiology and aetiology

 Epilepsy is a group of disorders characterised by two or more unprovoked seizures.

The average prevalence of epilepsy is 5.5 per 1,000 people in Europe, 6.8 per 1,000
people in the US and 7.5 per 1,000 people in Australia.
 Prevalence rates reported in developing countries vary considerably, with rates as
high as 74.4 per 1,000 people for sub-Saharan Africa.
 The annual incidence rates of epilepsy are 24-56 per 100,000 people in Europe.
Reported incidence rates for developing countries are considerably higher.
Approximately 3% of people will be diagnosed with epilepsy during their lifetime.

Classification

 Seizures are broadly classified into focal onset (simple focal, complex focal and
secondary generalised tonic-clonic seizures) and generalised onset (categorised as
generalised tonic-clonic, absence, myoclonic, tonic and atonic seizures).
 Epilepsy may be caused by a variety of disorders affecting the brain and can be
classified by cause. Genetic (previously termed idiopathic): where epilepsy is the
direct result of a presumed genetic defect.
 Structural/metabolic (previously termed symptomatic): resulting from tumour,
infection, head injury, cerebrovascular disease, degenerative or demyelinating
conditions.
 Unknown (previously termed cryptogenic): where the nature of the underlying cause
is unknown.1
 Temporal lobe epilepsy accounts for 60-70% of all focal epilepsies and may result
from viral or autoimmune encephalitides, mesial temporal sclerosis (MTS) or tumour.
Juvenile myoclonic epilepsy and childhood absence epilepsy account for most
presumed genetic epilepsies.
 Epilepsy is associated with comorbidities, particularly in the subset of patients with
chronic epilepsy, who are more at risk of sudden unexplained death. Depression
occurs in approximately one-third of all patients with epilepsy and is the second most
important predictor of quality of life. Identifying chronic epilepsy early may allow
early implementation of aggressive treatment, minimising long-term sequelae.

Section 2: Making the diagnosis

 Patients presenting with a first seizure or epilepsy should be seen within two weeks by
a specialist with clinical expertise in epilepsy.2 However, a proportion of patients will
be diagnosed by other healthcare professionals because of variable access to epilepsy
clinics or specialists in some parts of the UK.3
 Epilepsy is a clinical diagnosis based on an accurate and detailed clinical history. A
witness account should be sought wherever available. The clinician needs to
distinguish between seizures, syncope and non-epileptic attack disorder (NEAD).
Syncope can be physiological (vasovagal), cardiogenic or related to autonomic
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dysfunction. Myoclonic jerks (which may be multifocal and high amplitude) can
occur during a syncopal event and may mimic seizure activity. Bradyarrhythmias can
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occur as part of seizures and may cause syncope.

MRCGP THEORY
  NEAD accounts for one in five patients presenting to the epilepsy clinic. These events
are thought to have an underlying psychological basis.
 Neuropsychological assessment may unveil previous exposure to physical or sexual
abuse and maladaptive illness behaviour.

CLINICAL
FEATURES
Non-epileptic attack
Syncope Seizures disorder
Posture Upright Any posture Any posture
Onset Gradual Sudden/aura Gradual
Pallor and
sweating Invariable Uncommon Uncommon
Injury Unusual Not uncommon Not uncommon
Common (wax and
Convulsive jerks Not uncommon Common wane) non-rhythmical
Incontinence Rare Common Not uncommon
Unconsciousness Seconds Minutes Minutes to hours
Recovery Rapid Often slow Often rapid
Rare (tearful,
Postictal confusion Rare Common emotional)
Common (lateral Rare Common Rare
Tongue biting Rare border) (tip of tongue)
Precipitating Crowds, lack of food, Sleep Stress, anxiety,
factors unpleasant circumstances deprivation medical situations

History

 During history taking, information on child development and any illnesses (febrile
convulsions, meningitis or head injuries) needs to be sought. Family history of
blackouts or epilepsy, alcohol and drug use and current medications are also
important. Establishing whether the patient holds a driving licence and pregnancy
plans in women of childbearing age, are important facets of the history.

Investigations

 All patients presenting with seizure should have a 12-lead ECG to ascertain any
underlying arrhythmia or long QT syndrome.
 Interictal electroencephalography (EEG) is used in the setting of first epileptic seizure
to provide prognostic information on the risk of further seizures over the next two
16

years (27% versus 58% in patients with normal versus abnormal EEG).
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MRCGP THEORY
  In patients with newly-diagnosed epilepsy, EEG may provide information on
classification and seizure type. In patients with suspected NEAD, EEG may confirm
the diagnosis, demonstrating a lack of epileptiform correlate during a clinical event.
 Interictal EEG is normal in about 50% of patients with epilepsy and is not a
diagnostic tool for epilepsy. Video-EEG, where the patient is monitored during a five-
day hospital stay, is used in cases where there are frequent events of diagnostic
uncertainty.
 MRI (T1, T2, fluid attenuated inversion recovery sequences) is used to identify a
structural lesion (for example, hippocampal sclerosis, cortical dysplasia or low-grade
glioma) causing seizures. Early identification of lesions provides opportunity for
timely surgery and treatment planning.
 Other imaging techniques are also used in UK epilepsy centres to provide further
diagnostic information in presurgical evaluation.

Section 3: Managing the condition

 The MRC multicentre trial for early epilepsy and single seizures ascertained that there
was no long-term treatment advantage in commencing patients presenting with first
seizure on antiepileptic drugs (AEDs).
 However, AEDs may be offered to patients following a generalised tonic-clonic
seizure if there is a neurological deficit, the EEG shows unequivocal epileptic
discharges, there is a structural abnormality on imaging, or the patient (or carer)
considers the risk of seizure recurrence unacceptable.4
 The main aim of treating epilepsy is to achieve seizure freedom with minimal side-
effects. In patients with non-lesional epilepsy, this is achieved via AEDs. All are
widely considered to be effective in controlling focal onset seizures, although some
drugs (for example, carbamazepine) may exacerbate certain forms of generalised
seizures (for example, myoclonus and absences).
 The largest randomised clinical trial to date, Standard And Newer Anti-epileptic
Drugs (SANAD I) in newly-diagnosed epilepsy patients demonstrated that
lamotrigine was most effective for patients with newly diagnosed focal onset epilepsy
and sodium valproate was most effective for patients with newly diagnosed
generalised onset epilepsy.5,6 SANAD II, is examining newer AEDs with the most
effective AEDs from the first trial.

Choosing an AED

 There needs to be special consideration when choosing AEDs in patients of

childbearing age and in women on the combined oral contraceptive pill (COC).
 In patients who fail their first monotherapy, an alternative trial of monotherapy should
be considered. In patients failing two trials of appropriate treatment, a second AED
may be added to the current regimen.
 The proportion of patients achieving a reduction in seizure frequency by 50% varies
between 30% and 50% for newer AEDs used as add-on therapy.
 There is no clear evidence on which to base a choice among AEDs at present. Some
advocate the combination of AEDs with mechanistic actions, but there is no clear
evidence that mechanism of drug influences the response to treatment.
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 Surgical options

 In patients with MTS who do not achieve seizure control with AEDs, surgery should
be considered. Predictors of achieving seizure freedom include shorter duration of
epilepsy, younger age at surgery, absent secondary generalisation and concordance
between MRI and EEG.
 Vagal nerve stimulation (VNS) is used as adjunctive treatment in patients with focal
onset epilepsy who are medically refractory to AEDs and are not suitable for surgery.
Studies show that approximately 30% of patients may have a reduction of seizures by
50% with VNS.
 VNS also appears to improve depressive symptoms, with patients experiencing
enhanced psychological wellbeing. Adverse effects commonly include hoarse voice,
coughing and pharyngitis. Trigeminal nerve stimulation (TNS) via transcutaneous
patch has been licensed for use in Europe and the US. It is thought to work by
modification of thalamocortical pathways. TNS is yet to be evaluated by NICE for use
in the UK.

Annual review checklist for epilepsy patients suitable for primary care review
1. Seizure control (number of attacks, type of attack – use diary if necessary)
2. Date of last seizure
3. Any adverse effects of AEDs
4. Any cognitive problems as an adverse effect of AEDs
5. Consider checking folate/FBC in patients on enzyme-inducing AEDs whose diet might
be low in folate
6. Consider checking vitamin D levels in patients on enzyme-inducing AEDs who have
other risk factors for osteoporosis
7. Compliance (monitoring of AED levels is only recommended to check compliance if
seizure control is poor and in patients treated with phenytoin)
8. Continued education about epilepsy (refer to community epilepsy nurse where available)
9. Address lifestyle factors (driving, contraception, pregnancy planning, employment,
benefits)
10. Date of next review
11. Adjust AEDs according to agreed management plan

Section 4: Prognosis

 Approximately 60-70% of patients with epilepsy can expect to achieve seizure

remission. The remaining 30-40% develop chronic (medically refractory) epilepsy,
which may require multiple trials of treatment or co-medications to control seizures.
 Risk factors for recurrent seizures include high pretreatment seizure frequency,
earlyto mid-adult onset epilepsy, generalised and myoclonic seizures and an abnormal
EEG.
 Patients who achieve full control or have infrequent seizures may be suitable for
follow-up care in the community.
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 Criteria for Re-referral to a Secondary Care Epilepsy Specialist
1. Poor seizure control
2. Problems with AEDs
3. Neurological deterioration or impact of epilepsy on cognitive function
4. Further advice on management is required (for example, preconception counselling)
5. Acute problems, for example, recent admission for status epilepticus
6. Patients who are seizure-free wish to discuss possible withdrawal of AEDs
7. Patients with a diagnosis acquired elsewhere and new to the practice

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 Headache and migraine
Section 1: Epidemiology and aetiology

 Headache is common and most patients are managed in primary care. For most,
headache is an occasional annoyance, but for some it can be severely disabling.
 The International Headache Society (IHS) classification is fundamental to research
and to the evidence base.1 It uses a computing analogy to describe primary headache
as a common 'software' problem and secondary headache as a relatively uncommon
'hardware' problem.
 NICE guidance addresses the risk of secondary headache. Headache triggered by the
Valsalva manoeuvre or by exercise, abrupt onset headache, the older patient, and
known cancer are helpful pointers.
 A 'change in personality' and 'symptoms suggestive of giant cell arteritis' are less
helpful. Risk of secondary headache in new presentation to primary care is 0.1%.

Primary headache

 Primary headache is usually migraine, a dysfunction of the trigeminal nucleus in the

brainstem. The exceptions are the trigeminal autonomic cephalalgias (TACs), of
which cluster headache is the most commonly recognised. TACs arise in the midbrain
and give strictly unilateral pain, typically orbital, with ipsilateral autonomic features.
The treatment strategy differs from that of migraine.
 Tension-type headache (TTH) is featureless and non-disabling, so when present alone
does not need medical treatment.
 Migraine affects up to 20% of people and is a feature-full disabling headache. It was
thought to be episodic until 2004, when chronic migraine was defined. This useful
classification change acknowledges the comorbidity of migraine and TTH.
 Most people disabled by persistent headache have chronic migraine, that is, 15 or
more days of pain per month, for at least three months. At least eight of the 15 days
must be migrainous.
 Medication overuse headache (MOH) is essentially the same as chronic migraine, but
accompanied by the use of rescue medication for more than 10-15 days a month.
 The IHS criteria for chronic migraine exclude MOH, although this is likely to be
revised soon. The most important matter in managing chronic headache is to address
MOH, which is probably a specific complication of migraine, being absent in pure
TAC. MOH often complicates resolved secondary headache.

Section 2: Making the diagnosis

 Careful enquiry is needed to assess the diagnostic features associated with migraine.
 'Queasy' is a useful word, rather than 'sick' or 'sickness', because light, noise and smell
sensitivity are easily overlooked.
 Stoical patients may deny feeling a need to rest. Pulsating or thumping pain is
subjective and not essential for diagnosis. Lateralisation is also in the diagnostic
criteria, although migraine may be bilateral and is often asymmetrical.
 Recurrent head pain with queasiness, or light or noise sensitivity, or a preference for
20

rest, and a normal examination, is migraine.

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  Aura, a transient cortical or brainstem dysfunction, occurs in up to a third of patients
with migraine and is usually easily recognised. Aura without headache is common.
 Prodrome occurs hours before many migraine attacks; typically, a change in mood or
diet. Yawning is a common prodrome.
 When there is doubt about the history, a headache diary is invaluable. One to three
months is usually sufficient. Record all pain and associated features, leave a blank if
no pain and record all medication, whether prescribed or OTC.
 All patients with new headache require a brief neurological examination that can
easily be carried out in a routine primary care consultation. Look in particular for
papilloedema, eye movement disorder, ataxia and hemianopia.
 Diagnosis of MOH hangs on the history, which can be difficult to obtain. Most
patients take triptans, opiates or combination analgesia and the threshold is 10 days a
month, over three months or longer.
 Simple analgesia taken for 15 or more days a month also fulfils the criteria for MOH,
but most patients will have stepped up to stronger drugs long before a diagnosis of
MOH.
 TAC is suggested by severe orbital pain with autonomic features.

When to scan

 A brain scan is the key test. Although it may be tempting to scan everyone with
headache, this is impractical and creates demand for repeat scanning in persistent
headache.
 Incidental abnormalities affect one in 40 to one in four healthy people;2 their
detection can harm health. Scanning must be selective. MRI is more sensitive than CT
and avoids irradiation.
 NICE advises against scanning for reassurance, but when a patient demands a scan it
is often pragmatic to agree to just one. After a normal MRI, it is reasonable to refuse a
further scan in the absence of a specific new indication.

Section 3: Managing the condition

 Patients with migraine should avoid dehydration and excess caffeine or alcohol, and
aim to reduce stress.

Acute rescue

 Aim for the abolition of pain and resumption of normal activities two hours post-dose.
 Some patients respond well to a simple analgesic, such as aspirin 900mg or ibuprofen
600mg, preferably dissolved in water; adding domperidone 20mg to address gastric
stasis (even if no nausea or vomiting) can be helpful. This may be used during
prodrome, aura, or at pain onset and repeated as appropriate.
 Triptans are not always adequate in anticipation of pain and should not be repeated
following an ineffective dose. There are seven triptans, all available as tablets, three
as mouth-dispersible (convenient but no other advantage), two as nasal sprays (extent
of nasal absorption is contentious) and one as a self-injection which usually brings
relief in 30 minutes, at an NHS cost of about £20. This is the only triptan licensed for
21

patients with cluster headache.

 Most patients use triptan tablets; a meta-analysis describes their relative merits.3
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MRCGP THEORY
 Prophylaxis

 Prophylaxis is considered after addressing the above strategies.

 Indications for starting prophylaxis may be a monthly disabling attack unresponsive
to acute medication, but not weekly attacks responding well to acute rescue.
 A headache diary and long-term planning are important. With a minimum three
months of treatment, titrate to the maximum tolerable dose. The following may be
tried, but not all are licensed in this indication.

 Nutraceuticals, for example, vitamin B2 400mg daily after breakfast, or co-enzyme Q10
100mg three times daily, are worth considering.
 BP drugs, particularly beta-blockers, are a popular choice in primary care, although they
can worsen depression or sleep disturbance.
 Antidepressants, particularly tricyclics (probably not SSRIs), are widely used, although
their side-effects and stigma are problematic.
 Pizotifen is widely used in primary care. Weight gain and drowsiness are common side-
effects.
 Antiepilepsy drugs are increasingly used. Topiramate is licensed in this indication,
although cognitive and affective toxicity are common.
 Botulinum toxin is licensed for prophylaxis only of chronic migraine.

Managing MOH

 MOH requires cessation of overused medications. Transient worsening can last two,
rarely four, weeks. This requires planning by the patient, perhaps time off work or
family support.
 Naproxen 250mg or 375mg three times after meals, and/or domperidone 20mg three
times daily before meals, to address pain, and nausea, vomiting or gastric stasis
respectively, can be considered for a few weeks.

Section 4: Prognosis

 Migraine improves naturally with age. Frequency and impact vary over time, often
leading to confidence in ineffective therapies.
 In childhood, episodes tend to be shorter, with prominent vomiting, symmetrical pain
and abdominal rather than head pain.
 The female preponderance begins at puberty but menstrual migraine is mostly a
disorder of younger adults. In middle age, presentation is often as aura without
headache, chronic migraine, or MOH, which is the most common but not the only
reason for the headache becoming chronic.
 Migraine usually improves from the second trimester of pregnancy until cessation of
breastfeeding.
 Migraine aura in younger women is associated with a small increase in cardiovascular
risk. This risk is very small but it is a contraindication to the estrogen contraceptive
pill.
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 Classification of the headache
Headache is formally classified by the International Headache Society.1 As the brain has no
sensory fibres, intracranial pain arises from invasion, stretching, pressure on or inflammation
of the meninges. Headaches can be classified as primary and secondary.

Primary headache

 Primary headaches account for 90 per cent of presentations in primary care. There is
no demonstrable underlying cause.

Migraine:
 85 per cent of GP headache presentations are migraines.
 Severe episodic pain with or without aura and associated with nausea, photophobia and
phonophobia.
 Five per cent of these patients have chronic migraine, experiencing >15 days of migraine
each month.
Tension-type headache:
 Ten per cent of GP presentations but high population prevalence.
 Poorly understood.
 Dull, pressing pain usually bilateral with no nausea, photophobia or phonophobia.
 Episodic or chronic.
Cluster headache and autonomic cephalalgias:
 Cluster headache and other autonomic cephalalgias account for less than 1 per cent of GP
headache presentations.
 Patients experience very severe unilateral pain with autonomic features rarely with nausea,
photophobia or phonophobia.

Secondary headache

 In these headaches an underlying cause is demonstrable.

Subarachnoid haemorrhage:
 Characterised by thunderclap headache - worst headache ever rising to a maximum within
a minute.
 Ten per cent of thunderclap headaches are due to subarachnoid haemorrhage.
 Medical emergency with high mortality.
 Sentinel headaches may be recognised in retrospect.
Temporal arteritis:
 Occurs over the age of 50.
 Forty per cent will have polymyalgia rheumatica.
 Can be systemically unwell.
 May have jaw claudication.
 Raised ESR or CRP in 97 per cent of cases.
 Temporal artery biopsy may confirm diagnosis.
Hypertension:
 Apart from malignant hypertension, the contri-bution of hypertension to headache is
overrated and in practice is negligible.
23

Carotid/vertebral artery dissection:

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 Pain can radiate anywhere in face and neck.

MRCGP THEORY
  May occur after trauma.
 Collagen disease is a risk factor.
Stroke:
 Non-specific headache can be associated with stroke.
Tumour:
 Headache is common during course of illness, but only 10 per cent of tumours present
with isolated headache.
Idiopathic intracranial hypertension:
 Common in young obese women.
 Headache and papilloedema often with pulsatile tinnitus.
 Can lead to permanent loss of vision.
 Refer.
Intracranial hypotension:
 Intracranial hypotension occurs due to cerebrospinal fluid volume depletion as a result of
leakage.
 Headache is worse on standing and alleviated by lying down.
 Classically post lumbar puncture but spontaneous leaks can occur.
 Refer.
Headache attributed to trauma:
 Can occur up to seven days post trauma.
 Intensity of pain may not be related to degree of trauma.
 Most resolve in less than six months but 25 per cent can go on for longer.
 Watch for development of depression.
 Headache can be part of a post-concussive syndrome associated with other non-specific
symptoms.
Referred headache:
 Cervicogenic pain is most common but is overrated as cause of headache.
 Eyes, tempero-mandibular joint, teeth and sinus (85 per cent of diagnosed chronic sinusitis
is migraine) are all possible but overestimated as causes of headache.
Activity-associated headache
During sexual activity the patient may experience a dull headache that increases with sexual
activity or a sudden severe headache at orgasm.

 The latter needs investigation.

 Exercise-induced headache may be a co-existing primary headache induced by
exertion. Underlying pathology must be excluded.
 Treatment of both is pre- emptive (indometacin) or preventative (beta blocker).

Other causes
 Obstructive sleep apnoea may be due to CO2 retention or poor sleep. It is reversible
with treatment of the cause.
 Renal failure, thyroid disease and raised calcium can also cause headache. Carbon
monoxide poisoning may cause headaches and fatalities. Alcohol and drugs can be a
cause.
 Meningitis, encephalitis, TB or a systematic infection may cause headache.
 Medication overuse headache affects up to 3 per cent of the population. It can occur
with regular analgesia or triptan use. All analgesics and NSAIDs are implicated,
24

particularly codeine compounds.

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 Cranial neuralgias
 Trigeminal neuralgia is most common.
 Burning or stabbing pain lasting less than two minutes, often provoked by mild pressure or
triggers. Vascular compression of a nerve is the most common cause.
 Trigeminal neuralgia may be confused with idiopathic stabbing headache, particularly
with co-existing migraine

Differentiate causes of primary and secondary headaches.

 Onset of headaches >50 years

 Thunderclap headache - subarachnoid haemorrhage
 Neurological symptoms or signs
 Meningism
 Immunosuppression or malignancy
 Red eye and haloes around lights - acute angle closure glaucoma
 Worsening symptoms
 Symptoms of temporal arteritis

 Headache is a common neurological presentation in primary care and may be primary

or secondary.
 Primary headache includes tension-type headaches, cluster headaches and migraine.
Secondary headache may be caused by glaucoma, sinusitis, intracranial malignancy,
haemorrhage, idiopathic intracranial hypertension and infection.1
 Headaches may cause significant morbidity and can result in absence from work or
school. The most common types are tension-type headaches and migraines.
 Red flag symptoms should be excluded to rule out more serious causes of headache. It
is of note that intracranial masses do not usually cause headache.1

Clinical assessment

 History taking involves assessing the location of the headache, its onset, severity, duration,
and exacerbating and relieving factors.
 Possible triggers may include coughing, sneezing, exercising, changes in posture and onset of
menses. It is helpful to assess whether there have been previous episodes and if so, whether
there has been a change in the pattern or severity of the headache.
 The nature of the pain, as well as how debilitating the headache is, should be assessed. It is
useful to find out what treatments have been tried and any response to them.
 New headaches presenting in a patient over the age of 50 years may indicate temporal
arteritis.1
 Other relevant features may include nausea and vomiting, fever, and visual symptoms
including red eye, visual field defects, blurring and diplopia. The presence of lacrimation and
facial flushing may be suggestive of cluster headaches.1
 Carbon monoxide poisoning may present with headaches, vomiting, muscle weakness and
diplopia.1 There may be a history of an aura in migraine and pulsatile tinnitus may be
suggestive of idiopathic intracranial hypertension. If clinically appropriate, asking the patient
to keep a headache diary may be helpful.
 Focal neurology may indicate intracerebral pathology, a bleed or infection. Neurological signs
may include impaired level of consciousness, weakness, new onset seizures or papilloedema.
Headache associated with vomiting, drowsiness or changes in posture may be caused by
25

raised intracranial pressure.

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  A thunderclap headache refers to a severe headache of sudden onset - this may
indicate subarachnoid haemorrhage. It is helpful to exclude head trauma occurring
within the past three months of the headache.1
 Red eye and haloes around lights may indicate acute angle closure glaucoma. Risk
factors include a family history and hypermetropia.1
 A rare cause of headache, found more commonly in young obese women, is
idiopathic intracranial hypertension.1 The history may suggest features of raised
intracranial pressure and papilloedema may be found on clinical examination.
 Physical examination should include vital signs and a full neurological examination.
Eye examination should include pupillary reflexes, extraocular movements,
fundoscopy and visual field assessment. It may be necessary to exclude meningism.
 If temporal arteritis is suspected, the scalp should be examined for swelling and
tenderness, and there may be a history of jaw claudication.

Management

 Depending on the clinical cause, it may be appropriate to arrange blood tests. The
presentation may warrant immediate referral to hospital, for example, in suspected
subarachnoid haemorrhage.
 In cases of suspected temporal arteritis, immediate management with high-dose steroids is
required to prevent blindness.
 If a patient presents with recent headaches associated with signs of raised intracranial
pressure, urgent referral should be made via the two-week wait pathway.2
 If a patient presents with headaches associated with focal or non-focal neurology, urgent
referral should be made, if appropriate.2
 Non-focal neurology may refer to cognitive changes and altered mental status. Urgent referral
is recommended by NICE if there is a change in the usual pattern of headache, with
increasing severity.2
 If there is a history of malignancy in a patient with new onset seizures, neurological deficit or
signs, persistent headaches and/or altered mental status or cognitive changes, urgent referral is
recommended.2
 A history of new onset headache in patients who are immunocompromised, for example, in
relation to HIV or immunosuppressive therapy, a history of malignancy known to cause
26

cerebral metastases and vomiting in the absence of other causes may warrant referral for
further investigation.
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 Delirium
Section 1 Epidemiology and aetiology

 In the present day, delirium is also known by the more descriptive term 'acute
confusion'. It describes the sudden onset of mental confusion, accompanied by a
degree of disturbed consciousness, cognitive function and/or perception.
 The condition develops over 24-48 hours and is commonly associated with a
reversible medical, surgical or pharmacological insult to the body.2
 Delirium can present as hyperor hypoactive. In the former, the patient may be agitated
or even aggressive, while in the latter, they may be withdrawn and drowsy.
 It is possible for delirium to present as a mixture of the two states; this can be difficult
to diagnose and often leads to delays in management.
 According to NICE guidelines,2 in the UK, about 20-30% of medical inpatients will
develop delirium during their admission, while the same is true of 10-50% of surgical
inpatients.
 The clinical and social outcomes of delirium are poor if management is not addressed
early on in its evolution. This can also have an adverse economic impact.

Section 2 Making the diagnosis

Recognition of delirium requires brief cognitive screening and clinical observation. In all of
the three subtypes - hyperactive, hypoactive and mixed - the following domains may be
affected:

 Consciousness
 Orientation
 Memory
 Thought
 Perception
 Behaviour

 Patients with the hyperactive subtype of delirium may experience restlessness,

agitation, hypervigilance, thought disorder and perceptual abnormalities. Those with
the hypoactive subtype may be lethargic and sedated, and may demonstrate
psychomotor retardation.
 Standard diagnostic criteria are given in DSM-5, the fifth edition of the American
Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders,3 and
ICD-10, the WHO Classification of Mental and Behavioural Disorders.4
 Another important factor to consider when making a diagnosis is whether the patient
is presenting with a picture of acute or chronic confusion, or acute-on-chronic.
 The clinical history is of vital importance in answering this question. Factors to
consider include:
 History and time course - was the onset sudden or gradual? Has it lasted days or
longer? Have there been similar episodes in the past?
 Cognition against a baseline - what was cognition like before this episode? Consider
27

using formal cognitive tests or, if short of time, brief assessment of orientation and
attention (a digit span or serial sevens subtraction test).
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MRCGP THEORY
  Fluctuations in consciousness/cognition/sleep - are deficits consistent over time, or
transient and changeable?
 Potential causes - have there been any recent physical insults (commonly, infections
or orthopaedic procedures), complications or changes in medication?5 Withdrawal
from benzodiazepines or alcohol can precipitate delirium.
 Symptoms that are of sudden onset, quickly progressing, fluctuating and temporally
associated with a physical insult suggest a delirium-type picture. The most commonly
used instrument for the identification of delirium is the confusion assessment method

Section 3 Managing the condition

 Effective communication with the patient, their family8 and colleagues in the
multidisciplinary team is the key to effective management of patients with delirium.
 This is especially true if the patient presents as anxious or distressed. Calm verbal de-
escalation should always be a first-line intervention in these scenarios.
 If a diagnosis of delirium has been established and a cause identified, management
should focus on treating the cause. Further management options can be divided into
non-pharmacological and pharmacological interventions.

Non-pharmacological

 Non-pharmacological interventions should be tried first and should include efforts to

orientate the patient in time and place.

These can include:

 Establishing physiological stability: adequate oxygenation, restore electrolyte imbalance,

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restore hydration
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MRCGP THEORY
  Optimising the environment: avoid sensory deprivation and overload, minimise noise,
optimise lighting, provide familiar objects
 Addressing modifiable risk factors: manage pain, correct sensory deficits, support normal
sleep pattern
 Optimising communication: calm, supportive approach, avoid confrontation, reorientation
(try using a clock or calendar), staff consistency, involve the patient's friends or family
 Reviewing medication: if medication is deemed necessary, consider the lowest effective
therapeutic dose
 Mobilisation
 Structured routine
 Encouraging self-care

A behavioural chart (also known as an Antecedent, Behaviour, Consequence, or ABC, chart) can be
useful in determining specific triggers for agitation and can help to shape practical management.

Pharmacological

 There is little robust evidence for the use of pharmacological interventions for
delirium.5 Pharmacological methods should only be used if non-pharmacological methods
have failed and there is concern regarding risk to the patient or others secondary to agitation
or aggression.2
 A low dose of an antipsychotic, such as haloperidol or olanzapine, can be considered.
Haloperidol is a high-potency medication, with relatively few anticholinergic side-effects and
a wide range of doses and routes of administration.
 Patients should be commenced on 0.25-0.5mg orally in the first instance. In patients with MS,
Lewy body dementia or Parkinson's disease, haloperidol is best avoided, owing to the risk of
severe extrapyramidal side-effects. In these patients, quetiapine 12.5mg could be considered.
 Benzodiazepines are best avoided if possible, owing to their propensity for worsening
confusion. However, they may be considered if antipsychotics are contraindicated, or in
situations where the delirium is due to alcohol or benzodiazepine withdrawal.
 The following are important points to consider with pharmacological interventions for
patients with delirium:

 Psychotropics should be reserved for patients exhibiting symptoms of agitation or psychosis

 In the absence of psychotic symptoms, treating hypoactive delirium with psychotropics is not
recommended
 Psychotropics are not indicated for wandering
 Always consider monotherapy, and use the lowest possible dose of these medications

Section 4 Prognosis

 Studies have suggested that symptoms of delirium can persist after discharge in up to 51% of
patients.9,10 This can lead to impaired function.
 It is now evident that delirium is also associated with brain injury, because delirium is a
strong risk factor for new-onset dementia,11as well as acceleration of existing dementia.12
 This highlights the importance of prompt diagnosis and management of patients with the
condition, to lower the risk of any long-term complications.
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 Hallucinations
 Frightening hallucinations
 Symptoms suggestive of psychosis
 Neurological disorder
 Focal neurological deficit
 Recreational drug use
 Delirium

 A hallucination, which may be defined as a sensory perception in the absence of an

external stimulus, may be olfactory, auditory, visual, tactile or gustatory.
 It has been reported that up to 30% of patients experiencing delirium may have visual
hallucinations.
 Hallucinations are often thought of as manifestations of mental illness, but those
without mental illness may experience them, especially gustatory and olfactory
hallucinations.
 Moreover, hypnagogic (occurring on falling asleep) and hypnopompic (occurring on
waking) hallucinations can occur in all individuals.

 This means hallucinations may not necessarily be pathological - recently bereaved

people may report visual or auditory hallucinations.
 Hallucinations may occur in the presence of increased external stimulation, for
example, in the presence of others, or in conditions of decreased external stimulation.
 Hallucinations may be the presenting feature in schizophrenia, conversion reactions
and affective disorders. Auditory hallucinations are the most common in
schizophrenia, although visual hallucinations may also be reported.
 Auditory hallucinations may accompany severe depression, with voices talking
directly to the patient, the content of which is congruent to the patient's low mood.
They may also be seen in manic states and are again congruent with the patient's
mood.
 An association between hallucinations and childhood sexual abuse has previously
been described.
 Auditory hallucinations have also been reported in post-traumatic stress disorder.
Auditory hallucinations resulting in self-harm may be seen in patients with borderline
personality disorder.
 Hallucinations may occur in neurological conditions, such as epilepsy, migraines,
30

Parkinson's disease and Lewy body dementia. They are more common in Parkinson's
disease with advancing age, length of illness, cognitive impairment and depression.
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MRCGP THEORY
  In moderate to severe Alzheimer's disease, if hallucinations occur, they are most
likely to be visual.
 Visual hallucinations may result from cortical lesions that involve the occipital and
temporoparietal areas. Olfactory and gustatory hallucinations may arise as a result of
a temporal lobe lesion.
 Retinal disease, age-related macular degeneration and cataracts may result in visual
hallucinations.
 Charles Bonnet syndrome describes the presence of visual hallucinations after loss of
visual acuity, where there has been no cognitive impairment. It is thought this may be
related to increased cortical compensation in the temporal cortex, striatum and
thalamus.
 Auditory hallucinations may be reported in patients with unilateral and bilateral
hearing loss.
 Drug misuse may be causative in the case of alcohol misuse, cannabis and MDMA
use. Vivid and colourful images may be seen following ingestion of psychoactive
drugs.
 Auditory hallucinations may occur in substance-induced psychoses. Cocaine and
amphetamine use may result in tactile hallucinations, such as the sensation of insects
crawling on the skin. Flashbacks in the form of visual hallucinations may occur in the
drug-free state.
 Hallucinations associated with delirium tremens may involve visual hallucinations of
animals; these hallucinations tend to be frightening.

Clinical assessment

 In patients presenting with hallucinations, a thorough history and neurological

examination are required to assess the underlying cause and determine the prognosis.
 Auditory hallucinations are the most common type overall, but in brain disorders,
visual hallucinations are the most common.
 It is important to assess the modality of the hallucinations and any associated factors.
Assess any risk to the patient as a result of them - for example, ask about the nature of
the hallucinations and if the patient is frightened of them.
 This is particularly relevant if psychosis is suspected because there may be a possible
risk of self-harm, including suicide.
 Schneider's first-rank symptoms of schizophrenia consist of auditory hallucinations
where there is thought echo and a running commentary discussing the patient in the
third person.
 According to the ICD-10 classification, these symptoms may support a diagnosis of
schizophrenia.
 Subclinical hallucinations may be seen in children and occur more frequently in those
with conduct and/or emotional disorders.

Management

 Hallucinations are often thought to be the manifestation of psychiatric disease, but

many other conditions may present with them.
 Hallucinations may respond to antipsychotic medications and to treatment of the
31

underlying cause. If they persist, CBT and supportive psychotherapy may be useful.
Specialist neurological and/or psychiatric referral should be considered.
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MRCGP THEORY
 Tremor
 Sudden onset
 Progressive
 Stepwise (suggestive of stroke or MS)
 Neurological deficits
 Age under 50 years in the absence of family history of essential tremor

 Tremor may be described as involuntary, rhythmic, oscillatory movements. It may be

physiological or pathological, with varying degrees of severity.
 It may involve the head and neck area, the trunk or the limbs. There may be voice
changes or writing difficulties.
 Tremor may be caused by pathology affecting the brain stem, the cerebellum and/or
the extrapyramidal system.
 A patient may delay presenting with tremor, mistakenly believing it to be a normal
part of ageing. Up to 4% of people aged over 65 years in the UK are affected by
essential tremor (action or postural tremors).
 Physiological tremor may affect both hands equally and may become apparent with
anxiety, fatigue, hyperthyroidism, hypoglycaemia, alcohol or other drug withdrawal,
and caffeine consumption.
 The most common pathological tremors include resting tremor associated with
parkinsonism, essential tremor and intention tremor, which may be due to cerebellar
dysfunction. In the latter, possible causes include MS, spinocerebellar degeneration
and stroke.
 Tremor may be described as having slow or fast oscillations that vary in amplitude.

 Resting tremor occurs at rest and may not be apparent during physical activity
 Action tremor is exacerbated on movement
 Intention tremor also occurs during voluntary movement when directed towards a target,
with the tremor becoming worse as the target is approached
 Complex tremor may have components of the aforementioned types of tremor. For
example, Holmes tremor may occur in MS if the midbrain is affected

 Essential tremor tends to be symmetrical and may affect the voice. It may be
suspected if there is a positive family history of this condition.
 If Parkinson's disease is suspected, there may be other symptoms, such as cogwheel
rigidity and a shuffling gait. Extrapyramidal symptoms and cognitive problems may
be suggestive of progressive supranuclear palsy.
 Some medications may cause tremor, including salbutamol, haloperidol and
metoclopramide.

Possible causes
 Resting tremor
 Parkinson's disease
 Secondary parkinsonism, often drug-related
 Postural tremor
 Essential tremor
32

 Alcohol withdrawal
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 Hyperthyroidism

MRCGP THEORY
  Hypoglycaemia
 Intention tremor
 Stroke
 Cerebellar space-occupying lesions
 MS
 Flapping tremor
 Acute hepatic failure

Clinical assessment

 It is important to evaluate tremor by taking a thorough history, which should include its onset
and the body part affected.
 Possible exacerbating factors include rest, movement, stress, anxiety and alcohol.
 In the case of a sudden onset of tremor, recent illness or addition of a new medication should
be considered.
 A neurological disorder may be responsible, depending on the presence of other symptoms,
such as weakness, numbness, dysarthria, confusion, postural problems, shuffling gait and
cogwheel rigidity. Weight loss, palpitations and diarrhoea may point towards
hyperthyroidism.
 It is relevant to ask about a positive family history of tremor in first- degree relatives. It is also
important to ask about alcohol and/or drug misuse and caffeine consumption. The effect on
activities of daily living should be elicited.
 Physical examination should include a full neurological assessment of the CNS and peripheral
nervous system, as well as routine observations, such as temperature. Lying and standing BP
measurements may be helpful.
 Cerebellar function should be tested. This may be done by heel-to-shin and finger-to-nose
testing.
 It may be relevant to examine the neck to assess the thyroid gland and to assess for any
associated eye signs.
 Other useful tests include asking the patient to write a sentence to evaluate their handwriting,
as well as asking them to hold a glass of water.
 It may be relevant to look for cognitive dysfunction; for example, Lewy body dysfunction
may present with resting tremor, cognitive dysfunction and visual hallucinations.
 The tremor should be assessed at rest, with the arms outstretched and when the patient is
distracted.
 Parkinson's disease may be suspected in the presence of a resting tremor - this may affect the
chin, voice or lower limbs.
 Cerebellar dysfunction is more likely in the presence of intention tremor. Physiological or
essential tremor is more likely to be postural.
 Clinical evaluation is likely to reveal the underlying aetiology, although neurological referral
may be necessary.
 TFTs, calcium and glucose levels may be checked. Brain imaging may be required.

Management

 Management can include avoiding known triggers, such as caffeine and anxiety.
Essential tremor may respond to beta-blockers.
 Occupational therapy and physiotherapy may be helpful in cerebellar tremors.
Specific therapy may be considered in patients who have Parkinson's disease.
33

 For severe tremor, surgical management, such as thalamic deep brain stimulation,
may be appropriate.
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MRCGP THEORY
 Brain tumours
Section 1 Epidemiology and aetiology

The incidence has a bimodal peak, with almost 25% of all cases being diagnosed in patients
aged over 75 years and at the other end of the spectrum, CNS tumours accounting for
approximately 25% of cancers diagnosed in children.1

The incidence of brain tumours has risen over the past decades; this is primarily thought to be
because of advances in diagnostic imaging, along with improved tumour registries, rather
than reflecting a true increase in incidence.

Brain tumours are heterogeneous and are classified by the cell of origin and the tumour grade.
Treatment depends on the tumour subtype, with standard treatment options including
surveillance, surgery, radiotherapy and/or chemotherapy.

34
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Risk factors

MRCGP THEORY
  The incidence of brain tumours increases with age, with meningiomas (benign
tumours of the brain lining) occurring more commonly in women and invasive
malignant gliomas, also known as glioblastomas, more commonly in men.
 There are few established risk factors for the development of a brain tumour, other
than prior ionising radiation.3
 Genetic predisposition to brain tumours is rare, although there are some documented
familial conditions which confer an increased risk of developing CNS tumours. These
include neurofibromatosis, tuberous sclerosis complex, Li-Fraumeni syndrome, Von
Hippel-Lindau syndrome, Turner syndrome, Turcot syndrome and Gorlin syndrome.
 Smoking has been demonstrated to increase risk in some, but not all, studies.4 No
particular diet (including level of alcohol intake) has been shown to affect brain
tumour risk. Mobile phones have not been proven to cause brain tumours.5
 There is evidence of a hormonal effect in the case of meningioma, with some studies
showing an increased risk in women taking the oral contraceptive pill or
HRT.6,7 Despite extensive work on the aetiology of brain tumours, the main causative
incident has still to be identified.
 Brain or spinal cord tumours represent a wide variety of tumour types, with differing
behaviour and a variety of treatment modalities. This article focuses on management
of glioblastoma, which has the greatest implications for primary care.

Section 2 Making the diagnosis

 Making the initial diagnosis of a brain tumour can be difficult.

 Primary tumour associated symptoms are mostly non-specific and can mimic those of
benign causes. Confusion and altered cognition are common presenting symptoms for
patients with glioblastoma. This symptom can be difficult to distinguish from other
causes of confusion, particularly in elderly patients with confounding comorbidities.
 A 'first fit' occurring in patients over the age of 50 years should always raise suspicion
of an intracranial malignancy.
 Other frequent neurological symptoms include those related to the tumour location,
for example, paraplegia, dysphasia, visual impairment or personality changes. A full
neurological examination is necessary, including an assessment of the patient's
cognition, a deficit often disregarded as too non-specific.

Imaging

The cornerstone of establishing the correct diagnosis in brain tumours is imaging.
 Patients are often initially diagnosed on emergency CT scans that identify an
abnormality in the brain tissue (with or without associated oedema, bleeding or
calcification).
 However, the standard of care requires an MRI to characterise the extent and nature of
the space- occupying lesion.
 MRI also guides surgical planning, aiming to establish a pathological diagnosis, and
helps to identify satellite lesions or gliosis - diffuse abnormality of a wider area of the
brain.
35
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MRCGP THEORY
 Biopsy and histology

 Histological diagnosis is mandatory in most patients with a suspected malignancy of

the brain.
 Biopsy only may be considered in tumours located in eloquent areas of the brain, but
it has been shown that surgical debulking, ideally a macroscopic complete resection
of visible disease on imaging, improves outcomes. Histology defines treatment and
thus prognosis.
 Further assessment of pathological tumour-specific markers helps to guide treatment
and predict prognosis. Patients whose tumours harbour O(6)-methylguanine-DNA
methyltransferase (MGMT) promoter methylation have an improved response to
chemotherapy with an alkylating agent and derive greater benefit from the addition of
chemotherapy to surgery and radiotherapy, compared with those who have
unmethylated glioblastomas.8
 Another prognostic marker is isocitrate dehydrogenase 1 and 2 (IDH1/2).9 Mutations
in this gene give an indication that the tumour has most likely arisen in a lower-grade
tumour which has undergone malignant change. Such tumours are referred to as
secondary glioblastoma and carry a better prognosis than primary de novo
glioblastoma.

Section 3 Managing the condition

 Detailed assessment of the patient's clinical and neurological condition is required

before treatment.
 Corticosteroids are often given before surgery to help control acute tumour-related
symptoms. Cognitive testing is essential at all stages as patients with substantial
cognitive deficits have worse outcomes.

Current treatment

 The most common tumour treated by (adult) neuro-oncologists in the UK is

glioblastoma. Patients require intense input from a range of clinical services,
including GPs and the primary care team.
 One of the cornerstones in the treatment of patients with glioblastoma is surgery.
Maximal safe debulking is the goal, aiming for a gross total macroscopic resection if
clinically achievable.
 In selected cases, this may be performed via awake craniotomy or with
immunofluorescence such as 5-aminolevulinic acid, which accumulates in tumour
cells and fluoresces in dark light, allowing easier identification of tumour tissue.10
 Cortical mapping may be used to aid maximal resection with minimal risk to the
patient of a permanent postoperative neurological deficit.
 Surgical intervention allows the acquisition of tissue to establish the histopathological
diagnosis and assessment of prognostic molecular markers (IDH1, MGMT).
 Following surgery, patients are discussed by the site-specific multidisciplinary team,
when further treatment strategy is defined.
 The neuro-oncology team then assesses the patient, to consider non-surgical
management. In patients with a good performance status (ECOG 0-2) under the age of
36

65-70 years, consideration is given to treatment with fractionated radiotherapy over

six weeks, and concomitant and adjuvant chemotherapy according to NICE
Page

guidelines.

MRCGP THEORY
  Those for whom this may not be appropriate will be considered for a short course of
palliative radiotherapy, or in some cases (those who are MGMT-methylated) for
primary chemotherapy.12 Radical radiotherapy in combination with temozolomide
chemotherapy, followed by adjuvant chemotherapy, was shown to improve median
survival by 2.5 months (14.6 versus 12.1).
 In some cases, depending on the clinical circumstances and the patient's wishes,
treatment may consist of best supportive care, led by the GP and the community
palliative care team.

New developments

 Despite many studies, no other chemotherapy agent has been shown to improve
overall survival first-line in patients with glioblastoma.
 One recent option is bevacizumab, a monoclonal antibody targeting vascular
endothelial growth factor (VEGF).14 This is postulated to cause regression of tumour
vasculature and to inhibit new and recurrent tumour vessel growth. It has been shown
to improve the time to progression in patients with glioblastoma, but not overall
survival.15
 Bevacizumab is currently licensed in the US for treatment at relapse, but its
appropriate place in the management of glioblastomas remains uncertain. Other trials
of therapies targeting the VEGF/EGFR pathway have proved unsuccessful.16
 Glioblastomas have been the target of a number of trials using personalised vaccines,
such as dendritic cell tumour adaptive vaccines, and off-the-shelf targeted vaccines,
such as rindopepimut. Early data show some encouraging positive signals, but
dendritic cell and targeted vaccines remain experimental options and are the subject of
international trials. These results are awaited.
 A better understanding of the molecular changes underlying glioblastoma has led to
their classification into proneural, mesenchymal and proliferative subtypes.17
 It is known there are abnormalities along multiple pathways of the cell cycle in such
tumours. Current phase 1 studies target the PI3K pathway, among others. The role of
poly (ADP-ribose) polymerase inhibition is also under investigation.
 Recent successes in immune checkpoint modulation in other solid tumours have
sparked an interest in such therapies in glioblastoma; several studies are investigating
the role of PD-1 and CTLA-4 inhibition.

Section 4 Prognosis

 The prognosis for patients with glioblastoma depends on several factors that have
been grouped into a recursive partitioning analysis (RPA).
 RPA is a means of grouping patients in prognostic distinct groups according to
clinical factors including age, neurological function and degree of surgical resection
 Follow-up should be managed in the multidisciplinary setting, with close links to
primary care. Regular imaging may be performed on an outpatient basis if further
treatment is considered in recurrent disease. The input of local rehabilitation services
is vital in patients with focal deficits, to preserve remaining function.
37
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MRCGP THEORY
 Motor neurone disease
Section 1: Epidemiology and aetiology

 The lifetime incidence of MND is one in 400 and the short survival time means there
are only approximately 5,000 patients with MND in the UK at any one time.1A small
number of atypical cases have a longer chronic course, which can last decades.
 Factors contributing to the development of MND include genetic and environmental
factors and there is a recognised overlap between MND and other neurodegenerative
diseases in patients and their families.
 Approximately 10% of patients with MND have frontotemporal dysfunction, and a
smaller number have Parkinsonism.
 Less than 10% of patients have a family history of MND, with 70% of those having
an identifiable genetic cause.2
 Forty per cent of familial cases of MND are associated with a recently discovered
variable length hexonucleotide repeat expansion in the C9ORF72 gene and families
carrying this are more likely to develop other neurodegenerative diseases together
with, or in the absence of, MND.

Classification

 MND can affect upper and lower motor neurones. Upper motor neurone degeneration
causes stiffness and spasticity, weakness, speech and swallowing difficulties, and
emotional lability. Lower motor neurone degeneration causes wasting, fasciculations
and weakness. Death is usually due to respiratory failure.
 Most patients with MND have amyotrophic lateral sclerosis (ALS). They develop
upper and lower motor neurone degeneration and have an average life expectancy of
two to three years. However, individual prognosis is highly variable and can range
from weeks to decades, with 5% surviving more than 10 years.
 Patients with primary lateral sclerosis (PLS) have predominantly upper motor neurone
dysfunction, while those with primary muscular atrophy (PMA) have lower motor
problems. These patients tend to progress more slowly, but there is much overlap and
many eventually develop typical ALS.

Section 2 Making the diagnosis

 MND is predominantly a disease of the older adult, with peak incidence in the 70s and
80s, but it can affect adults of any age.1
 The symptoms can be subtle at first, with an absence of signs and limited to a single
area of the body, and may require close observation over months to detect changes.
 The RCGP (www.rcgp.org.uk) and the MND Association (www.mndassociation.org)
have produced a Red Flags toolkit diagnostic tool and e-learning site for GPs,
highlighting signs which should alert doctors to the early presence of MND.
 MND is a clinical diagnosis and investigations are used to exclude alternative causes,
but neurophysiological tests can support the diagnosis in the absence of a large
number of clinical signs.
 Several conditions may mimic MND. Isolated fasciculations in the absence of other
38

symptoms or signs are likely to be due to benign cramp fasciculation syndrome.

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MRCGP THEORY
  Primary progressive multiple sclerosis or cervical myelopathy can present with purely
upper motor neurone features, or in the case of a myeloneuropathy, may have lower
motor neurone features if nerve roots are affected.

Red flags for possible MND

Section 3 Managing the condition

 The establishment of specialist multidisciplinary teams has significantly improved

patients' survival and quality of life.5 Each team should include speech, occupational
and physiotherapists, with specialist doctors; ideally, each patient should have a
named care co-ordinator.

Prolonging survival

 Riluzole, the only drug that improves survival (by an average three months),6 is
usually well tolerated. Mild side-effects (GI upset and fatigue) tend to resolve with
time.
 Significant abnormalities in liver function are uncommon, with regular liver function
and blood count monitoring recommended three monthly after initiation.
 Use of hepatic enzyme inducers and inhibitors should be avoided, but most common
antibiotics and analgesics can be used safely.
39

 Non-invasive ventilation (NIV) improves survival with sustained quality of life in

patients who have respiratory failure.7
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MRCGP THEORY
  Patients usually find symptoms of fatigue, sleepiness and poor appetite substantially
improved.
 Patients may become dependent on NIV, but nasal or full-face masks allow eating and
communication, and lightweight batteries are available for travel.
 Poor nutrition is associated with poorer outcomes.8 Oral intake may be affected by
limb weakness, poor swallowing and fatigue. Early involvement of a speech therapist
and a dietitian can prevent weight loss, but insertion of a gastrostomy feeding tube is
recommended early in the disease course.

Symptom management

 Timely symptom management, with support to overcome disability, is an important

role for the multidisciplinary team and the GP. For painful cramps and spasms,
quinine, gabapentin and baclofen should be combined with physiotherapy and
assessment for exacerbating factors, such as constipation, pain or infection.
 Neck weakness can cause head and shoulder girdle ache. A supportive collar and
seating may help. Arm weakness can cause a frozen shoulder, which should be treated
with physiotherapy and analgesia.
 Hyoscine patches reduce excessive saliva. Atropine eyedrops placed under the tongue,
glycopyrrolate and amitriptyline are also effective.
 Botulinum toxin injected into the salivary glands reduces saliva, but has a small risk
of worsening swallowing. Artificial saliva lubricates the mouth. Carbocysteine thins
secretions.
 Physiotherapy, nebulised saline, suction and cough augmentation machines help
expectoration.
 NIV may be helpful in managing dyspnoea. Laryngospasm can be precipitated by
respiratory secretions or acid reflux. Sublingual lorazepam can be helpful. The use of
drugs such as benzodiazepines and opiates can be very effective.
 Constipation and urinary urgency, worsened by poor mobility, are treated on the same
principles as other diseases. Fertility and sexual function are not affected.
 Fatigue is often out of proportion with disability. No medications are particularly
helpful, but patients need support to adapt their lifestyle.
 Low-dose citalopram or amitriptyline are usually extremely effective in treating
emotional lability. Depression and anxiety are treated with standard approaches.
 Many patients have mild behavioural or cognitive difficulties and it is helpful for
families to recognise that they are due to the MND, rather than the individual.

Section 4 Prognosis

 It is impossible to predict prognosis as cases vary so widely, but features suggesting a

worse outcome are:

 Older patients
 Bulbar or respiratory onset
 ALS patients are likely to progress faster than PLS or PMA
 Short time between symptom onset and diagnosis
 Rapid disease progress
40

 Patients should be given the opportunity to devise an advance directive and have
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access to palliative care.

MRCGP THEORY
  Opportunities to introduce these topics may be when considering NIV or feeding
tubes, at the emergence of distressing symptoms, or in response to questions about
prognosis.
 Anxiety and fear can be alleviated by ensuring adequate symptom control, facilitating
communication, treating depression and effective care planning.
 Medication that can be given by carers can be reassuring. NIV can help with
dyspnoea, although some patients opt to withdraw from it at the end of their life.
 Breathlessness, anxiety and excessive saliva can be managed using syringe drivers;
most MND patients will die peacefully in their sleep.

The role of the GP

 Consider MND in patients complaining of painless, progressive stiffness, weakness or

speech change, particularly asymmetrical symptoms or where more than one part of
the body is involved. Signs of MND might be subtle in early disease.
 Look for wasting, fasciculations or brisk reflexes. Signs of respiratory failure include
changes in breathing, poor sleep and low appetite.
 GPs can prescribe standard medication for pain, secretions and depression. In most
cases, MND is not due to lifestyle and is unlikely to be passed on to family members.

41
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MRCGP THEORY
 Bell's palsy
Section 1: Epidemiology and aetiology

 Bell's palsy is a lower motor neurone palsy of the facial nerve of idiopathic aetiology.
Sir Charles Bell, the Scottish anatomist, in 1821 first described facial muscle paralysis
following damage to the facial nerve.
 Bell's palsy is the most common cause of facial paralysis, accounting for 70 per cent
of facial palsies, when other causes have been eliminated.
 It has an incidence of 11-40 per 100,000 per year, and most commonly occurs in
females in their teens and twenties. The distribution is almost equal in the thirties,
with a slight predominance in males over 40.
 A correlation between facial palsy and pregnancy has been noted, especially during
the third trimester, and in the presence of pre-eclampsia. Pregnancy is associated with
a worse prognosis. Immunodeficiency due to HIV can predispose to facial palsy.

Viral aetiology

 There are many reports of an association of Bell's palsy with a viral aetiology, based
on clinical, experimental and post-mortem observations.
 Herpes simplex virus (HSV) has been isolated from the nasopharynx of patients with
Bell's palsy, and HSV autoantibodies are more prevalent in affected patients than age
and gender-matched controls.
 Autopsy studies have demonstrated HSV particles in sensory ganglia of cranial
nerves, such as the geniculate ganglion of the facial nerve and trigeminal ganglion of
the trigeminal nerve.
 HSV DNA has been identified in facial nerve endoneurial fluid and posterior auricular
muscle in patients who underwent surgical decompression of the facial nerve, which
was not responding to treatment.1
 It is thought that latent viral reinfection of the facial nerve predisposes to Bell's palsy.

Vulnerable facial nerve

 An alternative theory is small-vessel ischaemia of the facial nerve, resulting in venous

stasis, reduced capillary flow, oedema and elevated intraneural pressure. Tissue
damage occurs through acidosis and anoxia.2 The mechanism of primary ischaemia is
unclear.
 A final theory is immunological damage to the facial nerve, as evidenced by
segmental demyelination of the nerve associated with lymphocytic infiltration of the
perineurium.3 Immune complexes have been found in the chorda tympani branch of
the facial nerve, characteristic of a viral-antibody (Type III) immunological reaction.
 Regardless of the mechanism of insult, inflammation, compression and ischaemia of
the facial nerve can occur as it traverses the temporal bone within its bony canal.
 The bony canal is narrowest where the facial nerve exits the internal auditory meatus,
and in the labyrinthine segment of the canal the nerve occupies at least 80 per cent of
the cross-sectional area. For these reasons, the facial nerve is vulnerable in the
presence of oedema at both these sites.
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MRCGP THEORY
 Section 2: Making the diagnosis

 Bell's palsy typically presents as an acute unilateral paresis or paralysis of the face
due to lower motor neurone dysfunction, with all branches of the facial nerve
involved (see photos below). The onset and progression are rapid, usually in less than
48 hours. Patient with Bell's palsy below, showing paralysis of the left facial muscles
at rest (Figure A) and on being asked to raise his eyebrows and smile (Figure B).

 Diagnosis is clinical, and requires exclusion of less common causes of facial nerve
palsy, such as acute or chronic otitis media, cholesteatoma, parotid tumour and
temporal bone fracture, once otoscopy and parotid and cranial nerve examination have
been performed.
 Unlike Bell's palsy, a stroke will present with signs of an upper motor neurone lesion,
with sparing of the forehead, due to bilateral cortical innervation of the upper facial
muscles.

Other cranial nerves

 Other cranial nerves in close proximity to the facial nerve in the skull base, such as
the trigeminal (V), abducent (VI), vestibulocochlear (VIII), glossopharyngeal (IX)
and vagus (X), may be involved, suggesting the facial weakness is the inflammatory
motor component of a more extensive cranial polyneuropathy.4
 There may be pain (50 per cent of cases) or numbness in the ear, face and tongue (40
per cent), hyperacusis (33 per cent), reflecting involvement of the vestibulocochlear
nerve and nerve to stapedius, and dysgeusia (33 per cent), due to involvement of the
chorda tympani branch of the facial nerve (subserving taste to the anterior two-thirds
of the tongue), and more rarely the lingual branch of the glossopharyngeal (taste to
the posterior one-third).
 Rarely, there may be reduced lacrimation due to involvement of the greater petrosal
nerve, which supplies the lacrimal gland and exits the facial nerve at the geniculate
ganglion. A viral prodrome is present in 31 per cent of patients.5
 Otoscopy will exclude haemotympanum and acute or chronic inflammation of the
43

external and middle ear. Of particular note is herpes zoster oticus (Ramsay Hunt
syndrome), a syndrome of acute facial palsy with otalgia and painful varicelliform
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MRCGP THEORY
 cutaneous vesicles, which affects the external auditory meatus and pre-auricular skin,
or soft palate.
 This condition accounts for 10-15 per cent of cases of facial palsy. It is more
commonly associated with other cranial neuropathies, in particular hearing loss,
dysacusis and vertigo, than Bell's palsy.6 It is thought to be due to latent reactivation
of varicella zoster virus in the geniculate ganglion.

House-Brackmann scale

 The extent of facial palsy can be assessed using a grading system, such as the House-
Brackmann scale (see box below), which is the preferred standard of the American
Academy of Otolaryngology.7
 This can provide clinical information at the time of initial presentation, which acts as
a prognostic indicator and a point of comparison on follow-up.

House-Brackmann facial nerve grading scale7

Grade Function
I  Normal symmetrical function at rest and on movement
 Normal tone and symmetry at rest
 Slight weakness on close inspection
 Good to moderate movement of forehead
 Complete eye closure with minimal effort
II  Slight asymmetry of mouth with movement
 Normal tone and symmetry at rest
 Obvious but not disfiguring asymmetry
 Slight to moderate forehead movement
 Complete eye closure with effort
 Slight weakness of mouth with maximum effort
III  Obvious but not disfiguring synkinesis*, hemifacial spasm or contracture
 Obvious disfiguring weakness
 Inability to raise brow
 Incomplete eye closure
 Asymmetry of mouth with maximum effort
IV  Severe synkinesis and spasm
 Asymmetrical facial appearance at rest
 Motion hardly perceptible
 Incomplete eye closure
 Slight movement of corner of mouth
V  Synkinesis and spasm usually absent
 No facial function perceptible
 No synkinesis or spasm
VI  Intermittent spasm of orbicularis oculi
*reflex movement of groups of muscles that do not normally contract together, for example:
44

blinking may occur with movement of the corner of the mouth.

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 Section 3: Managing the condition

 Treatment aims to reduce the disability of facial paresis, and address the inability to
fully close one eye.
 To prevent corneal dehydration, abrasion and ulceration, drops or lubricants can be
applied.
 The lower eyelid can be elevated with tape running towards the orbital rim to improve
lid closure, and a patch can be applied for sleeping.

Antiviral treatment

 Historically, based on the assumption that the nerve palsy is due to viral
inflammation, treatment comprised steroids and antivirals.
 Two RCTs compared prednisolone with and without aciclovir with
placebo.8,9 Prednisolone alone resulted in a statistically higher recovery rate at three
months than placebo, and also at nine months.
 However, the addition of aciclovir to prednisolone compared with placebo showed no
significant improvement at three months.
 More recently, a meta-analysis of 18 trials involving 2,786 patients concluded that
anti-virals alone are ineffective.10
 Administration of antivirals plus steroids showed a possible increased benefit
compared with steroids alone, but results were not significant.
 The recommended regimen for prednisolone is 1mg/kg/day for five days (in divided
doses) followed by a 10-day taper.
 Aciclovir is of questionable value, but if used in addition to prednisolone, it is
prescribed at 800mg five times daily for five days.
 The antivirals used prevent viral replication by disrupting DNA polymerase. The virus
is not destroyed, and this may explain why antivirals fail to have a significant benefit
in treating Bell's palsy.

Referral to ENT

 Refer to ENT if there is no improvement in facial palsy after three weeks. A pure tone
audiogram will establish any hearing loss.
 In patients with long-standing facial palsy who have been referred to ENT,
transcutaneous electrical stimulation of the facial muscles can be used to preserve
membrane conductivity, minimise muscle atrophy and improve facial function.
 Inability to close the eye in such cases may require implantation of a gold weight in
the upper lid. Alternatively, a tarsorrhaphy (suturing the upper and lower lid margins
laterally) will reduce the palpebral fissure, thereby protecting the cornea.
 Nerve grafting, rhytidectomy, blepharoplasty, brow lift and facial slings can improve
resting muscle tone.
 Botulinum toxin can reduce tonic contractions, hemifacial spasm and synkinesis.

Section 4: Prognosis and follow-up

45

 Incomplete Bell's palsy at the time of first presentation is a good prognostic sign, with
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99 per cent of patients making a complete recovery.

MRCGP THEORY
  Only 75 per cent of patients with a full palsy will undergo complete resolution.
Seventy-one per cent of untreated cases resolve by one year, and the remaining 29 per
cent have residual paralysis, synkinesis and contracture.
 Early onset of recovery increases the chance of complete resolution: 100 per cent of
patients who start to recover in the first week make a full recovery, but only 61 per
cent do so if recovery begins in the third week.5
 If a patient's facial palsy has progressed or not started to recover three to six weeks
after first presentation, referral to an ENT specialist will enable further investigation
of an underlying neoplasm.
 Recurrent facial nerve paralysis can occur in up to 12 per cent of patients. Patients
with a recurrence are 2.5 times more likely to have a positive family
history.13 Ipsilateral recurrence is an indication for referral to ENT, again to exclude a
tumour. Contralateral recurrence is usually benign.
 The prognosis for Ramsay Hunt syndrome is worse, with persistent facial weakness in
30-50 per cent of patients, and full recovery in only 10 per cent after total loss of
function without treatment.

Investigating nerve function

 An ENT specialist may arrange evoked electromyography (EEMG) or

electroneuronography (ENoG) to investigate facial nerve function in a case of
complete paralysis which fails to improve.
 Such tests are, however, time-consuming, expensive and only of use soon after onset
of paralysis, usually before the patient has been referred to hospital.
 ENoG delivers a stimulus to the facial nerve as it passes through the stylomastoid
foramen, and measures an evoked compound muscle action potential. Its prognostic
potential is greatest when used from three days to three weeks after onset of paralysis.
 EEMG records post-synaptic potentials with electrodes in the nasolabial fold, and is
most reliable during the onset of denervation, i.e. two to three weeks from onset of
paralysis.
 The earlier the EEMG response drops to less than 10 per cent of normal, the worse the
prognosis.
 Surgical decompression of the facial nerve can be offered in the third week if EEMG
amplitudes are less than 10 per cent of the normal side, but long-term trials are
awaited.
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 Parkinson's disease
Section 1: Aetiology and epidemiology

 Parkinson's disease (PD) is one of the most common neurodegenerative diseases, and
is principally due to the progressive loss of dopaminergic neurons in the substantia
nigra of the brainstem.
 Its prevalence is 100-190 per 100,000. The incidence increases with age: it is
uncommon below 50 years, but rises progressively thereafter, to 300 per 100,000 in
those aged over 80.1
 While there is some variation between studied populations, it is not clear how much
of this is due to methodological differences.
 In general, however, it appears that PD occurs with a similar frequency across the
world, although it is probably more common in men.

Genetic susceptibility

 As with many conditions, PD is thought to be the result of an interaction between

genetic susceptibility and environmental factors.
 In those relatively rare cases with onset below 50 years of age, genetic susceptibility
plays a much more dominant role than in typical, sporadic, late-onset disease.2
 Studies of familial PD have identified several genes which may cause PD with
Mendelian inheritance, especially in young (<50 years) onset disease.
 While uncommon compared with sporadic late-onset PD, the genes involved have
highlighted potential pathogenic mechanisms which may turn out to be relevant to
idiopathic PD, including oxidative stress, mitochondrial dysfunction and abnormal
cellular protein handling.
 Twin studies have failed to show a higher concordance for the diagnosis of PD in
monozygotic versus dizygotic pairs, suggesting that environmental factors are more
important in late-onset PD.

Neurotoxins

 In the 1980s, a group of illicit drug users developed a severe Parkinsonian syndrome
after injecting narcotics contaminated with the neurotoxin MPTP, leading to its use in
experimental models of PD, and furthermore stimulating the search for other
environmental toxins relevant to human disease.
 Epidemiological studies suggest it is possible that agrochemicals act as neurotoxins,
with rural residence and drinking of well water increasing the risk of PD.
 Several herbicides and pesticides have been implicated, although a major causal effect
remains unproven.

Protective factors

 Two potential 'protective' factors are notable: the most robust epidemiological
phenomenon in PD, other than the influence of age, is the negative association with
smoking.
47

 When compared with non-smokers, PD is less common in current smokers, recent ex-
smokers and those who smoked in early adult life but stopped. The reason is
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MRCGP THEORY
 unknown. It is postulated that a biologically determined factor, which makes people
less likely to smoke, is linked to a higher risk of PD.
 Controversy exists as to whether exposure to NSAIDs may protect against PD.

Section 2: Making the diagnosis

 PD is characterised clinically by four cardinal motor symptoms, represented by the

acronym TRAP (tremor, rigidity, akinesia, and postural instability).3
 The typical patient presents with an asymmetric, upper limb, tremor-dominant
akinetic-rigid syndrome.

Tremor and rigidity

 Tremor usually manifests at rest, such as sitting watching television, but may also
occur with posture or movement of the limb (kinetic or action tremor), although it is
usually worse at rest.
 Rigidity is an increased resistance to the passive movement of a limb and has a
'leadpipe' quality. The superimposition of rest tremor on rigidity gives the
characteristic 'cogwheeling'.
 Akinesia, or more accurately bradykinesia, is a slowness of initiating and executing
voluntary movement, often associated with additional difficulty performing sequential
motor tasks. It is the principal motor symptom/sign in PD, and its absence should lead
to reconsideration of the diagnosis.
 Postural instability is common in PD, and may lead to falls, but not usually until later
in the course of the disease.

Non-motor symptoms

 In recent years, the importance of non-motor symptoms in PD has been increasingly

recognised; indeed these may be more important causes of morbidity than motor
symptoms, compounded by their usual resistance to dopaminergic therapy.
 Symptoms include hyposmia (reduced sense of smell), constipation and sleep
disorders, any of which may predate the onset of classic motor PD, possibly by years
or even decades. Pain and other sensory symptoms are also common in PD.
 Other non-motor symptoms, such as autonomic dysfunction, usually occur later in
disease, while dementia in PD, characterised by visual hallucinations, daytime
somnolence and fluctuating cognitive performance, occurs in at least 80 per cent
eventually.
 Dementia preceding or occurring within one year of the onset of motor symptoms is
called dementia with Lewy bodies (DLB), whereas if more than one year has elapsed,
the term Parkinson's disease dementia (PDD) is used - the common pathology is
extensive cortical Lewy body disease.

Imaging

 The diagnosis of PD is predominantly clinical. Imaging (usually MRI) may be helpful

in excluding other conditions.
48

 Diagnostic uncertainty may sometimes be resolved with nuclear medicine studies,

which measure (indirectly) striatal dopamine. The imaging above shows the typical
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appearance, with the characteristic asymmetric loss of tracer uptake.

MRCGP THEORY
 UK Brain Bank Criteria for the diagnosis of Parkinson's
Step 1: Bradykinesia
At least one of the following criteria:
 Rigidity.
 Four to six Hz rest tremor.
 Postural instability not caused by primary visual,
vestibular, cerebellar or proprioceptive dysfunction.

Step 2: Exclude other causes of Parkinsonism.

Step 3: At least three of the following supportive

(prospective) criteria:

 Unilateral onset.
 Rest tremor.
 Progressive disorder.
 Persistent asymmetry primarily affecting side of onset.
 Excellent response (70-100 per cent) to levodopa.
 Severe levodopa-induced chorea (dyskinesia).
 Levodopa response for five years or more.
 Clinical course of 10 years or more.

Section 3: Managing the condition

 PD cannot currently be prevented or cured, but reasonably effective symptomatic

treatment of the motor symptoms is achievable, at least for the first few (usually four
to six) years.
 After this, motor complications, which may be treatment related, cause management
to become difficult.
 The onset of neuropsychiatric symptoms (hallucinations, cognitive impairment and
later dementia) is particularly problematic, and severely restricts the physician's
pharmacological options.

Side-effects

 The choice of initial treatment is usually between levodopa (L-dopa) or a dopamine

receptor agonist.4 L-dopa produces a superior symptomatic effect to an agonist, and
can have fewer side-effects.
 After, on average, four to six years' use this 'honeymoon' period is replaced by motor
fluctuations, where patients may rapidly enter an 'off' state (freezing), while at other
times manifest an excess of movement - dyskinesias (usually chorea).
 To some extent, these fluctuations can be smoothed out by fractionation of the total
dose with more frequent dosing, or by the addition of a catechol-O-methyltransferase
(COMT) inhibitor (entacapone or tolcapone), which delays L-dopa degradation and
hence prolongs its duration of action. Tolcapone requires monitoring of liver
biochemistry.
49

 Most neurologists deploy a dopamine agonist initially in younger patients (under 70)
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MRCGP THEORY
 patients do not usually tolerate agonists due to neuropsychiatric side-effects, and L-
dopa is preferred.
 The situation has become even more complicated, as agonists have been linked with a
number of potentially destructive behavioural side-effects (impulse control disorders),
including pathological gambling and compulsive shopping.

Antipsychotics

 Antipsychotics are all dopamine receptor antagonists to some degree, and will
therefore almost invariably lead to deterioration in PD motor features if deployed to
treat hallucinations or delusions.
 'Typical' neuroleptics, such as haloperidol, may be fatal if given to patients with PD
(or DLB).
 Abrupt discontinuation of treatment in PD may provoke a similar crisis and should be
avoided. Newer 'atypical' anti psychotics worsen PD motor symptoms far less, and an
acceptable balance between motor and psychiatric symptoms may be obtained: the
usual choice is quetiapine.
 Cognitive impairment and/or hallucinations may improve with an anticholinesterase
inhibitor, such as rivastigmine.
 Freezing may be treated by a subcutaneous bolus of apomorphine, administered by
patient or carer, and moderate to severe motor fluctuations may improve with a
continuous ambulatory subcutaneous apomorphine infusion.
 If this fails, patients may be referred for subthalamic nucleus surgery, where a
stereotactically inserted electrode is attached to a subcutaneous stimulator device,
similar to a pacemaker.4
 Section 4: Prognosis
PD is incurable and no convincing neuroprotective therapy exists. The median
survival after symptom onset is around 15 years (compared with symptomatic
survival in the so-called Parkinson's plus syndromes of seven to eight years).
 PD will therefore probably shorten a patient's life, if they do not succumb to another
disease first.

Motor complications

 Those with a younger onset can have a more indolent course, but may experience
worse motor complications.
 This may in part be due to physicians' more aggressive treatment with higher doses of
medication earlier in the disease. Those with a tremor at onset also do better, while
older patients, and those with early gait disorder often fare poorly.
 The onset of neuropsychiatric symptoms usually marks an extended palliative phase
of the disease, in which treatment options are restricted.
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 Neuropathic pain
Section 1: Aetiology and epidemiology

 The International Association for the Study of Pain has defined more than 600 pain
syndromes. Patients with complex or persistent pain present with physical and
behavioural symptoms.
 Nociceptive pain is classically defined as tissue damage that releases local mediators
that stimulate healthy A(delta) and C fibres to transmit pain signals to the spinal cord,
via the spinothalamic tract to the thalamus and higher centres.
 However, in reality, nociceptive mechanisms are much more complex; many other
pathways are involved in pain processing.
 The nervous system is plastic; it responds to afferent stimulation with neuronal and
gene changes in the periphery, spinal cord and brain.
 Neuropathic pain is defined as 'pain arising as a direct consequence of a lesion or
disease affecting the somatosensory system'.1 It is commonly seen in primary care and
may be caused by a wide variety of disease processes (see box).
 Neuropathic pain can be classified into four categories: focal/multifocal lesions in the
peripheral nervous system (PNS), generalised peripheral neuropathies, CNS lesions
and complex neuropathic disorders.2
 In western Europe, chronic pain prevalence is one in five. Some 70 million adults
experience persistent pain and a third of households are affected.
 A European telephone survey of more than 46,000 householders showed that 11-30
per cent of people had significant chronic pain that led to effects on quality of life.3
 A more detailed assessment was made of a UK subset (n=300), average age 49 years;
70 per cent had pain at least daily. Quality of life, mood and capacity to work were all
adversely affected by pain.
 Neuropathic pain occurs in about 6-8 per cent of the general population.4 It is
associated with advancing age, female gender and lower socioeconomic groups. It is
more common in certain conditions, for example diabetes (24 per cent), and after
shingles (20 per cent).
 However, the most common causes are radicular pain from spinal pathology or after
trauma/surgery.
 Several studies have shown that neuropathic pain has a greater deleterious effect on
quality of life than nociceptive pain, leading to poorer physical and mental health.

Baron's classification of neuropathic pains

 PNS (focal and multifocal)
 Trigeminal neuralgia
 Postherpetic neuralgia
 Diabetic mononeuropathy
 Postamputation pain
 Plexus avulsions
 Nerve entrapments e.g. carpal tunnel syndrome
 Postoperative nerve pains e.g. post-hernia repair
PNS (generalised)
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 Toxic e.g. alcohol, chemotherapy, heavy metal poisons

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MRCGP THEORY
  Metabolic e.g. diabetes, hypothyroid
 Nutritional e.g. vitamin B deficiency
 Infective e.g. HIV, Guillain-Barre syndrome
 Malignant e.g. carcinonatous neuropathy
CNS

 Infarction in brain or spinal cord

 Multiple sclerosis
 Spinal cord tumour or trauma
 Disc prolapse
Complex neuropathic disorders

 Complex regional pain syndromes (CRPS) I and II

Section 2: Diagnosis

 Those we label as 'chronic pain patients' may be disadvantaged if this leads to

healthcare professionals failing to assess pain causation.
 Detailed assessment is an essential prerequisite of successful pain management. This
involves recognising that neuropathic pain is not a single disorder but a constellation
of symptoms and physical signs.

Presentation

 The classical presentation is painful symptoms arising from an area of altered

sensation, which may be numb or hyperexcitable. There is often spontaneous pain or
abnormal responses to non-painful and painful stimuli.
 Allodynia is pain evoked by a stimulus that is not usually painful. There are three
types of allodynia: mechanical (static and dynamic), thermal (warm and cold) and
movement.
 Hyperalgesia is a response of exaggerated severity following a noxious stimulus such
as a pinprick. Hyperpathia is an increased reaction to a painful, often repetitive,
stimulus.
 There can also be spatial abnormalities, so for example a stimulus in one area causes
pain in another. This could manifest as a noxious stimulus to a normal limb causing
pain in the contra-lateral phantom limb.
 There may also be autonomic dysfunction, for example skin temperature, sweating,
hair and nail changes. Patients may have impaired sensation and muscle
wasting/weakness.

Clinical assessment

 The diagnosis of neuropathic pain is made by careful clinical history and examination.
 This diagnosis may be supported by the use of validated tools to assess neuropathic
pain, for example the Leeds Assessment of Neuropathic Symptoms and Signs
(LANSS)5 or the painDETECT questionnaires.
52

 These tools have about 80 per cent accuracy but cannot replace good clinical
assessment. Clinical assessment involves comparing the affected area to an unaffected
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adjacent or contra-lateral site.

MRCGP THEORY
  Light stroking of the skin may show allodynia. Numbness or an exaggerated response
to pinprick is important. Inability to differentiate warm and cold suggest alteration in
thermal thresholds.
 Painful symptoms and altered sensations such as these are very suggestive of
neuropathic pain mechanisms.
 It is often the case that there will be a mixed presentation and it is uncommon to have
pain that is purely nociceptive or purely neuropathic. However, pain with a
neuropathic component requires different management and so it is essential to seek
and identify neuropathic pain qualities.

Section 3: Non-pharmacological treatment

 About a third of patients with chronic neuropathic pain do not receive any treatment.7
 Treatment often needs to be both pharmacological and non-pharmacological. These
are not mutually exclusive strategies and should be explored when deciding the most
appropriate management plan.
 It is also vital to consider the patient's capabilities and carefully manage their
expectations to ensure maximum concordance with treatments.
 Non-invasive therapies include exercise, heat and cold therapy, ultrasound,
transcutaneous electrical nerve stimulation (TENS), orthotics and acupuncture.
 However, the evidence for some of these strategies needs to be carefully considered
before they can be included in common clinical practice.
 In patients with neuropathic pain, some physical treatments can be difficult to
administer because of areas of absent sensation or allodynia. Some techniques, such
as TENS and acupuncture, rely on reasonable function within the nervous system that
may be lacking in patients with neuropathic pain.
 Invasive therapies can help some patients. These range from a variety of nerve blocks
or radio-frequency lesioning to neuromodulation such as spinal cord stimulation,
intrathecal drug delivery or deep brain stimulation.
 More ablative procedures may be needed for refractory pain, for example
microvascular decompression for trigeminal neuralgia, cordotomy for cancer pain,
chemical sympathectomy for vascular pain and dorsal root entry zone lesions for
plexus pain.
 These therapies are usually offered by specialists in pain management or
neurosurgery.

Psychological therapies

 It is important to maintain emotional as well as physical function, so psychological

therapies are often helpful. Treatments are multimodal and incorporate a range of
behavioural and cognitive interventions. Many treatment programmes are delivered in
a group setting.
 In addition to specific interventions such as pacing and shaping of behavioural
change, central features include an attempt to engage patients in a collaborative
partnership and the provision of education about chronic pain.
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 Section 4: Pharmacological treatment

 In primary care an important part of treatment for neuropathic pain is

pharmacological.
 Anticonvulsants (gabapentin or pregabalin) and tricyclic antidepressants are first-line
therapy in neuropathic pain. Tertiary amines (amitriptyline, imipramine) are often less
well tolerated than secondary amines (nortriptyline).
 SNRIs (duloxetine, venlafaxine) can be used as firstor second-line choices; they may
be less effective but they have better tolerability.
 Topical 5% lignocaine patches can be used for localised areas of pain, especially if
there is allodynia. Capsaicin cream, which acts via depletion of the neurotransmitter
substance P, may help peripheral nerve pains and postherpetic neuralgia. However it
needs diligent, regular and prolonged use.
 Strong opioids are effective in neuropathic pain and may be required. These are
usually second or third line. They should be used according to the British Pain Society
guidelines on prescribing.

Combination therapy

 It is usual to start with monotherapy, but there may be a need to move to

combinations of drugs quite quickly if pain proves difficult to control.
 Effective pain relief with a single drug is achieved in less than 50 per cent of patients
with neuropathic pain.9
 It is safest to start with a low dosage, up-titrate slowly and assess the patient
frequently.
 It is necessary to provide a two to 8-week trial of each drug. There needs to be at least
two weeks at the maximum tolerable dosage before assessing efficacy.
 The patient must be made aware that if pain is long-standing in nature it is unlikely to
be completely relieved, titration may be slow and that the goal is pain management
rather than cure.
 Drug side-effects mean that it may not be possible to reach the therapeutic window in
all cases. This often requires several appointments and careful drug trials to ensure
maximum efficacy with the minimum acceptable side-effects.

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 Dizziness
Red flag symptoms

 Headache
 Ataxia
 Loss of consciousness
 Focal neurologic deficit
 Severe, continuous symptoms for >1 hour

Definition of dizziness

 'Dizzy' may describe light-headedness, feeling unsteady (gait disturbance) or vertigo.

It may be associated with nausea and vomiting or difficulty with balance. In patients
presenting with dizziness, clarify what this means.
 Dizziness can be acute or chronic and is more likely to present with increasing age.
 The vestibular system is important in balance, and comprises the vestibular nuclei in
the brain stem and cerebellum, and the vestibular apparatus in the inner ear.
Conditions affecting the vestibular system can therefore cause dizziness.

Dizziness with vertigo

 Benign paroxysmal positional vertigo (BPPV), Meniere's disease, vestibular neuritis

and labyrinthitis may cause dizziness with vertigo. Other causes include migraine and
disorders affecting visual or proprioceptive input to the brain.

Dizziness without vertigo

 Dizziness without vertigo tends to be multi-factorial and may be related to drug side
effects. The following conditions may produce dizziness:

 hypotension
 anaemia
 valvular heart disease
 hypoglycaemia
 pregnancy
 thyroid disease
 hyperventilation

 In elderly patients, dizziness may be caused by reduced proprioceptive ability, as well

as reduced visual and vestibular input on a background of comorbidities.
 Neurological conditions such as Parkinson's disease and peripheral neuropathy may
cause unsteadiness, interpreted as dizziness. Anxiety and depression may cause light-
headedness, secondary to hyperventilation.
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MRCGP THEORY
 Possible causes

 Central vertigo
 Intracranial bleed
 Space-occupying lesion
 Carotid or vertebral artery dissection
 Vertebrobasilar insufficiency
 Cerebellar stroke
 Meningitis
 Peripheral vertigo
 BBPV
 Acute otitis media
 Labyrinthitis
 Meniere's disease

Clinical assessment

After clarifying what a patient means by dizziness, establish the severity of any episode and
associated symptoms. The latter may include:

 hearing loss
 tinnitus
 headaches
 vomiting
 visual impairment
 weakness
 difficulty walking due to gait disturbance

 If symptoms are episodic, establishing frequency and duration is important.

Exacerbating and relieving factors are relevant.
 Systemic review may elucidate the underlying cause. Physical examination should
include observations such as lying and standing BP, if relevant. Neurological
examination should include looking for nystagmus, assessing gait and coordination,
and carrying out the Romberg test. Down-beating or bidirectional gaze-evoked
nystagmus indicate central nervous system involvement.
 Assessment of hearing may be carried out. Vertigo associated with hearing loss may
be caused by Meniere's disease or labyrinthitis; however, if vertigo occurs without
hearing loss, BPPV or vestibular neuritis is likely.
 Persistent vertigo may occur with vestibular neuritis or labyrinthitis, while episodic
vertigo occurs in BPPV or Meniere's disease.

CVD and stroke

 Cardiovascular disease may cause dizziness. Most patients with supraventricular

tachycardia experience feeling dizzy. If symptoms relate to postural changes, consider
orthostatic hypotension.
 Cardiovascular medications may increase the risk of this occurring. Stroke or transient
56

ischaemic attack may present with dizziness but usually other symptoms are present.
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MRCGP THEORY
 Recurrent episodes

 Vestibular neuritis may present with acute, severe dizziness with nausea and
vomiting. This causes vertigo that may be severe for a couple of days, but resolves
over weeks.
 A similar clinical picture may be produced by a small stroke affecting the brain stem
or cerebellum, so asking about focal numbness or weakness or slurred speech is
relevant, although these may not be present.
 Dizziness may affect up to half of patients with stroke at presentation in conjunction
with focal neurology.
 Recurrent short episodes of dizziness triggered by changes in head position may be
caused by BPPV. They last less than a minute.
 Central positional vertigo is caused by a lesion affecting the cerebellum or brain stem.
 Cerebellar tumour, MS and migrainous vertigo may present with positional vertigo
and nystagmus. Gait ataxia, dysarthria, dysdiadochokinesia and intention tremor may
be features of cerebellar pathology.
 Meniere's disease causes episodes of vertigo associated with hearing loss, tinnitus or
ear fullness, which may last for hours.
 Recurrent episodes of dizziness that last for minutes may indicate a transient
ischaemic attack. If the episodes are increasing in frequency this may be suggestive of
crescendo transient ischaemic attacks.
 Recurrent episodes may be indicative of basilar artery occlusion. Auditory symptoms
may be present as the anterior inferior cerebellar artery may be involved.

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 Headaches in children
Red flag symptoms

 Sudden-onset headache
 Recent trauma
 Photophobia
 Neck stiffness
 Fever
 Non-blanching rash
 Speech disturbance
 Weakness of arm, face or leg
 Decreased consciousness
 Affecting attendance at school
 Fits
 Change in behaviour
 Change in gait or balance
 Headache associated with vomiting
 Headache worse in morning or with bending forward
 Collapse

 Headaches in children are a relatively uncommon presentation. Children will

generally present with a parent or other relative/carer and it is important to develop an
idea of what both the family member and the child are concerned about.
 It may be that the parent or relative is more concerned about the problem than the
child, and this may affect your management.
 Try and speak to the child where able.

Key questions to ask

 When did the headaches start? Try to establish a timeline for the headaches. If they are
chronic, establish when the first one started, what the patient was doing at the time, or
what the relative/carer noticed at the time.
 How often do the headaches occur and have they become more frequent? Establish the
frequency and how long each headache lasts for.
 Where is the headache? Ask the child to describe it and ask if the pain ever moves around.
 Does anything make the headache worse or better (for example, sleep)?
 Are there associated symptoms? Find out if there are any warning symptoms, if vision is
affected and if there is vomiting, any weakness of the arm, face or leg, any speech
disturbance or change in behaviour or personality. Is there any relationship to food?
 Is there any family history of migraine? It may be appropriate to ask about the occurrence
of any 'funny turns'.
 How much analgesia is used?
 Have the headaches been reported at school? If so, is this affecting the child's ability to
perform at school? Is it affecting attendance at school, college or any work if the child is
older? Are there any concerns at school? Have the headaches coincided with any
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examinations?
 Has there been any reported visual problem, for example difficulty in distance vision? If
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  How is everything at home? You may choose to see the child alone. Abuse can manifest
as physical symptoms, so be alert to this and note if there is anything significant. For older
female children, check if they are taking any contraception.
 Were there any concerns at the child's birth, and is their immunisation schedule
completely up to date?
 For an acute-onset headache, ask when it started. Is the child unwell? Is there any
associated fever, photophobia, vomiting, neck stiffness or rash? Has there been any recent
trauma? If so, is there any reported discharge from the ear or nose? Has there been any
decrease in consciousness? It may be important to know if the child has any leg pain. Is
there any other associated viral symptom, such as sore throat, cough or cold-like
symptoms? Is there any facial pain?

Examination

 The type of examination depends on whether the headaches are acute or chronic in
presentation.
 With any child, observation in the first few seconds will provide a lot of information,
such as if the child is interactive, floppy or irritable. An acute-onset headache will
require assessment of consciousness, temperature, capillary refill time and ability to
tolerate light.
 You may wish to check for a petechial rash, if relevant, or signs of any obvious
trauma. Check for any obvious otorrhoea or rhinorrhoea. Check pulse rate, warmth of
peripheries, facial tenderness and any meningism, as required.
 If the headache is chronic, assess the gait and power in the arms.
 Examine the pupils for any discrepancy in reaction to light and accommodation.
Examine the fundi, looking for papilloedema.

Possible causes

Acute headache
 Meningitis
 Sinusitis
 URTI
 Trauma
Chronic headache
 Migraine: these tend to be unilateral and throbbing in nature. There may be some warning
such as flashing lights or funny smells. They tend to be associated with nausea, vomiting,
and photophobia but eased with sleep.
 Tension
 Analgesia overuse: this is more common in adults but children using regular paracetamol
or ibuprofen may develop analgesic overuse headache, which tends to ease as you wean
the medication. The pain relief may be being used to control a different sort of headache
or pain.
 Space-occupying lesion: headaches worse in morning and with bending forward. It may be
associated with vomiting and other focal neurological symptoms.
 Temporomandibular joint disorder. This may be worse on chewing. There may be a
history of excessive chewing gum use or grinding. There maybe be an area of tenderness
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over the TMJ

 Iatrogenic
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  Psychological
 Refractive errors

Investigations

 Investigations depend on the acuteness of the presentation, history and examination,

although you may wish to consider the use of a headache diary, obtaining further
history, or prescribing treatment for migraine if this seems a likely diagnosis.

Referral

 If the child becomes drowsy, floppy, irritable, or develops a severe headache

associated with photophobia, neck stiffness and/or non-blanching rash then an A&E
admission should be arranged.
 Red flags in head injury include reduced consciousness level, being floppy or
irritable, severe headache with vomiting, or any clear discharge from the ears or the
nose – if these are present, arrange an urgent admission.
 If the headache is chronic, consider referral to paediatrics if there is significant
parental concern or lack of response to early treatment. If you suspect a psychological
cause, a child and adolescent mental health team might be more appropriate.

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 Loss of consciousness
 Preceding chest pain
 Preceding dyspnoea
 Preceding headaches
 Preceding palpitations
 Preceding abdominal pain
 Associated weakness of arm, face or leg
 Associated with exercise or posture
 Blood loss
 Evidence of GI bleeding
 Associated tongue biting, urinary incontinence or prolonged limb jerking

Taking a detailed history often leads to diagnosis of the cause of loss of consciousness
without requiring further investigations. A collateral history will also be useful.

Patients have often researched their own symptoms, so it is important to find out why they
have presented now and to establish their thoughts and fears about what happened and the
possible diagnosis.

Explore the patient's agenda and if they have a plan in mind.

Key questions to ask

 When did the episodes start?

 What happens before the episodes occur?
 In general, what is the patient doing when loss of consciousness occurs?
 Does this happen in warm or crowded environments?
 Do they have warning symptoms?
 Is there any associated light-headedness, headaches, chest pain, palpitations, abdominal
pain or shortness of breath?
 Are the episodes ever witnessed? If so, what does the witness notice? Useful information
may include the colour the patient goes before the event.
 Is there any limb jerking during the event? If so, ask the patient to demonstrate it, if
possible. How long does this last?
 Does the patient report any tongue biting or urinary incontinence during the event?
 How long does it take the patient to come round and how do they feel when they do?
 Has the patient ever experienced these episodes before and if so, did they seek medical
attention and receive a diagnosis?
 Has there been any obvious GI bleeding?
 Does the patient take any regular prescribed or non-prescribed medication?

 Enquire about any family history of sudden death and complete the history by asking
about smoking and alcohol consumption. Establish the patient's occupation.
 It may be important to know if the patient drives, because their diagnosis may need to
be reported to the DVLA.
 Consider if any additional measures might be necessary to support the patient at
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home.
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 Examination

 Important things to check will include BP and pulse. Check if the pulse rate is regular.
Check lying and standing BP.
 Auscultate the heart sounds, listening for any added sounds or murmurs.
 A focused neurological examination may be necessary. Examine the pupils and their
reaction to light and accommodation. You might also examine the fundi. Palpate for
the aorta if indicated.

Possible investigations

 Blood tests, including FBC, U&Es, ferritin, HbA1c

 BP
 ECG
 Echocardiogram
 Gastroscopy
 Colonoscopy
 Abdominal ultrasound scan

When to refer

 If the patient is acutely unwell or a life-threatening emergency is suspected, you will

need to admit them directly to hospital.
 Refer to neurology if a diagnosis of epilepsy is suspected. The patient may require a
CT head and EEG.
 Refer to falls clinic if the diagnosis is unclear and the patient is having recurrent
episodes.
 Discovery of iron deficiency anaemia may require referral to your local iron
deficiency anaemia clinic, depending on local policy.
 A diagnosis of abdominal aortic aneurysm (AAA) will require urgent referral to a
vascular surgeon, depending on the size of the AAA.
 Detection of arrhythmia, heart block or cardiomyopathy will require assessment by a
cardiologist.
 Regarding the patient's fitness to drive, refer to DVLA guidance if the diagnosis is
unclear and the symptoms are still occurring.
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