Neurology Summary

This file was done by:

★ Razan Alrabah ★ Mohammed Alhumud
★ Taif Alotaibi ★ Jehad AlOrainy
★ Lama Alzamil ★ Abdulaziz Alshomar
★ Sedra Elsirawani
★ Amirah Alzahrani
★ Ghalia Alnufaei
★ Njoud Alali
★ Shahad Selayem
★ Ajeed Alrashoud
★ Rahaf Alshabri

Team leaders:
Color index:★ Raghad AlKhashan ★ Mashal AbaAlkhail
★ Amirah Aldakhilallah ★ Nawaf Albhijan
 L53- CNS infections 2

Bacterial meningitis
● Inflammation of the (meninges) pia mater and the arachnoid mater (dura mater is
Definition usually spared),with suppuration of the cerebrospinal fluid

● Classic triad: fever, neck stiffness and confusion.

● Severe Headache, Photophobia (intolerance of light) and Phonophobia (intolerance
to loud noises) can be specific to bacterial meningitis.
● Bulging fontanel in infants, sometimes with hydrocephalus

Kernig's sign Brudzinski's neck sign

While patient is lying supine, with Flexion of the neck causes

the hip and knee flexed to 90 involuntary flexion of the knee and
degrees pain limits passive hip.
Signs and extension of the knee.
Symptoms

What’s the most useful sign?

● Jolt accentuation maneuver: ask patient to rapidly rotate his or her head
horizontally: Headache worsens, In healthy individuals it might be uncomfortable but
a pt with meningitis will avoid doing it.
● Sensitivity of 100%, specificity of 54% (Low, unlike kernig and Brudzinski signs),

How to manage a patient with meningitis?

● Step 1: Give empirical therapy!! Whenever you suspect meningitis or encephalitis,
start empirical therapy! (In real life the pt will be started on empirical therapy in the
ER, before you see him)
● Step 2: CT (To exclude herniation, supratentorial tumor, bleeding, pus collection
(Subdural empyema) before doing LP bc it may kill the pt). NEVER do LP before CT.
Management ● Step 3: LP.
(Based on Dr ○ Contraindications to LP: Herniation, Infection at the site of LP (e.g. Cellulitis),
notes) bleeding disorders, Low platelet count <100, anticoagulants . If one of these
contraindication is present you can delay LP but NEVER delay the treatment
What antibiotics should be given?
● Ceftriaxone + Vancomycin (to cover highly penicillin resistant pneumococcus)
● Add ampicillin if there’s suspicion of listeria
Note: Dexamethasone should be given concomitant with 1st dose Abx to block TNF
production
 L53- CNS infections (cont.) 3

Special cases of bacterial meningitis

Meningococcal ● Fulminate meningococcemia with purpura caused by Neisseria meningitidis

meningitis ○ Overwhelming sepsis, DIC
● Classic: Meningitis with rash (Petechiae) + Headache + Fever
(Emergency)
● Lumbar puncture should not be performed if meningococcal sepsis
is suspected because coning of the cerebellar tonsils may follow – the
organism is confirmed by blood culture.
● Treatment and prophylaxis:
○ Droplet Isolation: 48h post Abx
○ Treatment: Ceftriaxone or Pen G 7 days Recall: Ceftriaxone is
C.I in neonates, give
○ Eradicate nasopharyngeal carriage: cefotaxime instead.
■ House hold contact
■ Health care providers who examined patient closely
○ Prophylaxis (Not done routinely): Rifampin 600 mg for 2 d or Ciprofloxacin
500mg once or Ceftriaxone 125mg I.M once

Listeria ● Pathology: It causes brain stem, cerebellum inflammation (Rhombencephalitis)

Monocytogenes and meningitis
● Risk groups:
meningitis
○ Age <1y or >50y
○ Alcoholics
○ Pregnancy: up to 30%
○ Immunocompromised 70 %
● Routes of transmission:
○ Mainly food borne: survives refrigeration
■ linked to poultry, hotdogs, cold cuts, coleslaw, ice-cream
○ Cheeses, particularly soft cheeses, have been implicated in listeriosis
outbreaks worldwide.
○ Inform micro lab: special media (Mueller-Hinton agar)
Note: Whenever you see a pt with changing signals in brain stem and cerebellum MRI ,
think of Listeria.
● Treatment:
○ Ampicillin 2gm IV Q4h +/- Gentamicin 2mg/kg loading dose then 1.7mg/kg
Q8h
○ 21 day duration
○ Penicillin allergy patients: TMP-SMX or Meropenem

Neuro ● Treatment:
Brucellosis ○ Doxycycline
○ Plus Rifampin
○ Plus Ceftriaxone 2gm IV q12h

What’s the most common organism in neonates?

● Group B Streptococci (occurs ONLY in neonates)
What’s the most common organism in older infants and children?
● Streptococcus pneumonia
What’s the most common organism in adults?
● Streptococcus pneumonia
What’s the most common complication?
● CN palsies (esp. deafness)
 L53- CNS infections (cont.) 4

Aseptic meningitis

● Inflammation of meninges with sterile CSF

● CSF: pleocytosis 100s, Normal Glucose, Protein normal, Neg Culture
Definition Note: Pleocytosis is the hallmark of aseptic meningitis, since it’s sterile inflammation usually it has
neutrophilic pleocytosis (there might be some lymphocytes, but the main cells are neutrophils)

● Enteroviruses: most common cause 80%

● HSV-2 (HSV-1 can cause it but it usually causes encephalitis)
● Partially treated bacteria (Think of it when the pt has taken abx in the past 2-3 days. When
you suspect viral meningitis it is important to verify that the patient has not received
Causes antibiotics (for whatever cause) prior to the lumbar puncture, as CSF lymphocytosis can
also be found in partially treated bacterial meningitis.)
● Drugs: Metronidazole, TMP-SMX, NSAIDs, carbamazepine (Given to epileptic pts), IVIG-
headache is very common (Given to pts with myasthenia gravis and Guillain barre syndrome
(GBS))

Viral encephalitis
● Encephalitis: means acute infection/inflammation of brain parenchyma, and is often seen
simultaneously with meningitis, usually viral.
● Meningoencephalitis: inflammation of brain + meninges
● In viral encephalitis, fever (90%) and meningism are usual; in contrast to meningitis,
however, the clinical picture is dominated by brain parenchyma inflammation.
● Personality and behavioural change is a common early manifestation, which progresses
to a reduced level of consciousness and even coma.
General info ● Seizures (focal and generalized) are very common and focal neurological deficits, such as
speech disturbance, often occur (especially in herpes simplex encephalitis).
What’s the most common organism?
● Most common: Herpes simplex (Either type 1 or 2):
○ How to confirm? Perform LP and PCR. MRI is also helpful (The limbic system and
the medial temporal are its favourable place)
○ Treat with Acyclovir

Cerebral abscess
● Bacteria may enter the cerebral substance through penetrating injury, by direct spread from
paranasal sinuses or the middle ear, or secondary to sepsis. Untreated congenital heart
disease is a recognised risk factor.
● Initial infection leads to local suppuration followed by loculation of pus within a
surrounding wall of gliosis, which in a chronic abscess may form a tough capsule.
General info ● Organisms:
○ Streptococci (60-70%), Bacteroides (20-40%), Enterobacteriacea (25-33%),
● S&S:
○ Fever, Headache, Meningism, Drowsiness
○ Seizures, raised intracranial pressure and focal hemisphere signs occur alone or in
combination.

Management ● Lumbar puncture is potentially hazardous in the presence of raised intracranial pressure
and CT should always precede it.
● CT with contrast: reveals single or multiple low-density areas, which show ring
enhancement with contrast and surrounding cerebral oedema
● CT brain: If abscess more than 2.5cm then surgical drainage. And if patient neurologically
unstable or decrease LOC drain regardless of size
● Antimicrobials: empirically Ceftriaxone with metronidazole, otherwise according
to susceptibility
 L54- Epilepsy 5

◄ Definitions:
● Epileptic seizure: Transient occurrence of signs and symptoms of sudden changes in neurological function due
to abnormal excessive and synchronous discharge of cortical neurons
● Epilepsy: recurrent (two or more) unprovoked seizures.
● Provoked seizures: occurs in the setting of acute medical and neurological illnesses in people with no prior
history of seizures
◄ Risk Factors: ◄ Triggers for seizures:
● Poor compliance
● Febrile convulsion
● Stress
● Family history
● Infection
● CNS mass lesion and infection
● Alcohol withdrawal
● Perinatal insult, abnormal gestation or delivery
● Sleep deprivation
● Developmental delay
● Menstrual cycle
● Head injury
● Stroke Types of Seizures

Generalized seizures
Focal Seizures Unclassified
comes with no aura (no warning) and
preceded by warning “Aura” seizures
leads to complete loss of consciousness.

Complex partial seizures

Simple partial seizures Partial seizures secondarily
→ Altered consciousness but
→ preserved consciousness generalised
not complete loss

● Always start in childhood. They are mistaken for daydreaming or poor concentration
Absence in school.
(petit mal) ● Characterized by fast recovery from seizure (No post-ictal phase), and can be
provoked by hyperventilation

● Rigid (tonic) and unconscious, falling heavily if standing and risking facial injury.
Generalized Seizures

During this phase, breathing stops and central cyanosis may occur.
● followed by jerking (clonic) movements emerge for 2 minutes at most.
Tonic-clonic ● Afterwards, there is a flaccid state of deep coma, which can persist for some minutes
“grand mal” ● During the attack, urinary incontinence and tongue-biting may occur.
● Subsequently, the patient usually feels unwell and sleepy, with headache and
myalgia.

Atonic Involving brief loss of muscle tone, usually resulting in heavy falls with or without loss of
“drop seizures” consciousness.

Myoclonic Typically brief, jerking movements, predominating in the arms.

◄ Seizure approach
● Non Invasive tests: ● Invasive monitoring
○ Clinical history
○ MRI and Nuclear medicine
○ Neuropsychological evaluation
○ Video EEG
 L54- Epilepsy (cont.) 6

Typical EEG Sign Localizes to Typical EEG Sign Localizes to

Oral Automatismes Temporal lobe Tonic arm elevation Supplementary motor area

Hypermotor
Frontal lobe Epigastric Aura Temporal lobe
automatism

Manual picking Throat tightening

Temporal lobe Insula
automatismes Sensation

Visual Hallucinations Occipital lobe Ictal pain Parietal lobe

Temporal neocortex Postcentral gyrus or

Auditory Hallucinations Somatosensory sensations
(Heschl’s Gyrus) Supplementary motor area

Olfactory
Mesial temporal lobe Clonic activity Precentral gyrus
Hallucinations

Nystagmus, eye
blinking, eye pulling De-ja-vu or jamais vu aura Mesial / Medial temporal lobe
sensation
Occipital lobe
Most often temporal, but also
Ictal amaurosis Fear
frontal lobe

◄ Medical Treatment (first line):

1. Reducing electrical excitability of cell membranes: by inhibition of sodium channel.

MOA
2. Enhancing GABA: By inhibiting GABA-transaminase or direct GABA-agonist properties.

1. Tonic-clonic (grand mal) seizures: phenytoin or valproate (drugs of choice)

2. Partial (focal) seizures: carbamazepine (drug of choice)
Clinical uses of
● valproate; clonazepam or phenytoin are alternatives.
Antiepileptic drugs
3. Absence seizures (petit mal): ethosuximide (drug of choice) or valproate
4. Myoclonic seizures: valproate or clonazepam

● Drug treatment should be simple, preferably using one anticonvulsant (monotherapy).

“Start low, increase slow“
Basic rules for
● Add-on therapy is necessary in some patients
drug treatment
● If patient is seizure-free for three years, withdrawal of pharmacotherapy should be
considered. Should be performed very carefully and slowly!

● Failure of at least TWO antiepileptic medications to completely control seizures

Drug resistant ○ Appropriately chosen for seizure type .
epilepsy ○ Taken as prescribed
○ Well tolerated (not failed due to side effects)

◄ Surgical Treatment (second line):

● Hemispherectomy: one of the two cerebral hemispheres is removed.
● Hemispherotomy: disconnects the cortex of a hemisphere from the other cutting the corpus callosum.
● Temporal lobectomy

➔ If the patient is not a good candidate for surgery?

◆ Vagus nerve stimulation (NS)
◆ Deep Brain Stimulation (DBS)
 L54- Epilepsy (cont.) 7

◄ Status epilepticus
● Definition: recurrent convulsions that last for more than 30 minutes (5 min in the last update) and are interrupted
by only brief periods of partial relief.
● Rhabdomyolysis is a complication of SE that may lead to acute kidney injury
● Treatment:
○ Early status (up to 30 min): lorazepam IV
○ Established status (30–90 min): Phenytoin
○ If ongoing seizures: Phenobarbital, and Valproate
○ Refractory status (>90 min): general anaesthesia

◄ Epilepsy treatment in pregnancy

The risk of teratogenicity is well known, especially with valproates, but withdrawing drug therapy in pregnancy is more
risky than continuation.
● All antiepileptic medications are not safe, however lamotrigine is the safest. .

◄ Seizures vs Syncope:

Cardiogenic Syncope Seizure Disorders

Loss of Consciousness Typical Common

Aura - +

Cyanosis - +

Episode Duration Seconds Minutes

Involuntary movements Common Typical

Amnesia Yes Yes

Postictal delirium & headache - +

Arrhythmia Common Rare

Electroencephalogram Slow waves Flattening Focal or General Spike

Responsive to AED No Often

Short Term Mortality High Low

 L55- Peripheral neuropathies 8

Weakness Severe Autonomic

Sensory UMN
symptoms
propriocep
signs
symptoms/ Diagnosis
tive loss signs
Proximal Distal Asymmetric Symmetric

Pattern 1:
symmetric
GBS,
proximal and distal + + + + CIDP
weakness with
sensory loss

Pattern 2:
CSPN1, metabolic,
Distal Sensory loss
with/ without
+ + + drugs, hereditary:
(CMT, Amyloidosis)
weakness

- Multiple: vasculitis,
HNPP2, MADSAM,
Pattern 3: infection (leprosy,
Distal weakness + + + lyme, sarcoid, HIV)
with sensory loss - Single:
Mononeuropathy,
radiculopathy

Pattern 4:
Asymmetric
Polyradiculopathy,
Proximal and distal + + + + plexopathy
weakness with
sensory loss

Pattern 5 : - LMN and UMN - ALS

- Pure UMN - PLS
Asymmetric distal
weakness without
+ + ± - Pure LMN - MMN3.
PMA4, BAD5, LAD6,
sensory loss MAMA7

Pattern 6 : b12 deficiency,

copper deficiency,
Symmetric sensory
loss and upper
+ + + + + friedreich ataxia,
adrenomyeloneuropat
motor neuron signs hy

Pattern 7: - Proximal and distal

SMA
Symmetric
weakness without
± + + - Distal
Hereditary motor
sensory loss neuropathy

Pattern 8:
Focal midline
+
Neck/extensor + +
proximal ALS
symmetric + + +
weakness Bulbar

Pattern 9:
Asymmetric Sensory
proprioceptive loss + + + Neuropathy
without weakness (Ganglionopathy)

Pattern 10: HSAN9, Diabetes,

Autonomic + GBS, amyloid,
dysfunction poryphyria, Fabry’s
 L55- Peripheral neuropathies (cont.) 9

● system involved: sensory and motor

● clinical features: numbness of medial hand (fourth and fifth digits). weakness of abduction
Ulnar nerve and adduction, atrophy of intrinsic muscles of the hand, wartenberg and froment signs will be
mononeuropathy evident there will also be grip weakness
● finger extensors are not involved (sign of radial nerve)
●

● system involved: sensory and motor

● clinical features: wasting of thenar eminences. weak thumb abduction, reduced sensation
carpal tunnel
over thumb, index, middle and ring fingers.
syndrome
● the most common focal neuropathy
● it is usually asymmetrical, however, it can occur bilaterally.

● they might deny family history

● sensory problems may not be present in the history but it can be present in the physical
Hereditary because it’s chronic.
neuropathy ● clinical features: Deformities e.g. high arched foot (Pes cavus), symmetric
weakness, distal more than proximal. absent reflexes. decreased proprioception,
vibration, heat and pinprick.

● history of Diabetes
● Clinical features: decreased sensation, numbness, and tingling that is progressive for a
Diabetic very long time (e.g 2 years) and pain
neuropathy ● usually symmetrical.
● most common Asymmetric neuropathy in Diabetics is Carpal tunnel syndrome
● most common symmetric is Distal symmetric polyneuropathy.

● clinical features: Weakness of hip extension, Weakness of knee flexion, Weakness of ankle
plantar flexion, Absent ankle reflex. sensory over lateral and plantar surfaces
S1 Radiculopathy
● How to differentiate sciatic from S1? by sensory distribution and the presence of hip
extension.

● clinical features: Foot drop ( difficulty in dorsiflexion). parasthesia in teh dorsum of

Common the foot. toe dorsiflexion weakness. ankle eversion is also affected. inversion is
peroneal nerve NORMAL.
damage ● loss of sensation is well demarcated. over the dorsum extending over the lateral
calf.

● Paralysis follows 1-3 weeks after an infection

● signs and symptoms include:
○ weakness of the distal limb muscles and/or distal numbness. (usually
symmetrical)
○ The weakness and sensory loss progress proximally, over several days (acute)
Guillain barre
○ Could be Motor, sensory, autonomic or combination
syndrome
○ Loss of tendon reflexes
● LP will show cytoalbuminologic dissociation (normal cells with high proteins)
● treated with IVIG or plasmapheresis NOT steroids
● regularly motor pulmonary functions
● CIDP is the chronic variant of the same presentation
 L56- Ischemic stroke 10

Stroke :
● Ischemic (blockage) → 80-85% of all strokes
● Hemorrhagic (bleeding) → 15-20% of strokes
Ischemic stroke :
● Persisting neurologic deficit after 24 hours and/or
● infarct on CT or MRI.
Transient ischemic attacks :
stroke-like symptoms that last for a very short time( <1hr) with complete recovery (most are <5 min) with the
absence of infarct in neuroimaging study.
Risk factors:
Modifiable :
- Hypertension. (Most important one)
- Diabetes mellitus.
- Hyperlipidemia.
Non- modifiable:
● Age
● Sex young women are at higher risk than men due to pregnancy, hormonal changes.
Subtypes:
● Blood vessels
○ Atheromatous (most common)
○ Non-atheromatous
■ Vasculitis
■ Dissection of blood vessels (common in young patient “50 and less”).
● Heart
○ Cardio Embolic
■ Atrial fibrillation
● Blood
○ Haemoglobinopathies
■ Sickle cell disease
○ Coagulopathy
■ Thrombophilia
Clinical presentation :
Middle cerebral artery occlusion:
● Hemiparesis: Arm + face (UE) more than leg weakness (LE)
● Hemisensory loss
● Higher cerebral dysfunction:
○ Aphasia if affecting the dominant (left) hemisphere.
■ Broca’s (expressive, anterior) aphasia: Damage in the left inferior frontal lobe causes
reduced speech fluency with relatively preserved comprehension
■ Wernicke’s (receptive, posterior) aphasia: Left temporo-parietal damage leaves fluency
of language but words are muddled. This varies from insertion of a few incorrect or
non-existent words
■ Nominal (anomic, amnestic) aphasia: difficulty naming familiar objects
■ Global (central) aphasia: combination of the expressive problems of Broca’s aphasia and
the loss of comprehension of Wernicke’s with loss of both language production and
understanding. Writing and reading are also affected.
○ Neglect if affecting the non-dominant hemisphere.
● homonymous hemianopia
 L56- Ischemic stroke (cont.) 11

Anterior Cerebral Artery (ACA) occlusion :

Symptoms :
● Weakness LE more than UE
● Emotional disturbance.
Internal carotid occlusion:
Symptoms : above and ophthalmic
Posterior cerebral artery :
Symptoms:
● Vision - visual field (homonymous hemianopia)
● memory
Vertebrobasilar
Symptoms
● Cranial nerve syndrome with crossed motor
● cerebellum (cerebellar syndrome)
● altered LOC.
● homonymous hemianopia
Midbrain
Symptoms:
● CN III: signs of complete CN III palsy:
○ dilated pupil
○ Unilateral complete ptosis (levator weakness)
○ Eye deviated down and out (unopposed lateral rectus and superior oblique
● Weber’s syndrome: Ipsilateral IIIrd nerve palsy with contralateral hemiplegia
Pons
Symptoms: CN V → Sensory:
● CN VI → lateral rectus palsy
● CN VII → facial weakness.
Medulla
Symptoms:CN VIII → vertigo, hearing loss.
● CN IX, X → dysphagia.
● CN XII → tongue weakness.
Small penetrating arteries (Lacunar syndrome)
Symptoms :
arms and face will be affected to the same degree.
no higher cerebral dysfunction or hemianopia
Pathophysiology :
● Core: area of irreversible damage.
● Penumbra: tissue at risk (ischemic but still viable cerebral tissue)
● Reduced blood blow (20-30cc) → tissue is still viable but stops functioning (penumbra) → needs to be
saved ASAP
● A drop to 10 cc in blood flow → severe ischemia
History taking in Ischemic stroke :

● Onset (Last time seen normal)

○ Symptoms: FAST
○ Headache
○ Neck pain/ trauma in case of dissection
● Past Medical history
○ Oral contraceptives
○ Antithrombotics
 L56- Ischemic stroke (cont.) 12

Physical examination in ischemic stroke : :

● keep it neurological (focused) and quick, use National Institution of Health Stroke Scale (NIHSS)
● ABC ( sometimes they add D for dextrose)
● BP Will be high (in both ischemic and hemorrhagic strokes)
● CN involvement and crossed motor typical presentation of brainstem strokes (ipsilateral CN
involvement & contralateral weakness)
● Tone : decreased on side of weakness early on, later on increased
● Reflexes: hyperreflexia on side of weakness, with upgoing toe.

Investigations of ischemic stroke :

● Coagulation profile
● Chemistry : Fasting glucose
● Imaging
a.
CT scan : non-contrast CT is the only way to differentiate between ischemic and hemorrhagic
strokes
b. MRI :
■ MRI is better overall, if immediately available
■ MRI is used when there is diagnostic uncertainty or delayed presentation, and when more
● Vascular imaging
a. Carotid U/S the least invasive
b. CTA: invasive
● Cardiac workup : ECG to detect Afib

Management of ischemic stroke :

● Acute stroke management code stroke
a. ABC
b. Reperfusion
■ Intravenous thrombolysis (IV t-PA): Effective up to 4.5 hours from onset.
● Exclusion criteria: Intracerebral hemorrhage , stroke in the past 3 months., major
surgery 14d,Pregnancy, active bleeding or acute trauma
■ aspirin (300 mg daily) should be started immediately after an ischaemic stroke if the
patient is not a candidate for thrombolysis. If the patient has already received tPA,
withhold aspirin for at least 24 hours.
● In case of atrial fibrillation → add warfarin.
● In case of significant carotid stenosis → surgery
● In case of vasculitis → steroids
■ Intra-arterial thrombolytic & Mechanical thrombectomy
● Only in case of blockage in large vessels e.g. MCA, ACA, Internal carotid or basillar
● you could do for up to 6 hours.
■ Internal carotid endarterectomy: recommended in TIA or stroke patients with internal
carotid artery stenosis >70%.
c. Prevent progression and complications:
● BP and glycemic control
○ do not lower blood pressure abruptly in first week as it may reduce
cerebral perfusion
○ Control BP before thrombolysis bc of the risk of bleeding
● NPO, avoid aspiration.
● Dx and Rx temp
● PT, OT and early rehab.
● DVT prophylaxis
 L56- Ischemic stroke (cont.) 13

d. Other components of acute stroke management:

■ Nutrition:If dysphagia persists for >48 hrs, start feeding via nasogastric
■ Temperature: Control with antipyretics, as raised brain temperature may increase infarct
volume
● Long term stroke management:
a. Long term management of Risk factors (secondary prevention)
■ HTN: Transient hypertension, often seen in the first 24-48 hours following stroke, usually
does not require treatment provided (let BP autoregulate) given diastolic pressure does not
rise >100 mmHg, because high BP helps the cerebral circulation. unless
● Patient is candidate for thrombolysis
● patient has other risk factors that necessitate BP control
■ DM,Lipid , Smoking , A-fib, and Exercise
b. Anti-platelet: for atherosclerosis Long-term soluble aspirin (75 mg daily)
Anticoagulant
● Heparin and warfarin should be given when there is:
○ atrial fibrillation
○ Hypercoagulability
● Anticoagulants are potentially dangerous in the two
weeks following infarction
c. Rehabilitation
Transient ischemic attack :
● The term TIA traditionally also includes patients with amaurosis fugax : sudden transient loss of vision in
one eye. the first clinical evidence of internal carotid artery stenosis – and forerunner of a hemiparesis.
● Duration: most TIA’s last 5-20 mins
● Features depend on: anterior circulation carotid system posterior vertebrobasilar circulation.
system
● Prognosis: up to ⅓ will have a stroke (usually within 48 hours)
Clinical findings :
Consciousness is usually preserved in TIA.
There may be clinical evidence of a source of embolus, e.g.:
● Carotid arterial bruit (stenosis)
● Atrial fibrillation or other dysrhythmia
Approach to TIA :
1. Needs urgent assessment (ER)
2. Rule out other causes
3. Work up: (labs, CT scan or MRI)
● Vascular image of carotid CTA, MRA, US.
● Cardiac work up: (EKG، echo, +/- holter)
4. Start stroke prevention measures (like ischemic stroke)
Hemorrhagic transformation :
● > 50% of ischemic stroke have some hemorrhage
● Risk factors:
a. Older age
b. Larger stroke size
c. Anticoagulant use
d. Thrombolytic therapy/recanalization: increases the risk of haemorrhagic transformation
Prognosis :
● Why does hemorrhagic stroke carries worse prognosis? Because the blood can compress the neurons,
blood vessels. Also, it will cause edema and herniation
 L57- Hemorrhagic stroke 14

Intracranial hemorrhage (ICH):

● meningeal space hemorrhage: ● intracerebral:
○ epidural hemorrhage. ○ brain parenchyma.
○ subdural hemorrhage.. ○ IVH.
○ subarachnoid hemorrhage.
Risk factors:
- Hypertension. - excessive alcohol use. -smoking. -obesity. - physical inactivity. -older age.
- ethnicity/race. - medications (antiplatelet or anticoagulant). -sympathomimetics (cocaine & amphetamine
in young age).
Etiology :
- Hypertensive ICH: 1- Essential: rupture of microaneurysms (Charcot-Bouchard aneurysm). 2- Eclampsia.
- Non-hypertensive ICH:
1- Vascular malformation: aneurysm, cavernous hemangioma, bleeding disorders, venous and cavernous
angiomas.
2- anticoagulant (more than antiplatelets)
3- Amyloid angiopathy: elderly especially Alzheimer pt. usually in cortical and subcortical areas (lobar area).
4- Trauma: commonly causes subdural hemorrhage or epidural hemorrhage.
5- Tumor
6- Drug abuse: amphetamine, cocaine, and PPA.
- other causes:
1- Cerebral venous thrombosis (CVT): young female due to OCP use.
2- Intracranial neoplasm.
3- Moya Moya.
4- Vasculitis.
Pathophysiology :
● Primary immediate effect: hemorrhage growth and increase intracranial pressure.
● Secondary effect: downstream effect, edema, and ischemia.
● Site: basal ganglia, lobar regions, thalamus, pons, and cerebellum.
clinical presentation :
● Alteration in level of consciousness
● Nausea and vomiting
● Headache
● Headache
Investigations:
● LAboratory studies:
○ CBC → looking for thrombocytopenia.
○ coagulogram
● Imaging
○ CT brain without contrast (essential to differentiate ischemic from hemorrhagic)
■ Hyperdense signal intensity.
■ Multifocal hemorrhages suggests a traumatic etiology.
■ Hematoma volume can be approximately by (AxBxCx)/2.
○ CT vessels: CT angiography screening for AVMs, vasculitis.
● the workup:
○ MRI brain: with gado if looking for neoplasm, MRI diffusion-weighted.
○ MRA/MRV: if allergic to CT dye of if you’re looking at venous outfkow.
■ MRA → for AVM and aneurysm.
■ MRV → for cerebral venous thrombosis.
○ Cerebral angiography.
Management of ICH:
● Medical:
○ Control blood pressure:
■ Reduction of SBP to 140 is save. why not less? to preserve blood perfusion to small vessel and
preventing ischemia resulted from small blood vessel compression. in the area around the
hemorrhage.
■ Use labetalol and/or nicardipine drip to titrate blood pressure.
○
 L57- Hemorrhagic stroke (cont.) 15

Intracranial hemorrhage (ICH):

Management of ICH:
● Medical:
○ Control blood pressure:
■ Evidence-based practice nursing care:
- Watch for neuro decline -Type and cross with your labs -Head of bed > 30o elevation -Head midline
-Treat hyperthermia -Prevent vagal maneuvers -Control SBP (120-140) -Treat hyperglycemia
-Treat hyperthermia -Seizure prophylaxis -DVT prophylaxis only after 48hrs & no haemorrhage
○ Cerebral edema: soduim (hypoosmolar hyponatremia) and CO2
■ Use the ventilator to manage CO2.
■ Get the Sodium levels up to 145- 155.
■ Mannitol 3% Given to prevent brain herniation that’s caused by the cerebral edema.
● Give them hypertonic saline e.g. 3% sodium or mannitol to lower edema
● Surgical:
○ Surgery never works except in only two scenarios:
■ Cerebellar hemorrhage if the hemorrhage is small we will observe the patient for any deterioration
■ Labor superficial hemorrhage: if small observe the pt deterioration to take him to the OR.
subarachnoid hemorrhage (SAH):
Etiology:
● Aneurysm rupture: usually berry aneurysm rupture, most common sites are: anterior communicating artery,
posterior communicating artery, and middle cerebral artery.
○ Can be perimesencephalic SAH.
● Arteriovenous malformation (AVM).
Differential diagnosis of SAH:
● Migraine: presence of neck stiffness usually indicates SAH.
● Acute bacterial meningitis.
● Cervical dissection.
Clinical presentation:
● Sudden acute severe headache: thunderclap headache (often occipital), could be followed by vomiting and death.
● Other features: raised PB, neck stiffness or pain, straining, sexual excitement, papilloedema, and loss of
consciousness at the onset.
● Physical examination:
- Distress & Irritability. - Photophobia. -Positive Kernig’s sign: (may take hours to develop).
- Focal hemisphere signs, such as hemiparesis or aphasia.
Investigations:
● CT brain scan: negative result does not completely exclude SAH
○ if CT is negative and the presentation is suggestive of subarachnoid hemorrhage then you do spinal tap to
look for blood in the CSF.
● Lumbar puncture: performed 12 hr after symptom onset, to allow detection of xanthochromia → yellow CSF.
● CT angiogram: if wither CT of LP is +ve, angiogram is required to determine the optimal approach to prevent
recurrent bleeding.
Management:
● Surgery: Coil/Clip
● Medication:
○ NIMOTOP/ NIMODIPINE: all the patient should be given, CCB prevent and treat the vasospasm, given for 21 days.
■ If patient develops vasospasm while on Nimodipine you should do angioplasty of the vasospasm.
● strict BP control.
● Check Sodium Levels → Treat the central Hyponatremia:
○ best managed by fluid restriction & 3% NaCl
● Check Urine output.
● Treat the obstructive hydrocephalus (a complication of SAH) → may require drainage via a shunt
 L58- Dementia 16

Characteristic Delirium Dementia

Metabolic, Toxic, Infectious, Drugs, Surgery Vascular, Neurodegenerative, Infective,

Causes & CNS disorders. Toxic/Nutritional, Traumatic,Hydrocephalus,
Inflammatory, Neoplastic & Prion.

Attention Impaired (fluctuating (worse at night)) Usually alert

Onset Acute (Hours/Days) Gradual

Fluctuating from hour to hour (waxing and Progressive deterioration

Course
waning)

Consciousness Clouded Intact

Hallucinations/ Present (often visual or tactile) Rare, only in highly advanced disease
Delusions Delusions of Harm

1) Disturbance in attention 1) Evidence of significant cognitive

2) Change in cognition decline from a previous level of
3) The disturbance develops over a performance in one or more
short period (usually hours to cognitive domains:
days) and tends to fluctuate during - Learning and memory - Language
the course of the day. - Executive function - Complex attention
Diagnostic 4) There is evidence from the history, - Perceptual-motor - Social cognition
Criteria physical examination, or laboratory 2) The cognitive deficits interfere with
DSM-V findings that the disturbance is independence in everyday activities.
caused by a direct physiologic 3) The cognitive deficits do not occur
consequence of a general medical exclusively in the context of a
condition delirium.
4) The cognitive deficits are not better
explained by another mental
disorder.

Prognosis Reversible Irreversible

Treatment Treat the underlying cause Cholinesterase inhibitors

Acute presentation with

altered level of
Delirium
consciousness1
(See criteria)

Cognitive complaints
(Memory problems, language
problems or disorientation)
Normal consciousness, Non-delirious
non-acute presentation (Dementia)
 L58- Dementia (cont.) 17

Alzheimer’s Disease
(Most common cause of dementia)

Clinical features Risk factors Pathophysiology Diagnosis Management

● Decreased memory and ● Increasing age ● Accumulation of ● Diagnosis is clinical ● Donepezil,

new learning ● APOE ε4 amyloid beta > senile ● Brain structure on rivastigmine and
● Language impairment ● Down Syndrome plaques MRI may galantamine which
● Apraxia ● vascular risk ● Accumulation of demonstrate medial increase central
● Unawareness of illness factors(DM, HTN, hyperphosphorylate temporal atrophy nervous system
● Delusions Hyperlipidemia & d tau protein > bilaterally acetylcholine
● Passivity Lack of exercise) neurofibrillary ● PET scans can ● Does not stop
● Delusions ● Brain trauma tangles demonstrate disease progression,
● Depression, Circadian ● Resultant loss of decreased only provides
rhythm disturbances & neurons and metabolism in transient clinical
Weight loss synapses, (esp. in temporal and stability.
basal forebrain parietal regions ● Not a treatment, but
leading to education and
cholinergic deficit) physical activity
The picture is not important, I simply find it fascinating.
(Most beneficial)

Lewy body dementia (LBD): dementia and signs of Parkinson’s disease.

(Second most common cause of dementia)

Clinical features Notes Pathophysiology Diagnosis Management

● Visual hallucinations Parkinson’s Disease ● intracytoplasmic ● Diagnosis is ● Same as Alzheimer’s

● Parkinsonism Dementia (PDD) is “Lewy Bodies” primarily clinical Disease.
● Fluctuations in cognitive similar to LBD, The present in neurons, ● PET scan may show
ability and level of difference is that a which are the result decreased occipital
consciousness. clear history of PD of abnormal lobe metabolism
● Visual spatial impairment with NO cognitive α-synuclein protein ● Myocardial
● Sensitivity to impairment precedes accumulation scintigraphy may be
neuroleptics the development of abnormal due to
● REM sleep behavior dementia by at least a abnormal cardiac
disorder year. sympathetic
● Autonomic dysfunction innervation

Frontotempol Dementia:
A number of different syndromes characterised by behaviour abnormalities and impairment of language.

● Associated with personality changes, inappropriate social behavior (disinhibited), lack of insight,
Behavioral Variant Binging on certain foods, emotional blunting, rigidity & decreased attention modulation.
● MRI: atrophy in the frontal lobes (may be asymmetric).

Primary Progressive ● Slowly progressive non-fluent aphasia: Patients present first with a non-fluent type of aphasia.
Aphasia ● MRI : focal left frontal atrophy

● Usually have intact fluency, but comprehension is impaired and decreased naming ability.
Semantic Dementia ● MRI may show focal left temporal atrophy.

Vascular Dementia

Clinical features Risk factors ● A single stroke in a region important to cognition such as hippocampus or
thalamus, or a large stroke that affects multiple lobes.
● Frequently coexists with ● Hypertension ● Recurrent strokes that accumulate over time, there is a step-wise
Alzheimer's disease ● Hyperlipidemia development of cognitive deficits.
● DM ● Slowly progressing cognitive deficits due to subclinical progressing of
● Smoking small vessel disease.
 L58- Dementia (cont.) 18

Normal pressure hydrocephalus (NPH) (Rare)

Clinical features Notes Pathophysiology Diagnosis Management

Classically triad of: - In 2ry NPH, there is a ● Impaired CSF ● CSF shunting
● Gait impairment history of a previous absorption at the ● Improvement after procedure is
“magnetic” meningitis, level of the a LP that removes performed.
● Dementia inflammatory arachnoid villi 30-50 cc of CSF
● Urinary disorder, or SAH. ● MRI: dilated
incontinence - Idiopathic NPH is ventricles (CSF
when there is no pressure is
preceding explanation normal)
for the condition.

Creutzfeldt-Jakob Disease (CJD) (Rare, 1 in a million)

Clinical features Notes Pathophysiology Diagnosis Management

● Rapidly Prion disorder ● abnormally formed ● CSF Analysis: ↑

progressing proteins that induce 14-3-3 protein
dementia, disease pathological ● EEG shows
● No treatment,
duration (usually 6 transformations in characteristic
patients die within
months). other proteins periodic sharp
a year.
● Myoclonic jerks leading to leading wave complexes
may occur. to spongiform ● abnormal signal
pathology in brain intensity in the
basal ganglia and
cortical ribbon

Feel free to vent here, no one will read it..

 L59- Parkinsonism 19

◄ Types of movement Disorders

● Hyperkinesia: Myoclonus, Tremor, Dystonia and Chorea.
● Hypokinesia: Bradykinesia.

◄ Parkinsonism
● Clinical syndrome characterised primarily by bradykinesia, with associated increased tone (rigidity), tremor and
loss of postural reflexes.
● Most common cause is idiopathic parkinson’s disease.

◄ Idiopathic Parkinson’s disease

Pathophysiology
● Presence of neuronal inclusions called Lewy bodies which contains tangles of α-synuclein.
● Loss of the dopaminergic neurons from the substantia nigra
Risk Factors
● Older age, men, pesticide exposure, MPTP (potent mitochondrial toxin) and non-smokers.
Clinical features
● Pre-motor → Ansomia, REMBD, autonomic dysfunction and Depression/anxiety.
● Motor →
○ Bradykinesia; slowness of movement and progressive fatiguing, mask like semblance of the face.
○ Parkinsonian tremor “pill-rolling”; rhythmic oscillatory, predominantly at rest, re-emergence with
maintained posture.
○ Rigidity; “lead-pipe” “cogwheel”, independent of velocity.
○ Postural gait changes; stooped posture, shuffling.
● Quit speech and drooling, Visual hallucination.
Diagnosis
● Clinical with normal imaging.
Management

Levodopa/Carbidopa (LD/CD) Dopamine agonists (Pramipexole, rotigotine) other drugs

- Mainstay of treatment - Used in combination with levodopa or as initial - (MAO)-B inhibitor: Selegiline
- Relieving akinesia and rigidity monotherapy in younger patients < 65–70 with mild - COMT inhibitors : Entacapone
- Combined with dopa decarboxylase to moderate impairment. - Anticholinergic: help tremor,
inhibitor (carbidopa). - Apomorphine: short-acting DA administered cause confusion and cognitive
- ADRs: ON-OFF phenomenon; ON with subcutaneously, It is used in advanced PD impairment in older patients.
dyskinesia happens when the levels of - ADRs: fibrotic reactions, including cardiac valvular
L-dopa are too high. fibrosis.

Other management options

● Deep brain stimulation (DBS) → LD/CD responsive patients only) as an adjunct to treatment.

◄ Red flags
If present, suspect conditions other than Parkinson's disease.
● Neuroleptic or anti-emetic drug use.
● Early/prominent autonomic dysfunction
● Limited eye movements
● Pyramidal, cerebellar or sensory symptoms
● Cognitive impairment
 L59- Parkinsonism (cont.) 20

◄ Other akinetic-rigid syndromes

Drug induced
- Metoclopramide or haloperidol
Parkinsonism

Progressive - Parkinsonism + the inability to look up & down due to degeneration in the part of the midbrain.
Supranuclear Gaze Palsy - Path: Shrunken midbrain “hummingbird sign” and Tau deposition.

- Cerebellar signs, extrapyramidal system and severe early autonomic dysfunction.

Multiple System Atrophy
- Path: α-synuclein inclusion and hot cross bun sign”.

Vascular Parkinsonism - Upper motor neuron signs, results from multiple strokes.

Corticobasal
- Cortical impairment: Sensory, Astereognosis, Agraphesthesia, Apraxia.
degeneration

- Copper deposition occurs in the basal ganglia, the cornea and liver causing cirrhosis.
Wilson’s disease - Young patients <50
- Check serum copper and ceruloplasmin.

◄ Hyperkinetic disorders

- Hereditary, benign condition but impairing.

- Slowly progressive, bilateral, asymmetric, upper limbs action tremor, that disappears at rest.
Essential Tremor - There is no bradykinesia, rigidity, or dystonia.
- Cerebellar tremor could look exactly like an essential tremor.
- Treated with Propranolol

- same movement happening persistently or repetitively, usually there’s contraction of both agonist +
antagonist muscles at the same time.
Dystonia
- Ballismus: large amplitude choreiform movement, seen after subthalamic strokes usually, botulinum
toxin injections or DBS may be useful.

- continuous flow of random muscle contractions (‘dance-like’).

Chorea
- Can occur in “Sydenham’s Chorea” and in Huntington's disease (HD)

- Involuntary single quick contraction of a muscle group (or its inhibition). Can be
Myoclonus
repeated but not rhythmic

Tics - stereotyped movements or vocalizations (may be temporarily suppressed)

 L60- Myopathies 21

Polymyositis (PM): inflammatory myopathy affecting the proximal skeletal muscles

Dermatomyositis (DM): inflammatory myopathy that presents similarly to polymyositis, with the
addition of skin involvement
Inclusion body myositis (IBM)

● Skin features (Specific for DM): Gottron papules, heliotrope rash, and the shawl sign
● Malignancies are associated with DM > PM
● Patients with IM typically complain of muscle weakness with difficulties reaching overhead,
climbing the stairs, and/or standing up. Advanced disease may present with dysphagia and
Inflammatory aspiration because of oropharyngeal muscle involvement, or even respiratory failure if breathing
Myopathies muscles are affected.
● DM is primarily distinguished from PM by the characteristic rash.
● The best initial test is CPK and aldolase
● Muscle biopsy is the pivotal investigation (most accurate test)!
○ DM: Perifascicular atrophy
○ PM: No Perifascicular atrophy
● interstitial lung disease is strongly associated with the presence of antisynthetase (Jo-1)
antibodies
● Management: Steroids & screen for underlying malignancies

Inclusion body myositis (IBM): inflammatory myopathy affecting both the proximal and distal skeletal
muscles (mainly Distal). Common after age 50
● Quadriceps muscle weakness (Thigh): knees lack support → frequent falling
○ Usually spares rectus femoris muscle
Inclusion body
● +/- long finger Finger flexors: difficulties gripping, e.g., shopping bags or a briefcase
myositis
● Severe Oropharyngeal dysphagia
● Biopsy (most accurate test): Inflammatory cells invading non-necrotic muscle fibers,
Rimmed vacuoles.
● Relentless progression, lacks effective therapies

● Steroid myopathy: due to chronic exposure to steroids

○ Biopsy: type 2 fiber atrophy and lipid accumulation in type 1 fibers.
Drug Induced
● Statin Induced Myopathy: Statins inhibit HMG-CoA reductase, rate-limiting enzyme of cholesterol
Myopathies biosynthesis. Can cause:
○ Discontinuation of the statin → resolution of symptom

● They are x-linked recessive disorders (manifest in males). Duchenne (early age) and
becker (late age).
● Mutation in the dystrophin gene (Xp21) → absent (in duchenne) or reduced (in becker)
Dystrophin
DMD:
● Symmetrical progressive (Proximal > distal) muscle weakness (Legs & Arms)
● Course: Onset age 2 to 5 yrs, Wheelchair at 10/
Dystrophinopa ● Gower’s sign, Loss of ambulation at age 9-13 years, Muscle hypertrophy: Especially calf
thies ● Dilated cardiomyopathy: common after age 15 (usually the cause of death)
Becker:
● Older age at onset, Muscle weakness starts from > 7 yrs. Slowly progressive. “Becker is
Better.” Loss of ambulation usually in the 4th decade
Investigations & Management:
● Muscle biopsy: absent dystrophin staining (DMD). Partial loss of dystrophin staining (BMD)
 L60- Myopathies (cont.) 22

● Manifestations are Asymmetrical

○ Face: Initial manifestation, 95% you will detect it at the age of 30 with examination
○ Eyes: Often early in disease course
○ Lid closure: Incomplete
○ Sleeping: With eyes open
Facioscapulohu
○ Shoulder: Pain in shoulder girdle, scapular winging, triple humb
meral dystrophy
○ Ear: deafness
● Screen for:
○ Hearing loss
○ Retinal vascular disease
● No screening for cardiac needed unless symptomatic

● Weakness: Humeroperoneal
○ Bilateral, Symmetrical
○ Arms: Biceps & triceps; Deltoids spared.
○ Scapular winging
○ Legs: Late
○ Face: Mild weakness or normal
Emery – dreifuss ★ Contractures occurs before weakness and it is often more limiting to function than
muscular weakness.
dystrophy ○ in elbow, achilles tendon
○ Spine:
■ Posterior neck (extension), Lower back: Usually later onset, but may present
with rigid spine syndrome.
● Testing:
○ CK, EMG, Cardiac screening for arrhythmia and cardiomyopathy (leads to sudden
death)

● The most prevalent inherited neuromuscular disease in adults (Autosomal dominant).

● Tandem repeats at DMPK gene (Anticipation phenomenon)
Myotonic
● difficulty releasing hand grip on a doorknob or handle.
Dystrophy
● Frontal balding, Cardiorespiratory weakness
● EMG: myopathic plus myotonic discharges. Genetic testing (confirmatory test)

● Triggered: Anesthetics, Depolarizing neuromuscular blocking agents

Malignant ● Clinical features: Tachypnea, tachycardia, Rigidity, Acidosis ,Hyperkalemia
Hyperthermia Rhabdomyolysis, High CK, Hyperthermia.
● Treatment: Remove anesthetic agent, Dantrolene sodium

● Acute Syndrome of muscle necrosis due to extensive injury of skeletal muscle with
release of intracellular muscle materials into the circulation.
● What is the commonest muscle disorder that causes myoglobinuria? Metabolic
myopathies
● Clinical features:
Rhabdomyolysis ○ Cola or tea color “dark” urine (Myoglobinuria)
○ Elevated blood and urine myoglobin
○ Fever, leukocytosis
○ Markedly elevated CK
● Complications: ↑ K+ → arrhythmia → death
● Management: IV hydration to avoid acute tubular necrosis (ATN) and renal failure !!!
 L61- Multiple sclerosis 23

Multiple sclerosis

● A chronic autoimmune, T-cell- mediated, inflammatory disorder of the CNS.

○ Myelin is produced by:
◆ Schwann cells: Peripheral nerves.
Definition
◆ Oligodendrocytes: CNS
● The most common chronic inflammatory, demyelinating and neurodegenerative disease of
the CNS in young adults

● EBV Infection: Most common

● Vitamin D: Sun exposure & serum vitamin D are inversely related (Sunlight may be
Risk factors protective)
● Smoking: also increase the severity of MS
● Obesity & Genetics

● The life expectancy of patients is reduced by 7–14 years.

Epidemiology ● MS is the main cause of death in more than 50% of patients. Mostly due to MS complications
e.g. aspiration pneumonia or Neurogenic bladder ( → Infections → sepsis)

1. Characterized by breakdown of the blood—brain barrier (BBB) → entry of activated T

lymphocytes & other inflammatory cells nto the CSF (1st change in MS)
2. Recognise myelin-derived antigens on the surface the microglia → initiates destruction of
Patho-
the oligodendrocyte–myelin unit by macrophages
physiology
3. Most easily recognized in the white matter as focal areas of demyelination, inflammation,
and glial (astrocytes) reaction → Plaques
● Recurrent relapses lead to permanent myelin and axonal damage and oligodendrocytes loss

● Plaques of demyelination, 2–10 mm in size, are the cardinal features.

● Lesions are most easily recognized in the white matter. There has to be multiple lesions, if
only one then it’s not MS
● Plaques occur anywhere in CNS white matter but most commonly sites:
○ Optic nerves
○ Periventricular region
Pathology
○ Corpus callosum
○ The brainstem and its cerebellar connections
○ Cervical cord (corticospinal tracts and posterior columns)
■ Spinal lesions:
● In MS: short and peripheral (visualized on axial images)
● In NMO: long and central or circumferential.

★ CIS is the first clinical episode that is suggestive of MS

● Why don’t we classify them under MS? Bc it’s only one episode and not all of them
Clinically develop MS (Many ppl in their 20s may get this attack and then live normal for the rest of
isolated their lives)
syndrome ● Monophasic episode with symptoms and objective findings that reflect inflammatory
(Pre-MS) demyelinating event in the CNS.
● lasting for at least 24 hrs. (If less than 24hrs then it’s NOT an MS attack)
● Occurs in the absence of fever or infection
● Resembles a typical MS relapse (attack) but occurs in a patient not known to have MS
 L61- Multiple sclerosis (cont.) 24

Relapsing-remitting MS (RRMS) (85–90%)

● The typical and most common pattern of MS

● A purely RRMS is characterized by the absence of worsening neurological function outside
of individual relapses
● The majority will eventually enter a secondary progressive phase

Secondary progressive (SPMS)

● Worsening irreversible neurological function, preceded by RRMS that cannot be

explained purely by worsening associated with ongoing relapses
● This late stage of MS consists of gradually worsening disability progressing slowly over
years.
Four main ● Starting early treatment in RRMS can delay the onset of SPMS and hopefully even prevent it.
clinical pattern
Primary progressive (PPMS) (10-15%)

● Irreversibly continuous worsening neurological function, without preceding relapses

● Patients older at onset or with PPMS have shorter survival.
Example: a 40 years old lady presenting with slowly progressing weakness in the lower limb. At first she was able to walk independently, then
she depended on a cane to help her walk for months, afterwards she noticed that she needs a walker (bilateral support) to walk, which she kept
using for a few months to years, and now she needs a wheelchair.

Relapsing–progressive MS (<5%).

● This is the least common form of MS.

● It is similar to PPMS but with occasional supra-added relapses on a background of
progressive disability from the outset.

Clinical feature of Multiple sclerosis

● Blurred vision usually in one eye. NOT double vision, seeing black dots, can’t see clear in
the dark.
● Pain exacerbated by eyes movement.
Optic Neuritis ● Reduced perception of colors. (red desaturation, the color will be pale in the affected eye)
● Flashes of light on moving the eyes.
● Enlarged blind spot. because the optic nerve is inflamed and swollen
Note: Blurred vision in one eye + Pain on eye movement = Almost always optic neuritis

● Diplopia if the nucleus of 3rd,4th and 6th nerves affected (the CNs themselves aren’t
affected, what’s affected is their nucleus)
● Trigeminal neuralgia: is a severe pain that happen when one of the divisions of V CN
distribution is touched and lasts for a few seconds, happens if involve trigeminal nerve
(sensory).
● Vertigo (spinning sensation) and nystagmus, happens if there is a plaque in the
cerebellum
Brain Stem
● Facial numbness and weakness: if the facial nerve is involved
Related
● Internuclear ophthalmoplegia (INO): Bilateral internuclear ophthalmoplegia is
Symptoms
pathognomonic of MS
○ A Specific gaze abnormality, characterized by impaired horizontal eye movement
with weak adduction of the affected eye and abduction nystagmus of the
contralateral eye
○ Resulting from a lesion in the medial longitudinal fasciculus in the dorsomedial
brainstem tegmentum of either the pons or the midbrain.
○ If you see it in young patient almost always MS (If elderly, think stroke)
 L61- Multiple sclerosis (cont.) 25

Clinical feature of Multiple sclerosis (Cont)

● Oscillopsia: (A visual disturbance in which the object in the visual field appears to oscillate
Cerebellum due to nystagmus)
Related
● Dysarthria: (Slurred speech)
Symptoms
● Imbalance: (Wide-based gait)

● Lhermitte’s sign: electric like sensation induced by neck flexion, very serious almost
always indicate spinal cord lesion (any cervical cord lesion, not specific to MS)
● Sphincter dysfunction. urine incontinence, neurogenic bladder and stool incontinence,
Brain And commonly seen if there is spinal cord lesion
Spinal Cord ● Cognitive dysfunction: memory, concentration, processing speed. (Uncommon in
Symptoms MS,and usually does not happen with the first attack)
● Sensory loss/numbness/pain
● Weakness (monoparesis, paraparesis, quadriparesis).

● A general term that indicates inflammation of the spinal cord with cord swelling and loss of
function. Typically, one or two spinal segments are affected with part or all of the cord area
at that level involved
Transverse
● Spinal cord related motor, sensory &/or autonomic dysfunction. transverse in the name
Myelitis
means involve more than one area of the spinal cord
● Sensory level, means the is loss of sensation in a specific level eg. patient has complete
loss of sensation from mid abdomen and below, this sign indicate a spinal cord lesion

● Temporary worsening of pre-existing symptoms with increases in body temperature,

e.g. after exercise or a hot bath
Uhthoff ● Less than 24 h, Reversible if last for more than 24h think about relapse
phenomenon
● It does not indicate that there’s ongoing damage, it only indicates that there was an area of
inflammation and demyelination

Diagnosis of MS: To diagnosis of MS you must have both:

Dissemination in time Dissemination in space

● History of at least two attacks separated by at least ● Clinical evidence of involvement of two CNS sites
one month. OR of one lesion with historical evidence of
● if 2 attacks occur in the same month it’s counted another site being affected.
as 1

● The presence of multiple lesions on MRI (dissemination in space) or the demonstration of additional
clinical attacks on MRI (by showing lesions of different densities (dissemination in time)) fulfills the
criteria for MS despite the presence of one attack in the patient's history (enhancing are new,
non-enhancing are old)

● it is essential to ask about previous episodes of neurological symptoms

● MRI is both the best initial test and the most accurate test.
● Lumbar puncture and CSF analysis: if you not sure about the diagnosis another way to confirm it is to do
lumbar puncture and look for oligoclonal IgG bands, BUT with presence of relapse and remitting
symptoms. Rarely used anymore
 L61- Multiple sclerosis (cont.) 26

Management of MS

● Steroids (IV or orally Methylprednisone)

● Most of the time relapses resolve on their own but steroids shorten the relapse
Acute
episode.
treatment of
● Only given when relapse is significant or affecting their life (e.g. a pilot comes with blurred
relapses
vision = needs immediate attention = use steroids)
● Plasma exchange is used for those who don’t respond to steroids

● Low efficacy DMT (eg: interferon, teriflunomide) vs high efficacy DMT (eg: natalizumab)
Examples:
● Patient with depression: do not give interferon as it worsens depression
● Patient with cardiac condition: do not give fingolimod - causes heart block and
seriously arrhythmias
Disease ● Patient came with only tingling, no residual disabilities after the attack, few lesions
modifying on MRI→ give low efficacy DMT (interferon or teriflunomide)
treatments ● Patient with only numbness, but had a previous relapse in which she described
ataxia and difficulty walking, do we give her low efficacy DMT? No (if u check MRI,
you might find extensive lesions, multiple on spinal cord (very bad prognostic sign)) →
start on fingo (medium efficacy DMT) or Natalizumab (high efficacy DMT)
○ Natalizumab can cause: Progressive multifocal leukoencephalopathy PML
(fatal) & leukemia

Other Demyelinating Diseases

● Characterized by longitudinally extensive transverse myelitis (>3 segments) and bilateral

or recurrent optic neuritis.
Neuromyelitis
● Mean age is 10 years later than MS.
Optica
● Affects mainly the optic nerves and the spinal cord
Spectrum
● More severe attacks than in MS. (presenting with nausea, vomiting and hiccups are
Disorder
important red flags in NMO)
(Devic’s
● Usually negative OCB in the CSF. While 90% of MS has positive OCB
disease)
● Serum antibodies to aquaporin-4 water channels on astrocytes are diagnostic (should
be done for every suspected case)

● Acute monophasic demyelinating condition.

● Frequently preceded by vaccination or infection.
Acute ● More common in children.
Disseminated ● Usually a monophasic illness (no relapses).
Encephalomye ● Pathology: Wide spread white and gray matter peri venous ‘‘sleeves’’ of
litis inflammation and Axons are relatively spared unlike MS and NMO.
● Symptoms: Encephalopathy, Multifocal neurological deficit, May fluctuates over a 3
months period for one single attack (If more than 3 months, it’s not ADEM)

● Behçet’s principal features are recurrent oral and/or genitalulceration,

inflammatory ocular disease (uveitis) and neurological syndromes.
Behçet’s ● Brainstem and cord lesions, aseptic meningitis, encephalitis and cerebral
disease venous thrombosis occur.
● There is a predilection for ethnic groups along the ancient ‘Silk Road’ – Turkey,
the Middle East and Asia. Behçet’s is associated with the HLA- B51 allele.
 L62- Neuromuscular junction disorders (NMJ) 27

Neuromuscular junction physiology :

● This binding of ACh to ACh receptors in the motor end plate causes ion channels to open & so allow the
sodium (Na+) ions to flow across (influx) the membrane into the muscle cell , generates a muscle action
potential.
Classification of NMJ disorders :
1. According to the mechanism of action or etiology
a. Immune mediated : Myasthenia gravis and lambert eaton syndrome
b. Toxic / metabolic : Snake venom, Botulism, Organophosphates and Hypermagnesemia.
c. Congenital : Congenital myasthenic syndrome
2. According to the location of the disruption:
a. Presynaptic : decrease in the release of acetylcholine and impair the calcium channels
■ Lambert Eaton Syndrome , Botulism, and Congenital myasthenic syndrome
b. Synaptic : Organophosphate
c. Postsynaptic : The highest number of diseases affect the neuromuscular junction
postsynaptically. either affects the Na+ channels or the ACh receptors : Immune mediated
myasthenia gravis (most common)
Myasthenia gravis Definition :
The hallmark of the disorder is a fluctuating degree and variable combination of weakness in ocular either alone
or in combination with , bulbar, limb, and respiratory muscles.
Epidemiology :
● Myasthenia gravis occurs at any age, but there is a bimodal distribution to the age of onset:
Pathophysiology of MG :
- In MG, there is reduction of postsynaptic AChRs due to production of anti-AChR antibodies that block
receptors from binding to Ach and causes damage the postsynaptic membrane.
- Reduction in the number of AChRs available at the muscle endplate and flattening of the postsynaptic
folds.
- Patients become symptomatic once the number of AChRs is reduced to approximately 30% of normal.
- Cause of fatigability in MS? inefficient neuromuscular transmission (pathological) + presynaptic
rundown phenomenon (normal)
- Which receptors are affected in MS? ONLY nicotinic (skeletal muscles), while cholinergic (smooth
&cardiac) are NOT affected.
Clinical features:
● >50% of patients present with ocular symptoms of ptosis (drooping of eyelids) and/or diplopia .
● half (80%) will develop generalized disease within two years.
● The distinguishing clinical feature in MG is fatigable weakness.
● Ocular myasthenia : The weakness is limited to the eyelids and extraocular muscles. Medial rectus muscle
is usually most severely involved extraocular muscle
● Generalized disease : The weakness commonly affects ocular muscles, but it also involves a variable
combination of bulbar, limb, and respiratory muscles.
● maximum severity is usually in first year of disease, if After 2 years with no limb symptoms, disease usually
remains purely ocular.
● Ocular muscles: Asymmetric ptosis (fluctuating), binocular diplopia, and Pupils spared
● Bulbar muscles
○ fatigable- prolonged chewing). Sometimes this can be severe to the extent that it will lead to jaw
drop.
○ dysarthria , dysphagia and difficulty clearing secretions, and breathy nasal speech and nasal
regurgitation
● Facial muscles
○ expressionless face, Transverse smile, and Weak eye closure
● Neck and limb muscles :
○ Neck extensor and flexor (Musk : NE>NF), Dropped head syndrome, Limb weakness: Proximal >
distal, usually symmetric, and Wrist and finger extensors and foot dorsiflexors.
● Respiratory muscles :
○ orthopnea, and respiratory insufficiency and pending respiratory failure "myasthenic crisis
 L62- NMJ (cont.) 28

Investigations:
● Acetylcholine Receptor (AChR) Antibodies. (Best initial) :confirm the diagnosis.
● Anti- MuSK antibodies : If they were seronegative to antiAchR do anti Musk.
● SFEMG. (MOST SENSITIVE TEST)
○ Time required for EPP to reach threshold varies – JITTER
○ Sometimes EPP fails to reach threshold – BLOCKING
● Ocular Cooling/“ice-pack” Test .
● Edrophonium Chloride (Tensilon) Test, causes bradycardia
● Repetitive Nerve stimulation (RNS) :decline in the CMAP amplitude with the first four to five stimuli
(characteristic decremental) response
● CT mediastinum : Thymic hyperplasia is most common 85%. All patients should have a thoracic CT to
exclude thymoma
● Other Autoimmune disorders
Management of MG :
Symptomatic treatment (anticholinesterase agents) :
● Cholinesterase Inhibitors: Pyridostigmine (Mestinon).
chronic Immunotherapy:
● Prednisone (Main one), Azathioprine (Imuran),Mycophenolate (CellCept)
MG crisis (Rapid therapy):
● Plasma exchange and intravenous immune globulin [IVIG]
Refractory MG :
● rituximab
Thymectomy::
- Patient has thymoma Or Positive ACh receptor antibodies + Generalised MG + Young patient

Lambert-Eaton Myasthenic Syndrome (LEMS):

● Itis a rare presynaptic disorder of neuromuscular transmission in which quantal release of acetylcholine
(ACh) is impaired.
Epidemiology :
associated with a malignancy, mainly small cell lung cancer (SCLC).
Pathophysiology :
1. Caused by an autoimmune attack directed against the voltage-gated calcium channels (VGCCs) on the
presynaptic motor nerve terminal
2. Parasympathetic, sympathetic, and enteric neurons are all affected Ca++ channels.
Clinical features:
● Weakness/Fatigue (LL>UL) in Limb-Girdle Distribution ,weakness improves with use in LEMS
● slowly progressive proximal muscle weakness, particularly involving the legs
● Autonomic symptoms including dry mouth
● Post-tetanic potentiation: Recovery of lost deep tendon reflexes or improvement in muscle strength with
vigorous, brief muscle activation is a unique aspect of LEMS
Diagnosis :
1. The diagnosis of LEMS is usually clinical and confirmed by the presence of antibodies to voltage-gated
calcium channel (VGCC)
2. High frequency (10, 20 to 50 Hz) repetitive nerve stimulation (RNS) or brief (10 seconds) maximal
isometric muscle activation result in significant increment (>60%, unlike MG in which there’s decrement)
with a marked increase in the CMAP amplitude
Treatment:
1. treat a primary underlying malignancy
2. Symptomatic therapies : These are guanidine hydrochloride, aminopyridines such as 3,4-diaminopyridine
(3,4-DAP, aka Amifampridine), and acetylcholinesterase inhibitors such as pyridostigmine
3. Immunologic therapies include intravenous immune globulin (IVIG)
 L62- NMJ (cont.) 29

Botulism:
Clinical features:
● Acute onset (Unlike MG) of bilateral cranial neuropathies associated with symmetric descending
weakness.
● initial GI symptoms (nausea & vomiting)
● Pupils dilated , Ptosis, and EOM
● Bulbar weakness, Limb weakness, and Respiratory weakness.
● Absence of fever, The patient remains responsive
Diagnosis:
Repetitive nerve stimulation (RNS) at low frequencies of 2 to 5 Hz causes decremental response.
RNS at high frequencies stimulation or exercise causes incremental response,
The amount of facilitation seen with botulism (40-100%) is usually less than that seen in Lambert-Eaton
myasthenic syndrome (200%).
Treatment:
● antitoxin.
● Supportive.
● Equine serum heptavalent botulism antitoxin is used to treat children older than one year of age and
adults.
Human-derived botulism immune globulin is used for infants less than one year of age
Tick paralysis:
● inhibits transmission at the neuromuscular junction by blocking influx of sodium ions In the postsynaptic
membrane
● Symptoms include anorexia, lethargy, muscle weakness, nystagmus, and an ascending flaccid
● paralysis.
● The diagnosis of tick paralysis usually relies on the finding of a tick attached to the patient.
● Removal of the tick is the primary treatment of tick paralysis.
Snake venom :
● Presynaptic junction toxin: beta-bungarotoxin (krait) / mechanism: inhibit Ach release by inhibiting
reformation of the vesicles after exocytosis /management: only supportive, no response to anti venom.
● Postsynaptic junction toxin: alpha-bungarotoxin / mechanism: toxins bind irreversibly to the
acetylcholine receptor site / management: Antivenom
Clinical features:
● ptosis, ophthalmoplegia, dysarthria, dysphagia, and drooling.
● Weakness of limb muscles.
● impaired coagulation profile.
● The postsynaptic toxins produce findings on electrodiagnostic studies identical to those seen in
● myasthenia gravis, Repetitive nerve stimulation produces a decremental response
Organophosphate and carbamates toxicity:
● potent inhibitors of acetylcholinesterase, causing excess acetylcholine concentrations in the synapse.
● Commonly used as pesticides.
Clinical features :
- Both sympathetic and parasympathetic systems are involved.
- Symptoms include muscarinic signs and nicotinic signs .
Management & diagnosis:
● Emergency management (ABC management) often requires endotracheal intubation and volume
resuscitation
● Atropine is used for symptomatic relief of muscarinic symptoms.
● It does not reverse the paralysis
Hypermagnesemia / hypocalcemia
● Causes inhibition of a acetylcholine release
● Magnesium has a calcium channel blocking effect.
● This produces proximal muscle weakness , ocular muscles are generally spread.