MULTIPLE SCLEROSIS

DEFINITION
Multiple sclerosis (MS) is the most
common autoimmune disease of the
nervous system. MS is characterized by
chronic and continuous demyelination of
the corticospinal tract neurons in two or
more regions of the brain and spinal cord.

Etiology
MS involves autoimmune-mediated inflammation that
leads to demyelination and axonal injury. The cause of MS
remains unknown; however, it is widely held that the
disease is triggered by an infectious agent.
Over the past century, several microbes (e.g., rabies virus,
measles virus, herpesviruses, Chlamydia pneumoniae)
have been purported to be associated with MS. In recent
years, human herpesvirus type 6 has been identified in
active demyelinated regions of the CNS in patients who
have MS.
However, not all persons who are infected with human
herpesvirus type 6 develop MS, suggesting that genetic
factors and other environmental factors also are important.
 Pathophysiology and Complications
 Demyelination of MS occurs in scattered white matter regions in
the brain. Affected regions show inflammatory demyelination
and axonal damage with accumulation of macrophages, B and T
lymphocytes, and plasma cells. Specifically, myelin-reactive
type 1 helper T cells (TH1) that produce lymphotoxin and
interferon-γ, but little interleukin-4 (IL-4), appear to be central
to the pathogenesis of this disease. The acute MS lesion is
accompanied by generation of inflammatory cytokines and
antimyelin immunoglobulins that influence macrophages to
attack myelin, resulting in tissue destruction, swelling, and
breakdown of the blood-brain barrier. Demyelinated disease
areas or “plaques” show impairment in axonal conduction; such
changes constitute the basic pathophysiologic defect. The most
commonly affected regions are the optic nerve, periventricular
cerebral white matter, and cervical spinal cord.
Signs and Symptoms
The first clinical signs of MS often appear in young
adulthood. Clinical manifestations vary according to
which region of the CNS is involved (motor or
sensory region) and what degree of disruption occurs
in the myelin sheath. Disturbances in visual function
(sometimes resulting in blindness) and abnormal eye
movements (nystagmus and double vision) are the
most common presenting manifestations. Motor
disturbances that affect walking and use of the hands
(incoordination, spasticity, difficulty in walking, loss
of balance and vertigo, coordination or weakness,
tremor or paralysis of a limb) and that cause bowel
and bladder incontinence,
spastic paresis of skeletal muscles (imprecise
speech or tremor), and sensory disturbances,
including loss of touch, pain, temperature, and
proprioception (numbness, pins and needles
sensations), are common. Fatigue is a major
symptom (occurring in up to 90%), and
worsening fatigue occurs in the afternoon.
Symptoms are exacerbated by heat (hot baths,
sun exposure) and dehydration .
A typical presentation consists of attacks and
relapses that recur for several years. The course is
unpredictable and depends on the frequency of
attacks and the extent of recovery. Four categories
have been used to describe the course of the
disease: relapsing-remitting (occurs in 85% of
patients), primary progressive, secondary
progressive, and progressive-relapsing. Recovery
in most cases is temporary, because remyelination
is only transient.

MEDICAL MANAGEMENT
Patients with relapsing forms of MS are given
anti-inflammatory medications in the form of
intravenous corticosteroids
(methylprednisolone) for acute attacks or
interferon beta-1a or interferon beta-1b
injections.
DENTAL MANAGEMENT
Medical Considerations
1-The dentist can play an important role in directing the
patient with clinical findings suggestive of MS to the
appropriate health care provider for definitive diagnosis.
2-Reports of abnormal facial pain (mimicking
trigeminal neuralgia), numbness of an extremity, visual
disturbance, or muscle weakness require the dentist to
perform a neuromuscular examination to rule out MS.
The disease should be suspected if onset is progressive
over several days, the patient is between 20 and 35 years
of age, and afternoon fatigue is a feature. Referral to a
neurologist is the next step in confirming the diagnosis.
3- Emergency dental care can be provided but is
affected by the medications these patients take. In
particular, corticosteroids are immunosuppressive,
and during stressful surgical procedures, an increase
in dose may be required . The physician should be
consulted before emergency dental care is provided
to these patients.
The two major factors influencing the
recommendation for supplemental corticosteroids
are the type of
adrenal insufficiency and the level and type of 
.stress
 Currently, only patients with primary adrenal insufficiency are
recommended to receive supplementation, and this
recommendation applies only when surgery is being performed
and/or in the management of a dental or systemic infection .
Patients with secondary adrenal insufficiency and those who
take daily or alternate-day corticosteroids have enough
exogenous and endogenous cortisol to handle routine dental
procedures and surgery, if their usual steroid dose (or parenteral
dose equivalent) is taken the morning of the procedure. Thus,
the recommendation is for patients to take their usual daily dose
of steroid within 2 hours of the surgical procedure.
 Surgery should be scheduled in the morning when cortisol
levels are highest. Proper stress reduction should be provided
because fear and anxiety increase cortisol demand. Nitrous
oxide–oxygen inhalation and benzodiazepine sedation, are
helpful in minimizing stress and reducing cortisol demand.
4-Anesthesia: Provide adequate operative and
postoperative anesthesia; routine use of epinephrine
(1 : 100,000) is appropriate. Consider using long-
acting local anesthetics (e.g., bupivacaine) at the
end of the procedure to provide longer postoperative
pain control. General anesthesia increases
glucocorticoid demand and could render an adrenal-
insufficient patient susceptible to adrenal crisis;
therefore use cautiously.

5-Anxiety: Anxiety and stress increase the risk of
adrenal crisis, if adrenal insufficiency present.
Use anxiety/stress reduction techniques as needed.
6-Blood pressure :Monitor blood pressure
throughout stressful and invasive procedures.
Postoperative monitoring for at least 8 hours is
recommended for procedures involving more than
moderate surgery. If blood pressure drops below
100/60 mm Hg and the patient is unresponsive to
fluid replacement and vasopressive measures,
administer supplemental steroid.
7-Chair position: Hypotension (e.g., from severe
adrenal insufficiency) may dictate a supine position.
Otherwise, normal chair position can be used.
Patients who take corticosteroids for prolonged periods have -9 
an increased likelihood of having hypertension, diabetes, delayed
wound healing, osteoporosis, and peptic ulcer disease. To
minimize the risk of an adverse outcome, blood pressure should
be taken at baseline and monitored during dental appointments.
Blood glucose levels should be determined and invasive
procedures should be performed during periods of good glucose
control. Follow-up appointments should be arranged to assess
proper wound healing. Because osteoporosis has a relationship
with periodontal bone loss, implant placement and bone fracture,
periodic measures of periodontal bone loss are indicated, and
measures should be instituted that promote bone mineralization
and avoid extensive neck manipulation if osteoporosis is severe.
Because of the risk of peptic ulceration, postoperative analgesics
for long-term steroid users should not include aspirin and other
.nonsteroidal antiinflammatory drugs (NSAIDs)
10-The optimal time for treating patients with MS is
during periods of remission. The dental care plan
should take into consideration the potential effects on
oral health of the medications used in management of
MS. In particular, the anticholinergics and tricyclic
antidepressants can cause a dry or burning mouth,
which may require the use of salivary substitutes for
relief. If additional relief is needed, the use of
pilocarpine should be discussed with the physician.

11-Several of the medications used in the treatment of
MS are immunosuppressants, thus placing patients at
risk for opportunistic and community-acquired
infections .
12-Emergencies: Acute adrenal crisis is a medical
emergency. Apply wet/ice packs, assess and monitor
vital signs, start intravenous saline solution, inject
100 to 300 mg IV of hydrocortisone, start
intravenous infusion of glucose solution, and
transport patient to emergency medical facility.
13-Postsurgery patients should be monitored
for good fluid balance and adequate blood
pressure during the first 24 hours.
Communicate with the patient at the end of the
appointment and within 4 hours
postoperatively to determine whether features
of weak pulse, hypotension, dyspnea,
myalgias, arthralgia, and fever are present.
Signs and symptoms of adrenal crisis dictate
transport to a hospital for emergency care.
Parkinson’s disease is a progressive
neurodegenerative disorder of neurons that
produce dopamine. Loss of these neurons
results in characteristic motor disturbances—
resting tremor, muscular rigidity, bradykinesia,
and postural instability.
In 2013 PD was present in 53 million people and
resulted in about 103,000 deaths globally. The
disease is named after the English doctor
James Parkinson, who published the first detailed
description in An Essay on the Shaking Palsy, in
1817. People with parkinsonism who have increased
the public's awareness of the condition include
actor Michael J. Fox, Olympic cyclist Davis
Phinney, and professional boxer Muhammad Ali.
Etiology
Parkinson’s disease is caused by death and
depletion of dopaminergic neurons, which are
manufactured in the substantia nigra .The etiology
of Parkinson’s disease is believed to be a variable
combination of poorly understood genetic and
environmental factors. Both autosomal dominant
and recessive genes can cause classic Parkinson’s
disease. Other causes include stroke, brain tumor,
and head injury (e.g., boxing) that damage cells in
the nigrostriatal pathway. Exposure to manganese
(in miners and welders), mercury, carbon disulfide,
and street heroin.
Signs and Symptoms
A major manifestation of Parkinson’s disease is
resting tremor (that is attenuated during activity),
muscle rigidity, slow movement (bradykinesia,
shuffling gait), and facial impassiveness (mask of
Parkinson’s disease). The tremor, which is rhythmic
and fine and is best seen in the extremity at rest,
produces a “pillrolling rest tremor” and handwriting
changes. Cogwheel type rigidity (decreased arm
swing with walking and foot dragging), stooped
posture, unsteadiness, imbalance (gait instability),
and falls also are common features.
In addition, pain, (musculoskeletal, sensory
[burning, numbness, tingling], orthostatic
hypotension, and bowel and bladder
dysfunction occur in approximately 50% of
patients. Mood disturbances (depression,
anxiety), insomnia, and fatigue occur in
approximately 40% of patients; dementia
occurs in approximately 25%.
MEDICAL MANAGEMENT
Therapy is begun with the goal of
increasing dopamine levels in the brain.
The mainstay of treatment for advanced
Parkinson’s disease is carbidopa-levodopa
(Sinemet), an immediate precursor of the
neurotransmitter dopamine.
 Management of progressive disease
requires a careful balance between the
beneficial effects of Sinemet or
controlled-release levodopa (Sinemet CR)
and the use of adjunctive medications such
as (1) dopamine agonists and (2) catechol-O-
methyltransferase (COMT) inhibitors
(entacapone) used to diminish motor
fluctuations, as well as (3) serotonin
reuptake inhibitors used to manage
depression and (4) acetylcholinesterase
inhibitors given for dementia.
Physical therapy is important for providing
patients with safe methods for rising from a
chair, walking around a room, navigating
stairs, and combating immobility and
contractures.
If symptoms progress despite drug therapy,
surgery involving replacement of dopamine
neurons by grafting of fetal nerve tissue
appears to be an encouraging alternative for
patients with advanced Parkinson’s disease.

DENTAL MANAGEMENT
Medical Considerations
1-The dentist who treats adult patients can
play an important role in recognizing the
features of Parkinson’s disease and making a
referral to a physician for thorough evaluation
of persons who exhibit features of the disease.
Once the patient is under good medical
management, the dental treatment plan is
unaffected. However, consultation with the
patient’s physician to establish the level of
control is recommended as part of the
management program.
2-Once the diagnosis has been made,
concerns in dental management are two-
fold: (1) minimizing the adverse outcomes
of muscle rigidity and tremor and (2)
avoiding drug interactions.
 3-Drug interactions , although no adverse
interactions have been reported between COMT
inhibitors ( entacapone [Comtan]) and epinephrine
at dosages typically used in dentistry, they can
potentially interact, and it is advisable to limit the
dose of epinephrine to two carpules containing 1 :
100,000 epinephrine in patients who take COMT
inhibitors. It is very important to obtain adequate
anesthesia to reduce stress, which may worsen the
movement disturbance. Epinephrine (1 : 100,000)
in local anesthetics generally is well tolerated.

4-Patients with untreated or poorly
controlled disease may experience
exaggerated trembling and involuntary
shaking movements and appear very
anxious and stressed. Use of special
anxiety and stress reduction techniques
may be indicated.
5-This usually is not a problem if the patient
is under good medical management; with
symptoms of impending syncope, however, a
supine position may not be tolerated. The
patient taking dopamine may experience
hypotension, warranting precautions with
getting seated or on arising. The chair may
need adjustment for adequate support to help
reduce unnecessary movement or to stabilize
the patient in a comfortable position.
Orthostatic hypotension and rigidity are
common in patients who have Parkinson’s
disease. Orthostatic hypotension is an
adverse effect associated with COMT
inhibitors. To reduce the likelihood of a
fall from the dental chair, the patient
should be assisted to and from the chair.
At the end of the appointment, the chair
should be inclined slowly to allow for
reequilibration.
6-Tremors most commonly are self-
limited, but rarely the movement
disturbance may be severe enough to
interrupt dental treatment or to necessitate
cessation of treatment.
7-Erythromycin should not be given to
patients who take the dopamine agonist
(Mirapex). The clinician should be aware
that antiparkinsonian drugs can be CNS
depressants, and a dentally prescribed
sedative may have an additive effect to
those of such agents.
8-Patients should receive dental care
during the time of day at which their
medication has maximum effect
(generally, 2 to 3 hours after taking it).
9-the drugs used to manage the disease
(anticholinergics, dopaminergics) often result
in xerostomia, nausea, and dyskinesia.
If the patient is experiencing xerostomia,
dysphagia and poor denture retention are
likely to result. Salivary substitutes are
beneficial in alleviating symptoms. Topical
fluoride should be considered for use in
dentate patients with xerostomia, to prevent
root caries.