Inflammatory diseases of the

CNS
 Multiple sclerosis(MS)
• CNS Demyelinating disorders are immune-mediated
conditions characterized by preferential destruction
of central nervous system (CNS) myelin: ( brain and
spinal cord). The peripheral nervous system is spared
• MS is the most common ds in this category
• Others:
- Acute disseminated encephalomyelitis
- Neuritis-neuromyelitis optica (Devic's disease)
- Transverse myelitis
 MS: definition
• Multiple sclerosis is defined as a chronic immune
mediated inflammatory demyelinating ds of the CNS
• MS is characterized by inflammation, demyelination,
gliosis (scarring), and neuronal loss
• The clinical course can be relapsing-remitting or
progressive

• MS Lesions typically occur at different times and in

different CNS locations ( Diagnosis of MS requires that the
CNS lesions as seen on MRI be disseminated in time and space)
 MS: Physiology
MS: ?? relapsing- remitting:
Nerve conduction physiology:
Nerve conduction in myelinated nerves occurs in a
saltatory manner with the nerve impulse jumping
from one node of Ranvier to the next, without
depolarization of the axonal membrane
underlying the myelin sheath between nodes.
This leads to faster conduction velocities than in
unmyelinated nerves
Conduction in a myelinated nerve
 MS: Physiology
• Demyelination causes a conduction block:
conduction velocities are slowed initiially, but
with time, conduction through the demyelinated
axon is reestablished, albeit slow:
Results to the clinical picture of neurological
deficits that resolve and recurr
• Heat and exercise worsen the conduction block
(The Uhthoff phenomenon in clinical features of MS)
Conduction following demyelination
 MS: epidemiology
Epidemiology:
• MS is second only to trauma as a cause of neurologic
disability in early to middle adulthood
• MS is upto 3 times more common in women than men
• Median age of onset is 20-40yrs, but can occur at any
age, abt 10% occurs before 18yrs age
• Prevalence differs with geographic locations, being
lowest in the tropics: Asia, Equitorial Africa, middle East
(sun exposure has a protective effect- vit D related)
 MS
Pathogenesis:
• The cause of MS remains unknown
• Both genetic and environmental factors play a
causative role
• The most widely accepted theory is that MS begins as
an inflammatory autoimmune disorder mediated by
autoreactive lymphocytes
- T cells, B cells, and macrophages are seen on
histopathologic examination of MS lesions at biopsy
and autopsy
 MS: pathogenesis
• Alternate theories of MS pathogenesis:
1. A possible immune (but not autoimmune)
reaction to a chronic viral infection
2. A nonimmune noninflammatory etiology due
to a genetically determined degenerative
process
 MS: clinical
NBS:
• There are no clinical findings that are unique to
MS, but there are some clinical features that are
highly characteristic/suggestive of the disease
• Can affect any part of the brain and spinal cord
• The typical patient presents as a young adult
with two or more clinically distinct episodes of
CNS dysfunction with at least partial resolution
 MS: clinical
Clinical features suggestive of multiple sclerosis:
1. Relapses and remissions
2. Onset between ages 15 and 50yrs
3. Optic neuritis: acute or subacute unilateral eye pain during
ocular movements, followed by a variable degree of visual loss
4. Lhermitte's sign/ phenomenon: is a transient sensory
symptom described as an electric shock radiating down the
spine or into the limbs with flexion of the neck
5. Heat sensitivity (Uhthoff phenomenon) small increases in the
body temperature can temporarily worsen preexisting signs
and symptoms
 MS: clinical
Other clinical signs/symptoms ( CN, CST, STT edrosal
collumns…………..)
Lower back pain
Vertigo
Nystagmus
Spastic Paraparesis or paraplegia
Spinal cord syndrome
Sensory symptoms
Autonomic symptoms: Bowel/bladder/sexual function
Cognitive dysfunction
Seizure etc
 MS: Disease pattern 
The pattern and course of MS is categorized as follows:
1. Relapsing remitting multiple sclerosis (RRMS)
Characterized by clearly defined relapses with full
recovery or with residual deficit upon recovery (>80% of
pts at presentation)
2. Secondary progressive multiple sclerosis (SPMS): Started
with a RRMS disease course, later becomes progressive
with or without occasional relapses /remissions
3. Primary progressive multiple sclerosis (PPMS):
characterized by disease progression from onset
 Diagnosis / investigations
• Diagnosis of MS is based on a combination of clinical, imaging,
laboratory findings: MRI brain and spinal cord9 opaque/hyerdense
plaques or hypodense lesions called ‘black holes’, LP a must
• The McDonald criteria:
1. Clinical features: Clinical features suggestive of multiple sclerosis (
as above)
2. Imaging: MS plaques in the brain and spinal cord on MRI:
A diagnosis of MS requires the demonstration of CNS lesions, for
which there is no other explanation, in more than one anatomical
site, at more than one time ( dissemination in time and space)
3. Cerebrospinal fluid : evidence of oligoclonal bands
 MS: Treatment
• The management of MS involves:
- Treatment of the acute episode
- Prevention of future relapses
- Treatment of complications and management
of the patient's disability
 MS: Treatment
1. Acute episodes/ exacerbation of MS:
- pulses of IV high-dose methylprednisolone ( 500mg-1gm
for 3-5days)
- Plasmaphareis, IV Ig – intravenous
immunoglobulins( tried in severe exacerbations)
2. Prevention of future relapses:
1. Immune modulators: Interferon beta, Glatiramer
acetate, Natalizumab (Monoclonal antibody)
2. Immune suppressants: Azathioprine,
cyclophosphamide, mitoxantrone
 MS: treatment
Managing the disability ( supportive ttreatment):
1. Spasticity : Physiotherapy, Baclofen, Dantrolene
2. Ataxia : Clonazepam
3. Nerve pain: Carbamazepine,  Gabapentin,
Phenytoin, Amitriptyline
4. Impotence : Sildenafil
5. Psychological support
6. Bladder and bowel care
 Prognosis
1. Begnin MS: refers to disease in which the
patient remains fully functional in all
neurologic systems 15 years after the disease
onset
2. Malignant MS: refers to disease with a rapid
progressive course, leading to significant
disability in multiple neurologic systems or
death in a relatively short time after disease
onset.
 MS: prognosis
• prognosis of MS is difficult to predict
- Patients with relapsing and remitting MS
have, on average, 1-2 events every 2 years
- Approximately 5% of patients die within 5
years of onset (malignant MS)
- Overall, about 50% of patients are disabled to
the point of needing help with walking after
15 years of MS