AUTOIMMUNE

NEUROLOGICAL DISEASES
NI MADE SUSILAWATHI
Autoimmune Neurological Disorders

■ Nervous system disorders caused by aberrant immune response

■ Antigen-specific
■ May be paraneoplastic or idiopathic
■ Guillain-Barre syndrome, myasthenia gravis and multiple sclerosis are neurological
diseases induced by abnormal autoimmunity
GUILLAIN BARRE
SYNDROME
NI MADE SUSILAWATHI
INTRODUCTION
■ Acute autoimmune neuropathies
■ There is no known genetic factors
■ 2/3 of cases follow a respiratory or GI infection
■ There are several potential triggers of GBS including
– viral (e.g. chikungunya, dengue, HIV) and
– bacterial (e.g. campylobacter jejuni) infections.
■ GBS has been reported to follow:
– Vaccination
– Epidural anesthesia
– Thrombolytic agents
– Surgery
A clinical case of GBS

■ Bilateral and symmetric weakness

of the limbs
■ Decreased or absent deep tendon
reflexes in the weak limbs
■ monophasic illness pattern
■ interval between the onset and
nadir of weakness ranging from 12
hours to 28 days with a subsequent
clinical plateau; and
■ absence of an identified alternative
cause for the weakness
Cerebrospinal fluid (CSF) examination
■ Cerebrospinal fluid (CSF) albuminocytological dissociation
– (CSF protein level above laboratory normative value and
CSF total white blood cell count < 50 cell/ul )

■ Albuminocytological dissociation is present in 50-66% of

patients with GBS in the first week after symptom onset and
in over 75% of patients in the third week
Immunobiology
of GBS
Guillain-Barré syndrome time course
Neurophysiology studies

■ Neurophysiology studies support the diagnosis of GBS and

discriminate between GBS subtypes
■ Nerve conduction studies enable clinicians to categorize
GBS into different types such as
– acute inflammatory demyelinating polyneuropathy,
– acute motor axonal neuropathy, or
– acute motor and sensory axonal neuropathy
Management of GBS
■ GBS is a potentially life-threatening illness.
■ Supportive medical care and monitoring and evaluation of the
need for immunotherapy should be performed rapidly and
concurrently.
■ Intravenous immunoglobulin or therapeutic plasma exchange
should be used for the treatment of GBS
■ Immunotherapy confers a benefit within the first four weeks,
preferably within two weeks from onset of symptoms in patients
with GBS who are unable to walk unaided (GBS disability score
>2) or those who develop progressive bulbar weakness,
MYASTHENIA GRAVIS
NI MADE SUSILAWATHI
INTRODUCTION
■ Myasthenia Gravis (MG) is a prototypic and
■ Perhaps the best characterized antibody (Ab) mediated
autoimmune disease
■ Auto antibody against the nicotinic acetylcholine receptor
(AChR) at the neuromuscular junction (NMJ) cause the
myasthenic symptoms
Myasthenia gravis
■ The key manifestation of MG
is fluctuating muscle
weakness which typically
increases during effort.
■ MG is chronic autoimmune
disease
■ The prevalence of MG
between 25-100 per million
population
■ MG present most commonly
between the ages of 20-40
and 60-70
(female: male ratio 3: 1)
Pathophysiology MG
■ Normal communication
between the nerve and
the muscle is interrupted
at the neuromuscular
junction (NMJ)

■ Normally, nerve endings

release acethylcholine
which travels through the
NMJ and binds to
receptors (ACh-R), causing
muscle contraction
Pathophysiology MG

■ In myasthenia gravis, these

receptors are blocked or destroyed
by antibodies
■ Results in:
– Decreased number of ACh-R
receptors
– Reduced postsynaptic membrane
folds
– Widened synaptic cleft
The Thymus Gland and the Origin of MG
Thymic
hyperplasia

AChR

T Thymoma

Tumor cell

AChR
Management MG

■ Long acting anticholinesterase (Pyridostigmine bromide, Neostigmine bromide)

■ Immunosuppressive (Steroid, Azathioprine, Cyclophospamide
■ Surgical Thymectomy
■ Plasmapharesis or Intravenous imunoglobulin
 MULTIPLE
SCELROSIS
NI MADE SUSILAWATHI
Multiple Sclerosis

■ Inflamatory, demyellinating, neurodegenerative

disease of the central nervous system
■ Unkwon etiology
■ Presumbly involves interaction between genetic
environmental and other factor triggering an
aberrant autoimmune attack resulting in damage to
myelin and axons
Potential risk factors for multiple
sclerosis
■ Female gender
■ Caucasian race
■ Genetic (HLA DR 15/DQ6, IL2Ra and IL7RA alleles)
■ Infections (Epstein-Barr virus (EBV) infection
■ Temperate climate
■ Low vitamin D level
■ Lack of sunlight exposure
■ Cigarette smoking
MULTIPLE SCLEROSIS

■ 2.5 milion people worldwide are afflicted with MS

■ A chronic neuroinflamatory disease of the brain and spinal
cord that is a common cause of serious physical dis ability
in young adults, especially in women
■ Average age of disease onset is 30 years, and 25 years
after diagnosis, app. 50 % of patients requires permanent
use of wheelchair.
The Heterogeneity of Multiple Sclerosis
■ The disease course and symptomatology of MS are heterogenous that can
include:
– Sensory and visual disturbances
– Motor impairments
– Fatique
– Pain
– Cognitive deficits
■ The variation in clinical manifestations correlates with the spatial-temporal
dissemination of lesional sites of pathology within central nervous system
(CNS)
■ The most common form, affecting approximately 85% of patients, is
relapsing-remitting multiple sclerosis
single disease, and what implications diagnostic accuracy will have on the understanding general , com
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The Pathology of Multiple Sclerosis
■ confluent demyelinated areas in the white and grey matter
of the brain and spinal cord that are called plaques or
lesions and that indicate a loss of myelin sheaths and
oligodendrocytes
■ These lesions are caused by immune cell infiltration across
the blood brain Barrier (BBB) that promotes
– inflammation, demyelination, gliosis and neuroaxonal
degeneration, leading to disruption of neurosignaling
The Pathology of Multiple Sclerosis