Autoimmune disorders of the nervous system

• 1. Direct (subacute)
• -Cell mediated: multifocal, episodic
• -Antibody mediated: diffuse, continuous or monophasic
• 2. Vasculitic
• -Large vessel injury: infarctions, acute
• -Microvascular injury: indolent, diffuse, subacute or chronic

• Clinical Presentation: Episodes of subacute onset (hours - days), with partial or full
• resolution (weeks - months), affect any part of CNS
• -UMN syndromes
• -Cranial neuropathies
• -autonomic dysfunction
• -optic neuritis

Multiple lesions in time and space

• Pathophysiology:
• CD4 T cells react against myelin antigens and secrete cytokinesdemyelination, inflammationineffective remyelination impairs saltatory conductionDiagnosis:Imaging: T2 MRICSF: oligoclonal bands (IgG)Evoked potentials (slower conduction)

• Acute Relapse:IV glucocorticoids (decrease recovery time but don't change overall courseChronic Disease Modification:Glatiramer acetate
• InterferonsNatalizumabFingolimodSymptomatic Therapy:Neuropathic pain (caramazepine, gapapentin, duloxetine)Spasticity (baclofen, tizanidine)Urinary Urges (oxybutinin)Fatigue (amantadine, modafinil, methylfenidate)

Types:

• 1. Relapsing-Remitting
• 2. Secondary Progressive
• 3. Primarily Progressive (older, male > female)

• Epidemiology: more common in far northern and southern latitudes, strong
• genetic component, 2-3x more common in women, ages 20-40

Pathophysiology:

• CD4 T cells react against
• myelin antigens and secrete cytokinesdemyelination, inflammationineffective remyelination
• impairs saltatory conduction

Diagnosis:

Imaging: T2 MRICSF: oligoclonal bands (IgG)

Evoked potentials (slower conduction)

Acute Relapse:

• IV glucocorticoids (decrease
• recovery time but don't change overall course

Chronic Disease Modification:

Glatiramer acetate InterferonsNatalizumabFingolimod

Symptomatic Therapy:

• Neuropathic pain (caramazepine,
• gapapentin, duloxetine)Spasticity (baclofen,
• tizanidine)Urinary Urges (oxybutinin)

Fatigue (amantadine, modafinil, methylfenidate)

• MOA:
• -synthetic peptide similar to MBP, exact mechanism unknown

• Effects:
• -decreases relapses by 1/3
• -no neutralizing antibodies develop

• Adverse Effects:
• -delayed onset by months
• -injection site reactions

• MOA:
• -decrease expression of pro-inflammatory cytokines
• -reduce T cell migration across BBB
• -increases production of NGF

• Effects:
• -similar to glatiramer

• Adverse Effects:
• -injection site reaction
• -neutralizing antibodies
• -flu-like symptoms
• -liver dysfunction (rare)
• -depression (rare)

• MOA:
• -monoclonal antibody that inhibits alpha-4 integrins
• -prevents lymphocytes from entering CNS

• Effects:
• -decrease relapse by 60%
• -decrease MRI lesions by 90%

• Adverse Effects:
• -1/1000 risk of progressive multifocal leukoencephalopathy (PML)

• MOA:
• -binds S1P receptors
• -blocks lymphocytes from exiting LNs

• Effects:
• -only oral drug for MS
• -more effective than IFN

• Adverse Effects:
• -bradycardia
• -leukopenia

• Clinical Presentation:
• -subacute to chronic HA, jaw claudication, nodular temporal artery, blindness

• Epidemiology:
• -most common in the elderly

• Pathophysiology:
• -chronic, granulomatous inflammation of large arteries (most often temporal
• artery)
• -initial T cell response against vascular wall antigen
• -segmental regions of nodular intimal thickening with lumen narrowing

• Diagnosis:
• -Clinical suspicion
• -ESR
• -temporal artery bx

• Treatment:
• -high dose glucocorticoids (prednisone)

• Clinical Presentation:
• -subacute onset progressive ascending paralysis
• -early mild sensory change
• -painful
• -typical LMN syndrome
• -autonomic dysfunction
• -out of degree areflexia
• -85% recover (usually 2-3 mo, some 6-18 mo)

• Epidemiology:
• -60% preceeded by URI or GI illness
• -relation to C. jejuni

• Pathophysiology:
• -T cells initiate response against myelin
• -segmental demyelination throughout PNS
• -the longer the nerves, the more lesions --> distal polyneuropathy

• Treatment:
• -ABCs
• -Plasmapheresis
• -IVIg
• -Glucocorticoids are NOT effective

• Clinical Presentation:
• -fluctuating weakness
• -weakness that worsens with exercise and improves with rest
• -affects small, constantly used muscles first (EOMs, hands)

• Epidemiology:
• -third decade for women
• -sixth decade for men
• -associated with thymoma or thymic hyperplasia

• Pathophysiology:
• -antibodies block AChR
• -increased degradation of AChRs
• -Abs cause C' mediated degradation of postsynaptic folds

• Diagnosis:
• -serum antibodies
• -decrementing response
• -pharmacologic challenge (edrophonium or tensilon)

• Treatment:
• -Anticholinesterase drugs
• -Chronic glucocorticoids
• -plasmapheresis
• -IVIg
• -thymectomy

-subacute to chronic progressive diffuse lesion

• 1. Cerebellar degeneration
• 2. Encephalomyelitis
• 3. Opsoclonus-myoclonus-ataxia
• 4. Subacute sensory neuropathy
• 5. Lambert-Eaton myasthenic syndrome

• -onset: weeks to months
• -symmetrical ataxia, dysarthria, nystagmus
• -imaging: subtle enhancement of cerebellum
• -associated with ovarian and lung cancer

• -subacute onset
• -often bilateral
• -medial temporal lobe
• -confusion, agitation, amnesia, dementia
• -associated with lung, prostate, lymphoid, ovarian, testicular CA

• -predominantly childhood syndrome
• -"bouncing eyes"
• -associated with Neuroblastoma

• -rapid onset polyneuropathy
• -small cell lung cancer, lymphoma
• -often rapidly leads to death, refractory to tx

• -NMJ dysfunction due to failure of
• vesicle fusion
• -anti-voltage gated Ca channel antibodies
• -improves with exercise (incrementing response)
• -small cell lung cancer

• -multifocal areas of myelin breakdown
• -monophasic (all lesions enhance on MRI)
• -typically follows an acute infection

• Clinical Presentation:
• -rapid subacute progression
• -HA, confusion, fever, ataxia

• Epidemiology:
• -children more commonly affected in adults
• -in adults can be associate with small pox vaccine

• Clinical Presenation:
• -muscle weakness
• -heliotrope rash
• -childhood variant is different

• Pathophysiology:
• -inflammatory infiltrates around small blood vessels and in perimysial CT
• -B cell mediated

• Clinical Presentation:
• -painless symmetrical weakness

• Pathophysiology:
• -inflammation in the endomesium scattered throughout the fascicles
• -due to CD8 T cells