Autoimmune disease


See MS section.


Optic Neuritis

  • In adults, MS diagnosis in 38%, and >80% if MRI abnormalities
  • In children, unilateral ON in 58%, bilateral in 42%
  • In children, MS diagnosis in 36%, more if bilateral ON, all show MRI abnormalities
  • Other clinical findings or other MRI lesions strongly correlated with MS outcome


Acute disseminated encephalomyelitis (ADEM)

  • Acute polysymptomatic neurological dysfunction with encephalopathy
  • Variably seizures, fever, meningism
  • 50-70% preceding viral illness reported
  • Laboratory findings:
    • CSF pleocytosis, elevated protein in 50%
    • CSF oligoclonal bands in up to ½
  • MRI:
    • Multifocal, bilateral, asymmetric T2 hypertense lesions in white matter and deep grey nuclei
    • Longitudinal spinal cord lesions with multiple segment involvement
  • Treatment:
    • IV corticosteroids (20-30mg/kg/d x3-5d, then 3-4 week 1mg/kg/d PO prednisone taper)
    • IVIG (2g/kg div 2-5 days) if steroid-resistant or life-threatening
    • PLEX (7 treatments in 14 days) in acute life-threatening demyelination
  • Outcome:
    • Monophasic, 85% excellent outcome
    • 15% residual motor/cognitive impairment
    • Can be first attack of MS


Acute hemorrhagic leukoencephalitis (AHLS)

  • Severe variant of ADEM with necrotizing angiitis of venules and capillaries with ball and ring hemorrhage, myelin edema, and demyelination


Neuromyelitis optica (Devic’s disease)

  • Absolute criteria:
    • Optic neuritis
    • Acute myelitis
  • Supportive criteria (at least 2 of 3 required):
    • Brain MRI not meeting criteria for MS at disease onset
    • Spinal cord MRI with contiguous T2 signal abnormalities extending over 3+ vertebral segments, indicating a relatively large lesion in the spinal cord
    • NMO-IgG+ (antibodies against the aquaporin 4 antigen)


CNS vasculitis


Primary CNS vasculitis

  • Diagnosis requires pathological confirmation and exclusion of systemic vasculitis
  • Two types:
    • Small vessel involvement
      • Gradual with headaches, focal seizures, multiple neuro deficits, behavioural changes
      • Investigations:
        • MRI showing multiple ischemic or tumour-like lesions
        • ESR, CSF normal
        • Angiogram normal
        • Nongranulomatous vasculitis on biopsy
      • Treatment and outcome:
        • Immunosuppression with prednisone and cyclophosphamide
        • 4/5 cases alive with no recurrence
    • Medium/large artery involvement
      • Presents acutely with TIA, arterial stroke, subarachnoid hemorrhage
      • High mortality rate from stroke complications
      • Investigations:
        • High ESR, inflammatory CSF
        • Angiogram abnormal
        • Granulomatous vasculitis on autopsy
  • Benign angiopathy of the CNS
    • Subgroup of PACNS described in adults, monophasic course, normal CSF
  • Transient cerebral arteriopathy
    • Benign, monophasic transient cerebral arteriopathy in childhood
    • Spontaneous resolution with no recurrence
    • But not benign due to permanent neurological sequelae
    • Association seen with recent VZV infection


Secondary CNS vasculitis

  • Large artery vasculitis
    • Giant cell arteritis (temporal arteritis)
      • See also neuroophthalmology notes
      • Onset >50 years
      • New headache, temporal artery tenderness/decreased pulsation
      • ESR > 50mm/hr
      • Temporal artery biopsy shows necrotizing vasculitis and granulomatous inflammation
      • Severe visual loss, swollen disc, central retinal artery occlusion
      • Headache, malaise, weakness, weight loss, fever, jaw pain, polymyalgia rheumatica
      • Response to steroids (protect vision in other eye)
    • Takayasu’s arteritis
      • Vasculitis of aorta and branches, including carotid arteries of neck
      • Hypertensive encephalopathy, thromboembolic disease
      • Granulomatous transmural inflammation (panarteritis) with scarring and destruction
    • Kawasaki disease
      • Fever of 5+ days plus:
        • Bilateral nonpurulent conjunctivitis
        • Injected/dry, fissured lips, strawberry tongue
        • Edema, erythema of hands and feet with desquamation
        • Polymorphous rash
        • Unilateral cervical lymphadenopathy
      • Coronary artery aneurysms
      • Treatment with IVIG and ASA
      • Irritability, lethargy, aseptic meningitis
  • Small vessel disease
    • Polyarteritis nodosa
      • Multifocal panarteritis of small/medium vessels
      • Neutrophil infiltration and fibrinoid necrosis, post-inflammatory scarring
      • Affects all organs except lung and spleen
      • CNS and PNS involvement
        • Headache, encephalopathy, stroke, seizures, neuropathies
      • Hypertension
      • Immune complex vasculitis associated with hepatitis B antigenemia
      • High WBC, ESR, HBsAg, c-ANCA
    • Churg-Strauss syndrome
      • Allergic angiitis and granulomatosis
      • Asthma, eosinophilia, multi-organ vasculitis
      • PNS involvement only – mononeuritis multiplex, symmetric polyneuropathy
    • Wegener’s granulomatosis
      • Granulomatous vasculitis of respiratory tract and glomerulonephritis
      • ANCA+ (anti-neutrophil cytoplasmic antibodies), anti-PR3 antibodies
      • Peripheral neuropathy, cranial neuropathies, seizures, cerebral vasculitis
    • Goodpasture syndrome
      • Pulmonary hemorrhage
      • Glomerulonephritis
      • Anti-glomerular basement membrane (anti-GBM) antibodies
    • Henoch-Schonlein purpura
      • Petechiae, purpura, ecchymotic rash, abdo pain, fever, renal involvement, HTN
      • Elevated IgA levels, microscopic hematuria, occult blood in stool
      • Headaches, seizures, vasculitis, intracranial hemorrhage, chorea
      • Neuropathies, GBS, mononeuritis multiplex
  • Connective tissue disorders
    • Systemic lupus erythematosus
      • Neuropsychiatric symptoms – psychosis, behavioural/cognitive dysfunction
      • Infarcts (embolic from endocarditis or hypertension from renal disease)
      • Headache, encephalopathy, chorea, seizures, aseptic meningitis
      • Neuropathy, myelitis
      • Antiphospholipid antibodies (APLAs), ANA, low C3/C4, pancytopenia, hematuria, proteinuria, anti-dsDNA, anti-Sm, VDRL+, lupus anticoagulant, ACLA
    • Scleroderma
      • Seizures, blurred vision, bulbar palsy, optic neuritis, trigeminal neuropathy
      • High ANA, RF
    • Mixed connective tissue disease
      • Same as SLE plus anti RNP, high CK
    • Sjogren’s syndrome
      • Localized morphea, coup-de-sabre lesions vs. systemic
      • Vasculitis ipsilateral to coup-de-sabre skin lesions on face/scalp
      • Encephalopathy, optic neuritis, aseptic meningitis, recurrent paresis, myelopathy, neuropathy, autonomic dysfunction
      • ANA, RF, anti-SSA/Ro, anti-SSB/La
  • Chronic arthropathies
    • Juvenile idiopathic arthritis (juvenile rheumatoid arthritis)
      • Pauciarticular, polyarticular, and systemic onset disease
      • Uveitis
      • Systemic juvenile idiopathic arthritis
        • Acute encephalopathy with macrophage activation syndrome
          • Fever, rheumatoid rash, seizures, encephalopathy, HSM, lymphadenopathy
          • Cardiac, pulmonary, renal failure
          • Cytopenias, hypoalbuminemia, elevated D-dimers, high ferritin, LDH, LFTs, TG, ESR
          • Associated with ASA, NSAIDs, gold treatment
          • Treatment with steroids or cyclosporine A
        • Reye-like syndrome
          • Associated with ASA use
          • Hepatic failure, hyperammonemia, cerebral edema, seizures, encephalopathy
        • Mononeuritis multiplex – more seen in adults
        • Mood disorders
        • Myositis
          • Elevated CK
      • Polyarticular juvenile rheumatoid arthritis
        • Cervical myelopathy from cervical arthritis – more in adults
      • Inflammatory bowel disease
        • Myasthenia gravis, myopathy, neuropathy, seizures, cognitive changes
        • Uveitis
        • High ESR, microcytic anemia, melena
      • Acute rheumatic fever
        • Sydenham’s chorea, personality changes, seizures
        • Positive ASO titers, high ESR/CRP, abnormal ECG
      • Lyme disease
        • Aseptic meningitis, headache, chorea, cranial neuropathies
        • Late myelitis, MS-like symptoms, subtle encephalopathy, radiculopathy, mononeuritis multiplex
        • IgG Lyme titer by ELISA, serum protein by western blot, CSF Lyme PCR
        • Borrelia burgdorferi – spirochete from tick bite
  • Other autoimmune disorders
    • Thrombotic thrombocytopenic purpura
      • Haemolytic anemia, thrombocytopenia, renal insufficiency, purpuric rash on trunk/limbs
      • Grey matter involvement
      • Microvascular thrombosis resulting in multiple end-organ ischemia
    • Sarcoidosis
      • Chronic, multisystem granulomatous disease
      • Polyarthritis, uveitis, cutaneous sarcoid lesions, pulmonary symptoms, hilar adenopathy, high ESR, high immunoglobulins
      • Obstructive hydrocephalus, transient CN7 palsies, myelopathy
      • Reports of optic nerve, orbital, pituitary, hypothalamic, meningeal involvement, seizures
    • Behcet’s disease
      • Recurrent oral/genital ulcers, uveitis, erythema nodosum, pathergy
      • CNS involvement patterns:
        • Diffuse: acute meningoencephalitis, organic psychosis, dementia
        • Brainstem/spinal cord, cranial neuropathies, hemiparesis, ataxia
        • Thrombosis of dural sinuse and intracranial veins, intracranial HTN











Young adults

Children or adults

Assoc infection

Diarrhea (E. coli)














Peripheral smear





Kidney involvement

ARF, hematuria


ARF, proteinuria




(dialysis, transfusions)


(dialysis, transfusions)

Plasmapheresis, NSAIDs


Steroids, splenectomy

Key points


Rash, abdo pain, arthritis, melena

CNS changes

Antiplatelet antibodies



Nonvasculitic autoimmune meningoencephalitis (NAIM)


  • Hashimoto’s encephalopathy
    • A.K.A. steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT)
    • Rare, steroid-responsive syndrome associated with autoimmune thyroiditis
    • Occurs even if euthyroid, due to specific inflammation in the CNS
    • Clinical presentation:         
      • Mental status change, altered LOC, stroke-like events, seizures, tremor, myoclonus
    • Responsive to steroids. Reported responsiveness to IVIG, PLEX, immune modulation
  • Antiphospholipid antibody syndrome
  • Sjogren syndrome
  • Hypereosinophilic syndrome


Immunotherapy in Neurology




Side effects


2g/kg div 2-5 days

Headache, dermatitis, viral infection, fluid overload, anaphylaxis, hepatitis, acute renal failure, venous thrombosis, aseptic meningitis

Plasma exchange


Hematoma, pneumothorax, septicemia, bleeding, cardiovascular instability, hypocalcemia, blood pressure fluctuations, distal paresthesias



Psychosis, mood disorders, cataracts, acne, striae, thinning of skin, Cushing’s syndrome (fat pads, moon facies), hypertension, gastritis, gastric hemorrhage and anemia, hyperphagia, weight gain, osteoporosis, avascular necrosis of femoral head, immune suppression and opportunistic infections, gynecomastia, testicular atrophy, hyperglycemia, glucose intolerance