Autoimmune EncephalitidesDr.Roopchand.P.SSenior Resident AcademicDepartment of Neurology
Introduction.• Autoimmune Encephalitis resulting from anattack of the brain by the bodys immunesystem– Acute Disseminated Encephalitis (ADEM)– Hashimotos Encephalitis– Rasmussens Encephalitis– NMDA-Receptor Antibody Encephalitis– Limbic Encephalitis
ADEM• occurs in association with an immunization orvaccination (postvaccinationencephalomyelitis) or systemic viral infection(parainfectious encephalomyelitis).• perivascular inflammation, edema, anddemyelination within the CNS incharacteristic.
• Postvaccination Acute DisseminatedEncephalomyelitis.– subject of medicolegal controversy.• Measles-Induced Acute DisseminatedEncephalomyelitis.– complicate 1 in 400 to 1 in 1000 cases of measlesinfection.• Idiopathic Acute DisseminatedEncephalomyelitis– in the setting of nonspecific viral illness.
• bilateral ON• loss of consciousness,• Meningismus• loss of deep tendon reflexes and retainedabdominal reflexes in the presence of Babinskisign• central body temperature over 100°F• severe shooting limb pains.
• development of a focal or multifocalneurological disorder following exposure tovirus or receipt of vaccine.• peak dysfunction within several days.• Recovery can begin within days• Complete resolution day to months.• Measles virus–associated ADEM may carry aworse prognosis.
Investigations• MRI: multifocal CNS lesions.– majority of the T2 lesions enhance, suggestingthey were of recent onset.– after several weeks, lesions show at least partialresolution.• CSF:– Normal pressure, cells <100/mm3, moderateincrease in protein.– OCB not usually seen.
• The current favored therapy for ADEM is high-dose corticosteroids.• Acute Hemorrhagic Leukoencephalitis.• Isolated ON• Cerebellitis• ATM.• c/c recurrent.
Hashimoto encephalopathy• acute to subacute• evidence of cognitive impairment• variable psychiatric symptoms, alteration inconsciousness, hallucinations• Involuntarymovements, seizures, myoclonus, opsoclonus,chorea, ataxia, stroke like episodes, andmyelopathy.• Adolescent females are mostly affected.
• Diagnosis:– Clinical triad of neuropsychiatricsymptoms, detection of antimicrosomal orantithyroglobulin antibodies, and exclusion ofother causes.– antithyroid– peroxidase, antithyroglobulin,– lesser extent thyroid-stimulating hormonereceptor–blocking antibodies.– α-enolase• autoimmune cerebral vasculitis perhapsrelated to immune complex deposition.
• CSF show moderately elevated protein, maybe positive for anti thyroid Ab, OCB seen• EEG: slowing, triphasic waves, epileptiformdischarges.• MRI usually normal, occasionally non-specificsub cortical white matter T2 signal changes.• Thyroid status may be normal.• Treatment: short course high dose steroids(55% full recovery)• Recurrence – continued steroids, IVIG, otherimmunomodulatory drugs.
Rasmussens encephalitis• chronic focal encephalitis (CFE)• rare inflammatory neurological disease• frequent and severe seizures, loss of motorskills and speech, hemiparesis encephalitisand dementia.• Usually <15 yrs• Affects one cerebral hemisphere.
• auto-antibodies against the glutamatereceptor GluR3.• T lymphocyte mediated destruction ofneurons.• C/F:– mostly affects children(avg 6yrs)– prodromal stage ,Acute stage and residual stage.
• Diagnosis is usually clinical.• EEG shows slowing in affected hemisphere.• MRI : gradual shrinkage of the affectedhemisphere with signs of inflammation orscarring.• Treatment:– Control of seizures– Steroids, IVIG– Severe cases Hemispherectomy.
Anti-NMDA receptor encephalitis:• acute form of encephalitis.• Potentially Lethal.• caused by autoimmune reaction against NR1- andNR2-subunits of the glutamate NMDA receptor.• Associated with ovarian teratomas.• Previously thought entirely as a paraneoplasticmanifestation.• psychiatric symptoms or memoryproblems, seizures, unresponsiveness, dyskinesias, autonomicinstability, hypoventilation.
• MC in young women and children.• Treatment with Steroids, IVIG.– PLEX– Cyclophosphamide and /or rituximab.
Limbic and Brainstem Encephalitis:• Limbic encephalitis:Confusion,depression, agitation, anxiety, memory deficits, dementia, and partial complexseizures.• Brainstem encephalitis:oscillopsia, diplopia, dysarthria, dysphagia, gaze abnormalities, and subacute hearing loss.• Symptoms can overlap.
• MRI:– unilateral or bilateral mesial temporal lobeabnormalities on T2-weighted and FLAIR images’– The temporal-limbic regions may be hypointense onT1-weighted sequences and may enhance withcontrast.• Associated with testicular germ celltumors, Hodgkin lymphoma, thymoma.• Antigens:– Intra cellular: Hu, Ma2, CV2/CRMP5– Cell surface antigens: AMPA receptors, leucine-richglioma inactivated 1 (LGI1) and γ-aminobutyric acidtype B [GABA-B] receptors.
Graus and Saiz criteria(2005)All four of• Subacute onset (<12 weeks) of seizures, short-termmemory loss, confusion, and psychiatric symptoms• Neuropathologic or radiologic evidence (MRI, SPECT, PET)of involvement of the limbic system• Exclusion of other possible aetiologies of limbicdysfunction• Demonstration of a cancer within 5 years of the diagnosisof neurologic symptoms, or the development of classicsymptoms of limbic dysfunction in association with a well-characterized paraneoplastic antibody(Hu, Ma2, CV2, amphiphysin, Ri)
Treatment:• immunomodulation with steroids and IVIg.– The likelihood of improvement is higher if thedisorder is associated with antibodies to cell-surface receptors or ion channels.• removal of the antigenic source (tumor) andantibodies with antibody depleting treatmentsare often successful.• Treatment is disappointing when antigens areintracellular.