Autoimmune encephalitis (AE) is a rare and complex disease of the central nervous system, which can present with neurological and psychiatric symptoms of acute onset. It is primarily due to auto-antibody mediated inflammation against intracellular and cell surface neuronal antigens. Autoimmune encephalitis can mimic other neuropsychiatric conditions presenting a diagnostic challenge. Certain clinical syndromes of AE present with characteristic Imaging (MR) findings (involving limbic structures), hence it is vital to recognize the same and follow a proper diagnostic workup, since early immunotherapy improves patient outcome and good recovery.
A 67 Year old gentleman known hypertensive and diabetic on insulin presented with history of intermittent high grade fever and generalized fatigue for a period of 10 days. He became drowsy from day 5 of illness and got admitted to a nearby hospital and was treated with Antibiotics. Covid -19 ruled out. His condition improved for a brief period, however due to persistent low GCS and suspected bacterial/viral Encephalitis IV Acyclovir, Anti-malarials and dexamethasone also initiated. On family’s request, transferred to Kauvery on Day 10 of illness.
On arrival, he was drowsy with poor attention span ; physical exam showed – Erythematous macular rash over forearms, trunk and anterior chest wall, dry tongue, bilateral pitting pedal edema, no murmurs/ added sounds on auscultation. CNS exam revealed mild neck stiffness with paucity of speech, B/L Pupils- equally reacting to light , Normal tone of limbs, B/L UL/LL power – 2/5, Weak deep tendon reflexes and mute plantars, Occasional myoclonic jerks of upper limbs+.
Hippocampal Hyperintensity suggestive of Limbic encephalitis
MRI Brain showed diffuse Gyral FLAIR Hypertintensities in B/L Cerebral Hemispheres, a subtle restricted diffusion in right corona radiata. EEG ruled out active seizures. Acyclovir, Antimalarials and Antibiotics were continued and an LP was performed to rule out infective/ autoimmune etiology. CSF analysis was negative for cells, normal glucose, mildly elevated protein (58.6), Negative bacterial/viral/fungal PCR profile and Gene Xpert for MTB. Blood investigations revealed normocytic anaemia with neutrophilia, normal white cell count, hyponatremia (126), hypokalemia (3.1) and mildly elevated liver enzymes. Dengue serology, Malarial parasite and Scrub typhus were negative.
Covid Ig G Antibody was positive. ECHO was normal. Due to further decline in GCS to E1V1M1, hypotension, oliguria, he was intubated and started on inotropic support. Nephrologist consult sought in view of AKI, advised SLED. Owing to persistant low GCS, poor clinical improvement despitea good course of IV Antibiotics, antivirals ,an autoimmune etiology was suspected and initiated on IV Methyprednisolone 1g / day for 5 days . Serum ANA , autoimmune encephalitis panel were negative and Atypical pANCA positive. He showed a gradual improvement after 3rd day of IV MPS, favouring autoimmune etiology following which he received IV Cyclophophamide and underwent Plasmapheresis (5 cycles). He started showing gradual neurological improvement by obeying simple commands, grasping objects with fingers and purposeful lower limb movements. There was an episode of malena, OGD scopy revealed Dieulafoy’s lesion of stomach and treated with local adrenaline therapy. Steroid tapering could not be continued in view of malena steroids were stopped. There was steady improvement in urine output, decrease in urea, creatinine and CRP levels. Tracheostomy was planned due to prolonged ventilatory support. He was gradually weaned of ventilation and mobilized out of bed. Rheumatologist consult obtained. Repeat Serum PR3 and MPO became negative. Skin biopsy results of erythematous macular rash awaited. He was managed in the Intensive care unit by a multidisciplinary team. Currently he is being treated for secondary bacterial infection, anaemia and is due to receive 2nd course of IV Cyclophophamide. He developed further decline in alertness and motor activity despite treating secondary bacterial complications. After further multidisciplinary discussion, IV Rituximab recommended.
Autoimmune encephalitis and its subtypes can be differentiated based upon the type of auto-antibody causing immune mediated brain inflammation. Most common areas affected by AE are Limbic system followed by involvement of neocortex, striatum, hindbrain, spine, and peripheral nervous system. It can present with new-onset altered sensorium, seizures, loss of speech, vision, psychiatric symptoms such as hallucinations, delusions, abnormal behavior, rapid decline in mental status and even coma. (TABLE 1). Even in the absence of detectable auto antibodies, AE should still be considered as its prevalence is roughly around 20%. Prompt identification of clinical features, imaging findings is important to diagnose AE, to decide appropriate treatment regimen and prevent devastating complications.
Antibody-mediated CNS disorders can be classified into paraneoplastic (associated with underlying malignancy) or non-paraneoplastic. Paraneoplastic syndromes are most commonly associated with small-cell lung cancer. Other malignancies which present as paraneoplastic syndromes include neuroblastoma, germ cell tumor of the testis, breast cancer, Hodgkin lymphoma, thymoma, and immature ovarian teratomas.
Paraneoplastic limbic encephalitis, affects the temporal lobe and limbic structures with post inflammatory changes causing progressive decline in memory loss. A study, conducted by Gultekin et al in 2000, proposed the first diagnostic criteria for paraneoplastic limbic encephalitis, which included the following: 1) short-term memory loss, seizures, or psychiatric symptoms; 2) <4 years between symptom onset and cancer diagnosis; 3) exclusion of metastases, infection, metabolic, or other causes; and 4) one of the following: inflammatory CSF findings, temporal lobe T2 or FLAIR hyperintensity on MR imaging, or electroencephalogram abnormality in the temporal lobe
TABLE 1 :
Autoimmune encephalitis is an important diagnostic consideration in patients presenting with new onset of altered mental status of unclear etiology. It is possible to make a positive diagnosis of AE with clinical criteria and serologic testing. Some patients with AE may have no neuroimaging findings despite neuropsychiatric dysfunction, serum antibody testing can still ultimately lead to the diagnosis in such cases. While there is no single diagnostic feature for AE, it is essential to identify certain important findings during the work-up of patients who present with new-onset altered sensorium to confirm the diagnosis with initiate treatment as early as possible for a good outcome.
Dr Sivarajan Thandeswaran MBBS, MRCP(UK), CCT in Stoke Medicine Senior Consultant- Stroke & Neuro Vascular Medicine Program Director- Stroke Services Kauvery Hospital
Dr. S. Sivaram Kannan M.B.B.S., M.D.(General Medicine), F.R.C.P.(Glasgow) Senior Consultant Internal Medicine & Diabetology Kauvery Hospital
Dr. Sridhar Nagaiyan M.B.B.S., M.D.(Anesthesiology), F.R.C.A.(Anaesthetists) U.K., F.F.I.C.M. Consultant Intensivist Kauvery Hospital
Dr. Balasubramaniam Raju M.B.B.S., D.N.B.(General Medicine) D.N.B.(Nephrology) Chief Nephrologist Kauvery Hospital
Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis- B.P. Kelley, S.C. Patel, H.L. Marin, J.J. Corrigan, P.D. Mitsias and B. Griffith American Journal of Neuroradiology June 2017, 38 (6) 1070-1078; DOI: https://doi.org/10.3174/ajnr. A5086 Update on the diagnosis and management of autoimmune encephalitis. -Mark A Ellul, Greta Wood, Harriet Van Den Tooren, Ava Easton, Ashik Babu and Benedict D Michael Systematic Review: Syndromes, Early Diagnosis, and Treatment in Autoimmune Encephalitis-Christina Hermetter, Franz Fazekas, and Sonja Hochmeister*
Dr Athiya Parveen Lathif Resident Neurology
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