SPIRIT TO AUTOANTIBODIES

Transcription

1 SPIRIT TO AUTOANTIBODIES JOURNEY OF LIMBIC DISORDERS FROM PHILOSOPHY TO AFFECTIVE NEUROSICENCE Dr. Ubaidur Rahaman M.D. Internist and Critical Care Specialist

2 Education is a progressive discovery of our own ignorance Will Durant

3 CASE VIGNETTE 28 Y F History of psychiatric illness on medications, Presented with headache, vomiting, convulsions and altered mentation, Routine Lab revealed no abnormality, CSF examination inconclusive, CT brain unremarkable MRI brain showed dubious hyperintenisity in temporal lobes, as metal artifact related to dental brace

4 LIMBIC SYSTEM ARISTOTLE Heart as center of intelligence and emotions GALEN Brain as center of intelligence and emotions BROCA, PAPEZ AND MCLEAN Objective scientific explanation PHILOSOPHY SPIRIT AFFECTIVE NEUROSCIENCE NEUROCHEMICALS

5 LIMBIC SYSTEM The hypothalamus, the anterior thalamic nucleus, the cingulate gyrus, the hippocampus and their interconnections, constitute a harmonious mechanism which may elaborate the functions of central emotion as well as participate in the emotional expression. James Papez, 1937 a visceral brain that interprets and gives expression to its incoming information in terms of feeling, being incapable perhaps of getting at the meaning of things at the level of symbolic language. Maclean, 1952

6 LIMBIC SYSTEM More of a functional concept than anatomical Ring of interconnected structures around the "stem" that connects the cerebral hemispheres to the top end of the brain stem. It function include EMOTION, behavior, motivation, memory,

7 LIMBIC SYSTEM DISEASES NEUROPYCHIATRIC MANIFESTATIONS ADHD OCD ANXIEITY DISORDER SCHIZOPHRENIA AFFECTIVE DISORDERS EPILEPSY LIMBIC ENCEPHALITIS KORSAKOFF PSYCHOSIS AUSTISM KLUVER BACHY SYNDROME DEMENTIA

8 LIMBIC ENCEPHALITIS ERA of HISTOPATHOLOGY: Paraneoplastic LE Patients of atypical encephalitis Abnormal behavior and motor movement Autopsy showed inflammation in limbic area 3 Patients of bronchial CA: with severe short term amnesia, 2 with amnesia and dementia Autopsy: inflammation and degeneration mainly in limbic area Reviewed 8 previously reported cases and suggested relationship between LE and CA

9 PARANEOPLASTIC LIMBIC ENCEPHALITIS (PLE) CLINICO-PATHO-RADIOLOGICAL DIAGNOSIS Characterized by neuropsychiatric symptoms like personality changes, irritability, depression, seizures, memory loss and sometimes dementia. Associated with neoplasms: lung (50%), testis (20%) and breast (8%). The diagnosis is difficult because clinical markers are often lacking, and symptoms usually precede the diagnosis of cancer in 60% of patients Distinct radiologic and pathologic finding in temporal lobe

10 AUTOIMMUNE LIMBIC ENCEPHALITIS Era of NEUROCHEMISTY AND NEURORADIOLOGY Thirty (60%) patients had antineuronal antibodies (18 anti-hu, 10 anti-ta, 2 anti-ma), and 20 were antibody-negative or had uncharacterized antibodies Treatment of the tumor appeared to have more effect on the neurological outcome than the use of immune modulation Improvement was observed in 38% of anti-hu patients, 30% of anti-ta patients and 64% of patients without these antibodies Brain Jul;123 ( Pt 7): Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J

11 FLAIR IMAGE MRI of limbic encephalitis AUTOIMMUNE LIMBIC ENCEPHALITIS Era of NEUROCHEMISTY AND NEURORADIOLOGY Paraneoplastic encephalitis and anti-hu antibodies. Atypical limbic encephalitis and VGKC antibodies. The Neurologist 2007;13: Limbic Encephalitis and Variants: Classification, Diagnosis and Treatment Erdem Tu zu n, MD, and Josep Dalmau, MD, PhD

12 AUTOIMMUNE LIMBIC ENCEPHALITIS NOT A UNCOMMON DISEASE ERA OF NEURORAGIOLOGY AND NEUROCHEMISTRY Recognition and reporting of Autoimmune LE of varied neuronal antibodies Excellent response to immunosuppressive therapy if diagnosis is confirmed by the clinical picture and MRI findings, Start immunosuppressive therapy, without waiting for the antibody results as its negativity does not exclude the diagnosis Neurologia Jan-Feb;20(1): [Limbic encephalitis: a probably under-recognized syndrome]. [Article in Spanish] Graus F, Saiz A

13 AUTOIMMUNE LIMBIC ENCEPHALITIS SYMPTOMATOLOGY Neuropsychiatric symptoms Behavioral problems, changed personality Depression, anxiety, fear, psychosis, hallucinations ADHD, OCD Anorexia, bulimia Nephrologic Hyponatriaemia Neurological features Memory loss or amnesia Movement disorders & dystonia: motor or vocal tics, chorea, catatonia, parkinsonism, rigidity, acute dystonia Epilepsy: generalized, partial, myoclonus Aphasia, mutism Nystagmus, ataxia drowsiness, stupor, sleep inversion Decreased level of consciousness Autonomic features: instability of BT, hypoventilation, respiratory failure Autoimmune encephalitis - History & current knowledge By Finn E. Somnier, M.D., D. Sc. (Med.), Department of Clinical Biochemistry, Immunology and Genetics, Staten s Serum Institute, Copenhagen, Denmark

14 AUTOIMMUNE LIMBIC ENCEPHALITIS AUTOANTIBODIES PARANEOPLASTIC Anti-Hu Anti-CV2 (CRMP5) Anti-Ta (Ma2) Anti-Ri Anti-Amphiphysin Anti-mGluR5 NON NEOPLASTIC Anti-LGI1 ( anti-vgkc ) Anti-NMDAR (NR1) Anti-AMPAR (GluR1, GluR2) Anti-AMPAR (GluR3) Anti-GABABR1 Anti-AQP4 Anti-D1, anti-d2, anti-lyso-gm1 Anti-Alpha-enolase (ENO1) Anti-GAD Anti-GlyR alpha1 Autoimmune encephalitis - History & current knowledge By Finn E. Somnier, M.D., D. Sc. (Med.), Department of Clinical Biochemistry, Immunology and Genetics, Staten s Serum Institute, Copenhagen, Denmark

15 LIMBIC ENCEPHALITIS DIFFERENTIAL DIAGNOSIS The Neurologist 2007;13: Limbic Encephalitis and Variants: Classification, Diagnosis and Treatment Erdem Tu zu n, MD, and Josep Dalmau, MD, PhD

16 ANTI NMDA RECETPOR ANTIBODY ENCEPHALITIS NMDAR ANTIBODY ENCEPHALITIS Ann Neurol October ; 58(4): Paraneoplastic Encephalitis, Psychiatric Symptoms, And Hypoventilation in Ovarian Teratoma Roberta Vitaliani, Josep Dalmau, MD four young women with acute psychiatric symptoms and ovarian teratoma seizures, memory deficits, Decreased LOC and central hypoventilation NMDA RECEPTOR N-methyl-D-aspartate receptor, excitatory glutamate receptor important in controlling synaptic plasticity and memory function

17 Young Women Psychiatric symptoms USG Pelvic cyst (ovarian dermoid or teratoma) CSF Mild Increases protein Lymphocytic pleocytosis MRI Median temporal lobe hyperintensity (25%) ANTI NMDA RECETPOR ANTIBODY ENCEPHALITIS NMDAR ANTIBODY ENCEPHALITIS Diagnosed as anxiety, schizophrenia and admitted in psychiatric ward Neurologic al symptoms Seizures, movement disorders, altered consciousness, Autonomic instability Hypoventilation Intubation Agitation or decrease LOC Prolong weaning due to hypoventilation Death or Recovery The Neurologist 2007;13: Limbic Encephalitis and Variants: Classification, Diagnosis and Treatment Erdem Tu zu n, MD, and Josep Dalmau, MD, PhD

18 MANAGEMENT SUSPICION ANTI NMDA RECETPOR ANTIBODY ENCEPHALITIS NMDAR ANTIBODY ENCEPHALITIS IF IT QUAKS LIKE DUCK, BUT REFUSES TO BEHAVE LIKE DUCK, ITS SOMETHING NOT DUCK IMMUNOTHE RAPY CORTICOSTEROIDS, PLASMA EXCHANGE, IVIG, CYCLOPHOSPHAMIDE, RITUXIMAB REMOVAL of TUMOUR Patients starts recovering 2-3 weeks of tumor excision and immunotherapy The Neurologist 2007;13: Limbic Encephalitis and Variants: Classification, Diagnosis and Treatment Erdem Tu zu n, MD, and Josep Dalmau, MD, PhD

19 ENCEPHALITIS RELEARNED.. EPIDEMIOLOGY Autoimmune encephalitis - History & current knowledge By Finn E. Somnier, M.D., D. Sc. (Med.), Department of Clinical Biochemistry, Immunology and Genetics, Staten s Serum Institute, Copenhagen, Denmark

20 SOCIETY AND CULTURE People who fought Anti NMDAR Encephalitis ANNELIESE MICHEL, Genmany 1970 died following a year of exorcism by catholic church. Her symptoms were suggestive of anti NMDAR encephalitis. The movies "The Exorcism of Emily Rose" and "Requiem" are based on her. AMOBI OKOYE, football player (DALLAS COWBOY) Diagnosed anti-nmdar encephalitis. Battled for 17 months. he experienced a 145-day memory gap and lost 78 pounds. He returned to practice on October 23, SUSANNAH CAHALAN, New York Post reporter suffered anti NMDAR encephalitis, and wrote a book titled Brain on Fire: My Month of Madness about her experience with the disease WILL GRAHAM, The protagonist of the Hannibal TV series diagnosed with anti-nmdar encephalitis after an MRI scan in the 10th episode of the first season Source wikipedia

21 Hello. My name is Leonard Lowe. It has been explained to me that I've been away for quite some time. I'm back.