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SPIRIT TO AUTOANTIBODIESJOURNEY OF LIMBIC DISORDERS
FROM PHILOSOPHY TO AFFECTIVE NEUROSICENCE
Dr. Ubaidur Rahaman
M.D.
Internist and Critical Care Specialist
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
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
LIMBIC SYSTEM
“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
“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
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,
LIMBIC SYSTEM
LIMBIC SYSTEM DISEASESNEUROPYCHIATRIC MANIFESTATIONS
• ADHD
• OCD
• ANXIEITY DISORDER
• SCHIZOPHRENIA
• AFFECTIVE DISORDERS
• EPILEPSY
• LIMBIC ENCEPHALITIS
• KORSAKOFF PSYCHOSIS
• AUSTISM
• KLUVER BACHY SYNDROME
• DEMENTIA
LIMBIC ENCEPHALITISERA of HISTOPATHOLOGY: Paraneoplastic LE
1960
1968
3 Patients of atypical encephalitis
Abnormal behavior and motor movement
Autopsy showed inflammation in limbic area
3 Patients of bronchial CA:
1 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
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
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. 2000 Jul;123 ( Pt 7):1481-94.
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
AUTOIMMUNE LIMBIC ENCEPHALITISEra of NEUROCHEMISTY AND NEURORADIOLOGY
Paraneoplastic encephalitis
and anti-Hu antibodies.
Atypical limbic encephalitis
and VGKC antibodies.
FLA
IR I
MA
GE
MR
I of lim
bic
encephalit
is
The Neurologist 2007;13: 261–271Limbic Encephalitis and Variants: Classification, Diagnosis and Treatment
Erdem Tu¨zu¨n, MD, and Josep Dalmau, MD, PhD
AUTOIMMUNE LIMBIC ENCEPHALITISNOT A UNCOMMON DISEASE
ERA OF NEURORAGIOLOGY AND NEUROCHEMISTRY
Neurologia. 2005 Jan-Feb;20(1):24-30.
[Limbic encephalitis: a probably under-recognized
syndrome]. [Article in Spanish]Graus F, Saiz A
• 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
AUTOIMMUNE LIMBIC ENCEPHALITISSYMPTOMATOLOGY
NephrologicHyponatriaemia
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
Neuropsychiatric symptoms Behavioral problems, changed personality
Depression, anxiety, fear, psychosis, hallucinations ADHD, OCD
Anorexia, bulimia
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
AUTOIMMUNE LIMBIC ENCEPHALITISAUTOANTIBODIES
PARANEOPLASTICAnti-Hu
Anti-CV2 (CRMP5) Anti-Ta (Ma2)
Anti-RiAnti-Amphiphysin
Anti-mGluR5
NON NEOPLASTICAnti-LGI1 (“anti-VGKC”)
Anti-NMDAR (NR1) Anti-AMPAR (GluR1, GluR2)
Anti-AMPAR (GluR3) Anti-GABABR1
Anti-AQP4Anti-D1, anti-D2, anti-lyso-GM1 Anti-Alpha-enolase (ENO1)
Anti-GADAnti-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
LIMBIC ENCEPHALITISDIFFERENTIAL DIAGNOSIS
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ANTI NMDA RECETPOR ANTIBODY ENCEPHALITISNMDAR ANTIBODY ENCEPHALITIS
four young women with acute psychiatric symptoms and ovarian teratoma
seizures, memory deficits, Decreased LOC and central hypoventilation
Ann Neurol. 2005 October ; 58(4): 594–604.
Paraneoplastic Encephalitis, Psychiatric Symptoms, And Hypoventilation in Ovarian Teratoma
Roberta Vitaliani, Josep Dalmau, MD
NMDA RECEPTORN-methyl-D-aspartate receptor, excitatory glutamate receptor
important in controlling synaptic plasticity and memory function
ANTI NMDA RECETPOR ANTIBODY ENCEPHALITISNMDAR ANTIBODY ENCEPHALITIS
Psychiatric symptoms
• Diagnosed as anxiety, schizophrenia and admitted in psychiatric ward
Neurological
symptoms
• Seizures, movement disorders, altered consciousness,
• Autonomic instability
• Hypoventilation
Intubation Agitation or
decrease LOC• Prolong weaning due to hypoventilation
Death or Recovery
Young Women
USGPelvic cyst (ovarian dermoid or
teratoma)
CSFMild Increases protein
Lymphocytic pleocytosis
MRIMedian temporal lobe hyperintensity (25%)
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ANTI NMDA RECETPOR ANTIBODY ENCEPHALITISNMDAR ANTIBODY ENCEPHALITIS
SUSPICION• IF IT QUAKS LIKE DUCK, BUT REFUSES TO BEHAVE LIKE
DUCK, ITS SOMETHING NOT DUCK
IMMUNOTHERAPY
• CORTICOSTEROIDS, PLASMA EXCHANGE, IVIG,
• CYCLOPHOSPHAMIDE, RITUXIMAB
REMOVAL of TUMOUR
MA
NA
GEM
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Patients starts recovering 2-3 weeks of tumor excision and immunotherapy
ENCEPHALITISRELEARNED….. 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
SOCIETY AND CULTUREPeople 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, 2014.
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
Sourcewikipedia