Spirit to autoantibodies: Journey of limbic disorders from philosophy to affective neuroscience

SPIRIT TO AUTOANTIBODIESJOURNEY OF LIMBIC DISORDERS

FROM PHILOSOPHY TO AFFECTIVE NEUROSICENCE

Dr. Ubaidur Rahaman

M.D.

Internist and Critical Care Specialist

“Education is a progressive discovery of our own ignorance”Will Durant

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.

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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



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


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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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

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Patients starts recovering 2-3 weeks of tumor excision and immunotherapy

ENCEPHALITISRELEARNED….. EPIDEMIOLOGY



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

“Hello. My name is Leonard Lowe.

It has been explained to me that I've been away for quite some time.

I'm back.”

Spirit to autoantibodies: Journey of limbic disorders from philosophy to affective neuroscience

Education

Transcript of Spirit to autoantibodies: Journey of limbic disorders from philosophy to affective neuroscience