Limbic encephalitis usually presents with neuropychiatric symptomatology, often remain undiagnosed, treated as psychiatry disorders with various antipsychotic medications and die. Early diagnosis and treatment of autoimmune limbic encephalitis has good outcome, establishing these patients back into the society

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
“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

6. 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

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
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

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. 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

11. AUTOIMMUNE LIMBIC ENCEPHALITIS
Era of NEUROCHEMISTY AND NEURORADIOLOGY
Paraneoplastic encephalitis
and anti-Hu antibodies.
Atypical limbic encephalitis
and VGKC antibodies.
FLAIRIMAGEMRIoflimbicencephalitis
The Neurologist 2007;13: 261–271
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
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

13. AUTOIMMUNE LIMBIC ENCEPHALITIS
SYMPTOMATOLOGY
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
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

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
TheNeurologist2007;13:261–271
LimbicEncephalitisandVariants:Classification,DiagnosisandTreatment
ErdemTu¨zu¨n,MD,andJosepDalmau,MD,PhD

16. ANTI NMDA RECETPOR ANTIBODY ENCEPHALITIS
NMDAR 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 RECEPTOR
N-methyl-D-aspartate receptor,
excitatory glutamate receptor
important in controlling synaptic
plasticity and memory function

17. ANTI NMDA RECETPOR ANTIBODY ENCEPHALITIS
NMDAR ANTIBODY ENCEPHALITIS
Psychiatric
symptoms
• 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
Young
Women
USG
Pelvic cyst (ovarian dermoid or
teratoma)
CSF
Mild Increases protein
Lymphocytic pleocytosis
MRI
Median temporal lobe
hyperintensity (25%)
TheNeurologist2007;13:261–271
LimbicEncephalitisandVariants:Classification,DiagnosisandTreatment
ErdemTu¨zu¨n,MD,andJosepDalmau,MD,PhD

18. ANTI NMDA RECETPOR ANTIBODY ENCEPHALITIS
NMDAR ANTIBODY ENCEPHALITIS
SUSPICION
• 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
MANAGEMENT
TheNeurologist2007;13:261–271
LimbicEncephalitisandVariants:Classification,DiagnosisandTreatment
ErdemTu¨zu¨n,MD,andJosepDalmau,MD,PhD
Patients starts recovering 2-3 weeks of tumor excision and immunotherapy

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, 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
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.”