Transcript Wake up, Mommy! - McGill University

Anti-NMDAR Encephalitis:
The McGill Experience
Dr. Amy Yu, R2 Neurology
Dr. Suhail Al-Rukn, R5 Neurology
February 12th 2010
Case presentation
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ID: 29F presents to ER September 20th 2009
RFC: Persistent headache, memory changes, and
sensations of “déjà vu”
PMHx:
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Vaginal delivery July 6th 2009 (11 weeks post-partum)
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Headache (CSF leak from epidural, Rx with caffeine pills)
Married for 3 years, denies EtOH/drugs/tobacco
 Works as Program Coordinator at McGill Genetics
Department
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No medications, NKDA
Case presentation – HPI
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2-3 weeks difficulty dealing with the newborn,
decreased sleep/energy/appetite
Patient reported 3/10 constant headache,
bilateral fronto-occipital, worse in the morning,
relieved with Tylenol, no N/V
Denies hallucinations, infanticidal
thoughts/actions
During the H&P, patient appears anxious,
repetitive questioning E.g. “Why did I loose my
memory?” “Haven’t you asked me this before?”
Case presentation – Physical exam
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Vitals were within normal limits, afebrile
Unremarkable cardiopulmonary exam
Neurological
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Mental status: Oriented to time, date, place, registration 3/3,
recall 0/3
CN exam unremarkable
Motor: normal tone, 5/5 power, and 3+ reflexes
symmetrically
Sensory: normal to light touch and pinprick
No limb dysmetria, normal gait
Initial labs were within normal limits (normal WBC)
Plain CT head were unremarkable
Overview of initial course in JGH
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Sept 20: Admission to psychiatry
 Post-partum depression with psychotic features
 Started on antipsychotics and received ECT
 Catatonic state, minimal PO intake, family reports
abnormal movements
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Sept 28: “Code blue” for status epilepticus and
transfer to ICU
Continuous chewing movement around ETT
 Athetotic movement of the hands and fingers
 Variable ocular exam (ocular bobbing, convergence
spasm)
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Investigations
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MRI head with Gadolinium
3 non-specific FLAIR hyperintensities (occipital horn
of left lateral ventricle) subcentimetric, non-enhancing
 Symmetric temporal lobes, no enhancement
 MRV revealed no venous thrombosis
 Pineal region epidermoid cyst
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CSF analysis
WBC 47 (lymphocytes mainly)
 Protein 0.42, Glucose 4.7
 Gram stain & culture negative
 HSV and enterovirus PCR negative
 Viral culture negative
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Differential diagnosis
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Infectious
Covered broadly with antibiotics, antifungal,
acyclovir
 Viral, bacterial, fungal
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Metabolic
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Hepatic, renal failure, deficiency
Autoimmune
 SLE, Hashimoto, CNS vasculitis
Paraneoplastic
? Neuroleptic malignant syndrome
? Substance abuse
Paraneoplastic workup
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CSF for paraneoplastic antibody panel negative
(Mayo clinic laboratories, Rochester)
2 negative -hCG
CT abdomen and pelvis October 6th 2009
Right ovarian teratoma
 Resection October 8th 2009
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CSF and Serum positive for anti-NMDA
receptor antibodies (J Dalmau laboratory,
Pennsylvania)
Aydiner A et al, J Neuro-Onc, 37:63-66, 1998
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1st report of PLE with immature ovarian teratoma
39F presented 1 mth following resection of Rt immature
ovarian teratoma with acute psychiatric depression,
delusions of persecution, 2ry generalized seizure
Workup unremarkable except for CSF lymphocytic
pleocytosis and mildly elevated protein
6mths after onset of sxs: dependant for ADL, mood
disorder, gluttony and hypersexuality, Korsakoff-like
amnestic state
Immunologic studies with the known antibodies are
negative (Dr. J Posner in NY)
Vitaliani R et al, Ann Neurol, 58:594-604, 2005
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Identification of new antibodies in 4 cases of
young women with psychiatric sxs, seizures,
 LOC with ovarian teratoma
 Intense
reactivity in hippocampal neurons
 Antigen seems to be located on the cell surface
 Decrease serum antibody titers after
neurological improvement
Teratoma associated encephalitis
antibodies
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Immunolabeling at the plasma membrane and
dendritic processes
Dalmau J et al, Ann Neurol, 61:25-36, 2007
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Identification of the autoantigen from case
series of 12 female patients
Antibodies mainly reacted to subunits of
NMDA receptor in the hippocampus and
forebrain
Later studies suggestive that antibodies are more
targeted against the more widely expressed NR1
subunit
Dalmau J et al, Lancet Neurol, 7:1091-98, 2008
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Initial report of 12 patients in 2007
Overall 159 patients identified
Case series of 100 patients
Anti-NMDAR encephalitis
A)
B)
C)
Intense reactivity in
rat brain
hippocampus
Surface
immunolabelling of
hippocampal neurons
Reactivity with
HEK293 transfected
with NR1 and NR2B
Who were the controls?
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250 individuals were used as controls
 50 limbic encephalitis (25 paraneoplastic, 25
idiopathic)
 25 Morvan’s syndrome (Voltage-gated potassium
channel antibodies)
 20 Rasmussen’s encephalitis
 10 viral encephalitis
 25 chronic epilepsy of unknown cause
 50 other paraneoplastic disorders
 50 cancer without neurological symptoms (10
ovarian teratoma)
 20 blood donors, healthy individuals
A-NMDAR encephalitis Presentation
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Prodromal state
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Psychiatric sxs
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H/A, low-grade fevers,
viral-like illness
Anxiety, agitation,
bizarre bhvr, delusions,
paranoia, hallucinations
Neurologic sxs
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STM loss, seizures
A-NMDAR encephalitis Progression
A-NMDAR encephalitis Investigations
Paraneoplastic?
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59% neoplasm
1 patient had tumour dx
prior to neuro sxs
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Median 8 wks
Range 1-380 wks
All teratoma contained
nervous tissue & 25/25
positive for NMDA
receptor expression
Take home messages
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Anti-NMDA receptor encephalitis is not as rare
as initially thought
Young patients, mainly women
Prominent, rapidly progressive psychiatric
manifestations
Normal or atypical MRI findings
Consider paraneoplastic limbic encephalitis &
search for the tumour