26 Oct 2021

1/21/21: Anti-NMDA Receptor Encephalitis

PGY3 Rose Monahan presented a case of 39 year old female with no known past medical history presents from jail for altered mental status.  Per jail report, she was found lying naked in her jail cell covered with trash and unkempt.  She was documented to have “acute psychosis, underlying psychotic illness and now more confused, disorganized and moving slowly”.  Since the arrest, patient was placed on 5150 hold and extended to 5250 hold due to grave disability.  Per family, prior to the arrest, patient had ~2 months of decreased sleeping/eating, impulsivity, reckless spending and was noted to be hyperverbal. 

Jail medications included Seroquel 50mg qhs, Trazodone 100mg qhs and Haldol PRN.  The patient was born in Thailand, previously married but now divorced and living with ex-husband in Malibu.  She completed college with BA degree and previously worked as a masseuse.  Denies any substance abuse and no prior history of incarceration/criminal history.

Vitals: T 36.6, HR 107, RR 16, BP 153/92,O2 sat 100% on RA

Physical Exam significant for Asian female, intermittently agitated and mumbling, dried blood on occiput, dried blood behind ear, normal cardiac/respiratory/abdominal exam, A&O x 0-1, not following commands, sensation intact, withdraws to noxious stimuli in all extremities, 2+ DTR, no Babinski, odd affect, intermittently agitated, mumbling incoherently with limited eye contact.

CBC: WBC 7.1> Hb 11.3/Hct 34.9 <Plt 197 (MCV 82.1, RDW 14%)

CMP:

Na 154/K 4.1/Cl 110/HCO3 29/BUN 46/Cr 1.08<Glucose 102

ALP 38>T.protein 6.4/Albumin 3.8/AST 90/ALT 46/Tbili 0.7/Dbili 0.3

Ca 10.1, Mg 2.4, Phos 4.9

Coags: PT 14.8, INR 1.17

Infectious workup initiated, with the following findings:

  • BCx, UA, UCx negative
  • HIV negative
  • RPR negative
  • Hepatitis panel negative
  • LP done with the following results:
    • RBC: 11
    • Nucleated cells: 19 (lymph 95%, monocytes/histiocytes 5%)
    • Glucose 74
    • Protein 20
    • CSF Culture: Cutibacterium (Propionibacterium) acnes isolated and identified from broth culture only
    • Fungal CSF culture: negative
    • AFB CSF culture: no growth x7 weeks
    • Biofire viral panel negative
    • VDRL, West Nile negative

Rheum workup:

  • ANA: 1:40, speckled
  • dsDNA negative
  • ANCA negative
  • GAD-65 elevated

Neuro workup:

  • B12 normal, Ammonia level wnl
  • TSH wnl
  • Tox screen including APAP, ASA, ETOH, UTox negative
  • CTH: no acute intracranial hemorrhage, large territory infarct, mass effect or midline shift.  R Frontoparietal scalp soft tissue swelling with underlying hematoma
  • EEG: moderate diffuse background slowing
  • MRI brain: prominent T2 weighted signal with peripheral reduced diffusion along the bilateral hippocampi.

Further CSF studies were sent including autoimmune panel resulted with NMDA Ab positive.

Treatment: Once diagnosis made, patient was treated with solumedrol and IVIg with minimal response.  Her hospital course was complicated by GI bleed and patient was briefly transferred to ICU with flex sig showing rectal ulceration.  She received 7 session PLEX and multiple rituximab infusions with clinical response.  At the time of discharge, MD noted improving clinical picture and patient was able to answer simple questions, follow commands and eat on her own.  She was transferred to a rehab facility to continue with her recovery.

Teaching points:

  1. Signs and Symptoms of Anti-NMDA receptor encephalitis
    1. Usually gradual onset with prodromal headache, fever, or a viral like process, followed in a few days by a multistage progression of symptoms that include: psychiatric symptoms (anxiety, agitation, hallucinations, delusions, disorganized thinking), insomnia, memory deficits, seizures, decreased level of consciousness, stupor with catatonic features, frequent dyskinesias, autonomic instability and language dysfunction
  2. Diagnosis
    1. CSF: lymphocytic pleocytosis or oligoclonal bands
    1. EEG with infrequent epileptic activity but frequent slow, disorganized activity
    1. Brain MRI: normal or shows transient fluid attenuated inversion recovery or contrast enhancing abnormalities in cortical or subcortical
    1. Confirmation: detection of IgG Ab to the GluN1 subunit of the NMDA receptor in serum or CSF
  3. ~50% of female patients older than 18 have uni or bilateral ovarian teratomas so need CT A/P, Pelvic US or MR abdomen to evaluate female patients with NMDA encephalitis
  4. Treatment:
    1. First line: IVIG or plasma exchange, methylprednisolone, tumor resection if indicated
    1. Second line: Rituximab, Cyclophosphamide
  5. Prognosis: if untreated, most often progresses to death, although some cases of spontaneous resolution are recorded.  50% of the patients improve after 4 weeks of first line therapy.  15-24% of patients have been reported to have relapse episode.

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