It’s not a rare disease anymore !

It's not a rare disease anymore !

Autoimmune Encephalitis - The under-recognized disorder

Reason for the consult: 60-year-old patient with rapidly progressive cognitive decline. While I was walking downstairs in the hospital, I met one of the internal medicine attendings who asked for a consult. "This lady was completely normal till last month when she started to show marked cognitive decline. It looks like dementia, but she is "weird", sometimes she looks normal and sometimes she is completely demented!"

Story:  It is a little bit long story, I had to describe all the details.

This is a 60-year-old woman with known hypertension who was admitted to internal medicine service for having UTI. On admission, patient was reported to be confused, not oriented to time or place with no focal weakness or sensory loss on exam. Patient was treated with ceftriaxone for 3 days with improvement in the urinalysis picture but not the confusion and disorientation. Medicine team ordered MRI of the brain, ammonia, TSH, B12/folate, all of which were normal.

Husband says that she hasn't been herself for the past month. She has been more "confused", doesn’t remember their conversations, sometimes she doesn’t know where she is or what day is it. He reported that her memory problems may have been waxing and waning. Prior to that she was completely healthy with no memory problems.

First visit: When I went to see the patient, she was completely normal. Alert and oriented x4, able to tell names of 5 previous presidents, attentive with intact 5 digit span, 3 word recall, serial subtraction. She was even smiling and able to make some jokes. Also normal motor and sensory exam. While finishing my exam I got a stroke alert. I had to excuse my self and headed to the ED. The stroke patient took me about an hour, then I returned back to this patient to finish my exam.

Second visit: When I entered the room for the second time, she was a totally different person. She was awake, alert but not able to talk. She had expressive aphasia, was able to follow only simple one step commands. On motor exam, she had a right arm drift with weak hand grip. At this point, I felt I should call stroke alert. I asked the husband, what happened?, he said nothing, she has been always like that, sometimes doing well and sometimes confused. He reported no seizure like activity and no twitches. While talking with him I felt the patient was staring, called her name repeatedly and was able to answer only after 4-5 seconds. Asked the husband, did she do that before, he said "yea, sometimes when i talk with her she does that...".

Analysis: 

  • Complex partial seizures which can be subtle and recurrent to the point that it may look like cognitive decline (if it is back to back).
  • Etiology wise, given that has been going on for a month, these were my top differentials:
    • Brain lesions or head trauma related --> MRI was reviewed
    • Chronic CNS infectious process
    • Medication induced seizures --> no change in medications over past month, no quinolones used for her UTI.
    • Baseline of dementia with brain atrophy that may cause complex partial seizures -> no history or prior dementia - no marked brain atrophy
    • Autoimmune encephalitis (as VGKC)
    • Para-neoplastic syndrome

What happened next

  • Loaded with levetiracetam and started on maintenance.
  • EEG ordered -> normal.
  • MRI with contrast reviewed -> reported as normal but I could appreciate left medial temporal Flair hyper-intensity.
  • CSF analysis: 5 WBCs, 72mg/dl protein and negative infectious workup.
  • Patient continued to have staring spells -> added fosphenytoin -> continued to have staring spells.
  • After discussion with primary team, started on a trial of Solumedrol 1gm daily for 5 days -> marked improvement with no staring spells "seizures" after first dose.
  • Sent autoimmune encephalitis panel from blood and CSF to Mayo and patient was discharged on Keppra only.
  • A week later, panel came positive for anti-ganglionic AChR antibodies. One of the infrequent antibodies that can cause seizures.
  • Cancer screening was negative
  • Called patient a month later -> she answered the phone and said "Don't worry, I'm still doing well, no seizures since I left and started laughing...". She was back to her self. This was one of the most cheerful phone calls I did in a while!

What if? 

  • What if autoimmune encephalitis was not on the differential? I believe patient will be continued on anti-epileptic drugs and steroids will not be tried. She may get the diagnosis of dementia, may be "rapidly progressive dementia" and patient will likely be sent to a nursing home.

Some common pitfalls regarding autoimmune encephalitis: 

  • Autoimmune encephalitis is usually in young women: wrong, actually it is more common in the middle age and elderly, both men and women.
  • Autoimmune encephalitis should have signs of encephalitis, severe confusion and may be coma: wrong, encephalitis here means irritation which can be focal to certain parts of the brain causing seizures or loss of certain brain functions, not diffuse encephalitis.
  • Autoimmune encephalitis usually don't respond that quickly to steroids: wrong, it depends on the auto-antibody. Autoantibodies against cell membrane (as voltage gated K channel) usually show marked response to steroids. Cytoplasmic autoantibodies on the other side are difficult to treat.
  • If it was autoimmune encephalitis, she must relapse after steroid effect subsides? not necessarily. Autoimmune encephalitis presents with relapses, once relapse is treated, the time to next relapse is very variable, can be weeks or years. If patient had a severe form, benefits from long-term maintenance will outweigh the risks of immunosupressive therapy (rituximab, mycophenolate, steroid taper.....).
  • What if autoimmune encephalitis panel came back negative? still would leave the diagnosis of "possible autoimmune encephalitis". Remember, autoimmune panel is negative in 50% of patients who meet the criteria for autoimmune encephalitis.

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