Case Presentation:
A previously healthy 13-year-old Korean-American girl presented with acute altered mental status. She had fatigue, leg and abdominal pain, and was initially diagnosed with “the flu.” Two days later she progressed to worsening pain, emesis, and inability to walk. On admission she was afebrile and had nystagmus, delayed responses, slow speech, weakness, myoclonic jerks, dysmetria, and ataxia on exam. A CBC and urine toxicology screen were unremarkable. A brain MRI showed symmetric abnormal T2 hyperintensity of dentate nuclei of the cerebellum bilaterally and an EEG demonstrated focal slowing at the bilateral temporal lobes. Cerebral spinal fluid (CSF) analysis showed mild pleocytosis but negative culture. Her anti-nuclear antibody was positive at 1:1280 in a speckled pattern and CSF N-methyl-D-aspartate receptor (NMDAR) antibody was negative. All infectious studies were negative and further imaging of the body failed to identify an occult tumor. Her neurologic impairment worsened as she became non-verbal and minimally responsive with urinary retention. The working diagnosis was a nonspecific autoimmune encephalitis, but without a confirmed diagnosis the family was reluctant to agree to immunosuppression and sought Complementary and Alternative Medicine (CAM) therapies. She was treated with acupuncture, herbal remedies, methylprednisolone and intravenous immunoglobulin with minimal improvement. A repeat CSF neurotransmitter study ultimately revealed the neuronal voltage-gated potassium channel (VGKC) antibody was positive, confirming an autoimmune encephalitis. Her family agreed to rituximab treatment. After an eight week inpatient stay she was more interactive and able to participate in an inpatient rehabilitation program. At discharge she regained speech but still required a high level of assistance with activities of daily living.
Discussion:
The differential for acute altered mental status is broad and includes stroke, trauma, ingestions, meningitis and encephalitis. Characteristics of autoimmune encephalitis include psychosis, febrile prodrome, autonomic instability, abnormal EEG, neuroimaging abnormalities and lymphocytic pleocytosis; all of which our patient had. Anti-NMDAR antibody is the most recognized cause of autoimmune encephalitis, but there is growing evidence of other autoantibodies, such as neuronal VGKC antibody, causing similar presentations. It is hypothesized that an infection causes an autoimmune response in the central nervous system through molecular mimicry or bystander activation. Early consideration allows for prompt, effective treatment and early aggressive immune therapy improves overall outcomes. The family struggled with an unconfirmed diagnosis and her treatment ultimately incorporated CAM.
Conclusions:
There is ongoing work to identify the numerous autoantibodies that cause autoimmune encephalitis. In patients who fit the clinical picture, prompt early immunosuppression can improve long-term outcomes.