A 33-year-old male with a recent diagnosis of type 1 diabetes mellitus (T1DM) was hospitalized with a change in mental status. The patient was found by his roommate to be unresponsive in his bed, awake, eyes opened but unable to move or communicate. Six months before admission, he was admitted for diabetic ketoacidosis, and diagnosed with T1DM, with low titer positive anti-glutamic acid decarboxylase (GAD) antibodies, after which he was discharged on subcutaneous insulin regimen of short and long-acting insulin analogs (aspart and glargine insulin). He had a past medical history of alcohol use, with daily or every other day drinking of one to three beers, with no history of illicit drug use, and no psychiatric history. There was no recent travel history or exposure to animals or pets. His family history and occupational history were non-contributory.
On physical examination, the patient was hemodynamically stable, afebrile, alert, and in a catatonic state, with eyes opened but unable to express himself or follow commands. He had minimal spontaneous movement from side to side, with slow movements of his extremities, but was unable to maintain a fixed posture when tested. The rest of the physical examination was unremarkable. The initial laboratory profile was unremarkable, with normal glucose levels (Table 1). Imaging showed cerebral atrophy relative to age but no mass lesion or abnormal intensity on T2-weighted imaging (Figure 1).
Lumbar puncture (LP) was done due to concern for meningoencephalitis, with initial cerebrospinal fluid (CSF) studies significant for elevated protein, with otherwise normal cell count, with no evidence of pleocytosis (Table 2). He had normal opening pressure, cytology, and polymerase chain reaction (PCR) for common pathogens were negative, as well as Gram stain, acid-fast stain, and cultures. No evidence of an oligoclonal band. Another sample was sent to test for autoantibodies.
CSF was also tested for Lyme disease, and western blot was positive for anti-p41 IgG (band 41) that normally targets the flagellin protein of Borrelia, with equivocal IgM against the same band and equivocal anti-p93 IgG. Otherwise all other antibodies were negative (anti-p18, p28, p30, p31, p39, p45, p58, p66, and p93, both IgG and IgM) (Table 2). The serum was negative for Borrelia antibodies. The test for latent tuberculosis with interferon-gamma release assay was negative, test for syphilis with serum and CSF venereal disease research laboratory (VDRL) and serology (antibodies) was also negative. Electroencephalogram (EEG) showed a slow posterior dominant rhythm of 6-7 Hz, diffuse delta and theta slowing with occasional right temporal focal delta slowing and moderate diffuse cerebral dysfunction. These findings suggest moderate diffuse cerebral dysfunction, non-specific in etiology, and focal right temporal dysfunction.
Given the presentation of catatonia, the patient was started on lorazepam challenge (intramuscular injection of 2 mg) with no measurable response. With equivocal findings of single band (anti-p41) antibodies on western blot for Lyme disease, the patient was treated with ceftriaxone 2 g daily for 21 days without a clinically appreciable response.
Of note, he was also noticed to have cyclical neutropenia throughout his lengthy hospitalization course ranging from 2,100 cells/microL to 4,000 cells/microL (Table 1). He was also noticed to have chronic diarrhea, and workup revealed low stool elastase pointing to chronic pancreatitis. Infectious workup, duodenal biopsy, and celiac serology were negative. The patient clinically responded to replacement of pancreatic enzyme (pancrelipase).
Due to concern for seronegative autoimmune encephalitis, the score for antibody prevalence in epilepsy and encephalitis (APE2 score) was calculated. APE2 score was 4, calculated as the following: 1 point for rapid onset neurological syndrome within a year, 1 point for neuropsychiatrist manifestations (catatonia), and 2 points for markers of inflammation in the CSF (protein >50 g/dL). As such, the patient was treated with methylprednisolone 100 mg daily for five days (pulse steroids therapy) and intravenous immunoglobulin (IVIg) 0.4 mg/kg/day for five days. Six weeks later, given the lack of response, electroconvulsive therapy (ECT) was tried for 18 sessions, followed by another 12 sessions, with minimal response, as the patient could move but was still very slow and unresponsive. Next, haloperidol was added and titrated up to 5 mg daily. Given the lack of response, amantadine was then added and titrated up to 200 mg three times daily. Further testing was done for thyroid function, serum autoantibodies, heavy metals, ceruloplasmin, and protein electrophoresis, all of which were within the normal reference range (Table 3).
LP was repeated with similar findings as previously described and was significant for only elevated opening pressure. CSF was tested for other antibodies and was positive for low titer of anti-GAD antibodies (0.07 nmol/L) and weak antinuclear antibodies (ANA), further raising the suspicion of an autoimmune process. Plasma exchange (PLEX) was introduced with no clinical response, after which a second-line treatment was considered. The patient was treated with two infusions of rituximab 1000 mg two weeks apart. After that, the patient started to respond to calling his name and gradually started answering questions, moving his extremities. In a few weeks, he was able to walk again. A month later, he was discharged to a rehabilitation facility (Figure 2). 
Six months later, the patient had two seizures during sleep. They were witnessed as shaking, unresponsiveness, and tongue biting, accompanied by stool incontinence, followed by a period of postictal state. Workup for seizures was unremarkable (normal EEG, MRI, and LP) and thus was empirically started on levetiracetam 1500 mg twice daily, with no recurrence of seizures. A year later, the patient was seen in the endocrinology clinic, able to walk, talk, express his needs, inject himself with insulin and perform his daily activities, with no recurrence of seizures or catatonic state. The clinical course is shown in Figure 2.