A 54-year-old man with no significant history complained of episodic stinging pain in his left eye along with weakness and numbness in his right upper and lower extremities for 1 month. The episodes initially lasted for 3-5 min each and occurred only during the daytime but progressively increased in frequency and duration to last up to 10-15 min and occurred during the night. The patient had not gone to the hospital until he developed progressively worsening symptoms. His neurological examination was unremarkable, and the brain MRI showed bilateral paraventricular demyelination.
The episodes were suggestive of TIAs and the patient underwent computed tomography (CT) angiography, which showed significant stenosis of the left internal carotid (60%) and vertebral (70%) arteries. He underwent left internal carotid artery stenting following 200 ml of intravenous contrast administration and was intubated during the procedure. After the procedure, he did not regain consciousness, and half an hour later, he developed flexion and spasticity in the right arm. His temperature was 36.5 C, heart rate was 110/min, blood pressure was 148/106 mmHg, respiratory rate was 22/min, and SpO2 was 98% (on ventilator support). The pupillary diameter was 1.5 mm in ambient light, and the pupillary light reflex was sluggish. On motor examination, he had hypertonia in the extremities and trunk and showed abnormal flexion to pain. His Glasgow Coma Scale score was 4T (E1VTM3). The patient developed recurrent generalized tonic-clonic seizures, lasting from 10 s to several minutes. The lactic acid in his blood was high (12.3 mmol/L). He was treated with midazolam and vecuronium. The Richmond Agitation Sedation Scale score was -4. The control of seizures required continuous intravenous infusion of midazolam for 48 h. Subsequently, oral levetiracetam was administered to allow a reduction in the midazolam dose. Several investigations were performed 2 days later (day 15 of hospitalization): His brain MRI showed edema and generalized high signal in the meninges (Figure 1). His electroencephalogram showed low voltage with no epileptiform discharges. The abdomen and testicle ultrasound were normal; the CT chest was normal. Rheumatism immune-related antibodies, including antinuclear antibody (ANA), antineutrophil cytoplasmic antibody (ANCA), anti-ribonucleoprotein antibody (anti-RNP), double-stranded DNA (anti-dsDNA), and Sjogren syndrome-related antigens A and B (anti-SS-A/SS-B), were negative. In addition, the T-cell-based test for tuberculosis infection and the tuberculin skin test were negative. The result of the cerebrospinal fluid (CSF) analysis is presented in Table 1. The patient was empirically treated with the antiviral medication acyclovir.
After 21 days of his hospitalization, serum anti-neurexin-3alpha IgG came back positive with a ratio of 1:10. The anti-neurexin-3alpha IgG antibodies were not detected in the CSF. The patient was diagnosed with anti-neurexin-3alpha-associated AIE and treated with a single dose of IV immunoglobulin (0.4 g/kg/day for 5 days). In the following days, the patient developed psychiatric symptoms, including agitation, auditory and visual hallucinations, cognitive dysfunction, and significantly reduced sleep duration. His Bech-Rafaelsen Mania Rating Scale score was 23, indicating severe mania. He was treated with olanzapine to control psychiatric symptoms. On day 28 of hospitalization, CSF analysis was repeated, which was normal, except for raised proteins, and the anti-neurexin-3alpha antibody was negative in both serum and CSF (Table 1). The brain MRI showed improved both brain edema and high signal in the meninges (Figure 1). Steroids were added to the patient's treatment.
On day 35 of hospitalization, the patient was discharged because of significant improvement and was asked to continue mycophenolate mofetil. The patient presented for follow-up after 2 months and reported significant improvement in the psychotic symptoms, with only mild irritability and agitation. His CSF QAlb was 6.17, anti-neurexin3alpha IgG was positive at 1:10, and serum anti-neurexin-3alpha antibody IgG was 1:32. Therefore, we added cyclophosphamide for 2 months in addition to mycophenolate mofetil. After 4 months, his CSF QAlb was 7.79, anti-neurexin-3alpha antibody IgG was negative, serum anti-neurexin-3alpha antibody IgG was 1:10, and the brain MRI was normal. Thus, the patient was asked to continue mycophenolate mofetil. After 7 months, both the CSF analysis and the brain MRI were normal (Figure 1), the anti-neurexin-3alpha antibody IgG was negative in CSF and serum, and the patient had a complete recovery and had been back to work for several months. The case timeline was showed in Figure 2.