Multiple drugs

Abstract

No improvement: case report A 31-year-old woman experienced no improvement during treatment with methylprednisolone and immune-globulin for anti-Nmethyl-D-aspartate (anti-NMDA) receptor encephalitis. Additionally, she experienced no improvement during treatment with phenobarbital, levetiracetam, topiramate, perampanel and sodium valproate for generalised clonic seizures secondary to antiNMDA receptor encephalitis [not all routes and dosages stated]. The woman had fever, diarrhoea, headache and pharyngalgia for 4 days. She then became disoriented and showed memory disturbances and childish behaviour for 2 days. She was therefore admitted to the hospital. On admission, she had fever. Neurological examination showed impaired orientation and memory disturbances without motor and cerebellar signs, hyperreflexia and meningeal signs. Her CSF examination indicated lymphocytic pleocytosis, positive oligoclonal bands, an elevated IgG index, as well as increased levels of protein and total tau protein. Brain diffusion-weighted MRI (DW-MRI) and fluid attenuated inversion recovery (FLAIR) images revealed hyperintensities in the bilateral medial temporal lobes. An electroencephalography showed diffuse delta activity. No apparent tumour was detected on initial whole-body computed tomography. She was initially treated with IV methylprednisolone 1 g/day for 3 days along with ceftriaxone and aciclovir [acyclovir] until no evidence of bacterial or viral infection was found; however, her condition deteriorated rapidly, and she presented with agitation, abnormal behaviour, generalised clonic seizures and central hypoventilation. She required mechanical ventilation in the ICU as there was no improvement, despite administration of intensive first-line immunotherapies, including IV immune-globulin [immunoglobulin] 0.4 g/kg/day for five days, plasma exchange and IV methylprednisolone, in addition to sequential administration of various anti-epileptic drugs, including phenobarbital, levetiracetam, topiramate, perampanel and sodium valproate. Anti-NMDA receptor antibodies were subsequently detected in both, the serum and CSF by a cell-based assay: she was therefore diagnosed with anti-NMDA receptor encephalitis. The pelvic CT scan on day 79 after admission demonstrated a cystic lesion (5mm) within her left ovary that was suspected to be a teratoma. On day 86 after admission, laparoscopic surgery revealed a mature teratoma, which contained hair, squamous epithelium and a glandular system. Although first-line immunotherapy and cyclophosphamide were intensively continued after the surgery, no favourable response was noted. After administering cyclophosphamide for the third time at 395 days after admission, it was suspended because of frequent infection [aetiology of frequent infection not stated]. Approval was obtained from the institutional committee for the evaluation of highly difficult new medical technologies, and written consent was obtained from the patient’s family for administration of rituximab, which was administered weekly for 4 weeks from day 945 after admission. B-cells in the peripheral blood were completely depleted 54 days after the initial administration of rituximab. Hypoventilation and disturbances of consciousness (Glasgow Coma Scale score of 7) improved gradually from 1163 days after admission (approximately 6 months after rituximab initiation), and she was weaned off mechanical ventilation (ventilator-dependent period of 1176 days). A brain MRI revealed brain atrophy without abnormal intensities in the medial temporal lobes on DWI and FLAIR images, 972 days after admission. Fifty-six months after admission, she could walk without any assistance, and her mini-mental state examination score was 28. The brain MRI showed mild improvement in medial temporal atrophy 1931 days after admission. On day 2062 after admission, she showed a mild decline in Wechsler Adult Intelligence Scale-III (full intelligent quotient 77) scores with preserved Wechsler Memory Scale-Revised scores.