Rituximab Treatment in Acute Disseminated Encephalomyelitis
Acute disseminated encephalomyelitis (ADEM) is an inflammatory, demyelinating, and rapidly progressive disorder of the central nervous system. This condition is also known as postinfectious encephalomyelitis, and it is characterized by multifocal lesions in the brain and spinal cord with widespread neurological findings. High doses of intravenous (IV) methylprednisolone, intravenous immunoglobulin (IVIG), and plasma exchange (PLEX) treatments comprise the first-line therapy. A 17-year-old previously healthy girl presented with complaints of headache, numbness in the arms and legs, weakness, and change in consciousness. She presented with complaints of vomiting and fatigue 15d before her history; she had had headache and vomiting for 3d previously and no history of any illness or medication use. On physical examination, she was drowsy and had impaired cooperation orientation. Her blood pressure was 110/70mmHg; respiratory rate, 20/min; pulse, 80/min; oxygen saturation, 96%; and body temperature, 36.5°C. Upon neurological examination, her admission Glasgow coma score (GCS) was 9, and she had hyperactive deep tendon reflexes, bilateral Babinski signs, and no signs of meningeal irritation. Laboratory test results were within normal limits. Neither intracranial hemorrhage nor space-occupying lesion was detected on brain computed tomography (BCT). The patient became unconscious and thus regressed to GCS 6, whereupon she was intubated and admitted to the Pediatric Intensive Care Unit (PICU). Cefotaxime (10d) and acyclovir (7d) administration were initiated to treat possible infection.

Levetiracetam and phenytoin treatments were initiated after she sustained several episodes of generalized tonic-clonic convulsions. On the day of admission, cerebral arterio-venous magnetic resonance angiography results were normal. On BMRI, confluent subcortical white matter lesions were observed in bilateral frontal and parietal lobes and brain stem. Punctate and arc lile contrast enhancement was seen in these areas. High doses of IV methylprednisolone (1g/d for 7d) and IVIG (0.5g/kg/d for 4d) were concomitantly initiated. The opening pressure of the cerebrospinal fluid (CSF) increased in the lumbar puncture; CSF biochemistry values were in normal ranges, and cell microscopy and culture results were negative on the tenth day of admission. Nasal and CSF polymerase chain reaction testing was negative. Anti-toxoplasma gondii, anti-cytomegalovirus, anti-treponema pallidum western blot, anti-herpes virus 1/2, Borrelia burgdorferi, Ebstein-Barr virus, Varicella zoster antibodies, Mycoplasma pneumoniae, anti-HAV-IgM, Anti-HCV and anti-human immunodeficiency 1/2 antibodies, and Brucella agglutination test results were negative. Blood and urine cultures were also negative. The Gruber–Widal test result was positive, with a Salmonella typhi O antigen titer of 1/160 (control as 1/80). She developed global hypertonia, decerebrate posture, and hyperreflexia with clonus during follow-up. Given her lack of improvement with high-dose methylprednisolone and IVIG, as of the fifth-day postadmission, PLEX was performed five times (i.e., once every other day); this was followed by immunoabsorption once. During PICU hospitalization, vancomycin, meropenem, and amphotericin B treatments were given due to healthcare-associated infection.

Twenty-three days after admission (18 days after high-dose steroid therapy, 13 days after PLEX), given the occurrence of repetitive seizures and no improvement in mental status, a rituximab off-label protocol (375mg/m2 once per week, four times; compassionate use after parent's consent and the approval by Ministry of Health) was initiated. Following the first dose, her mental and general condition improved and she was extubated. She was transferred to the ward after one month of hospitalization in the Pediatric Intensive Care Unit. During her routine follow-up visit, she had no symptoms and signs; MRI findings regressed within 5 months, and no new lesions were seen in follow-up MRI scans.