Rituximab ameliorates anti-N-methyl-D-aspartate receptor encephalitis by removal of short-lived plasmablasts.

We measured anti-N-methyl-D-aspartate receptor (NMDAR) autoantibody levels and assessed B cell subsets using multicolor flow cytometry of peripheral blood mononuclear cells (PBMCs) from a recurrent anti-NMDAR encephalitis case to evaluate the effectiveness of rituximab treatment. Rituximab depleted CD20(+) fractions of naïve and memory B cell subsets and reduced the number of CD20(-) plasmablasts. This study suggests that short-lived plasmablasts are removed by rituximab-induced depletion of the CD20(+) B cell population. Increased numbers of plasmablasts in PBMCs may be a candidate predictive factor for unfavorable prognosis of anti-NMDAR encephalitis and an indication of when to commence second-line immunotherapy.

Temporal lobe epilepsy with hippocampal sclerosis in acute lymphoblastic leukemia.

Of 71 acute lymphoblastic leukemia survivors at our hospital over the past 10 years, 2 children developed mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This is the first report to describe the clinical course of MTLE-HS observed longitudinally by EEG and MRI. Patient 1 experienced a seizure during chemotherapy involving intrathecal methotrexate. Postseizure MRI suggested methotrexate encephalopathy or leukemic invasion. Anticonvulsant therapy was initiated; subsequent EEGs and MRIs revealed normal results. Three years after chemotherapy, a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. Five years after chemotherapy, the patient developed MTLE-HS comprising complex partial seizures, typical temporal spikes on EEG, and hippocampal sclerosis (HS). Patient 2 did not experience seizures during chemotherapy. Four years later, the patient started experiencing complex partial seizures, and a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. A clinical picture of MTLE-HS developed 2 years later. In both patients, nonspecific EEG abnormalities (ie, diffuse, irregular spike-and-wave activity) preceded the appearance of HS on MRI by 2 years, suggesting an insidious advance of HS during the latent period. Such atypical EEG findings may indicate MTLE-HS during follow-up of leukemia patients. MTLE-HS develops several years after an initial precipitating incident such as prolonged seizures, central nervous system infection, and brain trauma. In our cases, the initial precipitating incident may have been chemotherapy and/or prolonged seizures. Thus, MTLE-HS associated with leukemia may not be as rare as generally believed. A large cohort study of late neurologic complications is warranted.

De novo mutations in the autophagy gene WDR45 cause static encephalopathy of childhood with neurodegeneration in adulthood.

Static encephalopathy of childhood with neurodegeneration in adulthood (SENDA) is a recently established subtype of neurodegeneration with brain iron accumulation (NBIA). By exome sequencing, we found de novo heterozygous mutations in WDR45 at Xp11.23 in two individuals with SENDA, and three additional WDR45 mutations were identified in three other subjects by Sanger sequencing. Using lymphoblastoid cell lines (LCLs) derived from the subjects, aberrant splicing was confirmed in two, and protein expression was observed to be severely impaired in all five. WDR45 encodes WD-repeat domain 45 (WDR45). WDR45 (also known as WIPI4) is one of the four mammalian homologs of yeast Atg18, which has an important role in autophagy. Lower autophagic activity and accumulation of aberrant early autophagic structures were demonstrated in the LCLs of the affected subjects. These findings provide direct evidence that an autophagy defect is indeed associated with a neurodegenerative disorder in humans.

Hemimegalencephaly accompanied by myoclonic status epilepticus.

We describe a boy (aged 2 years and 7 months) with hemimegalencephaly who developed myoclonic status, which improved dramatically after total callosotomy. The patient experienced seizures beginning at age 2 days, at which time electroencephalography revealed a right unilateral burst suppression pattern, and cranial magnetic resonance imaging revealed an enlarged right hemisphere. At age 8 months, habitual seizures increased to more than daily frequency. At the same time, myoclonic status epilepticus appeared with frequent erratic, partial, massive myoclonic seizures and clouding of consciousness. These signs were accompanied by diffuse spike and spike-wave patterns on electroencephalography, indicating myoclonic status in nonprogressive encephalopathy. Total callosotomy performed at age 10 months resulted in the complete disappearance of myoclonic status and prominent decrease in habitual seizures. This description of hemimegalencephaly is the first, to our knowledge, in which total callosotomy alleviated myoclonic status epilepticus. Although the mechanism of myoclonic status epilepticus remains unknown, our results suggest that cortico-cortical pathways are involved in this type of myoclonic status.