Fifty-nine acute flaccid myelitis cases were reported nationwide, coincident with enterovirus D68 (EV-D68) outbreak from August to December 2015. Strong temporal association was noted, and EV-D68 was detected from some cerebrospinal fluid and blood specimens. Antiganglioside antibodies were identified in some patients, and prognostic factors were analyzed.

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.

Bearden et al 1 reported an impressive antiepileptic effect of quinidine on 1 patient initiated at 25 months with KCNT1 (c.1283G>A; p.Arg428Gly, R428Q) mutation diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). R428Q was proven to be a gain-of-function pathogenic KCNT1 mutation, with an increase of current observed in electrophysiological study. 2 The reported patient was completely seizure free and showed improved psychomotor development. Due to the promising effect, we started the therapy on an unclassified early onset epileptic encephalopathy patient who had the same R428Q mutation.The patient is currently a 6-year-old male who was born at term with no family history of neurologic disorders. He was brought to us at 6 weeks of life with seizures characterized by a brief episode of staring and right hemiclonic seizures. Interictal electroencephalogram (EEG) showed multifocal sharp waves, and ictal EEG at 3 months displayed rhythmic delta-wave activity in bilateral occipital areas. Intracranial magnetic resonance imaging was normal at 1 month. At 4 years, whole exome sequencing revealed a heterozygous de novo KCNT1 R428Q mutation by a previously published method (Patient 11). 3Seizure control was refractory to multiple antiepileptic drugs, with seizure frequency peaking at 200 times/day. Ketogenic diet and vagal nerve stimulation reduced the seizure frequency to half. He was bedridden with poor neurodevelopment. Quinidine therapy was started at 5 years. The dose was titrated slowly, adjusted by monitoring the trough serum levels of quinidine at the range of 1.5 to 3.0 lg/ml. The patient was monitored for side effects, and no major adverse event was noted. Frequency of daily seizures was recorded, with monthly seizure frequency before and after quinidine therapy presented in the Figure. Contrary to expectations, quinidine was ineffective in seizure reduction. Seizure frequency per month after quinidine therapy was 103 6 27.7, compared to 106 6 13.3 for the same period before.In a recent literature concerning KCNT1-positive epilepsies, whereas quinidine showed 80% seizure reduction in one 3-year-old EIMFS patient (K629N), it was ineffective in an 11-year-old patient with unclassified epilepsy (Y796H).4 Therapy initiation at a later age and electroclinical syndrome other than EIFMS are possible reasons for poor response to quinidine in our case. Earlier FIGURE: Seizure frequency per month before and after quinidine therapy for a period of 8 months is presented. Seizure frequency was documented by reviewing the patient's daily seizure calendar, kept reliably by the patient's family. Quinidine therapy was started on X month with slow titration. Quinidine dose used (mg/kg/day) is shown in a line graph; the maximum dosage used was 73mg/kg/day. Therapeutic drug monitoring of quinidine was performed, and the trough serum levels were adjusted between 1.5 and 3.0 lg/ml (not shown). Effective seizure reduction compared to the same period before therapy was not observed.502 V C 2016 American Neurologic...

Next-generation sequencing (NGS) is widely used for the detection of disease-causing nucleotide variants. The challenges associated with detecting copy number variants (CNVs) using NGS analysis have been reported previously. Disease-related exome panels such as Illumina TruSight One are more cost-effective than whole-exome sequencing (WES) because of their selective target regions (~21% of the WES). In this study, CNVs were analyzed using data extracted through a disease-related exome panel analysis and the eXome Hidden Markov Model (XHMM). Samples from 61 patients with undiagnosed developmental delays and 52 healthy parents were included in this study. In the preliminary study to validate the constructed XHMM system (microarray-first approach), 34 patients who had previously been analyzed by chromosomal microarray testing were used. Among the five CNVs larger than 200 kb that were considered as non-pathogenic CNVs and were used as positive controls, four CNVs was successfully detected. The system was subsequently used to analyze different samples from 27 patients (NGS-first approach); 2 of these patients were successfully diagnosed as having pathogenic CNVs (an unbalanced translocation der(5)t(5;14) and a 16p11.2 duplication). These diagnoses were re-confirmed by chromosomal microarray testing and/or fluorescence in situ hybridization. The NGS-first approach generated no false-negative or false-positive results for pathogenic CNVs, indicating its high sensitivity and specificity in detecting pathogenic CNVs. The results of this study show the possible clinical utility of pathogenic CNV screening using disease-related exome panel analysis and XHMM.

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