Involvement of Cerebellum in Leigh Syndrome: Case report and review of literature
Publication date: Available online 19 May 2017 Source:Pediatric Neurology Author(s): Nitish Chourasia, Rahmat Adejumo, Rajan Patel, Mary Kay Koenig A 6 year old male with Leigh syndrome developed recurrent cerebellar involvement. The patient was diagnosed with Leigh syndrome at 2 years of age with bilateral basal ganglia lesions on brain magnetic resonance imaging (MRI). Genetic testing confirmed a diagnosis of Leigh syndrome secondary to a homoplasmic mitochondrial DNA mutation (m.9176T>C). The patient experienced regressive episodes (ages 5, and 6 years). All the regressive episodes had a similar presentation with worsening of baseline ataxia and dysarthria. The first episode mimicked infectious cerebellitis, with elevated cerebral spinal fluid (CSF) protein and white blood cell count. No organisms were isolated from the CSF/blood during any of the regressive episodes. Brain MRI consistently showed cerebellar lesions, however cerebellar spectroscopy during the second episode found: an elevated lactate peak, a decrease of the N-acetylaspartate peak, and elevation of the choline peak; consistent with an acute exacerbation of Leigh syndrome. We therefore hypothesize that, although rare, Leigh syndrome can present primarily with involvement of the cerebellum and should be considered in the differential diagnosis for acute cerebellitis.
Dexamethasone, IVIg, and Rituximab Combination Immunotherapy for Pediatric Opsoclonus-Myoclonus Syndrome
Publication date: Available online 19 May 2017 Source:Pediatric Neurology Author(s): Michael R. Pranzatelli, Elizabeth D. Tate BackgroundAlthough pulse-dose dexamethasone is increasingly favored for treating pediatric opsoclonus-myoclonus syndrome (OMS), and multimodal immunotherapy is associated with improved clinical response, there have been no neuroimmunological studies of dexamethasone-based multimodal disease-modifying therapy.MethodsIn this observational retrospective study, 19 children with OMS (with or without associated neuroblastoma) underwent multi-biomarker evaluation for neuroinflammation. Nine of varying OMS severity, duration, and treatment status were treated empirically with pulse dexamethasone, IVIg, and rituximab combination immunotherapy (DEXIR-CI). Another 10 children on dexamethasone alone or with IVIg at initial evaluation only provided a comparison group. Motor severity (Total Score) was scored blinded from videotapes using the validated OMS Evaluation Scale.ResultsDEXIR-CI was associated with a 69% reduction in group Total Score (P = 0.004), and was well-tolerated clinically. Patients given the dexamethasone combination exhibited significantly lowered B cell frequencies in CSF (-94%) and blood (-76%), normalizing the CSF B cell percentage. The number of patients with positive inflammatory markers dropped 87% (P = 0.002), as did the number of markers. CSF OCB were positive in 4/9 pre- but 0/6 post-treatment. In the comparison group, partial response to dexamethasone alone or with IVIg was associated with multiple positive markers for neuroinflammation despite an average of 7 months of treatment.ConclusionsMulti-mechanistic dexamethasone-based combination immunotherapy increases the therapeutic armamentarium for OMS, providing a viable option for less severe cases. Partial response to dexamethasone with or without IVIg is indicative of ongoing neuroinflammation and should be treated promptly and accordingly.
Publication date: May 2017 Source:Pediatric Neurology, Volume 70 Author(s): Kenneth A. Myers, Ingrid E. Scheffer BackgroundDravet syndrome is a developmental and epileptic encephalopathy that occurs as a result of SCN1A mutations in more than 80% of affected individuals. The core clinical features of Dravet syndrome include febrile and afebrile seizures beginning before 12 months; multiple seizure types, usually medically refractory, including hemiclonic, generalized tonic-clonic, focal impaired awareness, myoclonic, and absence seizures; status epilepticus; and normal early development with plateau or regression by age two years. Myoclonic absence seizures have not previously been described.Patient descriptionThis 20-year-old man had infantile-onset epilepsy with the classical clinical features of Dravet syndrome and a de novo A1326P SCN1A mutation. By five years of age, photosensitive myoclonic absence seizures had become his dominant seizure type, occurring up to 20 times per day.ResultsThe seizures were refractory to multiple antiepileptic medications and a vagus nerve stimulator.ConclusionsAlthough photosensitivity is well recognized in Dravet syndrome, myoclonic absence seizures have not been previously reported. This rare seizure type may be underreported in Dravet syndrome, as the myoclonic features may be subtle and can be missed if thorough history taking and video recordings are not available.
Barriers to Genetic Testing for Pediatric Medicaid Beneficiaries with Epilepsy
Publication date: Available online 20 April 2017 Source:Pediatric Neurology Author(s): Eric J. Kutscher, Sucheta Joshi, Anup D. Patel, Baria Hafeez, Zachary M. Grinspan ObjectiveChildren with public insurance (Medicaid) have increased barriers to specialty care in the United States. For children with epilepsy, the relationship between public insurance and barriers to genetic testing is understudied.MethodsWe surveyed a sample of US child neurology clinicians. We performed quantitative and qualitative analysis of responses.ResultsThere were 302 responses (of 1982 surveyed; response rate 15%) from clinicians from 46 states, the District of Columbia, and Puerto Rico, including board-certified child neurologists (82%), resident physicians (6%), nurses (3%), and nurse practitioners (3%). More clinicians felt it was more difficult to get genetic testing for patients with Medicaid insurance compared to commercial insurance, (43% vs. 12%, p<0.05), though many felt it was about the same degree of difficulty (25%) or were not sure (20%). Increased availability of testing was associated with less complex testing (p<0.001), in-house testing (p<0.001), and no pre-authorization requirements (p<0.001). Qualitative responses described barriers related to cost, clinician familiarity and comfort, commercial laboratories, healthcare organization, payer, and patient concerns. Descriptions of facilitators included lowered cost, availability of clinical genetics expertise, clinician knowledge, commercial laboratory assistance, healthcare organizational changes, improved payer coverage, and increased interest by parents.Significance.Pediatric Medicaid beneficiaries with epilepsy have barriers to genetic testing, compared to children with commercial insurance, particularly for more advanced testing. Potential strategies to improve access include broader coverage, lower co-pays, increased capacity for testing outside of specialty labs, fewer pre-authorization requirements, improved clinician education, ongoing development and dissemination of guidelines, improved availability of clinical genetics services, and continued assistance programs from commercial laboratories.
The Use of Natalizumab in Pediatric Patients With Active Relapsing Multiple Sclerosis: A Prospective Study
Publication date: May 2017 Source:Pediatric Neurology, Volume 70 Author(s): Raed Alroughani, Samar Farouk Ahmed, Raed Behbehani, Jasem Al-Hashel BackgroundPediatric multiple sclerosis (MS) has been increasingly recognized. In the absence of approved disease-modifying therapies (DMTs) for pediatric patients, clinicians resort to data extrapolated from clinical trials conducted in adults with MS. The objective of this article was to study the effectiveness and safety of natalizumab in with pediatric MS.MethodsPatients with pediatric MS (aged less than 18 years) who had been treated with natalizumab were followed up prospectively as part of the national MS registry. Data of relapsing patients who had at least a one-year follow-up were analyzed. The primary outcome measure was the annual relapse rate after natalizumab treatment. Secondary outcomes measures included the mean change in disease progression measured by the expanded disability status scale and the proportion of patients with radiologic activity (gadolinium-enhancing or new T2 lesions) at the last follow-up visit.ResultsThirty-two patients with pediatric MS had been treated with natalizumab for at least 12 months, of whom 72% were females. The mean age at onset and disease duration were 14.9 ± 2.6 and 5.1 ± 3.1 years, respectively. Most patients (n = 21, 66%) had breakthrough disease on first-line disease-modifying therapies. The mean number of natalizumab infusions was 34.5 ± 18. The annual relapse rate was significantly reduced (1.66 ± 0.5 vs 0.06 ± 0.25; P < 0.001), whereas the mean expanded disability status score improved (3.3 ± 1.3 vs 2.2 ± 1.0; P < 0.001) at the last follow-up visits. The proportion of patients with magnetic resonance imaging activity was significantly reduced (93.8% versus 12.5%; P < 0.001). No major adverse events were observed.ConclusionIn our pediatric MS cohort with aggressive or breakthrough disease, treatment with natalizumab was effective in reducing clinical and radiologic disease activity. Natalizumab has a similar clinical efficacy and safety profile as in adult MS.