Quantitative analysis of myokymic discharges in radiation versus nonradiation cases.

INTRODUCTION: Myokymic discharges are classically associated with nerve injury from prior radiation but may occur in other neuromuscular disorders. Using quantitative analysis we aimed to identify the spectrum of conditions in which myokymic discharges are present and determine if there are electrophysiological features that distinguish postradiation from nonradiation causes of myokymia. METHODS: We reviewed the clinical history of all patients examined in our electromyography labs with myokymic discharges recorded from June 2017 to February 2020. Quantitative analysis of each myokymic discharge was performed using a custom MATLAB script, assessing features such as burst frequency, spikes per burst, and burst regularity. RESULTS: Eighty-eight distinct myokymic discharges (70 patients) were analyzed: 51 postradiation recordings from 35 patients and 37 recordings from 35 nonradiation patients. The diagnostic spectrum of nonradiation cases was diverse, with common causes being median neuropathy (n = 8), cervical (n = 7), and lumbar (n = 5) radiculopathy, and motor neuron disease (n = 5). On quantitative analysis, postradiation myokymia had an increased burst-to-silence ratio (median, 0.29; nonradiation, 0.08) and greater peak number (median, 15; nonradiation, 7). Except for one patient with hereditary peripheral nerve hyperexcitability, all patients who had two or more muscles demonstrating myokymic discharges belonged to postradiation group. CONCLUSIONS: Myokymic discharges can be seen in diverse neuromuscular conditions; most common in our cohort was chronic median neuropathy. Postradiation myokymia appears to have distinguishing morphological features when quantitatively analyzed compared with nonradiation cases.

Iron Deficiency and Its Role in Sleep Disruption in Patients With Angelman Syndrome.

OBJECTIVE: To determine if Angelman syndrome patients with sleep complaints have an increased risk of iron deficiency, and if iron therapy improves their sleep difficulties. BACKGROUND: About two-thirds of Angelman syndrome patients experience sleep difficulties, which are likely multifactorial. Because iron deficiency can contribute toward restlessness in sleep, we investigated whether it might be a contributing factor in this special population. METHODS: This retrospective study involved medical record review of Angelman syndrome patients <18 years old who had attended our multidisciplinary Angelman syndrome clinic and had sleep complaints. Serum ferritin levels were compared to age- and sex-matched controls. Sleep history and nocturnal polysomnogram findings of the Angelman syndrome patients were also characterized. RESULTS: Nineteen Angelman syndrome patients (9 female, mean age 6.2±4.4 years) were identified. All 19 reported sleep difficulties. The mean serum ferritin level was 19.9±8.5 µg/L, while that in controls was 27.8±17.8 µg/L (P value .13). The odds ratio of iron deficiency in Angelman syndrome compared to controls was 4.17 (95% confidence interval 1.23-14.10), using normal serum ferritin level of 24 µg/L based on literature. Fifteen Angelman syndrome patients underwent nocturnal polysomnogram with 9/15 showing an elevated periodic limb movement index (overall mean 9.8±10.4). Seventeen of 19 received iron therapy. Twelve had follow-up after iron therapy, with parents reporting improved sleep quality. Eight had serum ferritin levels rechecked after iron therapy, showing a mean increase of 24±5.1 µg/L. CONCLUSIONS: Sleep difficulties in Angelman syndrome, though multifactorial, may in part be related to iron deficiency. Treatment with iron improved sleep to a modest degree in this population.

Long-term incidence of glioma in Olmsted County, Minnesota, and disparities in postglioma survival rate: a population-based study.

BACKGROUND: We assessed glioma incidence and disparities in postglioma survival rate in the Olmsted County, Minnesota, population. METHODS: This population-based study assessed the incidence of pathologically confirmed primary gliomas between January 1, 1995, and December 31, 2014. Age- and sex-adjusted incidence rates per 100 000 person-years were calculated and standardized to the US white 2010 population. We compared incidence trends of glioma during our study period with previously published Olmsted County data from 1950 to 1990. We assessed postglioma survival rates among individuals with different socioeconomic status (SES), which was measured by a validated individual HOUsing-based SES index (HOUSES). RESULTS: We identified 135 incident glioma cases (93% white) with 20 pediatric (50% female) and 115 adult cases (44% female). Overall incidence rate during our study period, 5.51 per 100 000 person-years (95% CI: 4.56-6.46), showed no significant changes and was similar to that seen in 1950 to 1990, 5.5 per 100 000 person-years. The incidence of pediatric (age < 20 years) glioma was 2.49 (95% CI: 1.40-3.58), whereas adult glioma incidence was 6.47 (95% CI: 5.26-7.67). Among those with grade II to IV gliomas, individuals with lower SES (< median HOUSES) had significantly lower 5-year survival rates compared to those with higher SES, adjusted hazard ratio 1.61 (95% CI: 1.01-2.85). CONCLUSION: In a well-defined North American population, long-term glioma incidence appears stable since 1950. Significant socioeconomic disparities exist for postglioma survival.

Establishing Normal Values for F-Wave Latencies in Diagnosing Peripheral Neuropathies for the Pediatric Population.

PURPOSE: We present a unique technique applying F-wave latencies to assist in the diagnosis of peripheral neuropathy within the pediatric age group. METHODS: We calculated an F-wave estimated deviance adjusted for limb length measurements, distal motor conduction velocity, and distal motor latencies. We compared the F-wave estimated deviance from the normal subjects with those with peripheral neuropathy (both axonal and demyelinating) to establish diagnostic accuracy in pediatric patients. RESULTS: The normal range for the F-wave estimated deviance in the upper limb was -1 to +6 ms and in the lower limb was -8 to +5 ms. When compared with 82 subjects with peripheral neuropathy, there was a significant difference between the normal subjects and those with neuropathy (P values between 0.002 and 0.0005 for each of the individual nerves tested). CONCLUSIONS: The F-wave estimated deviance is independent of age and can be accurately applied to the electrodiagnostic testing of pediatric patients with suspected neuropathy.

Asthma and risk of glioma: a population-based case-control study.

OBJECTIVES: Literature suggests an inconsistent, but largely inverse, association between asthma and risk of glioma, which is primarily due to methodological inconsistency in sampling frame and ascertainment of asthma. The objective of the study was to clarify the association between asthma and risk of glioma by minimising methodological biases (eg, recall and detection bias). DESIGN: A population-based case-control study. SETTING: General population in Olmsted County, Minnesota, USA. PARTICIPANTS: All eligible biopsy-proven incident glioma cases (1995-2014) and two sets of controls among residents matched to age and sex (first set: community controls without glioma; second set: MRI-negative controls from the same community). METHODS: The predetermined asthma criteria via medical record review were applied to ascertain asthma status of cases and controls. History of asthma prior to index date was compared between glioma cases and their matched controls using conditional logistic regression models. Propensity score for asthma status was adjusted for multivariate analysis. RESULTS: We enrolled 135 glioma cases (median age at index date: 53 years) and 270 controls. Of the cases, 21 had a history of asthma (16%), compared with 36 of MRI controls (27%) (OR (95% CI) 0.48 (0.26 to 0.91), p=0.03). With MRI controls, an inverse association between asthma and risk of glioma persisted after adjusting for the propensity score for asthma status, but did not reach statistical significance probably due to the lack of statistical power (OR (95% CI) 0.48 (0.21 to 1.09); p=0.08). Based on comparison of characteristics of controls and cases, community controls seem to be more susceptible to a detection bias. CONCLUSIONS: While differential detection might account for the association between asthma and risk of glioma, asthma may potentially pose a protective effect on risk of glioma. Our study results need to be replicated by a larger study.

Nerve conduction normal values for electrodiagnosis in pediatric patients.

INTRODUCTION: Existing normal value references for pediatric nerve conduction studies (NCS) are based on limited sample sizes with uncertain reliability, suggesting a need for better normative data. METHODS: Electronic medical records were reviewed for pediatric patients (0 to <18 years) with normal findings on electromyography and NCS during the period from January 1, 1997 through September 20, 2017. Electrodiagnostic and demographic data were collected. Gaussian and descriptive statistics were used to establish normal values by age group. RESULTS: In this study we analyzed 1,918 normal NCS on 1,849 unique pediatric patients. Patients were stratified by age: 0 to <1 month; 1 to <6 months; 6 to <12 months; 12 to <24 months; 2 to <3 years; 3 to <4 years; 4 to <5 years; 5 to <10 years; 10 to <15 years; and 15 to <18 years. Normal reference ranges for amplitude, conduction velocity, and distal latency were established for each age group for 4 motor and 4 sensory nerves. DISCUSSION: The large sample size of this study provides reliable reference values for interpreting pediatric NCS. Muscle Nerve 60: 155-160, 2019.

De Novo DNM1L Variant in a Teenager With Progressive Paroxysmal Dystonia and Lethal Super-refractory Myoclonic Status Epilepticus.

BACKGROUND: The dynamin 1-like gene ( DNM1L) encodes a GTPase that mediates mitochondrial and peroxisomal fission and fusion. We report a new clinical presentation associated with a DNM1L pathogenic variant and review the literature. RESULTS: A 13-year-old boy with mild developmental delays and paroxysmal dystonia presented acutely with multifocal myoclonic super-refractory status epilepticus. Despite sustained and aggressive treatment, seizures persisted and care was ultimately withdrawn in the context of extensive global cortical atrophy. Rapid trio-whole exome sequencing revealed a de novo heterozygous c.1207C>T (p.R403C) pathogenic variant in DNM1L. Immunofluorescence staining of fibroblast mitochondria revealed abnormally elongated and tubular morphology. CONCLUSIONS: This case highlights the diagnostic importance of rapid whole exome sequencing within a critical care setting and reveals the expanding phenotypic spectrum associated with DNM1L variants. This now includes progressive paroxysmal dystonia and adolescent-onset super-refractory myoclonic status epilepticus contributing to strikingly rapid and progressive cortical atrophy and death.

Clinical and genetic characterization of AP4B1-associated SPG47.

The hereditary spastic paraplegias (HSPs) are a heterogeneous group of disorders characterized by degeneration of the corticospinal and spinocerebellar tracts leading to progressive spasticity. One subtype, spastic paraplegia type 47 (SPG47 or HSP-AP4B1), is due to bi-allelic loss-of-function mutations in the AP4B1 gene. AP4B1 is a subunit of the adapter protein complex 4 (AP-4), a heterotetrameric protein complex that regulates the transport of membrane proteins. Since 2011, 11 individuals from six families with AP4B1 mutations have been reported, nine of whom had homozygous mutations and were from consanguineous families. Here we report eight patients with AP4B1-associated SPG47, the majority born to non-consanguineous parents and carrying compound heterozygous mutations. Core clinical features in this cohort and previously published patients include neonatal hypotonia that progresses to spasticity, early onset developmental delay with prominent motor delay and severely impaired or absent speech development, episodes of stereotypic laughter, seizures including frequent febrile seizures, thinning of the corpus callosum, and delayed myelination/white matter loss. Given that some of the features of AP-4 deficiency overlap with those of cerebral palsy, and the discovery of the disorder in non-consanguineous populations, we believe that AP-4 deficiency may be more common than previously appreciated.