Gait is not Affected by Hemispherotomy-Case Report from Two Children.

In children with therapy refractory epilepsy, the functional disconnection of one hemisphere (hemispherotomy) may be considered as a treatment option. The visual field defects and hand function effects associated with the procedure have been extensively studied. However, the effect of the hemispherotomy on gait pattern has thus far only been analyzed qualitatively, and there is limited quantitative data. At the Children's Hospital, we regularly perform standardized quantitative gait analysis studies and care for children with complex epilepsies. During the standard routine of care for two children with structural therapy refractory epilepsy, gait analysis was performed prior to and after hemispherotomy. Both patients had prenatal ischemic brain lesions, had developed severe epilepsy during the first 3 years of life, and were treated with the hemispherotomy at about 7 years of age. Interestingly, one patient did not show any changes in gait pattern, while for the other patient, differences could be observed by means of three-dimensional gait analysis. However, greater deviations to controls postoperatively may also be related to day-to-day variability.

Epidemiology, Clinical Features, and Use of Early Supportive Measures in PHACE Syndrome: A European Multinational Observational Study.

BACKGROUND: PHACE syndrome is a rare inborn condition characterized by large facial hemangiomas and variable malformations of the arterial system, heart, central nervous system, and eyes. According to Orphanet estimates, the prevalence is <1.0 per million. Data from Europe are limited to small case series, and there are no population-based data available. OBJECTIVES: We conducted the present study to provide population-based estimates of the disease prevalence of PHACE syndrome in children in Germany, Switzerland, and Austria. We compared these first systematic data on PHACE syndrome from Europe to published data from the PHACE Syndrome International Clinical Registry and Genetic Repository (USA). Clinical features in our cohort with PHACE syndrome were assessed in detail, including the need for early supportive measures. METHODS: We used a population-based approach by means of a previously well-established network of child neurologists from Germany, Switzerland, and Austria ("ESNEK") to identify potential patients. The patients' guardians and child neurologists were asked to fill in questionnaires developed in collaboration with the International PHACE Registry. RESULTS: We identified 19 patients with PHACE syndrome. Estimated prevalence rates were 6.5 per million in Switzerland, 0.59 per million in Germany, and 0.65 per million in Austria. A subset of 10 patients from Germany and Switzerland participated in our study, providing detailed clinical assessment (median age: 2.5 years; 9 females, 1 male). Cerebrovascular involvement was frequent (80%). Facial hemangioma extent correlated significantly with the number of organs involved (p = 0.011). In 9 out of 10 patients, facial hemangiomas were treated successfully with oral propranolol. Baseline demographic data as well as the rate of cerebrovascular and cardiovascular anomalies were in line with those from the US International PHACE Registry and other published PHACE cohorts. CONCLUSIONS: Our study provides population-based estimates for PHACE syndrome in 3 German-speaking countries. The data from Switzerland indicate that PHACE syndrome may be more prevalent than demonstrated by previous reports. Underreporting of PHACE syndrome in Germany and Austria likely accounts for the differences in prevalence rates. The clinical observation of a potential association between the size of facial hemangioma and extent of organ involvement warrants further investigation.

First Clinical Experience with Anti-myelin Oligodendrocyte Glycoprotein Antibody-Positive Optic Neuritis.

BACKGROUND: Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been consistently found in a range of demyelinating disorders. In this context, MOG-IgG-associated optic neuritis (ON) has been suggested as a new subset of optic neuropathy. However, clinical manifestations and distinctive characteristics have only rarely been described. PATIENTS AND METHODS: A retrospective case series of three patients with MOG-IgG-associated ON. Clinical morphological features using imaging techniques are presented. RESULTS: Three patients (8-year-old boy, 28-year-old female, 48-year-old male) were included. An 8-year-old boy suffered from a bilateral ON with severe visual loss. The best-corrected visual acuity (BCVA) was 0.05 in the right eye and finger counting in the left eye. The patient had a previous episode of acute disseminated encephalomyelitis (ADEM) with a right abducens nerve palsy. Visual acuity recovered after repeated cycles of intravenous methylprednisolone pulse therapy and 10 cycles of plasma exchange. During the last follow-up, BCVA was 0.9 in the right eye and 0.8 in the left eye. A 28-year-old female presented with a bilateral ON. Her BCVA was 0.5 in the right eye and 0.8 in the left eye. She fully recovered with pulse methylprednisolone therapy (1000 mg/d) with tapering after the second cycle and had a BCVA of 1.0 during the last follow-up visit. A 48-year-old male suffered from a relapsing bilateral ON. At first presentation, BCVA was 0.1 in the right eye and finger counting in the left eye. BCVA fully recovered after each pulse therapy with intravenous methylprednisolone (two cycles). Since the first relapse, the patient has been receiving long-term immunosuppression with rituximab. Despite rituximab and low-dose oral prednisone, the patient had another relapse with a left ON. After a third cycle with intravenous methylprednisolone, he partially recovered. BCVA at last follow-up was 1.0 in the right and 0.8 in the left eye. CONCLUSIONS: MOG-IgG antibodies have been identified in different acquired demyelinating syndromes. The patients reported had an ADEM followed by bilateral ON, an isolated bilateral ON, and a relapsing bilateral ON. Individual treatment strategies led to substantial visual recovery in all patients. We recommend inclusion of MOG-IgG antibodies in the diagnostic workup at least after the first recurrence of ON since they can serve as a diagnostic and potential prognostic tool and might lead to specific therapeutic recommendations.

Correlation between age and the sciatic nerve diameter in the first 2 years of life: A high-resolution ultrasound study.

AIM: To investigate the maturation of the peripheral nervous system by analyzing the cross-sectional area of the sciatic nerve during the first 2 years of life. METHODS: The sciatic nerve was examined by high-resolution ultrasound imaging in 52 children aged 0 days to 10 years, 45 of whom were younger than 2 years. The correlation between the cross-sectional area of the nerve and the age was statistically tested. A logarithmic regression analysis was performed to develop a logarithmic growth model of the cross-sectional area. RESULTS: There is a highly significant correlation between the age and the cross-sectional area of the sciatic nerve. The growth rate can well be described by a logarithmic model. INTERPRETATION: Based on the literature on the maturation of the median nerve and nerve roots and the findings of the present study, we conclude that both the proximal and the distal parts of the nerves of the peripheral nervous system increase simultaneously. WHAT THIS PAPER ADDS: Normative values for the size of the sciatic nerve in children.

Slowing of Peripheral Nerve Conduction Velocity in Children and Adolescents With Type 1 Diabetes Is Predicted by Glucose Fluctuations.

Nerve conduction velocity (NCV) abnormalities are the forerunners of diabetic peripheral neuropathy (DPN). Therefore, this study aimed to analyze the effect of glucose profile quality on NCV in children and young adults with type 1 diabetes. Fifty-three children age 5 to 23 years with type 1 diabetes were recruited to participate in the study, which was conducted prospectively at the Children's Hospital of Eastern Switzerland from 2016 to 2022. Glycemic targets were recorded, and a cross-sectional nerve conduction study analyzing the peroneal, tibial, median motor, and median sensory nerves was performed. Data were compared with those of a control group of 50 healthy children. In the age- and height-matched diabetes subgroup aged 10-16 years, all four nerves showed significantly slower NCV, most pronounced for the peroneal nerve. Because height has a retarding effect on peroneal NCV, NCV was adjusted for height (dNCV). Peroneal dNCV correlated negatively with long-term glycated hemoglobin and highly significantly with glucose variability. Because high glucose variability clearly increases the risk of neuropathy, together with but also independently of the mean glucose level, this aspect of glycemic control should be given more attention in the care of individuals with diabetes. ARTICLE HIGHLIGHTS: There is a strong need for the better identification of early subclinical manifestations of microvascular complications, such as diabetic peripheral neuropathy, in young individuals with diabetes. To identify peripheral neuropathy and contributing factors at an asymptomatic disease stage, and to exclude height as a known modifying factor, we performed association studies of height-adjusted nerve conduction velocity. We identified high glucose variability, especially the SD of mean glucose, as an unexpectedly strong predictor of slowed nerve conduction velocity. More attention should be paid to the goal of low glucose variability in the care of individuals with diabetes.

Functional MRI-guided probabilistic tractography of cortico-cortical and cortico-subcortical language networks in children.

In this study, we analyzed the structural connectivity of cortico-cortical and cortico-subcortical language networks in healthy children, using probabilistic tractography based on high angular resolution diffusion imaging. In addition to anatomically defining seed and target regions for tractography, we used fMRI to target inferior frontal and superior temporal cortical language areas on an individual basis. Further, connectivity between these cortical and subcortical (thalamus, caudate nucleus) language regions was assessed. Overall, data from 15 children (8f) aged 8-17 years (mean age 12.1 ±3 years) could be included. A slight but non-significant trend towards leftward lateralization was found in the arcuate fasciculus/superior longitudinal fasciculus (AF/SLF) using anatomically defined masks (p>.05, Wilcoxon rank test), while the functionally-guided tractography showed a significant lateralization to the left (p<.01). Connectivity of the thalamus with language regions was strong but not lateralized. Connectivity of the caudate nucleus with inferior-frontal language regions was also symmetrical, while connectivity with superior-temporal language regions was strongly lateralized to the left (p<.01). To conclude, we could show that tracking the arcuate fasciculus/superior longitudinal fasciculus is possible using both anatomically and functionally-defined seed and target regions. With the latter approach, we could confirm the presence of structurally-lateralized cortico-cortical language networks already in children, and finally, we could demonstrate a strongly asymmetrical connectivity of the caudate nucleus with superior temporal language regions. Further research is necessary in order to assess the usability of such an approach to assess language dominance in children unable to participate in an active fMRI study.

Counter-movement jump characteristics in children with Charcot-Marie-Tooth type 1a disease.

BACKGROUND: Poor performance in sports, especially activities that require explosive movements, is a common reason for initial presentation of children with Charcot-Marie-Tooth type 1a (CMT1a) to the paediatric neuromuscular specialist. RESEARCH QUESTION: The aim of this descriptive, retrospective study was to analyse counter-movement jump characteristics in children with CMT1a in comparison to those in typically developing children (TDC). METHODS: This retrospective study included seven patients with CMT1a and 44 TDC from our data pool. All the participants performed counter-movement jumps, and jump height, peak force, time to peak force, average and peak rate of force development and net vertical impulse were then calculated. For statistical comparison by means of an independent Student's t-test, children with CMT1a were compared to seven sex- and age-matched TDC. Correlation coefficients were calculated to determine the relationship between the force-time variables and jump height. RESULTS: Peak force, net vertical impulse and jump height values in the CMT1a group were significantly lower than those in the TDC group. There were no between-group differences in the time to peak force or average and peak rate of force development. In terms of task symmetry, the correlation between the time-force curve of the left and right leg in the CMT1a group was reduced as compared with that in the TDC group. In both groups, among the parameters measured, there was a significant correlation between jump height and net vertical impulse. SIGNIFICANCE: This study showed that reduced jump performance in children with CMT1a, as demonstrated by decreased counter-movement jump height, was due to a reduced net impulse during this explosive movement task. This finding is critical for children with CMT1a and has to be considered in clinical management and activities of daily living (e.g. sports lessons in school).

Correlation of age and the diameter of the cervical nerve roots C5 and C6 during the first 2 years of life analyzed by high-resolution ultrasound imaging.

AIM: To analyze the increase in diameter of the nerve roots C5 and C6 in early childhood. METHODS: The nerve roots of 56 children aged 0 days to 10 years (47 younger than 2 years) were examined by high-resolution ultrasound imaging. The correlation of diameter and age was statistically tested and a logarithmic regression analysis was performed to develop a logarithmic growth model. RESULTS: The increase in nerve root diameter is greatest during the first 2 years of life and then the growth rate decreases steadily. The relationship between age and diameter follows a logarithmic curve (p < 10-8 ). INTERPRETATION: The main increase in the diameter of the nerve roots happens in the first 2 years of life. Comparing data from a previous study, our data also suggest that the maturation of the proximal part of the median nerve is comparable to the maturation of its distal segments. This suggests a synchronous maturation of the axons and myelin sheath for the whole extent of the nerve, from the radix to its very distal part. WHAT THIS PAPER ADDS: Normative values for the size of the cervical nerve roots C5 and C6; an insight into the maturation of the proximal parts of the peripheral nervous system; and the correlation between age and cervical root diameter.

Precision treatment of Singleton Merten syndrome with ruxolitinib: a case report.

BACKGROUND: Singleton-Merten syndrome 1 (SGMRT1) is a rare type I interferonopathy caused by heterozygous mutations in the IFIH1 gene. IFIH1 encodes the pattern recognition receptor MDA5 which senses viral dsRNA and activates antiviral type I interferon (IFN) signaling. In SGMRT1, IFIH1 mutations confer a gain-of-function which causes overactivation of type I interferon (IFN) signaling leading to autoinflammation. CASE PRESENTATION: We report the case of a nine year old child who initially presented with a slowly progressive decline of gross motor skill development and muscular weakness. At the age of five years, he developed osteoporosis, acro-osteolysis, alveolar bone loss and severe psoriasis. Whole exome sequencing revealed a pathogenic de novo IFIH1 mutation, confirming the diagnosis of SGMRT1. Consistent with constitutive type I interferon activation, patient blood cells exhibited a strong IFN signature as shown by marked up-regulation of IFN-stimulated genes. The patient was started on the Janus kinase (JAK) inhibitor, ruxolitinib, which inhibits signaling at the IFN-α/ß receptor. Within days of treatment, psoriatic skin lesions resolved completely and the IFN signature normalized. Therapeutic efficacy was sustained and over the course muscular weakness, osteopenia and growth also improved. CONCLUSIONS: JAK inhibition represents a valuable therapeutic option for patients with SGMRT1. Our findings also highlight the potential of a patient-tailored therapeutic approach based on pathogenetic insight.

Optically pumped magnetometers detect altered maximal muscle activity in neuromuscular disease.

Optically pumped magnetometers (OPM) are quantum sensors that enable the contactless, non-invasive measurement of biomagnetic muscle signals, i.e., magnetomyography (MMG). Due to the contactless recording, OPM-MMG might be preferable to standard electromyography (EMG) for patients with neuromuscular diseases, particularly when repetitive recordings for diagnostic and therapeutic monitoring are mandatory. OPM-MMG studies have focused on recording physiological muscle activity in healthy individuals, whereas research on neuromuscular patients with pathological altered muscle activity is non-existent. Here, we report a proof-of-principle study on the application of OPM-MMG in patients with neuromuscular diseases. Specifically, we compare the muscular activity during maximal isometric contraction of the left rectus femoris muscle in three neuromuscular patients with severe (Transthyretin Amyloidosis in combination with Pompe's disease), mild (Charcot-Marie-Tooth disease, type 2), and without neurogenic, but myogenic, damage (Myotonia Congenita). Seven healthy young participants served as the control group. As expected, and confirmed by using simultaneous surface electromyography (sEMG), a time-series analysis revealed a dispersed interference pattern during maximal contraction with high amplitudes. Furthermore, both patients with neurogenic damage (ATTR and CMT2) showed a reduced variability of the MMG signal, quantified as the signal standard deviation of the main component of the frequency spectrum, highlighting the reduced possibility of motor unit recruitment due to the loss of motor neurons. Our results show that recording pathologically altered voluntary muscle activity with OPM-MMG is possible, paving the way for the potential use of OPM-MMG in larger studies to explore the potential benefits in clinical neurophysiology.

Temporal Dynamics of MOG Antibodies in Children With Acquired Demyelinating Syndrome.

BACKGROUND AND OBJECTIVE: The spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) comprises monophasic diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), and transverse myelitis and relapsing courses of these presentations. Persistently high MOG antibodies (MOG immunoglobulin G [IgG]) are found in patients with a relapsing disease course. Prognostic factors to determine the clinical course of children with a first MOGAD are still lacking. The objective of the study is to assess the clinical and laboratory prognostic parameters for a risk of relapse and the temporal dynamics of MOG-IgG titers in children with MOGAD in correlation with clinical presentation and disease course. METHODS: In this prospective multicenter hospital-based study, children with a first demyelinating attack and complete data set comprising clinical and radiologic findings, MOG-IgG titer at onset, and clinical and serologic follow-up data were included. Serum samples were analyzed by live cell-based assay, and a titer level of ≥1:160 was classified as MOG-IgG-positive. RESULTS: One hundred sixteen children (f:m = 57:59) with MOGAD were included and initially diagnosed with ADEM (n = 59), unilateral ON (n = 12), bilateral ON (n = 16), myelitis (n = 6), neuromyelitis optica spectrum disorder (n = 8) or encephalitis (n = 6). The median follow-up time was 3 years in monophasic and 5 years in relapsing patients. There was no significant association between disease course and MOG-IgG titers at onset, sex, age at presentation, or clinical phenotype. Seroconversion to MOG-IgG-negative within 2 years of the initial event showed a significant risk reduction for a relapsing disease course. Forty-two/one hundred sixteen patients (monophasic n = 26, relapsing n = 16) had serial MOG-IgG testing in years 1 and 2 after the initial event. In contrast to relapsing patients, monophasic patients showed a significant decrease of MOG-IgG titers during the first and second years, often with seroconversion to negative titers. During the follow-up, MOG-IgG titers were persistently higher in relapsing than in monophasic patients. Decrease in MOG-IgG of ≥3 dilution steps after the first and second years was shown to be associated with a decreased risk of relapses. In our cohort, no patient experienced a relapse after seroconversion to MOG-IgG-negative. DISCUSSION: In this study, patients with declining MOG-IgG titers, particularly those with seroconversion to MOG-IgG-negative, are shown to have a significantly reduced relapse risk.

Robust subdivision of the thalamus in children based on probability distribution functions calculated from probabilistic tractography.

Virtually all information that enters the cortex must first pass through the thalamus. This prominent role has made the human thalamus a target for detailed imaging studies. It has previously been shown that probabilistic tractography together with cortical parcellation allowed subdivision of the thalamus into its constituent substructures. A new method is presented that allows the subdivision of the thalamus according to its cortical projection targets based on the assumption that any cortical region receives input from the thalamus and calculates the probability of connectivity distribution functions based on probabilistic tractography. The feasibility of the method was tested in a data set of 43 healthy children aged between 8 and 13 years. A thalamic parcellation pattern similar to that previously found in adults and children below the age of 2 years was obtained. However, no evidence for an age related change in cortical parcellation volumes were found in line with previously reported studies of thalamic volumes during development. Lower standard deviations were found for the two smallest projections, the sensory and occipital projection using the new method. Furthermore it was found, through comparison with a published thalamic atlas, that the method allowed the localization of the center of the different thalamic projection areas within an accuracy of 2 mm.

Optically pumped magnetometers disclose magnetic field components of the muscular action potential.

AIM: Aiming at analysing the signal conduction in muscular fibres, the spatio-temporal dynamics of the magnetic field generated by the propagating muscle action potential (MAP) is studied. METHOD: In this prospective, proof of principle study, the magnetic activity of the intrinsic foot muscle after electric stimulation of the tibial nerve was measured using optically pumped magnetometers (OPMs). A classical biophysical electric dipole model of the propagating MAP was implemented to model the source of the data. In order to account for radial currents of the muscular tubules system, a magnetic dipole oriented along the direction of the muscle was added. RESULTS: The signal profile generated by the activity of the intrinsic foot muscles was measured by four OPM devices. Three OPM sensors captured the spatio-temporal magnetic field pattern of the longitudinal intrinsic foot muscles. Changes of the activation pattern reflected the propagating muscular action potential along the muscle. A combined electric and magnetic dipole model could explain the recorded magnetic activity. INTERPRETATION: OPM devices allow for a new, non-invasive way to study MAP patterns. Since magnetic fields are less altered by the tissue surrounding the dipole source compared to electric activity, a precise analysis of the spatial characteristics and temporal dynamics of the MAP is possible. The classic electric dipole model explains major but not all aspects of the magnetic field. The field has longitudinal components generated by intrinsic structures of the muscle fibre. By understanding these magnetic components, new methods could be developed to analyse the muscular signal transduction pathway in greater detail. The approach has the potential to become a promising diagnostic tool in peripheral neurological motor impairments.

Investigation of the temporal and spatial dynamics of muscular action potentials through optically pumped magnetometers.

AIM: This study aims to simultaneously record the magnetic and electric components of the propagating muscular action potential. METHOD: A single-subject study of the monosynaptic stretch reflex of the musculus rectus femoris was performed; the magnetic field generated by the muscular activity was recorded in all three spatial directions by five optically pumped magnetometers. In addition, the electric field was recorded by four invasive fine-wire needle electrodes. The magnetic and electric fields were compared by modelling the muscular anatomy of the rectus femoris muscle and by simulating the corresponding magnetic field vectors. RESULTS: The magnetomyography (MMG) signal can reliably be recorded following the stimulation of the monosynaptic stretch reflex. The MMG signal shows several phases of activity inside the muscle, the first of which is the propagating muscular action potential. As predicted by the finite wire model, the magnetic field vectors of the propagating muscular action potential are generated by the current flowing along the muscle fiber. Based on the magnetic field vectors, it was possible to reconstruct the pinnation angle of the muscle fibers. The later magnetic field components are linked to the activation of the contractile apparatus. Interpretation MMG allows to analyze the muscle physiology from the propagating muscular action potential to the initiation of the contractile apparatus. At the same time, this methods reveals information about muscle fiber direction and extend. With the development of high-resolution magnetic cameras, that are based on OPM technology, it will be possible to image the function and structure of the biomagnetic field of any skeletal muscle with high precision. This method could be used both, in clinical medicine and also in sports science.

Etiology of Carpal Tunnel Syndrome in a Large Cohort of Children.

(1) Background: Carpal tunnel syndrome (CTS), a compressive mononeuropathy of the median nerve at the wrist, is rare in childhood and occurs most frequently due to secondary causes. (2) Methods: Medical history, electrodiagnostic findings, and imaging data of patients with CTS from two pediatric neuromuscular centers were analyzed retrospectively. The etiology of CTS was investigated and compared with the literature. (3) Results: We report on a cohort of 38 CTS patients (n = 22 females, n = 29 bilateral, mean age at diagnosis 9.8 years). Electrodiagnostic studies of all patients revealed slowing of the antidromic sensory or orthodromic mixed nerve conduction velocities across the carpal tunnel or lack of the sensory nerve action potential and/or prolonged distal motor latencies. Median nerve ultrasound was diagnostic for CTS and confirmed tumorous and vascular malformations. Etiology was secondary in most patients (n = 29; 76%), and mucopolysaccharidosis was the most frequent underlying condition (n = 14; 37%). Idiopathic CTS was rare in this pediatric cohort (n = 9; 24%). (4) Conclusion: Since CTS in childhood is predominantly caused by an underlying disorder, a thorough evaluation and search for a causative condition is recommended in this age group.

Optically pumped magnetometers reveal fasciculations non-invasively.

OBJECTIVE: This proof-of-principle-study evaluated the extent to which spontaneous activity (SA) of the muscle can be detected via non-invasive magnetomyography (MMG) with optically pumped magnetometers (OPM). METHODS: Five patients, who together exhibited all forms of SA (fibrillations, positive sharp waves, fasciculations, myotonic discharges, complex-repetitive discharges) with conventional needle electromyography (EMG), were studied by OPM-MMG and simultaneous surface EMG (sEMG) while at rest, during light muscle activation, and when a muscle stretch reflex was elicited. Three healthy subjects were measured as controls. SA was considered apparent in the OPM-MMG if a signal could be visually detected that corresponded in shape and frequency to the SA in the respective needle EMG. RESULTS: SA in the context of fasciculations could be detected in 2 of 5 patients by simultaneous OPM-MMG/sEMG. Other forms of SA could not be detected at rest, during light muscle activation, or after provocation of a muscle stretch reflex. CONCLUSIONS: Results show that fasciculations could be detected non-invasively via a new method (OPM). SIGNIFICANCE: We show that other forms of SA are not detectable with current OPM and propose necessary technical solutions to overcome this circumstance. Our results motivate to pursue OPM-MMG as a new clinical neurophysiological diagnostic.

Muscle Fatigue Revisited - Insights From Optically Pumped Magnetometers.

So far, surface electromyography (sEMG) has been the method of choice to detect and evaluate muscle fatigue. However, recent advancements in non-cryogenic quantum sensors, such as optically pumped magnetometers (OPMs), enable interesting possibilities to flexibly record biomagnetic signals. Yet, a magnetomyographic investigation of muscular fatigue is still missing. Here, we simultaneously used sEMG (4 surface electrode) and OPM-based magnetomyography (OPM-MMG, 4 sensors) to detect muscle fatigue during a 3 × 1-min isometric contractions of the left rectus femoris muscle in 7 healthy participants. Both signals exhibited the characteristic spectral compression distinctive for muscle fatigue. OPM-MMG and sEMG slope values, used to quantify the spectral compression of the signals, were positively correlated, displaying similarity between the techniques. Additionally, the analysis of the different components of the magnetic field vector enabled speculations regarding the propagation of the muscle action potentials (MAPs). Altogether these results show the feasibility of the magnetomyographic approach with OPMs and propose a potential alternative to sEMG for the study of muscle fatigue.

Change in cross-sectional area of the median nerve with age in neonates, infants and children analyzed by high-resolution ultrasound imaging.

AIM: To analyze age dependencies in the cross-sectional area (CSA) of the median nerve during early childhood. METHOD: A total of 43 participants (32 of whom were children younger than 2 years) were included in this cross-sectional study to analyze the age dependency of the CSA of the median nerve at three locations (wrist, forearm and upper arm) using high-resolution ultrasound images. RESULTS: A strong and highly significant correlation was found between age and CSA (p < 0.001). When plotted, the relationship followed a logarithmic curve (p < 0.001) with a growth rate that decreases with age. Based on the regression analysis, a temporally similar increase in CSA for all three locations was found. The nerve reaches 70% of its final CSA by 2 years of age at all three locations. INTERPRETATION: Similar to the nerve conduction speed, the increase in CSA is greatest during the first 2 years of life. Then, the rate gradually and synchronously slows at the proximal and distal locations. Measurement of the CSA in the clinical setting might offer a new method to assess the maturation of the nervous system in infants with minimal interference.

The Phenotypic Spectrum of PRRT2-Associated Paroxysmal Neurologic Disorders in Childhood.

Pathogenic variants in PRRT2, encoding the proline-rich transmembrane protein 2, have been associated with an evolving spectrum of paroxysmal neurologic disorders. Based on a cohort of children with PRRT2-related infantile epilepsy, this study aimed at delineating the broad clinical spectrum of PRRT2-associated phenotypes in these children and their relatives. Only a few recent larger cohort studies are on record and findings from single reports were not confirmed so far. We collected detailed genetic and phenotypic data of 40 previously unreported patients from 36 families. All patients had benign infantile epilepsy and harbored pathogenic variants in PRRT2 (core cohort). Clinical data of 62 family members were included, comprising a cohort of 102 individuals (extended cohort) with PRRT2-associated neurological disease. Additional phenotypes in the cohort of patients with benign sporadic and familial infantile epilepsy consist of movement disorders with paroxysmal kinesigenic dyskinesia in six patients, infantile-onset movement disorders in 2 of 40 individuals, and episodic ataxia after mild head trauma in one girl with bi-allelic variants in PRRT2. The same girl displayed a focal cortical dysplasia upon brain imaging. Familial hemiplegic migraine and migraine with aura were reported in nine families. A single individual developed epilepsy with continuous spikes and waves during sleep. In addition to known variants, we report the novel variant c.843G>T, p.(Trp281Cys) that co-segregated with benign infantile epilepsy and migraine in one family. Our study highlights the variability of clinical presentations of patients harboring pathogenic PRRT2 variants and expands the associated phenotypic spectrum.

Automated axon length quantification for populations of labelled neurons.

Virus-based methods for labelling populations of cortical neurons, when combined with cell-type specific recombinant promoters and techniques allowing temporal control of gene expression, provide neuroscience with new opportunities to examine the connectivity between brain regions and how this connectivity is modified by experience or disease. However, to take full advantage of these technical advances, it is necessary to develop new methods for quantification of the axonal projections revealed. Here we describe a method for quantitative analysis of axonal projection patterns emanating from populations of labelled cells, using transmitted light bright field microscopy. A single high resolution image of an area to be analysed is first acquired using mosaic extended focus image microscopy. This image is then analysed by specifically developed image processing algorithms that identify and track axon segments present. For quantitative analysis, measurement grids consisting of a user-defined number of individual elements are placed over an area of interest, with the computer-based method then returning the summed length of the axon segments in each element. Axon density plots can thus be generated. We present an example from rat brain showing, over a whole coronal section, axon densities emanating from a population of layer 2/3 somatosensory neurons.