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In recent months various disorders and diseases of the peripheral nerves (including cranial nerves) and the musculature have been described in association with the pulmonary disease coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the first part of our review the current knowledge about a potential association of a SARS-CoV-2 infection with dysfunction and diseases of cranial and peripheral nerves is discussed. Anosmia, ageusia, motor cranial nerve involvement and Guillain-Barre syndrome (GBS) were described in a temporal association with a SARS-CoV-2 infection. Several studies could show that anosmia and ageusia were frequent symptoms of a SARS-CoV-2 infection. In contrast the failure of other cranial nerves has so far only been sporadically described. A number of case reports and case series indicate a causal association between a SARS-CoV-2 infection and GBS but epidemiological evidence is still lacking.

Apart from disorders and diseases of the peripheral nerves, symptoms and disorders of the musculature and the neuromuscular transmission have also been described in association with coronavirus disease 2019 (COVID-19). In the second part of our review we provide an overview about frequently reported symptoms, such as myalgia as well as defined disorders, such as rhabdomyolysis, myositis, myasthenia and intensive care unit (ICU)-acquired weakness, which have been described during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections or COVID-19.Furthermore, the criteria for a causality, such as association strength, plausibility, time course, and experimental evidence for a causal association that should be applied for the COVID-19-asssociated neuromuscular conditions described in the two parts of the review are discussed. At present, in addition to anosmia, which is also known in the lay press, myalgia in particular as a nonspecific symptom are frequent sequelae of a symptomatic SARS-CoV-2 infection. Other neuromuscular complications seem to be principally plausible (considering the pathogenesis) but apparently rare consequences of a SARS-CoV-2 infection. Prospective or cohort studies are necessary to confirm a causality and assess the risk.

Background and purpose The aim was to assess the organization and short-term changes of motor units in adult patients with spinal muscular atrophy (SMA) treated with nusinersen. Methods In this single-centre cross-sectional and longitudinal study 15 adult patients with SMA type 3 were assessed and compared to 15 age-matched healthy controls and nine patients with amyotrophic lateral sclerosis. Moreover, 10 patients with SMA were followed up after 4-8 months. All patients were investigated clinically and by the motor unit number estimation method MScanFit of the abductor pollicis brevis muscle. Results The number of motor units (p < 0.001) was significantly lower in patients with SMA compared to healthy controls at study entry. Mean unit amplitude, median amplitude and largest unit (p < 0.001) were significantly increased in patients with SMA. Patients with amyotrophic lateral sclerosis showed a significant reduction of compound muscle action potential (p = 0.005) and number of motor units (p = 0.03) compared to patients with SMA, accompanied by a larger median amplitude (p = 0.03). A prospective analysis identified patients with the ability to walk to improve the number of motor units (p = 0.046) accompanied by a decreased median amplitude (p = 0.03). Electrophysiological measures showed a moderate to strong correlation with clinical scores. Conclusion Patients with SMA show loss of motor units in distal muscles. MScanFit variables indicate that compound muscle action potential amplitudes are maintained by collateral sprouting. Prospective analyses suggest that milder affected adult patients with SMA preferentially benefit from nusinersen treatment through recovery of smaller motor units. Correlations with clinical scores underline the potential of MScanFit as a surrogate marker.

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder characterized by the degeneration of motor neurons in the spinal cord, and comprises a broad clinical spectrum. With the advent of new therapies (e.g., Nusinersen) for patients of all ages and disease stages, sensitive clinical measures are needed to detect slight changes in muscle force even in immobilized, severely affected patients often unable to move limbs. As for these patients, well-established outcome scales set out to evaluate motor function do not work properly, we propose measurement of maximum bite force which is able to detect subtle changes of bulbar function. Requirements for this approach are mentioned, challenges are discussed, and first insights from a pilot study are presented. Finally, a study design is proposed to evaluate the measurement of maximum bite force during the follow up of SMA patients with and without a disease modifying therapy.

We aimed to systematically investigate the neuromuscular involvement of individuals with PRUNE mutations who may have a major spinal motor neuron involvement as part of the PRUNE-associated neurodegenerative phenotype. The complex neurological phenotypes associated with Prune mutations include microcephaly with brain abnormalities, spasticity, seizures, severe developmental delay and developmental regression. We used whole exome sequencing to identify the mutation and electrophysiological and muscle biopsy studies to evaluate the signs of spinal motor neuron involvement. The affected individuals carry homozygous PRUNE mutation (NM_021222.1, c.316G>A, p.D106N), showing the signs of spinal motor neuron involvement supported by electrophysiological and muscle biopsy findings and also persistent high creatine kinase levels. We confirm that individuals with PRUNE mutations may have a major spinal motor neuron involvement as part of the PRUNE-associated neurodegenerative phenotype. The PRUNE gene should be considered in all the individuals with non-5q spinal muscular atrophy. High creatine kinase values may be a part of PRUNE disease spectrum.

Background: Small fiber neuropathy (SFN) is a challenging subtype of peripheral neuropathies. Once the diagnosis has been established, there is an uncertainty how SFN may progress, whether larger fibers will become involved over time, whether quality of life may be compromised, or whether repeated diagnostic workup in patients with unknown underlying cause may increase the yield of treatable causes of SFN. Methods: We evaluated 16 patients with documented longtime course of idiopathic SFN. Results: Clinical and electro-physiological course remained stable in 75% of the patients, while 25% SFN-patients developed large fiber neuropathies. Conclusions: Our data suggest that SFN represents a benign disease course in the majority of patients without severely limiting the quality of life. (C) 2018 S. Karger AG, Basel

Spinal muscular atrophies (SMAs) are a heterogeneous group of disorders characterized by muscular atrophy, weakness, and hypotonia due to suspected lower motor neuron degeneration (LMND). In a large cohort of 3,465 individuals suspected with SMA submitted for SMN1 testing to our routine diagnostic laboratory, 48.8% carried a homozygous SMN1 deletion, 2.8% a subtle mutation, and an SMN1 deletion, whereas 48.4% remained undiagnosed. Recently, several other genes implicated in SMA/LMND have been reported. Despite several efforts to establish a diagnostic algorithm for non-5q-SMA (SMA without deletion or point mutations in SMN1 [5q13.2]), data from large-scale studies are not available. We tested the clinical utility of targeted sequencing in non-5q-SMA by developing two different gene panels. We first analyzed 30 individuals with a small panel including 62 genes associated with LMND using IonTorrent-AmpliSeq target enrichment. Then, additional 65 individuals were tested with a broader panel encompassing up to 479 genes implicated in neuromuscular diseases (NMDs) with Agilent-SureSelect target enrichment. The NMD panel provided a higher diagnostic yield (33%) than the restricted LMND panel (13%). Nondiagnosed cases were further subjected to exome or genome sequencing. Our experience supports the use of gene panels covering a broad disease spectrum for diseases that are highly heterogeneous and clinically difficult to differentiate.

History A 30-year-old man presented with a history of progressive muscle weakness, difficulty in concentrating, and a slender habitus since early childhood. Marfan syndrome was suspected since the age of 14. Examinations 13 years later he was examined by Marfan experts and by genetic testing and Marfan syndrome could not be confirmed. Further neurological examination revealed the suspected diagnosis of myotonic dystrophy type 1, which was confirmed by genetic testing. Treatment and course Similar to Marfan syndrome, myotonic dystrophy is a multisystemic disorder with the risk of cardiac arrythmias. It is necessary to provide an interdisciplinary care by neurologists, internists, ophthalmologists, speech therapists, and physiotherapists. Conclusion It is not enough to take the habitus as the principle sign to diagnose Marfan syndrome. Furthermore, it is essential to consider symptoms that are not typical for Marfan syndrome, such as cognitive deficiencies or progressive paresis.