GNE myopathy (GNEM) is a rare hereditary disease, but at the same time, it is the most common distal myopathy in several countries due to a founder effect of some pathogenic variants in the GNE gene. We collected the largest cohort of patients with GNEM from Russia and analyzed their mutational spectrum and clinical data. In our cohort, 10 novel variants were found, including 2 frameshift variants and 2 large deletions. One novel missense variant c.169_170delGCinsTT (p.(Ala57Phe)) was detected in 4 families in a homozygous state and in 3 unrelated patients in a compound heterozygous state. It was the second most frequent variant in our cohort. All families with this novel frequent variant were non-consanguineous and originated from the 3 neighboring areas in the European part of Russia. The clinical picture of the patients carrying this novel variant was typical, but the severity of clinical manifestation differed significantly. In our study, we reported two atypical cases expanding the phenotypic spectrum of GNEM. One female patient had severe quadriceps atrophy, hand joint contractures, keloid scars, and non-classical pattern on leg muscle magnetic resonance imaging, which was more similar to atypical collagenopathy rather than GNEM. Another patient initially had been observed with spinal muscular atrophy due to asymmetric atrophy of hand muscles and results of electromyography. The peculiar pattern of muscle involvement on magnetic resonance imaging consisted of pronounced changes in the posterior thigh muscle group with relatively spared muscles of the lower legs, apart from the soleus muscles. Different variants in the GNE gene were found in both atypical cases. Thus, our data expand the mutational and clinical spectrum of GNEM.

Transthyretin amyloidosis (ATTR-amyloidosis) is a systemic progressive fatal disease, for which a modifying therapy has recently been proposed that delays the progression of the disease and improves the patient’s quality of life. The delay in the diagnosis of ATTR-amyloidosis is associated with the heterogeneity of the manifestations of the disease, as well as insufficient awareness of doctors of different specialties about the disease. A review of recent studies on the symptomatology, diagnosis, molecular genetic characteristics of ATTR-amyloidosis and the most common forms of the disease with the predominant involvement of peripheral nerves and the heart, as well as the kidneys, gastrointestinal tract, and eyes is presented. The international consensus recommendations for the diagnosis of suspected ATTR-amyloidosis using modern methods that facilitate early and accurate diagnosis are discussed. The reasons and the most frequent misdiagnoses of ATTR-amyloidosis, which also lead to a delay in the timely appointment of therapy, are considered. Molecular genetic testing should be considered early in the evaluation of a patient with unexplained peripheral neuropathy and cardiomyopathy. A diagnostic algorithm based on the initial symptoms and manifestations of the cardiovascular and nervous systems facilitates the identification of a patient with clinical suspicion of ATTR-amyloidosis by the general practitioner. Early diagnosis is critically important for patients with ATTR polyneuropathy, since the early prescription of Vyndaqel (tafamidis), registered in the Russian Federation in 2017, allows a significant clinical effect to be obtained. Timely administration of Vyndaqel significantly slows down the progression of the disease, improves the prognosis and quality of life in patients with ATTR polyneuropathy.

Background. Onasemnogene abeparvovec is the first gene replacement therapy medication based on the adeno-associated viral vector (AAV9). One injection to a patient with 5q spinal muscular atrophy (SMA) leads to replacement of the missing or defective SMN1 gene with its functional copy. It leads to normalization of survival motor neuron protein (SMN) production.Objective. The aim of the study is to evaluate efficacy, safety, and causes of different responses to therapy after single administration of onasemnogene abeparvovec in 5 patients with 5q SMA (types I and II) comparing the baseline status with the results of continued monitoring in real clinical practice in Russian Federation.Methods. Interim results of continued follow-up of children with 5q SMA with 2–3 copies of the SMN2 gene are presented: 2 boys and 1 girl with type I who received single dose of onasemnogene abeparvovec at 4 and 7 months of age; and 2 girls with type II who received therapy at 11 and 16 months of age.Results. Short-term controlled fever was observed in 4 out of 5 patients during first 2 weeks after viral vector therapy administration (max in patient 5 — up to 38.5 ° C). All 5 children had transaminases increase, 1 patient — significant transaminases increase during the sensitisation period (> 10 from upper normal level (UNL)), 1 patient — delayed significant transaminases increase (> 20 UNL), 1 patient — transaminases increase (> 3 UNL) after discontinuation of longterm therapy with glucocorticosteroids (according to prescribing information). All patients had shown positive and sustained response to therapy over time at motor status assessment via CHOP INTEND / HFMSE scales. The more significant response was observed in patients with less aggressive baseline 5q SMA type II with 3 copies of the SMN2 gene.Conclusion. Onasemnogene abeparvovec is relatively safe medication for management of children with 5q SMA. Thus, the development of adverse events and their mechanisms should be further studied, as well as long-term follow-up of recipients is required to gather knowledge on this medication effects on human body.

Evaluation and interpretation of electrophysiological phenomena often plays an important role in the diagnosis of neuromuscular diseases. Motor nerve conduction block is a reduction of either amplitude or area of the compound motor action potential elicited by proximal to distal motor nerve stimulation. Today, the value of conduction block in the diagnosis of demyelinating and axonal neuropathies, as well as the diagnostic criteria for these disorders, are still under discussion.Objective of the review of the literature is to highlight the value of conduction block as an electrophysiological phenomenon in the light of clinical manifestations. There is no consensus in the literature which motor response parameters should be used as partial conduction block criteria. The diversity of pathogenic forms in which conduction block can be registered does not allow to consider the phenomenon as a sign of only demyelinating lesions, and the term conduction block should be considered as a pure electrophysiological phenomenon. Different pathophysiological mechanisms of conduction block formation should be studied separately within each nosology. Conduction block detection does not allow to specify a particular diagnosis, however, in conjunction with clinical and anamnestic data, it may be the main argument in the diagnosis of a number of peripheral nerves diseases.

To describe clinical and sonographic features of confirmed intraneural perineurioma in 5 patients. We report clinical and sonographic features and retrospective follow-up data in 5 patients with intraneural perineurioma verified by biopsy. In all cases, symptoms were represented by a slowly progressive painless mononeuropathy with muscle atrophy and impaired tendon reflexes. Ultrasound examination revealed locally enlarged cross-sectional area of the nerve that was confirmed by intraoperative visualization. Intraneural perineurioma should be obligatory suspected in case of fusiform thickening of the nerve with locally changed echogenicity. Pooled multiple-center studies with large samples are needed to determine sensitivity and specificity of the main ultrasound parameters including changes in cross-sectional area and echogenicity of the nerve.