Therapeutic apheresis in the complex pathogenetic therapy of anti-NMDA encephalitis associated with ovarian teratoma at a late stage of the disease

Anti‑NMDA encephalitis is a rare autoimmune disease of the central nervous system caused by the synthesis of autoantibodies to the NR1/NR2 subunits of the NMDA receptor, characterized by the development of acute mental, cognitive, motor, autonomic disorders, epileptic syndrome and central hypoventilation.The article presents a three‑year observation of patient 34 years old with anti‑NMDA ncephalitis associated with late‑ stage ovarian teratoma, accompanied by an increase titer of antibodies to NMDA receptors in serum to 1:640.Based on a detailed analysis of clinical, neurological, neuropsychological (MMSE, MoСA, FAB, 10 words test A.R. Luria) and laboratory‑instrumental characteristics of the disease (titer anti‑NMDA, level of IgG, IgM, IgA, lymphocyte subpopulations, EEG, MRI of the brain, pelvis) suggested a combination scheme of first and second line therapy. The sequential use of two cycles of medium‑volume membrane plasmapheresis (25–30 % of the circulating plasma volume, No. 5 + 5) was carried out in combination with pulse therapy with methylprednisolone 1.0 (No. 4 + 3) and cyclophasphamide 1.0 (No. 2 + 1) on background of persistent ovarian teratoma. Symptom regression was achieved by the end of the first cycle, and full recovery to the initial level of cognitive functions occurred after the second cycle, while maintaining the anti‑NMDA antibody titer to 1:160. After removal of ovarian teratoma, the level of anti‑NMDA decreased in a month to 1:40, and after 7 months it reached normal values (<1:10) against the background of basic pill therapy with methotrexate 12.5 mg/week.Thus, a rational combination and sequence of first and second line therapy and therapeutic apheresis, taking into account the pathogenetic features of each phase of the disease, can quickly achieve complete stable remission in patient with anti‑NMDA encephalitis.

Ramsey Hunt syndrome in the child: case report and treatment approach

Herpes zoster is a manifestation of the reactivation of an infection after chickenpox. One of the manifestations of herpes zoster is Ramsey Hunt syndrome, which develops when the ganglion of the VII pair of cranial nerves is involved in process. Diagnosis of Ramsey Hunt syndrome is often based on a combination of a rash in the outer ear and peripheral paresis of the facial muscles. The article describes a rare clinical case of herpes zoster in a child without clinical signs of immunodeficiency, with the development of unilateral paralysis of the facial muscles, pleocytosis in the cerebrospinal fluid. Therapy was performed with a combination of acyclovir and high doses of methylprednisolone with a good clinical effect. It is first mentioning of deviations in the immune status (decreased concentration of the number of markers of naive T‑lymphocytes (TREC)) were revealed, which could be associated with the development of herpes zoster in a child.

Practical aspects of therapy for glutaric aciduria type 1

Treatment of many of the diseases in the panel of expanded newborn screening includes dietary therapy. Glutaric aciduria type 1 (GA1) is a hereditary disorder caused by mutations in the gene GCDH, encoding glutaryl‑CoA dehydrogenase, an enzyme in the amino acid metabolic pathways. The decreased activity of the enzyme leads to accumulation of neuro‑ toxic metabolites. The recommended treatment approaches for GA1 are the prescription of specialized nutrition products, levocarnitine, and symptomatic management. In 2021, clinical guidelines for the treatment of this rear disease were published in Russian Federation. To provide for the timely treatment, it is essential for a practitioner involved in the care patients with such a rare disorder as GA1 to have the knowledge of the principles of management, as well as practical algorithms for diet calculation.The article gives a detailed case‑based description of management during metabolic decompensation and the choice of dietary therapy for GA1 patients of different age groups.

Inflammatory Neuropathy Cause and Treatment (INCAT) Scale for the assessment of disability level in patients with chronic inflammatory demyelinating polyneuropathy: linguocultural ratification in Russia

Background. Chronic inflammatory demyelinating polyneuropathy (CIDP) is a treatable dysimmune polyneuropathy. An objective response for pathogenic therapy is essential in diagnosis and management of CIDP. For proper assessment of patient’s complaints and evaluation of disease progression, it is recommended to use validated scales and questionnaires. The paper presents the results of the first step of Inflammatory Neuropathy Cause and Treatment (INCAT) validation in patients with CIDP.Objective: the development of the Russian version of the INCAT scale and its linguocultural ratification.Materials and methods. 15 patients with definite CIDP (according to EFNS/PNS criteria) were enrolled. Linguocultural ratification was conducted according to the standard protocol.Results. The Russian version of the INCAT scale was developed.Conclusion. We conducted the first stage of INCAT scale validation in patients with CIDP.

Aymé–Gripp syndrome in a Russian patient with a newly detected mutation in the MAF gene

Aymé–Gripp syndrome is a rare autosomal dominant syndrome caused by mutations in the MAF gene and is characterized by a pronounced phenotypic polymorphism. The core of clinical signs consists of congenital cataracts, sensorineural hearing loss, specific dysmorphic facial features and intellectual disabilities. With varying frequency, patients have: radioulnar synostosis, Arnold–Chiari malformation, aseptic pericarditis, dental anomaly and osteoarthritis. The article presents the clinical and genetic characteristics of the first Russian patient with Aymé–Gripp syndrome caused by a newly identified mutation s.173C>A (p.Thr58Asn NM_005360.4) in a heterozygous state in the MAF gene. The influence of the lo calization and type of amino acid substitutions in the protein product of the gene on the severity and specificity of the clinical manifestations of the syndrome is discussed.

Russian-language dictionary of terms used in clinical electromyography and ultrasound examination of the neuromuscular system

Modern electrodiagnostics (ED) and ultrasound examination of the neuromuscular system dictates the need to use unified terminology in order to avoid inter-expert variability in describing the results of the study and drawing up a conclusion in accordance with international criteria. The results of a survey of clinical electromyography specialists and the methodology of translation of the latest version of the English-language glossary on electrodiagnostic medicine are presented.The purpose of the publication is to popularize the use of modern nomenclature among the professional community. An anonymous survey was conducted on the use of the most common terms ED. The translation of the latest English-language version of the glossary on ED and ultrasound examination of the neuromuscular system was carried out, followed by editing and discussion by an expert group. 236 people from 68 cities of Russia and neighboring countries took part in the survey. The survey results demonstrated maximum disunity, as well as conservatism in the use of terms. The nomenclature of ED terms was first compiled in 1980 by the American Association of Electromyography and Electrodiagnostics and subsequently regularly revised and supplemented in accordance with new data. The unification of terms is necessary for the standardization of conclusions, multicenter research and scientific publications.

New mutation in the TRIP4 gene associated with congenital muscular dystrophy Davignon–Chauveau type (clinical case)

Congenital muscular dystrophies are heterogeneous groups of neuromuscular diseases leading to hypotonia, progressive muscle weakness and dystrophic or structural signs in muscle biopsy. At the present time, 34 genes associated with congenital muscular dystrophy have been described. The clinical case of a rare form of congenital muscular dystrophia associated with a homozygous mutation in the TRIP4 gene in a patient with respiratory failure requiring respiratory support, neurological symptoms, muscular hypotonia, and multiple congenital malformations of skeletal system is presented for the first time in Russia. The undescribed pathogenic homozygous variant of the nucleotide sequence in the TRIP4 gene (chr15:64686179, c.136C>T, p.Arg46Ter, 2 exon, NM_016213.4) was detected by whole exome sequencing. The mutation in the TRIP4 gene was validated by Sanger sequencing in a child and its origin was investigated. The mother and father of the girl are carriers of the heterozygous variant in the TRIP4 gene. Identification of the genetic cause of a rare form of neuromuscular disease is important for determining the tactics of patient management and medical and genetic counseling of the family, as well as clarifying the pathogenesis of a rare pathology.

Diagnostic criteria for spinal muscular atrophy 5q

Background. The variety of phenotypic manifestations of spinal muscular atrophy 5q (5qCMA) is the reason for the difficulty in diagnosing and delaying the diagnosis, which is of particular importance today due to the emergence of new etiopathogenetic therapeutic possibilities.Objective: determination of the main clinical features and symptoms of 5qCMA with onset at different age periods, and the development of an algorithm that can help in making decisions regarding the need for testing the SMN1 gene by primary care and hospital doctors.Materials and methods. A retrospective analysis of the case histories of patients observed at the Research Center of Medical Genetics with a confirmed diagnosis of 5qCMA was carried out.Results. The study included data from 315 patients, including: 173 with type I, 95 and 47 with types II and III 5qCMA. In all cases, the presence and diagnostic significance of 27 signs and symptoms were analyzed, depending on the age of disease manifestation. An attempt was made to isolate the main symptoms, which are the basis for the mandatory exclusion of 5qCMA by molecular genetic methods in patients with the onset of the disease before and after 18 months of life.

Phenotypic heterogeneity and diagnostic features of transthyretin amyloidosis with polyneuropathy

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 Vindakel (tafamidis), registered in the Russian Federation in 2017, allows a significant clinical effect to be obtained. Timely administration of Vindakel significantly slows down the progression of the disease, improves the prognosis and quali ty of life in patients with ATTR polyneuropathy.

Medial plantar nerve: normative parameters of an electroneuromyographic study in adults

Background. The study of the sensitive portion of the medial plantar nerve is relevant not only in the examination of patients with tibial nerve mononeuropathy or its branches, but also in the diagnosis of polyneuropathies.Objective: to analyze the normative parameters of the sensory potential recorded during the study of the medial plantar nerve by the orthodromic method in healthy adults.Materials and methods. 126 sensitive fibers of the medial plantar nerves were studied on the Dantec Keypoint G4 device (Denmark) in 63 healthy individuals (31 men and 32 women; age from 20 to 80 years). 3 groups were identified taking into account age: group 1 included healthy people aged 20 to 39 years (n = 23); group 2 consisted of people aged 40 to 60 years (n = 20); and 3 – older than 60 years (n = 20). The parameters of the sensory potential of the medial plantar nerve are analyzed.Results. The sensory potential in the study of the sensitive portion of the medial plantar nerve was registered in all 126 healthy subjects. Comparative statistical analysis did not demonstrate significant differences between groups 1–3 in the values of such parameters of the sensory potential as the latency of the onset, the duration of the negative phase and the rate of propagation of excitation. At the same time, in groups 2 and 3, the magnitude of the amplitude from peak to peak of the sensory potential was significantly lower compared to group 1, and averaged 8.92 and 7.86 MV, respectively.Conclusion. Knowledge of the regulatory parameters will allow expanding the use of electroneuromyography of the sensitive portion of the medial plantar nerve in clinical and research practice.