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Cardiac wtATTR is caused by extracellular deposition of misfolded proteins in the heart. It mostly affects elderly men and is still clearly underdiagnosed. Recognizing red flags suggesting wtATTR is key for a timely diagnosis, enabling the patient to profit from effective therapies. If general practitioners suspect cardiac amyloidosis, it is crucial to rapidly exclude AL-amyloidosis by immunoelectrophoresis, immunofixation as well as light-chain assay, because AL-amyloidosis needs urgent hematologic therapy. After that, the patient should be referred to the cardiologist for further assessment. Die kardiale wtATTR wird durch extrazelluläre Ablagerungen von fehlgefalteten Proteinen im Herzen verursacht. Sie betrifft meist ältere Männer und wird immer noch deutlich unterdiagnostiziert. Das Erkennen von Anzeichen, die auf wtATTR hindeuten, ist entscheidend für eine rechtzeitige Diagnose, damit der Patient von wirksamen Therapien profitieren kann. Wenn der Hausarzt den Verdacht auf eine kardiale Amyloidose hat, ist es wichtig, eine AL-Amyloidose durch Immunelektrophorese, Immunfixation und Leichtkettenbestimmung rasch auszuschliessen, da die AL-Amyloidose einer dringlichen hämatologischen Therapie bedarf. Danach sollte der Patient zur weiteren Abklärung an eine Kardiologin/einen Kardiologen überwiesen werden.

The new strain of coronavirus SARS CoV-2 can affect any organ and system of the body. The pathogenesis of these lesions is due to both direct damage to body cells by the virus and the development of immunopathological reactions that can lead to demyelinating diseases of the nervous system. The article presents a clinical case of the development of Guillain-Barré syndrome associated with coronavirus disease in a 71-year-old man who developed after infection with a new strain of SARS CoV-2 virus. The man was hospitalized on the seventh day of the disease with complaints of unproductive cough, weakness, fever in the range of 37.5-38.7°C, shortness of breath during exercise. The clinical diagnosis was confirmed by the presence of SARS CoV-2 RNA in the nasopharyngeal secretion. According to digital radiography, the presence of interstitial pneumonia was determined. Against the background of treatment, the condition gradually improved and on the 14th day after the onset of the disease, a negative PCR result (SARS CoV-2 (-) RNA) was obtained. However, on the 16th day of hospital stay (23-24th days of the disease) he was diagnosed with polyneuropathy (Guillain-Barré syndrome), severe tetraparesis. Despite the therapy, the condition gradually deteriorated due to the progression of polyneuropathy. On the 9th day after the onset of neurological symptoms (25th days of illness), on the background of severe neurological deficits, the signs of respiratory and cardiovascular insufficiency developed, which led to the death of the patient. It has been shown that the course of Guillain-Barré syndrome, which developed after infection with a new strain of SARS CoV-2 virus, in this case has a severe course and lethal outcome of the disease. It is necessary to look for clinical predictors that would predict the occurrence of neurological complications in patients with coronavirus disease.

We evaluated the clinical and neurophysiological efficacy of rituximab (RTX) in a neurophysiologically homogeneous group of patients with monoclonal gammopathy and immunoglobulin M (IgM) anti-myelin-associated glycoprotein antibody (anti-MAG) demyelinating polyneuropathy.Twenty three anti-MAG-positive polyneuropathic patients were prospectively evaluated before and for 2 years after treatment with RTX 375 mg/msup2/sup. The Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale (INCAT-ds), modified INCAT sensory score (mISS), Medical Research Council sum score, Patients' Global Impression of Change scale were used, IgM levels were assessed and extensive electrophysiological examinations were performed before (T0) and 1 year (T1) and 2 years (T2) after RTX treatment.At T1 and T2 there was a significant reduction from T0 both in mISS and in INCAT-ds, with a p valuelt; 0.001 in the inferential Friedman's test overall analysis. Ulnar nerve Terminal Latency Index and distal motor latency significantly changed from T0 to T1 and in the overall analysis (p = 0.001 and p = 0.002), and ulnar nerve sensory nerve action potential (SNAP) amplitude was significantly increased at T2 from T1, with a p valuelt; 0.001 in the overall analysis. Analysis of the receiver-operating characteristic curves showed that a 41.8% increase in SNAP amplitude in the ulnar nerve at T2 from T0 was a fair predictor of a mISS reduction of ≥2 points (area under the curve 0.85; p = 0.005; sensitivity: 90.9%, specificity: 83.3%).This study suggests that RTX is effective in patients with clinically active demyelinating anti-MAG neuropathy over 2 years of follow-up, and that some neurophysiological variables might be useful for monitoring this efficacy.

Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy classically thought to be caused by infections through the process of molecular mimicry. We report a case of GBS caused by intracerebral haemorrhage and postulate potential theories for the development of GBS following intracerebral haemorrhage and other non-infectious aetiologies by association. We highlight that GBS is an important differential diagnosis in patients developing generalised paresis following intracerebral haemorrhage.

Objectives Neurological complications including pain are common after treatment for breast cancer. This prospective study investigated the symptoms, intensity and interference of chemotherapy-induced peripheral neuro-pathy. (CIPN) in the feet and hands compared to surgery- and radiation-induced neuropathy in the breast and upper arm. Methods Consecutive patients referred to surgery for breast cancer were included in a prospective study and completed a questionnaire at baseline and a follow-up questionnaire and interview after one year. CIPN was assessed with the CIPN20 questionnaire and the Michigan Neuropathy Screening Instrument questionnaire (MNSIq). Pain intensity was rated on a numeric rating scale (NRS, 0–10). Results In total 144 patients were included, of which 73 received chemotherapy. At one-year follow-up, symptoms of polyneuropathy were more common in patients treated with chemotherapy. Tingling or numbness in the feet in those treated/not treated with chemotherapy was reported by 44 (62%) and 15 (21%), respectively. Pain was present in 22 (30%) and 10 (14%), respectively. Pain in the area of surgery was reported by 66 (46%). Although less common, pain in the feet in those treated with chemotherapy was rated as more intense and with more daily life interference than pain in the surgical area (NRS 5.5 (SD 1.9) vs. 3.1 (SD 1.9). Conclusions Neurological complications including pain following surgery and chemotherapy represent a burden to breast cancer survivors. In those who had received chemotherapy, pain in the feet was less common than pain in the surgical area, but pain in the feet was more intense and had a higher interference with daily life. Our study emphasizes the need for either baseline data or a control population for improved estimation of the presence and severity of CIPN and pain from questionnaires.

This 18-year-old boy presented to the hospital with symptoms of cerebellar dysfunction preceded by an acute febrile illness with rash. Examination showed evidence of left-sided cerebellar dysfunction and polyneuropathy. Empirical treatment for leptospirosis and scrub typhus was initiated. MRI was normal. Other organ dysfunctions in the form of thrombocytopenia and transaminitis were also observed. He recovered without sequelae. A diagnosis of acute cerebellar ataxia and polyneuropathy due to scrub typhus was made.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare but disabling disorder that often requires long-term immunomodulatory treatment. Background incidence rates and prevalence and risk factors for developing CIDP are still poorly defined. In the current study, we used a longitudinal population-based cohort study in The Netherlands to assess these rates and demographic factors and comorbidity associated with CIDP. We determined the incidence rate and prevalence of CIDP between 2008 and 2017 and the occurrence of potential risk factors in a retrospective Dutch cohort study using the Integrated Primary Care Information (IPCI) database. Cases were defined as CIDP if the diagnosis of CIDP was described in the electronic medical file. In a source population of 928 030 persons with a contributing follow-up of 3 525 686 person-years, we identified 65 patients diagnosed with CIDP. The overall incidence rate was 0.68 per 100 000 person-years (95% CI 0.45-0.99). The overall prevalence was 7.00 per 100 000 individuals (95% CI 5.41-8.93). The overall incidence rate was higher in men compared to woman (IRR 3.00, 95% CI 1.27-7.11), and higher in elderly of 50 years or older compared with people

A 41-year-old woman was diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome based on polyneuropathy, hepatosplenomegaly, sclerotic bone lesions, IgA-λ M-protein, and an elevated level of serum vascular endothelial growth factor. One month after the initiation of lenalidomide-dexamethasone with prophylactic aspirin, she developed facial paralysis, dysarthria, and left hemiplegia. Multiple cerebral infarctions and internal carotid artery stenosis were detected. Five months after switching to pomalidomide-dexamethasone, she again developed cerebral infarction. Progressed stenotic lesions in the bilateral internal carotid artery terminal portions were detected, showing a moyamoya disease-like appearance. Quasi-moyamoya disease can be an important phenotype of systemic vasculopathies of POEMS syndrome.

The diagnosis of polyneuropathy usually requires neurophysiological investigation, necessitating specialised testing and interpretation thereby increasing the time to final diagnosis. We investigated the predictive value of the clinical examination in patients with potential neuropathies. Patients were recruited based on their referral requesting neurophysiological testing. Two examiners tested ankle jerk reflexes and gradient to temperature sensation prior to the patient undergoing neurophysiology investigations, blinded to subsequent testing results. The neurophysiology investigations were either standard nerve conduction study (NCS) or thermal threshold testing (TTT) or both. These data were then analysed to determine the Kappa between examiners as well as sensitivity, specificity, and positive and negative likelihood ratios. There was a modest level of agreement between examiners for ankle jerk testing (Kappa=0.6) but poor agreement for gradient temperature testing (Kappa=0.3). Bilateral absence of ankle jerk reflexes was moderately associated with abnormal NCS, with the following characteristics: sensitivity 72%, specificity 91%, positive likelihood ratio 7.6, and negative likelihood ratio 0.3. The presence of a temperature gradient was poorly diagnostic for abnormal TTT: sensitivity 87%, specificity 14%, with positive and negative likelihood ratios close to 1. In conclusion, the absence of ankle jerks performed moderately well in identifying patients likely to have large fibre neuropathy and could potentially be used to help decide who should be sent for NCS. Gradient temperature testing was much more subjective and did not change the likelihood of abnormal TTT. This article is protected by copyright. All rights reserved.

Purpose The purpose of this study was to investigate the effectiveness of photobiomodulation (PBM) therapy for the prevention of chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer patients. Methods A prospective, randomized placebo-controlled pilot trial (NEUROLASER) was set up with 32 breast cancer patients who underwent chemotherapy (ClinicalTrials.gov; NCT03391271). Patients were randomized to receive PBM (n = 16) or placebo treatments (n = 16) (2 × /week) during their chemotherapy. The modified Total Neuropathy Score (mTNS), six-minute walk test (6MWT), Numeric pain Rating Scale (NRS), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Taxane (FACT/GOG-Taxane) were used to evaluate the severity of CIPN and the patients’ quality of life (QoL). Outcome measures were collected at the first chemotherapy session, 6 weeks after initiation of chemotherapy, at the final chemotherapy session, and 3 weeks after the end of chemotherapy (follow-up). Results The mTNS score increased significantly over time in both the control and the PBM group. A significantly higher score for FACT/GOG-Taxane was observed in the PBM group during chemotherapy compared to the control group. Questions of the FACT/GOG-Taxane related to sensory peripheral neuropathy symptoms showed a significant increase in severeness over time in the control group, whereas they remained constant in the PBM group. At follow-up, a (borderline) significant difference was observed between both groups for the 6MWT and patients’ pain level, in benefit of the PBM group. Conclusions This NEUROLASER trial shows promising results concerning the prevention of CIPN with PBM in breast cancer patients. Furthermore, a better QoL was observed when treated with PBM.

Knowledge about the exact underlying pathophysiological changes involved in the genesis and progression of spinocerebellar ataxia type 3 (SCA3) is limited. Lower extremity peripheral nerve lesions in clinically, genetically and electrophysiologically classified ataxic and pre-ataxic SCA3 mutation carriers were characterized and quantified by magnetic resonance neurography (MRN).Eighteen SCA3 mutation carriers and 20 age-/sex-matched healthy controls were prospectively enrolled. All SCA3 mutation carriers underwent detailed neurological and electrophysiological examinations. 3 T MRN covered the lumbosacral plexus and proximal thigh to the tibiotalar joint by using T2-weighted inversion recovery sequences, dual-echo relaxometry sequences with spectral fat saturation, and two gradient-echo sequences with and without an off-resonance saturation rapid frequency pulse. Detailed quantification of nerve lesions by morphometric and microstructural MRN markers, including T2 relaxometry and magnetization transfer contrast imaging, was conducted in all study participants.MRN detected peripheral nerve damage in ataxic and pre-ataxic SCA3. The quantitative markers proton spin density (ρ), T2 relaxation time, magnetization transfer ratio and cross-sectional area were decreased in SCA3, indicating chronic axonopathy. MTR and ρ identified early, subclinical nerve damage in pre-ataxic SCA3 and in SCA3 mutation carriers without polyneuropathy and were superior in differentiating between all subgroups. Additionally, microstructural markers correlated well with clinical symptom scores and electrophysiological results.Our data provide a comprehensive characterization of peripheral nerve damage in SCA3 and assist in understanding the mechanisms of the multisystemic disease evolution. Evidence of peripheral nerve involvement prior to the onset of clinically overt ataxia might have important implications for designing early intervention studies.

Background and objective Transthyretin amyloidosis (ATTR) is a rare disease that is part of systemic amyloidosis and is life-threatening. It can affect all organs and systems, the most frequent being neurological and cardiac involvement. This study aims to detect possible ATTR cases and carry out a descriptive study of them. Material and methods Descriptive single-centre study carried out in a tertiary hospital, which included patients with suspected ATTR between September 2016 and January 2020. Results A total of 190 suspected ATTR patients were detected. The study includes 100 of these patients, as well as 10 relatives of patients in whom ATTR was detected in its genetic variant (ATTRv). In total, ATTRv was detected in 7 individuals (3 with a presymptomatic mutation of the disease), 16 patients with age-related ATTR and 31 individuals with unknown cardiac amyloidosis with the tests performed, which confirms the presence of this disease in non-endemic areas. Conclusions ATTR is a disease that must be taken into account in the differential diagnosis of patients with heart failure with preserved LVEF, especially if associated with neurological symptoms.

Introduction Heart Transplantation (HT) is a rational therapy for advanced transthyretin cardiac amyloidosis (ATTR-CA), but the impact of ongoing amyloid deposition is not well defined. We evaluated a cohort of patients who underwent HT for ATTR-CA to determine the incidence of de novo or progression of post-HT ATTR deposition. Methods All patients who were followed post-HT for ATTR-CA at our center were included. Baseline demographics and post-HT manifestations of TTR deposition were collected. All patients completed the Composite Autonomic Symptom Score (COMPASS-31 quantifies autonomic symptoms, with a higher score [0 – 100] indicating more severe autonomic dysfunction) and Polyneuropathy Disability Score (PND, range from 0 [asymptomatic] to IV [confined to wheelchair/bed]) questionnaires. Results Twelve patients (5 wild-type, 7 variant [6 p.Val142Ile, 1 p.Thr80Ala]) were included. Mean age at HT was 64.6 (SD: 4.8) years, 83.3% male, and 50% Black. At a median of 4.0 years (IQR 2.4, 5.9) post-HT, 8 patients had symptoms of ATTR deposition (5 with gastrointestinal involvement, 4 orthopedic and 4 neurologic), with 4 patients having ≥ 2 body systems involved. There were no patients with recurrent cardiac involvement. Median COMPASS-31 score was 17.3 (IQR 11.3, 23.5) at 3.9 years (IQR 2.4, 5.9) post-HT. Four patients had a PND score of stage 1 (sensory disturbance), 1 patient was stage 2 (impaired walking) and 1 patient stage 3b (required a walking aid). Conclusion More than 50% of patients had evidence of progressive or de novo ATTR deposition post-HT, impairing quality of life despite a well-functioning cardiac allograft. These observations highlight an unmet need to establish the role of formal surveillance and treatment of TTR using TTR disease-modifying therapies, which may maintain or improve quality of life post-HT for ATTR-CA.

Relevance. Peripheral neuropathy (PNP) in urogenital chlamydia reactive arthritis (CRA) is described as single observations, and many clinical and pathogenetic aspects of this lesion of the nervous system remain unclear. Objective of the study: to evaluate the incidence and nature of the clinical course of PNP in CRA, the connection of the nerve and joint injuries, to explore the questions of pathogenetic constructions of this neuropathy, to identify risk factors. Material and methods. We observed 101 patients with CRA, mean age of them was 32 years, disease duration — 4 years, and the male to female ratio — 1 : 1. In 90 % of CRA cases, Chlamydia trochamatis was found in prostatic secretions, in scraps from the urethra, the cervix, the vaginal wall, in 83 % — positive serologic tests for chlamydia infection. Results. Signs of PNP in CRA were in 19 % of patients in the ratio of mononeuropathy to polyneuropathy as 1 : 1, with motor, sensory and mixed disorders in a ratio of 1 : 3 : 6, the presence of autonomic changes in every second patient and more frequent distal localization of the process in the hands, which is influenced by the severity of the articular syndrome, high levels of antichlamydia antibodies in the blood, and the axonal and demyelinating indicators of electroneuromyography — by the severity of urogenital lesions and the presence of Guillain-Barre syndrome. A high rate of arthritis progression is a prognosis-negative sign of PNP course in patients with CRA. The pathogenic constructions of PNP involve the inflammatory immune proteins, disturbances of vascular endothelial function and physicochemical surface rheological pro­perties of the serum. Conclusion. PNP takes place in every fifth patient with CRA, correlates with clinical and laboratory signs of joint disease, and in the future will be useful to identify actively this pathology of the nervous system for the subsequent timely rehabilitation, and CRA seropositivity for cyclic citrullinated peptide antibodies is a risk factor for such PNP.

Background. Genetic polyneuropathies belong to systemic degenerative diseases of the nervous and muscular systems of genetic nature, which quite often lead to disorders of the musculoskeletal system. The purpose of our study was to evaluate the neurological condition of persons with genetic polyneuropathies at the stage of preoperative preparation. Materials and methods. 87 patients of the decreed group aged 12 to 57 years were examined. The control group consisted of 10 patients with traumatic injury of soft tissues and peripheral nerves of lower extremities and 10 patients with longitudinal flatfoot of young and middle age. All patients were subject to detailed orthopedic and neurological examination. Results. In all patients with genetic polyneuropathies, we have detected even, on both sides, reduction of tendon and periosteous reflexes in the lower extremities, which correlated with duration of the disease and the nature of genetic malformations. There was recorded a reduction of pain attenuation by the distal type: in the mild lesion — at the level of toes, in the moderate form — these violations have spread to the level of the tibia, and in the severe forms they reached the middle third of the tibia or the level of the knee joints. In mild genetic polyneuropathy, vibration sensitivity in feet was decreased up to 12–14 seconds (in patients in the control group it was about 15–16 seconds or more), in the moderate level of the process — up to 7–11 seconds, in severe forms — up to 0–4 seconds. Motor function disorders in polyneuropathic foot were reduced to the symmetric decrease of muscle strength in the distal limbs, and 12 patients with the severe form of Charcot-Marie-Tooth had paresis of the feet, 2 patients had the symptoms of proximal amyotrophy of the leg muscles. The vast majority of patients had significant vegetative trophic disorders of the segmental level, mainly in the distal segments of legs. In particular, changes occurred in the skin. In the distal segments of legs in 48 patients, it was dry, desquamated, with numerous fissures, hyperkeratosis, roughness, calluses (especially in soles). Swelling on the dorsum of the foot was diagnosed in the lower third of the tibia as well. The vascular pattern was abnormal in 36 patients by parasympathicotonic type, and in 19 patients — by sympathicotonic. Nails were atrophic, with their color changed. Trophic changes were also observed in soft tissues located deeper. Conclusions. Genetic neuropathies are accompanied with severe orthopedic disorders, predominantly in the skeletal structures of the foot. Pathognomonic characteristics for the choice of surgical treatment in patients with genetic polyneuropathies are the nature of autonomic trophic disorders and the degree of changes in the complex types of sensitivity in feet, in particular, vibration sensitivity.

Lead belongs to the group of blood poisons that impair the synthesis of porphyrins and heme. Under industrial conditions, only chronic lead poisoning can develop. Lead belongs to the poisons that have the effect of material cumulation. The half-life of lead is 20 years. Once in the body, it is deposited in many organs in the form of the insoluble tribasic lead phosphates. A significant part of the lead is deposited in the trabeculae of the bones. Under the influence of provoking factors, an intensive lead release from the depot can be observed. In such cases, the amount of lead in the circulating blood increases sharply, and remission is replaced by an exacerbation. There is a wavy course of chronic lead intoxication. Lead and its inorganic compounds belong to the group of poisons that have a polytropic effect on the body, affecting many organs and systems. The blood system (anemia with specific characteristics) and the nervous system (polyneuropathy and encephalopathy) are primarily affected. A number of other organs and systems are also affected. The most severe specific syndrome of gastrointestinal tract damage is lead colic. Due to the impaired synthesis of porphyrins and heme in certain biological substrates of the body — in the blood, erythrocytes and urine, substances unused in the synthesis of heme are accumulated. They are markers of chronic intoxication caused by lead, in the presence of a relevant clinical picture. The diagnosis is based on data from a professional history, sanitary and hygienic characteristics of working conditions, clinical and objective characteristics of the disease and data from laboratory examination. The main thing is to stop contact with lead and remove it from the body. Antidotes for lead poisoning are chelators: tetacinum-calcium, pentacinum, D-penicillamine. In combination with technical and sanitary-hygienic measures to prevent chronic intoxication caused by lead, preliminary and periodic medical examinations of persons in contact with lead are of great importance., Свинець належить до групи кров’яних отрут, що викликають порушення синтезу порфіринів і гему. У виробничих умовах можливий розвиток лише хронічних отруєнь свинцем. Свинець належить до отрут, які мають ефект матеріальної кумуляції. Період напіввиведення свинцю становить 20 років. Потрапляючи в організм, він депонується в багатьох органах у вигляді нерозчинного трьохосновного фосфату свинцю. Значна частина свинцю відкладається в трабекулах кісток. Під впливом провокуючих факторів може спостерігатись інтенсивне виділення свинцю з депо. В таких випадках кількість свинцю в циркулюючій крові різко збільшується й ремісія змінюється загостренням. Спостерігається хвилеподібний перебіг хронічної інтоксикації, викликаної свинцем. Свинець і його неорганічні сполуки належать до групи отрут, що справляють політропну дію на організм, уражаючи багато органів і систем. В першу чергу уражаються система крові (анемія зі специфічними характеристиками) та нервова система (поліневропатія та енцефалопатія). Уражається також низка інших органів і систем. Найбільш тяжким специфічним синдромом ураження шлунково-кишкового тракту є свинцева коліка. Внаслідок порушення синтезу порфіринів і гему в певних біологічних субстратах організму — в крові, еритроцитах та сечі — накопичуються не використані у синтезі гему речовини. Вони є маркерами хронічної інтоксикації, викликаної свинцем, за наявності відповідної клінічної картини. Діагноз базується на даних професійного анамнезу, санітарно-гігієнічної характеристики умов праці, клініко-об’єктивної характеристики захворювання та результатах лабораторних методів обстеження. Основним є припинення контакту зі свинцем і виведення його з організму. Антидотами при отруєнні свинцем є комплексони: тетацин-кальцій, пентацин, D-пеніциламін. У комплексі з технічними і санітарно-гігієнічними заходами щодо попередження хронічних інтоксикацій, викликаних свинцем, велике значення мають попередні та періодичні медичні огляди осіб, які контактують зі свинцем.

PURPOSE Proteasome inhibitors are effective in Waldenström's macroglobulinemia (WM) but require parenteral administration and are associated with polyneuropathy. We investigated efficacy and toxicity of the less neurotoxic oral proteasome inhibitor ixazomib combined with rituximab, in patients with relapsed WM. METHODS We conducted a multicenter phase I/II trial with ixazomib, rituximab, and dexamethasone (IRD). Induction consisted of eight cycles IRD wherein rituximab was started in cycle 3, followed by rituximab maintenance. Phase I showed feasibility of 4 mg ixazomib. Primary end point for phase II was overall response rate (ORR [≥ minimal response]) after induction. RESULTS A total of 59 patients were enrolled (median age, 69 years; range, 46-91 years). Median number of prior treatments was 2 (range, 1-7); 70% had an intermediate or high WM-IPSS (International Prognostic Scoring System for WM) score. After eight cycles, ORR was 71% (42 out of 59) (14% very good partial response [PR], 37% PR, and 20% minor response). Depth of response improved until month 12 (best ORR 85% [50 out of 59]: 15% very good PR, 46% PR, and 24% minor response). Median duration of response was 36 months. The average hematocrit level increased significantly (0.33-0.38 L/L) after induction ( P < .001). After two cycles of ixazomib and dexamethasone, immunoglobulin M levels decreased significantly (median 3,700-2,700 mg/dL, P < .0001). Median time to first response was 4 months. Median progression-free survival and overall survival were not reached. After median follow-up of 24 months (range, 7.4-54.3 months), progression-free survival and overall survival were 56% and 88%, respectively. Toxicity included mostly grade 2 or 3 cytopenias, grade 1 or 2 neurotoxicity, and grade 2 or 3 infections. No infusion-related reactions or immunoglobulin M flare occurred with use of subcutaneous rituximab. Quality of life improved significantly after induction. In total, 48 patients (81%) completed at least six cycles of IRD. CONCLUSION Combination of IRD shows promising efficacy with manageable toxicity in patients with relapsed or refractory WM.

Although diabetic peripheral neuropathy is the most common diabetic microangiopathic complication, several other neuropathy syndromes can occur in the context of diabetes. We describe a rare case of polyneuropathy associated with diabetic ketoacidosis in a patient with new-onset type 1 diabetes. A 42-year-old man with diabetic ketoacidosis was admitted to our hospital with complications of respiratory and renal failure requiring mechanical ventilation and hemodialysis, respectively. After diabetic ketoacidosis improved from the critical state, he developed upper- and lower-limb paralysis with sensory disturbances and pain, as well as right facial paralysis, left recurrent nerve paralysis, and left hypoglossal nerve paralysis. Autonomic nervous function was also impaired. As the pathophysiology, prevention, and treatment of polyneuropathy associated with diabetic ketoacidosis are unclear, the neurologic function of diabetic ketoacidosis patients should be closely monitored.

BACKGROUND AND PURPOSE: Guillain-Barré syndrome (GBS) may be fatal in the acute phase but also affect long-term prognosis due to irreversible sequelae and secondary medical complications. We determined the short-term, intermediate, and long-term mortality of GBS compared to the general population.METHODS: Individual-level data from nationwide registries were linked in this matched cohort study of all first-time hospital-diagnosed GBS patients in Denmark between 1987 and 2016 and 10 individuals from the general population, matched on age, sex, and index date. We used Cox regression analysis to calculate matched mortality hazard ratios (HRs) following GBS, assessing short-term (0-6 months), intermediate (>6 months-4 years), and long-term (>4 years) mortality.RESULTS: We identified 2414 patients with GBS and 23,909 matched individuals from the general population. Short-term mortality was 4.8% (95% confidence interval [CI] = 4.0-5.8) and 0.8% (95% CI = 0.7-0.9) for GBS patients and general population members, respectively, resulting in an HR of 6.6 (95% CI = 4.0-5.8). Intermediate mortality was 7.6% (95% CI = 6.5-8.9), compared with 5.8% (95% CI = 5.5-6.1) for general population members, corresponding to an HR of 1.5 (95% CI = 1.3-1.8). After the first 4 years, long-term mortality showed similar results for GBS patients and general population members (HR = 1.1, 95% CI = 0.9-1.2).CONCLUSIONS: During the first 6 months after GBS hospital admission, GBS was associated with a 6.6-fold increased mortality as compared with the background population of the same age. Mortality remained increased for approximately 4 years following GBS, and then leveled off to a similar long-term mortality rate.

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.

Comprehensive data on variant transthyretin amyloidosis polyneuropathy (ATTRv-PN) in Greece are lacking. We presently provide an overview of ATTRv-PN in Greece, focusing on unexplored non-endemic regions of the country. In total, we identified 57 cases of ATTRv-PN diagnosed over the past 25 years, including 30 from the island of Crete, an apparent endemic region. Patients carried 10 different TTR mutations (C10R; P24S; V30M; R34G; R34T; I68L; A81T; E89Q; E89K and V94A). Carriers of the common V30M mutation constituted 54.3 % of the cohort. A known founder effect for the V30M mutation was present on the island of Crete. Non-endemic cases identified outside the island of Crete are presently reported in more detail. The age of onset ranged from 25 to 77 years, with a mean of 51.1 years. A mean diagnostic delay of 3.2 years was observed. V30M patients had earlier onset and less cardiac involvement than patients carrying other mutations. Genotype-phenotype correlations were largely consistent with published data. We conclude that, with the exception of the Cretan cluster, ATTRv-PN is not endemic in the Greek population. This makes timely diagnosis more challenging, yet absolutely essential given the availability of therapies that can alter the long-term course of the disease.

INTRODUCTION Physical exercise appeared to be effective, when implemented as an adjuvant to the pharmacotherapy option, in a variety of painful conditions. Peripheral neuropathic pain (PNP) is very prevalent and affects up to two-thirds of individuals with polyneuropathy (PN), regardless of etiology. The aim of this systematic review was to evaluate the currently available studies that assess adjuvant physical exercise for the management of PNP. METHODS A systematic literature search was conducted in the PubMed international database. For the systematic search, three medical subject headings (MeSH) were used. Term A was 'physical exercise' OR 'exercise' OR 'activity' OR 'workout' OR 'training'; term B was 'pain' OR 'painful'; term C was 'neuropathy' OR 'polyneuropathy.' Additionally, three filters were used: human subjects, English language, and full text. The reference lists of eligible papers and relevant reviews were also meticulously searched in order to include further relevant studies. Six papers eligible to be included were identified. RESULTS Physical exercise in various forms can be of benefit in the management of PNP when used as an adjuvant to the standard care. Overall, using the American Society of Interventional Pain Physicians (ASIPP) criteria, the current best available evidence exists for both aerobic and muscle strengthening exercise programs (level II evidence). The intensity of the exercise seems to play a significant role, with higher intensity interval training programs being more promising, though this remains to be confirmed in future studies. CONCLUSIONS Physical exercise is a promising non-pharmacological intervention for the management of PNP. Future RCTs should be conducted to make a face-to-face comparison of the available exercise treatments with the aim to design specific exercise programs for patients with PNP.

Introduction/Aims The development and persistence of neurological symptoms following severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is referred to as “long‐haul” syndrome. We aimed to determine whether small fiber neuropathy (SFN) was associated with SARS‐CoV‐2 infection. Methods We retrospectively studied the clinical features and outcomes of patients who were referred to us between May 2020 and May 2021 for painful paresthesia and numbness that developed during or after SARS‐CoV‐2 infection and who had nerve conduction studies showing no evidence of a large fiber polyneuropathy. Results We identified 13 patients, Eight women and five men with age ranging from 38–67 y. Follow‐up duration ranged from 8 to 12 mo. All patients developed new‐onset paresthesias within 2 mo following SARS‐CoV‐2 infection, with an acute onset in seven and co‐existing autonomic symptoms in seven. Three patients had pre‐existing but controlled neuropathy risk factors. Skin biopsy confirmed SFN in six, all of whom showed both neuropathy symptoms and signs, and two also showed autonomic dysfunction by autonomic function testing (AFT). Of the remaining seven patients who had normal skin biopsies, six showed no clinical neuropathy signs and one exhibited signs and had abnormal AFT. Two patients with markedly reduced intraepidermal nerve fiber densities and one with normal skin biopsy had severe and moderate coronavirus disease 2019 (COVID‐19); the remainder experienced mild COVID‐19 symptoms. Nine patients received symptomatic neuropathy treatment with paresthesias controlled in seven (77.8%). Discussion Our findings suggest that symptoms of SFN may develop during or shortly after COVID‐19. SFN may underlie the paresthesias associated with long‐haul post‐COVID‐19 symptoms.

Coronavirus infection, according to modern data, poses a threat not only to the respiratory system, in more than 15% of patients it can lead to cardiovascular complications, including in young and middle-aged people. COVID-19 is probably the trigger of a detailed clinical picture of chronic diseases occurring in a latent form. The article considers the case of sinus node dysfunction and polyneuropathy in a young patient after coronavirus infection against the background of concomitant diseases such as Sjogrens disease and Thompsons myotonia. To observe the dynamics of the three diseases, the timely organization of a multidisciplinary approach is important. It is necessary to consider all three diseases in the paradigm of the main and concomitant in order to timely and adequate therapy. Further study of the clinical features, therapeutic approaches and complications in patients with COVID-19 is required.

В статье дана клиническая характеристика полинейропатий при различных заболеваниях и патологических состояниях, представлен перечень обследований для диагностического поиска причин полинейропатии, алгоритм проведения дифференциальной диагностики полинейропатий. Рассмотрено место витаминов группы В в комплексной терапии полинейропатий.

Distal symmetrical sensorimotor syndrome is quite common in clinical practice. It is very important to establish the cause of polyneuropathy in time and most accurately. There are about 100 causes of damage to the peripheral nervous system. Recently, increasing attention is paid to instrumental and laboratory research methods, while clinical diagnosis, careful history taking, careful examination can give more than 70 % of the diagnosis. It is very important not to stop searching for a possible etiological factor, even when at first glance the cause is obvious, but clinically there are discrepancies. In the process of finding the causative factors, it is important not to waste time and start treatment as early as possible. For this purpose, drugs can be used that are aimed at universal factors of pathogenesis — free radical oxidation, inflammation, edema, microcirculation disorders., Дистальный симметричный сенсомоторный синдром довольно часто встречается в клинической практике. Очень важно вовремя и наиболее точно установить причину развития полинейропатии. Насчитывается около 100 причин поражения периферической нервной системы. В последнее время все больше внимания уделяется инструментальным и лабораторным методам исследования, тогда как клиническая диагностика, тщательный сбор анамнеза, внимательный ­осмотр могут дать более 70 % диагноза. Очень важно не прекращать поиск возможного этиологического фактора, даже когда на первый взгляд причина очевидна, но клинически наблюдаются несоответствия. В процессе поиска причинных факторов важно не терять время и начать лечение как можно раньше. Для этого подходят препараты, направленные именно на универсальные факторы патогенеза — свободнорадикальное окисление, воспаление, отек, нарушение микроциркуляции., Дистальний симетричний сенсомоторний синдром досить часто зустрічається в клінічній практиці. Дуже важливо вчасно й найбільш точно встановити причину розвитку полінейропатії. Налічується близько 100 причин ураження периферичної нервової системи. Останнім часом усе більше уваги приділяється інструментальним і лабораторним методам дослідження, тоді як клінічна діагностика, ретельний збір анамнезу, уважний огляд можуть дати понад 70 % діагнозу. Дуже важливо не припиняти пошук можливого етіологічного чинника, навіть коли на перший погляд причина очевидна, але клінічно спостерігаються невідповідності. У процесі пошуку причинних факторів важливо не втрачати час і розпочати лікування якомога раніше. Для цього підходять препарати, спрямовані саме на універсальні чинники патогенезу — вільнорадикальне окислення, запалення, набряк, порушення мікроциркуляції.

We herein report a case of multiple myeloma and polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome. The patient experienced exacerbated gait disturbance due to weakness and numbness in the lower limbs. Thoracic magnetic resonance imaging revealed an extramedullary tumor with spinal compression that required surgical resection. Plasmacytoma was diagnosed based on a biopsy. Radiation, betamethasone, and chemotherapy were therefore administered. Surgical removal of extramedullary tumors improved his symptoms, motor conduction velocity, and amplitude of the muscle action potential in the peroneal and tibial nerves, as shown by the nerve conduction study. Surgery also decreased the serum vascular endothelial growth factor levels. The patient required additional chemotherapy due to multiple myeloma and showed better outcomes nine months after discharge. The benefits of some treatments remain controversial due to the small number of patients. However, our findings reveal that an early diagnosis and comprehensive treatment may result in better outcomes in such patients.

Introduction Hereditary transthyretin related amyloidosis (h-ATTR) classically presents as a small fiber neuropathy with positive family history, but can also be revealed by various other types of peripheral neuropathy. Objective To describe the initial electro-clinical presentation of patients from in a single region (northern France) of h-ATTR when it presents as a polyneuropathy of unknown origin. Method We reviewed the records of patients referred to two neuromuscular centers from northern France with a peripheral neuropathy of unknown origin who were subsequently diagnosed with h-ATTR. Results Among 26 h-ATTR patients (10 Val30Met, 16 Ser77Tyr), only 14 patients had a suspicious family history (53.8%). The electro-clinical presentation was mostly a large-fiber sensory motor polyneuropathy (92.3%), which could be symmetric or not, length-dependent or not, or associated with nerve entrapment or not. Demyelinating signs were observed in 17 patients (70.8%), among whom nine fulfilled the criteria for a definite diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (37.5%). Conclusion h-ATTR may have a wide spectrum of clinical profiles, and should be considered in the screening of polyneuropathies of unknown origin.

Granulomatosis with polyangiitis (GPA) typically presents with upper or lower respiratory tract symptoms and/or with renal involvement. Although it can affect the peripheral nervous system frequently, with mononeuritis multiplex being the most common pattern, the occurrence of peripheral sensory-motor polyneuropathy as a presenting manifestation is distinctly rare. Prevalence of digital gangrene is also extremely rare in GPA. We describe a 46-year-old woman presenting with severe peripheral sensorimotor polyneuropathy affecting bilateral lower limbs preceded by a purpuric skin rash and multiple painful ulcers confined to the lower limbs. She had evidence of digital ischemia affecting multiple toes and dry gangrene of the left 4th toe. Diagnosis of GPA was made based on skin biopsy, positive ANCA serology, and clinical criteria. She made a good recovery following aggressive immunosuppressive treatment with methylprednisolone and cyclophosphamide and was maintained on prednisolone and azathioprine. This case highlights the importance of suspecting GPA in a patient presenting with sensorimotor polyneuropathy and/or digital ischemia even in the absence of more classic presenting features and underlies the necessity of accurate differential diagnosis in evaluating a case of peripheral neuropathy.

BACKGROUND: Ramsay Hunt Syndrome (RHS) is a neurotological disorder involving the reactivation of the varicella-zoster virus (VZV) in the geniculate ganglion of the facial nerve (Sweeney and Gilden in J Neurol Neurosurg Psychiatry 71:149-154, 2001). The characteristic presentation involves ipsilateral lower motor neuron type facial paresis, auricular pain with or without hearing impairment, and vesicular lesions of the external auditory canal and outer ear. Involvement of the facial and vestibulocochlear nerve is typical in RHS, whilst multiple cranial neuropathies are rare and associated with poorer prognosis and systemic complications (Arya et al. in Am J Case Rep 19:68-71, 2017; Shinha and Krishna in IDCases 2:47-48, 2015; Shim et al. in Acta Otolaryngol 131:210-215, 2011; Coleman et al. in J Voice 26:e27-e28, 2012; Morelli et al. in Neurol Sci 29:497-498, 2008;). Likely mechanisms involved in the pathogenesis of cranial polyneuropathy include direct peri-neural and trans-axonal spread of viral inflammation between contiguous cranial nerves and haematogenous dissemination between nerves with shared blood supply. Impairments in speech, swallowing, hearing, and oculo-protection can contribute to morbidity and requires a multidisciplinary approach to patient care. METHODS: We present a rare case of RHS with multiple cranial neuropathies followed by a comprehensive review of current literature with regard to the pathophysiology, diagnostic workup, and the management strategies employed in these patients. CONCLUSION: RHSs with multiple cranial neuropathies are important to recognise as they are associated with significant morbidity and poor prognosis. A multidisciplinary approach to patient management is required to address the several complications that can arise from cranial nerve deficits, especially in regard to speech and swallow.

Background/aim Ganglioside antibodies are identified not only in patients with inflammatory neuropathies but also several central nervous system disorders and paraneoplastic neuropathies. Our aim was to investigate whether ganglioside antibodies are found in autoimmune encephalitis patients and may function as a diagnostic and prognostic biomarker. Materials and methods Sera and cerebrospinal fluid (CSF) samples of 33 patients fulfilling the criteria for probable autoimmune encephalitis were collected within the first week of clinical manifestation. None of the patients had evident symptoms and findings of peripheral polyneuropathy. Well-characterized anti-neuronal and paraneoplastic antibodies were investigated in sera and CSF and anti-ganglioside (anti-GM1, GM2, GM3, GD1a, GD1b, GT1b and GQ1b) IgG and IgM antibodies were measured in sera using commercial immunoblots. Results Twenty-eight of 33 autoimmune encephalitis patients displayed antibodies against neuronal surface or onco-neural antigens with N-methyl-D-aspartate receptor (NMDAR), glutamic acid decarboxylase (GAD) and Hu antibodies being the most prevalent. While no anti-ganglioside IgG antibodies were found, 4 patients (2 anti-NMDAR+, 1 anti-GAD+ and 1 antibody negative) with autoimmune limbic encephalitis displayed anti-GM1, anti-GM2, anti-GM3 or anti-GQ1b IgM antibodies. There was no apparent association between anti-ganglioside positivity and clinical and demographic features. Conclusion Serum ganglioside IgM antibodies may infrequently emerge during the clinical course of autoimmune limbic encephalitis without evident polyneuropathy. Absence of the IgG response suggests that these antibodies might have developed as a hyperacute immune response to neuro-axonal destruction. Nevertheless, potential impact of ganglioside antibodies on axonal degeneration and neuronal loss in limbic encephalitis pends to be further investigated.

Background. The Hemoblastoses are one of the urgent problems of oncohematology. Modern methods for the treatment of hemoblastoses have improved the prognosis significantly. However, the use of chemotherapy is accompanied by a high frequency of drug complications, including those associated with neurotoxicity. The addition of neurological symptoms to the main clinical picture of the disease significantly aggravates the patients condition, affects the prognosis and quality to life. Aim. Compare clinical picture and neurophysiological signs of chemo-induced polyneuropathy in children with acute lymphoblastic leukemia. Materials and methods. Neurological examination and electromyography (EMG), were conducted in 21 children aged 3 to 17 years in Regional Children Clinical Hospital of Yekaterinburg from 2019 to 2020. Results. In the study group, the signs of peripheral polyneuropathy, were revealed in almost all patients receiving induction chemotherapy (95.2%) while clinical neurological symptoms were found in 25% patients. During a 4-month follow-up, all children with subclinical signs of peripheral nerve damage developed corresponding neurological symptoms. According to EMG, the number of patients with mixed polyneuropathy increased by 1.7 times. In every third child, the amplitude of the M-response and nerve conduction velocity, were decreased. Conclusions. Therefore, neurophysiological examination should be performed at an early stage to identify high-risk groups for neurotoxic complications in children with acute lymphoblastic leukemia receiving chemotherapy as timely administration of therapeutic treatment is required.

BACKGROUND Despite the high prevalence of depression and anxiety in chronic pain conditions, current knowledge concerning emotional distress among painful diabetic polyneuropathy (pDSPN) and other diabetes mellitus (DM) sufferers is limited. METHODS This observational multicentre cohort study employed the Hospital Anxiety and Depression Scale, the Beck Depression Inventory II and the State-Trait Anxiety Inventory to assess symptoms of depression and anxiety in several groups with diabetes, as well as in a control group. The study cohort included 347 pDSPN patients aged 63.4 years (median), 55.9% males; 311 pain-free diabetic polyneuropathy (nDSPN) patients aged 63.7 years, 57.9% males; 50 diabetes mellitus (DM) patients without polyneuropathy aged 61.5 years, 44.0% males; and 71 healthy controls (HC) aged 63.0 years, 42.3% males. The roles played in emotional distress were explored in terms of the biological, the clinical (diabetes-, neuropathy- and pain-related), the socio-economic and the cognitive factors (catastrophizing). RESULTS The study disclosed a significantly higher prevalence of the symptoms of depression and anxiety not only in pDSPN (46.7% and 60.7%, respectively), but also in patients with nDSPN (24.4% and 44.4%) and DM without polyneuropathy (22.0% and 30.0%) compared with HCs (7.0% and 14.1%, p

Purpose Serious immune checkpoint inhibitor (ICI)-related neurotoxicity is rare. There is limited data on the specifics of care and outcomes of patients with severe neurological immune related adverse events (NirAEs) admitted to the Intensive Care Unit (ICU). Materials and methods Retrospective study of patients with severe NirAEs admitted to the ICU at 3 academic centers between January 2016 and December 2018. Clinical data collected included ICI exposure, type of NirAE (central [CNS] or peripheral nervous system [PNS) disorders), and patient outcomes including neurological recovery and mortality. Results Seventeen patients developed severe NirAEs. Eight patients presented with PNS disorders; 6 with myasthenia gravis (MG), 1 had a combination of MG and polyneuropathy and 1 had Guillain-Barre syndrome. Nine patients had CNS disorders (6 seizures and 5 had concomitant encephalopathy. During ICU admission, 65% of patients required mechanical ventilation, 35% vasopressors, and 18% renal replacement therapy. The median ICU and hospital length of stay were 7 (2–36) and 18 (4–80) days, respectively. Hospital mortality was 29%. At hospital discharge, 18% of patients made a full neurologic recovery, 41% partial recovery, and 12% did not recover. Conclusion Severe NirAEs while uncommon, can be serious or even life-threatening if not diagnosed and treated early.

Background: Chronic idiopathic polyneuropathy is asymmetrical, axonal damage involving large fibres of insidious onsets is disclosed in neurophysiologic long-dependent neuropathy and slowly progressive course over a minimum of six months without aetiology can be identified despite the appropriate investigations. This research was designed to investigate idiopathic polyneuropathy individuals. Methods: The comparative patient control research comprised 20 patients selected from 127 polyneuropathic and 20 matching age or sex controls from the Al-Azhar University Neurology Clinic at Assuit Hospitals, April 2019 to May 2021. Results: Age of onset of idiopathic polyneuropathy patients (47-73), length of disease (1-6) years (60%), DN4 score (5–7), abnormal pine brick (80%), abnormal vibrations (90%), abnormal fine touch (75%), distal weaknesses (70%) losing ankle (90%) and wasting (20 percent ). This represents significant variations in the amplitude of decreased motor-action compounds and the reduced speed of median,ulnar, tibial peroneal nerves across the tested groups. Significant variations between tibial and peroneal tissues are also seen in prolonged distal latency, decreased sensory amplitude and extended latency between sensory (median, ulnar, and sural) nerves. The delay differences and a reduced amplitude of sympathetic cutaneous response across the investigated groups are significant. There are also substantial differences in the intraepidermal nerve fibre density decrease in skin biopsy from the distal leg between idiopathic polyneuropathical patients and control groups. Conclusion: Intraepidermal nerve fibre density in skin biopsy is responsive to idiopathic polyneuropathy than standard neurophyological investigations.

Peripheral neuropathies account for the most frequent disorders seen by neurologists, and causes are manifold. The traditional diagnostic gold-standard consists of clinical neurologic examinations supplemented by nerve conduction studies. Due to well-known limitations of standard diagnostics and atypical clinical presentations, establishing the correct diagnosis can be challenging but is critical for appropriate therapies. Magnetic resonance neurography (MRN) is a relatively novel technique that was developed for the high-resolution imaging of the peripheral nervous system. In focal neuropathies, whether traumatic or due to nerve entrapment, MRN has improved the diagnostic accuracy by directly visualizing underlying nerve lesions and providing information on the exact lesion localization, extension, and spatial distribution, thereby assisting surgical planning. Notably, the differentiation between distally located, complete cross-sectional nerve lesions, and more proximally located lesions involving only certain fascicles within a nerve can hold difficulties that MRN can overcome, when basic technical requirements to achieve sufficient spatial resolution are implemented. Typical MRN-specific pitfalls are essential to understand in order to prevent overdiagnosing neuropathies. Heavily T2-weighted sequences with fat saturation are the most established sequences for MRN. Newer techniques, such as T2-relaxometry, magnetization transfer contrast imaging, and diffusion tensor imaging, allow the quantification of nerve lesions and have become increasingly important, especially when evaluating diffuse, non-focal neuropathies. Innovative studies in hereditary, metabolic or inflammatory polyneuropathies, and motor neuron diseases have contributed to a better understanding of the underlying pathomechanism. New imaging biomarkers might be used for an earlier diagnosis and monitoring of structural nerve injury under causative treatments in the future. Supplementary Information The online version contains supplementary material available at 10.1007/s13311-021-01166-8.

Purpose This case report aimed to investigate the effects of supervised home-based resistance training (RT) on functional capacity and mental health on a man with idiopathic peripheral polyneuropathy (PP). Method A 50-year-old man diagnosed with PP with no previous experience in RT performed 24 session of home-based RT for 12 weeks. Resistance training consisted of 3 exercises performed with 3 sets and lasted approximately 30 min per session. Exercises were performed with minimal implements (e.g., elastic tubes and light dumbbells). The Patient was evaluated for muscle performance, functionality, anxiety levels, and depressive symptoms before and after intervention period. Muscle performance was evaluated though 30-s push up test (PU30), functional capacity was evaluated through functional tests [sit to stand test (SST), arm curl (AC), and 2-min step test (2-MST)] and anxiety levels and depressive symptoms were evaluated through the State-Trait Anxiety Inventory (STAI) and Beck's depression inventory (BDI), respectively. Results After 12 weeks, the performance on PU30 increased 40% (from 8 to 11 repetitions), while the performance on SST, AC and 2-MST increased 100% (from 4 to 8 repetitions), 44% (from 16 to 23 repetitions) and 157% (from 47 to 121 repetitions), respectively. Anxiety state and trait levels have been reduced 24% (from 42 to 32 scores) and 4% (from 47 to 45 scores), respectively. There was no change for BDI. Conclusion Supervised home-based RT using low cost and affordable equipment was a feasible strategy to provide functional capacity and mental health benefits in a patient with PP.

Reliable and responsive tools for monitoring disease activity and treatment outcomes in patients with neuropathies are lacking. With the emergence of ultrasensitive blood bioassays, proteins released with nerve damage are potentially useful response biomarkers for many neurological disorders, including polyneuropathies. In this review, we provide an overview of the existing literature focusing on potential applications in polyneuropathy clinical care and trials. Whilst several promising candidates have been identified, no studies have investigated if any of these proteins can serve as response biomarkers of longitudinal disease activity, except for neurofilament light (NfL). For NfL, limited evidence exists supporting a role as a response biomarker in Guillain-Barré syndrome, vasculitic neuropathy, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Most evidence exists for NfL as a response biomarker in hereditary transthyretin-related amyloidosis (hATTR). At the present time, the role of NfL is therefore limited to a supporting clinical tool or exploratory endpoint in trials. Future developments will need to focus on the discovery of additional biomarkers for anatomically specific and other forms of nerve damage using high-throughput technologies and highly sensitive analytical platforms in adequality powered studies of appropriate design. For NfL, a better understanding of cut-off values, the relation to clinical symptoms and long-term disability as well as dynamics in serum on and off treatment is needed to further expand and proceed towards implementation. Supplementary Information The online version contains supplementary material available at 10.1007/s13311-021-01136-0.

Paraproteinemia is associated with different peripheral neuropathies. The major causes of neuropathy correlated with paraproteinemia are the deposition of immunoglobulin in the myelin, represented by anti-myelin-associated glycoprotein (MAG) neuropathy; deposition of immunoglobulin or its fragment in the interstitium, represented by immunoglobulin light chain amyloidosis (AL amyloidosis); and paraneoplastic mechanisms that cannot be solely attributed to the deposition of immunoglobulin or its fragment, represented by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin change (POEMS) syndrome. Patients with anti-MAG neuropathy and POEMS syndrome present with slowing of nerve conduction parameters. This characteristic fulfills the electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) defined by the European Academy of Neurology and Peripheral Nerve Society (EAN/PNS). Although direct damage caused by the deposition of amyloid can induce axonal damage in AL amyloidosis, some patients with this condition have features fulfilling the EAN/PNS electrodiagnostic criteria for CIDP. Conventional immunotherapies for CIDP, such as steroids, intravenous immunoglobulin, and plasma exchange, offer no or only minimal-to-modest benefit. Although rituximab can reduce the level of circulating autoantibodies, it may only be effective in some patients with anti-MAG neuropathy. Drugs including melphalan, thalidomide, lenalidomide, and bortezomib for POEMS syndrome and those including melphalan, thalidomide, lenalidomide, pomalidomide, bortezomib, ixazomib, and daratumumab for AL amyloidosis are considered. Since there will be more therapeutic options in the future, thereby enabling appropriate treatments for individual neuropathies, there is an increasing need for early diagnosis.

HIV infection is rarely considered a possible etiological factor of neurological pathology, that causes the late diagnosis of the disease and the untimely start of a specific therapy. The neurological manifestations of the disease may be due to the direct impact of HIV on the nervous system, opportunistic infections and malignancies, neurotoxic effects of antiretroviral treatment, and other systemic complications. HIV-associated neurological disorders are variable and presented with neurocognitive disorders, encephalopathy, myelopathy, polyneuropathy, aseptic meningitis (meningoencephalitis). HIV-encephalopathy in children manifests with emotional, cognitive, motor and speech disorders. In adults, chorea syndrome is considered a possible clinical variant of HIV encephalopathy. In the literature available, we have not encountered reports about the development of choroid syndrome in HIV-infected children. The described clinical case demonstrates the diagnosis of late-stage HIV infection in a 13-year-old child with chorea syndrome. The presented clinical observation demonstrates the complexity of diagnosing HIV encephalopathy in a child, which has been associated with the rare manifestation of this disease in childhood as generalized hyperkinesis, as well as the concealment of anamnestic HIV infection in a mother. Thus, in children with chorea, the diagnosis is possible only with the exclusion of the diseases that cause it, namely: acute rheumatic fever, systemic connective tissue disease, demyelinating diseases, tumours of the central nervous system, Wilson-Konovalov disease, as well as HIV., ВИЧ-инфекция среди возможных этиологических факторов неврологической патологии пока рассматривается редко, что приводит к поздней диагностике заболевания и несвоевременному началу специфической терапии. Неврологические проявления заболевания могут возникать в связи с прямым воздействием ВИЧ на нервную систему, оппортунистическими инфекциями и злокачественными новообразованиями, нейротоксичными эффектами антиретровирусного лечения и другими системными осложнениями. ВИЧ-ассоциированные неврологические расстройства вариабельны и представлены нейрокогнитивными нарушениями, энцефалопатией, миелопатией, полинейропатией, асептическим менингитом (менингоэнцефалитом). ВИЧ-энцефалопатия у детей проявляется в форме эмоциональных, когнитивных, двигательных, речевых нарушений. У взрослых больных как возможный клинический вариант ВИЧ-энцефалопатии рассматривается синдром хореи. В доступной литературе мы не встретили сообщений о развитии хорееподобного синдрома у ВИЧ-инфицированных детей. Описанный клинический случай демонстрирует диагностику поздней стадии ВИЧ-инфекции у ребенка 13 лет с синдромом хореи. Представленное клиническое наблюдение демонстрирует сложности диагностики ВИЧ-энцефалопатии у ребенка, что было связано с редким проявлением данного заболевания в детском возрасте в виде генерализованных гиперкинезов, а также с сокрытием матерью анамнестических данных о наличии у нее ВИЧ-инфекции. Таким образом, у детей с хореей диагноз возможен только при исключении заболеваний, ее вызывающих, а именно острой ревматической лихорадки, системного заболевания соединительной ткани, демиелинизирующих заболеваний, объемно-органической патологии центральной нервной системы, болезни Вильсона — Коновалова, а также ВИЧ-инфекции., ВІЛ-інфекція серед можливих етіологічних факторів неврологічної патології поки розглядається рідко, що приводить до пізньої діагностики захворювання та несвоєчасного початку специфічної терапії. Неврологічні прояви захворювання можуть виникати у зв’язку з прямим впливом ВІЛ на нервову систему, опортуністичними інфекціями та злоякісними новоутвореннями, нейротоксичними ефектами антиретровірусного лікування та іншими системними ускладненнями. ВІЛ-асоційовані неврологічні розлади варіабельні та представлені нейрокогнітивними порушеннями, енцефалопатією, мієлопатією, полінейропатією, асептичним менінгітом (менінгоенцефалітом). ВІЛ-енцефалопатія в дітей проявляється у формі емоційних, когнітивних, рухомих, мовних порушень. У дорослих хворих як можливий клінічний варіант ВІЛ-енцефалопатії розглядається синдром хореї. У доступній літературі ми не зустріли повідомлень щодо розвитку хореєподібного синдрому у ВІЛ-інфікованих дітей. Описаний клінічний випадок демонструє діагностику пізньої стадії ВІЛ-інфекції в дитини 13 років із синдромом хореї. Представлене клінічне спостереження демонструє складності діагностики ВІЛ-енцефалопатії в дитини, що було пов’язано з рідкісним проявом даного захворювання в дитячому віці у вигляді генералізованих гіперкінезів, а також із приховуванням матір’ю анамнестичних даних щодо наявності в неї ВІЛ-інфекції. Таким чином, у дітей із хореєю діагноз можливий лише при виключенні захворювань, що її викликають, а саме гострої ревматичної лихоманки, системного захворювання сполучної тканини, демієлінізуючих захворювань, об’ємно-органічної патології центральної нервової системи, хвороби Вільсона — Коновалова, а також ВІЛ-інфекції.

The aim of the study was to check the risk factors for subjects with motor conduction velocity (MCV) reduction of the ulnar nerve across the elbow without symptoms/signs of ulnar neuropathy at the elbow (UNE) using a database of a previous multicenter case–control study on UNE patients. From the previous database, we extracted all asymptomatic UNE (A-UNE) and matched for age and sex with a control and UNE groups with a ratio of 1:2. Anthropometric factors were measured and all participants filled in a questionnaire on demographic, lifestyle factors, and medical history. One-sample proportion test and univariate and multivariate logistic regression analyses were performed. We enrolled 64 A-UNE, 124 UNE, and 124 controls (mean age 53 years). There were more males with A-UNE than females (74.2%). The predominantly or exclusively concerned side of A-UNE was the right. Logistic regression showed that A-UNE was associated with diabetes (OR = 2.99, 95% CI = 1.21–7.39) and width of cubital groove (CGW) (OR = 0.89, 95% CI = 0.81–0.97). Risk factors for A-UNE are different from UNE. The prevalence of right side in A-UNE was not due to particular elbow postures. Diabetes is a risk factor, probably because MCV reduction of the ulnar nerve across the elbow was an early manifestation of asymptomatic polyneuropathy in diabetes. A-UNE is associated with narrow CGW as already demonstrated in UNE, even if the OR was higher in UNE than in A-UNE. Only future longitudinal studies will be able to check whether the A-UNE subjects develop symptoms and signs of true mononeuropathy with time.

The advent of next generation sequencing has revolutionized diagnostic approaches to hereditary polyneuropathies. Recently, mutations on the membrane metallo-endopeptidase (MME) gene, encoding neprilysin, have been related to the development of late-onset Charcot-Marie-Tooth disease type 2 (CMT2). Here, we report the first Greek patient presenting with a slowly progressive late-onset axonal polyneuropathy and a novel, likely pathogenic, heterozygous variant in the MME gene. In addition, we have performed a systematic review of all published case reports of patients with MME mutations. The results of the studies show that MME variants can be inherited as both fully penetrant autosomal-recessive and incompletely penetrant autosomal-dominant traits. A number of heterozygous variants characterized as incompletely penetrant impose an increased risk of developing a CMT2-like phenotype late in life, identical to the case study described here. Greater mutation numbers in different populations and mutation-specific functional studies will be essential to identify the pathogenicity and inheritance of more MME variants.

Introduction Neurological complications of SARS-CoV-2 disease have received growing attention, but only few studies have described to date clinical and neurophysiological findings in COVID patients during their stay in intensive care units (ICUs). Here, we neurophysiologically assessed the presence of either critical illness neuropathy (CIP) or myopathy (CIM) in ICU patients. Materials and Methods Patients underwent a neurophysiological assessment, including bilateral examination of the median, ulnar, deep peroneal and tibial motor nerves and of the median, ulnar, radial and sural sensory nerves. Needle electromyography (EMG) was performed for both distal and proximal muscles of the lower and upper limbs. In order to differentiate CIP from CIM, Direct Muscle Stimulation (DMS) was applied either to the deltoid or tibialis anterior muscles. Peak to peak amplitudes and onset latencies of the responses evoked by DMS (DMSamp, DMSlat) or by motor nerve stimulation (MNSamp, MNSlat) were compared. The ratio MNSamp to DMSamp (NMR) and the MNSlat to DMSlat difference (NMD: MNSlat − DMSlat) were also evaluated. Results Nerve conduction studies showed a sensory-motor polyneuropathy with axonal neurogenic pattern, as confirmed by needle EMG. Both MNSamp and NMR were significantly reduced when compared to controls (p

The review presents the pathogenetic mechanisms of central and peripheral nervous system pathology in primary hypothyroidism. Lack of thyroid hormones leads to changes in the organization of the central nervous system, decrease in the energy supply of neurons, changes in the synthesis of some specific proteins of the nervous system that cause the development of cretinism in children. The role of hypothyroidism in the development of cognitive impairment in adults, such as decreased cognitive function, memory and attention, has been proved. The impairment of logical thinking is found already in patients with subclinical hypothyroidism. Disorders in mediation exchange lead to the development of depression. Neuromuscular disorders (hypothyroid myopathy and myotonic phenomenon) and affection to the peripheral nerves are best studied in hypothyroidism. Primary hypothyroidism may be masked by tunnel neuropathy, polyneuropathy and atactic syndrome. Despite the existing papers on the problem of hypothyroidism and its neurological complications, some issues of pathogenesis, diagnosis, course and treatment of neurological pathology in primary hypothyroidism require further research.

Background. The purpose of the study is to determine the dynamics of clinical and laboratory characteristics and functional state of peripheral nerves in patients with type 2 diabetes mellitus (DM) complicated by distal symmetrical polyneuropathy (DSPN) depending on the frequency distribution of the G894T genotypes of endothelial NO-synthase (eNOS) gene polymorphism during the recommended therapy. Mate­rials and methods. 110 patients were examined, they were divided into groups: with initial manifestations of DSPN — 32 (29.1 %), with moderate course — 58 (52.7 %) and with severe course — 20 (18.2 %). Patients received L-arginine preparation during basic treatment. All patients were neurologically examined using Neuropathic Symptomatic Score, Neuropathic Dysfunctional Score, electroneuromyographic testing of the peripheral nerves of the lower extremities; parameters of carbohydrate metabolism, pro- and antioxidant defense, functional state of the endothelium were evaluated. Results. In patients with DSPN and type 2 DM, homozygotes for the minor T allele of the eNOS gene G894T polymorphism, the likelihood of developing severe complications of diabetic polyneuropathy increases: the odds ratio was 2.91 (95 % confidence interval 1.19–7.14; p < 0.05). In patients with GT and GG genotypes, the highest efficacy of the recommended therapy is determined, in contrast to patients with homozygous TT genotype, whose dynamics of clinical, laboratory and functional indicators was significantly lower. Conclusions. Homozygotes for the minor T allele of the eNOS gene G894T polymorphism have an increase in the incidence and the severity of DSPN course on the background of type 2 DM, and also a less stable effect from the treatment of this complication.

The article presents the pathogenesis of polyneuropathy symptoms in patients with hypothyroidism, whereby the approaches to the pathogenetic therapy are substantiated. The article represents the most important aspects of hypothyroid polyneuropathy treatment according to the latest international guidelines and perspective scientific approaches to optimize the medical care for patients with this pathology.

Мета дослідження — виявити електронейроміографічні особливості ураження периферичної нервової системи в пацієнтів iз первинним гіпотиреозом на фоні автоімунного тиреоїдиту (АІТ) та післяопераційного гіпотиреозу шляхом проведення стимуляційної електрoнейроміографії (ЕНМГ). Матеріали та методи. Обстежено 56 хворих на гіпотиреоз на фоні АІТ та 19 пацієнтів iз післяопераційним гіпотиреозом. Контрольну групу становили 20 практично здорових осіб. П’ятдесят сім (76 %) пацієнтів отримували замісну терапію синтетичними похідними L-тироксину, у 18 (24 %) хворих був субклінічний гіпотиреоз. Проведено комплексне клініко-неврологічне та електрофізіологічне обстеження хворих, що включало ЕНМГ-тестування моторних (малогомілкові, великогомілкові, серединні) та сенсорних (малогомілкові, литкові) нервів. При дослідженні моторних нервів оцiнювали наступні показники: амплітуду та тривалість М-відповіді, площу М-відповіді на стимуляцію нерву в дистальній та проксимальній точках, термінальну латентність, резидуальну латентність, швидкість проведення збудження (ШПЗ), при вивченні сенсорних нервів — амплітуду потенціалу дії та ШПЗ. Результати. За АІТ спостерігалось ураження сенсорних нервів нижніх кінцівок (поверхневi малогомілковi та литковi) за змішаним типом. Аксонопатія проявлялась у зменшенні амплітуди потенціалу дії поверхневого малогомілкового нерва на 32,7 % (p

Objective To assess axonal function prior to subcutaneous immunoglobulin (SCIG) therapy or placebo in relation to relapse in chronic inflammatory demyelinating polyneuropathy (CIDP) to determine whether axonal damage can predict therapy response. Methods Relapse rates in patients from the Polyneuropathy and Treatment with Hizentra (PATH) study, where patients were treated with placebo or SCIG (IgPro20), were analyzed by baseline (post-intravenous immunoglobulin stabilization) axonal damage (≤1 mV peroneal compound muscle action potential) status. Results In patients with non-axonal damage, relapses were significantly higher with placebo (73.0%) than IgPro20 (0.2 g/kg: 39.1%, 0.4 g/kg: 19.2%). In patients with axonal damage, IgPro20 had no effect on relapse (placebo: 25.0%, IgPro20: 0.2 g/kg: 30.0%, 0.4 g/kg: 19.4%). Patients with axonal damage relapsed significantly less on placebo versus non-axonal damage, but they also demonstrated higher baseline disability. Conclusion Axonal damage may correspond to relapse upon treatment withdrawal; patients with axonal damage relapse less, possibly reflecting poor response to immunoglobulin therapy, while non-axonal damage patients may experience more relapse, perhaps indicating better treatment response. Significance In CIDP patients with axonal loss, immunoglobulin therapy may not be as effective. Assessing axonal damage could help guide therapy, with immunoglobulins ideally used before substantial axonal damage arises.

In course of diabetes, some 20-90% of individuals eventually develop diabetic neuropathy. Looking at the disease burden research studies in Homoeopathy were conducted and have shown positive results. These studies were not robust enough to prove the efficacy of individualized homoeopathy.To assess efficacy of individualized homoeopathic medicines in management of DDSP.A multi-centric double-blind, placebo controlled, randomised clinical trial was conducted by the Central Council for Research in Homoeopathy at six centres with a sample size of 84. Based on earlier observational studies and repertorial anamnesis of DDSP symptoms 15 homoeopathic medicines were shortlisted and validated scales were used for evaluating the outcomes post-intervention. Primary outcome measure was change in Neuropathy Total Symptom Score-6 (NTSS-6) from baseline to 12 months. Secondary outcomes included changes in peripheral nerve conduction study (NCS), World Health Organization Quality of Life BREF (WHOQOL-BREF) and Diabetic Neuropathy Examination (DNE) Score at 12 months.Data of 68 enrolled cases was considered for data analysis. Statistically significant difference (p0.014) was found in NTSS-6 post intervention in the Verum group. Positive trend was noted for Verum group as per the graph plotted for DNE score and assessment done for NCS. No significant difference was found between the groups for WHOQOL-Bref. Out of 15 pre-identified homoeopathic medicines 11 medicines were prescribed in potencies in ascending order from 6C to 1M.Further studies must be taken up with larger sample size and defined parameters for NCS to assess the effectiveness of homoeopathy.

Introduction: Occupational polyneuropathy of upper extremities induced by physical overload is often registered among workers of various occupations. Yet, modern science lacks up-to-date results of a comprehensive assessment of the condition of such patients in terms of occupational disease severity and the presence of concomitant non-occupational diseases. Objective: To establish severity of the occupational disease and comorbidity status in workers of various occupations, to assess their significance for planning measures aimed at professional rehabilitation of patients. Materials and methods: Severity of occupational polyneuropathy and comorbidity status were established in agricultural, construction, industrial, and mining workers. Results: In all cohorts of workers, occupational polyneuropathy is generally registered in middle-aged and elderly people usually experiencing moderate symptoms; in most cases, it is combined with other occupational diseases of the musculoskeletal system and the peripheral nervous system. Miners suffering from this type of polyneuropathy are often diagnosed with chronic industrial bronchitis. Of non-occupational disorders, ischemic heart disease, hypertension, dorsopathies, and osteoarthritis of various sites prevail in all occupational cohorts and limit the ability of patients to work. Discussion: The severity of polyneuropathy and comorbidity status of patients from different occupational cohorts vary and this fact shall be taken into account when planning medical and professional rehabilitation of workers, which is usually hampered due to imperfection of the current regulations on examining professional suitability, according to which occupational peripheral neuropathy cases shall not stop working in conditions of physical overload. Conclusions: It is critical to attend to the flaws of current regulations, which impede effective rehabilitation of patients with occu¬pational polyneuropathy and other associated diseases.