Rare among Rare: Phenotypes of Uncommon CMT Genotypes

(1) Background: Charcot–Marie–Tooth disease (CMT) is the most frequent form of inherited chronic motor and sensory polyneuropathy. Over 100 CMT causative genes have been identified. Previous reports found PMP22, GJB1, MPZ, and MFN2 as the most frequently involved genes. Other genes, such as BSCL2, MORC2, HINT1, LITAF, GARS, and autosomal dominant GDAP1 are responsible for only a minority of CMT cases. (2) Methods: we present here our records of CMT patients harboring a mutation in one of these rare genes (BSCL2, MORC2, HINT1, LITAF, GARS, autosomal dominant GDAP1). We studied 17 patients from 8 unrelated families. All subjects underwent neurologic evaluation and genetic testing by next-generation sequencing on an Ion Torrent PGM (Thermo Fischer) with a 44-gene custom panel. (3) Results: the following variants were found: BSCL2 c.263A > G p.Asn88Ser (eight subjects), MORC2 c.1503A > T p.Gln501His (one subject), HINT1 c.110G > C p.Arg37Pro (one subject), LITAF c.404C > G p.Pro135Arg (two subjects), GARS c.1660G > A p.Asp554Asn (three subjects), GDAP1 c.374G > A p.Arg125Gln (two subjects). (4) Expanding the spectrum of CMT phenotypes is of high relevance, especially for less common variants that have a higher risk of remaining undiagnosed. The necessity of reaching a genetic definition for most patients is great, potentially making them eligible for future experimentations.

A case of motor and sensory polyneuropathy induced by primary hyperparathyroidism

Primary hyperparathyroidism (PHP) is a disease in which excessive amounts of parathyroid hormone (PTH) are secreted and calcium levels in the blood increase. Hypercalcemia caused by PHP has a major influence on the peripheral nervous system and produces symptoms such as muscle cramps, paresthesia, and proximal muscle weakness. Here we report a rare case of sensory-dominant polyneuropathy caused by PHP, which improved after surgery.

PRECISION ASSESSMENT OF THE STATE OF BONE TRABECULAE AND MINERAL SATURATION OF BONE SPONGY STRUCTURES IN WORKERS EXPOSED TO CONTACT ULTRASOUND

A comparative retrospective analysis of the results of a clinical - X-ray examination of 93 women doctors of ultrasound examinations of working age and 60 people was performed. control groups of age and experience comparable work with persons of major groups (nurses not associated with exposure to occupational ultrasound). Degenerative-dystrophic changes were revealed in the form of: osteorthrosis of the shoulder, elbow, wrist and interphalangeal joints, periarthrosis of the shoulder and elbow joints, small cyst-like clearances and enostoses in the bones of the wrists of the most loaded upper limb. The level of decrease in the mineral saturation and thickness of bone trabeculae in the areas of interest of the radius bones and distal phalanges of the hands was dependent on the severity of the clinical picture of vegetative-sensory polyneuropathy. Indicators of bone density and the state of bone trabeculae in the spongy structures of the distal radial bones and distal phalanges can be a kind of marker of the severity of OP. The use of modern methods for assessing the density and structure of bone tissue allows us to reduce the negative role of the so-called "human factor" and thus

A CRITICAL REVIEW ON MADHUMEHA JANYA TWAK-GATA VATA WITH SPECIAL REFERENCE TO DIABETIC PERIPHERAL NEURITIS

With the increasing prevalence of Diabetes mellitus especially in the middle age group, the chances of developing neuro-vascular complications are very high. One such complication is Diabetic Peripheral Neuropathy / Distal Symmetric sensory Polyneuropathy (DSPN). Diabetes mellitus can be correlated to Madhumeha and its complication Peripheral neuropathy to that of Twak-gata vata. Twakgata vata is one such vatavyadhi which can manifest in a Madhumeha Rogi. According to Acharya Charaka, Prakupita vata localized in twak brings about dryness of skin, skin cracks open, numbness in that part, emaciation, black discolouration, pricking type of pain, a feeling of stretching in that part, redness, and pain in small joints. Charaka has explained the special reason for the manifestation of a vatavyadhi. He says that depending upon the specific cause and site the aggravated vata produces different types of vyadhis, like twak-gata vata, raktagata vata, etc. Though, Daha as a lakshana has not been mentioned under Twakgata vata lakshanas, when there is anubandha of vata with pitta, daha is seen. Sushruta says in rasa-rakta etc., if vata gets associated with other doshas it produces various disorders. Ex: If there is daha, then association of vata with pitta should be inferred.

Occurrence of Pure Sensory Neuropathy in a 45-Year-Old Female with Primary Sjögren’s Syndrome: A Case Report Study

: Complications of Sjögren’s syndrome (SS) and neuropathies may occur in some cases. Almost this complication occurs with peripheral neuropathy. Different forms of sensory neuropathy, multiple mononeuropathy, trigeminal neuropathy, multiple cranial neuropathy, radiculoneuropathy, and autonomic neuropathy can occur in SS. In this novel case presentation, polyneuropathy in a 45-year-old female patient with SS is reported with a complaint of ataxia, vertigo, dysarthria, abnormal gait, foreign body sensation, and deterioration of quadriparesis from six months ago. Fluorescent antinuclear antibody (FANA), anti-RO, anti-RO-52, and RF were strongly detected positive in her rheumatologic examination. Pure sensory polyneuropathy (ganglionopathy) was also reported in electromyography and nerve conduction velocity (EMG-NCV). Although peripheral neuropathy is the major and most common neurological aspect of neuron involvement in patients with SS, here, pure sensory polyneuropathy is reported in a 45-year-old female patient with SS. In conclusion, in this novel case presentation, a novel case of polyneuropathy concurrent with SS is demonstrated in a 45-year-old female patient.

Application of ischemic preconditioning in the rehabilitation of miners suffered from the vibration disease

Introduction. Vibration disease is characterized by the early development of sensory polyneuropathy. Sensitive disorders significantly worsen the quality of life and increase the duration of the unemployable period of miners, which requires the search for new modern methods of correction and rehabilitation. Ischemic preconditioning is a promising direction in the treatment of occupationally caused polyneuropathies. However, its potential neuroprotective effect has not been sufficiently studied. The aim of the study was to evaluate the effectiveness of ischemic preconditioning of the upper extremities for the correction of sensory polyneuropathy manifestations in miners with vibration disease. Material and methods. Seventy-eight persons with a proven diagnosis of vibration disease were examined. According to a specially elaborated technique, the ischemic preconditioning of the upper extremities was performed in 46 patients who were included in the leading group; 32 patients made up the control group. The clinical and electroneuromyographic examination was carried out before the ischemic preconditioning procedure and on the 5th day of the study. Results. The initial clinical and neurophysiological indices in both groups did not differ statistically significant and indicated sensory polyneuropathy. After ischemic preconditioning, the subjects of the leading group showed an improvement in clinical and functional indices (reduction of numbness and paresthesia, improvement of vibration sensitivity, an increase in the sensory conduction velocity of impulse and the amplitudes of sensory responses) of the peripheral nerves of the upper extremities. In contrast, in the control group, there was no statistically significant change in objective indices. Conclusion. Ischemic preconditioning of the upper extremities is effective in the rehabilitation of miners with vibration disease, helps to reduce the manifestations of sensory polyneuropathy, sensitive disorders and normalize neurophysiological indices.

Vibration disease from exposure to general vibration: methodology of diagnosis and place of electroneuromyography

The article describes the features of the state of the neuromuscular apparatus in vibration diseases of various degrees of severity using electroneuromyographic research on the basis of the department of occupational Pathology of the regional center of Occupational Pathology of the Samara Medical and Sanitary Unit No. 5 of the Kirov district. It was found that patients with vibration disease are characterized by changes in the excitability and functional mobility of the sensorimotor system, the formation of vegetative-sensory polyneuropathy, depending on the severity of the vibration disease, the length of work in contact with vibration.

Paresthesia Predicts Increased Risk of Distal Neuropathic Pain in Older People with HIV-Associated Sensory Polyneuropathy

Objective Distal sensory polyneuropathy (DSP) is a disabling consequence of HIV, leading to poor quality of life and more frequent falls in older age. Neuropathic pain and paresthesia are prevalent symptoms, however there are currently no known curative treatments and the longitudinal course of pain in HIV-associated DSP is poorly characterized. Methods This was a prospective longitudinal study of 265 PWH enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study with baseline and 12-year follow-up evaluations. Since pain and paresthesia are highly correlated, statistical decomposition was used to separate the two symptoms at baseline. Multivariable logistic regression analyses of decomposed variables were used to determine the effects of neuropathy symptoms at baseline on presence and worsening of distal neuropathic pain at 12-year follow-up, adjusted for covariates. Results Mean age was 56 ± 8 years, and 21% were female at follow-up. Nearly the entire cohort (96%) was on antiretroviral therapy (ART) and 82% had suppressed (≤50 copies/mL) plasma viral loads at follow-up. Of those with pain at follow-up (n = 100), 23% had paresthesia at the initial visit. Decomposed paresthesia at baseline increased the risk of pain at follow-up (OR 1.56; 95% CI 1.18, 2.07), and decomposed pain at baseline predicted a higher frequency of pain at follow-up (OR 1.96 [1.51, 2.58]). Conclusions Paresthesias are a clinically significant predictor of incident pain at follow-up among aging PWH with DSP. Development of new therapies to encourage neuroregeneration might take advantage of this finding to choose individuals likely to benefit from treatment preventing incident pain.

IgM paraprotein and anti-MAG sensory polyneuropathy associated with Waldenstrom’s macroglobulinaemia and medullary carcinoma of the thyroid

A previously fit and well 76-year-old man, presented with distal lower limb sensory symptoms suggestive of peripheral sensory neuropathy, associated with positive anti-MAG antibodies (myelin associated glycoprotein) and IgM paraprotein. Bone marrow biopsy showed lymphoplasmocytoid lymphoma (Waldenstrom’s macroglobulinaemia, WM), consequently positive for MYD88 mutation. He subsequently developed medullary carcinoma of the thyroid, most likely secondary to WM. He underwent a successful total thyroidectomy and four treatment doses of rituximab, which proved beneficial. He is currently stable and under multidisciplinary monitoring. His sensory symptoms have improved following rituximab treatment and his WM is under control.