Distal Sensory Polyneuropathy Research Articles

Mitochondrial DNA and Electron Transport Chain Protein Levels Are Altered in Peripheral Nerve Tissues from Donors with HIV Sensory Neuropathy: A Pilot Study.

Distal sensory polyneuropathy (DSP) and distal neuropathic pain (DNP) remain significant challenges for older people with HIV (PWH), necessitating enhanced clinical attention. HIV and certain antiretroviral therapies (ARTs) can compromise mitochondrial function and impact mitochondrial DNA (mtDNA) replication, which is linked to DSP in ART-treated PWH. This study investigated mtDNA, mitochondrial fission and fusion proteins, and mitochondrial electron transport chain protein changes in the dorsal root ganglions (DRGs) and sural nerves (SuNs) of 11 autopsied PWH. In antemortem standardized assessments, six had no or one sign of DSP, while five exhibited two or more DSP signs. Digital droplet polymerase chain reaction was used to measure mtDNA quantity and the common deletions in isolated DNA. We found lower mtDNA copy numbers in DSP+ donors. SuNs exhibited a higher proportion of mtDNA common deletion than DRGs in both groups. Mitochondrial electron transport chain (ETC) proteins were altered in the DRGs of DSP+ compared to DSP- donors, particularly Complex I. These findings suggest that reduced mtDNA quantity and increased common deletion abundance may contribute to DSP in PWH, indicating diminished mitochondrial activity in the sensory neurons. Accumulated ETC proteins in the DRG imply impaired mitochondrial transport to the sensory neuron's distal portion. Identifying molecules to safeguard mitochondrial integrity could aid in treating or preventing HIV-associated peripheral neuropathy.

Elevated Biomarkers of Inflammation and Vascular Dysfunction Are Associated with Distal Sensory Polyneuropathy in People with HIV.

Distal sensory polyneuropathy (DSP) is a disabling, chronic condition in people with HIV (PWH), even those with viral suppression of antiretroviral therapy (ART), and with a wide range of complications, such as reduced quality of life. Previous studies demonstrated that DSP is associated with inflammatory cytokines in PWH. Adhesion molecules, essential for normal vascular function, are perturbed in HIV and other conditions linked to DSP, but the link between adhesion molecules and DSP in PWH is unknown. This study aimed to determine whether DSP signs and symptoms were associated with a panel of plasma biomarkers of inflammation (d-dimer, sTNFRII, MCP-1, IL-6, IL-8, IP-10, sCD14) and vascular I integrity (ICAM-1, VCAM-1, uPAR, MMP-2, VEGF, uPAR, TIMP-1, TIMP-2) and differed between PWH and people without HIV (PWoH). A cross-sectional study was conducted among 143 participants (69 PWH and 74 PWoH) assessed by studies at the UC San Diego HIV Neurobehavioral Research Program. DSP signs and symptoms were clinically assessed for all participants. DSP was defined as two or more DSP signs: bilateral symmetrically reduced distal vibration, sharp sensation, and ankle reflexes. Participant-reported symptoms were neuropathic pain, paresthesias, and loss of sensation. Factor analyses reduced the dimensionality of the 15 biomarkers among all participants, yielding six factors. Logistic regression was used to assess the associations between biomarkers and DSP signs and symptoms, controlling for relevant demographic and clinical covariates. The 143 participants were 48.3% PWH, 47 (32.9%) women, and 47 (33.6%) Hispanics, with a mean age of 44.3 ± 12.9 years. Among PWH, the median (IQR) nadir and current CD4+ T-cells were 300 (178-448) and 643 (502-839), respectively. Participants with DSP were older but had similar distributions of gender and ethnicity to those without DSP. Multiple logistic regression showed that Factor 2 (sTNFRII and VCAM-1) and Factor 4 (MMP-2) were independently associated with DSP signs in both PWH and PWoH (OR [95% CI]: 5.45 [1.42-21.00], and 15.16 [1.07-215.22]), respectively. These findings suggest that inflammation and vascular integrity alterations may contribute to DSP pathogenesis in PWH, but not PWoH, possibly through endothelial dysfunction and axonal degeneration.

Ayurvedic Treatment Modalities of Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy is the damage of the nerves due to the uncontrolled diabetes. It can affect any of the neurons can affect any of the neurons. Diabetic distal symmetric sensory and sensorimotor polyneuropathy is the most prevalent type of diabetic neuropathy. The symptoms appear as sensory loss, first in the toes and progressively moving up the legs, fingers, and arms over time. Tingling sensation, Burning sensation, Deep aching pain are other related symptoms. A patient age 54 years with diabetes for past 15 years, hypertension, dyslipidemia, complains of burning sensation of both feet (right>left), numbness, pricking pain, unsteadiness while walking, brownish red discolouration of both lower limbs. The symptoms were gradual in onset. Nerve Conduction Study showed axonal type of motor and sensory affecting peroneal nerve neuropathy. He admitted in Vaidyaratnam Ayurveda College Hospital, done Vibrotherm Neuropathy Analyzer and revealed small and large fibre neuropathy with severe loss of sensations. The main intention of the study is to improve the quality of life of the patient by reducing the symptoms that is disturbing his day today routine. Patient given with anti diabetic Ayurvedic formulations internally. Externally Rookshana, Vatahara, Brimhana treatments were done. After the treatment, Michigan neuropathy screening instrument, diabetic Neuropathy symptom score, Toronto clinical scoring system score were reduced. Neuropathy Analyzer showed mild to moderate loss of sensation. By adopting Prameha hara chikitsa coupled with Vata vyadhihara chikitsa, complications of diabetes can be managed. It is important to focus on diet and regimen since diabetes is a lifestyle disorder and, in ayurveda it is considered as an Anushangi Vyadhi.

Rate and characteristics of inflammatory neuropathies associated with brentuximab vedotin therapy.

Peripheral neuropathy is a frequent complication of brentuximab vedotin (BV), used in CD30+ lymphoma treatment. Classic BV-induced neuropathy (BV-CN) is a mild distal sensory axonal polyneuropathy. Severe BV-induced inflammatory neuropathies (BV-IN) have been described. BV-IN contribute to lymphoma-associated morbidity but might be immunotherapy-responsive. Our primary objective was to evaluate the rate of BV-IN. Our secondary objectives were to determine risk factors and warning signs. We conducted a retrospective cohort study on all patients treated with BV at our center between April 2014 and September 2021. Clinical, biological, and electrophysiological data were collected. BV-induced neuropathy was defined as the occurrence of neuropathy up to 3 months after BV discontinuation. BV-IN was defined with criteria adapted from European Academy of Neurology/Peripheral Nerve Society 2021 electrodiagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy. Other neuropathies were classified as BV-CN. Among 83 patients, 41 (49%) developed neuropathy: 35 BV-CN and 6 BV-IN. Thus, the rate of BV-IN was 7.2%. Compared to patients with BV-CN, no predisposing factor was identified. However, patients with BV-IN more frequently presented muscle weakness (67% vs. 5.7%, p < 0.05), gait disorders (83% vs. 20%, p < 0.05), or acute or subacute onset (67% vs. 14%, p < 0.05). BV-IN was frequently more severe (Common Terminology Criteria for Adverse Events grade ≥3; 50% vs. 0%, p < 0.05). Four patients were treated with immunotherapy. Brentuximab vedotin-induced neuropathy is an overlooked complication. Based on four easily identifiable "red flags", we provide an algorithm to help non-neurologist physicians that care for BV-treated patients to detect BV-IN. The aim of the algorithm is to decrease the diagnostic and management delay of this disabling neuropathy.

Evaluation of Brain Stem Function in Diabetics with and Without Distal Symmetrical Polyneuropathy Using the Blink Reflex

Background: Diabetic peripheral neuropathy (DPN) is the commonest complication of T2DM. Neuropathy is a descriptor for a spectrum of clinical and subclinical symptoms with varying anatomical distributions, clinical histories, and perhaps underlying pathogenetic mechanisms. The distal Symmetrical sensory polyneuropathy is chronic, symmetrical, length-dependent sensorimotor. Studies of the blink reflex have shown potential as a method of assessing brainstem activity. Objective: The primary purpose of this research was to assess the function of the blink reflex in the early detection of cranial nerves and brain stem dysfunction in diabetes patients with and without polyneuropathy. We also aimed to see whether there were differences in blink reflex abnormalities between diabetes individuals with and without polyneuropathy. Patients and Methods: The study included a group of sixty-60 diabetic patients. Clinician and electrophysiologist evaluations were used to determine the severity of neuropathy. Patients with diabetes were separated into two groups: those with and without neuropathy. Results: A statistically significant difference between the two groups was for C.R.2 latency, and I.R.2 latency with a P-value &lt;0.001. Except for blink reflex’s R1 latency (P-value &gt;0.2), all other Blink reflex parameters were statistically different between patients who experience diabetic neuropathy and those who didn’t. Regarding HbA1c, a significant positive association with IR2 latency and C.R.2 latency was noted (Pvalue &lt;0.001) and also, a statistically significant negative association was found with I.R.2 duration and C.R.2 duration (P-value &lt;0.001). Amplitudes of sural, tibial and peroneal nerves were negatively associated with Blink reflex Latencies and positively associated with blink reflex duration. Conclusion: In conclusion, blink-reflex parameters (including ipsi-lateral R.2 latency, contra-lateral R.2 latency) are significantly associated with HBA1C level and degree of peripheral diabetic neuropathy. Received Sept. 2022 Accepted Nov. 2023 Published Jan. 2024

Neuroinflammation in the Dorsal Root Ganglia and Dorsal Horn Contributes to Persistence of Nociceptor Sensitization in SIV-Infected Antiretroviral Therapy-Treated Macaques

Despite the development of antiretroviral therapy (ART), HIV-associated distal sensory polyneuropathy remains prevalent. Using SIV-infected rhesus macaques, this study examined molecular mechanisms of peripheral and central sensitization to infer chronic pain from HIV infection. Previous studies identified atrophy in nociceptive neurons during SIV infection, which was associated with monocyte infiltration into the dorsal root ganglia (DRG). However, the sensory signaling mechanism connecting this pathology to symptoms remains unclear, especially because pain persists after resolution of high viremia and inflammation with ART. We hypothesized that residual DRG and dorsal horn neuroinflammation contributes to nociceptive sensitization. Using three cohorts of macaques [uninfected (SIV-), SIV-infected (SIV+), and SIV infected with ART (SIV+/ART)], this study showed an increase in the cellular and cytokine inflammatory profiles in the DRG of SIV+/ART macaques compared with uninfected animals. It found significant increase in the expression of nociceptive ion channels, TRPV1, and TRPA1 among DRG neurons in SIV+/ART compared with uninfected animals. SIV-infected and SIV+/ART animals showed reduced innervation of the nonpeptidergic nociceptors into the dorsal horn compared with uninfected animals. Finally, there were a significantly higher number of CD68+ cells in the dorsal horn of SIV+/ART macaques compared with uninfected animals. In summary, these data demonstrate that neuroinflammation, characteristics of nociceptor sensitization, and central terminal atrophy persists in SIV+/ART animals.

Assessment of neurophysiological parameters of the nervous system in non-ferrous foundry workers

A comprehensive assessment of the health status includes the functional exploration of the central and peripheral nervous systems. Results of the neurophysiological examination allow elaboration of effective personified therapeutic and preventive programs for the core personnel of non-ferrous metal industry. Our objective was to study functional disorders of the central and peripheral nervous systems in smelter operators for further development of risk-based rehabilitation programs for workers engaged in production of non-ferrous metals. Two cohorts of male workers were examined. The case cohort included 60 smelter operators of a large metallurgical plant situated in the Sverdlovsk Region and the control cohort consisted of 50 unexposed employees. The cohorts were matched by age and years of work experience. The mean age of smelter operators was 37.8 ± 7.9 years and their mean length of current employment was 4.1 ± 4.6 years, while the total length of work under hazardous occupational conditions was 7.1 ± 6.0 years. The case cohort included 39 operators of refinery boilers (mean age: 35.6 ± 7.2 years, mean length of employment: 4.2 ± 4.7 years) and 21 operators of the ore thermal furnace (mean age: 41.9 ± 7.6 years, mean length of current employment: 3.9 ± 4.4 years). All subjects underwent a neurocognitive examination (higher brain function testing), electroneuromyography, the somatosensory evoked response test, and electroencephalography. The results of examining the higher brain function enabled us to form the neurocognitive profile of the workers. We revealed signs of mild cognitive impairment in 30 % and a decrease in the cognitive reserve in 35 % of the cases. The diagnosed peripheral nervous system disorders included distal sensory polyneuropathy of the upper and lower extremities, carpal and cubital tunnel syndromes, cervical and lumbar radiculopathy. The comprehensive neurophysiological examination helps detect early changes in the central and peripheral nervous systems. The findings should be taken into account when developing personal medical rehabilitation programs.

Association of reproductive factors and exogenous hormone use with distal sensory polyneuropathy among postmenopausal women in the United States: results from 1999 to 2004 NHANES

Postmenopausal status is a risk factor for distal sensory polyneuropathy—the most common type of peripheral neuropathy. We aimed to investigate associations between reproductive factors and history of exogenous hormone use with distal sensory polyneuropathy among postmenopausal women in the United States using data from the National Health and Nutrition Examination Survey 1999–2004, and to explore the modifying effects of ethnicity on these associations. We conducted a cross-sectional study among postmenopausal women aged ≥ 40 years. Women with a history of diabetes, stroke, cancer, cardiovascular disease, thyroid disease, liver disease, weak or failing kidneys, or amputation were excluded. Distal sensory polyneuropathy was measured using a 10-g monofilament test, and a questionnaire was used to collect data on reproductive history. Multivariable survey logistic regression was used to test the association between reproductive history variables and distal sensory polyneuropathy. In total, 1144 postmenopausal women aged ≥ 40 years were included. The adjusted odds ratios were 8.13 [95% confidence interval (CI) 1.24–53.28] and 3.18 (95% CI 1.32–7.68) for age at menarche < 11 years and time since menopause > 20 years, respectively, which were positively associated with distal sensory polyneuropathy; adjusted odds ratios were 0.45 for the history of breastfeeding (95% CI 0.21–0.99) and 0.41 for exogenous hormone use (95% CI 0.19–0.87) were negatively associated. Subgroup analysis revealed ethnicity-based heterogeneity in these associations. Age at menarche, time since menopause, breastfeeding, and exogenous hormone use were associated with distal sensory polyneuropathy. Ethnicity significantly modified these associations.

Stability of High Concentration Capsaicin in Transfersome Carriers in Gel Dosage Form

Topical capsaicin with high concentrations (8%) is effective in the treatment of pain in Post-Herpetic Neuralgia (PHN) and HIV-Associated Distal Sensory Polyneuropathy (HIV-DSP) patients. High concentrations of capsaicin encapsulated in transfersome nanovesicles aim to reduce the irritating ability of capsaicin when using as drugs. Gel preparations were chosen in the formulation because they are non-sticky, easy to wash, easy to apply, and more practical. The components contained in the gel affect the stability of the gel. Physical and chemical stability tests need to be carried out to ensure the quality, safety and efficacy of the gel so that it meets the expected specifications during its shelf life. This study aims to determine the stability of selected gel formulas containing high concentrations of transfersome capsaicin. The selected gel formula is a gel containing a mixture of phosphatidylcholine (Phospholiphon 90G®) and Tween 80 (80:20). Stability was carried out at high temperature (40±2oC), room temperature (30±2oC), low temperature (5±3oC), and cycling test. The stability parameters tested included organoleptic, pH, viscosity, and assay. The results of the transfersom capsaicin gel stability test showed no change in pH, viscosity, and assay in all storage conditions, but the gel showed a change in color, smell, and taste when stored at high temperatures (40 ± 2oC). It can be concluded that the resulting capsaicin transfersome gel formula with a phospholipid:tween ratio of 80 (80:20) was less stable during 12 weeks of storage at 40 oC

Association Between Breastfeeding and Reduced Distal Sensory Polyneuropathy in Postmenopausal Women Aged 40-70 Years: Analysis of Data from the 1999-2004 National Health and Nutrition Examination Survey.

Background: Distal sensory polyneuropathy (DSP) is a common peripheral neuropathy subtype. We aimed to determine the association between breastfeeding and DSP among postmenopausal women aged 40-70 years, and the effect modification of obesity on this association. Methods: A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey 1999-2004. Postmenopausal women aged 40-70 years were included. Women with diabetes, stroke, cancer, cardiovascular disease, thyroid disease, liver disease, weak/failing kidneys, or amputation were excluded. Binary logistic regression was used to analyze the association between breastfeeding and DSP. Results: Among 798 participants, 386 (44.30%) reported breastfeeding history and 51 (5.29%) were defined as having DSP using the monofilament test. A significant inverse association was observed between breastfeeding and DSP (odds ratio [OR] = 0.29; 95% confidence interval [CI]: 0.11-0.79; p = 0.017) after adjusting for other confounding variables. In subgroup analysis, this adjusted association was observed only in the obese group (OR = 0.21; 95% CI: 0.06-0.73, p = 0.013). Conclusions: Breastfeeding was found to have potential benefits in the presence of DSP in postmenopausal women aged 40-70 years, and obesity modified the association between breastfeeding and DSP. Promoting breastfeeding may reduce the burden of peripheral neuropathy in middle-aged postmenopausal women.

A novel deletion mutation in the ATP6V0A2 gene in an Iranian patient affected by autosomal recessive cutis laxa.

Cutis laxa (CL) can be caused by mutations in a number of genes. Cutis laxa with autosomal recessive inheritance due to mutations in several genes, including mutations in the ATP6V0A2 gene, causes autosomal recessive cutis laxa type 2A (ARCL2A). The ATP6V0A2 gene encodes the a2 subunit in the V-ATPases pump. The V-ATPases are located in the membrane of some organelles, including the Golgi or some vesicles, and act as ATP-dependent proton pumps to pH adjustment intracellular segments. Mutations in the ATP6V0A2 gene consist present in ARCL2A patients. We present the case of a 12-year-old girl who was referred to Rasad Laboratory (Tehran, Iran) at the age of 5 with a set of symptoms of congenital disorders. Her clinical phenotype contains distal symmetrical sensory and motor polyneuropathy, loose joints, large nasal roots, growth delay, and wrinkled skin. Also, there was a history of the parental marriage of consanguinity. A potentially pathogenic homozygous deletion mutation was detected in the ATP6V0A2 gene related to ARCL2A. This mutation has not been reported in the other patients with ARCL2A. A novel homozygous deletion mutation in ATP6V0A2 is supposed to be the reason for disease in our proband.

Higher Levels of Cerebrospinal Fluid and Plasma Neurofilament Light in Human Immunodeficiency Virus-Associated Distal Sensory Polyneuropathy.

Neurofilament light (NFL) chain concentrations, reflecting axonal damage, are seen in several polyneuropathies but have not been studied in human immunodeficiency virus (HIV) distal sensory polyneuropathy (DSP). We evaluated NFL in cerebrospinal fluid (CSF) and plasma in relation to DSP in people with HIV (PWH) from 2 independent cohorts and in people without HIV (PWoH). Cohort 1 consisted of PWH from the CHARTER Study. Cohort 2 consisted of PWH and PWoH from the HIV Neurobehavioral Research Center (HNRC). We evaluated DSP signs and symptoms in both cohorts. Immunoassays measured NFL in CSF for all and for plasma as well in Cohort 2. Cohort 1 consisted of 111 PWH, mean ± SD age 56.8 ± 8.32 years, 15.3% female, 38.7% Black, 49.6% White, current CD4+ T-cells (median, interquartile range [IQR]) 532/µL (295, 785), 83.5% with plasma HIV RNA ≤50 copies/mL. Cohort 2 consisted of 233 PWH of similar demographics to PWH in Cohort 1 but also 51 PWoH, together age 58.4 ± 6.68 years, 41.2% female, 18.0% Black, Hispanic, non-Hispanic White 52.0%, 6.00% White. In both cohorts of PWH, CSF and plasma NFL were significantly higher in both PWH with DSP signs. Findings were similar, albeit not significant, for PWoH. The observed relationships were not explained by confounds. Both plasma and CSF NFL were elevated in PWH and PWoH with DSP. The convergence of our findings with others demonstrates that NFL is a reliable biomarker reflecting peripheral nerve injury. Biomarkers such as NFL might provide, validate, and optimize clinical trials of neuroregenerative strategies in HIV DSP.

HIV peripheral neuropathy‐related degeneration of white matter tracts to sensorimotor cortex

Human immunodeficiency virus-associated distal sensory polyneuropathy (HIV-DSP) affects up to 50% of people with HIV and is associated with depression, unemployment, and generally worsened quality of life. Previous work on the cortical mechanism of HIV neuropathy found decreased gray matter volume in the bilateral midbrain, thalamus, and posterior cingulate cortex, but structural connectivity in this context remains under-studied. Here we examine alterations in white matter microstructure using diffusion imaging, hypothesizing that cortical white matter degeneration would be observed in continuation of the peripheral white matter atrophy previously observed in HIV-DSP. Male HIV seropositive patients (n = 57) experiencing varying degrees of HIV neuropathy underwent single-shell diffusion tensor imaging with 51 sampling directions. The scans were pooled using tractography and connectometry to create a quantitative map of white matter tract integrity, measured in generalized fractional anisotropy (GFA). The relationship between GFA and neuropathy severity was evaluated with linear regression. Correction for multiple comparisons was done using false discovery rate (FDR), a statistical method commonly used in genomics and imaging to minimize false positives when thousands of individual comparisons are made. Neuropathy severity was associated with decreased GFA along thalamocortical radiations leading along the lateral thalamus to sensorimotor cortex, with r = -0.405 (p < 0.001; FDR), as well as with the superior bilateral cingulum (r = -0.346 (p < 0.05; FDR)). Among a population of HIV neuropathy patients, greater neuropathy severity was correlated with lower white matter integrity running from midbrain to somatosensory cortex. This suggests ascending deafferentation extending from damaged peripheral nerves further downstream than seen previously, into the axons of third-order neurons. There is also evidence of cingulum degeneration, implying some more complex mechanism beyond the ascending atrophy observed here.

Neuropathic pain correlates with worsening cognition in people with human immunodeficiency virus.

Neuropathic pain and cognitive impairment are among the HIV-related conditions that have most stubbornly resisted amelioration by virally suppressive antiretroviral therapy. Overlaps between the regional brain substrates and mechanisms of neuropathic pain and cognitive disorders are increasingly recognized, yet no studies have examined the longitudinal relationship between these two disorders. Participants in the prospective, observational CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort underwent standardized clinical evaluations for clinical examination findings of distal sensory polyneuropathy, reporting distal neuropathic pain and neurocognitive performance at study entry (baseline) and an average of 12 years later. Change in neuropathic pain and neuropathy status from baseline to follow-up was by self-report and repeat examination, and change in neurocognitive performance was assessed using a previously published summary regression-based change score. Relationships between incident or worsened neuropathic pain and neurocognitive change were evaluated using uni- and multivariable regressions, including age at baseline and other relevant covariates. Participants were 385 people with HIV, 91 (23.6%) females, mean ± standard deviation (SD) age at baseline 43.5 (7.81) years, ethnicity 44.9% African American, 10.6% Hispanic, 42.6% non-Hispanic white and 1.82% other. Baseline median (interquartile range) nadir CD4 was 175 (34 309) cells/µl and current CD4 was 454 (279 639). Incident or worsened distal neuropathic pain occurred in 98 (25.5%) over the follow-up period. People with HIV with incident or worsened distal neuropathic pain had significantly worsened neurocognitive performance at follow-up compared to those without incident or worsened distal neuropathic pain (summary regression-based change score mean ± SD -0.408 ± 0.700 versus -0.228 ± 0.613; P = 0.0158). This effect remained significant when considering viral suppression on antiretroviral therapy, incident diabetes and other covariates as predictors. Overall neurocognitive change related to neuropathic pain was driven primarily by changes in the domains of executive function and speed of information processing. Those with incident distal neuropathy signs did not have neurocognitive worsening, nor did individuals who used opioid analgesics or other pain-modulating drugs such as amitriptyline. Worsened neurocognitive performance in people with HIV was associated with worsened neuropathic pain but not with changes in physical signs of neuropathy, and this was not attributable to therapies for pain or depression or to differences in viral suppression. This finding implies that incident or worsened pain may signal increased risk for neurocognitive impairment, and deserves more investigation, particularly if better pain management might stabilize or improve neurocognitive performance.

Comparison of diabetic and idiopathic sensory polyneuropathies with respect to nerve fibre affection and risk factors

Background and purposeChronic distal sensory or sensorimotor polyneuropathy is the most common pattern of polyneuropathy. The cause of this pattern is most often diabetes or unknown. This cross-sectional study is...

Evaluation and treatment of peripheral nervous system dysfunction in patients with prediabetes

The worldwide prevalence of prediabetes is steadily increasing, with up to a third of patients already showing signs of diabetic neuropathy (DN). Prediabetes includes impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or a combination of both.Recent diagnostic criteria of prediabetes according to Russian, European, and American clinical guidelines are presented. The review covers the most common forms of DN in patients with prediabetes (distal symmetric sensory polyneuropathy, painful DN, cardiovascular autonomic neuropathy) and their prevalence. Recommended methods of DN screening are discussed: diagnostic scales, sensory testing, nerve conduction study, autonomic testing, corneal confocal microscopy. The results of studies evaluating instrumental methods for diagnosing peripheral nervous system (PNS) dysfunction in prediabetes are discussed. Management tactics in patients with prediabetes and PNS dysfunction should include non-pharmacological and pharmacological interventions. Combining a low-calorie diet and regular physical activity can delay the development of diabetes mellitus and reduce the severity of neuropathic pain. In patients with painful DN, the first-line therapy includes pregabalin, gabapentin, and duloxetine. Since there is no current data on the effect of hypoglycemic therapy on the risks of development and/or progression of DN in patients with prediabetes, antioxidants are considered pathogenetic therapy. Alpha-lipoic acid (Berlition®) in the management of patients with prediabetes is discussed.

Association of painful human immunodeficiency virus distal sensory polyneuropathy with aberrant expectation of pain relief: functional magnetic resonance imaging evidence.

Mechanisms underlying chronic neuropathic pain associated with HIV-associated distal sensory polyneuropathy are poorly understood, yet 40% of those with distal neuropathy (or 20% of all people with HIV) suffer from this debilitating condition. Central pain processing mechanisms are thought to contribute to the development of HIV neuropathic pain, yet studies investigating central mechanisms for HIV neuropathic pain are few. Considering the motivational nature of pain, we aimed to examine the degree to which expectation of pain onset and expectation of pain offset are altered in sixty-one male patients with HIV-related distal sensory polyneuropathy with (N = 30) and without (N = 31) chronic neuropathic pain. By contrasting painful (foot) and non-painful (hand) sites between those with and without neuropathic pain, we could identify unique neural structures that showed altered activation during expectation of pain offset or relief. Our results showed no evidence for peripheral mechanisms evidenced by lack of significant between group differences in thermo-sensation, subjective pain response or epidermal nerve fibre density. Likewise, we found no significant differences between groups in subjective or brain mechanisms underlying the expectation of pain onset. Conversely, we found significant interaction within right anterior insula during expectation of pain offset in our study in that individuals in the pain group compared to the no-pain group exhibited increased anterior insula activation on the painful compared to the non-painful site. Our findings are consistent with abnormal processing of expectation of pain offset or abnormal pain relief-related mechanisms potentially due to increased emotional distress regarding the experience of chronic endogenous pain.

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.

P-PN033. Chronic inflammatory demyelinating polyneuropathy in HIV infected patient responding to plasmapheresis: A case report

Introduction . Chronic Inflammatory Demyelinating Polyradiculoneuropathy or CIDP is a neurological disorder characterized by chronic progressive weakness and impairment of sensory function of the limbs and arms, accompanied by decreased tendon reflexes. CIDP can occur in the setting of HIV, as are other immune-mediated neurologic disorders including a wide spectrum of neuropathies. Results . Male, 27 years old, with thick and tingling complaints in both feet and hands followed by ascending, symmetrical, progressive weakness of all four limbs for 3 months. Physical examination showed decreased muscle strength, areflexia, and hypoesthesia in the distal four extremities. In addition, there was oral candidiasis in the patient so there was a suspicion of an immunodeficiency condition. Repeat HIV antibody testing returned positive. The ENMG results shows demyelinating and axonopathy in peripheral nerve. Six sessions of plasmapheresis measures were performed in this patient as therapy. Muscle strength and complaints of numbness improved with therapy, patient was expected to continue to improve with intensive rehabilitation after discharge. The diagnosis of CIDP meets the EFNS clinical criteria and EFNS definite electrophysiologic criteria. This case can be distinguished from HIV-related distal sensory polyneuropathy because of motor nerve involvement. Conclusion . CIDP may occur in early stages of HIV infection, is probably autoimmune in etiology, clinically shows sensorimotor neuropathy and nerve conduction studies show demyelination. This case report shows HIV-infected patients with CIDP displayed a progressive course of sensorimotor involvement. Plasma exchange showed a good therapeutic response in this case.

Prevention of HIV-1 TAT Protein-Induced Peripheral Neuropathy and Mitochondrial Disruption by the Antimuscarinic Pirenzepine.

HIV-associated distal sensory polyneuropathy (HIV-DSP) affects about one third of people with HIV and is characterized by distal degeneration of axons. The pathogenesis of HIV-DSP is not known and there is currently no FDA-approved treatment. HIV trans-activator of transcription (TAT) is associated with mitochondrial dysfunction and neurotoxicity in the brain and may play a role in the pathogenesis of HIV-DSP. In the present study, we measured indices of peripheral neuropathy in the doxycycline (DOX)-inducible HIV-TAT (iTAT) transgenic mouse and investigated the therapeutic efficacy of a selective muscarinic subtype-1 receptor (M1R) antagonist, pirenzepine (PZ). PZ was selected as we have previously shown that it prevents and/or reverses indices of peripheral neuropathy in multiple disease models. DOX alone induced weight loss, tactile allodynia and paw thermal hypoalgesia in normal C57Bl/6J mice. Conduction velocity of large motor fibers, density of small sensory nerve fibers in the cornea and expression of mitochondria-associated proteins in sciatic nerve were unaffected by DOX in normal mice, whereas these parameters were disrupted when DOX was given to iTAT mice to induce TAT expression. Daily injection of PZ (10 mg/kg s.c.) prevented all of the disorders associated with TAT expression. These studies demonstrate that TAT expression disrupts mitochondria and induces indices of sensory and motor peripheral neuropathy and that M1R antagonism may be a viable treatment for HIV-DSP. However, some indices of neuropathy in the DOX-inducible TAT transgenic mouse model can be ascribed to DOX treatment rather than TAT expression and data obtained from animal models in which gene expression is modified by DOX should be accompanied by appropriate controls and treated with due caution.