The severity of distal sensory polyneuropathy increasing with HIV/AIDS stage.

Distal sensory polyneuropathy (DSP) is the most common neurological problem in HIV/AIDS Patients. It represents a complex symptom that occurs because of peripheral nerve damage related to advanced HIV disease and in association with the use of antiretroviral therapy. DSP is a frequent symptom in which the specific pathophysiology is not well understood. Recently, mitochondrial toxicity and antiretroviral toxic neuropathies have been more identified as a possible etiology of DSP. This study's objective was to determine factors associated with DSP severity in HIV/AIDS patients. This cross-sectional study was followed by 50 HIV/AIDS outpatients at some hospitals in Makassar, Indonesia who met the inclusion criteria. DSP is diagnosed using non-invasive screening tools subjective peripheral neuropathy screen (SPNS) which can determine the severity of DSP in advance. Some factors were analyzed by using Pearson's chi-square test and Spearman's correlation test. Forty-three participants (86%) had diagnosed DSP which is mostly moderate in severity (48%). Statistical analysis showed significant correlation between HIV/AIDS Stage and DSP severity (p=0.032) meanwhile CD4 count, antiretroviral, body mass index (BMI), and hemoglobin level have no significant correlation to DSP severity. In conclusion, HIV/AIDS stage and DSP severity correlate where the later the stage the more severe DSP.

Idiopathic Distal Sensory Polyneuropathy and Fibromyalgia Syndrome: A Comparative Phenotyping Study.

INTRODUCTION: Painful idiopathic distal sensory polyneuropathy (IDSP) and fibromyalgia syndrome (FMS) are cryptogenic chronic pain syndromes. The contribution of small fibre pathology (SFP) in FMS remains controversial. This study aims to quantify small nerve pathology in participants with IDSP and FMS and identify relationships of SFP with sensory phenotypes. METHODS: In this study, 73 individuals (FMS: 25, IDSP: 23, healthy volunteers: 25) underwent comprehensive assessment, including neurological exams, questionnaires, sensory tests, and corneal confocal microscopy. RESULTS: IDSP participants displayed lower wind-up ratio (WUR) relative to FMS (p < 0.001), loss of function to thermal and mechanical stimuli and elevated neuropathy disability scores compared to FMS and healthy volunteers (all p < 0.001). FMS participants demonstrated gain of function to heat and blunt pressure pain responses relative to IDSP, and healthy volunteers (heat: p = 0.002 and p = 0.003; pressure: both p < 0.001) and WUR (both p < 0.001). FMS participants exhibited reduced corneal nerve fibre density (p = 0.02), while IDSP participants had lower global corneal nerve measures (density, branch density, and length) relative to healthy volunteers (all p < 0.001). Utilising corneal nerve fibre length, SFP was demonstrated in 66.6% of participants (FMS: 13/25; IDSP: 22/23). CONCLUSION: Participants with SFP, in both FMS and IDSP, reported symptoms indicative of small nerve fibre disease. Although distinctions in pain distributions are evident between individuals with FMS and IDSP, over 50% of participants between the two conditions displayed both a loss and gain of thermal and mechanical function suggestive of shared mechanisms. However, sensory phenotypes were associated with the presence of SFP in IDSP but not in FMS.

In people with painful idiopathic neuropathy (pain related to nerve damage where the cause of nerve damage is unknown), fibromyalgia syndrome (a long-term condition causing widespread pain), and healthy volunteers, the small nerve fibres of the peripheral nervous system, which may be involved in generating pain were assessed. These nerve fibres can be measured at the front of the eye (cornea) which can provide details on whether they are damaged in the body. The response to temperature, light touch, pressure and pinprick stimuli can also be used to determine if there is a loss or gain of sensation, which may contribute to pain. The aim of this study was to identify the degree of damage to these nerve fibres and to determine whether this damage is associated with a loss (cannot feel or requires more intense stimulus to feel) or gain (stimulus is felt earlier or is painful earlier at lower intensity) of sensory function. The pattern of loss or gain in sensory function is known as a sensory phenotype. It was found that people with painful idiopathic neuropathy had more severe nerve damage, loss of function to temperature and touch, and fewer small nerve fibres in the cornea compared to those with fibromyalgia syndrome and healthy volunteers. People with fibromyalgia syndrome were more sensitive to heat and pressure and had fewer corneal nerve fibres relative to healthy volunteers. The presence of corneal nerve fibre damage was associated with sensory phenotypes (types of sensation felt) in painful idiopathic neuropathy but not in fibromyalgia syndrome.

Electrophysiological and radiological diagnosis of hereditary motor and sensory polyneuropathy.

Hereditary motor and sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth disease (CMT), is a member of the inherited neuropathy family with specific clinical and genetical manifestations. More than twenty genes have been linked to HMSN, and the number might increase. Regarding diagnosis, a healthcare provider should be suspicious if the patient is young with a family history. Integrative diagnosis, which includes electrophysiological, radiological, and genetic screening, is of great value to exclude metabolic, nutritive-toxic, infectious, and inflammatory or autoimmunological causes and to reach the exact subtype of hereditary neuropathy. Nowadays, next-generation sequencing-based analysis is becoming a routine diagnostic tool for inherited neuropathy, but if this facility is not available, electrophysiological and radiological diagnoses are the best diagnostic tools to be used. Differentiation between hereditary neuropathy and diabetic neuropathy is essential for primary care physicians to have the right plan.

Leprosy Neuropathy in a Non-Endemic Area: A Clinical and Pathological Study.

The extent of nerve involvement in leprosy is highly variable in distribution and clinical presentation. Mononeuropathies, multiple mononeuropathies, and polyneuropathies can present both in the context of a cutaneous and/or systemic picture and in the form of pure neuritic leprosy (PNL). The differential diagnosis of leprosy neuropathy remains challenging because it is a very rare condition and, especially in Western countries, is often overlooked. We report one case of the polyneuropathic form of PNL (P-PNL) and one case of multiple mononeuropathy in paucibacillary leprosy. In both cases, the diagnosis was achieved by performing a sural nerve biopsy, which showed subverted structure, severe infiltration of inflammatory cells in nerve fascicles, granulomatous abnormalities, and the presence of alcohol-acid-resistant, Ziehl-Neelsen-positive bacilli inside the nerve bundles. Leprosy remains an endemic disease in many areas of the world, and globalization has led to the spread of cases in previously disease-free countries. In this perspective, our report emphasizes that the diagnostic possibility of leprosy neuropathy should always be taken into account, even in Western countries, in the differential diagnostic process of an acquired sensory polyneuropathy or multineuropathy and confirms that nerve biopsy remains a useful procedure in working up neuropathies with unknown etiology.

Article Topic: Neuropathies Due to Infections and Antimicrobial Treatments.

Purpose of eview: The aim of this review is to discuss the presentation, diagnosis, and management of polyneuropathy (PN) in selected infections. Overall, most infection related PNs are an indirect consequence of immune activation rather than a direct result of peripheral nerve infection,  Schwann cell infection, or toxin production, though note this review will describe infections that cause PN through all these mechanisms. Rather than dividing them by each infectious agent separately, we have grouped the infectious neuropathies according to their presenting phenotype, to serve as a guide to clinicians. Finally, toxic neuropathies related to antimicrobials are briefly summarized. Recent findings: While PN from many infections is decreasing, increasing evidence links infections to variants of GBS. Incidence of neuropathies secondary to use of HIV therapy has decreased over the last few years. Summary: In this manuscript, a general overview of the more common infectious causes of PN will be discussed, dividing them across clinical phenotypes: large- and small-fiber polyneuropathy, Guillain-Barré syndrome (GBS), mononeuritis multiplex, and autonomic neuropathy. Rare but important infectious causes are also discussed.

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.

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.

Early Detection of Diabetic Peripheral Neuropathy: A Focus on Small Nerve Fibres.

Diabetic peripheral neuropathy (DPN) is the most common complication of both type 1 and 2 diabetes. As a result, neuropathic pain, diabetic foot ulcers and lower-limb amputations impact drastically on quality of life, contributing to the individual, societal, financial and healthcare burden of diabetes. DPN is diagnosed at a late, often pre-ulcerative stage due to a lack of early systematic screening and the endorsement of monofilament testing which identifies advanced neuropathy only. Compared to the success of the diabetic eye and kidney screening programmes there is clearly an unmet need for an objective reliable biomarker for the detection of early DPN. This article critically appraises research and clinical methods for the diagnosis or screening of early DPN. In brief, functional measures are subjective and are difficult to implement due to technical complexity. Moreover, skin biopsy is invasive, expensive and lacks diagnostic laboratory capacity. Indeed, point-of-care nerve conduction tests are convenient and easy to implement however questions are raised regarding their suitability for use in screening due to the lack of small nerve fibre evaluation. Corneal confocal microscopy (CCM) is a rapid, non-invasive, and reproducible technique to quantify small nerve fibre damage and repair which can be conducted alongside retinopathy screening. CCM identifies early sub-clinical DPN, predicts the development and allows staging of DPN severity. Automated quantification of CCM with AI has enabled enhanced unbiased quantification of small nerve fibres and potentially early diagnosis of DPN. Improved screening tools will prevent and reduce the burden of foot ulceration and amputations with the primary aim of reducing the prevalence of this common microvascular complication.

De novo DNM1L variant presenting with severe muscular atrophy, dystonia and sensory neuropathy.

DNM1L encodes dynamin-related protein 1 (DRP1), a multi-domain GTPase essential for mitochondrial and peroxisomal division. Autosomal dominant and recessive variants in DNM1L cause encephalopathy due to defective mitochondrial and peroxisomal fission 1 (EMPF1), which presents as a complex and clinically heterogeneous neurological disorder of variable severity, often accompanied by seizures. Clinical features are diverse, and no clear phenotype-genotype correlations were drawn to date. DNM1L-related sensory neuropathy has recently been reported as a predominant feature in one case with a de novo variant in the GTPase domain. Herein we present a second case with DNM1L-related sensory neuropathy as the predominant underlying feature without motor neuron involvement, which resulted in severe muscular atrophy and generalized dystonia.

Paraneoplastic Sensory Polyneuropathy Related to Anti-PD-L1-including Anticancer Treatment in a Patient with Lung Cancer.

Paraneoplastic neurological syndromes (PNS), such as sensory polyneuropathy, are rare, and serum neuronal antibodies that are used for diagnosing this syndrome are occasionally positive. Similarly, neurological immune-related adverse events due to immune checkpoint inhibitors (ICIs) are also rare. However, their etiologies and the relationship between them remain unclear. We herein report a patient with suspected small cell lung cancer who showed sensory polyneuropathy after treatment with atezolizumab in combination with cytotoxic agents (carboplatin and etoposide) and was doubly positive for serum anti-Hu and anti-SOX-1 antibodies. Treatment with ICI and cytotoxic agents may sometimes lead to the development of PNS.

Metabolic syndrome and peripheral neuropathy.

Diabetic peripheral neuropathy and metabolic syndrome (MetS) are both global health challenges with well-established diagnostic criteria and significant impacts on quality of life. Clinical observations, epidemiologic evidence, and animal models of disease have strongly suggested MetS is associated with an elevated risk for cryptogenic sensory peripheral neuropathy (CSPN). MetS neuropathy preferentially affects small unmyelinated axons early in its course, and it may also affect autonomic and large fibers. CSPN risk is linked to MetS and several of its components including obesity, dyslipidemia, and prediabetes. MetS also increases neuropathy risk in patients with established type 1 and type 2 diabetes. In this review we present animal data regarding the role of inflammation and dyslipidemia in MetS neuropathy pathogenesis. Several studies suggest exercise-based lifestyle modification is a promising treatment approach for MetS neuropathy.

[A case of motor and sensory polyneuropathy and respiratory failure with novel heterozygous mutation of the senataxin gene].

The patient was a 29-year-old male. He took his first steps at two-and-a-half years old, but his physical strength deteriorated and he became non-ambulatory at 12 years old. He had respiratory failure at the age of 20, and finally underwent tracheostomy with invasive positive-pressure ventilation (TPPV). He showed distal dominant muscle weakness and atrophy, including the face. Spinal scoliosis was recognized. He had peripheral predominance of sensory disorders. Nerve conduction studies showed a decrease of compound muscle action potential and a reduction of motor nerve conduction velocity. Sensory nerve action potential was not evoked. In genetic analysis, c.23 C> T (p. T8M) heterozygous mutation was found in the senataxin gene (SETX). Although SETX is a causative gene of familial amyotrophic lateral sclerosis type 4 (ALS4), this case suggests that SETX mutation can also cause motor and sensory polyneuropathy.

Acute sensorimotor polyneuropathy as an early sign of polyarteritis nodosa. A case report.

We examined a patient aged 31 who had a sudden burning paraesthesia, pain and numbness in the lower legs together with an increased temperature of 39°C. Clinical examination showed asymmetrical sensory polyneuropathy more clearly seen in the lower legs and the left wrist, with high ESR (up to 44 mm/h), leukocytosis, slight anemia and proteinuria. CSF was normal. After three weeks the temperature suddenly increased again up to 39°C and severe flaccid distal tetraparesis was seen more clearly with foot drop in the left lower leg and dense oedema in the left wrist, purple cyanosis and haemorrhagic foci appeared on the skin of the toes, feet, lower legs and left wrist. ESP increased up to 65 mm/h, CK was 200 IU (normal ≤ 190 IU) and hypergammaglobulinaemia developed. An EMG study showed sensorimotor, mainly axonal, polyneuropathy with different degrees of involvement of some nerves and with conduction block in the left ulnar nerve. Muscle biopsy revealed findings of inflammatory vasculitis that resembled polyartheritis nodosa with secondary denervation atrophy and non-specific myositis. The patient was treated with high doses of prednisolone, dexamethasone and cyclophosphamide with plasmapheresis. Motor disturbances and pain decreased and the patient began walking with a stick. However, the necrosis of the toes gradually progressed to dry gangrene and amputations of the toes were carried out three months after the disease began. At that time the patient had the clinical features of multisystem disease with progressive heart, lung, liver and kidney failure. The patient died suddenly of pulmonary artery thrombo-embolism a year after the onset of the disease. An autopsy confirmed the diagnosis of polyarteritis nodosa (PN). Thus, in this patient the asymmetrical sensory polyneuropathy progressed rapidly in symmetrical sensorimotor peripheral polyneuropathy which preceded the clinical multisystem involvement in polyarteritis nodosa.

Jules Sottas (1866-1945) forgotten despite the eponym: "Dejerine-Sottas syndrome".

The eponym "Dejerine Sottas" makes 21st-century neurologists think of a form of heredity peripheral neuropathy leading to amyotrophy and secondary to a mutation of one of the many genes responsible for the formation of myelin. The seminal description was the work of Sottas and Jules Dejerine (1849-1917); Dejerine was the prestigious second successor of Jean-Martin Charcot at the Clinic of Nervous System Diseases at the La Salpêtrière hospital. Jules Sottas (1866-1945) has almost been forgotten, but as a young man he was a brilliant resident under Dejerine. However, Sottas eventually gave up medicine, even though he could have had a successful career as a neurologist, to devote himself to his passion for history, especially the history of navigation. But during his time as a physician he published several original works, always supported by detailed neuro-pathological studies, the result of his very close collaboration with Dejerine at Bicêtre then at La Salpêtrière. After a brief biography of Sottas, we will analyse his neurological work and then highlight the quality of his publications on naval and maritime history, which are still relevant today.

Electrophysiological Characterization of C9ORF72-Associated Amyotrophic Lateral Sclerosis: A Retrospective Study.

OBJECTIVE: C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS). The aim of the present study was to determine whether C9ORF72-associated ALS (C9-ALS) patients present distinctive electrophysiological characteristics that could differentiate them from non C9ORF72-associated ALS (nonC9-ALS) patients. METHODS: Clinical and electrodiagnostic data from C9-ALS patients and nonC9-ALS patients were collected retrospectively. For electroneuromyography, the mean values of motor conduction, myography, and the mean values of sensory conduction were considered. Furthermore, the proportion of ALS patients with electrophysiological sensory neuropathy was determined. RESULTS: No significant difference was observed between 31 C9-ALS patients and 22 nonC9-ALS patients for mean motor conduction and myography. For sensory conduction analyses, mean sensory conduction was not significantly different between both groups. In total, 38% of -C9-ALS patient and 21% of nonC9-ALS patients presented electrophysiological sensory neuropathy (p = 0.33). In -C9-ALS patients with electrophysiological sensory neuropathy, 80% (8/10) were male and 67% (6/9) presented spinal onset compare to 25% (4/16, p = 0.014) male and 25% (4/16, p = 0.087) with spinal onset in those without electrophysiological sensory neuropathy. CONCLUSION: Although not different from nonC9-ALS, these results suggest that sensory involvement is a frequent feature of C9-ALS patients, expanding the phenotype of the disease beyond the motor and cognitive domains.

Distal sensory polyneuropathy among HIV-infected patients at Parakou University Hospital, Benin, 2011.

Distal sensory polyneuropathy (DSP) is the most frequent neurological complication among HIV patients, and its risk increases with use of highly active antiretroviral therapy (HAART). We aimed to assess the prevalence of DSP and the factors associated with it among HIV-infected outpatients treated at Parakou University Hospital. This cross-sectional study took place from April 15 to July 15, 2011, and included 262 patients. All patients underwent a neurological examination by two neurologists with training and clinical experience in these examinations and in the Brief Peripheral Neuropathy Screening (BPNS), which was the primary tool used here. Data from nutritional status (body mass index: BMI), social and demographic information, HAART status, and CD4 count were recorded. The factors associated with DSP were studied with multivariate analysis, using a logistic regression model and a significance level of 0.05. The study included 60 men (22.9 %). Patients' ages ranged from 16 to 74 years and averaged 36.8±10 years. All patients but one patient were infected by HIV type 1 only; that one was coinfected by types 1 and 2. The mean BMI was 22.5+/-4.2 kg/m2. In all, 213 (81.3 %) received HAART, and the mean CD4 count was 355.0 cells/mm3+/-236.1. The prevalence of DSP was 42.4 %. The factors associated with it on univariate analysis were age, marital status, HAART status, duration of HIV infection, and duration of HAART. Only advanced age (OR 1.8, 95 % CI 1.1-5.3) and HAART use (OR 2.3, 95 % CI 1.5-4.9) were associated with DSP in the multivariate analysis. The main symptoms were paresthesia (numbness:75.7%; burning: 39.6%; pins and needles sensation 32.4 %) and pain (23.4 %). Vibration perception at the toes was missing or reduced for 84.4 %. According to the sensory symptoms grade, 93.7 % of patients were classified in Grades 2 or 3. This study showed that the prevalence of DSP is high and that it is associated with age and HAART.

Risk factors for autonomic and somatic nerve dysfunction in different stages of glucose tolerance.

AIM: The present study evaluates autonomic and somatic nerve function in different stages of glucose tolerance and its correlation with different cardio-metabolic parameters. MATERIAL AND METHODS: Four hundred seventy-eight subjects, mean age 49.3±13.7years and mean BMI 31.0±6.2kg/m2, divided according to glucose tolerance: 130 with normal glucose tolerance (NGT), 227 with prediabetes (125 with impaired fasting glucose (IFG) and 102 with isolated impaired glucose tolerance (iIGT)), and 121 with newly-diagnosed T2D (NDT2D), were enrolled. Glucose tolerance was studied during OGTT. Antropometric indices, blood pressure, HbA1c, serum lipids, hsCRP and albumin-to-creatinine ratio were assessed. Body composition was estimated by a bioimpedance method (InBody 720, BioSpace). Tissue AGEs accumulation was assessed by skin autofluorescence (AGE-Reader-DiagnOpticsTM). Electroneurography was performed by electromyograph Dantec Keypoint. Cardiovascular autonomic neuropathy (CAN) was assessed by ANX-3.0 method applying standard clinical tests. RESULTS: CAN was found in 12.3% of NGT, 19.8% of prediabetes (13.2% of IFG and 20.6% of iIGT), and 32.2% of NDT2D. The prevalence of diabetic sensory polyneuropathy (DSPN) was 5.7% in prediabetes and 28.6% in NDT2D. The panel of age, QTc interval, waist circumference, diastolic blood pressure, and 120-min plasma glucose was related to sympathetic activity (F [5451]=78.50, p<0.001). The panel of age, waist circumference, and QTc interval was related to parasympathetic power (F [3453]=132.26, p<0.001). HbA1c and age were related to sural SNAP (F [2454]=15.12, p<0.001). HbA1c and AGEs were related to sural SNCV (F [2454]=12.18, p<0.001). CONCLUSIONS: Our results demonstrate a high prevalence of autonomic and sensory nerve dysfunction in early stages of glucose intolerance. Age, postprandial glycemia, central obesity, diastolic blood pressure and QTc interval outline as predictive markers of CAN; hyperglycemia, glycation and age of DSPN.