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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.

International audience; BackgroundGrowing numbers of indications for intravenous immunoglobulins (IVIg) in recent years has resulted in an increase in the consumption of these products. A lack of raw material has led to IVIg shortage. The objective of this work was to evaluate the impact of this situation on patient care in one French referral centre considering practice modifications and clinical impact.MethodsAll patients treated with IVIg for chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy and myasthenia gravis from October 2017 to October 2018 were included.ResultsOut of 142 patients, 111 (78%) had a modification of their IVIg treatment. We noted that 75 (68%) patients had a delay in IVIg treatment, 41 (37%) patients had a decrease in IVIg doses and 31 (28%) experienced IVIg treatment interruption. Thirty percent of patients for whom IVIg treatment was discontinued were switched to other treatments mainly plasma exchange (16%) or corticosteroids (13%). Switches to plasma exchange or corticosteroids were carried out in order to save immunoglobulins for patients who had no other alternatives. Fifty-eight (52%) patients presented a deterioration of their clinical score after IVIg treatment changes including 31 (28%) patients who had a moderate or a clinically significant deterioration. Concerning practice modifications, we noted a substantial though not significant decrease in median IVIg dose for myasthenia gravis and a significant increase in the delay between IVIg courses for chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy (P = 0.011 and P = 0.018 respectively).ConclusionOur study showed a rather important number of changes in IVIg treatment related to IVIg shortage during the period considered. These changes had a negative impact on the clinical status of some patients.

INTRODUCTION/AIMS Progressive axonal loss in multifocal motor neuropathy (MMN) is often assessed with nerve conduction studies (NCS), by recording maximum compound muscle action potentials (CMAPs). However, reinnervation maintains the CMAP amplitude until a significant portion of the motor unit (MU) pool is lost. We therefore performed more informative CMAP scans to study MU characteristics in a large cohort of patients with MMN. METHODS We derived the maximum CMAP amplitude (CMAPmax ), a MU number estimate (MUNE) and the largest MU amplitude, stimulus current required to elicit 5%-50%-95% of CMAPmax (S5, S50, S95) and relative ranges ([S95-S5]x100/S50) from the scans. These metrics were compared with clinical, laboratory and NCS results. RESULTS 40 MMN patients and 24 healthy controls were included. CMAPmax and MUNE were reduced in MMN patients (both p

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 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.

Background The most frequently used ability outcome measure in Guillain-Barre syndrome (GBS) is the GBS disability scale (GDS). Recently developed inflammatory Rasch-built overall disability (I-RODS) scale has been suggested to be used in inflammatory polyneuropathies. In the present study, we wanted to assess the comparative responsiveness of I-RODS and GDS in subjects who were diagnosed with GBS during a follow-up period of 6 months. Methods Our prospective, multicentric study included 72 subjects. Patients were tested, using GDS and I-RODS, on day 14, day 28, month 3, and month 6 from the start of the symptoms. We defined improvement as a reduction for 1 or more points on GDS or improvement on I-RODS as defined by Draak (2014). Results Between days 14 and 28 there was an improvement in 28% of patients as measured with GDS and only in 10% patients as measured with I-RODS. At month 3 compared with day 14, we noticed an improvement in GDS score in 90% of GBS patients and I-RODS score in 65%. At month 6 improvements were noticed in 94% of patients measured by GDS and 78% according to I-RODS. Conclusion Our findings support the use of GDS in an acute phase of GBS. I-RODS have their role mostly during a longer follow-up period when the majority of patients are ambulant and their other abilities besides walking are also of great importance.

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.

Neurotherapeutics 18(4), 2425-2435 (2021). doi:10.1007/s13311-021-01141-3, Published by Springer, New York, NY

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.

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

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.

Summary Background Loss of sensations in the sole following diabetic sensorimotor polyneuropathy (DSPN) leads to diabetic foot ulcers and its sequelae. We hypothesized that sensory reinnervation of sole by transfer of saphenous nerve (SN) to sensory fascicles of posterior tibial nerve (PTN) in these patients may reverse the neuropathy. Methods This prospective interventional case series included patients with advanced DSPN and intact sensory supply of SN. PTN was neurotized by transfer of SN nerve in the tarsal tunnel and postoperatively sensations of the sole were tested. Any existing ulcers on sole were noted and their healing was monitored. Finding A total of 17 patients (22 feet), 9 male and 8 female, were included. Seven patients had ulcers in the feet. At 6 months follow-up all patients developed protective sensation in the sole. The average 2 PD improved from 60 mm to 45.5 mm, average vibration perception improved from 34.12 V to 24.33, Medical Research Council (MRC) score improved from S0 in 12 feet and S1 in 10 feet to S3+ in 13 feet, S3 in 5 feet, and S2 in 2 feet at 6 months along with healing of ulcers in all 7 feet. Interpretation Transfer of SN to PTN for sensory neurotization is an innovative and simple option to prevent complications of DSPN. This procedure has the potential to change the natural history of DSPN.

BACKGROUND The goal of this study was to demonstrate that the paresthesia-independent 10 kHz spinal cord stimulation (SCS) can provide long-term pain relief in patients with peripheral polyneuropathy (PPN). Clinically diagnosed subjects with PPN refractory to conventional medical management were enrolled in this prospective, multicenter study between November 2015 and August 2016, after institutional review board approval and patient informed consent were obtained. METHODS Subjects underwent trial stimulation utilizing 2 epidural leads, and if successful, were implanted with a permanent 10 kHz SCS system and followed up for 12 months post-implant. Outcome measures included adverse events, pain, neurological assessments, disability, function, quality of life, pain interference, sleep, satisfaction, and global impression of change. Data are presented as descriptive statistics. Permanent implant population results are reported as mean ± standard error. RESULTS Twenty-one of the 26 trialed subjects had a successful trial and 18 received a permanent implant. All subjects had the leads placed anatomically without the need for paresthesia. Subjects experienced significant and sustained pain relief (at least 65% at all timepoints) whereas physicians noted improvements in neurological function. Significant improvements in disability, function, sleep, sensory, and affective dimensions of pain were reported at all timepoints. All adverse events were resolved without sequelae. CONCLUSION Findings from this study suggest that 10 kHz SCS may provide sustained pain relief and disability improvements in patients suffering from PPN.

One in 5 patients with diabetes suffers from chronic pain with neuropathic characteristics, but the pathophysiological mechanisms underlying the development of neuropathic pain in patients with diabetic distal symmetrical polyneuropathy (DSP) are poorly understood. Systemic low-grade inflammation has been implicated, but there is still a considerable knowledge gap concerning its scope and meaning in this context. The aim of the study was to establish the broad inflammatory signature of painful diabetic DSP in serum samples from the Pain in Neuropathy Study, an observational cross-sectional multicentre study in which participants underwent deep phenotyping. In the present two cohorts exploration-replication study (180 participants in each cohort), serum samples from Pain in Neuropathy Study participants were analyzed with the Olink INFLAMMATION panel (Olink Bioscience, Uppsala, Sweden) that enables the simultaneous measurement of 92 inflammation-related proteins (mainly cytokines, chemokines, and growth factors). In both the exploration and the replication cohort, we identified a high-inflammation subgroup where 14 inflammation-related proteins in particular were associated with more neuropathy and higher pain intensity. The top 3 proteins were hepatocyte growth factor, colony-stimulating factor 1, and CD40 in both cohorts. In the exploratory cohort, additional clinical data were available, showing an association of inflammation with insomnia and self-reported psychological distress. Hence, this cross-sectional exploration-replication study seems to confirm that low-grade systemic inflammation is related to the severity of neuropathy and neuropathic pain in a subgroup of patients with diabetic DSP. The pathophysiological relevance of these proteins for the development of neuropathic pain in patients with diabetic DSP must be explored in more depth in future studies.

Peripheral polyneuropathy (PPN) can occur in diabetes mellitus (DM), obesity, and after bariatric surgery (BS). We decided to evaluate PPN prevalence before (PreBS-PPN) and after BS (PostBS-PPN) and to look for variables that may be independently associated with both. In this cross-sectional study, we evaluated 1467 participants with obesity and without DM before and 10.4 ± 6.8 months after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). The Michigan Neuropathy Screening Instrument and the International Physical Activity Questionnaire were used to define the presence of PPN and the Metabolic Equivalent Task (MET) spent per week, respectively. Using Poisson regression models with a robust estimator, the prevalence of PreBS-PPN and PostBS-PPN was analyzed as dependent variables. Prevalence of PostBS-PPN (10.5%) was lower than PreBS-PPN (20.4%, p < 0.001), with a prevalence of 12.7% post-RYGB and 8.4% post-SG (p = 0.072). In the univariate analysis, PreBS-PPN was associated with post-menopausal status (PMS), older age, and taller height. In twelve regression models, we found an independent association of PreBS-PPN with older age, PMS, and taller height. PostBS-PPN prevalence was associated with a higher fasting glycemia and stature, and a lower MET on univariate analysis, and with higher fasting glycemia, stature and RYGB in four multivariate regression models. PPN occurs frequently in subjects with obesity without DM and is lower after BS. SG is not likely to be harmful in the development of neuropathy. Studies of PPN incidence and persistence after BS should clarify these factors.

Background The immunological pathophysiologies of chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) differ considerably, but neither has been elucidated completely. Quantitative magnetic resonance imaging (MRI) techniques such as diffusion tensor imaging, T2 mapping, and fat fraction analysis may indicate in vivo pathophysiological changes in nerve architecture. Our study aimed to systematically study nerve architecture of the brachial plexus in patients with CIDP, MMN, motor neuron disease (MND) and healthy controls using these quantitative MRI techniques. Methods We enrolled patients with CIDP (n = 47), MMN (n = 29), MND (n = 40) and healthy controls (n = 10). All patients underwent MRI of the brachial plexus and we obtained diffusion parameters, T2 relaxation times and fat fraction using an automated processing pipeline. We compared these parameters between groups using a univariate general linear model. Results Fractional anisotropy was lower in patients with CIDP compared to healthy controls (p, With this study, we show that quantitative MRI techniques reveal differences in the brachial plexus between patients with CIDP, MMN, MND and healthy controls. CIDP is characterized by lower FA and higher RD than MMN, MND and healthy controls, whilst MMN is characterized by higher FA values than CIDP and MND. These differences between CIDP and MMN are the most remarkable and important finding as they emphasize important differences in the underlying pathophysiologies.

Background: Hypereosinophilic syndrome is a rare disease that increases the number of circulating eosinophils in the body. It has many complications, including peripheral polyneuropathy. Peripheral polyneuropathy often does not respond well to conventional therapies. Transcutaneous neurostimulatory treatment, also known as scrambler therapy, is an alternative modality for the treatment of chronic retractable pain. Case: A 47-year-old woman presented with complaints of bilateral calf pain. She had been under treatment for peripheral polyneuropathy induced by hypereosinophilic syndrome for 7 years. Pharmacologic treatment did not affect the patient’s symptoms. Conclusions: Transcutaneous neurostimulatory treatment was administered to the patient. It was effective on her symptoms, and the effect of pain alleviation continued for 3 months.

Background: This mini-review aims to summarize and discuss previous and recent advances in the clinical presentation, pathophysiology, diagnosis, treatment, and outcome of SARS-CoV-2-associated peripheral neuropathies. Methods: Literature review. Results: Altogether, 105 articles about SARS-CoV-2-associated neuropathy describing 261 patients were retrieved. Peripheral neuropathy in patients with COVID-19 is frequent and predominantly due to immune mechanisms or neurotoxic side effects of drugs used to treat the symptoms of COVID-19 and, to a lesser extent, due to the compression of peripheral nerves resulting from prolonged bedding in the Intensive Care Unit (ICU) and pre-existing risk factors such as diabetes. SARS-CoV-2 does not cause viral neuropathy. Neurotoxic drugs such as daptomycin, linezolid, lopinavir, ritonavir, hydro-chloroquine, cisatracurium, clindamycin, and glucocorticoids should be administered with caution and patients should be appropriately bedded in the ICU to prevent SARS-CoV-2-associated neuropathy. Patients with Guillain-Barré syndrome (GBS) benefit from immunoglobulins, plasma exchange, and steroids. Conclusions: Neuropathies of peripheral nerves in patients with COVID-19 are frequent and mostly result from immune mechanisms or neurotoxic side effects of drugs used to treat the symptoms of COVID-19 and, to a lesser extent, from the compression of peripheral nerves due to prolonged bedding on the ICU. SARS-CoV-2 does not cause infectious neuropathy.

To evaluate the effect of supervised and home sensorimotor training on static postural balance (SPB), quality of life (QL), and neuromuscular responses of Type 2 Diabetics (DM-2).Randomized controlled blind study with DM-2 patients, between 45 and 64 years old, of both sexes, divided into 3 groups: Control Group - CG (n = 27), Home Training Group - HTG (n = 27), and Supervised Training Group - STG (n = 26). The subjects were evaluated before and at the end of 3 months of treatment, with a four-week follow-up. The intervention was held twice a week, for 45 min, divided into three phases: warm-up, sensorimotor training, and cool-down. The primary outcome was SPB, using the force platform. Secondary outcome: questionnaires and clinical measures related to diabetic foot and knee flexor-extensors using isokinetic dynamometry.In the baseline, the characteristics were similar between groups and between times. Tactile and vibratory sensitivity demonstrated the absence of symptoms of peripheral neuropathy in diabetic patients. In the intra-group comparison, there was a significant increase in the classification without symptoms of diabetic distal polyneuropathy in the HTG and STG groups (p 0.05) and there were no significant effects on other clinical outcomes and QL and SPB, muscle strength, and sense of knee joint position.The intervention showed no improvement in SPB, QL, and other clinical outcomes of DM-2 patients. Thus, no differences were found between the groups, considering that the patients did not present clinical characteristics of diabetic distal polyneuropathy.

Study of intraepidermal nerve fiber density (IENFD) by skin biopsy represents a promising tool in the evaluation of patients with ATTRv polyneuropathy (ATTRv-PN). Herein, we retrospectively analyze intraepidermal innervation and quantitative sensory test (QST) data from an Italian cohort of Italian ATTRv-PN patients and asymptomatic carriers aimed to provide insights into early nerve pathological and functional changes in this disease. IENFD and QST data of 14 ATTRv-PN patients and 14 asymptomatic carriers were retrospectively analyzed together with clinical and paraclinical data such as disease stage and severity, neuropathic pain scales, and sural SNAP amplitude. Given an estimated time to the predicted age of onset of symptomatic disease of 20.27 + / − 7.9 years, small nerve fiber loss seems to be unexpectedly early in carriers. Moreover, carriers showed skin denervation at the proximal (thigh) site, suggesting a non-length-dependent neuropathic process. IENFD at ankle correlated with disease severity and other paraclinical variables such as sural nerve potential amplitude and QST parameters. Patients at earlier stages of the disease did not show significant differences in ankle IENFD compared with asymptomatic carriers, but significant differences in terms of QST parameters, small fiber neuropathy symptoms, and neuropathic pain. Skin biopsy can disclose an early non-length-dependent small fiber loss in ATTRv-PN and, together with QST, could provide a useful insight disease onset and progression.

Background and purpose Chronic axonal polyneuropathy is a common, usually multifactorial, disease for which there is no treatment yet available. We investigated the association between cardiovascular health, defined by the health score of the American Heart Association, and chronic axonal polyneuropathy. Methods Between June 2013 and January 2017, we investigated participants of the Rotterdam Study, a population‐based cohort study. Participants were screened for polyneuropathy and categorized as having no, possible, probable or definite polyneuropathy. The cardiovascular health score (range 0–14; higher score reflecting better health) consisted of four health behaviours (diet, physical activity, smoking and body mass index) and three health factors (blood pressure, serum cholesterol and fasting glucose level). Results We included 1919 participants, of whom 120 (6.3%) had definite polyneuropathy. The median (interquartile range [IQR]) age was 69.0 (58.6–73.7) years and 53.4% were women. A higher cardiovascular health score was associated with a lower prevalence of definite polyneuropathy (per point increase: odds ratio [OR] 0.90, 95% confidence interval [CI] 0.84–0.96). Optimal cardiovascular health (score≥10) was strongly associated with a lower prevalence of definite polyneuropathy (OR 0.55, 95% CI 0.32–0.90). An increase in health factors and health behaviour scores separately was associated with a lower prevalence of polyneuropathy (per point increase: OR 0.82, 95% CI 0.71–0.95 and OR 0.86, 95% CI 0.78–0.96, respectively). The association between a lower cardiovascular health score and lower sural nerve amplitude was not significant after correction for covariates (difference 0.07µV, 95% CI −0.02–0.17). Conclusions Better cardiovascular health, consisting of both modifiable health behaviours and health factors, is associated with a lower prevalence of chronic axonal polyneuropathy., Chronic axonal polyneuropathy is a common, disabling disease for which there is no treatment yet available. This highlights the need to identify modifiable risk factors. In this population‐based study, we investigated the association between cardiovascular health, defined by the seven‐item American Heart Association score, and chronic axonal polyneuropathy. Better cardiovascular health, consisting of both modifiable health behaviour and health factors, is associated with lower prevalence of chronic axonal polyneuropathy in the general population. This is of interest because individuals can potentially modify their health behaviour.

Chronic idiopathic axonal polyneuropathy is a disorder of unknown etiology resulting in progressive weakness and sensory disturbances predominantly in the hands and feet. Nerve conduction studies and electromyography confirm axonal damage in the nerves of the upper and lower extremities. The pathology is symmetrical with a distal predilection. Patients usually do not respond to the classical treatment with steroids, intravenous immunoglobulin, plasmapheresis, or immunosuppressant drugs. We describe 2 cases of chronic idiopathic axonal polyneuropathy who received intravenous rituximab as a last resort because of the severity of their symptoms. Both patients showed dramatic improvement in their weakness, muscle atrophy, numbness, and paresthesias only few weeks after the induction dose. Their daily functional activities improved to self-independence.

Hereditary transthyretin amyloidosis (ATTRv) is a condition with adult onset, caused by mutation of the transthyretin (TTR) gene and characterized by extracellular deposition of amyloid fibrils in tissue, especially in the peripheral nervous system (PNS) and heart. PNS involvement leads to a rapidly progressive and disabling sensory‐motor axonal neuropathy. Although awareness among neurologists increased in recent years thanks to new treatment options, ATTRv is frequently misdiagnosed, and thus a correct diagnosis can be delayed by several years. This review aims to draw the history and features of polyneuropathy in ATTRv based on pathological and electrophysiological correlates. We assessed original articles and case reports based on their relevance to ATTRv neuropathy and we included those appropriate for the scheme of this narrative review. Amyloid fibrils initially deposit in ganglia, causing an axonal neuropathy without amyloid deposits in distal segments (eg, sural nerve biopsy). Over time, amyloid fibrils spread along the nerves, leading to some demyelinating features in the context of severe axonal loss. This review highlights how the features of neuropathy change based on type of ATTRv (early vs late onset) and stage of disease.

After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that RFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy) from our general neuropathy clinics in Italy and the UK. All patients underwent full neurological evaluation and a blood sample was collected for RFC1 testing. Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy and in none with sensory-motor neuropathy. Forty-two per cent of RFC1-positive patients had isolated sensory neuropathy or sensory neuropathy with chronic cough, while vestibular and/or cerebellar involvement, often subclinical, were identified at examination in 58%. Although the sensory ganglia are the primary pathological target of the disease, the sensory impairment was typically worse distally and symmetric, while gait and limb ataxia were absent in two-thirds of the cases. Sensory amplitudes were either globally absent (26%) or reduced in a length-dependent (30%) or non-length dependent pattern (44%). A quarter of RFC1-positive patients had previously received an alternative diagnosis, including Sjögren’s syndrome, sensory chronic inflammatory demyelinating polyneuropathy and paraneoplastic neuropathy, while three cases had been treated with immune therapies., Currò et al. investigate the prevalence of RFC1 expansions in a cohort of patients with chronic idiopathic axonal polyneuropathy. RFC1 expansions were found in 34% of patients with sensory neuropathy, but in none with sensory-motor neuropathy. Clinical features and diagnostic clues that should lead to suspicion of RFC1 neuropathy are discussed.

To gain further insight in the immunopathology underlying multifocal motor neuropathy (MMN) by exploring the association between MMN and the human leukocyte antigen (HLA) class II DRB1, DQB1, and DQA loci in depth and by correlating associated haplotypes to detailed clinical and anti-ganglioside antibody data.We performed high-resolution HLA-class II typing for the DRB1, DQB1, and DQA1 loci in 126 well-characterized MMN patients and assessed disease associations with haplotypes. We used a cohort of 1305 random individuals as a reference for haplotype distribution in the Dutch population.The DRB1*15:01-DQB1*06:02 haplotype (OR 1.6 [95% CI 1.1-2.2], p0.05) and the DRB1*12:01-DQB1*03:01 haplotype (OR 2.7 [95% CI 1.2-5.5], p0.05) were more frequent in patients with MMN than in controls. These haplotypes were not associated with disease course, response to treatment or anti-ganglioside antibodies.MMN is associated with the DRB1*15:01-DQB1*06:02 and DRB1*12:01-DQB1*03:01 haplotypes. These HLA molecules or gene variants in their immediate vicinity may promote the specific inflammatory processes underlying MMN.

Nerve conduction studies and electromyography are useful diagnostic tools that neurologists use to diagnose diseases of the peripheral nerves, neuromuscular junction, and muscles. These tests are considered an extension of clinical history and examination, and their results should always be interpreted with the clinical context. Neuromuscular diseases are common and affect a large proportion of the elderly population. With an aging population in expansion, these diseases are expected to become even more prevalent. It is important to highlight the basics of electrophysiology and provide a reference for providers who are planning to send their patients to electromyographers for these studies.V.

Guillain-Barré syndrome (GBS) is an acute autoimmune neuropathy that can cause motor, sensory, and autonomic symptoms. Although GBS primarily is a neuropathic disorder, multiple organ systems can be affected during the disease course, and older patients may be more vulnerable to systemic complications. Close clinical monitoring and early interventions using pharmacologic and nonpharmacological treatments may lead to an improved long-term outcome.

Critical illness-associated weakness (CIAW) is an umbrella term used to describe a group of neuromuscular disorders caused by severe illness. It can be subdivided into three major classifications based on the component of the neuromuscular system (i.e. peripheral nerves or skeletal muscle or both) that are affected. This includes critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and an overlap syndrome, critical illness polyneuromyopathy (CIPNM). It is a common complication observed in people with critical illness requiring intensive care unit (ICU) admission. Given CIAW is found in individuals experiencing grave illness, it can be challenging to study from a practical standpoint. However, over the past 2 decades, many insights into the pathophysiology of this condition have been made. Results from studies in both humans and animal models have found that a profound systemic inflammatory response and factors related to bioenergetic failure as well as microvascular, metabolic, and electrophysiological alterations underlie the development of CIAW. Current management strategies focus on early mobilization, achieving euglycemia, and nutritional optimization. Other interventions lack sufficient evidence, mainly due to a dearth of large trials. The goal of this Physiology in Medicine article is to highlight important aspects of the pathophysiology of these enigmatic conditions. It is hoped that improved understanding of the mechanisms underlying these disorders will lead to further study and new investigations for novel pharmacologic, nutritional, and exercise-based interventions to optimize patient outcomes.

Background Ala97Ser transthyretin amyloidosis-associated polyneuropathy (ATTRA97S-PN) is a rare form of inherited polyneuropathy, usually manifesting with late-onset (> 50) progressive polyneuropathy. This mutation is mostly prevalent in Taiwanese and Han-Chinese individuals. The aim of this study was to describe the clinical and comprehensive neurophysiological profiles of ATTRA97S-PN in Thai patients. Methods The clinical profiles and serial neurophysiologic studies (nerve conduction study (NCS), quantitative sensory test (QST), and comprehensive autonomic function test (AFT)) of symptomatic ATTRA97S-PN patients who had been followed-up at King Chulalongkorn Memorial Hospital during 2010–2020 were retrospectively reviewed. Results Nine symptomatic patients (55.6 % were male) from four unrelated families were included. All were Thais of mixed Thai Chinese descent. The mean age of onset was 48.3 (32–60) years. The mean age at diagnosis was 54.8 (33–66) years. Three patients developed early-onset ( Conclusions This clinical study is the first of ATTRA97S-PN in Thai patients. The mixed polyneuropathy-cardiopathy phenotype was the most common manifestation. In this cohort, the age of onset was lower, and the course of neuropathy was relatively longer, than that in previous studies. Some patients may develop early-onset polyneuropathy. This mutation has not yet been documented in any population other than Han Chinese-related populations, probably suggesting a founder effect. Further studies are warranted.

Purpose Peripheral neuropathy has been reported commonly in several spinocerebellar ataxia (SCA) types. To date, there is a lack of robust evidence for neuropathy or neuronopathy in SCA type 6 (SCA6). Here, we aim to evaluate the presence of neuropathy or neuronopathy in a cohort of SCA6 patients. Methods Twenty-four individuals with genetically confirmed SCA6 underwent detailed neurophysiological assessment. This included nerve conduction studies, and in some, cutaneous silent periods, blink reflexes, tilt table tests, quantitative sudomotor axon reflex tests, and somatosensory (median and tibial) evoked potentials. Results Mean age was 56.1 years (range, 22-94 years) at the time of testing. Four patients were presymptomatic of SCA6 at recruitment. The mean disease duration of symptomatic patients was 11.9 years (range, 1-40 years). Most patients (79.2%, 19/24) had no neurophysiological evidence of a peripheral neuropathy. One with impaired glucose tolerance had mild, large, and small fiber sensorimotor polyneuropathy. One elderly patient had length-dependent axonal sensorimotor polyneuropathy. Two had minor sensory abnormalities (one had type II diabetes and previous chemotherapy). One other had minor small fiber abnormalities. Ten patients (41.7%) had median neuropathies at the wrist. All somatosensory evoked potential (15/15), and most autonomic function tests (13/14) were normal. Conclusions A large proportion of subjects (79.2%) in our cohort had no evidence of large or small fiber neuropathy. This study does not support the presence of neuropathy or neuronopathy as a common finding in SCA6 and confirms the importance of considering comorbidities as the cause of neurophysiological abnormalities.

Berg balance scale (BBS) is a widely used outcome measure in rehabilitation. We wanted to check if it can discriminate among levels of use of walking aid in patients with Guillain-Barré syndrome or polyneuropathy. A retrospective audit of 109 such patients (aged 16-85 years) who had completed inpatient rehabilitation in the period 2012-2017 was conducted. Receiver operating characteristic curve analysis was used to estimate the thresholds that optimise the prediction of the patient's walking aid. Statistically, significant threshold BBS score was estimated for the ability to walk without walking aid (≥49 points, yielding 88% sensitivity, 68% specificity and 83% classification accuracy) and the necessity to walk with a walker (≤37 points, yielding 62% sensitivity, 83% specificity and 78% classification accuracy). BBS score thresholds can therefore help clinicians choose the appropriate walking aid for patients with Guillain-Barré syndrome or polyneuropathy undergoing rehabilitation.

Background Critical illness polyneuropathy and myopathy (CIPNM) is a frequent neurological manifestation in patients with acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID‐19) infection. CIPNM diagnosis is usually limited to clinical evaluation. We compared patients with ARDS from COVID‐19 and other aetiologies, in whom a neurophysiological evaluation for the detection of CIPNM was performed. The aim was to determine if there were any differences between these two groups in frequency of CINPM and outcome at discharge from the intensive care unit (ICU). Materials and Methods This was a single‐centre retrospective study performed on mechanically ventilated patients consecutively admitted (January 2016‐June 2020) to the ICU of Careggi Hospital, Florence, Italy, with ARDS of different aetiologies. Neurophysiological evaluation was performed on patients with stable ventilation parameters, but marked widespread hyposthenia (Medical Research Council score

Multifocal motor neuropathy (MMN) is a rare disease with a prevalence of less than 1 per 100,000 people. Intravenous immunoglobulin (IVIG) therapy, performed for a long-term period, has been demonstrated able to improve the clinical picture of MMN patients, ameliorating motor symptoms and/or preventing disease progression. Treatment with subcutaneous immunoglobulin (SCIg) has been shown to be as effective as IVIG. However, previously published data showed that follow-up of MMN patients in treatment with SCIg lasted no more than 56 months. We report herein the results of a long-term SCIg treatment follow up (up to 96 months) in a group of 8 MMN patients (6 M; 2F), previously stabilized with IVIG therapy. Clinical follow-up included the administration of Medical Research Council (MRC) sum-score, the Overall Neuropathy Limitation Scale (ONLS) and the Life Quality Index questionnaire (LQI) at baseline and then every 6 months. Once converted to SCIg, patients’ responsiveness was quite good. Strength and motor functions remained stable or even improved during this long-term follow-up with benefits on walking capability, resistance to physical efforts and ability in hand fine movements.

Focal chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is defined as involving the brachial or lumbosacral plexus, or one or more peripheral nerves in one upper or one lower limb (monomelic distribution). However, other auto-immune neuropathies such as Lewis-Sumner syndrome (LSS) and multifocal motor neuropathy (MMN) can also have a focal onset. From a retrospective cohort of 30 focal CIDP patients with a monomelic onset dating back at least 2 years, we distinguished patients with plexus involvement (focal demyelinating plexus neuropathy [F-PN], n = 18) from those with sensory or sensorimotor (F-SMN, n = 7), or purely motor (F-MN, n = 5) impairment located in one or several peripheral nerves. Few (39%) F-PN patients had motor nerve conduction abnormalities, but the majority showed proximal conduction abnormalities in somatosensory evoked potentials (80%), and all had focal hypertrophy and/or increased short tau inversion recovery image signal intensity on plexus MRI. Impairment remained monomelic in most (94%) F-PN patients, whereas abnormalities developed in other limbs in 57% of F-SMN, and 40% of F-MN patients (P = .015). The prognosis of F-PN patients was significantly better: none had an ONLS score > 2 at the final follow-up visit, vs 43% of F-SMN patients and 40% of F-MN patients (P = .026). Our findings from a large cohort of focal CIDP patients confirm the existence of different entities that are typically categorized under this one term: on the one hand, patients with a focal plexus neuropathy and on the other, patients with monomelic sensori-motor or motor involvement of peripheral nerves. These two last subgroups appeared to be more likely to evolve to LSS or MMN phenotype, when F-PN patients have a more distinctive long-term, focal, benign course.

Objective To report clinical and electroneuromyographic (ENMG) characteristics of patients affected by severe COVID-19 infection, evaluated for muscular weakness. Materials and methods ENMGs performed for evaluation of diffuse weakness in patients who could not be discharged from semi-intensive care COVID unit because of difficulties in ventilation weaning were reviewed. Patients with severe COVID-19 infection who had undergone endotracheal intubation and able to co-operate were considered. ENMG protocol was focused on neurophysiological items that excluded or confirmed critical illness polyneuropathy (CIP), myopathy (CIM), or polyneuromyopathy (CIPM). Standardized clinical evaluation was performed using Medical Research Council (MRC) sum score. Results Eight patients were included in the study. All presented known risk factors for intensive care unit-acquired weakness (ICU-AW), and none of them had history of underlying neuromuscular disorders. ENMG findings were normal in two patients, while only two patients had an altered MRC sum score (< 48). Neuromuscular involvement was diagnosed in 6/8 patients (75%): 2 had CIP, 1 had possible CIM, 1 had CIPM, while 1 patient, with clinically evident weakness but equivocal ENMG findings, was classified as ICU-AW. Finally, 1 patient was diagnosed with acute demyelinating neuropathy. Patients with neuromuscular involvement were those with longer intubation duration and higher levels of IL-6 at admission. Conclusion Neuromuscular complications are frequent in severe COVID-19 and cannot be excluded by MRC sum scores above 48. Standardized ENMG is helpful in guiding diagnosis when clinical evaluation is not reliable or possible. Elevated IL-6 at admission may be a predictor biomarker of ICU-AW in COVID-19.

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease caused by mutations in the TTR gene leading to multisystem organ dysfunction. Pathogenic TTR aggregation, misfolding, and fibrillization lead to deposition of amyloid in multiple body organs and frequently involve the peripheral nerve system and the heart. Common neurologic manifestations include: sensorimotor polyneuropathy (PN), autonomic neuropathy, small-fiber PN, and carpal tunnel syndrome. Many patients have significant progression due to diagnostic delays as hATTR PN is not considered within the differential diagnosis. Recently, two effective novel disease-modifying therapies, inotersen and patisiran, were approved by Health Canada for the treatment of hATTR PN. Early diagnosis is crucial for the timely introduction of these disease-modifying treatments that reduce impairments, improve quality of life, and extend survival. In this guideline, we aim to improve awareness and outcomes of hATTR PN by making recommendations directed to the diagnosis, monitoring, and treatment in Canada.Lignes directrices sur la prise en charge de l’amylose héréditaire à transthyrétine, accompagnée de polyneuropathie, au Canada.L’amylose héréditaire à transthyrétine (ATTRh) est une maladie évolutive, causée par des mutations du gène de la transthyrétine (TTR), qui entraînent un dysfonctionnement plurisystémique. L’agrégation, le mauvais repliement et la fibrillisation pathogènes de la TTR aboutissent au dépôt de protéines amyloïdes dans plusieurs organes, et affectent souvent le système nerveux périphérique et le cœur. Les troubles neurologiques fréquents comprennent une polyneuropathie sensorimotrice (PN), une neuropathie autonome, une polyneuropathie des petites fibres et le syndrome du canal carpien. Chez bon nombre de patients, la maladie a connu une évolution importante en raison de la pose tardive du diagnostic, la PN-ATTRh ne faisant pas l’objet d’un diagnostic différentiel. Santé Canada a approuvé, depuis peu, deux nouveaux médicaments modificateurs de la PN-ATTRh et efficaces contre l’affection, soit l’inotersen et le patisiran. La pose précoce du diagnostic revêt une importance cruciale dans l’instauration, en temps opportun, de ces tout nouveaux traitements qui atténuent les troubles, améliorent la qualité de vie et prolongent la survie. Les auteurs, par l’élaboration de la nouvelle ligne directrice, espèrent sensibiliser la communauté médicale à la PN-ATTRh, et améliorer les résultats cliniques qui y sont associés, en formulant des recommandations sur le diagnostic et le traitement de la maladie au Canada ainsi que sur la surveillance de son évolution.

Introduction In multifocal motor neuropathy (MMN), knowledge about the pattern of treatment response in a wide spectrum of muscle groups, distal as well as proximal, after intravenous immunoglobulin (IVIg) initiation is lacking. Methods Hand‐held dynamometry data of 11 upper and lower limb muscles, from 47 patients with MMN was reviewed. Linear mixed models were used to determine the treatment response after IVIg initiation and its relationship with initial muscle weakness. Results All muscle groups showed a positive treatment response after IVIg initiation. Changes in SD scores ranged from +0.1 to +0.95. A strong association between weakness at baseline and the magnitude of the treatment response was found. Discussion Improved muscle strength in response to IVIg appears not only in distal, but to a similar degree also in proximal muscle groups in MMN, with the largest response in muscle groups that show the greatest initial weakness.

RESUMEN La enfermedad de Parkinson es una entidad neurodegenerativa con alteraciones principalmente extrapiramidales, del sistema nervioso autónomo y, en etapas finales, alteraciones cognitivas y neuropsiquiátricas. Desde 1976 se reconocen además síntomas neurosensoriales dependientes del sistema nervioso periférico, presentes en casi la mitad de los pacientes y que preceden incluso a los síntomas motores. Los síntomas sensitivos fueron inicialmente atribuidos a distonías o a niveles indebidos de levodopa en ausencia de medicación apropiada; sin embargo, estudios recientes sugieren una etiología intrínseca a la propia enfermedad. Se reconocen tres formas de presentación: polineuropatía crónica (la más común), aguda y subaguda. La clínica de la polineuropatía es concurrente con la de la enfermedad de Parkinson y el diagnóstico es básicamente clínico, aun cuando se cuenta con el apoyo de la electromiografía y de la velocidad de conducción nerviosa, cuya normalidad no descartaría a esta entidad. El manejo actual está basado en la presunción etiológica, por lo que la reposición de vitaminas como la B12, B1 y folatos puede considerarse como parte del mismo. La etiología, el pronóstico y la fisiopatología son aún temas de debate y requieren, por lo tanto, más investigaciones. SUMMARY Parkinson´s disease is a neurodegenerative entity with predominant extrapyramidal and dysautonomic features and, in the final stages, cognitive and neuropsychiatric manifestations. Since 1976, the involvement of the peripheric nervous system has been recognized, mainly through neurosensorial symptoms affecting almost half of the Parkinson patients, even before the onset of motor symptoms. Initially, these symptoms were attributed to dystonia or the use of levodopa in the absence od medications; however, recent studies suggest an intrinsic etiology in idiopathic Parkinson´s disease. Chronic (the most frequently described), subacute and acute polyneuropathy are the main clinical forms. The sensory symptoms coexist with those of Parkinson´s disease. The diagnosis is essentially based on a clinical examination supported by electromyography and tests of neuro-conduction velocity whose normality does not rule out this entity, however. Its management depends on the etiological assumptions, and includes the eventual use of vitamin B12, B1 and folates replacement therapy. The etiology, the prognosis and the physiopathology are still topics of debate whose clarification requires further research.

Introduction Several studies of patients with polyneuropathy failed to show differences between patients with and without pain. In the current study, we aimed to explore the association between neuropathic symptoms, mainly pain, and polyneuropathy characteristics. Methods A prospective cross-sectional study recruiting 151 patients with non-diabetic polyneuropathy was performed between November 2016 and May 2017. 38 patients with chronic inflammatory demyelinating neuropathy were excluded. Patients underwent clinical, electrophysiological and functional assessments of their polyneuropathy. Polyneuropathy characteristics were compared depending on the presence and severity of neuropathic symptoms. Results The presence and the severity of weakness were associated with a more severe neuropathy as measured by clinical, electrophysiological and functional assessments, while the presence of pain was associated with higher sural amplitudes, and the severity of pain showed a curvilinear association with neuropathy severity. Discussion Our study shows a novel finding of a curvilinear association between pain and polyneuropathy severity. This article is protected by copyright. All rights reserved.

Background Despite its initial association with sensory neuropathies, anti-fibroblast growth factor receptor 3 (FGFR3) antibodies have been since reported with a broad range of neuropathies and clinical features. The aim of the study is to report the clinical and electro diagnostic findings in a cohort of patients with sensory or sensorimotor polyneuropathy and anti-FGFR3 antibodies. Methods We performed a retrospective chart review to assess the clinical characteristics of patients with sensory or sensorimotor neuropathy related to FGFR3 antibodies. Descriptive statistics were reported using frequencies and percentages for categorical variables and median and interquartile range (IQR) for continuous variables. Results This study included 14 patients (9 women) with a median age of 51.9 years (IQR 48–57). The most common presenting symptoms were painful paresthesia (100%), gait instability (42.9%), constitutional symptoms (42.9%), and autonomic symptoms (28.6%). Onset of symptoms was chronic (≥12 weeks) in eight patients (57.1%). Examination showed a distal loss of sensation to pin prick (100%), as well as impaired vibration sensation (78.6%) and proprioception (35.7%), in the distal extremities. We also observed mild weakness in the distal lower-extremities (42.9%). Three patients (21.4%) had trigeminal neuralgia, three patients (21.4%) had co-existing autoimmune disease, and one patient (7.1%) had a history of renal cell carcinoma. The mean titer of FGFR3 antibody was 14,285.71 (IQR 5000–16,750). All 14 patients produced normal results in the neuropathy workup. Nerve conduction study and electromyography showed sensory axonal neuropathy in four patients (28.6%), sensorimotor axonal neuropathy in seven patients (50%), and a normal result in three patients (21.4%). For those with a normal NCS/EMG, a skin biopsy showed a non-length-dependent small fiber neuropathy. Conclusions Neuropathy related to FGFR3 antibodies can potentially involve small and large fibers, sensory and motor fibers, and even the trigeminal nerve, which contributes to a highly variable clinical presentation.

Objective Thalamus is essential in processing of sensory information. This study explored the associations between thalamic volume and intra-thalamic metabolites and associations to clinical and experimental characteristics of sensory function in adults with diabetic polyneuropathy. Methods 48 adults with type 1 diabetes and confirmed distal symmetric peripheral neuropathy (DPSN) and 28 healthy controls participated in a cross-sectional study and underwent a brain magnetic resonance imaging scan. Estimates for thalamic volume were extracted using voxel-based morphometry and intra-thalamic N-acetylaspartate/creatine (NAA/cre) levels were assessed by magnetic resonance spectroscopy. Associations between thalamic volume and clinical measures, quantitative sensory testing and neuropathic phenotype were explored. Results In diabetes, reduced gray matter volume was identified including bilateral thalamus (all p≤0.001) in comparison to healthy participants. Thalamic volume estimates were positively associated to intra-thalamic NAA/cre (r=0.4; p=0.006), however not to diabetes duration (p=0.5), severity of DSPN (p=0.7), or presence of pain (p=0.3). Individuals with the lowest thalamic volume had greatest loss of protective sensation (light touch using von Frey-like filaments, p=0.037) and highest pain tolerance to electric stimulation (tetanic stimulation, p=0.008) compared to individuals with the highest thalamic volume. Conclusions In this cohort with type 1 diabetes and severe DSPN, thalamic atrophy was present and associated with reduced NAA/cre, indicating thalamic structural loss and dysfunction. Thalamic atrophy was associated to reduced sensory function involving large fiber neuropathy and sensation to tetanic stimulation that may reflect synaptic transmission. This may ultimately contribute to the current understanding of the pathophysiology behind the perception changes evident in DSPN.

Background Disease-modifying therapies provide new horizons for hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) to slow neuropathic progression. Initiating treatment at the earliest time requires biomarkers reflecting both small- and large-fiber degeneration in carriers. Methods This study included examinations of pathology [intraepidermal nerve fiber (IENF) density], physiology (nerve conduction studies, autonomic function test and nerve excitability), and psychophysics (thermal thresholds) in carriers to compare to healthy controls and asymptomatic diabetic patients. Results There were 43 carriers (44.2±11.4 years, p.Ala117Ser in 42 carriers), 43 controls (43.4±12.7 years) including 26 noncarrier families, and 50 asymptomatic diabetic patients (58.1±9.5 years). Carriers had lower IENF densities than controls and similar densities as diabetic patients. Median nerve conduction parameters, especially distal motor latency, (1) were the most frequent neurophysiological abnormality in carriers, (2) could differentiate carriers from controls and diabetic patients, (3) were correlated with IENF densities in carriers but not in controls and diabetic patients, and (4) were correlated with nerve excitability parameters in carriers but not in controls. Fifteen carriers (34.9%) with electrophysiological evidence of median nerve entrapment at wrist had lower IENF densities and more abnormal conduction parameters than carriers without. We defined nerve dysfunction index (the ratio of median distal motor latency to IENF density) which differentiated carriers from controls. Conclusions In late-onset ATTRv-PN carriers with predominant p.Ala117Ser, median conduction parameters were the most common neurophysiological abnormalities, and served as surrogate signatures of small- and large-fiber impairment. Combination of median distal motor latency and IENF density can reflect early neuropathy in carriers.

A 76-year-old man, who received atezolizumab for the treatment for small cell lung cancer, acutely developed limb weakness with sensory disturbance after the third course of the treatment. Nerve conduction studies were consistent with demyelinating polyneuropathy and acute demyelinating polyneuropathy caused by atezolizumab was suggested. Atezolizumab was immediately withdrawn, and intravenous immunoglobulin (IVIg) and methylprednisolone pulse therapies with subsequent oral administration of prednisolone were initiated, after which neurological deficits steadily improved. Although Guillain-Barré syndrome-like neuropathy caused by immune checkpoint inhibitor (ICI) was occasionally reported, this is the first case of acute demyelinating polyneuropathy triggered by atezolizumab, monoclonal antibody targeting programmed death-ligand 1. This case suggests that combined treatments with IVIg and corticosteroids are effective for neuropathy induced by atezolizumab as same as those by other ICI.

Background: Peripheral nerve ultrasound (US) has been used as a promising diagnosing technique for peripheral nerve disorders. This study aimed to compare the US findings of Guillain-Barre syndrome (GBS) with chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: This case-control study was done on 25 patients with GBS at 3 weeks after onset of disease and 25 patients with CIDP. Demographic information and US results of median nerve at 2 points, ulnar nerve at 3 points, and tibial and peroneal nerves were collected. Results: Left median nerve diameter in patients with CIDP with the mean of 0.141 ± 0.047 was more than GBS group with the mean of 0.095 ± 0.034 (P < 0.001). Both sides of median nerve diameter in patients with CIDP were higher than patients with GBS (P < 0.050), but in the left side, it was more in patients with CIDP (P = 0.003). Conclusion: The diameter and circumference of median, ulnar, and tibial nerves in forearm and elbow of patients with CIDP are more than patients with GBS; therefore, it may be possible to use US findings based on these differences in diagnosis and differentiation of the two diseases.

© 2020 Elsevier Ltd. All rights reserved., Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.

Background:Wild-type transthyretin amyloidosis (wtATTR) is an important cause of heart failure (HF); however, the prevalence and clinical significance of neurologic complications remains uncertain.Methods:This analysis reports findings from a single-centre experience of routine neuropathy screening at the time of wtATTR diagnosis by nerve conduction studies and neurologist assessment, compared with age-matched controls.Results:Forty-one wtATTR patients were included, 39 (95%) males, mean age 78.4 ± 7.7 years, 22 (54%) New York Heart Association (NYHA) class III–IV HF, along with 15 age-matched controls (mean age 77.1 ± 4.2 years, 80% male). Twenty-one (51%) wtATTR patients were diagnosed with polyneuropathy, 15 (37%) with spinal stenosis, 36 (88%) with carpal tunnel syndrome (CTS) and 14 (34%) with ulnar neuropathy. Comparison diagnoses among controls were 1 (7%), 0, 1 (7%) and 3 (20%), respectively. Among patients with NYHA class III–IV HF, 16 (73%) had polyneuropathy compared with 5 (26%) with class I–II (p < 0.01), odds ratio of 7.5 (95% confidence interval 1.9–29.9). After neuropathy screening, 19 (46%) patients were offered neurologic therapy and/or additional diagnostic evaluation. This included CTS release surgery (16, 39%), neuropathic pain medication (3, 7%), nerve block (1, 2%), wrist splinting (2, 5%) and foot care (1, 2%). Spine imaging was performed for 3 (7%) patients, and deltoid muscle and sural nerve biopsy for 1 (2%) patient.Conclusions:Screening of wtATTR patients for neurologic complications resulted in a management change for nearly half. CTS, polyneuropathy and ulnar neuropathy were common. This approach warrants consideration as part of routine assessment for newly diagnosed wtATTR patients.

ObjectiveTo present standardized diagnostic criteria for idiopathic distal sensory polyneuropathy (iDSP) and its subtypes: idiopathic mixed fiber sensory neuropathy (iMFN), idiopathic small fiber sensory neuropathy (iSFN), and idiopathic large fiber sensory neuropathy (iLFN) for use in research.MethodsThe Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION) public-private partnership with the Food and Drug Administration convened a meeting to develop consensus diagnostic criteria for iMFN, iSFN, and iLFN. After background presentations, a collaborative, iterative approach was used to develop expert consensus for new criteria.ResultsAn iDSP diagnosis requires at least 1 small fiber (SF) or large fiber (LF) symptom, at least 1 SF or LF sign, abnormalities in sensory nerve conduction studies (NCS) or distal intraepidermal nerve fiber density (IENFD), and exclusion of known etiologies. An iMFN diagnosis requires that at least 1 of the above clinical features is SF and 1 clinical feature is LF with abnormalities in sensory NCS or IENFD. Diagnostic criteria for iSFN require at least 1 SF symptom and at least 1 SF sign with abnormal IENFD, normal sensory NCS, and the absence of LF symptoms and signs. Diagnostic criteria for iLFN require at least 1 LF symptom and at least 1 LF sign with normal IENFD, abnormal sensory NCS, and absence of SF symptoms and signs.ConclusionAdoption of these standardized diagnostic criteria will advance research and clinical trials and spur development of novel therapies for iDSPs.