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To examine the efficacy and safety of patisiran, an RNA interference therapeutic, in patients from Taiwan with hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy. The APOLLO phase 3 trial included patients from Taiwan who received patisiran 0.3 mg/kg intravenously or placebo once every 3 weeks (q3w) for 18 months (18 M), followed by patisiran 0.3 mg/kg q3w in an ongoing global open-label extension (OLE) study. The primary endpoint was change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 18 M. Eighteen Taiwanese patients were enrolled in APOLLO (patisiran, n = 8; placebo, n = 10; all A97S gene variant) and 14 continued in the global OLE. In this Taiwanese sub-population, beneficial treatment effects at 18 M were observed in mNIS+7 (least squares mean difference in change from baseline [patisiran-placebo], −26.5 points; 95% confidence interval: −45.5, −7.5). Patients who switched from placebo to patisiran demonstrated slowing of polyneuropathy progression at month 12 in the global OLE, while those who received patisiran in APOLLO maintained the beneficial treatment effects. Patisiran had an acceptable safety profile in the Taiwanese sub-population. This analysis suggests that patisiran is well tolerated and may provide a substantial clinical benefit for Taiwanese patients with hATTR amyloidosis with polyneuropathy. The studies were registered on the ClinicalTrials.gov. The APOLLO study ClinicalTrials.gov identifier is NCT01960348 (https://clinicaltrials.gov/ct2/show/NCT01960348), with the registration date of October 10, 2013, and the first patient was enrolled on December 13, 2013. For the global OLE, the ClinicalTrials.gov identifier is NCT02510261 (https://clinicaltrials.gov/ct2/show/NCT02510261) with the registration date of July 29, 2015, and the first patient was enrolled on July 13, 2015. This study provides Class II evidence that treatment with patisiran is safe and efficacious in Taiwanese patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. [ABSTRACT FROM AUTHOR]

Hereditary transthyretin amyloidosis (ATTRv) is associated with polyneuropathy, cardiomyopathy, or both. The effects of eplontersen on cardiac structure and function were assessed. NEURO-TTRansform was an open-label trial involving 144 adults with ATTRv polyneuropathy (49 patients [34%] with cardiomyopathy) receiving eplontersen throughout and compared with a historical placebo group (n = 60; 30 patients [50%] with cardiomyopathy) from the NEURO-TTR trial at week 65. Treatment effect (eplontersen vs placebo), presented as mean difference (95% confidence interval) was analyzed after adjusting for age, sex, region, baseline value, ATTRv disease stage, previous ATTRv treatment, and V30M transthyretin variant. There were notable differences at baseline between the eplontersen group and historical placebo. In the cardiomyopathy subgroup, 65 weeks of eplontersen treatment was associated with improvement from baseline relative to placebo in left ventricular ejection fraction of 4.3% (95% confidence interval 1.40–21.01; P =.049) and stroke volume 10.64 mL (95% confidence interval 3.99–17.29; P =.002) while the remainder of echocardiographic parameters remained stable. Eplontersen was associated with stable or improved measures of cardiac structure and function vs historical placebo in patients with ATTRv polyneuropathy and cardiomyopathy. Further investigation into eplontersen's effect on transthyretin amyloid cardiomyopathy is being conducted in the CARDIO-TTRansform trial. vATTR, variant transthyretin; LV, left ventricle; E/e′, ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity; NT-proBNP, N-terminal prohormone of brain natriuretic peptide. [Display omitted] [ABSTRACT FROM AUTHOR]

Peripheral neuropathy (PN) is one of the most heterogeneous and poorly understood or characterized manifestations in systemic lupus erythematosus (SLE). The aim of this study was to describe the clinical and electrophysiological features, and neuropathic disease associations, in Cuban SLE patients. One hundred and two consecutive SLE patients admitted to the Psychoneuroimmunology service at the National Institute of Nephrology were included in the study. Patients with other disorders known to cause neuropathy were excluded. Demographic, clinical and laboratory data were obtained using a pre-defined questionnaire. Nerve conduction studies were carried out in both upper and lower limbs. Neuropathy was defined as the presence of clinical symptoms and/or signs and bilateral abnormal nerve conduction study parameters. The 102 patients were 99 females and 3 males with mean age of 46 ± 12 years and disease duration 8 ± 9 years. PN was found in 55/102 (53.9%) patients; 48 (87.3%) had clinical peripheral neuropathy manifestations and 7 (12.7%) were asymptomatic. Nerve conduction studies suggested asymmetric axonal-demyelination neuropathy pattern. Mixed sensory-motor neuropathy was the most common involvement in 23(41.8%) cases. The most frequent pattern was polyneuropathy. Compared to those without neuropathy, SLE-related polyneuropathy patients were significantly older, but had no other significant associations with demographic, disease duration or serological/immunological data. Peripheral nervous system manifestations are common in SLE; may be related to an increased susceptibility of peripheral nerves to effects of aging. Nerve conduction studies are recommended, therefore, for inclusion in the follow-up of SLE patients especially in the older population. [ABSTRACT FROM AUTHOR]

Excessive fragmentary myoclonus (EFM) is an incidental finding in video-polysomnography (VPSG) and listed among "Sleep Related Movement Disorders – Isolated symptoms and normal variants" in the ICSD-3. We aimed to prospectively evaluate EFM in the upper and lower extremities in a large sleep laboratory cohort and to investigate clinical characteristics and peripheral nerve pathology in patients with and without EFM. Two-hundred consecutive sleep laboratory patients with EFM according to ICSD-3 criteria were included and matched to 100 patients without EFM for age, sex and presence or absence of sleep-related breathing disorder. Patients additionally underwent peripheral neurophysiological work-up. In 31/200 (15.5%) patients EFM was present not only in the lower extremities, but also in the upper extremities. Patients with EFM had less REM sleep (%/SPT; median (IQR); 13.8 (9.1–18.2) vs. 17.1 (10.1–20.5); p = 0.008) and the PLMS-Index was higher in patients with EFM than in those without (16.2 vs. 8.8/h; p = 0.009). Polyneuropathy (PNP) and nerve root lesions L5 and S1 were more frequent in patients with than in those without EFM (31.5% vs. 21% and 5% vs. 0%; p = 0.003). In this large cohort we systematically investigated upper and lower extremities with surface electromyography during sleep and show that EFM is much more frequent in the lower extremities than in the upper extremities and corroborate the association of EFM with peripheral nerve pathology and PLMS. • This study involved 200 patients with excessive fragmentary myoclonus (EFM). • We show that EFM was present in upper and lower extremities in 31/200. • We confirmed association of EFM and peripheral nerve pathology. [ABSTRACT FROM AUTHOR]

The lumbosacral plexus originates from the anterior rami of the lumbar and sacral nerve roots forming a network of nerves which supply the lower half of the body. The lumbar plexus (L1–L4) is situated within the upper two-thirds of psoas major and gives rise to the iliohypogastric nerve, ilioinguinal nerve, genitofemoral nerve, lateral femoral cutaneous nerve, femoral nerve and obturator nerve. The sacral plexus (L4–S4) is located within the pelvis and gives rise to the superior gluteal nerve, inferior gluteal nerve, sciatic nerve, posterior cutaneous nerve, perforating cutaneous nerve and the pudendal nerve. Peripheral neuropathy of these nerves may occur from an autoimmune, inflammatory, endocrine, infective, congenital, traumatic, neoplastic, vascular, degenerative or metabolic cause. This article will give an overview of the relevant anatomy of the lumbosacral plexus and neuropathies which affect the peripheral nerves of the lower limb. [ABSTRACT FROM AUTHOR]

Childhood cancer survivors (CCS) are at risk of polyneuropathy due to chemotherapy, but studies in young survivors are scarce and diagnosis is challenging. We aimed to study the presence of polyneuropathy and the possible effect of cumulative doses of chemotherapeutic agents in a representative group of adolescent survivors. CCS aged nine to 18 years and age- and sex-matched controls were recruited from the cross-sectional Physical Activity and Fitness among Childhood Cancer Survivors (PACCS) study. CCS with various cancer diagnoses who had ended cancer treatment one year or more before study were included. Polyneuropathy was evaluated clinically and with nerve conduction studies (NCSs) in three motor and five sensory nerves. We used mixed-effects linear regression models to compare CCS and controls, and investigate possible associations between cumulative chemotherapy doses and NCS amplitudes. A total of 127 CCS and 87 controls were included, with 14% CCS having probable or confirmed polyneuropathy. NCS amplitudes were lower in survivors compared with controls in all nerves. The largest mean difference was 3.47 μV (95% confidence interval [CI], 2.18 to 4.75) in the tibial plantar medial sensory and 1.91 mV (95% CI, 0.78 to 3.04) in the tibial motor nerve. The cumulative dose of platinum derivatives was associated with lower tibial motor nerve amplitude (−0.20; 95% CI, −0.35 to −0.04 mV for 100 mg/m2 dose increase) but not in other nerves. We found no significant associations between vinca alkaloids cumulative dose and amplitudes. CCS without clinical signs or symptoms of polyneuropathy may have subtle nerve affection. The clinical long-term impact of this novel observation should be evaluated in larger, longitudinal studies. [ABSTRACT FROM AUTHOR]

• AHP results from abnormal heme biosynthesis causing neurological symptoms during acute attacks. • Various triggers stimulate heme synthesis, elevate heme precursors and cause acute attacks. • Elevated ALA and PBG cause acute abdominal pain, seizures, hallucinations, and polyneuropathy. • A high index of suspicion is vital, and diagnosis requires a substantial increase in urine PBG. • Givosiran, an RNA silencer, suppresses production of ALAS and reduces ALA and PBG concentrations. Acute hepatic porphyrias (AHP) comprise four rare monogenic autosomal conditions. Each is linked to a deficiency of heme metabolizing enzymes. Common manifestations include severe abdominal pain, nausea, confusion, hyponatremia, hypertension, tachycardia, and neuropathy. Diagnosis is challenging due to a non-specific, variable presentation with symptoms mimicking other common conditions. Initial diagnosis of AHP can be made with a test for urinary porphobilinogen, δ-aminolevulinic acid and porphyrins using a single random (spot) sample. However, many patients have complications due to delays in diagnosis and management. A novel small interfering RNA-based agent, givosiran, has demonstrated efficacy in reducing acute attacks in a recent Phase III trial, leading to its approval for the management of AHP. Early diagnosis is crucial for the timely introduction of disease-modifying treatments that reduce impairments, enhance quality of life, and extend survival. In this guidance, we aim to improve awareness and outcomes of AHP by making recommendations about diagnosis, monitoring, and treatment in Canada. [ABSTRACT FROM AUTHOR]

• Common age-related cervical neuroforaminal stenoses on MRI/CT are not per se associated with nerve root enlargement on ultrasound. • Degeneration of the cervical spine is unlikely to confound the ultrasound assessment of cervical nerve roots in polyneuropathy. • Older age is associated with neuroforaminal stenosis, but is not a significant covariate of nerve root diameter in this cohort. Ultrasound can detect enlargement of cervical nerve roots, which has been described in polyneuropathies (PNP), mainly of demyelinating pathology. This study investigates whether neuroforaminal stenosis, as a common but often asymptomatic degenerative change, is associated with nerve root enlargement on ultrasound and whether neuroforaminal stenosis thus confounds cervical nerve root ultrasound findings in the diagnostic assessment of PNP. We retrospectively studied 182 patients (62 demyelinating, 71 axonal PNP; 49 without evidence of PNP) who had undergone ultrasound of the cervical nerve roots C5 and C6 and magnetic resonance or computed tomography of the cervical spine that was reviewed with respect to neuroforaminal stenoses. Patients with demyelinating PNP had larger nerve roots than those with axonal/without PNP. No significant differences in cervical nerve root diameters were found between groups with vs. without neuroforaminal stenosis. The diagnostic performance of the discrimination of PNP subtypes based on ultrasound nerve root measurements did not differ significantly when including or excluding subjects with neuroforaminal stenoses. Neuroforaminal stenosis per se does not entail relevant cervical nerve root enlargement detectable by nerve ultrasound. Ultrasound assessment of cervical nerve root size in the diagnostic evaluation of PNP is unlikely to be confounded by common degenerative changes of the cervical spine. [ABSTRACT FROM AUTHOR]

• In anti-MAG neuropathy; widenings of myelin lamellae (WML) are classically observed in the nerve biopsy (electron microscopy). • WML may be observed in polyneuropathy associated to IgM monoclonal gammopathy without anti-MAG activity. • IgM may target an unknown myelin antigen responsible for the nerve lesions similar to those observed in anti-MAG polyneuropathy. • The good response to plasma exchange and/or rituximab suggests an autoimmune origin. • Nerve biopsy may help to confirm the dysimmune process and to select an efficient treatment. We report the case of a patient with a very severe predominantly demyelinating sensorimotor polyneuropathy (with axonal loss) that had developed over several months, along with an immunoglobulin-M monoclonal gammopathy without anti-myelin associated glycoprotein antibodies (or other antibodies against myelin). Widening of myelin lamellae were frequently observed by electron microscopic examination of a nerve biopsy: immunoglobulin-M targeting an unknown myelin antigen appears to be responsible for the nerve lesions similar to those observed in anti-myelin associated glycoprotein polyneuropathy. Usually, if in anti-myelin associated glycoprotein neuropathy the response to immunotherapies is not optimal, in this case the combination of plasma exchanges and rituximab was effective, suggesting an autoimmune origin. [ABSTRACT FROM AUTHOR]

Aim: To detect the prevalence of diabetic polyneuropathy (DPN) in children with type 1 diabetes (T1D) and to identify associated the risk factors.Methods: This cross-sectional study evaluated children aged between 2 and 16y with T1D for ≥2 y. Detailed neurological examination, neuropathy symptom score, and nerve conduction studies were done in all children to assess nerve dysfunction. Disease-related factors were evaluated for the prediction of neuropathy.Results: Sixty-six children (67% boys) were enrolled. The mean age at the time of diagnosis of T1D was 7.1 ± 2.6 years. The mean duration of diabetes was 4 ± 1.8 years. None of the patients had neuropathy on clinical examination or on the neuropathy symptom score. The prevalence of subclinical DPN was 18.2% (n = 12/66). The type of neuropathy was pure motor (n = 11, 91.6%) and mixed sensorimotor (n = 1, 8.3%). The common peroneal nerve was most commonly affected (n = 6, 50%), followed by the tibial (n = 4, 33.3%) nerve. The most common patterns of nerve involvement were mixed axonal and demyelination (n = 7, 58.3%), followed by axonal (n = 3, 25%) and demyelinating type (n = 2, 16.6%). Children with subclinical DPN had a significant reduction in velocity of tibial, common peroneal, median motor, and ulnar motor nerves; delayed latency in common peroneal, median motor, ulnar motor, and median sensory nerves compared to those without DPN (p value <0.05). A higher body mass index predicted the development of subclinical DPN (p value <0.05).Conclusion: Nearly one-fifth of children with T1D have subclinical neuropathy as early as two years of the disease. A higher body mass index is significantly associated with DPN. Electrophysiological studies should be performed regularly to screen for nerve dysfunction and its progression. [ABSTRACT FROM AUTHOR]

Clinical manifestations of malformations of cortical development (MCD) are variable and can range from mild to severe intellectual disability, cerebral palsy and drug-resistant epilepsy. Besides common clinical features, non-specific or more subtle clinical symptoms may be present in association with different types of MCD. Especially in severely affected individuals, subtle but specific underlying clinical symptoms can be overlooked or overshadowed by the global clinical presentation. To facilitate the interpretation of genetic variants detailed clinical information is indispensable. Detailed (neurological) examination can be helpful in assisting with the diagnostic trajectory, both when referring for genetic work-up as well as when interpreting data from molecular genetic testing. This systematic literature review focusses on different clues derived from the neurological examination and potential further work-up triggered by these signs and symptoms in genetically defined MCDs. A concise overview of specific neurological findings and their associations with MCD subtype and genotype are presented, easily applicable in daily clinical practice. The following pathologies will be discussed: neuropathy, myopathy, muscular dystrophies and spastic paraplegia. In the discussion section, tips and pitfalls are illustrated to improve clinical outcome in the future. [ABSTRACT FROM AUTHOR]

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). 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. 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. 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. [ABSTRACT FROM AUTHOR]

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

Background: 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.Objective: To assess efficacy of individualized homoeopathic medicines in management of DDSP.Methods: 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.Results: Data of 68 enrolled cases was considered for data analysis. Statistically significant difference (p<0.014) 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.Conclusion: Further studies must be taken up with larger sample size and defined parameters for NCS to assess the effectiveness of homoeopathy. [ABSTRACT FROM AUTHOR]

• 20 patients with persistent neuromuscular symptoms including fatigue, 77–255 (median: 216) days after acute COVID-19 were examined. • Nerve conduction studies did not show signs of neuropathy but 11 patients (55%) had myopathic changes with quantitative electromyography. • Myopathy may be an important cause of physical fatigue and myalgia in long-term COVID-19 even in non-hospitalized patients. To investigate the peripheral nerve and muscle function electrophysiologically in patients with persistent neuromuscular symptoms following Coronavirus disease 2019 (COVID-19). Twenty consecutive patients from a Long-term COVID-19 Clinic referred to electrophysiological examination with the suspicion of mono- or polyneuropathy were included. Examinations were performed from 77 to 255 (median: 216) days after acute COVID-19. None of the patients had received treatment at the intensive care unit. Of these, 10 patients were not even hospitalized. Conventional nerve conduction studies (NCS) and quantitative electromyography (qEMG) findings from three muscles were compared with 20 age- and sex-matched healthy controls. qEMG showed myopathic changes in one or more muscles in 11 patients (55%). Motor unit potential duration was shorter in patients compared to healthy controls in biceps brachii (10.02 ± 0.28 vs 11.75 ± 0.21), vastus medialis (10.86 ± 0.37 vs 12.52 ± 0.19) and anterior tibial (11.76 ± 0.31 vs 13.26 ± 0.21) muscles. All patients with myopathic qEMG reported about physical fatigue and 8 patients about myalgia while 3 patients without myopathic changes complained about physical fatigue. Long-term COVID-19 does not cause large fibre neuropathy, but myopathic changes are seen. Myopathy may be an important cause of physical fatigue in long-term COVID-19 even in non-hospitalized patients. [ABSTRACT FROM AUTHOR]

• Acute tetraparesis is a debilitating and sometimes life-threatening condition. • History and examination are essential in establishing the correct diagnosis. • A practical approach is to use the neuroaxis as an anatomical guide. • Updated information on new neurological entities and treatments are also mentioned. Potentially life-threatening disorders may present in the emergency department with acute tetraparesis, and their recognition is crucial for an appropriate management and timely treatment. Our review aims to systematize the differential diagnosis of acute non-traumatic tetraparesis. Causes of tetraparesis can be classified based on the site of defect: upper motor neuron (UMN), peripheral nerve, neuromuscular junction or muscle. History of present illness should include the distribution of weakness (symmetric/asymmetric or distal/proximal/diffuse) and associated clinical features (pain, sensory findings, dysautonomia, and cranial nerve abnormalities such as diplopia and dysphagia). Neurological examination, particularly tendon reflexes, helps further in the localization of nerve lesions and distinction between UMN and lower motor neuron. Ancillary studies include blood and cerebral spinal fluid analysis, neuroaxis imaging, electromyography, muscle magnetic resonance and muscle biopsy. Acute tetraparesis is still a debilitating and potentially serious neurological condition. Despite all the supplementary ancillary tests, the neurological examination is the key to achieve a correct diagnosis. The identification of life-threatening neurologic disorders is pivotal, since failing to identify patients at risk of complications, such as acute respiratory failure, may have catastrophic results. [ABSTRACT FROM AUTHOR]

We report a case of a 36 year old gentleman presenting with polyneuropathy and Korsakkoff Syndrome complicating Sleeve Gastrectomy. [ABSTRACT FROM AUTHOR]

• Alaskan Malamute dogs with NDRG1 mutation develop a demyelinating neuropathy. • Ultrastructural changes are characterized by inclusion material and myelin folds. • Distinct changes in peripheral nerve lipid composition are present. • NDRG1 is necessary to maintain myelin homeostasis. Mutations in the N-myc downstream-regulated gene 1 (NDRG1) cause degenerative polyneuropathy in ways that are poorly understood. We have investigated Alaskan Malamute dogs with neuropathy caused by a missense mutation in NDRG1. In affected animals, nerve levels of NDRG1 protein were reduced by more than 70% (p < 0.03). Nerve fibers were thinly myelinated, loss of large myelinated fibers was pronounced and teased fiber preparations showed both demyelination and remyelination. Inclusions of filamentous material containing actin were present in adaxonal Schwann cell cytoplasm and Schmidt-Lanterman clefts. This condition strongly resembles the human Charcot-Marie-Tooth type 4D. However, the focally folded myelin with adaxonal infoldings segregating the axon found in this study are ultrastructural changes not described in the human disease. Furthermore, lipidomic analysis revealed a profound loss of peripheral nerve lipids. Our data suggest that the low levels of mutant NDRG1 is insufficient to support Schwann cells in maintaining myelin homeostasis. [ABSTRACT FROM AUTHOR]

Introduction: This study reports a large series of patients with a clinical picture dominated by spastic paraplegia in whom variants in the NEFL gene, a known cause for Charcot-Marie-Tooth disease, were identified.Methods: Index patients referred for a suspicion of hereditary spastic paraplegia (HSP) were clinically assessed and genetic analysis by next-generation sequencing was undertaken. Additional family members were clinically examined and subjected to targeted testing.Results: We identified two different heterozygous dominant variants in the NEFL gene in 25 patients from 14 families. Most of them (21/25) had a clinical diagnosis of HSP, often with a concomitant clinical diagnosis of polyneuropathy (16/21). Two patients were identified with a polyneuropathy with a pyramidal reflex pattern, but without spasticity. Two patients had isolated polyneuropathy. Out of the 21 patients with a diagnosis of HSP, two had co-occurring cerebellar signs. The c.262A > C p.(Thr88Pro) variant was detected in 13 families. Genealogical analysis showed shared ancestors or a similar geographical origin in 12, suggesting a founder effect. The other variant, c.296A > C p.(Asp99Ala), was found in only one family, in which limited segregation analysis could be performed.Discussion: Variants in the NEFL gene can cause HSP, with or without co-existing polyneuropathy, and should be included in diagnostic testing strategies for HSP patients. [ABSTRACT FROM AUTHOR]

• Hereditary myofibrillar myopathy with axonal polyneuropathy, long QT 'interval and familial atrial fibrillation. • Phenotype of adult onset and distal leg weakness resembled CMT. • Remarkable semitendinosus muscle atrophy was observed. • Heterozygous P470S mutation in BAG3 may not be associated with apparent cardiomyopathy. We report a family with adult-onset myofibrillar myopathy with BAG3 mutation who presented peroneal weakness and axonal polyneuropathy, mimicking axonal Charcot-Marie-Tooth disease. The male proband noticed difficulty in tiptoeing at age 34. At age 42, the examination showed muscle weakness and atrophy in distal lower extremities with diminished patellar and Achilles tendon reflexes. Thermal and vibration sensations were also impaired in both feet. The serum CK level was 659 U/L. On muscle imaging, predominant semitendinosus muscle atrophy coexisted with atrophies in the quadriceps, gastrocnemius and lumbar paraspinal muscles. The muscle biopsy showed myofibrillar myopathy with fiber type grouping. His 68-year-old mother also had suffered from distal leg weakness and sensory impairment since her forties. A heterozygous mutation in BAG3 (P470S) was identified in both patients. Clinical features of myofibrillar myopathy with axonal polyneuropathy were consistent with BAG3-related myopathy. Our patients showed remarkably mild presentations without cardiomyopathy, unlike the majorities of previously reported cases. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling complication related to taxanes. Underlying mechanisms are not completely understood and no specific treatment exists. We investigated the role of nerve conduction studies (NCS) and of serum osteopontin (OPN) measurement as a means to stratify the risk of developing taxane-induced neuropathy (TIN). We enrolled 50 women with breast cancer treated with taxanes (docetaxel or paclitaxel) in a 3-month prospective study. They were evaluated before chemotherapy (time-point T0) and followed up at 1 (T1) and 3 (T2) months with clinical examinations/scales, quality of life (QoL) questionnaires, NCS, and serum OPN dosages. A reduction of sural and superficial peroneal sensory action potentials was seen at T1, with a progression at T2 (P < 0.001). In contrast, a significant impact of neuropathic symptoms on QoL only occurred at T2 (P < 0.01). OPN levels at T0 inversely correlated to axonal loss in the sural nerve (T0–T2, P < 0.01). OPN levels at T0 were lower in the intermediate and poor outcome patient subgroups, compared to the good outcome subgroup, as specifically defined (P < 0.05). Lower limb NCS changes occurred earlier than the detrimental effects of TIN on patients' QoL. Low serum OPN levels before chemotherapy may represent a novel biomarker of TIN risk. [ABSTRACT FROM AUTHOR]

• Late-onset Pompe disease is caused by multi-organ glycogen deposition. • We report four LOPD patients having a polyneuropathy of undetermined etiology. • Polyneuropathy could be an additional morbid condition in LOPD patients. • Polyneuropathy in LOPD patients needs specific additional care. Late-onset Pompe disease is caused by a glycogen deposition involving mainly striated muscle. It may also target many other tissues such as liver, smooth muscles or spine anterior horn. Glycogen accumulation in Schwann cells and in the perineurium of peripheral nerves was shown in Pompe's disease mouse models. Moreover two late-onset Pompe disease patients were reported as having a small fiber neuropathy. To the best of our knowledge an involvement of large nerve fibers was never depicted. We describe four late-onset Pompe disease patients having a concomitant polyneuropathy of undetermined etiology. Our observations reinforce the proof-of-concept supporting a potential involvement of peripheral nerves as additional organ targeted by late-onset Pompe disease. It has clinical care consequences since peripheral neuropathy in late-onset Pompe disease could worsen patient's disability and needs particular care such as proprioceptive physiotherapy. [ABSTRACT FROM AUTHOR]

Hereditary transthyretin amyloidosis with polyneuropathy (ATTR-PN) results from specific TTR gene mutations. In this study, we generated two induced pluripotent stem cell (iPSC) lines derived from ATTR-PN patients with heterozygous TTR gene mutations (Ala97Ser and Phe64Leu). These iPSC lines exhibited normal morphology, karyotype, high pluripotency marker expression, and differentiation into cells representing all germ layers. The generation of these iPSC lines serve as a valuable tool for investigating the mechanisms of ATTR-PN across various cell types and facilitating patient-specific in vitro amyloidosis modeling. [ABSTRACT FROM AUTHOR]

Insulin-like growth factors (IGFs) have neuroprotective effects. IGF activity is partly controlled by pregnancy-associated plasma protein-A (PAPP-A), an enzyme which enhances IGF-action by cleavage of IGF-binding protein-4 (IGFBP-4). To study the role of PAPP-A and the IGF system in diabetic polyneuropathy (DPN), we measured immunoreactive (total) concentrations of IGF-I and IGF-II, bioactive IGF by cell-based bioassay, PAPP-A, as well as intact and PAPP-A-cleaved IGFBP-4 in cerebrospinal fluid (CSF) and serum from patients with type 2 diabetes (T2D) with and without DPN. Twenty-three patients with T2D were included. Based on clinical examination, vibratory perception thresholds and nerve conduction studies, patients were diagnosed with (n = 9) or without (n = 14) DPN. In CSF, PAPP-A activity, as estimated by IGFBP-4 fragment levels, was higher in patients with than without DPN (34.57 vs 13.79 μg/L, p =.003) and concentrations correlated with peripheral nerve impairment measures (r = 0.73, p <.01). Furthermore, serum bioactive IGF was lower in patients with than without DPN (0.8 vs 1.3 μg/L, p =.006) and correlated inversely to the severity of DPN (r = −0.67, p <.01). In both CSF and serum, members of the IGF system correlated with measures of peripheral nerve impairment in patients with T2D. This supports a relationship between the IGF system and the development of DPN. Further studies are needed to clarify if these changes are causally linked to the pathogenesis of DPN. • PAPP-A activity is increased in the cerebrospinal fluid in type 2 diabetic patients with polyneuropathy. • PAPP-A activity in the cerebrospinal fluid correlates with the severity of diabetic polyneuropathy. • Serum bioactive IGF is decreased in participants with type 2 diabetes and polyneuropathy. • Serum bioactive IGF correlates inversely with severity of diabetic polyneuropathy. • The IGF system may be linked to the development of diabetic polyneuropathy. [ABSTRACT FROM AUTHOR]

Despite growing numbers of patients diagnosed with late-onset hereditary ATTR V30M amyloidosis with polyneuropathy (ATTRv-PN), this condition remains poorly characterized in Brazil. Characterize late-onset V30M ATTRv-PN in Brazil. Demographic and clinical data at the time of enrolment for Brazilian subjects with symptomatic V30M ATTRv-PN were extracted from the ongoing, multinational, longitudinal, observational Transthyretin Amyloidosis Outcomes Survey (THAOS; cut-off date: January 30, 2017). Subjects were divided into those with symptom onset at age <50 years (EO-V30M), and at age ≥50 years (LO-V30M). A total of 96 Val30Met patients were symptomatic. LO-V30M (n = 25, 26.0%) had a longer time to diagnosis (mean 5.1 vs. 2.8 yrs.; p = 0.006) and less frequently positive family history (40% vs. 95.8%; p < 0.0001) than EO-V30M. Clinically, subjects with LO-V30M had more imbalance (92% vs. 54.9%; p = 0.006), deep sensory loss (100% vs. 80%; p = 0.0178), electrocardiogram abnormalities (88.9% vs. 59.4; p = 0.0241), and interventricular septum hypertrophy (69.2% vs. 0%; p < 0001) and less frequently sensory dissociation (12% vs. 74%; p < 0.0001). Also, LO-V30M tended to have more severe mean Neurologic Composite Score (101 vs. 70 pts.; p = 0.1136). LO-V30M ATTRv-PN is not unusual in Brazil, tending to be more difficult to diagnose and present with a more severe phenotype, with more large nerve fibers and cardiac involvement than EO-V30M. Trial Registration: ClinicalTrials.gov : NCT00628745 • Late-onset V30M ATTRv is not unusual in the Brazilian population. • LO-V30M presents with more severe neurologic and cardiac impairments than EO-V30M. • Misdiagnosis and delays in diagnosis are more common in LO-V30M. • LO-V30M sensation loss has similar impairment of small and large sensory fibers. • Brazilian LO-V30M phenotype is similar to LO-V30M from other parts of the world. [ABSTRACT FROM AUTHOR]

PNKP gene encodes for a kinase/phosphatase involved in DNA damage response, controlled and stabilized by ATM phosphorylation. PNKP deficiency, thus far described in 40 subjects, has been associated with a complex neurological phenotype encompassing microcephaly, seizures, developmental delay, ataxia, oculomotor apraxia and polyneuropathy. We report a new case expanding the clinical phenotype of this rare disorder. This 25 years old girl presented with chorea at the age of 2 years and remained stable up to the adult age when the emergence of fatigability and asthenia of lower limbs prompted a new examination disclosing a sensory-motor axonal demyelinating neuropathy. Clinical exome sequencing revealed two previously described variants in PNKP gene. This case highlights the phenotypic variability of PNKP associated disorders, showing that an early onset apparently non progressive chorea can be the presenting symptoms of this rare condition. [ABSTRACT FROM AUTHOR]

To describe the known predictors and pathophysiological mechanisms of chronic painful chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors and the challenges in assessing and managing it. PubMed/Medline, CINAHL, Scopus, and PsycINFO. The research on chronic painful CIPN is limited. Additional research is needed to identify the predictors and pathophysiological mechanisms of chronic painful CIPN to inform the development of assessment tools and management options for this painful and possibly debilitating condition. Recognition of the predictors of chronic painful CIPN and proactive CIPN assessment and palliative management are important steps in reducing its impact on physical function and quality of life. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to investigate the prevalence of restless leg syndrome (RLS) in type-2 diabetes mellitus (DM) patients and to determine the risk factors.Methods: Patients were recruited from the Dr. Lütfi Kırdar Kartal Training and Research Hospital Diabetes Center. Patients between 18-80 years of age and meeting a minimum 5 years diagnosis of type-2 DM were included. All patients were examined by the same neurologist in terms of having RLS. The diagnosis was made according to the updated International Restless Legs Syndrome Study Group consensus criteria. Mimicking conditions such as myalgia, venous stasis, leg edema, arthritis, leg cramps, positional discomfort and habitual foot tapping were carefully investigated and excluded. Laboratory data, insulin use, family history and other related co-morbidities connected to RLS patients were recorded. RLS severity assessment was scored and recorded.Results: 318 patients were included in the study. The prevalence of RLS in type-2 DM patients was found to be 28.3%. RLS prevalence in females was 33.3% and 20.6% in males. 39 patients (43.3%) had a family history of RLS. 43 patients with RLS had a co-morbidity link with RLS. Any co-morbidity linked to RLS was not seen in 47 patients. The prevalence rate of RLS in patients without co-morbidities was 17.1%. Mean duration of DM in patients with RLS was 15.6±6.7years while in DM patients without RLS was 13.7±6.3years. The relationship between RLS and the duration of diabetes was found to be statically significant. (p=0.025). 68 (75.6%) of patients diagnosed with RLS were treated with insulin. A statistical significance was found in the development of RLS and insulin usage (p=0.035).Conclusions: This is the first study which shows the RLS prevalence and risk factors in Turkish type-2 diabetes mellitus patients. The results indicated that RLS is much more frequent in DM patients even after excluding polyneuropathy than in general Turkish population. The duration of diabetes and insulin use are related to RLS. [ABSTRACT FROM AUTHOR]

Aims: We conducted a nationwide educational initiative to determine the prevalence and risk factors of diagnosed and undiagnosed painful and painless distal sensory polyneuropathy (DSPN).Methods: Among 1850 participants, 781 had no history of diabetes (ND), 126 had type 1 diabetes (T1D), and 943 had type 2 diabetes (T2D). Painful DSPN was defined as polyneuropathy detected by bedside tests with pain and/or burning in the feet, while painless DSPN was defined as polyneuropathy with paresthesias, numbness, or absence of symptoms.Results: DSPN was detected in 48.2% of ND, 44.3% of T1D, and 55.3% of T2D subjects. DSPN was painful, painless, or atypical in 62.1, 24.8, and 13.1% of the participants. Painful DSPN was more severe than painless DSPN. Painful and painless DSPN were previously undiagnosed in 61.5 and 81.1% of the participants, respectively. In T2D subjects, painful and painless DSPN were associated with a higher and lower BMI, respectively. Among ND participants 39.2% had HbA1c levels indicating prediabetes/diabetes.Conclusions: Around half of participants in an educational initiative had DSPN, 62% of whom had the painful entity that correlated with BMI in T2D. Since many cases of neuropathy and diabetes remain undiagnosed, effective strategies to timely detect both conditions should be implemented. [ABSTRACT FROM AUTHOR]

Summary Objective Although ultrasonographic (US) visualization of peripheral nerves is becoming more and more frequently used, there are few studies on its actual contribution to the diagnosis and management of patients with peripheral nerve disorders. Methods The electronic records of consecutive patients referred to our US laboratory over an eight-month period were retrospectively analyzed. The contribution of US examination to patient management was evaluated. Results Two hundred and thirty one consecutive patients (43% men) were analyzed. The US result was pathologic in 71% of patients. US provided a new diagnosis in 3% of patients (including 4 with tumors), contributed other additional information in 60%, and only confirmed the referral diagnosis in 11%. In 26% of patients, US was neither confirmatory nor contributive, nor did it provide a new diagnosis. US sensitivity in electrodiagnostically (EDx) confirmed ulnar neuropathy at the elbow (UNE) was 77% and median neuropathy at the wrist 84%. In EDx negative patients, US sensitivities were 47% and 40%, respectively. Discussion The study demonstrated the ability of peripheral nerve US to provide useful diagnostic information in the majority of adequately referred patients. [ABSTRACT FROM AUTHOR]

Background Methylenetetrahydrofolate-reductase (MTHFR) deficiency is a rare autosomal recessive disorder affecting intracellular folate metabolism with affection of different organ systems and clinical manifestation usually in childhood. Objective We report on four adult members of a family with MTHFR deficiency presenting with neurological and thromboembolic complications in adulthood. Methods Extensive diagnostic work-up including genetic testing was performed in four adult members. Results The male siblings aged 42 and 32 years presented with various neurological symptoms, and a recent history of deep vein thrombosis. Extensive diagnostic work-up revealed total homocysteine (tHcy) plasma concentrations of 135 μmol/L and 231 μmol/L. and compound heterozygosity for two novel MTHFR gene mutations in exon 2 (c.202C > G, p.Arg68Gly) and intron 10 (c.1632 + 2T > G), and the known polymorphic variant MTHFR c.665C > T (p.Ala222Val, MTHFR 677C > T). Their mother was heterozygous for MTHFR c.1632 + 2T > G and c.665C > T, and a paternal relative was heterozygous for MTHFR c.202.C > G and MTHFR c.665C > T mutation. Both brothers showed partial response to therapy with betaine and multivitamins with clinical improvement. MTHFR activity was determined in fibroblast extracts and was around 4% of the mean control. Cell culture analysis indicated a re-methylation defect due to MTHFR deficiency. Conclusion Severe hyperhomocysteinemia due to two mutations of the MTHFR gene resulted in severe neurological symptoms in adulthood. Vitamin and methionine supplementation stabilize tHcy plasma levels. Severity of clinical manifestation varied greatly between the siblings. Damages to the nervous system may be present for years before becoming clinically manifest. [ABSTRACT FROM AUTHOR]

Objective Polyneuropathies are increasingly analyzed by ultrasound. Summarizing, diffuse enlargement is typical in Charcot-Marie Tooth type 1 (CMT1a), regional enlargement occurs in inflammatory neuropathies. However, a distinction of subtypes is still challenging. Therefore, this study focused on fascicle size and pattern in controls and distinct neuropathies. Methods Cross-sectional area (CSA) of the median, ulnar and peroneal nerve (MN, UN, PN) was measured at predefined landmarks in 50 healthy controls, 15 CMT1a and 13 MMN patients. Additionally, largest fascicle size and number of visible fascicles was obtained at the mid-upper arm cross-section of the MN and UN and in the popliteal fossa cross-section of the PN. Results Cut-off normal values for fascicle size in the MN, UN and PN were defined (<4.8 mm 2 , <2.8 mm 2 and <3.5 mm 2 ). In CMT1a CSA and fascicle values are significantly enlarged in all nerves, while in MMN CSA and fascicles are regionally enlarged with predominance in the upper arm nerves. The ratio of enlarged fascicles and all fascicles was significantly increased in CMT1a (>50%) in all nerves (p < 0.0001), representing diffuse fascicle enlargement , and moderately increased in MMN (>20%), representing differential fascicle enlargement (enlarged and normal fascicles at the same location) sparing the peroneal nerve ( regional fascicle enlargement ). Based on these findings distinct fascicle patterns were defined. Conclusion Normal values for fascicle size could be evaluated; while CMT1a features diffuse fascicle enlargement, MMN shows regional and differential predominance with enlarged fascicles as single pathology. Significance Pattern analysis of fascicles might facilitate distinction of several otherwise similar neuropathies. [ABSTRACT FROM AUTHOR]

Polyneuropathy is a debilitating condition which may be associated with large burns. The aim of this integrative review is to identify factors that contribute to the development of critical care polyneuropathy in patients admitted to an intensive care unit with a severe burn injury. PubMed, Scopus, CINHAL and EMBASE were searched up until July 2016. Studies/case reports focusing on critical care polyneuropathy for burn injured patients were included. The ten studies, included a total of 2755 burns subjects and identified 128 critical care polyneuropathy patients with an incidence of 4.4%. Three case reports identified prolonged ventilation and development of critical care neuropathy. Overall, factors identified as contributing to the development of critical care polyneuropathy in burn injured patients included prolonged ventilation (>7 days), large and deep total body surface area burns (mean TBSA 40%), and sepsis. Critical care polyneuropathy in burn patients remains challenging to diagnose and treat. To date, there is a lack of long term studies describing the impact of critical care polyneuropathy on functional performance or participation in activities of daily living in the burns population and this is consistent with the general literature addressing the lack of follow up assessments and long term consequences of persistent muscle weakness. [ABSTRACT FROM AUTHOR]

Objective The electrodiagnosis of polyneuropathy (PNP) may benefit from examination using near-nerve needle technique (NNT) and from inclusion of distal nerves. This study compared the diagnostic utility of distal nerve conduction studies (NCS) and NNT recording. Methods Bilateral NNT and surface recording of the sural nerve and surface recording of the dorsal sural and medial plantar nerves were prospectively done in 91 patients with clinically suspected PNP. Distal NCS were additionally done in 37 healthy controls. Diagnostic reference standard was the final clinical diagnosis retrieved from the patients medical records after 1–4 years. Results The clinical follow-up diagnosis confirmed PNP in 68 patients. Equally high sensitivities of the dorsal sural (72%), medial plantar (75%), and sural nerve with NNT recording (77%) were seen, while the sensitivity of conventional surface recording of the sural nerve was lower (60%). Sural NCS with both NNT and surface recording and dorsal sural NCS showed high specificities (85–95%) and positive predictive values (94–98%), while a lower specificity was seen for the medial plantar nerve (68%). Conclusion NCS of distal nerves, especially the dorsal sural nerve, have high diagnostic power equalling sural NNT recording. Significance The electrodiagnostic evaluation of patients with suspected PNP benefits from NCS of distal nerves. [ABSTRACT FROM AUTHOR]

Introduction Diabetic sensorimotor polyneuropathy (DSP) is the most frequent complication in patients with diabetes mellitus (DM), and is associated with age, DM duration, and HbA1c levels. In addition, higher uric acid (UA) levels are reported in patients with DSP. Objectives To explore whether UA levels correlate with DSP severity. Methods We extracted the demographic data, clinical history, neurological and electrophysiological examinations and laboratory findings of 115 patients diagnosed with DSP from January 2012 to December 2015. Results The mean age of the total cohort was 62 ± 13 years, with 61% men. A positive correlation was demonstrated between uric acid levels and increasing sensory symptoms, and more abnormal electrophysiological findings and vibration perception thresholds. In addition, correlations with gait abnormality, the presence of paraproteinemia and creatine kinase levels were found. Discussion Our study results show that uric acid levels correlate with clinical and electrophysiological severity of DSP, providing additional evidence for the relationship between the two, and a potential therapeutic target for DSP. [ABSTRACT FROM AUTHOR]

Objective To analyze the clinical characteristics of patients with POEMS presenting with polyneuropathy and discuss associated diagnostic challenges. Method Retrospective analysis of 6 patients from 2 tertiary-care institutions. Results Six patients presented with progressive sensorimotor deficits predominantly or exclusively in the lower extremities and were diagnosed with POEMS syndrome. In 4 patients, a diagnosis of chronic inflammatory demyelinating polyradiculopathy (CIDP) was mistakenly made. Low concentration of serum paraprotein and elevated vascular endothelial growth factor (VEGF) were detected in all 6 patients. Initial serum immunofixation and skeletal survey were normal in 2 patients each. On nerve conduction studies, motor and sensory responses were absent in the lower extremity in all 6 patients. Conduction velocity slowing and F-wave latency prolongation appear slightly more pronounced than distal motor latency prolongation in the upper extremity. Spinal MRI showed diffuse lumbosacral nerve root enhancement in all. In 3 patients, targeted bone marrow biopsy was needed for confirming the POEMS diagnosis. Treatment with corticosteroids, chemotherapy agent, focal radiation and/or autologous stem cell transplantation led to significant improvement in 5 of 6 patients. Conclusion Diagnosis of POEMS should be considered in patients with progressive polyneuropathies of mixed demyelinating and axon loss features, including CIDP patients not responding to standard treatment. A polyradiculoneuropathy rather than a pure polyneuropathy seems to exist in POEMS. [ABSTRACT FROM AUTHOR]

Background Parkinson's disease (PD) has been associated with peripheral neuropathy (PN). PN has been demonstrated in some rare genetic forms of PD (e.g. PARK2 mutations) but has also been linked to levodopa exposure. Objective The aim of this systematic review is to clarify any evidence of peripheral nervous system involvement in idiopathic PD. Methods A systematic computer-based literature search was conducted on PubMed database. Findings The pooled estimate of the prevalence of large fiber PN in PD was 16.3% (based on 1376 patients). The pooled estimate of the prevalence of biopsy-proven small fiber neuropathy was 56.9% (based on 72 patients). Large fiber PN in PD is in the majority of cases distal, symmetrical, axonal and predominantly sensory. There are, however, few reports of chronic idiopathic demyelinating polyneuropathy and very occasional cases of acute neuropathies. Although nerve conduction studies have been performed in the majority of the studies, they included only a limited number of nerves, mainly in the lower limbs. There is little evidence to support a direct link between levodopa treatment and the development of PN in idiopathic PD. In the majority of the cases PN has been linked to abnormalities in vitamin B12, methylmalonic acid or fasting homocysteine levels. Additional aetiological risk factors for PN may be responsible for any apparent link between PD and PN. Conclusions Large-scale prospective studies with long-term follow-up with detailed baseline assessments are needed in order to understand the natural history of PN in PD, both on clinical and neurophysiological parameters. [ABSTRACT FROM AUTHOR]

Background Zika virus has been associated with increases in Guillain-Barré syndrome (GBS) incidence. A GBS incidence estimation and clinical description was performed to assess baseline GBS epidemiology before the introduction of Zika virus in Puerto Rico. Methods Hospitalization administrative data from an island-wide insurance claims database and U.S. Census Bureau population estimates provided a crude GBS incidence for 2013. This estimate was adjusted using the proportion of GBS cases meeting Brighton criteria for confirmed GBS from nine reference hospitals. Characteristics of confirmed GBS cases in the same nine hospitals during 2012–2015 are described. Results A total of 136 GBS hospitalization claims were filed in 2013 (crude GBS incidence was 3.8 per 100,000 population). The adjusted GBS incidence was 1.7 per 100,000 population. Of 67 confirmed GBS cases during 2012–2015, 66% had an antecedent illness. Median time from antecedent illness to GBS onset was 7 days. Most cases (67%) occurred during July–September. Conclusions Puerto Rico's GBS incidence for 2013 was estimated using a combination of administrative data and medical records review; this method could be employed in other regions to monitor GBS incidence before and after the introduction of GBS infectious triggers. [ABSTRACT FROM AUTHOR]

Objective The neurofibromatoses (NF) type 1 and 2 are hereditary tumor predisposition syndromes caused by germline mutations in the NF1 and NF2 tumor suppressor genes. In NF1 and 2, peripheral nerve tumors occur regularly. For further characterizing nerve ultrasound was performed in patients with NF1 and 2. Methods Patients with established diagnosis of NF1 ( n = 27) and NF2 ( n = 10) were included. Ultrasound of peripheral nerves and cervical roots was performed during routine follow-up visits. Healthy volunteers were studied for comparison. Results In patients with NF1, median cross-sectional area (CSA) of most nerves was significantly increased compared to controls and to NF2 due to generalized plexiform tumors, which arose out of multiple fascicles in 23 of 27 patients (85%). These were often accompanied by cutaneous or subcutaneous neurofibromas. In NF2, the overall aspect of peripheral nerves consisted of localized schwannomas (80%) and, apart from that, normal nerve segments. Conclusion Nerve ultrasound is able to visualize different nerve pathologies in NF1 and NF2. It is a precise and inexpensive screening method for peripheral nerve manifestation in neurofibromatosis and should be considered as the first choice screening imaging modality for all peripheral nerves within reach of non-invasive ultrasound techniques. Significance Ultrasound patterns of peripheral nerve pathologies are described for the first time in a large cohort of patients with NF1 and NF2. It is a suitable screening tool and enables targeted MRI analysis. [ABSTRACT FROM AUTHOR]

Objective To systematically study peripheral nerve morphology in patients with transthyretin (TTR) amyloidosis and TTR gene mutation carriers using high-resolution ultrasonography (US). Methods In this prospective cross-sectional study we took a structured history, performed neurological examination, and measured peripheral nerve cross-sectional areas (CSAs) bilaterally at 28 standard locations using US. Demographic and US findings were compared to controls. Results Peripheral nerve CSAs were significantly larger in 33 patients with familial amyloid polyneuropathy (FAP) compared to 50 controls, most dramatically at the common entrapment sites (median nerve at the wrist, ulnar nerve at the elbow), and in the proximal nerve segments (median nerve in the upper arm, sciatic nerve in the thigh). Findings in 21 asymptomatic TTR gene mutation carriers were less marked compared to controls, with CSAs being larger only in the median nerve in the upper arm. Nerve CSAs correlated with abnormalities on nerve conduction studies. Conclusion Using US, we confirmed previous pathohistological and imaging reports in FAP of the most pronounced peripheral nerve thickening in the proximal limb segments. Significance Similar to US findings in diabetic and vasculitic neuropathies these predominantly proximal locations of nerve thickening may be attributed to ischaemic nerve damage caused by poor perfusion in the watershed zones along proximal limb segments. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle strength is poorly described and understood in diabetic participants with diabetic peripheral neuropathy. This study aimed to investigate the extensor and flexor torque of the knee and ankle during concentric, eccentric, and isometric contractions in men with diabetes mellitus type 2 with and without diabetic peripheral neuropathy. Methods: Three groups of adult men (n = 92), similar in age, body mass index, and testosterone levels, were analyzed: 33 non-diabetic controls, 31 with type 2 diabetes mellitus, and 28 with diabetic peripheral neuropathy. The peak torques in the concentric, eccentric, and isometric contractions were evaluated using an isokinetic dynamometer during knee and ankle flexion and extension. Findings: Individuals with diabetes and diabetic peripheral neuropathy presented similar low concentric and isometric knee and ankle torques that were also lower than the controls. However, the eccentric torque was similar among the groups, the contractions, and the joints. Interpretation: Regardless of the presence of peripheral neuropathy, differences in skeletal muscle function were found. The muscle involvement does not follow the same pattern of sensorial losses, since there are no distal-to-proximal impairments. Both knee and ankle were affected, but the effect sizes of the concentric and isometric torques were found to be greater in the participants' knees than in their ankles. The eccentric function did not reveal differences between the healthy control group and the two diabetic groups, raising questions about the involvement of the passive muscle components. [ABSTRACT FROM AUTHOR]

Recently published studies show that the prevalence of polyneuropathy (PNP) is higher in patients with Parkinson's disease (PD) than in age-matched controls. Its pathogenesis, however is a matter of controversy. The major hypothesis is the toxicity of high concentrations of homocysteine (Hcy) possibly related to levodopa (LD) therapy. The aim of the present study was to determine the prevalence of PNP, independent of other etiologies, and to determine the relationship to demographic and clinical factors in LD-treated Parkinson's patients. A total of 102 patients (51 patients with PD and 51 sex- and age-matched healthy controls) were enrolled in the study. The presence of any risk factors for PNP, ascertained from the history and laboratory tests, was an exclusion criterion. The Toronto Clinical Scoring System (TCSS) was used for clinical assessment of PNP. The objective assessment was based on electroneurography (ENG) studies in which motor nerves (peroneal and tibial nerves) as well as sensory nerves (sural and superficial peroneal nerves) were bilaterally examined. The severity of the disease was determined using the UPDRS scale (Unified Parkinson's Disease Rating Scale) and the Hoehn-Yahr (H-Y) scale. In the PD group, the clinical and neurophysiological indicators of PNP, manifested as a symmetrical and predominantly sensory axonal neuropathy, were more frequent then in the control group and observed in 43.1% vs. 13.7% and 15.7% vs. 2% of subjects respectively. The presence of PNP correlated with age and the severity of PD. Patients with PD and PNP had a higher level of Hcy as compared to PD patients without PNP, however the difference was not statistically significant. The frequency of PNP in PD patients is higher than in controls. The characteristics and discrepancy between the number of patients with clinical and ENG detected PNP may suggest the small fiber neuropathy (SFN) as the dominant form of neuropathy in PD patients. [ABSTRACT FROM AUTHOR]

Aims: We aimed to explore axonal excitability parameters in patients with diabetes mellitus (DM) and polyneuropathy (PNP) as well as those without PNP.Methods: We used the short TROND protocol by QTRAC to measure axonal excitability parameters (strength-duration time constant (SDTC), rheobase, etc.) in 12 healthy subjects and 14 DM patients with PNP and 10 DM patients without PNP. The short TROND protocol was performed before and after 20min of deep hyperventilation in healthy subjects and patients with DM. Also, venous blood pH and partial pressure of O2 and CO2 were recorded before hyperventilation (HPV) and after 20min of HPV. A "hyperventilation score" was evaluated before and after HPV.Results: When the values of DM with PNP group and control group before HPV were compared, SDTC and latency were statistically significant. Comparing the values of the excitability parameters after HPV showed statistically significant changes in the SDTC, rheobase, and refractoriness at 2.5ms in controls and DM patients without PNP. HPV resulted in no changes in SDTC in DM patients with PNP.Conclusion: The results of this study suggest that patients with DM and healthy subjects have different responses to HPV, and pH changes have different effects on diabetic PNP compared with healthy controls and DM patients without PNP. [ABSTRACT FROM AUTHOR]

Objective To investigate the use of nerve ultrasound in the differentiation between Charcot–Marie Tooth hereditary neuropathy (CMT1) and chronic inflammatory demyelinating polyradiculoneuropathies (CIDP), multifocal motor neuropathy (MMN) and multifocal acquired demyelinating sensory and motor neuropathies (MADSAM). Methods Ultrasound/electrophysiology of predefined nerves was performed in CMT1a/b, immunoneuropathies, and healthy controls. Ultrasound pattern sum score (UPSS, sum of the amount of 12 predefined measurement points), homogeneity score (HS) and regional nerve enlargement index (RNEI) in ulnar, median, and tibial nerve were used for evaluation of morphology. Results 13 CMT1, 27 CIDP, 10 MADSAM, 12 MMN, and 23 controls were included. Significant enlargement was shown in all neuropathies compared to the controls, ( p < 0.001), however the amount of enlargement as evaluated by the UPSS was most prominent in CMT compared to the others (median UPSS 18 vs. 11/8.5/5 in CIDP/MADSAM/MMN, p < 0.001). Homogeneous enlargement was significantly more often seen in CMT (67%, HS 6 vs. 2–3 in immune-mediated PNP, p < 0.001), while in CIDP the enlargement was regional, homogeneous or inhomogeneous with equal contribution. In MMN and MADSAM regional enlargement (48%/40%) next to normal segments (∼20%) predominated (RNEI in MMN = 2, in MADSAM = 1 vs. 0 in the others). CSAs were inversely correlated with motor conduction velocity. Conclusion Ultrasound, quantified by UPSS, HS, and RNEI facilitates a reliable and reproducible differentiation of immunoneuropathies and hereditary neuropathies by the use of boundary values. Significance By the use of quantitative scores, ultrasound differentiation of demyelinating neuropathies is operationalized and ameliorated compared to CSA measurements only. [ABSTRACT FROM AUTHOR]

Objectives: Excessive fragmentary myoclonus is a frequent incidental finding in patients undergoing polysomnography for other reasons. The aim of this study was to evaluate whether electrophysiological examination in patients with excessive fragmentary myoclonus during sleep according to American Academy of Sleep Medicine (AASM) criteria shows findings of peripheral nerve dysfunction.Methods: Ninety-eight of 100 patients with excessive fragmentary myoclonus detected as an incidental finding during routine polysomnography underwent electrophysiological workup. Motor nerve conduction studies of the right peroneal and tibial nerves, F-wave recordings of the tibial nerve, antidromic sensory nerve conduction studies of the left sural nerve and needle electromyography of the right tibialis anterior muscle were performed and classified as normal, peripheral neuropathy, lumbar 5 (L5) nerve root lesion, or benign fasciculations.Results: Fifty percent (49 out of 98) presented with electrophysiological abnormalities, most frequently polyneuropathy (32 out of 49, 65.3%), followed by L5 nerve root lesions (13 out of 49, 26.5%) and benign fasciculations (4 out of 49, 8.2%). Patients with electrophysiological abnormalities were older than those without.Conclusions: The high prevalence of abnormal neurophysiological findings in patients with excessive fragmentary myoclonus during polysomnography suggests that excessive fragmentary myoclonus during sleep according to AASM criteria is not primarily a sleep-related phenomenon, but only persists during sleep and points to peripheral nerve pathology at least in part of the cases. Patients with incidental EFM during polysomnography should undergo electrophysiological workup for peripheral nerve pathology. [ABSTRACT FROM AUTHOR]

Aim: This study explored the possibility of developing an alternative, simple and rapid test for the screening of distal symmetrical polyneuropathy (DSPN), for use in local primary care facilities.Methods: 4023 patients with type 2 diabetes mellitus (T2DM), aged 18-80 years, from 21 hospitals in China were screened for inclusion in a prospective diagnostic assessment of DSPN, between April 2011 and March 2012. Patients underwent nerve conduction study (NCS; as the gold standard) and clinical assessments of ankle reflexes (AR) and thermal (T), vibration (V), pressure (P), and pinprick (PP) sensations.Results: Results from various combinations of these clinical assessments were compared to determine the optimal screening regimens. The Toronto Consensus Panel definition was used to confirm clinical DSPN (symptoms or signs plus abnormal NCS). 3883 of the 4023 patients (M:F, 2162:1721; mean age, 56.79±13.16 years) were included. No significant differences were found between the two most efficient clinical assessment combinations, AR+PP+T+V and AR+T+V (P=0.9612). Compared to the diagnosis made using AR+T+V, the same diagnosis was reached using AR+PP+P+V+T in 100% of patients with probable clinical DSPN, 84.05% with possible clinical DSPN, and 96.84% with no DSPN. The AR+T+V assessment was also ∼40% faster than the AR+PP+P+V+T assessment.Conclusions: Combined AR+T+V assessment is a valuable tool for screening diabetic patients for DSPN, potentially decreasing costs to local primary care facilities and making care more available to underserved populations. [ABSTRACT FROM AUTHOR]

Objectives (1) To evaluate the relationship between the thickness and compound muscle action potential (CMAP) of the extensor digitorum brevis (EDB) muscle; (2) to obtain reference values for distal lower extremity muscle thickness as a possible measure of peripheral neuropathy; and (3) to evaluate various factors associated with unexplained EDB atrophy. Methods We measured the thickness of EDB, abductor hallucis brevis (AHB) and tibialis anterior (TA) muscles in 80 healthy volunteers with ultrasound and assessed EDB CMAP with fibular nerve stimulation. Two foot muscle-associated lifestyle factors were assessed and sociodemographic information was collected. Results A significant correlation was observed between the amplitude of the fibular nerve CMAP and EDB thickness. The thickness of each of the three muscles was greater in men compared to women. EDB thickness decreased significantly with age although the thicknesses of the AHB and TA muscles were not correlated with age. Conclusions EDB thickness was closely associated with fibular nerve CMAP but with less variation and differed among groups by age and sex; it was not associated with lifestyle factors. Significance The ability to obtain this measure painlessly with ultrasound and its low variation recommend it as a potentially useful complementary measure of distal neuromuscular function. [ABSTRACT FROM AUTHOR]

Polyneuropathy associated with IgM monoclonal gammopathy (IgM-PNP) is a slowly progressive, sensorimotor neuropathy. It is assumed that complement activation contributes to IgM-PNP pathogenesis. We investigated whether innate differences in complement activity of the classical and mannose binding lectin (MBL) pathways are associated with IgM-PNP or its severity. We measured complement activity using ELISA and determined MBL serum concentrations and MBL gene polymorphisms in 83 patients and 83 healthy controls. We did not observe differences between IgM-PNP patients and healthy controls nor associations with different disease severities. Differences in innate complement activity are not likely to explain susceptibility to or severity of IgM-PNP. [ABSTRACT FROM AUTHOR]

Background The neonatal screening and early start of the dietary therapy have improved the outcome of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). The acute symptoms of LCHADD are hypoketotic hypoglycemia, failure to thrive, hepatopathy and rhabdomyolysis. Long term complications are retinopathy and neuropathy. Speculated etiology of these long term complications are the accumulation and toxicity of hydroxylacylcarnitines and long-chain fatty acid metabolites or deficiency of essential fatty acids. Aims To study the possible development of polyneuropathy in LCHADD patients with current dietary regimen. Methods Development of polyneuropathy in 12 LCHADD patients with the homozygous common mutation c.G1528C was evaluated with electroneurography (ENG) studies. The ENG was done 1–12 times to each patient, between the ages of 3 and 40 years. Clinical data of the patients were collected from the patient records. Results The first sign of polyneuropathy was detected between the ages of 6–12 years, the first abnormality being reduction of the sensory amplitudes of the sural nerves. With time, progression was detected by abnormalities in sensory responses extending to upper limbs, as well as abnormalities in motor responses in lower limbs. Altogether, eight of the patients had polyneuropathy, despite good compliancy of the diet. Conclusions This study is the first to report the evolution of polyneuropathy with clinical neurophysiological methods in a relative large LCHADD patient group. Despite early start, and good compliance of the therapy, 6/10 of the younger patients developed neuropathy. However, in most patients the polyneuropathy was less severe than previously described. [ABSTRACT FROM AUTHOR]