Current practice of podiatrists in testing for diabetic polyneuropathy and implementing foot care (PROTECT Study Survey 2).

AIMS: Podiatrists constitute a key member of a multidisciplinary foot care team, but their services remain underutilized. We sought to gain insights into the daily practice of podiatrists focusing on screening for and monitoring of diabetic sensorimotor polyneuropathy (DSPN) as well as foot management. METHODS: This cross-sectional survey included 125 podiatrists from 12 federal states across Germany who responded to an online questionnaire. RESULTS: The majority of patients treated in podiatry practices were referred by general practitioners and diabetologists. Screening for or follow-up of DSPN was performed by 36% of the respondents at least once a year, by 28% only at initial examination, by 21% only at suspicion, and by 10% basically at each treatment visit. Instruments to assess vibration, touch/pressure, and temperature sensation were used by 81-94% of the podiatrists. Previously undiagnosed DSPN and foot ulcers were detected frequently/very frequently (≥6 cases/month) by 24.0 and 18.4% of the podiatrists, respectively. Almost all podiatrists advised daily self-monitoring of feet and appropriate foot care and >50% gave advice on medical treatment. CONCLUSIONS: Podiatrists play an important role in the detection, monitoring, and management of both DSPN and diabetic foot ulcers, suggesting that the utilization of their services should be fostered.

Nodes of Ranvier in skin biopsies of patients with diabetes mellitus.

Paranodal demyelination has been discussed as a potential mechanism of nerve fiber damage in diabetic neuropathy (DNP). Studies on human tissue are limited, as nerve biopsies are invasive and only rarely performed in patients with confirmed DNP. Skin biopsy has recently been suggested as a tool to analyze paranodal and nodal changes of myelinated fibers. We analyzed the myelinated fibers of skin biopsies of 35 patients with DNP, 17 patients with diabetes mellitus (DM) without neuropathy, and 30 normal controls. Immunofluorescence of skin sections with antibodies against Caspr, neurofascin, sodium channels, and myelin basic protein was performed to assess paranodal/nodal architecture, segmental demyelination, and myelinated nerve fibers. Staining with antibodies against protein gene product 9.5 was used to quantify unmyelinated nerve fibers. There was an increase of elongated Ranvier nodes and a dispersion of neurofascin at the distal leg in patients with DM with and without neuropathy and at the finger in patients with DNP. An increased dispersion of Caspr was only found in biopsies of the finger in patients with DNP. Skin biopsy may be an appropriate tool to analyze nodes of Ranvier in patients with DM. Structural nodal changes are detectable in DNP and even in diabetic patients without neuropathy.

Small fibre pathology in patients with fibromyalgia syndrome.

Fibromyalgia syndrome is a clinically well-characterized chronic pain condition of high socio-economic impact. Although the pathophysiology is still unclear, there is increasing evidence for nervous system dysfunction in patients with fibromyalgia syndrome. In this case-control study we investigated function and morphology of small nerve fibres in 25 patients with fibromyalgia syndrome. Patients underwent comprehensive neurological and neurophysiological assessment. We examined small fibre function by quantitative sensory testing and pain-related evoked potentials, and quantified intraepidermal nerve fibre density and regenerating intraepidermal nerve fibres in skin punch biopsies of the lower leg and upper thigh. The results were compared with data from 10 patients with monopolar depression without pain and with healthy control subjects matched for age and gender. Neurological and standard neurophysiological examination was normal in all patients, excluding large fibre polyneuropathy. Patients with fibromyalgia syndrome had increased scores in neuropathic pain questionnaires compared with patients with depression and with control subjects (P < 0.001 each). Compared with control subjects, patients with fibromyalgia syndrome but not patients with depression had impaired small fibre function with increased cold and warm detection thresholds in quantitative sensory testing (P < 0.001). Investigation of pain-related evoked potentials revealed increased N1 latencies upon stimulation at the feet (P < 0.001) and reduced amplitudes of pain-related evoked potentials upon stimulation of face, hands and feet (P < 0.001) in patients with fibromyalgia syndrome compared to patients with depression and to control subjects, indicating abnormalities of small fibres or their central afferents. In skin biopsies total (P < 0.001) and regenerating intraepidermal nerve fibres (P < 0.01) at the lower leg and upper thigh were reduced in patients with fibromyalgia syndrome compared with control subjects. Accordingly, a reduction in dermal unmyelinated nerve fibre bundles was found in skin samples of patients with fibromyalgia syndrome compared with patients with depression and with healthy control subjects, whereas myelinated nerve fibres were spared. All three methods used support the concept of impaired small fibre function in patients with fibromyalgia syndrome, pointing towards a neuropathic nature of pain in fibromyalgia syndrome.

Diagnosis, Treatment and Long-Term Management of Vitamin B12 Deficiency in Adults: A Delphi Expert Consensus.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Screening test for malignant hyperthermia in patients with persistent hyperCKemia: a pilot study.

INTRODUCTION: Persistently elevated serum creatine kinase (CK) is frequently associated with predisposition to malignant hyperthermia (MH). We investigated whether a minimally invasive metabolic test is suitable to diagnose MH susceptibility among patients with hyperCKemia. METHODS: Thirty-nine participants were included: 10 were MH susceptible (MHS); 21 MH were non-susceptible (MHN); and 8 had MHN with persistent hyperCKemia >500 U/L. Microdialysis probes were inserted into the vastus lateralis muscle, and halothane or caffeine was injected via an attached microtubing catheter. Lactate concentrations in dialysis samples were measured spectrophotometrically. RESULTS: Baseline lactate did not differ between the groups. After local application of halothane or caffeine, a significant lactate increase was detected only in the MHS group. CONCLUSIONS: Test results were not influenced by hyperCKemia. To avoid risks and complications of a surgical muscle biopsy this microdialysis test might be a useful screening tool for MH susceptibility among patients with persistent CK elevation.

Association between diabetes and thiamine status - A systematic review and meta-analysis.

BACKGROUND: Thiamine (vitamin B1) is an essential cofactor in glucose metabolism, but it remains unclear whether thiamine status is lower in individuals with diabetes compared to individuals with normal glucose metabolism. AIMS: We conducted a systematic review and meta-analysis to study whether the circulating concentrations of various thiamine analytes differ between people with and those without diabetes. METHODS: PubMed and the Cochrane Central Register of Controlled Trials were searched according to the study protocol. The standardized mean difference (SMD) and 95 % confidence intervals (CI) of thiamine markers between individuals with and without diabetes were used as effect size (random effects model). Subgroup analysis considered albuminuria as an additional variable. RESULTS: Out of the 459 articles identified, 24 full-texts were eligible for the study, 20 of which qualified for the data analysis and four were evaluated for coherence. Compared to controls, individuals with diabetes showed lower concentrations of thiamine (pooled estimate SMD [95 % CI]: -0.97 [-1.89, -0.06]), thiamine monophosphate (-1.16 [-1.82, -0.50]), and total thiamine compounds (-1.01 [-1.48, -0.54]). Thiamine diphosphate (-0.72 [-1.54, 0.11] and erythrocyte transketolase activity (-0.42 [-0.90, 0.05]) tended to be lower in persons with diabetes than in controls without reaching statistical significance. Subgroup analysis showed that individuals with diabetes and albuminuria had lower thiamine levels than the controls (-2.68 [-5.34, -0.02]). CONCLUSIONS: Diabetes is associated with lower levels of various thiamine markers, suggesting that individuals with diabetes may have higher thiamine requirements than those without diabetes, but well-designed studies are required to confirm these findings.

Screening and diagnosis of diabetic polyneuropathy in clinical practice: A survey among German physicians (PROTECT Study Survey).

AIMS: We sought to obtain detailed information on the procedures and appraisal of screening for and diagnosing diabetic sensorimotor polyneuropathy (DSPN) in clinical practice. METHODS: This cross-sectional survey included 574 physicians from 13 federal states across Germany who responded to a tripartite questionnaire. RESULTS: The vast majority of the respondents reported to screen for DSPN at least once a year (87 %), while 65 % reported to examine the feet of DSPN patients at least twice a year. However, only 28 % and 20 % of the respondents used questionnaires and scores to assess the severity of neuropathic symptoms and signs, respectively. The rates of participants reporting that they do not use a standardized testing procedure were 58 % for pressure sensation, 62 % for pain sensation, and 54 % for thermal sensation. The rates of respondents reporting that they do not deploy a standardized assessment were 41 % for vibration sensation, 73 % for pressure sensation, 77 % for pain sensation, and 66 % for thermal sensation. Half of the physicians oriented themselves towards clinical guidelines when diagnosing DSPN. CONCLUSIONS: Despite relatively high screening rates, the willingness to implement both standardized testing procedures and assessment and to follow guidelines is low among physicians when screening for and clinically diagnosing DSPN.

Loss of topographic specificity of LTD-like plasticity is a trait marker in focal dystonia.

In focal hand dystonia, long-term potentiation (LTP) and depression (LTD)-like neuronal plasticity, as assessed by paired associative stimulation (PAS) targeting the hand-associated motor cortex, is enhanced and the topographic organization of plasticity is lost. However, if any of these abnormalities alone is sufficient to cause focal dystonia (FD) remains unknown. Ten patients with cervical dystonia (CD), 9 with blepharospasm (BS) and 16 age- and sex-matched controls were examined. PAS was performed by combining repetitively electric stimulation of the median nerve with subsequent transcranial magnetic stimulation of the contralateral motor cortex at 21.5ms (PAS21.5) and 10ms (PAS10). Corticospinal excitability was indexed by the magnitude of motor evoked potentials (MEPs) recorded from abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. In controls, MEP size of the homotopically conditioned APB increased after PAS21.5 whereas the MEP size of the heterotopically conditioned ADM remained stable. PAS10 led to a decrease of MEP size of the APB and to an increase of the heterotopic ADM. In contrast, after PAS21.5 and PAS10 in CD and BS MEP size increased and decreased, respectively, in both muscles. The magnitude of excitability changes, however, did not differ between dystonic patients and healthy controls. In FD the topographic organization of PAS21.5 and PAS10-induced plasticity is deranged in cortical areas not involved in the control of the dystonic body part. Somatotopical disorganization of plasticity may represent an endophenotypic trait in FD but may not be sufficient to generate a dystonic phenotype. Development of a dystonic phenotype may require that the gain of plasticity is additionally enhanced. This article is part of a Special Issue entitled "Advances in dystonia".

Vasculitis-like neuropathy in amyotrophic lateral sclerosis unresponsive to treatment.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with variable involvement of other systems. A pathogenetic role of immune-mediated mechanisms has been suggested. We retrospectively analyzed sural nerve pathology and the clinical course in 18 patients with ALS. These patients had undergone sural nerve biopsy because of clinical or neurophysiological signs indicating sensory involvement (ALS+). Eleven of the 18 ALS+ patients had inflammatory cell infiltrates (ALS(vasc)) resembling infiltrates seen in patients with vasculitic neuropathy. Data were compared with the 7 patients without vasculitic infiltrates (ALS(nonvasc)) and with those of 16 patients with isolated peripheral nerve vasculitis (NP(vasc)). Biopsy specimens were processed with standard histological stains and with immunohistochemistry for a panel of inflammatory markers, with the hypothesis that the composition of infiltrates should differ between ALS(vasc) and NP(vasc). Immunoreactive cells were quantified in a blinded manner. Unlike patients with NP(vasc), those with ALS(vasc) had only minor neurophysiological abnormalities in the sural nerve and, except for the infiltrates, almost normal nerve morphology on semithin sections. The difference in epineurial T cell count was significant between ALS(vasc) and ALS(nonvasc) (p = 0.031). Surprisingly, the cellular composition of epineurial infiltrates in sural nerve biopsies was indistinguishable between ALS(vasc) and NP(vasc) despite a significant difference in fiber pathology (p < 0.0001). Standard immunosuppressive treatment did not prevent clinical progression of the motor neuron disease in any of the patients with ALS(vasc). ALS(vasc) appears as a neuropathological subtype in ALS+ suggesting immune-mediated disease components but without response to standard immunosuppressive treatment.

Small fibers in Fabry disease: baseline and follow-up data under enzyme replacement therapy.

Fabry disease (FD) is an X-linked lysosomal storage disorder which may lead to impaired peripheral nerve function, mostly affecting small nerve fibers, and to neuropathic pain. Characteristics of the neuropathy associated with FD and the covariates for its development and temporal course have not been described in a large cohort. We studied small fiber function and morphology in 120 Fabry patients at baseline and in subgroups of these until 4-year follow-up. Baseline neurological (89/120) and electrophysiological (106/120) examination was mostly normal. Quantitative sensory testing revealed impaired cold detection thresholds in 84% of men and 39% of women. Lower leg intraepidermal nerve fiber density (IENFD) was reduced to 46% in Fabry patients compared to controls and to 12.5% in men with impaired renal function. Patients with abnormal IENFD more often had pain. Group means for IENFD did not improve under enzyme replacement therapy (ERT), but IENFD in the back increased under ERT in 4/15 patients with good renal function and clinical improvement. Cutaneous cytokine gene expression did not differ from controls. We conclude that ERT may improve proximal skin innervation in patients with good renal function, but does not protect small fiber function in men with impaired renal function.

Polyneuropathy is inadequately treated despite increasing symptom intensity in individuals with and without diabetes (PROTECT follow-up study).

AIMS/INTRODUCTION: Despite its major clinical impact, distal symmetric polyneuropathy remains frequently undiagnosed and undertreated in clinical practice. We previously reported in the PROTECT Study that 70% of type 2 diabetes patients with distal symmetric polyneuropathy were unaware of having the latter condition. MATERIALS AND METHODS: In the present follow up after 2.5 ± 0.7 years, 122 and 85 participants with and without type 2 diabetes, respectively, completed questionnaires to obtain information about the further course of disease and its management. RESULTS: At follow up, 49 and 48% of the respondents with type 2 diabetes and without diabetes, respectively, reported that the intensity of paresthesia or numbness in the feet increased, whereas for burning and pain in the feet the corresponding percentages were 56 and 61%. However, 33 and 40% of the respondents with type 2 diabetes and without diabetes, respectively, reporting neuropathic symptoms at follow up did not receive any pharmacotherapy. Pharmacotherapy of neuropathic symptoms at follow up among participants with type 2 diabetes and without diabetes included mainly World Health Organization Step 1 analgesics (17% each; excluding acetylsalicylic acid), pregabalin/gabapentin (20 and 12%), vitamin B complex (13 and 22%), benfotiamine (13 and 2%), opioids (7 and 12%), antidepressants (4 and 5%) and α-lipoic acid (4 and 2%). CONCLUSIONS: These findings point to insufficient care, inadequate treatment adherence or limited efficacy of treatments in patients with polyneuropathy, suggesting that effective measures should be implemented to correct these healthcare deficits.

Substantia nigra echogenicity: A structural correlate of functional impairment of the dopaminergic striatal projection in Parkinson's disease.

Transcranial sonography (TCS) reveals abnormal spatial extension of substantia nigra (SN) echogenicity in a high proportion of patients with Parkinson's disease (PD). It has been proposed that this abnormality represents a structural trait that is mechanistically distinct from degeneration of dopaminergic nigrostriatal projection neurons. We sought to clarify the relationship between sonographic abnormalities of SN and dysfunction of striatal dopaminergic neurotransmission. We studied 50 patients with PD. The spatial extension of the echogenic SN area was compared with the activity of presynaptic striatal dopamine reuptake transporters, assessed in the same patients by I-123-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane (beta-CIT) single-photon emission computed tomography (SPECT). Extension of echogenic SN area correlated (inversely) with striatal activity of presynaptic dopamine reuptake transporter in PD patients (R = -0.417; P = 0.003) and with the equivalent levodopa dose (R = 0.380; P = 0.006; linear regression analysis). Findings support the hypothesis that in PD abnormal extension of echogenic SN area provides a direct structural marker of degeneration of SN neurons. Therefore, in PD, TCS and beta-CIT assess pathophysiologically related phenomena.

[Perioperative management of patients with neuromuscular disorders]. / Besonderheiten im prä- und perioperativen Management.

Patients with neuromuscular disorders undergoing anaesthesia are at risk of various complications due to muscular weakness and the involvement of other organ systems. This article reviews the anaesthetic approach with regard to preoperative considerations and perioperative management in this heterogeneous group of patients.

Single-dose application of CNTF and BDNF improves remyelination of regenerating nerve fibers after C7 ventral root avulsion and replantation.

Although axonal regeneration has been observed after replantation of avulsed ventral roots (VR) into the spinal cord, the functional outcome of this treatment in terms of motor reinnervation is unsatisfactory. In the present study, effects of single-dose ciliary and/or brain-derived neurotrophic factor (CNTF, BDNF) application on axon regeneration after C7 VR avulsion and replantation in adult rabbits were morphologically assessed by analysis of numbers, calibers, and myelination of axons in replanted VRs. Electromyography (EMG) was carried out to document the time course of de- and reinnervation in individual animals. After 3 weeks, replanted C7 VRs were almost devoid of myelinated axons. At week 8, active EMG-denervation was confirmed in affected muscles, but was less pronounced in neurotrophic factor (NF)-treated animals than in controls. Reinnervation potentials were identified in paraspinal muscles in more NF-treated animals than in controls. After 6 months, the number of myelinated axons in replanted VRs was approximately 45% of that in unlesioned roots in all groups, with small-sized axons constituting the majority of axons. At this time, more NF-treated animals than controls featured reinnervation. Moreover, myelination deficits of regenerated axons in controls were less pronounced in NF-treated animals. Especially in CNTF + BDNF-treated animals, myelination of regenerated axons of specific sizes was significantly increased compared to regenerated controls. In summary, NFs stimulated reinnervation early after the lesion and, for the first time, our morphological data quantitatively indicate positive effects of CNTF + BDNF on remyelination.

Task-specific craniocervical dystonia.

The pathophysiology of dystonia is incompletely understood. Unlike many other focal dystonias, cervical dystonia, a frequent dystonia leading to twisting of the head, does not appear to be related to overuse or acquisition of a demanding motor skill. Here, we report development of task-specific dystonia of the neck muscles in a 67-year-old patient following bilateral traumatic arm amputation at the age of 15. To compensate for the amputation, the patient learned to write with a pen held in his mouth. After several years of practicing this unusual and demanding skill, symptoms of task-specific cervical dystonia (CD) developed. This dystonia later became permanent, and independent of the motor activity that initially triggered the dystonic muscular contractions. This singular case raises the possibility that the pathophysiology of CD may share common elements with that of focal dystonias in different body regions.

Painful and painless neuropathies are distinct and largely undiagnosed entities in subjects participating in an educational initiative (PROTECT study).

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.

The two sides of associative plasticity in writer's cramp.

Neuronal plasticity is to be kept within operational limits to serve its purpose as a safe memory system that shapes and focuses sensory and motor representations. Temporal and spatial properties of motor cortical plasticity were assessed in patients with writer's cramp using a model of long-term potentiation (LTP) and long-term depression (LTD) of synaptic efficacy. Paired associative stimulation (PAS) combined repetitive electric stimulation of the median or ulnar nerve (MN or UN) with subsequent transcranial magnetic stimulation of the contralateral dominant motor cortex at 21.5 ms (MN-PAS21.5; UN-PAS21.5) or 10 ms (MN-PAS10). Motor-evoked potentials were recorded from abductor pollicis brevis (APB) muscle and abductor digiti minimi (ADM) muscles in 10 patients with writer's cramp and 10 matched healthy control subjects. Following MN-PAS21.5 or UN-PAS21.5 in non-dystonic subjects, motor responses increased if the afferent PAS-component came from a homologous peripheral region and remained stable with a non-homologous input. In contrast, following either MN-PAS21.5 or UN-PAS21.5, both APB- and ADM-amplitudes increased in patients. Compared with controls, this increase started earlier, its magnitude was larger and its duration longer. Following MN-PAS10 in controls, APB-amplitudes decreased, while ADM-amplitudes increased. In writer's cramp, the decrease of APB-amplitudes started earlier and lasted longer. Of note, ADM-amplitudes were decreased, too. LTP-like as well as LTD-like plasticity is abnormal with respect to both gain and spatial organization. These findings may help to develop a pathophysiological model explaining core features of focal dystonia.

ALS and MMN mimics in patients with BSCL2 mutations: the expanding clinical spectrum of SPG17 hereditary spastic paraplegia.

Silver syndrome/SPG17 is a motor manifestation of mutations in the BSCL2 gene and usually presents as a complicated form of hereditary spastic paraplegia (HSP). We present clinical data, follow-up, and genetic results of seven patients with Silver syndrome/SPG17 including a family with a variable intrafamilial phenotype ranging from subclinical signs to a severe and rapidly progressing amyotrophic lateral sclerosis (ALS)-like phenotype. For molecular diagnosis of the family, we used the TruSight Exome sequencing panel consisting of 2761 genes. We filtered for variants common to affected family members and for exclusive variants in the ALS-like index patient to find possible modifier mutations. We found that de novo mutations and/or incomplete penetrance in BSCL2 has been taken into account for Silver syndrome/SPG17 and confirm the large phenotypical heterogeneity of BSCL2 mutations. Our findings broaden the reported spectrum of the disease to an ALS-like and multifocal motor neuropathy phenotype and underline the need for further research for genetic modifiers due to the striking interindividual and intrafamilial variability.

Non-systemic vasculitic neuropathy: single-center follow-up of 60 patients.

The objective of this study is to report the clinical presentation and long-term outcome of patients with non-systemic vasculitic neuropathy (NSVN) seen at our neuromuscular center. In this retrospective analysis, we assessed medical records of 60 patients with biopsy-proven NSVN (39 men, 21 women; median age: 64 years, 24-80), who were seen at our department between 1999 and 2008 and were followed up until 2014. The initial neurological findings, laboratory and neurophysiological data, treatment regimens, and outcome were analyzed in all patients. NSVN was mostly asymmetric (48/60, 80%), sensorimotor (45/60, 75%), and painful (38/60, 63%), with walking impairment as one major sign (51/60, 85%). No compound action potentials could be recorded in 29/60 (48%) sural nerves (later biopsied side) and in 6/60 (10%) tibial (motor) nerves. Pathology of sural nerve was informative in all cases irrespective of neurophysiological findings and prior immunosuppression. After initial treatment with i.v. methylprednisolone, all patients reported overall improvement. Of the 46 patients who were followed for >1 year, those with mild to moderate affliction were stable with azathioprine (19/46, 41%), while 18/46 (39%) patients were treated with cyclophosphamide and other immunosuppressants due to progression or relapse. At 4 years, 24/46 (52%) patients had either discontinued (n = 21) or had primarily refused immunosuppressive treatment (n = 3) without relapse. Age younger than the group median of 64 years was associated with better outcome. No patient evolved to systemic vasculitis. NSVN is a potentially treatable disorder of the peripheral nervous system.