Peripheral neuropathy in hepatitis C virus infection with and without cryoglobulinaemia

OBJECTIVES: Hepatitis C virus (HCV) infection is often associated with cryoglobulinaemia (CG). Peripheral neuropathy (PN) is a comparatively common complication of CG associated with HCV infection and it is thought to be attributable to nerve ischaemia. Only few HCV CG patients with PN have been reported. The recent finding of HCV RNA in nerve biopsy specimens has suggested a possible direct role of HCV in the pathogenesis of PN. The authors studied 51 HCV patients to determine the prevalence of CG and to clarify the possible mechanism by which HCV determines the PN. METHODS: All the patients were studied clinically, by laboratory tests and electrophysiologically. Twenty eight patients underwent sural nerve biopsy where both morphological and morphometric evaluation of the biopsy specimen was performed, as well as statistical analysis. RESULTS: CG was found in 40 of 51 cases (78%). Polyneuropathy was significantly prevalent in CG+ patients compared with CG- (18 of 40 compared with 1 of 11 patients; p=0.01). HCV CG- patients more frequently developed well defined mononeuropathy or multiple neuropathy when compared with HCV CG+ (10 of 11 compared with 22 of 40; p<0.03). HCV CG+ patients showed significantly higher proportion of rheumatoid factor positivity (p<0.001) and low C4 levels (p=0.001). Nerve biopsy was performed in 25 of 40 HCV CG+ patients and in 3 of 11 HCV CG- patients: epineurial vasculitis was present in 8 of 25 HCV CG+ (32%) and in 2 of 3 HCV CG-. Differential fascicular loss of axons was found in 10 of 25 CG+ (40%) and 1 of 3 CG-, signs of both demyelination and axonal degeneration were present in 7 of 25 CG+ (28%). No significant difference was found in neuropathological features, while histometrical analysis disclosed more severe involvement in CG+ patients. CONCLUSIONS: These findings suggest that the presence of CG is a negative predictive factor for the associated PN. Morphological findings in the sural nerve from HCV CG- and CG+ are consistent with an ischaemic mechanism of nerve damage and are against a direct role of the virus in causing the associated PN.     

Peripheral neuropathy associated with essential mixed cryoglobulinaemia: a role for hepatitis C virus infection?

BACKGROUND--The prevalence of hepatitis C virus (HCV) infection has been estimated at 43 to 84% in patients with essential mixed cryoglobulinaemia in recent large series. Some of these cases have been successfully treated with interferon-alpha. The objective was to evaluate the prevalence and the possible role of HCV infection in essential mixed cryoglobulinaemia. METHODS--Fifteen patients (eight men and seven women; mean age: 61.2 (SD 16.5) years) with peripheral neuropathy (10 polyneuropathies and five multifocal mononeuropathies) and essential mixed cryoglobulinaemia were tested for serum anti-HCV antibodies. RESULTS--Antibodies were found in 10 of 15 patients involving either polyneuropathies (seven patients) or multifocal mononeuropathies (three patients). Electrophysiological studies and teased nerve fibre studies (in seven patients) allowed neuropathies to be classified as predominantly sensory axonopathies. Compared with HCV-negative (HCV -) patients, HCV-positive (HCV +) patients had a more pronounced and more widespread motor deficit; motor nerve conduction velocities in peroneal and median nerves were more impaired in HCV + patients, although significance was not reached except for the mean value of the amplitude of the compound muscle action potentials of the median nerves (P < 0.05); necrotising vasculitis was found in two of nine nerve biopsies from the HCV + patients studied and in none of the three HCV - patients. In addition, HCV + patients had more frequent cryoglobulin related cutaneous signs, higher aminotransferase and serum cryoglobulin concentrations, lower total haemolytic complement concentrations, and more frequent presence of rheumatoid factor. A liver biopsy performed in eight HCV + patients disclosed a range of lesions, from chronic active hepatitis (six patients) to persistent hepatitis (two patients). Lastly, treatment with interferon-alpha conducted over six months in two patients seemed to improve the peripheral neuropathy. CONCLUSIONS--Patients with peripheral neuropathy and essential mixed cryoglobulinaemia should be tested for anti-HCV antibodies to determine the appropriate treatment.     

Sensory neuropathy in patients with cryoglobulin negative hepatitis-C infection

There is growing evidence that hepatitis-C virus (HCV) infection might cause peripheral neuropathy. We aimed to investigate the prevalence, clinical and electrophysiological features of sensory neuropathy in patients with cryoglobulin negative HCV infection. We studied 46 consecutive cryoglobulin negative HCV positive patients (24 of them with and 22 without neuropathic symptoms, NS) and compared to 28 age and gender matched controls. In all patients and controls, clinical neuropathy symptom (NSS) and neuropathy deficit scores (NDS) were assessed and standard nerve conduction velocity (SNCV) and pain related-evoked potentials (PREP) were recorded. Both, SNCV and PREP were abnormal in 13 NS positive patients (13/46, 28%). Abnormal PREP but normal SNCV were found in 5 (5/46, 11%) NS positive and in 2 NS negative patients (2/46, 4%). PREP abnormalities correlated positive with both clinical neuropathy scores (NSS r = 0.62; p < 0.001; NDS r = 0.57; p < 0.001), but not with the duration of the disease, current viral load, or the virus subtype. PREP abnormalities were more frequent (16/33, 48.5%) in HCV patients treated with interferon than in therapy naïve patients (4/13, 30.8%); the difference was, however, not significant. In our present study (1) all virus subtypes are capable of inducing neuropathy, (2) no differences were found between interferon therapy and treatment naive patients, (3) the prevalence of peripheral sensory neuropathy including small sensory fibers (20/46, 43.5%) is higher than previously reported and (4) we found that detection of HCV associated neuropathy depends on the evaluation method.     

Axonal sensorimotor neuropathy in patients with beta-thalassaemia

OBJECTIVE: The purpose of this study was to investigate the prevalence of peripheral neuropathy in patients with beta-thalassaemia. METHODS: Thirty six patients with a mean age of 29.2+/-8.2 years and 17 healthy controls with a mean age of 27.6+/-9.1 were included in this study. Measurements included the neuropathy symptoms score (NSS), the neuropathy disability score (NDS) as well as nerve conduction studies of two motor (ulnar and peroneal) and two sensory (ulnar and sural) nerves of the right limbs. RESULTS: A mainly sensory axonal polyneuropathy was present in 19 out of 36 patients (52.7%). Eight out of these 19 patients also had abnormal NDS values. The neuropathy correlated significantly with the age of the patients and the hematocrit. However, it did not correlate with the presence of antibodies against HCV, the ferritin levels, or with a history of transfusions, desferrioxamine treatment, or splenectomy. CONCLUSIONS: This study showed a high prevalence of a predominantly sensory neuropathy in patients with beta-thalassaemia. The electrophysiological data suggest that the underlying pathology is an axonopathy. Chronic hypoxia of the nerves resulting from severe anaemia may contribute to the pathogenesis of this neuropathy.     

Electrophysiological determinants of the clinical severity of axonal peripheral neuropathy

Introduction: Electrophysiological diagnosis of axonal peripheral neuropathy (PN) is based on the attenuated amplitudes of nerve conduction studies (NCS), or a reduced sural/radial amplitude ratio (SRAR). We aimed to identify the electrophysiological determinants of the clinical severity of PN. Methods: Patients with chronic axonal PN underwent detailed NCS. The clinical severity of PN was determined based upon the overall neuropathy limitations scale (ONLS). Results: Ninety-five patients (71.6% males, mean age 71.9 ± 9.0 years) were recruited. Significant correlations were observed between the radial sensory nerve action potential (SNAP) and the ONLS total score (Spearman's rho -0.382, p < 0.001); and between the tibial compound muscle action potential and the ONLS leg score (Spearman's rho -0.283, p = 0.005). No correlations between the SRAR and the ONLS scores were found. Discussion: The radial SNAP is the strongest electrophysiological determinant of PN severity and might be useful for monitoring disease progression or response to treatment. Muscle Nerve 59:491–493, 2019     

Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial

Sensory peripheral neuropathy (PN) remains a common complication in HIV-positive patients despite effective combination anti-retroviral therapy (ART). Data on PN on second-line ART is scarce. We assessed PN using a standard tool in patients failing first-line ART and for 96 weeks following a switch to PI-based second-line ART in a large Randomised Clinical Trial in Sub-Saharan Africa. Factors associated with PN were investigated using logistic regression. Symptomatic PN (SPN) prevalence was 22 % at entry (N?=?1,251) and was associated (p?<?0.05) with older age (OR?=?1.04 per year), female gender (OR?=?1.64), Tuberculosis (TB; OR?=?1.86), smoking (OR?=?1.60), higher plasma creatinine (OR?=?1.09 per 0.1 mg/dl increase), CD4 count (OR?=?0.83 per doubling) and not consuming alcohol (OR?=?0.55). SPN prevalence decreased to 17 % by week 96 (p?=?0.0002) following similar trends in all study groups (p?=?0.30). Asymptomatic PN (APN) increased over the same period from 21 to 29 % (p?=?0.0002). Signs suggestive of PN (regardless of symptoms) returned to baseline levels by week 96. At weeks 48 and 96, after adjusting for time-updated associations above and baseline CD4 count and viral load, SPN was strongly associated with TB (p?<?0.0001). In summary, SPN prevalence was significantly reduced with PI-based second-line therapy across all treatment groups, but we did not find any advantage to the NRTI-free regimens. The increase of APN and stability of PN-signs regardless of symptoms suggest an underlying trend of neuropathy progression that may be masked by reduction of symptoms accompanying general health improvement induced by second-line ART. SPN was strongly associated with isoniazid given for TB treatment.     

Peripheral neuropathy in systemic lupus erythematosus.

The prevalence of clinically apparent peripheral neuropathy in systemic lupus erythematosus is reported to be between 2% to 18%. The purpose of this prospective case-control study was to determine the prevalence of peripheral neuropathy (PN) using electrodiagnostic criteria. Subgroup analysis was performed to determine whether PN correlated with disease activity, renal involvement, or serum immune markers. Fifty-four systemic lupus erythematosus patients and 30 controls were recruited in the study. The right median, ulnar, peroneal, tibial, and sural sensory and motor nerve conduction studies were obtained. PN in our study was defined as any abnormal values in motor and sensory distal latency, sensory action potential, motor action potential, or conduction velocity affecting 2 or more nerves. Of the 54 patients studied, PN was present in 15 patients (27.8%) of which 4 were symptomatic. There was a significant correlation between PN and anti-SM antibody, and there was a trend showing decreased motor and sensory action potential amplitudes in our systemic lupus erythematosus group compared to the controls. This observation was also seen in an active disease group when compared to those with inactive disease. The amplitude of the action potential was more often affected than the distal latency, and sensory nerves were more susceptible than motor nerves. The sural sensory action potential amplitude appears to be the most sensitive indicator of PN which may be used as an index to monitor disease activity.     

Peripheral neuropathy in type 2 diabetes mellitus in Isfahan, Iran: prevalence and risk factors

BACKGROUND: To estimate the prevalence and risk factors of peripheral neuropathy (PN) in people with type 2 diabetes mellitus. METHODS: A total of 810 patients with type 2 diabetes (289 men and 521 women) from Isfahan Endocrinology and Metabolism Research Centre outpatient clinics, Iran, were examined. Part of examination included an assessment of neurological function including neuropathic symptoms and physical signs and nerve conduction velocity. RESULTS: The prevalence of PN was 75.1% (95% confidence interval 72.1, 78.0). PN was associated with age, proteinuria, and duration of diabetes, insulin-treatment, and presence of any retinopathy and ischaemic heart disease (IHD). The age-adjusted prevalence rate of PN was 78% higher among patients with IHD, 64% higher among patients with any retinopathy, 66% higher among insulin-treated type 2 diabetes, and it was greater with duration of diabetes. Using a stepwise binary logistic regression model, age, duration of diabetes and proteinuria were significant independent predictors of PN. CONCLUSION: Peripheral neuropathy is a common complication in this population of Iranian type 2 diabetic patients. It increases with age, duration of diabetes and proteinuria.     

Diabetic neuropathy: comparison between Bangladeshi immigrants and Greek‐born subjects

The aim of this study was to compare Bangladeshi immigrants with diabetes to native Greeks with diabetes and to distinguish the different risk factors for polyneuropathy (PN) in the two ethnic groups. Subjects were recruited from the outpatient diabetic clinic of a general hospital. A total of 111 Bangladeshi immigrants (97 men and 14 women of mean age 47 years) and 101 native Greeks (82 men and 19 women of mean age 49 years) were included in the study. Sex, mean age, age at diabetes diagnosis, and diabetes duration did not differ between the two groups. PN was diagnosed in 53 (48%) Bangladeshi and in 59 (58%) Greek patients (p = 0.12). Large fiber neuropathy was less prevalent among Bangladeshis (18%) than in Greeks (53%) (p < 0.01). Small fiber neuropathy on the contrary were more frequent in Bangladeshis (18% vs. 7%) (p < 0.02). Regarding the risk factors for PN, Greek patients were taller, with higher BMI, and smoked more cigarettes (p < 0.001). They were also treated with more anti‐lipid and antihypertensive agents. The higher percentage of SFN in Bangladeshi was mainly a result of the significantly greater incidence of erectile dysfunction (ED) in their group (68 Bangladeshi vs. 38 Greek men). It is well known that there are many causes of ED aside from SFN which were not evaluated in this study. Thus this conclusion should be taken with caution.     

Leprosy late-onset neuropathy: an uncommon presentation of leprosy

Clinical and pathological findings in leprosy are determined by the natural host immune response to Mycobacterium leprae. We previously described cases of painful neuropathy (PN) with no concurrent cause apart from a past history of leprosy successfully treated. Four leprosy previously treated patients who developed a PN years after multidrug therapy (MDT) are reported. The mean patient age was 52.75 years (47-64). The mean time interval of the recent neuropathy from the previous MDT was 19 years (12-26). A painful multiplex neuritis or polyneuropathy were observed respectively in two cases. Electrophysiological studies disclosed a sensory axonal neuropathy in two cases. Microvasculitis with no bacilli was seen in nerve biopsy. Neuropathic symptoms were improved with prednisone. We consider these cases as being a leprosy late-onset neuropathy (LLON) form of presentation. A delayed immune reaction could explain the late appearance of LLON.     

Serum methylmalonic acid correlates with neuropathic pain in idiopathic Parkinson’s disease

Recent studies have shown a relatively higher prevalence of peripheral neuropathy in idiopathic Parkinson’s disease (IPD). The hypothesis is that prolonged levodopa exposure causes vitamin B12 deficiency, which leads to peripheral neuropathy. The aim of our study was to find the relationship between vitamin B12 and its precursor methylmalonic acid (MMA) in IPD patients with neuropathic pain. We performed a cross-sectional study by enrolling consecutive 43 patients who were clinically tested positive for F-18 FP-CIT PET and 15 patients were diagnosed with peripheral neuropathy according to the Toronto clinical scoring system (TCSS). The severity of neuropathic pain was evaluated using total neuropathy scale, revised (TNSr), and Korean Neuropathic Pain Questionnaire (KNPQ). The correlations between age, IPD duration, levodopa equivalent dose (LED), UPDRS III, vitamin B12, MMA, and homocysteine levels were assessed. The prevalence rate of peripheral neuropathy in IPD patients was 35%. Among the serums assessed, MMA levels showed a positive correlation to TNSr and KNPQ in the IPD patients with peripheral neuropathy (TNSr r = 0.882, p < 0.001, KNPQ r = 0.710, p = 0.004), while Vitamin B12 and homocysteine showed no statistically significant correlation. Our study showed a prevalence of peripheral neuropathy in 35% of Korean IPD patients. The serum MMA positively correlated with the severity of neuropathic pain and this can be used as a useful marker in assessment of peripheral neuropathy in Parkinson’s disease.     

Neurological involvement in Wegener's granulomatosis: An analysis of 324 consecutive patients at the Mayo Clinic

Neurological involvement in Wegener's granulomatosis was studied by reviewing the charts of 324 consecutive patients in whom the diagnosis was made at the Mayo Clinic. One hundred nine patients (33.6%) had neurological involvement. Peripheral neuropathy occured in 53; cranial neuropathy, in 21; external ophthalmoplegia, in 16; cerebrovascular events, in 13; seizures, in 10; cerebritis, in 5; and miscellaneous involvement, in 25. The mean age and sex ratio were similar in the patients with and those without neurological involvement. Among the patients with peripheral neuropathy, 42 had mononeuropathy multiplex; 6, distal symmetrical polyneuropathy; and 5, unclassified peripheral neuropathy. Multiple mononeuropathy was a major presenting symptom in 8 patients. A significantly higher percentage of patients with peripheral neuropathy, compared to those without peripheral neuropathy, had kidney involvement (p < 0.001). The second, sixth, and seventh cranial nerves were most frequently affected. Multiple cranial nerves were affected in 8 patients. Unusual neurological manifestations in the miscellaneous group were spastic paraparesis, temporal arteritis, Horner's syndrome, and papilledema.     

Ischemia-reperfusion injury of peripheral nerve in experimental diabetic neuropathy

The pathogenesis of human diabetic neuropathy likely involves the interplay of hyperglycemia, ischemia, and oxidative stress. Mild-moderate ischemia-reperfusion to streptozotocin (STZ)-induced diabetes results in florid fiber degeneration in diabetic but not in normal nerves. Uncertainty exists as to the influence of duration of diabetes on this susceptibility. We therefore studied diabetic tibial and sciatic nerves using a rat ischemia-reperfusion (IR) model after 1 month and 4 months of diabetes utilizing electrophysiological, behavioral, and neuropathological methods. Electrophysiological abnormalities were present in 1-month diabetic rats (D) and persisted over 4 months. Behavioral scores were decreased markedly at 4 months (p<0.05). Endoneurial edema and ischemia fiber degeneration (IFD) were observed at both the 1-month (p<0.01 and p<0.001) and 4-month (p<0.001) durations in diabetic nerves, whereas only mild or no damage was observed in age-matched control nerves. These findings demonstrate that STZ-induced diabetes exacerbates the morphological and electrophysiological pathology in peripheral nerve to IR injury both in the early timepoint of 1 month and late timepoint of 4 months, although there was a gradation of injury, which is more severe at the later timepoint. Reperfusion exaggerated morphological pathology in 1-month STZ-induced diabetic peripheral nerve.     

Oesophageal motility disorders in type 1 diabetes mellitus and their relation to cardiovascular autonomic neuropathy

The relationship between cardiovascular autonomic neuropathy (CVAN) and oesophageal dysfunction in diabetes mellitus has not been well established because reports are contradictory. The aim of this study was to assess oesophageal function and its correlation with CVAN in type 1 diabetic patients without oesophageal symptoms. Forty-six type 1 diabetic patients without oesophageal symptoms (DG) and 34 healthy volunteers (CG) were studied. Both groups underwent CVAN tests and oesophageal manometry and pH-metry. Differences between groups regarding results of cardiovascular autonomic tests and oesophageal studies were statistically analysed. Compared with the CG, the DG group showed insufficient lower oesophageal sphincter (LOS) relaxation and a higher percentage of simultaneous waves (P < 0.01). Patients with CVAN (n = 22) showed a higher prevalence of pathological simultaneous contractions (>10%), and the prevalence of simultaneous waves related to the degree of autonomic neuropathy was: 9% of patients without CVAN, 7% of those suspected to have it and 50% of patients with CVAN (P < 0.001). Factors associated with the presence of pathological simultaneous waves (>10%) were the presence of CVAN and duration of diabetes (P < 0.05, logistic regression analysis). Increase in simultaneous waves and impaired relaxation of LOS are more frequent in diabetic patients with CVAN.     

Ultrasonographic Assessment of the Prevalence of Fasciculations in Lesions of the Peripheral Nervous System

In previous studies, ultrasonography was a very sensitive method in detecting fasciculations. The present study was intended to examine the prevalence of ultrasonographically visible fasciculations in patients with neuromuscular diseases affecting the lower extremities. Ultrasonography of 9 muscles (rectus femoris, vastus lateralis, vastus intermedius, vastus medialis, sartorius, semitendinosus, tibialis anterior, gastrocnemius, and soleus muscles) was performed bilaterally in 70 adult healthy subjects and 172 patients with various neuromuscular diseases. Fasciculations were detected in 109 (63%) of 172 patients. The median value of affected muscles was 10 (range 1–18). Patients with spinal muscular atrophy (37/38, p < 0.001), hereditary motor and sensory neuropathy (24/25, p < 0.001), and lumbosacral radiculopathy with motor deficits (24/29, p < 0.001) exhibited fasciculations more frequently than did healthy volunteers. Radiculopathy with sensory deficits, lesions of either plexus or peripheral nerves, compartment syndrome, and myopathy were not associated with a significantly enhanced prevalence of fasciculations in the patient group compared to the control group. In summary, fasciculations are a frequent ultrasonographic sign in neuromuscular diseases. They are almost regularly found in patients with spinal muscular atrophy and those with hereditary motor and sensory neuropathy. Thus, the absence of fasciculations in ultrasonographic assessment should give cause for reconsidering these diagnoses.     

Large and small fiber neuropathy in chronic alcohol-dependent subjects

The aim of the present study was to evaluate the occurrence of large and small fiber neuropathy among alcohol-dependent subjects and to correlate neuropathy with the pattern of alcohol abuse, age of the subjects, nutritional status, and biochemical parameters. The study sample comprised 98 consecutive alcohol-dependent subjects without signs of malnutrition treated for detoxification voluntarily in the specialized unit of the Athens University Psychiatric Clinic in an inpatient basis. Polyneuropathy (PN) was graded using the neuropathy symptoms score and neurologic disability score, conduction velocity studies, and quantitative sensory tests. Seventy-seven men and 21 women aged 27-70 years took part in the study. PN was diagnosed in 57 subjects (58.2%). PN of both large and small fibers was found in 25 patients (25.5%); exclusively small fiber neuropathy was observed in 12 (12.2%) and exclusively large fiber neuropathy in 20 patients (20.4%). Neuropathy was significantly correlated with the age of the subjects, duration of alcohol abuse, liver dysfunction, macrocytosis, and blood sugar levels upon admission. PN was significantly more frequent in males than in females. The two groups of exclusively large and exclusively small fiber neuropathy did not differ significantly in any clinical and laboratory parameter. Subclinical neuropathy (stage 1) was observed in 11.2%, which also did not differ significantly in any clinical and laboratory parameter from the stage 2 PN group subjects. Our findings indicate the direct toxic effect of alcohol on peripheral nerve fibers as the main etiologic factor of alcoholic PN. Long-standing hyperglycemia may be another contributing factor. Impaired vitamin B(12) utilization may be also involved.     

Peripheral neuropathy in young-old and old-old patients.

Diabetes is said to account for most cases of neuropathy in the elderly. We reviewed records of 223 young-old (65-79 years) and 77 old-old (>or=80 years) patients referred for evaluation of neuropathic symptoms over a 9-year period. We prospectively validated our findings in 102 consecutive elderly (77 young-old) patients receiving intensive evaluation for neuropathy. Diabetes was the most common cause of neuropathy (41%), but was less common in the old-old (25% versus 46%, P < 0.001). Idiopathic neuropathies were more common in the old-old (39% versus 9%, P < 0.001). Alcoholic and nutritional neuropathies were uncommon in the old-old. Electrophysiological studies showed that most patients had an axonal type of neuropathy. Sural and peroneal response amplitudes were poorly correlated with age. We obtained similar results in our prospective study. The distribution of causes of neuropathies in young-old and old-old patients, in a hospital-based sample, is age-related. Future studies need to include the old-old to better understand the nature of neuropathy in the elderly.     

Neuropathy Associated With Anti-Chondroitin Sulfate C IgM Antibodies

Chondroitin Sulfate C (ChS-C), is a glycosaminoglycan present in the membranes of neurons and axons. Anti-ChS-C IgM antibodies have been reported in patients with predominantly sensory neuropathy (PN) often associated with IgM monoclonal gammopathy, but also in some neurological controls. In order to evaluate the frequency and clinical correlate of anti-ChS-C IgM antibodies, we tested them by a new Covalink ELISA technique in sera from 206 patients with IgM monoclonal gammopathy including 79 with PN (PN+IgM) with unknown IgM reactivity, 65 with PN with antibodies to the myelin-associated glycoprotein and 62 without PN, and from 33 patients with PN of other causes, 30 with other neurological and non-neurological diseases and 23 normal subjects. We only found high titers of anti-ChS-C IgM in two patients (1/128,000 and 1/256,000 respectively) with IgM monoclonal gammopathy: one had Waldenström Macroglobulinemia diagnosed seven years before and a 3 year history of slowly progressive limb weakness, finger paresthesias, unsteady gait and occasional nocturnal cramps. Neurological examination revealed a predominantly large-fiber sensory neuropathy with mild distal atrophy and weakness in upper and lower limbs. Electrophysiological and morphological studies were suggestive of a predominantly demyelinating neuropathy. The other patient had IgM MGUS without PN at the time of antibody testing but developed finger paresthesias seven years later, when he had decreased position sense and abnormal sensory nerve conduction studies. In conclusion high titers of anti-ChS-C IgM, though infrequent, were always associated with the presence or development of sensory PN in patients with IgM M-protein, supporting a possible role for these antibodies in the neuropathy.     

Restless legs syndrome is frequently overlooked in patients being evaluated for polyneuropathies

Restless legs syndrome (RLS) often presents with paresthesias and dysesthesisas. We have investigated the prevalence and clinical features of RLS in a cohort of patients referred for clinical suspicion of peripheral neuropathy (PN). Sixty-four patients with sensory symptoms, and 101 age-matched controls were prospectively evaluated for RLS, PN and causes of both conditions. In the 64 patients (60 ± 14 years), none were referred with a suspicion of RLS. Forty-one had a sensori-motor PN of which 22 had a definite RLS (54%). When excluding other causes of RLS, 8 of 41 patients had a RLS associated with a neuropathy (20%). The proportion of RLS in the healthy controls was 10%, lower than in the cohort of patients. In patients without PN, 57% had a RLS, and 55% in the whole cohort, a higher proportion than in the healthy controls ( P  < 0.0001). Patients with PN and RLS had more sleep disorders ( P  < 0.04), and legs and calves symptoms ( P  = 0.09) than patients with PN without RLS. Toes symptoms were more frequently observed in patients with PN but without RLS ( P  < 0.02). We conclude that RLS frequently presents with symptoms suggestive of peripheral neuropathy, and therefore, is often overlooked.