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.     

HIV peripheral neuropathy progression: protection with glucose-lowering drugs?

The purpose of this study is to evaluate risk factors for progression from asymptomatic peripheral neuropathy (APN) to symptomatic peripheral neuropathy (SPN). Antiretroviral therapy (ART)-na?ve patients initiating combination ART were followed longitudinally and screened for signs/symptoms of PN. Having APN was associated with higher odds of future SPN (odds ratio (OR)?=?1.58, 95?% confidence interval (CI)?=?(1.08, 2.29), p?=?0.027). Neurotoxic ART use was associated with increased odds of progression to SPN (OR?=?2.16, 95?% CI?=?(1.21, 3.85), p?=?0.009) while use of glucose-lowering drugs (non-insulin) was protective (OR?=?0.12, 95?% CI?=?(0.02, 0.83), p?=?0.031). Use of glucose-lowering drugs (non-insulin) may prevent progression from APN to SPN.     

Prevalence and characteristics of peripheral neuropathy in hepatitis C virus population

OBJECTIVE: To assess the prevalence of peripheral neuropathy (PN) and its correlation with cryoglobulinemia (CG) in an unselected, untreated referral hepatitis C virus (HCV) population. PATIENTS AND METHODS: Two hundred and thirty four patients (120 women and 114 men) with untreated HCV infection were consecutively enrolled by seven Italian centres. Clinical neuropathy was diagnosed when symptoms and signs of peripheral sensory or motor involvement were present. Median, ulnar, peroneal, and sural nerves were explored in all patients and distal symmetric polyneuropathy was diagnosed when all explored nerves or both lower limb nerves were affected. Mononeuropathy and mononeuropathy multiplex were diagnosed when one nerve or two non-contiguous nerves with asymmetrical distribution were affected. Screening for CG was done in 191 unselected patients. RESULTS: Clinical signs of PN were observed in 25 of the 234 patients (10.6%). Electrophysiological PN was found in 36 (15.3%). CG was present in 56/191 patients (29.3%). The prevalence of CG increased significantly with age (p<0.001) and disease duration (p<0.05). PN was present in 12/56 (21%) patients with CG and 18/135 (13%) without CG (p=NS). PN increased significantly with age (p<0.001) and logistic regression analysis confirmed age as the only independent predictor of PN (OR 1.10 for each year; 95% CI 1.04 to 1.15; p<0.001). CONCLUSIONS: Electrophysiological examination detected subclinical neuropathy in 11 patients (4.7%). Statistical analysis showed that CG was not a risk factor for PN whereas PN prevalence increased significantly with age.     

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.     

Long-term levodopa/carbidopa intestinal gel in advanced Parkinson’s disease

The short-term benefits of levodopa/carbidopa intestinal gel (LCIG) in patients with advanced Parkinson’s disease (PD) are well documented, but the long-term benefits are still uncertain. The aim of this study was to investigate the motor and cognitive outcome of LCIG treatment in advanced PD after a follow-up period of at least 24 months. We assessed 29 patients with advanced PD who started LCIG infusion at our centre between 2007 and 2013. Motor fluctuations, parkinsonian symptoms, activities of daily living and impact on quality of life were evaluated. We also investigated the cognitive outcome using a battery of neuropsychological tests. All adverse events were recorded. Of the 29 PD patients who initiated LCIG, 16 patients reached the follow-up evaluation (24 months), after a mean time period of 32.2 ± 12.4 months. Six patients did not fulfil the 24-month follow-up visit and were evaluated after a mean time period of 8.6 ± 5.4 months. Seven patients discontinued the treatment before the scheduled visit. “Off” time and “On” dyskinesia duration were significantly reduced. LCIG improved quality of life and non motor symptoms, despite overall unchanged total levodopa doses prior to LCIG beginning. Motor and cognitive decline were detected. A relatively high number of adverse events occurred during the follow-up, above all, technical problems with the infusion device and mild problems related with gastrostomy. There were four cases of peripheral neuropathy (PN), 2 of which were considered serious. Our data confirm that LCIG is beneficial in the long-term treatment of advanced PD patients despite a decline in cognitive functions in a subgroup of patients, probably due to disease progression. PN in patients with LCIG may be more frequent than the published date suggest.     

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.     

Factors Associated with Favorable Response to Hyperbaric Oxygen Therapy among Patients Presenting with Iatrogenic Cerebral Arterial Gas Embolism

Background

Iatrogenic cerebral arterial gas embolism (CAGE) is an uncommon but potentially a fatal condition. Hyperbaric oxygen (HBO₂) therapy is the only definitive treatment for patients with CAGE presenting with acute neurologic deficits.

Methods

We reviewed medical records and neuroimaging of consecutive CAGE patients treated with HBO₂ at a state referral hyperbaric facility over a 22-year period. We analyzed the effect of demographics, source of intra-arterial gas, signs and symptoms, results of imaging studies, time between event and HBO₂ treatment, and response to HBO₂ treatment in 36 consecutive patients. Favorable outcome was defined by complete resolution or improvement of CAGE signs and symptoms at 24 h after HBO₂ treatment. Unfavorable outcome was defined by unchanged or worsened neurologic signs and symptoms or in hospital death.

Results

A total of 26 (72%) of the 36 patients had favorable outcome. Patients with favorable outcome were younger compared to those with unfavorable outcome (mean age [years, SD] 44.7 ± 17.8 vs. 58.1 ± 24.1, p = 0.08). Cardiopulmonary symptoms were significantly more common in CAGE related to venous source of gas compared to arterial source (p = 0.024) but did not influence the rate of favorable outcomes. Adjusted multivariate analysis demonstrated that time from event to HBO₂ ≤6 h (positively) and the presence of infarct/edema on head computerized tomography (CT)/magnetic resonance imaging (MRI) before HBO₂ (negatively) were independent predictors of favorable outcome at 24 h after HBO₂ treatment [odds ratio (OR) 9.08 confidence interval (CI) (1.13–72.69), p = 0.0376, and (OR) 0.034 (CI) (0.002–0.58), p = 0.0200, respectively]. Two of the 36 patients were treated with thrombolytics because of acute focal deficits and suspected ischemia—one with intravenous and the second with intra-arterial thrombolysis. The latter patient developed fatal intracerebral hemorrhage.

Conclusions

A high proportion of CAGE patients treated with HBO₂ had favorable outcomes. Time-to-HBO₂ ≤6 h increased the odds of favorable outcome, whereas the presence of infarct/edema on CT/MRI scan before HBO₂ reduced the odds of a favorable outcome. Timely diagnosis and differentiation from thrombo-embolic ischemic events appears to be an important determinant of successful HBO₂ treatment.     

Differences in oligoclonal bands and visual evoked potentials in patients with radiologically and clinically isolated syndrome

The aim of this study was to determine the prevalence of cerebrospinal fluid (CSF) and visual evoked potentials (VEP) abnormalities, and ANA titers in patients with either clinically or radiologically isolated syndrome (CIS and RIS). We gathered records from 330 hospitalized patients diagnosed with CIS/RIS within a 3-year period. Symptoms, CSF findings, VEP and ANA titers were analyzed. Incomplete transverse myelitis was the presenting symptom in 32.7 %, optic neuritis in 22.7 %, brainstem/cerebellar symptoms in 19.4 %, hemispheral symptoms in 2.7 % and multifocal symptoms in 15.2 % of patients in the CIS cohort. We identified 24 (7.3 %) patients with atypical or no symptoms—RIS cohort. Positive oligoclonal bands (OCB) were found in 75.5 % patients. When we divided the patients into CIS and RIS groups, the presence of OCB was 82.4 and 44 %, respectively. VEP were performed in 87.3 % patients and prolonged latencies were found in 39.6 % of them (43.8 and 14.3 % in the CIS and RIS cohort, respectively). ANA were positive in 15.2 % (14.7 and 16 % in the CIS and RIS cohort, respectively) of patients. RIS patients had statistically significant lower percentages of positive OCB and positive VEP (P = 0.002 and 0.001, respectively). Detection of OCB and VEP still has an important role for satisfying the “no better explanation for the clinical presentation” criteria when presented with a patient with a first “radiological” demyelinating episode.     

Autonomic neuropathy in mixed cryoglobulinemia

A retrospective, cross-sectional study was performed on a series of HCV-related mixed cryoglobulinemia (HCV-MC) patients to assess autonomic neuropathy (AN) and its relation to peripheral neuropathy (PN). Thirty consecutive patients affected by HCV-MC underwent clinical, neurological and electrodiagnostic examinations. Autonomic nervous system (ANS) involvement was assessed by functional cardiovascular tests and sympathetic skin response (SSR) evaluation. Sural nerve biopsy was performed in 10 patients with PN. All patients received steroids, 15 also received recombinant interferon-α2b (RIfn-α2b). PN occurred in 27 patients (90.0%) and AN in 4 (13.3 %) all with signs of PN. SSR was the autonomic test more frequently altered. Biopsy disclosed axonal degeneration more evident in the 4 patients with AN. Three out of 4 patients with AN received steroids and rIFN-α2b and 1 steroids alone. In our study on HCV-MC, it was concluded that AN can occur also without dysautonomic symptoms, SSR appears to be one of the optional tests to use together with dysautonomic tests to identify AN and finally PN and AN do not seem to be positively influenced by addition of rIFN-α2b to steroid treatment. Received in revised form: 4 April 2006     

Peripheral neuropathy in Parkinson's disease: Levodopa exposure and implications for duodenal delivery

In advanced Parkinson's disease (PD) patients, continuous intra-duodenal infusion of levodopa/carbidopa intestinal gel (LCIG) is an established approach in the management of motor complications that cannot be further improved by conventional oral therapy. In general, tolerability of LCIG has resembled that of oral dopaminergic therapy; however, cases of symptomatic peripheral neuropathy (PN), sometimes severe, have been reported in patients receiving LCIG. Cases are generally a sensorimotor polyneuropathy with both subacute and chronic onsets, often associated with vitamin B12 and/or B6 deficiency. Rare cases clinically resemble Guillain-Barré syndrome. In the absence of prospectively collected data on possible associations between LCIG and PN, it is prudent to explore potential mechanisms that may explain a possible relationship. The PN may be linked to use of high-dose levodopa, promoting high levels of homocysteine and methylmalonic acid or reduced absorption of vitamins essential for homocysteine metabolism. Cases of LCIG-associated PN often have responded to vitamin supplementation without need for LCIG cessation, although LCIG cessation is sometimes necessary. It may be advisable to monitor vitamin B12/B6 status before and after patients start LCIG and be vigilant for signs of PN. Prospective, large-scale, long-term studies are needed to clarify whether vitamin supplementation and routine use of a catechol-O-methyltransferase inhibitor may help prevent PN in LCIG recipients and whether these measures should be routine practice in patients with PD on high-dose oral levodopa.     

Prevalence of peripheral neuropathy in antiretroviral therapy na?ve HIV-positive patients and the impact on treatment outcomes—a retrospective study from a large urban cohort in Johannesburg, South Africa

Peripheral neuropathy (PN) is associated with advanced HIV disease and may be a complication of antiretroviral therapy (ART) or anti-tuberculosis (TB) drugs, specifically isoniazid (INH). The effect of non-ART-drug-related PN on treatment outcomes is yet to be determined. We analysed prospectively collected cohort data for HIV-infected ART-naive adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa from June 2004 to June 2009. Patients who presented with signs and symptoms of numbness or dysesthesia prior to initiation of ART were defined as having PN. Cox proportional hazard models were used to estimate the effect of PN alone (HIV-related PN) or PN with a history of INH use (TB-related PN) on mortality, lost to follow-up (LTFU), persistent and recurrent PN by 12 months of follow-up. Of the 9,399 patients initiating ART, 3.9 % had HIV-related PN while a further 1.8 % had TB-related PN. Patients with PN did not have a significantly higher risk of mortality compared to those without PN (hazard ratio (HR) 1.17 95 % CI 0.92-1.49). Patients with TB-related PN were less likely to be LTFU by 12 months (HR 0.65 95 % CI 0.44-0.97) compared to those without PN. Patients with HIV-related PN were at increased risk of persistent PN at 3 months post-ART initiation. Patients with HIV-related PN had a similar risk of recurrent PN compared to those with TB-related PN (HR 1.28 95 % CI 0.72-2.27). We demonstrate that patients with PN at initiation of ART present with advanced HIV disease. Completion of TB treatment may reduce the risk of persistent PN in patients with TB-related PN. Use of HIV drugs, even neurotoxic ones, may overall limit neuropathy.     

Is psychiatric residential facility discharge possible and predictable? A multivariate analytical approach applied to a prospective study in Italy

Background

A growing number of severely ill patients require long-term care in non-hospital residential facilities (RFs). Despite the magnitude of this development, longitudinal studies surveying fairly large resident samples and yielding important information on this population have been very few.

Aims

The aims of the study were (1) to describe the socio-demographic, clinical, and treatment-related characteristics of RF patients during an index period in 2010; (2) to identify predictors and characteristics associated with discharge at the 1-year follow-up; (3) to evaluate clinicians’ predictions about each patient’s likelihood of home discharge (HD).

Methods

A prospective observational cohort study was conducted involving all patients staying in 23 medium-long-term RFs of the St John of God Order with a primary psychiatric diagnosis. A comprehensive set of socio-demographic, clinical, and treatment-related information was gathered and standardized assessments (BPRS, HONOS, PSP, PHI, SLOF, RBANS) were administered to each participant. Logistic regression analyses were run to identify independent discharge predictors.

Results

The study involved 403 patients (66.7 % male), with a mean age of 49 years (SD = 10). The participants’ average illness duration was 23 years; median value for length of stay in the RF was 2.2 years. The most frequent diagnosis was schizophrenia (67.5 %). 104 (25.8 %) were discharged: 13.6 % to home, 8.2 % to other RFs, 2.2 % to supported housing, and 1.5 % to prison. Clinicians’ predictions about HD were generally erroneous.

Conclusions

Very few patients were discharged to independent accommodations after 1 year. The main variables associated with a higher HD likelihood were: illness duration of <15 years and effective social support during the previous year. Lower severity of psychopathology and higher working skill levels were also associated with a significantly greater HD likelihood.     

Neuropathy-Inducing Effects of Eribulin Mesylate Versus Paclitaxel in Mice with Preexisting Neuropathy

Eribulin mesylate (E7389, INN:eribulin mesilate Halaven^®) is a non-taxane microtubule dynamics inhibitor currently in clinical use for advanced breast cancer. Other microtubule-targeting agents for breast cancer, including paclitaxel and ixabepilone, display a common treatment dose-limiting toxicity of peripheral neuropathy (PN). In an earlier study, we found eribulin mesylate had a lower propensity to induce PN in mice than either paclitaxel or ixabepilone. In the current study, we compared additional PN induced by paclitaxel versus eribulin mesylate when administered to mice with preexisting paclitaxel-induced PN. Initially, paclitaxel at 0.75 × its maximum tolerated dose (MTD; 22.5 mg/kg) was given on a Q2Dx3 regimen for 2 weeks. The second chemotherapy was 0.5 MTD eribulin mesylate (0.875 mg/kg) or paclitaxel (15 mg/kg) on a similar regimen, starting 2 weeks after the first. Initial paclitaxel treatment produced significant decreases in caudal nerve conduction velocity (NCV; averaging 19.5 ± 1 and 22.2 ± 1.3 %, p < 0.001) and amplitude (averaging 53.2 ± 2.6 and 72.4 ± 2.1 %, p < 0.001) versus vehicle when measured 24 h or 2 weeks after dosing cessation, respectively. Additional 0.5 MTD paclitaxel further reduced caudal NCV and amplitude relative to immediately before initiation of the second regimen (by 11 ± 2.1 and 59.2 ± 5 %, p < 0.01, respectively). In contrast, 0.5 MTD eribulin mesylate caused no further decrease in caudal NCV. In conclusion, unlike additional paclitaxel treatment, eribulin mesylate administered to mice with preexisting paclitaxel-induced PN had limited additional deleterious effects at 6 weeks. These preclinical data suggest that eribulin mesylate may have reduced tendency to exacerbate preexisting paclitaxel-induced PN in clinical settings.     

Add-on fluvoxamine treatment for schizophrenia: an updated meta-analysis of randomized controlled trials

We performed an updated meta-analysis of fluvoxamine add-on therapy in patients with schizophrenia treated with antipsychotics based on two previous meta-analyses (Sepehry et al., in J Clin Psychiatry 68:604–610, 2007 and Singh et al., in Br J Psychiatry J Mental Sci 197:174–179, 2010). We searched PubMed, the Cochrane Library database, and PsycINFO up to January 2013. We conducted a systematic review and meta-analysis of individual patient data from randomized controlled trials comparing fluvoxamine add-on therapy with placebo. The risk ratio (RR), 95 % confidence intervals (CI), and standardized mean difference (SMD) were calculated. Seven studies (total n = 272) were identified. These included two clozapine studies, one olanzapine study, one second-generation antipsychotic (SGA) monotherapy study, and three first-generation antipsychotics (FGAs) monotherapy studies. There were significant effect of fluvoxamine add-on therapy on overall (SMD = ?0.46, CI = ?0.75 to ?0.16, p = 0.003, I ² = 0 %, 5 studies, n = 180) and negative symptoms (SMD = ?0.44, CI = ?0.74 to ?0.14, p = 0.004, I ² = 0 %, 5 studies, n = 180). However, fluvoxamine add-on therapy showed no significant effects on positive symptoms, depressive symptoms, and discontinuations from any cause or adverse events. Fluvoxamine add-on therapy in patients primarily treated with SGAs improved overall (p = 0.02) but not negative symptoms (p = 0.31). On the other hand, fluvoxamine add-on therapy in patients primarily treated with FGAs improved both overall (p = 0.04) and negative symptoms (p = 0.004) compared with control groups. Our results suggest that fluvoxamine add-on therapy is more beneficial on the psychopathology (especially negative symptoms) than controls in patients with schizophrenia who are primarily treated with FGAs. Given that a small number of studies were included in this meta-analysis, the results should be treated with caution.     

Prevalence and risk factors of psychotic symptoms: in the city of Izmir, Turkey

Background

Psychotic symptoms, psychotic-like experiences and schizotypal signs can emerge in different socio-cultural circumstances and cause clinical or non-clinical pictures. Transient or self-limiting psychotic-like experiences are more prevalent than clinical psychotic disorders. The aim of this study is to determine the prevalence and sociodemographic correlates of psychotic symptoms in an urban area.

Methods

A cross-sectional study was conducted among the residents of two districts in the urban area of Izmir, Turkey. Among the systematically selected 1,500 residents of 85,212-study population, a total of 1,268 individuals (response rate: 84.5%) were screened for any lifetime psychotic symptoms.

Results

Composite International Diagnostic Interview (CIDI) was used to assess psychotic symptoms. CIDI (+) psychotic symptoms were found in 3.6% of the screened sample. Logistic regression analysis showed that being a female (OR = 2.4, 95% CI = 1.2–5.1), having a first degree family history of any mental disorders (OR = 13.9, 95% CI = 5.7–34.3), lack of social support (OR = 4.5, 95% CI = 2.3–8.6) and alcohol use (OR = 4.9, 95% CI = 2.3–10.6) were all related to psychotic symptoms.

Conclusion

Prevalence of any psychotic symptom is lower compared to European studies. Alcohol might be considered as a risk factor for developing psychotic symptoms in the Turkish cultural setting.     

Neuropathy and myopathy in primary Sjögren''s syndrome: neurophysiological, immunological and muscle biopsy results

Seventeen consecutive patients with primary Sjögren's syndrome (PSS) received neurophysiological examination, analysis of antibodies against peripheral nerve-myelin (PNM) and muscle biopsy, to show the prevalence and characteristics of peripheral neuropathy (PN) and myopathy; 3 PSS cases showed a clinical mild sensorimotor polyneuropathy, 1 of them had been treated with cytostatic drugs; 1 had mononeuropathia multiplex; and 1 clinical carpal tunnel syndrome. In these 5 patients neurophysiological investigation verified the clinical diagnosis of peripheral nerve involvement; 2 with PN had serum-antibodies against PNM; 1 of IgM-, and 1 of IgA-isotype. Muscle biopsies were taken from 15 PSS patients; 11 showed inflammatory myositis or inflammatory perivascular infiltrates and 3 showed signs of denervation. A combination of inflammation and morphological signs of myopathy, compatible with the biopsy diagnosis of polymyositis, was seen in 4, 1 of whom showed clinical signs of polymyositis. We conclude that the peripheral nervous and muscular systems are often involved in PSS, but commonly with relatively mild symptoms and laboratory findings. The common findings of inflammatory myopathy indicate an immune reaction in muscles in addition to other autoimmune manifestations of the disease.     

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.     

Clinical, genetic, and brain sonographic features related to Parkinson’s disease in Gaucher disease

Homozygous or compound heterozygous mutations in the glucocerebrosidase gene cause Gaucher disease. Moreover, heterozygous glucocerebrosidase gene mutations represent the most common genetic risk factor for Parkinson’s disease (PD) known so far. Substantia nigra (SN) hyperechogenicity, a sonographic feature thought to reflect iron accumulation, has been described in both PD and Gaucher disease patients. Here we studied how clinical, genetic, and brain sonographic findings relate to the occurrence of PD in Gaucher disease. Sixteen Gaucher disease patients, 12 PD patients, and 32 control subjects were enrolled. The glucocerebrosidase genotypes were identified by DNA sequencing. All subjects underwent transcranial ultrasound, and eight Gaucher disease patients additionally MRI for comparison with SN ultrasound findings. SN hyperechogenicity and reduced echogenicity of brainstem raphe were more frequent in Gaucher disease patients (62, 37 %) than in controls (12, 12 %; p < 0.001, p < 0.05). SN hyperechogenicity in Gaucher disease patients was unrelated to type or severity of glucocerebrosidase gene mutation, but correlated with iron-sensitive MRI-T2 hypointensity of SN pars compacta, and with age at start of enzyme replacement therapy. While none of the five Gaucher disease patients with signs of PD (definite PD, n = 4; early PD, n = 1) had severe glucocerebrosidase gene mutations known to cause neuronopathic Gaucher disease, all carried a N370S allele, previously reported to predict non-neuronopathic Gaucher disease. Hyposmia, higher non-motor symptoms score (constipation, depression, executive dysfunction), and SN hyperechogenicity were characteristic features of Gaucher disease-related PD. We conclude that the combined clinical, genetic, and transcranial sonographic assessment may improve the PD risk evaluation in Gaucher disease.     

Neuropathy as a potential complication of levodopa use in Parkinson's disease

The presence and potential etiologies of peripheral neuropathy (PN) in patients with Parkinson's Disease (PD) is unknown. We examined for presence of PN in patients with PD. From a PD patient population of 500 patients screened for features of symptomatic PN, patients were further selected for clinical, electrophysiological, and laboratory studies related to PN. This PD patient population with idiopathic PN (PD‐IPN) was compared to a group of PD patients without PN (PD‐only), and a large group of patients without PD with idiopathic PN (IPN) for abnormalities in Cbl, fasting homocysteine (Hcy), and fasting methylmalonic acid (MMA) levels. PD‐IPN and IPN patients identified with abnormalities in Cbl, Hcy, or MMA levels were treated with intramuscular Cbl for 1 to 2 years. Of 49 PD patients with symptomatic PN, 34 patients (69%) had PD‐IPN, and 32/34 (94%) had abnormal Hcy or MMA levels as compared to 26/258 (10%) of IPN patients. Cumulative lifetime L ‐dopa dosage and fasting MMA levels were associated with PN severity. Cbl therapy led to improvements in Hcy and MMA levels in all groups, and PN in PD‐IPN patients stabilized during therapy. PN in PD patients may be associated with iatrogenic Cbl metabolic abnormalities. Alternatively PN may be a peripheral nervous system manifestation of PD. © 2008 Movement Disorder Society     

Autism spectrum disorders are prevalent among patients with dystrophinopathies

Recent studies have reported a higher prevalence of autism spectrum disorders among patients with dystrophinopathies. The aim of this study was to investigate the prevalence of autism spectrum disorder (ASD) among those with dystrophinopathies. The possible role of dystrophin isoforms in patients was also explored. Fifty-six patients recruited from Toneyama National Hospital were included in this study (mean age?=?12.9 years, SD?=?5.2 years). Autistic symptoms were evaluated using the Pervasive Developmental Disorders/Autism Spectrum Disorders Rating Scale (PARS), a clinician rating scale. Eleven patients (19.6%; 95% confidence interval 10.2–32.4) met the criteria for ASD based on their PARS scores. Patients were separated into two groups based on the cumulative loss of dystrophin isoforms predicted from the mutation location. The prevalence of ASD was examined between these groups. Infantile and current autistic symptoms did not differ between the groups, except on one subscale of the PARS. This study revealed that there was a high prevalence of ASD in patients with dystrophinopathies.