Myotonia congenita in a Greek cohort: Genotype spectrum and impact of the CLCN1:c.501C > G variant as a genetic modifier.

INTRODUCTION/AIMS: Myotonia congenita (MC) is the most common hereditary channelopathy in humans. Characterized by muscle stiffness, MC may be transmitted as either an autosomal dominant (Thomsen) or a recessive (Becker) disorder. MC is caused by variants in the voltage-gated chloride channel 1 (CLCN1) gene, important for the normal repolarization of the muscle action potential. More than 250 disease-causing variants in the CLCN1 gene have been reported. This study provides an MC genotype-phenotype spectrum in a large cohort of Greek patients and focuses on novel variants and disease epidemiology, including additional insights for the variant CLCN1:c.501C > G. METHODS: Sanger sequencing for the entire coding region of the CLCN1 gene was performed. Targeted segregation analysis of likely candidate variants in additional family members was performed. Variant classification was based on American College of Medical Genetics (ACMG) guidelines. RESULTS: Sixty-one patients from 47 unrelated families were identified, consisting of 51 probands with Becker MC (84%) and 10 with Thomsen MC (16%). Among the different variants detected, 11 were novel and 16 were previously reported. The three most prevalent variants were c.501C > G, c.2680C > T, and c.1649C > G. Additionally, c.501C > G was detected in seven Becker cases in-cis with the c.1649C > G. DISCUSSION: The large number of patients in whom a diagnosis was established allowed the characterization of genotype-phenotype correlations with respect to both previously reported and novel findings. For the c.501C > G (p.Phe167Leu) variant a likely nonpathogenic property is suggested, as it only seems to act as an aggravating modifying factor in cases in which a pathogenic variant triggers phenotypic expression.

Rituximab as a sole steroid-sparing agent in generalized myasthenia gravis: Long-term outcomes.

BACKGROUND: Rituximab, a B-cell depleting monoclonal antibody, represents an option for the treatment of refractory myasthenia gravis (MG). Its use is more established in muscle-specific tyrosine kinase positive (MuSK +) patients, while its role in managing acetylcholine receptor positive (AChR +), or double seronegative (DSN) patients, remains less clear. This study evaluates the long-term effectiveness and safety of rituximab in MG of various serotypes. METHODS: We conducted an open-label study of MG patients receiving rituximab. Adults with generalized refractory MG, either anti-AChR + or DSN, and anti-MuSK + , refractory or not, who had follow-up > 12 months were selected. Change in quantitative myasthenia gravis (QMG) score at last follow-up, compared with baseline was a primary outcome, as well as factors affecting response to treatment. Secondary outcomes included, long-term safety, the steroid-sparing effect and relapse rates post-rituximab. RESULTS: Thirty patients (16 anti-AChR + , 6 anti-MuSK + , 8 DSN) followed for a mean of 33.3 months were included. Mean scores pre-rituximab compared to last follow-up significantly decreased (p < 0.001), from 11 ± 4.1 to 4.3 ± 3.8, and from 1.9 to 0.3 regarding QMG and relapse rate per patient/year, respectively, while in 93.1% a daily steroid dose ≤ 10 mg was achieved. Antibody status was the only factor independently influencing several endpoints. Throughout the study period no crises or deaths occurred. CONCLUSION: The present study supports that rituximab is an effective and well tolerated treatment for refractory anti-AChR + and DSN MG patients, while anti-MuSK + remains the group experiencing the greater benefits.

Cognitive function in amyotrophic lateral sclerosis: a cross-sectional and prospective pragmatic clinical study with review of the literature.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) can present with either bulbar or spinal symptoms, and in some cases, both types of symptoms may be present. In addition, cognitive impairment has been observed in ALS. The study aimed to evaluate the frontal and general cognitive performance in ALS not only cross-sectionally but also longitudinally. METHODS AND MATERIALS: The Frontal Assessment Battery (FAB) and the Montreal Cognitive Assessment (MoCA) were employed to assess cognitive function in 52 adults with ALS and 52 cognitively healthy individuals. The statistical analyses encompassed the Pearson Chi square test, the Skillings-Mack test, the Spearman's rank correlation coefficient, and the Proportional Odds Logistic Regression Model (POLR). RESULTS: Cross-sectionally, lower cognitive performance was associated with ALS diagnosis, older age, and motor functional decline. The cognitive impairment of individuals with bulbar and spinal-bulbar symptoms showed faster deterioration compared to those with spinal symptoms. The spinal subgroup consistently performed worst in delayed recall and attention, while the spinal-bulbar and bulbar subgroups exhibited inferior scores in delayed recall, attention, visuospatial skills, orientation, and verbal fluency. CONCLUSION: The incorporation of cognitive screening in the diagnostic workup of ALS may be beneficial, as early detection can enhance symptom management and improve the quality of life for both individuals with ALS and their care partners.

Apolipoprotein E Gene in α-Synucleinopathies: A Narrative Review.

In this narrative review, we delved into the intricate interplay between Apolipoprotein E (APOE) alleles (typically associated with Alzheimer's disease-AD) and alpha-synucleinopathies (aS-pathies), involving Parkinson's disease (PD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple-system atrophy (MSA). First, in-vitro, animal, and human-based data on the exacerbating effect of APOE4 on LB pathology were summarized. We found robust evidence that APOE4 carriage constitutes a risk factor for PDD-APOE2, and APOE3 may not alter the risk of developing PDD. We confirmed that APOE4 copies confer an increased hazard towards DLB, as well. Again APOE2 and APOE3 appear unrelated to the risk of conversion. Of note, in individuals with DLB APOE4, carriage appears to be intermediately prevalent between AD and PDD-PD (AD > DLB > PDD > PD). Less consistency existed when it came to PD; APOE-PD associations tended to be markedly modified by ethnicity. Finally, we failed to establish an association between the APOE gene and MSA. Phenotypic associations (age of disease onset, survival, cognitive-neuropsychiatric- motor-, and sleep-related manifestations) between APOE alleles, and each of the aforementioned conditions were also outlined. Finally, a synopsis of literature gaps was provided followed by suggestions for future research.

The utility of diaphragm ultrasound thickening indices for assessing respiratory decompensation in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) leads to diaphragmatic weakness at some point during its course, which is a major cause of respiratory insufficiency. The aim of this study was to evaluate ultrasound-based measures for assessing the diaphragmatic competency and the need for ventilatory support. METHODS: Twenty-six subjects with ALS and 12 healthy controls were enrolled. All participants underwent B-mode diaphragm ultrasound (DUS). Diaphragm thickness and thickening indices were recorded. In the subjects with ALS, further assessments included functional scales and spirometry. We investigated the diagnostic accuracy of DUS thickening indices in predicting diaphragmatic dysfunction and the correlation between clinical, spirometric, and DUS data. RESULTS: Significant relationships were found between forced vital capacity and all diaphragmatic thickening indices. Similarly, all diaphragmatic thickening indices correlated with both Milano Torino staging and disease progression rate. Only thickening fraction (TFdi) correlated with score on the revised ALS Functional Rating Scale (r = 0.459, P = .024). TFdi had better accuracy in predicting diaphragmatic dysfunction (area under the curve [AUC] = 0.839, 95% confidence interval [CI] 0.643 to 0.953) and the need for initiation of noninvasive ventilation (NIV) (AUC = 0.989, 95% CI 0.847 to 1.000) compared with the other indices. A TFdi cut-off point of 0.50 was a sensitive threshold to consider NIV. DISCUSSION: DUS successfully identifies diaphragmatic dysfunction in ALS, being a valuable accessory modality for investigating respiratory symptoms. TFdi was found to be the most useful DUS index, which encourages further investigation.

Identical late motor responses in early Guillain-Barré syndrome: A-waves and repeater F-waves.

Electrodiagnostic (EDx) studies play a key role in the investigation of suspected Guillain-Barré syndrome (GBS), providing diagnostic and prognostic information. However, initial EDx findings may not fulfill the neurophysiological criteria for the disease. The aim of this study was to estimate the occurrence and characteristics of A-waves and repeaters F-waves (Freps), both late motor responses identical in latency and configuration, in early stages of GBS. We retrospectively analyzed the initial nerve conduction study (NCS) of 26 GBS patients performed within 10 days from symptom onset. The final subtype diagnosis was acute inflammatory demyelinating polyneuropathy (AIDP) in 16 patients (six met the criteria at the initial EDx study and 10 at follow-up) and acute motor axonal neuropathy (AMAN) in 10 patients (six initially). Identical late responses were commonly found in the majority of nerves (84%). A-waves were present in 59% and an increased frequency of Freps was calculated in 61% of the 105 studied nerves. A-waves morphology (single or complex) could not distinguish between AIDP and AMAN. Nerves with normal NCS had a significantly higher frequency of A-waves, either isolated or in combination with increased index total Freps, as compared to nerves with low compound muscle action potential (CMAP) amplitudes or conduction block. Our findings suggest that both late responses can be useful as early markers of conduction changes of various pathophysiology, being frequently present even prior to abnormalities of CMAP parameters.

Mutational screening of Greek patients with axonal Charcot-Marie-Tooth disease using targeted next-generation sequencing: Clinical and molecular spectrum delineation.

BACKGROUND AND AIMS: Axonal forms of Charcot-Marie-Tooth disease (CMT) are classified as CMT2, distal hereditary motor neuropathy (dHMN) or hereditary sensory neuropathy (HSN) and can be caused by mutations in over 100 genes. We presently aimed to investigate for the first time the genetic landscape of axonal CMT in the Greek population. METHODS: Sixty index patients with CMT2, dHMN or HSN were screened by a combination of Sanger sequencing (GJB1) and next-generation sequencing custom-made gene panel covering 24 commonly mutated genes in axonal CMT. RESULTS: Overall, 20 variants classified as pathogenic or likely pathogenic were identified in heterozygous state in 20 index cases, representing 33.3% of the cohort. Of these, 14 were known pathogenic/likely pathogenic and six were designated as such according to ACMG classification, after in silico evaluation, testing for familial segregation and further literature review. The most frequently involved genes were GJB1 (11.7%), MPZ (5%) and MFN2 (5%), followed by DNM2 (3.3%) and LRSAM1 (3.3%). Single cases were identified with mutations in BSCL2, HSPB1 and GDAP1. INTERPRETATION: A wide phenotypic variability in terms of severity and age of onset was noted. Given the limited number of genes tested, the diagnostic yield of the present panel compares favourably with studies in other European populations. Our study delineates the genetic and phenotypic variability of inherited axonal neuropathies in the Greek population and contributes to the pathogenicity characterization of further variants linked to axonal neuropathies.

Hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: The ADVANCE-CIDP 1 randomized controlled trial.

BACKGROUND AND AIMS: ADVANCE-CIDP 1 evaluated facilitated subcutaneous immunoglobulin (fSCIG; human immunoglobulin G 10% with recombinant human hyaluronidase) efficacy and safety in preventing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse. METHODS: ADVANCE-CIDP 1 was a phase 3, double-blind, placebo-controlled trial conducted at 54 sites in 21 countries. Eligible adults had definite or probable CIDP and adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores of 0-7 (inclusive), and received stable intravenous immunoglobulin (IVIG) for ≥12 weeks before screening. After stopping IVIG, patients were randomized 1:1 to fSCIG 10% or placebo for 6 months or until relapse/discontinuation. fSCIG 10% was administered at the same dose (or matching placebo volume) and interval as pre-randomization IVIG. The primary outcome was patient proportion experiencing CIDP relapse (≥1-point increase in adjusted INCAT score from pre-subcutaneous treatment baseline) in the modified intention-to-treat population. Secondary outcomes included time to relapse and safety endpoints. RESULTS: Overall, 132 patients (mean age 54.4 years, 56.1% male) received fSCIG 10% (n = 62) or placebo (n = 70). CIDP relapse was reduced with fSCIG 10% versus placebo (n = 6 [9.7%; 95% confidence interval 4.5%, 19.6%] vs n = 22 [31.4%; 21.8%, 43.0%], respectively; absolute difference: -21.8% [-34.5%, -7.9%], p = .0045). Relapse probability was higher with placebo versus fSCIG 10% over time (p = .002). Adverse events (AEs) were more frequent with fSCIG 10% (79.0% of patients) than placebo (57.1%), but severe (1.6% vs 8.6%) and serious AEs (3.2% vs 7.1%) were less common. INTERPRETATION: fSCIG 10% more effectively prevented CIDP relapse than placebo, supporting its potential use as maintenance CIDP treatment.

Autoantibody profile in myasthenia gravis patients with a refractory phase.

INTRODUCTION/AIMS: A subgroup of myasthenia gravis (MG) patients fail to respond adequately to recommended treatments, a condition referred to as refractory MG. During the refractory phase, patients experience persistent debilitating symptoms with potential life-threatening events or inability to reduce immunosuppressant dosages and minimize long-term toxicities. METHODS: We conducted a retrospective, single-center study of 113 MG patients to investigate the autoantibody profile and clinical characteristics of refractory MG patients, compared with nonrefractory patients, based on predefined criteria. RESULTS: Fifteen patients (13.3%) were classified as refractory. Double-seronegative MG (DSNMG), without detectable nicotinic acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) antibodies, was identified in six refractory patients, significantly higher than those with nonrefractory MG (40% vs 16.3%; P = .031). None of the refractory patients had MuSK antibodies. Patients in the refractory group more frequently had an earlier disease onset, thymic pathology, and thymectomy (P ≤. 03 for all). DISCUSSION: In this study, patients with refractory MG were more likely than those with nonrefractory MG to be DSN; and refractory DSNMG patients had worse MGFA classes in their recent visit compared with anti-AChR positive refractory patients. Refractory DSNMG patients may represent a distinct group that requires more individualized and targeted treatment approaches.

Man-in-a-barrel syndrome: a rare presentation of giant cell arteritis.

We present herein the case of a patient with brachial plexopathy, the first manifestation of giant cell arteritis (GCA). A 71-year-old woman presented with a subacute-onset weakness of her upper extremities; the patient had an initially good clinical response to steroid treatment. However, a few weeks after steroid discontinuation, she manifested fever and fatigue and increased serum markers consistent with a systemic inflammatory response. A PET-CT scan revealed an increased uptake in the subclavian arteries and a temporal biopsy was typical for GCA. Oral administration of high dosage steroids improved the patient's clinical symptoms and normalised her inflammatory serum markers.

Neurophysiological and ultrasonographic comparative study of autonomous nervous system in patients suffering from fibromyalgia and generalized anxiety disorder.

BACKGROUND: Fibromyalgia (FM) and generalized anxiety disorder (GAD) share common clinical features: they both affect women more than men, their diagnosis is based solely on clinical criteria, and some of the symptoms such as anxiety, aches and muscle tension, sleep disorders, and cognitive dysfunction occur in both diseases. For both conditions, an underlying dysregulation of the autonomic nervous system (ANS) has been proposed. OBJECTIVE: The aims of this study were to investigate ANS dysfunction in FM and GAD and compare them with controls. METHODS: Sympathetic skin response (SSR) from palm and sole and cross-sectional area (CSA) of bilateral vagus nerves (VN) were measured in 28 healthy controls, 21 FM patients, and 24 GAD patients. RESULTS: CSA of VN was significantly smaller in FM patients (right: 1.97 ± 0.74mm2, left: 1.75 ± 0.65 mm2) and GAD patients (right: 2.12 ± 0.97mm2, left: 1.71 ± 0.86 mm2) compared to controls (right: 3.21 ± 0.75 mm2, left: 2.65 ± 1.13 mm2, p < 0.001, but did not differ between the two patient groups. SSR parameters were similar between patients and controls. SSR latency correlated to clinical scales (FM Widespread Pain Index) in the FM group (r = 0.515, p = 0.02 and r = 0.447, p = 0.05) for the upper and lower limbs respectively, but no other correlation between clinical and neurophysiological parameters was identified. CONCLUSION: This study confirms similar ANS abnormalities in FM and GAD that fairly distinguish them from controls and support the hypothesis of a common pathophysiological substrate underlying both conditions.

Can Gait Features Help in Differentiating Parkinson's Disease Medication States and Severity Levels? A Machine Learning Approach.

Parkinson's disease (PD) is one of the most prevalent neurological diseases, described by complex clinical phenotypes. The manifestations of PD include both motor and non-motor symptoms. We constituted an experimental protocol for the assessment of PD motor signs of lower extremities. Using a pair of sensor insoles, data were recorded from PD patients, Elderly and Adult groups. Assessment of PD patients has been performed by neurologists specialized in movement disorders using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)-Part III: Motor Examination, on both ON and OFF medication states. Using as a reference point the quantified metrics of MDS-UPDRS-Part III, severity levels were explored by classifying normal, mild, moderate, and severe levels of PD. Elaborating the recorded gait data, 18 temporal and spatial characteristics have been extracted. Subsequently, feature selection techniques were applied to reveal the dominant features to be used for four classification tasks. Specifically, for identifying relations between the spatial and temporal gait features on: PD and non-PD groups; PD, Elderly and Adults groups; PD and ON/OFF medication states; MDS-UPDRS: Part III and PD severity levels. AdaBoost, Extra Trees, and Random Forest classifiers, were trained and tested. Results showed a recognition accuracy of 88%, 73% and 81% for, the PD and non-PD groups, PD-related medication states, and PD severity levels relevant to MDS-UPDRS: Part III ratings, respectively.

Effect of beam attenuation on muscle ultrasound echogenicity measurement in muscular dystrophies.

PURPOSE: In advanced muscular dystrophies (AMD), quantification of muscle echo-intensity (EI) may be influenced by ultrasound beam attenuation, due to fibrosis and fatty infiltration of muscle tissue. Objective of the study was to compare EI measurements using grayscale analysis between a superficial and whole-muscle region of interest (ROI) in subjects with advanced and mild-to-moderate muscular dystrophy (MMD). METHODS: Thirty-two adult subjects diagnosed with a muscular dystrophy and twenty-five matched healthy controls underwent ultrasound assessment of the biceps brachii (BB), rectus femoris (RF) and tibialis anterior (TA) muscles. Based on Heckmatt grading scale of muscles, two disease groups, an AMD (Heckmatt grades 3 or 4) and a MMD (Heckmatt grade 2), were analyzed. Superficial ROI was set as one-fourth of the whole-muscle area, located immediately below the superficial fascia and always inside muscle boundaries. RESULTS: Muscle EI was significantly higher in the superficial compared to whole-muscle ROI, in all evaluated muscle groups of AMD subjects (BB, p = 0.004/RF, p = 0.027/TA, p = 0.002). EI values in superficial ROIs, for individual muscle analysis using z-scores, were more representative in assessments of muscle abnormality in advanced stages of the disease course (Heckmatt grades 3 and 4). In MMD and healthy muscles, no statistical difference was found in EI measurements between the two ROI types. CONCLUSIONS: In AMD, selection of superficial ROI is better representative of changes in muscle texture, although caution should be exercised when comparing ROIs of different sizes.

A Greek National Cross-Sectional Study on Myotonic Dystrophies.

Myotonic Dystrophies (DM, Dystrophia Myotonia) are autosomal dominant inherited myopathies with a high prevalence across different ethnic regions. Despite some differences, mainly due to the pattern of muscle involvement and the age of onset, both forms, DM1 and DM2, share many clinical and genetic similarities. In this study, we retrospectively analyzed the medical record files of 561 Greek patients, 434 with DM1 and 127 with DM2 diagnosed in two large academic centers between 1994-2020. The mean age at onset of symptoms was 26.2 ± 15.3 years in DM1 versus 44.4 ± 17.0 years in DM2 patients, while the delay of diagnosis was 10 and 7 years for DM1 and DM2 patients, respectively. Muscle weakness was the first symptom in both types, while myotonia was more frequent in DM1 patients. Multisystemic involvement was detected in the great majority of patients, with cataracts being one of the most common extramuscular manifestations, even in the early stages of disease expression. In conclusion, the present work, despite some limitations arising from the retrospective collection of data, is the first record of a large number of Greek patients with myotonic dystrophy and emphasizes the need for specialized neuromuscular centers that can provide genetic counseling and a multidisciplinary approach.

Prevalence, clinical characteristics and outcomes of Guillain-Barré syndrome spectrum associated with COVID-19: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Mounting evidence supports an association between Guillain-Barré syndrome spectrum (GBSs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, GBSs in the setting of coronavirus disease 2019 (COVID-19) remains poorly characterized, whilst GBSs prevalence amongst COVID-19 patients has not been previously systematically evaluated using a meta-analytical approach. METHODS: A systematic review and meta-analysis of observational cohort and case series studies reporting on the occurrence, clinical characteristics and outcomes of patients with COVID-19-associated GBSs was performed. A random-effects model was used to calculate pooled estimates and odds ratios (ORs) with corresponding 95% confidence intervals (CIs), compared to non-COVID-19, contemporary or historical GBSs patients. RESULTS: Eighteen eligible studies (11 cohorts, seven case series) were identified including a total of 136,746 COVID-19 patients. Amongst COVID-19 patients, including hospitalized and non-hospitalized cases, the pooled GBSs prevalence was 0.15‰ (95% CI 0%-0.49‰; I2  = 96%). Compared with non-infected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds for demyelinating GBSs subtypes (OR 3.27, 95% CI 1.32%-8.09%; I2  = 0%). In SARS-CoV-2-infected patients, olfactory or concomitant cranial nerve involvement was noted in 41.4% (95% CI 3.5%-60.4%; I2  = 46%) and 42.8% (95% CI 32.8%-53%; I2  = 0%) of the patients, respectively. Clinical outcomes including in-hospital mortality were comparable between COVID-19 GBSs patients and non-infected contemporary or historical GBSs controls. CONCLUSION: GBSs prevalence was estimated at 15 cases per 100,000 SARS-CoV-2 infections. COVID-19 appears to be associated with an increased likelihood of GBSs and with demyelinating GBSs variants in particular.

Ultrasound pattern of anterolateral leg muscles in facioscapulohumeral muscular dystrophy.

BACKGROUND/AIMS OF STUDY: To evaluate the degree of tibialis anterior (TA) and peroneus longus (PL) muscle involvement in facioscapulohumeral muscular dystrophy (FSHD) patients using ultrasound. METHODS: We performed qualitative and quantitative assessments of muscle echogenicity, using Heckmatt's rating scale and gray scale analysis, respectively, in eight patients (five males, mean age 36.9 ± 8.4 years) with genetically confirmed FSHD 1. RESULTS: Both methods demonstrated a distinct pattern of preferential TA involvement and PL sparing in all FSHD patients, irrespective of the degree of muscle involvement. More specifically, echogenicity was higher in TA compared to PL according to Heckmatt score in the patient group (TA 3.43 ± 0.49/PL 1.43 ± 0.49, p < .001). In the gray-scale histogram, ranging from 0 (black) to 255 (white), the mean measurements of TA were significantly increased in patients compared to healthy (71.60 ± 10.28 vs. 53.70 ± 10.05, p = .012) and significantly higher than PL measurements in the patient group, but not in healthy subjects (p-values .012 and .779, respectively). A strong correlation between TA hyperechogenicity and muscle weakness was demonstrated in patients with mild-to-moderate weakness, but not in patients with severe weakness (r = -.949 and r = .644, respectively). CONCLUSIONS: This study shows a consistent US pattern of proximal anterolateral leg muscle involvement in FSHD, in agreement with findings of MRI studies and suggests that anterolateral leg muscle US may be a practical, fast and low-cost alternative to MRI.

Ischemia-Reperfusion Injury of Sciatic Nerve in Rats: Protective Role of Combination of Vitamin C with E and Tissue Plasminogen Activator.

An ischemia/reperfusion injury of rat's sciatic nerve was experimentally developed. In this model, we measured the in vivo production of superoxide radical, as a marker of oxidative stress and the occludin expression as an indicator of blood-nerve barrier function and we examined potential protective innervations against these abnormalities. Right sciatic nerves of the animals underwent 3 h of ischemia followed by 7 days of reperfusion and were divided into three groups: ischemic, pretreated with vitamin C in conjunction with vitamin E and treated with tissue plasminogen activator. Compared to measurements from left sciatic nerves used as sham, the ischemic group showed significantly increased superoxide radical and reduced expression of occludin in western blot and immunohistochemistry. No such differences were detected between sham and nerves in the vitamin or tissue plasminogen activator groups. It is suggested that the experimental ischemia/reperfusion model was suitable for studying the relationship between oxidative state and blood-nerve barrier. The reversion of abnormalities by the applied neuroprotective agents might prove to be a clinically important finding in view of the implication of vascular supply derangement in various neuropathies in humans.

Pure sensory chronic inflammatory polyneuropathy: rapid deterioration after steroid treatment.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) as a pure sensory variant is rarely encountered. Therefore the best treatment option is hard to define. CASE PRESENTATIONS: We reported two middle-aged patients of Caucasian origin, one female and one male, who over a period of several months presented limbs and gait ataxia. Clinical and neurophysiological examination revealed only sensory abnormalities. A diagnosis of atypical CIDP was suggested, considering the elevated CSF protein level and the presence of anti-gangliosides antibodies. Ten and 15 days respectively after initiation of prednisolone treatment both patients experienced exacerbation of sensory symptoms and emerging of muscle weakness. Steroids were then substituted by rituximab in the first patient and intravenous immunoglobulin in the second patient resulting in gradual decrement of symptoms and signs. Two-year follow-up showed no further deterioration. CONCLUSION: Caution should be exercised when treating cases of pure sensory polyneuropathy with high dose steroids since an unfavorable outcome is possible.