Nusinersen for adults with spinal muscular atrophy.

INTRODUCTION: Nusinersen was effective in improving motor function and survival in infantile and childhood-onset spinal muscular atrophy (SMA), and the value of real-world experiences in adult SMA patients increase gradually. Here, we present our clinical experience in adult SMA patients treated with nusinersen according to CHERISH study. MATERIAL AND METHODS: Thirty-two SMA patients treated with nusinersen were included in the study. RESULTS: Median age at nusinersen initiation was 33.5 (20.0-60.0) years and 23 of SMA patients were male. Six (18.8%) patients had SMA type 2, and 26 (81.2%) had SMA type 3. Median follow-up period of patients under nusinersen treatment was 17 months (9-21). Twenty-three patients improved by at least 3 Hammersmith Functional Motor Scale Expanded (HFMSE) points after loading doses. There was significant HFMSE score increase in type 3 patients at each time point, whereas type 2 patients seem to benefit from nusinersen loading doses, subsequently stayed stable. Motor improvement was positively correlated with baseline HFMSE scores in patients whose baseline HFMSE scores were ≤47. There was a correlation between the changes in Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) score and HFMSE scores. Ambulatory patients who could not show clinically meaningful increase in HFMSE scores improved at least 30 m by 6-min walk test (6MWT). CONCLUSION: Overall, 78% of patients have responded to treatment according to HFMSE or 6MWT. ALSFRS-R and 6MWT may be alternative tools to monitor nusinersen effect.

One Disease with two Faces: Semidominant Inheritance of a Novel HTRA1 Mutation in a Consanguineous Family.

OBJECTIVES: To identify the underlying genetic defect for a consanguineous family with an unusually high number of members affected by cerebral small vessel disease. MATERIALS AND METHODS: A total of 6 individuals, of whom 3 are severely affected, from the family were clinically and radiologically evaluated. SNP genotyping was performed in multiple members to demonstrate genome-wide runs-of-homozygosity. Coding variants in the most likely candidate gene, HTRA1 were explored by Sanger sequencing. Published HTRA1-related phenotypes were extensively reviewed to explore the effect of number of affected alleles on phenotypic expression. RESULTS: Genome-wide homozygosity mapping identified a 3.2 Mbp stretch on chromosome 10q26.3 where HTRA1 gene is located. HTRA1 sequencing revealed an evolutionarily conserved novel homozygous c.824C>T (p.Pro275Leu) mutation, affecting the serine protease domain of HtrA1. Early-onset of cognitive and motor deterioration in homozygotes are in consensus with CARASIL. However, there was a clear phenotypic variability between homozygotes which includes alopecia, a suggested hallmark of CARASIL. All heterozygotes, presenting as CADASIL type 2, had spinal disk degeneration and several neuroimaging findings, including leukoencephalopathy and microhemorrhage despite a lack of severe clinical presentation. CONCLUSION: Here, we clearly demonstrate that CARASIL and CADASIL type 2 are two clinical consequences of the same disorder with different severities thorough the evaluation of the largest collection of homozygotes and heterozygotes segregating in a family. Considering the semi-dominant inheritance of HTRA1-related phenotypes, genetic testing and clinical follow-up must be offered for all members of a family with HTRA1 mutations regardless of symptoms.

The altered expression of perineuronal net elements during neural differentiation.

BACKGROUND: Perineuronal nets (PNNs), which are localized around neurons during development, are specialized forms of neural extracellular matrix with neuroprotective and plasticity-regulating roles. Hyaluronan and proteoglycan link protein 1 (HAPLN1), tenascin-R (TNR) and aggrecan (ACAN) are key elements of PNNs. In diseases characterized by neuritogenesis defects, the expression of these proteins is known to be downregulated, suggesting that PNNs may have a role in neural differentiation. METHODS: In this study, the mRNA and protein levels of HAPLN1, TNR and ACAN were determined and compared at specific time points of neural differentiation. We used PC12 cells as the in vitro model because they reflect this developmental process. RESULTS: On day 7, the HAPLN1 mRNA level showed a 2.9-fold increase compared to the non-differentiated state. However, the cellular HAPLN1 protein level showed a decrease, indicating that the protein may have roles in neural differentiation, and may be secreted during the early period of differentiation. By contrast, TNR mRNA and protein levels remained unchanged, and the amount of cellular ACAN protein showed a 3.7-fold increase at day 7. These results suggest that ACAN may be secreted after day 7, possibly due to its large amount of post-translational modifications. CONCLUSIONS: Our results provide preliminary data on the expression of PNN elements during neural differentiation. Further investigations will be performed on the role of these elements in neurological disease models.

Transcript levels of plastin 3 and neuritin 1 modifier genes in spinal muscular atrophy siblings.

BACKGROUND: In single gene disorders, patients with the same genotype may have variations in severity. One of the main factors affecting disease severity is modifier genes. Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by degeneration of alpha motor neurons. Plastin 3 (PLS3) is a phenotypic modifier of SMA, and neuritin 1 (NRN1) has also been suggested as a possible modifier gene. The aim of the present study was therefore to analyze PLS3 and NRN1 expression in SMA siblings in four families. METHODS: The study group consisted of four SMA families with seven with discordant phenotype and two affected siblings. Total RNA was isolated from whole blood. PLS3 and NRN1 expression was analyzed on quantitative real-time polymerase chain reaction. RESULTS: In family 1 only NRN1 expression was increased in the mildly affected sister. In family 2 only PLS3 had a modifier effect. Family 3, which had type III siblings with identical clinical phenotypes, had similar PLS3 expression between the siblings but no NRN1 expression. In family 4, neither PLS3 nor NRN1 had any correlation with severity. CONCLUSION: On analysis of the expression of NRN1 in SMA patients for the first time, NRN1 could be a potential modifier gene. PLS3 expression does not always modify SMA phenotype. In patients with no modifier effect of known genes, genome sequencing and transcriptome analysis are promising for the identification of novel modifiers and understanding of SMA pathophysiology.

Fulminant Central Plus Peripheral Nervous System Demyelination without Antibodies to Neurofascin.

BACKGROUND: Combined central and peripheral nervous system demyelination is a rare and poorly described phenomenon. Recently, anti-neurofascin antibodies were reported to be positive in 86% of these patients in a Japanese cohort. Yet, there seems to be a clinical, radiological, and serological heterogeneity among these patients. In this report, our aim is to describe characteristics of our patients with this entity and compare with others in the literature. METHODS: We report clinical, electrophysiological, radiological, and laboratory characteristics of five patients with both multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy from our institutional database containing 1890 MS patients. RESULTS: Three patients presented with extensive, active demyelination of both central nervous system and peripheral nervous system with hypertrophic peripheral nerves. Plexuses, trunks, division and cords were involved in the process. Oligoclonal band was negative. Conduction block was not detected. Corticosteroid treatment was not adequate. Others had a slowly progressive clinical course. Serum anti-neurofascin antibody was negative. Review of the literature revealed similar cases with active disease, early-onset hypertrophic peripheral nerves, and central demyelination, in addition to other cases with an insidious course. CONCLUSIONS: Patients with combined central and peripheral demyelination form a spectrum. Some patients may have an antibody-mediated syndrome with or without anti-neurofascin antibodies and others seem to represent a coincidence.

A novel desmin mutation leading to autosomal recessive limb-girdle muscular dystrophy: distinct histopathological outcomes compared with desminopathies.

BACKGROUND: Autosomal recessive limb girdle muscular dystrophy (LGMD2) is a heterogeneous group of myopathies characterised by progressive muscle weakness involving proximal muscles of the shoulder and pelvic girdles including at least 17 different genetic entities. Additional loci have yet to be identified as there are families which are unlinked to any of the known loci. Here we have investigated a consanguineous family with LGMD2 with two affected individuals in order to identify the causative gene defect. METHODS AND RESULTS: We performed genome wide homozygosity mapping and mapped the LGMD2 phenotype to chromosome 2q35-q36.3. DNA sequence analysis of the highly relevant candidate gene DES revealed a homozygous splice site mutation c.1289-2A>G in the two affected family members. Immunofluorescent staining and western blot analysis showed that the expression and the cytoskeletal network formation of mutant desmin were well preserved in skeletal muscle fibres. Unlike autosomal dominant desminopathies, ultrastructural alterations such as disruption of myofibrillar organisation, formation of myofibrillar degradation products and dislocation/aggregation of membranous organelles were not present. This novel splice site mutation results in addition of 16 amino acids within the tail domain of desmin, which has been suggested to interact with lamin B protein. We also detected a specific disruption of desmin-lamin B interaction in the skeletal muscle of the patient by confocal laser scanning microscopy. CONCLUSIONS: Our study reveals that autosomal recessive mutations in DES cause LGMD2 phenotype without features of myofibrillar myopathy.

The course of myasthenia gravis with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is one of the autoimmune diseases, which is rarely reported with Myasthenia Gravis (MG). In the literature, the clinical features of MG in these patients were not mentioned in detail. Here, we want to present our five patients with MG and SLE. METHODS: Between 2000 and 2010, 132 MG patients were evaluated and have been followed up in our institution. Five patients had MG with SLE and eleven patients had antinuclear antibody (ANA) positivity without SLE symptoms. The clinical, laboratory findings and treatment responses were reviewed. RESULTS: All patients had generalized MG and four of five patients experienced at least one myasthenic crisis. The response to corticosteroid was poor; consequently, they needed immunosuppressive treatments, IVIg or plasmapheresis. Although in the literature thymectomy was accused of the precipitation of SLE, in our series SLE symptoms preceded thymectomy. CONCLUSION: We would like to point out that MG and SLE being two autoimmune diseases may coexist. This coexistence might cause a more severe myasthenic course compared to MG alone; therefore, these patients need a close and frequent follow-up.

Differentiating recurrent Guillain-Barre syndrome and acute-onset chronic inflammatory polyneuropathy: literature review.

Guillain-Barre syndrome (GBS) is an acute-onset immune-mediated polyneuropathy characterized by ascending symmetrical muscle weakness, diminished reflexes, and sensory symptoms. While GBS typically follows a monophasic course, some patients experience treatment-related fluctuations or recurrences, posing diagnostic challenges in distinguishing GBS from acute-onset chronic inflammatory polyneuropathy (A-CIDP). A-CIDP, may present acutely, simulating GBS, with a nadir in less than 8 weeks, subsequently evolving into a chronic or relapsing course. The distinction between recurrent GBS and A-CIDP is crucial, as A-CIDP necessitates long-term immunosuppression. A PubMed search was conducted using the search terms 'recurrent Guillain Barre syndrome' and 'acute onset CIDP' focusing on studies in the English language, published between January 1, 2004 and April 30, 2023. Overlapping clinical features, particularly in the early stages, complicate differentiation between recurrent GBS and CIDP. Electrophysiological studies, ultrasonography, and immunological markers have been explored for discrimination; however, definitive criteria for differentiation remain elusive. Recent follow-up studies have further blurred the boundaries between recurrent GBS and A-CIDP, suggesting the persistence of underlying immune processes even in GBS patients without clinical deterioration. This emphasizes the necessity of reevaluating diagnostic criteria and treatment strategies. In conclusion, distinguishing recurrent GBS from A-CIDP remains an ongoing challenge. Existing evidence questions the categorization of recurrent GBS as a distinct entity, challenging its very existence. Continued research is necessary to refine diagnostic criteria and deepen our understanding of these conditions, ultimately advancing patient care. This review delves into the intricacies of recurrent GBS and A-CIDP differentiation and highlights the need for a reevaluation of the recurrent GBS concept.

The evaluation of small fibers in multiple sclerosis.

BACKGROUND: Dysesthetic or ongoing extremity pain is a common symptom in all multiple sclerosis (MS) types. Although the pathology of the disease is the demyelination of central neurons, the patients may also complain of neuropathic pain in distal extremities that is generally related to A-delta and C fiber dysfunction. It is not known whether thinly myelinated and unmyelinated fibers are affected in MS patients. We aim to investigate the small fiber loss and its length dependency. METHODS: We evaluated the skin biopsy taken from proximal and distal leg of MS patients with neuropathic pain. Six patients with primary progressive MS (PPMS), seven with relapsing-remitting MS (RRMS), seven with secondary progressive MS (SPMS) and as a control group ten age and sex-matched healthy controls were included. Neurological examination, electrophysiological evaluation and DN4 questionnaire were performed. Subsequently, skin punch biopsy from 10 cm above the lateral malleolus and proximal thigh were done. The biopsy samples were stained with PGP9.5 antibody and intraepidermal nerve fiber density (IENFD) was determined. RESULTS: The mean proximal IENFD was 8.58±3.58 fibers/mm among MS patients and 14.72±2.89 fiber/mm among healthy controls (p=0.001). However, the mean distal IENFD did not differ between MS patients and healthy controls (9.26±3.24 and 9.75±1.6 fiber/mm respectively. Although proximal and distal IENFD tends to be lower in MS patients with neuropathic pain, there was no statistically significant difference between MS patients with and without neuropathic pain CONCLUSION: Although MS is a demyelinating disease, unmyelinated fibers can also be affected. Our findings suggest non-length dependent small fiber neuropathy in MS patients.

Expert opinion on the diagnostic odyssey and management of late-onset Pompe disease: a neurologist's perspective.

This consensus statement by a panel of neurology experts aimed to provide a practical and implementable guidance document to assist clinicians with the best clinical practice in terms of diagnosis, treatment, and monitoring of late-onset Pompe disease (LOPD). The participating experts consider the clinical suspicion of LOPD by the physician to be of utmost importance in the prevention of diagnostic and therapeutic delay in LOPD patients. A diagnostic algorithm is proposed to facilitate the diagnosis of LOPD in patients presenting with unexplained proximal/axial weakness (with or without respiratory symptoms) or restrictive respiratory insufficiency with hyperCKemia and/or exercise intolerance as the red flag symptoms/signs that raise the index of suspicion for LOPD diagnosis. The diagnosis is based on the subsequent use of dried blood spot (DBS) assay, and the DBS assay can be confirmed by acid alpha-glucosidase (GAA) tissue analysis in leukocytes, fibroblasts, or muscle fibers and/or genetic mutation analysis. Accordingly, experts consider increased awareness among physicians about potential presenting characteristics with a high index of suspicion for LOPD to be crucial to suspect and consider LOPD in the differential diagnosis, while strongly suggesting the use of a diagnostic algorithm combined with DBS assay and confirmatory tests in the timely diagnosis of LOPD and implementation of best practice patterns.

Efficacy and Safety of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease After 97 Weeks: A Phase 3 Randomized Clinical Trial.

Importance: In the previously reported Comparative Enzyme Replacement Trial With neoGAA Versus rhGAA (COMET) trial, avalglucosidase alfa treatment for 49 weeks showed clinically meaningful improvements in upright forced vital capacity (FVC) percent predicted and 6-minute walk test (6MWT) compared with alglucosidase alfa. Objective: To report avalglucosidase alfa treatment outcomes during the COMET trial extension. Design, Setting, and Participants: This phase 3 double-blind randomized clinical trial with crossover in the extension period enrolled patients 3 years and older with previously untreated late-onset Pompe disease (LOPD) between November 2, 2016, and February 10, 2021, with primary analysis after 49 weeks. Patients were treated at 55 referral centers in 20 countries. Efficacy outcomes were assessed at 97 weeks and safety outcomes to last follow-up, with data cutoff at February 10, 2021. Data were analyzed from May to June 2021. Interventions: Random assignment (1:1) to receive 20 mg/kg of avalglucosidase alfa or alglucosidase alfa by intravenous infusion every other week for 49 weeks; thereafter, all patients received 20 mg/kg of avalglucosidase alfa every other week. Main Outcomes and Measures: The primary outcome was the least squares (LS) mean change from baseline in FVC percent predicted. Secondary outcomes included the LS mean change from baseline in 6MWT, muscle strength, motor function, quality of life, and disease biomarkers. Safety and tolerability were also assessed. Results: Of 100 participants from the double-blind treatment period, 95 entered the extension period. Of these, 51 (54%) were men, and the mean (range) age was 48.3 (10-79) years. At the start of this study, mean upright FVC percent predicted was similar between treatment arms, and 6MWT distance was greater in the avalglucosidase alfa arm. From baseline to week 97, LS mean (SE) FVC percent predicted increased by 2.65 (1.05) for those who continued avalglucosidase alfa and 0.36 (1.12) for those who switched to avalglucosidase alfa. The LS mean (SE) 6MWT distance increased by 18.60 (12.01) m and 4.56 (12.44) m, respectively. For participants who switched to avalglucosidase alfa, FVC percent predicted remained stable (LS mean [SE] change from week 49 to 97, 0.09 [0.88]) and 6MWT distance improved (LS mean [SE] change from week 49 to 97, 5.33 [10.81] m). Potentially treatment-related adverse events were reported in 29 patients (56.9%) who continued avalglucosidase alfa and in 25 patients (56.8%) who switched. Conclusions and Relevance: In this randomized clinical trial extension, maintenance of positive clinical outcomes was demonstrated for patients continuing avalglucosidase alfa treatment and, to a lesser extent, patients who switched from alglucosidase alfa. No new safety concerns were observed. Trial Registration: ClinicalTrials.gov Identifier: NCT02782741.

Diabetic muscular infarct: an unusual cause of extremity pain and dysfunction.

Diabetic muscular infarct (DMI) is a rare condition, which begins with acute onset of extremity pain and swelling. Patients usually have long-standing disease and poorly controlled diabetes mellitus (DM). Thigh muscle group is the most commonly involved side, while lower leg involvement is rare. We represent herein a 22-year-old patient with type I DM who admitted to our outpatient clinic due to painful swelling of the left leg. In physical examination, anterior left leg was painful and firm on palpation; there was diffuse swelling extending to the knee and ankle with mild local fever and redness. T2-weighted MRI demonstrated hyperintensity in left leg muscles. A biopsy confirmed the diagnosis of DMI. She was treated with glucose regulation, analgesics, antiplatelet treatment and rest. At her 6 months, recurrence of DMI was observed. DMI should be considered in diabetic patients with extremity pain and swelling. Treatment plan should include the regulation of the blood glucose and evaluation of end-organ complications, analgesia, and bed rest.

Two distinct skeletal muscle microRNA signatures revealing the complex mechanism of sporadic ALS.

Skeletal muscle pathology is thought to have an important role in the onset and/or progression of amyotrophic lateral sclerosis (ALS), which is a neurodegenerative disorder characterized by progressive muscle weakness. Since miRNAs are recognized as important regulatory factors of essential biological processes, we aimed to identify differentially expressed miRNAs in the skeletal muscle of sporadic ALS patients through the combination of molecular-omic technologies and bioinformatic tools. We analyzed the miRnome profiles of skeletal muscle biopsies acquired from ten sALS patients and five controls with Affymetrix GeneChip miRNA 4.0 Array. To find out differentially expressed miRNAs in patients, data were analyzed by The Institute for Genomic Research-Multi Experiment Viewer (MeV) and miRNAs whose expression difference were statistically significant were identified as candidates. The potential target genes of these miRNAs were predicted by miRWalk 2.0 and were functionally enriched by gene ontology (GO) analysis. The expression level of priority candidates was validated by quantitative real-time PCR (qRT-PCR) analysis. We identified ten differentially expressed miRNAs in patients with a fold change threshold ≥ 2.0, FDR = 0. We identified ten differentially expressed miRNAs in patients with a fold change threshold ≥ 2.0, FDR = 0. Nine out of the ten miRNAs were found to be related to top three enriched ALS-related terms. Based on the qRT-PCR validation of candidate miRNAs, patients were separated into two groups: those with upregulated miR-4429 and miR-1825 expression and those with downregulated miR-638 expression. The different muscle-specific miRNA profiles in sALS patients may indicate the involvement of etiologic heterogeneity, which may allow the development of novel therapeutic strategies.

Multimodal assessment of intensive care unit-acquired weakness in severe stroke patients.

BACKGROUND: Intensive care unit-acquired weakness (ICUAW) defines generalized muscle weakness seen in critically ill patients in the absence of other causative factors. Herein, we aimed to evaluate ICUAW in stroke patients by electrodiagnostic testing, histopathology, and assessment of respiratory complex activities (RCA), to define the frequency of ICUAW in this patient group, and to reach new parameters for early prediction and diagnosis. METHODS: We prospectively recruited twenty-four severe acute stroke patients during a sixteen-month period. In addition to serial nerve conduction studies (NCS), we performed muscle biopsy and RCA analysis on the non-paretic side when ICUAW developed. Patients undergoing orthopedic surgery without metabolic and neuromuscular diseases constituted the control group for RCA. Survival and longitudinal data were analyzed by joint modeling to determine the relationship between electrophysiological parameters and ICUAW diagnosis. RESULTS: Eight patients (33%) developed ICUAW, and six of them within the first two weeks. Extensor digitorum brevis, abductor digiti minimi (ADM), rectus femoris and vastus medialis (VM) compound muscle action potential (CMAP) amplitudes showed a significant decrease in the ICUAW group. VM CMAP amplitude (BIC = 358.1574) and ADM CMAP duration (BIC = 361.1028) were the best-correlated parameters with ICUAW diagnosis. The most informative electrophysiological findings during the entire study were obtained within the first 11 days. Muscle biopsies revealed varying degrees of type 2 fiber atrophy. Complex I (p = 0.003) and IV (p = 0.018) activities decreased in patients with ICUAW compared to controls. CONCLUSION: VM CMAP amplitude and ADM CMAP duration correlate well with ICUAW diagnosis, and may aid in the early diagnosis.

The functional and structural evaluation of small fibers in asymptomatic carriers of TTR p.Val50Met (Val30Met) mutation.

Therapeutic advances in hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy extended life expectancy and delayed symptom progression especially in patients with early disease. Thus, detection and monitoring of asymptomatic carriers gained importance. However, there is still limited consensus on genetic screening of ATTRv-polyneuropathy patients' family members and diagnostic tests that must be done in the follow-up. In this study, we followed prospectively five asymptomatic carriers of a family with ATTRV30M (p.Val50Met) mutation by different diagnostic tests for three years. The carriers were followed by neurological examination, nerve conduction studies, sympathetic skin response test, heart rate variability, SFN-SIQ and DN4 questionnaires, quantitative sensory testing (QST), skin biopsy and in vivo corneal confocal microscopy. Nerve conduction studies, sympathetic skin response test and heart rate variability were normal in all for three years. Baseline QST and SFN-SIQ were normal but became abnormal during follow-up of two individuals who developed small fiber neuropathy symptoms. Baseline intraepidermal nerve fiber density was low in three carriers and decreased to below normative values in all during follow-up, while corneal sub-basal nerve density was low in all carriers compared to controls during the entire follow-up. Thus, our study showed that SFN-SIQ and QST are useful diagnostic tools to detect the transition to symptomatic ATTRv-polyneuropathy.

The effects of spinal stabilization exercises in patients with myasthenia gravis: a randomized crossover study.

PURPOSE: The effects of spinal stabilization exercises (SSE) on fatigue, muscle strength, respiratory functions, functional capacity, and quality of life (QoL) in myasthenia gravis (MG) patients were investigated. MATERIALS AND METHODS: This study which was designed a single-blinded, randomized crossover trial were included mild to moderate 10 MG patients, aged between 18 and 65. SSE and home program were applied to the patients for six weeks, four weeks between each exercise program. Fatigue assessed with Fatigue Severity Scale (FSS) and Visual Analog Fatigue Scale (VAFS). Muscle strengths were assessed with dynamometric measures. Respiratory Function Test, 6 Minute Walk Test (6MWT), Quantitative Myasthenia Gravis Score (QMGS), Myasthenia Gravis Quality of Life Scale-15 (MGQOL-15) were used. RESULTS: All parameters were improved in SSE group, but not neck muscles strength, QMGS, and respiratory functions in home program group. FSS, VAFS, muscle strength, 6MWT, MGQOL-15 values were found significantly different in SSE group (p = .005 in all parameters). CONCLUSIONS: SSE are safe and effective on fatigue, muscle strength, respiratory functions, functional capacity, and QoL for MG patients, so it may be suggested to include SSE in rehabilitation programs of MG patients.Implications For RehabilitationSpinal stabilization exercises are safe and effective for Myasthenia Gravis patients.Home exercise program which included breathing exercises and callisthenic exercises tailored to the patients' needs is safe and effective for Myasthenia Gravis patients.Rehabilitation programs of Myasthenia Gravis patients should include spinal stabilization exercises.

Overexpression of amyloid beta precursor protein enhances expression and secretion of ST6Gal1 in C2C12 myogenic cell line.

The Abeta (amyloid-beta) peptide is derived from the sequential cleavage of AbetaPP (amyloid-beta precursor protein) by two enzymes, the ß- and γ-secretases. The major ß-secretase, identified as the novel transmembrane aspartic protease BACE1 (beta site APP-cleaving enzyme 1), mediates the primary amyloidogenic cleavage of AbetaPP and initiates the production of Abeta. It has been implicated in the proteolytic processing of another substrate, namely ST6Gal1 (ß galactoside α2,6-sialyltransferase 1), which is the major α2,6-sialyltransferase responsible for the broad synthesis of glycoproteins and glycolipids. The present study investigated the effect of overexpression of AbetaPP on expression and secretion of ST6Gal1 in skeletal muscle cells by inducing overexpression of wild-type full-length 751-AbetaPP in the mouse myogenic cell line C2C12. Expression and secretion of the ST6Gal1 enzyme were analysed by Western blot and/or immunofluorescence staining. The results of our study demonstrated that AbetaPP overexpression in C2C12 cells increased the expression and the secretion of ST6Gal1 enzyme in vitro.

Toscana virus associated with Guillain-Barré syndrome: a case-control study.

Guillain-Barré syndrome (GBS) is an acute-onset, immune-mediated polyradiculoneuropathy, often precipitated by an antecedent infection. An association of GBS with vector-borne viral infections has been suggested, with evidence for the involvement of Zika, Dengue, Chikungunya and West Nile virus (WNV). This prospective case-control study was conducted to identify vector-borne viral infections in GBS. Thirteen individuals newly diagnosed as GBS were enrolled. Disease severity, prognostic factors and nerve conduction patterns were assessed. Eleven individuals with non-infectious conditions requiring cerebrospinal fluid (CSF) analysis were included as controls. Plasma, CSF and urine specimens were evaluated via nucleic acid amplification assays aimed to detect a broad spectrum of viruses. WNV and Toscana virus (TOSV) IgM/IgG antibodies were screened using commercial immunofluorescence assays and confirmed via virus neutralization tests (VNT). Partial TOSV nucleocapsid and genotype 1 polymerase sequences were detected in CSF of a patient with normal pressure hydrocephalus. Two control subjects had VNT-confirmed TOSV IgM in plasma. VNT-confirmed WNV and TOSV IgG were detected in 15.4% and 61.5% of GBS patients, respectively. Variations in WNV IgG and TOSV IgM detection rates were not statistically significant among study cohorts. However, TOSV IgG was significantly more frequent in GBS patients. No difference was observed for disease form or prognostic scores for virus markers. Follow-up serological profiles were identical to the initial findings. We have identified TOSV as a potential precipitating agent in GBS, with some rare clinical presentations of symptomatic TOSV infections.

Neuropathic Pain Frequency in Neurology Outpatients: A Multicenter Study.

INTRODUCTION: Neuropathic pain is common, but the frequency of misdiagnosis and irrational treatment is high. The aim of this study is to evaluate the rate of neuropathic pain in neurology outpatient clinics by using valid and reliable scales and review the treatments of patients. METHODS: The study was conducted for 3 months in eleven tertiary health care facilities. All outpatients were asked about neuropathic pain symptoms. Patients with previous neuropathic pain diagnosis or who have neuropathic pain symptoms were included and asked to fill painDETECT and douleur neuropathic en 4 questions (DN4) questionnaire. Patients whose DN4 score is higher than 3 and/or painDETECT score higher than 13 and/or who are on drugs for neuropathic pain were considered patients with neuropathic pain. The frequency of neuropathic pain was calculated and the treatments of patients with neuropathic pain were recorded. RESULTS: Neuropathic pain frequency was 2.7% (95% CI: 1.5-4.9). The most common cause was diabetic neuropathy. According to painDETECT, the mean overall pain intensity was 5.7±2.4, being lower among patients receiving treatment. Pharmacological neuropathic pain treatment was used by 72.8% of patients and the most common drug was pregabalin. However, 70% of those receiving gabapentinoids were using ineffective doses. Besides, 4.6% of the patients were on medications which are not listed in neuropathic pain treatment guidelines. CONCLUSION: In our cohort, the neuropathic pain severity was moderate and the frequency was lower than the literature. Although there are many guidelines, high proportion of patients were being treated by ineffective dosages or irrational treatments.

Reliability and Validity of Turkish Myasthenia Gravis-Activities of Daily Living Scale.

Linguistic, reliable, and valid secondary efficacy measures are important in clinical settings and studies. The aim of the study is to report test-retest reliability and construct validity of Turkish version of Myasthenia Gravis-Activities of Daily Living Scale (MG-ADL-T) in Myasthenia Gravis (MG) patients. Fifty-two ocular and generalized individuals with MG, applying to rehabilitation center, were included in the study. MG-ADL-T, MG quality-of-life questionnaire (MG-QoL), MG composite (MGC), quantitative MG score (QMGS), and pulmonary function test were administered. Reliability was assessed with intraclass correlation coefficient (ICC) and Cronbach's alpha. Spearman correlation test and receiver operating characteristic (ROC) analysis were performed for construct validity. MG-ADL-T had fair internal consistency (Cronbach's α = .67), excellent test-retest reliability (ICC = 0.96) and moderate construct validity (MG-QoL, r = 0.59; QMGS, r = .58; MGC, r = .68). MG-ADL, a unique scale that evaluates activities of daily living (ADL), has good test-retest reliability and construct validity in Turkish MG patients.