Effect of Follicular T Helper and T Helper 17 Cells-Related Molecules on Disease Severity in Patients with Myasthenia Gravis.

INTRODUCTION: Contribution of T helper 1 and 2 cells-related cytokines to pathogenesis of myasthenia gravis (MG) is well known. Recently, the contribution of follicular T helper (Tfh) and T helper 17 cells-related molecules to the pathogenesis has gained importance. In this study, we aimed to evaluate the changes in Tfh- and Th17-related molecules before and after rescue therapy in patients with myasthenic crisis (cMG) and to reveal the molecular differences between stable MG and cMG patients. METHODS: Patients with stable generalized MG (gMG) and cMG were classified according to Myasthenia Gravis Foundation of America (MGFA) classification. Serum samples were collected from cMG patients both before and after rescue therapy (plasmapheresis or intravenous immunoglobulin [IVIg]). Serum levels of Tfh- and selected Th17-related molecules (IL-22, IL-17A, CXCL13, sPD-L1, sICOSLG, and sCD40L) were analyzed by commercial ELISA kits. RESULTS: Twelve cMG (6 for IVIg, 6 for plasmapheresis) and 10 gMG patients were included in the study. A decrease in serum sPD-L1 and CXCL13 levels was observed in cMG patients after treatment, regardless of the treatment modality (p < 0.05). In contrast, serum sICOSLG levels decreased only in patients treated with IVIg (p < 0.05) and serum IL-22 levels increased in patients receiving plasmapheresis (p < 0.05). cMG patients had higher serum IL-17A levels compared to stable patients (p < 0.001) and its level was positively correlated with disease severity (r = 0.678, p = 0.001). CONCLUSION: Our results confirm the contribution of Tfh- and Th17-related cell pathways to MG pathogenesis. Both IVIg and plasmapheresis appear to be effective in reducing Tfh- and Th17-related cytokine/molecule levels in cMG patients. Increased serum IL-17A levels may contribute to disease severity.

Recurrent simultaneous central nervous system demyelination with possible peripheral demyelination / nodopathy in a seronegative patient.

Combined central and peripheral demyelination (CCPD) is a rare disease entity. Onset with the simultaneous central nervous system (CNS) and peripheral nervous system (PNS) involvement and its recurrence are exceptional. Anti-neurofascin antibodies have been shown to be present in up to 70% of cases, yet seronegative patients also exist. We present a case of seronegative recurrent CCPD. The PNS involvement was compatible with two episodes of recurrent Guillain-Barre syndrome (GBS), whereas the CNS involvement pattern was not typical for either multiple sclerosis (MS) or acute disseminated encephalomyelitis. The prognosis was excellent with pulse methylprednisolone, intravenous immunoglobulin, and plasmapheresis. This case highlights the varied clinical presentations of CCPD, extending beyond the realms of MS and chronic inflammatory demyelinating polyneuropathy, and underscores the potential for relapse. Importantly, to the best of our knowledge, this represents the inaugural instance of CCPD featuring PNS involvement in the form of recurrent GBS.

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.

Patient with recurrent neuralgic amyotrophy; right brachial plexitis and left posterior interosseous neuropathy.

Neuralgic amyotrophy (NA), also known as Parsonage-Turner syndrome or idiopathic brachial plexopathy, is a multifocal inflammatory neuropathy that usually affects the upper limbs. The classic picture is a patient with acute onset of asymmetric upper extremity symptoms, excruciating pain, rapid onset of multifocal paresis often involving winged scapula, and a monophasic course of the disease. 
We present an unusual case of recurrent NA characterized first by right brachial plexitis and then isolated left posterior interosseous nerve palsy. 

Revisiting the complex architecture of ALS in Turkey: Expanding genotypes, shared phenotypes, molecular networks, and a public variant database.

The last decade has proven that amyotrophic lateral sclerosis (ALS) is clinically and genetically heterogeneous, and that the genetic component in sporadic cases might be stronger than expected. This study investigates 1,200 patients to revisit ALS in the ethnically heterogeneous yet inbred Turkish population. Familial ALS (fALS) accounts for 20% of our cases. The rates of consanguinity are 30% in fALS and 23% in sporadic ALS (sALS). Major ALS genes explained the disease cause in only 35% of fALS, as compared with ~70% in Europe and North America. Whole exome sequencing resulted in a discovery rate of 42% (53/127). Whole genome analyses in 623 sALS cases and 142 population controls, sequenced within Project MinE, revealed well-established fALS gene variants, solidifying the concept of incomplete penetrance in ALS. Genome-wide association studies (GWAS) with whole genome sequencing data did not indicate a new risk locus. Coupling GWAS with a coexpression network of disease-associated candidates, points to a significant enrichment for cell cycle- and division-related genes. Within this network, literature text-mining highlights DECR1, ATL1, HDAC2, GEMIN4, and HNRNPA3 as important genes. Finally, information on ALS-related gene variants in the Turkish cohort sequenced within Project MinE was compiled in the GeNDAL variant browser (www.gendal.org).

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.

The effects of electrical stimulation and exercise therapy in patients with limb girdle muscular dystrophy. A controlled clinical trial.

OBJECTIVE: To evaluate and compare the effects of exercise therapy and electrical stimulation on muscle strength and functional activities in patients with limb-girdle muscular dystrophy (LGMD). METHODS: This controlled clinical trial included 24 subjects who were diagnosed with LGMD by the Neurology Department of the Hacettepe University Hospital, Ankara, Turkey and were referred to the Physical Therapy Department between May 2013 and December 2014. Subjects were enrolled into an electrical stimulation (11 patients) group, or an exercise therapy (13 patients) group. RESULTS: The mean age of patients was 31.62 years in the electrical stimulation group, and 30.14 years in the exercise therapy group. The most important results in this controlled clinical study were that the muscle strength in both groups was significantly decreased and post-treatment evaluation results indicated that muscle strength of the Deltoideus was higher in the electrical stimulation group, and the difference between the groups was maintained in the follow-up period (p<0.05). However, the muscle strength of quadriceps was similar in both groups, according to the post-treatment and follow-up evaluation results (p>0.05). Additionally, the electrical stimulation group presented more obvious overall improvements than the exercise therapy group according to muscle strength, endurance, and timed performance tests. CONCLUSION: Since no definitive treatments currently exist for patients with LGMD, these results provide important information on the role of exercise therapy and electrical stimulation for clinicians working in rehabilitation.

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.

Clinical and laboratory remission with rituximab in anti-MuSK-positive myasthenia gravis.

BACKGROUND: Increasing data are available on the use and efficacy of rituximab (RTX) in patients with anti-muscle-specific tyrosine kinase (MuSK)-positive myasthenia gravis (MG), especially those steroid-dependent or unresponsive to traditional immunotherapies. AIMS: We aimed to evaluate the clinical characteristics and treatment responses of adult patients with generalized anti-MuSK-positive MG treated with RTX. METHODS: We retrospectively recruited 16 patients who were on RTX, between January 2010 and September 2023. RTX was given 1000 mg/day intravenously twice, two weeks apart. Maintenance treatment was administered at intervals of 3-6 months based on clinical evaluation. The outcome was assessed by Myasthenia Gravis Foundation of America (MGFA) and Myasthenia Gravis Status and Treatment Intensity (MGSTI) scores. Additionally, anti-MuSK antibody levels were retested after treatment in all patients except one. RESULTS: Twelve patients were female. The mean age at disease onset was 35.3 ± 17.3 years. The median duration between disease onset and RTX administration was 2.4 years (min-max: 0.5-36.5 years). The worst MGFA class before RTX was between IIIb-V. After RTX treatment, 81.3% of patients achieved MGFA minimal manifestations or better and MGSTI level 1 or better. Anti-MuSK antibodies became negative in 12 patients, while they remained positive in three. The changes in antibody levels seemed associated with clinical outcomes. CONCLUSIONS: RTX is an effective treatment in anti-MuSK-positive MG. Furthermore, our results support the inhibition of antibody production by RTX and we recommend monitoring anti-MuSK antibody titers to follow disease progression and treatment response.

Immunotherapy Provides Electrophysiological Recovery and Excellent Clinical Response in Sjogren's Syndrome-Linked Quite Severe Autonomic Neuropathy.

INTRODUCTION: The autonomic system is frequently affected in Sjogren's syndrome (SS), but presentation with severe autonomic neuropathy is infrequent. Herein, we present a patient with primary SS-linked autonomic neuropathy, which is significantly clinic and electrophysiological responsive to immunotherapy. CASE REPORT: A 29-year-old female patient was admitted to our neurology department with recurrent syncope, postural light-headedness, and weight loss. Neurological examination revealed tonic pupils. The baseline composite autonomic symptom score-31 was 51 (0 to 75), and baseline functional ability score was 10 (0 to 100%). In the follow-up, syncope episodes that frequently develop during the day required the patient to lie in the supine position in bed all day and were triggered even by coming to a slightly sitting position. Neurophysiologic testing showed evidence of cardiovagal and sudomotor impairment. The patient was diagnosed with SS after detailed investigations. A 5-day course of intravenous immunoglobulin (IVIg) was given, and she continued IVIg once a month. After 6 months, she could walk long distances without support, and gastrointestinal complaints and syncopes had significantly decreased. After ~1.5 years, she had a composite autonomic symptom score-31 score of 11 and a functional ability score of 80%. Control heart rate variability analysis showed a significant improvement in the values of SD of the RR interval and root mean square of successive RR interval differences. CONCLUSIONS: In SS-linked severe autonomic neuropathy, immunotherapy can provide electrophysiological recovery in addition to excellent clinical response.

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.

IgG4-related pachymeningitis-Long term follow up and outcome of six patients.

OBJECTIVE: Our understanding of IgG4-RD and pachymeningitis has grown substantially, but the optimal approach for diagnosis, management, and long-term outcomes is still an area of uncertainty. METHODS: HUVAC is a database for IgG4-RD patients, this database was retrospectively evaluated for pachymeningeal disease. Demographic, clinical, serological, imaging, histopathological data, and treatment details were re-interpreted in patients with pachymeningitis. RESULTS: Among 97 patients with IgG4-RD, 6 (6.2%) had pachymeningitis. None of these patients had extracranial features, and also, in most of the patients, serum IgG4 levels were normal. Tentorium cerebelli and transverse sinus dura were the most commonly involved in the posterior fossa. During 18 months of median follow-up on steroid+-rituximab, none of them relapsed as pachymeningitis. CONCLUSION: Our patients were mainly older males with sole neurological involvement. Non-specific headache was the most common manifestation, and serum IgG4 levels were not useful for diagnosis. Typical radiology and tentorial thickening should suggest IgG4-RD and prompt an early biopsy. Moreover, accompanying hypophysitis could also be a clue. With steroids+ rituximab treatment, no relapse related to meningeal involvement was seen in long-term follow-up.

A combined clinical and computational approach to understand the SOD1A4T-mediated pathogenesis of rapidly progressive familial amyotrophic lateral sclerosis.

Here, we aim to provide a comprehensive clinical and biomolecular description of familial amyotrophic lateral sclerosis (fALS) in a 25-year-old female patient with respect to the SOD1A4T genotype. The clinical diagnosis of the disease was based on family history, neurological examination, electroneurophysiological studies, and revised El Escorial criteria. The heterozygous presence of the A4T mutation in the proband was confirmed by PCR coupled with Sanger sequencing of exon 1 of the SOD1 gene. The mutation was introduced in silico into the three-dimensional structure of the native protein. After energy minimization and quality assessment, non-covalent interactions around threonine-4 and changes in protein stability were calculated computationally. The patient differed widely in age at onset, initial neurological symptoms and findings, and survival time from her kindred, in which several members are affected. SOD1A4T-linked fALS in this case had bulbar involvement at onset, a combination of lower and upper motor neuron signs and showed rapid progression. Unlike alanine-4, threonine-4 failed to engage in hydrophobic interactions with the vicinal non-polar amino acids. The overall fold of the modeled SOD1A4T mutant remained intact, but unfolding free energy estimations disclosed a decrease in the protein's stability. We report a phenotypically distinct patient with fALS due to the SOD1A4T mutation and further expand the largest pedigree ever published for SOD1A4T-linked fALS. Genotype‒phenotype correlation in fALS is complex, and it demands detailed clinical investigation and advanced scientific research. Awareness of the broadened phenotypic spectrum might potentially enhance the diagnosis and genetic counseling of fALS.

Bilateral Wrist Drop Caused by Non-invasive Continuous Monitoring of Blood Pressure During Severe COVID-19 Pneumonia: A Case Report.

Compressive peripheral nerve injury can be observed as a long-term outcome during the treatment of severe COVID-19 pneumonia. In this case study, we report a man with bilateral wrist drop due to prolonged noninvasive blood pressure monitoring. A 52-year-old man who had undergone invasive ventilation because of severe COVID-19 pneumonia was admitted with bilateral loss of function of the wrist, digital, and thumb extensors and hypoesthesia in the dorsum of the forearm and hand. The patient had not been treated with prone positioning respiratory therapy. However, he had undergone bilateral automated sphygmomanometry that measured his blood pressure every ten minutes during his ICU stay. His electrophysiological findings were compatible with the presence of bilateral radial nerve compression at the level of the spiral groove. Awareness of potential compressive peripheral nerve injury is important for rehabilitation after the treatment of COVID-19-associated pneumonia.

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.

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.

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.

A case with Neurofascin-155 IgG antibody-associated combined central and peripheral demyelination: Successfully treated with anti-CD20 monoclonal antibody.

Combined central and peripheral demyelination (CCPD) is an infrequent entity in which demyelination is observed in central (CNS) and peripheral nervous systems (PNS). Potentially, it may develop due to a shared immune mechanism or possible co-occurrence between two unrelated demyelinating diseases such as multiple sclerosis (MS) and chronic inflammatory demyelination polyneuropathy (CIDP). A small number of CIDP patients have autoantibodies against nodal and paranodal proteins such as neurofascin155 (NF155). NF acts as a cell adhesion molecule between nodal and paranodal proteins. Glial NF 155 coexists in the PNS and CNS and can lead to combined demyelination. Although NF antibody-positive CIDP cases and case series have been reported, the number of patients with overt manifestations of central nervous system demyelination is very low in this group. The response to intravenous immunoglobulin (IVIg) in anti NF155 antibody-positive (NF155 +) CIDP is known to be poor. Rituximab, a B-cell-targeted anti-CD20 monoclonal antibody, has made good progress in therapy. Here, we report a case with Neurofascin-155 IgG antibodies related to CCPD who responded well to Rituximab. NF155+ CIDP usually affects young adults, and early administration of appropriately combined immunotherapy can prevent severe disability. NF antibody testing should be performed in unresponsive patients to IVIg therapy.