Clinical pitfalls and serological diagnostics of MuSK myasthenia gravis.

BACKGROUND: We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of anti-acetylcholine receptor (AChR) Ab-negative generalized myasthenia gravis (MG), and also to investigate clinical contexts for the diagnosis of MuSK MG. METHODS: A retrospective study of 160 patients with a clinical suspicion of AChR Ab-negative generalized MG was performed. The serum samples were tested for anti-clustered AChR Ab by cell-based assay (CBA), anti-MuSK Ab by ELISA, CBA and/or radioimmunoprecipitation assay (RIPA). Clinical data were compared between anti-MuSK Ab-positive MG and double seronegative (AChR and MuSK) MG groups. RESULTS: After excluding non-MG and clustered AChR Ab-positive patients, we identified 89 patients as a cohort of AChR Ab-negative generalized MG. Anti-MuSK Ab was positive by ELISA in 22 (24.7%) patients. While CBA identified five additional anti-MuSK Ab-positive patients, the results of ELISA were mostly consistent with CBA and RIPA with Cohen's kappa of 0.80 and 0.90, respectively (p < 0.001). The most frequent differential diagnosis was motor neuron disease particularly of bulbar onset which showed remarkably overlapping clinical and electrophysiological features with MuSK MG at presentation. CONCLUSION: While confirming the highest sensitivity of CBA for detecting anti-MuSK Ab, our results highlight the clinical pitfalls in making a diagnosis of MuSK MG and may support a diagnostic utility of MuSK-ELISA in clinical practice.

Factors affecting contralateral wrist surgery after one carpal tunnel release in bilateral carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) can be bilateral, with varying incidence. Carpal tunnel release (CTR) in one wrist may relieve the symptoms of the contralateral wrist, avoiding the need for second surgery; conversely, the symptoms may persist or worsen, requiring contralateral surgery in some cases. The present study investigated whether surgical treatment was finally required for the non-operated CTS wrist, and in what cases non-operative treatment was possible. We compared baseline characteristics, risk factors and electrodiagnostic data between CTS patients who underwent only unilateral CTR and those who subsequently underwent bilateral surgery at various time intervals. This single-center retrospective study included 188 patients with bilateral CTS managed between 2010 and 2020; 137 patients (group 1, 73%) underwent only unilateral CTR, and 51 (group 2, 27%) subsequently underwent contralateral CTR. In group 1, contralateral CTS symptoms were assessed in 4 categories and compared to the presenting symptoms in the index wrist. There were no significant differences in age, gender, preoperative symptom duration, body status, addictive behavior, electrodiagnostic study or comorbidities, other than a higher rate of dialysis in group 2. The contralateral wrist showed partial or complete symptom relief in 57% of patients undergoing unilateral CTR. High BMI and history of diabetes were risk factors for persistent severe CTS or subsequent contralateral CTR.

Characteristics of surgically treated Guyon canal syndrome: A multicenter retrospective study.

Guyon canal (GC) syndrome is a rare peripheral neuropathy involving the distal part of the ulnar nerve. Several causes are associated with GC syndrome, including anatomic variations, space-occupying tumors, and trauma. Because of disease rarity, the only reported studies of GC syndrome are case series with small sample size. We conducted a multicenter study to identify the basic characteristics of patients with surgically treated GC syndrome and the risk factors for the disease. This retrospective multicenter study was conducted between January 2001 and December 2020. We screened 70 patients who underwent GC release surgery by seven hand surgeons at six institutes. A total of 56 patients were included in this study, including 38 patients (67.9%) who underwent isolated GC decompression and 18 (32.1%) who underwent combined peripheral nerve decompression. The mean patient age was 48.4 years (range: 20-89 years), and 40 patients (71.4%) were male. The average preoperative symptom duration was 18.5 months, and most patients were office workers. Ultrasound was positive for GC syndrome in 7/10 patients evaluated, CT in 2/5, MRI in 17/23, and electrodiagnostic studies in 35/44. The most common cause of GC syndrome was tumor (n = 23), followed by idiopathic (n = 17), trauma (n = 12), anatomic variants (n = 3), and inflammation (n = 3). In conclusion, most patients with GC syndrome in this study were male and had symptoms in one wrist. The most common cause of GC syndrome in this study was a tumor, including a ganglion cyst. Level of Evidence: Level IV case series.

Carpal Tunnel Release Despite Normal Nerve Conduction Studies in Carpal Tunnel Syndrome Patients.

PURPOSE: Carpal tunnel syndrome (CTS) is a common entrapment neuropathy, often requiring carpal tunnel release (CTR) surgery. Often, a nerve conduction study (NCS) is performed before CTR; however, there are various reports questioning the sensitivity of NCS, and some patients do undergo CTR despite normal NCS results. We had the following purposes: (1) to report clinical outcome of CTS patients who undergo CTR despite normal NCS, (2) to identify the characteristics and compare those with abnormal NCS patients in terms of basic features and risk factors, and (3) to analyze and compare normal and abnormal NCS results. MATERIALS AND METHODS: Medical records of 546 CTS (30 normal NCS and 516 abnormal NCS) patients were retrospectively reviewed. Of 30 normal NCS patients, 7 were excluded, leaving 23 patients in the experimental group. We investigated the influence of age, sex, operative arm, and body mass index, as well as medical conditions known to be risk factors for CTS. In normal NCS patients, as a functional score, we investigated Boston carpal tunnel scores before and after CTR. The NCS results were compared in terms of median motor and median sensory testing. In normal NCS patients, NCS data were compared with that of the contralateral nonoperated wrists. RESULTS: There were 18 women and 5 men in the normal NCS group (mean age 43.7 years). On physical examination, 22 (94.7%) patients showed a positive Tinel test, 19 (82.6%) showed a positive Phalen test, 8 (34.8%) complained of nocturnal paresthesia, and only 1 (4.3%) presented with thenar atrophy. In 19 of 23 patients, the Boston CTS scores showed significant improvement after CTR. Normal NCS patients were significantly younger and significantly heavier and more likely to be a current smoker. In NCS analysis of normal NCS patients, the operated wrists were closer to the reference values than nonoperated wrists. CONCLUSIONS: Surgeons should evaluate the possibility of other combined lesions before CTR in normal NCS patients. Normal NCS can be present with a CTS diagnosis, especially in younger patients. Nevertheless, CTR after failed conservative management, despite normal NCS, could relieve subjective symptoms and function.

Reversible reddish skin color change in a patient with compressive radial neuropathy.

BACKGROUND: The motor and sensory symptoms caused by compressive radial neuropathy are well-known, but the involvement of the autonomic nervous system or the dermatologic symptoms are less well known. We report an unusual case of compressive radial neuropathy with reversible reddish skin color change. CASE PRESENTATION: A 42-year-old man was referred for left wrist drop, finger drop and a tingling sensation over the lateral dorsum of the left hand. Based on clinical information, neurologic examinations and electrophysiologic studies, he was diagnosed with compressive radial neuropathy. In addition, a reddish skin color change was observed at the area of radial sensory distribution. After two weeks of observation without specific treatment, the skin color had recovered along with a marked improvement in weakness and aberrant sensation. CONCLUSIONS: Compressive radial neuropathy with a reversible reddish skin color change is unusual and is considered to be due to vasomotor dysfunction of the radial autonomic nerve. Compressive radial neuropathy is presented with not only motor and sensory symptoms but also autonomic symptoms; therefore, careful examination and inspection are needed at diagnosis.

Correction: Myasthenia gravis seronegative for acetylcholine receptor antibodies in South Korea: Autoantibody profiles and clinical features.

[This corrects the article DOI: 10.1371/journal.pone.0193723.].

Myasthenia gravis seronegative for acetylcholine receptor antibodies in South Korea: Autoantibody profiles and clinical features.

Acquired myasthenia gravis (MG) is a prototype autoimmune disease of the neuromuscular junction, caused in most patients by autoantibodies to the muscle nicotinic acetylcholine receptor (AChR). There seem to be ethnic and regional differences in the frequency and clinical features of MG seronegative for the AChR antibody. This study aimed to describe the autoantibody profiles and clinical features of Korean patients with generalized MG seronegative for the AChR antibody. A total of 62 patients with a high index of clinical suspicion of seronegative generalized MG were identified from 18 centers, and we examined their sera for antibodies to clustered AChR, muscle-specific tyrosine kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (LRP4) by cell-based assays (CBA) and to MuSK by radioimmunoprecipitation assay (RIPA). We also included 8 patients with ocular MG, 3 with Lambert-Eaton myasthenic syndrome, 5 with motor neuron disease, and 9 with other diagnoses as comparators for the serological testing. Antibodies were identified in 25/62 (40.3%) patients: 7 had antibodies to clustered AChR, 17 to MuSK, and 2 to LRP4. Three patients were double seropositive: 1 for MuSK and LRP4, and 2 for MuSK and clustered AChR. The patients with MuSK antibodies were mostly female (88.2%) and characterized by predominantly bulbar involvement (70%) and frequent myasthenic crises (58.3%). The patients with antibodies to clustered AChR, including 2 with ocular MG, tended to have a mild phenotype and good prognosis.

Altered nucleocytoplasmic proteome and transcriptome distributions in an in vitro model of amyotrophic lateral sclerosis.

Aberrant nucleocytoplasmic localization of proteins has been implicated in many neurodegenerative diseases. Evidence suggests that cytoplasmic mislocalization of nuclear proteins such as transactive response DNA-binding protein 43 (TDP-43) and fused in sarcoma (FUS) may be associated with neurotoxicity in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. This study investigated the changes in nucleocytoplasmic distributions of the proteome and transcriptome in an in vitro model of ALS. After subcellular fractionation of motor neuron-like cell lines expressing wild-type or G93A mutant hSOD1, quantitative mass spectrometry and next-generation RNA sequencing (RNA-seq) were performed for the nuclear and cytoplasmic compartments. A subset of the results was validated via immunoblotting. A total of 1,925 proteins were identified in either the nuclear or cytoplasmic fractions, and 32% of these proteins were quantified in both fractions. The nucleocytoplasmic distribution of 37 proteins was significantly changed in mutant cells with nuclear and cytoplasmic shifts in 13 and 24 proteins, respectively (p<0.05). The proteins shifted towards the nucleus were enriched regarding pathways of RNA transport and processing (Dhx9, Fmr1, Srsf3, Srsf6, Tra2b), whereas protein folding (Cct5, Cct7, Cct8), aminoacyl-tRNA biosynthesis (Farsb, Nars, Txnrd1), synaptic vesicle cycle (Cltc, Nsf), Wnt signalling (Cltc, Plcb3, Plec, Psmd3, Ruvbl1) and Hippo signalling (Camk2d, Plcb3, Ruvbl1) pathways were over-represented in the proteins shifted to the cytoplasm. A weak correlation between the changes in protein and mRNA levels was found only in the nucleus, where mRNA was relatively abundant in mutant cells. This study provides a comprehensive dataset of the nucleocytoplasmic distribution of the proteome and transcriptome in an in vitro model of ALS. An integrated analysis of the nucleocytoplasmic distribution of the proteome and transcriptome demonstrated multiple candidate pathways including RNA processing/transport and protein synthesis and folding that may be relevant to the pathomechanism of ALS.

Is antiplatelet treatment effective at attenuating the progression of white matter hyperintensities?

OBJECTIVE: We performed this study to assess the effect of an antiplatelet agent on the progression of white matter hyperintensities (WMH). METHODS: From August 2003 to May 2005, we consecutively enrolled patients who underwent brain magnetic resonance imaging (MRI) for health check-up purposes and showed no significant findings other than WMH of any degree. Patients were divided into two groups based on whether or not they received antiplatelet therapy. All patients had a follow-up brain MRI after 5 years and WMH volume change was measured using imaging analysis software. To minimize selection bias potentially arising from antiplatelet treatment assignment, analyses were inverse probability weighted. RESULTS: Among the 93 patients who met the inclusion criteria, 54 patients (58.1%) were grouped as the antiplatelet group (AG), and the remaining 39 patients (41.9%) as the non-antiplatelet group (NAG). After inverse propensity weighting, all baseline characteristics were similar between the two groups, and antiplatelet treatment did not show any significant effect on the total WMH volume change (p = 0.957). CONCLUSION: Antiplatelet medication may not alter the progression of WMH.

Relapsing Polychondritis Presented with Encephalitis Followed by Brain Atrophy.

Relapsing polychondritis (RP) is a rare autoimmune disease that is characterized by inflammatory reaction of unknown etiology and destruction of cartilaginous structures. Characteristic symptoms of this disease include cartilage inflammation of the ear, nose, larynx, trachea, bronchi, joints, eyes, heart and skin. Concomitance with neurologic symptom is very rare in RP, and the detailed underlying mechanism of neurological involvement associated with RP is not fully understood. We herein described an unusual recurrent case of inflammatory brain lesions associated with RP, with attention to clinical manifestations, autoimmune disease involvement, and therapeutic effects.

Takotsubo cardiomyopathy in amyotrophic lateral sclerosis.

OBJECTIVE: To investigate the frequency, features, and prognosis of takotsubo cardiomyopathy (TTC) in patients with amyotrophic lateral sclerosis (ALS). METHODS: We reviewed detailed clinical, laboratory, and cardiovascular data from 64 ALS patients (38 men and 26 women) who underwent echocardiographic evaluation for various reasons at a single referral center between January 2011 and December 2015. RESULTS: TTC was diagnosed in 9 ALS patients (4 men and 5 women). Mean age was 61.3years (range 55-71years), and median disease duration was 51.5months (range 18-134months). All patients were bulbar or cervical onset, and were at advanced stages of ALS when TTC was diagnosed. Acute exacerbation of dyspnea was an invariable presentation, and chest discomfort mimicking acute coronary syndrome was present in 2 patients. Six patients had significant hypotension requiring intravenous fluid challenge and inotropic support. Three patients showed altered mentality, and 2 of them suffered cardiopulmonary arrest. CONCLUSIONS: TTC should be suspected in ALS patients presenting with acute exacerbation of dyspnea and chest discomfort, particularly at advanced stages of the disease. This study highlights the need for proper evaluation and management of cardiac dysfunction in ALS.

Rapid Progression of Sporadic ALS in a Patient Carrying SOD1 p.Gly13Arg Mutation.

Amyotrophic lateral sclerosis (ALS), the most common adult onset motor neuron disease, is pathologically characterized by progressive loss of the upper and lower motor neurons. Mutations in the Cu/Zn superoxide dismutase gene (SOD1) account for about 20% of familial ALS cases and a small percentage of sporadic ALS (SALS) cases, and have revealed a validated genotype-phenotype correlation. Herein, we report a p.Gly13Arg mutation in SOD1 exon 1 in a patient with SALS who presented with a rapidly progressive course, predominantly affecting the lower motor neurons. A 48-year-old man presented with progressive weakness and muscle atrophy of the left upper and lower limbs, followed by muscle fasciculation and cramping. The clinical features of the patient were clearly suggestive of ALS, and implied a sporadic form with rapid progression, predominantly affecting the lower motor neurons. Sequencing of the SOD1 gene by PCR revealed a missense mutation of G to C (c.37G>C) in exon 1, and amino acid substitution of glycine by arginine (p.Gly13Arg). This is the first case identifying the p.Gly13Arg mutation of SOD1 in the Korean population, and clinical assessments of this patient revealed a different phenotype compared with other cases.

A Case of Turner Syndrome with Multiple Embolic Infarcts.

Only a few cases of Turner syndrome (TS) with ischemic stroke have been reported. Various arteriopathies of the cerebral arteries, including fibromuscular dysplasia, congenital hypoplasia, moyamoya syndrome, and premature atherosclerosis have been assumed to be the cause of ischemic stroke in TS. There has been no case report of a TS patient presenting with an embolic stroke pattern without any cerebral arteriopathy. A 28-year-old woman with TS was referred to our hospital because of abnormal brain magnetic resonance imaging (MRI) findings. She underwent brain MRI at the referring hospital because she experienced sudden-onset diffuse headache. Diffusion-weighted imaging revealed multiple acute embolic infarcts in different vascular territories. Intracranial and extracranial arterial disease was not detected on cerebral magnetic resonance angiography and carotid sonography. Embolic source workups, including transthoracic and transesophageal echocardiography, Holter monitoring, and transcranial Doppler shunt study, were all negative. Hypercoagulability and vasculitis panels were also negative. Our patient was diagnosed with cryptogenic embolic stroke. This is the first report of a TS patient with an embolic stroke pattern. Our case shows that ischemic stroke in TS could be due to embolism as well as the various cerebral arteriopathies documented in previous reports.

Neuro-Behçet's Disease Presenting as Hypertrophic Pachymeningitis.

A 25-year-old man presented with blurred vision and chronic headache. His brain MRI revealed bilateral frontal pachymeningeal enhancement with leptomeningeal enhancement. The patient had experienced recurrent oral ulcer and had anterior uveitis and papulopustules skin lesion. We diagnosed him with hypertrophic pachymeningitis (HP) associated with neuro-Behçet's disease (NBD). There have been few reports describing HP in patients with NBD. We report a case of NBD presenting as HP.

Comparison between Flail Arm Syndrome and Upper Limb Onset Amyotrophic Lateral Sclerosis: Clinical Features and Electromyographic Findings.

Flail arm syndrome (FAS), an atypical presentation of amyotrophic lateral sclerosis (ALS), is characterized by progressive, predominantly proximal, weakness of upper limbs, without involvement of the lower limb, bulbar, or respiratory muscles. When encountering a patient who presents with this symptomatic profile, possible diagnoses include upper limb onset ALS (UL-ALS), and FAS. The lack of information regarding FAS may make differential diagnosis between FAS and UL-ALS difficult in clinical settings. The aim of this study was to compare clinical and electromyographic findings from patients diagnosed with FAS with those from patients diagnosed with UL-ALS. To accomplish this, 18 patients with FAS and 56 patients with UL-ALS were examined. Significant differences were observed between the 2 groups pertaining to the rate of fasciculation, patterns of predominantly affected muscles, and the Medical Research Council scale of the weakest muscle. The presence of upper motor neuron signs and lower motor neuron involvement evidenced through electromyography showed no significant between-group differences.