Whole-Body Muscle Magnetic Resonance Imaging in 81 Patients with Spinal and Bulbar Muscular Atrophy: A Prospective Study.

OBJECTIVE: Spinal and bulbar muscular atrophy (SBMA) is characterized by slow, progressive bulbar and limb muscle weakness; however, the pattern of progression of muscle fat infiltration remains unclear. We assessed the progression of muscle involvement in 81 patients with SBMA using whole-body muscle magnetic resonance imaging (MRI), alongside clinical and laboratory findings. METHODS: This prospective study included patients with genetically confirmed SBMA who underwent whole-body muscle MRI. We analyzed muscle fat infiltration and the pattern of involved muscles using cluster analysis, visualizing the sequential progression of fat infiltration. Muscle clusters demonstrated correlation with clinical scales and laboratory findings. Additionally, linear regression analysis was performed to identify the MRI section most strongly associated with 6-minute walk test (6MWT). RESULTS: We included 81 patients with SBMA (age = 54.3 years). After categorizing the patients into 6 clusters based on the pattern of muscle fat infiltration, we observed that muscle involvement began in the posterior calf and progressed to the posterior thigh, pelvis, trunk, anterior thigh, medial thigh, anterior calf, and upper extremity muscles. These muscle clusters correlated significantly with disease duration (τ = 0.47, p < 0.001), 6MWT (τ = -0.49, p < 0.001), and serum creatinine level (τ = -0.46, p < 0.001). The whole-body MRI indicated the thigh as the section most significantly correlated with 6MWT. INTERPRETATION: We used whole-body muscle MRI to determine the sequential progression of the fat infiltration in SBMA. Our findings may enable the identification of objective and reliable imaging outcome measures in the study of the natural history or future clinical trials of SBMA. ANN NEUROL 2024;95:596-606.

Neurofilament light chain as a biomarker in neuromyelitis optica spectrum disorder: a comprehensive review and integrated analysis with glial fibrillary acidic protein.

BACKGROUND: In the context of neuromyelitis optica spectrum disorder (NMOSD), there are several measures that serve as a biomarker. However, each of the methods has the intrinsic limitations. While neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have emerged as an additional biomarker for NMOSD, a thorough investigation of their role remains incomplete. Our aim is to provide a comprehensive review of the current literature regarding NfL and GFAP as a biomarker and explore their potential utility in NMOSD. METHODS: We performed a comprehensive search using PubMed and Google Scholar to identify peer-reviewed articles investigating NfL and GFAP as a biomarker in NMOSD. RESULTS: Our search identified 13 relevant studies. NfL consistently showed promise in distinguishing NMOSD patients from healthy individuals, although it had limited specificity in distinguishing NMOSD from other demyelinating diseases. NfL offered certain advantages over GFAP, notably its ability to predict disability worsening during attacks. In contrast, GFAP provided valuable insight, particularly in distinguishing NMOSD from multiple sclerosis and identifying clinical relapses. In addition, GFAP showed predictive potential for future attacks. Some studies even suggested that NfL may serve as an indicator of treatment response in NMOSD. CONCLUSIONS: NfL and GFAP hold promise as biomarkers for NMOSD, demonstrating their usefulness in distinguishing patients from healthy individuals, assessing disease severity, and possibly reflecting treatment response. However, it is important to recognize that NfL and GFAP may, at some point, have different roles.

Reversible cerebral vasoconstriction syndrome in Guillain-Barre syndrome: a case report and literature review.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by transient constriction of cerebral arteries, leading to severe headache and potential complications. The association between RCVS and Guillain-Barre syndrome (GBS) is rare and poorly understood and warrants further investigation. METHODS: A detailed case of RCVS in a patient with GBS was presented, followed by a comprehensive literature review. PubMed, Embase, and Google Scholar were searched for relevant cases and studies. RESULTS: The case involved a 62-year-old woman with GBS who developed RCVS. The literature review identified three additional reported cases. RCVS in GBS primarily affected middle-aged women and presented with a variety of neurological symptoms. Neuroimaging showed reversible vasoconstriction in the cerebral arteries, along with other complications such as posterior reversible encephalopathy syndrome, subarachnoid hemorrhage, and infarcts. While the treatment for GBS consisted mainly of intravenous immunoglobulin, specific treatments for RCVS remain unclear. CONCLUSIONS: The coexistence of RCVS and GBS is a rare occurrence. RCVS in GBS may result from the disruption of cerebral vascular tone regulation, possibly influenced by GBS-related dysautonomia and consequent high blood pressure. Recognizing RCVS in GBS patients is critical for appropriate management.

Impact of COVID-19 Infection and Its Association With Previous Vaccination in Patients With Myasthenia Gravis in Korea: A Multicenter Retrospective Study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

Evaluation of the safety profile of COVID-19 vaccines in patients with MS, NMOSD, and MOGAD.

INTRODUCTION: Vaccination against the coronavirus disease 2019 (COVID-19) is recommended for patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, vaccine safety in these patients taking immunotherapeutic agents is unclear as they were not included in the vaccine trials. OBJECTIVES: To evaluate the safety of COVID-19 vaccines in patients with MS, NMOSD, and MOGAD. METHODS: We reviewed the medical records of MS, NMOSD, and MOGAD patients at the Keimyung University Dongsan Hospital. Information regarding vaccination schedules and adverse events was collected. RESULTS: A total of 56 patients (19, 22, and 15 patients with MS, NMOSD, and MOGAD, respectively) with a median age of 48.18 ± 15.72 years (range, 16-81 years) were included. Of them, 42 (75.0%) were female. In total, 76.8% (43/56) of all patients were vaccinated, and the vaccination rate was the highest for NMOSD patients (81.8%) and the lowest for MS patients (68.4%). All vaccinated patients were administered mRNA vaccines at least once in single or multiple vaccination doses. Only 3 of 43 (7.0%) vaccinated patients experienced clinical relapse following vaccination. Facial sensory changes with a brainstem lesion developed in an MS patient taking dimethyl fumarate, while myelitis occurred in a MOGAD patient receiving azathioprine maintenance therapy. The first episode of optic neuritis occurred in a patient who was later diagnosed with MOGAD. CONCLUSIONS: Our study demonstrated a favorable safety profile with no serious adverse events associated with COVID-19 vaccines in patients with MS, NMOSD, and MOGAD.

Finger Drop-Dominant Variant of Guillain-Barre Syndrome in a Patient With COVID-19: A Case Report.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that may trigger Guillain-Barre syndrome (GBS) in selected patients. We describe a case of GBS presenting as marked finger extensor weakness in a 73-year-old woman with COVID-19. Her clinical and electrophysiological findings were consistent with a diagnosis of acute motor axonal neuropathy subtype of GBS with prominent finger dropping. Treatment with intravenous immunoglobulin for 5 days completely resolved her finger extension weakness after 19 months, although other involved extremities recovered earlier at 3 months. This study highlights that COVID-19-associated GBS can present in various forms aside from the classic variant, even in patients without any COVID-19 symptoms. Therefore, it is important to always consider the diagnosis of GBS in patients with COVID-19.

Serum FAM19A5 in neuromyelitis optica spectrum disorders: Can it be a new biomarker representing clinical status?

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) targets astrocytes and elevates the levels of astrocyte-injury markers during attacks. FAM19A5, involved in reactive gliosis, is secreted by reactive astrocytes following central nervous system (CNS) damage. OBJECTIVE: To investigate the significance of serum FAM19A5 in patients with NMOSD. METHODS: We collected clinical data and sera of 199 patients from 11 hospitals over 21 months. FAM19A5 levels were compared among three groups: NMOSD with positive anti-aquaporin-4 antibody (NMOSD-AQP4), other CNS demyelinating disease, and healthy controls. RESULTS: The median serum FAM19A5 level was higher in the NMOSD-AQP4 (4.90 ng/mL (3.95, 5.79)) than in the other CNS demyelinating (2.35 ng/mL (1.83, 4.07), p < 0.001) or healthy control (1.02 ng/mL (0.92, 1.14), p < 0.001) groups. There were significant differences in the median serum FAM19A5 levels between the attack and remission periods (5.89 ng/mL (5.18, 6.98); 4.40 ng/mL (2.72, 5.13), p < 0.001) in the NMOSD-AQP4 group. Sampling during an attack (p < 0.001) and number of past attacks (p = 0.010) were independently associated with increased serum FAM19A5. CONCLUSION: Serum FAM19A5 was higher in patients with NMOSD-AQP4 and correlated with clinical characteristics. Thus, serum FAM19A5 may be a novel clinical biomarker for NMOSD-AQP4.

Symptom-related changes in current perception threshold of restless legs syndrome.

Few studies have investigated the mechanisms responsible for the symptoms of restless legs syndrome (RLS). However, these studies were mainly performed during the asymptomatic period and therefore their findings might not apply to changes in sensory processing that occur during the symptomatic period. The objective of this study was to investigate the function of sensory nerve fibres in RLS patients using the current perception threshold (CPT) test during the daytime and in the presence of symptoms. Ninety-three patients with RLS and 34 healthy controls were included in the study. RLS patients were further divided into two subgroups, those who were experiencing RLS symptoms during the CPT test (symptom+) and those without symptoms (symptom-). Demographic data, RLS rating scale score and visual analogue scale were collected. Of the 127 enrolled subjects, CPT values were significantly lower in RLS patients than in controls for all three frequencies. Among the control and RLS subgroups (53 symptom+, 40 symptom-), symptom+ patients showed lower CPT values than controls. This finding indicates a relative hyperaesthetic state in the sensory afferents of peripheral nerves in symptom+ patients. There were no significant differences between the symptom- group and controls. The significantly lower CPT values for all three frequencies in symptom+ patients suggest that central sensory processing disturbance of sensory nerve fibres' input may be involved in the development of symptoms in RLS patients.

Quantitative evaluation of hand motor function using a gyrosensor in mild and moderate carpal tunnel syndrome.

INTRODUCTION: The objective of this study was to determine whether patients with carpal tunnel syndrome (CTS) manifest changes in early-stage motor function and to investigate the utility of a gyrosensor for quantitative evaluation of motor function. METHODS: Angular velocity signal was measured during finger tapping in 52 patients with mild-to-moderate CTS and 45 controls. Four finger-tapping performance (FTP) values-root-mean-squared (RMS) velocity, RMS angle, peak power, and total power-were derived from the signal. RESULTS: All FTP values were significantly lower in patients with CTS than in controls (P = 0.001 or P < 0.001). There were no significant differences between the mild and moderate CTS subgroups. DISCUSSION: FTP measurement with a gyrosensor represents a valuable tool for the evaluation of median nerve motor function in patients with CTS. It facilitates the detection of subclinical motor dysfunction in patients with early stage CTS. Muscle Nerve 59:465-469, 2019.

Under-recognized primary spontaneous pneumothorax in ALS: a multicenter retrospective study.

Primary spontaneous pneumothorax (PSP) is not an uncommon disease, especially in patients with risk factors such as male gender, history of smoking, and low body mass index (BMI). Amyotrophic lateral sclerosis (ALS) is a rare disease caused by neurodegeneration of the motor neurons that share risk factors with PSP. The aim of this study was to determine the prevalence of PSP in ALS and find the significant risk factors related to PSP. We retrospectively reviewed the data from 86 patients with clinically probable or definite ALS from three different centers. Clinical characteristics, including age, sex, subtype, disease duration, body mass index, history of smoking, tracheostomy state, and ventilator use, were obtained. The ALS Functional Rating Scale-Revised Form (ALSFRS-R) total score and subscores were also retrieved from the medical records. In the results, six of the 86 patients (7%) had PSP. There were no statistically significant differences among the clinical characteristics and the ALSFRS-R scores between the patients with and without PSP, except for BMI and smoking (p < 0.022 and p < 0.019, respectively). A multivariate logistic regression analysis of smoking and BMI showed an odds ratio of 19.25. In conclusion, the existence of PSP in ALS may be under-recognized. Further well-designed, large studies are needed to elucidate the prevalence and pathophysiology of pneumothorax in ALS.

Split hand muscle echo intensity index as a reliable imaging marker for differential diagnosis of amyotrophic lateral sclerosis.

OBJECTIVE: The objective of this study was to investigate the usefulness of muscle ultrasound in evaluating dissociated small hand muscle atrophy, termed 'split hand', and its feasibility in the diagnosis of amyotrophic lateral sclerosis (ALS). METHODS: Forty-four patients with ALS, 18 normal subjects and 9 patients with other neuromuscular disorders were included in this study. The hand muscles were divided into three regions, the median-innervated lateral hand muscle group (ML), the ulnar-innervated lateral hand muscle (UL) and the ulnar-innervated medial hand muscle (UM), and the muscle echo intensity (EI) and compound muscle action potential (CMAP) were measured. We calculated the split hand index (SHI) using muscle EI (SHImEI) and CMAP (SHICMAP) for comparison among groups. The SHI was derived by dividing muscle EI (or CMAP) measured at the ML and UL by that measured at the UM. RESULTS: The SHImEI was significantly higher in patients with ALS (51.7±28.3) than in normal controls (29.7±9.9) and disease controls with other neuromuscular disorders (36.5±7.3; P<0.001), particularly in upper limb-onset ALS (66.5±34.0; P<0.001). Receiver operating characteristic curve analysis indicated that the SHImEI had significantly better diagnostic accuracy than the SHICMAP. CONCLUSIONS: The SHImEI was more sensitive in evaluating dissociated small hand muscle atrophy compared with the SHICMAP and may be a reliable diagnostic marker for differentiating ALS from other neuromuscular disorders and healthy controls.