Search

Background Rare neuromuscular diseases such as spinal muscular atrophy, spinal bulbar muscular atrophy, muscular dystrophy, Charcot-Marie-Tooth disease, distal myopathy, sporadic inclusion body myositis, congenital myopathy, and amyotrophic lateral sclerosis lead to incurable amyotrophy and consequent loss of ambulation. Thus far, no therapeutic approaches have been successful in recovering the ambulatory ability. Thus, the aim of this trial was to evaluate the efficacy and safety of cybernic treatment with a wearable cyborg Hybrid Assistive Limb (HAL, Lower Limb Type) in improving the ambulatory function in those patients. Results We conducted an open-label, randomised, controlled crossover trial to test HAL at nine hospitals between March 6, 2013 and August 8, 2014. Eligible patients were older than 18 years and had a diagnosis of neuromuscular disease as specified above. They were unable to walk for 10 m independently and had neither respiratory failure nor rapid deterioration in gait. The primary endpoint was the distance passed during a two-minute walk test (2MWT). The secondary endpoints were walking speed, cadence, and step length during the 10-m walk test (10MWT), muscle strength by manual muscle testing (MMT), and a series of functional measures. Adverse events and failures/problems/errors with HAL were also evaluated. Thirty patients were randomly assigned to groups A or B, with each group of 15 receiving both treatments in a crossover design. The efficacy of a 40-min walking program performed nine times was compared between HAL plus a hoist and a hoist only. The final analysis included 13 and 11 patients in groups A and B, respectively. Cybernic treatment with HAL resulted in a 10.066% significantly improved distance in 2MWT (95% confidence interval, 0.667–19.464; p = 0.0369) compared with the hoist only treatment. Among the secondary endpoints, the total scores of MMT and cadence at 10MWT were the only ones that showed significant improvement. The only adverse effects were slight to mild myalgia, back pain, and contact skin troubles, which were easily remedied. Conclusions HAL is a new treatment device for walking exercise, proven to be more effective than the conventional method in patients with incurable neuromuscular diseases. Trial registration: JMACTR, JMA-IIA00156

We herein report a 45-year-old man with dentatorubropallidoluysian atrophy (DRPLA) who presented with mild dementia, ataxia, and involuntary movement and developed constipation, dysuria, and orthostatic hypotension. Thermography revealed an abnormal thermal response of the skin to cold stimulation. Skin temperature reflects the skin blood flow and is regulated by the sympathetic nervous system. Thermography is currently used to study diseases associated with vasomotor dysfunction of the skin. The thermography results suggested the possibility of autonomic dysfunction. Although little is known regarding autonomic dysfunction in DRPLA, this report demonstrates the importance of autonomic dysfunction in DRPLA.

Background Commercially available Illumina DNA methylation arrays (HumanMethylation 27K, HumanMethylation450, and MethylationEPIC BeadChip) can be used for comprehensive DNA methylation analyses of not only the human genome but also other mammalian genomes, ranging from those of nonhuman primates to those of rodents. However, practical application of the EPIC array to the crab‐eating macaque has not been reported. Methods Through bioinformatic analyses involving cross‐species comparison and consideration of probe performance, we selected array probes that can be reliably used for the crab‐eating macaque genome. A DNA methylation assay using an EPIC array was performed on genomic DNA extracted from the brains of five crab‐eating macaques. The obtained DNA methylation data were compared with a publicly available dataset. Results Among the 865 918 probes in the EPIC array, a total of 183 509 probes (21.2%) were selected as high‐confidence array probes in the crab‐eating macaque. Subsequent comparisons revealed that the data from these probes showed good concordance with other DNA methylation datasets of the crab‐eating macaque. Conclusion The selected high‐confidence array probes would be useful for high‐throughput DNA methylation assays of the crab‐eating macaque., Epigenetic research in the non‐human primates, such as crab‐eating macaque, will be important to understand the pathophysiology of psychiatric disorders. Among the methylation array probes for human genome, the probes that can reliably measure DNA methylation levels of the crab‐eating macaque are reported.

We herein report a 39-year-old woman who had aggravated body pain, waddling gait, and fatigability for the past 2 years. A neurological examination showed hyperreflexia and proximal muscle weakness. The serum calcium level was normal (10.1 mg/dL). However, serum alkaline phosphatase (3,855 IU/I) and parathyroid hormone (1,008 pg/mL) levels were remarkably high. Cervical ultrasonography revealed parathyroid goiter. The patient was diagnosed with hyperparathyroidism. Her muscle weakness and pain improved within three months after parathyroidectomy. Our findings suggest that clinicians should consider hyperparathyroidism as a differential diagnosis in patients with proximal muscle weakness, even if the serum calcium level is normal.

BACKGROUND Aplastic or twiglike middle cerebral artery (Ap/T-MCA) is a rare anomaly characterized by a unilateral MCA occlusion with plexiform vessels that causes hemorrhagic and (less commonly) ischemic strokes. The reasons for this are rarely discussed, and thus optimal treatment for ischemic Ap/T-MCA remains controversial. Here, the authors report a case of Ap/T-MCA with transient ischemic attacks treated by bypass surgery and discuss the mechanism of ischemic development and treatment methods. OBSERVATIONS A 62-year-old hypertensive man with transient, recurrent left hemiparesis visited the authors’ hospital. Magnetic resonance angiography showed proximal occlusion of the right MCA and stenosis in the left MCA. Digital subtraction angiography revealed occlusion of the right MCA and abnormal vascular networks, leading to a diagnosis of Ap/T-MCA with contralateral MCA stenosis. Antiplatelet therapy with aspirin was insufficient, and a superficial temporal artery–MCA bypass was performed. There were no ischemic or hemorrhagic events postoperatively. LESSONS Atherosclerosis seems to have a significant impact on the development of ischemic stroke in patients with Ap/T-MCA, and the presence of coexisting atherosclerotic stenotic vascular lesions outside the Ap/T-MCA site is substantial in its development. Bypass surgery is a promising treatment option for ischemic Ap/T-MCA.

Article, Internal Medicine. 59(1): 125-128 (2020)

Background: Most coronavirus disease 2019 (COVID-19)-related cerebrovascular disorders are ischemic while hemorrhagic disorders are rarely reported. Among these, subarachnoid hemorrhage (SAH) is very rarely reported and nonaneurysmal SAH has been reported in only about a dozen cases. Here, we report a case of nonaneurysmal SAH as the only clinical manifestation of COVID-19 infection. In addition, we reviewed and analyzed the literature data on cases of nonaneurysmal SAH caused by COVID-19 infection. Case Description: A 50-year-old woman presented to an emergency department with a sudden headache, right hemiparesis, and consciousness disturbance. At that time, no fever or respiratory failure was observed. Laboratory data were within normal values but the rapid antigen test for COVID-19 on admission was positive, resulting in a diagnosis of COVID-19 infection. Computed tomograms (CTs) showed bilateral convexal SAH with a hematoma but three-dimensional CT angiograms showed no obvious sources, such as a cerebral aneurysm. Therefore, the patient was diagnosed with nonaneurysmal SAH associated with COVID-19 infection. With conservative treatment, consciousness level and hemiparesis both improved gradually until transfer for continued rehabilitation. Approximately 12 weeks after onset, the patient was discharged with only mild cognitive impairment. During the entire course of the disease, the headache, hemiparesis, and mild cognitive impairment due to nonaneurysmal SAH with small hematoma were the only abnormalities experienced. Conclusion: Since COVID-19 infection can cause nonaneurysmal hemorrhaging, it should be considered (even in the absence of characteristic infectious or respiratory symptoms of COVID-19) when atypical hemorrhage distribution is seen as in our case.

Objective To evaluate the efficacy and safety of perampanel in patients with sporadic amyotrophic lateral sclerosis (SALS). Methods This randomized, double-blind, placebo-controlled, multicenter, phase 2 clinical study was conducted at 12 sites. Patients with probable or definite ALS as defined by revised El Escorial criteria were enrolled. Sixty-six patients were randomly assigned (1:1:1) to receive placebo, 4 mg perampanel, or 8 mg perampanel daily for 48 weeks. Adverse events (AEs) were recorded throughout the trial period. The primary efficacy outcome was the change in Amyotrophic Lateral Sclerosis Rating Scale-Revised (ALSFRS-R) score after 48 weeks of treatment. Results One patient withdrew before starting the treatment. Of 65 patients included, 18 of 22 patients randomized to placebo (82%), 14 of 22 patients randomized to 4 mg perampanel (64%), and 7 of 21 patients randomized to 8 mg perampanel (33%) completed the trial. There was a significant difference in the change of ALSFRS-R scores [− 8.4 (95% CI − 13.9 to − 2.9); p = 0.015] between the placebo and the perampanel 8 mg group, primarily due to worsening of the bulbar subscore in the perampanel 8 mg group. Serious AEs were more frequent in the perampanel 8 mg group than in the placebo group (p = 0.0483). Conclusions Perampanel was associated with a significant decline in ALSFRS-R score and was linked to worsening of the bulbar subscore in the 8 mg group.

CGG repeat–derived RNA G-quadruplexes accelerate liquid-to-solid transition of FMRpolyG., Fragile X-related tremor/ataxia syndrome (FXTAS) is a neurodegenerative disease caused by CGG triplet repeat expansions in FMR1, which elicit repeat-associated non-AUG (RAN) translation and produce the toxic protein FMRpolyG. We show that FMRpolyG interacts with pathogenic CGG repeat-derived RNA G-quadruplexes (CGG-G4RNA), propagates cell to cell, and induces neuronal dysfunction. The FMRpolyG polyglycine domain has a prion-like property, preferentially binding to CGG-G4RNA. Treatment with 5-aminolevulinic acid, which is metabolized to protoporphyrin IX, inhibited RAN translation of FMRpolyG and CGG-G4RNA–induced FMRpolyG aggregation, ameliorating aberrant synaptic plasticity and behavior in FXTAS model mice. Thus, we present a novel therapeutic strategy to target G4RNA prionoids.

Summary In the mammalian cerebral neocortex, different regions have different cytoarchitecture, neuronal birthdates, and functions. In most regions, neuronal migratory profiles are speculated similar based on observations using thymidine analogs. Few reports have investigated regional migratory differences from mitosis at the ventricular surface. In this study, we applied FlashTag technology, in which dyes are injected intraventricularly, to describe migratory profiles. We revealed a mediolateral regional difference in the migratory profiles of neurons that is dependent on developmental stage; for example, neurons labeled at embryonic day 12.5–15.5 reached their destination earlier dorsomedially than dorsolaterally, even where there were underlying ventricular surfaces, reflecting sojourning below the subplate. This difference was hardly recapitulated by thymidine analogs, which visualize neurogenic gradients, suggesting a biological significance different from the neurogenic gradient. These observations advance our understanding of cortical development and the power of FlashTag in studying migration and are thus resources for future neurodevelopmental studies., Graphical abstract, Highlights • FlashTag visualized mediolateral regional differences of cortical migratory profiles • Mediolateral differences were observed when neurons were labeled at E12.5–15.5 • Late-born neurons transiently sojourned below the dorsolateral subplate (SP) cells • The difference was unclear in reeler cortex, where SP cells position superficially, Biological Sciences ; Neuroscience ; Developmental Neuroscience ; Neuroanatomy ; Techniques in Neuroscience

Shock wave generation by collapse of a single explosive bubble exposed to an underwater shock wave in water has been studied experimentally and numerically. The explosive bubble was made of a stoichiometric ethylene-oxygen mixture and its initial volume-equivalent radius was varied from 1.0 to 2.9 mm. The underwater shock wave, whose strength ranged from 7 to 19 MPa, was driven by gasous detonation in a vertical detonation tube. It was found that after passage of the underwater shock wave, the bubble starts to shrink, resulting in explosion just before reaching the minimum radius. In the bubble rebound phase a shock wave is generated whose strength is about twice as compared to that for the air bubble. The maximum pressure of the shock wave nondimensionalized by the ambient pressure behind the underwater shock wave was found to be inversely proportional to the non-dimensional distance. The conversion rate of the bubble energy to the shock energy was estimated to be 0.10, regardless of chemical heat release. Simple numerical analysis of bubble dynamics including compressibility of water was performed. The calculated bubble motion and the shock propagation agree with the experimental results, although the calculated shock strength is overestimated mainly because of non-sphericity of the initial shape of the bubble floating up in water. There is also a good agreement between the experimental and the calculated results in regard to the ratio of the shock pressure for the explosive bubble to that for the air bubble.

CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is an inflammatory central nervous system disorder that gives rise to brainstem symptoms such as diplopia and articulatory disorders. It shows characteristic "salt-and-pepper" enhancing brainstem lesions on magnetic resonance imaging (MRI) scans. We present an unusual case of CLIPPERS, in which a 29-year-old man initially presented with a seizure. Brain MRI revealed faint open-ring enhancements in the right frontal lobe, and a brain biopsy was performed to make a definitive diagnosis. Immunohistological tests showed perivascular infiltration by primarily CD3- and CD20-positive cells, albeit including a few CD68-positive cells, which confirmed a diagnosis of CLIPPERS. Both the symptoms and the MRI findings were markedly improved by 3 courses of steroid (methylprednisolone) pulse therapy, followed by oral steroid (prednisolone) administration. This case shows that CLIPPERS can present as a phenotype of cortical lesions and seizures as the first signs. A brain biopsy should therefore be actively carried out for differential diagnosis, especially when other, cortically based inflammatory disorders are suspected.

In the year 2003, the residents of Kamisu, Japan, were exposed to pentavalent organic arsenic diphenylarsinic acid (DPAA[V]) via their normal drinking water. Following the exposure, they developed cerebellar and brainstem symptoms. Although the relatively high dose of DPAA(V) is assumed to have caused their symptoms, the relationship between the exposed dose of DPAA(V) and the level of their deposition in the central nervous system (CNS) remains unclear. Using liquid chromatography–tandem mass spectrometry, we examined the deposition of DPAA(V) and its pentavalent metabolites in the CNS tissues of Crl:CD(SD) rats following the administration of DPAA(V) for 28 days. We found that the concentrations of DPAA(V) in the CNS were very high, given a dose of 5.0 mg/kg/day. However, very low concentrations of DPAA(V) were detected at a dose of 0.3 or 1.2 mg/kg/day, suggesting the absence of a linear dose-response relationship between the dose and deposition of DPAA(V). We also found that this non-linear relationship was commonly observed in various non-CNS tissues, including the excretory system. Our study showed for the first time the exact relationship between the dose and tissue deposition of the organic arsenic following its subchronic administration.

Mitochondrial dysfunction is implicated in the pathological mechanism of Alzheimer's disease (AD). Amyloid β-protein (Aβ), which plays a central role in AD pathogenesis, is reported to accumulate within mitochondria. However, a question remains as to whether Aβ is generated locally from amyloid precursor protein (APP) within mitochondria. We investigated this issue by analyzing the expression patterns of APP, APP-processing secretases, and APP metabolites in mitochondria separated from human neuroblastoma SH-SY5Y cells and those expressing Swedish mutant APP. APP, BACE1, and PEN-2 protein levels were significantly lower in crude mitochondria than microsome fractions while those of ADAM10 and the other γ-secretase complex components (presenilin 1, nicastrin, and APH-1) were comparable between fractions. The crude mitochondrial fraction containing substantial levels of cathepsin D, a lysosomal marker, was further separated via iodixanol gradient centrifugation to obtain mitochondria- and lysosome-enriched fractions. Mature APP, BACE1, and all γ-secretase complex components (in particular, presenilin 1 and PEN-2) were scarcely present in the mitochondria-enriched fraction, compared to the lysosome-enriched fraction. Moreover, expression of the β-C-terminal fragment (β-CTF) of APP was markedly low in the mitochondria-enriched fraction. Additionally, immunocytochemical analysis showed very little co-localization between presenilin 1 and Tom20, a marker protein of mitochondria. In view of the particularly low expression levels of BACE1, γ-secretase complex proteins, and β-CTF in mitochondria, we propose that it is unlikely that Aβ generation from APP occurs locally within this organelle.

Background: Perampanel, a non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist, arrested disease progression in a sporadic ALS (SALS) mouse model, suggesting its potential use in humans. Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2 study was conducted at 12 sites in Japan. Patients with probable or definite ALS as defined by revised El Escorial criteria were enrolled. Using a computerised interactive system with the following minimization factors: change in ALSFRS-R score during the observation period, sex, age, and the use of riluzole or edaravone, patients were randomly assigned in a 1:1:1 ratio to receive placebo, 4 mg perampanel daily, or 8 mg perampanel daily. The primary efficacy outcome was the change in ALSFRS-R scores after 48 weeks of treatment. All patients in the intention-to-treat population were analysed. Patients and investigators were masked to treatment assignment. Findings: Between April 2017 and January 2020, 65 patients were randomised to perampanel 4 mg (n=22), 8 mg (n=21), or placebo groups (n=22). There was a significant difference (−8·4 [95% confidence interval −13·9–−2·9]; p=0·015) between the placebo and the perampanel 8 mg group, primarily due to worsening of the bulbar subscore in the perampanel 8 mg group. Serious adverse events were significantly more frequent in the perampanel 8 mg group than in the placebo group (p=0·0483). The most common event was dysphagia requiring gastrostomy in two (9·1%) of 22 patients treated with placebo, four (18·2%) of 22 patients treated with 4 mg of perampanel, and six (28·6%) of 21 patients treated with 8 mg of perampanel. Interpretation: Perampanel did not prevent an overall decline of ALSFRS-R score and was linked to worsening of bulbar subscore in the 8 mg group. Trial Registration: This trial is registered with ClinicalTrials.gov, # NCT03019419. Funding: This study received funding from the Japan Agency for Medical Research and Development. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the institutional review board at each study site. Written informed consent was obtained from the patients.

Overuse of natural resources by humans is a major threat to biodiversity. Overuse often involves species of economic or esthetic value, and fish are a typical example for a group that is exploited both for economic reasons (for human consumption) and for esthetic reasons (e.g. by aquarists). Pseudorhodeus tanago (Tanaka, 1909) (formerly known as Tanakia tanago) is a small colorful but legally protected (fishing, keeping and transfer are banned) bitterling fish distributed around Tokyo, Japan. Whereas it is critically endangered and more and more habitat loss has occurred, at least four stocks have been newly found during the last decade. To explore whether emergence of these newly found habitats is a consequence of incomplete survey, we genotyped mitochondrial cytochrome b sequence of P. tanago from 17 localities and an illegal home aquarium. Populations known by the past extensive survey (13 localities) showed geographically structured population genetic characteristics. Population-specific haplotypes were common indicating past divergence and bottleneck events. Four (north, {center + west}, south_1, south_2) or five (north, center, west, south_1, south_2) geographic groups were detectable as for these known localities. On the other hand, newly found stocks were polymorphic and showed identical haplotypes from distant known localities. If we assume historical basis of distribution and genetic characteristics of these newly found stocks, it must be a series of unlikely geological events and haplotype sorting. We discuss potential issues posed by these questionable stocks.

In the present study, the self-ignition of high-pressure hydrogen released in atmospheric air through a diaphragm is visualized under various test conditions. The experimental results indicate that the hydrogen that jets through the rupturing diaphragm is mixed with the heated air near the tube wall. The self-ignition event originated from this mixing. The self-ignition was strongly dependent on the strength of an incident shock wave generated at the diaphragm rupture. As a result, a cylindrical flame that formed after the self-ignition shows a tendency to become longer as it propagates in the downstream direction. The head velocities of the hydrogen-air mixture and the cylindrical flame are consistent with that of a contact surface calculated from the measured shock speed. A modified self-ignition mechanism is proposed based on the experimental observations.

In order to clarify the mechanisms associated with a local explosion leading to deflagration to detonation transition (DDT) in a rectangular channel, detonation initiation behind the incident shock wave with a weak spark discharge was caused. In this approach the incident shock wave plays a role of the precursor shock wave, while the propagating flame is replaced with a flame kernel generated by the spark discharge. This method was successful in controlling the time and location of detonation initiation with good repeatability. The DDT process was visualized in two perpendicular directions to understand the three-dimensional behavior of the flame and the shock wave generated from flame acceleration. The following conclusions on the DDT process are deduced. (1) A shock wave coupled with a propagating flame eventually reflects off the wall as Mach reflection, behind which an accelerating flame and a shock wave ahead of it are caused. (2) The shock wave interacts with the other shock wave (shock–shock interaction) with more than a Mach number of 3. (3) This shock–shock interaction increases the temperature and pressure of the mixture locally, leading to the generation of a sufficiently strong shock wave with a larger M CJ . (4) The induced chemical energy release sustains the shock wave that decays to M CJ , resulting in propagation as detonation. Because the emergence of the accelerating flame and the shock–shock interaction process are completely three-dimensional phenomena, an understanding of three-dimensional flame and shock behavior is essential to reveal the DDT mechanism.

To study the effects of the boundary layer on the deflagration to detonation transition (DDT) process, the mixture behind an incident shock wave was ignited using laser breakdown. Ignition timing was controlled so that the interaction of the resulting flame with a laminar or turbulent boundary layer could be examined. In the case of the interaction with a laminar boundary layer, wrinkling of the flame was observed after the flame reached the corner of the channel. On the other hand, interaction with the turbulent boundary layer distorted the flame front and increased the spreading rate of the flame followed by prompt DDT. The inner structure of the turbulent boundary layer plays an important role in the DDT process. The region that distorted the flame within the turbulent boundary layer was found to be the intermediate region $$0.01< y/\delta < 0.4$$ , where y is the distance from the wall and $$\delta $$ is the boundary layer thickness. The flame disturbance by the turbulent motions is followed by the flame interaction with the inner layer near the wall, which in turn generates a secondary-ignition kernel that produced a spherical accelerating flame, which ultimately led to the onset of detonation. After the flame reached the intermediate region, the time required for DDT was independent of the ignition position. The effect of the boundary layer on the propagating flame, thus, became relatively small after the accelerating flame was generated.

In the present work, self-ignition of high-pressure hydrogen that is released to air through a ruptured diaphragm is studied experimentally under various test conditions. Diaphragms with several thicknesses and scores are ruptured by high-pressure hydrogen, and the formation of a shock wave in the tube is experimentally observed. The behavior of the ruptured diaphragm and the subsequent self-ignition is photographed using a high-speed camera, while the self-emission intensity from a flame is measured using a photomultiplier. The experimental results show that the diaphragm rupturing condition is one of the main factors affecting the self-ignition phenomena. In addition, the self-ignition causes a ring-shaped flame that travels downstream, along a boundary between the hydrogen jet and the shock-heated air.

Rationale Cerebral cavernous malformation (CCM) of the familial type is caused by abnormalities in the CCM1, CCM2, and CCM3 genes. These 3 proteins forming a complex associate with the maintenance of vascular endothelial cell-cell junctions. Dysfunction of these proteins results in the development of hemangiomas and abnormal intercellular junctions. Patient concerns We report a 68-year-old man with familial cerebral cavernous malformation with initial presentation as convulsions at an advanced age. Brain magnetic resonance imaging revealed multiple cavernous hemangiomas in the right occipital lobe. The convulsions were considered to be induced by hemorrhage from cavernous hemangioma in the right occipital lobe. Diagnoses Genetic screening of the CCM1, CCM2, and CCM3 genes revealed a novel mutation in the CCM2 gene (exon4 c: 359 T>A, p: V120D). No abnormalities were found in CCM1 or CCM3. Therefore, we diagnosed the patient with familial CCM caused by a CCM2 mutation. Interventions This patient was treated with the administration of levetiracetam at a dosage of 1000 mg/day. Outcomes No seizures have been observed since the antiepileptic drug was administered. We performed brain magnetic resonance imaging (MRI) regularly to follow-up on appearance of new cerebral hemorrhages and cavernous hemangiomas. Lessons This report reviews cases of familial cerebral cavernous malformations caused by abnormalities in the CCM2 gene. This mutation site mediates interactions with CCM1 and CCM3. The mutation occurs in the phosphotyrosine binding (PTB) site, which is considered functionally important to CCM2.

GDF-15, a member of the transforming growth factor beta superfamily, regulates inflammatory and apoptotic pathways in various diseases, such as heart failure, kidney dysfunction, and cancer. We aimed to clarify potentially confounding variables affecting GDF-15 and demonstrate its utility as a mitochondrial biomarker using serum samples from 15 patients with mitochondrial diseases (MD), 15 patients with limbic encephalitis (LE), 10 patients with multiple sclerosis/neuromyelitis optica spectrum disorders (MS/NMOSD), and 19 patients with amyotrophic lateral sclerosis (ALS). GDF-15 and FGF-21 were significantly elevated in MD. GDF-15 and FGF-21 showed a good correlation in MD but not in LE, MS, and ALS. GDF-15 was potentially influenced by age in LE, MS/NMOSD, and ALS but not in MD. FGF-21 was not correlated with age in MS/NMOSD, ALS, LE, and MD. GDF-15 was not correlated with clinical features in LE or BMI or body weight in ALS. GDF-15 positively correlated with the Expanded Disability Status Scale (EDSS) in MS/NMOSD, while EDSS showed no correlation with age. In conclusion, the results revealed that GDF-15 may be influenced by EDSS in MS/NMOPSD and by age in LE, MS/NMOSD, and ALS but not in MD. Mitochondrial damage in MS/NMOSD is a potentially confounding variable affecting GDF-15.