Aberrantly higher functional connectivity in the salience network is associated with transient global amnesia.

Triple intrinsic brain networks including the salience network (SN), default mode network (DMN), and central executive network (CEN), are known to be important in human cognition. Therefore, investigating those intrinsic brain networks in transient global amnesia (TGA) may offer novel insight useful for the pathophysiology of TGA. Fifty TGA patients underwent the resting state functional magnetic resonance imaging (rsfMRI) within 24 h, at 72 h, and 3 months after TGA onset. Twenty-five age, gender matched controls also underwent rsfMRI. Within 24 h of TGA onset, TGA patients showed greater functional connectivity in the SN and lower functional connectivity in the DMN, while relatively preserved functional connectivity was observed in the CEN. Interestingly, TGA patients continued to show decreased connectivity in the DMN, while no alterations were shown in the SN 72 h after illness onset. Three months after TGA onset, alterations of functional connectivity in the SN or the DMN were normalized. Our findings suggest that TGA is associated with transient greater functional connectivity in the SN and lower connectivity in the DMN.

Microbiota dysbiosis and functional outcome in acute ischemic stroke patients.

Currently, few studies are reported on the composition of microbiota in stroke patients and the association with stroke prognosis. This study investigated the differing microbiota composition in stroke patients and confirmed the association of microbiota composition with poor functional outcome. Between January of 2018 and December of 2019, 198 patients with acute cerebral infarction were included in this study. For the case-control study, age and sex-matched normal healthy subjects (n = 200) were included when receiving their health screening examinations. We isolated bacterial extracellular membrane vesicles and extracted DNA from blood samples. Taxonomic assignments were performed by using the sequence reads of 16S rRNA genes following blood microbiota analysis. Statistical analysis was conducted appropriately by using Statistical Analysis System software. The mean age of the stroke patients were 63.7 ± 12.5 years, and the male sex was 58.5%. Of the total enrolled patients, poor functional outcome (modified Rankin Score ≥ 3) was noted in 19.7%. The principal component analysis of microbiota composition revealed significant differences between healthy control subjects and stroke patients. At the genus level, Aerococcaceae(f), ZB2(c), TM7-1(c), and Flavobacterium were significantly increased in stroke patients compared to the healthy controls, whereas Mucispirillum, rc4-4, Akkermansia, Clostridiales(o), Lactobacillus, and Stenotrophomonas were decreased considerably. For the functional outcome after ischemic stroke, Anaerococcus, Blautia, Dialister, Aerococcaceae(f), Propionibacterium, Microbacteriaceae(f), and Rothia were enriched in the group with good outcomes, whereas Ruminococcaceae(f) and Prevotella were enriched in the group with poor outcome. There was apparent dysbiosis of blood microbiota in patients with acute ischemic stroke compared to healthy people. Ruminococcaceae(f) and Prevotella were elevated in stroke patients with poor functional outcome.

White Matter Integrity Is Associated With the Amount of Physical Activity in Older Adults With Super-aging.

Previous studies have introduced the concept of "SuperAgers," defined as older adults with youthful memory performance associated with the increased cortical thickness of the anterior cingulate cortex. Given that age-related structural brain changes are observed earlier in the white matter (WM) than in the cortical areas, we investigated whether WM integrity is different between the SuperAgers (SA) and typical agers (TA) and whether it is associated with superior memory performance as well as a healthy lifestyle. A total of 35 SA and 55 TA were recruited for this study. Further, 3.0-T magnetic resonance imaging (MRI), neuropsychological tests, and lifestyle factors related to cognitive function, such as physical activity and duration of sleep, were evaluated in all participants. SA was defined as individuals demonstrating the youthful performance of verbal and visual memory, as measured by the Seoul Verbal Learning Test (SVLT) and the Rey-Osterrieth Complex Figure Test (RCFT), respectively. Tract-based spatial statistics (TBSS) analysis was used to compare the diffusion values such as fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) between the SA and TA. SA exhibited better performance in memory, attention, visuospatial, and frontal executive functions than the TA did. SA also exhibited greater amounts of physical activity than the TA did. As compared to TA, SA demonstrated higher FA with lower MD, RD, and AD in the corpus callosum and higher FA and lower RD in the right superior longitudinal fasciculus (SLF), which is significantly associated with memory function. Interestingly, FA values of the body of corpus callosum were correlated with the amount of physical activity. Our findings suggest that WM integrity of the corpus callosum is associated with superior memory function and a higher level of physical activities in SA compared to TA.

Four-Week, Home-Based, Robot Cognitive Intervention for Patients with Mild Cognitive Impairment: a Pilot Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Previous studies suggest that cognitive intervention can mitigate the development of dementia in patients with mild cognitive impairment (MCI). However, the previous cognitive intervention was mostly provided as a group session, in which MCI patients sometimes had difficulty in regularly attending sessions or were reluctant to participate in group-based classes. Additionally, experienced instructors for traditional cognitive intervention may be unavailable in some chronic-care facilities or community centers. Considering these reasons, we have developed 5 programs for home-based cognitive intervention using a personal robot for MCI patients. In this preliminary study, we aimed to demonstrate the effects of our newly developed home-based cognitive intervention with robots on cognitive function in MCI patients. METHODS: We conducted a single-blind randomized controlled trial enrolling 46 MCI patients. Participants were randomized into 2 groups: the robot cognitive intervention (robot) (n=24) group and without cognitive intervention (control) (n=22) group. The interventions comprised 60-min sessions per day for 4 weeks. The primary outcome was the change in cognitive function measured using the Cambridge Neuropsychological Test Automated Battery. RESULTS: There were no significant baseline demographic or clinical differences between the robot and control groups. After the 4-week cognitive intervention, the robot group showed greater improvement in working memory than did the control group. CONCLUSIONS: Our home-based cognitive intervention with a personal robot improved the working memory in MCI patients. Further studies with larger samples and longer study periods are required to demonstrate the effects of these programs in other cognitive domains in MCI patients.

Comparison of Neuropathic Pain in Neuromyelitis Optica Spectrum Disorder and Multiple Sclerosis.

BACKGROUND AND PURPOSE: To compare the characteristics of neuropathic pain in neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). METHODS: From 2016 to 2018, 500 patients with NMOSD and MS from 6 referral hospitals in Korea underwent pain investigation. After the patients with current pain were matched for sex ratio and disease duration as confounding factors, PainDETECT questionnaires were assessed in 99 NMOSD and 58 MS patients to investigate neuropathic pain. The short form of the Brief Pain Inventory from 74 patients with neuropathic pain component was also analysed. RESULTS: According to the PainDETECT questionnaire, mechanical allodynia (p=0.014) and thermal hyperalgesia (p=0.011) were more severe in NMOSD patients than in MS patients. Strong involvements (score >3) of the pain in domains of tingling/prickling sensation (p=0.024), mechanical allodynia (p=0.027), sudden pain attacks (p=0.018), and thermal hyperalgesia (p=0.002) were significantly more frequent in NMOSD compared to MS patients. Among the patients experiencing pain with a neuropathic component, total pain-related interference (p=0.045) scores were significantly higher in NMOSD patients than in MS patients. In daily life, pain interfered with normal work (p=0.045) and relationships with other people (p=0.039) more often in NMOSD patients than in MS patients. Although pain medication was prescribed more frequently in NMOSD patients, the percentage of patients experiencing medication-related pain relief was lower in those patients. CONCLUSIONS: The severity of neuropathic pain and the pain-related interference in daily life were greater in NMOSD patients than in MS patients. Individualized analgesic management should be considered based on a comprehensive understanding of neuropathic pain in these patients.

Proteomic analysis of the skeletal muscles from dysferlinopathy patients.

Dysferlinopathy is an autosomal recessive disease caused by pathogenic variants in DYSF gene. We compared muscle protein extracts from dysferlinopathy patients and control subjects to identify new biomarkers of this myopathy. We reviewed the medical records from January 2002 to October 2016. Eight vastus lateralis muscle samples from five dysferlinopathy patients and three control subjects were selected. We separated proteins/peptides from all eight muscle protein extracts using two-dimensional electrophoresis (2DE). Data were acquired from liquid chromatography-mass spectrometry protein fragmentation patterns after comparing the spot volumes. Western blotting revealed total dysferlin loss in the dysferlinopathy patients but normal expression in the control subjects. 2DE indicated somewhat diverse protein constellations between the dysferlinopathy and control groups. Image analysis showed that 80 spots were differently expressed between two dysferlinopathy and one control samples. We selected 44 spots with consistently different volume between dysferlinopathy and control groups. Liquid chromatography-mass spectrometry indicated 26 differently expressed proteins. Western blotting revealed that creatine kinase M-type, carbonic anhydrase III (muscle specific) and desmin were significantly elevated in dysferlinopathy muscle. Additionally, four proteins (myosin light chain 1/3, skeletal muscle isoform; lamin A/C; ankyrin repeat domain 2; and eukaryotic translation initiation factor 5A-1) were inconsistently elevated in the dysferlinopathy samples. We confirmed the usefulness of the classic biomarker and have newly identified the altered expression of proteins in the skeletal muscles of dysferlinopathy patients.

Comparative transcriptome analysis of skeletal muscle in ADSSL1 myopathy.

ADSSL1 myopathy was recently identified as the cause of muscular disorders in Korean patients with distal myopathy. We generated transcriptome profiles of muscles from control subjects and patients with ADSSL1 myopathy. In the present study, RNA sequencing was conducted with seven vastus lateralis muscle samples from four patients with ADSSL1 myopathy and three control subjects. The hierarchical clustering result revealed a separation between myopathy and control groups. A total of 1,260 transcripts were significantly differentially expressed (|fold change| ≥ 2, p < 0.05), with 740 upregulated transcripts and 520 downregulated transcripts in myopathy group. Eighteen transcripts that mapped to purine metabolism pathway were significantly differentially expressed between the two groups, with ten downregulated transcripts and eight upregulated transcripts in myopathy group. In particular, three genes involved in purine nucleotide cycle (ADSSL1, ADSL, and AMPD1) were significantly downregulated in myopathy group. Ten transcripts in glycolysis/gluconeogenesis pathway were also significantly differentially expressed. This is the first study on the altered expression of transcripts in muscle tissues from patients with ADSSL1 myopathy. Our results provide new insights into the pathogenesis of ADSSL1 myopathy.

Partial Conduction Block as an Early Nerve Conduction Finding in Neurolymphomatosis.

BACKGROUND AND PURPOSE: Neurolymphomatosis is a rare manifestation of hematological malignancy and is characterized by direct infiltration of the peripheral nervous system. The objective of this study was to identify the clinical and electrophysiological features of neurolymphomatosis. METHODS: We retrospectively analyzed the medical records of 13 patients with neurolymphomatosis. Seven (54%) of the patients were men, and the median age at symptom onset was 60.0 years. RESULTS: The most common type of underlying malignancy was diffuse large B-cell lymphoma (69%). Twelve patients had painful asymmetric neuropathies. The median survival time after diagnosis was 7 months, and 12 patients died during the study period. Thirty-eight motor nerve conduction studies (NCSs) were performed in the affected nerves. Ten and 28 motor nerves were classified into the conduction-block and simple-axon-degeneration groups, respectively. The median time interval between symptom onset and the NCS was significantly shorter in the conduction-block group than in the simple-axon-degeneration group (p=0.032). However, no significant differences in the motor nerve conduction velocities, terminal latencies, and distal compound muscle action potential amplitudes were identified between the conduction-block and simple-axon-degeneration groups. The conduction-block group showed excessive temporal dispersion in only five of the ten NCSs (50%). Follow-up NCSs revealed that partial conduction blocks had changed into axonal degeneration patterns. CONCLUSIONS: This is the first study to analyze the electrophysiological features of patients with neurolymphomatosis. Our findings showed that a partial conduction block is not rare and is an early nerve conduction abnormality in neurolymphomatosis.

FAT1 Gene Alteration in Facioscapulohumeral Muscular Dystrophy Type 1.

Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is caused by contraction of the D4Z4 repeat array. Recent studies revealed that the FAT1 expression is associated with disease activity of FSHD, and the FAT1 alterations result in myopathy with a FSHD-like phenotype. We describe a 59-year-old woman with both contracted D4Z4 repeat units and a FAT1 mutation. Shoulder girdle muscle weakness developed at the age of 56 years, and was followed by proximal leg weakness. When we examined her at 59 years of age, she displayed asymmetric and predominant weakness of facial and proximal muscles. Muscle biopsy showed increased variation in fiber size and multifocal degenerating fibers with lymphocytic infiltration. Southern blot analysis revealed 8 D4Z4 repeat units, and targeted sequencing of modifier genes demonstrated the c.10331 A>G variant in the FAT1 gene. This FAT1 variant has previously been reported as pathogenic variant in a patient with FSHD-like phenotype. Our study is the first report of a FAT1 mutation in a FSHD1 patient, and suggests that FAT1 alterations might work as a genetic modifier.

Diagnostic and prognostic values of cerebrospinal fluid CYFRA 21-1 in patients with leptomeningeal carcinomatosis.

OBJECTIVES: To investigate the diagnostic and prognostic values of cerebrospinal fluid (CSF) CYFRA 21-1 in patients with leptomeningeal carcinomatosis (LMC). METHODS: Concentration of CSF CYFRA 21-1 was detected using electro-chemiluminescent immunoassay. The difference in level of CYFRA 21-1 between 61 patients with LMC and 200 patients with other neurological disease was evaluated, and diagnostic performance of CSF CYFRA 21-1 was investigated. In LMC patients treated with ventriculo-lumbar perfusion (VLP) chemotherapy, prognostic performance of CSF CYFRA 21-1 was evaluated. RESULTS: The CSF CYFRA 21-1 was significantly higher in LMC patients than that in patients with other neurological diseases (p<0.001). The sensitivity, specificity, accuracy, and positive and negative predictive values were 80.3%, 95.0%, 91.6%, 83.1%, and 94.1% for CSF CYFRA 21-1, and 65.6%, 100%, 92.0%, 100%, and 90.5% for CSF cytology, respectively. The use of high CSF CYFRA 21-1 and/or positive CSF cytology findings resulted in an increased sensitivity of 85.3%, without compromising specificity. LMC patients with high CSF CYFRA 21-1 were more frequently accompanied by positive CSF cytology results than those with low CSF CYFRA 21-1. The median overall survival was longer in LMC patients with low CSF CYFRA 21-1 than in those with high CSF CYFRA 21-1 (p=0.031). During VLP chemotherapy, the clinical responses were found to be correlated with the biological responses, including the level of CSF CYFRA 21-1 and intracranial pressure. CONCLUSIONS: CSF CYFRA 21-1 might be regarded as an additional diagnostic tool for LMC and a potential significant prognostic biomarker in LMC patients treated with VLP chemotherapy.

Distal myopathy with ADSSL1 mutations in Korean patients.

To understand the characteristics of ADSSL1 myopathy, we investigated the clinical manifestation in Korean patients with ADSSL1 mutations. We developed a targeted panel of 16 distal-myopathy genes and recruited a total of 12 patients with genetically undetermined distal myopathy. We found four (33%) with ADSSL1 mutations and one (8%) with GNE mutations. ADSSL1 mutations consisted of c.910G>A, c.1048delA and c.1220T>C mutations. Patients with ADSSL1 mutations demonstrated distal muscle weakness in adolescence, followed by quadriceps muscle weakness in the early 30s. All patients had mild facial weakness and two patients complained of easy fatigue while eating and chewing. Vastus lateralis muscle biopsies revealed non-specific chronic myopathic features with a few nemaline rods. Whole body muscle MR imaging showed more fatty replacement in the distal limb and tongue muscles than in the proximal limb and axial muscles. This study showed that ADSSL1 myopathy was not rare among distal myopathy patients of Korean origin, and expanded the clinical and genetic spectrum. Therefore, we suggest that the screening test of ADSSL1 gene should be considered for the diagnosis of distal myopathy.

Laryngeal myofascial pain syndrome as a new diagnostic entity of dysphonia.

OBJECTIVE: To consider the feasibility of diagnosing intrinsic laryngeal muscle myofascial pain syndrome (MPS) in dysphonic patients who demonstrated immediate symptom and stroboscopic finding improvement after laryngeal electromyography (LEMG) without further treatment. METHODS: A chart review of patients who showed subtle vocal fold movement abnormalities on a stroboscopic examination and underwent ultrasonography (US)-guided LEMG was performed. Patients with vocal fold paralysis, mucosal lesions, spasmodic dysphonia, and vocal tremor on stroboscopic examination were excluded. Among them, patients with normal EMG findings were included in this study. The patients who reported voice symptom improvement after LEMG without further treatment were placed in laryngeal MPS (LMPS) group and the other patients were placed in non-laryngeal MPS (non-MPS) group. Predisposing factors, voice symptom, symptom-duration, and stroboscopic findings of these patients were reviewed. RESULTS: Among the 16 patients, LEMG findings were normal, five (31%) were included in the LMPS group and the other 11 patients (69%) were included in the non-MPS group. All LMPS group patients had a history of voice abuse and reported odynophonia. The Korean Voice Handicap Index-10 score decreased significantly after US-guided LEMG without additional treatment in the LMPS group. The stroboscopic findings revealed that vocal fold hypomobility was the most common finding in the LMPS group, and two patients showed a muscle tension dysphonia pattern. The LMPS groups showed improvement of vocal fold mobility on 1-week stroboscopic evaluation. CONCLUSION: LMPS is a potential diagnosis for patients with vocal fold hypomobility finding on stroboscopic findings but with normal EMG results. Diagnosis of LMPS could be considered in patients who showed symptom and vocal fold movement improvement after LEMG.

Clinical predictors of seizure recurrence after the first post-ischemic stroke seizure.

BACKGROUND: The number of patients suffering post-stroke seizure after ischemic stroke (PSSi) is quite considerable, especially because ischemic stroke is more prevalent than hemorrhage in the general population. This study aimed to determine the predicting factors for seizure recurrence in ischemic stroke survivors and develop a clinical scoring system for the prediction of risks for seizure recurrence after the first PSSi. METHODS: We reviewed 3792 ischemic stroke patients who had admitted to Ewha Womans University hospital between 2001 and 2012. A total of 124 (3.3 %) patients who experienced PSSi were recruited (mean follow-up for 44.4 months). Medical records concerning the etiology, functional disability, seizure onset latency from stroke, type of seizure, electroencephalography (EEG), and neuroimaging findings were statistically analyzed to derive a seizure recurrence risk scoring system. RESULTS: Seizures recurred in 35.4 % (17/48) of early PSSi patients (≤1 week since stroke onset) and 48.7 % (37/76) of late PSSi (>1 week) patients. Atrial fibrillation, large sized, and cortical stroke lesion were more common in late onset PSSi compared to those in early onset PSSi (p < 0.05). Seizure recurrence tended to be more prevalent in early PSSi patients with male gender, atrial fibrillation or cortical stroke lesion, severe functional disability, and partial seizures. Seizure recurrence in late PSSi group was more common in patients of young age (≤65 years old), male gender, large lesion size, and partial seizure type. The validity of seizure recurrence risk score in the early PSSi group was better when evaluating based on gender, atrial fibrillation, cortical lesion, functional disability, and partial seizure type, with sensitivity of 70.6 % and specificity of 71.0 %. CONCLUSIONS: Our study characterized the high risk group for seizure recurrence in patients with the first PSSi. PSSi patients with high risk score of seizure recurrence had a greater chance of developing epilepsy later. Therefore, they should be considered for further treatment such as antiepileptic drug medication in clinical practice.

Clinical and Pathological Heterogeneity of Korean Patients with CAPN3 Mutations.

PURPOSE: This study was designed to investigate the characteristics of Korean patients with calpainopathy. MATERIALS AND METHODS: Thirteen patients from ten unrelated families were diagnosed with calpainopathy via direct or targeted sequencing of the CAPN3 gene. Clinical, mutational, and pathological spectra were then analyzed. RESULTS: Nine different mutations, including four novel mutations (NM_000070: c.1524+1G>T, c.1789_1790inA, c.2184+1G>T, and c.2384C>T) were identified. The median age at symptom onset was 22 (interquartile range: 15-28). Common clinical findings were joint contracture in nine patients, winged scapula in four, and lordosis in one. However, we also found highly variable clinical features including early onset joint contractures, asymptomatic hyperCKemia, and heterogeneous clinical severity in three members of the same family. Four of nine muscle specimens revealed lobulated fibers, but three showed normal skeletal muscle histology. CONCLUSION: We identified four novel CAPN3 mutations and demonstrated clinical and pathological heterogeneity in Korean patients with calpainopathy.