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Osmotic demyelination syndrome (ODS) is an acute demyelinating disorder characterized by the loss of myelin in the center of the basis pons, defined as central pontine myelinolysis (CPM), and demyelination in locations outside the pons, defined as extrapontine myelinolysis (EPM). ODS including CPM and EPM is mainly caused by rapid correction of hyponatremia. However, there are several reports of ODS in medical conditions such as malnutrition; alcoholism; liver transplantation; malignancy; sepsis; and electrolyte imbalance including hypernatremia, hypokalemia, hypophosphatemia, and chronic illness. ODS caused by rapid correction of hyperammonemia or continuous hyperbilirubinemia without sodium fluctuations has rarely been reported. Because ODS may be irreversible, prevention is crucial. Herein, we report a case of ODS secondary to rapid correction of hyperammonemia and continuous hyperbilirubinemia.

Mutations in the SACS gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of Charcot-Marie-Tooth disease (CMT). This study aimed to identify SACS mutations in a Korean CMT cohort with cerebellar ataxia and spasticity by whole exome sequencing (WES). As a result, eight pathogenic SACS mutations in four families were identified as the underlying causes of these complex phenotypes. The prevalence of CMT families with SACS mutations was determined to be 0.3%. All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was performed in four patients and all had fatty replacements. Of note, they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without SACS mutations who had distal dominant fatty involvement. Therefore, these findings were considered a characteristic feature in CMT patients with SACS mutations. Although further studies with more cases are needed, our results highlight lower extremity MRI findings in CMT patients with SACS mutations and broaden the clinical spectrum. We suggest screening for SACS in recessive CMT patients with complex phenotypes of ataxia and spasticity.

The electrons, accelerated by the laser ponderomotive force and subsequent plasma wakefields, radiate broadband emission continuously along the laser propagation direction, resulting in multi-mJ THz radiation in the far field.

Triplet–triplet fusion (TTF) has been an efficiency-enhancing mechanism in fluorescent organic light-emitting diodes (OLEDs) caused by the collision of two triplet excitons. However, achieving a high TTF ratio in fluorescent OLEDs has been difficult despite device strategies to maximize the triplet exciton density within a narrow recombination zone near the electron blocking layer (EBL) due to charge imbalance and hole accumulation between the TTF type emitter and EBL. Based on a trap-detrap mechanism, we were able to realize an improved TTF ratio and reduce hole accumulation by adding a TTF-assisting material (TTF-AM) in the TTF emitter. The TTF-AM served as the hole transport channel, triggering hole trap and detrap while improving the hole transport character of the emitting layer. Through the process of hole detrapping, the improved hole transport properties balanced carriers and generated more triplet excitons in order to activate the TTF mechanism from low to high current density ranges. By adjusting the TTF-AM, the TTF ratio of the anthracene-based emitter was increased from 5.5/20.1% to 13.4/25.5% (low/high current density), thereby resulting in more than doubled external quantum efficiency at low current density.

Abstract Charcot–Marie–Tooth disease (CMT) is the most common hereditary peripheral neuropathy. Mutations in the neurofilament light polypeptide (NEFL) gene produce diverse clinical phenotypes, including demyelinating (CMT1F), axonal (CMT2E), and intermediate (CMTDIG) neuropathies. From 2005 to 2020, 1,143 Korean CMT families underwent gene sequencing, and we investigated the clinical, genetic, and neuroimaging spectra of NEFL‐related CMT patients. Ten NEFL mutations in 17 families (1.49%) were identified, of which three (p.L312P, p.Y443N, and p.K467N) were novel. Eight de novo cases were identified at a rate of 0.47 based on a cosegregation analysis. The age of onset was ≤3 years in five cases (13.5%). The patients revealed additional features including delayed walking, ataxia, dysphagia, dysarthria, dementia, ptosis, waddling gait, tremor, hearing loss, and abnormal visual evoked potential. Signs of ataxia were found in 26 patients (70.3%). In leg MRI analyses, various degrees of intramuscular fat infiltration were found. All compartments were evenly affected in CMT1F patients. The anterior and anterolateral compartments were affected in CMT2E, and the posterior compartment was affected in CMTDIG. Thus, NEFL‐related CMT patients showed phenotypic heterogeneities. This study's clinical, genetic, and neuroimaging results could be helpful in the evaluation of novel NEFL variants and differential diagnosis against other CMT subtypes.

Objective To evaluate the effects of extracorporeal shockwave therapy (ESWT) on improving lymphedema, quality of life, and fibrous tissue in patients with stage 2 lymphedema. Methods Breast cancer-related lymphedema patients referred to the rehabilitation center were recruited. We enrolled stage 2 lymphedema patients who had firmness of the skin at their forearm, a circumference difference of more than 2 cm between each arm, or a volume difference between upper extremities greater than 200 mL, confirmed by lymphoscintigraphy. The patients were randomly divided into the ESWT group and the control group. ESWT was performed for 3 weeks (two sessions per week); both groups received complex decongestive physical therapy. All patients were evaluated at baseline and at 3 weeks after treatment. The measurements performed included visual analog scale score, volume, circumference, QuickDASH (Quick Disabilities of the Arm, Shoulder and Hand) score, bioelectrical impedance, and skin thickness. Results The patients in both groups (n=15 in each group) completed the 3-week therapy experiment. No significant differences were observed in demographic characteristics between groups. After the 3-week treatment period, improvement was noted in the circumference difference below the elbow, volume, ratio of extracellular water to total body water, and skin thickness in the ESWT group. A significant difference was found in all the above-mentioned areas except in circumference below the elbow in the ESWT group. Conclusion ESWT reduced edema and skin fibrosis without significant complications. Therefore, ESWT can be used together with complex decongestive physical therapy for treating lymphedema.

Abstract Background Charcot‐Marie‐Tooth disease (CMT) is the most common disorder of inherited peripheral neuropathies characterized by distal muscle weakness and sensory loss. CMT is usually classified into three types, demyelinating, axonal, and intermediate neuropathies. Mutations in myelin protein zero (MPZ) gene which encodes a transmembrane protein of the Schwann cells as a major component of peripheral myelin have been reported to cause various type of CMT. Methods This study screened MPZ mutations in Korean CMT patients (1,121 families) by whole exome sequencing and targeted sequencing. Results We identified 22 pathogenic or likely pathogenic MPZ mutations in 36 families as the underlying cause of the CMT1B, CMTDID, or CMT2I subtypes. Among them, five mutations were novel. The frequency of CMT patients with the MPZ mutations was similar or slightly lower compared to other ethnic groups. Conclusions We showed that the median onset ages and clinical phenotypes varied by subtypes: the most severe in the CMT1B group, and the mildest in the CMT2I group. This study also observed a clear correlation that earlier onsets cause more severe symptoms. We believe that this study will provide useful reference data for genetic and clinical information on CMT patients with MPZ mutations in Korea.

Objective To investigate the effect of decreased Skeletal Muscle Index (SMI) and hand grip strength on functional recovery in subacute ambulatory stroke patients. Methods Subacute stroke patients who were referred to the rehabilitation center were recruited. Decreased SMI and hand grip strength were diagnosed according to the Asian Working Group on Sarcopenia. Diagnostic criteria were decreased SMI and decreased unaffected hand grip strength. SMI was measured by bioelectrical impedance analysis. Unaffected hand grip strength was measured with a hand dynamometer. Patients were divided into two groups, decreased group (DG) and not-decreased group (NDG), according to the presence of decreased SMI and hand grip strength. Both groups received conventional stroke rehabilitation for 3 weeks. All patients were evaluated at the baseline and at 3 weeks after treatment. Functional status was evaluated with 4-meter walk test (4MWT), 6-minute walk test (6MWT), Timed Up and Go test (TUG), and Modified Barthel Index (MBI). Results Both groups showed improvement in 4MWT, TUG, and MBI. NDG showed improvement in 6MWT. Comparing improvements between the two groups, NDG showed more improvement in 6MWT and TUG than DG. Conclusion The presence of decreased SMI and hand grip strength had negative effects on functional recovery in subacute ambulatory stroke patients.

Objective To determine positive effect of neuromuscular electrical stimulation (NMES) in conventional dysphagia therapy on masseter muscle oral dysfunction of patients after subacute stroke. Methods Among subacute stroke patients who were diagnosed as oropharyngeal dysphagia by videofluoroscopy swallowing study (VFSS), those with oral dysfunction were enrolled. They were randomly assigned to a study group or a control group. The study group received NMES on masseter muscle and suprahyoid muscle simultaneously, while the control group received NMES only on suprahyoid muscle. NMES therapy session as applied 30 minutes each time, two times per day for a total of 20 sessions. Both groups received conventional dysphagia therapy for 2 weeks. All enrolled patients were evaluated by VFSS after 2 weeks. Oropharyngeal swallowing function was evaluated by Penetration-Aspiration Scale, Functional Dysphagia Scale (FDS), and American Speech-Language-Hearing Association National Outcome Measurement System swallowing scale based on results of VFSS. Results Patients were randomly assigned to the study group (n=20) or the control group (n=20). There were no significant differences in baseline characteristics or initial values between the two groups. After 2 weeks of NMES, both groups showed improvement in scores of total FDS and pharyngeal phase FDS. Additionally, the study group showed improvement in oral phase FDS. Changes in all measurements were similar between the two groups. Conclusion In this preliminary study, NMES for masseter muscle has a therapeutic effect on oral dysfunction of patients after subacute stroke.

Objective To investigate the effects of combination functional electrical stimulation (FES) and standing frame training on standing balance in stroke patients. Methods Patients who had hemiparesis and postural instability after stroke were randomly assigned to one of the two groups; study group underwent FES on the quadriceps and tibialis anterior muscle simultaneously with standing balance training. The control group received standing frame training and FES separately. Both the groups received their respective therapies for 3 weeks. Stability index in Biodex Balance master system, Berg Balance Scale (BBS), manual muscle test, the Korean version of Modified Barthel Index, and Korean version of Mini-Mental State Examination were used to evaluate the effects of the treatment. Results In total, 30 patients were recruited to the study group and 30 to the control group. Three weeks after treatment, both the groups showed improvement in postural stability scores and physical and cognitive functions. When changes in postural stability were compared between the groups, the study group showed more significant improvement than the control group with regards to the scores of BBS and the stability indices. Conclusion In this study, we found the therapeutic effectiveness of combined therapy of FES and standing frame in subacute stroke patients. The presented protocol is proposed as time-saving and can be applied easily in the clinical setting. Thus, the proposed combined therapy could be a useful method for improving standing balance in subacute stroke patients.

Duplication and deletion of the peripheral myelin protein 22 (PMP22) gene cause Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP), respectively, while point mutations or small insertions and deletions (indels) usually cause CMT type 1E (CMT1E) or HNPP. This study was performed to identify PMP22 mutations and to analyze the genotype–phenotype correlation in Korean CMT families. By the application of whole-exome sequencing (WES) and targeted gene panel sequencing (TS), we identified 14 pathogenic or likely pathogenic PMP22 mutations in 21 families out of 850 CMT families who were negative for 17p12 (PMP22) duplication. Most mutations were located in the well-conserved transmembrane domains. Of these, eight mutations were not reported in other populations. High frequencies of de novo mutations were observed, and the mutation sites of c.68C>G and c.215C>T were suggested as the mutational hotspots. Affected individuals showed an early onset-severe phenotype and late onset-mild phenotype, and more than 40% of the CMT1E patients showed hearing loss. Physical and electrophysiological symptoms of the CMT1E patients were more severely damaged than those of CMT1A while similar to CMT1B caused by MPZ mutations. Our results will be useful for the reference data of Korean CMT1E and the molecular diagnosis of CMT1 with or without hearing loss.

Objective To investigate the effect of upper limb rehabilitation combining robot with low-frequency repetitive transcranial magnetic stimulation (rTMS) on unilateral spatial neglect in stroke patients. Methods Patients who had hemispatial neglect after right hemisphere stroke were randomly divided into rTMS only group, robot only group, and combined group. All groups received conventional neglect therapy and additional treatment for each group. rTMS group received rTMS therapy. Robot group received robot therapy, while combined group received both therapies. The effect of therapy was assessed with Motor-Free Visual Perception Test-3 (MVPT-3), line bisection test, star cancellation test, Catherine Bergego Scale (CBS), Mini-Mental State Examination (MMSE), and the Korean version of Modified Barthel Index (K-MBI). These measurements were evaluated before and after treatment. Results For each group, 10 patients were recruited. There were no significant differences in baseline characteristics or initial values among the three groups. Two weeks after the therapy, all groups showed significant improvement in MVPT-3, line bisection test, star cancellation test, CBS, MMSE, and K-MBI. However, changes in measurements showed no significant differences among groups. Conclusion Treatment effect of the combined therapy of robotic therapy and low-frequency rTMS therapy for hemispatial neglect was not statistically different from that of each single treatment. Results of this study did not prove the superiority of any of the three treatments. Further study with large number of patients is needed to evaluate the superiority of these treatments.

Objective: To investigate the therapeutic effects of mechanical inspiration and expiration exercise using mechanical cough assist on velopharyngeal incompetence in patients with subacute stroke. Design: Pilot, randomized controlled study. Setting: University-based rehabilitation centre. Subjects: Thirty-six patients with subacute stroke diagnosed with velopharyngeal incompetence by videofluoroscopic swallowing study. Methods: Subjects were randomly assigned to 2 groups. The study group received conventional dysphagia therapy and additional mechanical inspiration and expiration exercise. The control group received conventional dysphagia therapy only. Swallowing function was evaluated according to the American Speech-Language-Hearing association scale, functional dysphagia score, and the penetration aspiration scale, based on the videofluoroscopic swallowing study. Coughing function was measured using peak cough flow. Results: Eighteen patients in each group completed the protocol and were analysed. After treatment, the study group showed significant improvement in functional dysphagia score with regard to nasal penetration degree. Comparing the treatment effect between the 2 groups, nasal penetration degree and peak cough flow showed greater improvement in the study group. Conclusion: Mechanical inspiration and expiration exercise had a therapeutic effect on velopharyngeal incompetence in subacute stroke patients with dysphagia. This therapy is easy to provide clinically and could be a useful therapeutic strategy for velo-pharyngeal incompetence with dysphagia in patients with stroke.

Objective To investigate the effects of hand training using low-frequency repetitive transcranial magnetic stimulation (rTMS) within the aftereffect period on hand function in patients with subacute stroke. Methods The subacute stroke patients with hand weaknesses were divided randomly into two groups. Patients in the intervention group underwent hand training within the aftereffect period, that is, immediately after receiving low-frequency rTMS treatment. Patients in the control group underwent hand training 2 hours after the low-frequency rTMS treatment. A manual function test (MFT) for ‘grasp and pinch’ and ‘hand activities’; a manual muscle test (MMT) for ‘grasp’, ‘release’, and ‘abductor pollicis brevis (APB)’; and the Modified Ashworth Scale for finger flexion were performed and measured before and immediately after combined therapy as well as 2 weeks after combined therapy. Results Thirty-two patients with hand weakness were enrolled in this study. The intervention group patients showed more improvements in grasp MMT and MMT APB tested immediately after combined therapy. However, the changes in all measurements were not significantly different between the two groups 2 weeks after the combined therapy. In both groups, hand functions improved significantly immediately after combined therapy and 2 weeks after combined therapy. Conclusion Hand training immediately after low-frequency rTMS showed more rapid improvement in the motor power of hands than hand training conducted 2 hours after low-frequency rTMS. Our results suggest that conducting hand training immediately after low-frequency rTMS could be an improved useful therapeutic option in subacute stroke patients.

ObjectiveTo evaluate the effect of caregiver driven robot-assisted in-ward training in subacute stroke patients.MethodsA retrospective evaluation was performed for patients treated with caregiver driven robot-assisted in-ward training to retain gait function from June 2014 and December 2016. All patients received more than 2 weeks of caregiver driven robot-assisted in-ward training after undergoing conventional programs. The robot was used as a sitting device, a standing frame, or a high-walker depending on functional status of the patient. Patients were evaluated before and after robot training. Patient records were assessed by Korean version of Modified Barthel Index (K-MBI), Functional Independence Measure (FIM), and Functional Ambulation Category (FAC).ResultsInitially, patients used the robot as a sitting device (n=6), a standing frame (n=7), or a partial body-weight support high-walker (n=2). As patient functions were improved, usage level of the robot was changed to the next level. At the end of the treatment, the robot was used as a sitting device (n=1), a standing frame (n=6), or high-walker (n=8). Scores of K-MBI (Δ17.47±10.72) and FIM (Δ19.80±12.34) were improved in all patients.ConclusionPatients' usage level of the robot and functional scores were improved. Therefore, performing additional caregiver driven robot-assisted in-ward training is feasible and beneficial for subacute stroke patients.

ObjectiveTo demonstrate the usefulness of early videofluoroscopic swallowing study (VFSS) and to investigate change patterns in dietary methods in stroke patients with dysphagia.MethodsThe VFSS was performed within 7 days of stroke onset in neurologically stable patients. The patients were divided into three groups according to type of brain lesion: cortical lesion (CL), subcortical lesion (SCL), and brainstem/cerebellar lesion (BCL). Based on the VFSS results, this study investigated change patterns in feeding method and discrepancies in the aspiration risk predicted by the Water Swallowing Test (WST) and the VFSS. Complications, such as aspiration pneumonia, were also evaluated.ResultsA total of 163 patients met the inclusion criteria and the VFSS was performed within 7 days of stroke. Patients considered at risk for aspiration (Penetration-Aspiration Scale [PAS] scores of 6 to 8) were found in all three groups using the VFSS (47.5% of the CL group, 59.3% of the SCL group, and 47.9% of the BCL group). After early VFSS, 79.7% of the patients were assessed to require restricted feeding methods. A 19.0% discrepancy was found between the WST and VFSS results. At 3-week follow-up after the VFSS, aspiration pneumonia was observed in 12 patients (7.4%) with restricted feeding methods.ConclusionEarly VFSS during the acute period can facilitate determination of the most appropriate feeding method, and support effective dysphagia management for stroke patients.

Charcot–Marie–Tooth disease (CMT) is the most common inherited peripheral neuropathy. Mutations in the GNB4 gene cause dominant intermediate CMT type F (CMTDIF). The aim of this study is to investigate phenotypic heterogeneities and characteristics of CMT patients with GNB4 mutations. We enrolled 1143 Korean CMT families and excluded 344 families with a PMP22 duplication. We further analyzed the 799 remaining families to find their GNB4 mutations using whole-exome sequencing (WES). We identified two mutations (p.Gly77Arg and p.Lys89Glu) in three families, among which a heterozygous p.Gly77Arg mutation was novel. In addition, a significant uncertain variant (p.Thr177Asn) was observed in one family. The frequency of the GNB4 mutation in the Korean population is 0.38% in PMP22 duplication-negative families. All three families showed de novo mutation. Electrophysiological findings regarding the p.Lys89Glu mutation showed that the motor nerve conduction velocity (MNCV) of the median nerve was markedly reduced, indicating demyelinating neuropathy, and sural nerve biopsy revealed severe loss of myelinated axons with onion bulb formation. Lower extremity Magnetic Resonance Imaging (MRI) demonstrated relatively more severe intramuscular fat infiltrations in demyelinating type (p.Lys89Glu mutation) patients compared to intermediate type (p.Gly77Arg mutation) patients. The anterolateral and superficial posterior compartment muscles of the distal calf were preferentially affected in demyelinating type patients. Therefore, it seems that the investigated GNB4 mutations do cause not only the known intermediate type but also demyelinating-type neuropathy. We first presented three Korean families with GNB4 mutations and found phenotypic heterogeneities of both intermediate and demyelinating neuropathy. We suggest that those findings are useful for the differential diagnosis of CMT patients with unknown GNB4 variants.

Abstract Understanding the water sorption behavior of protein powders is important in applications such as the preservation of protein-based pharmaceuticals. Most globular proteins exhibit a characteristic sigmoidal water adsorption isotherm at ambient conditions. However, it is not well understood how water sorption behavior is influenced by intrinsic factors that are related to structural properties of proteins. We investigate computationally how structural constraints on proteins influence the water sorption isotherms of amorphous protein powders. Specifically, we study the effects of non-local disulfide linkages and backbone connectivity using pheromone ER-23 and lysozyme as model proteins. We find that non-local disulfide linkages can significantly restrict structural changes during hydration and dehydration, and this in turn greatly reduces the extent of hysteresis between the adsorption and desorption branches. Upon removing the backbone connectivity by breaking all peptide bonds in lysozyme, we find that the hysteresis shifts towards the lower humidity regime, and the water uptake capacity is significantly enhanced. We attribute these changes to the higher aggregation propensity of the constraint-free amino acids in dehydrated condition, and the formation of a spanning water network at high hydration levels.

This is a case report of a patient with soft palate muscle weakness that caused difficulties with phonation. A provisional palatal lift prosthesis (PLP) was developed, and the patient underwent simultaneous speech therapy. The elevation level of the palatal lift was subjectively assessed along with nasalance analysis and the Urimal Test of Articulation and Phonation results. The final PLP was applied to improve comfort and efficiency, and the patient continually underwent regular speech therapy. The patient showed satisfactory improvement in speech and pronunciation. PLP development combined with speech therapy can improve the accuracy of pronunciation in patients with palatal incompetence, thereby improving quality of life. [ABSTRACT FROM AUTHOR]