Peripheral Nerve Regeneration Using a Nerve Conduit with Olfactory Ensheathing Cells in a Rat Model

BACKGROUND@#Autologous nerve grafts are the gold standard treatment for peripheral nerve injury treatment. However, this procedure cannot avoid sacrificing other nerves as a major limitation. The aim of the present study was to evaluate the potential of olfactory ensheathing cells (OECs) embedded in a nerve conduit. @*METHODS@#A 10-mm segment of the sciatic nerve was resected in 21 rats, and the nerve injury was repaired with one of the following (n = 7 per group): autologous nerve graft, poly (ε-caprolactone) (PCL) conduit and OECs, and PCL conduit only. The consequent effect on nerve regeneration was measured based on the nerve conduction velocity (NCV), amplitude of the compound muscle action potential (ACMAP), wet muscle weight, histomorphometric analysis, and nerve density quantification. @*RESULTS@#Histomorphometric analysis revealed nerve regeneration and angiogenesis in all groups. However, there were significant differences (p  0.05). No significant results in NCV, wet muscle weight, and nerve density quantification were observed among the 3 groups. @*CONCLUSION@#A PCL conduit with OECs enhances the regeneration of injured peripheral nerves, offering a good alternative to autologous nerve grafts.

Peripheral Nerve Regeneration Using a Nerve Conduit with Olfactory Ensheathing Cells in a Rat Model

BACKGROUND@#Autologous nerve grafts are the gold standard treatment for peripheral nerve injury treatment. However, this procedure cannot avoid sacrificing other nerves as a major limitation. The aim of the present study was to evaluate the potential of olfactory ensheathing cells (OECs) embedded in a nerve conduit. @*METHODS@#A 10-mm segment of the sciatic nerve was resected in 21 rats, and the nerve injury was repaired with one of the following (n = 7 per group): autologous nerve graft, poly (ε-caprolactone) (PCL) conduit and OECs, and PCL conduit only. The consequent effect on nerve regeneration was measured based on the nerve conduction velocity (NCV), amplitude of the compound muscle action potential (ACMAP), wet muscle weight, histomorphometric analysis, and nerve density quantification. @*RESULTS@#Histomorphometric analysis revealed nerve regeneration and angiogenesis in all groups. However, there were significant differences (p  0.05). No significant results in NCV, wet muscle weight, and nerve density quantification were observed among the 3 groups. @*CONCLUSION@#A PCL conduit with OECs enhances the regeneration of injured peripheral nerves, offering a good alternative to autologous nerve grafts.

Rehabilitation of spinal muscular atrophy: current consensus and future direction

Spinal muscular atrophy (SMA) is a neuromuscular disease that requires multidisciplinary medical care, including rehabilitation management. The emergence of a genetic therapy-based approach for SMA has markedly changed the disease course.Nonetheless, currently, updated physical therapy and rehabilitation are warranted for individuals with SMA in the era of gene therapy. In this review, we discuss the physical therapy and rehabilitation strategies currently performed for people with SMA, such as positioning and bracing, supported standing, management of musculoskeletal deformities, stretching, physical exercise training like aerobics and strengthening exercises, assistive devices, pulmonary rehabilitation, and dysphagia treatment.

Rehabilitation of spinal muscular atrophy: current consensus and future direction

Spinal muscular atrophy (SMA) is a neuromuscular disease that requires multidisciplinary medical care, including rehabilitation management. The emergence of a genetic therapy-based approach for SMA has markedly changed the disease course.Nonetheless, currently, updated physical therapy and rehabilitation are warranted for individuals with SMA in the era of gene therapy. In this review, we discuss the physical therapy and rehabilitation strategies currently performed for people with SMA, such as positioning and bracing, supported standing, management of musculoskeletal deformities, stretching, physical exercise training like aerobics and strengthening exercises, assistive devices, pulmonary rehabilitation, and dysphagia treatment.

Correlation Between Vanishing White Matter Disease and Novel Heterozygous EIF2B3 Variants Using Next-Generation Sequencing: A Case Report

Vanishing white matter (VWM) disease is an autosomal recessive disorder that affects the central nervous system of a patient, and is caused by the development of pathogenic mutations in any of the EIF2B1-5 genes. Any dysfunction of the EIF2B1-5 gene encoded eIF2B causes stress-provoked episodic rapid neurological deterioration in the patient, followed by a chronic progressive disease course. We present the case of a patient with an infantile-onset VWM with the pre-described specific clinical course, subsequent neurological aggravation induced by each viral infection, and the noted consequent progression into a comatose state. Although the initial brain magnetic resonance imaging did not reveal specific pathognomonic signs of VWM to distinguish it from other types of demyelinating leukodystrophy, the next-generation sequencing studies identified heterozygous missense variants in EIF2B3, including a novel variant in exon 7 (C706G), as well as a 0.008% frequency reported variant in exon 2 (T89C). Hence, the characteristic of unbiased genomic sequencing can clinically affect patient care and decisionmaking, especially in terms of the consideration of genetic disorders such as leukoencephalopathy in pediatric patients.

Chromosomal Microarray Analysis as a First-Tier Clinical Diagnostic Test in Patients With Developmental Delay/Intellectual Disability, Autism Spectrum Disorders, and Multiple Congenital Anomalies: A Prospective Multicenter Study in Korea

BACKGROUND: To validate the clinical application of chromosomal microarray analysis (CMA) as a first-tier clinical diagnostic test and to determine the impact of CMA results on patient clinical management, we conducted a multicenter prospective study in Korean patients diagnosed as having developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA). METHODS: We performed both CMA and G-banding cytogenetics as the first-tier tests in 617 patients. To determine whether the CMA results directly influenced treatment recommendations, the referring clinicians were asked to complete a 39-item questionnaire for each patient separately after receiving the CMA results. RESULTS: A total of 122 patients (19.8%) had abnormal CMA results, with either pathogenic variants (N=65) or variants of possible significance (VPS, N=57). Thirty-five well-known diseases were detected: 16p11.2 microdeletion syndrome was the most common, followed by Prader-Willi syndrome, 15q11-q13 duplication, Down syndrome, and Duchenne muscular dystrophy. Variants of unknown significance (VUS) were discovered in 51 patients (8.3%). VUS of genes putatively associated with developmental disorders were found in five patients: IMMP2L deletion, PTCH1 duplication, and ATRNL1 deletion. CMA results influenced clinical management, such as imaging studies, specialist referral, and laboratory testing in 71.4% of patients overall, and in 86.0%, 83.3%, 75.0%, and 67.3% of patients with VPS, pathogenic variants, VUS, and benign variants, respectively. CONCLUSIONS: Clinical application of CMA as a first-tier test improves diagnostic yields and the quality of clinical management in patients with DD/ID, ASD, and MCA.

Patient With Delayed Development Resulting From De Novo Duplication of 7q36.1-q36.3 and Deletion of 9p24.3

Patients with a duplication from 7q36 to the terminus or a deletion of 9p24 have been reported, whereas those harboring both mutations have not. Here, we report a patient with simultaneous de novo 7q36.1-q36.3 duplication and 9p24.3 deletion. A 6-year-old boy presented with speech developmental delay, microcephaly, and dysmorphic features, including a long face and small nose. Chromosome and array comparative genomic hybridization analyses revealed 46,XY,dup(7)(q36.1-q36.3) and del(9)(p24.3). The sizes of the duplication and deletion were 9.9 Mb and 1.9 Mb, respectively. The duplication of chromosome 7 contained 68 known genes, of which 3 are related with entries in the Developmental Disorders Genotype-to-Phenotype (DDG2P) database. The deletion of chromosome 9 contained 6 known genes, of which 2 are in the DDG2P database. We investigated the genotype and phenotype in this patient, and reviewed the relevant literatures for possible clinical presentation in these variations.

Relationship Between Mobility and Self-Care Activity in Children With Cerebral Palsy

OBJECTIVE: To investigate the factors influencing the development of self-care activity, and the association between mobility and self-care activity in children with cerebral palsy (CP). METHODS: A total of 63 CP children aged ≥4 years, were studied retrospectively. Children with severe intellectual disability or behavioral problems were excluded. The relationship between the Gross Motor Function Classification System (GMFCS), the Manual Ability Classification System (MACS), and the Pediatric Evaluation of Disability Inventory (PEDI) was analyzed. Simple and multiple linear regression analyses were conducted for continuous variables, such as verbal intelligence quotient (IQ) and PEDI subscales. RESULTS: Final evaluation was done for 25 children, ranging from 4 to 11 years of age. According to GMFCS levels, the differences in PEDI-self-care scores, showed statistically borderline significance (p=0.051). Conversely, differences in PEDI-self-care scores according to CP types and MACS levels were not statistically significant. Simple linear regression analysis showed that PEDI mobility and PEDI social function significantly influence the PEDI self-care. Multiple linear regression analysis showed that PEDI mobility was the only factor significantly influencing PEDI self-care in children aged ≥7 years (R²=0.875, p=0.03). CONCLUSION: Mobility is important for the acquisition of self-care abilities in children with CP aged ≥7 years.

Sonographic Findings of Polyneuropathy Associated With Cerebrotendinous Xanthomatosis: A Case Report

Cerebrotendinous xanthomatosis is a rare autosomal recessive disease that involves multiple organs, including the peripheral nervous system. The present study is the first to report the ultrasonographic findings of peripheral nerves in a patient with cerebrotendinous xanthomatosis. The patient presented with bilateral Achilles tendon enlargement and foot hypesthesia. Sonographic examination revealed hypoechoic, swollen peripheral nerves with enlarged bilateral Achilles tendons. Since the ultrasonographic findings revealed peripheral involvement, the diagnosis of cerebrotendinous xanthomatosis was established after laboratory and genetic studies along with clinical findings.

Novel Mutation (c.8725T>C) in Two Siblings With Late-Onset LAMA2-Related Muscular Dystrophy

No abstract available.

Novel Mutation (c.8725T>C) in Two Siblings With Late-Onset LAMA2-Related Muscular Dystrophy

No abstract available.

Phenotype of a Patient With a 1p36.11-p35.3 Interstitial Deletion Encompassing the AHDC1

No abstract available.

Identification of a Heterozygous SPG11 Mutation by Clinical Exome Sequencing in a Patient With Hereditary Spastic Paraplegia: A Case Report

Next-generation sequencing, such as whole-genome sequencing, whole-exome sequencing, and targeted panel sequencing have been applied for diagnosis of many genetic diseases, and are in the process of replacing the traditional methods of genetic analysis. Clinical exome sequencing (CES), which provides not only sequence variation data but also clinical interpretation, aids in reaching a final conclusion with regards to genetic diagnosis. Sequencing of genes with clinical relevance rather than whole exome sequencing might be more suitable for the diagnosis of known hereditary disease with genetic heterogeneity. Here, we present the clinical usefulness of CES for the diagnosis of hereditary spastic paraplegia (HSP). We report a case of patient who was strongly suspected of having HSP based on her clinical manifestations. HSP is one of the diseases with high genetic heterogeneity, the 72 different loci and 59 discovered genes identified so far. Therefore, traditional approach for diagnosis of HSP with genetic analysis is very challenging and time-consuming. CES with TruSight One Sequencing Panel, which enriches about 4,800 genes with clinical relevance, revealed compound heterozygous mutations in SPG11. One workflow and one procedure can provide the results of genetic analysis, and CES with enrichment of clinically relevant genes is a cost-effective and time-saving diagnostic tool for diseases with genetic heterogeneity, including HSP.

Clinical Findings of Asymptomatic Carpal Tunnel Syndrome in Patients With Diabetes Mellitus

OBJECTIVE: To evaluate the clinical differences between patients with diabetes mellitus (DM) who have asymptomatic carpal tunnel syndrome (CTS) and those who have symptomatic CTS. METHODS: Sixty-three patients with DM were assessed using the Boston Carpal Tunnel Questionnaire (BCTQ), nerve conduction studies (NCS), and ultrasonographic evaluation of the cross-sectional area (CSA) of the median nerve. According to the BCTQ responses and NCS results, the patients were divided into the following three groups: group 1 (n=16), in which NCS results did not reveal CTS; group 2 (n=19), in which NCS results revealed CTS but the group scored 0 points on the BCTQ (asymptomatic); and group 3 (n=28), in which NCS results revealed CTS and the group scored >1 point on the BCTQ (symptomatic). The clinical findings, NCS results, and CSA of the median nerve were compared among the three groups. RESULTS: There were no significant differences in age, DM duration, glycated hemoglobin levels, and presence of diabetic polyneuropathy among the three groups. The peak latency of the median sensory nerve action potential was significantly shorter in group 1 than in groups 2 and 3 (p<0.001); however, no difference was observed between groups 2 and 3. CSA of the median nerve at the carpal tunnel in group 2 was significantly larger than that in group 1 and smaller than that in group 3 (p<0.05). CONCLUSION: The results of our study suggest that the symptoms of CTS in patients with diabetes are related to CSA of the median nerve, which is consistent with swelling of the nerve.

Language-specific Dysgraphia in Korean Patients with Right Brain Stroke: Influence of Unilateral Spatial Neglect

The purpose of the present study was to investigate the relationship between Korean language-specific dysgraphia and unilateral spatial neglect in 31 right brain stroke patients. All patients were tested for writing errors in spontaneous writing, dictation, and copying tests. The dysgraphia was classified into visuospatial omission, visuospatial destruction, syllabic tilting, stroke omission, stroke addition, and stroke tilting. Twenty-three (77.4%) of the 31 patients made dysgraphia and 18 (58.1%) demonstrated unilateral spatial neglect. The visuospatial omission was the most common dysgraphia followed by stroke addition and omission errors. The highest number of errors was made in the copying and the least was in the spontaneous writing test. Patients with unilateral spatial neglect made a significantly higher number of dysgraphia in the copying test than those without. We identified specific dysgraphia features such as a right side space omission and a vertical stroke addition in Korean right brain stroke patients. In conclusion, unilateral spatial neglect influences copy writing system of Korean language in patients with right brain stroke.

Language-specific Dysgraphia in Korean Patients with Right Brain Stroke: Influence of Unilateral Spatial Neglect

The purpose of the present study was to investigate the relationship between Korean language-specific dysgraphia and unilateral spatial neglect in 31 right brain stroke patients. All patients were tested for writing errors in spontaneous writing, dictation, and copying tests. The dysgraphia was classified into visuospatial omission, visuospatial destruction, syllabic tilting, stroke omission, stroke addition, and stroke tilting. Twenty-three (77.4%) of the 31 patients made dysgraphia and 18 (58.1%) demonstrated unilateral spatial neglect. The visuospatial omission was the most common dysgraphia followed by stroke addition and omission errors. The highest number of errors was made in the copying and the least was in the spontaneous writing test. Patients with unilateral spatial neglect made a significantly higher number of dysgraphia in the copying test than those without. We identified specific dysgraphia features such as a right side space omission and a vertical stroke addition in Korean right brain stroke patients. In conclusion, unilateral spatial neglect influences copy writing system of Korean language in patients with right brain stroke.

Electrophysiologic Investigation During Facial Motor Neuron Suppression in Patients With Hemifacial Spasm: Possible Pathophysiology of Hemifacial Spasm: A Pilot Study

OBJECTIVE: To evaluate the pathophysiological mechanism of hemifacial spasm (HFS), we performed electrophysiological examinations, such as supraorbital nerve stimulation with orbicularis oris muscle recording and lateral spread tests, after suppressing the patient's central nervous system by administering intravenous diazepam. METHODS: Six patients with HFS were recruited. Supraorbital nerve stimulation with orbicularis oris muscle recording and the lateral spread test were performed, followed by intravenous application of 10 mg diazepam to achieve facial motor neuron suppression. Subsequently, we repeated the two electrophysiological experiments mentioned above at 10 and 20 minutes after the patients had received the diazepam intravenously. RESULTS: Orbicularis oris muscle responses were observed in all patients after supraorbital nerve stimulation and lateral spread tests. After the diazepam injection, no orbicularis oris muscle response to supraorbital nerve stimulation was observed in one patient, and the latencies of this response were evident as a slowing tendency with time in the remaining five patients. However, the latencies of the orbicularis oris muscle responses were observed consistently in all patients in the lateral spread test. CONCLUSION: Our results suggest that ectopic excitation/ephaptic transmission contributes to the pathophysiological mechanisms of HFS. This is because the latencies of the orbicularis oris muscle responses in the lateral spread test were observed consistently in the suppressed motor neuron in our patients.

The Effect and Complication of Botulinum Toxin Type A Injection with Serial Casting for the Treatment of Spastic Equinus Foot

OBJECTIVE: To identify the effect of serial casting combined with Botulinum toxin type A (BTX-A) injection on spastic equinus foot. METHOD: Twenty-nine children with cerebral palsy who had equinus foot were recruited from the outpatient clinic of Rehabilitation Medicine. The children were divided into 2 groups, one of which received serial casting after BTX-A injection, and the other which only received BTX-A injection. Serial casting started 3 weeks after the BTX-A injection, and was changed weekly for 3 times. Spasticity of the ankle joint was evaluated using the modified Ashworth scale (MAS), and the modified Tardieu scale (MTS). Gait pattern was measured using the physician's rating scale (PRS). RESULTS: The degree of ankle dorsiflexion and the MAS improved significantly until 12 weeks following the BTX-A injection in the serial casting group (p<0.001), while the BTX-A injection-only group improved until 6 weeks following injection (p<0.05). The combined group showed a significantly greater increase in the degree of dorsiflexion compared to the BTX-A injection-only group at post-injection weeks 6 and 12 (p<0.05). Three children (11.5%) suffered from foot ulcers as a complication caused by the serial casting. CONCLUSION: Our study demonstrated that the effect of BTX-A injection with serial casting was superior and lasted longer than the effect of BTX-A injection only in patients with spastic equinus foot. We therefore recommend BTX-A injection with serial casting for the treatment of equinus foot. However, physicians must also consider the possible complications associated with serial casting.

Neuroprotective Effects of Growth Hormone Against Hypoxic-Ischemic Brain Injury in Neonatal Rats: 1H Magnetic Resonance Spectroscopic Study

Using 1H-MRS, we evaluated the effects of growth hormone (GH) as a caspase inhibitor on hypoxic-ischemic injury in neonatal rat brains. The right common carotid arteries of rats were ligated, allowed to recover for 3 hr, and exposed to 8% oxygen for 2 hr. GH was given just prior to HI insult and animals were divided into four groups: control, intracerebroventricular (ICV), intracerebroventricular/intraperitoneal (ICV/IP), and intraperitoneal (IP). Localized in vivo 1H-MRS and TUNEL staining were performed 24 hr after HI injury. Lipid/N-acetyl aspartate (NAA) and lipid/creatine (Cr) ratios were used as apoptotic markers. Gross morphologic changes at 2 weeks were used to evaluate the effects of GH. The lipid/NAA ratio was lower in the ICV and ICV/IP groups than in the control, and the lipid/Cr ratio was lower in the ICV group than in the control. The number of TUNEL positive cells was decreased in the ICV and ICV/IP groups, and the degree of morphologic change indicative of brain injury was lower in the ICV group and somewhat lower in the ICV/IP group. The degree of morphologic change correlated with the lipid/NAA and lipid/Cr ratios. These findings suggest that GH exerts neuroprotective effects in cerebral hypoxicischemic injury.

The Functional Prognosis of Ambulation in Each Type of Cerebral Palsy

OBJECTIVE: This study is to investigate the prognosis of functional ambulation in each type of cerebral palsy (CP). METHOD: Medical records of 385 patients were retrospectively reviewed that visited outpatients department and were diagnosed as CP. Various information was surveyed including CP type, gestational age at birth, birth weight and associated problems such as mental retardation and seizure and gross motor functional status such as ambulational status and Gross Motor Functional Classification System (GMFCS). All of them were compared between each type. The influences of seizure and mental retardation on gross motor function were also investigated. RESULTS: Functional ambulation was achieved in 58.2% in overall. Inspecting in each type, 93.7% of spastic hemiplegia, 67.6% of spastic diplegia, 12.2% of spastic quadriplegia, 78.7% of dyskinetic type can ambulate functionally. Birth weight or gestational age had no independent influences on ambulation within each type. Seizure influenced negatively on ambulation of diplegic CPs with significance and mental retardation in diplegic CPs and quadriplegic CPs than any other type. CONCLUSION: Over the half of CP patients achieved functional ambulation. Hemiplegia and diplegia had good prognosis among all types. Seizure and mental retardation negatively affected ambulation function of CP patients, especially in diplegic CPs and quadriplegic CPs.