Dae-Hyun Jang

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.

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 patients 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 Influence of Arm Swelling Duration on Shoulder Pathology in Breast Cancer Patients with Lymphedema

Purpose To evaluate the pathological effect of the duration of arm swelling on the shoulder pathology in patients with breast cancer-related lymphedema. Methods Forty seven breast cancer patients with unilateral arm lymphedema were assessed. The duration of the arm swelling and shoulder pain were recorded. Ultrasound examination of the shoulder joint was performed in all patients to detect any lesions. Results Abnormalities were detected by ultrasound in 41/47 (87.2%) study participants. Subacromial subdeltoid bursal thickening was found in 26/47 (55.3%) participants, distension of the biceps brachii tendon sheath was found in 14/47 (29.8%) and a supraspinatus tendon tear was found in 13/47 (27.7%). Patients with a supraspinatus tendon tear were found to have a significantly longer duration of lymphedema (1310 days vs. 398 days, p = 0.032). Conclusions The duration of arm lymphedema has a progressive pathological effect on rotator cuff. Clinicians should adopt an early management approach of shoulder pain in patients with breast cancer-related lymphedema.

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

Min-Wook Kim, M.D., Dae-Hyun Jang, M.D., Jun Kang, M.D., Seungok Lee, M.D., Sun Young Joo, M.D., Ja-Hyun Jang, M.D., Eun-Hae Cho, M.D., Young-Chul Choi, M.D., and Jung Hwan Lee, M.D. Departments of Rehabilitation, Hospital Pathology, Laboratory Medicine, and Orthopaedic Surgery, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul; Green Cross Genome, Yongin; Green Cross Laboratories, Yongin; Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

Effectiveness of levetiracetam in an acetazolamide-unresponsive patient with episodic ataxia type 2 by a novel CACNA1A nonsense mutation

Episodic ataxia type 2 (EA-2) is an autosomal dominant channelopathy characterized by intermittent vertigo and ataxia. The underlying cause of EA-2 is a genetic alteration of the voltage-dependent calcium channel (CACNA1A) a-1 subunit. Acetazolamide is the treatment of choice for EA-2. In this study, we report a patient with EA-2 from a novel CACNA1A nonsense mutation. The patient was not responsive to acetazolamide, but concomitant use of levetiracetam significantly reduced the frequency and severity of episodes. The effectiveness of antiepileptic drugs for intermittent ataxic episodes in EA-2 has not been previously reported. A 22-year-old man presented with intermittent episodes of dizziness, dysarthria and dysequilibrium since the age of 5 years. The frequency of the episodes was approximately three times per week and the episodes lasted for an average of 2 h, but, occasionally, they lasted for the whole day. Between episodes, neurological examination was normal, except for gaze-evoked downbeat nystagmus. Magnetic resonance images of the brain were unremarkable. Electroencephalography showed frontal intermittent rhythmic delta activity. Acetazolamide was started and gradually increased up to 750 mg/day. During the initial month with 750 mg of acetazolamide, the frequency of episodes decreased to half that without acetazolamide. However, this partial improvement gradually reverted to the previous frequency without acetazolamide. We therefore added levetiracetam 750 mg/ day and the symptom attacks decreased substantially to about one per month with lesser severity. This significant improvement has been sustained for 1 year. Three of the patient’s family members had similar symptoms (Fig. 1a). The patient was analyzed by genetic testing using targeted gene sequencing with the MiSeq platform (Illumina, San Diego, CA, USA). We found a heterozygous nonsense variation in the patient’s CACNA1A gene in exon 23 (c.3855C>G/p.Tyr2319*), resulting in a stop codon (Fig. 1b), which is a novel variation. This was confirmed by conventional Sanger sequencing. This variation has not been reported to control databases, and it was suggested as the pathogenic element based on the guidelines [1]. Acetazolamide can prevent attacks by reducing the abnormally increased intracellular pH with the consequent activation and inactivation of sodium and calcium channels, respectively [2]. However, acetazolamide may not be effective in some individuals, particularly if the pathogenic variant distorts the pore region of the channel, altering the stabilizing effect of H ions. Thus, its clinical effect is known to be partial with the response rate being approximately 50– 70% in patients with EA-2 as well as being only transient in many cases [3]. Levetiracetam is one of the antiepileptic drugs that bind with synaptic vesicle glycoprotein SV2A and inhibit pre-synaptic calcium channels. We think that the effectiveness of levetiracetam in this patient might operate through the inactivation of calcium channels, which was also a presumed treatment mechanism of acetazolamide in EA-2. In this study, we identified a novel gene mutation in a patient with EA-2. He exhibited a poor response to (a)

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.

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.

Iliopsoas Sarcoma-Induced Femoral Mononeuropathy Radiologically Presenting as Focal Myositis of the Thigh: A Case Report.

A 55-yr-old man visited the orthopedic department with acute right anterior thigh pain. Magnetic resonance imaging of the right thigh showed diffuse enhancement of the vastus lateralis, vastus intermedius, and vastus medialis muscles, which was suspicious of an inflammatory myopathy or acute denervation injury (Fig. 1). He was then referred for an electrodiagnostic study at 1 mo after symptom onset. Nerve conduction study showed no response of the right saphenous nerve and right femoral motor nerve. Needle electromyography revealed prominent abnormal spontaneous activities and reduced interference patterns of motor unit action potentials in the right iliopsoas and vastus medialis muscles. Ultrasonography revealed a marked swelling of the right femoral nerve and a large cystic mass below the femoral nerve (Fig. 2). Abdominal and pelvic computed tomography revealed a 9.5 8.5 15.5-cm lobulating solid mass along the right iliopsoas muscle and enlarged lymph node in the bilateral inguinal area (Fig. 3). A gun biopsy was performed and histopathologic examination revealed a high-grade fibrosarcoma. Positron emission tomography/ computed tomography of the torso showed a known fluorodeoxyglucose-avid malignant tumor in the right iliopsoas muscle with multiple bone metastases and right lung metastatic nodules. Palliative chemotherapy with ifosfamide and etoposide was initiated. The patient died at 4 mos after symptom onset. Femoral mononeuropathy caused by primary malignant tumors of the iliopsoas muscle has rarely been reported because both femoral mononeuropathy and primary iliopsoas tumor are rare disease entities. Further more, a sarcoma of the iliopsoas muscle can grow undetected for long periods because they are deep-seated.