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.

Occurrence of Intestinal Pseudo-obstruction in a Brainstem Hemorrhage Patient

Intestinal pseudo-obstruction is a massive colonic dilation with signs and symptoms of colonic obstruction, but without a mechanical cause. A 49-year-old female patient complained of nausea, vomiting, and abdominal distension 1 month after a massive brainstem hemorrhage. No improvement was seen with conservative treatments. An extended-length rectal tube was inserted to perform glycerin enema. In addition, bethanechol (35 mg per day) was administered to stimulate colonic motility. The patient's condition gradually improved over a 2-month period without any surgical intervention. Extended length rectal tube enema and bethanechol can be used to improve intestinal pseudo-obstruction in stroke patients.

Persistent Autonomic Dysfunction in Guillain-Barre Syndrome: A case report

Autonomic dysfunction is a common manifestation in Guillain-Barre syndrome (GBS), but it rarely persists. We report a case involving a 22-year-old man who presented with glove-and-stocking type sensory loss, symmetric weakness, urinary distension, orthostatic hypotension, decreased perspiration, and the syndrome of inappropriate secretion of antidiuretic hormone. He was subsequently diagnosed as having GBS with autonomic failure that persisted for more than six months, despite regaining muscle strength. Orthostatic hypotension progressively improved after rehabilitation and administration of midodrine and fludrocortisone. Extensive evaluation and management should be performed in patients with GBS because severe autonomic dysfunction is a major source of disability.

Reference Values of Normal Femoral Condylar Cartilage Thickness and Its Ultrasonographic Findings

OBJECTIVE: To establish reference values for the femoral condylar cartilage thickness and to observe the cartilage clarity and sharpness between different age groups of healthy Koreans employing a ultrasonographic scanner. METHOD: 105 healthy volunteers from the ages of twenties to the fifties, without clinical signs of osteoarthritis were recruited for the study. Cartilage thickness at both intercondylar notch, medial condylar and lateral condylar area were obtained with 12 MHz linear transducer, in supine position under maximum flexion of the knee joints. Cartilage sharpness and clarity were also recorded in grade between 0 to 3. RESULTS: The thickness of cartilage significantly decreased with the increment of age (p<0.05) and the cartilage of the man was much thicker than woman (p=0.000). Grade of the sharpness and clarity was not different between age groups and the checked grade was mostly grade 1 and there was no grade 3. CONCLUSION: This study defines standard reference values of femoral condylar cartilage for musculoskeletal ultrasonography to prevent misinterpretation of thinning of cartilage thickness in difference age groups and sex. With these findings, we can specify the range of normal degenerative change of femoral condylar cartilage.

Abduction Motion Analysis of Hemiplegic Shoulders with a Fluoroscopic Guide

PURPOSE: We investigated the usefulness of video based, fluoroscopically guided abduction motion analysis of hemiplegic shoulders. PATIENTS AND METHODS: Twenty-two stroke patients with Brunnstrom stages 3-4 (Group 1) or 5-6 (Group 2) were enrolled in this study. Patients with shoulder pain and significant spasticity (MAS 2) were excluded. We recorded motion pictures of the abductions of affected and unaffected shoulder joints under an AP fluoroscopic guide. Lateral scapular slide distances (D1: T2- superior angle, D2: T3- scapular spine, D3: T7-inferior angle) were measured at 30 degrees, 60 degrees, 90 degrees during glenohumeral abduction in a captured photographic image. The angles of scapular rotation and trajectory (stromotion) of the humeral head center, relative to the 3rd thoracic spine in the abduction motion were analyzed. RESULTS: In Group 1, a significant difference was found in the lateral scapular slide distance between the affected and sound sides. However, no significant side to side difference was found in Group 2. Scapular angles in abduction were also increased in Group 1. Patients with a more synergistic movement pattern showed less scapular stabilizing muscle activity and, instead, exhibited a compensatory "shrugging" like motion accomplished by spinal tilting. CONCLUSION: The present findings support the notion that the above parameters of fluoroscopically guided shoulder abduction motion analysis correlate well with clinical findings. These parameters should be useful for evaluations of hemiplegic shoulder biomechanics.

Modulation of H Reflex and Reciprocal Inhibition of Soleus Muscle via Electrical and Transcranial Magnetic Stimulation of Antagonist Muscle

OBJECTIVE: To evaluate the effect of a transcranial magnetic stimulation on reciprocal inhibition of the human leg. METHOD: Twenty healthy human subjects who showed significant inhibition of soleus H reflex after conditioning electrical stimulation of tibialis anterior at a conditioning-test interval of 2 ms were included in this study. Changes in the amount of reciprocal inhibition by conditioning electrical stimulus were compared after transcranial magnetic stimulation of tibialis anterior. RESULTS: Approximately 12% inhibition of H reflex was produced by motor threshold stimulation, and 14% inhibition by maximum stimulation of common peroneal nerve. When a submotor threshold cortical shock was given with test-conditioning interval 0 ms, this inhibition was not significantly changed. There was no significant change of H reflex amplitude ratio by conditioning electrical stimulation after delivering supramotor threshold cortical shock. Amplitude of H reflex was enhanced by transcranial magnetic stimulation at each same conditioning electrical stimulation. CONCLUSION: We conclude that TMS can produce excitatory effects on spinal motor neurons rather than Ia inhibitory interneuron and there is no evidence for convergence onto Ia inhibitory interneurons from the fiber systems excited by magnetic stimulation over the cortex.

Multiple System Atrophy Overlaps Stroke: A case report

Multiple system atrophy (MSA) is an idiopathic neurodegenerative disorder involving many neuronal structures. It is a heterogeneous system disorder affecting extrapyramidal, cerebellar and autonomic nervous system. Only a minority of MSA patients are diagnosed before reaching the full blown stage. Its autonomic features like orthostatic hypotension, vocal cord paralysis are directly related to mortality. Up to now, rehabilitation of MSA patients had been rarely reported. Early, proper diagnosis and comprehensive rehabilitation for their heterogeneous clinical features are important. We experienced 54 year old hemiplegic paient who overlaps MSA. He showed some improvement in ADL and cerebellar symptoms after comprehensive rehabilitation programs.