Re: Comments on “Pure or Complex Hereditary Spastic Paraplegia Type 4?”: The Authors Respond

No abstract available.

Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

Novel Pathogenic Variant of SPAST (c.1413+4A>G) in a Patient with Hereditary Spastic Paraplegia

No abstract available.

Clinical Efficacy of Solifenacin in the Management of Diabetes Mellitus-Associated Versus Idiopathic Overactive Bladder Symptoms: A Multicenter Prospective Study / 대한배뇨장애요실금학회지

PURPOSE: To compare the clinical efficacy of anticholinergics for managing diabetes mellitus-associated overactive bladder (DM OAB) versus idiopathic overactive bladder (OAB) in Korean women. METHODS: We conducted a multicenter, prospective, parallel-group, open-label, 12-week study. Women (20–65 years old) with OAB symptoms for over 3 months were assigned to the DM OAB and idiopathic OAB groups. Changes in the Overactive Bladder Symptom Score (OABSS), urgency, urinary urgency incontinence, nocturia, daytime frequency according to a voiding diary, uroflowmetry, and postvoid residual urine volume (PVR) at the first visit (V1), week 4 (V2), and week 12 (V3) were compared. RESULTS: No significant difference was found between the baseline patient characteristics of the DM OAB and idiopathic OAB groups. Treatment with solifenacin was associated with improvements in urgency, urinary urgency incontinence, nocturia, frequency according to a voiding diary, and the total OABSS between V1 and V2 and between V1 and V3. Moreover, a significant improvement in urgency and urge incontinence was found between V2 and V3 in the DM OAB group. However, no significant changes were found in any other parameters. There were no significant differences between the DM OAB group and the idiopathic OAB group except for urgency and urge incontinence at V2 (3.71 vs. 2.28 and 0.47 vs. 0.32, respectively). CONCLUSIONS: The patients who received solifenacin demonstrated improved urgency, urinary urgency incontinence, nocturia, frequency according to a voiding diary, and total OABSS. Management with solifenacin was equally effective for both DM-related OAB and idiopathic OAB.

Atypical Acute Motor Axonal Neuropathy with Cerebrospinal Pleocytosis Mimicking Myelitis

No abstract available.

Intraoperative Motor-Evoked Potential Disappearance versus Amplitude-Decrement Alarm Criteria During Cervical Spinal Surgery: A Long-Term Prognosis

BACKGROUND AND PURPOSE: We studied the clinical significance of amplitude-reduction and disappearance alarm criteria for transcranial electric muscle motor-evoked potentials (MEPs) during cervical spinal surgery according to different lesion locations [intramedullary (IM) vs. nonintramedullary (NIM)] by evaluating the long-term postoperative motor status. METHODS: In total, 723 patients were retrospectively dichotomized into the IM and NIM groups. Each limb was analyzed respectively. One hundred and sixteen limbs from 30 patients with IM tumors and 2,761 limbs from 693 patients without IM tumors were enrolled. Postoperative motor deficits were assessed up to 6 months after surgery. RESULTS: At the end of surgery, 61 limbs (2.2%) in the NIM group and 14 limbs (12.1%) in the IM group showed MEP amplitudes that had decreased to below 50% of baseline, with 13 of the NIM limbs (21.3%) and 2 of the IM limbs (14.3%) showing MEP disappearance. Thirteen NIM limbs (0.5%) and 5 IM limbs (4.3%) showed postoperative motor deficits. The criterion for disappearance showed a lower sensitivity for the immediate motor deficit than did the criterion for amplitude decrement in both the IM and NIM groups. However, the disappearance criterion showed the same sensitivity as the 70%-decrement criterion in IM (100%) and NIM (83%) surgeries for the motor deficit at 6 months after surgery. Moreover, it has the highest specificity for the motor deficits among diverse alarm criteria, from 24 hours to 6 months after surgery, in both the IM and NIM groups. CONCLUSIONS: The MEP disappearance alarm criterion had a high specificity in predicting the long-term prognosis after cervical spinal surgery. However, because it can have a low sensitivity in predicting an immediate postoperative deficit, combining different MEP alarm criteria according to the aim of specific instances of cervical spinal surgery is likely to be useful in practical intraoperative monitoring.

Subacute Sensorimotor Polyneuropathy Associated with Autoimmune Hepatitis

No abstract available.

A confusing case of multiple sclerosis and central nervous system graft versus host disease

No abstract available.

Leiomyoma of the Male Urethra

Leiomyomas are benign tumors of smooth muscle origin that can occur at any location in the urinary tract. The kidney capsule is the most common location in the genitourinary tract. Leiomyomas of the urethra are a very rare entity; they are more frequent in females than in males. Only eight cases leiomyomas of the male urethra have been reported in the English-language medical literature. We report one additional case of pedunculated leiomyoma originating from the posterior wall of the male prostate urethra; this tumor appeared to be a bladder tumor on computed tomography.

Diagnosis and management of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disorder characterized by progressive loss of upper and lower motor neurons. The clinical diagnosis is confirmed by careful history taking, neurologic examination and electromyography. Like other neurodegenerative disease, ALS has many genetic and environmental factors. There are many studies reported about the pathogenesis and treatment of ALS. Many clinical trials are currently in progress. Herein we review about the epidemiology, genetics, pathophysiology, diagnosis and treatment of ALS.

Multiple Symmetric Lipomatosis Presenting with Bilateral Brachial Plexopathy

No abstract available.

History of Korean Thyroid Association and Recent Debates on Diagnosis and Treatment of Thyroid Cancer in Korea / 대한갑상선학회지

It is an undeniable fact that the establishment of the Korean Thyroid Association (KTA) in 2008 will reinforce growing thyroidology in Korea. It is worthwhile to recall the histories behind the foundation of the KTA and to remember the efforts of the founders. Since 2005, there has been a massive increase in thyroid cancer incidence in Korea, which is much higher than in other countries. A large majority of cases fall into papillary microcarcinoma (less than 1 cm). Much debate has been sparked since early 2014 through mass media as well as among medical professionals on the issues of early screening and detection of small thyroid cancer, overdiagnosis and overtreatment of thyroid cancer. Based on the author's past 30 years of clinical practice in endocrinology with a focus on thyroid disease, this article presents my opinion on such debate and provides thoughts on future directions. This article only represents the author's personal, possibly limited, perspective thought. For this reason, readers are recommended to use their own judgement in weighing the opinions.

Modulation of SOD1 Subcellular Localization by Transfection with Wild- or Mutant-type SOD1 in Primary Neuron and Astrocyte Cultures from ALS Mice

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by selective degeneration of motor neurons. Mutant superoxide dismutase 1 (SOD1) is often found as aggregates in the cytoplasm in motor neurons of various mouse models and familial ALS patients. The interplay between motor neurons and astrocytes is crucial for disease outcome, but the mechanisms underlying this phenomenon remain unknown. In this study, we investigated whether transient transfection with wild-type and mutant-type SOD1 may lead to amplification of mutant SOD1-mediated toxicity in cortical neurons and astrocytes derived from wild-type and mutant-type (human G93A-SOD1) mice. In transgenic mice expressing either wild- or mutant-type SOD1, we found that green fluorescent protein (GFP)-wtSOD1 was present in the cytoplasm and nuclei of wild-type cortical neurons and astrocytes, whereas GFP-mutant SOD1 was mainly cytoplasmic in wild- and mutant-type cortical neurons and astrocytes. These findings indicate that intracellular propagation of misfolding of GFP-wt or mtSOD1 are possible mediators of toxic processes involved in initiating mislocalization and aggregation. Here, we provide evidence that cytoplasmic aggregates induce apoptosis in G93A-SOD1 mouse cortical neurons and astrocytes and that the toxicity of mutant SOD1 in astrocytes is similar to the pathological effects of ALS on neurons in vitro. Collectively, our results indicate that mtSOD1 probably interacts with wtSOD1 via an unknown mechanism to produce augmented toxicity and may influence aggregate formation and apoptosis.

Neuro-Behcet's Disease Presenting as Hypertrophic Pachymeningitis

A 25-year-old man presented with blurred vision and chronic headache. His brain MRI revealed bilateral frontal pachymeningeal enhancement with leptomeningeal enhancement. The patient had experienced recurrent oral ulcer and had anterior uveitis and papulopustules skin lesion. We diagnosed him with hypertrophic pachymeningitis (HP) associated with neuro-Behcet's disease (NBD). There have been few reports describing HP in patients with NBD. We report a case of NBD presenting as HP.

Pattern of Respiratory Deterioration in Sporadic Amyotrophic Lateral Sclerosis According to Onset Lesion by Using Respiratory Function Tests

Most amyotrophic lateral sclerosis (ALS) patients show focal onset of upper and lower motor neuron signs and spread of symptoms to other regions or the other side clinically. Progression patterns of sporadic ALS are unclear. The aim of this study was to evaluate the pattern of respiratory deterioration in sporadic ALS according to the onset site by using respiratory function tests. Study participants included 63 (42 cervical-onset [C-ALS] and 21 lumbosacral-onset [L-ALS]) ALS patients and 31 healthy controls. We compared respiratory function test parameters among the 3 groups. Age was 57.4+/-9.6 (mean+/-SD), 60.8+/-9, and 60.5+/-7 years, and there were 28, 15, and 20 male participants, in the C-ALS, L-ALS, and control groups, respectively. Disease duration did not differ between C-ALS and L-ALS patients. Sniff nasal inspiratory pressure (SNIP) was significantly low in C-ALS patients compared with controls. Maximal expiratory pressure (MEP) and forced vital capacity percent predicted (FVC% predicted) were significantly low in C-ALS and L-ALS patients compared with controls. Maximal inspiratory pressure to maximal expiratory pressure (MIP:MEP) ratio did not differ among the 3 groups. Eighteen C-ALS and 5 L-ALS patients were followed up. DeltaMIP, DeltaMEP, DeltaSNIP, DeltaPEF, and DeltaFVC% predicted were higher in C-ALS than L-ALS patients without statistical significance. Fourteen C-ALS (77.8%) and 3 L-ALS (60%) patients showed a constant MIP:MEP ratio above or below 1 from the first to the last evaluation. Our results suggest that vulnerability of motor neurons in sporadic ALS might follow a topographic gradient.

Diffusion Tensor Tractography Analysis of the Corpus Callosum Fibers in Amyotrophic Lateral Sclerosis

BACKGROUND AND PURPOSE: Involvement of the corpus callosum (CC) is reported to be a consistent feature of amyotrophic lateral sclerosis (ALS). We examined the CC pathology using diffusion tensor tractography analysis to identify precisely which fiber bundles are involved in ALS. METHODS: Diffusion tensor imaging was performed in 14 sporadic ALS patients and 16 age-matched healthy controls. Whole brain tractography was performed using the multiple-region of interest (ROI) approach, and CC fiber bundles were extracted in two ways based on functional and structural relevance: (i) cortical ROI selection based on Brodmann areas (BAs), and (ii) the sulcal-gyral pattern of cortical gray matter using FreeSurfer software, respectively. RESULTS: The mean fractional anisotropy (FA) values of the CC fibers interconnecting the primary motor (BA4), supplementary motor (BA6), and dorsolateral prefrontal cortex (BA9/46) were significantly lower in ALS patients than in controls, whereas those of the primary sensory cortex (BA1, BA2, BA3), Broca's area (BA44/45), and the orbitofrontal cortex (BA11/47) did not differ significantly between the two groups. The FreeSurfer ROI approach revealed a very similar pattern of abnormalities. In addition, a significant correlation was found between the mean FA value of the CC fibers interconnecting the primary motor area and disease severity, as assessed using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale, and the clinical extent of upper motor neuron signs. CONCLUSIONS: Our findings suggest that there is some degree of selectivity or a gradient in the CC pathology in ALS. The CC fibers interconnecting the primary motor and dorsolateral prefrontal cortices may be preferentially involved in ALS.

A Case of Adult Onset Glycogen Storage Myopathy / 대한임상신경생리학회지

Primary metabolic myopathy as a type of congenital myopathies was first described by McArdle in 1951. Glycogen storage disease is a disease caused by genetic mutations involved in glycogen synthesis, glycogenolysis or glycolysis. Several types of glycogen storage disease are known to cause metabolic myopathies. We report a case of adult onset metabolic myopathy with glycogen storage.

Relationship Between Uncommon Computed Tomography Findings and Clinical Aspects in Patients With Acute Pyelonephritis

PURPOSE: Computed tomography (CT) has become popular in the diagnosis of acute pyelonephritis (APN) and its related complications in adults. The aim of this study was to investigate the relationship between uncommon CT findings and clinical and laboratory data in patients with APN. MATERIALS AND METHODS: From July 2009 to July 2012, CT findings and clinical data were collected from 125 female patients with APN. The six uncommon CT findings (excluding a wedge-shaped area of hypoperfusion in the renal parenchyma) studied were perirenal fat infiltration, ureteral wall edema, renal abscess formation, pelvic ascites, periportal edema, and renal scarring. The clinical parameters analyzed were the age and body mass index of the patients as well as the degree and duration of fever. Laboratory parameters related to inflammation and infection included white blood cell count, C-reactive protein (CRP) level, erythrocyte sedimentation rate, pyuria, and bacteriuria. RESULTS: The most common CT finding was perirenal fat infiltration (69 cases, 55%). A longer duration of fever, higher CRP level, and grade of pyuria were related with perirenal fat infiltration (p=0.010, p=0.003, and p=0.049, respectively). The CRP level was significantly higher in patients with renal abscess and ureteral wall edema (p=0.005 and p=0.015, respectively). CONCLUSIONS: The uncommon CT findings that were related to aggravated clinical and laboratory parameters of APN patients were perirenal fat infiltration, ureteral wall edema, and renal abscess formation. The inflammatory reaction and tissue destruction may be more aggressive in patients with these CT findings.

Evaluation of the T-KB-H and 3-HB Kits for the Measurement of Serum Ketone and beta-Hydroxybutyric Acid

BACKGROUND: Diabetes mellitus and alcohol consumption are the most common causes of ketoacidosis in adults. Recently, beta-hydroxybutyric acid (betaHBA) was reported to be a potential serum biomarker in the diagnosis and monitoring of ketoacidosis. We evaluated the performance of T-KB-H and 3-HB kits for the measurement of ketone bodies [acetoacetate (AcAc)+betaHBA] and betaHBA, respectively. METHODS: Quantitative enzymatic assays were performed using the T-KB-H and 3-HB kits (Nittobo Medical Co., Japan) and the Architect ci16200 Integrated System (Abbott Laboratories, USA). Simultaneously, the ketone body levels in these serum samples were determined by gas chromatography-mas spectrometry (GC-MS). We evaluated precision and linearity of these kits and correlation with GC-MS, and established reference intervals in children and adults. RESULTS: The coefficients of variation for the T-KB-H and 3-HB kits were less than 4.0% at analyte levels of 50, 100, and 400 micromol/L. Linearity was observed for AcAc and betaHBA over a 0-1,000 micromol/L range (R2<0.99). Results from the T-KB-H and 3-HB kits were in good agreement with those from the GC-MS analysis, with correlation coefficients of 0.94 for AcAc and 0.96 for betaHBA. Reference intervals determined for the T-KB-H kit were 9.8-270.1 micromol/L and 18.5-531.8 micromol/L in children and adults, respectively. For the 3-HB kit, the reference intervals were 6.4-234.0 micromol/L and 16.0-437.2 micromol/L in children and adults, respectively. CONCLUSIONS: The T-KB-H and 3-HB kits displayed good precision, clinically acceptable linearity, and reliable correlation with an established assay. This indicates that the kits can be used clinically for measuring serum ketone bodies.

Comparison between Flail Arm Syndrome and Upper Limb Onset Amyotrophic Lateral Sclerosis: Clinical Features and Electromyographic Findings

Flail arm syndrome (FAS), an atypical presentation of amyotrophic lateral sclerosis (ALS), is characterized by progressive, predominantly proximal, weakness of upper limbs, without involvement of the lower limb, bulbar, or respiratory muscles. When encountering a patient who presents with this symptomatic profile, possible diagnoses include upper limb onset ALS (UL-ALS), and FAS. The lack of information regarding FAS may make differential diagnosis between FAS and UL-ALS difficult in clinical settings. The aim of this study was to compare clinical and electromyographic findings from patients diagnosed with FAS with those from patients diagnosed with UL-ALS. To accomplish this, 18 patients with FAS and 56 patients with UL-ALS were examined. Significant differences were observed between the 2 groups pertaining to the rate of fasciculation, patterns of predominantly affected muscles, and the Medical Research Council scale of the weakest muscle. The presence of upper motor neuron signs and lower motor neuron involvement evidenced through electromyography showed no significant between-group differences.