PURPOSE: To evaluate the classification, diagnosis, and natural course of ophthalmoplegia associated with mitochondrial disease. MATERIALS AND METHODS: Among 372 patients with mitochondrial disease who visited our hospital between January 2006 and January 2016, 21 patients with ophthalmoplegia were retrospectively identified. Inclusion criteria included onset before 20 years of age, pigmentary retinopathy, and cardiac involvement. The 16 patients who were finally included in the study were divided into three groups according to disease type: Kearns-Sayre syndrome (KSS), KSS-like, and chronic progressive external ophthalmoplegia (CPEO). RESULTS: The prevalences of clinical findings were as follows: ptosis and retinopathy, both over 80%; myopathy, including extraocular muscles, 75%; lactic acidosis, 71%; and elevated levels of serum creatine kinase, 47%. Half of the patients had normal magnetic resonance imaging findings. A biochemical enzyme assay revealed mitochondrial respiratory chain complex I defect as the most common (50%). The prevalence of abnormal muscle findings in light or electron microscopic examinations was 50% each, while that of large-scale mitochondrial DNA (mtDNA) deletions in a gene study was 25%. We compared the KSS and KSS-like groups with the CPEO patient group, which showed pigmentary retinopathy (p < 0.001), cardiac conduction disease (p=0.013), and large-scale mtDNA deletions (p=0.038). KSS and KSS-like groups also had gastrointestinal tract disorders such as abnormal gastrointestinal motility (p=0.013) unlike the CPEO group. CONCLUSION: Patients with KSS had gastrointestinal symptoms, which may indicate another aspect of systemic involvement. The presence of large-scale mtDNA deletions was an objective diagnostic factor for KSS and a gene study may be helpful for evaluating patients with KSS.
Acidosis, Lactic ; Classification ; Creatine Kinase ; Diagnosis ; DNA, Mitochondrial ; Electron Transport ; Enzyme Assays ; Gastrointestinal Motility ; Gastrointestinal Tract ; Genes, vif ; Humans ; Kearns-Sayre Syndrome ; Magnetic Resonance Imaging ; Mitochondrial Diseases* ; Muscles ; Muscular Diseases ; Ophthalmoplegia* ; Ophthalmoplegia, Chronic Progressive External ; Prevalence ; Retinitis Pigmentosa ; Retrospective Studies

OBJECTIVE: To evaluate the effects of functional electrical stimulation (FES) to ankle dorsiflexor (DF) and ankle plantarflexor (PF) on kinematic and kinetic parameters of hemiplegic gait. METHODS: Fourteen post-stroke hemiplegic patients were considered in this study. Electrical stimulation was delivered to ankle DF during the swing phase and ankle PF during the stance phase via single foot switch. Kinematic and kinetic data were collected using a computerized motion analysis system with force plate. Data of no stimulation (NS), DF stimulation only (DS), DF and PF stimulation (DPS) group were compared among each other. RESULTS: Peak ankle dorsiflexion angle during swing phase is significantly greater in DS group (-1.55degrees+/-9.10degrees) and DPS group (-2.23degrees+/-9.64degrees), compared with NS group (-6.71degrees+/-11.73degrees) (p<0.05), although there was no statistically significant difference between DS and DPS groups. Ankle plantarflexion angle at toe-off did not show significant differences among NS, DS, and DPS groups. Peak knee flexion in DPS group (34.12degrees+/-13.77degrees) during swing phase was significantly greater than that of NS group (30.78degrees+/-13.64degrees), or DS group (32.83degrees+/-13.07degrees) (p<0.05). CONCLUSION: In addition to the usual FES application stimulating ankle DF during the swing phase, stimulation of ankle PF during stance phase can help to increase peak knee flexion during the swing phase. This study shows the advantages of stimulating the ankle DF and PF using single foot switch for post-stroke gait.
Ankle* ; Biomechanical Phenomena ; Electric Stimulation* ; Foot* ; Gait ; Gait Disorders, Neurologic ; Hemiplegia* ; Humans ; Knee ; Stroke*

X-linked adrenoleukodystrophy (X-ALD) shows a wide range of phenotypic expression, but clinical presentation as an isolated lesion of the cerebellar white matter and dentate nuclei has not been reported. We report an unusual presentation of X-ALD only with an isolated lesion of the cerebellar white matter and dentate nuclei. The proband, a 37-year-old man presented with bladder incontinence, slurred speech, dysmetria in all limbs, difficulties in balancing, and gait ataxia. Brain magnetic resonance imaging showed an isolated signal change of white matter around the dentate nucleus in cerebellum. With high level of very long chain fatty acid, gene study showed a de novo mutation in exon 1 at nucleotide position c.277_296dup20 (p.Ala100Cysfs*10) of the adenosine triphosphate-binding cassette D1 gene. It is advised to consider X-ALD as a differential diagnosis in patients with isolated cerebellar degeneration symptoms.
ATP-Binding Cassette Transporters/*genetics ; Adrenoleukodystrophy/blood/*genetics ; Adult ; Cerebellar Diseases/blood/*genetics ; Fatty Acids/blood ; Humans ; Male ; Mutation

OBJECTIVE: To examine the neurophysiologic status in patients with idiopathic facial nerve palsy (Bell's palsy) and Ramsay Hunt syndrome (herpes zoster oticus) within 7 days from onset of symptoms, by comparing the amplitude of compound muscle action potentials (CMAP) of facial muscles in electroneuronography (ENoG) and transcranial magnetic stimulation (TMS). METHODS: The facial nerve conduction study using ENoG and TMS was performed in 42 patients with Bell's palsy and 14 patients with Ramsay Hunt syndrome within 7 days from onset of symptoms. Denervation ratio was calculated as CMAP amplitude evoked by ENoG or TMS on the affected side as percentage of the amplitudes on the healthy side. The severity of the facial palsy was graded according to House-Brackmann facial grading scale (H-B FGS). RESULTS: In all subjects, the denervation ratio in TMS (71.53+/-18.38%) was significantly greater than the denervation ratio in ENoG (41.95+/-21.59%). The difference of denervation ratio between ENoG and TMS was significantly smaller in patients with Ramsay Hunt syndrome than in patients with Bell's palsy. The denervation ratio of ENoG or TMS did not correlated significantly with the H-B FGS. CONCLUSION: In the electrophysiologic study for evaluation in patients with facial palsy within 7 days from onset of symptoms, ENoG and TMS are useful in gaining additional information about the neurophysiologic status of the facial nerve and may help to evaluate prognosis and set management plan.
Action Potentials ; Bell Palsy ; Denervation ; Facial Muscles ; Facial Nerve ; Facial Paralysis ; Herpes Zoster ; Herpes Zoster Oticus ; Humans ; Muscles ; Paralysis ; Prognosis ; Transcranial Magnetic Stimulation

PURPOSE: Papillary thyroid carcinoma (PTC) is the most common malignancy that develops from the thyroid gland and its prognosis is quite excellent. One of the characteristic behaviors of PTC is that it often occurs at multiple foci. The purpose of this study was to investigate the clinicopathologic features and risk factors of multifocal papillary thyroid cancer. METHODS: A retrospective review was carried out on 624 patients with PTC and who underwent surgery from January 2005 to December 2007. Two hundred twenty-nine of them were found to have multiple tumor foci (≥2 foci). The risk factors that included gender, age at diagnosis, tumor size, capsular invasion, extrathyroidal extension (ETE), cervical lymph node (LN) involvement, the TNM classification, local recurrence and distant metastasis were comparatively analyzed between the solitary PTC and multifocal PTC groups. RESULTS: The enrolled patients were 59 male and 565 females. The mean age was 46 years (range: 15~77 years). Age (P=0.025), tumor size (P=0.027), capsular invasion (P<0.001), ETE (P<0.001) and cervical LN metastasis (P=0.002) were the significantly related factors for multifocal papillary thyroid cancer. However, gender was not significantly related with multifocality. CONCLUSION: The results of this study showed that multifocal tumors were significantly associated with age, tumors size, capsular invasion, ETE and cervical LN metastasis in patients with PTC. LN metastasis was mostly influenced by multifocality in the PTC patients. It seems certain that total thyroidectomy and formal central node dissection with postoperative adjuvant therapy are essential treatment for these patients, and closely surveying the nodal status is needed on the follow up of patients with multifocal PTC.
Classification ; Diagnosis ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes ; Male ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Retrospective Studies ; Risk Factors ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

To evaluate the prognostic importance of chromosomal instability (CIN) in squamous cell carcinoma (SCC) of the lung, the relationship between CIN detected by fluorescence in situ hybridization (FISH) and survival in SCC patients was examined. Forty-seven surgical specimens of lung SCC were analyzed. To identify tumors with CIN, p16 and multi-target DNA FISH assays for c-myc, chromosome 6, EGFR, and chromosome 5 (LAVysion, Vysis) were performed on nuclei extracted from paraffin-embedded tumor tissues. Survival rates were compared in terms of age, T factor, N factor, CIN, and smoking status. A sample was defined as CIN-positive if at least four of the five chromosomes were positive. Among the 47 specimens, 9 (19%) were CIN-positive. The overall survival rate was 66%. Overall survival rates were estimated as 33.3% for CIN-positive patients and 76.7% for CIN-negative patients (Hazard ratio 3.47; 95% Confidence interval, 1.25-9.67; P=0.017). In multivariate analysis, the presence of CIN was a predictive factor for survival. CIN-positive based on FISH can be prognostic factor of lung SCC.

Matrix metalloproteinase-9 (MMP-9) may play an important role in emphysematous change in chronic obstructive pulmonary disease (COPD), one of the leading causes of mortality and morbidity worldwide. We previously reported that simvastatin, an inhibitor of HMG-CoA reductase, attenuates emphysematous change and MMP-9 induction in the lungs of rats exposed to cigarette smoke. However, it remained uncertain how cigarette smoke induced MMP-9 and how simvastatin inhibited cigarette smoke-induced MMP-9 expression in alveolar macrophages (AMs), a major source of MMP-9 in the lungs of COPD patients. Presently, we examined the related signaling for MMP-9 induction and the inhibitory mechanism of simvastatin on MMP-9 induction in AMs exposed to cigarette smoke extract (CSE). In isolated rat AMs, CSE induced MMP-9 expression and phosphorylation of ERK and Akt. A chemical inhibitor of MEK1/2 or PI3K reduced phosphorylation of ERK or Akt, respectively, and also inhibited CSE-mediated MMP-9 induction. Simvastatin reduced CSE-mediated MMP-9 induction, and simvastatin-mediated inhibition was reversed by farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP). Similar to simvastatin, inhibition of FPP transferase or GGPP transferase suppressed CSE-mediated MMP-9 induction. Simvastatin attenuated CSE-mediated activation of RAS and phosphorylation of ERK, Akt, p65, IkappaB, and nuclear AP-1 or NF-kappaB activity. Taken together, these results suggest that simvastatin may inhibit CSE-mediated MMP-9 induction, primarily by blocking prenylation of RAS in the signaling pathways, in which Raf-MEK-ERK, PI3K/Akt, AP-1, and IkappaB-NF-kappaB are involved.
1-Phosphatidylinositol 3-Kinase/metabolism ; Alkyl and Aryl Transferases/metabolism ; Animals ; Anticholesteremic Agents/pharmacology ; Cells, Cultured ; Enzyme Inhibitors/metabolism/pharmacology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gene Expression Regulation, Enzymologic/*drug effects ; I-kappa B Kinase/antagonists & inhibitors/metabolism ; Macrophages, Alveolar/cytology/*drug effects/*enzymology ; Matrix Metalloproteinase 9/genetics/*metabolism ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Polyisoprenyl Phosphates/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Sesquiterpenes/metabolism ; Signal Transduction/physiology ; Simvastatin/*pharmacology ; Smoke/*adverse effects ; *Tobacco/adverse effects/chemistry

PURPOSE: Mitochondrial disorders are a clinical entity characterized by diverse symptoms and signs of involvement of various systems. Furthermore, the disorders are known to show ophthalmologic manifestations as well as neurological findings. Visually evoked potential is a sensitive measure to check the integrity of the visual pathway. In this study, we have investigated the value of visually evoked potential in mitochondrial disorders with respiratory chain defects. METHODS: Nineteen patients diagnosed with mitochondrial respiratory chain complex I defect as confirmed by spectrophotometric enzyme assay in muscle samples were enrolled for this study. The patients underwent a visually evoked potential study. We classified the results into four groups and compared these with clinical ophthalmologic findings. RESULTS: Among the 19 patients, 14 showed abnormal visually evoked potential findings. Seven patients showed abnormal clinical ophthalmologic findings. All patients with abnormal ophthalmologic findings showed abnormal visually evoked potential findings. Among the 12 patients with normal ophthalmologic findings, seven showed abnormal results in visually evoked potential. CONCLUSION: Visually evoked potential study could be used as an effective screening tool for mitochondrial disorders to detect ophthalmologic and neurological abnormalities.
Child ; Electron Transport ; Enzyme Assays ; Evoked Potentials ; Eye ; Humans ; Mass Screening ; Mitochondria ; Mitochondrial Diseases ; Muscles ; Visual Pathways

Benign schwannomas arise in neural crest-derived Schwann cells. They can occur almost anywhere in the body, but their most common locations are the central nervous system, extremities, neck, mediastinum, and retroperitoneum. Schwannomas occurring in the biliary tract are extremely rare and mostly present with obstructive jaundice. We recently experienced a case of extrahepatic biliary schwannomas in a 64-yr-old female patient who presented with intra- and extrahepatic bile duct and gallbladder stones during a screening program. To the best of our knowledge, extrahepatic biliary schwannomas associated with bile duct stones have not been reported previously in the literature.
Adult ; Bile Ducts/pathology ; Bile Ducts, Extrahepatic/*metabolism/*pathology ; Central Nervous System/pathology ; Cholangiography/methods ; Endoscopy ; Female ; Humans ; Male ; Middle Aged ; Neurilemmoma/*diagnosis/*pathology ; Tomography, X-Ray Computed

OBJECTIVE: Promoter methylation of Bcl-2 family genes in cancer cells were studied to verify possible correlation between DNA methylation pattern of Bcl-2 family members and cancer. METHODS: The genomic DNAs were extracted from different cancer cell lines, HeLa, CaSki and K562, and ovarian cancer tissue from patients. The cytosine residues were converted to uracil by sodium bisulfite treatment. MSP (methylation specific PCR) was performed to determine the methylation status of Bcl-2, Mcl-1, Noxa, and Harakiri promoters. Using primers that distinguish methylated DNA from unmethylated DNA after bisulfite modification of DNA, MSP was conducted to observe the methylation pattern of Bcl-2 family genes in different cancer cells. RESULTS: The promoter regions of Bcl-2 family genes including Mcl-1, Bcl-2, and Noxa were not methylated in cancer cells, whereas the proapoptotic Bcl-2 family gene Harakiri was detected as methylated in the cancer cell lines and hypomethylated in the ovarian cancer tissue. CONCLUSION: The present study demonstrated the differential methylation profiles of Bcl-2 family genes in cancerous cells, which suggests a possible connection between the methylation pattern of some of Bcl-2 family genes and ovarian cancer.
Cell Line ; Cytosine ; DNA Methylation* ; DNA* ; Humans ; Methylation ; Ovarian Neoplasms ; Promoter Regions, Genetic ; Sodium ; Uracil