Paraparesia espástica complicada como fenótipo neurológico em OPA1 / Complex spastic paraplegia as a neurological phenotype in an opa1 patient

RESUMO: A atrofia óptica autossômica dominante (ADOA) é uma das formas mais comuns de atrofias ópticas hereditárias, e causada por mutações no gene OPA1. Os pacientes afetados por essa doença geralmente apresentam perda visual na primeira década de vida, podendo apresentar manifestações extraoftalmológicas no decorrer dos anos, configurando uma síndrome chamada OPA1 plus ou ADOA-plus. Objetivos: Relatar caso de paciente portadora da síndrome ADOA-plus, estabelecendo correlações com casos descritos na literatura. Relato de caso: Paciente feminino, 30 anos, foi encaminhada para avaliação de quadro de atrofia óptica progressiva associada a sintomas de neuropatia periférica. Aos dois anos, foi diagnosticada com perda visual parcial em consulta de puericultura. Não relatou outros sintomas associados durante a infância e a adolescência. Aos 20 anos, apresentou dificuldades de deambular, fraqueza em membros inferiores e falta de equilíbrio. Aos 25 anos, após extensa investigação, foi identificada, através de sequenciamento de exoma, mutação patológica no gene OPA1 confirmando o diagnóstico ADOA-plus e iniciado tratamento com Coenzima Q10. Atualmente a paciente relata ataxia sensitiva, diminuição da acuidade visual progressiva, fasciculações e câimbras em MMII, disfagia e dispneia. Discussão: Muitos pacientes com ADOA-plus apresentam surdez neurossensorial como sintoma extraoftalmológico mais comum, além de quadros de parkinsonismo e demência, ataxia e ptose. Paciente relatada constitui um caso de atrofia óptica associado à neuropatia periférica, ataxia e miopatia. Devido à ampla variabilidade clínica dessa doença, deve-se investigar mutações no OPA1 em casos de paraparesia espástica progressiva associada à atrofia óptica, visto que possibilidade de tratamento com Coenzima Q10. (AU)

ABSTRACT: Introduction: Autosomal dominant optic atrophy (ADOA) is one of the most common forms of inherited optic atrophies and is caused by mutations in the OPA1 gene. Patients affected by this disease usually present visual loss in the first decade of life, and may present extra-ophthalmologic manifestations over the years, configuring a syndrome called OPA1 plus or ADOA-plus. Objectives: to report the case of a patient with ADOA-plus syndrome, establishing correlations with cases described in the literature, Case report: a 30-year-old female patient was referred for evaluation of progressive optic atrophy associated with symptoms of peripheral neuropathy. At two years of age, she was diagnosed with partial visual loss during a childcare visit. She reported no other associated symptoms during childhood and adolescence. At the age of 20, she presented with difficulty walking, lower limb weakness, and poor balance. At 25, after extensive investigation, a pathological mutation in the OPA1 gene was identified through exome sequencing, confirming the diagnosis of ADOA-plus, and treatment with Coenzyme Q10 was initiated. Currently the patient reports sensory ataxia, progressive decrease in visual acuity, fasciculations and cramps in the lower limbs, dysphagia and dyspnea. Discussion: Many patients with ADOA-plus present sensorineural deafness as the most common extra-ophthalmologic symptom, in addition to parkinsonism and dementia, ataxia and ptosis. The patient reported is a case of optic atrophy associated with peripheral neuropathy, ataxia and myopathy. Due to the wide clinical variability of this disease, OPA1 mutations should be investigated in cases of progressive spastic paraparesis associated with optic atrophy, since the possibility of treatment with Coenzyme Q10. (AU)

Comparative study of cold compress and liniment treatment as an adjunct to massage therapy for Exercise-Associated Muscle Cramps (EAMC) among young athletes in the Philippine setting

@#Exercise-associated muscle cramps (EAMC) is prevalent among athletes during training or competitions where they are subjected to strenuous activities for a prolonged period. To manage this painful condition, health practitioners have used numerous treatment modalities having massage done with adjunct application such as cold compress or liniment. Studies show that it is debatable which combination of treatment modalities is more effective on people affected by EAMC. Hence, this study aimed to present evidence-based data to show if there is a difference in the effectiviteness of the two modalities in treating EAMC. A total of thirty-two (32) athletic participants were enrolled in this study and a total of 40 treatment trials were included in the analysis of data. Each participant performed strenuous exercises meant to induce muscle cramps. The onset of muscle cramps was identified using a set criteria. After which, treatment was applied and the length of time that the cramp was resolved was recorded. Determining relief from muscle cramps was based on the characteristic of muscle hardness and the level of pain by using a numerical rating scale. Results showed that though majority of the participants verbalized preference for the ice treatment, analysis of data using one-way ANOVA revealed that there is no evidence to prove that there is a difference in the effectivity among the treatment modalities performed. In conclusion, though all modalities performed were able to relieve the EAMC, the use of adjunct treatment in addition to massage and stretching may have a placebo effect component, which improves the patient's perception of greater efficacy.

Efficacy of L-carnitine on ribavirin-induced hemolytic anemia in patients with hepatitis C virus infection

BACKGROUND/AIMS: L-carnitine not only alleviates hyperammonemia and reduces muscle cramps in patients with liver cirrhosis, but also improves anemia in patients with chronic hepatitis and renal dysfunction. This study prospectively evaluated the preventative efficacy of L-carnitine supplementation against hemolytic anemia during antiviral treatment using ribavirin in patients with hepatitis C virus (HCV)-related chronic liver disease. METHODS: A total of 41 patients with chronic hepatitis were consecutively enrolled in this study. Group A (n=22) received sofosbuvir plus ribavirin for 3 months, whereas group B (n=19) was treated with sofosbuvir, ribavirin, and L-carnitine. Hemoglobin concentration changes, the effects of antiviral treatment, and the health status of patients were analyzed using short form-8 questionnaires. RESULTS: A significantly smaller decrease in hemoglobin concentration was observed in group B compared to group A at every time point. Moreover, the prescribed dose intensity of ribavirin in group B was higher than that of group A, resulting in a higher ratio of sustained virological response (SVR) 24 in group B compared with group A. The physical function of patients in group B was also significantly improved compared to group A at the end of antiviral treatment. CONCLUSIONS: L-carnitine supplementation alleviates ribavirin-induced hemolytic anemia in patients with HCV and helps relieve the physical burden of treatment with ribavirin-containing regimens. These advantages significantly increase the likelihood of achieving SVR.

Clinical features and COL4A1 genotype of a toddler with hereditary angiopathy with nephropathy, aneurysms and muscle cramps syndrome / 中国当代儿科杂志

Hereditary angiopathy with nephropathy, aneurysms and muscle cramps (HANAC) syndrome is an autosomal dominant genetic disease caused by COL4A1 gene mutation, with major clinical manifestations of white matter lesion, aneurysm, retinal artery tortuosity, polycystic kidney, microscopic hematuria and muscle cramps. This article reports the clinical features and genotype of one toddler with HANAC syndrome caused by COL4A1 gene mutation. The boy, aged 1 year and 8 months, had an insidious onset, with the clinical manifestations of pyrexia and convulsion, white matter lesions in the periventricular region and the centrum semiovale on both sides, softening lesions beside the left basal ganglia, retinal arteriosclerosis, microscopic hematuria and muscle cramps. Whole exome sequencing revealed a pathogenic de novo heterozygous mutation in the COL4A1 gene, (NM_001845) c.4150+1(IVS46)G>T, and therefore, the boy was diagnosed with HANAC syndrome. COL4A1 gene mutation detection should be performed for children with unexplained white matter lesion, stroke, hematuria, polycystic kidney, cataract and retinal artery tortuosity or families with related history.

Elucidation of the pathophysiology of intradialytic muscle cramps: pharmacokinetics applied to translational research

In the conventional concept of translational research, investigations flow from the laboratory bench to the bedside. However, clinical research can also serve as the starting point for subsequent laboratory investigations that then lead back to the bedside. This article chronicles the evolution of a series of studies in which a detailed analysis of pharmacokinetics in hemodialysis patients revealed new physiological insight that, through a systems approach incorporating kinetic, physicochemical, physiologic, and clinical trial results, led to an elucidation of the pathophysiology of intradialytic skeletal muscle cramps. Based on this understanding, a therapeutic path forward is proposed.

Chemical colitis caused by hydrogen peroxide enema in a child: case report and literature review

A 2-year-old girl, previously healthy, was brought to the emergency department because of significant cramping abdominal pain with recurrent hematochezia after an accidental hydrogen peroxide enema (35%, 5 mL) by her caregiver. She was hospitalized to the pediatric department and treated with nothing per mouth, intravenous fluid and parenteral antibiotic therapy. Laboratory, radiologic and endoscopic evaluation was performed during the admission period. She was discharged in a fully recovered state on the tenth hospital day, and this is the first case report of acute chemical colitis by accidental hydrogen peroxide enema in children.

A Case of Pseudohypoparathyroidism Type Ib Caused by Aberrant Methylation in the GNAS Complex Locus

Pseudohypoparathyroidism (PHP) is a rare disorder caused by genetic and epigenetic aberrations in the GNAS complex locus resulting in impaired expression of stimulatory G protein (Gsα). PHP type Ib (PHP-Ib) is characterized by hypocalcemia and hyperphosphatemia due to renal resistance to the parathyroid hormone, and is distinguished from PHP-Ia by the absence of osteodystrophic features. An 11-yr-old boy presented with poor oral intake and cramping lower limb pain after physical activity. Laboratory studies revealed hypocalcemia, hyperphosphatemia, and increased parathyroid hormone levels. The GNAS complex locus was evaluated using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Gain of methylation in the NESP55 domain and loss of methylation in the antisense (AS) transcript, XL, and A/B domains in the maternal allele were observed. Consequently, we present a case of PHP-Ib diagnosed using MS-MLPA.

Rheumatoid arthritis accompanied by Gitelman syndrome / 영남의대학술지

Gitelman syndrome is a condition caused by a mutation of the thiazide sensitive Na-Cl cotransporter gene on the distal convoluted tubule. It results in a variety of clinical features, including hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. It is often diagnosed in asymptomatic adults presented with unexplained hypokalemia; however, it is sometimes associated with muscular cramps, numbness, fatigue, weakness, or paralysis. We experienced a case of rheumatoid arthritis accompanied by Gitelman syndrome, presented with hand tremor. We diagnosed her using renal clearance study and genetic analysis. Here, we report our experiences regarding this case along with a literature review.

Management Dilemma in Olanzapine Induced Restlessness and Cramps in Legs

No abstract available.

A Retrospective Study of Long Acting Risperidone Use to Support Treatment Adherence in Youth with Conduct Disorder

OBJECTIVE: Risperidone has been widely used to control aggression and conduct disorder (CD) in youth; however, treatment compliance is a major problem in CD. Our aim is to evaluate the effectiveness and tolerability of long-acting risperidone (LAR) in treating nonadherent cases. METHODS: The medical records of children and adolescents who had CD and were nonadherent to conventional drugs and psychosocial interventions (and therefore taking LAR) were reviewed. Informed consent on offlabel use of LAR was obtained from the parents. Clinical Global Impression (CGI) Severity (CGI-S) and CGI-Improvement scales were used and baseline and end points were compared. RESULTS: The study comprised 14 children and adolescents (5 girls, 9 boys). All had comorbid disorders: substance use disorder (n=8), attention deficit hyperactivity disorder (n=6), and major depression (n=2). Mean duration of LAR use was 3.1 months (1.5–8 months). We observed significant improvements in the baseline and endpoint CGI-S scores for CD in all but one patient (Z=−3.198; p < 0.001). Only mild adverse effects were observed: weight gain (n=2), sedation (n=1), leg cramps (n=1), and increased appetite with no weight gain (n=1). CONCLUSION: LAR is effective and tolerable for patients with CD who can’t be medicated with oral preparations due to non-adherence to treatment. Even short-term LAR use is effective to get compliance. As CD predicts numerous problems in adulthood, appropriate treatment is crucial. To our knowledge, this is the first study on LAR use in youth with CD. The use of LAR deserves careful consideration and further controlled studies are needed to confirm our findings.

Rheumatoid arthritis accompanied by Gitelman syndrome / 영남의대학술지

Gitelman syndrome is a condition caused by a mutation of the thiazide sensitive Na-Cl cotransporter gene on the distal convoluted tubule. It results in a variety of clinical features, including hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. It is often diagnosed in asymptomatic adults presented with unexplained hypokalemia; however, it is sometimes associated with muscular cramps, numbness, fatigue, weakness, or paralysis. We experienced a case of rheumatoid arthritis accompanied by Gitelman syndrome, presented with hand tremor. We diagnosed her using renal clearance study and genetic analysis. Here, we report our experiences regarding this case along with a literature review.

Chemical colitis caused by hydrogen peroxide enema in a child: case report and literature review

A 2-year-old girl, previously healthy, was brought to the emergency department because of significant cramping abdominal pain with recurrent hematochezia after an accidental hydrogen peroxide enema (35%, 5 mL) by her caregiver. She was hospitalized to the pediatric department and treated with nothing per mouth, intravenous fluid and parenteral antibiotic therapy. Laboratory, radiologic and endoscopic evaluation was performed during the admission period. She was discharged in a fully recovered state on the tenth hospital day, and this is the first case report of acute chemical colitis by accidental hydrogen peroxide enema in children.

A novel mutation of CLCNKB in a Korean patient of mixed phenotype of Bartter-Gitelman syndrome / 소아과

Bartter syndrome (BS) is an inherited renal tubular disorder characterized by low or normal blood pressure, hypokalemic metabolic alkalosis, and hyperreninemic hyperaldosteronism. Type III BS is caused by loss-of-function mutations in CLCNKB encoding basolateral ClC-Kb. The clinical phenotype of patients with CLCNKB mutations has been known to be highly variable, and cases that are difficult to categorize as type III BS or other hereditary tubulopathies, such as Gitelman syndrome, have been rarely reported. We report a case of a 10-year-old Korean boy with atypical clinical findings caused by a novel CLCNKB mutation. The boy showed intermittent muscle cramps with laboratory findings of hypokalemia, severe hypomagnesemia, and nephrocalcinosis. These findings were not fully compatible with those observed in cases of BS or Gitelman syndrome. The CLCNKB mutation analysis revealed a heterozygous c.139G>A transition in exon 13 [p.Gly(GGG)465Glu(GAG)]. This change is not a known mutation; however, the clinical findings and in silico prediction results indicated that it is the underlying cause of his presentation.

A Systematic Review on Drug Safety for Molsidomine, Nicorandil and Trimetazidine

BACKGROUND: Ischemic heart disease is the most common type of heart disease and an important cause of death in Korea. Among marketed anti-anginal medications, molsidomine, nicorandil, and trimetazidine are approved in Korea with unique mechanism of actions. As these drugs are not approved by the US Food and Drug Administration, the access to the up-to-dated and comprehensive safety-related information has been less than optimal from drug information resources used by Korean pharmacists. METHODS: A systematic review was conducted using Embase and Korean manuscripts to compile safety updates for these medications. Out of 418 articles from keyword searches, 52 studies were reviewed in full to compare adverse effects (AEs) with the approved package inserts (PI). RESULTS: Molsidomine related adverse effects were mostly mild or moderate, but anxiety, palpitation, epigastric pain, and sexual potency reduction were additional AEs found from the review not listed in PI. Although PI has included ulceration in oral cavity and gastrointestinal tracts including anus by nicorandil, the Korea FDA recently recommended adding corneal, genital, and skin ulcers to the approved PI. Trimetazidine induced Parkinsonism, worsening of the symptoms for patients diagnosed with Parkinson's disease, gastrointestinal burning, and muscle cramps were additionally identified AEs not listed in PI for trimetazidine. CONCLUSION: Continuous evaluations of the safety profile of these agents are needed to balance the risks and benefits to provide evidence-based safety counseling to the patients. In addition, more focused efforts on spontaneous reporting are warranted by healthcare professionals to safeguard patients against AEs.

Adjuvant Teriparatide Therapy for Surgical Treatment of Femoral Fractures; Does It Work? / 대한고관절학회지

PURPOSE: Atypical femoral fracture (AFF), periprosthetic femoral fracture (PPFF) and femoral nonunion (FNU) are recalcitrant challenges for orthopedic surgeons. Teriparatide (TPTD) had been demonstrated to have anabolic effects on bone in various studies. We postulated that adjuvant TPTD after operation would enhance biologic stimulation for bone formation. We investigated (1) whether the adjuvant TPTD could achieve satisfactory union rate of surgically challenging cases such as displaced AFF, PPFF and FNU; (2) whether the adjuvant TPTD could promote development of abundant callus after surgical fixation; (3) whether the adjuvant TPTD had medically serious adverse effects. MATERIALS AND METHODS: Thirteen patients who agreed to off label use of TPTD in combination of operation were included in this retrospective case series. Median patients' age was 68.7 years, and there were three male and ten female patients. Their diagnoses were nonunion in six patients and acute fracture in seven. Medical records and radiographic images were reviewed. RESULTS: Twelve of thirteen fractures were united both clinically and radiologically within a year after adjuvant TPTD. Union completed radiologically median 5.4 months and clinically 5.7 months after the medication, respectively. Callus appeared abundantly showing median 1.4 of fracture healing response postoperatively. There was no serious adverse reaction of medication other than itching, muscle cramp, or nausea. CONCLUSION: Even appropriate surgical treatment is a mainstay of treatment for AFF, PPFF, and FNU, the current report suggested that adjuvant TPTD combined with stable fixation results in satisfactory outcome for the challenging fractures of femur.

Rapid Progression of Sporadic ALS in a Patient Carrying SOD1 p.Gly13Arg Mutation

Amyotrophic lateral sclerosis (ALS), the most common adult onset motor neuron disease, is pathologically characterized by progressive loss of the upper and lower motor neurons. Mutations in the Cu/Zn superoxide dismutase gene (SOD1) account for about 20% of familial ALS cases and a small percentage of sporadic ALS (SALS) cases, and have revealed a validated genotype-phenotype correlation. Herein, we report a p.Gly13Arg mutation in SOD1 exon 1 in a patient with SALS who presented with a rapidly progressive course, predominantly affecting the lower motor neurons. A 48-year-old man presented with progressive weakness and muscle atrophy of the left upper and lower limbs, followed by muscle fasciculation and cramping. The clinical features of the patient were clearly suggestive of ALS, and implied a sporadic form with rapid progression, predominantly affecting the lower motor neurons. Sequencing of the SOD1 gene by PCR revealed a missense mutation of G to C (c.37G>C) in exon 1, and amino acid substitution of glycine by arginine (p.Gly13Arg). This is the first case identifying the p.Gly13Arg mutation of SOD1 in the Korean population, and clinical assessments of this patient revealed a different phenotype compared with other cases.

Precise Muscle Selection Using Dynamic Polyelectromyography for Treatment of Post-stroke Dystonia: A Case Report

Dystonia has a wide range of causes, but treatment of dystonia is limited to minimizing the symptoms as there is yet no successful treatment for its cause. One of the optimal treatment methods for dystonia is chemodenervation using botulinum toxin type A (BTX-A), alcohol injection, etc., but its success depends on how precisely the dystonic muscle is selected. Here, we reported a successful experience in a 49-year-old post-stroke female patient who showed paroxysmal repetitive contractions involving the right leg, which may be of dystonic nature. BTX-A and alcohol were injected into the muscles which were identified by dynamic polyelectromyography. After injection, the dystonic muscle spasm, cramping pain, and the range of motion of the affected lower limb improved markedly, and she was able to walk independently indoors. In such a case, dynamic polyelectromyography may be a useful method for selecting the dominant dystonic muscles.

Precise Muscle Selection Using Dynamic Polyelectromyography for Treatment of Post-stroke Dystonia: A Case Report

Dystonia has a wide range of causes, but treatment of dystonia is limited to minimizing the symptoms as there is yet no successful treatment for its cause. One of the optimal treatment methods for dystonia is chemodenervation using botulinum toxin type A (BTX-A), alcohol injection, etc., but its success depends on how precisely the dystonic muscle is selected. Here, we reported a successful experience in a 49-year-old post-stroke female patient who showed paroxysmal repetitive contractions involving the right leg, which may be of dystonic nature. BTX-A and alcohol were injected into the muscles which were identified by dynamic polyelectromyography. After injection, the dystonic muscle spasm, cramping pain, and the range of motion of the affected lower limb improved markedly, and she was able to walk independently indoors. In such a case, dynamic polyelectromyography may be a useful method for selecting the dominant dystonic muscles.

Eventos associados ao cotidiano de idosos em hemodiálise / Events associated with the daily life of elderly under hemodialysis

Estudo tevepor objetivo analisar os eventos associados ao cotidiano de hemodiálise e as percepções de incômodo de idosos renais crônicos em tratamento hemodialítico. Estudo transversal, analítico de abordagem quantitativa realizado com 35 idosos em hemodiálise em uma Unidade Nefrológica do noroeste do Rio Grande do Sul. A coleta de dados ocorreu nos meses de maio, junho e julho de 2010, por meio de formulário de caracterização sociodemográfica/clínica o Kidney Disease and Quality of Live-Short Form(KDQOL-SFTM). Os dados foram analisados pela estatística descritiva e Correlação de Spearmann. Quanto às características sociodemográficas, 74,3% eram homens, 65,7% com idade entre 60 e 70 anos, 60% casados. Quanto aos eventos associados ao tratamento hemodialítico, câimbras (60%) e fraqueza (57,1%) foram os mais apontados pelos idosos. Em relação às percepções dos idosos sobre os problemas que os incomodaram "extremamente" durante as quatro últimas semanas, os com maiores percentuais foram fraqueza ou tontura, esgotamento e dores musculares. Verificou-se correlação estatisticamente significativa (p<0,05) entre dores musculares, dor no peito, esgotamento e fraqueza/tontura e interferência da doença renal em suas vidas. Conclui-se que esses resultados permitem compreender aspectos peculiares envolvidos no cuidado de enfermagem e proporciona aos profissionais maiores subsídios para embasar sua atuação.

This study aimed to analyzing the events associated with daily hemodialysis and the perceptions of nuisance in elderly CKD on hemodialysis. Cross-sectional analytical study of quantitative approach carried out with 35 elderlies under hemodialysis in a northwestern Nephrological Unit of Rio Grande do Sul. Data collection took place during the months of May, June and July 2010, through a socio-demographic/clinical form, the Kidney Disease and Quality of Live-Short Form (KDQOL-SFTM). Data were analyzed usingdescriptive statistics and Spearman Correlation. Regarding the socio-demographic characteristics 74,3% were men, 65,7% aged 60 to 70 years old, 60% were married. In respect for the events associated with hemodialysis, cramps (60%) and weakness (57,1%) were the most frequently reported by the elderly. Regarding perceptions of the elderly about the problems that bother "extremely" during the last four weeks, with the highest percentages were weakness or dizziness, exhaustion and muscle pain. Statistically significant correlation was found (p<0,05) muscle aches, chest pain, exhaustion and weakness/dizziness and interference of renal disease in their lives. In conclusion, these results allow us to understand specific aspects involved in nursing care and providethe largest professional knowledge to sustain their actions.