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Pharmacoresistant epilepsy presenting during infancy poses both diagnostic and therapeutic challenges. We aim to identify diagnostic yield and treatment implications of exome sequencing (ES) as first-tier genetic testing for infantile-onset pharmacoresistant epilepsy. From June 2016 to December 2020, we enrolled patients with infantile-onset (age ≤ 12 months) pharmacoresistant epilepsy. 103 unrelated patients underwent ES. Clinical characteristics and changes in management due to the molecular diagnosis were studied. 42% (43/103) had epilepsy onset within the first month of life. After ES as first-tier genetic testing, 62% (64/103) of the cases were solved. Two partially solved cases (2%; 2/103) with heterozygous variants identified in ALDH7A1 known to cause autosomal recessive pyridoxine dependent epilepsy underwent genome sequencing (GS). Two novel large deletions in ALDH7A1 were detected in both cases. ES identified 66 pathogenic and likely pathogenic single nucleotide variants (SNVs) in 27 genes. 19 variants have not been previously reported. GS identified two additional copy number variations (CNVs). The most common disease-causing genes are SCN1A (13%; 13/103) and KCNQ2 (8%; 8/103). Eight percent (8/103) of the patients had treatable disorders and specific treatments were provided resulting in seizure freedom. Pyridoxine dependent epilepsy was the most common treatable epilepsy (6%; 6/103). Furthermore, 35% (36/103) had genetic defects which guided gene-specific treatments. Altogether, the diagnostic yield is 64%. Molecular diagnoses change management in 43% of the cases. This study substantiates the use of next generation sequencing (NGS) as the first-tier genetic investigation in infantile-onset pharmacoresistant epilepsy.
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Variaciones en el Número de Copia de ADN , Epilepsia , Humanos , Lactante , Secuenciación del Exoma , Piridoxina , Pruebas Genéticas/métodos , Epilepsia/genéticaRESUMEN
Translocations involving PLAG1 occur in several tumors, most commonly pleomorphic adenoma and lipoblastoma. Recently, a distinctive soft tissue tumor with a PLAG1 fusion has been reported in the pediatric age group. These are low grade tumors with a fibroblastic or mixed fibroblastic and myxoid morphology but no other lines of differentiation. They are typically immunopositive for desmin and CD34. The partner genes for these tumors have included YWHAZ, EEF1A1, ZFHX4l, CHCHD7, and PCMTD1. We report another case of this fibromyxoid tumor with a PLAG1 fusion, this time with COL3A1 as the partner gene. The fusion placed expression of a full-length PLAG1 protein under the control of the constitutively active COL3A1 promoter. Overexpression of PLAG1 was confirmed by diffusely positive immunostaining for PLAG1. The most novel aspect of this tumor is the intracranial location. Opinion has been divided over whether these tumors are a specific entity, or related to lipoblastoma, since that tumor also typically occurs in soft tissue in the pediatric age group and shows many of the same gene fusions. However, lipoblastoma has never been reported in an intracranial location and, thus, our case provides compelling evidence that this fibromyxoid tumor is indeed a distinct entity.
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Adenoma Pleomórfico , Lipoblastoma , Adenoma Pleomórfico/genética , Adenoma Pleomórfico/patología , Niño , Proteínas de Unión al ADN/genética , Fusión Génica , Humanos , Lipoblastoma/genética , Lipoblastoma/patología , Factores de Transcripción/genética , Translocación GenéticaRESUMEN
Due to the rapid growth in sleep medicine's professional content, several countries have recognized sleep medicine as an independent specialty. The practice of sleep medicine and the demand for this service in Asian countries are expanding. At this point of growth, the accreditation of sleep medicine specialists is paramount to patient care and the training of physicians and technologists. The Asian Society of Sleep Medicine (ASSM) mandated a taskforce committee for the accreditation of sleep medicine practice. This taskforce developed Asian accreditation practice guidelines for sleep medicine physicians and technologists. This paper presents the newly approved Asian accreditation practice guidelines for sleep medicine physicians and technologists by the ASSM.
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Médicos , Medicina del Sueño , Acreditación , Asia , Humanos , SueñoRESUMEN
BACKGROUND: Epilepsy is a common pediatric neurologic disease in Thailand. However, the mainstay antiepileptic pharmacotherapies can induce severe side effects. While the benefit of playing Mozart K.448 music has been studied as an alternative, supplementary, nonpharmacologic treatment for epilepsy, the literature features limited few randomized controlled trial studies of children. OBJECTIVE: We aimed to study the effect of Mozart K.448 for two pianos on interictal epileptiform discharges (IEDs), quantitative electroencephalogram (qEEG), and heart rate variability (HRV) in patients with epilepsy. METHODS: We employed a single-blinded randomized trial design with a placebo control. The treatment group listened to the first 8â¯min of Mozart K.448 for two pianos during EEG recording. The control group underwent an EEG recording of the same duration in a quiet environment. Interictal epileptiform discharges were manually counted for 8â¯min before, during, and after the song was plated. Quantitative electroencephalogram and HRV were analyzed in each period. RESULT: A total of 32 patients aged 0-18â¯years were enrolled. There were 12 patients in the music group and 14 patients in the control group; 67% of the patients in the former exhibited significantly decreased IEDs while listening to the music compared with 42% of the patients in the quiet group (RR [Relative Risk Reduction]: 0.72, p-value: <0.001, 95% confidence interval [CI]: 0.69-0.74). During music exposure, qEEG demonstrated an increase in the delta/theta to alpha/beta ratio relative to that of controls (median in music: +3% and control: -6%, p-value: 0.520). Heart rate variability analyses showed a decrease in the ratio of low frequency to high frequency (LF/HF), which represents parasympathetic activity during music exposure (decrease of 34%, p-value: 0.382). CONCLUSION: The present study showed that Mozart K.448 reduced the number of IEDs in children with epilepsy and that Mozart K.448 could enhance parasympathetic activity. However, possibly because of the small study population, statistical significance was not reached. Our study revealed the considerable potential of music in the treatment of pediatric epilepsy.
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Epilepsia , Musicoterapia , Estimulación Acústica , Adolescente , Niño , Preescolar , Electroencefalografía , Epilepsia/terapia , Humanos , Lactante , Recién Nacido , Proyectos Piloto , TailandiaRESUMEN
BACKGROUND: In approximately half of patients with epilepsy and intellectual disability (ID), the cause is unidentified and could be a mutation in a new disease gene. PATIENT DESCRIPTION: To determine the discovery of disease-causing mutation in a female patient with epilepsy and ID, we performed trio whole-exome sequencing, reverse transcription polymerase chain reaction (RT-PCR) followed by Sanger sequencing. RESULTS: Trio whole-exome sequencing was performed and revealed a novel de novo heterozygous stop-loss c.467A > T (p.*156Leuext*35) mutation in the ATP6V0C gene. Using RNA from leukocytes, RT-PCR followed by Sanger sequencing showed the existence of the mutant RNA, and real-time PCR demonstrated that the patient's ATP6V0C RNA level was approximately half of that in her parents, suggesting haploinsufficiency as a pathomechanism. CONCLUSION: These findings, along with previous reports of individuals with similar phenotypes and variants in the same gene, substantiate ATP6V0C as a gene causing epilepsy with ID.
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Epilepsia/genética , Discapacidad Intelectual/genética , ATPasas de Translocación de Protón Vacuolares/genética , Femenino , Humanos , MutaciónRESUMEN
PURPOSE: Explore etiology, clinical course and outcome of infant epilepsy in Bhumibol Adulyadej Hospital. METHOD: Retrospective and prospective descriptive analysis of infants 1â¯month to 1â¯year diagnosed with epilepsy between January 1, 2012, and April 30, 2018. RESULTS: Total 57 infants. Average age of seizure onset was 4.7â¯months. Follow-up period averaged 34.2â¯months. Prenatal risk factors were found in 28.1 percent (16/57). Of these, 50 percent (8/16) had seizure in neonatal period. An additional 6 infants without any prenatal risk factor had seizure in the neonatal period, bringing the total newborn with seizure to 24.6 percent (14/57). Family history of seizure was positive in only 15.8 percent (9/57). Neuroimaging was done 68.4 percent (39/57) and electroencephalogram 50.9 percent (29/57). The etiology was mostly structural 38.6 percent (22/57), followed by unknown 35.1 percent (20/57), genetics 14 percent (8/57), infection 10.5 percent (6/57) and metabolic 1.8 percent (1/57). Status epilepticus was found 21.1 percent of the times (12/57). Antiepileptic drugs were discontinued 19.3 percent (11/57). Intractable seizure was found 29.8 percent (17/57) and developmental delay 56.1 percent (32/57). By multivariate logistic regression analysis, status epilepticus and developmental delay predicted intractable seizure, whereas, abnormal neurological examination and abnormal neuroimaging predicted developmental delay. Mortality rate was 3.5 percent. CONCLUSION: The study shows that early onset of epilepsy in children under a year is similar to that found in children less than 2-3â¯years as found in prior studies. High percentages of intractable seizure and developmental delay were found.
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Discapacidades del Desarrollo/epidemiología , Discapacidades del Desarrollo/etiología , Epilepsia , Femenino , Humanos , Lactante , Recién Nacido , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , TailandiaRESUMEN
AIM: To assess the clinical trial and real-world data for adjunctive perampanel in adolescents and develop consensus recommendations to guide the use of perampanel in this population in clinical practice. METHODS: In May 2015, 15 epilepsy experts attended a Consensus Development Meeting to assess the clinical trial data for perampanel, specific to the adolescent age group (12-17 years) and develop consensus treatment recommendations. RESULTS AND DISCUSSION: Analysis of the adolescent subgroup data of three pivotal placebo-controlled, double-blind, phase 3 trials investigating perampanel in patients with ongoing focal epileptic seizures despite receiving one to three antiepileptic drugs found that perampanel 4-12 mg was superior to placebo. The tolerability profile of perampanel was generally acceptable. Adolescent patients receiving long-term treatment with perampanel in an open-label extension study maintained improvements in seizure control compared with baseline, with a favorable risk-benefit profile. A phase 2 study showed that perampanel had no clinically important effects on cognitive function, growth, and development. CONCLUSION: Perampanel is a welcome addition to the armamentarium of existing antiepileptic drugs as it represents a new approach in the management of epilepsy, with a novel mechanism of action, and the potential to have a considerable impact on the treatment of adolescents with epilepsy.
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BACKGROUND: Literature has addressed the increased prevalence of gastroesophageal reflux disease (GERD) in obstructive sleep apnea (OSA). Significant improvement of GERD has been found after OSA treatment. However, precise mechanisms underlying this correlation remain unclear. We examined the association between nocturnal gastroesophageal reflux (GER) and sleep events in patients with coexisting OSA and GERD. METHODS: A case-crossover study among 12 patients with coexisting moderate-severe OSA and GERD was conducted. Participants underwent simultaneous polysomnography and esophageal impedance and pH monitoring. GER subtypes (ie, acid reflux, non-acid reflux) were defined as outcomes. Respective control time points were selected in all eligible control periods. Each sleep event was assessed individually. Estimated odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed. A p-value of < 0.05 was considered significant. RESULTS: Patients were determined as moderate to severe OSA (respiratory disturbance index of 42.66 [±22.09]). There were a total of 50 GER episodes, 22 acid reflux and 28 non-acid reflux. Arousals and awakenings were significantly associated with subsequent GER events. The OR for GER following an arousal was 2.31 (95% CI 1.39-3.68; p < 0.001) and following an awakening was 3.71 (95% CI 1.81-7.63; p < 0.001). GER events were significantly less likely to occur after other respiratory events (OR 0.38 [95% CI 0.18-0.82]; p = 0.01). No sleep events followed GER events (p > 0.05). CONCLUSIONS: Both awakening and arousal appear to precipitate any subtype of GER events in patients with coexisting GERD and moderate to severe OSA. However, GER events were significantly less likely to occur after other respiratory events and did not appear to cause sleep-related events.
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Nivel de Alerta/fisiología , Reflujo Gastroesofágico/complicaciones , Apnea Obstructiva del Sueño/complicaciones , Estudios Cruzados , Monitorización del pH Esofágico/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , PolisomnografíaRESUMEN
OBJECTIVE: To evaluate the prevalence of sleep disorders in Thai children who underwent polysomnography at a single institution. METHODS: A retrospective analysis of pediatric polysomnographic studies was performed from January 2011 through December 2014. RESULTS: One hundred sixty-six studies were conducted; 142, 7, and 17 were diagnostic, split-night, and positive airway pressure (PAP) titration studies, respectively. In total, 136 diagnostic/split-night studies were performed to diagnose sleep disorders with presentation of snoring (92.6 %), heavy breathing (0.7 %), witnessed apnea (14.7 %), excessive daytime sleepiness (10.3 %), hyperactivity (2.2 %), restless sleep (11.0 %), enuresis/nocturia (5.9 %), abnormal behavior (4.4 %) and poor weight gain (0.7 %). Eleven diagnostic studies and one split-night study were performed to follow-up obstructive sleep apnea (OSA) after adenoidectomy and/or tonsillectomy. One diagnostic study was conducted to follow-up OSA after postmandibular distraction. OSA was the most common diagnosis with a prevalence of 92.7 %; 40.4 % of patients were diagnosed with severe OSA. The prevalence of sleep-related hypoventilation was 15.4 %. The second most common diagnosis was periodic limb movement disorder with a prevalence of 20.6 %. Seventeen PAP titration studies were performed. Four CPAP titration studies were conducted for OSA treatment. Twelve bi-level (BiPAP) titration studies were performed in eight children with hypoventilation. One BiPAP/average volume-assured pressure support titration was conducted in a patient with congenital central hypoventilation syndrome (CCHS). CONCLUSIONS: The prevalence of sleep disorders in Thai children who underwent polysomnography at a tertiary-care hospital is very high. The factors that contribute are the limited availability and high costs of polysomnography in Thailand. This information will encourage pediatricians to look for sleep disorders in children.
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Trastornos del Sueño-Vigilia/epidemiología , Niño , Femenino , Humanos , Masculino , Polisomnografía , Prevalencia , Estudios Retrospectivos , Apnea Obstructiva del Sueño , Tailandia/epidemiologíaRESUMEN
OBJECTIVE: Extratemporal lobe epilepsy is difficult to localize. We aimed to define the best parameter(s) of SPECT for confirmation of seizure origin among the region of maximum cerebral perfusion in ictal phase (MP), maximum change of cerebral perfusion from interictal to ictal phase (MC), and maximum extent of hyperperfusion in ictal phase (ME) of (99m)Tc ECD brain perfusion SPECT as well as combined SPECT parameters, and combined SPECT and MRI for seizure localization in extratemporal lobe epilepsy. MATERIALS AND METHODS: Twenty intractable extratemporal lobe epilepsy patients who had (99m)Tc-ECD brain SPECT were reviewed. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of single SPECT parameter, combined SPECT parameters, and combined SPECT and MRI parameters for localization of seizure origin were calculated using pathology and surgical outcomes (Engel class I and II) as gold standards. RESULTS: Combined SPECT parameters provided more specificity, PPV and accuracy than single SPECT parameters. The best combined SPECT parameters was MP+MC with 80.6 % accuracy, 92.4 % specificity and 43.8 % PPV. Combination of SPECT parameter with MRI (ME+MRI) was the most sensitive (41.7 %), specific (97.5 %), accurate (88.2 %) parameter and had highest PPV (76.9 %) and NPV (89.3 %) for seizure localization. It improved specificity and PPV when compared to MRI alone. CONCLUSION: Combined SPECT parameters improved the specificity and accuracy in seizure localization. The most specific and accurate SPECT combination is MP+MC. The combined SPECT parameter with MRI further improved sensitivity, specificity, accuracy, PPV and NPV. The authors recommend using SPECT combination, MP+MC, when MRI is negative and ME+MRI when there is MRI lesion.
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Encéfalo/diagnóstico por imagen , Epilepsias Parciales/diagnóstico por imagen , Convulsiones/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adolescente , Adulto , Encéfalo/patología , Encéfalo/cirugía , Niño , Preescolar , Cisteína/análogos & derivados , Epilepsias Parciales/patología , Epilepsias Parciales/cirugía , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética/métodos , Masculino , Imagen Multimodal/métodos , Compuestos de Organotecnecio , Periodo Preoperatorio , Radiofármacos , Estudios Retrospectivos , Convulsiones/patología , Convulsiones/cirugía , Sensibilidad y Especificidad , Resultado del Tratamiento , Adulto JovenAsunto(s)
Errores Diagnósticos , Trastornos del Metabolismo del Hierro/diagnóstico , Distrofias Neuroaxonales/diagnóstico , Adolescente , Trastorno Autístico/diagnóstico , Femenino , Humanos , Trastornos del Metabolismo del Hierro/patología , Trastornos del Metabolismo del Hierro/fisiopatología , Imagen por Resonancia Magnética , Distrofias Neuroaxonales/patología , Distrofias Neuroaxonales/fisiopatologíaRESUMEN
INTRODUCTION: Unlike Caucasians, many Asians with obstructive sleep apnea (OSA) are non-obese but are affected by the disease due to predisposing craniofacial structure. Therefore, non-obese and obese OSA may represent different disease entities. The associated risk factors for developing cardiovascular-related diseases, consequently, may be considered separately for the two types of OSA. METHOD: We reviewed polysomnographic studies performed in adults (aged ≥ 18 years) diagnosed with OSA (respiratory disturbance index [RDI] ≥ 5). We divided the patients into obese (body mass index [BMI] ≥ 25) and non-obese (BMI < 25) groups. We aimed to determine the differences between these two groups in terms of clinical presentations, polysomno-graphic findings, and association with cardiovascular-related diseases including hypertension, diabetes mellitus, coronary artery disease, and/or cerebrovascular disease. RESULTS: Among 194 patients with OSA (RDI ≥ 5), 63.4% were non-obese and 36.6% were obese. Compared with obese OSA patients, non-obese OSA patients were noted to have smaller neck size, less prevalence of hypertension, and less history of frequent nocturia (> 3-4/week), with equal prevalence of excessive daytime sleepiness. Overall, non-obese OSA patients were noted to have milder disease indicated by lower total, supine, and non-supine, NREM RDI and higher mean and nadir oxygen saturations. In the non-obese group, only total obstructive apnea index (OAI) was noted to be a predictor for developing any of the cardiovascular-related diseases after controlling for age, sex, and RDI (odds ratio = 9.7). However, in the obese OSA group, frequent snoring (> 50% of total sleep time), low sleep efficiency (≤ 90%), and low mean oxygen saturation (< 95%) were noted to be significant predictors of cardiovascular-related diseases (odds ratios = 12.3, 4.2, and 5.2, respectively). CONCLUSION: Among Asians, most OSA patients were not obese. Compared to obese OSA patients, non-obese OSA patients were noted to have less prevalence of hypertension and less history of nocturia. They were also noted to have overall milder OSA. Only OAI was noted to be a significant predictor for cardiovascular-related disease in the non-obese OSA group.
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Pueblo Asiatico , Enfermedades Cardiovasculares/etnología , Obesidad/etnología , Apnea Obstructiva del Sueño/etnología , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Estudios Retrospectivos , Factores de Riesgo , Tailandia/epidemiologíaRESUMEN
Benign Adult Familial Myoclonic Epilepsy (BAFME) is an autosomal dominant disorder characterized by adult-onset cortical tremor or action myoclonus predominantly in the upper limbs, and generalized seizures. We investigated a Thai BAFME family. Clinical and electrophysiological studies revealed that 13 were affected with BAFME. There were a total of 24 individuals studied. Genetic analysis by genome-wide linkage study (GWLS) was performed using 400 microsatellite markers and excluded linkage of the previous BAFME loci, 8q23.3-q24.1, and 2p11.1-q12.2. GWLS showed that the disease-associated region in our Thai family was linked to a newly identified locus on chromosome 3q26.32-3q28. This locus represents the fourth chromosomal region for BAFME.
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Epilepsias Mioclónicas , Ligamiento Genético , Repeticiones de Microsatélite/genética , Adulto , Mapeo Cromosómico , Cromosomas Humanos Par 3/genética , Electroencefalografía , Epilepsias Mioclónicas/genética , Epilepsias Mioclónicas/fisiopatología , Humanos , Linaje , Temblor/fisiopatologíaRESUMEN
The aim of this study was to determine the prevalence and associated factors for obstructive sleep apnea (OSA) among children with severe beta-thalassemia. Children with severe beta-thalassemia without a history of bone marrow transplantation were studied. Polysomnography (PSG) was performed in those who habitually snored to identify OSA. One hundred twenty children (aged 9.3 +/- 3.7 years; 42% male) were studied. Nineteen patients (15.8%) habitually snored. Sixteen had PSG performed. OSA was demonstrated in 10 patients. Six had moderate-to-severe OSA. The estimated prevalence of OSA was 8.3%. All OSA patients had adenoid hypertrophy and 80% had associated tonsil enlargement. The OSA group had a higher serum ferritin level compared to the non-OSA group (3,785 +/- 1,780 vs 1,885 +/- 677 ng/ml; p = 0.03). Six of 10 patients who had OSA underwent adenotonsillectomy. Reactive lymphoid hyperplasia was demonstrated in all cases. The estimated prevalence of OSA in children with severe beta-thalassemia was high (8.3%) and some had severe OSA. Adenotonsillar lymphoid hyperplasia was common among those who had OSA. A high serum ferritin level was associated with the occurrence of OSA. A history of snoring and OSA symptoms should be periodically assessed in children with severe beta-thalassemia.
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Apnea Obstructiva del Sueño/etiología , Talasemia beta/complicaciones , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Polisomnografía , Prevalencia , Factores de Riesgo , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/fisiopatología , TailandiaRESUMEN
BACKGROUND: Previous studies have often investigated the association of obstructive sleep apnea (OSA) with cardiovascular morbidity and mortality, but the possibility of reverse causation has not been clearly defined. OBJECTIVE: To examine if the presence of any of the cardiovascular-related diseases, including hypertension, diabetes mellitus, coronary artery disease, and/or cerebrovascular disease, correlates with more severe OSA. METHODS: This was a retrospective study where all patients age ≥ 18 years referred to our sleep laboratory for suspected OSA were included. The data from the full-night baseline and split-night polysomnographic reports were reviewed. Data were then evaluated by logistic regression analysis to compare between 2 groups, the severity of OSA (respiratory disturbance index [RDI] < 15 vs RDI ≥ 15, and RDI < 5 vs RDI ≥ 5), other polysomnographic variables and daytime sleepiness score (Epworth Sleepiness Scale [ESS] score < 10 and ≥ 10). RESULTS: 190 patients were analyzed. The patients with any of the cardiovascular-related diseases were noted to have more severe sleep apnea (RDI ≥ 15), with an adjusted odds ratio of 3.24. Sleep efficiency ≥ 90% and mean oxygen saturation ≥ 95% were observed less commonly in the patients with any of the cardiovascular-related diseases (adjusted odds ratios of 0.45 and 0.36, respectively). There was no statistically significant difference in ESS score. CONCLUSIONS: Patients with any of the cardiovascular-related diseases are at a higher risk of having moderate to severe OSA without significant increase in daytime sleepiness. Therefore, we suggest that patients with any of the cardiovascular-related diseases should be screened for OSA, even if they are asymptomatic.
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Enfermedades Cardiovasculares/complicaciones , Trastornos de Somnolencia Excesiva/complicaciones , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/fisiopatología , Adulto , Factores de Edad , Anciano , Índice de Masa Corporal , Enfermedades Cardiovasculares/fisiopatología , Trastornos de Somnolencia Excesiva/fisiopatología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Cuello/anatomía & histología , Oportunidad Relativa , Oximetría , Polisomnografía , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Sueño/fisiologíaRESUMEN
INTRODUCTION: In Asian population, facial structure may contribute to the primary pathophysiology of obstructive sleep apnea (OSA). We hypothesized that sleep position may have more effect on OSA in Asians compared to the Western population. If this hypothesis is accurate, positional therapy will have a major impact on treatment of OSA among Asians. PATIENTS/METHODS: We reviewed 263 polysomnographic studies from our laboratory from January 1, 2010 to June 30, 2010. Criteria for positional and non-positional OSA were (1) supine respiratory disturbance index (RDI)/non-supine RDI ≥2 and total RDI ≥5 and (2) supine RDI/non-supine RDI <2 and total RDI ≥5, respectively. We aimed to determine the difference in baseline characteristics, polysomnographic findings, and predictors for positional OSA. RESULTS: We found 144 patients diagnosed with OSA (RDI ≥5), and 96 patients met the criteria for positional OSA (67%), in which in almost half of these patients (47%), RDI was normalized (RDI < 5) in non-supine position. Snoring frequency were significantly lower among positional OSA and OSA was less severe indicated by lower RDI and arousal index, higher mean and nadir oxygen saturation, and higher %NREM3. We also found that low snoring frequency (less than 20% of total sleep time) was a significant predictor for positional OSA (odd ratio of 3.27; p = 0.011), contrarily to low mean oxygen saturation (<95%) which was found to be a negative predictor (odd ratio of 0.31; p = 0.009). Among OSA patients, low RDI (<15) was a significant predictor for normalization of RDI in non-supine position (odd ratio of 8.77; p = < 0.001), contrarily to low mean oxygen saturation (<95%) which was also found to be a negative predictor (odd ratio of 0.13; p = 0.001). CONCLUSION: Positional OSA is very prevalent and noted in almost 70% of our patients. Low snoring frequency was noted to be a positive predictor for positional OSA, contrarily to low mean oxygen saturation which was found to be a negative predictor. These findings are encouraging that positional therapy can be very beneficial as the treatment modality for OSA among Asians.
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Comparación Transcultural , Países en Desarrollo , Polisomnografía , Postura , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/etiología , Adulto , Anciano , Cefalometría , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Oxígeno/sangre , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/etnología , Ronquido/diagnóstico , Ronquido/epidemiología , Ronquido/etnología , Ronquido/etiología , TailandiaRESUMEN
PURPOSE: Previous studies found a strong association between HLA-B*1502 and carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) in Han Chinese, but not in Caucasian populations. Even in Han Chinese, the HLA-B*1502 was not associated with CBZ-induced maculopapular eruptions (MPE). This study seeks to identify whether HLA-B*1502 is associated with CBZ- or phenytoin (PHT)-induced SJS or MPE in a Thai population. METHODS: Eighty-one Thai epileptic patients between 1994 and 2007 from the Chulalongkorn Comprehensive Epilepsy Program were recruited. Thirty-one subjects had antiepileptic drug (AED)-induced SJS or MPE (6 CBZ-SJS, 4 PHT-SJS, 9 CBZ-MPE, 12 PHT-MPE), and 50 were AED-tolerant controls. RESULTS: For the first time, a strong association between HLA-B*1502 and PHT-induced SJS was found (p = 0.005). A strong association was also found between the HLA-B*1502 and CBZ-induced SJS (p = 0.0005), making Thai the first non-Chinese population demonstrating such an association. Some patients, who were HLA-B*1502 and suffered from CBZ-induced SJS, could be tolerant to PHT and vice versa. This suggests that HLA-B*1502 may be a common attribute required for a Thai patient to develop SJS from these two AEDs; other different elements, however, are also needed for each AED. In addition, no association between HLA-B alleles and CBZ- or PHT-induced MPE was found. CONCLUSIONS: CBZ- and PHT-induced SJS, but not MPE, is associated with HLA-B*1502 allele in Thai population.
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Anticonvulsivantes/efectos adversos , Carbamazepina/efectos adversos , Antígenos HLA-B/genética , Farmacogenética , Fenitoína/efectos adversos , Síndrome de Stevens-Johnson/inducido químicamente , Síndrome de Stevens-Johnson/genética , Adolescente , Adulto , Niño , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Femenino , Predisposición Genética a la Enfermedad/etnología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tailandia/etnología , Adulto JovenRESUMEN
Studies of human chromosomal aberrations and knockout (KO) mice have suggested SATB2 as a candidate gene for a human malformation syndrome of craniofacial patterning and brain development. Of 59 unrelated patients with craniofacial dysmorphism, with or without mental retardation, one 36-year-old man had a nonsynonymous mutation in SATB2. The affected individual exhibited craniofacial dysmorphisms including cleft palate, generalized osteoporosis, profound mental retardation, epilepsy and a jovial personality. He carries a de novo germline nonsense mutation (c.715C>T, p.R239X) in the exon 6 of SATB2. Expression studies showed that the mutant RNA was stable, expected to produce a truncated protein predicted to retain its dimerization domain and exert a dominant negative effect. This new syndrome is the first determined to result from mutation of a gene within the family that encodes nuclear matrix-attachment region (MAR) proteins.
Asunto(s)
Fisura del Paladar/genética , Codón sin Sentido , Trastornos del Conocimiento/genética , Heterocigoto , Proteínas de Unión a la Región de Fijación a la Matriz/genética , Osteoporosis/genética , Factores de Transcripción/genética , Adulto , Secuencia de Bases , Cartilla de ADN , Exones , Humanos , Masculino , Reacción en Cadena de la PolimerasaRESUMEN
The recent success in treating a human rabies patient in Milwaukee prompted the use of a similar therapeutic approach in a 33-year-old male Thai patient who was admitted in the early stages of furious rabies. He received therapeutic coma with intravenous diazepam and sodium thiopental to maintain an electroencephalographic burst suppression pattern, which was maintained for a period of 46 h, as well as intravenous ketamine (48 mg/kg/day) as a continuous infusion and ribavirin (48 to 128 mg/kg/day) via a nasogastric tube. He never developed rabies virus antibodies and he died on his 8th hospital day. At least three other patients have been treated unsuccessfully with a similar therapeutic approach. Because of the lack of a clear scientific rationale, high associated costs, and potential complications of therapeutic coma, the authors recommend caution in taking this approach for the therapy of rabies outside the setting of a clinical trial. More experimental work is also needed in cell culture systems and in animal models of rabies in order to develop effective therapy for human rabies.
Asunto(s)
Coma/inducido químicamente , Antagonistas de Aminoácidos Excitadores/uso terapéutico , Ketamina/uso terapéutico , Rabia/terapia , Adulto , Animales , Encéfalo/virología , Modelos Animales de Enfermedad , Resultado Fatal , Humanos , Masculino , Virus de la Rabia/aislamiento & purificación , Médula Espinal/virología , Insuficiencia del TratamientoRESUMEN
This 2-month-old child presented with paraplegia. The authors observed a dermal sinus with purulent discharge in the lumbosacral area. Magnetic resonance (MR) imaging of the spine revealed an intramedullary enhancing cavity spanning C-1 to the conus medullaris. Intraoperatively the dermal sinus was seen to infiltrate the lower end of the conus medullaris, and it also communicated directly with the central canal. The L2-5 laminae were removed, and a myelotomy was undertaken on the conus medullaris. A No. 8 French pediatric feeding tube was passed into the abscess cavity and advanced rostrally to the level of C-1. Aspiration was applied via the feeding tube to drain the intramedullary abscess of the spinal cord (IASC). Postoperatively, a 6-week course of intravenous cloxacillin was instituted. Follow-up MR imaging revealed complete resolution of abscess. When the patient was 26 months of age, examination showed complete neurological recovery. The authors describe what, to their knowledge, is the first case of a holocord IASC treated successfully by the aforementioned technique, and review of the related literature.