RESUMEN
PURPOSE: To evaluate the incidence of mosaicism in de novo neurofibromatosis 2 (NF2). METHODS: Patients fulfilling NF2 criteria, but with no known affected family member from a previous generation (n = 1055), were tested for NF2 variants in lymphocyte DNA and where available tumor DNA. The proportion of individuals with a proven or presumed mosaic NF2 variant was assessed and allele frequencies of identified variants evaluated using next-generation sequencing. RESULTS: The rate of proven/presumed mosaicism was 232/1055 (22.0%). However, nonmosaic heterozygous pathogenic variants were only identified in 387/1055 (36.7%). When variant detection rates in second generation nonmosaics were applied to de novo cases, we assessed the overall probable mosaicism rate to be 59.7%. This rate differed by age from 21.7% in those presenting with bilateral vestibular schwannoma <20 years to 80.7% in those aged ≥60 years. A mosaic variant was detected in all parents of affected children with a single-nucleotide pathogenic NF2 variant. CONCLUSION: This study has identified a very high probable mosaicism rate in de novo NF2, probably making NF2 the condition with the highest expressed rate of mosaicism in de novo dominant disease that is nonlethal in heterozygote form. Risks to offspring are small and probably correlate with variant allele frequency detected in blood.
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Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mosaicismo , Neurofibromatosis 2/genética , Neurofibromina 2/genética , Adulto , Femenino , Frecuencia de los Genes , Mutación de Línea Germinal , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Tasa de Mutación , Linaje , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
PURPOSE: We have evaluated deficiencies in existing diagnostic criteria for neurofibromatosis 2 (NF2). METHODS: Two large databases of individuals fulfilling NF2 criteria (n = 1361) and those tested for NF2 variants with criteria short of diagnosis (n = 1416) were interrogated. We assessed the proportions meeting each diagnostic criterion with constitutional or mosaic NF2 variants and the positive predictive value (PPV) with regard to definite diagnosis. RESULTS: There was no evidence for usefulness of old criteria "glioma" or "neurofibroma." "Ependymoma" had 100% PPV and high levels of confirmed NF2 diagnosis (67.7%). Those with bilateral vestibular schwannoma (VS) alone aged ≥60 years had the lowest confirmation rate (6.6%) and reduced PPV (80%). Siblings as a first-degree relative, without an affected parent, had 0% PPV. All three individuals with unilateral VS and an affected sibling were proven not to have NF2. The biggest overlap was with LZTR1-associated schwannomatosis. In this category, seven individuals with unilateral VS plus ≥2 nondermal schwannomas reduced PPV to 67%. CONCLUSIONS: The present study confirms important deficiencies in NF2 diagnostic criteria. The term "glioma" should be dropped and replaced by "ependymoma." Similarly "neurofibroma" should be removed. Dropping "sibling" from first-degree relatives should be considered and testing of LZTR1 should be recommended for unilateral VS.
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Bases de Datos Factuales , Neurofibromatosis 2/diagnóstico , Adolescente , Adulto , Niño , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Técnicas de Diagnóstico Molecular , Neurofibromatosis 2/fisiopatología , Terminología como Asunto , Adulto JovenRESUMEN
OBJECTIVES: Schwannomatosis is a dominantly inherited condition predisposing to schwannomas of mainly spinal and peripheral nerves with some diagnostic overlap with neurofibromatosis-2 (NF2), but the underlying epidemiology is poorly understood. We present the birth incidence and prevalence allowing for overlap with NF2. METHODS: Schwannomatosis and NF2 cases were ascertained from the Manchester region of England (population=4.8 million) and from across the UK. Point prevalence and birth incidence were calculated from regional birth statistics. Genetic analysis was also performed on NF2, LZTR1 and SMARCB1 on blood and tumour DNA samples when available. RESULTS: Regional prevalence for schwannomatosis and NF2 were 1 in 126 315 and 50 500, respectively, with calculated birth incidences of 1 in 68 956 and 1 in 27 956. Mosaic NF2 causes a substantial overlap with schwannomatosis resulting in the misdiagnosis of at least 9% of schwannomatosis cases. LZTR1-associated schwannomatosis also causes a small number of cases that are misdiagnosed with NF2 (1%-2%), due to the occurrence of a unilateral vestibular schwannoma. Patients with schwannomatosis had lower numbers of non-vestibular cranial schwannomas, but more peripheral and spinal nerve schwannomas with pain as a predominant presenting symptom. Life expectancy was significantly better in schwannomatosis (mean age at death 76.9) compared with NF2 (mean age at death 66.2; p=0.004). CONCLUSIONS: Within the highly ascertained North-West England population, schwannomatosis has less than half the birth incidence and prevalence of NF2.
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Neurilemoma/epidemiología , Neurilemoma/genética , Neurofibromatosis/epidemiología , Neurofibromatosis/genética , Neurofibromina 2/genética , Proteína SMARCB1/genética , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/genética , Factores de Transcripción/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Inglaterra/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neurofibromatosis 2/epidemiología , Neurofibromatosis 2/genética , Prevalencia , Adulto JovenRESUMEN
We present the analysis of a prospective multicentre study to investigate genetic effects on the prognosis of newly treated epilepsy. Patients with a new clinical diagnosis of epilepsy requiring medication were recruited and followed up prospectively. The clinical outcome was defined as freedom from seizures for a minimum of 12 months in accordance with the consensus statement from the International League Against Epilepsy (ILAE). Genetic effects on remission of seizures after starting treatment were analysed with and without adjustment for significant clinical prognostic factors, and the results from each cohort were combined using a fixed-effects meta-analysis. After quality control (QC), we analysed 889 newly treated epilepsy patients using 472 450 genotyped and 6.9 × 10(6) imputed single-nucleotide polymorphisms. Suggestive evidence for association (defined as Pmeta < 5.0 × 10(-7)) with remission of seizures after starting treatment was observed at three loci: 6p12.2 (rs492146, Pmeta = 2.1 × 10(-7), OR[G] = 0.57), 9p23 (rs72700966, Pmeta = 3.1 × 10(-7), OR[C] = 2.70) and 15q13.2 (rs143536437, Pmeta = 3.2 × 10(-7), OR[C] = 1.92). Genes of biological interest at these loci include PTPRD and ARHGAP11B (encoding functions implicated in neuronal development) and GSTA4 (a phase II biotransformation enzyme). Pathway analysis using two independent methods implicated a number of pathways in the prognosis of epilepsy, including KEGG categories 'calcium signaling pathway' and 'phosphatidylinositol signaling pathway'. Through a series of power curves, we conclude that it is unlikely any single common variant explains >4.4% of the variation in the outcome of newly treated epilepsy.
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Epilepsia/diagnóstico , Epilepsia/genética , Estudio de Asociación del Genoma Completo , Adulto , Anticonvulsivantes/uso terapéutico , Señalización del Calcio/genética , Cromosomas Humanos Par 15 , Cromosomas Humanos Par 6 , Cromosomas Humanos Par 9 , Epilepsia/tratamiento farmacológico , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Fosfatidilinositoles/genética , Polimorfismo de Nucleótido Simple , Pronóstico , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND & AIMS: Dysphagia in patients with Parkinson's disease, persisting despite dopaminergic treatment, affects intake of nutrients and medication, and reduces quality of life (QOL). We investigated the neurophysiologic mechanisms that contribute to dysphagia in these patients, on and off L-3,4-dihydroxyphenylalanine (levodopa), using transcranial magnetic stimulation. METHODS: We studied 26 patients with Parkinson's disease (age, 65 ± 9 y; 10 men). Dysphagia and QOL were first assessed with qualitative questionnaires. Twelve hours after patients were taken off levodopa, they underwent cortical transcranial magnetic stimulation mapping of the pharyngeal musculature and trigeminal (bulbar) transcranial magnetic stimulation, as well as videofluoroscopy to examine swallowing. The analyses were repeated after administration of levodopa. RESULTS: Eleven patients initially reported dysphagia and reduced QOL scores. Videofluoroscopy identified 10 patients with swallowing impairments on and off levodopa, and 6 patients with swallowing impairments only on levodopa; the remaining 10 subjects showed no swallowing impairments, on or off the drug. While patients were on levodopa, those with swallowing impairments had bilateral increases in pharyngeal cortical excitability compared with those with no swallowing impairment (P < .05). By contrast, with medication, amplitudes of brainstem reflexes were altered only in patients with swallowing impairments on levodopa; these were decreased compared with when the patients were off levodopa. CONCLUSIONS: In patients with Parkinson's disease, dopaminergic medications such as levodopa can negatively affect swallowing. The increased cortical excitability observed in dysphagic patients after they begin taking levodopa likely results from compensatory mechanisms, perhaps secondary to subcortical disease, because we observed associated inhibition of brainstem reflexes in patients with affected swallowing on medication. UK clinical trials registration no., 9882.
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Trastornos de Deglución/fisiopatología , Enfermedad de Parkinson/complicaciones , Tractos Piramidales/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Antiparkinsonianos/efectos adversos , Antiparkinsonianos/uso terapéutico , Femenino , Fluoroscopía , Humanos , Levodopa/efectos adversos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Estimulación Magnética Transcraneal , Reino UnidoRESUMEN
This study explores the natural history of vestibular, trigeminal and lower cranial nerve schwannomas (VS, TS, LCNS) in patients with Neurofibromatosis type 2 (NF2), to understand how pathogenic variants (PVs) of the NF2 gene affect tumour burden and growth rate, via a retrospective analysis of a UK NF2 centre database and imaging. VS, TS and LCNS location and size were measured in accordance with a standardised protocol. PVs were categorised in accordance with the UK NF2 Genetic Severity Score (GSS). 153 patients (age 5-82) had 458 schwannomas, of which 362 were previously untreated comprising: 204 VS, 93 TS, and 65 LCNS (IX, X, XI). 322 schwannomas had sequential imaging allowing growth rate analysis with a mean follow-up of 45 months. VS were universally present, and bilateral in 146/153 cases. 65% of tumours grew >2 mm during the study period at mean rate 2.0 mm/year. Significant association was found between increasing GSS and growth rate. TS occurred in 66/153 patients (bilateral in 27/153); 31% of tumours showed growth (mean 1.8 mm/yr). Significant increase in tumour prevalence was noted with increasing GSS. LCNS were found in 47/153 patients (bilateral in 19/153); 27% of tumours showed growth (mean 1.9 mm/yr). The trend for increased prevalence with increasing GSS did not reach significance. VS growth rate was significantly influenced by GSS and they were much more likely to grow than TS and LCNS. TS prevalence also correlated with increasing GSS.
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Neurilemoma , Neurofibromatosis 2 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Humanos , Persona de Mediana Edad , Neurilemoma/epidemiología , Neurilemoma/genética , Neurilemoma/patología , Neurofibromatosis 2/epidemiología , Neurofibromatosis 2/genética , Neurofibromatosis 2/patología , Prevalencia , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES/HYPOTHESIS: Unilateral vestibular schwannoma (VS) occurs with a lifetime risk of around 1 in 1,000 and is due to inactivation of the NF2 gene, either somatically or from a constitutional mutation. It has been postulated that familial occurrence of unilateral VS occurs more frequently than by chance, but no causal mechanism has been confirmed. STUDY DESIGN: Retrospective database analysis. METHODS: The likelihood of chance occurrence of unilateral VS, or occurring in the context of neurofibromatosis type 2 (NF2), was assessed using national UK audit data and data from the national NF2 database. Families with familial unilateral VS (occurrence in first- and second-degree relatives) were assessed for constitutional NF2 and LZTR1 genetic variants, and where possible the tumor was also analyzed. RESULTS: Approximately 1,000 cases of unilateral VS occurred annually in the United Kingdom between 2013 and 2016. Of these, 2.5 may be expected to have a first-degree relative who had previously developed a unilateral VS. The likelihood of this occurring in NF2 was considered to be as low as 0.05 annually. None of 28 families with familial unilateral VS had a constitutional NF2 intragenic variant, and in nine cases where the VS was analyzed, both mutational events in NF2 were identified and excluded from the germline. Only three variants of uncertain significance were found in LZTR1. CONCLUSIONS: Familial occurrence of unilateral VS is very unlikely to be due to a constitutional NF2 or definitely pathogenic LZTR1 variant. The occurrence of unilateral VS in two or more first-degree relatives is likely due to chance. This phenomenon may well increase in clinical practice with increasing use of cranial magnetic resonance imaging in older patients. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:967-973, 2019.
Asunto(s)
Genes de la Neurofibromatosis 2 , Neuroma Acústico/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes. METHODS: SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm A recruited 1721 patients for whom carbamazepine was deemed to be standard treatment, and they were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Primary outcomes were time to treatment failure, and time to 12-months remission, and assessment was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748. FINDINGS: For time to treatment failure, lamotrigine was significantly better than carbamazepine (hazard ratio [HR] 0.78 [95% CI 0.63-0.97]), gabapentin (0.65 [0.52-0.80]), and topiramate (0.64 [0.52-0.79]), and had a non-significant advantage compared with oxcarbazepine (1.15 [0.86-1.54]). For time to 12-month remission carbamazepine was significantly better than gabapentin (0.75 [0.63-0.90]), and estimates suggest a non-significant advantage for carbamazepine against lamotrigine (0.91 [0.77-1.09]), topiramate (0.86 [0.72-1.03]), and oxcarbazepine (0.92 [0.73-1.18]). In a per-protocol analysis, at 2 and 4 years the difference (95% CI) in the proportion achieving a 12-month remission (lamotrigine-carbamazepine) is 0 (-8 to 7) and 5 (-3 to 12), suggesting non-inferiority of lamotrigine compared with carbamazepine. INTERPRETATION: Lamotrigine is clinically better than carbamazepine, the standard drug treatment, for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures.
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Anticonvulsivantes/uso terapéutico , Epilepsias Parciales/tratamiento farmacológico , Calidad de Vida , Adolescente , Adulto , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/economía , Niño , Análisis Costo-Beneficio , Epilepsias Parciales/clasificación , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: Valproate is widely accepted as a drug of first choice for patients with generalised onset seizures, and its broad spectrum of efficacy means it is recommended for patients with seizures that are difficult to classify. Lamotrigine and topiramate are also thought to possess broad spectrum activity. The SANAD study aimed to compare the longer-term effects of these drugs in patients with generalised onset seizures or seizures that are difficult to classify. METHODS: SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm B of the study recruited 716 patients for whom valproate was considered to be standard treatment. Patients were randomly assigned to valproate, lamotrigine, or topiramate between Jan 12, 1999, and Aug 31, 2004, and follow-up data were obtained up to Jan 13, 2006. Primary outcomes were time to treatment failure, and time to 1-year remission, and analysis was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748. FINDINGS: For time to treatment failure, valproate was significantly better than topiramate (hazard ratio 1.57 [95% CI 1.19-2.08]), but there was no significant difference between valproate and lamotrigine (1.25 [0.94-1.68]). For patients with an idiopathic generalised epilepsy, valproate was significantly better than both lamotrigine (1.55 [1.07-2.24] and topiramate (1.89 [1.32-2.70]). For time to 12-month remission valproate was significantly better than lamotrigine overall (0.76 [0.62-0.94]), and for the subgroup with an idiopathic generalised epilepsy 0.68 (0.53-0.89). But there was no significant difference between valproate and topiramate in either the analysis overall or for the subgroup with an idiopathic generalised epilepsy. INTERPRETATION: Valproate is better tolerated than topiramate and more efficacious than lamotrigine, and should remain the drug of first choice for many patients with generalised and unclassified epilepsies. However, because of known potential adverse effects of valproate during pregnancy, the benefits for seizure control in women of childbearing years should be considered.
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Anticonvulsivantes/uso terapéutico , Análisis Costo-Beneficio , Epilepsia Generalizada/tratamiento farmacológico , Fructosa/análogos & derivados , Triazinas/uso terapéutico , Ácido Valproico/uso terapéutico , Adolescente , Adulto , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/economía , Niño , Preescolar , Epilepsia Generalizada/fisiopatología , Epilepsia Generalizada/prevención & control , Femenino , Estudios de Seguimiento , Fructosa/efectos adversos , Fructosa/uso terapéutico , Humanos , Lamotrigina , Masculino , Años de Vida Ajustados por Calidad de Vida , Factores de Tiempo , Topiramato , Insuficiencia del Tratamiento , Triazinas/efectos adversos , Ácido Valproico/efectos adversosRESUMEN
Neuroferritinopathy is a progressive potentially treatable adult-onset movement disorder caused by mutations in the ferritin light chain gene (FTL1). Features overlap with common extrapyramidal disorders: idiopathic torsion dystonia, idiopathic Parkinson's disease and Huntington's disease, but the phenotype and natural history have not been defined. We studied a genetically homogeneous group of 41 subjects with the 460InsA mutation in FTL1, documenting the presentation, clinical course, biochemistry and neuroimaging. The mean age of onset was 39.4 years (SD = 13.3, range 13-63), beginning with chorea in 50%, focal lower limb dystonia in 42.5% and parkinsonism in 7.5%. The majority reported a family history of a movement disorder often misdiagnosed as Huntington's disease. The disease progressed relentlessly, becoming generalized over a 5-10 year period, eventually leading to aphonia, dysphagia and severe motor disability with subcortical/frontal cognitive dysfunction as a late feature. A characteristic action-specific facial dystonia was common (65%), and in 63% there was asymmetry throughout the disease course. Serum ferritin levels were low in the majority of males and post-menopausal females, but within normal limits for pre-menopausal females. MR brain imaging was abnormal on all affected individuals and one presymptomatic carrier. In conclusion, isolated parkinsonism is unusual in neuroferritinopathy, and unlike Huntington's disease, cognitive changes are absent or subtle in the early stages. Depressed serum ferritin is common and provides a useful screening test in routine practice, and gradient echo brain MRI will identify all symptomatic cases.
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Apoferritinas/genética , Trastornos del Movimiento/genética , Adolescente , Adulto , Edad de Inicio , Encéfalo/patología , Corea/genética , Corea/metabolismo , Corea/patología , Distonía/genética , Distonía/metabolismo , Distonía/patología , Salud de la Familia , Femenino , Ferritinas/sangre , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/metabolismo , Trastornos del Movimiento/patología , Músculo Esquelético/patología , Mutación/genética , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Fenotipo , Factores SexualesRESUMEN
BACKGROUND: The Manchester criteria for neurofibromatosis type 2 (NF2) include a range of tumors, and gliomas were incorporated in the original description. The gliomas are now widely accepted to be predominantly spinal cord ependymomas. OBJECTIVE: To determine whether these gliomas include any cases of malignant glioma (WHO grade III and IV) through a database review. METHODS: The prospective database consists of 1253 patients with NF2. 1009 are known to be alive at last follow-up. RESULTS: There was a single case of glioblastoma multiforme (GBM; World Health Organization grade IV) in the series and no WHO grade III gliomas. The GBM was in a patient who had previously undergone stereotactic radiosurgery for a vestibular schwannoma. CONCLUSION: High-grade gliomas are not a feature of NF2 in the unirradiated patient and should be excluded from the diagnostic criteria.
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Glioma/etiología , Neurofibromatosis 2/complicaciones , Adulto , Femenino , Glioma/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Neurofibromatosis 2/radioterapia , Estudios Prospectivos , Radiocirugia/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: The published literature suggests that malignant peripheral nerve sheath tumors (MPNST) occur at increased frequency in neurofibromatosis type 2 (NF2). A recent review based on incidence data in North America showed that 1 per 1000 cerebellopontine angle nerve sheath tumors were malignant. OBJECTIVE: To determine whether MPNST occurred spontaneously in NF2 by reviewing our NF2 database. METHODS: The prospective database consists of 1253 patients with NF2. One thousand and nine are known to be alive at last follow-up. The presence and laterality/pathology of vestibular schwannoma at diagnosis and last follow-up was sought. RESULTS: There were no cases of spontaneous MPNST with 2114 proven (n = 1150) and presumed benign (n = 964) vestibular schwannomas found. Two patients had developed MPNST (1 presumed) after having previously undergone stereotactic radiosurgery for a vestibular schwannoma. CONCLUSION: In this series, and from the literature, malignant transformation of a vestibular schwannoma was not a feature of NF2 in the unirradiated patient. NF2 patients should not be told that they have an increased risk of malignant change in a vestibular schwannoma unless they undergo radiation treatment. However, very much larger datasets are required before it can be determined whether there is any association between NF2 and MPNST in the unirradiated patient.
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Neoplasias de la Vaina del Nervio/epidemiología , Neurofibromatosis 2/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Transformación Celular Neoplásica/patología , Niño , Preescolar , Bases de Datos Genéticas , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Neoplasias de la Vaina del Nervio/genética , Neurofibromatosis 2/patología , Neuroma Acústico/genética , Neuroma Acústico/patología , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: We aimed to characterize the clinical and electrophysiological features of patients with slow orthostatic tremor. CASE REPORT: The clinical and neurophysiological data of patients referred for lower limb tremor on standing were reviewed. Patients with symptomatic or primary orthostatic tremor were excluded. Eight patients were identified with idiopathic slow 4-8 Hz orthostatic tremor, which was associated with tremor and dystonia in cervical and upper limb musculature. Coherence analysis in two patients showed findings different to those seen in primary orthostatic tremor. DISCUSSION: Slow orthostatic tremor may be associated with dystonia and dystonic tremor.
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Acatisia Inducida por Medicamentos/tratamiento farmacológico , Acatisia Inducida por Medicamentos/etiología , Antiparkinsonianos/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Levodopa/uso terapéutico , Trastornos Parkinsonianos/tratamiento farmacológico , Adulto , Acatisia Inducida por Medicamentos/diagnóstico por imagen , Antiparkinsonianos/efectos adversos , Infecciones por VIH/complicaciones , Humanos , Levodopa/efectos adversos , Imagen por Resonancia Magnética/métodos , Masculino , Trastornos Parkinsonianos/complicaciones , Trastornos Parkinsonianos/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodos , TropanosAsunto(s)
Antiparkinsonianos/uso terapéutico , Benzotiazoles/uso terapéutico , Identidad de Género , Enfermedad de Parkinson/complicaciones , Fenotipo , Disfunciones Sexuales Psicológicas/inducido químicamente , Disfunciones Sexuales Psicológicas/complicaciones , Adulto , Antiparkinsonianos/efectos adversos , Benzotiazoles/efectos adversos , Humanos , Masculino , Enfermedad de Parkinson/tratamiento farmacológico , PramipexolRESUMEN
BACKGROUND: The antiepileptic drug topiramate reduces levodopa-induced dyskinesia without exacerbating parkinsonism in animal models. We report a randomized, double-blind, placebo-controlled crossover trial in patients with Parkinson's disease and levodopa-induced dyskinesia. METHODS: Fifteen patients with Parkinson's disease and stable levodopa-induced dyskinesia were enrolled into the study, of whom 13 were randomized to topiramate or placebo. The study medication was titrated to 100 mg/day over four weeks, and assessments were carried out after a further two weeks. Dyskinesia severity assessed by a blinded rater from video recordings was the primary outcome measure. RESULTS: Seven patients (mean age 58.9 ± 12.8 years) completed the study. Patients taking topiramate vs. placebo showed a significant increase in dyskinesia severity compared to baseline (Wilcoxon signed rank test, P = 0.043). Five patients withdrew from the study whilst taking topiramate due to adverse effects. CONCLUSIONS: Topiramate tended to worsen dyskinesia in patients with Parkinson's disease, and was poorly tolerated.
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Anticonvulsivantes/uso terapéutico , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Fructosa/análogos & derivados , Enfermedad de Parkinson/tratamiento farmacológico , Adulto , Anciano , Antiparkinsonianos/efectos adversos , Estudios Cruzados , Método Doble Ciego , Femenino , Fructosa/uso terapéutico , Humanos , Levodopa/efectos adversos , Masculino , Persona de Mediana Edad , TopiramatoAsunto(s)
Anticonvulsivantes/uso terapéutico , Enfermedades Cerebelosas/tratamiento farmacológico , Fructosa/análogos & derivados , Postura , Temblor/tratamiento farmacológico , Adulto , Anticonvulsivantes/efectos adversos , Astrocitoma/cirugía , Enfermedades Cerebelosas/diagnóstico , Neoplasias Cerebelosas/cirugía , Electromiografía , Fructosa/efectos adversos , Fructosa/uso terapéutico , Humanos , Masculino , Complicaciones Posoperatorias/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Topiramato , Temblor/diagnósticoRESUMEN
There is accumulating evidence for the benefits of exercise in Parkinson's disease (PD), but less is known about group exercise interventions. We evaluated the effect of gym-training programme on people with PD. Thirty-two adults with mild to moderate PD, not currently exercising formally, were randomised to an immediate 20-week biweekly gym training programme at a local leisure complex, or a 10-week programme starting 10 weeks later. Assessments at baseline (T1), 10 weeks (T2) and 20 weeks (T3) included reaction time, motor performance (UPDRS), quality of life and illness perceptions. Experiences of the programme were assessed via questionnaire and a focus group. Overall UPDRS motor function score did not change over time. However, gym training was associated with significant improvements in reaction times and some timed tests in the immediate training group (T1-T2). The delayed group showed similar improvements following gym training (T2-T3). Participants reported enjoyment, obtaining social benefits, and increased confidence. However, the questionnaire measures did not show improvements in subjective health ratings or illness perceptions. Although benefits were not apparent in the questionnaire measures or overall UPDRS scores, our findings suggest that a 10-week gym training programme in a community setting can provide some benefits for people with PD.