RESUMO
Essential tremor is one of the most frequent movement disorders of humans and can be associated with substantial disability. Some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. In a six-generation consanguineous Turkish kindred with both essential tremor and Parkinson disease, we carried out whole exome sequencing and pedigree analysis, identifying HTRA2 p.G399S as the allele likely responsible for both conditions. Essential tremor was present in persons either heterozygous or homozygous for this allele. Homozygosity was associated with earlier age at onset of tremor (P < 0.0001), more severe postural tremor (P < 0.0001), and more severe kinetic tremor (P = 0.0019). Homozygotes, but not heterozygotes, developed Parkinson signs in the middle age. Among population controls from the same Anatolian region as the family, frequency of HTRA2 p.G399S was 0.0027, slightly lower than other populations. HTRA2 encodes a mitochondrial serine protease. Loss of function of HtrA2 was previously shown to lead to parkinsonian features in motor neuron degeneration (mnd2) mice. HTRA2 p.G399S was previously shown to lead to mitochondrial dysfunction, altered mitochondrial morphology, and decreased protease activity, but epidemiologic studies of an association between HTRA2 and Parkinson disease yielded conflicting results. Our results suggest that in some families, HTRA2 p.G399S is responsible for hereditary essential tremor and that homozygotes for this allele develop Parkinson disease. This hypothesis has implications for understanding the pathogenesis of essential tremor and its relationship to Parkinson disease.
Assuntos
Tremor Essencial/genética , Mitocôndrias/enzimologia , Proteínas Mitocondriais/genética , Doença de Parkinson/genética , Serina Endopeptidases/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Serina Peptidase 2 de Requerimento de Alta Temperatura A , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Adulto JovemRESUMO
The aim of this study was to investigate the efficacy and side effects of botulinum toxin (BTX) in the treatment of hemifacial spasm (HFS). We also focused on the divergence between different injection techniques and commercial forms. We retrospectively evaluated 470 sessions of BTX injections administered to 68 patients with HFS. The initial time of improvement, duration and degree of improvement, and frequency and duration of adverse effects were analysed. Pretarsal and preseptal injections and Botox (Allergan, Irvine, CA, USA) and Dysport (Ipsen Biopharmaceuticals, Paris, France) brands were compared in terms of efficacy and side effects, accompanied by a review of papers which reported BTX treatment of HFS. An average of 34.5 units was used per patient. The first improvement was felt after 8 days and lasted for 14.8 weeks. Patients experienced a 73.7% improvement. In 79.7% of injections, no adverse effect was reported, in 4.9% erythema, ecchymosis, and swelling in the injection area, in 3.6% facial asymmetry, in 3.4% ptosis, in 3.2% diplopia, and in 2.3% difficulty of eye closure was detected. Patients reported 75% improvement on average after 314 sessions of pretarsal injections and 72.7% improvement after 156 sessions of preseptal injections (p=0.001). The efficacy and side effects of Botox and Dysport were similar. BTX is an effective and safe treatment option for HFS. No difference was determined between Botox and Dysport, and pretarsal injection is better than preseptal injection regarding the reported degree of improvement.