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1.
Arch Phys Med Rehabil ; 101(12): 2243-2249, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32971100

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on the provision of medical care. As the curve progresses and patients are discharged, the rehabilitation wave brings a high number of postacute COVID-19 patients suffering from physical, mental, and cognitive impairments threatening their return to normal life. The complexity and severity of disease in patients recovering from severe COVID-19 infection require an approach that is implemented as early in the recovery phase as possible, in a concerted and systematic way. To address the rehabilitation wave, we describe a spectrum of interventions that start in the intensive care unit and continue through all the appropriate levels of care. This approach requires organized rehabilitation teams including physical therapists, occupational therapists, speech-language pathologists, rehabilitation psychologists or neuropsychologists, and physiatrists collaborating with acute medical teams. Here, we also discuss administrative factors that influence the provision of care during the COVID-19 pandemic. The services that can be provided are described in detail to allow the reader to understand what services may be appropriate locally. We have been learning and adapting real time during this crisis and hope that sharing our experience facilitates the work of others as the pandemic evolves. It is our goal to help reduce the potentially long-lasting challenges faced by COVID-19 survivors.


Assuntos
COVID-19/reabilitação , Unidades de Terapia Intensiva/organização & administração , Medicina Física e Reabilitação/organização & administração , Sobreviventes , Atividades Cotidianas , Continuidade da Assistência ao Paciente/organização & administração , Avaliação da Deficiência , Escala de Coma de Glasgow , Humanos , Unidades de Terapia Intensiva/normas , Medicare/organização & administração , Pandemias , Medicina Física e Reabilitação/normas , SARS-CoV-2 , Estados Unidos
2.
Eur J Paediatr Neurol ; 22(6): 1110-1117, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30194039

RESUMO

OBJECTIVE: To describe the clinical spectrum of benign nocturnal alternating hemiplegia of childhood (BNAHC) including long-term follow-up data of previously published cases and to propose an underlying genetic cause of this disorder. METHODS: We studied the medical data of two novel patients, reviewed the literature on BNAHC, and gathered information of the most recent follow-up of published cases regarding the course of episodes, further development, attempted drugs, ancillary investigations, and sequelae. RESULTS: All patients, i.e. two novel cases and twelve patients identified in the literature (13 boys, 1 girl, age at onset four months to three years), experienced episodes of hemiplegia during nocturnal or daytime sleep heralded by inconsolable crying. Possible triggers included stress and sleep deprivation. Eleven of fourteen patients had a family history of migraine or 'intermittent headache' and two sets of siblings are reported. In one case, exome sequencing revealed a heterozygous 16p11.2 deletion involving 33 genes, including the PRRT2 gene. EEG showed ictal and/or interictal contralateral slowing in four patients. Treatment efficacy was generally disappointing. A complete disappearance of attacks appeared in nearly all cases at most recent follow-up. In a remarkably high number of cases (10/14, 71%), hyperactive behaviour was reported during follow-up. CONCLUSION: We underscore the phenotypic homogeneity including the self-limiting course of BNAHC episodes and suggest the condition be renamed 'benign childhood hemiplegia during sleep' (BCHS). We propose a role for the PRRT2 gene and the resulting neuronal hyperexcitability as one of its possible underpinning mechanisms and discuss the clinical similarities of BCHS with the recognized PRRT2-related disorders.


Assuntos
Hemiplegia , Pré-Escolar , Progressão da Doença , Deleção de Genes , Hemiplegia/complicações , Hemiplegia/genética , Heterozigoto , Humanos , Lactente , Masculino , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Fenótipo , Resultado do Tratamento
3.
Pediatr Neurol ; 73: 101-105, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28647130

RESUMO

BACKGROUND: We identified a group of patients with ATP1A3 mutations at residue 756 who display a new phenotype, distinct from alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism, and cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss syndromes. METHODS: Four patients with c.2267G>A (R756H) mutations from two families and two patients with c.2267G>T (R756L) mutations from one family are described and compared with the previously reported patients with mutations resulting in R756H and R756C protein variants. RESULTS: Patients with ATP1A3 R756H have onset in childhood of infrequent, fever-triggered paroxysms of encephalopathy and weakness with slowly improving but persistent deficits. Motor findings of weakness are mostly generalized, and patients may also have bulbar or oculomotor problems. Longer-term outcomes range from mild motor apraxia with near-normal function to persistent dysphagia, dysarthria, cognitive deficit, motor apraxia, and inability to walk because of ataxia. Patients with ATP1A3 R756L have a similar phenotype that includes paroxysmal, stepwise progression of ataxia associated with infections. CONCLUSIONS: ATP1A3 mutations affecting residue 756 result in a clinical syndrome, separate from those associated with previously described ATP1A3 mutations, which consists chiefly of fever-induced paroxysmal weakness and encephalopathy (FIPWE). Patients with R756L and R756C protein variants display more prominent ataxia, overlapping with the relapsing encephalopathy with cerebellar ataxia syndrome previously described in a patient with the c.2266C>T (R756C) mutation. All patients reported with mutations at residue 756 to date have had a similar episodic course and clinical features. Patients with mutations of ATP1A3 residue 756 appear to have a distinct clinical phenotype compared with patients with other ATP1A3 mutations, with fever-induced encephalopathy as key differentiating feature.


Assuntos
Encefalopatias/etiologia , Febre/complicações , Febre/genética , Debilidade Muscular/complicações , Mutação/genética , ATPase Trocadora de Sódio-Potássio/genética , Criança , Saúde da Família , Feminino , Humanos , Masculino , Fenótipo
4.
Neurol Genet ; 3(2): e139, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28293679

RESUMO

OBJECTIVE: ATP1A3-related neurologic disorders encompass a broad range of phenotypes that extend well beyond initial phenotypic criteria associated with alternating hemiplegia of childhood (AHC) and rapid-onset dystonia parkinsonism. METHODS: In 2014, the Alternating Hemiplegia of Childhood Foundation hosted a multidisciplinary workshop intended to address fundamental challenges surrounding the diagnosis and management of individuals with ATP1A3-related disorders. RESULTS: Workshop attendees were charged with the following: (1) to achieve consensus on expanded diagnostic criteria to facilitate the identification of additional patients, intended to supplement existing syndrome-specific diagnostic paradigms; (2) to standardize definitions for the broad range of paroxysmal manifestations associated with AHC to disseminate to families; (3) to create clinical recommendations for common recurrent issues facing families and medical care providers; (4) to review data related to the death of individuals in the Alternating Hemiplegia of Childhood Foundation database to guide future efforts in identifying at-risk subjects and potential preventative measures; and (5) to identify critical gaps where we most need to focus national and international research efforts. CONCLUSIONS: This report summarizes recommendations of the workshop committee, highlighting the key phenotypic features to facilitate the diagnosis of possible ATP1A3 mutations, providing recommendations for genetic testing, and outlining initial acute management for common recurrent clinical conditions, including epilepsy.

6.
PLoS One ; 10(5): e0127045, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25996915

RESUMO

Mutations in ATP1A3 cause Alternating Hemiplegia of Childhood (AHC) by disrupting function of the neuronal Na+/K+ ATPase. Published studies to date indicate 2 recurrent mutations, D801N and E815K, and a more severe phenotype in the E815K cohort. We performed mutation analysis and retrospective genotype-phenotype correlations in all eligible patients with AHC enrolled in the US AHC Foundation registry from 1997-2012. Clinical data were abstracted from standardized caregivers' questionnaires and medical records and confirmed by expert clinicians. We identified ATP1A3 mutations by Sanger and whole genome sequencing, and compared phenotypes within and between 4 groups of subjects, those with D801N, E815K, other ATP1A3 or no ATP1A3 mutations. We identified heterozygous ATP1A3 mutations in 154 of 187 (82%) AHC patients. Of 34 unique mutations, 31 (91%) are missense, and 16 (47%) had not been previously reported. Concordant with prior studies, more than 2/3 of all mutations are clusteredin exons 17 and 18. Of 143 simplex occurrences, 58 had D801N (40%), 38 had E815K(26%) and 11 had G947R (8%) mutations [corrected].Patients with an E815K mutation demonstrate an earlier age of onset, more severe motor impairment and a higher prevalence of status epilepticus. This study further expands the number and spectrum of ATP1A3 mutations associated with AHC and confirms a more deleterious effect of the E815K mutation on selected neurologic outcomes. However, the complexity of the disorder and the extensive phenotypic variability among subgroups merits caution and emphasizes the need for further studies.


Assuntos
Hemiplegia/genética , ATPase Trocadora de Sódio-Potássio/genética , Criança , Pré-Escolar , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Hemiplegia/fisiopatologia , Humanos , Lactente , Masculino , Sistema de Registros
8.
Pediatr Neurol ; 49(1): 64-7, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23827430

RESUMO

Neuroblastoma associated with the paraneoplastic syndrome of opsoclonus-myoclonus is well-described. However, presentation with narcolepsy-cataplexy is not well-documented in the literature. Narcolepsy with cataplexy is also rare in children younger than 5 years of age. Here we describe three patients, each presenting in early childhood with complex neurological symptoms including narcolepsy with cataplexy that were subsequently found to have paraspinal neuroblastoma. In two of the cases, neurological symptoms resolved with treatment of the tumor and/or immunosuppression, but in one case, the child persistently had a devastating course despite complete resection of the tumor and aggressive immunosuppression.


Assuntos
Cataplexia/diagnóstico , Narcolepsia/diagnóstico , Neoplasias Primárias Desconhecidas/diagnóstico , Neuroblastoma/diagnóstico , Cataplexia/etiologia , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Narcolepsia/etiologia , Neoplasias Primárias Desconhecidas/complicações , Neuroblastoma/complicações
9.
J Neuropsychiatry Clin Neurosci ; 24(2): 247-54, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22772674

RESUMO

Anti-NMDAR (N-methyl-d-aspartate receptor) encephalitis is a novel autoimmune and paraneoplastic disease often presenting as acute psychosis. Few studies exist in the psychiatric literature on neuroimmunity and behavioral management. This article reviews the epidemiology, diagnosis, pathophysiology, and management of this disease from a neuropsychiatric perspective. Patients have potential for near-complete recovery with early diagnosis and intervention. In addition to immune-suppression and tumor removal, electroconvulsive therapy may be an important tool in treatment of the underlying process in cases developing life-threatening catatonia. Psychiatrists should be familiar with treatment options, since they may be consulted within the context of a multispecialty team.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Gerenciamento Clínico , Neoplasias Ovarianas/cirurgia , Equipe de Assistência ao Paciente/organização & administração , Teratoma/cirurgia , Adolescente , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Encefalite Antirreceptor de N-Metil-D-Aspartato/epidemiologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/fisiopatologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/cirurgia , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Eletroconvulsoterapia/psicologia , Feminino , Humanos , Imageamento por Ressonância Magnética/psicologia , Psicotrópicos/uso terapêutico
10.
Nat Genet ; 44(9): 1030-4, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22842232

RESUMO

Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurological manifestations. AHC is usually a sporadic disorder and has unknown etiology. We used exome sequencing of seven patients with AHC and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation in a case of familial AHC. Notably, most AHC cases are caused by one of seven recurrent ATP1A3 mutations, one of which was observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset dystonia-parkinsonism, AHC-causing mutations in this gene caused consistent reductions in ATPase activity without affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3.


Assuntos
Hemiplegia/genética , Mutação , ATPase Trocadora de Sódio-Potássio/genética , Adulto , Animais , Células COS , Criança , Chlorocebus aethiops , Família , Feminino , Predisposição Genética para Doença , Células HeLa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Modelos Biológicos , Mutação/fisiologia , Linhagem , Estrutura Secundária de Proteína , ATPase Trocadora de Sódio-Potássio/química , ATPase Trocadora de Sódio-Potássio/fisiologia
11.
Orphanet J Rare Dis ; 6: 73, 2011 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-22074552

RESUMO

BACKGROUND: Menkes disease (MD) is an X-linked, fatal neurodegenerative disorder of copper metabolism, caused by mutations in the ATP7A gene. Thirty-three Menkes patients in whom no mutation had been detected with standard diagnostic tools were screened for exon duplications in the ATP7A gene. METHODS: The ATP7A gene was screened for exon duplications using multiplex ligation-dependent probe amplification (MLPA). The expression level of ATP7A was investigated by real-time PCR and detailed analysis of the ATP7A mRNA was performed by RT-PCR followed by sequencing. In order to investigate whether the identified duplicated fragments originated from a single or from two different X-chromosomes, polymorphic markers located in the duplicated fragments were analyzed. RESULTS: Partial ATP7A gene duplication was identified in 20 unrelated patients including one patient with Occipital Horn Syndrome (OHS). Duplications in the ATP7A gene are estimated from our material to be the disease causing mutation in 4% of the Menkes disease patients. The duplicated regions consist of between 2 and 15 exons. In at least one of the cases, the duplication was due to an intra-chromosomal event. Characterization of the ATP7A mRNA transcripts in 11 patients revealed that the duplications were organized in tandem, in a head to tail direction. The reading frame was disrupted in all 11 cases. Small amounts of wild-type transcript were found in all patients as a result of exon-skipping events occurring in the duplicated regions. In the OHS patient with a duplication of exon 3 and 4, the duplicated out-of-frame transcript coexists with an almost equally represented wild-type transcript, presumably leading to the milder phenotype. CONCLUSIONS: In general, patients with duplication of only 2 exons exhibit a milder phenotype as compared to patients with duplication of more than 2 exons. This study provides insight into exon duplications in the ATP7A gene.


Assuntos
Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Éxons/genética , Duplicação Gênica , Síndrome dos Cabelos Torcidos/genética , Adulto , Pré-Escolar , ATPases Transportadoras de Cobre , Cútis Laxa/genética , Síndrome de Ehlers-Danlos/genética , Feminino , Humanos , Masculino , Síndrome dos Cabelos Torcidos/patologia , Técnicas de Sonda Molecular , Reação em Cadeia da Polimerase Multiplex , Mutação , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
12.
J Child Neurol ; 26(2): 244-7, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21183724

RESUMO

Neuromyelitis optica is a central nervous system disease characterized by optic neuritis and transverse myelitis. It is a devastating illness, and early treatment may prevent future relapses and severe disability. However, there is much variability in protocols used for treatment. In limited studies, rituximab has shown efficacy in adult neuromyelitis optica patients. There is a paucity of literature on the efficacy and tolerability of rituximab in the pediatric population. The authors report the use of rituximab in 2 pediatric patients with neuromyelitis optica, demonstrating its efficacy, dosing, and tolerability. This report may be a useful guide for administering rituximab safely in pediatric neuromyelitis optica patients.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Neuromielite Óptica/terapia , Adolescente , Anticorpos Monoclonais Murinos/efeitos adversos , Criança , Feminino , Humanos , Rituximab , Resultado do Tratamento
13.
J Registry Manag ; 36(1): 16-20, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19670694

RESUMO

The basic logic of designing an occupational cohort study has changed little since William R. Gaffey outlined the issues of follow-up, measurement of exposure, and analysis of data. However, many new avenues of tracking workers for epidemiological studies have been developed since Gaffey wrote his paper in 1973. Many disease registries also perform follow-up of subjects for vital status determination, so the procedures used with this process are common to the two applications. This article speaks to cohort construction for this occupational research as well as describes the 2007 methods for vital status follow-up. Rises in concern about work-related disease risks and the scientific resources for performing these studies coincided with the computer revolution. Government and private sources of data on vital status have changed in several ways over the 35 years since Gaffey's seminal paper. Some systems make the process of follow-up more rapid and productive, and some barriers have been imposed as societal concerns for privacy have risen. We describe the process of linking 5 sources of data to compile a roster of 6,820 workers employed at the Paducah Gaseous Diffusion Plant from 1953 to 2003. The record linkage processes achieved a final death cohort of 1672 deaths--the ascertainment of these deaths (by time period) was 1379 (1979-2003) and 293 (1953-1978); follow-up then was 100% for this cohort.


Assuntos
Estudos de Coortes , Métodos Epidemiológicos , Doenças Profissionais/epidemiologia , Exposição Ocupacional , Saúde Ocupacional , Acesso à Informação , Coleta de Dados , Humanos , Kentucky/epidemiologia , Medição de Risco , Tennessee/epidemiologia , Fatores de Tempo
14.
Mov Disord ; 24(7): 1048-53, 2009 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-19353721

RESUMO

To report a novel treatment approach, pallidotomy and deep brain stimulation (DBS), in two sisters with dystonic storm due to Batten's disease. This study is based on long-term follow-up of two sisters, presenting with dystonic storm and their response to pallidotomy and DBS. These sisters, who had visual loss, seizures, and progressive psychomotor decline, experienced progressive disabling abnormal movements culminating in dystonic storm at the age of 15 and 17 years, respectively. In addition to intubation and sedation, multiple medications, including botulinum toxin injections and intrathecal baclofen infusion were tried in both patients without any benefit. The old sister underwent bilateral pallidotomy. Within 10 days postoperatively, there was marked improvement in dystonic storm. She was free of abnormal movements for 9 months. Then she started having opisthotonus lasting 20 seconds to an hour several times/day, but over 6 years abnormal movements are markedly improved, and not returned to pre-pallidotomy level. The young sister underwent both bilateral pallidotomy and DBS, 3 weeks apart. She was free of abnormal movements for 7 months and able to maintain reduction in the abnormal movements by adjusting DBS settings. Pallidotomy and DBS should be considered in dystonic storm due to Batten's disease.


Assuntos
Estimulação Encefálica Profunda/métodos , Distonia/etiologia , Distonia/terapia , Lipofuscinoses Ceroides Neuronais/complicações , Palidotomia/métodos , Adulto , Feminino , Humanos , Estudos Longitudinais , Adulto Jovem
15.
Neurorehabil Neural Repair ; 23(7): 735-44, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19307434

RESUMO

BACKGROUND AND OBJECTIVE: Following stroke, subjects retain the ability to adapt interlimb symmetry on the split-belt treadmill. Critical to advancing our understanding of locomotor adaptation and its usefulness in rehabilitation is discerning whether adaptive effects observed on a treadmill transfer to walking over ground. We examined whether aftereffects following split-belt treadmill adaptation transfer to overground walking in healthy persons and those poststroke. METHODS: Eleven poststroke and 11 age-matched and gender-matched healthy subjects walked over ground before and after walking on a split-belt treadmill. Adaptation and aftereffects in step length and double support time were calculated. RESULTS: Both groups demonstrated partial transfer of the aftereffects observed on the treadmill (P<.001) to overground walking (P<.05), but the transfer was more robust in the subjects poststroke (P<.05). The subjects with baseline asymmetry after stroke improved in asymmetry of step length and double limb support (P=.06). CONCLUSIONS: The partial transfer of aftereffects to overground walking suggests that some shared neural circuits that control locomotion for different environmental contexts are adapted during split-belt treadmill walking. The larger adaptation transfer from the treadmill to overground walking in the stroke survivors may be due to difficulty adjusting their walking pattern to changing environmental demands. Such difficulties with context switching have been considered detrimental to function poststroke. However, we propose that the persistence of improved symmetry when changing context to overground walking could be used to advantage in poststroke rehabilitation.


Assuntos
Adaptação Fisiológica , Reabilitação do Acidente Vascular Cerebral , Caminhada , Adulto , Idoso , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise e Desempenho de Tarefas
16.
Pediatrics ; 123(3): e534-41, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19254988

RESUMO

OBJECTIVES: Alternating hemiplegia of childhood is a predominantly sporadic neurodevelopmental syndrome of uncertain etiology. In more than 3 decades since its description, little progress has been made in understanding its etiology or in identifying effective treatments. In 1998, in collaboration with the Alternating Hemiplegia of Childhood Foundation, an international registry was established to help document clinical outcomes and promote research efforts. PATIENTS AND METHODS: We present phenotypic data on 103 patients who met existing diagnostic criteria for alternating hemiplegia of childhood. Although some of these subjects may have been included in previously published reviews, our focus was directed toward the earliest manifestations of symptoms and evolution of features over time. Data sources included written questionnaires, face-to-face and telephone interviews, clinical examination, and medical charts. Characteristics of disease onset, medical comorbidities, episode triggers, diagnostic workup, and treatment are presented. RESULTS: Paroxysmal eye movements were the most frequent early symptom, manifesting in the first 3 months of life in 83% of patients. Hemiplegic episodes appeared by 6 months of age in 56% of infants. Background slowing shown by electroencephalography during typical paroxysmal events, including hemiplegic, tonic, or dystonic episodes was frequent (21 of 42 cases). Distinct convulsive episodes with altered consciousness believed to be epileptic in nature were reported in 41% of patients. Ataxia (96%) and cognitive impairment (100%) were frequent nonepisodic symptoms. Empiric pharmacologic treatment approaches offered little benefit in most subjects and resulted in adverse effects in 20% of patients. Prolonged episodes were completely or temporarily aborted during sleep in all subjects. CONCLUSIONS: This descriptive analysis of a large cohort of children indicates that paroxysmal ocular movements are an early, highly suggestive symptom, followed by paroxysmal episodes of focal dystonia or flaccid, alternating hemiplegia in early infancy in the majority of subjects. Current challenges in diagnosis and management contribute to poor outcomes. Early diagnosis and multicenter collaboration are needed to facilitate trials to identify more effective therapies.


Assuntos
Hemiplegia/diagnóstico , Adolescente , Fatores Etários , Ataxia/diagnóstico , Ataxia/etiologia , Encéfalo/patologia , Criança , Pré-Escolar , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Estudos de Coortes , Eletroencefalografia , Feminino , Seguimentos , Hemiplegia/etiologia , Humanos , Lactente , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Exame Neurológico , Transtornos da Motilidade Ocular/diagnóstico , Transtornos da Motilidade Ocular/tratamento farmacológico , Transtornos da Motilidade Ocular/etiologia , Tomografia por Emissão de Pósitrons , Psicotrópicos/efeitos adversos , Psicotrópicos/uso terapêutico , Convulsões/diagnóstico , Convulsões/etiologia , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento , Adulto Jovem
17.
Arch Neurol ; 64(11): 1629-34, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17998446

RESUMO

BACKGROUND: Mucopolysaccharidosis type IIID (MPS-IIID), or Sanfilippo syndrome type D, is a rare autosomal recessive lysosomal storage disorder caused by mutations in the N-acetylglucosamine-6-sulfatase (GNS) gene, leading to impaired degradation of heparan sulfate. OBJECTIVES: To report the natural history of MPS-IIID in 2 siblings described by Kaplan and Wolfe in 1987 and to study the phenotype in 2 other unrelated families with MPS-IIID. Design, Setting, and Patients Case series of 4 patients with MPS-IIID: 2 siblings followed up at the Montreal Neurological Hospital and Institute, 1 patient followed up at the UZ Brussel, and 1 patient recruited through the prenatal counseling program at the UZ Brussel. MAIN OUTCOME MEASURES: Clinical and molecular data collected from 3 families with enzyme-based diagnosis of MPS-IIID. RESULTS: The course of the disease was characteristic of MPS-IIID in all patients, although survival may be longer than was previously reported. In family 1, both siblings were homozygous for a novel nonsense mutation in the GNS gene (c.1168C>T). In family 2, the proband carried a heterozygous mutation occurring in a splice recognition site in the intron 7 boundary (c.876-2A>G). The second mutation in this patient remains to be identified. In family 3, the proband was homozygous for a novel frameshift mutation in GNS due to the insertion of 5 nucleotides (c.1138_1139insGTCCT). CONCLUSIONS: Major issues in the care of patients with MPS-IIID include behavioral problems, sleep problems, recurrent infections, dysphagia, and pain from orthopedic complications. To date, all mutations in GNS predict protein truncation, and there is no obvious genotype-phenotype correlation.


Assuntos
Mucopolissacaridose III/genética , Mutação , Sulfatases/genética , Adolescente , Adulto , Ácido Aspártico/genética , Análise Mutacional de DNA , Progressão da Doença , Saúde da Família , Feminino , Glutamina/genética , Glicina/genética , Humanos , Masculino , Mucopolissacaridose III/patologia , Mucopolissacaridose III/fisiopatologia
18.
Brain ; 130(Pt 7): 1861-72, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17405765

RESUMO

Human locomotion must be flexible in order to meet varied environmental demands. Alterations to the gait pattern occur on different time scales, ranging from fast, reactive adjustments to slower, more persistent adaptations. A recent study in humans demonstrated that the cerebellum plays a key role in slower walking adaptations in interlimb coordination during split-belt treadmill walking, but not fast reactive changes. It is not known whether cerebral structures are also important in these processes, though some studies of cats have suggested that they are not. We used a split-belt treadmill walking task to test whether cerebral damage from stroke impairs either type of flexibility. Thirteen individuals who had sustained a single stroke more than 6 months prior to the study (four females) and 13 age- and gender-matched healthy control subjects were recruited to participate in the study. Results showed that stroke involving cerebral structures did not impair either reactive or adaptive abilities and did not disrupt storage of new interlimb relationships (i.e. after-effects). This suggests that cerebellar interactions with brainstem, rather than cerebral structures, comprise the critical circuit for this type of interlimb control. Furthermore, the after-effects from a 15-min adaptation session could temporarily induce symmetry in subjects who demonstrated baseline asymmetry of spatiotemporal gait parameters. In order to re-establish symmetric walking, the choice of which leg is on the fast belt during split-belt walking must be based on the subject's initial asymmetry. These findings demonstrate that cerebral stroke survivors are indeed able to adapt interlimb coordination. This raises the possibility that asymmetric walking patterns post-stroke could be remediated utilizing the split-belt treadmill as a long-term rehabilitation strategy.


Assuntos
Adaptação Fisiológica , Marcha , Locomoção , Reabilitação do Acidente Vascular Cerebral , Adulto , Idoso , Teste de Esforço/métodos , Terapia por Exercício/métodos , Extremidades/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desempenho Psicomotor , Processamento de Sinais Assistido por Computador , Acidente Vascular Cerebral/fisiopatologia
19.
Neuromuscul Disord ; 17(4): 285-9, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17336067

RESUMO

Mutations in the gene encoding fukutin related protein (FKRP) produce a spectrum of disease including congenital muscular dystrophy and limb girdle muscular dystrophy. FKRP is one member of a class of molecules thought to be glycosyltransferases that mediate O-linked glycosylation. The primary target of these glycosyltransferases is thought to be dystroglycan. We now report two unrelated Mexican children with congenital muscular dystrophy who each have the identical, novel 1387A>G, N463D mutation. Muscle biopsies from these children show a reduction of alpha-dystroglycan and also show reduction of beta-dystroglycan, and alpha-, beta-, and gamma-sarcoglycan, suggesting that FKRP mutations can perturb membrane associated proteins beyond dystroglycan.


Assuntos
Distrofina/metabolismo , Glicoproteínas/metabolismo , Distrofias Musculares/genética , Distrofias Musculares/metabolismo , Mutação/genética , Proteínas/genética , Asparagina/genética , Ácido Aspártico/genética , Pré-Escolar , Feminino , Humanos , Distrofias Musculares/patologia , Pentosiltransferases
20.
Stroke ; 36(10): 2206-11, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16151035

RESUMO

BACKGROUND AND PURPOSE: Physical inactivity propagates disability after stroke through physical deconditioning and learned nonuse. We investigated whether treadmill aerobic training (T-AEX) is more effective than conventional rehabilitation to improve ambulatory function and cardiovascular fitness in patients with chronic stroke. METHODS: Sixty-one adults with chronic hemiparetic gait after ischemic stroke (>6 months) were randomized to 6 months (3x/week) progressive T-AEX or a reference rehabilitation program of stretching plus low-intensity walking (R-CONTROL). Peak exercise capacity (Vo2 peak), o2 consumption during submaximal effort walking (economy of gait), timed walks, Walking Impairment Questionnaire (WIQ), and Rivermead Mobility Index (RMI) were measured before and after 3 and 6 months of training. RESULTS: Twenty-five patients completed T-AEX and 20 completed R-CONTROL. Only T-AEX increased cardiovascular fitness (17% versus 3%, delta% T-AEX versus R-CONTROL, P<0.005). Group-by-time analyses revealed T-AEX improved ambulatory performance on 6-minute walks (30% versus 11%, P<0.02) and mobility function indexed by WIQ distance scores (56% versus 12%, P<0.05). In the T-AEX group, increasing training velocity predicted improved Vo2 peak (r=0.43, P<0.05), but not walking function. In contrast, increasing training session duration predicted improved 6-minute walk (r=0.41, P<0.05), but not fitness gains. CONCLUSIONS: T-AEX improves both functional mobility and cardiovascular fitness in patients with chronic stroke and is more effective than reference rehabilitation common to conventional care. Specific characteristics of training may determine the nature of exercise-mediated adaptations.


Assuntos
Terapia por Exercício , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/terapia , Idoso , Análise de Variância , Isquemia Encefálica/patologia , Isquemia Encefálica/reabilitação , Sistema Cardiovascular , Método Duplo-Cego , Exercício Físico , Teste de Esforço , Tolerância ao Exercício , Feminino , Marcha , Transtornos Neurológicos da Marcha/reabilitação , Hemiplegia/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Resistência Física , Aptidão Física , Inquéritos e Questionários , Fatores de Tempo
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