The Etiology, Pathogenesis, and Natural History of the Leukodystrophies
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Neuropsychological evaluation to measure baseline cognitive function and detect signs of dementia over time
研究概览
简要总结
The purpose of this study is to:
- define novel homogeneous groups of patients with LDs and
- work toward finding the cause of these disorders.
详细描述
Patients with leukodystrophies (LDs) of unknown etiology are a heterogeneous group but constitute the second largest group of genetic white matter diseases. In order to find the cause of leukodystrophies, patients with LDs of unknown cause will be analyzed clinically, neurophysiologically, biochemically and genetically. Patients would have been diagnosed as having no known leukodystrophies at outside centers. At the Baylor University Medical Center, such patients will undergo a series of neuropsychological, blood, urine, spinal fluid, radiological, and peripheral tissue pathological tests. Some of these tests will be part of a standard battery while others will be tailored to individual patients. Patients will be followed yearly or as necessary. Patients will be screened for mutations in genes coding for structural myelin proteins. In some patients in whom all tests yielded no information regarding the etiology of their disease, and in whom there is evidence to suggest involvement of the peripheral nervous system, a sural nerve biopsy will be considered. Sural nerve biopsy tissue will be evaluated using a novel combination of approaches including detailed pathological, immunohistochemical, and biochemical analysis of myelin proteins and lipids. Schwann cell biology and expression of myelin genes in the brain will also be investigated in situ. It is hoped that the present study will help clarify the nosology of the leukodystrophies and significantly advance our understanding of the pathogenesis of these diseases.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must:
- •have clinical and radiographic signs of leukodystrophy without a specific etiology
- •no diagnosis of adrenoleukodystrophy, adrenomyeloneuropathy, metachromatic leukodystrophy, Krabbe disease, Canavan disease, a well-defined amino acid organic acid disorder, or a systemic mitochondrial cytopathy.
- •First-degree relatives of patients with leukodystrophies of unknown etiology (father, mother, siblings, or sons and daughters of the patients)
- •Be able to travel to Baylor University Medical Center in Dallas Texas for evaluation and spend 5-8 working days on site
- •Be able to tolerate a general exam and neurological exam
- •Be able to tolerate a modest amount of blood drawing, provide a urine specimen, and have a skin biopsy(if not previously done)
- •Be able to tolerate the performance of necessary neuroimaging studies to include EEG and Head MRI
- •Be able to tolerate a neuropsychological testing and rehabilitation evaluation
- •Be able to tolerate spinal tap or nerve biopsy if needed
排除标准
- •Unable to travel to Baylor University Medical Center in Dallas Texas for evaluation
- •Refusal to sign a study consent form
- •Unable to tolerate the performance of the required testing
结局指标
主要结局
Neuropsychological evaluation to measure baseline cognitive function and detect signs of dementia over time
时间窗: Every 52 weeks up to 5 years
Neuropsychological status is evaluated at Baseline and no less than once every year for the duration of the study to assess for any deterioration in function
次要结局
- MRI of the brain to assess involvement of different areas of the brain over time(Every 52 weeks)
- Electroencephalogram to assess involvement of different areas of the brain over time(Every 52 weeks up to 5 years)
- DNA Studies to search for mutations in genes of structural myelin proteins or genes that control myelin production(Baseline)
- Electromyelogram to assess for changes in muscle function over time(Every 52 weeks up to 5 years)
- Nerve Conduction study to assess abnormalities in affected nerves(Every 52 weeks up to 5 years)
- Spinal Tap to look for diagnostic markers of leukodystrophy(Baseline)
- Nerve Biopsy to look for pathological abnormalities in affected nerves(Baseline)
- Neuro-ophthalmological exam to assess for abnormalities in the eye(Every 52 weeks up to 5 years)
- Evoked potentials to assess involvement of different areas of brain over time(Every 52 weeks up to 5 years)
- Skin biopsy for to look for evidence of storage disease(Baseline)