Characterization of the Natural History of Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Track Natural History of LBSL patients using medical record review
研究概览
简要总结
In this study, we will conduct retrospective chart and imaging reviews and prospective longitudinal virtual assessments of individuals with LBSL.
详细描述
LBSL (leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation) is a rare genetic disorder characterized by slowly progressive cerebellar ataxia and spasticity with dorsal column dysfunction (decreased position and vibration sense) in most patients. Manual dexterity becomes impaired to a variable degree. Associated problems include dysarthria, mild cognitive decline and learning problems, and epilepsy. LBSL is diagnosed by identification of biallelic pathogenic variants in DARS2, encoding mitochondrial aspartyl tRNA synthetase and characteristic abnormalities observed on the brain and spinal cord MRI. Most of the literature consists of case reports and case series and there are only limited data that provide details on genotype-phenotype correlations. There is very little quantitative or semi-quantitative information about neurocognitive and neuromotor impairment in LBSL. There are currently no targeted therapies or guidelines about supportive therapies for LBSL.
In this study, we will conduct retrospective chart and imaging reviews and prospective longitudinal virtual assessments of individuals with LBSL.
We hypothesize that 1) there will be a broad phenotypic spectrum of neuromotor and neurocognitive deficits in LBSL patients; 2) most impairment will likely be related to gait; 3) there will be a threshold of impairment in gait that is associated with poorer quality of life for these patients; 4) and that even in patients with apparently mild disease there will be neurocognitive deficits related to cortical and cerebellar white matter abnormalities.
Answering these hypotheses will form the basis of a better understanding of the natural history of LBSL. It will help further characterize the expected level of impairment based on a patient's genotype. This will be particularly helpful for providing anticipatory guidance for newly diagnosed infants and children with LBSL. The information will also help identify priorities for existing supportive therapies and help clarify the common or clinically meaningful symptoms that should be targeted for new treatments.
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
- •Confirmed DARS2 mutation through genetic analysis
- •Ability of the caregiver or participant to speak and understand English at an 8th-grade level
排除标准
- •The vulnerable populations of prisoners, non-viable neonates, pregnant women, adults lacking the capacity to consent, non-English speakers or children who are in foster care or wards of the state.
结局指标
主要结局
Track Natural History of LBSL patients using medical record review
时间窗: 4/1/2018 - 3/31/2023
Participants will be asked to provide all prior neurological, developmental and genetics medical records and available neuroimaging studies. We will first confirm eligibility by review of MRI and DARS2 mutation analysis. We will determine information about disease duration, rate of symptom progression and prevalence of specific neurological symptoms and the level of disability. We have derived an MRI severity score by modifying a standard leukodystrophy MRI scoring system, referred to as the Loes severity score (developed by Dr. Daniel Loes). This score is routinely used by radiologists. We will be reviewing and scoring participant neuroimages to better understand correlation with disease severity and progression.
Assessment of social communication in patients with LBSL using standardized neurocognitive surveys.
时间窗: 4/1/2018 - 3/31/2023
After the participant is enrolled, they will receive several neurocognitive assessments that will be sent digitally, including the Social Communication Questionnaire (SCQ) The SCQ used by the International Autism Network will be used to screen individuals for Autism Spectrum Disorder and is completed by a caregiver. The SCQ is a 40 item, parent report screening measure that identifies whether a child has the associated symptoms of autism spectrum disorder.
Assessment of behavior in patients with LBSL using standardized neurocognitive surveys.
时间窗: 4/1/2018 - 3/31/2023
After the participant is enrolled, they will receive several neurocognitive assessments that will be sent digitally, including the Child or Adult Behavior Checklist (CBCL/ABCL). The CBCL/ABCL is one of most widely used measures in psychology to identify behavioral problems or mood disorders in children or adults, respectively. The scoring of this checklist is grouped by eight empirically based syndrome scales. These include aggressive behavior, anxious/depressed, attention problems, rule-breaking behavior, somatic complaints, social problems, thought problems, withdrawal/depression symptoms. The CBCL has standardized scores for children of the same gender and similar age and are interpreted as falling in the normal, borderline, or clinical range.
Assessment of quality of life in patients with LBSL using standardized surveys.
时间窗: 4/1/2018 - 3/31/2023
After the participant is enrolled, they will receive several quality of life assessments that will be sent digitally. Information on quality of life in LBSL will be collected using well-validated scales addressing physical, emotional, social and school functioning. Relevant scales include quality of life in children and adults with spasticity, quality of life in children and adults with ataxia, and quality of life in children and adults with chronic medical conditions.
Assessment of executive function in patients with LBSL using standardized neurocognitive surveys.
时间窗: 4/1/2018 - 3/31/2023
After the participant is enrolled, they will receive several neurocognitive assessments that will be sent digitally, including the Behavioral Rating Inventory of Executive Function (BRIEF).The BRIEF assesses impairment of executive function by evaluating eight clinical scales of executive function including inhibit, shift, emotional control, initiate, working memory, plan/organize, organization of materials, and monitor.The BRIEF exists for preschool children (2-5) and there are self-report versions for adolescents and adults.
Assessment of adaptive function in patients with LBSL using standardized neurocognitive surveys.
时间窗: 4/1/2018 - 3/31/2023
After the participant is enrolled, they will receive several neurocognitive assessments that will be sent digitally, including the Adaptive Behavior Assessment System version 3 (ABAS-3). The ABAS-3 survey assesses eleven essential skill areas in 3 major adaptive domains including conceptual, social and practical, and assists in diagnosing various developmental, learning, and behavioral disabilities. This complete battery of adaptive skills can be administered across the life span for ages Birth-89 years.
Assessment of balance in patients with LBSL using wearable sensor technology.
时间窗: 4/1/2018 - 3/31/2023
The study team will collect information about gait and balance ability over time using functional surveys as well as wearable sensors to be used at the participant's homes. This series of tests will require the participant to stand in several different poses for 2 trials of 30 seconds each to assess their balance. This will include standing with their eyes open and their feet apart and together, as well as with their eyes closed and their feet apart and together.
Timed Up and Go Test
时间窗: 4/1/2018 - 3/31/2023
This test will require the participant to sit in a chair. When the participant is instructed to, they will stand up from the chair, walk 3 meters in a straight line, turn around and walk back to the chair. The test duration and variables such as walking and turning speed will be obtained.
Assessment of ataxia in patients with LBSL using wearable sensor technology and standardized clinical scales.
时间窗: 4/1/2018 - 3/31/2023
The study team will collect information about ataxia using wearable sensors and by administering the Standardized Assessment and Rating of Ataxia (SARA) scale at participant's homes. The SARA scale is an 8-item performance based scale that assesses upper and lower extremity ataxia. A total score of 0 indicates no ataxia and the maximum score of 40 indicates severe ataxia.
Long Walk Test
时间窗: 4/1/2018 - 3/31/2023
This test will require the participant to walk 22 feet in a straight line for a duration of 2 minutes. Variables such as walking and turning speed, stride length and step-to-step variability will be obtained.
次要结局
未报告次要终点