Faculty of Medicine, Health and Human Sciences, School of Biomedical Sciences, Dementia Research Centre, Macquarie University, Sydney, NSW, Australia.
Faculty of Medicine and Health, Discipline of Pathology and Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
Eur J Neurol. 2021 Jul;28(7):2192-2199. doi: 10.1111/ene.14849. Epub 2021 Apr 16.
Amyotrophic lateral sclerosis (ALS) is associated with a range of clinical phenotypes and shows progressive degeneration of upper and/or lower motor neurons, and phosphorylated 43 kDa TAR DNA-binding protein (pTDP-43) inclusions in motor and non-motor pathways. Parkinsonian features have been reported in up to 30% of ALS patients, and Lewy bodies, normally associated with Lewy body disease (LBD), have been reported in a small number of ALS cases, with unknown clinical relevance. This study investigates the prevalence of clinically relevant LBD in a prospectively studied ALS cohort to determine whether concomitant pathology contributes to the clinical heterogeneity.
All ALS cases held by the New South Wales Brain Bank (n = 97) were screened for coexisting LBD consistent with clinical disease (Braak ≥ stage IV). Relevant clinical and genetic associations were determined.
Six cases had coexisting LBD Braak ≥ stage IV pathology. The age at symptom onset (69 ± 7 years) and disease duration (4 ± 3 years) in ALS cases with coexisting LBD did not differ from ALS cases. Three patients had lower limb onset and two patients had bulbar onset. Two patients developed the clinical features of Parkinson's disease, with one receiving a dual diagnosis. All cases had no known relevant family history or genetic abnormalities.
The prevalence of clinically relevant LBD pathology in ALS is higher than in the general population, and has implications for clinical and neuropathological diagnoses and the identification of biomarkers.
肌萎缩侧索硬化症（ALS）与多种临床表型相关，表现为上运动神经元和/或下运动神经元进行性退化，以及在运动和非运动通路上存在磷酸化 43kDa TAR DNA 结合蛋白（pTDP-43）包涵体。高达 30%的 ALS 患者出现帕金森特征，少数 ALS 病例中报告存在与路易体病（LBD）相关的路易体，但其临床相关性未知。本研究通过前瞻性研究 ALS 队列，调查临床上相关的 LBD 患病率，以确定共存病理学是否导致临床异质性。
新南威尔士脑库（n=97）保存的所有 ALS 病例均进行了 LBD 共存的筛选，与临床疾病相符（Braak≥IV 期）。确定了相关的临床和遗传关联。
6 例伴有共存的 LBD Braak≥IV 期病理学。伴有共存 LBD 的 ALS 病例的发病年龄（69±7 岁）和疾病持续时间（4±3 年）与 ALS 病例无差异。3 例患者下肢起病，2 例患者球部起病。2 例患者出现帕金森病的临床特征，其中 1 例为双重诊断。所有病例均无已知的相关家族史或遗传异常。
ALS 中临床上相关的 LBD 病理学患病率高于普通人群，这对临床和神经病理学诊断以及生物标志物的识别具有重要意义。
