Department of Neurology, Mayo Clinic Florida, Jacksonville, FL.
Department of Pathology, Mayo Clinic Florida, Jacksonville, FL.
Ann Neurol. 2011 Jun;69(6):1014-1025. doi: 10.1002/ana.22340.
Pallido-ponto-nigral degeneration (PPND), caused by an N279K mutation of the MAPT gene, is 1 of a family of disorders collectively referred to as frontotemporal dementia and parkinsonism linked to chromosome 17. This study aims to characterize the nature of the sleep disturbance in PPND and compare these findings to those in other progressive neurological illnesses. Pathological findings are also provided.
Ten subjects were recruited from the PPND kindred; 5 affected and 5 unaffected. The subjects underwent clinical assessment, polysomnography, and wrist actigraphy. Available sleep-relevant areas (pedunculopontine/laterodorsal tegmentum, nucleus basalis of Meynert, thalamus, and locus ceruleus) of affected subjects were analyzed postmortem.
The affected group's total sleep time was an average of 130.8 minutes compared to 403.6 minutes in the control group (p < 0.01). Initial sleep latency was significantly longer in affected subjects (range, 58-260 minutes vs 3-34 minutes). Affected subjects also had an increase in stage I sleep (8.5% vs 1%), and less stage III/IV sleep (8.5% vs 17%). At the time of autopsy, all cases had severe neuronal tau pathology in wake-promoting nuclei, as well as decreases in thalamic cholinergic innervations. There was no difference in orexinergic fiber density in nucleus basalis of Meynert or locus ceruleus compared to controls.
The PPND kindred showed severe sleep disturbance. Sleep abnormalities are common in neurodegenerative illnesses, but this is the first study of sleep disorders in PPND. Unlike most neurodegenerative conditions, PPND is characterized by decreased total sleep time, increased sleep latency, and decreased sleep efficiency, without daytime hypersomnolence.
由 MAPT 基因 N279K 突变引起的苍白球-桥脑-黑质变性（PPND）是一组统称为与 17 号染色体相关的额颞叶痴呆和帕金森病的疾病之一。本研究旨在描述 PPND 中睡眠障碍的性质，并将这些发现与其他进行性神经疾病进行比较。还提供了病理学发现。
从 PPND 家族中招募了 10 名受试者；5 名受影响者和 5 名未受影响者。受试者接受了临床评估、多导睡眠图和手腕活动记录仪检查。对受影响受试者的可用睡眠相关区域（脚桥核/外侧背盖核、基底前脑核、丘脑和蓝斑）进行了死后分析。
受影响组的总睡眠时间平均为 130.8 分钟，而对照组为 403.6 分钟（p<0.01）。受影响者的初始睡眠潜伏期明显更长（范围，58-260 分钟与 3-34 分钟）。受影响者的 I 期睡眠也增加（8.5%与 1%），III/IV 期睡眠减少（8.5%与 17%）。在尸检时，所有病例的促醒核中均存在严重的神经元 tau 病理学，以及丘脑胆碱能传入减少。与对照组相比，基底前脑核或蓝斑的食欲素纤维密度没有差异。
PPND 家族表现出严重的睡眠障碍。睡眠异常在神经退行性疾病中很常见，但这是 PPND 睡眠障碍的第一项研究。与大多数神经退行性疾病不同，PPND 的特征是总睡眠时间减少、睡眠潜伏期延长和睡眠效率降低，而白天嗜睡不明显。
