Tu Sicong, Huang Mengjie, Caga Jashelle, Mahoney Colin J, Kiernan Matthew C
Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia.
Front Neurol. 2021 Jul 8;12:704059. doi: 10.3389/fneur.2021.704059. eCollection 2021.
Pseudobulbar affect is a disorder of emotional expression commonly observed in amyotrophic lateral sclerosis (ALS), presenting as episodes of involuntary laughter, or crying. The objective of the current study was to determine the association between frequency of pathological laughter and crying (PLC) episodes with clinical features, cognitive impairment, and brainstem pathology. Thirty-five sporadic ALS patients underwent neuropsychological assessment, with a subset also undergoing brain imaging. The Center for Neurological Study Lability Scale (CNS-LS) was used to screen for presence and severity of pseudobulbar affect (CNS-LS ≥ 13) and frequency of PLC episodes. Presence of pseudobulbar affect was significantly higher in bulbar onset ALS ( = 0.02). Frequency of PLC episodes was differentially associated with cognitive performance and brainstem integrity. Notably pathological laughter frequency, but not crying, showed a significant positive association with executive dysfunction on the Trail Making Test B-A ( = 0.14, = 0.04). Similarly, only pathological laughter frequency demonstrated a significant negative correlation with gray matter volume of the brainstem ( = 0.46, < 0.01), and mean fractional anisotropy of the superior cerebellar peduncles (left: = 0.44, < 0.01; right: = 0.44, < 0.01). Hierarchical regression indicated brainstem imaging in combination with site of symptom onset explained 73% of the variance in pathological laughter frequency in ALS. The current findings suggest emotional lability is underpinned by degeneration across distinct neural circuits, with brainstem integrity critical in the emergence of pathological laughter.
假性球麻痹是一种常见于肌萎缩侧索硬化症（ALS）的情感表达障碍，表现为不自主的笑或哭发作。本研究的目的是确定病理性笑和哭（PLC）发作频率与临床特征、认知障碍和脑干病理学之间的关联。35例散发性ALS患者接受了神经心理学评估，其中一部分还接受了脑部成像。使用神经学研究易激惹量表（CNS-LS）筛查假性球麻痹的存在和严重程度（CNS-LS≥13）以及PLC发作频率。球部起病的ALS患者中假性球麻痹的发生率显著更高（P = 0.02）。PLC发作频率与认知表现和脑干完整性存在差异关联。值得注意的是，病理性笑的频率而非哭的频率，在连线测验B-A中与执行功能障碍呈显著正相关（P = 0.14，FDR = 0.04）。同样，只有病理性笑的频率与脑干灰质体积呈显著负相关（r = 0.46，P < 0.01），以及与上小脑脚的平均分数各向异性呈显著负相关（左侧：r = 0.44，P < 0.01；右侧：r = 0.44，P < 0.01）。分层回归表明，脑干成像结合症状发作部位可解释ALS患者病理性笑频率变异的73%。目前的研究结果表明，情绪不稳定是由不同神经回路的退化所支撑，脑干完整性在病理性笑的出现中至关重要。
