From the Departments of Neurology (A.G.-J., T.B., S.T.G., D.M., J.S., J.B.K., H.B.H.), Neuroradiology (H.L., S.P.K.), and Anaesthesiology (T.K.), University of Erlangen-Nuremberg, Erlangen, Germany.
Stroke. 2016 May;47(5):1239-46. doi: 10.1161/STROKEAHA.116.013003. Epub 2016 Apr 12.
Stroke-associated immunosuppression is an increasingly recognized factor triggering infections and thus potentially influencing outcome after stroke. Specifically, lymphocytopenia after intracerebral hemorrhage (ICH) has only been addressed in small-sized retrospective studies of mixed intracranial bleedings. This cohort study investigated the natural course of lymphocytopenia, parameters associated with lymphocytopenia on admission (LOA) and during stay, and evaluated the clinical impact of lymphocytopenia in solely ICH patients.
This observational study included 855 consecutive patients with ICH. Patient demographics, clinical and neuroradiological data as well as laboratory and in-hospital measures were retrieved from institutional prospective databases. Functional 3-month outcome was assessed by mailed questionnaires. Lymphocytopenia was defined as <1.0 (10(9)/L) and was correlated with patient's characteristics and outcome.
Prevalence of LOA was 27.3%. Patients with LOA showed significant associations with poorer neurological status (18 [10-32] versus 13 [5-24]; P<0.001), larger hematoma volume (18.5 [6.2-46.2] versus 12.8 [4.4-37.8]; P=0.006), and unfavorable outcome (74.7% versus 63.3%; P=0.0018). Natural course of lymphocyte count during hospital stay revealed a lymphocyte nadir of 1.1 (0.80-1.53 [10(9)/L]) at day 5. Focusing on patients with day-5-lymphocytopenia, compared with patients with LOA, revealed increased rates of infections (63 [71.6] versus 113 [48.5]; P<0.001) and poorer functional outcome at 3 months (76 [86.4] versus 175 [75.1); P=0.029). Adjusting for baseline confounders, multivariable logistic and receiver operating characteristics analyses documented independent associations of day-5-lymphocytopenia with unfavorable outcome (day-5-lymphocytopenia: odds ratio, 2.017 [95% confidence interval, 1.029-3.955], P=0.041; LOA: odds ratio, 1.391 [0.795-2.432], P=0.248; receiver operating characteristics: day-5-lymphocytopenia: area under the curve=0.673, P<0.0001, Youden's index=0.290; LOA: area under the curve=0.513, P=0.676, Youden's index=0.084), whereas receiver operating characteristics analyses revealed no association of age or hematoma volume with day-5-lymphocytopenia (age: area under the curve=0.540, P=0.198, Youden's index=0.106; volume: area under the curve=0.550, P=0.0898, Youden's index=0.1224).
Lymphocytopenia is frequently present in patients with ICH and may represent an independent parameter associated with unfavorable functional outcome. Developing lymphocytopenia affected outcome even stronger than LOA, a finding that may open up new therapeutic avenues in specific subsets of patients with ICH.
卒中相关性免疫抑制是触发感染的一个日益受到关注的因素，因此可能会影响卒中后的转归。具体而言，脑出血（ICH）后淋巴细胞减少仅在混合颅内出血的小型回顾性研究中被报道过。本队列研究调查了淋巴细胞减少的自然病程、与入院时（LOA）和住院期间淋巴细胞减少相关的参数，并评估了仅ICH 患者中淋巴细胞减少的临床影响。
本观察性研究纳入了 855 例连续的 ICH 患者。从机构前瞻性数据库中检索了患者的人口统计学、临床和神经影像学数据以及实验室和住院期间的测量值。通过邮寄问卷评估 3 个月的功能结局。淋巴细胞减少定义为<1.0（10（9）/L），并与患者的特征和结局相关联。
LOA 的发生率为 27.3%。存在 LOA 的患者与更差的神经状态显著相关（18[10-32]与 13[5-24]；P<0.001）、更大的血肿体积（18.5[6.2-46.2]与 12.8[4.4-37.8]；P=0.006）和不良结局（74.7%与 63.3%；P=0.0018）相关。住院期间淋巴细胞计数的自然病程显示第 5 天的淋巴细胞计数最低点为 1.1（0.80-1.53[10（9）/L]）。关注第 5 天淋巴细胞减少的患者，与存在 LOA 的患者相比，感染发生率更高（63[71.6]与 113[48.5]；P<0.001），3 个月时的功能结局更差（76[86.4]与 175[75.1]；P=0.029）。在调整基线混杂因素后，多变量逻辑和接收者操作特征分析证明了第 5 天淋巴细胞减少与不良结局独立相关（第 5 天淋巴细胞减少：比值比，2.017[95%置信区间，1.029-3.955]，P=0.041；LOA：比值比，1.391[0.795-2.432]，P=0.248；接收者操作特征：第 5 天淋巴细胞减少：曲线下面积=0.673，P<0.0001，Youden 指数=0.290；LOA：曲线下面积=0.513，P=0.676，Youden 指数=0.084），而接收者操作特征分析显示年龄或血肿体积与第 5 天淋巴细胞减少无关（年龄：曲线下面积=0.540，P=0.198，Youden 指数=0.106；体积：曲线下面积=0.550，P=0.0898，Youden 指数=0.1224）。
ICH 患者常存在淋巴细胞减少，且可能是与不良功能结局相关的独立参数。与 LOA 相比，发展为淋巴细胞减少对结局的影响更大，这一发现可能为特定 ICH 患者亚群开辟新的治疗途径。
