From the Experimental Neuropathology Unit (P.S., T.R., T.D., L.P., A.Q., N.R.), Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute; Neurology Unit (P.S., T.R., M.F.), Neurophysiology Unit (P.S., U.D.C., M.F.), and Neurorehabilitation Unit (P.S., M.F.), IRCCS San Raffaele Scientific Institute; Clinical Neuroimmunology Unit (A.M., R.F.), Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Scientific Institute; Division of Genetics and Cell Biology (P.C.), Unit of Genomics for Human Disease Diagnosis, Laboratory of Clinical Molecular Biology, IRCCS Ospedale San Raffaele; Neuroimaging Research Unit (F.A., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute; Vita-Salute San Raffaele University (F.A., M.F.); and 3rd Neurology Unit and Motor Neuron Disease Centre (N.R.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Neurology. 2023 Aug 22;101(8):352-356. doi: 10.1212/WNL.0000000000207223. Epub 2023 Mar 16.
Differentiation between primary (PLS) and amyotrophic lateral sclerosis (ALS) entails relevant consequences for prognosis and management but is mostly unreliable at early stages. The objectives of the study are (1) to determine the features at onset that could help to differentiate between PLS and ALS, (2) to evaluate the diagnostic performance of an integrated serum biomarker panel, and (3) to identify the prognostic factors for patients presenting with upper motor neuron (UMN) syndrome.
We selected and retrospectively analyzed the clinical data of patients presenting with UMN syndrome. At the first evaluation, when available, serum biomarkers were measured using ultrasensitive single molecule array.
The study population included 55 patients with PLS and 50 patients with ALS. Patients with PLS presented a longer time to first neurologic evaluation (PLS: 35.0 months, interquartile range [IQR] 17.0-38.0 months; ALS: 12.5 months, IQR 7.0-21.3 months; < 0.01) and lower levels of neurofilament light chain (NfL) (PLS: 81.8 pg/mL, IQR 38.4-111.1 pg/mL; ALS: 155.9 pg/mL, IQR 85.1-366.4 pg/mL; = 0.01). Two patients with PLS and 3 patients with ALS carried the expansion. NfL resulted an independent predictor of final diagnosis (odds ratio 1.01, 95% CI 1.00-1.02; = 0.04) and an independent prognostic factor (hazard ratio 1.01, 95% CI 1.00-1.01; < 0.01).
NfL might help to differentiate patients with PLS from patients with ALS and to predict prognosis in patients with UMN syndrome.
原发性侧索硬化症（PLS）和肌萎缩侧索硬化症（ALS）的鉴别对预后和治疗具有重要意义，但在早期阶段大多不可靠。本研究的目的是：（1）确定有助于鉴别 PLS 和 ALS 的首发特征；（2）评估综合血清生物标志物组的诊断性能；（3）确定出现上运动神经元（UMN）综合征患者的预后因素。
我们选择并回顾性分析了出现 UMN 综合征患者的临床资料。在首次评估时，如果有条件，使用超敏单分子阵列测量血清生物标志物。
研究人群包括 55 例 PLS 患者和 50 例 ALS 患者。PLS 患者首次神经评估的时间更长（PLS：35.0 个月，四分位距[IQR]17.0-38.0 个月；ALS：12.5 个月，IQR 7.0-21.3 个月；<0.01），神经丝轻链（NfL）水平更低（PLS：81.8 pg/mL，IQR 38.4-111.1 pg/mL；ALS：155.9 pg/mL，IQR 85.1-366.4 pg/mL；=0.01）。2 例 PLS 患者和 3 例 ALS 患者携带 C9orf72 重复扩展。NfL 是最终诊断的独立预测因素（比值比 1.01，95%可信区间 1.00-1.02；=0.04），也是独立的预后因素（风险比 1.01，95%可信区间 1.00-1.01；<0.01）。
NfL 可能有助于鉴别 PLS 患者和 ALS 患者，并预测 UMN 综合征患者的预后。
