by Elena Moro
For February 2018, we have selected: Feneberg E, Oeckl P, Steinacker P, et al. Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis. Neurology 2018;90:e22-30. doi:10.1212/WNL.0000000000004761.
Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder affecting motor neurons. The course of the disease is progressive with life span of 3 to 5 years from the onset of the symptoms. The diagnosis is made using mainly clinical criteria, supported by electrophysiological data. Nowadays there is no efficient treatment and it is important to different ALS from ALS-like syndromes (motor neuron disease (MND) mimics). There are currently no neurochemical biomarkers involved in the diagnostic criteria, although neurofilaments (Nf) light chain (NfL) and phosphorylated Nf heavy chain (pNfH) have been found elevated both in the CSF and serum in patients with symptomatic sporadic ALS. Nf levels might be useful for differential diagnosis at early stage of disease.
In this multicenter European study, early ALS patients with symptom onset £ 6 months from sampling, later ALS patients with symptoms onset ³ 6 months from sampling, patients with other neurological disorders, patients with a differential diagnosis of a motor neuron disease, and patients with other MND variants were included. Patients with ALS were followed-up for at least 3 months, and categorized into clinically definite, probable, laboratory probable or possible ALS using the revised El Escorial criteria. Severity of physical symptoms was classified according to the Revised ALS Functional Rating Scale (ALSFRS-R).
A total of 54 CSF samples and 45 serum samples were collected from early ALS, whereas 135 CSF and 118 serum samples from later ALS. Sixty-five CSF samples and 48 serum samples from patients with other neurological diseases, 27 CSF and 21 serum samples from MND mimics, and 21 CSF and 16 serum samples from patients with other MND were also collected. CSF NfL and pNfH were measured using commercially available ELISA kits, whereas Simoa platform was used for serum measures. Multiple regression was used to assess the impact of age and study center on neurofilaments’ levels.
Concerning the clinical characteristics of patients, no differences were found in age between patients with early or later ALS. Progression rate was higher in the early symptomatic phase compared to the later phase. Compared to all other patients, the ones with both early and later symptomatic ALS had significantly elevated Nf level in both the CSF and serum. No differences were found in Nf levels between early and later symptomatic phase, although CSF pNfH concentrations were higher in early ALS phase. Sensitivity (80-100%) and specificity (86-98%) were powerful to distinguish between patients with ALS and other neurological diseases or MND mimics. CSF and serum levels from early and later ALS patients were independent of the clinical diagnosis according to the El Escorial criteria. Only CSF pNfH levels were significantly lower in suspected ALS compared to probable and definite ALS.
“This study confirms the role of elevated NF levels in CSF and serum in differential diagnosis between ALS and other neurological disorders, including MND mimics. Particularly in the first months after diagnosis, Nf level are high in ALS patients”, says Prof. Vitalie Lisnic, Department of Neurology, University of Medicine and Pharmacy, Chisinau, Moldova. “Moreover, neurofilaments levels seem to be independent of the clinical phenotype and reliable across centers. Findings from this paper support the role of measuring neurofilaments levels in CSF and serum to diagnose ALS patients.”
The other nominees for the February 2018 Paper of the month are:
- Stupp R, Taillibert S, Kanner A, et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma. JAMA 2017;318:2306-2316. In this open-label clinical trial, 695 patients with glioblastoma were randomized to receive tumor-treating fields (an antimitotic treatment modality) plus maintenance temozolomide chemotherapy versus temozolomide alone. The group that received tumor-treating fields together with temozolomide had a significant better progressios-free survival (6.7 months versus 4.0 months) and overall survival (20.9 months versus 16.0 months).
- Froheler MT, Saver JL, Zaidat OO, et al., on behalf of the STRATIS Investigators. Interhospital transfer before thrombectomy is associated with delayed treatment and worse outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke). Circulation 2017;136:2311-2321. In this large prospective, multicenter, observational study 1,000 patients with severe stroke and treated within 8 hours with mechanical thrombectomy (with or without intravenous tissue plasminogen activator) were analyzed in terms of outcomes differences between direct access and interhospital transfer modalities in the hospital. Patients who had direct access to thrombectomy had significantly better outcome (functional independence at 90 days). Intravenous tissue plasminogen activator did not impact outcomes.
