Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis.

OBJECTIVE: To examine neurofilament (Nf) concentrations according to symptom onset and clinical diagnostic certainty categories of amyotrophic lateral sclerosis (ALS). METHODS: We measured Nf light chain (NfL) and phosphorylated Nf heavy chain (pNfH) CSF and NfL serum levels in patients with ALS with first symptom onset ≤6 months (n = 54) or >6 months (n = 135) from sampling, and patients with other neurologic diseases, differential diagnoses of a motor neuron disease (MND mimics), and other MND variants to determine the diagnostic accuracy in patients with ALS with early symptom onset. Samples were received multicentric and analyzed by ELISA and Simoa platform and related to other clinical measures. RESULTS: NfL and pNfH in CSF and NfL in serum were increased in early and later symptomatic phase ALS (p < 0.0001). CSF and serum NfL and CSF pNfH discriminated patients with ALS with early symptom onset from those with other neurologic diseases and MND mimics with high sensitivity (94%, 88%, 98%, and 89%, 100%, 78%) and specificity (86%, 92%, 91%, and 94%, 90%, 98%) and did not vary between clinical diagnostic categories of ALS in the early symptomatic phase group. Baseline NfL and pNfH levels were not significantly different in patients with ALS with clinical progression to definite or probable ALS at follow-up. CONCLUSION: The measurement of Nf has potential to enhance diagnostic accuracy of ALS in those presenting soon after symptom onset, and is measurable across multiple centers. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that CSF and serum Nf concentrations discriminate ALS with early symptom onset from other neurologic diseases.

Nerve compression syndromes in ALS: a retrospective analysis in 554 patients.

We retrospectively screened a large cohort of 554 ALS patients with regard to documented nerve compression syndromes and identified 23 patients, mostly with carpal tunnel syndrome. Patients could be subdivided into three groups. Group A comprised 13 patients in whom nerve compression was apparently confused with early ALS signs. Group B consisted of six patients diagnosed with carpal tunnel syndrome who had experienced improvement after surgery years before they eventually developed ALS. Group C consisted of four patients who, after diagnosis of ALS, additionally developed a nerve compression syndrome. Altogether, the frequency of true nerve compression syndromes in our ALS cohort (1.8%) was no higher than in the general population (0.3-10.8%). In group A, the initial confusion with a nerve compression syndrome led to a slight though not significant delay (15.2 vs. 12.9 months; p = 0.32) of the diagnosis of ALS. Survival was no different between group A and the cohort. It can also be concluded that the misdiagnoses could have been avoided by thorough electrophysiological examination using a standardized protocol.