Plasma neurofilament heavy chain levels and disease progression in amyotrophic lateral sclerosis: insights from a longitudinal study
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Volume
86
Pagination
565 - 573
Publisher
DOI
10.1136/jnnp-2014-307672
Journal
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
Issue
ISSN
0022-3050
Metadata
Show full item recordAbstract
Objective To investigate the role of longitudinal
plasma neurofilament heavy chain protein (NfH) levels
as an indicator of clinical progression and survival in
amyotrophic lateral sclerosis (ALS).
Methods A cross-sectional study involving 136
clinically heterogeneous patients with ALS and 104
healthy and neurological controls was extended to
include a prospective analysis of 74 of these ALS cases,
with samplings at approximately 3-month intervals in a
follow-up period of up to 3 years. We analysed the
correlation between longitudinal NfH-phosphoform levels
and disease progression. Temporal patterns of NfH
changes were evaluated using multilevel linear
regression.
Results Baseline plasma NfH levels were higher than
controls only in patients with ALS with short disease
duration to baseline sampling. Compared with controls,
fast-progressing patients with ALS, particularly those
with a short diagnostic latency and disease duration,
had higher plasma NfH levels at an early stage and
lower levels closer to end-stage disease. Lower NfH
levels between visits were associated with rapid
functional deterioration. We also detected antibodies
against NfH, NfH aggregates and NfH cleavage products.
Conclusions Disease progression in ALS involves
defined trajectories of plasma NfH levels, reflecting
speed of neurological decline and survival. Intervisit
plasma NfH changes are also indicative of disease
progression. This study confirms that longitudinal
measurements of NfH plasma levels are more informative
than cross-sectional studies, where the time of sampling
may represent a bias in the interpretation of the results.
Autoantibodies against NfH aggregates and NfH
cleavage products may explain the variable expression of
plasma NfH with disease progression
Authors
Lu, C-H; Petzold, A; Topping, J; Allen, K; Macdonald-Wallis, C; Clarke, J; Pearce, N; Kuhle, J; Giovannoni, G; Fratta, PCollections
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