Neurofilament Light Chain as Prognostic Biomarker in ALS
March 12, 2017 - als
11 Mar 2017
A retrospective, longitudinal investigate of patients with opposite clinical subtypes of ALS supports a value of neurofilament light sequence (NfL) as a biomarker for illness progression. In a work, published Mar 6 in JAMA Neurology, Gianni Sorarù and colleagues during a University of Padua in Padova, Italy, fact a clever association between cerebrospinal liquid NfL and quick course or shorter presence in a organisation of 94 patients. NfL fared reduction good as a justification marker. The researchers found poignant overlie in NfL levels among patients with ALS, frontotemporal insanity (FTD), and other motor neuronopathies.
“This investigate supports prior commentary that NfL is towering in ALS and FTD, and provides plain information on NfL in opposite forms of ALS,” pronounced Lucie Bruijn of a ALS Association, Washington, D.C. “Perhaps many important, a work confirms that NfL could be an critical apparatus for specifying quick and delayed progressors. For that reason, it could be a good stratifying magnitude in clinical trials,” Bruijn said. She combined that a investigate adds some critical sum about NfL, including display that levels are not influenced by sex or age.
When axons tumble apart, they recover neurofilament protein, that scientists are posterior as a biomarker for neurodegeneration in many diseases. Researchers initial reported a remarkable betterment of NfL in a cerebrospinal liquid (CSF) of patients with amyotrophic parallel sclerosis dual decades ago (Rosengren et al., 1996). Subsequent work determined that high CSF or blood levels of NfL tracked with poorer augury and shorter presence (see Jun 2015 news; Weydt et al., 2016; Steinacker et al., 2016).
To ask either NfL competence be diagnostically useful, initial author Alexandra Gaiani and colleagues analyzed CSF collected from 176 patients in Padua between 2010 and 2016. The organisation enclosed a 94 patients diagnosed with ALS, 20 with FTD, 18 with engine neuropathies, and 44 controls. Each CSF representation was performed between 6 months and dual years after illness conflict and stored. All were analyzed for NfL in 2016.
As expected, a ALS organisation had significantly aloft CSF NfL than a other engine neuropathies or a control group. The FTD patients had middle levels. NfL in ALS and FTD had formerly usually been complicated separately, Sorarù told Alzforum.
The researchers serve divided a ALS patients into customary ALS (58 subjects), beat arm or beat leg syndrome (11 patients), on-going robust atrophy (PMA, 9), on-going bulbar palsy (PBP, 9), and top engine neuron widespread ALS (UMND, 7). The top NfL levels occurred in patients with normal ALS and in variants compared with top engine neuron lapse (progressive bulbar palsy and top engine neuron widespread ALS). Only medium elevations accompanied a clinically milder forms (flail arm or beat leg syndrome and on-going robust atrophy), that engage especially reduce motor neurons.
Those formula harken behind to a strange 1996 news in that researchers already remarkable a disproportion in neurofilament in top and reduce engine neuron forms of a illness (see also Brettschneider et al., 2012). More recently, freeing tensor imaging, that measures a firmness of vast axons, has directly related plunge of top engine neurons in a corticospinal tract to a arise in NfL in ALS (Menke et al., 2015).
What about prognosis? The researchers followed patients for adult to 80 months after their lumbar puncture. In agreement with prior findings, NfL thoroughness in a CSF inversely correlated with speed of illness course as good as with altogether survival, even after adjusting for sex, age, ALS subtype, and disease duration.
UMND ALS presented a one disproportion to a rule. Although it is amiable and slow-progressing, patients with this form had CSF NfL as high as customary ALS. The authors speculated this reflects a primarily top corticospinal tract relapse in UMND ALS.
Could NfL be useful for diagnosis? Based on their numbers, a authors advise NfL on a possess can heed ALS from controls with scarcely 90 percent attraction and specificity. However, a pen can't heed ALS from FTD or other engine neuron illness with such certainty.
“I’m reduction assured about a justification partial of their study, though we cruise a justification that correlates NfL to presence is unequivocally strong,” pronounced Merit Cudkowicz, Harvard Medical School. “Because they looked during a larger farrago of engine neuron diseases and mimics, they have some-more energy to uncover a widespread of neurofilament values, and a strength as a good premonitory marker.” Cudkowicz forked out that in cases of reduce engine neuron involvement, clinicians don’t know if patients will stay that approach or rise exemplary ALS. “A reduce NfL value during a commencement is a good premonitory sign,” she said.
The parsimonious couple to course means that NfL could assistance clinicians name subjects for clinical trials. “If we take all comers, we get outrageous variability in how people progress, and afterwards we need vast representation sizes to see any effects,” remarkable Cudkowicz. That’s a large plea for a field, she added. “If NfL could assistance to collect a organisation of people who are surpassing faster, afterwards we competence be means to investigate smaller groups,” she said.
“The investigate is unequivocally clever and well-conducted,” pronounced Henrik Zetterberg, University of Gothenberg, Sweden. By replicating prior studies, it creates a box for NfL in ALS even stronger, he said.
The latest growth in a field, a unequivocally supportive blood exam for NfL formed on singular proton array analysis, should enhance a strech of a exam to many some-more people, and concede for easier, repeat, longitudinal analysis, remarkable Zetterberg (see Feb 2017 news).—Pat McCaffrey
Pat McCaffrey is a author formed in Newton, Massachusetts.
- Blood Marker May Predict ALS Progression 4 Jun 2015
- Touchdown for NfL: Blood Test Tells Parkinson’s from Related Disorders 10 Feb 2017
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