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Cerebrospinal fluid phosphorylated neurofilament heavy chain and chitotriosidase in primary lateral sclerosis

Primary lateral sclerosis (PLS) is a rare degenerative disease of upper motor neurons (UMNs) manifesting with progressive spasticity. Disease progression is definitely slower than in amyotrophic lateral sclerosis (ALS). Clinical distinction between PLS and ALS can be challenging, as the UMN-dominant form of ALS may sometimes not manifest lower motor neuron (LMN) signs for a long time after symptom onset.1 Therefore, traditional PLS diagnostic criteria allowed diagnosis only after 3 or 4 years of documented absence of LMN signs,2 which poses a psychological burden on patients, hinders correct clinical management and prevents enrolment in clinical trials. In order to overcome these issues, new diagnostic criteria have been recently formulated, shortening the time required for a diagnosis of probable PLS to 2 years.1

Diagnostic uncertainties in PLS are complicated by the lack of specific neurochemical biomarkers. Whereas cerebrospinal fluid (CSF) neurofilament levels are clearly increased in ALS, making them a well-established ALS biomarker reflecting axonal degeneration, few studies reported lower increases in PLS3; a similar pattern was observed for the putative ALS microglial biomarker chitotriosidase (Chit1).4 Here we measured phosphorylated neurofilament heavy chain (pNFH) and Chit1 in the CSF of patients with PLS, ALS and non-neurodegenerative neurological conditions, focusing on the ability of each biomarker to distinguish PLS from controls and from ALS.

### Patients

In this retrospective study we included those 10 patients (5 men, 5 women) from our consecutive PLS series (n=52) whose CSF was stored in our biobank. They all fulfilled—at the time of sampling or on later evaluations—the recently published diagnostic criteria for definite (n=9) or probable (n=1) PLS.1 Patients with ALS and neurological controls (NCs) were selected randomly from our biobank to form two cohorts with sex and age distributions similar to PLS. Patients with ALS (n=28; 16 men, 12 women) fulfilled …