51成人动漫

Neurofilament light chain (NfL), a measure of axonal damage, showed promise as a prognostic biomarker in Guillain-Barré syndrome (GBS), a prospective study in Spain suggested.

High serum NfL levels in GBS patients were linked to higher disability and acute motor axonal neuropathy (AMAN), reported Luis Querol, MD, PhD, of Hospital de la Santa Creu i Sant Pau in Barcelona, and co-authors.

Serum NfL levels also predicted the ability to run independent of age and other disability scores at 1 year, they wrote in the .

The findings are important on several levels, Querol said. "First, they confirm that residual long-term disability in GBS is clearly associated to the degree of axonal damage that happens at the onset of the disease," he told 51成人动漫.

"They also suggest that serum NfL could be used to stratify patients at admission, and in the future, select patients who may be candidates for more aggressive therapies or those who may have good prognosis independently of the apparent severity they have at onset," he said.

Serum NfL could be used as a surrogate marker of disease activity in clinical trials and may increase accuracy in phase II studies to select therapies for phase III trials, Querol noted. "It also provides proof of principle that soluble biomarkers can inform about nerve status in a clinically meaningful way," he added.

Axonal degeneration is an important determinant of poor outcomes in GBS, said Bart Jacobs, MD, PhD, of Erasmus Medical Center in Rotterdam, the Netherlands, in an .

"Axonal injury may occur in AMAN as well as acute inflammatory demyelinating polyneuropathy and in severe cases may result in irreversible degeneration. Treatment with immunoglobulins or plasma-exchange aims to prevent further axonal injury, but clinicians currently have no methods to monitor the response directly," he wrote.

"Clinical deficits only partly reflect the axonal damage and depend on other causes of nerve dysfunction, including demyelination," Jacobs noted. "Nerve conduction studies may be normal or changeable in the early phase and require considerable expertise. We have prognostic models based on clinical features, but their performance could be improved by biomarkers for early axonal injury."

Neurofilament light is "probably the first of many biomarkers for peripheral nerve injury that can be measured by the current ultrasensitive technologies," he added.

In their study, Querol and colleagues measured NfL in 98 serum samples and 24 cerebrospinal fluid (CSF) samples of GBS patients in Spain in the ongoing International GBS Outcome Study () using single-molecule array technology, comparing them with samples from 53 age-matched healthy controls.

GBS patients were an average age of 57, and 57.1% were men. Most (68.4%) presented with GBS symptoms after an infectious event; median time from symptom onset to inclusion in the study was 4 days. Two-thirds of patients presented with the typical sensorimotor variant of GBS. Most patients were treated with intravenous immunoglobulin (77.6%) or intravenous immunoglobulin plus plasma exchange (10.2%).

At baseline, median serum NfL levels were five times higher for GBS patients than controls (55.49 pg/mL vs 9.83 pg/mL, P<0.0001). CSF levels were also higher (1308.5 pg/mL vs 440.24 pg/mL, P=0.034). GBS patients with preceding diarrhea had higher serum NfL levels than patients with respiratory symptoms or those who had no preceding infection (134.90 pg/mL vs 47.86 pg/mL vs 38.02 pg/mL, P=0.016).

Patients with pure motor GBS variant and Miller Fisher syndrome showed higher serum NfL levels than patients with typical GBS (162.18 pg/mL vs 95.50 pg/mL vs 38.02 pg/mL, P=0.025). Patients with AMAN had higher serum NfL levels than other variants (199.53 pg/mL vs 46.77 pg/mL, P=0.006).

At every time point over 1-year follow-up, serum NfL levels correlated with GBS Disability Score () and Inflammatory Rasch-built Overall Disability Scale ( results.

At 1 year, serum NfL returned to normal levels. About 74.5% of patients could walk independently at 1 year, and 67% of patients could run. High baseline serum NfL levels were associated with an inability to run (OR 1.65, 95% CI 1.14-2.40, P=0.009) and lower I-RODS (β -2.60, 95% CI -4.66 to -0.54, P=0.014) at 1 year.

A limitation of the study is the lack of exclusion criteria in the IGOS cohort. "All patients with GBS are included in IGOS and data on previous neurologic diseases influencing NfL levels or clinical outcomes were not recorded," the researchers noted. Seven patients had comorbidities affecting mobility and were not excluded from multivariable analyses. The study also could not report time to recovery in GBS patients with high versus low levels of serum NfL.

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