Background and Aims:

Axonal sensorimotor neuropathy with a chronic, indolent course is a frequent occurrence in middle-aged and older adults, often in the absence of a definite diagnosis after thorough investigations. Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS) is an ataxic disorder recently associated with Replication Factor C subunit 1 (RFC1) repeat expansion mutation, presenting as a slowly evolving sensory neuro(no)pathy at onset in many cases.

We described clinical and pathological findings in RFC1-mutated patients identified in a biopsy-investigated Chronic Idiopathic Axonal Polyneuropathy (CIAP) population.

Methods:

We abstracted clinical, instrumental and pathology characteristics from 234 CIAP cases identified out of 594 consecutive patients with peripheral neuropathy evaluated at a single tertiary-care referral center for sural nerve biopsy. Patients were classified as pure sensory, predominantly sensory or sensorimotor according to clinical examination and screened for biallelic RFC1 AAGGG expansion.

Results:

A biallelic RFC1 AAGGG expansion was common in patients with pure sensory neuropathy (21/40, 53%) and more frequent compared to both predominantly sensory (10/56, 18%, P<0.001) and sensorimotor cases (3/138, 2%, P<0.001). Compared to non-mutated patients, RFC1-positive cases presented with greater sensory ataxia and autonomic disturbances, but often retained deep tendon reflexes. Cerebellar or vestibular involvement, on the other hand, was infrequent. On pathology, mutated patients showed scant regenerative changes and loss of both myelinated and unmyelinated nerve fibers, suggestive for sensory neuronopathy.

Conclusions:

RFC1 AAGGG expansion is frequently detected in patients with slowly progressive sensory axonal neuropathy of unknown cause. Specific clinical characteristics should prompt genetic testing in thoroughly investigated patients.

Background and Aims:

Single cases and series of Guillain-Barré syndrome (GBS) were reported during the SARS-CoV-2 outbreak worldwide. We aimed to evaluate the incidence and clinical features of GBS in a cohort of patients from two regions of northern Italy with the highest number of COVID-19 patients.

Methods:

GBS cases diagnosed in 12 referral hospitals in March and April 2020 were retrospectively collected. As a control population, GBS patients diagnosed in March and April 2019 in the same hospitals were considered.

Results:

Incidence of GBS in March and April 2020 was 0.202/100,000 per month (estimated rate 2.43/100.000 per year; C.I. 0.140-0.282) versus 0.077/100.000 per month (estimated rate 0.93/100.000 per year; C.I.: 0.041-0.132) in March and April 2019 with a 2.6-fold increase. Estimated incidence of GBS in COVID-19 positive patients was 47.9/100,000 and in the COVID-19 positive hospitalized patients was 236/100,000.

COVID-positive GBS were compared with COVID-negative patients and a higher frequency of demyelinating subtype (AIDP) (76.6% vs 35.3%; p. 0.005), a lower MRC sum score (26.33 +/- 18.31 vs 41.41 +/- 14.85; p 0.006) and more frequent admission to ICU (66.6% vs 17.6%; p 0.002) were observed.

Conclusions:

This study shows an increased incidence of GBS during the first COVID-19 wave in northern Italy. This might not be unexpected considering that GBS is unanimously considered a post-infectious disease with several new infectious agents even recently added as possible trigger for GBS, including Zika and Hepatitis E viruses. We suggested that a correlation might exist between the COVID-19 and the increase in GBS incidence.