Are Miller Fisher syndrome and CANDA due to a paranodopathy?

Abstract

Objective: To study the pathological characteristics of acute and chronic ataxic peripheral neuropathy at the level of the node of Ranvier.

Study design and setting: We performed the pathological study (nerve biopsy of a sural nerve) of two patients, one with an acute form of ataxic peripheral neuropathy called 'Miller Fisher syndrome' (MFS), the other one with a chronic form called 'chronic ataxic neuropathies with disialosyl antibodies' (CANDA).

Results: A dysimmune process involving peripheral nerves commences in myelin, at the internodal area or/and in the paranodal and nodal regions. Our electron microscopic observations suggest that both patients present lesions in favor of a paranodopathy.

Conclusion: Many of the immune-mediated peripheral neuropathies are now classified as nodoparanodopathies. This subtype of auto-immune neuropathy may present various clinical phenotypes such as 'Acute Motor Axonal Neuropathy' (AMAN), 'Acute Motor and Sensory Neuropathy' (AMSAN) or 'chronic inflammatory demyelinating polyradiculoneuropathy' (CIDP), and are associated with anti-disialosyl antibodies. In our two cases, some paranodes seem to be associated with macrophages and we hypothesized that these lesions are in favor of a complement-mediated dysfunction/disruption of the nodal region due to disialosyl antibodies against gangliosides which are mainly located at the level of the axolemma of the paranode.

Keywords: CANDA; CANOMAD; Miller Fisher syndrome; Nodopathy; Paranodopathy.