Acquired sensory neuronopathies encompass a group of paraneoplastic, dysimmune, toxic or idiopathic disorders characterized by degeneration of peripheral sensory neurons in dorsal root ganglia. As dorsal root ganglia cannot easily be explored, the clinical diagnosis of these disorders may be difficult. The question as to whether there exists a common clinical pattern of sensory neuronopathies, allowing the establishment of validated and easy-to-use diagnostic criteria, has not yet been addressed. In this study, logistic regression was used to construct diagnostic criteria on a retrospective study population of 78 patients with sensory neuronopathies and 56 with other sensory neuropathies. For this, sensory neuronopathy was provisionally considered as unambiguous in 44 patients with paraneoplastic disorder or cisplatin treatment and likely in 34 with a dysimmune or idiopathic setting who may theoretically have another form of neuropathy. To test the homogeneity of the sensory neuronopathy population, likely candidates were compared with unambiguous cases and then the whole population was compared with the other sensory neuropathies population. Criteria accuracy was checked on 37 prospective patients referred for diagnosis of sensory neuropathy. In the study population, sensory neuronopathy showed a common clinical and electrophysiological pattern that was independent of the underlying cause, including unusual forms with only patchy sensory loss, mild electrical motor nerve abnormalities and predominant small fibre or isolated lower limb involvement. Logistic regression allowed the construction of a set of criteria that gave fair results with the following combination: ataxia in the lower or upper limbs + asymmetrical distribution + sensory loss not restricted to the lower limbs + at least one sensory action potential absent or three sensory action potentials <30% of the lower limit of normal in the upper limbs + less than two nerves with abnormal motor nerve conduction study in the lower limbs.

A anti-FGFR3 Abs identify a subgroup of patients with SN in whom an underlying autoimmune disorder affecting sensory neurons in the dorsal root and trigeminal nerve ganglia is suspected.

Our study highlights the extended clinical spectrum of patients with anti-MAG neuropathy, which appears unrelated to antibody titre. Besides, it may also suggest beneficial use of rituximab in the early phase of anti-MAG neuropathy.

ObjectiveSensory neuropathies (SNs) are often classified as idiopathic even if immunological mechanisms can be suspected. Antibodies against the intracellular domain of the fibroblast growth factor receptor 3 (FGFR3) possibly identify a subgroup of SN affecting mostly the dorsal root ganglion (DRG). The aim of this study was to identify the frequency of anti-FGFR3 antibodies and the associated clinical pattern in a large cohort of patients with SN.MethodsA prospective, multicentric, European and Brazilian study included adults with pure SN. Serum anti-FGRF3 antibodies were analysed by ELISA. Detailed clinical and paraclinical data were collected for each anti-FGFR3-positive patient and as control for anti-FGFR3-negative patients from the same centres (‘center-matched’).ResultsSixty-five patients out of 426 (15%) had anti-FGFR3 antibodies, which were the only identified autoimmune markers in 43 patients (66%). The neuropathy was non-length dependent in 89% and classified as sensory neuronopathy in 64%, non-length-dependent small fibre neuropathy in 17% and other neuropathy in 19%. Specific clinical features occurred after 5–6 years of evolution including frequent paresthesia, predominant clinical and electrophysiological involvement of the lower limbs, and a less frequent mixed large and small fibre involvement. Brazilians had a higher frequency of anti-FGFR3 antibodies than Europeans (36% vs 13%, p<0.001), and a more frequent asymmetrical distribution of symptoms (OR 169, 95% CI 3.4 to 8424).ConclusionsAnti-FGFR3 antibodies occur in a subgroup of SN probably predominantly affecting the DRG. Differences between Europeans and Brazilians could suggest involvement of genetic or environmental factors.

ObjectiveTo identify and characterize autoantibodies (Abs) as novel biomarkers for an autoimmune context in patients with central and peripheral neurologic diseases.MethodsTwo distinct approaches (immunoprecipitation/mass spectrometry–based proteomics and protein microarrays) and patients' sera and CSF were used. The specificity of the identified target was confirmed by cell-based assay (CBA) in 856 control samples.ResultsUsing the 2 methods as well as sera and CSF of patients with central and peripheral neurologic involvement, we identified Abs against the family of Argonaute proteins (mainly AGO1 and AGO2), which were already reported in systemic autoimmunity. AGO-Abs were mostly of immunoglobulin G 1 subclass and conformation dependent. Using CBA, AGO-Abs were detected in 21 patients with a high suspicion of autoimmune neurologic diseases (71.4% were women; median age 57 years) and only in 4/856 (0.5%) controls analyzed by CBA (1 diagnosed with small-cell lung cancer and the other 3 with Sjögren syndrome). Among the 21 neurologic patients identified, the main clinical presentations were sensory neuronopathy (8/21, 38.1%) and limbic encephalitis (6/21, 28.6%). Fourteen patients (66.7%) had autoimmune comorbidities and/or co-occurring Abs, whereas AGO-Abs were the only autoimmune biomarker for the remaining 7/21 (33.3%). Thirteen (61.9%) patients were treated with immunotherapy; 8/13 (61.5%) improved, and 3/13 (23.1%) remained stable, suggesting an efficacy of these treatments.ConclusionsAGO-Abs might be potential biomarkers of autoimmunity in patients with central and peripheral nonparaneoplastic neurologic diseases. In 7 patients, AGO-Abs were the only biomarkers; thus, their identification may be useful to suspect the autoimmune character of the neurologic disorder.Classification of EvidenceThis study provides Class III evidence that AGO-Abs are more frequent in patients with autoimmune neurologic diseases than controls.