Double trouble: para-neoplastic anti-PCA-2 and CRMP-5-mediated small fibre neuropathy followed by chorea associated with small cell lung cancer and evolving radiological features

Abstract

Patients with Purkinje cell cytoplasmic autoantibody type 2 (PCA-2) and collapsin response-mediator protein-5 (CRMP-5) autoantibody can present with multifocal elements of encephalomyeloneuropathy. Except for an anecdotal report, case descriptions of paraneoplastic small fibre neuropathy are lacking. We report paraneoplastic small fibre neuropathy followed by chorea associated with small cell lung cancer. A man aged 57 years with a 35 pack-year smoking history presented with painless subacute paresthesia and weight fluctuation. A non-length-dependent small fibre neuropathy was confirmed by skin biopsy. Further testing revealed positive serum PCA-2 and CRMP-5 autoantibodies, which after positron emission tomography-CT led to histological confirmation of a small cell lung cancer. Initially, abnormal MRI and cerebrospinal fluid studies suggested central nervous system (CNS) involvement which was subclinical; however, 6 months later during antitumour therapy, the patient became symptomatic with choreoathetosis. After combined chemoradiation as well as immunosuppressive and symptomatic therapies, the clinical course stabilised, although residual neurological deficits remained at follow-up a year later. Coexistent PCA-2 and CRMP-5 autoantibodies may occur in the setting of small fibre peripheral neuropathy and choreoathetosis and predict cancer type. Two paraneoplastic syndromes can present successively over months; subclinical CNS involvement with evolving basal ganglia abnormalities can be a paraneoplastic manifestation. In the appropriate clinical setting, paraneoplastic testing should be considered in patients presenting with small fibre neuropathy.

Non‐length‐dependent small fiber neuropathy: Not a matter of stockings and gloves

“…Paraneoplastic neuropathy is usually a sensory ataxic neuronopathy, but it may be painful, 188 and rarely presents as NLD‐SFN 52,161,162 …”

“…46,47,[156][157][158] Paraneoplastic neuropathy is usually a sensory ataxic neuronopathy, but it may be painful, 188 and rarely presents as NLD-SFN. 52,161,162 The existence of small fiber-targeting acute inflammatory neuropathies resembling GBS has been proposed. 189,190 Some of these patients present with diffuse 163 proximal, 147 or multifocal sensory topography.…”

Paraneoplastic Neuropathies: What's New Since the 2004 Recommended Diagnostic Criteria

“…SFN has been documented in cases of Morvan syndrome (78). Although examples of SF involvement have been described in PN in solid cancers (79) and hematological diseases (80), it remains unclear whether the SF involvement is exclusive, or part of a general neuropathy syndrome.…”

Approach to Neuropathic Pain

“…Patients usually present with length-dependent temperature dysregulation and pain symptoms, though a lengthindependent pattern with patchy distribution of symptoms has also been described, particularly in paraneoplastic or immune-mediated cases. 90,91 Skin biopsy with reduced intraepidermal nerve fiber density is the pathologic gold standard for the diagnosis of SFN (►Fig. 3) and has been shown to impact management in cases of probable SFN.…”