Acute Sensorimotor Neuropathy Associated With Anti-CV2/CRMP5 Antibodies Resembling Guillain–Barré Syndrome

Dear Editor,

Sensorimotor neuropathy is a common clinical manifestation of paraneoplastic neurological syndrome (PNS),1 which typically presents with a subacute progression over a multiple-month timescale. We report a case of PNS neuropathy associated with anti-CV2/CRMP5-antibody positivity. The condition was characterized by acute progressive sensorimotor neuropathies resembling Guillain–Barré syndrome (GBS).

A 76-year-old male presented with a 5-day history of progressive weakness, which had started in the bilateral legs and then worsened while expanding to the arms. He was admitted to another hospital with suspected GBS due to a history of herpes zoster pharyngitis 3 weeks prior to the onset of his symptoms, which is consistent with a preceding immune trigger for GBS. He was subsequently transferred to our hospital due to the rapid progression of weakness 5 days after symptom onset.

A physical examination produced the following results: blood pressure, 192/100 mm Hg; heart rate, 110 bpm; respiration rate, 23 cpm; and body temperature, 37.2℃. His neurological findings included moderate facial paralysis, weakness in the upper and lower extremities (Medical Research Council muscle strength grades of 2/5 and 1/5, respectively), loss of tendon reflexes in the extremities, and severe sensory loss below the third thoracic segment. He did not exhibit signs of consciousness disturbance, involuntary movements, or visual abnormalities. The presence of severe limb weakness meant that he could not be assessed for ataxia.

Lumbar puncture performed on the day of admission revealed a high protein level in the cerebrospinal fluid (283 mg/dL) and slight pleocytosis (cell count of 8/mm³). Nerve conduction studies revealed severe disturbance of the motor and sensory nerves indicating axonal neuropathies2 (Fig. 1A, Supplementary Tables 1 and 2 in the online-only Data Supplement). Gadolinium signals were abnormally enhanced in cervical magnetic resonance imaging of the bilateral cervical nerve roots. These findings were consistent with a diagnosis of the classic sensorimotor type of GBS.3 The patient received intravenous immunoglobulin (IVIg) therapy, but his muscle weakness worsened, and so he was intubated and placed on mechanical ventilation on day 2 of hospitalization (Fig. 1B). He could move his neck, shoulder, and face only slightly. A second course of IVIg was administered on hospitalization day 19, but his condition did not improve.

Fig. 1
Clinical features of the patient. A: Nerve conduction studies showed decreased CMAP amplitudes in the right median and tibial nerves. No SNAP was evoked in the right median or sural nerve. B: IVIg therapy was not effective in improving the patient’s symptoms. On day 43 of hospitalization, colonoscopy revealed adenocarcinoma of the sigmoid colon. On day 60 of hospitalization, the patient received IVMP, and PSL was administered via a feeding tube. The patient’s symptoms improved with steroid therapy. CMAP, compound muscle action potential; IVIg, intravenous immunoglobulin; IVMP, intravenous methylprednisolone; PSL, prednisolone; SNAP, sensory nerve action potential.

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A colonoscopy performed on hospitalization day 43 revealed sigmoid colon adenocarcinoma. Further analysis of antiautosomal antibodies revealed the presence of anti-CV2/CRMP5 antibodies in the patient’s serum and cerebrospinal fluid, with serum and cerebrospinal fluid diluted to standard dilution ratios of 1:200 and 1:1, respectively (Ravo PNS+2 blot, Ravo Diagnostika). Antiganglioside antibodies were not detected in the patient’s serum (Supplementary Table 3 in the online-only Data Supplement). Based on these findings, he was diagnosed with PNS neuropathy. Steroid therapy was started, and within a few days he presented slight but clear improvements in facial paresis, limb weakness, and sensory loss. He communicated using facial expressions and lip language. After a few weeks, on day 128 of hospitalization, he was discharged and admitted to a nursing home.

Anti-CV2/CRMP5 antibodies are one of the main antibodies detected in patients with PNS,1 and neuropathy is the most common clinical phenotype associated with anti-CV2/CRMP5-antibody-associated PNS.4 This type of neuropathy often presents as axonal sensorimotor neuropathy (51%) or axonal sensory neuropathy (27%).5 Typical clinical presentations include neuropathic pain (79%), autonomic dysfunction (31%), gastrointestinal hypomotility (24%), and optic neuritis and/or retinitis (11%).5 Common primary tumors have been reported with small-cell lung cancer (56%), thymoma (11%), and adenocarcinoma of the lung (4%) or breast (4%).5 Although PNS neuropathy generally has a subacute clinical course, there have been a few case reports of acute progressive sensorimotor neuropathy that mimic GBS, as in our case.

A PubMed search identified four cases of PNS neuropathy resembling GBS.2, 6, 7, 8 In these cases, GBS was defined as the presence of progressive sensorimotor neuropathy resulting in severe leg weakness (modified Rankin Scale [mRS] score ≥4) within 4 weeks after disease onset. Supplementary Table 4 (in the online-only Data Supplement) presents the clinical profiles of these cases. The time to deterioration of the mRS score (≥4) was shorter for our case than for these four previous cases. Three of the four previous patients predominantly presented with sensorimotor neuropathy,2, 6, 7, 8 similar to our case. One patient had limbic encephalitis and sensorimotor neuropathy.6 This finding indicates that some cases of PNS neuropathy can be difficult to distinguish from GBS in the early stages of the disease.

The therapeutic approach for acute sensorimotor neuropathy makes accurate diagnoses crucial. No therapies other than IVIg and plasma exchange (including steroids) have been found to be effective in GBS.3 Although there are no established therapeutic approaches for PNS neuropathy, early detection and antitumor therapies are recommended. Additionally, a few studies have showing that steroid therapy is effective against PNS neuropathy.4, 9 While our case did not respond to repeated IVIg treatment, his symptoms improved with steroid therapy. Therefore, to propose therapeutic options other than IVIg therapy and plasma exchange, it is important to explore antineural antibodies associated with PNS and latent tumors in patients with GBS-like neuropathy.