Chronic inflammatory demyelinating polyneuropathy associated with contactin-1 antibodies in a child

Clinical case

A previously healthy 2-year and 9-month old boy was brought to the emergency department for a 6-day history of weakness in the legs and frequent falls, rendering him unable to walk 1 day before admission. He did not have pain, dysphagia, bladder dysfunction, or sensory symptoms. There was no history of trauma, but he developed diarrhea 3 days before symptom onset. Family history was negative for consanguinity or neurologic diseases. At examination, he had bilateral leg weakness requiring substantial aid to walk a few steps and was unable to stand up from the floor. He had absent tendon reflexes in the lower extremities and flexor plantar responses. Strength and reflexes in upper extremities and the rest of the examination were normal. CSF showed a protein concentration of 125 mg/dL (NR: 15–45), with normal white blood cell count and glucose concentration. Blood cell count and chemistry were normal, and stool culture was negative. Nerve conduction studies (NCSs) and EMG showed decreased amplitudes in both peroneal nerves (table e-1, links.lww.com/NXI/A131). The patient was treated with IV immunoglobulins (IVIg) 2 g/kg administered in 3 days. During the next 2 weeks, there was mild improvement in motor strength as he was able to walk and stand up with support (the Guillain-Barré syndrome disability scale [GBSds]¹ score remained 3), and he was discharged home. Two weeks later (4 weeks after symptom onset), he was brought back for worsening weakness in the legs and new onset weakness in the arms. This time, the examination revealed weakness in legs and arms, generalized areflexia, and impossibility to stand up from the floor (GBSds 4). Repeat CSF studies showed a protein concentration of 148 mg/dL and normal white blood cell count and glucose level. No toxic or infectious etiologies were identified, and serum was negative for ganglioside antibodies. NCSs showed prolonged distal motor latencies, conduction slowing, and decreased amplitude of compound muscle action potentials, along with EMG features of chronic denervation, fibrillation, and positive sharp waves (table e-1, links.lww.com/NXI/A131). Treatment with IVIg was ineffective, but IV methylprednisolone (30 mg/kg/d for 5 days) resulted in substantial improvement, leaving the patient with normal strength except for mild distal lower extremity weakness (GBSds 1).

One year later, after an episode of diarrhea, the patient developed similar clinical and electrophysiologic abnormalities confined to the lower extremities (GBSds 3) fulfilling clinical and electrophysiologic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). This time, the symptom recrudescence improved with IVIg, and he returned to his baseline (GBSds 1).

A recent follow-up, 5 years after symptom onset, showed that the neurologic deficits were stable, and the patient had not had further relapses. Current serum studies for antibodies against components of the nodal and paranodal regions of peripheral nerves were negative, but analysis of archived serum and CSF samples obtained at disease onset (5 years earlier) showed intense reactivity with teased nerve fibers from pig and human embrionic kidney (HEK) 293 cells expressing contactin-1 demonstrating the presence of these antibodies in both assays (figure).

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Figure Demonstration of anti–contactin-1 antibodies in a serum of a child with CIDP

The presence of anti–contactin-1 antibodies was confirmed with contactin-1–transfected human embrionic kidney (HEK) 293 cells. Patient serum (B) showed strong reactivity against contactin-1 and colocalized with the reactivity of a commercial antibody (A) in merged images (C). Patient serum showed strong reactivity against the paranode on pig teased nerve fibers (E) and colocalized with the reactivity of a commercial antibody (D) in merged images (F).