CASPR2-Positive Isaac’s Syndrome Presenting as Sciatica-Like Thigh Pain with Normal Imaging: A Steroid-Responsive Diagnostic Pitfall

Abstract

Background Isaac’s syndrome, or acquired neuromyotonia, is a rare disorder of peripheral nerve hyperexcitability. Anti-CASPR2 antibodies represent a distinct autoimmune subtype but remain under-recognized. The presentations often mimic radiculopathy or musculoskeletal pain, especially when accompanied by nonspecific MRI findings.

Case Presentation A 29-year-old male patient presented with 2 months of continuous, involuntary worm-like muscle movements in both thighs and shoulders, associated with nocturnal pain without weakness or sensory loss. Early MRI of the spine revealed diffuse L4–L5 and L5–S1 disc bulges without nerve root compression, which raised an initial suspicion for bilateral radiculopathy. Neurological examination showed continuous myokymia with strength, reflexes, and sensation being preserved. Laboratory studies were normal. Immunological studies were strongly positive for anti-CASPR2 antibodies and clinically insignificant for anti-LGI1, thus confirming the diagnosis of autoimmune Isaac’s syndrome. The patient improved substantially after methylprednisolone pulse therapy.

Discussion This case underscores a critical diagnostic pitfall— attributing neuromyotonia to incidental MRI findings. In young patients with persistent thigh pain, visible myokymia, and normal imaging, CASPR2-associated peripheral nerve hyperexcitability should be considered. The pure neuromyotonia phenotype, absence of neuropathy, and strong steroid response make this case clinically meaningful.

Conclusion CASPR2-positive Isaac's syndrome should be considered in patients with persistent limb pain and visible myokymia despite normal neuroimaging. Clinical–radiological mismatch with preserved neurology favors autoimmune peripheral nerve hyperexcitability over radiculopathy. Early immunotherapy provides rapid symptom relief and prevents unnecessary spinal interventions.