Rationale: Autoimmune encephalitis associated with contactin-associated protein-like 2 (CASPR2) antibodies encompasses a wide spectrum of central and peripheral nervous system manifestations. While focal seizures are a recognized feature, the subtlety and variability of other presenting symptoms may delay recognition. This case highlights the diagnostic complexity of CASPR2 antibody-associated autoimmune encephalitis in a patient with a 6-month history of progressive lightheadedness, transient visual disturbances, and gait instability with bilateral leg “heaviness.”
Methods: We present a 64-year-old right-handed man with history of coronary artery disease, hypertension, and inferior vena cava thrombus, who developed vague symptoms of gait imbalance, positional lightheadedness, bilateral leg “heaviness,” episodic peripheral visual distortion, dysarthria and intermittent confusion. MRI of the brain with and without contrast was unremarkable. Orthostatic vital signs were positive for orthostatic hypotension. Due to fluctuating symptoms, EEG monitoring was initiated and revealed electrographic seizures —either with no apparent clinical signs or subtle oral automatisms— arising from the right fronto-temporal region. There were no epileptiform discharges. Levetiracetam was started but later switched to lacosamide due to adverse mood effects. Persistent symptoms suggestive of autonomic dysfunction and peripheral neuropathy prompted evaluation for autoimmune encephalitis.
Results: Cerebrospinal fluid (CSF) analysis showed mild pleocytosis (WBC 8), and elevated protein (81 mg/dL). CASPR2 IgG antibodies were identified in both CSF and serum (titer 1:100). CT and PET imaging ruled out an underlying malignancy. Repeat 5-day EEG monitoring was normal and neuropsychological testing showed no cognitive impairment. The patient had significant improvement of dizziness, gait disturbance and cognition following 5 days of high-dose intravenous methylprednisolone followed by oral prednisone taper. However, symptoms recurred, including more diffuse weakness now involving both upper and lower extremities. Steroid therapy was re-escalated, and the patient was scheduled for initiation of rituximab.
Conclusions: This case underscores the diagnostic challenges posed by CASPR2 antibody-associated autoimmune encephalitis, particularly when presenting with non-specific symptoms of orthostatic hypotension and suspected peripheral neuropathy in the context of unrevealing imaging. Early clinical suspicion and initiation of immunotherapy are critical to optimizing neurologic and functional outcomes.
Funding: Not Applicable