Nitrous-oxide-induced polyneuropathy and subacute combined degeneration of the spine: clinical and diagnostic characteristics in 70 patients, with focus on electrodiagnostic studies

Abstract

Background and purpose: Nitrous oxide (N2O) induced neurological symptoms are increasingly encountered. Our aim is to provide clinical and diagnostic characteristics with a focus on electrodiagnostic studies. Methods: Patients with neurological sequelae due to N2O presenting in our hospital between November 2018 and December 2021 reporting clinical and diagnostic data were retrospectively reviewed. Results: Seventy patients (median 22 years) were included. Median N2O usage was 4 kg/week during 12 months. Patients’ history revealed a higher rate of sensory symptoms compared to motor (97% vs. 57%) and 77% walking difficulties. Clinical diagnosis was polyneuropathy (PNP) in 44%, subacute combined degeneration (SCD) of the spine in 19%, both in 37%. Median vitamin B12 level was low (159 pmol/L), normal in 16%. The median methylmalonic acid was increased (2.66 μmol/L). Electrodiagnostic abnormalities were observed in 91%, with 72% fulfilling axonal PNP criteria, 20% showing mild to intermediate slowing. One patient fulfilled demyelinating PNP criteria not related to N2O abuse (Charcot−Marie−Tooth type 1a). More prominent motor nerve conduction abnormalities were found; lower limbs were more affected. In 64% with normal conduction, myography showed signs of axonal loss. Magnetic resonance imaging showed cervical myelopathy in 58% involving generally five to six segments. Conclusions: Nitrous oxide (N2O) leads to neurological symptoms by causing PNP and/or SCD primarily involving the legs. Distinguishing PNP and SCD clinically was shown to be insufficient. Electrodiagnostic studies showed axonal PNP. Demyelinating PNP due to N2O abuse was not present in our cohort. Therefore, further diagnostic work-up is warranted if demyelinating features are present.