How to distinguish Guillain‐Barré syndrome from nitrous oxide‐induced neuropathy: A 2‐year, multicentric, retrospective study

Abstract

BackgroundRecreational use of nitrous oxide (N2O) has dramatically increased in recent years, resulting in numerous cases of acute sensorimotor tetraparesis secondary to nitrous oxide‐induced neuropathy (N2On). Challenging clinical features can mimic Guillain‐Barré syndrome (GBS), the main differential diagnosis upon admission. The most sensitive biomarkers for distinguishing between these two conditions remain to be determined.MethodsFifty‐eight N2On patients from three referral centers were retrospectively included over a 2‐year period and compared to GBS patients hospitalized during the same timeframe (47 patients). Collected demographic, clinical, biological, and electrophysiological data were compared between the two groups.ResultsThe typical N2On clinical pattern included distal sensorimotor deficit in lower limbs with absent reflexes, proprioceptive ataxia, and no cranial involvement (56.7% of our cohort). Misleading GBS‐like presentations were found in 14 N2On patients (24.1%), and 13 patients (22.4%) did not report N2O use during initial interview. Only half the N2On patients presented with reduced vitamin B12 serum levels upon admission. A slightly increased cut‐off (<200 pmol/L) demonstrated 85.1% sensitivity and 84.5% specificity in distinguishing N2On from GBS. Only 6.9% of N2On patients met the criteria for primary demyelination (p < 0.01), with only one presenting conduction blocks. A diagnostic algorithm combining these two biomarkers successfully classified all GBS‐like N2On patients.ConclusionsVitamin B12 serum level < 200 pmol/L cut‐off and conduction blocks in initial electrophysiological study are the two most sensitive biomarkers for rapidly distinguishing N2On from GBS patients. These two parameters are particularly useful in clinically atypical N2On with GBS‐like presentation.

What biological markers could be used for diagnosis and monitoring of nitrous oxide abuse?

“…We carefully read the article published in the European Journal of Neurology entitled "How to distinguish Guillain-Barré syndrome from nitrous oxide-induced neuropathy: a 2-year, multicenter, retrospective study" [1]. We aim to propose suggestions regarding the use of vitamin B12 as a biomarker of nitrous oxide (N 2 O) intoxication.…”

“…In N 2 O abuse, vitamin B12 is neither specific (prevalence of about 25% in the general population) nor sensitive: only about 50% of N 2 O consumers exhibit vitamin B12 deficiency [1,3].…”

Nitrous Oxide Abuse: Clinical Outcomes, Pharmacology, Pharmacokinetics, Toxicity and Impact on Metabolism

“…At first evaluation, median lower limb Medical Research Council (MRC) sum score was 26 (normal: 30), median Romberg score was 2 (meaning significant imbalance without falls on Romberg maneuver; from 0 normal to 3 fall), median modified INCAT Sensory Sumscore was 3.5 (normal: 0, maximum score: 16). Another recent study found that in patients with N 2 O-induced neuropathy, at least half of the MRC sum score reduction was due to anterior tibialis weakness in 60.4% of patients [ 10 ]. Additionally, in a Taiwanese study from 2019, authors compared N 2 O abusers and vitamin B12 deficiency patients, and found that the former had more severe motor deficit quantified by the MRC and the Neuropathy impairment Score, predominantly in the lower limbs [ 11 ].…”

“…Many of these patients were treated inappropriately with intravenous immunoglobulins [ 23 ]. To avoid unnecessary treatment, some authors investigated clinical or electrophysiological clues, and established a list of elements to differentiate the two conditions ( Table 1 ) [ 10 , 24 ].…”

“…Many of these patients were treated inappropriately with intravenous immunoglobulins [23]. To avoid unnecessary treatment, some authors investigated clinical or electrophysiological clues, and established a list of elements to differentiate the two conditions (Table 1) [10,24]. Finally, N 2 O abusers seem to have prominent motor super excitability changes and less prominent sensory super excitability changes, suggesting a unique pathological process affecting the paranodal region [11].…”