Marked increase in severe neurological disorders after nitrous oxide abuse: a retrospective study in the Greater Paris area.

BACKGROUND: Recreational nitrous oxide (N2O) use has become more widespread worldwide, leading to an increase in myelopathies and peripheral neuropathies. The aim of this study was to describe clinical and socioeconomical characteristics of severe N2O-induced (NI) neurological disorders (NI-NDs), to determine its incidence in the Greater Paris area and to compare it with that of similar inflammatory neurological disorders. METHODS: We performed a retrospective multicentric cohort study of all adult patients with severe NI-NDs in the neurology and general internal medicine departments of the Greater Paris area from 2018 to 2021. The incidence was compared with that of non-NI-myelitis and Guillain-Barré syndrome (GBS) using a sample of 91,000 hospitalized patients sourced from health insurance data. RESULTS: Among 181 patients, 25% had myelopathy, 37% had peripheral neuropathy and 38% had mixed disease. Most were aged between 20 and 25 years, lived in socially disadvantaged urban areas, and exhibited high rates of unemployment (37%). The incidence of NI-NDs increased during 2020 and reached a peak mid-2021. The 2021 incidence in 20-25-year-olds was 6.15 [4.72; 8.24] per 100,000 persons for NI-myelopathy and 7.48 [5.59; 9.37] for NI-peripheral neuropathy. This was significantly higher than for non-NI-myelitis (0.35 [0.02; 2.00]) and GBS (2.47 [0.64; 4.30]). The incidence of NI-NDs was two to three times higher in the most socially disadvantaged areas. CONCLUSION: The recent increase in recreational N2O use has led to a rise in the incidence of severe NI-NDs, particularly in young adults with low socioeconomic status for whom NI-NDs strongly outweigh similar neurological disorders.

EEG and acute confusional state at the emergency department.

OBJECTIVES: Acute confusional state (ACS) is a common cause of admission to the emergency department (ED). It can be related to numerous etiologies. Electroencephalography (EEG) can show specific abnormalities in cases of non-convulsive status epilepticus (NCSE), or metabolic or toxic encephalopathy. However, up to 80% of patients with a final diagnosis of NCSE have an ACS initially attributed to another cause. The exact place of EEG in the diagnostic work-up remains unclear. METHODS: Data of consecutive patients admitted to the ED for an ACS in a two-year period and who were referred for an EEG were collected. The initial working diagnosis was based on medical history, clinical, biological and imaging investigations allowing classification into four diagnostic categories. Comparison to the final diagnosis was performed after EEG recordings (and sometimes additional tests) were performed, which allowed the reclassification of some patients from one category to another. RESULTS: Seventy-five patients (mean age: 71.1 years) were included with the following suspected diagnoses: seizures for 8 (11%), encephalopathy for 14 (19%), other cause for 34 (45%) and unknown for 19 (25%). EEG was recorded after a mean of 1.5 days after symptom onset, and resulted in the reclassification of patients as follows: seizure for 15 (20%), encephalopathy for 15 (20%), other cause for 29 (39%) and unknown cause for 16 (21%). Moreover, ongoing epileptic activity (NCSE or seizure) and interictal epileptiform activity were found in eight (11%) patients initially diagnosed in another category. DISCUSSION: In our cohort, EEG was a key examination in the management strategy of ACS in 11% of patients admitted to the ED. It resulted in a diagnosis of epilepsy in these patients admitted with unusual confounding presentations.

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

BACKGROUND: Recreational use of nitrous oxide (N2 O) has dramatically increased in recent years, resulting in numerous cases of acute sensorimotor tetraparesis secondary to nitrous oxide-induced neuropathy (N2 On). 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. METHODS: Fifty-eight N2 On 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. RESULTS: The typical N2 On 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 N2 On patients (24.1%), and 13 patients (22.4%) did not report N2 O use during initial interview. Only half the N2 On 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 N2 On from GBS. Only 6.9% of N2 On 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 N2 On patients. CONCLUSIONS: Vitamin B12 serum level < 200 pmol/L cut-off and conduction blocks in initial electrophysiological study are the two most sensitive biomarkers for rapidly distinguishing N2 On from GBS patients. These two parameters are particularly useful in clinically atypical N2 On with GBS-like presentation.

Parasympathetic autonomic dysfunction is more often evidenced than sympathetic autonomic dysfunction in fluctuating and polymorphic symptoms of "long-COVID" patients.

Several disabling symptoms potentially related to dysautonomia have been reported in "long-COVID" patients. Unfortunately, these symptoms are often nonspecific, and autonomic nervous system explorations are rarely performed in these patients. This study aimed to evaluate prospectively a cohort of long-COVID patients presenting severe disabling and non-relapsing symptoms of potential dysautonomia and to identify sensitive tests. Autonomic function was assessed by clinical examination, the Schirmer test; sudomotor evaluation, orthostatic blood pressure (BP) variation, 24-h ambulatory BP monitoring for sympathetic evaluation, and heart rate variation during orthostatism, deep breathing and Valsalva maneuvers for parasympathetic evaluation. Test results were considered abnormal if they reached the lower thresholds defined in publications and in our department. We also compared mean values for autonomic function tests between patients and age-matched controls. Sixteen patients (median age 37 years [31-43 years], 15 women) were included in this study and referred 14.5 months (median) [12.0-16.5 months] after initial infection. Nine had at least one positive SARS-CoV-2 RT-PCR or serology result. Symptoms after SARS-CoV-2 infection were severe, fluctuating and disabling with effort intolerance. Six patients (37.5%) had one or several abnormal test results, affecting the parasympathetic cardiac function in five of them (31%). Mean Valsalva score was significantly lower in patients than in controls. In this cohort of severely disabled long-COVID patients, 37.5% of them had at least one abnormal test result showing a possible contribution of dysautonomia to these nonspecific symptoms. Interestingly, mean values of the Valsalva test were significantly lower in patients than in control subjects, suggesting that normal values thresholds might not be appropriate in this population.

Nitrous oxide-induced predominantly motor neuropathies: a follow-up study.

OBJECTIVES: Recreational nitrous oxide (N2O) abuse is increasingly popular among youth. We report a systematic clinical, electrophysiological and biological follow-up of patients with neuropathy caused by N2O. METHODS: We retrospectively report seven patients with neuropathy attributed to N2O abuse and their comprehensive follow-up. Demographic, toxicological, clinical, biological and electrophysiological data were collected at first and second examination. Functional data were collected at the last evaluation. RESULTS: Seven patients aged 18-30, consuming more than 140 gas-filled balloons (one balloon is filled with approximately 8 g of N2O) per week for over a month, developed a severe, predominantly motor, length-dependent, progressive neuropathy over 3 to 6 weeks. Two-thirds presented associated signs of myelopathy. Distal lower limbs motor deficit and ataxia led to moderate disability. Spinal cord imaging was frequently normal. Nerve conduction studies disclosed an almost exclusively motor axonal neuropathy affecting the lower limbs with active denervation. Homocysteine plasma level was systematically elevated, whereas cobalamin plasma levels were normal in almost all patients. At short-term follow-up after intoxication discontinuation, ataxia and motor deficit only partially resolved despite vitamin B12 supplementation, while active denervation and homocysteinemia decreased. At last follow-up (median 9.2 months, IQR 7.5-10.75), mean ONLS was 2.0 (IQR 2.0-2.0). DISCUSSION: Young patients, with induced N2O motor neuropathy remain disabled after 5 to 14.5 months of gas withdrawal, despite vitamin B12 supplementation. A longer follow-up is needed to fully appraise the severity of these toxic neuropathies.