A Young Woman With Unusual Progressive Neuropathy: A Case of Nitrous Oxide Abuse

Juan Qiu, MD, PhD
Volume 57 - Issue 3 - March 2017

A 23-year-old college student presented with a 1- to 2-month history of progressive ascending numbness and tingling of all her extremities along with an unsteady gait. Her symptoms initially had been transient but had become constant 1 week prior to presentation. She also said that she felt mildly depressed, with a decreased ability to concentrate and declining academic performance. Findings from the review of systems were otherwise negative.

History and Physical Examination

She had a 2-year history of 1 pack/day tobacco use and of moderate social alcohol consumption. She reported having regularly inhaled “laughing gas”—nitrous oxide (N2O)—for the past 6 months, starting with 1 canister once a week and gradually increasing to numerous canisters daily for the past 2 months. She denied the use of other illicit drugs.

She was not sexually active. She ate a balanced diet. Her only medication was vitamin B12 (cyanocobalamin), 5000 µg/d, which she had started taking 1 week prior to presentation.

On physical examination, the patient was alert and oriented to person, place, and time. Her affect and speech were normal. Her gait was grossly ataxic. Sensory deficit was noted in both upper extremities distal to the wrists and in both lower extremities from the toes to just above the knees in a stocking distribution. She was unable to walk heel-to-toe and could not stand with her eyes closed. Muscle strength was 5/5 in all extremities, with deep tendon reflexes normal (2+) and equal. The rest of the physical examination findings were unremarkable.

Pursuing a Diagnosis

In addition to N2O poisoning with associated vitamin B12 deficiency, the differential diagnosis included brain tumor, multiple sclerosis, HIV infection, syphilis, Lyme disease, and alcohol-induced neuropathy.

Magnetic resonance imaging of the brain yielded normal findings. The results of a complete blood cell count were normal, except for an elevated mean corpuscular volume (MCV) of 103.4 µm3 (reference range, 80-100 µm3) and an elevated mean corpuscular hemoglobin (MCH) value of 35.3 pg/cell (reference range, 26-34 pg/cell). The erythrocyte sedimentation rate and results of a comprehensive metabolic panel were normal. Rapid plasma reagin test results were negative for syphilis. Test results for HIV and Lyme disease antibodies were negative, as were serum drug screening results. Her vitamin B12 level was found to be greater than 2000 pg/mL (reference range, 160-950 pg/mL).

Based on these findings and her presentation, the patient received a diagnosis of neuropathy related to the abuse of N2O.

DISCUSSION

N2O, commonly known as laughing gas, is used as a volatile anesthetic in medicine and dentistry, as an engine accelerant, and as an oxidizer in rocket engines. N2O also is used as a propellant in whipped cream dispensers and thus is easily accessible to the public under the name “whippets.” The rate of N2O abuse has increased over the past decade in the United States, and it is one of the most common inhaled substances of abuse, especially among young people.1 However, N2O abuse is underrecognized among patients in the primary care setting.

N2O is a known cause of vitamin B12 deficiency in that it converts vitamin B12 from the active monovalent form to the inactive bivalent form.2 Vitamin B12 deficiency causes myelinolysis—most pronounced in the posterior column of the spinal cord, wherein it is known as subacute combined degeneration (SCD)3—and macrocytic anemia.4 Although this patient did not have anemia, her MCV and MCH were slightly elevated.

No specific diagnostic test exists to detect a person’s use of N2O. Diagnosis is based on the characteristic symptoms of SCD, a history of N2O abuse, a low or low-normal vitamin B12 level, an increased level of homocysteine and/or methylmalonic acid, and clinical improvement upon vitamin B12 supplementation and the cessation of N2O use. Needle electromyography studies may demonstrate nonspecific delayed motor and sensory nerve conduction.5

The neurotoxic effects of N2O include polyneuropathy,6-9 ataxia,6,7 and psychosis.6,10 The neurotoxicity is potentially reversible with the initiation of vitamin B12 supplementation and abstinence from N2O use; significant to complete recovery usually occurs within 14 days to 21 months. Nevertheless, persistent neurologic deficits and deaths have been reported in cases of N2O overdose.6-8

While no standardized method of treatment exists for N2O-induced neurotoxicity, a common approach is intramuscular vitamin B12, 1000 µg/d for a minimum of 5 days, with intermittent dosing until symptoms resolve.5,7-10

This patient had self-treated with a high dose of vitamin B12 1 week prior to presentation. She also delayed having her blood drawn for laboratory testing until the day after she had started the regimen of daily 1000-µg B12 injections. These decisions likely contributed to the higher-than-normal vitamin B12 value in the initial laboratory evaluation results. Homocysteine and methylmalonic acid levels were not included in the patient’s initial laboratory evaluation.

Chronic alcohol abuse also can cause peripheral neuropathy, ataxia, and megaloblastic anemia. However, chronic alcohol abuse was a less likely diagnosis given the patient’s moderate intake of and relative short duration of alcohol use.

THE TAKEAWAY

Unlike other drugs of abuse, N2O abuse is frequently overlooked among patients in primary care. This could be a result of a lack of knowledge among primary care providers about the prevalence of and clinical presentation of N2O toxicity and the fact that some who abuse N2O self-treat with vitamin B12.

Because the complications of N2O toxicity often are reversible with abstinence and vitamin B12 supplementation, primary care providers should be familiar with the clinical presentation of N2O abuse and have high index of suspicion when evaluating patients, particularly young patients, who develop progressive neuropathy. When eliciting a drug-use history, primary care providers should ask about N2O abuse in addition to better known and more often used drugs of abuse such as marijuana, cocaine, and heroin.

Outcome of the Case

The patient was instructed to stop N2O inhalation immediately and was treated with vitamin B12 injections, 1000 µg/d, after which her symptoms gradually improved. At a 2-month follow-up visit, her sensory deficit and ataxia had completely resolved, Romberg test results were negative, and heel-to-toe walking was intact. She also reported improvement in her mood and her ability to concentrate.

Juan Qiu, MD, PhD, is an associate professor in the Department of Family and Community Medicine at the Pennsylvania State University College of Medicine and a family medicine physician at Penn State Hershey Medical Group–Colonnade in State College, Pennsylvania.

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