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Quick reference : Symptoms: paresthesia of the lower extremities and… : Emergency medicine news


subacute combined degeneration, nitrous oxide


A 26-year-old man presented with three months of progressive, bilateral, tingling paresthesias in the lower limbs, which had become painful over the previous three days. He also had an unsteady gait and needed help walking.

The patient had been involved in a car accident a year earlier, but had no recent trauma or new back pain. He also had no recent diarrhea, viral syndrome, vaccinations, fever, bowel or bladder incontinence, or history of malignancy or intravenous drug use. He reported previous alcohol and cocaine use, current daily marijuana use, and frequent recreational nitrous oxide use.

He was afebrile at the time of presentation and his vital signs were within normal limits. His midline spine had no tenderness or deformity. His neurological examination was notable for decreased strength (4/5) in his lower extremities only with intact light touch sensation and absent proprioception and vibrational sense in his bilateral big toes. He had an ascending Babinski sign, normal rectal tone and stool sensation.

His post-void residual was 40 mL, and his laboratory evaluation was notable for a hemoglobin level of 13.1 g/dL with macrocytosis (a mean corpuscular volume of 98.6 fL) and a B12 level of 160 pg/mL (normal: > 232 pg/mL). His thyroid-stimulating hormone, folate, electrolytes, kidney function, and liver function were within normal limits. HIV and syphilis tests were negative.

Magnetic resonance imaging of the patient’s spine was ordered to confirm the cause of his symptoms. What is the diagnosis?

Find a case discussion on the next page.

Diagnosis: SCD due to chronic use of nitrous oxide

Subacute Combined Degeneration (SCD) is a neurological condition involving demyelination of the dorsal and lateral columns of the spinal cord. Demyelination occurs as a sequel to a functional deficiency of vitamin B12, an important cofactor in the myelination process. Vitamin B12 deficiency is more common in patients with longstanding veganism or malabsorption syndromes, but an increase in recreational use of nitrous oxide has also contributed to the number of sickle cell disease cases. (StatPearls [Internet]. treasure island [FL]: StatPearls Publishing; June 2022;

Nitrous oxide, commonly known as laughing gas, is a colorless gas that dentists began using as an anesthetic in the 1940s. It is known recreationally as whippets or nos, and has gained popularity among teenagers (mainly males) and young adults for its immediate euphoric high that wears off quickly. (Neurotox Res. 2021;39[3]:975.) Individuals can take multiple hits in one session given its multi-minute effects. No dose-dependent relationship has been established, making it difficult to quantify how much nitrous oxide can be used before symptoms of sickle cell disease appear. (J.Neurol. 2022;269[5]:2720.)

Nitrous oxide oxidizes cobalt ions in B12, inactivating methionine synthetase. The result is an inability to convert homocysteine ​​to methionine, an essential component of nerve myelination. Patients with SCD have several symptoms related to the affected pathways. Damage to the dorsal column can lead to impaired proprioception and vibration, while damage to the lateral column leads to weakness and spasticity. (StatPearls [Internet]. treasure island [FL]: StatPearls Publishing; June 2022;

Involvement of these pathways means that most patients with SCD initially present with lower extremity weakness, numbness, or unsteady gait. (toxic. 2022;10[3]:112; Symptoms usually progress slowly over a period of weeks, and SCD can also be associated with incontinence and sexual dysfunction in severe cases. (J Neurol Sci. 2020;414:116817.) Physical examination findings reveal sensory loss, decreased proprioception, and decreased tendon reflexes, particularly at the ankle. Patients with SCD may have a positive Romberg’s sign and an ascending Babinski’s sign. (StatPearls [Internet]. treasure island [FL]: StatPearls Publishing; June 2022;

A detailed history is needed to identify nitrous oxide use or dietary risk factors for SCD. History and laboratory studies can help distinguish sickle cell disease from other conditions such as Guillain-Barré syndrome, neurosyphilis, HIV-associated vacuolar myelopathy, and other myelopathies such as transverse myelitis and multiple sclerosis. (StatPearls [Internet]. treasure island [FL]: StatPearls Publishing; June 2022;

The short half-life of nitrous oxide makes it difficult to identify using laboratory studies. It creates a functional vitamin B12 deficiency, so levels of this vitamin can sometimes be normal in patients with SCD due to the use of nitrous oxide. (toxic. 2022;10[3]:112; Studies have shown that a high homocysteine ​​level is a more sensitive lab value, but it is possible to obtain a level in most facilities. (J.Neurol. 2022;269[5]:2720.) MRI results usually show symmetrical T2 hyperintensity in the dorsal columns, most often in the cervical region. (J Neurol Sci. 2020;414:116817.)

Treatment consists of B12 supplementation and stopping the use of nitrous oxide. Supplementation is aggressive, usually consisting of 1000 mcg injections several times a week for the first two weeks, then once a month until symptoms improve. Patients are usually kept in the hospital for further testing and initial injections of cyanocobalamin. The prognosis is variable, with some patients improving in three to 12 months with treatment, but some neurological deficits may be irreversible. (StatPearls [Internet]. treasure island [FL]: StatPearls Publishing; June 2022;

MRI of our patient’s spine showed long segment signal abnormalities in the dorsal aspect of his thoracic spinal cord, which were of concern for subacute combined degeneration. He was admitted to the neurology ward where he received a brief course of intramuscular B12 and physiotherapy prior to discharge with an aggressive oral B12 supplementation plan, outpatient physiotherapy and support services for brain disorders. substance use. He is currently ambulatory with the aid of a cane.

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Dr Santanais a second-year emergency medicine resident at LAC+ USC Medical Center in Los Angeles. Follow her on Twitter@maria_santana3. Dr Burkholderis assistant professor of clinical emergency medicine at the Keck School of Medicine at the University of Southern California. Follow him on Twitter@tayburkholder. Read the quick reference columns at