A man in his twenties with weakness and numbness in his legs

A man in his twenties was referred to the emergency department due to weakness and numbness in his legs. For around three months, he had been experiencing pain and soreness in his toes, which gradually spread up his legs and towards his thighs. In the last month prior to attending, he also developed reduced strength and numbness in both lower limbs, and he visited the out-of-hours primary emergency care service due to increasing difficulties walking. He had a good level of fitness and played sport actively, but was now experiencing pain on exertion. He had no pain at rest. He had been diagnosed with type I diabetes and started on insulin treatment a few months before onset of the current symptoms. The disease had been detected following an unintentional weight loss of 25 kg (around 20 % of his body weight) over 2–3 months. He was not a smoker, reported moderate alcohol consumption and denied using recreational drugs.

Findings of a systems review and vital signs were normal, and he was afebrile. Neurological examination revealed no alteration in his level of consciousness or cognitive function. He had no cranial nerve deficit. There were no changes in muscle tone, visible atrophy or involuntary movements. He had normal movement and strength in the upper limbs, while examination of the lower limbs revealed symmetrical weakness, particularly in ankle and foot movements (strength grade 4/5). He was not able to sit down or rise from a squatting position without support. Pain only occurred during strength testing.

He was experiencing numbness in the fingertips of both hands, but this could not be reproduced during testing. There was decreased sensitivity to light touch in both lower limbs, most pronounced distally, while examination of other sensory modalities (pain, temperature, vibration, proprioception, two-point discrimination) was normal. Heel-to-shin test revealed ataxia. Deep tendon reflexes were weaker (+) in the upper limbs, but no patellar or Achilles reflexes could be elicited. Plantar reflexes were indifferent. His gait was unsteady and slightly wide-based with inadequate foot rollover. Romberg's test was negative, but he struggled with static weight-bearing (i.e. standing straight upright). There were no skin changes or deformities in the feet.

Standard blood tests for polyneuropathy showed low haemoglobin of 13.1 g/dL (reference range 13.4–17.0) and borderline-high mean corpuscular volume (MCV) of 96 fL (82–98). HbA1c was slightly elevated at 46 mmol/mol (20–42). Renal, hepatic, biliary and thyroid parameters were otherwise normal. He had low levels of vitamin B₁₂ (135 pmol/L (150–650)) and vitamin B₉/folate (6 nmol/L (> 7)). Protein electrophoresis showed no monoclonal protein indicating amyloidosis or haematological malignancy. Anti-ganglioside, anti-myelin-associated glycoprotein (anti-MAG), anti-glutamic acid decarboxylase (anti-GAD) and paraneoplastic antibodies were all negative.

Lumbar puncture the day after admission revealed normal findings for leukocytes (< 4 × 10⁶/L), glucose and protein (< 0.45 g/L) in cerebrospinal fluid, without detection of B. burgdorferi or neurotropic viruses (herpes simplex, varicella zoster, Epstein-Barr and cytomegalovirus).

Neurography, also performed on day 2, found almost no motor response distally in both lower limbs, while electromyography revealed decreased recruitment and sparse denervation activity in all muscles examined in the lower limbs (vastus lateralis, tibialis anterior and medial head of gastrocnemius muscles). Findings of low amplitudes on neurography and denervation activity on electromyography indicated axonal injury. Sensory neurography of the lower limbs showed normal findings, apart from an absence of response from both medial plantar nerves. Findings of neurography and electromyography were normal in the upper limbs, except for slightly prolonged F-responses in general, indicating moderate motor involvement in the upper limbs as well.

On contrast-enhanced MRI of the central nervous system on day 5, a sagittal section of a T2-weighted image showed a subtle high signal intensity in the spinal cord at C2/C3 (Figure 1), and an axial section showed contrast accumulation at the dorsal column (Figure 2). However, there was no uptake of contrast along lumbar nerve roots or the conus medullaris.

CT scanning of the chest, abdomen and pelvis prior to discharge on day 8 found no abnormalities.

Due to the patient's vitamin B₁₂ deficiency, we confirmed that he was not vegetarian, had no gastrointestinal symptoms, and was not using antacids or metformin. On repeat questioning about recreational drugs, he now reported that he used moderate amounts of marijuana, but nothing else.

At this point, the findings consisted of a triad of central and peripheral nerve injury as well as vitamin B₁₂ deficiency without any underlying cause having been detected. While admitted, the patient's clinical presentation had stabilised, and his pain had subsided. This strengthened the suspicion that he had been exposed to something neurotoxic prior to admission. He was again asked if other recreational drugs could be involved, but he denied this. Since vitamin B₁₂ deficiency has been reported in the literature as a possible adverse effect of nitrous oxide, this was proposed as a potential cause. On direct questioning about nitrous oxide, he reported a consumption of up to 2–3 canisters every weekend for the last 6 months. Since nitrous oxide is not illegal, he did not regard it as a recreational drug and had therefore failed to mention it.

The patient was treated with 1 mg vitamin B₁₂ intramuscular injections for five days, followed by maintenance treatment with 2 mg vitamin B₁₂ and 5 mg folic acid supplementation in tablet form. He ceased all use of nitrous oxide immediately and started physiotherapy. At a check-up six months after admission, the patient was found to still have motor impairment of the distal lower limbs on neurography/EMG, but almost entirely normal sensory findings from the soles of the feet. He had made a considerable clinical improvement with good levels of strength and normalisation of sensory function in the lower limbs.