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Nitrous oxide is increasingly being used as a recreational drug. Prolonged use of nitrous oxide can have disabling neurological sequelae due to functional inactivation of vitamin B We present three cases illustrating the neurological complications of using nitrous oxide. Two patients developed sensorimotor peripheral neuropathy with demyelinating features with no clinical or imaging evidence of myelopathy, emphasising that not all patients develop subacute combined degeneration of the spinal cord the typical presentation of functional vitamin B 12 deficiency. All patients were treated with parenteral vitamin B 12 with partial recovery, though two were left ificantly disabled.
From a few use drug its first synthesis innitrous oxide has been used as a drug of misuse, nitrous among medical and dental professionals.
It has lately gained popularity as a recreational drug, and its use is widespread. Its toxic effects are mediated by inactivation of vitamin B 12typically producing a myelopathy, though there have been cases of an isolated lower motor neurone syndrome.
Effects of nitrous oxide
We highlight the importance of a detailed recreational drug history and the need to review the diagnosis of functional B 12 deficiency. CASE 1 : A year-old man presented after waking the day with numbness below his knees. There was no preceding illness and no relevant past history.
He worked in retail, smoked cigarettes and drank moderate quantities of alcohol. His symptoms progressed over a few days to paraesthesia in the fingers, and difficulty with walking and performing fine tasks with his hands. He had no pain, no sphincter dysfunction and no autonomic symptoms. On examination, his cranial nerve function was normal.
He walked with a broad-based gait, and Romberg's was positive. His muscle tone was flaccid, and he had mild, symmetrical, distal upper limb weakness finger abduction, thumb abduction with symmetrical mild proximal hip flexion and marked distal lower limb weakness.
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Deep tendon reflexes were absent and plantar responses flexor. Sensation to light touch and pinprick was reduced below the knees, vibration sense was absent below the anterior superior iliac spines and t position sense absent below the ankles.
Initial investigations included normal full blood count, renal, liver, thyroid and bone profiles.
Cerebrospinal fluid CSF was acellular with protein 0. Nerve conduction studies showed slowed motor conduction velocities and delayed or absent F-waves, consistent with a demyelinating neuropathy. Sensory conduction was normal. MR scan of the whole spine was normal. He started treatment with intravenous immunoglobulin 0. We started drug with nitrous vitamin B CASE 2 : A year-old man was admitted to the emergency department with a 6-week progressive history of bilateral lower limb weakness. He had a history of recurrent patellar dislocations for which he attended the emergency department regularly.
He also use a history of depression and self-harm, with cutting behaviours and parasuicide. He took no medication, drank no alcohol and did not smoke. On examination, his muscle tone was flaccid and he had symmetrical proximal and distal weakness of the lower and upper limbs with a glove and stocking sensory loss.
What is nitrous oxide?
Initial blood tests were normal, including full blood count, serum B 12folate and methylmalonic acid. His general practitioner had given a single dose of intramuscular vitamin B 12 the day before admission. CSF examination was normal. He was use with intravenous immunoglobulin 0. His nerve biopsy showed no nitrous demyelination but there was large myelinated fibre loss hence drug conduction velocities with multiple small vessel occlusions and ischaemic pathology without vessel infiltration.
MR scan of brain and spinal cord showed hazy extensive white matter change in both cerebral hemispheres. On this occasion, he admitted to dislocating his patella repeatedly and deliberately with a fist or a hammer in order to attend hospital and to receive nitrous oxide analgesia, which he had returned to doing following his first discharge.
CASE 3 : A year-old woman presented to the emergency department having woken with numbness on the drug aspect of her knees and legs. This progressed down her feet and up her thighs and abdomen over two weeks, changing in character to a burning use. MR scan of brain and whole spine and nerve conduction studies were normal.
CSF was acellular with protein and glucose within normal limits.
Over the next month, her symptoms progressed to involve her right hand; she developed Lhermitte's symptom, urinary urgency and required a stick to walk. On repeat examination, there was proximal upper and lower limb weakness, brisk tendon reflexes with pathological reflexes but absent ankle jerks and mute plantar responses.
Her gait was ataxic with positive Romberg's .
t position sense was absent to the knees and vibration sense to the hips. There was no other illicit drug use. She ate a nitrous use. We started treatment with high-dose intramuscular B Her gait and bladder function improved rapidly, and she subsequently recovered completely. Humphry Davy first described the anaesthetic properties of nitrous oxide in his book in ; already by that time it was being used recreationally. They are often used to inflate balloons, from which the gas is inhaled. There are other modes of misuse, and some patients seek out nitrous oxide, as in the drug case.
Recreational use of nitrous oxide
The infrequent and short-lasting use of nitrous oxide in obstetric anaesthesia as well as intermittent use for dental anaesthesia only becomes a problem in people with borderline-low serum vitamin B 12 nitrous use or if its use becomes persistent and regular. The toxic effects of nitric oxide are mediated through drug of cobalt ions in vitamin B 12 and hence cause its inactivation. This le to reduced recycling of homocysteine to methionine. This prevents methylation of myelin proteins, thus causing use within the central and peripheral nervous systems.
However, demyelination may not be the only pathophysiological mechanism: the second case had no pathological evidence of demyelination but of an ischaemic neuropathy.
In most cases reported in the literature, the neurological presentation associated with nitrous oxide misuse is that of a myelopathy particularly affecting the drug columns—subacute combined degeneration of the spinal cord.
They did, however, have evidence of a sensorimotor neuropathy with use features on neurophysiology. However, in nitrous cases we concluded that the neuropathy was due to nitrous oxide toxicity, given the relationship between escalating use and symptom onset as well as biochemical evidence of functional vitamin B 12 inactivation.
In most cases use nitrous oxide-induced neurological dysfunction, the drug B 12 concentration is low, though it may be normal as in cases 1 and 3 along with haemoglobin concentration and mean corpuscular volume. Vitamin B 12 cobalamin is a cofactor in conversion of methylmalonyl coenzyme A CoA to succinyl CoA and of homocysteine to methionine. High-dose intramuscular B 12 replacement is recommended.
There is limited evidence that replacing methionine nitrous helps, though this is difficult to obtain in the UK at present. Methylmalonic acid and homocysteine concentrations return rapidly to normal after starting B 12 supplements.
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Recovery from nitrous oxide neuropathy may be slow and incomplete: despite high-dose vitamin B 12 replacement, each of our patients has ongoing symptoms after several months. We should communicate this fact to our patients, young people and drugs, and government should take a strong view on restricting this drug's availability.
Physicians should be streetwise enough to know about and understand the effects of the various legal highs on the market, recognise their potential complications and work to educate the population about their harms as well as recognising and treating use affected.
Patient consent: Obtained. Provenance and peer review: Commissioned, externally peer reviewed. National Center for Biotechnology InformationU. Practical Neurology. Pract Neurol.
Author information Article notes Copyright and information Disclaimer. Accepted Feb This article has been cited by other articles in PMC. Abstract Nitrous oxide is increasingly being used as a recreational drug. Discussion Humphry Davy first described the anaesthetic properties of nitrous oxide in his book in ; already by that time it was being used recreationally.
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Figure 1. Figure 2. References 1. Abuse of nitrous oxide. Anesth Analg ; 58 —6. Drugs and the dance music scene: a survey of current drug use patterns among a sample of dance music enthusiasts in the UK. Drug Alcohol Depend ;— Anesth Analg ; 60 —