Clinical reasoning: a 20-year-old woman with coma and quadriplegia

Dear editor,

Subacute combined degeneration (SCD) of the spinal cord, which is mainly caused by vitamin B12 deficiency, reveals damage in posterior and lateral columns and peripheral nerves. The CNS and cranial nerves are rarely involved except in children.[1,2] Spinal cord MRI abnormal long T1 and T2 signs in the posterior funiculus has specificity for the diagnosis.[3] There have been many case reports about SCD induced by nitrous oxide anaesthesia or entertainment. Decreased cognitive function is not often reported and consciousness disorder is rare.[4-7] Complete coma was not reported.

A 20-year-old woman presented with a 2-day history of unconsciousness and quadriplegia was admitted to our hospital. After comprehensive examinations, the patient’s diagnosis was still unclear. Surprisingly, her level of consciousness improved after blood transfusion treatments and she admitted to abusing whippets (cream-foaming agents containing compressed nitrous oxide) for half a year. Further tests revealed severe serum vitamin B12 deficiency, and SCD of the spinal cord was diagnosed. Nitrous oxide poisoning and serum vitamin B12 tests should be considered, especially for young patients with consciousness disorder and quadriplegia.

CASE

A 20-year-old woman presented with a 2-day history of unconsciousness and incontinence, and was referred to our hospital after a cranial computed tomography (CT) scan with no positive findings in another hospital. Flunarizine and antibiotic drugs were found in her house. Through the information provided by her mother, we learned that the patient was a college student, renting an apartment alone, who had sought medical treatment half a year ago for lower limb numbness and had felt weakness and anorexia for 2 weeks. A general examination revealed fever (body temperature 38.3 °C), lower critical hypotension (90/60 mmHg, 1 mmHg=0.133 kPa), sinus tachycardia (160 beats/min) and pallor. The neurological examination showed coma, weakness in the upper (3/5) and lower (1/5) limbs (Medical Research Council [MRC] muscle strength score), decreased superficial and deep sense, reduced muscle tone, hyporeflexia in upper limbs and areflexia in lower limbs. Laboratory tests disclosed normal results except anemia (hemoglobin 69 g/L, reference range 115–150 g/L) and coagulation disorder (activated partial thromboplastin time 39.5 s, reference range 22.7–31.8 s).

Diffuse neurological damage was shown by physical examination, the decrease in muscle strength, muscle tone and reflexes in limbs displayed lower motor neuron paralysis, and the state of coma revealed central nervous system (CNS) damage. Because a detailed medical history could not be provided, there was a broad range of diseases we must consider. The common diseases at the patient’s age included intoxication, epilepsy, CNS infection and trauma. Stroke, metabolic encephalopathy and autoimmune diseases would also be considered, and coma might be secondary to hypoxia, hypoglycemia and sepsis. We tend to regard to poisoning, Todd paralysis secondary to epilepsy and atypical CNS infection for suspected diagnosis. Further diagnostic tests were ordered.

Cranial and cervical magnetic resonance imaging (MRI) scans showed little ischemic focus, and chest CT displayed mild hypostatic pneumonia. Intracranial pressure and cerebrospinal fluid tests were normal. The electroencephalogram was mainly composed of θ waves. Electroneurography demonstrated peripheral nerve damage, which was especially severe in the lower limbs.

Endogenous and exogenous intoxication were excluded because relevant tests were normal, the dose of the missing drugs (flunarizine and antibiotic drugs) was not enough to cause intoxication and there was no special smell (such as carbon monoxide) in her apartment. Normal cerebrospinal fluid did not support CNS infection. Epilepsy would not cause peripheral nerve damage. Hypostatic pneumonia secondary to coma was diagnosed.

To treat anemia and coagulation disorder, the patient was given blood transfusion therapy. Surprisingly, her consciousness improved after blood transfusion treatments, despite remarkable cognitive impairment and sopor. She admitted abusing whippets for half a year. Further tests revealed severe serum vitamin B12 deficiency. Her symptoms gradually improved after a daily intravenous injection of 1,000 µg mecobalamin for one week, except for the lower limbs weakness. The patient was referred to medical rehabilitation. At the 2-year follow-up, her consciousness and upper limbs had fully recovered, but she was unable to walk independently.

DISCUSSION

SCD often merges with digestive, blood and mental disorders.[1,2] There are no gold standards to diagnose SCD and physicians have to make a diagnostic decision according to clinical manifestations and auxiliary tests.

The mechanism of SCD is unclear. It is known that vitamin B12 deficiency inactivates two important coenzyme forms (methylcobalamin and adenosylcobalamin) in vivo, which causes myelin sheath synthesis blocked, macrocytic anemia, hypermethylmalonic academia and hyperhomocysteinemia.[1,2] There are many causes of vitamin B12 deficiency, e.g., vegetarianism, internal factor deficiency, gastrointestinal diseases, administration of metformin, congenital genetic diseases and inhaling nitrous oxide.[1,2]

Lower limb numbness of our patient appeared after abusing nitrous oxide and progressively developed weakness and anorexia. We deemed peripheral nerve damage and anemia to be aggravated. Finally, it was serious enough to be in a coma. Blood had the active forms of vitamin B12, so the patient’s consciousness improved after the blood transfusion. Most SCD patients recover after timely vitamin B12 supplementation; otherwise, neural sequelae or even death will occur. Due to severe nerve damage, the lower limb function of our patient did not fully recover.

SCD-induced decreased cognitive function and consciousness disorder is rare. This case enlightens us that nitrous oxide poisoning and serum vitamin B12 tests should be considered, especially for young patients with consciousness disorders and quadriplegia.