Article Text
Statistics from Altmetric.com
Among all the possible causes of myelopathy, subacute combined degeneration of the spinal cord, neurological complication of vitamin B12 (cobalamin) deficiency, is one of the less often seen.
GE T2 weighted images of the cervical spine in the midsagittal (380/18/18:TR/TE/FA) and axial (510/15/15:TR/TE/FA) planes at the level of C2 at admission (A, C) and 8 months later after replacement therapy with cobalamin (B, D). At admission cord swelling is evident;high intensity lesions involve the posterior (C, arrows), and to a lesser degree, also the lateral (C, arrowheads) columns of the entire cervical spinal cord. Control examination shows the persistence of only faint hyperintensities in the posterior columns (D, arrow); the volume of the spinal cord is normal.
We report a case of subacute combined degeneration of the spinal cord occurring postoperatively after nitrous oxide anaesthesia in a patient previously undiagnosed to be vitamin B12 deficient.
A 73 year old woman underwent surgery for knee prothesis; forty days later she suffered a femoral fracture due to an accidental fall. Two weeks after surgical stabilisation performed under general anaesthesia with nitrous oxide, the patient complained of gradual onset of loss of gait and weakness of the upper limbs associated with hypoaesthesia of her hands and feet. Neurological deficits progressively worsened so that the patient was admitted to the hospital with severe tetraparesis with bowel and bladder dysfunction. Neurological examination disclosed paraplegia with pronounced loss of strength of the arms, generalised hyporeflexia, and loss of vibration sense; cranial nerves were normal, mental signs were not evident. Magnetic resonance imaging (1.0 T) of the cervicothoracic spine disclosed considerable cord swelling; no abnormalities of signal intensity in T1 weighted sagittal images were evident, whereas abnormally increased signal intensity lesions were detected in T2 weighted images in the posterior cord (figure, A) involving, to a lesser degree, also the lateral columns (figure, C). Brain MRI was unremarkable. Laboratory studies showed macrocytic (mean corpuscolar volume 110 fl, normal 82 to 96 fl; packed cell volume 38%) anaemia (12 g/dl), low concentrations of iron (16 μg/dl, normal 37–145 μg/dl), and vitamin B12 (53 pg/ml, normal>200 pg/ml); folate was within normal values.
Gastric endoscopy disclosed the presence of chronic atrophic gastritis. Iliac crest biopsy showed a hypercellular bone marrow with an appreciable number of megaloblastic forms.
Diagnosis of subacute combined degeneration of the spinal cord was established. Treatment with cobalamin was immediately started (1 mg intramuscularly daily for seven days and thereafter once monthly), with continuous and progressive improvement; vitamin B12 values became normal in two weeks and remained stable. At eight month follow up the patient was able to stand up and walk unassisted; strength was normal in the upper limbs whereas hypoaesthesia with impairment of vibratory sense, even if improved, persisted altered in four limbs. Magnetic resonance imaging showed considerable improvement of previous abnormalities, only faint hyperintensities in the posterior columns of the cervical spinal cord persisting; cord swelling was no longer detected (figure, B, D).
Pernicious anaemia is the most common cause of vitamin B12 deficiency. The spinal cord is usually affected first by vitamin B12 deficiency and often exclusively.
Neurological dysfunctions are due to progressive demyelination, sometimes followed by axonal loss, which starts in the posterior columns and spreads anteriorly involving the lateral and anterior columns; the process begins in the lower cervical and upper thoracic cord, spreading up and down the cord as well. The same neuropathological pattern can be found also in peripheral and optic nerves and, more rarely, in the white matter of the brain.1 2
The progression of pathological changes in the spinal cord is reflected in the course of the disease; this results in a clinical picture consisting of the association of myelopathy and polyneuropathy.
Mental signs are frequent, ranging from irritability, apathy, somnolence, suspiciousness, and emotional instability to a pronounced confusional or depressive psychosis with intellectual deterioration. Replacement therapy with cobalamin is usually followed by almost complete resolution of symptoms.
Demyelination is disclosed at MRI as high signal intensity lesions on T2 weighted images, explained by increased water content.2A slight degree of expansion was seldom noted.3Pronounced, multifocal contrast enhancement of the cervical and thoracic sections of the spinal cord after administration of gadolinium DTPA, indicating blood-CNS barrier disruption, was recently reported.3 Even if involvement of posterior columns is the origin of a characteristic MRI pattern, it is important to notice that similar findings can be found also in cases of purely spinal forms of multiple sclerosis, combined system disease of non-pernicious anaemia type, peripheral neuropathy (as in POEMS syndrome), and other rare pathological conditions.
Our patient, not known as vitamin B12 deficient, developed subacute combined degeneration of the spinal cord two weeks after nitrous oxide anaesthesia given during surgery for stabilisation of a femoral fracture.
At the present time there is growing acceptance that the clinical picture of neurological dysfunction due to contact with nitrous oxide takes the form of vitamin B12 deficiency. This finding is supported by a sizeable body of laboratory investigations indicating that nitrous oxide exerts its biological effects exclusively through interference with vitamin B12, necessary for DNA synthesis and for the maintenance of myelin sheaths.4
The neurological effects of long term nitrous oxide exposure were first reported in 1978 in several people who used nitrous oxide for recreational purpose.4 5 A neurological syndrome identical to that of vitamin B12 deficiency was noted.6
Whereas short term nitrous oxide exposure in healthy people seems to have no appreciable sequelae, the administration of nitrous oxide anaesthesia in patients with unsuspected vitamin B12 deficiency can induce neurological changes, highlighting a previous subclinical condition.
Preoperative vitamin B12 concentrations should be obtained in patients with increased mean corpuscular volume indexes, or affected with gastric mucosa atrophy or previous gastric or intestinal resections. In this way vitamin B12 deficiency would be easily corrected before and after anaesthesia and surgery to avoid possible neurological complications.