Subacute combined degeneration of the spinal cord despite prophylactic vitamin B12 treatment

We describe a 35 year-old man presenting with a four-week history of non-painful limb paraesthesias and unsteady gait causing falls. On examination he had an ataxic gait associated with dorsal column sensory loss. He had a medical history of a partial gastrectomy six years prior and anaemia. He had received monthly intramuscular hydroxycobalamin injections since the gastrectomy. Laboratory tests revealed normal vitamin B12 and holotranscobalamin levels, a reduced serum caeruloplasmin of 0.05 g/L (normal: 0.22-0.58 g/L), a copper-to-caeruloplasmin ratio of 1.9 μmol/L (11.0-22.0 μmol/L) and a reduced 24-hour urinary copper concentration of <0.30 μmol/L (0-0.3 μmol/L). Cerebrospinal fluid analysis, nerve conduction studies, electromyography and visual-evoked responses were unremarkable. MRI revealed abnormal hyperintense signal in the cervical dorsal columns. Hypocupric myelopathy was diagnosed and he was treated with daily oral elemental copper. Three months later, his walking and balance had improved although there was no change noted on MRI.     

Magnetic resonance imaging in subacute combined degeneration of the spinal cord

We describe the magnetic resonance imaging (MRI) abnormalities in a patient with subacute combined degeneration of the spinal cord (vitamin B12-deficient myelopathy). T2-weighted images revealed symmetric, high signal abnormalities in the posterior columns of the cervical cord, which resolved following recovery from the disease. Recognition of this MRI pattern is important because this is likely to represent an early, potentially reversible stage of the disease.     

Tethered spinal cord and lipoma. Contribution of magnetic resonance imaging

A 12 year-old boy was investigated for progressive deformity of the left foot developing over 2 years. The foot was hollow with equinus varus and claw toes. Signs of a lesion of left L5 and S1 roots were present and spina bifida at L5 was noted on X-rays. Magnetic resonance imaging (MRI) showed a tethered spinal cord associated with a lipoma at the level of the S1 vertebra. Modes of presentation and physiopathology of disorders related to tethered cords are reviewed and the diagnostic value of MRI is emphasized.     

Subacute combined degeneration of the spinal cord and the vitamin B12 metabolism, a clinical study.

In 28 patients suffering from subacute combined degeneration of the spinal cord, vitamin B12 metabolism was investigated. Two postulates, proving vitamin B12 deficiency and excluding another cause for the clinical symptoms, have to be fulfilled. Two patients had no disturbance in their vitamin B12 metabolism. Seven patients had a distinct vitamin B12 deficiency. In the remaining 19 patients we found a mild vitamin B12 deficiency. Of these patients, 5 had had a subtotal gastrectomy, one had had a low absorption of vitamin B12, and 13 patients we could not find a distinct cause for the vitamin B12 deficiency. It is not impossible that nutritional habits can be hold responsible for this deficiency. The question whether these 13 patients should be treated with vitamin B12 for the rest of their lives is difficult to answer. It is a conditio sine qua non that in the patients with S.C.D. the vitamin B12 metabolism is examined circumstantially. By so doing, it may be possible to detect, in cases with minor clinical signs and symptoms of S.C.D., the cause of their illness.     

Involuntary movements due to vitamin B12 deficiency

Abstract

Deficiency of vitamin B₁₂ produces protean effects on the nervous system, most commonly neuropathy, myelopathy, cognitive and behavioural symptoms, and optic atrophy. Involuntary movements comprise a relatively rare manifestation of this readily treatable disorder. Both adults and infants deficient in vitamin B₁₂ may present with chorea, tremor, myoclonus, Parkinsonism, dystonia, or a combination of these, which may precede diagnosis or become apparent only a few days after parenteral replacement therapy has begun. The pathogenesis of these movement disorders shows interesting parallels to certain neurodegenerative conditions. The clinical syndrome responds well to vitamin B₁₂ supplementation in most cases, and an early diagnosis is essential to reverse the haematological and neurological dysfunction characteristic of this disorder. In this article, we elucidate the association of vitamin B₁₂ deficiency with movement disorders in adults and in infants, discuss the pathogenesis of this association, review previously reported cases, and present a young adult male with severe generalized chorea that showed a salutary response to vitamin B₁₂ supplementation.     

An ultrastructural study of subacute combined degeneration of the spinal cord in vitamin B12-deficient rhesus monkeys.

Prolonged deprivation of vitamin B12 in rhesus monkeys produced changes in the central nervous system that were indistinguishable topographically and histologically from those of human subacute combined degeneration. Ultrastructural studies of early lesions of the spinal cord disclosed a degeneration of myelin characterized by separation of myelin lamellae and formation of intramyelinic vacuoles, leading eventually to complete destruction of myelin sheaths. At a later stage, there was degeneration and loss of axons, and marked gliosis. The theories of pathogenesis of subacute combined degeneration are reviewed in the light of these observations.     

A case of subacute combined degeneration of the spinal cord due to folic acid and copper deficiency

Subacute combined degeneration of the spinal cord (SACD) is a rare neurologic disorder manifesting progressive symptoms of paresthesia and spastic paralysis. Herein we present an autopsy case of SACD caused by folic acid and copper deficiency. A 16-year-old male presented with gradually worsening unsteady gait, and bladder and rectal dysfunction. He had a medical history of T-cell acute lymphoblastic leukemia (T-ALL), diagnosed 1.5?years previously. The patient had undergone chemotherapy, including methotrexate, as well as allogeneic bone mallow transplantation. Laboratory tests revealed normal vitamin B₁₂ and methylmalonic acid concentration, but reduced serum copper, ceruloplasmin and folic acid concentrations. Magnetic resonance imaging revealed symmetrical T2 signal hyperintensities in the posterior and lateral spinal cord. The patient was treated with oral copper, oral folate, and intravenous vitamin B₁₂. A month after this treatment, the patient’s symptoms were unchanged, and 2?months later he died of acute adrenal insufficiency. The pathological findings of the spinal cord were compatible with SACD. Because SACD is usually reversible with early treatment, it should be suspected in high-risk patients undergoing chemotherapy or those who are malnourished with characteristic symptoms of SACD, even in young patients.     

Organic psychosis without anemia or spinal cord symptoms in patients with vitamin B12 deficiency

The authors describe two patients with organic psychosis who had vitamin B12 deficiency and no hematologic or spinal cord abnormalities. They review the literature that supports a causal relationship between B12 deficiency and cerebral dysfunction, as measured by the EEG, and consequent organic mental changes. The authors cite evidence that these EEG and organic mental changes are reversible with B12 replacement. They emphasize that psychiatric manifestations may be the first symptoms of vitamin B12 deficiency and thus antedate anemia and spinal cord disease. They recommend consideration of B12 deficiency and serum B12 determinations in all patients with organic mental symptoms.