Subacute combined degeneration of spinal cord may develop as a consequence of deficient nutrition and is characterized by progressive demyelination of the dorsal and lateral columns of the spinal cord.
Patients suffering from SCD present with neurological symptoms arising from progressive demyelination of the spinal cord. However, the underlying nutrient deficiency will likely cause a variety of other disturbances. These may or may not affect the patient's life quality, but they are most certainly of diagnostic value. Symptom onset is insidious and complaints aggravate slowly.
Initially, spinal cord damage may manifest in form of sensory deficits, particularly in form of symmetric paresthesias and numbness. Pall hypoesthesia is considered an important early symptom of SCD. Proprioception may be significantly disturbed and with regards to affected parts of the body, patients may lose their position sense. Reflexes are generally blunted or absent, but hyperreflexia has also been reported. The latter suggests lesions of the corticospinal tract. If the legs are affected - which is most commonly the case - gait disorders may turn into ataxia and finally into the inability to stand. Spastic paraparesis and tetraparesis or tetraplegia are symptoms of advanced SCD.
Because the vast majority of SCD patients suffer from vitamin B12 deficiency, they also develop anemia (and consequent fatigue, weakness, palpitations, and dyspnea), glossitis, abdominal pain, and diarrhea. They may lose weight. Copper deficiency, folic acid deficiency and vitamin E deficiency may cause anemia and manifest similarly .
Magnetic resonance imaging and laboratory analyses of blood samples are the mainstays of SCD diagnosis. The former aims at a direct evaluation of spinal cord and brain damage. Characteristic findings are symmetric hyperintense lesions of the dorsal and lateral columns of the spinal cord; in most cases, such lesions are first recognized in the thoracic spinal cord. Similar pathological alterations may also be observed in the brain.
Analyses of blood samples should include a complete hemogram and measurement of serum levels of vitamin B12, copper, folic acid, and vitamin E. Values below reference ranges indicate nutrient deficiencies. However, in the case of functional nutrient deficiencies, serum concentrations of the respective nutrients will not be altered. Here, it is of utmost importance to consider the entirety of anamnestic data, findings of physical examination and diagnostic imaging as well as hematological alterations before confirming or ruling out a diagnosis :
Resolution of abnormal findings on magnetic resonance images, hemogram and blood biochemistry is a well-suited parameter to assess a patient's response to therapy. Even after finishing drug therapy, the respective exams should be carried out every three months until a complete resolution is achieved or no further improvement is expected. It may take more than a year to reach this point. Of course, remission of clinical symptoms is still the most important sign of therapeutic success.
Treatment consists in supplementation of the deficient nutrient, most commonly vitamin B12. Most physicians prefer to start by intramuscular application of 1 mg vitamin B12 per day for one or two weeks before prolonging the administration intervals to a week or month. Maintenance doses may be given.
Common protocols are:
Some patients may require life-long supplementation of vitamin B12. If vitamin B12 deficiency results from an underlying, curable disease, the latter should be adequately treated. In the case of pernicious anemia, high-dose supplementation is necessary to increase the absolute amount of vitamin B12 that is absorbed in the terminal ileum. This therapeutic approach is based on the fact that about 1% of orally administered vitamin B12 is absorbed as intrinsic factor-independent .
Patients should be queried regarding their dietary habits and need to be advised to keep a healthy, balanced diet.
Prognosis largely depends on disease progress at the time of diagnosis. The underlying nutrient deficiency is easily treated in most cases, but extensive damage to the central nervous system may be irreversible and result in permanent disability .
The most common cause of SCD is vitamin B12 deficiency. This vitamin serves as a cofactor for enzymes that affect myelin synthesis, which is why the corresponding nutrient deficiency leads to progressive demyelination and SCD. Vitamin B12 deficiency, in turn, may be caused by malabsorption due to intrinsic factor-related pathologies. In pernicious anemia, intrinsic factor secretion is reduced and it is not uncommon to see patients who suffer from both SCD and pernicious anemia. Malabsorption may also result from gastrointestinal disorders like celiac disease, Crohn disease or tropical sprue. Functional vitamin B12 deficiency may also lead to SCD but constitutes a diagnostic challenge since serum vitamin B12 levels are not altered in affected individuals . Moreover, vegetarians, vegans and people who underwent gastric surgery have increased risks of vitamin B12 deficiency .
Further causes of SCD are a copper deficiency, folic acid deficiency and vitamin E deficiency . Patients who receive enteral nutrition, who underwent gastric surgery or supplement large amounts of zinc are predisposed for copper deficiency. Dietary deficiency, pregnancy, and lactation are commonly associated with folic acid deficiency.
Of note, a plethora of legal and illicit drugs, either prescribed to treat comorbidities or used recreationally, may provoke the nutrient deficiencies described above.
Besides nutrient deficiencies, the following conditions have been related with SCD :
SCD is considered an uncommon disease and the lifetime risk of developing this demyelinating disease has been estimated to be about 1 in 10,000. These values are in accordance with those reported for pernicious anemia.
Minors and young adults are rarely affected; incidence rates increase when considering people in their fifth decade of life and peak in the elderly. However, this information should be interpreted with care: In most cases, years may pass from disease onset until first clinical symptoms occur. SCD prevalence among young people may indeed be similar to other age groups, but the diagnosis of the disease may not be easy during early stages .
Vitamin B12, sometimes also referred to as cobalamin, serves as a cofactor for methylmalonyl coenzyme A mutase and methionine synthase.
The former catalyzes the conversion of methylmalonyl coenzyme A to succinyl coenzyme A. Accumulation of methylmalonyl coenzyme A due to reduced enzymatic activity inhibits myelin synthesis and a variety of other metabolic processes . Therefore, vitamin B12 deficiency is associated with progressive demyelination and SCD.
As its name implies, methionine synthase is required for the synthesis of methionine, an essential amino acid. This enzyme transfers a methyl group from 5-methyltetrahydrofolate to homocysteine, a reaction that yields tetrahydrofolate and methionine. Thus, vitamin B12 deficiency leads to accumulation of homocysteine and inadequate synthesis of tetrahydrofolate and methionine. Homocysteine induces endothelial dysfunction ; tetrahydrofolate plays an important role in DNA synthesis. Insufficient synthesis of tetrahydrofolate limits cell proliferation and cells with a rapid turnover - hematopoietic stem cells for instance - will primarily be affected . Cells are unable to progress from the G2 stage into the mitosis stage, continue to grow but don't divide. This is what leads to megaloblastic anemia.
Of note, dietary folic acid is converted into 5-methyltetrahydrofolate and therefore, folic acid deficiency provokes symptoms very similar to those of vitamin B12 deficiency. Supplementation of folic acid may even cure vitamin B12 deficiency-induced anemia, but will rarely improve neurologic pathologies except for those rare cases of SCD due to folic acid deficiency.
Most people are able to prevent nutrient deficiencies by keeping a healthy, balanced diet. Vegetarians and vegans have particularly high risks of consuming little amounts of vitamin B12 and should consider the possibility of supplementing their diet.
Patients who suffer from nutrient deficiencies due to malabsorption or other, non-curable diseases should undergo regular blood testing.
Subacute combined degeneration of spinal cord (SCD) is a demyelinating disease triggered by deficiencies of certain nutrients. The vast majority of cases are associated with vitamin B12 deficiency. However, lack of copper, folic acid and vitamin E have been related with very similar clinical pictures . These nutrients are required for myelin synthesis and for a variety of other metabolic processes. Thus, patients may present with complex clinical pictures of neurologic, psychiatric, gastrointestinal and hematological disorders.
With regards to neurological symptoms, sensory deficits predominate. The legs are more frequently involved than the arms. Initially, patients experience paresthesias and numbness, loss of vibration and position senses. The latter may provoke gait disturbances and ataxia before sensory alterations are consciously perceived. SCD follows a progressive course and may lead to spastic paralysis. It may take several years until such severe symptoms occur .
As soon as the underlying nutrient deficiency is identified, causative treatment can be initialized. Most SCD patients respond well to dietary supplementation. However, extensive spinal cord damage may not be reversible and residual neurological deficits will remain in a significant share of cases. Concomitant symptoms like anemia, glossitis, abdominal pain and diarrhea rapidly remit under adequate therapy.
The direct cause of SCD is the progressive demyelination of the spinal cord, i.e., nerves passing through the spinal cord lose their myelin sheath. This myelin sheath serves as a layer of insulation and is essential for saltatory conduction.
In SCD patients, myelin synthesis is disturbed because nutrients required for distinct metabolic steps are lacking. Most SCD patients have a vitamin B12 deficiency, but the lack of copper, folic acid or vitamin E may also cause this disease.
Symptom onset is insidious. Most patients initially perceive tingling sensations or numbness in their limbs, most often in their legs. They may lose vibration and position sense and these complications lead to gait disorders and ataxia. Late stage SCD may manifest in form of partial or complete paralysis of legs and possibly arms.
Some patients claim visual impairment.
Spinal cord and possibly brain damage are diagnosed by means of magnetic resonance imaging. Additionally, laboratory analyses of blood samples will be performed to determine the underlying nutrient deficiency. Measurement of serum levels of vitamin B12, copper, folic acid or vitamin E is important when deciding for an optimum therapeutic approach.
Further diagnostic measures may become necessary to define the cause of a determined nutrient deficiency.
SCD treatment consists of supplementation of the nutrient whose shortage is interfering with nerve function. Thus, most SCD patients will receive vitamin B12 - initially in form of daily intramuscular injections, later in form of oral medication. Some patients may require dietary supplementation for life.
Maintenance of a healthy, balanced diet is of great importance to prevent diseases like SCD and to avoid relapses.