since mccully1 first reported the relationship between homocysteine and atherosclerosis , hyperhomocysteinemia ( hhcy ) has come to be recognized as an independent risk factor for atherosclerotic vascular disease.2 further , some studies have demonstrated that hhcy might be involved in the pathophysiology of many neuropsychiatric disorders , including brain atrophy , epilepsy , and alzheimer s disease.35 here we report a patient diagnosed with spinal cord demyelination who presented with hhcy and a homozygous mutation of the gene encoding methylenetetrahydrofolate reductase ( mthfr ) c.677c > t . a 53-year - old man was admitted to our hospital with a 7-day history of numbness below thoracic level ( t)10 . cervical and thoracic spinal magnetic resonance imaging ( mri ) demonstrated that the spinal cord was swollen at cervical level ( c)7t3 , which was considered to represent inflammatory lesions ( figure 1a ) . we treated him with a 7-day course of intravenous prednisone 10 mg / day , and however , this was ineffective . to further distinguish it from the subacute combined degeneration of the cord , we tested his serum homocysteine , vitamin b12 , and folate , which revealed normal serum vitamin b12 ( 268.00 pg / ml ; normal range 211.00911.00 pg / ml ) , elevated serum homocysteine ( 44.49 mol / l ; normal range 515 mol / l ) , and decreased serum folate ( 2.70 ng / ml ; normal range 3.117.5 ng / ml ) . using a previously described method,6 we detected genetic polymorphisms rs1801133 ( c.677c > t ) and rs1801131 ( c.1298a > c ) on the mthfr gene , which encodes the methylenetetrahydrofolate reductase , a key enzyme in homocysteine metabolism . the results showed that the patient carried the tt genotype of the mthfr c.677c > t gene variant and no mutation was found in rs1801131 of the mthfr gene ( figure 2 ) . in light of these findings , the patient was treated with intramuscular cobalamin injections ( 500 g / day ) , vitamin b6 orally ( 30 mg / day ) , and folate orally ( 5 mg / day ) . he was discharged on oral cobalamin 500 g / day and oral vitamin b6 30 mg / day . a subsequent spinal mri performed 3 months after symptom onset showed near resolution of the original lesion ( figure 1b ) . mol / l , normal range 515 mol / l ; vitamin b12 544.10 pg / ml , normal range 211.00911.00 pg / ml ; folate 12.20 ng / ml , normal range 3.117.5 ng / ml ) . here we describe a patient with spinal cord demyelination whose symptoms , initial laboratory findings , and imaging results suggested acute myelitis , and in whom prednisone was ineffective . he had neither anemia nor abnormal serum vitamin b12 , and there were no other clinical or laboratory signs ( red blood cell count , mean corpuscular volume , hematocrystallin , and albumin values were normal ) of malabsorption . a spinal mri then showed that the lesion was not confined to the dorsal and lateral spinal cord . further , considering the acute onset and atypical clinical presentation , it seemed inappropriate to make a diagnosis of spinal cord demyelination , at least of a typical type . further examination revealed that , except for the elevated plasma homocysteine and folate deficiency , the patient was homozygous for the gene encoding mthfr c.677c > t . based on these findings , we treated the patient with b vitamins , and his symptoms gradually improved . as an important enzyme in folate and homocysteine metabolism , mthfr c.677c > t polymorphisms have been associated with hhcy.7 many studies have demonstrated that high levels of homocysteine can increase the risk of vascular disease,2,8 but reports of spinal cord demyelination and hhcy are rare . our case suggests that people with mutation of the mthfr gene combined with hhcy and folate deficiency might be highly susceptible to demyelination . first , mthfr mutation - induced disturbances in methylation process can result in a lower methylation rate of myelin basic protein , which plays an important role in the tight compaction of myelin sheath through association with acidic lipids on the cytosolic side of the membrane bilayer , and the decreased methylation of it could cause conformational change and splitting of the myelin sheet.9 jaiser and winston10 have proposed that methylation of myelin protein is limited by disorders of the methylation cycle , which also contribute to both copper deficiency myelopathy and spinal cord demyelination . second , hhcy is proatherogenic and prothrombotic , so increases the risk of ischemic disease , and might indirectly promote demyelination . further potential mechanisms for demyelinating neuropathy may relate to hhcy , which can promote neuronal hypersensitivity to excitotoxicity and apoptosis.5,11 successful treatment with vitamin b supports such speculation . the mutation was found by chance in our patient and we still do not know how it occurred . in addition to heredity , internal and external environmental factors , such as infection and radiation during growth and development , may also contribute to this mutation . however , the possibility that the mthfr c.677c > t genotype , especially in the presence of folate deficiency , could promote hhcy and affect the spinal cord can not be ignored.12,13 in summary , it is important to pay attention to plasma homocysteine , vitamin b12 , and folate levels in the patient with spinal cord demyelination or other myeleterosis . if these are abnormal , treatment with b vitamins should be started promptly , particularly in those who also have mthfr gene mutation .