A Case report of ischaemic infarct secondary to vitamin B 12 deficiency induced hyperhomocystenaemia

Introduction

Epidemiological research has shown that increased total homocysteine (tHcy) levels are associated with an increased risk of thromboembolic disease; however, controversy still exists over which subtype of stroke is allied to hyperhomocysteinemia. Stroke caused by hyperhomocysteinemia secondary to vitamin B12 deficiency is rare and is a preventable cause of ischaemic stroke.

Case report

A 29year old right handed male presented to Basaweshvar hospital casualty at 9.30 pm on 14/02/18 with complaints of giddines and swaying to right side since 15 days, numbness in left upper limb since 15 days, and history of one episode of seizure at 7 pm on the day of presentation to the hospital.  Generalised tonic clonic seizure (GTCS) associated with uprolling of eyes followed by altered sensorium. There was no fever,headache, or  vomiting. No history of deviation of angle of mouth,nasal  regurgitation,  or  dysphagia.  There was history of diplopia and blurring of vision.  Patient was a smoker since 5years, smoking 10 cigarettes /day.  He was in the habit of consuming alcohol twice a week.  There was no significant past history of any co morbidities, no significant family history of similar complains.

On examination patient was in altered sensorium, BP:100/70mmHg ;PR:86bpm;CNS examination  revealed,pupilb/l equal and reactive,power 4/5  in left upper  limb  and  lower  limb, Deep tendon  reflexes in left upper limb and lower limb 3+,  Plantars  showed a flexor  response.MRI  T2/FLAIR  images revealed acute infarct in right peritrigonal area, right posterior parietal cortex and  subcortical white matter and centrum semiovale. MRA showing hypoplastic A1 segment of right ACA; MRV (Magnetic Resonance Venogram) was normal.

A diagnosis of acute infarct was made. To find out the underlying etiology all relevant investigations (Complete Blood picture, Erythrocyte sedimentation rate, Renal function Test, antiphospholipid antibody, Protein C, Protein S, antithrombin III, serum homocysteine, prothrombin time, aPTT-activated partial thromboplastic time, serum Vitamin B12 levels) were done.  All investigations were normal except serum Vitamin B12 which was reduced (158 pg/ mL; N:  211-911pg/ml) and serum homocysteine level was moderately elevated (52.25micromol/L ; N : <12micromol/L).

Patient was treated with low molecular weight heparin for 5 days, vitamin B12 supplements.  Patient was discharged with vitamin B 12and folic acid supplements with clopidogrel and atorvastatin. Repeat MRI with MRA was done which showed gliosis due to old parenchymal insult in right centrum semiovale, MRA was normal.

Discussion

Stroke is a heterogeneous condition and its subtypes have different pathophysiological mechanisms and etiologies.  Despite a gradual decline in overall stroke death rates in many industrialized countries, stroke remains a leading cause of death and disability in the world¹ Homocysteine (Hcy) is a four-carbon amino acid with a free thiol group, which is formed by demethylation of methionine, an essential amino acid derived from diet. Normal total Hcy (tHcy) concentrations ranges from 5-15 μmol/L in the fasting state.

Hyperhomocysteinemia (HHcy) has been  classified  into  moderate  (plasma  tHcy  concentrations  of  15-30  μmol/L),  intermediate  (plasma tHcy concentrations of 31-100  μmol/L),  and  severe  (plasma  tHcy  concentrations 100  μmol/L).²  Both  acquired  and  genetic  factors  can  have  an  impact  on  plasma  tHcy.  An independent and dose-related relationship between elevated total homocysteine (tHcy) and atherosclerotic diseases has been demonstrated by multiple studies. 

Elevated serum level of homocysteine is a well accepted risk  factor  for  ischaemic  stroke  and  IHD.No  randomized  trial  has  so  far  shown  that  lowering  tHcy  reduces  the  prevalence  of  cerebral  ischemicevents.³ Boushey et al  demonstrated that the administration  of  folate, vitamin  B12,  and  vitamin  B6  decreased  Hcy.⁴

Furthermore, Biswas et. al reported that taking 5 mg folate decreased Hcy significantly.⁵ However, large randomized trials are needed to determine whether decreased tHcy levels by multivitamin therapy can reduce the risk of cardiovascular disease. If a combination of vitamins is found to be effective, this safe, inexpensive, easily administered therapy will probably be widely used throughout the world and have a major effect on public health.