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Table of Contents
CASE REPORT
Year : 2020  |  Volume : 8  |  Issue : 4  |  Page : 209-211

Hyperhomocysteinemia – A treatable cause of cerebral venous thrombosis in young


Department of General Medicine, MR Medical College, Kalaburgi, Karnataka, India

Date of Submission26-Sep-2019
Date of Decision16-Nov-2019
Date of Acceptance24-Nov-2019
Date of Web Publication23-Oct-2020

Correspondence Address:
Dr. Vivekanand Kamat
Plot 16, 1st Cross Jamakhandimath Layout, Kelageri Road, Dharwad - 580 008, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJIM.AJIM_62_19

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  Abstract 


Mild hyperhomocysteinemia is an established risk factor for deep vein thrombosis. Here, we report a case of a 28-year-old male with complaints of severe headache and vomiting for 7 days, and he also had two episodes of generalised tonic clonic seizures (GTCS) type of convulsions. Magnetic resonance imaging + magnetic resonance venography showed acute infarct with hemorrhagic transformation in the right occipital region and venous thrombosis of the right transverse sinus, right sigmoid sinus, and superior sagittal sinus. All laboratory investigations including protein C, S, and B12levels were found to be normal except for serum homocysteine which was 29.20 μmol/L. After anticoagulation therapy, this young patient completely recovered without any residual neurological deficit. Hence, we suggest that hyperhomocysteinemia should also be a risk factor for cerebral venous thrombosis (CVT). Since this condition can be effectively and safely corrected by drugs, we suggest that homocysteine levels should be routinely determined in patients with idiopathic CVT, and even mildly increased levels corrected pharmacologically, in the hope of reducing the risks associated with this condition.

Keywords: Cerebral venous thrombosis, generalised tonic clonic seizures, hyperhomocysteinemia


How to cite this article:
Kamat V, Harsoor S. Hyperhomocysteinemia – A treatable cause of cerebral venous thrombosis in young. APIK J Int Med 2020;8:209-11

How to cite this URL:
Kamat V, Harsoor S. Hyperhomocysteinemia – A treatable cause of cerebral venous thrombosis in young. APIK J Int Med [serial online] 2020 [cited 2020 Nov 30];8:209-11. Available from: https://www.ajim.in/text.asp?2020/8/4/209/298941




  Introduction Top


Cerebral venous thrombosis (CVT) is a distinct cerebrovascular disorder that mostly affects young adults. It consists 0.5% of all the causes of stroke.

The estimated annual incidence is 3–4 cases per 1 million, with 75% of the adult cases occurring in women.[1]

The clinical symptoms vary and may include severe headache (90%), focal lateralized signs (50%), seizures (40%) as well as behavioral symptoms such as delirium, amnesia, and disturbances in consciousness.

In about 70% of the CVT cases, the cause is identifiable and may be related to inflammatory disease, infection, trauma, neoplasm, autoimmune disease, or oral contraceptives.

CVT may also be associated with genetic prothrombotic conditions, such as deficit of antithrombin III, protein C, or protein S, mutation of the factor V or II genes, resistance to activated protein C, and hyperhomocysteinemia. While more than 80% of all patients have good neurologic outcomes, mortality has been reported to be 5%–30%.[1],[2]


  Case Report Top


A 28-year-old right-handed male came to our casualty with complaints of headache for 7 days and its throbbing type of pain involving the bifrontal and occipital region.

It was associated with projectile type of vomiting 4–6 episodes.

The patient also suffered two episodes of convulsions, Generalised tonic clonic seizures type upon admission in the ward. He is a known smoker and alcoholic for 8 years.

He was not a known case of hypertension and diabetes mellitus. There was no family or personal history of venous thrombosis.

General physical examination and neurological examination were found within the normal limits. Magnetic resonance imaging + magnetic resonance venography (MRI + MRV) showed acute infarct with hemorrhagic transformation in the right occipital region and venous thrombosis of the right transverse sinus, right sigmoid sinus, and superior sagittal sinus [Figure 1] and [Figure 2].
Figure 1: Magnetic resonance imaging T1 image showing thrombosis of the right transverse sinus (April 12, 2019)

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Figure 2: Magnetic resonance venography showing sagittal sinus thrombosis (April 12, 2019)

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All laboratory investigations including protein C, S, and B12 levels were found to be normal except for serum homocysteine which was 29.20 μmol/L [Table 1].
Table 1: Investigations

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The patient was put on low-molecular-weight heparin with folate and B12 supplements.


  Discussion Top


This patient presented with intractable headache and was found to have thrombotic phenomenon involving the brain (CVT) which has been associated with mild-to-high circulating levels of homocysteine.

The Nutrition Committee of the American Heart Association proposed a fasting tHcy concentration of 10 μM/L as a reasonable cutoff level of hyperhomocysteinemia, though there is no general consensus on these cutoff values.[3]

Homocysteine is an intermediary amino acid formed by conversion of methionine to cysteine, which is metabolized by two divergent pathways – transsulfuration and remethylation. Elevation of plasma homocysteine concentrations can occur as a result of genetic defects (e.g., C677T mutation in the methylene tetrahydrofolate reductase [MTHFR] gene), nutritional deficiencies in vitamin cofactors, cigarette smoking, or other factors including some chronic medical conditions and the use of drugs (e.g. fibrates and nicotinic acid).[1]

In this CVT patient, the only risk factor we were able to identify after extensive investigation was an elevated blood homocysteine level because genetic and nutritional factors are two important determinants of homocysteine metabolism.

The common C677T mutation in the MTHFR gene has been associated with a thermo-labile variant and has approximately half-normal activity.[4]

Approximately 10% to 13% of the white population are homozygous for this mutation. On the other hand, because the blood levels of folate, Vitamin B12 and to a lesser extent Vitamin B6, are inversely correlated with the level of homocysteine, anyone with nutritional deficiency of these vitamins may also be at an increased risk of hyperhomocysteinemia.[4]

Hyperhomocysteinemia may be associated with thrombotic processes through several mechanisms, including increased platelet aggregation, increased activity of factor V, prothrombin activation, inhibition of protein C activation, and decreased tissue plasminogen activator binding to endothelial cells.[5]

For the patient discussed in this report, we hypothesize that the cause of CVT may be ascribable to hyperhomocysteinemia. After anticoagulation therapy, this young patient completely recovered without any residual neurological deficit.

MRI + MRV repeated after 1 week of admission showed significant improvement [Figure 3] and [Figure 4]. The anticoagulant, i.e., low-molecular-weight heparin, was discontinued, and he has been kept on folate and Vitamin B12 therapy thereafter to prevent further episodes.
Figure 3: Magnetic resonance imaging T1 image (taken a week later) showing improvement as in decrease in size of thrombus compared to Figure 1 (April 20, 2019)

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Figure 4: Magnetic resonance venography taken a week later showing recanalization of the sagittal sinus after treatment (April 20, 2019)

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Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med 2005;352:1791-8.  Back to cited text no. 1
    
2.
Smith WS, English JD, Johnson SC. Cerebrovascular diseases. In: Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, et al ., editors. Harrison's Principles of Internal Medicine. 20th ed., Vol. 2. New York, NY: McGrawHill; 2018. p. 3085-7.  Back to cited text no. 2
    
3.
Malinow MR, Bostom AG, Krauss RM. Homocyst(e)ine, diet, and cardiovascular diseases: A statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 1999;99:178-82.  Back to cited text no. 3
    
4.
Cantu C, Alonso E, Jara A, Martínez L, Ríos C, Fernández Mde L, et al . Hyperhomocysteinemia, low folate and vitamin B12 concentrations, and methylene tetrahydrofolate reductase mutation in cerebral venous thrombosis. Stroke 2004;35:1790-4.  Back to cited text no. 4
    
5.
Rigamonti A, Carriero MR, Boncoraglio G, Leone M, Bussone G. Cerebral vein thrombosis and mild hyperhomocysteinemia: Three new cases. Neurol Sci 2002;23:225-7.  Back to cited text no. 5
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1]



 

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