Atormac
Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 1698  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Search
 
  » Next article
  » Previous article 
  » Table of Contents
  
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
  »  Article in PDF (90 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

 
  In this Article
   References

 Article Access Statistics
    Viewed2509    
    Printed100    
    Emailed0    
    PDF Downloaded78    
    Comments [Add]    

Recommend this journal

 


 
INVITED COMMENTS
Year : 2006  |  Volume : 54  |  Issue : 1  |  Page : 51-52

Invited Comments


Departments of Neurology and Neurophysiology, Pandy Kalman County Hospital, H-5700 Gyula, Semmelweis 1, Hungary, H-5600 Bekescsaba, Pipacs koz 9, Hungary

Correspondence Address:
Login to access the Email id

Source of Support: None, Conflict of Interest: None


Rights and PermissionsRights and Permissions



How to cite this article:
Szolnoki Z. Invited Comments. Neurol India 2006;54:51-2

How to cite this URL:
Szolnoki Z. Invited Comments. Neurol India [serial online] 2006 [cited 2019 Nov 14];54:51-2. Available from: http://www.neurologyindia.com/text.asp?2006/54/1/51/24705


A strong association has been suggested between the folic acid level and the occurrence of a congenital neuronal tube defect.[1] Various epidemiological studies have confirmed the presumption that periconceptional folic acid supplementation can reduce the frequency of such a defect.[2] This has led to the introduction of an extensive program of prevention in the United States, in which cereal food productions are fortified with folic acid.

There are several other aspects of the daily folic acid intake in adults, which can influence the homocysteine level,[3],[4] a high homocysteine level being a strong predictor of death in patients with coronary artery disease.[5] A paper published in this issue of the journal raises the importance of folic acid intake on the basis of genotype against ischaemic stroke too.[6]

I approach the importance of the folic acid supply from the aspect of the disability caused by a cognitive deficiency. In addition to Alzheimer disease, the frequent causes of a cognitive deficiency can be ischaemic stroke and leukoaraiosis.

Leukoaraiosis is indicated by bilateral patchy or diffuse areas of hypointensity in CT scans, or hyperintensity in T2-weighted MRI scans. It involves only the white matter. One-quarter of subjects aged 65 years or over are affected by some degree of white matter changes. Leukoaraiosis can cause a mild cognitive impairment or severe subcortical dementia. Ischemic demyelination and small-vessel disease seem to be features of the underlying pathological process of this entity. Age and hypertension have been proved to be the main clinical risk factors. Diabetes mellitus and cardiac diseases, which can be associated with cerebrovascular diseases, have not proved to involve direct significant risks of leukoaraiosis directly. Clinical observations have suggested that vasoregulatory disturbances and chronic cerebral hypoperfusion may be the pathological states which can lead to leukoaraiosis.

A number of genetic susceptibility factors for leukoaraiosis have been put forward. With the assumption of polygenic etiological factors, it has been demonstrated that the 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-T mutation and angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism play important roles in leukoaraiosis. Both the ACE D and MTHFR 677T alleles are frequent in the normal population, but can be associated with an unfavorable vasoregulatory effect on the circulatory system. The former can lead to an elevated angiotensin II level in the serum and the tissues and the latter to an elevated serum homocysteine level. Leukoaraiosis has been stated to be positively correlated with the serum homocysteine level and inversely correlated with the serum folate level. It has been earlier reported that a clustering of the homozygous MTHFR 677TT and ACE D / D mutations in one person can mean a moderate (approximately 5-fold risk) but highly significant ( P <0.0005) risk of leukoaraiosis.[7] Alone, however, neither of the mutations proved to be a risk factor for leukoaraiosis. It has also been suggested that low doses of ACE inhibitor drugs can reduce the risk of stroke or a cardiovascular event. The finding of the interaction of two unfavourable mutations that alone are insignificant might open up a new clinical strategy for the prevention or treatment of leukoaraiosis. Although further clinical studies are clearly needed to investigate the clinical and preventive effects of different doses of folic acid supplementation on leukoaraiosis associated with a cognitive disability, I suggest regular folic acid supplementation in the middle aged and elderly if they carry the ACE D/D and homozygous MTHFR 677TT mutations together. It has been demonstrated that this genotype constellation implies a moderate genetic risk for leukoaraiosis.[7] The further question arises of whether co-administration of an ACE inhibitor and folic acid could reduce occurrence of leukoaraiosis.

Ischaemic stroke is a very regularly occurring entity underpinned by several genetic factors and clinical risk factors. The MTHFR 677TT genotype and decreased serum folic acid level can be risk factors for ischaemic stroke. The folic acid supplementation can be a preventive measure against ischaemic stroke too.[6] This question is also open and needs further studies. A regular folic acid intake seems to be important health issue in a wide range of nations in general. Its supplementation against general circulatory disorders raises hopes in a broad health issue. The new findings on the roles of folic acid and the genetic background might permit a selective prevention of leukoaraiosis and ischaemic stroke hence the cognitive decline they cause.

 
  References Top

1.Hibbard ED, Smithells RW. Folic acid metabolism and human embryopathy. Lancet 1965;1:1254.  Back to cited text no. 1    
2.Czeizel AE, Dudαs I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Eng J Med 1992;327:1832-5.   Back to cited text no. 2    
3.Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthew RG, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Gen 1995;10:111-3.  Back to cited text no. 3    
4.Welch GN, Lascalzo J. homocysteine and atherothrombosis. N Engl J Med 1998;338:1042-50.   Back to cited text no. 4    
5.Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997;337:230-6.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Panigrahi I, Chatterjee T, Biswas A, Behari M, Choudhry VP, Saxena R. Role of MTHFR C677T polymorphism in ischemic stroke. Neurol India 2006;54:48-52.  Back to cited text no. 6    
7.Szolnoki Z, Somogyvαri F, Kondacs A, Szabó M, Fodor L. Evaluation of the roles of common genetic mutations in leukoaraiosis. Acta Neurol Scand 2001;104:281-7.  Back to cited text no. 7    




 

Top
Print this article  Email this article
Previous article Next article
Online since 20th March '04
Published by Wolters Kluwer - Medknow