Stenosis of Carotid Arteries by Homocysteine: It’s Role in Neurological Events

    

    

    Figure 4: Color-Echography of right SAT. Reduction of flow in extracranial ECA and total obstruction of ICA.
    

Homocysteine

Hcy is an essential amino acid derived from the conversion of Methionine to Cysteine. It is metabolized via two pathwais: remethylation and trans-sulfuration. In the former, Hcy is re-converted to Methionine by a process requiring Methyltetrahydrofolate (derived from folic acid) and vitamin B12 as cofactors. On the contrary, when Methionine is in excess, Hcy metabolism is directed to the transsulfuration pathway, where it is sulfo-conjugated to cysteine by cystationine-B-synthase, having vitamin B6 as a cofactor [17].

Carotid plaques

As previously affirmed, elevated Hcy plasma levels have been indicated as an independent risk factor for atherosclerosis, responsible for carotid plaques. In HHcy-patients, approximately 20%-30% of stable ischemic strokes are due to stenosis of extracranial carotid branches, while intracranial carotid tracts account for 5%-10% of all vascular ischemic brain-events [18].

At morpho-histological examination, carotid plaques consist of lipid core with infiltration of inflammatory cells covered with fibrous cap. Referring to its consistency, a plaque can be stable or instable. This last is characterized by a thin cap with a large lipid core, active inflammation, accumulation of macrophages and platelets’ aggregation. From functional point of view, this can break, inducing a vessels-brain thrombo-embolization [18]. On the contrary, stable plaques are calcified and less inflamed. Obviously, the calcification is a marker of stability [15].

Plaques’ aetiology

Several mechanisms, such as endothelial dysfunction, oxidative stress, platelets’ adhesion and activation of coagulative cascade are responsible for atherosclerotic plaques in HHcy-patients [19-21]. But, HHcy can act also causing a reduction of HDL-lipoproteins for inhibition of Apo-lipoprotein-A (Apo-A) [22-25]. Apart these, some inflammatory events, as expression of adhesion molecules, recruitment of leukocytes, migration of monocyte and others are also present [26]. In these patients, all mechanisms previously described favor carotid stenosis that may be asymptomatic or symptomatic. Asymptomatic carotid artery atherosclerosis is evident by the presence of a significant amount of atherosclerotic buildup. Asymptomaticity refers to CCA or extracranial ICA stenosis without a history of recent ipsilateral acute events. On the contrary, symptomatic carotid artery atherosclerosis may result in intracerebral temporary or permanent accidents. These last are prone to rupture owing to their intrinsic composition, such as a large lipid score, thin fibrous cap, intraplaque hemorrhage and inflammatory cells infiltrates. Some of these (macrophages and T limphocytes) produce proteolytic enzymes and matrix metalloproteinases responsible for collagen breakdown and lesion instability [27-32].

Neurological sequences

The most frequent neurological findings derived from symptomatic carotid plaque rupture are: amaurosis fugax, TIA, minor stroke and stable, ischemic stroke.

Amaurosis fugax is a focal neurological deficit, characterized by a painless temporary loss of vision in one or both eyes. Obscured vision can be due to the papilledema and may last few seconds up to 1-5 minutes [33]. Minor stroke is defined as mild and non-disabling reduction/loss of some neurological functions with incomplete regression of these symptoms [34]. TIA is a sudden and temporary loss of blood flow to an area of the brain, usually lasting a few minutes to 1 hour. Symptoms disappear within 24 hours with complete recovery [35]. On the contrary, stable stroke is characterized from a persistence of the symptoms. The main symptoms that can characterize both cases (TIA and stable cerebral ischemia) are reported in table (Table 1). Ischemic stroke secondary to carotid plaques rupture represents about 20% of all ischemic strokes.

  

    
Main symptoms in TIA and    ischemic stroke 
  
  

    
*Sudden    weakness of an arm/leg on one side of the body;
  
  

    
*Sudden    paralysis of a limb (superior and/or inferior) on one site of the body;
  
  

    
*Loss    of coordination;
  
  

    
*Confusion,    headache, dizziness;
  
  

    
*Numbness    of loss sensation in the face, or in a limb;
  
  

    
*Temporary    loss of vision or blurred vision;
  
  

    
*Inability    to speak clearly or slurred-spech.
  

Table 1: Leading symptoms can be present in TIA (temporarily) and in ischemic
stroke (permanently).

  

    
TOAST subtypes of ischemic    stroke 
  
  

    
1)    Ischemic stroke by large-artery atherosclerosis;
  
  

    
2)    Ischemic stroke by small-artery atherosclerosis;
  
  

    
3)    Stroke of cardioembolic or embolic source; 
  
  

    
4)    Stroke of other determined etiology;
  
  

    
5)    Stroke of undetermined etiology.
  

Table 2: Stroke subtypes of ischemic stroke in relation to etiology.

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Citation: Cacciapuoti F. Stenosis of Carotid Arteries by Homocysteine: It’s Role in Neurological Events. Austin J Cerebrovasc Dis & Stroke. 2020; 7(1): 1084.

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