Stroke is an unhelpful word

Introduction

Stroke is a commonly used word describing a very common condition. It is used by patients, healthcare professionals and the general public. It is a common cause of death and disability. It has its own clinics and wards, charities, books, training programmes and royal college guidelines. But what is the anatomy and pathology of stroke, and is it useful to distinguish one type of cerebrovascular disease from another?

In this article we explore just some of the very obvious and relevant differences between large artery disease and small vessel disease to highlight the inadequacy of the term ‘stroke’.

What is a stroke?

Stroke is defined by the World Health Organization as a clinical syndrome consisting of “rapidly developing clinical signs of focal (at times global) disturbance of cerebral function, lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin”.¹

When thinking about diseases of vascular origin affecting the brain there are two broad categories of vessel to consider: the large and small vessels. There are important and clinically relevant differences in their anatomy and areas of supply, which inform the diagnostic and treatment approach at the bedside.

Vessel architecture

The anterior and middle cerebral arteries (ACA and MCA), both branches of the internal carotid artery, are examples of large cerebral vessels; they branch and usually have considerable anastomotic connections (with one another and with the distal branches of the posterior cerebral artery) which can sometimes maintain adequate perfusion in the presence of an occlusion.

In stark contrast, the lenticulostriate perforators, which are branches of the proximal ACA and MCA and which vary considerably in number within the population,² are much smaller end arteries (i.e. they have no anastomotic potential), occlusion of which invariably results in infarction.³

Whilst all of these arteries have walls composed of three layers – the tunica intima, tunica media and tunica adventitia – they differ considerably in size. The diameters of the middle and anterior cerebral arteries are 3400μm and 2200-2400μm respectively.^4,5 The lenticulostriate perforators vary in diameter from 80-1400μm².

Despite these differences it has been found that the proportion of vascular smooth muscle (VSM) in the vessel walls remains relatively similar in both types of artery.^6,7 However the smaller lumen of the lenticulostriate perforators may explain the association of hypertension with occlusive ‘small vessel disease’.³

It is recognised that hypertensive patients are more susceptible to VSM degradation in the lenticulostriate perforators, making them prone not only to rupture but also to occlusion possibly because the lumen is so easily compromised by changes in the integrity of the vessel wall.⁶

Area of supply: ACA and MCA

In common with all neurological diseases the nature of the presenting problem is related more to the area of involved brain than the disease affecting it.^8,9

The anterior cerebral artery (ACA) and middle cerebral artery (MCA) originate from the internal carotid artery, medially and laterally respectively,¹⁰ and the lenticulostriate perforators arise from their proximal segments.¹¹  The ACA supplies medial aspects of the frontal lobe and superior aspects of the medial parietal lobe, including the medial aspects of the motor and somatosensory cortex, and the supplementary motor  and somatosensory cortex.¹²

The MCA supplies the more lateral aspect of the superior frontal lobe, the parietal lobe and also the inferior temporal lobe.¹²  This includes Broca’s and Wernicke’s area on the dominant side,¹¹ as well as the lateral aspects of the motor cortex and somatosensory cortex.¹¹

The homunculus depicts the areas of motor and sensory cortex according to their anatomical correlates in the limbs, trunk and head.

The medial aspects of each hemisphere, i.e. the leg area of motor and sensory cortex, is supplied by the ACA,¹¹ which explains why an anterior cerebral artery infarct causes contralateral hemiparesis deficits affecting the leg more than the arm. Other frontal lobe features e.g social disinhibition, agitation, lack of motivation and behavioural abnormalities¹¹ may also occur depending on the extent and location of the lesion.

The key thing to remember with an occlusion of the MCA main stem is that symptoms will be mainly in the contralateral arm and face, rather than the legs.¹¹ As well as weakness patients may have unusual types of sensory loss as a result of infarction of sensory cortex in the parietal lobes, including dysgraphaesthesia (a loss of the ability to identify numbers drawn in the palm by the examiners finger), a loss of joint position sense,and impaired two-point discrimination.¹³ In addition, patients may experience a contralateral homonymous hemianopia or a syndrome of contralateral neglect.

In patients with left MCA occlusions the loss of normal language function is devastating.  Language is preserved in right MCA occlusions, however the loss of spatial awareness and skills dependent on an appreciation of topography can be just as devastating as the dysphasia of a left hemisphere problem.¹³

Area of supply: the lenticulostriate perforators

The lenticulostriate perforators do not supply cerebral cortex, which is why small vessel disease is not usually associated with cortical deficits such as dysphasia and agnosia. They supply subcortical structures including the putamen, caudate nucleus, globus pallidus and crucially the internal capsule the posterior limb of which is formed by the descending corticospinal fibres (which form the anterior 2/3rd) and the ascending sensory neurones (which form the posterior 1/3^rd).¹²

Therefore occlusion of these vessels causes a devastating contralateral weakness and/or sensory loss without an accompanying cortical deficit e.g. dysphasia. The motor or sensory loss¹¹ typically involves the arms, legs and face to a roughly similar extent¹³ in contrast to ACA and MCA occlusion. The sensory loss seen with a lenticulostriate perforator occlusion involves temperature, pain, vibration and touch (as a result of involvement of the sensory neurones in the internal capsule) in contrast to the loss of discriminative sensory functions (graphaesthesia and two point discrimination) seen in ACA and MCA occlusions (as a result of involvement of the cerebral cortex).

Occlusion of lenticulostriate arteries produces what are called lacunar infarcts, and as described here the resulting lacunar syndromes may be purely motor, purely sensory, mixed motor and sensory, or sometimes involve some ataxia of the affected limbs leading to the term ataxic hemiparesis.¹⁵

	LARGE VESSELS: Middle Cerebral Artery and Anterior Cerebral Artery	SMALL VESSELS: Lenticulostriate perforators
Vessel	Large MCA-3400μm ACA- 2200-2400μm	Small (80-1400μm)
Structure	Tunica Media Concentrated sheet of elastic tissue- IEL. (3) Many layers of concentrically arranged smooth muscle layers (7) VSMC-72% of tunica media (7)	Tunica Media Fewer layers of concentric SM, around 3-4 layers in smaller LSP’s (3) VSMC- 80% of tunica media (6)
Supply	ACA medial aspect of the frontal lobe and sup medial parietal lobe MCA lateral superior frontal lobe, inf temporal lobe and parietal lobe	Subcortical structures:   putamen   caudate nucleus   globus pallidus   internal capsule
Clinical Features	ACA- CL hemiparesis (leg>face and arms) CL hemiplegia, sensory loss, primitive reflexes, frontal lobe features MCA- Hemiparesis (face and arms>legs), sensory loss (higher order) , syndrome of unilateral neglect, Broca’s aphasia, homonymous hemianopia	Hemiparesis (leg=face= arm) Primary sensory loss Lacunar syndromes pure motor ataxic hemiparesis pure sensory mixed sensorimotor
Pathology	Atherothromboembolism Cardio-embolism	Lipohyalinosis Less commonly : atherothromboembolism, vasculitis hypoperfusion hypercoagulability arterial dissection and CADASIL

Table 1. Important differences between the large and small cerebral vessels

Pathology

A number of pathological processes can cause cerebrovascular ischaemia¹¹ but the vast majority of patients are affected by embolic disease from proximal donors, usually the heart and great vessels, and by a few diseases which involve the small vessels.

Large vessel pathology

The main pathological process affecting these vessels is atherothromboembolism.

An atherothrombotic plaque is a hardening and thickening of the vessel wall, promoted by factors including vessel tortuosity and branching.¹⁷ The distribution of lesions is determined partly by shear stress and endothelial cell wall damage. Vessel wall damage leads to infiltration of lipid and causes platelets to adhere and react with the vessel wall. Intracellular granules of platelet-derived growth factor (PDGF) are then released and smooth muscle cells proliferate. This causes formation of a fibrolipid plaque that can later become necrotic and calcified.¹⁷

Once an atherothrombotic plaque has formed there is chance of embolus generation. An embolus is an abnormal mass of material, transported in the bloodstream from one part of the circulation to another, blocking the lumen of the recipient vessel.¹⁷

A common scenario is for atheroma in the internal carotid artery (the donor vessel) to give rise to thrombi which embolise to the middle cerebral artery (the recipient vessel).  The heart is often a donor vessel: cardio-embolic events are a common cause of cerebrovascular disease in patients with atrial fibrillation, prosthetic heart valves or infective endocarditis.¹¹

Small vessel pathology

Intracranial small vessel disease is the cause of 25% of ischaemic events and affects the small, long, non-branching lenticulostriate perforators described above.¹⁸ There are a number of possible causes of small vessel occlusion, but the most significant is lipohyalinosis which is thought to cause in-situ obliteration.^19,20 Lipohyalinosis is a destructive vessel lesion causing loss of normal vessel architecture and fibrinoid vessel wall necrosis.^21,22 This leads to thickening of the vessel wall and narrowing of the lumen, eventually leading to complete obliteration of the vessel and in turn, ischaemia of the area of brain it supplies.

This important difference in the common causes of occlusion of large and small cerebral vessels, by emboli and in-situ obliteration respectively, informs both diagnosis and management.

As well as lipohyalinosis, there are less common causes of small vessel disease. These include atherothromboembolism (less commonly than in large vessels), vasculitis, infection, hypoperfusion, hypercoagulability, arterial dissection and rare small vessel vasculopathies such as CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) the commonest heritable form of cerebrovascular disease and vascular dementia in adults.^23,24

Summary

Stroke as a word does not do justice to the clinical features, pathologies, and vessels involved (Table 1), or to the potential for treatments to be tailored to the underlying disease process. By describing the constellation of clinical signs it is possible to speculate about the type of vessel involved, which in turn suggests the candidate pathology.

Armed with hypotheses generated by this sort of approach clinicians are in a much stronger position to discuss cases with radiologists and other colleagues to ensure that all patients have the best chance of an accurate anatomical and pathological diagnosis, and to the best treatment.

This article was first published in May 2014. It was updated in October 2021

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Tom Hughes, Neurologist, Cardiff

Gagan Singh, Bethan Percival, Sian Osborn

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