Cerebrovascular disorders | Central and peripheral nervous system | Pathology

The brain receives 20% of the cardiac output. When systolic blood pressure drops below 50 mmHg, the cerebral perfusion pressure falls predisposing to ischemia. Ischemia lasting 4-5 minutes can irreversibly damage hippocampal and neocortical pyramidal cells, striatal neurons, and Purkinje cells. More protracted ischemia can damage thalamic and brainstem neurons. In the neonatal brain, damage to the periventricular white matter is frequent in addition to the above-mentioned cortical damage.

Section A: Stroke

Stroke is classically characterized as a neurological deficit attributed to an acute focal injury of the central nervous system (CNS) by a vascular cause, including cerebral infarction, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH).

(I) Cerebral infarction: Ischemia of the brain can be due to atherosclerosis with or without thrombosis of the major blood vessels like MCA; embolization from heart or blood vessel clots; vasculitis, hypercoagulopathy like Factor V Leiden, polycythemia and small vessel disease (more common in women), etc. In older age groups, atherosclerosis with thrombosis is the most common cause. MCA is the most common artery involved in atherosclerotic and embolic strokes. In younger age groups non-atherosclerotic causes should be looked for especially embolization and hypercoagulopathy. Venous thrombosis is seen in estrogen therapy and OC pill use. Vascular spasm accompanying SAH can also cause cerebral infarcts.

Clinical features: Clinical features will depend on the area that is infarcted. The symptoms are acute to subacute and gradually evolve over hours to days. Acute presentation is seen in embolizations compared to arterial thrombosis.

Features of strokes according to arterial distribution

Artery involved	Presenting features
MCA	Hemiparesis and hemianesthesia of the contralateral face and body; contralateral homonymous hemianopia; deviation of eye toward the affected hemisphere. Left hemisphere involvement presents, in addition, with Broca’s, Wernicke’s, conduction or global aphasia. Right hemisphere lesions present, in addition, with contralateral hemineglect or speech alterations e.g. sounding like “computer generated” speech, talking in a foreign accent (dysprosody).
ACA	Hemiparesis and hemianesthesia of the contralateral lower limb; gait apraxia, urinary incontinence, primitive reflexes like grasping and sucking, frontal lobe involvement presenting as disinhibition, lack of motivation, impaired judgement.
PCA	Contralateral homonymous hemianopia typically with macular sparing; left PCA lesions will also have alexia without agraphia (can write but cannot read)
Vertebral artery or anterior spinal artery	Medial medullary syndrome presenting with contralateral spastic hemiparesis, loss of touch, vibration and pressure sensations in the limbs and trunk. Dysarthria (improper articulation of speech), paralysis and atrophy of tongue ipsilateral to the lesion, deviation of the tongue toward the side of lesion.
*Vertebral artery or PICA (posterior inferior cerebellar artery)**	Lateral medullary or Wallenberg’s syndrome presenting with contralateral loss of pain and temperature sensations in the body and limbs, ipsilateral Horner’s syndrome (miosis, anhidrosis, ptosis), vertigo, nausea, vomiting, vestibular nystagmus (fast phase away from the side of the lesion), ipsilateral sensory hearing loss, bulbar signs like dysphagia, hoarseness, deviation of uvula away from the side of lesion, absent gag reflex; loss of pain and temperature from ipsilateral hemi face and scalp, loss of taste from ipsilateral tongue
AICA or circumferential branches of the basilar artery	Lateral pontine syndrome presenting with vertigo, nausea, vomiting, vestibular nystagmus (fast phase away from the side of the lesion), ipsilateral sensory hearing loss, loss of pain and temperature from ipsilateral hemi face and scalp, weakness of muscles of mastication.
Paramedian branches of basilar artery	Medial pontine syndrome presenting with spastic hemiparesis of contralateral loss of pain and temperature sensations in the body and limbs, internal strabismus (eye moves medially due to paralysis of lateral rectus), diplopia, if medial lemniscus is involved then contralateral loss of touch, vibration, pressure sensations; is facial nerve is involved then ipslateral facial weakness, dry eyes, loss of taste from anterior ⅔ of the tongue.
Basilar artery (main stem)	Locked in syndrome presenting with the inability to move the body and limbs except III cranial nerve innervated eye muscles; hearing and sensations are preserved, patients are fully awake and aware.
Thalamoperforating branches of the PCA	Weber’s or medial midbrain syndrome presenting with contralateral spastic paresis, contralateral lower face weakness**, deviation of the tongue away from the lesion, oculomotor nerve palsy with dilated pupil, ptosis, external strabismus, ipsilateral loss of light reflex and accommodation reflex.

*Differentiate AICA from PICA stroke by the presence of bulbar signs only in PICA.

** An intact blink reflex means it is an UMN facial nerve lesion as it spares the upper half of the face.

#A fully awake and aware person suffering from locked - in syndrome can legally give consent.

Lacunar infarcts: They are typically seen in hypertension and diabetes as a result of severe atherosclerosis of the deep penetrating branches of the major cerebral arteries. Lipohyalinosis , hyaline arteriosclerosis of small vessels and aneurysm formation are seen. They cause small infarcts in the basal ganglia, thalamus, internal capsule and brainstem. Multiple or recurrent lacunar infarction leads to dementia. They may present as pure motor or pure sensory (thalamic pain syndrome etc.) strokes.

Watershed infarcts: Watershed infarcts involve the junction of the distal fields of 2 non anastomosing arterial systems. They are seen between the cortical territories of the ACA, MCA and PCA, also called cortical watershed areas. They are also seen in the white matter along and slightly above the lateral ventricle, between the deep and the superficial arterial systems of the MCA, or between the superficial systems of the MCA and ACA, also called deep watershed areas. Microemboli or hypotension due to any cause can reduce the perfusion pressure in the cerebral arteries leading to watershed zone ischemia and sometimes infraction. It is exacerbated by stenosis in the cerebral arteries. It presents as syncope, episodic or progressive weakness of the hand, partial seizures, proximal upper and lower limb paresis (“man in barrel sign”), mood changes and visual deficits. Bilateral, symmetrical watershed infarcts are seen in global ischemia and HIE.

**Hypoxic ischemic encephalopathy or HIE or global ischemia: **Global ischemia can result from hypovolemic shock, cardiac arrest, CO poisoning, hypoglycemia, severe anemia and status epilepticus etc. Neurons depend on a steady supply of glucose and ATP by oxidative phosphorylation to meet their high metabolic requirements. Global ischemia leads to reduced ATP formation and failure of the Na+K+ATPase pump. Na+ influx causes cellular edema and cell death. It also causes depolarization of the neuronal cell membrane and discharge of glutamate into the synaptic cleft. Opening of NMDA and AMPA glutamate receptors leads to an influx of Ca++ into the cell and resulting activation of lytic enzymes and free radical formation. Severe HIE is accompanied by cerebral edema and its effects are compounded by increased intracranial pressure. Cytotoxic or intracellular edema develops in the initial phase of the insult. Interstitial cerebral edema follows due to vascular injury. Cerebral atrophy occurs due to loss of neurons by apoptosis and necrosis.