ROLE OF IMAGING

1. Non-contrast CT and MRI

In the acute setting, CT is the most preferred investigation modality due to its speed and wide availability, which allows faster assessment to rule out intracranial hemorrhage and to initiate treatment with tPA in appropriate patients. Acute stroke evaluation with MRI is gaining popularity owing to its increased sensitivity and decreasing imaging times. Stroke MRI protocols with non-enhanced Diffusion weighted imaging (DWI), gradient-echo imaging, and fluid-attenuated inversion-recovery (FLAIR) imaging along with time of flight (TOF) non-contrast MR angiography of the head and neck can be performed in 6–15 minutes.

Fig 2: CT versus MRI in the diagnosis of young stroke

2. Cross-sectional angiography

CT and MR angiography are essential components of the standard workup for young stroke. Their noninvasive nature, high sensitivity and wide availability allow quick and accurate vascular interpretation. CT angiography, MRI and MR angiography have the advantage over catheter angiography of demonstrating the vessel walls of the larger arteries in the neck in the young population with an increased frequency of dissections. Cross-sectional venous imaging should also be done to rule out cortical venous or dural venous sinus thrombosis.

3. Perfusion Imaging

CT perfusion is a dynamic study yielding a first-pass time-attenuation curve from which perfusion parameters of cerebral blood flow, cerebral blood volume, time to peak, and mean transit time can be calculated. Automated post-processing methods are available, providing volumes of core infarction (cerebral blood flow <30% of normal) and penumbra (time to maximum residual function [Tmax] >6 seconds). It enables the differentiation of salvageable ischemic brain tissue (penumbra) from the irrevocably damaged infarcted brain (infarct core). This is useful when assessing a patient for treatment (thrombolysis/clot retrieval).

4. Vessel wall imaging

Vessel wall imaging (VWI) is a new technique that uses black-blood sequences, pre and post contrast acquisitions to evaluate vessel walls. VWI is used to differentiate between intracranial diseases such as reversible cerebral vasoconstriction syndrome (RCVS), Moya-Moya disease, vasculitis, dissection, and atherosclerosis by evaluating stenosis, eccentric versus concentric nature, location, and enhancement.

5. Catheter Angiography

Indications for catheter angiography include workup for intracranial steno-occlusive diseases like Moya-Moya disease, diagnostic angiography for non-atherosclerotic vasculopathy, and when planning interventions.

Fig 3: Various imaging modalities in young stroke

Fig 4: Algorithmic imaging approach to young stroke

CAUSES OF YOUNG STROKE

The most common classification of sub-types of ischemic stroke is the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. This scheme divides ischemic strokes into 5 categories which are discussed below.

Fig 5: TOAST Classification of ischemic stroke

1. Cardioembolic Stroke

They may be categorized on the basis of clot composition or cardiac disease into septic emboli, bland emboli (from cardiac masses, right-to-left shunts, arrhythmias, and cardiomyopathy), air emboli, and fat emboli.

Septic emboli

• Most common intracranial complication in infective endocarditis often associated with intraparenchymal hemorrhage, abscess, subarachnoid hemorrhage, or mycotic aneurysm.               
• Occult small embolic stroke (37%) and subcortical micro-hemorrhages (57%) are frequent in asymptomatic patients [4].

Fig 6: Case of a 39-year-old lady with history of diabetes mellitus who presented with high grade fever and generalized tiredness since 5 days. Total blood counts and inflammatory markers were elevated. MRI axial T1 weighted, FLAIR, DWI and ADC sequences reveal multiple scattered T2/FLAIR hyperintense, T1 hypointense foci with diffusion restriction in the brain parenchyma. Blood culture revealed growth of Staphylococcus Hominis. Final diagnosis : septic shock with embolic infarcts.

Bland emboli

• Most common causes of bland emboli include cardiac tumors like atrial myxoma, right-to-left shunts including patent foramen ovale (37%), arrhythmias like atrial fibrillation and cardiomyopathies.

Fig 7: Case of a 2 year old boy who presented with drooping of right eye lid and acute left sided hemiparesis since 3 hours. MRI axial DWI and ADC sequences revealed a large infarct with diffusion restriction along the right PCA territory. MR angiography revealed a filling defect in the P2 segment of right PCA – suggestive of acute occlusion. Echocardiography revealed a small patent foramen ovale in the right atrium with right to left shunt. Final diagnosis: bland emboli causing thromboembolic stroke due to a patent foramen ovale.

Intravascular air emboli

• Cerebrovascular air embolism can occur during many invasive procedures like central venous catheter placement.

• If the introduction of air is before the branching of aortic vessels, the infarcts are smaller involving multiple vascular territories, while if it's related to a carotid or vertebrobasilar interventional procedure, infarcts are typically confined to a single vascular territory.

Fat emboli

• Cerebral fat embolism syndrome is classically seen in patients with large displaced fractures or sickle cell disease [5].

• Displaced fracture marrow fat droplets released can traverse through a right-to-left cardiac shunt or can deform and travel through intact pulmonary capillary beds to reach the CNS.

• CT is usually normal. The classic“starfield” pattern of innumerable tiny foci of diffusion restriction and FLAIR hyperintensities are noted scattered throughout the brain parenchyma.

Fig 8: Case of a 21 year old gentleman who presented with left leg pain after a road traffic accident. Radiography of left knee AP view revealed displaced fractures in the shaft of left femur for which he underwent emergency reduction of the fracture with plate fixation. A few days later there was a sudden drop in GCS. MRI brain axial T2 weighted, FLAIR, DWI, ADC and SWI sequences reveal multiple T2/FLAIR hyperintense foci with diffusion restriction and blooming in the bilateral frontoparietal centrum semiovale, frontal and occipital cortical and subcortical white matter and bilateral gangliocapsular regions with a “STARRY SKY” pattern on DWI suggestive of fat embolism.

2. Other Demonstated Causes

Dissection

• Cervical carotid or vertebral artery dissection is one of the most common causes of stroke in young adults. They can be spontaneous or traumatic.

• The mechanism of stroke in patients with carotid dissection includes thromboembolic stroke (80%), hypoperfusion from high grade stenosis or occlusion (15%), and mixed mechanisms (5%).

• CT angiography can demonstrate a long irregular stenosis (string of pearls sign), tapering of true lumen (flame sign), or mural thickening from intramural hemorrhage.

• Fat-saturated T1-weighted MRI is the most sensitive imaging modality for depiction of a cervical arterial dissection. 

Fig 9: 27 year old gentleman with no prior history of trauma / surgery presented with acute onset left sided hemiplegia since 2 hours. MRI axial section FLAIR, DWI and ADC sequences reveal gyriform areas of diffusion restsriction along the right frontoparietotemporal subcortical white matter and insula. MR angiography reveals absent flow signal in the right ICA from C2-C7 vertebral levels with intraluminal hyperintensity in the C1 segment suggestive of long segment thrombosis. Vessel wall imaging MRI reveals right internal carotid artery dissection at the extracranial C1 segment, with a visible floating intimal flap and intramural hematoma causing severe luminal narrowing with reduced flow in intracranial segments from C2 to C7, accompanied by diffuse wall enhancement. Final diagnosis : Right ICA dissection with thromboembolic stroke along the right ICA territory

Vasculitis

• Vasculitis is a specific vasculopathy defined as inflammation of the blood vessel wall with or without necrosis.
• The cause of intracranial vasculitis include connective tissue disease or lupus, infection, malignancy, irradiation, or medications. VWI may help identify concentric focal intense wall enhancement, a unique finding indicating inflammation.

Fig 10: 32 year old lady, known case of diabetes mellitus with history of recurrent strokes presented to the neurology OPD for further evaluation. MRI brain axial FLAIR and DWI sequences reveal chronic infarcts in the right posterior parietal lobe with associated cortico-cerebral atrophy. MR angiography reveals poor flow related opacification in the right A1 segment of ACA and M1 segment of MCA with paucity of the right MCA branches. Digital subtraction angiography also revealed critical stenosis of right M1 MCA and A1 ACA. Detailed autoimmune profile was done in which anti cardiolipin antibody was found to be elevated. Final diagnosis: CNS vasculitis with multi-vessel occlusion and chronic infarcts

Reversible Cerebral Vasoconstriction Syndrome (RCVS)

RCVS is a combined clinical and radiographic diagnosis of unknown pathophysiology. Subarachnoid hemorrhage in RCVS involves the high convexities instead of the basal cisterns. Multifocal beaded appearance of the larger intracranial vessels in multiple vascular territories is diagnostic of cerebral vasoconstriction but not specific for RCVS. RCVS has no or mild enhancement in VWI, while vasculitis has intense enhancement.

Fig 11: 35 year old gentleman, known case of pancytopenia presented with history of headache since 2 weeks followed by right upper limb and lower limb weakness since 3 days. MRI brain axial DWI, ADC, FLAIR and SWI sequences reveal multiple areas of diffusion restriction in the bilateral frontal, occipital regions and in the watershed territory with a well defined area of blooming in the left parietal region. MR angiography reveal multiple short segment areas of luminal narrowing and vasospasm along the basilar artery, bilateral ACA, MCA and PCA. Final diagnosis: RCVS with multiple ACA-MCA and MCA-PCA watershed territory infarcts with hemorrhagic transformation.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

• CADASIL is caused by a genetic mutation in the NOTCH3 gene. 
• The typical imaging findings include subcortical and periventricular hyperintense white matter lesions on T2-weighted or FLAIR images involving the anterior temporal poles, insula, centrum semiovale, and external capsule [6]. The lesions are symmetric with relative sparing of the fronto-orbital and occipital regions and associated deep gray matter microhemorrhages.

Fig 12: 42 year old gentleman with previous history of a left MCA territory stroke, now presented with history of difficulty in walking, urinary urgency and bilateral pyramidal signs. MRI axial FLAIR and SWI sequences reveal multiple lacunar infarcts in the bilateral frontoparietal corona radiata and left hemipons, with multiple foci of blooming suggestive of microbleeds in the bilateral thalami and deep frontoparietal white matter. No significant stenosis of major intracranial vessels seen on MR angiogram. Detailed workup was done and NOTCH3 gene mutation was found – suggestive of CADASIL.

Moya - Moya

• Moya-moya disease is idiopathic. Secondary causes of moya-moya syndrome include sickle cell disease, neurofibromatosis type 1, radiation vasculopathy, and Down syndrome.

• Stroke occurs due to watershed infarction from steno occlusive disease of the ICA terminus that often involves the anterior cerebral artery and MCA origins. Classic “puff of smoke” appearance is seen on angiography.

Mitochondrial Encephalopathy, Lactic acidosis and Stroke like episodes (MELAS)

• MELAS is a maternally inherited mitochondrial disorder. 
• On imaging, it manifests as multifocal stroke like cortical lesions in different stages of evolution ("shifting spread" pattern), crossing various cerebral vascular territories, and showing a certain predilection to the posterior parietal and occipital lobes.
• Elevated lactate levels are seen on MR spectroscopy.

Fig 13: 10 year old boy with history of childhood stroke now presented with quadriplegia. MRI axial DWI, ADC, FLAIR and SWI sequences reveal symmetrical, confluent areas of T2/FLAIR hyperintensities with uniform diffusion restriction involving the bilateral frontal, parietal, temporal and occipital regions. Subcortical U fibers are affected more in frontoparietal regions with relative sparing in temporo-occipital lobes. MR Spectroscopy reveals the classic lactate peak confirming the diagnosis of MELAS.

Deficiency of adenosine deaminase 2 (DADA2)

• DADA2 is a monogenic autosomal recessive systemic vasculitis syndrome associated with mutations of ADA2 gene.
• Most common CNS presentation is recurrent strokes due to small vessel lacunar infarcts involving the deep grey matter and brainstem [7].

Fig 14: 4 year old boy with history of recurrent stoke due to adenosine deaminase (ADA) deficiency.

Prothrombotic disorders

• Prothrombotic disorders can induce venous, arterial, or microvascular thrombosis. Some of the causes include Factor V Leiden mutation, antiphospholipid antibody syndrome, oral contraceptive use, pregnancy and puerperium.
• The classic “empty delta sign” or absent cortical venous filling is observed on CT angiography, CT venography, or MR venography.

Fig 15: 24 year old lady, 16 days post-partum presented with complains of severe headache since 2 days associated with weakness of the left side of body. MRI axial DWI, ADC and SWI sequences reveal an area of diffusion restriction with blooming in the right perirolandic cortex. MR venogram reveals loss of flow related signals in the anterior two thirds of superior sagittal sinus. Features suggestive of evolved venous infarcts with hemorrhagic transformation in the right perirolandic cortex with associated superior sagittal sinus thrombosis.

3. Undetermined causes 

Ischemic infarcts due to undetermined causes should meet one of the following criteria: (a) two or more causes, (b) indeterminate cause, and (c) incomplete evaluation[8].

4. Small vessel occlusion

Small-vessel occlusion (lacunar) infarction accounts for only 7%–14% of ischemic strokes in young adults. Imaging features include small deep infarcts restricted to the basal ganglia, internal capsule, thalamus, or brainstem.

5. Large artery atherosclerosis

It's the least common subtype of ischemic infarction in young adults, accounting for only about 2-8%. A stroke can be attributed to large-artery atherosclerosis if the patient has an infarct of the cerebral cortex, brainstem, or cerebellum and evidence of accelerated atherosclerotic risk factors or symptomatic atherosclerosis in other anatomic locations.