Ischaemic Stroke Treatment: Time Windows and Thrombectomy

The treatment window for ischaemic stroke is 4.5 hours from symptom onset for a clot-dissolving drug and 6 hours for mechanical thrombectomy, the catheter procedure that pulls the clot out of a blocked brain artery. In selected patients chosen on brain imaging, thrombectomy can still help up to 24 hours after onset. Beyond those windows, treatment shifts from rescuing the brain to preventing the next stroke.

Dr. Tariq Matin, Director & Chief, Neurointerventional Surgery, Artemis Hospitals, Gurugram, India, calls thrombectomy a very powerful treatment, and the trials that proved it a landmark in medical history. This article covers how ischaemic stroke arises, how a large-vessel stroke is recognised, how thrombolysis and thrombectomy work and when each applies, how stroke networks move patients within the window, how stenting prevents a second stroke, and how the less familiar venous stroke is treated. The wider specialty is introduced in the complete guide to the role of neuro intervention; bleeding strokes and aneurysms are covered in the article on brain aneurysm treatment.

What causes an ischaemic stroke

An ischaemic stroke occurs when an artery supplying the brain is blocked and the tissue beyond it starves of blood. Strokes divide into ischaemic and haemorrhagic types; in Dr. Matin's figures, haemorrhagic strokes make up 15% of the total, so ischaemic strokes are the large majority. He groups the causes of ischaemic stroke as follows:

• The heart (cardioembolic stroke). A rhythm abnormality or a functional abnormality of the heart throws a clot into the brain's circulation.
• The large arteries. A plaque in the carotid or another large artery either narrows it enough to reduce flow, or breaks off and embolises into the vessels inside the skull.
• The small arteries. Penetrating artery disease, caused by lipohyalinosis (thickening and degeneration of the walls of tiny deep arteries), develops particularly after long-standing uncontrolled hypertension and diabetes.
• Intracranial atherosclerosis. Narrowing of the arteries inside the skull is much more prevalent in Asian populations.
• Hypoperfusion and cryptogenic stroke. A fall in overall blood flow, or no cause found despite investigation.

Knowing the cause matters, because it decides both the emergency treatment and what prevents a recurrence. As Dr. Matin put it when asked whether patients with long-standing stroke can benefit from intervention: the cause can be the heart, the blood or the tubes, and the team must work out which before deploying the right preventive measure. That approach works in most cases, he added, though nothing in medicine is 100%.

Why large-vessel strokes matter most

A large-vessel occlusion is a blockage of one of the main arteries at the base of the brain: the internal carotid artery, the middle cerebral artery, or the basilar artery at the back of the brain. Dr. Matin noted that these strokes account for only about one-third of all strokes, yet they cause the great majority of stroke deaths, which he put at 90%, and 75 to 80% of the disability seen after stroke.

A large-vessel stroke can often be suspected at the bedside before any vascular imaging is done. The signs he listed:

• complete paralysis of one side of the body (hemiplegia);
• with a right-brain stroke, the eyes deviating to the right and neglect of the left side of space;
• with a left-brain stroke, the eyes deviating to the left and loss of language (aphasia).

Pre-hospital stroke scales are built around these signs so that ambulance crews can identify likely large-vessel strokes.

The penumbra: what treatment is trying to save

When an artery blocks, a core of brain tissue dies quickly. Around it lies the penumbra, tissue that is starved of blood but still alive. If the artery is reopened in time, the dead core stays small. If not, the penumbra dies too and the whole territory is lost. Every treatment decision in acute stroke is a race to save the penumbra.

Thrombolysis: the first line in the stroke treatment window

Intravenous thrombolysis uses a clot-dissolving drug, such as alteplase (tissue plasminogen activator), given into a vein. In Dr. Matin's view there is no question about it: if the patient qualifies, the drug must be given, for both large and small vessel strokes. In his summary, the absolute contraindications are a bleed in the brain and recent surgery; most other factors are relative. Guidelines list further exclusions, including recent serious head injury and recent anticoagulant use, so eligibility is decided by the stroke team on the individual patient.

The drug alone, however, is not enough for large clots, and its benefit falls quickly with time. Dr. Matin noted that the number of patients who must be treated with thrombolysis for one to benefit is about 4 to 5 when it is given within 90 minutes, rising to about 9 later, and higher still beyond that. Large clots also respond poorly to the drug. As he put it, the specialty exists to reach places that drugs cannot, and for large clots mechanical thrombectomy was the answer.

Mechanical thrombectomy: how it works

Mechanical thrombectomy removes the clot directly. A catheter is passed from the groin or wrist up into the blocked brain artery, and a stent retriever, a self-expanding mesh device, is opened inside the clot to grip it and pull it out, or the clot is aspirated through a large catheter.

A case: from paralysis to walking the next day

Dr. Matin presented a 47-year-old man, shown with his permission, who arrived at the emergency department unable to move his right arm and unable to understand speech: a left-sided stroke. MRI showed the infarct forming and the left-sided artery failing to fill. In the angiography suite, the team found the blockage, passed a catheter to it and reopened the artery. The time from the patient being wheeled into the suite to reopening the artery was less than 7 minutes. The next day, the same man was moving his limbs and walking freely, without disability.

A decade and a half ago, Dr. Matin pointed out, such a patient would have faced a nihilistic outlook: death, or a life bedridden and dependent. That is the change neurointervention has made.

The evidence: a number needed to treat of 2.6

The number needed to treat (NNT) is the number of patients who must receive a treatment for one to have a good outcome; the lower it is, the more powerful the therapy. Dr. Matin put the NNT for thrombectomy within 6 hours at 2.6. For comparison, the figures on his slide gave an NNT of 28 for angioplasty in heart attack and 25 for coronary bypass surgery to prevent cardiac death. Treat fewer than three stroke patients with thrombectomy, in other words, and one more of them has a good result.

The trials were decisive enough that in 2015 the American Heart Association and American Stroke Association made thrombectomy a standard of care with the highest class of recommendation. The guidelines were updated again in 2018, and Dr. Matin noted that the latest, 2026 guidance now also covers occlusion of the basilar artery.

Who qualifies for thrombectomy

The core guideline criteria for thrombectomy within 6 hours are:

• independent function before the stroke (a pre-stroke modified Rankin Scale score of 0 to 1);
• a large-vessel occlusion causing the stroke;
• age 18 or over;
• a significant deficit, with a National Institutes of Health Stroke Scale (NIHSS) score of 6 or more;
• limited established damage on CT, with an ASPECTS score (a 10-point CT score of early ischaemic change) of 6 or more;
• treatment that can begin within 6 hours of symptom onset.

The extended-window trials DAWN and DEFUSE 3 showed that patients selected on advanced imaging, whose brains still contain salvageable tissue, benefit from thrombectomy up to 24 hours after onset. In Dr. Matin's practice, the extended window is used in selected patients chosen on imaging.

Drip and ship: moving patients within the window

Thrombectomy needs the man, the machine and the tools, and these are not yet available in every part of every city. Until they are, Dr. Matin's team works on a drip-and-ship model. He described a stroke in a city about 200 kilometres from his centre: the local doctors sent the images to his team on an AI-based platform, the team confirmed the stroke and advised thrombolysis, the local hospital gave the drug, and the patient was then shipped to his centre. There, the angiogram showed the same occlusion, a stent retriever removed the clot, and the patient had a good result.

The model has a hard limit. The patient must reach the thrombectomy centre within about 4 to 6 hours, occasionally up to 24 hours in selected cases, so it works only within a region, never across continents. That is why Dr. Matin insists that acute stroke systems must be developed in-house, in each country and around each centre. For large-vessel strokes, a distant centre is no substitute.

Secondary prevention: stenting to prevent a second stroke

Once the acute phase has passed, the aim changes from rescuing the brain to preventing a recurrence. Where investigation finds a vascular cause, an occlusive or stenotic lesion, treating it may prevent the next stroke. The procedures are:

• Carotid artery stenting. A filter is placed beyond the narrowing in the carotid artery in the neck to catch any debris, and a stent is deployed across the plaque to hold the artery open.
• Intracranial stenting and angioplasty. A narrowed artery inside the skull is widened and stented. Aggressive medical therapy is the first-line treatment for intracranial narrowing, and stenting is reserved for selected patients who continue to have strokes despite it. Dr. Matin describes intracranial angioplasty as a genuinely complex procedure that needs a good centre and experienced hands.
• Vertebral artery ostial stenting. A narrowing at the origin of the vertebral artery, which supplies the back of the brain, is stented.

Because these are planned procedures, patients can make a calculated decision and travel for them. Most of Dr. Matin's overseas ischaemic stroke patients come for this kind of revascularisation.

When carotid stenosis needs treatment

Carotid stenosis usually means narrowing at the carotid bifurcation in the neck, where the common carotid artery divides into the external carotid, supplying the face, and the internal carotid, supplying the brain. The narrowing typically sits at the origin of the internal carotid artery.

Dr. Matin distinguishes two terms. A significant stenosis is one that warrants revascularisation in a patient who has had a stroke. In symptomatic patients, a narrowing of 50% or more on catheter angiography is generally regarded as significant enough to consider carotid angioplasty and stenting or surgery. A severe stenosis, in Dr. Matin's definition, is a narrowing of 70 to 99%. Left untreated, he noted, a severe stenosis carries the risk of a stroke.

Venous stroke: cerebral venous thrombosis

Not every stroke is arterial. In cerebral venous thrombosis (CVT), a clot blocks the veins and venous sinuses that drain blood from the brain back to the heart and lungs. The literature puts CVT at less than 1% of strokes, but Dr. Matin believes it is much more common, because many cases are missed.

Causes. The risk factors he listed are infection, trauma, dehydration, pregnancy and the period after childbirth, coagulation disorders, oral contraceptives, hormone replacement therapy and steroid treatment.

Symptoms. Most patients present insidiously with headache. Others develop blurred vision, altered consciousness, behavioural symptoms, seizures, swelling of the optic disc (papilloedema) and focal neurological deficits, and some deteriorate into coma.

Diagnosis. CT may show a hyperdense (abnormally bright) venous sinus, and on MRI the clotted sinus appears bright on T1-weighted images once the clot is a few days old. An MR venogram confirms the diagnosis by showing the absence of flow in the blocked vessel.

Treatment. Anticoagulation is the treatment of choice, and most patients diagnosed early respond to it. Guidelines recommend anticoagulation even when CVT has caused a bleed in the brain. The role of neurointervention comes in when things go out of hand. The indications on Dr. Matin's slide were clinical deterioration despite anticoagulation, a contraindication to anticoagulation, coma, thrombosis of the deep cerebral veins and intracerebral haemorrhage.

In those cases, the team enters the veins through a transvenous route, recanalises the occluded sinuses with catheters and devices, and removes the clot. Dr. Matin described a man who arrived in a coma, on a ventilator, with a completely occluded venous system and bleeding in the brain. After the clot was removed and flow restored, he recovered; six months later he sent the team a video showing him back at work as a lawyer.

What recovery looks like after ischaemic stroke

The contrast with haemorrhagic stroke is sharp. In an acute ischaemic stroke, the intervention reverses the damage on the table: the team brings neurons back from the brink of death to function, which is why the 47-year-old patient could walk the next day. In a haemorrhagic stroke, the first aim is to save the patient's life, and function returns more gradually, as the aneurysm article explains.

The questions attending doctors put to Dr. Matin on treatment windows and carotid stenosis are on the Live Discussion page. Specialists who perform these procedures are listed under neurointervention.