Stroke and TIA Investigations

Learning objectives

Initial Tests

Investigations should be rational and appropriate. If you find a pathology e.g. dissection, there is questionable merit in then going to look for a PFO or doing a thrombophilia screen. Looking for antiphospholipid syndrome in elderly patients without specific indications will just lead to false positives. The more exotic tests should be done in series rather than as a one hit. Most are not urgent and can be done over a few weeks. Always ask if tests are appropriate and will they change management.

There needs to be a rationale for tests and unless you are in a a large teaching hospital with very easy access to you need to decide who needs what tests. We certainly do not do Echocardiograms on all patients but on those in whom there is evidence to suggest a cardiac aetiology. We look for investigations that will yield important information that will make a substantial difference to management.

Basic Investigations to be done on admission

• FBC: polycythaemia or anaemia can be important findings. If there is anaemia then look at the MCV. If low check Iron studies and consider initial tests to look for GI blood loss or other aetiology. If MCV high check B12 and folate.
• ESR: temporal arteritis, myeloma, vasculitis, malignancy
• CRP: Infection (Chest/Urine/other), SLE, Vasculitis, endocarditis, temporal arteritis
• Urea and electrolytes: often patients have been ill or been found lying in bed dehydrated and come in with an element of Acute kidney injury which usually responds to cautious rehydration. In some cases other causes of uraemia are found and many patents have degrees of chronic kidney disease related to longstanding diabetes or hypertension. A renal vasculitis is a rare cause but may co-exist with a cerebral vasculitis.
• Fasting lipids: Check Cholesterol, LDL, HDL
• Non Contrast Head CT scan: this is the primary imaging modality. Quick, cheap and very accurate for detecting haemorrhage and developed ischaemic stroke and other differentials such as tumours. Ischaemic stroke shows few changes acutely within the first 6 hours. Contrast can be given if a suspected tumour is seen.
• ECG - AF, LVH, STEMI, NSTEMI, Bundle branch block
• Chest X-Ray: Look for Cardiomegaly, enlarged LA, Lung cancer with cerebral metastases acting as a stroke mimic
• Random glucose: Exclude diabetes

Further Investigations depending on Assessment

• Coagulation screen (clotting + platelets) - if you suspect warfarin or a coagulopathy or thrombocytopenia
• Prolonged INR needs urgent reversal in Haemorrhagic Stroke or Subdural
  • Liver disease : Give IV Vitamin K 5 mg + FFP
  • Warfarin therapy : Give IV Vitamin K 5 mg + Prothrombin concentrates (Octaplex/Beriplex)
• Prolonged APTT
  • Heparin therapy
  • Lupus anticoagulant
  • Von Willebrand's disease
• Platelet count
  • Thrombocytopenia: haemorrhagic stroke especially if levels fall < 20 x 10 ⁹. Consider cause - Acute ITP, HITT syndrome, Drug induced. Stop antiplatelets.
  • Thrombocytosis: raised platelets and thrombotic stroke

Carotid dopplers

• Should only be done on those with TIA or non disabling stroke who would agree for endarterectomy
• Consider in suspected carotid dissection though CTA/MRA preferred

Transthoracic Echocardiography

• Varying availability and some do in all Ischaemic strokes
• Selective - Cardiac symptoms, Clinical signs/history of cardiac disease, Abnormal ECG
• Haemorrhagic strokes secondary to endocarditis
• Bubble test done to look for right to left shunting

24 hour tape or 7 Day tape

Done where there is suspected PAF but AF not detected during admission on ECG or telemetry. If AF does occur during admission it is vital to get a 12 lead ECG or at least a telemetry print out for the records. Have a very high index of suspicion for PAF in any older patient over 60 especially with a large vessel stroke anterior or posterior circulation. In practice I look for PAF in all ischaemic strokes. In high risk patients I would either get several 24 hour tapes or a 7 day monitor. It depends on what you have easiest access too. Multiple old strokes right and left and anterior and posterior circulation make cardio embolism very likely indeed. The reality is that despite best efforts it is not uncommon for the AF to be finally diagnosed when the patient represent with a new stroke and AF.

Additional focused Investigations

Transoesophageal echocardiography

All young strokes with no alternative cause should have a TOE. The operator is looking for a PFO, atrial septal aneurysm, ASD or an atrial myxoma or other structural disease. It may also be indicated with a patient with suspected endocarditis and an initial TTE that is either unequivocal or suspicious. A probe is swallowed in placed in the oesophagus which gives detailed pictures of the left atrium and nearby structures including the aorta. Agitated saline can be used as a contrast medium to identify any shunts though it is obviously difficult to demonstrate a Valsalva with a sedated patient.

Transcranial Doppler

Brain Imaging

Non contrast CT is the imaging of choice for most stroke patients. It is quick, readily accessible and informative in terms of high sensitivity for blood and can rule out some stroke mimics. See the stroke imaging link for more detailed information.

MRI can be useful when diagnosis perhaps shows a hypodense lesion with oedema and the diagnosis as to stroke or tumour is uncertain. Also useful in those with a recent haemorrhagic stroke where you might suspect underlying tumour. The temptation is always to get it as early as possibly but often more useful to wait a few weeks until much of the haematoma has resolved.

I would also consider an MRA in any suspicious bleed to look for any vascular lesion such as an Arteriovenous malformation or berry aneurysm where surgical intervention would be contemplated. Always more suspicious in a lobar haemorrhage in a younger patient (under 60). In an older patient with a deep subcortical bleed and a prominent history of hypertension the BP is usually the aetiology. MRI/MRA is also useful for suspected vasculitis or Reversible cerebral vasoconstriction syndrome.

A negative MRI-DWI can prove very useful for those where you suspect a functional stroke presentation or Migraine. It can also be invaluable in proving a stroke aetiology in those where the CT scan has been unhelpful and the clinical features could be anterior or posterior circulation or where the CT is unhelpful and you want to prove or disprove a stroke diagnosis. MRV is the imaging of choice for suspicion of a cerebral venous thrombosis.

Antiphospholipid antibodies (aPL)

The presence of aPL antibodies has been associated with thrombotic stroke. These are seen in those with SLE, RA, Sjogren's syndrome, Progressive systemic sclerosis and Takayasu's arteritis as well as other haematolgicoal disorders. Stroke associated with aPL tends to be associated with younger females. APLS may cause stroke by their effect on endogenous anticoagulants such as ATIII. Protein C, thrombomodulin and prostacyclin. There are two main tests and these are for

• Anticardiolipin (aCL) antibodies: commoner and less specific
• Lupus anticoagulant (LA) : less common but more specific

Routine screening for aPL is not recommended in stroke disease. A positive lupus anticoagulant or high anticardiolipin titres should be repeated 12 weeks later to meet the diagnostic criteria for the antiphospholipid syndrome.

Thrombophilia Screen

The SIGNS guidance recommends that the routine requesting of thrombophilia screens, antiphospholipid antibodies, other autoantibodies and homocysteine levels is not justified. Testing may be considered in those under 45 with cerebral venous thrombosis or found to have an unexplained acute large vessel stroke with a PFO and coexisting DVT or high index of suspicion for such. The relationship between arterial thrombosis and most thrombophilia is very poor indeed. This should not be a automatic test as false positives can lead to potential mismanagement. Ask about a family history of venous thrombosis. Other worrying features would be younger female with a history of late fetal loss in pregnancy. The testing includes

• Protein C and S
• Antithrombin III
• ANA, dsDNA, ANCA
• Anticardiolipin antibodies

Antithrombin III and protein S and C assessments should be done after the acute phase and are lowered by oral anticoagulants. Antithrombin III concentrations are also lowered by non-fractionated heparin. Abnormally low concentrations in the acute phase or in anticoagulated patients should be confirmed 6 weeks later or when oral anticoagulants are stopped

http://www.practical-haemostasis.com/ contains More information on Clotting test

Genetic Testing

Consider where there is suspicion of MELAS syndrome or CADASIL. CADASIL is often diagnosed by skin biopsy and typical changes.

Lumbar Puncture

• Suspected Vasculitis
• Suspected Subarachnoid Haemorrhage
• Multiple sclerosis/ADEM
• Meningitis - Bacterial, Neurosyphilis

Transcranial doppler

Possible Indications

• Sickle cell disease
• Post SAH
• Detecting Right to Left shunting with bubble test

Hypertension screen (young hypertensive)

• Urinary catecholamines
• Renal Ultrasound
• Renin/Aldosterone
• Dexamethasone suppression test
• CT Aorta

Metabolic disease

• Alpha galactosidase - Fabry's disease
• Urinary Homocysteine

Infections

• HIV testing is recommended in potential at risk groups. PML and lymphoma can easily resemble a subcortical white matter hypodensity and mimic a stroke.
• Syphilis - Blood/CSF VDRL/TPHA
• Bacterial meningitis especially Listeria as well as commoner causes
• Encephalitis

Toxicology

• Cocaine
• Amphetamines
• Alcohol

Young Person Ischaemic Stroke

In all younger strokes I have my own personal acronym - DVV and ask myself is this Dissection, Vasculitis or Venous. I will actively look to exclude these in a young person with a large vessel stroke. They have very distinct and different treatments. Don't send of all tests at once but work through logically. Stop once you find the cause.

Summary of Rare Causes and Investigations in Young adults [Adapted from Ferro JM et al. 2010]