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 |
|---|
|
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 cardioembolism 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.
| Clinical Indications for urgent CT i.e. within 1 hour of arrival at hospital |
|---|
|
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, Sjogrens 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 prostacylin. 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 thrombophilias 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]
| Finding | Clinical signs | Confirmatory tests |
|---|---|---|
| Carotid/Vertebral dissection | Minor head/neck trauma, headache, facial pain, Horner's syndrome, XII palsy | Cervical MRI with fat suppression, angiography |
| Atherosclerotic large vessel | Multiple vascular risk factors, TIA, Carotid bruit | Carotid/vertebral doppler, MRA |
| Small Vessel disease | HTN, DM, LACI syndrome, Capsular warning syndrome | MRI DWI |
| Patent Foramen Ovale | Stroke during valsalva, Stroke with DVT/Immobilisation | TOE or TCD with microbubbles |
| Other cardioembolic disease | History, large vessel cortical stroke, haemorrhagic transformation, multiple infarcts in different vascular territories | ECG, Holter, TTE, TOE, Holter |
| Pulmonary Fistulae | R to L shunt, no PFO, Osler-weber-rendu syndrome | Chest CT |
| SLE | Anaemia, arthralgia, Low platelets, high ESR, renal disease | Anti dsDNA, ANA, sm |
| Antiphospholipid syndrome | Miscarriages, Venous thrombosis, prolonged APTT | Lupus anticoagulant, anticardiolipin, beta-2, glycoprotein antibodies |
| Sneddon's syndrome | Livedo reticularis, Ischaemic and Haem strokes | Skin biopsy, digital artery biopsy |
| Takayasu's disease | Absent radial, brachial pulses. Blood pressure difference | CT/MRA thorax, aortic PET |
| Primary CNS Vasculitis | Multiple strokes, encephalopathy, fever | LP, DSA or MRA, meningeal brain biopsy |
| Moyamoya syndrome | Multiple strokes ischaemic and haemorrhagic, cognitive decline | Angiography (MRA/CTA/DSA) |
| Retinopathy and retinocochlearcerebral arteriopathy | Visual loss, progressive deafness | ENT/Ophthalmological review |
| Sickle Cell Disease | African origin | HB electrophoresis, genetic testing, TCD |
| Inherited thrombophilia | Venous mainly but and possibly arterial strokes | AT3, FVL, Protein C/S testing, genetic testing |
| CADASIL | Migraine with aura, small vessel strokes, dementia, psychosis | Skin biopsy, genetic testing |
| HANAC syndrome (COL4a1) | Small vessel disease, cerebral aneurysms, porencephaly, retinal artery tortuosity, kidney disease, muscle cramps | Genetic testing |
| Fabry's disease | Skin, ocular, renal disease, vertebrobasilar dolicooectasia | Genetic testing, a-galactosidase activity |
| MELAS | Migraine, seizures, deafness , short stature | EMG, muscle biopsy, Genetic testing |
| Hyperhomocystinaemia | Homocysteine levels | |
| Reversible Cerebral Vasoconstriction Syndrome | Repeated thunderclap headaches and stroke in middle aged females | Reversible vasoconstriction on angiography |
| Infections causing stroke | Serum levels for syphilis, borrelia, zoster, Hepatitis B, Hepatitis C (also cryoglobulins), HIV | |
| Infective endocarditis | Embolic stroke, Haemorrhage | Blood cultures, CRP, TOE |
| TB meningitis | Headache, coma, meningism | LP, CXR, Cultures, HIV, TCD test |
| HIV vasculopathy | Small vessel vasculopathy | HIV test, CD4, Viral load, LP |
| Cysticercosis | Affects MCA and PCA zones. Lacunar infarctions can occur as a result of inflammation of small penetrating arteries. Ischaemic strokes are less frequent in patients with parenchymal neurocysticercosis and usually arise in the vicinity of cysts. | CT, LP, TCD |
| Note: The plan is to keep the website free through donations and advertisers that do not present any conflicts of interest. I am keen to advertise courses and conferences. If you have found the site useful or have any constructive comments please write to me at drokane (at) gmail.com. I keep a list of patrons to whom I am indebted who have contributed. If you would like to advertise a course or conference then please contact me directly for costs and to discuss a sponsored link from this site. |