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Classification and diagnostic workup

TL;DR — Stroke is a tissue-based diagnosis encompassing symptomatic central-nervous-system infarction, intracerebral hemorrhage, and subarachnoid hemorrhage; a transient ischemic attack (TIA) is transient focal ischemia without demonstrable infarction (Sacco 2013, PMID 23652265; Sorensen 2011, PMID 21640301). The emergency workup must answer three questions in parallel: is this vascular, is there hemorrhage, and is there a treatable occlusion or perfusion mismatch? Non-contrast CT rapidly identifies hemorrhage but can be normal in early ischemia; CTA identifies occlusion, while MRI-DWI is more sensitive for small infarcts yet remains negative in a pooled 6.8% of clinically diagnosed acute ischemic strokes (Czap 2021, PMID 34785603; Edlow 2017, PMID 28615423). Etiologic classification begins after stabilization: TOAST assigns one dominant mechanism, whereas ASCOD records overlapping atherosclerotic, small-vessel, cardiac, other, and dissection phenotypes (Adams 1993, PMID 7678184; Amarenco 2013, PMID 23899749). Mimics are common enough that diagnosis must remain iterative, but uncertainty should not automatically delay time-dependent reperfusion.

What counts as stroke

The 2013 AHA/ASA statement joined clinical and tissue definitions. Central nervous system infarction is brain, spinal-cord, or retinal cell death attributable to ischemia, demonstrated by pathology, imaging, or persistent clinical evidence; ischemic stroke is infarction with overt symptoms, while silent infarction lacks recognized acute symptoms (Sacco 2013, PMID 23652265).

Entity Operational distinction Immediate implication Evidence
Ischemic stroke Symptomatic CNS infarction Assess reperfusion eligibility and mechanism Sacco 2013, PMID 23652265
Intracerebral hemorrhage (ICH) Non-traumatic blood within brain parenchyma or ventricles Reverse anticoagulation, manage pressure and mass effect Greenberg 2022, PMID 35579034
Subarachnoid hemorrhage (SAH) Non-traumatic bleeding into subarachnoid space Identify and secure aneurysm; prevent secondary injury Claassen 2022, PMID 35985353
TIA Transient focal ischemic dysfunction without acute infarction Urgent mechanism workup and early prevention Sorensen 2011, PMID 21640301
Silent CNS infarction Imaging/pathologic infarction without recognized acute syndrome Vascular-risk marker; not an acute symptomatic stroke Sacco 2013, PMID 23652265
Cerebral venous thrombosis Venous sinus/cortical-vein thrombosis, sometimes with venous infarction or hemorrhage Venous imaging and anticoagulation pathway Amarenco 2009, PMID 19342825

The tissue definition changes counts. In 47 studies including 9,078 specialist-diagnosed TIAs, 34.3% (95% CI 30.5–38.4) had an acute DWI lesion; the seven-fold between-study range means reclassification can materially change epidemiologic estimates (Brazzelli 2014, PMID 24085376).

The first diagnostic branch

Stabilize while localizing

Initial assessment establishes last-known-well time, airway and circulation, glucose, temperature, oxygenation, blood pressure, medications, recent surgery or bleeding, anticoagulant exposure, baseline function, and a focused neurological deficit. A standardized deficit scale improves communication but cannot replace syndrome recognition, particularly for posterior circulation disease (Yew 2015, PMID 25884860; Schneider 2023, PMID 37236792).

Question Minimum test or datum Why it cannot wait
Hemorrhage or ischemia? Non-contrast head CT, or rapid MRI where continuously available Determines thrombolysis versus hemorrhage pathway
Large-vessel occlusion? Head-and-neck CTA or MRA Determines thrombectomy candidacy and transfer destination
Salvageable tissue in an extended/uncertain window? CT perfusion or MR diffusion/perfusion, using validated thresholds Selects late-window treatment rather than diagnosing stroke alone
Hypoglycemia or major metabolic mimic? Point-of-care glucose and targeted laboratory testing Rapidly reversible and can reproduce focal deficits
Anticoagulation/coagulopathy? Medication history, platelet count, PT/INR; drug-specific tests when available Changes thrombolysis and reversal decisions
Cardiac source or acute myocardial injury? ECG and monitoring; troponin when indicated Detects AF and concurrent cardiac disease

Non-contrast CT

Non-contrast CT is the default first test because it is fast and highly effective at separating acute hemorrhage from an initially non-hemorrhagic presentation. A normal early CT does not exclude acute ischemic stroke; early ischemic change, hyperdense artery, loss of gray–white differentiation, and swelling increase over time (Vilela 2017, PMID 28551302; Czap 2021, PMID 34785603).

Vascular imaging

CTA from aortic arch through vertex identifies proximal and many medium-vessel occlusions, stenosis, dissection, aneurysm, and collateral routes. The thrombectomy trials made rapid vascular imaging a treatment-selection test rather than an optional etiologic study (Goyal 2015, PMID 25671798; Berkhemer 2015, PMID 25517348). MRA is an alternative when MRI is immediately accessible, but acquisition time and motion sensitivity matter in hyperacute care (Czap 2021, PMID 34785603).

Perfusion imaging

CT perfusion estimates hypoperfused tissue and an operational infarct core. In a diagnostic meta-analysis of 15 studies and 1,107 suspected strokes, sensitivity for infarction was 80% (95% CI 72–86) and specificity 95% (86–98); nearly two-thirds of false negatives were small lacunar infarcts (Biesbroek 2013, PMID 23736122). Perfusion maps are therefore selection tools with model-dependent thresholds, not an infallible binary diagnosis.

MRI and diffusion-weighted imaging

DWI is especially useful for small cortical, lacunar, brainstem, and uncertain-onset lesions, and susceptibility-sensitive sequences detect blood products and microbleeds (Czap 2021, PMID 34785603). Yet a meta-analysis of 12 studies and 3,236 acute ischemic strokes found 6.8% DWI-negative (95% CI 4.9–9.3); posterior-circulation syndromes had 5.1-fold higher odds (95% CI 2.3–11.6) of a negative scan (Edlow 2017, PMID 28615423). A clinically coherent disabling stroke can therefore remain treatable despite an initially negative DWI.

Syndrome localization

Territory or syndrome Typical findings Frequent diagnostic trap
Left anterior circulation Aphasia, right face/arm weakness, right visual-field loss Seizure with postictal aphasia or weakness
Right anterior circulation Neglect, left weakness, gaze preference, visual-field loss Delirium or functional symptoms when neglect is missed
Lacunar Pure motor, pure sensory, ataxic hemiparesis, dysarthria–clumsy hand Small lesions may be CT/CTP-negative
Posterior circulation Vertigo, diplopia, dysarthria, dysphagia, ataxia, crossed findings, visual loss Low NIHSS and early DWI negativity
SAH Sudden maximal-intensity headache, meningism, collapse, cranial-nerve palsy Migraine, syncope, or normal neurological examination
ICH Focal deficit with headache, vomiting, reduced consciousness or severe hypertension Clinical features alone cannot reliably distinguish it from ischemia

Posterior-circulation presentations deserve deliberate examination of eye movements, visual fields, gait/truncal stability, speech, swallowing, and crossed cranial-nerve/limb findings. Their symptoms are more often non-lateralizing, and conventional anterior-weighted scales under-represent their severity (Schneider 2023, PMID 37236792; Liberman 2017, PMID 28229398).

Stroke mimics and chameleons

A mimic is a non-vascular disorder presenting like stroke; a chameleon is a stroke presenting like another disorder (Moulin 2019, PMID 30239360). Reviews report wide incidence ranges because denominators differ—prehospital alerts, emergency evaluations, thrombolysis cohorts, and admitted suspected strokes are not interchangeable (Pohl 2021, PMID 34656244; Buck 2021, PMID 33678099).

Mimic family Clues supporting it Why stroke may still coexist
Seizure/postictal deficit Witnessed convulsion, fluctuating deficit, prior epilepsy Stroke can provoke the first seizure
Migraine aura Positive spreading symptoms, recurrent stereotyped episodes First or atypical aura remains a diagnosis of exclusion
Hypoglycemia/metabolic Abnormal glucose or systemic physiology Correction may reveal a persistent vascular deficit
Functional neurological disorder Internal inconsistency across tasks Functional signs do not exclude concurrent infarction
Peripheral vestibulopathy Isolated positional vertigo, peripheral ocular pattern Small brainstem/cerebellar strokes can mimic it closely
Tumor/infection/demyelination Subacute evolution, systemic features, characteristic MRI Acute hemorrhage or ischemia can complicate these disorders

Non-contrast CT alone does not prove an ischemic diagnosis when normal; multimodal CT or MRI can clarify difficult cases (Buck 2021, PMID 33678099). However, because alteplase benefit falls with delay, diagnostic testing should be chosen for whether it changes an immediate decision rather than for maximal completeness (Emberson 2014, PMID 25106063).

TIA: a diagnosis with a clock

The tissue-based TIA definition removes an arbitrary 24-hour symptom-duration threshold: transient symptoms plus acute infarction are classified as ischemic stroke (Sorensen 2011, PMID 21640301; Siket 2012, PMID 22974647). DWI positivity supports ischemia and predicts risk, but two-thirds of definite TIAs are DWI-negative in pooled data (Brazzelli 2014, PMID 24085376).

The workup is the same mechanism search compressed into hours: brain imaging, extracranial and intracranial vascular imaging, ECG/monitoring, risk-factor measurements, and targeted cardiac evaluation. Simple scores can triage risk but should not overrule symptomatic carotid stenosis, recurrent crescendo events, AF, or a clear high-risk mechanism (Siket 2012, PMID 22974647; Kleindorfer 2021, PMID 34024117).

Etiologic classification after acute decisions

TOAST

TOAST assigns one of five categories after clinical and ancillary evaluation (Adams 1993, PMID 7678184).

TOAST category Core evidence Important limitation
Large-artery atherosclerosis Relevant extracranial/intracranial plaque or stenosis with compatible infarct Coexisting AF or small-vessel disease can compete
Cardioembolism High-risk cardiac source and compatible distribution AF may be occult or incidental
Small-vessel occlusion Lacunar syndrome and small deep infarct without stronger cause Parent-artery plaque can mimic intrinsic arteriolar disease
Other determined etiology Dissection, vasculitis, thrombophilia, genetic arteriopathy, other defined cause Requires targeted testing; heterogeneous category
Undetermined etiology Incomplete evaluation, multiple plausible causes, or cryptogenic after adequate testing Conflates three very different states

TOAST was designed for trial stratification and had high agreement in its small initial test, but dominance rules discard overlapping disease (Adams 1993, PMID 7678184; Mehndiratta 2015, PMID 25398425).

ASCOD and causative systems

ASCOD grades each of five domains—atherosclerosis, small-vessel disease, cardiac pathology, other causes, and dissection—from potentially causal through present-but-unlikely, absent, or insufficiently investigated. It preserves multimorbidity and changed its significant stenosis threshold to 50% (Amarenco 2013, PMID 23899749). In 4,050 registry patients, overlapping diseases were common enough to motivate multidomain phenotyping rather than forced exclusivity (Sirimarco 2013, PMID 23860300).

Causative classification systems use explicit evidence hierarchies to select the most probable cause. Agreement and category yield differ across systems; the correct framework depends on whether the purpose is treatment, prognosis, genetics, surveillance, or trial reporting (Amarenco 2009, PMID 19342825; de Paiva Bezerra 2017, PMID 28844546).

Minimum mechanism-directed workup

Domain First-line evaluation Escalation when unresolved
Large arteries CTA/MRA head and neck; carotid ultrasound in selected settings Catheter angiography, vessel-wall MRI
Cardiac rhythm 12-lead ECG and inpatient telemetry Prolonged external or implantable monitoring
Cardiac structure Transthoracic echocardiography when findings would alter care Contrast study or transesophageal echocardiography
Small vessels MRI pattern, blood pressure, diabetes and renal assessment Genetic testing for early/familial or syndromic disease
Dissection CTA/MRA neck/head Fat-suppressed vessel-wall MRI or catheter angiography
Inflammation/infection History, examination, targeted inflammatory/infectious tests CSF, vessel-wall imaging, biopsy in selected cases
Hypercoagulability/cancer Clinical context rather than indiscriminate panels Targeted antiphospholipid, malignancy, or inherited testing

Testing should be pretest-probability driven. Broad panels generate incidental abnormalities, and an abnormality is not necessarily the stroke cause—the central reason ASCOD separates presence from causal likelihood (Amarenco 2013, PMID 23899749).

Common failure modes

  • Treating a negative CT as exclusion of ischemia: early ischemic stroke can be CT-normal (Czap 2021, PMID 34785603).
  • Treating a negative DWI as exclusion of stroke: pooled DWI-negative prevalence is 6.8%, enriched in posterior circulation (Edlow 2017, PMID 28615423).
  • Letting a low NIHSS exclude disabling posterior symptoms: scale content and disability are not equivalent (Schneider 2023, PMID 37236792).
  • Calling a mechanism from one incidental abnormality: causal confidence requires distribution, severity, timing, and competing-source analysis (Amarenco 2009, PMID 19342825).
  • Using “cryptogenic” for incomplete workup: TOAST undetermined includes incomplete, multiple, and fully investigated unknown causes (Adams 1993, PMID 7678184).
  • Missing SAH after a reassuring examination: sudden maximal headache may occur without a persistent focal deficit; CT timing and, when indicated, lumbar puncture or vascular imaging remain decisive (van Gijn 2007, PMID 17258671; Abraham 2016, PMID 27741994).

Open questions

  • Can a diagnostic pathway reduce posterior-circulation false negatives without delaying treatment, given the 5.1-fold enrichment of DWI-negative stroke in that territory? (Edlow 2017, PMID 28615423; Schneider 2023, PMID 37236792)
  • Which etiologic framework best predicts recurrence and treatment response when atherosclerosis, AF, and small-vessel disease coexist? (Sirimarco 2013, PMID 23860300; Amarenco 2013, PMID 23899749)
  • How should DWI-positive transient syndromes be counted across trials and burden estimates when DWI positivity varies from 9% to 67% across studies? (Brazzelli 2014, PMID 24085376)
  • Can imaging and bedside features distinguish seizure or migraine from ischemia accurately enough to reduce unnecessary treatment without increasing missed stroke? (Pohl 2021, PMID 34656244; Moulin 2019, PMID 30239360)

References

  1. Sacco RL, et al. An updated definition of stroke for the 21st century. Stroke. 2013. PMID 23652265
  2. Sorensen AG, Ay H. Transient ischemic attack: definition, diagnosis, and risk stratification. Neuroimaging Clin N Am. 2011. PMID 21640301
  3. Siket MS, Edlow JA. Transient ischemic attack: evolution of definition, diagnosis, risk stratification, and management. Emerg Med Clin North Am. 2012. PMID 22974647
  4. Adams HP Jr, et al. Classification of subtype of acute ischemic stroke: TOAST. Stroke. 1993. PMID 7678184
  5. Amarenco P, et al. Classification of stroke subtypes. Cerebrovasc Dis. 2009. PMID 19342825
  6. Amarenco P, et al. The ASCOD phenotyping of ischemic stroke. Cerebrovasc Dis. 2013. PMID 23899749
  7. Sirimarco G, et al. Overlap of diseases underlying ischemic stroke: ASCOD phenotyping. Stroke. 2013. PMID 23860300
  8. de Paiva Bezerra R, et al. Etiological classification using TOAST, CCS-TOAST, and ASCOD. J Stroke Cerebrovasc Dis. 2017. PMID 28844546
  9. Mehndiratta P, et al. Etiologic stroke subtypes: updated definition and workup strategies. Curr Treat Options Cardiovasc Med. 2015. PMID 25398425
  10. Czap AL, et al. Overview of imaging modalities in stroke. Neurology. 2021. PMID 34785603
  11. Edlow BL, et al. Diagnosis of DWI-negative acute ischemic stroke: a meta-analysis. Neurology. 2017. PMID 28615423
  12. Biesbroek JM, et al. Diagnostic accuracy of CT perfusion for detecting acute ischemic stroke. Cerebrovasc Dis. 2013. PMID 23736122
  13. Brazzelli M, et al. Diffusion-weighted imaging and diagnosis of transient ischemic attack. Ann Neurol. 2014. PMID 24085376
  14. Pohl M, et al. Ischemic stroke mimics: a comprehensive review. J Clin Neurosci. 2021. PMID 34656244
  15. Moulin S, Leys D. Stroke mimics and chameleons. Curr Opin Neurol. 2019. PMID 30239360
  16. Vilela P. Acute stroke differential diagnosis: stroke mimics. Eur J Radiol. 2017. PMID 28551302
  17. Buck BH, et al. Stroke mimics: incidence, aetiology, clinical features and treatment. Ann Med. 2021. PMID 33678099
  18. Liberman AL, Prabhakaran S. Stroke chameleons and stroke mimics in the emergency department. Curr Neurol Neurosci Rep. 2017. PMID 28229398
  19. Yew KS, Cheng E. Diagnosis of acute stroke. Am Fam Physician. 2015. PMID 25884860
  20. Schneider AM, et al. Posterior circulation ischaemic stroke diagnosis and management. Clin Med (Lond). 2023. PMID 37236792
  21. Goyal M, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015. PMID 25671798
  22. Berkhemer OA, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015. PMID 25517348
  23. Claassen J, et al. Spontaneous subarachnoid haemorrhage. Lancet. 2022. PMID 35985353
  24. van Gijn J, et al. Subarachnoid haemorrhage. Lancet. 2007. PMID 17258671
  25. Abraham MK, Chang WTW. Subarachnoid hemorrhage. Emerg Med Clin North Am. 2016. PMID 27741994
  26. Greenberg SM, et al. 2022 guideline for spontaneous intracerebral hemorrhage. Stroke. 2022. PMID 35579034
  27. Kleindorfer DO, et al. 2021 guideline for prevention after stroke or TIA. Stroke. 2021. PMID 34024117
  28. Emberson J, et al. Effect of treatment delay on intravenous alteplase outcomes. Lancet. 2014. PMID 25106063