What are the causes of stroke recurrence in patients with a history of stroke or transient ischemic attack (TIA)?

Causes of Stroke Recrudescence

Stroke recrudescence—the transient reemergence of prior stroke deficits without new infarction—is triggered primarily by systemic stressors including infection, hypotension, hyponatremia, sleep deprivation/stress, and benzodiazepine use, occurring in patients with chronic white matter tract involvement who have specific risk factors. 1

Clinical Definition and Timing

Recrudescence represents transient worsening of residual poststroke deficits or recurrence of prior stroke-related deficits without evidence of new ischemic injury. 1 This phenomenon occurs an average of 3.9 years after the index stroke and typically resolves within 18.4 hours, with 69% of episodes resolving by day 1. 1

Primary Triggers (Crossover Cohort Analysis)

The following triggers were significantly more prevalent during recrudescence admissions compared to non-recrudescence admissions in the same patients:

• Infection: The most common precipitant, causing systemic inflammation and metabolic stress 1
• Hypotension: Reduces perfusion pressure to chronically ischemic tissue with impaired autoregulation 1
• Hyponatremia: Electrolyte disturbances affecting neuronal function 1
• Insomnia or psychological stress: Sleep deprivation and stress-related physiological changes 1
• Benzodiazepine use: Sedative effects potentially unmasking marginal neurologic function 1

Patient Risk Factors (Case-Control Analysis)

Patients who experience recrudescence differ from stroke patients who do not:

• Demographics: More common in women and African American individuals 1
• Vascular risk factors: Higher prevalence of diabetes, dyslipidemia, and smoking history 1
• Index stroke characteristics: More severe initial deficits (higher baseline NIHSS scores) 1
• Stroke etiology: More frequent small-vessel disease and "other definite" causes 1

Anatomic Substrate

The underlying chronic strokes in recrudescence patients have distinctive features:

• White matter tract involvement: Predominantly affects white matter pathways rather than cortical regions 1
• Middle cerebral artery territory: 73% of cases involve MCA distribution 1
• Variable lesion size: Chronic strokes range from small to large but consistently involve critical white matter tracts 1

Clinical Phenotype

Recrudescence episodes have characteristic presentations:

• Deficit pattern: Typically motor-sensory or language dysfunction; isolated gaze paresis, hemianopia, or neglect are notably absent 1
• Severity: Mean NIHSS worsening of 2.5 points, with 38% of episodes affecting only a single NIHSS item 1
• Onset: Abrupt symptom emergence 1
• Duration: Brief, with most resolving within 24 hours 1

Distinction from Stroke Recurrence

This differs fundamentally from true stroke recurrence, which has separate risk factors and mechanisms:

Modifiable Risk Factors for True Recurrence

• Hypertension: The single most important modifiable risk factor, with population attributable risk as high as 50% in some groups 2
• Hyperlipidemia: Inadequately controlled LDL-C increases recurrence risk 2
• Diabetes mellitus: Independent predictor with 9.1% of recurrent strokes attributable to diabetes 3
• Atrial fibrillation: 54% increased risk of recurrence when present before index stroke (HR 1.54,95% CI 1.09-2.17) 4
• Medication nonadherence: Very low antithrombotic adherence increases recurrence risk 4.65-fold (95% CI 1.45-14.89); very low statin adherence increases risk 3.44-fold (95% CI 0.93-12.74) 5
• Blood pressure variability: For every 10-point increase in systolic BP variability, recurrent ischemic stroke risk increases by 15% (HR 1.15,95% CI 1.02-1.32) 6

Stroke Subtype-Specific Recurrence Patterns

• Large artery atherosclerosis: Highest recurrence rate, with 1-year rates up to 18% for severe (≥70%) intracranial stenosis 2
• Cardioembolic strokes: 54% of recurrences are the same subtype 4
• Hemorrhagic strokes: 51% of recurrences are hemorrhagic 4
• Small-vessel occlusion: Lowest 5-year recurrence risk at 36% 4

Clinical Pitfalls

Common misdiagnosis: Recrudescence is frequently mistaken for transient ischemic attack, leading to unnecessary thrombolysis. 1 In the study cohort, 4% of recrudescence patients received IV tPA without complications, but this represents overtreatment. 1

Key distinguishing features from TIA:

• Deficits match prior stroke territory exactly 1
• No acute lesion on diffusion-weighted imaging 1
• Presence of identifiable systemic trigger 1
• Resolution typically within 24 hours 1

Temporal Trends in True Recurrence

Stroke recurrence rates decreased from 18% (1995-1999) to 12% (2000-2005) at 5 years but have not improved since the mid-2000s, suggesting suboptimal implementation of preventive strategies particularly for cardioembolic and hemorrhagic stroke subtypes. 4