Recrudescence of Deficits After Stroke: Clinical and Imaging Phenotype, Triggers, and Risk Factors

Abstract

Importance: Reemergence of previous stroke-related deficits (or poststroke recrudescence [PSR]) is an underrecognized and inadequately characterized phenomenon.

Objective: To investigate the clinical features, triggers, and risk factors for PSR.

Design, setting, and participants: This retrospective study incorporated a crossover cohort study to identify triggers and a case-control study to identify risk factors. The study used the Massachusetts General Hospital Research Patient Data Repository to identify patients for the period January 1, 2000, to November 30, 2015, who had a primary or secondary diagnosis of cerebrovascular disease, who underwent magnetic resonance imaging of the brain at least once, and whose inpatient or outpatient clinician note or discharge summary stated the term recrudescence. In all, 153 patients met the preliminary diagnostic criteria for PSR: transient worsening of residual poststroke focal neurologic deficits or transient recurrence of prior stroke-related focal deficits, admission magnetic resonance imaging showing a chronic stroke but no acute infarct or hemorrhage, no evidence of transient ischemic attack or seizure, no acute lesion on diffusion-weighted imaging, and no clinical or electroencephalographic evidence of seizure around the time of the event.

Main outcomes and measures: Clinical and imaging features of PSR; triggers (identified by comparing PSR admissions with adjacent admissions without PSR); and risk factors (identified by comparing PSR cases with control cases from the Massachusetts General Hospital Stroke Registry).

Results: Of the 153 patients, 145 had prior infarct, 8 had hypertensive brain hemorrhage, and 164 admissions for PSR were identified. The patients' mean (SD) age was 67 (16) years, and 92 (60%) were women. Recrudescence occurred a mean (SD) of 3.9 (0.6) years after the stroke, lasted 18.4 (20.4) hours, and was resolved on day 1 for 91 of the 131 episodes with documented resolution time (69%). Deficits were typically abrupt and mild and affected motor-sensory or language function. No patient had isolated gaze paresis, hemianopia, or neglect. During PSR, the National Institutes of Health Stroke Scale (NIHSS) score worsened by a mean (SD) 2.5 (1.9) points, and deficits were limited to a single NIHSS item in 62 episodes (38%). The underlying chronic strokes were variably sized, predominantly affected white matter tracts, and involved the middle cerebral artery territory for 112 patients (73%). Infection, hypotension, hyponatremia, insomnia or stress, and benzodiazepine use were higher during PSR admissions. Compared with the control group (patients who did not experience recrudescence), the PSR group (patients who were hospitalized for recrudescence) had more women, African American individuals, and those who self-identified as being from "other" race. The PSR group also had more diabetes, dyslipidemia, smoking, infarcts from small-vessel disease, and "other definite" causes and worse onset NIHSS scores. Six patients (4%) received intravenous tissue plasminogen activator without complications.

Conclusions and relevance: The PSR features identified in the study should enable prompt diagnosis and distinguish recrudescence from mimics, such as transient ischemic attacks, migraine, Todd paralysis, and Uhthoff phenomenon. Prospective studies are required to validate the proposed diagnostic criteria and to decipher underlying mechanisms.

Figure 1.. Recrudescence After Ischemic Stroke

A woman in her 50s with chronic hypertension, diabetes, and a cryptogenic ischemic stroke 7 years prior to admission developed acute dysarthria, mild left facial weakness, and mild sensory loss in the left arm. The admission National Institutes of Health Stroke Scale (NIHSS) score was 3. Magnetic resonance imaging of the brain showed a chronic embolic-appearing ischemic stroke in the right middle cerebral artery territory (arrowhead in A, axial fluid-attenuated inversion recovery [FLAIR] image) but no acute lesion on diffusion-weighted images (B). Findings on magnetic resonance angiography of the head and neck were normal. Blood test results were normal except for an elevated blood glucose level (262 mg/dL) (to convert to millimoles per liter, multiply by 0.0555). Urinalysis results were positive, prompting treatment for urinary tract infection. Electroencephalogram showed no evidence of ongoing seizures. Her symptoms resolved completely in 10 hours. A review of her medical records showed that she had an NIHSS score of 12 at the time of the incident stroke with left face, arm, and leg weakness and left hemisensory loss, from which she recovered completely (NIHSS score of 0) over a period of 3 months. The clinical diagnosis was poststroke recrudescence from urinary tract infection and hyperglycemia.

Figure 2.. Serial National Institutes of Health Stroke Scale (NIHSS) Scores

Box-and-whisker plots show the distribution of NIHSS scores at the time of the index stroke, at poststroke baseline, and during recrudescence in patients with ischemic stroke and hemorrhagic stroke. There were no significant differences between NIHSS scores in the ischemic and hemorrhagic groups at the time of stroke onset (mean [SD], 10.0 [5.6] vs 12.9 [9.1]; P = .19), poststroke baseline (mean [SD], 2.7 [4.1] vs 3.4 [5.1]; P = .63), or recrudescence (mean [SD], 5.1 [4.7] vs 5.6 [5.3]; P = .75). There were no significant differences between groups in the degree of NIHSS score worsening (mean [SD], 2.4 [2.0] vs 2.3 [0.9]; P = .81) or the duration of recrudescence episodes (mean [SD], 18.5 [20.7] vs 16.6 [15.5] hours; P = .81). Boxes indicate the lower (25th) and upper (75th) quartiles; horizontal lines in the boxes, median values; whiskers, minimum and maximum values; and open circles beyond the whiskers, outliers.