Date of Award

January 2017

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Kevin N. Sheth

Abstract

Intracerebral hemorrhage (ICH) is associated with high mortality (40-50%) among stroke subtypes, however survivors may exhibit robust functional recovery. Research regarding ICH recovery has focused almost exclusively on motor domains at short time-points, three to six months. This prospective observational study was initiated to follow ICH recovery up to 12 months post-injury across motor and non-motor domains. Patients were enrolled and evaluated at discharge as well as three, six, and 12 months post-injury utilizing the modified rankin scale (mRS), Barthel Index (BI), Montrael Cognitive Assessment (MoCA), European Qualtiy of Life 5 Dimensions (EQ-5D), European Qualtiy of Life Visual Analogue Scale (EQ-VAS), and the Stroke Specific Quality of Life (SS-QoL).

As of October 2016, we have enrolled 173 ICH patients, with an average response rate (i.e. the ability to complete follow-up evaluations) of 85-89% across all follow-up time-points. Using either the mRS or BI, measures of motor disability, there was a significant improvement in scores (p values < 0.001) between discharge and three, six, and 12 months. The mRS scores failed to show a significant difference between follow-up time-points (i.e. three to six months, six to 12 months, etc.). However the BI showed significant improvement in scores between three and 12 months (p = 0.013), as well as between six and 12 months (p = 0.025). A subsequent analysis, comparing BI scores between three to 12 months, showed a significant relationship of time by age (p = 0.047; i.e. differences in improvement depending on the age of the patient), time by admission GCS (p = 0.010; i.e. differences in improvement depending on the admission GCS of the patient), time by ICH volume (p = 0.004; i.e. differences in improvement depending on the initial ICH volume of the patient), and time by location (p = 0.005; i.e. differences in improvement depending on the initial ICH location of the patient). Follow-up plots suggest patients with characteristically more disabling injury as traditionally measured through metrics like the ICH score (i.e. older patients, lower admission GCS, larger ICH volume, deeper location) showed the most improvement between three and 12 months. These results would suggest that ICH motor recovery will improve up to at least 12 months post-injury and patients with more debilitating injury will show improved recovery at the late-stage.

Across quality of life measures (i.e. EQ-5D, EQ-VAS, SS-QoL), patients showed the greatest recovery in motor domains (i.e. Mobility, Self-Care, Activities, Upper Extremities). Despite this improvement, patients self-reported health scores (EQ-VAS, a subjective 0 to 100 point score that patients use to describe their overall health) declined across time-points. There were additionally decreases in scores associated with the “Thinking” domain as well as increases in “Pain” symptoms. Since decreases in self-reported health score matched trends in the “Thinking” and “Pain” domains rather than the increases observed in motor-domains, patients may value non-motor domains when assessing their overall health compared to motor recovery. Finally, while there are improvements of cognitive impairment (measured via the MoCA, total score < 18) across time-points (discharge: 72%, three months: 65%, six months: 53%, 12 months: 48%), these results are more profound for deep compared to lobar ICH.

Preliminary analyses of the cohort enrolled thus far suggest ICH patients improve in motor recovery up to at least 12 months post-injury. However despite robust motor recovery, patients still exhibit high rates of cognitive impairment and impairment in quality of life. These results necessitate the need for long-term end-points in ICH interventional trials with further emphasis on non-motor domains. Continued enrollment and prospective evaluation of this cohort promises further insight into the recovery process.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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