Early imaging correlates of subsequent motor recovery after stroke

 Well, lesion volume from the initial CT or MRI scan completely misses the continuing death of neurons from the 5 causes of the neuronal cascade of death in the first week thus killing off millions to billions of neurons!

Does anyone in stroke actually think?

Early imaging correlates of subsequent motor recovery after stroke

Randolph S Marshall, MS, MD, Eric Zarahn, PhD, Leeor Alon, MS, Brandon Minzer, MS, Ronald M Lazar, PhD, and John W Krakauer, MD Department of Neurology, Columbia University Medical Center, New York 

INTRODUCTION 

There is unexplained variability in the extent to which patients recover after stroke, particularly from the reference point of the first few days after onset. Among studies tracking motor impairment and recovery, only 30–50% of the variance of recovery is explained by the most commonly reported predictors --lesion volume and initial stroke severity 1 , 2. We hypothesized that functional imaging early after stroke could provide information over and above initial severity and lesion volume about the degree of subsequent recovery. Several prior functional imaging studies have reported altered brain activation patterns in patients at various stages of motor recovery after stroke3 – 6. These studies describe brain activation related to concurrent recovered performance at the time of scanning that differs to varying degrees from what is seen in age-matched controls. In this study we used functional imaging to ask a specific and unique question about motor recovery after stroke: can functional imaging in the early period after stroke detect brain activation related to subsequent recovered performance? Should such activation be identified then it could serve as a physiological target for intervention (e.g. non-invasive brain stimulation) in this early time period. To investigate whether brain activation early after stroke can be correlated with subsequent recovery, we scanned patients approximately 48 hours after stroke using fMRI, and defined recovery as the change in motor impairment from the time of scanning to a follow up point 3 months later. We used 3 different statistical tests: 1) a multivariate test, which is most sensitive to spatially diffuse activation, 2) voxel-wise statistical parametric mapping (SPM), which is most sensitive to focal activation, and 3) primary motor cortex (M1) region of interest (ROI) analysis, which is most sensitive to average activation within this region. The ROI analysis was chosen to test existing hypotheses implicating M1 and the corticospinal tract in recovery.7 – 9 All tests controlled for lesion volume and initial stroke severity, as well as other established clinical variables. METHODS Subjects We recruited stroke patients from a large screening data base of all patients with the diagnosis of ischemic stroke admitted to Columbia University Medical Center between December, 2004 and April, 2007 (n=993), part of Columbia’s Specialized Program of Translational Research in Acute Stroke (SPOTRIAS), an NINDS-funded national network to investigate new pathophysiologic, diagnostic and clinical approaches in acute stroke. Thirty-three consecutive patients with first ever ischemic stroke and hemiparesis able to undergo fMRI within 48 hours of stroke onset were recruited. Five patients were eligible but refused the fMRI scan. Three underwent the fMRI, but did not complete the 3-month clinical follow up (1 developed dementia, 1 left the country, 1 was incarcerated). Two patients had recurrent stroke prior to the 3-month follow-up and were excluded from analysis. The final sample size of 23 was considered adequate for a functional imaging study of this type. Patients with aphasia or hemineglect alone were not included in this analysis. See Table 1 for more demographic and clinical details. All patients except for 4 underwent a single session of fMRI scanning at our target of 24–48 hours after stroke onset (the remaining 4 patients had their scans between 49 and 96 hours due to scheduling delays; mean time to scan=47.8±21.6h, median=46h). Exclusion criteria also included seizure at stroke onset, moderate to severe aphasia or other cognitive impairment that precluded training on the fMRI task, or any contraindication to MRI. None of the patients had neglect or apraxia on examination. Patients did not smoke on the day of scanning (they were inpatients); caffeine intake was not recorded. The strict eligibility criteria permitted us to control for unwanted variables while preserving the wide spectrum of initial motor severity that would contribute to the correlation analysis. Total lesion volumes were estimated by summing the volumes of the DWI lesion in each slice (length by width by slice thickness measured with the measurement tool in the PACS system software) in which the DWI was positive. Recovery measure Motor impairment was measured with the upper limb Fugl-Meyer assessment (FM)11, which has a maximum score of 66, and is valid and highly reliable over a wide spectrum of severities.12 – 16 FM was assessed on the day of scanning (FM initial ) and again at 3 months (FM 3 months ). Recovery (ΔFM) was defined as ΔFM = FM 3 months − FM initial . Our decision to use a change score as our measure of recovery was based on the idea that the degree of change, rather than the final level achieved, would better reflect a biological recovery process 17. In addition to the FM we also measured hand dynamometry at baseline on the day of scanning (DYN initial ). The reason for doing so was that hand dynamometry score should presumably correlate with the degree of difficulty subjects would have to perform the fMRI hand closure task. DYN initial was taken as an average of 3 measurements of maximal grip force. fMRI data acquisition Patients underwent gradient echo-echoplanar fMRI (GE 1.5 T, 64 × 64 matrix, FOV = 19 cm, 21 slices, slice thickness/skip = 4.5 mm/0 mm, TR = 4000 ms, TE = 52 ms, flip angle = 60°) while performing the repetitive hand closure task described below. One session (40 volumes) was performed per hand. The order in which the hands (affected/unaffected) were tested was counterbalanced across patients except for those with complete plegia (see below). Motor task used during fMRI The task was a simple repetitive hand closure in synchrony with a 1 Hz metronome click, following a block design: 20-second rest epochs alternating with 20-second task epochs (4 cycles total per hand). The instruction was: ”Close your hand gently in rhythm with the click you hear. Start and stop when you hear the instructions through the headphones.” The metronome click was played continuously via MRI-compatible headphones in the scanner. Marshall et al. Page 2 Ann Neurol. Author manuscript; available in PMC 2010 May 1. NIH-PA Author Manuscript NIH-PA Author Manuscript