Stroke can be classified into either hemorrhagic or ischemic stroke. Hemorrhagic stroke is caused by a rupture or internal bleeding in any of the cerebral arteries. On the other hand, ischemic stroke is due to blockage of blood supply to the brain, causing cell death due to lack of oxygen (infarct). This type of stroke is much more common to occur in either large arteries (atherosclerosis) or small penetrating arteries (lacunar infarct), or cardioembolism (the heart pumps blocking materials up to the brain). Neuroimaging has been useful as a diagnostic tool.
As most patients survive the initial injury, the next biggest challenge is the management of long-term impairment, limitation of daily activities or disability, and reduced participation or handicap. The main focus of the rehabilitation post-stroke is the recovery of the impaired movement (by physiotherapists), and the associated functions in daily living (by occupational therapists). Technically, we have to understand the difference between the recovery of function ("I am able to use the hand and arm in daily activities again") and resolution of impairment ("I can gain back my strength and movement"). Regardless of which, motor recovery after stroke is confusing. The term cannot be separated from compensatory mechanisms, where a new type of movement is produced to achieve the natural way prior to the stroke. Often during the assessment, clinicians do not separate motor compensation and recovery. In doing a prognosis, it has been known that there is a large inter-individual variability, patient heterogeneity. While clinical assessment has been very crucial in the early phase, there also exists a degree of inter-rater variability of the clinicians.
Stroke recovery in the early phase correlates to the resolution of dying tissue, edema, and inflammation (Furlan et al., 1996; Stinear and Byblow, 2014), while later recovery relates mainly to disinhibition of redundant neural circuits, recruitment of functionally homologous pathways, and the creation of neural connections to overtake the previous functions of the damaged neurons (Rossini et al., 2007; Murphy and Corbett, 2009; Ackerley et al., 2011). Interestingly, such processes may occur on the ipsilesional and contralesional hemispheres and are not completely understood (Hoyer and Celnik, 2011; Buetefisch, 2015).
Several studies have shown that patients commonly demonstrate increased M1 excitability on the contralesional hemisphere (equivalent to the ipsilateral hemisphere for healthy patients) for movements with the affected side (e.g. Shimizu et al., 2002; Butefisch et al., 2008; Murase et al., 2004; Ward and Cohen, 2004). Such theory, known as the interhemispheric competition model, says that an interhemispheric imbalance occurs in patients where the ipsilesional M1 no longer inhibits the contralesional hemisphere and the contralesional side appears to inhibit the ipsilesional, possibly through the transcallosal fibers. The magnitude of such an imbalance appears to positively correlate with the degree of motor impairment (Murase et al., 2004), and the interhemispheric imbalance in other functional networks may also contribute toward other cortical functional disruptions including neglect and aphasia.
Neuroimaging studies have shown that bilateral activation of the motor cortex leads to poorer motor recovery in most stroke patients. Conversely, studies by Nick Ward and colleagues show that a shift from bilateral activation to unilateral activation is a sign of good recovery. In other studies, it has been shown that this statement may have a limitation, i.e. significant mirror movements of the unaffected hand, causing an increase in contralesional activity.
In 2008, Krakauer's team studied the recovery of motor impairment using improvement in the Fugl-Meyer scale (FM) of the upper limb (UL). They defined recovery of impairment as the difference between FM score in the few days after stroke and at a later time point (3 months) (Prabakharan S. et al, 2008). They pointed to the idea of the proportional recovery rule which reflects spontaneous recovery. The maximum FM score for UL = 66. The proportional recovery rule states that, at 3 months, patients should get approximately 70% of their maximum potential recovery back. Example: a patient with moderate hemiparesis of 46 will recover (66-46) x 0.7 = 60. This rule has been validated in subsequent studies. Interestingly, some severe patients do not follow this rule while some other severe patients do. Such a categorical phenomenon bears two consequences. First, perhaps the current rehab therapy has little or, if it does, limited impact on the recovery within 3 months after the onset of stroke. Second, there are some underlying neurophysiological mechanisms unique to those non-fitter severe patients (see Krakauer et al, 2015).
TMS may provide a valuable assessment tool early in stroke. It can be used to test the functional integrity and excitability of the descending corticospinal pathways. Studies have shown that the ability to elicit MEP (motor evoked potential) within 2 weeks after stroke indicates a good corticospinal tract (CST) and it serves as a good predictor for recovery. However, most of these studies only targeted the upper limb, not the lower limb (LL), to the difficulty in accessing the "leg" area in the medial wall of the central sulcus. See Bembenek J.P, et al, (2012) for a review. Byblow et al (2015) did an important study using TMS very early in stroke, where they show that non-fitter patients do not follow the proportional recovery rule because they do not have intact CST useful for recovery. Patients who have their posterior limb of the internal capsule above 0.15, a threshold or point of no return, do not recover at later assessments. The resting motor threshold (RMT) also displays the proportional recovery rule. Interestingly, the authors show that adding regular therapy session does not yield significant results, suggesting that a more intensive behavioral intervention (e.g. using robots) may be needed. Feng W, et al (2015) did another relevant study where they formulated a neuroimaging biomarker of stroke. The authors used a weighted CST load, a method to better estimate the integrity of the CST in the ipsilesional hemisphere. An initial assessment using such measure, instead of an initial FM score, would be a more graded and sensitive predictor of recovery.
As most patients survive the initial injury, the next biggest challenge is the management of long-term impairment, limitation of daily activities or disability, and reduced participation or handicap. The main focus of the rehabilitation post-stroke is the recovery of the impaired movement (by physiotherapists), and the associated functions in daily living (by occupational therapists). Technically, we have to understand the difference between the recovery of function ("I am able to use the hand and arm in daily activities again") and resolution of impairment ("I can gain back my strength and movement"). Regardless of which, motor recovery after stroke is confusing. The term cannot be separated from compensatory mechanisms, where a new type of movement is produced to achieve the natural way prior to the stroke. Often during the assessment, clinicians do not separate motor compensation and recovery. In doing a prognosis, it has been known that there is a large inter-individual variability, patient heterogeneity. While clinical assessment has been very crucial in the early phase, there also exists a degree of inter-rater variability of the clinicians.
Stroke recovery in the early phase correlates to the resolution of dying tissue, edema, and inflammation (Furlan et al., 1996; Stinear and Byblow, 2014), while later recovery relates mainly to disinhibition of redundant neural circuits, recruitment of functionally homologous pathways, and the creation of neural connections to overtake the previous functions of the damaged neurons (Rossini et al., 2007; Murphy and Corbett, 2009; Ackerley et al., 2011). Interestingly, such processes may occur on the ipsilesional and contralesional hemispheres and are not completely understood (Hoyer and Celnik, 2011; Buetefisch, 2015).
Several studies have shown that patients commonly demonstrate increased M1 excitability on the contralesional hemisphere (equivalent to the ipsilateral hemisphere for healthy patients) for movements with the affected side (e.g. Shimizu et al., 2002; Butefisch et al., 2008; Murase et al., 2004; Ward and Cohen, 2004). Such theory, known as the interhemispheric competition model, says that an interhemispheric imbalance occurs in patients where the ipsilesional M1 no longer inhibits the contralesional hemisphere and the contralesional side appears to inhibit the ipsilesional, possibly through the transcallosal fibers. The magnitude of such an imbalance appears to positively correlate with the degree of motor impairment (Murase et al., 2004), and the interhemispheric imbalance in other functional networks may also contribute toward other cortical functional disruptions including neglect and aphasia.
Neuroimaging studies have shown that bilateral activation of the motor cortex leads to poorer motor recovery in most stroke patients. Conversely, studies by Nick Ward and colleagues show that a shift from bilateral activation to unilateral activation is a sign of good recovery. In other studies, it has been shown that this statement may have a limitation, i.e. significant mirror movements of the unaffected hand, causing an increase in contralesional activity.
In 2008, Krakauer's team studied the recovery of motor impairment using improvement in the Fugl-Meyer scale (FM) of the upper limb (UL). They defined recovery of impairment as the difference between FM score in the few days after stroke and at a later time point (3 months) (Prabakharan S. et al, 2008). They pointed to the idea of the proportional recovery rule which reflects spontaneous recovery. The maximum FM score for UL = 66. The proportional recovery rule states that, at 3 months, patients should get approximately 70% of their maximum potential recovery back. Example: a patient with moderate hemiparesis of 46 will recover (66-46) x 0.7 = 60. This rule has been validated in subsequent studies. Interestingly, some severe patients do not follow this rule while some other severe patients do. Such a categorical phenomenon bears two consequences. First, perhaps the current rehab therapy has little or, if it does, limited impact on the recovery within 3 months after the onset of stroke. Second, there are some underlying neurophysiological mechanisms unique to those non-fitter severe patients (see Krakauer et al, 2015).
TMS may provide a valuable assessment tool early in stroke. It can be used to test the functional integrity and excitability of the descending corticospinal pathways. Studies have shown that the ability to elicit MEP (motor evoked potential) within 2 weeks after stroke indicates a good corticospinal tract (CST) and it serves as a good predictor for recovery. However, most of these studies only targeted the upper limb, not the lower limb (LL), to the difficulty in accessing the "leg" area in the medial wall of the central sulcus. See Bembenek J.P, et al, (2012) for a review. Byblow et al (2015) did an important study using TMS very early in stroke, where they show that non-fitter patients do not follow the proportional recovery rule because they do not have intact CST useful for recovery. Patients who have their posterior limb of the internal capsule above 0.15, a threshold or point of no return, do not recover at later assessments. The resting motor threshold (RMT) also displays the proportional recovery rule. Interestingly, the authors show that adding regular therapy session does not yield significant results, suggesting that a more intensive behavioral intervention (e.g. using robots) may be needed. Feng W, et al (2015) did another relevant study where they formulated a neuroimaging biomarker of stroke. The authors used a weighted CST load, a method to better estimate the integrity of the CST in the ipsilesional hemisphere. An initial assessment using such measure, instead of an initial FM score, would be a more graded and sensitive predictor of recovery.
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