Evidence for transhemispheric diaschisis in unilateral stroke

Nineteen patients with strictly unilateral ischemic stroke as determined by clinical examination, computed tomography, magnetic resonance imaging, and standard angiography underwent cerebral blood flow (CBF) analysis using fluorine 18 fluoromethane and positron emission tomography. Mean flow values for averaged hemispheric, infarct, and homologous contralateral regions of interest (ROIs) were determined. All patient CBF values were significantly below comparable CBF ROIs in neurologically normal controls using Wilcoxon's two-sample rank testing. Multiple regression analysis disclosed a significant correlation between contralateral CBF are both localized CBF in the infarct ROI and patient age. Correlations between contralateral CBF and dependency score or severity of neurologic deficit at time of positron emission tomography, expired PCO2, mean arterial blood pressure, serum glucose or hematocrit, risk factor score, and number of days studied after stroke were not statistically significant. Although we did not identify the biologic mechanisms involved, we conclude that CBF reduction contralateral to a strictly unilateral ischemic infarction is due to a combination of aging and transhemispheric diaschisis.     

Crossed cerebellocerebral diaschisis in patients with cerebellar stroke

Objectives– We performed single‐photon emission computed tomography (SPECT) to investigate crossed cerebellocerebral diaschisis (CCCD) in patients with cerebellar stroke. Material and methods– Fifteen patients with unilateral cerebellar stroke underwent SPECT of the brain with N‐isopropyl‐p‐[¹²³I] iodoamphetamine (¹²³I‐IMP). Regional cerebral blood flow (rCBF) was measured by the autoradiographic method. Regions of interest were defined in the cerebral cortex, striatum, thalamus and cerebellum to compare structures (contralateral to the cerebellar lesion) with counterparts ipsilateral to the stroke. Results– In the frontal and parietal cortices, especially the posterior superior frontal, anterior midfrontal, precentral, postcentral, and supramarginal areas, rCBF contralateral to the lesion was significantly lower than on the side of the lesion (showing CCCD). Conclusion – This CCCD phenomenon is important to be aware of in clinical reading of images.     

The role of the unaffected hemisphere in motor recovery after stroke

The contribution of the ipsilateral (nonaffected) hemisphere to recovery of motor function after stroke is controversial. Under the assumption that functionally relevant areas within the ipsilateral motor system should be tightly coupled to the demand we used fMRI and acoustically paced movements of the right index finger at six different frequencies to define the role of these regions for recovery after stroke. Eight well‐recovered patients with a chronic striatocapsular infarction of the left hemisphere were compared with eight age‐matched participants. As expected the hemodynamic response increased linearly with the frequency of the finger movements at the level of the left supplementary motor cortex (SMA) and the left primary sensorimotor cortex (SMC) in both groups. In contrast, a linear increase of the hemodynamic response with higher tapping frequencies in the right premotor cortex (PMC) and the right SMC was only seen in the patient group. These results support the model of an enhanced bihemispheric recruitment of preexisting motor representations in patients after subcortical stroke. Since all patients had excellent motor recovery contralesional SMC activation appears to be efficient and resembles the widespread, bilateral activation observed in healthy participants performing complex movements, instead of reflecting maladaptive plasticity. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Neuroplasticity in stroke recovery. The role of microglia in engaging and modifying synapses and networks

Neuroplasticity after ischaemic injury involves both spontaneous rewiring of neural networks and circuits as well as functional responses in neurogenic niches. These events involve complex interactions with activated microglia, which evolve in a dynamic manner over time. Although the exact mechanisms underlying these interactions remain poorly understood, increasing experimental evidence suggests a determining role of pro‐ and anti‐inflammatory microglial activation profiles in shaping both synaptogenesis and neurogenesis. While the inflammatory response of microglia was thought to be detrimental, a more complex profile of the role of microglia in tissue remodelling is emerging. Experimental evidence suggests that microglia in response to injury can rapidly modify neuronal activity and modulate synaptic function, as well as be beneficial for the proliferation and integration of neural progenitor cells (NPCs) from endogenous neurogenic niches into functional networks thereby supporting stroke recovery. The manner in which microglia contribute towards sculpting neural synapses and networks, both in terms of activity‐dependent and homeostatic plasticity, suggests that microglia‐mediated pro‐ and/or anti‐inflammatory activity may significantly contribute towards spontaneous neuronal plasticity after ischaemic lesions. In this review, we first introduce some of the key cellular and molecular mechanisms underlying neuroplasticity in stroke and then proceed to discuss the crosstalk between microglia and endogenous neuroplasticity in response to brain ischaemia with special focus on the engagement of synapses and neural networks and their implications for grey matter integrity and function in stroke repair.     

The role of antiphospholipid antibodies in stroke.

Antiphospholipid antibodies may be found in about 10% of all subjects with acute stroke but probably are present in as many as 50% of young persons with stroke and perhaps even in high prevalence in persons who have coexisting rheumatologic diseases such as SLE. In these latter groups, the association may be as high as 50%. Probably the best related syndrome is Sneddon's syndrome, which has a high prediction to dementia. Furthermore, vascular dementia may be a prominent feature of the aPL syndrome in subjects under age 55. The cause and mechanism by which aPL are related to stroke remain unknown. Likewise, there is a dearth of information about prognosis, morbidity, and stroke recurrence in subjects who have these immunoglobulin markers. Thus therapy remains very problematic, but current strategies include the use of antiaggregate therapy, warfarin, and limited implementation with prednisone and plasmaphoresis. Data that demonstrate clear cut benefit of any of these therapies are lacking. Ultimately, unraveling these crucial problems concerning the aPL syndrome may provide great insight into certain stroke mechanisms.     

Contralateral flow reduction in unilateral stroke: evidence for transhemispheric diaschisis

Using clinical presentation, angiography, computed tomography, and nuclear magnetic resonance imaging, 7 patients were identified who had strictly unilateral hemispheric infarction and unilateral cerebrovascular disease. In 6, cerebral blood flow measured by fluorine-18-fluoromethane inhalation and positron emission tomography was reduced in the contralateral hemisphere (p less than 0.05). Multiple regression analysis demonstrated a high correlation between contralateral flow reduction and the degree of flow impairment in the infarcted area (r = 0.941, p = 0.0014) but not with age, risk factor profile, blood pressure, PCO2, hematocrit, or duration of stroke. We conclude that transhemispheric diaschisis best explains the contralateral flow reduction seen in supratentorial ischemic stroke.     

The role of the intact hemisphere in recovery of midline muscles after recent monohemispheric stroke

Transcranial magnetic stimulation (TMS) of the motor cortex was used to study basic mechanisms of motor reorganization after major hemispheric stroke in humans. We sought to clarify the possible role of the intact hemisphere in motor recovery of the lingual muscles, and to evaluate the compensatory use of preexisting uncrossed motor pathways projecting to these midline muscles. TMS and bilateral surface recordings from the lingual muscles were carried out in six selected stroke patients who presented with a unilateral lingual paralysis after a limited monohemispheric ischemia. The first examination was performed during the symptomatic stage (t ₁) and was repeated after complete recovery of lingual function had been established (t ₂). The cortical motor output patterns were analyzed and compared with the data from 40 healthy controls. In the controls TMS of either hemisphere invariably produced contralateral and ipsilateral compound muscle action potentials (CMAPs), elicited through crossed and uncrossed central motor pathways, respectively. In most individuals an asymmetric cortical motor output pattern was found, as significantly greater mean CMAPs of shorter onset latencies were recorded from the contralateral lingual muscles than from the ipsilateral responses. In the six patients with a unilateral lingual paralysis a similar pattern was found on initial examination by stimulating the intact hemisphere, whereas TMS of the affected hemisphere failed to elicit any CMAP bilaterally. At t ₂ all patients had regained normal lingual function. Only one patient showed evidence of a complete recovery of the primarily affected hemisphere, as TMS now elicited normal CMAPs bilaterally. In the remaining five patients the unilateral interruption of the corticonuclear pathways persisted in spite of complete functional recovery. In these subjects the recovery of symmetric lingual movements must be attributed to the intact hemisphere. From this it is concluded that recovery of a unilateral lingual paralysis after restricted monohemispheric lesions is possible without recovery of the cortical motor projections from the affected hemisphere. In these cases the intact hemisphere is responsible for restoration of normal lingual movements, most likely by potentiating the effect of preexisting uncrossed motor pathways. Received: 26 March 1998 Accepted: 24 June 1998     

Crossed cerebellar diaschisis in acute ischemic stroke: a study with serial SPECT and MRI.

This study evaluated the relationship between crossed cerebellar diaschisis (CCD) and (1) lesion volume and location in the acute phase and 1 week after stroke onset and (2) clinical outcome. Twenty-two patients with cerebral ischemic stroke underwent single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) within 48 h and on day 8 from onset. Interhemispheric asymmetric indices (AI) on SPECT were calculated for medial, intermediate, and lateral zones of the cerebellum. Lesion volumes and locations were obtained from diffusion-weighted MRI. Neurological status and 3-month clinical outcome were evaluated. Within 48 h, lesion locations in the temporal association cortex and pyramidal tract of the corona radiata were independent determinants for the AI of the medial zone (R(2)=0.439). Lesion locations in the primary, premotor, and supplementary motor cortices, primary somatosensory cortex, and anterior part of the posterior limb of the internal capsule were determinants for the AI of the intermediate zone (R(2)=0.785). Lesions in the primary motor cortex, premotor, and supplementary motor cortices and in the genu of the internal capsule were determinants for the AI of the lateral zone (R(2)=0.746). On day 8, the associations were decreased. The AIs of the intermediate and lateral zones and lesion location in the parietal association cortex were independently associated with the 3-month clinical outcome (R(2)>0.555). Acute CCD is a result of functional deafference, while in the subacute phase, transneuronal degeneration might contribute to CCD. CCD in the intermediate and later zones is a better indicator than that in the medial zone.     

The role of drugs in the etiology of stroke.

Drugs of many classes have been implicated in hemorrhagic and ischemic stroke. Alcohol in moderation may have a protective effect although in greater doses may predispose to stroke. Drugs such as cocaine, amphetamines and heroin have been associated with stroke by a number of mechanisms. Antiplatelet, anticoagulant and thrombolytic therapy carry risk of hemorrhagic complications. Oral contraceptives appear to slightly increase stroke risk whereas estrogen replacement therapy may decrease it. Anabolic steroid use in athletes has been linked to stroke. The antineoplastic agent L-asparaginase has been associated with cerebral hemorrhage, ischemic infarction and venous sinus thrombosis. Infarction has been reported in association with cisplatin-based combination chemotherapy. Stroke is an infrequent but recognized complication of some forms of drug therapy and drug abuse.     

Regional cerebral blood flow, diaschisis, and steal after stroke

Regional CBF was measured by 133Xe inhalation in unilateral cerebral infarction, carotid TIAs, and normal volunteers. Regional CBF values were bilaterally and symmetrically reduced in patients measured within 3 weeks after stroke. Later, rCBF values returned toward normal in the contralateral hemisphere of patients with infarction and in both hemispheres with carotid TIAs. In cases with carotid occlusive disease, flow reduction was seen in the contralateral posterior cerebral artery distribution, with hyperemia in ipsilateral occipital lobe caused by interhemispheric steal. Brainstem-cerebellar flow values were increased following acute cerebral infarction if patients were alert but reduced if consciousness was impaired.     

The hemiplegic arm after stroke: measurement and recovery.

Seven clinical tests have been used to study the recovery of arm function in 92 patients over 2 years following their stroke. These tests are simple and quick, and can be used by any interested observer. They form a hierarchical scale that measures recovery. Statistically significant improvement is only seen in the first 3 months. Fifty-six patients initially had non-functional arms; eight made a "complete recovery" and 14 a partial recovery. The tests described are inadequate on their own because they are not sufficiently sensitive at the upper range of ability. While recovery of lost function does relate to the degree of initial neurological loss in the arm, it seems to be largely independent of the overall severity of the stroke.     

The initial acute phase response predicts long-term stroke recovery.

Indicators of an acute phase response (APR) in acute ischemic stroke have been shown to correlate with infarct size and predict stroke recurrence. In this study, we examined how well the APR indicators predicted long-term stroke recovery compared with standard clinical predictors of recovery. Plasma levels of interleukin-6 (IL-6), fibrinogen, white blood cells (WBCs), and serum albumin were measured within 4+/-2 days of onset in 131 stroke patients who were free of apparent infections. Standard clinical predictors included initial National Institutes of Health Stroke Scale (NIHSS), infarct size on computed tomography (CT), and Glasgow scale. The individual correlations with 6-month Glasgow outcome were IL-6, 0.42; fibrinogen, 0.24; WBC, 0.35; albumin, 0.47; NIHSS, 0.53; infarct size, 0.19; and initial Glasgow, 0.57. (all P<.005). Multiple regression analysis yielded an adjusted R(2) of .31 for the APR indicators, compared with .38 for the clinical variables. These results indicate that the initial APR is highly correlated with 6-month stroke recovery and that this correlation approaches that observed with standard clinical predictors.     

Social interaction plays a critical role in neurogenesis and recovery after stroke

Stroke survivors often experience social isolation. Social interaction improves quality of life and decreases mortality after stroke. Male mice (20–25 g; C57BL/6N), all initially pair housed, were subjected to middle cerebral artery occlusion (MCAO). Mice were subsequently assigned into one of three housing conditions: (1) Isolated (SI); (2) Paired with their original cage mate who was also subjected to stroke (stroke partner (PH-SP)); or (3) Paired with their original cage mate who underwent sham surgery (healthy partner (PH-HP)). Infarct analysis was performed 72 h after stroke and chronic survival was assessed at day 30. Immediate post-stroke isolation led to a significant increase in infarct size and mortality. Interestingly, mice paired with a healthy partner had significantly lower mortality than mice paired with a stroke partner, despite equivalent infarct damage. To control for changes in infarct size induced by immediate post-stroke isolation, additional cohorts were assessed that remained pair housed for three days after stroke prior to randomization. Levels of brain-derived neurotrophic factor (BDNF) were assessed at 90 days and cell proliferation (in cohorts injected with 5-bromo-2′-deoxyuridine, BrdU) was evaluated at 8 and 90 days after stroke. All mice in the delayed housing protocol had equivalent infarct volumes (SI, PH-HP and PH-SP). Mice paired with a healthy partner showed enhanced behavioral recovery compared with either isolated mice or mice paired with a stroke partner. Behavioral improvements paralleled changes in BDNF levels and neurogenesis. These findings suggest that the social environment has an important role in recovery after ischemic brain injury.