BACKGROUND AND PURPOSE: In humans and rodents, cortical stroke can lead to cortex atrophy in long-term survivors. In the rodent, fetal brain neural precursors or stem cell-derived neurons grafted in the stroke-lesioned brain integrate successfully and reduce infarct in the short term. We have examined the fate, in the long term, of mouse embryonic stem cell-derived neural precursors grafted after permanent middle cerebral artery occlusion in mice.

METHODS: Green fluorescent protein-labeled neural precursors were grafted in the striatum of control and lesioned mice and their fate examined 9 months later.

RESULTS: In control mice, the neuronal progeny of mouse embryonic stem cells innervated distant brain structures, in a way remarkably similar between animals, displayed a laterality preference and remained polysialated neural cell adhesion molecule-immunoreactive. In lesioned mice, grafted cells were expelled out of the brain.

CONCLUSIONS: Stroke-related brain atrophy and reshaping were not prevented by cell grafting and, eventually, led to the expulsion of the graft.

Abstract Aims: Previous neuropathological studies documented that small vascular and microvascular pathology is associated with cognitive decline. More recently, we showed that thalamic and basal ganglia lacunes are associated with post-stroke depression and may affect emotional regulation. The present study examines whether this is also the case for late-onset depression. Methods: We performed a detailed analysis of small macrovascular and microvascular pathology in the postmortem brains of 38 patients with late-onset major depression (LOD) and 29 healthy elderly controls. A clinical diagnosis of LOD was established while the subjects were alive using the DSM-IV criteria. Additionally, we retrospectively reviewed all charts for the presence of clinical criteria of vascular depression. Neuropathological evaluation included bilateral semiquantitative assessment of lacunes, deep white matter and periventricular demyelination, cortical microinfarcts and both focal and diffuse gliosis. The association between vascular burden and LOD was investigated using Fisher’s exact test and univariate and multivariate logistic regression models. Results: Neither the existence of lacunes nor the presence of microvascular ischaemic lesions was related to occurrence of LOD. Similarly, there was no relationship between vascular lesion scores and LOD. This was also the case within the subgroup of LOD patients fulfilling the clinical criteria for vascular depression. Conclusions: Our results challenge the vascular depression hypothesis by showing that neither deep white matter nor periventricular demyelination is associated with LOD. In conjunction with our previous observations in stroke patients, they also imply that the impact of lacunes on mood may be significant solely in the presence of acute brain compromise.

BACKGROUND: Stroke is a devastating complication of tuberculous meningitis and is an important determinant of its outcome. AIM: To prospectively evaluate the predictive factors for stroke in patients with tuberculous meningitis and to assess the impact of stroke on the overall prognosis and outcome. METHODS: We evaluated and followed 100 patients of tuberculous meningitis for 6 months. Magnetic resonance imaging was performed at inclusion and after 6 months. We evaluated the predictors of stroke and also assessed the effect of stroke on the outcome. Outcome was defined with the help of modified Rankin scale. RESULTS: Of the 100 patients, 6 lost to follow-up. Thirty patients had stroke, 27 of them had stroke at inclusion. Three patients developed stroke during follow-up. In most of the patients, stroke was a manifestation of advanced stages of tuberculous meningitis. Internal capsule/basal ganglia were the most frequently involved sites. Infarcts commonly involved the middle cerebral arterial territory. On univariate analysis, predictors of stroke were aged >25 years (P < 0.001), cranial nerve involvement (P < 0.001), sylvian fissure exudates (P = 0.026), posterior fossa exudates (P = 0.016), optic chiasmal exudates (P = 0.04) and vision impairment (P = 0.004). Stage III tuberculous meningitis (P < 0.001) was also a predictor of stroke. On multivariate analysis aged >25 years was found a significant predictor of stroke. Strokes in patients with tuberculous meningitis were associated with poor prognosis. CONCLUSION: Stroke occurred in 30% of cases with tuberculous meningitis. Advanced stage of tuberculous meningitis, basal exudates, optochiasmatic arachnoiditis and vision impairment were significant predictors of stroke. Stroke independently predicted the poor outcome of tuberculous meningitis.

BACKGROUND AND PURPOSE: Gait disorders are common in the elderly and are related to loss of functional independence and death. White matter lesions (WMLs) may be related, but only a minority of individuals with WMLs has gait disorders. Probably other factors are involved, including location and the independent effect of frequently coinciding lacunar infarcts, the other aspect of cerebral small vessel disease. The aim of our study was to investigate the effect of both the severity and location of both WMLs and lacunar infarcts on gait. METHODS: Four hundred thirty-one independently living, nondemented elderly aged between 50 and 85 years with cerebral small vessel disease were included in this analysis and underwent MRI scanning. The number and location of lacunar infarcts were rated and WML volume was assessed by manual segmentation with automated delineating of different regions. Gait was assessed quantitatively with an electronic walkway as well as the semiquantitatively Tinetti and Timed-Up-and-Go test. RESULTS: WMLs and lacunar infarcts were both independently associated with most gait parameters with stride length as the most sensitive parameter related to WMLs. WMLs in the sublobar (basal ganglia/internal capsule) and limbic areas and lacunar infarcts in the frontal lobe and thalamus were related to a lower velocity. CONCLUSIONS: Cerebral small vessel disease is related to gait disturbances. Because small vessel disease may, in part, be preventable, it should be regarded as a potentially important target for postponing gait impairment.

INTRODUCTION: The exact mechanism of the mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) remain unclear. Diffusion-weighted imaging (DWI) is a magnetic resonance (MR) imaging technique for studying the pathophysiologic change of the MELAS. The purpose of the study is to see whether the apparent diffusion coefficient (ADC) of MELAS in the non-affected areas is different from the ADC of the normal subjects and to speculate the pathophysiological mechanisms of the MELAS. METHODS: Sixteen cases of MELAS were retrospectively analyzed. Thirty healthy subjects were chosen to constitute the control group. All of them were performed on the 3.0T whole-body MR scanner with axial view T2 fluid attenuated inversion recovery (flair), T2-weighted imaging, T1flair, and DWI. An ADC map was reconstructed in the workstation. Two to five regions of interest were put in the non-affected frontal lobe and basal ganglia. All data took statistical analysis. RESULTS: There were significant differences between the ADC of the patients with MELAS and the controls in the non-affected areas, including the superior frontal gyrus, precentral gyrus, corpus striatum, thalamus, and white matter of the semi-oval centrum. CONCLUSION: ADCs in the non-affected areas of the patients with MELAS are higher than those of the normal subjects. Pathological changes take place in the non-affected areas of the patients with MELAS.

Objective: To review the frequency, clinical correlates, and mechanism of anosognosia after stroke. Methods: We searched the most recent relevant literature on anosognosia after stroke and carried out a critical analysis of the main findings. Results: Anosognosia is present in about 10% of acute stroke patients and its diagnosis is relatively simple. Nevertheless, a valid and reliable standardization of diagnostic instruments and criteria for research purposes is more difficult to achieve. This limitation may partially account for various instruments available to assess anosognosia and the different strategies used to diagnose this phenomenon. Anosognosia is a fleeting phenomenon and chronic cases are infrequent. There is a robust association between anosognosia and right-hemisphere lesions involving cortical (insular, temporal, and parietal lobes) and subcortical structures (thalamus and basal ganglia). The main clinical correlates of anosognosia are the presence of neglect, cognitive deficits, previous strokes, and older age. Anosognosia has a negative impact on the rehabilitation of stroke patients. The mechanism of anosognosia remains unknown but was explained as owing to psychological denial, disconnexion between left and right hemispheres, and dysfunction of a system that monitors the intention to move and actual movements. Conclusion: Anosognosia is a relatively frequent complication of acute stroke and may become an excellent model to understand the mechanism of human awareness.

Objective: We will review the available evidence on the frequency, clinical correlates, mechanism, and treatment of apathy following stroke. Methods: We have explored relevant databases (that is, PubMed, MEDLINE, and PsycINFO) using the following key words and their combinations: apathy, motivation, abulia, stroke, cerebrovascular disease, basal ganglia, prefrontal cortex, anterior cerebral infarction, and thalamus. Results: The frequency of apathy following stroke has been consistently estimated between 20% and 25%. It appears to be associated with the presence of cognitive impairment, a chronic course characterized by progressive functional decline, and with disruption of neural networks connecting the anterior cingulate gyrus, the dorsomedial frontal cortex, and the frontal pole with the ventral aspects of the caudate nucleus, the anterior and ventral globus pallidus, and the dorsomedian and intralaminar thalamic nuclei. Published treatment studies have been mostly limited to anecdotal case reports, generally using dopamine agonists or stimulant medications. Cholinesterase inhibitors and nefiracetam may significantly reduce apathetic symptoms. However, their efficacy was examined in relatively small clinical trials that require replication. Conclusion: Apathy is a frequent neuropsychiatric complication of stroke that, although often associated with depression and cognitive impairment, may occur independently of both. Its presence has been consistently associated with greater functional decline. However, there is no conclusive evidence about which is the best treatment for this condition.

INTRODUCTION: Gliomatosis cerebri is a diffuse astrocytic neoplasm that involves more than two lobes of the brain. Treatment is not well defined and the prognosis is considered poor. METHODS: Retrospective analysis of 22 patients with gliomatosis cerebri. RESULTS: We identified 17 men and 5 women (median age 54 years) seen in a Division of Neuro-oncology over a 6 year period. Patients presented with focal sensorimotor or visual deficits (86.4%), seizures (36.4%), cognitive dysfunction (27.3%), or headache (27.3%), suggesting in some cases stroke, migraine, or limbic encephalitis. All patients had bilateral involvement; the regions involved included, temporal (19), basal ganglia (18), frontal (17), parietal (17), corpus callosum (10), and occipital (9). The most frequent pathological findings were grade III astrocytoma (36.4%), grade II astrocytoma (22.7%), and grade IV astrocytoma (18.3%). Nine patients were diagnosed within the first month of symptom development, 11 between the first month and 1 year, and 2 after one year. Seventeen patients received treatment with chemotherapy, radiotherapy or both, and 12 patients (70.6%) had a clinical or radiological response. The median follow-up was 13 months, median progression free survival 6 months, and median survival 9,5 months (15 months if the patients received treatment). Eight patients had thromboembolic events. CONCLUSIONS: Gliomatosis cerebri has a variable clinical course. Treatment often results in clinical responses. In this study de median survival of patients who received treatment was similar to that reported in series of glioblastoma multiforme.

Dopamine D2/3 receptor agonists have been widely used to treat motor symptoms in Parkinson’s disease and are also reported to improve cognitive and emotional disturbances. Here we describe a patient who developed severe apathy after cerebral infarction in the prefrontal cortex. After administration of ropinirole, his verbal output and spontaneity in daily life was improved remarkably. This improvement was associated with increased blood flow in the prefrontal cortex and basal ganglia. We suggest that ropinirole may be a treatment option for deficits in motivated behavior after prefrontal damage. Copyright 2009 Elsevier Ltd. All rights reserved.

Cerebral palsy (CP) is a group of disorders of the development of movement and posture, causing activity limitations, that are attributed to nonprogressing disturbances that occurred in the developing fetal or infant brain. The motor abnormalies are often accompanied by disturbances of sensation, perception, cognition, behavior and/or by a seizure disorder. The prevalence of CP has not decreased in developed countries over the past 30 years, despite the widespread use of electronic fetal heart rate monitoring and a 5- to 6-fold increase in the cesarean delivery rate. In the term newborn, CP may be attributed to perinatal asphyxia in case of metabolic acidosis in the cord blood (pH<7,00 and base deficit>12 mmol/L), followed by a moderate or severe neonatal encephalopathy within 24 hours and a further neurological impairement characterized by spastic quadriplegia and dyskinesia/dystonia. Dating the time of fetal asphyxia during delivery is possible when there are acute catastrophic complications during labor and unexpected acute or progressive fetal heart rate anomalies after a normal admission test, when there is a need for intensive neonatal resuscitation, a multi-organ failure within 72 hours of birth and visualization of acute non focal cerebral abnormalities, mainly by early magnetic resonance imaging (MRI). MRI sequences show either a brain-damaged pattern of the central basal ganglia, thalami and posterior limbs of internal capsules with relative cortical sparing, in acute, near-total asphyxial insults manifested by a continuous bradycardia or a pattern of cortical injury in the watershed zones and relative sparing of the central grey matter, in prolonged partial asphyxia, manifested by late or atypical variable decelerations with progressive fetal tachycardia, loss of reactivity and absent fluctuation. Prolongation of either type of asphyxial insult results in more global brain damage. In order to differentiate a CP occurring after perinatal asphyxia from other neurological sequelae in relation with infection, hemorrhage, stroke, malformations, genetic or metabolic diseases, it is essential that a definitive information from the brain by MRI and an extensive histological examination of the placenta are at disposal. Copyright 2010. Published by Elsevier SAS.