Mechanisms of post-radiation injury: cerebral microinfarction not a significant factor.

Post-radiation leukoencephalopathy is characterized by cognitive impairment and white matter alternations on imaging. Cerebral small vessel disease (SVD) is one of several suggested etiologies. Cerebral microinfarction (CMI) is a recently described marker of SVD. We sought to examine the rate of CMI as a biomarker of ongoing ischemia among patients who underwent brain radiotherapy (RT). 110 patients treated with RT for primary or metastatic brain tumors were enrolled. A total of 685 brain MRI tests performed 1-108 months post-radiation were examined. The annual incidence of CMI was calculated. Only 2 definite CMI were found (2/685, 0.3 %). The calculated annual incidence of CMI was 0.11. This incidence is similar to the normal population, and lower than the reported incidence in patients with intracerebral hemorrhage or cognitive impairment. CMI incidence in patients treated with brain RT is similar to the general population. This finding suggests that post-radiation leukoencephalopathy and cognitive impairment are not due to active SVD solely but rather secondary to other causes such as inflammation, metabolic or direct cell damage.

Computed Tomography Perfusion-Based Decision Making for Acute Ischemic Stroke-Missing the Mismatch.

The emerging use of mechanical thrombectomy for acute ischemic stroke treatment focuses on the importance of patient selection. Computed tomography perfusion (CTP) is one of widely used techniques. However, the accuracy and reliability of this modality is in debate among vascular neurologists. We present a case of an 80-year-old man admitted because of acute ischemic stroke. CT angiography demonstrated left proximal M2 occlusion. As CTP demonstrated signs of large ischemic core with no significant penumbra, mechanical thrombectomy was not performed following tPA administration. Twenty-four hours after thrombolysis, the patient was neurologically intact. Both non-contrast CT and magnetic resonance imaging (MRI) demonstrated small stroke involving the left caudate. Differences between CTP and MRI diffuse-weighted imaging were previously described. However, in the presented case, these differences were brought to extreme, precluding endovascular treatment. In our opinion, this case emphasizes why CTP should not be used for patient exclusion among patients in the early time frame for intervention. Such patients should be evaluated by MRI or by clinical-radiological mismatch only. CTP may have a role in selecting patients for endovascular intervention in borderline circumstances such as prolonged time window, wake-up stroke, etc.

Cognitive assessment in proximity to acute ischemic stroke/transient ischemic attack: comparison of the montreal cognitive assessment test and mindstreams computerized cognitive assessment battery.

BACKGROUND/AIMS: Even mild stroke survivors may sometimes experience residual cognitive damage. No consensus has emerged about which cognitive test is most appropriate for the diagnosis of poststroke cognitive impairment. We aim to compare a computerized battery of neuropsychological tests for memory, attention and executive functions (MindStreams®) with the Montreal Cognitive Assessment (MoCA) to detect mild-to-moderate cognitive impairments in poststroke patients. METHODS: Subjects enrolled to the TABASCO (Tel Aviv Brain Acute Stroke Cohort) study, a prospective study which includes consecutive first-ever mild-to-moderate stroke patients, were included. All participants underwent neurological and cognitive evaluations. RESULTS: A total of 454 patients with transient ischemic attack (TIA) or stroke are reported. Their mean MoCA and MindStreams scores were lower than normal; however, the TIA group presented significantly better scores using either method. The correlation between the MoCA and the computerized global score was 0.6 (p < 0.001). A significant correlation was found between the subcategory scores (executive function, memory and attention). However, the MoCA identified many more subjects with low scores (<26) compared to the MindStreams (70.6 vs. 15.7%). CONCLUSION: Our results demonstrate that either of the modalities alone is sensitive enough for identifying subtle cognitive impairment and none picks up substantially more cognitive losses than the other in patients with cerebrovascular disease.

Utility of hospitalization following a first unprovoked seizure.

OBJECTIVES: Hospital admission in otherwise healthy patients following a first unprovoked seizure is controversial. We aimed to evaluate the influence of admission in a neurology department on the identification of risk factors for seizure recurrence in patients with a first unprovoked seizure. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients with a first unprovoked seizure, who were admitted to the neurology departments at two medical centers between 2007 and 2009. Risk factors for seizure recurrence included the following: abnormal neurological examination, abnormal brain CT scan, and epileptiform discharges on the EEG. RESULTS: The study group included 97 patients (52 men) aged 18-85 years (mean 42). Eighty-seven (90%) patients were admitted following a generalized tonic-clonic seizure. Risk factors were identified in the emergency room (ER) in 36 (37%) patients, mainly including abnormalities of the neurological examination and brain CT scan. Nineteen (20%) patients had a risk factor which was not apparent during ER evaluation, consisting of epileptiform activity on the EEG. Five (5%) patients had recurrent seizures during admission, three of them without risk factors during the ER evaluation. CONCLUSIONS: Risk factors for seizure recurrence were detected during admission in nearly a quarter of the patients who presented to the emergency room with a first unprovoked seizure. Because the main advantage of admission is the EEG recording, we suggest that an early EEG should be obtained in these patients either during admission or through a special accelerated outpatient arrangement.

Stroke in the very elderly: characteristics and outcome in patients aged ≥85 years with a first-ever ischemic stroke.

BACKGROUND: Epidemiological and clinical features of very elderly patients with stroke are still uncertain. Our aim was to study the patient characteristics and outcomes in the very elderly (aged ≥85 years) with a first-ever ischemic stroke in the National Acute Stroke Israeli Survey (NASIS) registry. METHODS: The NASIS registry is a nationwide prospective hospital-based study performed triennially (2004, 2007, 2010). Patients with ischemic stroke aged ≥85 years were compared with those 65-84 years old regarding their baseline characteristics, stroke severity, etiology of stroke and stroke outcomes. Logistic regression analyses were used to adjust for potential confounders. Stroke severity was determined according to the National Institute of Health Stroke Scale (NIHSS) score. RESULTS: The proportion of very elderly (≥85 years) patients among the NASIS population increased from 18.3% in 2004 to 19.9% in 2007 and 24.5% in 2010 (p for trend = 0.005). The percentage of women was higher in patients aged ≥85 years (p < 0.0001). Atrial fibrillation, congestive heart disease and prior disability were significantly more common, while diabetes, current smoking and dyslipidemia were less frequent in the very elderly. The very elderly presented with more severe strokes: 36.3% of the ≥85-year-old patients had an NIHSS score ≥11 compared with 22.0% in the younger age group (p < 0.05). CONCLUSIONS: There is an increasing proportion of very elderly subjects, mostly women, among first-ever ischemic stroke patients. Current information on age-specific aspects of stroke in the very elderly is crucial to set up successful prevention pathways and implementing well-organized stroke care for this population.

Vasomotor reactivity as a predictor for syncope in patients with orthostatism.

OBJECTIVES: Syncope in patients with orthostatic hypotension (OH) may be the result of impaired cerebral autoregulation. Cerebral autoregulation status can be determined by assessing cerebral vasomotor reactivity (VMR). We assessed and compared VMR in patients with OH with and without syncope. MATERIAL AND METHODS: Twenty-nine patients with OH underwent transcranial Doppler (TCD) and the Diamox test (1 g acetazolamide IV) for assessing VMR during elaboration of their OH syndrome. The percent difference between cerebral blood flow velocities (BFV) in the middle cerebral (MCA) and vertebral (VA) arteries before and after acetazolamide was defined as VMR%. We considered increases of BFV of ≥ 40% as being indicative of good VMR and classified our study patients as having good or impaired VMRs accordingly. RESULTS: Mean VMR% values of the MCA and VA in patients with OH with syncope (n = 12) were significantly lower as compared with patients with OH without syncope (n = 17): 25.2 ± 20.5% and 42.5 ± 18.6%; 20.9 ± 15.5% and 40.8 ± 28.5%, respectively (P < 0.05). CONCLUSIONS: Among patients with OH, we found an association between the presence of syncope and impaired VMR. Assessment of VMR among patients with OH may predict those who are at higher risk to faint and fall and to support more aggressive intervention.

Delayed CTP-Derived Deep Venous Outflow: A Novel Predictor of Striatocapsular Infarction after M1 Thrombectomy.

BACKGROUND AND PURPOSE: Isolated striatocapsular infarction occurs commonly in patients with ischemic stroke following M1 thrombectomy. We aimed to explore the correlation between CTP-derived parameters of deep venous outflow at presentation and subsequent striatocapsular infarction in a retrospective cohort of such patients. MATERIALS AND METHODS: TTP and peak enhancement were measured on CTP-derived time-attenuation curves of the internal cerebral and thalamostriate veins bilaterally. The difference in TTP (ΔTTP) and the relative decrease in venous enhancement between the ischemic and normal sides were calculated. NCCT performed 24 (SD, 12) hours postthrombectomy was used to determine tissue fate in the caudate head, caudate body, lentiform nucleus, and internal capsule. Striatocapsular ischemia (striatocapsular infarction-positive) was defined as infarction and striatocapsular injury as either infarction, contrast enhancement, or hemorrhagic transformation in ≥1 of these regions. A striatocapsular ischemia score was calculated (0 = no ischemic region, 1 = 1 ischemic region, 2 = ≥2 ischemic regions). RESULTS: One hundred sixteen patients were included in the analysis. Sixty-one patients had striatocapsular infarction (striatocapsular infarction-positive). The mean thalamostriate ΔTTP was 1.95 (SD, 1.9) seconds for patients positive for striatocapsular infarction and 0.79 (SD, 2.1) for patients negative for it (P = .010). Results were similar for striatocapsular injury. The mean thalamostriate ΔTTP was 0.79 (SD, 2.1), 1.68 (SD, 1.4), and 2.05 (SD, 2) for striatocapsular infarction scores of 0, 1, and 2, respectively (P = .030). CONCLUSIONS: CTP-derived thalamostriate ΔTTP is an excellent surrogate marker for striatocapsular infarction in patients post-M1 thrombectomy. The novel approach of extracting venous outflow parameters from CTP has numerous potential applications and should be further explored.

Clinical, radiological and pathological correlates of leukoaraiosis.

INTRODUCTION: Leukoaraiosis is characterized by an abnormal appearance of the brain white matter on imaging. Its pathogenesis is still a matter of investigation. The purpose of this study was to investigate the radiological, clinical and pathological correlates of leukoaraiosis. METHODS: The study population consisted of 93 deceased patients. The pre-mortem T2W magnetic resonance images were evaluated for the presence and grading of leukoaraiosis. The clinical and pathological characteristics based on the clinical charts and autopsy reports were evaluated. Tissue specimens of the blocks of 19 brains that demonstrated severe leukoaraiosis and those of five control brains were excised and stained. RESULTS: The variables found to be significantly associated with leukoaraiosis were age and a clinical history of Parkinson's disease. Other risk factors and pathological markers of atherosclerosis were not significantly correlated with leukoaraiosis. No significant difference was found between the scoring of the myelin integrity, glial fibrillary acidic protein, cluster of differentiation 68 and smooth muscle actin. There was a significant difference with respect to thickening of vessels walls. CONCLUSIONS: Our pathological results indicate that structural vascular abnormalities characterized by vessel wall thickening are associated with leukoaraiosis, supporting the assertion that vascular changes and ischemia generate leukoaraiosis. The relations between parkinsonism and leukoaraiosis may be explicable through vascular effects on the circuitry of the basal ganglia.

Cerebral microinfarcts disruption of remote cortical thickness.

INTRODUCTION: Cerebral microinfarcts (CMI) are common lesions, carrying an important contribution to small-vessel-related cognitive impairment. CMIs were previously found to cause local microstructural damage and disruption of white matter integrity. This study examines CMIs influence on cortical thickness in remote brain areas. METHODS: Six small silent diffuse weighted imaging (DWI) lesions corresponding to subacute CMI were identified among five patients who underwent baseline and follow-up MRI scans from the Tel-Aviv Acute Brain Stroke Cohort (TABASCO). Regions of interest (ROIs) corresponding to the site of the DWI lesions and of the non-lesioned contralateral hemisphere (control ROI) were co-registered. DTI tractography was additionally performed to reconstruct the white matter tracts containing the ROIs. The normalized cortical thickness was calculated for the DWI lesional tract as well as for the contralateral non-lesional tract, and the lesion-to-control cortical thickness ratio (CTR) was calculated. RESULTS: Post-lesional scans, performed 25.1 ± 1.2 months after CMI detection, demonstrated reduced mean CTR within the ROI from 1.8 to 1.1 (p = 0.032). There was no difference between the CTR of the right hemisphere relative to those on the left hemisphere, or between the CTR change of the cortical and non-cortical CMI. DISCUSSION: This study demonstrated the prolonged influence of CMI on cortical thickness in remote ROI. The total number of CMIs is difficult to determine, however it has been shown that detecting even a single CMI suggests the existence of hundreds to thousands lesions. Therefore, the cumulative impact of these widely distributed lesions on cerebral cortex may have a significant contribution to the development of vascular cognitive impairment.

Neuroprotection in acute ischemic stroke--current status.

With the growing understanding of the mechanism of cell death in ischemia, new approaches for treatment such as neuroprotection have emerged. The basic aim of this strategy is to interfere with the events of the ischemic cascade, blocking the pathological processes and preventing the death of nerve cells in the ischemic penumebra. This concept involves inhibition of the pathological molecular events which eventually leads to the influx of calcium, activation of free radicals and neuronal death. Despite encouraging data from experimental animal models, all clinical trials of neuroprotective therapies have to date been unsuccessful. This article reviews some of the reasons for the failure of neuroprotection in the clinical trials so far. Despite all the negative reports, we believe it would be wrong to give up at this point, since there is still reasonable hope of finding an effective neuroprotection for stroke.

Cerebellar hemorrhages in patients with cerebral amyloid angiopathy.

BACKGROUND: Cerebral amyloid angiopathy (CAA) typically involves the cerebral cortex but whether it affects the cerebellum remains uncertain. METHODS: Patients with intracerebral hemorrhage (ICH) who underwent magnetic resonance imaging were prospectively enrolled. Patients were diagnosed with CAA according to the Boston criteria and their hemorrhage types were categorized as macro-hematoma (MH) or microbleeds (MB). Patients with CAA and cerebellar involvement were compared with CAA patients without cerebellar involvement. RESULTS: Out of 614 patients with ICH, 85 (14%) had a post-ICH MRI. Of those, 41 (48%) were diagnosed with possible (n = 19), probable (n = 21) or definite (n = 1) CAA. Cerebellar involvement was seen in 14/41 (34%) patients with CAA. Most cerebellar lesions were of the MB type (35%) and most patients had several cerebellar MB typically involving the cerebellar cortex (85%). Patients with cerebellar involvement had larger numbers of lobar MB but clinical variables including age, gender, risk factor profile, mRS scores at 90 days or survival did not differ between those with and without cerebellar involvement. CONCLUSIONS: Cerebellar involvement may be common in CAA. Most patients have multiple superficial cerebellar MB. Clinical characteristics do not differ between CAA patients with or without cerebellar involvement. Patients presenting with cerebellar ICH should be screened for CAA with MRI.

Clinical and radiological determinants of transient symptoms associated with infarction (TSI).

BACKGROUND: The definition of transient ischemic attack was traditionally based on clinical features only. The wide use of magnetic resonance imaging (MRI) led to the definition of a new entity - transient symptoms associated with infarction (TSI). It is unclear why patients with similar radiological infarctions may have different clinical manifestation - ranging from complete symptoms resolution to major neurological sequelae. We sought to determine which factors differentiate acute diffuse weighted imaging (DWI) lesion presentation - stroke versus TSI. METHODS: 282 Participants, recruited for the Tel-Aviv Brain Acute Stroke Cohort study (TABASCO), were enrolled consecutively. Participants underwent extensive cognitive evaluation, wide laboratory tests and brain MRI scans evaluated for cerebral small vessel disease (SVD) biomarkers, according to the STRIVE protocol. Demographic and clinical characteristics were also examined. RESULTS: A total of 239 patients had stroke and 43 patients had TSI. TSI patients had smaller average lesion volume (0.77 cm3 versus 2.64 cm3, p = 0.002). Lesion location did not differentiate TSI and stroke. Stroke patients had elevated inflammatory markers, unrelated to lesion size (CRP 4.2 mg/L versus 1.7 mg/L, p = 0.011). TSI patients had better global cognitive score and MoCA score at admission and 24 months following the index event (p < 0.001). TSI patients also had better Berg balance score (p = 0.004). No significant association was found with MRI SVD markers. CONCLUSIONS: Lesion size, but not location, differentiates TSI and stroke, especially at a cutoff value of 10 cm3. Elevated inflammatory response was linked to worse course independently of lesion volume. Cognitive and high function tests are associated to the clinical phenotype of ischemic lesion and may be a marker of brain reserve and compensatory abilities. SVD markers do not differ between TSI and stroke patients and probably do not fully capture the extent of brain vascular pathology and reserve.

High hair cortisol concentrations predict worse cognitive outcome after stroke: Results from the TABASCO prospective cohort study.

BACKGROUND AND PURPOSE: The role of stress-related endocrine dysregulation in the development of cognitive changes following a stroke needs further elucidation. We explored this issue in a longitudinal study on stroke survivors using hair cortisol concentrations (HCC), a measure of integrated long-term cortisol levels. METHODS: Participants were consecutive cognitively intact first-ever mild-moderate ischemic stroke/transient ischemic attack (TIA) survivors from the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study. They underwent 3T magnetic resonance imaging (MRI) scanning and were cognitively assessed at admission, and at 6, 12 and 24 months post-stroke. Scalp hair samples were obtained during the initial hospitalization. RESULTS: Full data on baseline HCC, MRI scans and 2 years neuropsychological assessments were available for 65 patients. Higher HCC were significantly associated with a larger lesion volume and with worse cognitive results 6, 12 and 24 months post-stroke on most of the neurocognitive tests. 15.4% of the participants went on to develop clinically significant cognitive decline in the follow-up period, and higher HCC at baseline were found to be a significant risk factor for this decline, after adjustment for age, gender, body mass index and APOE e4 carrier status (HR=6.553, p=0.038). CONCLUSIONS: Our findings suggest that individuals with higher HCC, which probably reflect higher long-term cortisol release, are prone to develop cognitive decline following an acute stroke or TIA.

Symptomatogenic acute cervical artery dissection following dental procedure - Case series.

INTRODUCTION: Cervical artery dissection (CAD) is an important cause of ischemic stroke which may occur following minor traumatic neck manipulations or hyperextension. This paper describes four cases of CAD secondary to dental procedures. CASES: Four patients were admitted to the neurology department due to various neurological deficits, which developed subsequently to dental procedure. CT angiography demonstrated CAD in all patients. No predisposing background disease or other neck manipulations were found. DISCUSSION: We describe four cases of dental procedure induced CAD. Since dental procedures are very common, CAD incidence may be higher than recognized. High clinical suspicion is crucial for promoting vascular imaging and diagnosis, especially among patients with non-neurologically symptomatic CAD. We suggest avoiding prolonged neck hyperextension during dental procedures, especially under general anesthesia, in order to prevent this rare but dramatic complication.

Microembolism, silent brain infarcts and dementia.

Cognitive decline becomes more prevalent than ever in parallel with the increasing life expectancy of the population. Alzheimer' disease (AD) and cerebral vascular lesions are common in the elderly and represent, with increased age, the most frequent contributors to cognitive decline. It is now believed that these pathologies frequently coexist in the same brain. The border discriminating vascular dementia from AD is blurred and challenges our understanding of these clinical entities. Further research, at both basic and clinical levels, is mandatory in order to better understand the interactions of vascular ischemic injury and primary degenerative physiopathologies of the brain, in order to prevent and better manage patients with cognitive decline. We review recent published clinical evidence of silent brain ischemia as a contributor to cognitive decline and dementia. Microemboli, from both cardiac and vascular origins, have been shown to be associated with structural changes in the brain. The role of transcranial Doppler as an objective tool for detecting and quantifying microemboli is discussed in light of recent clinical evidence.

Extra-cranial venous flow in patients with multiple sclerosis.

INTRODUCTION: Recently, a chronic state of impaired venous drainage from the central nervous system, termed chronic cerebrospinal venous insufficiency (CCSVI) was claimed to be a pathologic condition exclusively seen in patients with multiple sclerosis (MS), suggesting that cerebral venous congestion plays a significant role in the pathogenesis of MS. This hypothesis has gained enormous attention among patients and physicians but has been questioned since. METHODS: Twenty seven patients with MS and 32 healthy controls underwent color extra cranial Doppler exam aimed to detect four parameters of abnormal venous flow: no Doppler-detected flow in the IJV or vertebral veins (VV), reflux in the internal jugular veins (IJVs), venous flow stenosis in the IJVz (cross sectional area <0.3 cm) or reverted postural control in the IJV. RESULTS: Except for one healthy patient, blood flow direction in the IJVs was normal in all subjects. When aiming to detect at least one parameter of abnormal venous flow per subject, two parameters or three parameters no significant difference was found between subjects and controls (p = 0.707, 0.62, 0.849 respectively). CONCLUSION: We found no evidence to suggest that MS patients have excess of CCSVI. In addition we failed to observe a typical venous flow pattern in MS patients. Until carefully designed controlled studies to investigate CCVSI have been completed, invasive and potentially dangerous endovascular procedures as therapy for MS should be discouraged.

Characteristics of first ever ischemic stroke in the very elderly: profile of vascular risk factors and clinical outcome.

PURPOSE: Age is the most significant non-modifiable risk factor for ischemic stroke (IS). With increasing expectancy of life, the majority of IS patients will be elderly subjects. We studied the epidemiological, clinical and rehabilitation features of patients aged ≥85 years with first-ever IS. METHODS: Demographic data, prevalence of risk factors, etiology of stroke, severity of neurological deficit, major complications and mortality rates were collected from a hospital-based stroke registry and compared between patients at the age of 65-84 and ≥85. Clinical assessment was performed by means of the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS). RESULTS: Among 216 patients aged ≥85 years there was significantly higher proportion of a history of atrial fibrillation than in 128 patients at the age of 65-84 years and lower prevalence of hypertension, diabetes mellitus, hyperlipidemia and smoking. Large artery atherosclerosis was more frequently identified in the older patients (49% vs. 32%, p=0.002). Although NIHSS scores on admission were lower in the older patients they were more disabled at discharge. CONCLUSIONS: With respect to the patients aged <85 years very old IS patients showed different vascular risk factors profile, clinical and rehabilitation course. These findings suggest specializing stroke care in the very elderly.