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Brain lesions and cerebral functional impairment in migraine patients
Abstracts / Journal of the Neurological Sciences 283 (2009) 240–320
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factors, so that the evolution towards dementia could be prevented or at least postponed.
do not exhibit more decline on cognitive tests over time versus nonmigraineurs.
doi:10.1016/j.jns.2009.02.048
doi:10.1016/j.jns.2009.02.050
Seizures and dementia after stroke
Non-cadasil familial leuko-encephalopathies
A.B. Guekhta, N.V. Gulyaevab, E.I. Guseva a Department of Neurology and Neurosurgery, Russian State Medical University, Moscow, Russia b Institute of Higher Nervous Activity and Neurophysiology, RAS, Moscow, Russia
L. Pantonia, F. Pescinia, C. Sartia, S. Bianchib, M.T. Dottib, A. Federicob, D. Inzitaria a Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy b Department of Neurological and Behavioral Sciences, University of Siena, Siena, Italy
Seizures and dementia after stroke (S) increase exponentially with aging of the population. About 10% of all S. patients experience seizures, from onset until several years later. Five percent are early-onset seizures (ES, within 7 days of S.) and another 5% are late-onset seizures (LS) [Hauser et al., 1993]. Poststroke dementia occurs in up to one third of patients with clinically eloquent ischemic stroke after age 65 years [Pohjasvaara et al., 1997]. Pre-existing dementia was independently associated with the occurrence of LS, and ES were independent predictors of new-onset dementia within 3 years after S [Cordonnier et al., 2005, 2007]. Both conditions (dementia and seizures) share important risk factors, for example, hippocampal atrophy and atrial fibrillation. Besides, pre-existing vascular pathologies that may predispose to both seizures and new onset dementia could be white matter changes, silent infarcts or microbleedings. Though the mechanisms of seizures and dementia after S. are widely discussed in the literature, the mechanisms of interconnections between them are much less known. According to the results of our study, patients with ES have higher risk for ischemia-induced neurodegeneration, as CSF of patients with ES (compared to matched stroke patents without seizures) demonstrated higher ability to inhibit major cell death-related proteases (calpain and caspase-3). Prospective studies focused on interplay between dementia after S. and seizures (bearing in mind differences in mechanisms of ES and LS) are necessary; besides, this question is of importance for prevention and treatment of both conditions. Supported in part by Russian Scientific Humanitarian Fund grants. doi:10.1016/j.jns.2009.02.049
Brain lesions and cerebral functional impairment in migraine patients K. Paemeleire Headache Clinic, Department of Neurology, Ghent University Hospital, Ghent, Belgium Migraine is an independent risk factor for ischemic stroke, especially in female patients of childbearing age suffering from migraine with aura, but the absolute risk is small. In the cross-sectional population-based CAMERA study, subclinical brain lesions – including silent posterior fossa ischemic stroke and white matter lesions – were more frequently found in migraine patients. The presence of white matter hyperintensities in migraine patients was associated with female gender, oral contraceptive use and high migraine frequency, but independent of cardiovascular risk factors, type of migraine or triptan use. These hyperintensities were found in the supratentorial white matter as well as in the brainstem (mainly pontine). The nature of these lesions remains enigmatic, but they are not related to antiphospholipid antibodies or coagulation parameters. It is unclear whether the presence of white matter hyperintensities is a risk factor for future stroke and whether migraine may be considered a progressive disorder in a subset of patients because of accumulation of these lesions over time. Certainly a populationbased prospective MRI study is awaited. Heterogeneous methods have been used to study cognitive function in migraineurs and have yielded conflicting results. Two recent studies have provided reassuring news for the migraine patient. A population-based twin study showed that a lifetime migraine diagnosis was not associated with cognitive deficits in middle-aged subjects. A long-term prospective study, assessing cognitive and memory changes in ageing individuals with and without a history of migraine headaches, showed that migraineurs certainly
Background: Verrealt et al. [1] recently described a Portuguese family with an ischemic cerebral micro-angiopathy distinct from CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). While the clinical–radiological picture resembled that of CADASIL, the diagnosis of the disease was excluded because of the absence of Notch3 gene mutations and of negative skin biopsies. Methods: Since 2003, in our center we performed genetic testing for Notch3 mutations in 61 probands belonging to different families with suspected CADASIL. Inclusion criteria for screening were: 1) personal and family history of stroke, cognitive impairment, psychiatric disturbances, and migraine; 2) severe vascular leukoencephalopathy; 3) absence of conventional vascular risk factors. Results: Out of the 61 patients evaluated, 9 (15%) were diagnosed with CADASIL because a mutation leading to a cysteine substitution within the epidermal growth factor (EGF)-like repeats was found in one of the 22 exons of the Notch3 gene (exons 2–23). In other 10 patients (16%) with complete evaluation of these 22 exons no mutation leading to a cysteine substitution was found. In one of these patients also the skin biopsy resulted negative for granular osmiophilic material (GOM) search. Patients negative for Notch3 mutations presented with clinical, radiological, and familial characteristics superimposed to those of CADASIL patients. Discussion and conclusions: A form of CADASIL-like familial cerebral micro-angiopathy (i.e., without mutations on Notch3 exons involving cysteine residues) appears to be present also in Italy and its prevalence in comparison to that of CADASIL seems relevant. The actual genetic profile of these forms and possible phenotype differences with CADASIL remain to be explored. Reference [1] Verreault S, et al. A novel hereditary small vessel disease of the brain. Ann Neurol 2006;59:353–7.
doi:10.1016/j.jns.2009.02.051
Inherited cerebral amyloid angiopathies D. Leysa, C. Cordonnierb, V. Casoc University Lille II (EA 2691), France b Department of Neurology, Italy c Stroke Department, Lille, France
a
Cerebral amyloid angiopathies (CAA) are defined as the deposition of amyloid proteins in the wall of the cerebral vessels. The peptide deposited in the main type of CAA is called Aß. Aß is the 40–43 amino acid proteolysis product of a large precursor, the amyloid ß-protein precursor (APP), with features of a cell surface receptor. Hereditary cerebral hemorrhages with amyloidosis of the Dutch type (HCHWA-D) is an autosomal dominant disease characterized by cerebral hemorrhages occurring during the 4th and 5th decades. Neuropathological findings are similar to those of sporadic AD, with the following differences: (i) AD lesions are frequent, with only few neurofibrillary tangles, (ii) white matter changes occur early in the time-course of the disease; (iii) cerebral hemorrhages occur more frequently in posterior areas, (iv) a severe reduction of the lumen due to severe hyalinosis and sclerosis of the vessel walls is frequent. The underlying genetic defect is a point-mutation in the APP gene located on chromosome 21, leading to aberrant APP. The gene mutation leads to
251
factors, so that the evolution towards dementia could be prevented or at least postponed.
do not exhibit more decline on cognitive tests over time versus nonmigraineurs.
doi:10.1016/j.jns.2009.02.048
doi:10.1016/j.jns.2009.02.050
Seizures and dementia after stroke
Non-cadasil familial leuko-encephalopathies
A.B. Guekhta, N.V. Gulyaevab, E.I. Guseva a Department of Neurology and Neurosurgery, Russian State Medical University, Moscow, Russia b Institute of Higher Nervous Activity and Neurophysiology, RAS, Moscow, Russia
L. Pantonia, F. Pescinia, C. Sartia, S. Bianchib, M.T. Dottib, A. Federicob, D. Inzitaria a Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy b Department of Neurological and Behavioral Sciences, University of Siena, Siena, Italy
Seizures and dementia after stroke (S) increase exponentially with aging of the population. About 10% of all S. patients experience seizures, from onset until several years later. Five percent are early-onset seizures (ES, within 7 days of S.) and another 5% are late-onset seizures (LS) [Hauser et al., 1993]. Poststroke dementia occurs in up to one third of patients with clinically eloquent ischemic stroke after age 65 years [Pohjasvaara et al., 1997]. Pre-existing dementia was independently associated with the occurrence of LS, and ES were independent predictors of new-onset dementia within 3 years after S [Cordonnier et al., 2005, 2007]. Both conditions (dementia and seizures) share important risk factors, for example, hippocampal atrophy and atrial fibrillation. Besides, pre-existing vascular pathologies that may predispose to both seizures and new onset dementia could be white matter changes, silent infarcts or microbleedings. Though the mechanisms of seizures and dementia after S. are widely discussed in the literature, the mechanisms of interconnections between them are much less known. According to the results of our study, patients with ES have higher risk for ischemia-induced neurodegeneration, as CSF of patients with ES (compared to matched stroke patents without seizures) demonstrated higher ability to inhibit major cell death-related proteases (calpain and caspase-3). Prospective studies focused on interplay between dementia after S. and seizures (bearing in mind differences in mechanisms of ES and LS) are necessary; besides, this question is of importance for prevention and treatment of both conditions. Supported in part by Russian Scientific Humanitarian Fund grants. doi:10.1016/j.jns.2009.02.049
Brain lesions and cerebral functional impairment in migraine patients K. Paemeleire Headache Clinic, Department of Neurology, Ghent University Hospital, Ghent, Belgium Migraine is an independent risk factor for ischemic stroke, especially in female patients of childbearing age suffering from migraine with aura, but the absolute risk is small. In the cross-sectional population-based CAMERA study, subclinical brain lesions – including silent posterior fossa ischemic stroke and white matter lesions – were more frequently found in migraine patients. The presence of white matter hyperintensities in migraine patients was associated with female gender, oral contraceptive use and high migraine frequency, but independent of cardiovascular risk factors, type of migraine or triptan use. These hyperintensities were found in the supratentorial white matter as well as in the brainstem (mainly pontine). The nature of these lesions remains enigmatic, but they are not related to antiphospholipid antibodies or coagulation parameters. It is unclear whether the presence of white matter hyperintensities is a risk factor for future stroke and whether migraine may be considered a progressive disorder in a subset of patients because of accumulation of these lesions over time. Certainly a populationbased prospective MRI study is awaited. Heterogeneous methods have been used to study cognitive function in migraineurs and have yielded conflicting results. Two recent studies have provided reassuring news for the migraine patient. A population-based twin study showed that a lifetime migraine diagnosis was not associated with cognitive deficits in middle-aged subjects. A long-term prospective study, assessing cognitive and memory changes in ageing individuals with and without a history of migraine headaches, showed that migraineurs certainly
Background: Verrealt et al. [1] recently described a Portuguese family with an ischemic cerebral micro-angiopathy distinct from CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). While the clinical–radiological picture resembled that of CADASIL, the diagnosis of the disease was excluded because of the absence of Notch3 gene mutations and of negative skin biopsies. Methods: Since 2003, in our center we performed genetic testing for Notch3 mutations in 61 probands belonging to different families with suspected CADASIL. Inclusion criteria for screening were: 1) personal and family history of stroke, cognitive impairment, psychiatric disturbances, and migraine; 2) severe vascular leukoencephalopathy; 3) absence of conventional vascular risk factors. Results: Out of the 61 patients evaluated, 9 (15%) were diagnosed with CADASIL because a mutation leading to a cysteine substitution within the epidermal growth factor (EGF)-like repeats was found in one of the 22 exons of the Notch3 gene (exons 2–23). In other 10 patients (16%) with complete evaluation of these 22 exons no mutation leading to a cysteine substitution was found. In one of these patients also the skin biopsy resulted negative for granular osmiophilic material (GOM) search. Patients negative for Notch3 mutations presented with clinical, radiological, and familial characteristics superimposed to those of CADASIL patients. Discussion and conclusions: A form of CADASIL-like familial cerebral micro-angiopathy (i.e., without mutations on Notch3 exons involving cysteine residues) appears to be present also in Italy and its prevalence in comparison to that of CADASIL seems relevant. The actual genetic profile of these forms and possible phenotype differences with CADASIL remain to be explored. Reference [1] Verreault S, et al. A novel hereditary small vessel disease of the brain. Ann Neurol 2006;59:353–7.
doi:10.1016/j.jns.2009.02.051
Inherited cerebral amyloid angiopathies D. Leysa, C. Cordonnierb, V. Casoc University Lille II (EA 2691), France b Department of Neurology, Italy c Stroke Department, Lille, France
a
Cerebral amyloid angiopathies (CAA) are defined as the deposition of amyloid proteins in the wall of the cerebral vessels. The peptide deposited in the main type of CAA is called Aß. Aß is the 40–43 amino acid proteolysis product of a large precursor, the amyloid ß-protein precursor (APP), with features of a cell surface receptor. Hereditary cerebral hemorrhages with amyloidosis of the Dutch type (HCHWA-D) is an autosomal dominant disease characterized by cerebral hemorrhages occurring during the 4th and 5th decades. Neuropathological findings are similar to those of sporadic AD, with the following differences: (i) AD lesions are frequent, with only few neurofibrillary tangles, (ii) white matter changes occur early in the time-course of the disease; (iii) cerebral hemorrhages occur more frequently in posterior areas, (iv) a severe reduction of the lumen due to severe hyalinosis and sclerosis of the vessel walls is frequent. The underlying genetic defect is a point-mutation in the APP gene located on chromosome 21, leading to aberrant APP. The gene mutation leads to