Iron deposits in post-mortem brains of patients with neurodegenerative and cerebrovascular diseases: a semi-quantitative 7.0 T magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Accumulation of iron (Fe) is often detected in brains of people suffering from neurodegenerative diseases. However, no studies have compared the Fe load between these disease entities. The present study investigates by T2*-weighted gradient-echo 7.0 T magnetic resonance imaging (MRI) the Fe content in post-mortem brains with different neurodegenerative and cerebrovascular diseases. METHODS: One hundred and fifty-two post-mortem brains, composed of 46 with Alzheimer's disease (AD), 37 with frontotemporal lobar degeneration (FTLD), 11 with amyotrophic lateral sclerosis, 13 with Lewy body disease, 14 with progressive supranuclear palsy, 16 with vascular dementia (VaD) and 15 controls without a brain disease, were examined. The Fe load was determined semi-quantitatively on T2*-weighted MRI serial brain sections in the claustrum, caudate nucleus, putamen, globus pallidus, thalamus, subthalamic nucleus, hippocampus, mamillary body, lateral geniculate body, red nucleus, substantia nigra and dentate nucleus. The disease diagnosis was made on subsequent neuropathological examination. RESULTS: The Fe load was significantly increased in the claustrum, caudate nucleus and putamen of FTLD brains and to a lesser degree in the globus pallidus, thalamus and subthalamic nucleus. In the other neurodegenerative diseases no Fe accumulation was observed, except for a mild increase in the caudate nucleus of AD brains. In VaD brains no Fe increase was detected. CONCLUSIONS: Only FTLD displays a significant Fe load, suggesting that impaired Fe homeostasis plays an important role in the pathogenesis of this heterogeneous disease entity.

Superficial siderosis of the central nervous system: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates.

BACKGROUND: Superficial siderosis (SS) is a rare finding on T2*-weighted magnetic resonance imaging (MRI), regarded as a radiological marker of cerebral amyloid angiopathy (CAA). The present study investigates with 7.0-tesla MRI the prevalence of SS and its underlying pathological substrate in a consecutive series of post-mortem brains of elderly patients with various neurodegenerative and cerebrovascular lesions. MATERIALS AND METHODS: The prevalence of SS and associated lesions was screened using 7.0-tesla MRI and their neuropathological correlates in 120 post-mortem brains of patients with various neurodegenerative and cerebrovascular diseases. RESULTS: Eighty-three separate zones of SS were detected in 45 brains (37.5%), including 25 areas of disseminated SS (dSS) and 58 areas of focal SS (fSS), restricted to less than 3 sulci. dSS was spatially related to sequels of 14 lobar haematomas and 11 cerebral infarcts, while fSS was connected to 19 microbleeds and 39 micro-infarcts (p < 0.001). Comparison of the 15 CAA to the 30 non-CAA brains showed that dSS was due to an old lobar haematoma in 53% of the former group compared to 3% of the latter group (p = 0.003). fSS was due to a microbleed in 7% of the CAA brains and to 40% of the non-CAA brains (p = 0.03). CONCLUSIONS: SS is associated with both haemorrhagic and ischaemic underlying lesions. It is frequently observed on T2*-weighted 7.0-tesla MRI, and two types of SS may be described. Clinicians should keep in mind that SS may be found in other settings than CAA.

Detection of microbleeds in post-mortem brains of patients with frontotemporal lobar degeneration: a 7.0-Tesla magnetic resonance imaging study with neuropathological correlates.

BACKGROUND: Microbleeds (MBs) are frequently detected in brains of patients with Alzheimer dementia and rare in those with frontotemporal lobar degeneration (FTLD). This study investigates for the first time the topographic distribution of MBs on a T2*-weighted gradient-echo 7.0-T magnetic resonance imaging (MRI) in post-mortem FTLD brains. PATIENTS AND METHODS: The neuropathological and MRI findings in 12 FTLD brains were compared with eight age-matched controls. The presence of cerebrovascular lesions was evaluated on a coronal section of a cerebral hemisphere at the level of the mamillary body and on a horizontal section through pons and cerebellum. On MRI, the distribution and the number of cortical focal signal intensity losses, representing MBs, were assessed on coronal sections at the frontal, the central and the occipital level of a cerebral hemisphere. RESULTS: Overall, cerebrovascular lesions were rare. Only white matter damage was significantly more severe in FTLD brains compared with controls (P = 0.03). On MRI, MBs were only significantly prevalent in the deep cortical layers (P < 0.01) and borderline increased in the middle cortical layers (P = 0.07) of the frontal section. CONCLUSIONS: Cerebrovascular lesions are rare in FTLD. The white matter damage has to be considered as part of the neurodegenerative process. MBs prevail in the frontal regions with the most severe neuronal damage and probably represent associated disruption of the blood-brain barrier.

The impact of cerebral amyloid angiopathy on the occurrence of cerebrovascular lesions in demented patients with Alzheimer features: a neuropathological study.

OBJECTIVE: The aim of this neuropathological study was to determine the prevalence of the different cerebrovascular lesions to be attributed to cerebral amyloid angiopathy (CAA) and of those associated with the severity of the Alzheimer dementia (AD) itself. PATIENTS AND METHODS: The cerebrovascular lesions were compared separately in 40 brains of patients with mild and 50 with severe AD features. In the two groups, the number of lesions were compared between the brains with severe and those with mild of absent CAA. RESULTS: The age of the patients, the vascular risk factors and antithrombotic treatment were similar in all the compared groups. The brains with mild and severe AD features and with CAA contained more haematomas, cortical micro-infarcts and micro-bleeds, and more severe white matter changes, and cortico-subcortical and white matter mini-bleeds. In the CAA brains with severe AD features, also more cortical territorial infarcts were observed, compared to those with mild AD features. CONCLUSIONS: The increase in cortical infarcts cannot be attributed to the CAA alone, but also to the severity of the degenerative features, implying additional vascular factors in the pathogenesis of AD.

Comparison of 7.0-T T2*-magnetic resonance imaging of cerebral bleeds in post-mortem brain sections of Alzheimer patients with their neuropathological correlates.

BACKGROUND: In view of the increasing recognition of cerebral microbleeds (MCBs) with MRI, there is a need to validate their detection in post-mortem brains in patients with cerebrovascular diseases and dementia. MATERIALS AND METHODS: Out of 20 post-mortem brains of patients with Alzheimer dementia and with different cerebrovascular lesions, 45 large sections of the cerebral hemispheres, brainstem and cerebellum were submitted to a 7.0-T T2*-weighted MRI, and afterwards compared to the histological detection of haematomas, MCBs and mini-bleeds (MNBs). RESULTS: The sensitivity, specificity, predictive positive value and predictive negative value of the T2* imaging to detect MCBs and MNBs were excellent for those in the cortico-subcortical regions. There was a significant overestimation of MNBs in the striatum due to iron deposits unrelated to old haemorrhages. Also in the deep white matter, 42% of MNBs were not detected, while 31% of T2* hyposignals were not due to MNBs but to vessels filled with post-mortem thrombi. CONCLUSIONS: When evaluating the 'bleeding load' with 7.0-T T2*-weighted MRI in post-mortem brain sections of patients with dementia and vascular risk factors, only quantification of small cerebral bleeds in the cortico-subcortical regions is reliable.

Stroke characteristics in patients with pretreated arterial hypertension.

BACKGROUND: Arterial hypertension (AH) is one of the most important vascular risk factors for stroke that can be treated. The present retrospective study analyses the influence of pretreated AH on the outcome of patients with ischaemic and haemorrhagic strokes, compared to those with normal blood pressure (BP). PATIENTS AND METHODS: The demographic features, vascular risk factors, stroke type, stroke severity (according to the National Institutes of Health Stroke scale) and disability (according to the modified Rankin scale) were compared between 806 pretreated hypertensive patients and 320 ones with normal BP. RESULTS: The incidence and the severity of the ischaemic strokes were similar but the outcome was worse in patients with pretreated AH compared to those with normal BP. In the former patients, coronary artery disease and isolated atrial fibrillation were found as confounders on multivariate analysis. The incidence, the severity and the outcome of patients with a haemorrhagic stroke were similar in both groups. CONCLUSIONS: The outcome in ischaemic stroke is worse in pretreated AH patients, compared to normotensive ones, probably due to the higher incidence of other associated vascular risk factors. Pretreated AH improves the outcome of patients with a haemorrhagic stroke.

Vascular risk factors in patients with peripheral vestibular disorders.

OBJECTIVES: The present observational retrospective study investigates whether there are differences in vascular risk factors between patients with spontaneous benign paroxysmal positional vertigo (BPPV) and those with Ménière's disease (MD). PATIENTS AND METHODS: Out of a series of 1617 consecutive admitted patients, 36 presented isolated recurrent vertiginous events. Twenty patients with BPPV and 16 with MD were compared. In addition to extensive audiovestibular investigations, all patients had a complete cardio-vascular work-up. A computed tomography (CT) and a magnetic resonance imaging (MRI) of the brain were performed in all patients. The vascular risk factors and the CT/MRI findings were compared between the patients with BPPV and MD. RESULTS: Small old cerebral infarcts were observed in 25% of the BPPV and 31.2% of the MD patients, although none of them had a prior history of stroke. All other vascular risk factors tended to be more frequent in the former group although only a statistically significant difference was found for coronary artery disease (P = 0.03). CONCLUSIONS: In this pilot study BPPV does not appear to be such a benign condition but can indicate progression of general atherosclerotic disease.

Seizures in patients with symptomatic cervical artery occlusion by dissection and by atherosclerosis.

BACKGROUND AND PURPOSE: The outcome of patients with occlusion by cervical dissection (OCD) is considered to be better than of those with atherosclerotic occlusion (ATO) of cervical arteries. The present observational retrospective study investigates whether there are also differences in the occurrence of seizures between OCD and ATO patients. METHODS: The characteristics and the occurrence of seizures in 199 consecutive patients with a stroke due to a cervical artery occlusion are determined. Forty patients with OCD and 159 with ATO are compared. RESULTS: Occlusion by cervical dissection patients are significantly younger and have less vascular risk factors than those with ATO. Stroke type, vascular territory, NIHS score and outcome are similar. Three (7.5%) OCD and 29 (18.2%) ATO patients developed seizures. However, this difference is not statistically significant (P = 0.146). On multiple logistic regression analysis, ageing and arterial hypertension are independent variables. DISCUSSION: This study suggests a lower incidence of seizures in patients with OCD compared to those with ATO, although not statistically proven, due to the small sample size. Age and arterial hypertension can explain this difference.

Cognitive impairment and seizures in patients with lacunar strokes.

BACKGROUND: Lacunar infarcts and white matter changes have been linked to cognitive impairment. Patients with lacunar strokes can also develop seizures, although the relationship between the two remains unclear. The present study investigates whether seizures in patients with lacunar infarcts are related to the strokes or to an underlying neurodegenerative disorder leading to cognitive impairment. METHODS: The demographic features, vascular risk factors and scores on the National Institutes of Health Stroke Scale (NIHSS) on admission for the stroke and on the modified Rankin scale on discharge, as well as on the Mini-Mental State Examination (MMSE), were determined in patients with a lacunar stroke. They were compared between 44 patients with and 248 without subsequent seizures. RESULTS: Patients with seizures had a lower main NIHSS score (p = 0.00133) and a more severe MMSE score (p < 0.001). They remained significantly more dependent (p = 0.019) after hospital discharge. Smoking, as a vascular risk factor, appeared to occur less frequently in seizure patients (p = 0.039). On logistic regression analysis, only NIHSS and MMSE scores remained independent variables. CONCLUSIONS: Seizure occurrence in patients with a lacunar infarct is not related to the severity of the stroke but rather to the degree of cognitive impairment. The present study suggests that the seizures are not due to lacunar infarcts but are more probably the expression of an underlying neurodegenerative process that is also responsible for the mental deterioration.

Status epilepticus in stroke patients.

BACKGROUND: Status epilepticus (SE) is a life-threatening condition that occurs in only 1.5% of the overall stroke population but in more than 10% of patients with stroke-related seizures. This retrospective study compares the characteristics of stroke patients with SE to those with ordinary seizures (OS). PATIENTS AND METHODS: The demographic features, vascular risk factors, stroke type and etiology, stroke severity (according to the National Institute of Health Stroke scale) and disability (according to the modified Rankin scale), seizure type and onset, and post-ictal EEG findings were compared between 33 patients with SE and 288 with OS. SE was defined as a >30 min of either continuous seizure activity or multiple seizures without regaining consciousness. RESULTS: Patients with SE had more severe strokes and a worse outcome. Demographic features and stroke etiology were similar in both groups. Chronic obstructive pulmonary disease was only observed as a risk factor in patients with OS. There was a non-statistical trend that SE occurred more frequently at stroke onset. Seizure recurrence was the same in both groups. Post-ictal EEG was always abnormal in the SE patients and normal in 30% of the OS group. CONCLUSIONS: SE occurs mainly in patients with a severe stroke and with severe disability. Patients with a severe stroke are probably more at risk of early-onset SE.

Transient ischemic attacks and inhibitory seizures in elderly patients.

BACKGROUND: The new definition of a transient ischemic attack (TIA) makes it more difficult to distinguish it from an inhibitory seizure (IS). PURPOSE: The present study compares the characteristics of patients with an IS to those with a TIA, taking into account the old and the new definition of a TIA. PATIENTS AND METHODS: The clinical characteristics and the electroencephalogram (EEG) findings of 25 patients with an IS were compared to 252 patients with a TIA according to the old definition. Subgroups of 10 patients with an IS without structural lesions and 195 TIA patients according to the new definition were also analyzed. The differential diagnostic clues were examined. RESULTS: Differences in age, gender distribution and vascular risk factors were observed only when comparing the overall patient groups. However, these differences disappeared when the subgroups were analyzed. Temporary speech disturbance, associated with some partial amnesia for the event, was the most common clinical presentation of an IS. Additionally, specific and nonspecific postictal EEG abnormalities were observed in the majority of the IS patients, while the EEG was normal in more than 90% of the TIA patients. CONCLUSIONS: An IS must be suspected in a patient with a short temporary speech disturbance and partial amnesia for the event. In view of the new definition of a TIA, urgent EEG becomes mandatory in each patient with a brief episode of neurological dysfunction.

The classic lacunar syndromes: clinical and neuroimaging correlates.

BACKGROUND: Although lacunar syndromes (LSs) are aimed to be linked to lacunar infarcts, the relation between both is still not very well defined. PURPOSE: The present retrospective study tries to define more specifically the clinical and the neuroimaging characteristics of the five most classic LSs. PATIENTS AND METHODS: Out of a series of 1617 consecutive stroke patients, admitted to the Ghent University Hospital, 293 presented a classic LS. Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) was performed within 5 days after stroke onset in 227 patients. An acute territorial infarct was demonstrated in 54 patients. The study population finally consisted of 173 patients with a classic LS in whom the responsible lacune was demonstrated or in the absence of another type of infarct. RESULTS: The responsible lacune was demonstrated with DWI in 104 patients. Pure motor stroke (MS) correlated significantly with the presence of the responsible lacune in the internal capsule (P = 0.000147) and with the stroke severity (P = 0.00724). No significant correlation was observed between the location of the lacunes and the other LS's. CONCLUSION: Pure MS has to be considered as the most specific lacunar syndrome.

The cortical involvement of territorial infarcts as a risk factor for stroke-related seizures.

BACKGROUND: The cortical involvement of territorial infarcts is considered to be a significant risk factor for the development of early- as well as late-onset seizures. However, it is not known which cortical regions are more susceptible to the development of stroke-related seizures. PATIENTS AND METHODS: In this retrospective study of 687 patients with territorial infarcts, 184 with stroke-related seizures were compared to 503 without seizures. The extent and the location of the infarcts were determined by computed tomography (CT) scans and/or magnetic resonance imaging (MRI) scans of the brain. The infarcts of the seizure and the non-seizure group were compared on digital cerebral vascular maps by superimposing the CT and/or MRI slices. RESULTS: In patients with late-onset seizures, the infarcts were significantly more frequent in the temporal and parietal branches of the middle cerebral artery in comparison to the non-seizure group. In patients with early-onset seizures and in those with seizures due to a recurrent stroke, the territory of the temporal and occipital branches of the middle cerebral artery was the predilection side of the infarcts. Generalized tonic-clonic seizures occurred mainly in cases of infarction in the deep territory of the middle cerebral and of the anterior choroidal artery. Status epilepticus was significantly correlated with infarcts in the posterior temporal region. CONCLUSION: Some infarct regions are the sides of predilection for stroke-related seizures according to their type and their onset-time.

Characteristics and outcomes of patients with seizures according to the time of onset in relation to stroke.

BACKGROUND/AIM: Although most late-onset seizures (LS) appear within 2 years after stroke, some of them occur later and their characteristics are unknown. The aim of this study was to compare the characteristics of patients with very-late-onset seizures (VLS) to those with early-onset seizures (ES) and those with LS. PATIENTS: The study group consisted of 204 patients with stroke-related seizures (29 ES, 128 LS and 47 VLS). RESULTS: Intracranial haemorrhage was a more frequent cause of ES than of LS and no cause at all of VLS. On the other hand, 25% of the VLS were related to lacunar strokes. Status epilepticus occurred in 20.7% of the ES, in 11.7% of the LS and in 2.1% of the VLS patients. Seizure recurrences were 13.8% in the ES, 54.7% in the LS and 34.0% in the VLS group. Neurological impairment, at stroke onset, and the degree of disability were more severe in patients with ES compared to those with LS and were very mild in the VLS group. The EEG findings as a whole did not show significant differences between the three groups, although a normal EEG was more frequent in the VLS group. CONCLUSION: VLS occur in patients with minor ischaemic strokes with good recovery and benign disease course.

Stroke-related seizures in patients with a partial anterior circulation syndrome.

BACKGROUND: Partial anterior circulation syndrome (PACS), due to cerebral infarction, is the most common stroke presentation of patients with seizures. This study investigates the characteristics of such patients according to their seizure onset time. PATIENTS AND METHODS: The characteristics of 151 patients with a PACS and seizures were compared to 310 without seizures. The seizure groups were classified as those of early- (EO), of late- (LO) and of very late-onset (VLO) and those due to recurrent infarcts (RI). RESULTS: Temporal lobe infarction is the main risk factor for developing seizures (P < 0.02). Seizures are responsible for increased dependency except in patients with those of VLO (P < 0.03). Patients with EO seizures have the worse outcome (P = 0.0111) with a trend of more status epilepticus (P = 0.066) but less recurrence (P = 0.003). A cardiac-embolic source is more common in patients with seizures due to RI (P = 0.015). Post-ictal EEG patterns are significantly different from those in the patients without seizures (P < 0.001) except for seizures of VLO. CONCLUSIONS: There are significant differences in the seizure characteristics according to their time of onset.

Seizures and epilepsy in patients with lacunar strokes.

BACKGROUND: The relation between seizures and small subcortical infarcts is uncertain. The present retrospective study investigates whether differences are observed between patients with and without seizures following a lacunar stroke. PATIENTS AND METHODS: Thirty-seven patients with seizures and a prior history of a lacunar stroke were admitted to the Ghent University Hospital during 2000 and 2005. They were compared to 205 patients, admitted between 2002 and 2004, with an acute lacunar stroke and without epileptic spells on follow-up. Nine out of the 37 patients with seizures and 48 out of the 205 without seizures had a history of recurrent strokes. RESULTS: No differences in vascular risk factors, distribution and frequency of the lacunes, degree of severity of the white matter changes and outcome were observed. On the Mini-Mental State Examination moderate to severe cognitive disturbances were observed in the seizure group and in some patients of the non-seizure group. CONCLUSIONS: In the present study we found no evidence that seizures are directly induced by lacunar infarcts. The seizures appear to be part of a more global ongoing cerebral disorder probably leading to cognitive impairment.

Chronic obstructive pulmonary disease as a risk factor for stroke-related seizures.

Chronic obstructive pulmonary disease (COPD) is a risk factor for cardiovascular disorders and different types of stroke. The present retrospective study investigates whether COPD is also a risk factor for the development of seizures in stroke patients. The study population consisted of 237 patients with stroke-related seizures. The control population was composed of 939 patients, admitted for a stroke between 2002 and 2004 and who did not develop epileptic spells on a follow up of 2 years. The stroke type and aetiology, and the vascular risk factors, including COPD, were compared. The seizure patients were older (P = 0.009) and had more arterial hypertension (P = 0.046) and cardiac-embolic strokes (P = 0.045) than the control group. On logistic regression only partial anterior circulation syndrome/infarct (PACS/I) and COPD (P < 0.001) emerged as independent risk factors for the development of seizures in stroke patients. The occurrence of seizures was not related to the severity of the COPD or to its type of treatment. The present study confirms that seizures occur most frequently in patients with a PACS/I. Although we were unable to demonstrate why COPD is a risk factor for seizures in stroke patients, its frequent associated nocturnal oxygen desaturation seems to be the most plausible explanation. Further prospective are needed to assess the role of COPD as a possible independent risk factor for stroke-related seizures.

The topography of cortical microbleeds in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance study.

INTRODUCTION: Cerebrovascular lesions are rare in frontotemporal lobar degeneration (FTLD), in contrast to other neurodegenerative diseases. Cortical microbleeds (CoMBs) are frequent in Alzheimer's disease, in particular in cases associated with cerebral amyloid angiopathy. The present study investigates the gyral topographic distribution of CoMBs in post-mortem FTLD brains with 7.0-tesla magnetic resonance imaging. MATERIAL AND METHODS: The distribution of CoMBs in 11 post-mortem FTLD brains and in 12 control brains was compared on T2*-GRE MRI of six coronal sections of a cerebral hemisphere. The mean values of CoMBs were determined in twenty-two different gyri. The findings were correlated to those separately observed on neuropathological examination. RESULTS: As a whole there was a trend of more CoMBs in the prefrontal section of FTLD as well as of the control brains. CoMBs were significantly increased in the superior frontal gyrus and the insular cortex (p ≤ 0.001) and also in the inferior frontal gyrus and the superior temporal gyrus (p ≤ 0.01). CONCLUSIONS: CoMBs in FTLD are only increased in the regions mainly affected by the neurodegenerative lesions. They probably do not reflect additional cerebrovascular disease.

Comparison of age of onset and development of motor complications between smokers and non-smokers in Parkinson's disease.

BACKGROUND: There is growing evidence from case-control and from cohort studies that smoking is inversely related to the risk of developing Parkinson's disease (PD). However, it is still controversial if PD starts at an older age in ever-smoking patients compared to never-smoking ones. PATIENTS AND METHODS: The present retrospective study compares in a large series of 512 out-patients, collected over the last 24 years, the age of onset of the complaints, the age at which PD was diagnosed and the start of levodopa treatment between ever- and never-smokers. Also, the occurrence of long-term side-effects of the drug was evaluated. 184 PD patients with a history of smoking were compared with 328 who had never smoked. The subgroups with and without a family history of PD were analysed separately. RESULTS: In the overall ever-smoking group, as well as in the subgroup without a family history, the onset of the disease and the time of the diagnosis of PD and the time at which levodopa was started occurred at an older age than in the never-smoking group. This difference could not be demonstrated in the patients with a family history, due to the low number of cases and the lack of statistical power. Although the follow-up period was the same in both study groups, motor fluctuations and dyskinesia were more frequent and appeared earlier after levodopa treatment in the non-smoking compared to the ever-smoking PD patients. Only for cognitive impairment there was a non-significant trend in the smoking group. CONCLUSION: The present study confirms the protective action of smoking on PD and also suggests some modulating effect of smoking on the dopaminergic system.

Cerebral blood flow and oxygen metabolism in symptomatic internal carotid artery occlusion by (traumatic) cervical artery dissection.

The present study investigates whether cerebral infarction resulting from internal carotid artery occlusion by cervical dissection is due to emboli, released from a superimposed luminal thrombus, or is due to haemodynamic failure and hypoperfusion. Ten patients with a history of stroke and with a visible cerebral infarct on computed tomographic scan, due to cervical dissection and thrombosis of the internal carotid artery, were studied with positron emission tomography in order to assess the regional cerebral blood flow (rCBF), the regional cerebral metabolic rate of oxygen (rCMRO2) and the regional oxygen extraction fraction (rOEF) in different regions of the brain. rCBF and rCMRO2 were only decreased in the infarct area but not in the peri-infarct zone or elsewhere in the brain. As rOEF was not increased in the affected cerebral hemisphere, the present study suggests artery-to-artery embolism rather than a haemodynamic event as the cause of the stroke. Use of anticoagulants thus appears to be the appropriate treatment in the acute stage.