Because of population ageing, the prevalence of Alzheimer's disease (AD), the most common cause of dementia, increases progressively. This condition is now considered as a public health priority. New disease modifying therapeutic strategies could be available in the next few years that would necessitate an accurate and early diagnosis of the disease. Recently developed diagnostic tools are being assessed. Development of structural brain imaging allows to measure the hippocampus volume. Metabolic imaging can assess a broad range of functional parameters such as cerebral blood flow and dopaminergic activity with single photon emission computed tomography, cerebral glucose metabolism and cerebral amyloid burden with positron emission tomography. Those imaging methods are under evaluation to appreciate cerebral abnormalities that may occur earlier than structural ones. Cerebrospinal fluid biomarkers, in particular amyloid and tau peptides, allow us to look at in vivo biochemical cerebral changes related to AD, before possible serum biomarkers. Studies are under way to confirm the relevance of these new diagnostic tools. It will help us to improve evaluation of patients with AD or related diseases.
Duration of untreated psychosis (DUP) has been linked with poor prognosis and changes in the brain structure in schizophrenia at least at the beginning of the disease, but it is still unknown whether DUP relates to brain morphometry in the longer term. Our aim was to analyze the relation between DUP and the brain structure in schizophrenia in the general population, after several years of illness.
Brains of subjects with psychosis from the Northern Finland 1966 Birth Cohort (NFBC 1966) were scanned with MRI during 1999-2001 after an 11-year follow-up. DUP was assessed from medical records and regressed against global and local tissue density measurements. The brain morphometric and the DUP information were available for 46 subjects with DSM-III-R schizophrenia.
The DUP did not correlate with volumes of the total gray or white matter or the cerebrospinal fluid. The length of DUP associated positively with reduced densities of the right limbic area and the right hippocampus.
Long DUP was slightly associated with reductions of gray matter densities in the limbic area and especially the hippocampus after several years follow-up, supporting the hypothesis that, compared to short DUP, long DUP might be a marker of different disease trajectories including subtle morphometric changes.
PURPOSE: Cardiovascular dysregulation has been detected in patients with temporal lobe epilepsy (TLE) by using cardiovascular reflex tests and analysis of heart rate variability (HRV). The two methods have not previously been used in the same study to compare them in the assessment of cardioregulatory function. Magnetic resonance imaging (MRI) is considered the best method to reveal structural changes such as hippocampal sclerosis associated with TLE. It is not known whether these structural changes modify cardioregulatory function in patients with TLE. METHODS: Standard cardiovascular reflex tests and analysis of spectral and dynamic measures from 24-h electrocardiogram (ECG) recordings were performed for eight patients with and 31 patients without hippocampal sclerosis and for 72 control subjects. MRI also was performed in each patient to reveal hippocampal sclerosis. RESULTS: Various measures of cardiovascular reflexes and HRV were diminished in patients with TLE compared with the control subjects. No significant differences were found in the measures obtained from the cardiovascular reflex tests or analysis of HRV between those with and without hippocampal sclerosis, although a nonsignificant trend toward reduced values was seen among those with hippocampal sclerosis. The values of cardiovascular reflexes and spectral analysis of HRV correlated with each other. CONCLUSIONS: These results suggest that functional rather than structural changes related to TLE are involved mainly as a mechanism of altered cardioregulatory function. The cardiovascular reflex test and analysis of HRV both appear to be useful in studying cardioregulation in patients with TLE.
It is important to have a replicable easy method for monitoring atrophy progression in Alzheimer's disease. Volumetric methods for calculating hippocampal volume are time-consuming and commonly used in research. Visual assessments of medial temporal lobe atrophy (vaMTA) is a rapid method for clinical use. This method has not been tested in a large non-demented population in comparison with volumetry measurements. Since hippocampal volume decreases with time even in normal aging there is also a need to study the normal age differences of medial temporal lobe atrophy.
To compare visual assessment of medial temporal lobe atrophy (vaMTA) with hippocampal volume in a healthy, non-demented elderly population. To describe normal ageing using vaMTA.
Non-demented individuals aged 60, 66, 72, 78, 81, 84, and =87 years old were recruited from the Swedish National study on Ageing and Care in Kungsholmen (SNAC-K), Sweden. Standard magnetic resonance imaging (MRI) scans, vaMTA, and calculations of hippocampal volumes were performed in 544 subjects.
Significant correlation (r(s) = -0.32, P 80-year-old individuals.
To determine whether magnetic resonance imaging measurements observed in the Alzheimer Disease Neuroimaging Initiative (ADNI) convenience sample differ from those observed in the Mayo Clinic Study of Aging (MCSA) population-based sample.
Comparison of 2 samples.
Fifty-nine recruiting sites for the ADNI in the United States and Canada and the MCSA, a population-based cohort in Olmsted County, Minnesota.
Cognitively normal subjects and amnestic subjects with mild cognitive impairment were selected from the ADNI convenience cohort and MCSA population-based cohort. A simple random sample of subjects from both cohorts in the same age range was selected, and a second sample applied matching for age, sex, educational level, apolipoprotein E genotype, and Mini-Mental State Examination score.
Baseline hippocampal volumes and annual percentage of decline in hippocampal volume.
In the population-based sample, MCSA subjects were older, had less education, performed worse on the Mini-Mental State Examination, and had a family history of Alzheimer disease less often than did ADNI subjects. Baseline hippocampal volumes were larger in ADNI compared with MCSA cognitively normal subjects in the random sample, although no differences were observed after matching. Rates of decline in hippocampal volume were greater in the ADNI compared with the MCSA for cognitively normal subjects and those with amnestic mild cognitive impairment, even after matching.
Rates of decline in hippocampal volume suggest that ADNI subjects have a more aggressive brain pathologic process than MCSA subjects and hence may not be representative of the general population. These findings have implications for treatment trials that use ADNI-like recruitment mechanisms and for studies validating new diagnostic criteria for Alzheimer disease in its various stages.
Cites: Ann Neurol. 2009 Aug;66(2):200-819743450
Cites: Neurology. 2008 May 6;70(19 Pt 2):1778-8518184916
White matter hyperintensities (WMHs) and brain atrophy frequently coexist in older people. However, it is unclear whether the association between these two brain lesions is dependent on the aging process, a vascular mechanism or genetic susceptibility. It was therefore investigated whether the association between load of WMHs and brain atrophy measures is related to age, vascular risk factors (VRFs) or the APOE-e4 allele.
This population-based study included 492 participants (age =60 years, 59.6% women) free of dementia and stroke. Data on demographics, VRFs and APOE genotypes were collected through interviews, clinical examination and laboratory tests. WMHs on magnetic resonance images were assessed using manual visual rating and automatic volumetric segmentation. Hippocampal and ventricular volumes were manually delineated, whereas total gray matter (GM) volume was measured by automatic segmentation. Data were analyzed with multivariate linear regression models.
More global WMHs, assessed using either a visual rating scale or a volumetric approach, were significantly associated with lower GM volume and higher ventricular volume; the associations remained significant after adjusting for age, VRFs and the APOE-e4 allele. In contrast, the association between global WMHs and hippocampal volume was no longer significant after adjusting for age, whereas adjustment for VRFs and APOE-e4 had no influential effect.
The association of global WMHs with lower GM volume and higher ventricular volume is independent of age, VRFs and APOE-e4 allele, suggesting that the process of cerebral microvascular disease and neurodegeneration are associated independently of the normal aging process, vascular mechanisms or genetic susceptibility.
OBJECTIVE: To determine whether febrile seizures cause mesial temporal sclerosis (MTS), the occurrence of MTS was evaluated in an unselected series of patients with febrile seizures. METHODS: Twenty-four patients with a prolonged first febrile seizure, 8 with an unprovoked seizure after the first febrile seizure, and 32 age-, sex-, and handedness-matched control subjects with a single simple febrile seizure without later unprovoked seizures were selected from 329 febrile seizure patients followed up prospectively. The occurrence of MTS was evaluated after a mean follow-up time of 12.3 years by MR volumetry of amygdala and hippocampal formation and qualitative analysis of mesial temporal structures. RESULTS: None of the patients had MTS. The mean total volumes of the right and left hippocampal formations and amygdala did not differ significantly between any of the three groups. The qualitative analysis revealed no sclerotic changes in the mesial temporal area. The patients with a prolonged initial febrile seizure had a lower mean right-left volume difference in hippocampal formations than the control subjects, but this had no effect on the outcome. CONCLUSION: The occurrence of MTS following even prolonged febrile seizures is an uncommon event, confirming the good clinical outcome of febrile seizures.
Comment In: Neurology. 2003 Aug 26;61(4):588; author reply 588-912939457
Comment In: Neurology. 2003 Jan 28;60(2):E1-212552071
A gap of more than a hundred years occurred between the first accounts of mesial temporal sclerosis and recognition of its role in the pathogenesis of psychomotor seizures. This paper reviews how the understanding and surgical treatment of temporal lobe epilepsy developed, particularly from the work of Penfield, Jasper, and their associates at the Montreal Neurological Institute (MNI).
Publications on EEG and surgery for temporal lobe seizures from 1935 to 1953 were reviewed and charts of selected patients operated on at the MNI in the same period were examined. Attention was focused on the evolution of surgical techniques for temporal lobe epilepsy.
In the late 1930s, some EEG findings suggested deep-lying disturbances originating in the temporal lobe. However, it took another two decades before the correlation of clinical, neurophysiological, and anatomical findings provided evidence for the involvement of the mesial structures in psychomotor or temporal lobe seizures. From 1949 and onward, Penfield and his associates applied this evidence to extend the surgical resections to include the uncus and the hippocampus.
The collaborative work of a team led by Penfield and Jasper at the MNI helped to define the role of neurophysiological studies in epilepsy surgery. As a result, the importance of removing the mesial structures in order to obtain better seizure control in patients with temporal lobe epilepsy became firmly established.
We analyzed T1-weighted brain magnetic resonance imaging data of 100 cognitively normal elderly controls (NC), 127 cognitively normal Parkinson's disease (PD; PDCN) and 31 PD-associated mild cognitive impairment (PDMCI) subjects from the Norwegian ParkWest study. Using automated segmentation methods, followed by the radial distance technique and multiple linear regression we studied the effect of clinical diagnosis on hippocampal and ventricular radial distance while adjusting for age, education, and scanning site. PDCN subjects had significantly smaller bilateral hippocampal radial distance relative to NC. Nonamnestic PDMCI subjects showed smaller right hippocampal radial distance relative to NC. PDMCI subjects showed significant enlargement of all portions of the lateral ventricles relative to NC and significantly larger bilateral temporal and occipital and left frontal lateral ventricular expansion relative to PDCN subjects. Nonamnestic PDMCI subjects showed significant ventricular enlargement spanning all parts of the lateral ventricle while those with amnestic PDMCI showed changes localized to the left occipital horn. Hippocampal atrophy and lateral ventricular enlargement show promise as structural biomarkers for PD.
The outcome of surgery in patients with temporal lobe epilepsy (TLE) and normal high-resolution magnetic resonance imaging (MRI) has been significantly worse than in patients with unilateral hippocampal damage upon MRI. The purpose of this study was to determine the long-term outcomes of consecutive true MRI-negative TLE patients who all underwent standardized preoperative evaluation with intracranial electroencephalography (EEG) electrodes.
In this study we present all adult MRI-negative TLE surgery candidates evaluated between January 1990 and December 2006 at Kuopio Epilepsy Center in Kuopio University Hospital, which provides a national center for epilepsy surgery in Finland. During this period altogether 146 TLE surgery candidates were evaluated with intracranial electrodes, of whom 64 patients with normal high-resolution MRI were included in this study.
Among the 38 patients who finally underwent surgery, at the latest follow-up (mean 5.8 years), 15 (40%) were free of disabling seizures (Engel class I) and 6 (16%) were seizure-free (Engel class IA). Twenty-one (55%) of 38 patients had poor outcomes (Engel class III-IV). Outcomes did not change compared to 12-month follow-up. Histopathologic examination failed to reveal any focal pathology in 68% of our MR-negative cases. Only patients with noncongruent positron emission tomography (PET) results had worse outcomes (p = 0.044).
Our results suggest that epilepsy surgery outcomes in MRI-negative TLE patients are comparable with extratemporal epilepsy surgery in general. Seizure outcomes in the long-term also remain stable. Modern imaging techniques could further improve the postsurgical seizure-free rate. However, these patients usually require chronic intracranial EEG evaluation to define epileptogenic areas.