ABSTRACT
OBJECTIVE: To describe the clinical, biochemical, and neuropathological findings of an autosomal dominant globular glial tauopathy caused by the P301T mutation at the MAPT gene. METHODS: Five patients from two unrelated pedigrees underwent clinical evaluation. Genetic analysis, brain pathological examination, and biochemical analysis of tau were performed. RESULTS: The patients studied were 3 men and 2 women with a mean age at onset of 52.2 years and mean disease duration of 5.2 years. Three patients presented a corticobasal syndrome, one patient an asymmetric pyramidal syndrome compatible with primary lateral sclerosis, and one patient a frontotemporal dementia. In both pedigrees (4 patients) Sanger sequencing showed the p.P301T mutation in exon 10 of the MAPT gene. Neuropathological findings consisted of atrophy of frontal and temporal lobes with marked spongiosis and astrogliosis, and abundant phosphorylated tau protein deposits in the frontal and temporal cortex, limbic area, basal ganglia, and brain stem. The most striking finding was the presence of oligodendroglial 4R phospho-tau globular positive inclusions in the white matter and cortex. Globose-type neurofibrillary neuronal tangles, and in particular astrocytic globular inclusions and coarse tufts, were present in the grey matter. Biochemical analysis of sarkosyl-insoluble fractions revealed two tau bands of 64 and 68 kDa and case-dependent bands of lower molecular weight. CONCLUSION: This is the first pathological and biochemical study of the MAPT p.P301T mutation showing variable clinical manifestation and neuropathological phenotype of globular glial tauopathy not only among different families but also within families.
Subject(s)
Gray Matter , Neuroglia , Tauopathies , White Matter , tau Proteins/metabolism , Aged , Female , Gray Matter/metabolism , Gray Matter/pathology , Humans , Male , Middle Aged , Neuroglia/metabolism , Neuroglia/pathology , Pedigree , Spain , Tauopathies/genetics , Tauopathies/metabolism , Tauopathies/pathology , Tauopathies/physiopathology , White Matter/metabolism , White Matter/pathology , tau Proteins/geneticsABSTRACT
Los factores genéticos parecen tener un papel importante en el desarrollo de la enfermedad de Parkinson. La degeneración de la sustancia negra, característica de esta enfermedad, puede deberse al efecto tóxico de sustancias derivadas del metabolismo celular. El gen CYP2D6 codifica para la enzima metabolizadora debrisoquina-4- hidroxilasa implicada en la detoxificación de parte de estos productos. La presencia de determinadas mutaciones en el gen conlleva la falta de actividad enzimática y genera el fenotipo "pobre metabolizador". Se ha analizado mediante la técnica de PCR-RFLP la presencia de las mutaciones genéticas CYP2D6 3, CYP2D6 4, CYP2D6 6 y CYP2D6 8 en un grupo de 46 pacientes con EP y en 54 controles, con el fin de estudiar el posible valor del genotipo CYP2D6 como factor de riesgo para la enfermedad de Parkinson en la población navarra. Los alelos CYP2D6 3, 6 y 8 no están representados en la población de estudio. No hemos obtenido una mayor prevalencia de mutaciones CYP2D6 4 en los pacientes con respecto a los controles (30,43 por ciento vs 44,44 por ciento). No existe correlación entre la enfermedad de Parkinson y la presencia de las mutaciones CYP2D6 4 (odds ratio 0,55; 95 por ciento IC 0,24 a 1,25), en homocigosis (odds ratio 0,38; 95 por ciento IC 0,04 a 3,76) o en heterocigosis (odds ratio 0,62; 95 por ciento IC 0,27 a 1,44). En conclusión, el genotipo CYP2D6 no constituye un factor de EP (AU)
Subject(s)
Aged , Female , Male , Middle Aged , Humans , Parkinson Disease/enzymology , Cytochrome P-450 CYP2D6/genetics , Parkinson Disease/genetics , Mutation/genetics , Phenotype , Case-Control StudiesABSTRACT
Genetic factors seem to play an important role in the development of Parkinson's disease. The degeneration of the sustantia nigra, characteristic of this disease, might be due to the toxic effect of substances derived from cellular metabolism. The CYP2D6 gene codifies for the metabolising enzyme debrisoquie-4-hydroxilase involved in the detoxification of part of these products. The presence of determinate mutations in the gene implies a lack of enzymatic activity and generates the "poor metaboliser" phenotype. By means of the PCR-RFLP technique, the presence of the genetic mutations CYP2D6 3, CYP2D6 4, CYP2D6 6 and CYP2D6 8 has been analysed in a group of 46 patients with PD and in 54 controls, with the aim of studying the possible value of genotype CYP2D6 as a risk factor for Parkinson's disease in the population of Navarra. The alleles CYP2D6 3, 6 and 8 are not represented in the sample studied. We have not obtained a greater presence of CYP2D6 4 mutations in the patients with respect to the controls (30.43% vs. 44.44%). There is no correlation between Parkinson's disease and the presence of CYP2D6 4 mutations (odds ratio 0.55; 95% CI 0.24 to 1.25), in homozygosis (odds ratio 0.38; 95% CI 0.04 to 3.76) or in heterozygosis (odds ratio 0.62; 95% CI 0.27 to 1.44). In conclusion, the genotype CYP2D6 does not constitute a risk factor in PD.
ABSTRACT
No disponible
Subject(s)
Aged , Female , Male , Humans , Neurodegenerative Diseases/epidemiology , Alzheimer Disease/epidemiology , Parkinson Disease/epidemiology , Health Programs and Plans , Risk Factors , Spain/epidemiology , Cost of IllnessABSTRACT
UNLABELLED: Thirty-four patients with a probable Alzheimer's Disease (AD) (mild AD = 16; moderate AD = 18) and 12 matched controls were evaluated using semiquantitative SPECT-99mTc-HMPAO and neuropsychological tests (CERAD). RESULTS: Both temporal hypoperfusion (p < 0.01) and memory tests (p < 0.001) made it possible to differentiate the controls from mild AD patients. In these patients, significant correlations (p < 0.05) were also found between: 1) delayed recall test/temporal hypoperfusion, 2) learning memory test/temporoparietal and frontal hypoperfusion and 3) visual constructive praxis/posterior temporal hypoperfusion. In contrast to mild AD, moderate AD patients showed higher temporal (p < 0.01) parietal and frontal (p < 0.05) hypoperfusion along with worsening of praxis (p < 0.001) and memory tests (p < 0.05). CONCLUSIONS: SPECT imaging and neuropsychology evaluation can distinguish controls from AD patients with mild an moderate grades of dementia, showing a strong correlation from the early stages of AD.
Subject(s)
Alzheimer Disease/diagnosis , Brain/diagnostic imaging , Neuropsychological Tests , Tomography, Emission-Computed, Single-Photon , Aged , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/psychology , Cerebrovascular Circulation , Dementia/diagnosis , Dementia/diagnostic imaging , Dementia/psychology , Diagnosis, Differential , Female , Humans , Male , Memory Disorders/diagnosis , Memory Disorders/diagnostic imaging , Memory Disorders/psychology , Middle Aged , Sensitivity and Specificity , Severity of Illness Index , Technetium Tc 99m ExametazimeABSTRACT
AIM: To determine the incidence of Parkinson's disease in Navarra, province of Spain. PATIENTS AND METHODS: All patients diagnosed as suffering from Parkinson's disease or related disorders for the neurologists of the region during the period 1994-1995 inclusive were referred to the study. EUROPARKINSON protocol and an epidemiological questionnaire were employed for the assessment. RESULTS: A total of 132 cases of idiopathic (86) and secondary (45) Parkinson's disease were diagnosed during that period. Among men the age adjusted incidence of idiopathic Parkinson's disease was 10.06 x 10(5), while for women it was 4.92 x 10(5). Total adjusted incidence was 7.36 x 10(5). The average age at onset was 67.5 years in men and 72.6 years in women (p < or = 0.007). Men showed an age adjusted incidence of secondary parkinsonism of 3.34 x 10(5) and women of 4.23 x 10(5). Age at onset was earlier in women than in men (71.2 and 74.8 years, respectively). CONCLUSIONS: The incidence of idiopathic Parkinson's disease in Navarra is higher in men than in women, also supported for an earlier age at onset in men. The epidemiological pattern of secondary Parkinson's disease differs from that of the idiopathic disease.
Subject(s)
Parkinson Disease, Secondary/epidemiology , Parkinson Disease/epidemiology , Registries , Aged , Female , Humans , Incidence , Life Style , Male , Middle Aged , Spain/epidemiology , Surveys and QuestionnairesABSTRACT
An evaluation is made of the effect of smoking during the period of life between 20 and 50 years of age and idiopathic Parkinson's disease in a case-control study carried out in Navarra. An inverse association is observed: for the number of smokers (OR = 0.66, CI 90% 0.41-1.05); for the number of years smoking (OR =0.22, CI 90% 0.05-0.97); and for the quantity of cigarettes smoked (z = 2.2298, p = 0.02). Likewise, a dose-response relationship exists between the number of cigarettes consumed and the risk of Parkinson's disease (p = 0.01). The same effect is maintained on analysing the data by matching 1:1 (OR = 0.59, CI 90% 0.31-1.10). All of this contributes to giving consistency to the protective effect of smoking against idiopathic Parkinson's disease. The anti-oxidant status, measured by means of different parameters in peripheral blood, is lower in the cases than in the tests for reduced glutathione (GSH) (p = 0.001) and is an independent variable with respect to smoking.
ABSTRACT
The Mini-Mental-State Examination (MMSE) is widely used as a screening tool for dementia in epidemiological studies. Its applicability in population-based studies is nevertheless limited by its low specificity. The effect of age and educational level have been usually ignored when cut-off scores have been selected. The aim of this study was to evaluate the effect of age and educational level on the MMSE scores in a representative sample of subjects older than 70 and provide adjusted normalised data according to these two variables, after excluding subjects with dementia or cognitive decline. Population-based, cross-sectional and longitudinal study of a representative cohort of 1367 subjects older than 70. All subjects with suspected dementia or cognitive decline received a neurological evaluation where clinical and etiological diagnosis were established. Normal MMSE scores, as defined by the 10th percentile, varied significantly across age and educational level groups. Exclusion of demented or cognitively declined patients from the reference population reduced the variability and "range of normality", but this remained excessively high in the older and less educated groups. The use of different cut-off points for each age and educational level groups may improve the specificity and applicability of the MMSE in population-based epidemiological studies. However, the wide amplitude of the range of normality suggests that different approaches, other than this vibariate analysis, may prove more adequate in the selection of cut-off scores for the MMSE.
Subject(s)
Dementia/diagnosis , Dementia/epidemiology , Neuropsychological Tests , Age Distribution , Aged , Aged, 80 and over , Educational Status , Female , Humans , Male , Spain/epidemiologyABSTRACT
The etiology of Parkinson's disease (PD) is still unknown. Genetic factors and environmental exposure have been suggested in the etiopathogenesis of the disease. But the cause of dopaminergic cell loss in patients with PD remains unknown. During the last decade studies of the pathogenesis of PD have centred on the oxidative damage to the substantia nigra pars compacta. An increased free radical production and an inadequate antioxidant defence system have been reported, which could contribute to the biopathology of PD. The GSH levels in the brain are decreased, and iron levels in the substantia nigra are elevated. Moreover there are changes in SOD with an increased activity in the substantia nigra. The possible implication of oxidative stress in cell loss has encouraged research into the role of certain antioxidant agents, such as dietary compounds and drugs, as protective agents against PD.
ABSTRACT
We describe a Spanish adaptation and standardization of the Alzheimer's Disease Assessment Scale (ADAS) carried out as part of a prospective, coordinated study performed simultaneously in two Spanish health centers. Three diagnostic groups were defined: 21 healthy volunteers (normal group); 22 patients with cognitive deterioration but no dementia (CDND group); and 20 patients with Alzheimer type dementia (ATD group). The subjects were examined at the start of the study and after 3 and 6 months. The mean cognitive ADAS scores were significantly different in the 3 groups (F = 67.2, p = 0.0001), as follows: normal group, 7.6 +/- 2.1; CDND group, 12.4 +/- 4.5; and ATD group, 21.0 +/- 4.7. Likewise, the ADAS proved sensitive to the course of deterioration in the ATD group, while the other groups' scores improved. We conclude that the ADAS, and in particular the cognitive subscale, is useful for evaluating ATD patients, especially in the early phases of deterioration. It discriminates between ATD and CDND patients well.
Subject(s)
Alzheimer Disease/diagnosis , Neuropsychological Tests/standards , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Spain , TranslationsABSTRACT
In order to evaluate the relationship between perfusion brain SPECT and specific cognitive functions as well as the possible influence of the illness severity on them, 34 patients clinically diagnosed as probable Alzheimer disease (AD) and 12 elderly controls were studied. AD patients were subdivided according to severity as 16 mild AD and 18 moderate AD. Neuropsychological battery of CERAD protocol and a semiquantitative analysis of 99mTc-HMPAO-SPECT images was carried out in all groups. With regard to the regions affected in SPECT, involvement of temporo-parietal cortex were of most use in discriminating between AD patients and controls, but only temporal hipoperfusion distinguished mild disease from controls. Memory and praxis impairment correlated with temporo-parietal perfusion. Frontal involvement seemed to be a discriminator of disease progression, nevertheless, a significant correlation was present between memory and frontal hipoperfusion indicating the diffuse and sometimes heterogeneous distribution of AD pathology.
Subject(s)
Alzheimer Disease/diagnostic imaging , Cerebral Cortex/diagnostic imaging , Neuropsychological Tests , Tomography, Emission-Computed, Single-Photon , Aged , Alzheimer Disease/complications , Alzheimer Disease/psychology , Cerebral Cortex/blood supply , Disease Progression , Female , Frontal Lobe/blood supply , Frontal Lobe/diagnostic imaging , Humans , Male , Memory Disorders/diagnostic imaging , Memory Disorders/etiology , Middle Aged , Parietal Lobe/blood supply , Parietal Lobe/diagnostic imaging , Severity of Illness Index , Technetium Tc 99m Exametazime , Temporal Lobe/blood supply , Temporal Lobe/diagnostic imagingABSTRACT
We attempt to determine the utility of CERAD in detecting early Alzheimer's disease (AD). CERAD battery was administered to a group of 14 control subjects, 12 patients with possible dementia prodromes and to patients with Alzheimer's disease stratified according to severity (16 mild, 8 moderate). Other measures as some subtest of the Wechsler memory scale and the Rey Complex Figure Test were also applied. Delayed recall as well as logical memory of Wechsler memory scale were found to be the best discriminators for detecting very mild cases of AD (Prodromes) (p < 0.05). None of the memory test proved of value in staging the disorder. Visuospatial functions are better determinants of the progression of the illness. Fluency also distinguish between control subjects and very mild cases. These findings suggest that delayed recall memory and probably executive function are the most useful and sensitive indicators of Alzheimer's disease.
Subject(s)
Alzheimer Disease/diagnosis , Neuropsychological Tests , Aged , Alzheimer Disease/complications , Alzheimer Disease/psychology , Dementia/diagnosis , Dementia/psychology , Evaluation Studies as Topic , Female , Humans , Language Disorders/diagnosis , Language Disorders/etiology , Male , Memory Disorders/diagnosis , Memory Disorders/etiology , Mental Recall , Middle AgedABSTRACT
We investigated the prevalence of dementing disorders in the city of Pamplona, Spain, using a door-to-door two-phase approach. We first administered the Cambridge Examination of Mental Disorders of the Elderly (CAMDEX) to all survivors, as of March 1, 1991, of a probability sample of the total population identified in 1989 (n = 1,127). Using specified diagnostic criteria, the study neurologists extensively investigated those subjects who screened positive on CAMDEX. We found 194 subjects affected by dementia, 119 had Alzheimer's disease; 51 vascular or mixed dementia, and 16 secondary dementia. The prevalence of both dementia and Alzheimer's disease increased steeply with advancing age and was consistently higher in women. The prevalence of combined vascular and mixed dementia increased less rapidly with age, and was generally higher in men. Alzheimer's disease was the most common type of dementia. Our prevalence figures for dementia and Alzheimer's disease are similar to those previously reported in Europe.
Subject(s)
Alzheimer Disease/epidemiology , Dementia, Vascular/epidemiology , Dementia/epidemiology , Age Factors , Aged , Cohort Studies , Female , Humans , Incidence , Male , Prevalence , Sex Factors , Spain/epidemiologyABSTRACT
A patient with a bilateral striatal lesion secondary to anoxia presented reflex blepharospasm associated with parkinsonism and dystonia in the limbs. The blink reflex excitability curve was enhanced and the R-2 response prolonged as in patients with essential blepharospasm. The findings in this patient support the notion that blepharospasm may be secondary to basal ganglia dysfunction through abnormal facilitation of reticular formation neurons controlling facial nucleus motoneuron excitability.
Subject(s)
Basal Ganglia Diseases/physiopathology , Blepharospasm/physiopathology , Blinking/physiology , Dominance, Cerebral/physiology , Hypoxia, Brain/physiopathology , Intraoperative Complications/physiopathology , Adolescent , Basal Ganglia Diseases/diagnosis , Blepharospasm/diagnosis , Caudate Nucleus/physiopathology , Cerebral Infarction/diagnosis , Cerebral Infarction/physiopathology , Dystonia/diagnosis , Dystonia/physiopathology , Electromyography , Female , Humans , Hypoxia, Brain/diagnosis , Intraoperative Complications/diagnosis , Magnetic Resonance Imaging , Parkinson Disease, Secondary/diagnosis , Parkinson Disease, Secondary/physiopathology , Postoperative Complications/diagnosis , Postoperative Complications/physiopathology , Putamen/physiopathologyABSTRACT
We describe a patient with chronic renal failure who suffered multifocal action-induced jerks. Electromyography (EMG) recorded the typical silence of asterixis. Back-averaging the EEG activity preceding the EMG silent periods in the forearm showed a biphasic wave antedating the asterixis by 23 ms. Somatosensory evoked potentials (SEPs) after median nerve stimulation were pathologically enlarged on both hemispheres. Brain-mapping of the biphasic wave preceding asterixis and the giant SEPs indicated a common origin in the sensorimotor cortex. This observation provides further documentation of a cortical origin for some types of asterixis in humans.
