Henri Petit

Verbal fluency in dementia of frontal lobe type and dementia of Alzheimer type.

This study compares semantic (category) and letter-initial verbal fluency performance in dementia of frontal lobe type, dementia of Alzheimer type, and control subjects matched for age, sex, and level of education. As well as demographic characteristics, patients were matched for severity of dementia as estimated by the mini mental scale (23.2 (SD 4.9)). All patients with dementia of frontal lobe type had a frontal hypoperfusion on single photon emission computed tomography whereas patients with dementia of Alzheimer type showed mainly posterior deficits. Patients had significantly lower verbal fluency than controls but those with dementia of frontal lobe type did not differ from those with dementia of Alzheimer type in the number of words generated, intrusions, or preservations. Category fluency was more impaired than letter fluency in both dementias. No correlation between frontal index, frontal/parietal index, and fluency was found. Verbal fluency tests are sensitive tools for detecting dementia but do not seem useful in distinguishing between patients with dementia of Alzheimer type and those with dementia of frontal lobe type in early disease.

Chronic thalamic stimulation improves tremor and levodopa induced dyskinesias in Parkinson's disease.

Chronic thalamic stimulation was performed in 10 Parkinsonian patients with disabling tremor and poor response to drug therapy. During the stereotactic procedure, an electrode was introduced in the ventralis intermediate nucleus of the thalamus. Test stimulation was performed during the intra-operative procedure and a few days after surgery using an external stimulator. When tremor was obviously reduced by thalamic stimulation, an internal stimulator was implanted under the clavicle. Tremor was initially suppressed in all cases and reappeared whenever stimulation was stopped. Patients were followed for 22 to 34 months. Tremor was controlled in eight cases but reappeared after three months in two cases. Levodopa induced dyskinesias were observed before electrode implantation in 5 cases. They consisted of peak-dose choreic or ballistic dyskinesias in 4 cases and biphasic dystonic dyskinesias in 3 cases. Peak-dose dyskinesias were greatly improved or suppressed in all cases. Biphasic dyskinesias were improved in 2 cases. Thalamic stimulation was well tolerated. Mild dystonic hand posture related to the deep brain stimulation was observed in one case. No neuropsychological side-effects were noted. Thalamic stimulation could prove to be an adequate treatment for resistant tremor and levodopa induced dyskinesias.

Frontotemporal behavioral scale.

Summary:At autopsy, frontotemporal dementia (FTD) account for up to 20% of degenerative dementia cases, although FTDs are underrecognized in memory clinics. FTDs are confused with Alzheimer disease (AD) or vascular dementia (VaD). These misdiagnosis may affect the results of AD pharmacological trials. The first manifestations of FTD are behavioral abnormalities. The aim of this study was to assess a behavioral scale of frontal lobe dysfunction and to determine a behavioral cutoff to diagnose early FTD and distinguish it from AD and VaD. The score of the behavioral frontotemporal lobe dysfunction assessment scale was higher in FTD than in other dementias (p < 0.0001). With a cutoff of 3 points on the scale, FTD patients were diagnosed with a specificity of 95% and sensitivity of 91%. Noncognitive symptoms known to be institutionalization factors could contribute to differences between etiologies of mild dementia.

Evidence for a common network of brain structures involved in parkinsonian tremor and voluntary repetitive movement

Repeated measurements of regional cerebral blood flow (rCBF) were obtained in 7 patients who underwent a stereotactic thalamic electrode implantation in the nucleus ventralis intermedius (nVIM) of the thalamus for severe hemi-parkinsonian tremor. Using positron emission tomography and oxygen-15 labelled water, rCBF was studied in each patient in two conditions: in absence of tremor, e.g. under nVIM electrical stimulation, and in presence of tremor. X-ray tomograms permitted individual definition of anatomical regions of interest. In presence of tremor, normalized rCBF increases were observed in the following regions: postcentral (13.6 +/- 8.4%, P = 0.0003), precentral (7.7 +/- 8.8%, P = 0.016), paracentral (7.7 +/- 8.4%), supplementary motor (8.2 +/- 10.4%, P = 0.025), caudate nucleus (5.7 +/- 7.6%, P = 0.03), vermis (9.7 +/- 7.3%, P = 0.007), cerebellar grey nuclei (9 +/- 6%, P = 0.016) on the electrode side and on the contralateral vermis (17.8 +/- 7.5%, P = 0.0003) and cerebellar grey nuclei (22 +/- 6.3%, P = 0.0004). These results clearly indicate an activation of the sensory-motor cortex, as well as an involvement of the supplementary motor area and the cortico-cerebellar pathways in Parkinsonian resting tremor (PRT). They demonstrate that PRT shares common network of brain structures with repetitive voluntary movement.

Which factors predict cognitive decline in Parkinson's disease?

The study assessed cognitive decline in non-demented, non-depressed patients with well defined Parkinsons disease and determined the predictive value for cognitive decline of different motor symptoms. Motor disability was measured with the Unified Parkinsons disease rating scale, impairment in activities of daily living, levodopa test, and long term clinical follow up. Neuropsychological evaluations included modified mini mental state, fluency, Wechsler logical memory, Wisconsin card sorting test, and the Montgomery and Asberg depression rating scale. Fifty three patients fulfilling clinical criteria for idiopathic Parkinsons disease were studied. Cognitive performance on initial testing was significantly correlated with education and disease duration but not with age at disease onset. Cognitive performance on retesting after three years of follow up was significantly reduced. This reduction was significantly greater in the late onset group, in patients with isolated dystonic dyskinesiae, and in patients with a lower percentage of motor improvement on levodopa. Cognitive decline in idiopathic Parkinsons disease may depend on both the prevalence of non-dopaminergic lesions and the topography of dopaminergic denervation. Predictive factors for cognitive decline, especially in executive tasks, relate more to non-dopaminergic than to dopaminergic lesions.

Relevance of the quantification of apolipoprotein E in the cerebrospinal fluid in Alzheimer's disease

Apolipoprotein E (Apo E), one of the major structural and functional apolipoproteins, has recently been implicated in the pathogenesis of Alzheimers disease (AD). Several studies revealed that Apo E4 isoform is associated with the pathogenic process in AD. A significant reduction of cerebrospinal fluid (CSF) Apo E level in AD patients has been reported in two studies. To further investigate the physiopathological significance of such a variation of Apo E concentration in the CSF, we performed a quantification of Apo E by an enzyme linked immunosorbent assay (ELISA). There were no significant differences in CSF Apo E level between AD cases and control subjects or patients suffering from other neurological diseases. Gender, age and Apo E phenotype explained none of CSF Apo E concentration variability.

Tacrine efficacy in Lewy body dementia

Background. Response to tacrine varies among patients with Alzheimers disease (AD). Lewy body dementia (LBD) could be a high responder subtype of AD. The aim of the study was to compare the effects of tacrine in LBD and AD.

Medial temporal lobe atrophy in memory disorders

Abstract Medial temporal lobe atrophy determined by temporal lobe oriented computed tomography (CT), 1 year before death, is strongly associated with histopathologically confirmed Alzheimer’s disease (AD). The aim of this study was to assess the diagnostic accuracy of medial temporal lobe measurement for the diagnosis of AD in patients referred to a memory disorders clinic, especially those at an early stage of the disease. CT oriented to the temporal lobe was performed in 333 subjects aged 41–93 years consecutively recruited in a Memory Disorders Clinic: 124 had probable AD, Mini Mental State score (MMS) = 17 (8); 50 possible AD [MMS = 21 (5)]; and 119 patients had miscellaneous memory disorders [MMS = 22 (7): frontotemporal lobe dementia, subcortical dementia, cortical Lewy body disease, vascular dementia, Korsakoff syndrome, focal atrophy, etc.]. There were also 19 anxious/ depressed patients [MMS = 29 (1)] with normal performance on memory tests, and 21 controls. The minimum width of the medial temporal lobe was measured. The best cut-off to distinguish AD patients from non-AD patients was 11.5 mm, in agreement with data in the literature. At this threshold, 84% of probable AD patients had a positive test and 90% of controls and anxious/depressed patients had a negative test. For the diagnosis of probable AD, sensitivity of the measurement was 0.81, specificity 0.95, predictive positive value 0.99, predictive negative value 0.45, and diagnostic accuracy 0.83. The test was positive in half the possible AD patients, and half those with miscellaneous memory disorders. It was negative in all anxious/depressed patients. Therefore, temporal lobe oriented CT might be a valuable tool for assessment of medial temporal lobe atrophy in AD routine practice.

Cognitive and psychiatric impairment in herpes simplex virus encephalitis suggest involvement of the amygdalo-frontal pathways

The long-term neuropsychological and psychiatric sequelae of herpes simplex virus encephalitis (HSVE) and their relationship to the volume of temporal lesions and to amygdala and hippocampus damage remain undefined. We have conducted a prospective study of longterm sequelae in 11 patients with clinically presumed HSVE and detection of HSV DNA in the cerebrospinal fluid by polymerase chain reaction. Six months after encephalitis, patients underwent neuropsychological and language assessment. At the same stage, single photon emission computed tomography (SPECT) evaluated the occurrence of hypoperfusion with an index of asymmetry. MRI was used for the measurement of amygdala, hippocampus and cerebral lesions by two blind neurologists. The volume of the amygdala and hippocampus was compared with those of five controls, matched for age and level of education. Longterm memory disorders were seen in 6 patients, associated with the larger lesions and damage of at least two structures. Long-term behavioural changes with emotionalism, irritability, anxiety or depression were prominent in 7. Left prefrontal hypoperfusion appeared in 8 patients, associated with psychiatric disorders in 7 and left amygdala damage in 6. The reduction of amygdala and hippocampus volume was correlated with the overall volume of lesions. Different patterns of mesial temporal lobe damage occurred, involving either amygdala alone, or amygdala and hippocampus, but never hippocampus alone. MRI volumetric measurements in HSVE could be a good indicator of long-term prognosis. Persistant behavioural changes could be related to an amygdala and frontal dysfunction.

The Use of SPECT in a Multidisciplinary Memory Clinic

We tested the interobserver reliability of visual rating of HMPAO-SPECT imaging in 271 outpatients referred to a memory clinic, and followed over 1 year. The clinical diagnoses were Alzheimers disease (n = 156), frontotemporal dementia (n = 47); vascular dementia (n = 21), senile dementia of Lewy body type (n = 12), anxiety/depressive disorders (n = 14) and miscellaneous memory disorders (n = 21). The interobserver agreement was good (k = 0.68). However, the heterogeneity of the patterns-independent from demographic data, age at onset and duration of the disease- and their lack of sensibility and specificity limited the contribution of SPECT for diagnostic purposes in routine practice.