Dementia in hereditary cerebral hemorrhage with amyloidosis-Dutch type.

Sixteen patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type were examined neuropsychologically. Abnormalities were found in all patients, and dementia was present in 12 of them. Three patients were tested twice at an interval of some years. All three exhibited a progressive intellectual deterioration and memory disturbance; in two of them there was no evidence of intercurrent strokes. Cerebral amyloid angiopathy can lead to dementia because it produces multiple focal cerebral lesions, but a chronic ischemic or metabolic effect on brain parenchyma may play a contributing role.

Early cognitive and motor symptoms in identified carriers of the gene for Huntington disease.

OBJECTIVE: To study early motor and cognitive symptoms in Huntington disease. DESIGN: A follow-up cohort study after a DNA test procedure in which gene carriers and noncarriers were identified among people genetically at risk for Huntington disease. SETTING: Leiden University Medical Center, Department of Neurology, Leiden, the Netherlands, in cooperation with the Clinical Genetics Center Leiden and the Department of Medical Psychology and Psychotherapy, Erasmus University Rotterdam, Rotterdam, the Netherlands. PARTICIPANTS: Thirty-three individuals: 9 unaffected gene carriers, 6 gene carriers with motor symptoms, and 18 noncarriers of the gene for Huntington disease. MAIN OUTCOME MEASURES: A neuropsychologic examination covering a broad area of cognitive functioning, reaction time procedures, and motor tasks. RESULTS: The neuropsychologic assessment showed no significant differences between presymptomatic gene carriers and noncarriers. Three motor tasks differentiated between these 2 groups on a liberal .05 P level (analysis of variance followed by the Student test). The affected gene carriers performed less well than the presymptomatic gene carriers and the noncarriers in 10 motor tasks and 7 cognitive tasks. These differences were significant at P < .05. CONCLUSION: Motor symptoms play a more prominent and unequivocal role than cognitive symptoms in early stages of Huntington disease.

White matter lesions and cognitive deterioration in presymptomatic carriers of the amyloid precursor protein gene codon 693 mutation.

OBJECTIVE: To determine early manifestations of hereditary cerebral hemorrhage with amyloidosis (Dutch). DESIGN: Survey. SETTING: Neurologic outpatient department of the University Hospital Leiden in the Netherlands. PARTICIPANTS: Ten presymptomatic carriers of the amyloid precursor protein gene codon 693 mutation. MAIN OUTCOME MEASUREMENTS: Extensive neuropsychological examination and cerebral magnetic resonance imaging. RESULTS: Six subjects older than 40 years showed white matter hyperintensities on magnetic resonance imaging. Three of these six individuals had signs of cognitive deterioration. The four younger subjects (age, < 31 years) showed no abnormalities on magnetic resonance imaging or on neuropsychological examination. CONCLUSIONS: We suggest that white matter hyperintensities in hereditary cerebral hemorrhage with amyloidosis (Dutch) are probably caused by chronic ischemia due to stenosis of the meningocortical arterioles, which becomes visible on magnetic resonance imaging scans in individuals who are between the ages of 30 and 40 years. The finding of cognitive deterioration in three of 10 presymptomatic mutation carriers supports the finding that in hereditary cerebral hemorrhage with amyloidosis (Dutch), deterioration can occur without stroke. A direct relation between cognitive deterioration and white matter hyperintensities is unlikely, because only half of the individuals with white matter hyperintensities showed signs of deterioration.

Cognitive function after spinal or general anesthesia for transurethral prostatectomy in elderly men.

Cognitive functions in 53 elderly men who underwent a transurethral prostatectomy were assessed pre-operatively and 4 days and 3 months post-operatively. Thirteen patients had a preference for one particular type of anesthesia, and the remaining 40 were randomly allocated to receive either spinal or general anesthesia. Cognitive function was not different between the groups receiving different types of anesthesia at either time point and did not decrease post-operatively. No pre- or perioperative variable could distinguish the subgroup of patients who had a post-operative decrease of 2 points or more on the Mini-Mental State Examination. No difference in post-operative performance was found in the patient groups with pre-operative Mini-Mental State Examination scores above or under their age-specific norm. It is concluded that neither hospitalization nor the two forms of anesthesia investigated cause a decrease in cognitive function in elderly men.

A clinical trial with desglycinamide arginine vasopressin for the treatment of memory disorders in man.

In a double-blind cross-over trial the memory effect of the neuropeptide desglycinamide arginine vasopressin (DGAVP) was selected because of its well-documented facilitatory effects on memory components in rodents. Patients with stabilized or progressive amnesic disorders (Korsakoff disease, early stages of Alzheimer dementia, head injuries and other central nervous system diseases) did not respond to the drug. Factors possibly explaining the discrepancy with animal research are discussed.

Reaction time in ambulant multiple sclerosis patients. Part I. Influence of prolonged cognitive effort.

Reaction times (RT) were measured in 39 multiple sclerosis (MS) patients and 25 healthy controls, before and after comprehensive neuropsychological assessment lasting at least 4 h. The assessment required prolonged mental effort, which was assumed to induce fatigue. Simple and disjunctive RT were measured for visual and auditory stimuli. RT before and after prolonged effort were significantly longer in MS than in control subjects (with exception of auditory RT). This effect was related to disease duration and to simultaneous presence of brainstem, cerebellar and/or pyramidal signs. Age did not significantly contribute to the explanation of RT increase. In female patients, increasing distribution of functional lesions in the central nervous system was related with greater RT increase than in male patients. RT of MS and controls changed after prolonged mental effort and effort-related fatigue was experienced subjectively. Yet no differences in direction or degree of change in RT were found between controls and ambulant patients with stable MS who apparently had resources to overcome fatigue.

Reaction time in ambulant multiple sclerosis patients. Part II. Influence of task complexity.

Effects of task variables on reaction time (RT) were investigated in 39 multiple sclerosis (MS) patients and 25 matched control subjects, based on the premise that RT is sensitive to (subtle) changes of cognitive efficiency. The hypothesis to be tested held that inefficient cognitive processing in MS would be reflected in differences between RT patterns of MS and control subjects, and in inordinate RT increase in MS patients with increase of task complexity. No difference was found between MS patients and controls, or between MS subgroups, in (1) response to time uncertainty of stimulus presentations, (2) RT behaviour over stimulus presentations, and (3) RT change from simple to more complex conditions. No evidence of slowed cognitive processing was found in this sample of outpatients with relatively mild and stable MS. It is emphasised that executive and cognitive slowness have to be disentangled in research on MS and on so-called 'subcortical dementia', of which mental slowing is a key concept.

Performances of multiple sclerosis patients in tasks requiring language and visuoconstruction. Assessment of outpatients in quiescent disease stages.

In a group of 39 multiple sclerosis (MS) patients with at least average intelligence quotients (IQ), performances were examined in tests requiring language usage and figure copying. Numbers of correct, digressive and erroneous responses were analysed and compared with those obtained in 24 healthy volunteers, matched to the patients group for socio-economic status. The examined specific tasks yielded no additional contribution to the prevalence estimation of cognitive deterioration (18%), as based on an assessment of general intelligence. Linguistic or cognitive-constructional problems were no more severe or more frequent in MS patients than those in control subjects. Upon writing or copying figures, pencil stroke and pencil pressure were deficient. Speed of reading aloud and of colour naming was decreased in the MS group, the most probable explanation being impaired control of the phonatory apparatus, oculomotor problems or weakness of colour vision. Decreases in speed of performance are not necessarily of cognitive origin. Differences between the present and previous reports based on similar tasks, appear to be connected partly with differences in patient selection. Of the present group, all MS patients were in quiescent disease stages, depression was mild or absent and physical handicap was less than in most studies reporting definite specific deficits.

Memory and learning in outpatients with quiescent multiple sclerosis.

In 22 (56%) of 39 quiet-stage multiple sclerosis (MS) patients with at least average intelligence quotients, performances in memory and learning tasks were normal, as compared with those of a control group (24 healthy volunteers). Of the remaining 44% (n = 17), 2 patients were amnesic and 5 had been judged to have suffered cognitive decline. Auditory word learning was particularly vulnerable; however, acquisition rate was not significantly different between MS patients and controls.

Visuospatial problem solving, conceptual reasoning and sorting behaviour in multiple sclerosis out-patients.

Visuospatial problem solving, conceptual reasoning and shifting of set were studied in out-patients with definite and probable MS. The sample of MS patients was homogeneous with respect to 2 important dimensions. All were out-patients, leading a normal although handicap-restricted social life. Furthermore, in all patients relapse or obvious instability of the disease were absent for at least a month. On Raven's Progressive Matrices, the Category test and the Wisconsin Modified Card Sorting test, no significant differences were found between the group of MS patients and a control group of healthy volunteers. However, 18% of MS patients and 4% of controls were rated as performing slightly below the expected levels of cognition. Stepwise regression analysis failed to reveal effects of illness variables, and no difference between patients with definite and probable MS could be detected. Clearly, most socially integrated MS patients in stable disease stages are capable of normal visuospatial problem solving, abstract reasoning and shifting of set.

Cognition in patients with multiple sclerosis After four years.

This study reports on a 4-year follow-up of cognitive functioning in 33 MS patients and 18 healthy control subjects. As a group, and in agreement with the results in the previous assessment. MS patients have significantly weaker performances than controls in motor speed, reaction time, learning tasks, reading aloud and figure copying. Tasks addressing visuospatial problem solving, behavioural flexibility, and linguistic aspects of oral and written communication do not distinguish between the two groups. Influence of impaired movement is acknowledged in performances utilising speech and reading under instructions of speed, and in figure copying. Cognition per sé remained undisturbed in 25 patients (76%). A uniform MS-related development of cognitive deficits could not be identified, improvement, stability and further deterioration being found at reassessment.

Conventional and controlled release valproate in children with epilepsy: a cross-over study comparing plasma levels and cognitive performances.

We studied plasma levels and behavioural effects of a newly developed controlled release formulation of valproate (VPA-CR) in children with epilepsy. Valproate plasma levels and performances in attention and vigilance tasks were monitored during a 12-h period (daytime), both during monotherapy of conventional valproate (VPA) and 4 weeks after switching to a similar dosage of VPA-CR taken once daily. There was no significant difference between the two formulations with respect to mean diurnal trough and peak valproate plasma levels, and to mean fluctuation. The significantly higher Cmax/Cmin ratio during VPA-CR seems mainly due to low valproate plasma levels early in the morning. Neuropsychological assessment showed no significant differences, either between patients and controls, or within patients and controls when comparing the results obtained on the VPA and VPA-CR day. During both VPA and VPA-CR treatment, no correlation was found between cognitive performance and valproate plasma levels. The advantage of VPA-CR is that the once daily regimen may increase compliance and is more convenient for schoolchildren.

Reversible mental deterioration and neurological disturbances with o,p'-DDD therapy.

A patient with serious neurological and neuropsychological side-effects of a 2-year treatment with 1,1-dichloro-(o-chlorophenyl)-2-(p-chlorophenyl)ethane (o,p'-DDD) for adrenal carcinoma showed complete recovery after discontinuation of the drug. Studying a larger number of patients during and after long term treatment with o,p'-DDD is indicated. If results of this report are confirmed, therapy should not be discontinued even if serious side effects occur.

SPECT in the diagnosis of Alzheimer's disease and multi-infarct-dementia.

SPECT with Tc-99m HM-PAO as a radiopharmaceutical was performed in 17 patients meeting research criteria for Alzheimer's disease (AD), in 10 patients with a clinical diagnosis of multi-infarct-dementia (MID) and in 12 healthy volunteers. Regional tracer uptake was measured in frontal, parietal, and temporoparietal regions. A statistically significant decrease of tracer uptake in the temporoparietal region was found in AD-patients compared with controls. AD-patients showed less activity in this region than MID-patients, but this difference did not reach statistical significance. In both AD- and MID-patients decrease of tracer uptake was not correlated with dementia severity. We conclude that SPECT brain imaging is not yet ready for routine use in the distinction between AD and MID.

[Neuropsychological findings in children with Gilles de la Tourette syndrome]. / Neuropsychologische bevindingen bij kinderen met het syndroom van Gilles de la Tourette.

Eight children with the syndrome of Gilles de la Tourette underwent a neuropsychological assessment. The results were compared with those of eight children with proven lesions of the right cerebral hemisphere and with eight children with learning disabilities without neurological disturbances. Our findings do not support organicity or dysfunctions of the right hemisphere in children with Gilles de la Tourette syndrome.

[The Mini Mental Status test inadequate as screening test for cognitive deterioration in a neurological department]. / De 'Mini-mental state'-test ontoereikend als screeningstest voor cognitieve deterioratie op een afdeling Neurologie.

OBJECTIVE: To study the validity of the Mini-mental state (MMS) in a neurological population. DESIGN: Comparing the results of a neuropsychological examination and the MMS score. SETTING: Departments of Neurology/Neuropsychology of the University Hospital Leiden. METHODS: One hundred and forty-seven patients participated in the study. One hundred and eight patients were classified into two diagnostic groups according to the deterioration index (obtained from test results of the neuropsychological examination) and DSM-III-R criteria: 63 patients had dementia, 45 did not; the other 39 patients were found to have specific cognitive impairments and were excluded from the group comparisons. The discriminative powers of the deterioration index and the MMS were compared; sensitivity and specificity were determined with several cut-off scores of the MMS. RESULTS: The MMS had limited power to discriminate between demented and non-demented patients. The MMS score was strongly related to premorbid intelligence, occupational level and age. Increasing the original cut-off score to 25 points improved sensitivity and specificity to 79% and 84% respectively (with the original cut-off level these were 68% and 93%). CONCLUSION: The diagnostic value of the MMS is limited, especially in patients for whom a correct diagnosis is most relevant.