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Biomedical subjects

G Gainotti

Publications and source records attributed to G Gainotti.

At least 19 recordsLinked to original sources

Cognitive outcome 5 years after bilateral chronic stimulation of subthalamic nucleus in patients with Parkinson's disease.

AIM: To assess the long-term cognitive and behavioural outcome after bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients affected by Parkinson's disease, with a 5-year follow-up after surgery. METHODS: 11 patients with Parkinson's disease treated by bilateral DBS of STN underwent cognitive and behavioural assessments before implantation, and 1 and 5 years after surgery. Postoperative cognitive assessments were carried out with stimulators turned on. RESULTS: A year after surgery, there was a marginally significant decline on a letter verbal fluency task (p = 0.045) and a significant improvement on Mini-Mental State Examination (p = 0.009). 5 years after surgery, a significant decline was observed on a letter verbal fluency task (p = 0.007) and an abstract reasoning task (p = 0.009), namely Raven's Progressive Matrices 1947. No significant postoperative change was observed on other cognitive variables. No patient developed dementia 5 years after surgery. A few days after the implantation, two patients developed transient manic symptoms with hypersexuality and one patient developed persistent apathy. CONCLUSION: The decline of verbal fluency observed 5 years after implantation for DBS in STN did not have a clinically meaningful effect on daily living activities in our patients with Parkinson's disease. As no patient developed global cognitive deterioration in our sample, these findings suggest that DBS of STN is associated with a low cognitive and behavioural morbidity over a 5-year follow-up, when selection criteria for neurosurgery are strict.

Aged↗

In vivo cholinergic circuit evaluation in frontotemporal and Alzheimer dementias.

The test of short latency afferent inhibition (SAI) of the motor cortex is helpful in demonstrating dysfunction of central cholinergic circuits in Alzheimer disease (AD). The authors evaluated SAI in 20 patients with frontotemporal dementia (FTD) and compared data with those from 20 patients with AD and 20 controls. SAI was normal in FTD, whereas it was reduced in AD. SAI may represent an additional tool to discriminate FTD from AD.

Afferent Pathways↗

Neurophysiological predictors of long term response to AChE inhibitors in AD patients.

BACKGROUND: In vivo evaluation of cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with motor cortex TMS (short latency afferent inhibition, SAI). SAI is reduced in Alzheimer's disease (AD) and drugs enhancing cholinergic transmission increase SAI. METHODS: We evaluated whether SAI testing, together with SAI test-retest, after a single dose of the acetylcholinesterase (AChE) inhibitor rivastigmine, might be useful in predicting the response after 1 year treatment with rivastigmine in 16 AD patients. RESULTS: Fourteen AD patients had pathologically reduced SAI. SAI was increased after administration of a single oral dose of rivastigmine in AD patients with abnormal baseline SAI, but individual responses to rivastigmine varied widely, with SAI change ranging from an increase in inhibition of approximately 50% of test size to no change. Baseline SAI and the increase in SAI after a single dose of rivastigmine were correlated with response to long term treatment. A normal SAI in baseline conditions, or an abnormal SAI in baseline conditions that was not greatly increased by a single oral dose of rivastigmine, were invariably associated with poor response to long term treatment, while an abnormal SAI in baseline conditions in conjunction with a large increase in SAI after a single dose of rivastigmine was associated with good response to long term treatment in most of the patients. CONCLUSIONS: Evaluation of SAI may be useful for identifying AD patients likely to respond to treatment with AChE inhibitors.

Aged↗

The role of brain infarcts and hippocampal atrophy in subcortical ischaemic vascular dementia.

We investigated if, in patients with vascular lesions, the variable that best discriminated demented from non-demented patients was the severity of the vascular pathology or the degree of hippocampal atrophy. A total of 39 patients multiple subcortical infarcts, who could be considered as possible vascular dementia with small vessel pathology, with underwent a neuropsychological study and brain magnetic resonance imaging (MRI) DSM IV criteria supported by neuropsychological data were used to distinguish demented from non-demented patients. The MRI study took into account the degree of hippocampal atrophy (hippocampal height and interuncal distance) and the severity of vascular pathology (number of brain infarcts). The distribution of lesions and a factor analysis showed that hippocampal atrophy is a better predictor of dementia than the number of brain infarcts. Multiple subcortical infarcts alone are probably not able to cause clinical dementia but the presence of vascular lesions increases the expression of concomitant Alzheimer's disease.

Aged↗

Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer's disease.

OBJECTIVES: Recent transcranial magnetic stimulation (TMS) studies demonstrate that motor cortex excitability is increased in Alzheimer's disease (AD) and that intracortical inhibitory phenomena are impaired. The aim of the present study was to determine whether hyperexcitability is due to the impairment of intracortical inhibitory circuits or to an independent abnormality of excitatory circuits. METHODS: We assessed the excitability of the motor cortex with TMS in 28 patients with AD using several TMS paradigms and compared the data of cortical excitability (evaluated by measuring resting motor threshold) with the amount of motor cortex disinhibition as evaluated using the test for motor cortex cholinergic inhibition (short latency afferent inhibition) and GABAergic inhibition (short latency intracortical inhibition). The data in AD patients were also compared with that from 12 age matched healthy individuals. RESULTS: The mean resting motor threshold was significantly lower in AD patients than in controls. The amount of short latency afferent inhibition was significantly smaller in AD patients than in normal controls. There was also a tendency for AD patients to have less pronounced short latency intracortical inhibition than controls, but this difference was not significant. There was no correlation between resting motor threshold and measures of either short latency afferent or intracortical inhibition (r = -0.19 and 0.18 respectively, NS). In 14 AD patients the electrophysiological study was repeated after a single oral dose of the cholinesterase inhibitor rivastigmine. Resting motor threshold was not significantly modified by the administration of rivastigmine. In contrast, short latency afferent inhibition from the median nerve was significantly increased by the administration of rivastigmine. CONCLUSIONS: The change in threshold did not seem to correlate with dysfunction of inhibitory intracortical cholinergic and GABAergic circuits, nor with the central cholinergic activity. We propose that the hyperexcitability of the motor cortex is caused by an abnormality of intracortical excitatory circuits.

Afferent Pathways↗

The influence of limb crossing on left tactile extinction.

BACKGROUND: Previous research on patients with left tactile extinction has shown that crossing of hands, so that each hand is on the opposite side of the body midline relative to the other, improves detection of stimuli given to the left hand. OBJECTIVES: To study the influence of the spatial position of limbs on left tactile extinction, and its relations with left visual neglect. METHODS: Normal participants and patients with right cerebral hemisphere damage and left tactile extinction were asked to detect single or double light touch stimuli applied to their cheeks, hands, or knees with their arm and legs either in anatomical or in crossed position, increasing the attentional load of the task. RESULTS: In patients with left extinction, limb crossing caused a deterioration in performance for stimuli applied to right body parts, with only a tendency to an improvement in detection for left body parts (only two of 24 patients showed substantial (>20%) improvement in left extinction after limb crossing). After crossing, left limb detections of double stimuli decreased with increasing degrees of visual neglect. CONCLUSIONS: In conditions of high attentional load, limb crossing may impair tactile detection in most patients with left extinction, and particularly in those showing signs of left visual neglect. These results underline the importance of general attentional capacity in determining tactile extinction. Attentional and somatotopic mechanisms of extinction may assume different weights in different patients.

Aged↗

The Apolipoprotein E genotype in patients affected by syndromes with focal cortical atrophy.

The role of the Apolipoprotein E (APOE) alleles in syndromes associated with focal cerebral atrophy (fronto-temporal dementia, primary progressive aphasia, corticobasal degeneration) is still controversial. We studied the APOE allele distribution in 39 patients with clinically diagnosed syndromes associated with focal cerebral atrophy (FCA), in 50 patients with early-onset probable Alzheimer's disease (EOAD), and in 60 patients with late-onset probable AD (LOAD). The APOE genotype was determined from a blood sample, using polymerase chain reaction and restriction enzyme digestion. The APOE epsilon4 allele frequency was significantly higher in the EOAD (21.0%) and LOAD (33.3%) groups, but not in the FCA group (5.1%), as compared with controls. In our population, the epsilon2 allele frequency was significantly higher in patients with FCA (12.8%) than in controls (4.8%). These results show that the APOE epsilon4 allele is not a risk factor for syndromes associated with FCA. The potential role of the epsilon2 allele in these syndromes needs further investigation.

Age of Onset↗

Disorders of emotional behaviour.

After having stressed the distinction between general adaptive systems and specific functional systems, the author argues that emotions constitute a general adaptive system distinct from, but interacting with, the cognitive system, considered as the other (more evolved) adaptive system. The main characteristics of the emotional system are its componential nature and its hierarchical organization. These basic features of the emotional system, as well as the brain structures subserving the different components of emotions must, therefore, be taken into account in the neuropsychological study of emotional disorders. The main components of emotions considered in this educational review are: the evaluation of emotional situations; the emotional response with its expressive-motor and autonomic components and the inhibition of socially unacceptable spontaneous emotional responses. The main levels identified in the hierarchical structure of emotions are: a level of automatic, spontaneous functioning and a level of conceptual processing of emotional information and of controlled selection of the most appropriate response. The brain structures identified as critically involved in these different components and levels of emotions are: the amygdala, considered as the structure where the external stimuli are appraised in terms of their emotional significance; the insular cortex and the hypothalamus, crucially involved in the generation of the autonomic components of emotions; the ventral striatum, which subserves the execution of stereotyped emotional action patterns and the ventro-medial frontal cortex, playing a critical role in functions of control and inhibition of socially unacceptable emotional responses. The different emotional involvement of the right and left hemispheres in different aspects and levels of emotional processing is also shortly discussed and the quality of emotional disturbances resulting from injury to these brain structures is briefly considered.

Affective Symptoms↗

Laterally directed arm movements and right unilateral neglect after left hemisphere damage.

Signs of unilateral neglect for events occurring in one hemispace most often result from right hemisphere lesions. Right unilateral neglect after left hemisphere damage is much rarer, and has received less attention. The present study explores the relationships between right unilateral neglect and asymmetries in producing laterally directed arm movements in the horizontal plane in left brain-damaged (LBD) patients. Participants produced right- or left-directed arm movements with their left arm in response to centrally located visual stimuli. Results showed that LBD patients with signs of right unilateral neglect were consistently slowed when producing arm movements toward the right (neglected) side, as compared to left-directed movements. Taking into account patients with and without signs of neglect, this directional asymmetry positively correlated with a reaction-time measure of perceptual spatial bias. These findings stand in contrast with previous results obtained with the same experimental paradigm in right brain-damaged patients, in whom a consistent slowing of leftward-directed movements was rare and apparently unrelated to the presence and severity of left neglect. These conflicting results are discussed with respect to the hypothesis that different mechanisms may underlie left and right unilateral neglect.

Adult↗

A double dissociation between accuracy and time of execution on attentional tasks in Alzheimer's disease and multi-infarct dementia.

Two cancellation/attentional tasks: (i) Lines Cancellation (LC) and Multiple Features Targets Cancellation (MFTC) and (ii) a standard battery of neuropsychological tests, the Mental Deterioration Battery (MDB), were administered to 68 patients with dementia of the Alzheimer's type (DAT) and 40 patients with multi-infarct dementia (MID), who were accurately matched for the overall severity of dementia, and to 40 normal controls. Both accuracy and time of execution were considered in evaluating performance on the two cancellation tasks, which involved visuospatial exploration and psychomotor speed, but were differently demanding in terms of selective attention. On the first cancellation task (LC), requiring a lower attentional load, the two demented patient groups performed at the same level of accuracy. On the second cancellation task (MFTC), which was more demanding in terms of selective and divided attention, DAT patients were significantly less accurate than MID patients, making a higher number of 'false-alarm' errors. Conversely, the time employed in the execution of both LC and MFTC took longer for MID than for DAT patients, suggesting a greater impairment of psychomotor speed in MID. In the MDB, DAT patients scored significantly worse than MID patients on several measures of episodic memory (the immediate recall, delayed recall and delayed recognition of Rey's Auditory Verbal Learning Test) and on a test of visual-spatial memory. These data suggest that, while psychomotor speed and the lower (sensorimotor) levels of attention are preferentially impaired in subcortical forms of dementia such as MID, the higher levels of selective and divided attention are more markedly disrupted in the Alzheimer type of dementia.

Aged↗

Brain perfusion abnormalities in Alzheimer's disease: comparison between patients with focal temporal lobe dysfunction and patients with diffuse cognitive impairment.

OBJECTIVES: Patients with Alzheimer's disease (AD) showing a selective impairment of episodic and semantic memory have recently been classified as affected by focal temporal lobe dysfunction (FTLD) and considered as a distinct subgroup of patients affected by a particular form of AD. The aim was to compare the cerebral perfusion of patients with AD with FTLD and patients with AD with the more typical profile of diffuse cognitive impairment (dAD). METHODS: Ten patients with AD with FTLD, 14 patients with AD with dAD, and 12 normal controls were studied. All the 24 patients with AD underwent a complete neuropsychological assessment. SPECT examination with [(99m)Tc]-HMPAO, using a four head brain dedicated tomograph, was performed in patients and controls. Tracer uptake was quantified in 27 regions of interest (ROIs), including lateral and mesial temporal areas. Mean counts in the 27 ROIs of controls, patients with FTLD and those with dAD were compared using an ANOVA for repeated measures with Bonferroni's correction. A logistic regression analysis, followed by a receiver operating characteristic (ROC) analysis, was also applied to select SPECT patterns which significantly differentiated patients with FTLD and those with dAD. RESULTS: Two scintigraphic patterns of abnormalities, shaping a double dissociation between the FTLD and dAD groups, emerged: a bilateral mesial temporal hypoperfusion, characteristic of FTLD and a posterior parietal (and temporal parietal) hypoperfusion characteristic of patients with dAD. CONCLUSIONS: These scintigraphic findings provide further support to the hypothesis that FTLD is not a mere stage but a distinct anatomoclinical form of AD. The combination of neuropsychological tests and [(99m)Tc]-HMPAO SPECT may be very useful in identifying patients with FTLD from the wider group of patients with dAD. This issue is particularly worthwhile, as there is increasing evidence that patients with FTLD have a slower rate of cognitive decline.

Aged↗

Relation between depression after stroke, antidepressant therapy, and functional recovery.

The aim was to evaluate the effects of poststroke depression and antidepressant therapy on the improvement of motor scores and disability, to verify if the negative effects of poststroke depression on functional recovery could be counterbalanced by taking antidepressant drugs. RESULTS OBTAINED BEFORE, DURING, AND AFTER REHABILITATION: On the Barthel index, Canadian neurological scale, and Rivermead mobility index-by 49 depressed patients with stroke, who had been treated (n=25) or not treated (n=24) according to the different therapeutic approaches of their physicians, were compared with results similarly obtained by 15 non-depressed patients with stroke. Analysis was by multivariate analysis of variance for repeated measures There was a non-significant difference between the groups in their motor and functional scores, and a significant improvement on time. A significant interaction between group and time was seen. This interaction was particularly significant on the Rivermead mobility index, and was due to the fact that the recovery of non-treated depressed patients with stroke was less than the non-depressed and the depressed but treated patients with stroke. Furthermore, recovery from depression was significantly greater in treated than in non-treated depressed patients with stroke. In conclusion, poststroke depression has negative effects on functional recovery, and a pharmacological treatment of depression can counterbalance this effect.

Aged↗

What the locus of brain lesion tells us about the nature of the cognitive defect underlying category-specific disorders: a review.

Different models have been proposed to account for the nature of the cognitive defects underlying category-specific disorders for living and non-living things. One model assumes that the living/non-living distinction is the by-product of a more basic dichotomy, contingent upon the different weighting that visuo-perceptual and functional attributes have in the identification of members of these categories. A second model submits that evolutionary pressure resulted in the elaboration of dedicated neural mechanisms for the domains of living (animals and plants) and non-living (artefacts) things. A third model proposes that the different level of interconnections existing between perceptual and functional features in living and non living things may be more important than the weighting of these features. Each of these models makes implicit assumptions about the extent and the localization of brain lesions provoking category-specific disorders. However, it must also be considered that these disorders are heterogeneous in nature, resulting from defects located at the semantic, lexical or visual level. In the present review of the literature, we kept this distinction in mind in trying to analyze the neuroanatomical correlates of living and non-living disorders. Our findings showed that there is a correlation between the locus of lesion and the patterns of categorical impairment: (a) a bilateral injury to the antero-mesial and inferior parts of the temporal lobes was found in patients with a category-specific semantic impairment for living things; (b) a lesion of the infero-mesial parts of the temporo-occipital areas of the left hemisphere was found in a group of patients showing a specific lexical impairment for members of the 'plants' category; (c) an extensive lesion of the areas lying on the dorso-lateral convexity of the left hemisphere was found in patients with a category-specific semantic impairment for man-made artefacts. Taken together, these results seem to show that the category-specific disorder is crucially related to the kind of semantic information processed by the damaged areas.

Brain↗

Frequency, phenomenology and anatomical-clinical correlates of major post-stroke depression.

BACKGROUND: The meaning of post-stroke depression is controversial. AIMS: To investigate the hypothesis that major post-stroke depression (PSD) may be due to organic factors (left frontal lesions) immediately after the stroke, but to psychosocial factors in later stages. METHOD: We studied 153 consecutive stroke patients, categorised on the basis of time elapsed since stroke, lesion location and presence/absence of major PSD. Fifty-eight were examined in the first two months following the stroke, 52 between two and four months, and 43 after four months or more. The symptom profiles and anatomical-clinical correlates of major PSD were studied in each subgroup. A group of 30 patients affected by a functional form of major depression were also investigated. RESULTS: The symptom profiles and anatomical-clinical correlates of major PSD were not different in the acute and more chronic stages. Clear symptom differences were, however, observed between major PSD and endogenous major depression. Motivated (reactive) symptoms prevailed in the former, whereas unmotivated symptoms prevailed in the latter. CONCLUSIONS: Our data are more consistent with a psychological than with a neurological model of post-stroke depression.

Acute Disease↗

Perception and action in hemispatial neglect.

Hemispatial neglect is a neurological disorder which entails a spatial bias that penalizes events occurring in the hemispace contralateral to a brain lesion. Mechanisms operating upon various stages ranging from perception to action have been invoked to explain neglect. The present study explores the contribution of a defective programming of arm movements towards the neglected hemispace to neglect behaviour. Two reaction time tasks -- a "perceptual" task and a "motor" task -- were performed by right brain-damaged (RBD) patients with left hemispatial neglect, RBD patients without signs of neglect and control subjects. The perceptual task consisted of lateralized visual stimuli and central motor responses, whereas the motor task consisted of visual stimuli presented on the vertical midline and hand responses to be produced in either hemispace. Neglect patients showed a rightward bias on the perceptual task, but only two RBD patients (showing no signs of severe neglect) were consistently slowed in producing leftward motor responses. Different reference frames may thus be used in perceptual tasks and tasks involving arm movements. We conclude that hemispatial neglect commonly results from attentional impairments operating upon a visual perceptual frame of reference; additional deficits appear to be necessary to produce a directional motor disorder.

Adult↗

Sensitivity and specificity of some neuropsychological markers of Alzheimer dementia.

A standardized neuropsychological test battery was administered to 167 patients with different forms of mild-to-moderate dementia: probable Alzheimer dementia (AD: n = 49), multi-infarct dementia (n = 43), idiopathic Parkinson disease with dementia (n = 35), depressive pseudodementia (n = 26), and progressive supranuclear palsy (n = 14). Results obtained were used (a) to analyze the profiles of cognitive impairment shown by the different dementia groups; (b) to assess the incidence of some neuropsychological patterns that we hypothesized to be more characteristic of AD, in the various groups; and hence (c) to evaluate the reliability of these patterns as diagnostic markers of AD. Four of the patterns investigated were derived from a verbal learning task (Rey's Auditory Verbal Learning test): (1) absence of the primacy effect; (2) tendency to produce intrusion errors during free recall of a word list; (3) absolute decay of memory trace; and (4) tendency to produce false alarms during delayed recognition of the same word list. Two additional patterns were derived from visual-spatial tasks (copying drawings and Raven's Coloured Progressive Matrices): (5) occurrence of the closing-in phenomenon in copying drawings; and (6) tendency to choose globalistic or odd responses in Raven's matrices. Though all the six patterns were somewhat useful for identifying AD patients, no pattern met the criteria of being both highly sensitive and highly specific, which should characterize an ideal marker. In fact, intrusions and false alarms were observed in many AD patients, but also in patients affected by other forms of dementia. The absence of the primacy effect, the closing-in phenomenon, and the absolute decay of memory trace were more specific, but could be observed in only one-third of AD patients. We also computed the number of positive patterns shown by each patient and assumed the presence of two or more patterns as a global index suggestive of a dementia of the Alzheimer type. With this cumulative method, a higher level of sensitivity and specificity was achieved in the identification of AD patients.

Aged↗

Sexual behavior and hemispheric laterality of the focus in patients with temporal lobe epilepsy.

Various studies have described an unusually common incidence of sexual and reproductive dysfunction in patients affected by temporal lobe epilepsy (TLE). The purpose of the present study was to further investigate, by means of an ad hoc questionnaire, the relationship between sexual disorders and the hemispheric laterality of the epileptic focus in men and women with right (R) TLE and left (L) TLE. The results suggest a reduction of sexual interest in patients with R-TLE as compared with L-TLE in both men and women. This effect was fundamentally observed when sexual interest was implicitly explored. No significant difference was found between R-TLE and L-TLE groups concerning most aspects of sexual performance. Various hypotheses are discussed to interpret this effect of hemispheric lateralization on sexual interest.

Adult↗