The extensive infarction affecting the posterior vermis and the medial and posterior regions of b... more The extensive infarction affecting the posterior vermis and the medial and posterior regions of both cerebellar hemispheres, as well as the small central pontine lesion, seems to have disrupted multiple cerebral and brainstem cerebellar loops. These loops process information related to many cognitive domains, behavior and emotion, including decision making, empathy and theory of mind.
Journal of Clinical and Experimental Neuropsychology, 1995
Declarative and procedural learning were assessed in patients with probable Alzheimer's D... more Declarative and procedural learning were assessed in patients with probable Alzheimer's Disease (AD) and major depression, patients with AD and no depression, patients with major depression but no dementia, and a group of age-comparable nondemented and nondepressed normal controls. AD patients showed significant deficits in declarative but not in procedural learning, while depressed nondemented patients showed the opposite pattern (i.e., a significantly worse procedural than declarative learning). Patients with both AD and major depression showed a similar learning pattern to the AD nondepressed group (relatively preserved procedural learning but severe deficits in declarative memory). These findings provide further evidence for the independence between declarative and procedural learning, and demonstrate their different vulnerability in dementia and depressive-like states.
Journal of Neurology Neurosurgery and Psychiatry, 1996
OBJECTIVE: To examine neuropsychological and neuropsychiatric differences between patients with p... more OBJECTIVE: To examine neuropsychological and neuropsychiatric differences between patients with probable Alzheimer's disease and patients with Parkinson's disease and dementia. METHODS: Thirty three patients with probable Alzheimer's disease and 33 patients with Parkinson's disease and dementia were matched for age, sex, and mini mental state examination scores and given a battery of neuropsychological and neuropsychiatric tests. RESULTS: Patients with Parkinson's
Journal of Neurology Neurosurgery and Psychiatry, 2001
OBJECTIVEPosteroventral pallidotomy (PVP) has proved to be an effective method for the treatment ... more OBJECTIVEPosteroventral pallidotomy (PVP) has proved to be an effective method for the treatment of Parkinson's disease. However, data on bilateral procedures are still limited. To assess the effects of bilateral globus pallidus (GPi) lesion and to compare it with a combination of unilateral GPi lesion plus contralateral GPi stimulation (PVP+PVS), an open blind randomised trial was designed.METHODSA prospective series of
In order to assess the relationships among mood, peripheral autonomic output and circulating immu... more In order to assess the relationships among mood, peripheral autonomic output and circulating immunoinflammatory mediators in older individuals with decompensated heart failure (CHF), 20 consecutive patients (78+/-7 years, 35% women) admitted to the coronary care unit with a clinical diagnosis of acute/decompensated CHF of coronary origin were examined. Mood was evaluated by the 21-item Hamilton Depression Scale (HAM-D). Four patients met the criteria for major depression. Heart rate variability (HRV) analysis and the levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-4, IL-6 and IL-10 were measured within 24-72 h of admission. A significant positive relationship between score in HAM-D and serum IL-6 levels was detected with a similar trend as far as IL-2 levels. Circulating IL-2 levels were strongly associated with the HRV L/H quotient, an index of increased sympathetic and/or decreased parasympathetic thoracic activity. A negative correlation between vagal activity (as assessed by HRV) and IL-4 occurred. Neither TNF-alpha nor IL-10 were detectable in this group of elderly patients. The results add to the concept that mood and autonomic unbalance are associated with increased systemic inflammation in old patients with decompensated CHF, a potential mechanism for mood-related worsened prognosis of heart failure at an advanced age.
We examined the prevalence, phenomenology, and clinical correlates of delusions in a consecutive ... more We examined the prevalence, phenomenology, and clinical correlates of delusions in a consecutive series of 103 patients with probable Alzheimer's disease (AD). Patients were examined with the Present State Exam and the Dementia-Psychosis Scale. Twenty-one patients (20%) met DSM-III-R criteria for a delusional disorder. The most frequent delusion type was paranoid (71%), followed by hypochondriacal (67%), the Capgras syndrome (29%), house misidentification (29%), and grandiose delusions (29%). Out of the 21 AD patients with delusions, 76% had three or more different types of delusions simultaneously. The frequency of delusions was not significantly associated with age, education, or age at dementia onset, and the type and severity of cognitive impairments was similar for AD patients with and without delusions. However, AD patients with delusions had significantly higher mania and anosognosia scores.
Many reports published during the past 5 years have shown evidence of the beneficial effect of po... more Many reports published during the past 5 years have shown evidence of the beneficial effect of posteroventral pallidotomy (PVP) in large groups of patients for up to 3 years, but none of them have compared patients who underwent surgery with a control group. To compare the evolution of Parkinson's disease symptoms at 1-year follow-up between patients who underwent surgery and those who did not. Ten patients with idiopathic Parkinson's disease refractory to treatment who were included in the Core Assessment for Intracerebral Transplantation program for PVP did not undergo surgery because financial support was lacking. These patients were followed up for 1 year as if they had been operated on and were finally compared with 10 patients having similar characteristics in whom PVP had been performed during the same period of time. There were no significant differences at basal evaluation in the motor section scores of the Unified Parkinson's Disease Rating Scale between those patients who underwent surgery and those who did not, but a significant reduction in Unified Parkinson's Disease Rating Scale motor score in the group who underwent surgery at 1-year evaluation was found (P < 0.006). Dyskinesias, which was nonsignificantly different at basal evaluation, showed, at the 1-year follow-up, a significant reduction in the group who underwent surgery (P < 0.04). Scores from the subsets of the Unified Parkinson's Disease Rating Scale addressing rigidity, tremor, and bradykinesia also proved significantly different at the 1-year follow-up. The slope of the line generated by the two evaluations for each group showed a negative value in the group who underwent surgery (value of -0.21) and a positive value in the group who did not (value of 0.148). At the 1-year follow-up, microelectrode-guided PVP produced significant changes in patient motor status and disease progression versus a comparable group of patients who did not undergo surgery during the same period of time.
Previous studies have linked action recognition with a particular pool of neurons located in the ... more Previous studies have linked action recognition with a particular pool of neurons located in the ventral premotor cortex, the posterior parietal cortex and the superior temporal sulcus (the mirror neuron system). However, it is still unclear if transitive and intransitive gestures share the same neural substrates during action-recognition processes. In the present study, we used event-related functional magnetic resonance imaging (fMRI) to assess the cortical areas active during recognition of pantomimed transitive actions, intransitive gestures, and meaningless control actions. Perception of all types of gestures engaged the right pre-supplementary motor area (pre-SMA), and bilaterally in the posterior superior temporal cortex, the posterior parietal cortex, occipitotemporal regions and visual cortices. Activation of the posterior superior temporal sulcus/superior temporal gyrus region was found in both hemispheres during recognition of transitive and intransitive gestures, and in the right hemisphere during the control condition; the middle temporal gyrus showed activation in the left hemisphere when subjects recognized transitive and intransitive gestures; activation of the left inferior parietal lobe and intraparietal sulcus (IPS) was mainly observed in the left hemisphere during recognition of the three conditions. The most striking finding was the greater activation of the left inferior frontal gyrus (IFG) during recognition of intransitive actions. Results show that a similar neural substrate, albeit, with a distinct engagement underlies the cognitive processing of transitive and intransitive gestures recognition. These findings suggest that selective disruptions in these circuits may lead to distinct clinical deficits.
Depression has been associated with increased mortality among individuals with heart failure, but... more Depression has been associated with increased mortality among individuals with heart failure, but the mechanism for this association is unsettled. Depression is often found to result in autonomic dysfunction which, if present in heart failure, might help explain worsened outcomes. This study was a cross-sectional evaluation of the relationship between depressive symptoms and cardiac autonomic function, as assessed by short-term heart rate variability (HRV) analysis in aged patients with acute/decompensated heart failure of coronary origin (CHF). A 21-item Hamilton Depression score and measures of short-term HRV were obtained in 31 inpatients >or=65 years of age, 24-72 h after admission to the coronary care unit with a diagnosis of CHF. Clinical depression was present in 22.6% of participants. In the sample as a whole, increasing depressive symptoms were associated with decreased low-frequency HRV. These results may be important in light of recent indications that decreased low-frequency HRV is a predictor of mortality in patients with heart failure.
Current concepts regarding the organisation of the motor system indicate the existence of a front... more Current concepts regarding the organisation of the motor system indicate the existence of a frontoparietal circuit involved in prehension and manipulation, whose damage may result in a motor behavioural disorder strongly resembling the one originally described as limb-kinetic apraxia. To determine the specific clinical and kinematic features of this distinctive praxic disorder, 5 patients with corticobasal degeneration (apraxic group), 5 with Parkinson's disease (nonapraxic group), and 10 control subjects were studied by a comprehensive apraxic battery, three-dimensional motion analysis of manipulative movements and motor evoked potentials. A mathematical model [quality of movement coefficient (QMC)] was applied to quantify differential kinematic characteristics between elementary motor deficits and the praxic disorder. Transcranial magnetic stimulation was used to evaluate corticomotoneural projections and cortical inhibition. All five patients in the apraxic group exhibited a unilateral praxic deficit characterised by derangement of fractionated and segmental finger movements. QMC was significantly greater in apraxic than in nonapraxic patients (P < 0.02), revealing a chaotic movement with marked interfinger uncoordination. Conventional transcranial magnetic stimulation parameters were within normal limits in both groups of patients; however, the silent period was significantly shorter in the apraxic limb when compared with control subjects (P < 0.001). Limb-kinetic apraxia is a distinctive disorder affecting the performance of finger and hand postures and movements over and above a corticospinal or basal ganglion deficit. Disruption of the frontoparietal circuit devoted to grasping and manipulation, together with defective cortical inhibition, which would also interfere with the selection and control of hand muscle activity, are the most likely underlying physiopathological mechanisms of limb-kinetic apraxia in patients with corticobasal degeneration.
The extensive infarction affecting the posterior vermis and the medial and posterior regions of b... more The extensive infarction affecting the posterior vermis and the medial and posterior regions of both cerebellar hemispheres, as well as the small central pontine lesion, seems to have disrupted multiple cerebral and brainstem cerebellar loops. These loops process information related to many cognitive domains, behavior and emotion, including decision making, empathy and theory of mind.
Journal of Clinical and Experimental Neuropsychology, 1995
Declarative and procedural learning were assessed in patients with probable Alzheimer's D... more Declarative and procedural learning were assessed in patients with probable Alzheimer's Disease (AD) and major depression, patients with AD and no depression, patients with major depression but no dementia, and a group of age-comparable nondemented and nondepressed normal controls. AD patients showed significant deficits in declarative but not in procedural learning, while depressed nondemented patients showed the opposite pattern (i.e., a significantly worse procedural than declarative learning). Patients with both AD and major depression showed a similar learning pattern to the AD nondepressed group (relatively preserved procedural learning but severe deficits in declarative memory). These findings provide further evidence for the independence between declarative and procedural learning, and demonstrate their different vulnerability in dementia and depressive-like states.
Journal of Neurology Neurosurgery and Psychiatry, 1996
OBJECTIVE: To examine neuropsychological and neuropsychiatric differences between patients with p... more OBJECTIVE: To examine neuropsychological and neuropsychiatric differences between patients with probable Alzheimer's disease and patients with Parkinson's disease and dementia. METHODS: Thirty three patients with probable Alzheimer's disease and 33 patients with Parkinson's disease and dementia were matched for age, sex, and mini mental state examination scores and given a battery of neuropsychological and neuropsychiatric tests. RESULTS: Patients with Parkinson's
Journal of Neurology Neurosurgery and Psychiatry, 2001
OBJECTIVEPosteroventral pallidotomy (PVP) has proved to be an effective method for the treatment ... more OBJECTIVEPosteroventral pallidotomy (PVP) has proved to be an effective method for the treatment of Parkinson's disease. However, data on bilateral procedures are still limited. To assess the effects of bilateral globus pallidus (GPi) lesion and to compare it with a combination of unilateral GPi lesion plus contralateral GPi stimulation (PVP+PVS), an open blind randomised trial was designed.METHODSA prospective series of
In order to assess the relationships among mood, peripheral autonomic output and circulating immu... more In order to assess the relationships among mood, peripheral autonomic output and circulating immunoinflammatory mediators in older individuals with decompensated heart failure (CHF), 20 consecutive patients (78+/-7 years, 35% women) admitted to the coronary care unit with a clinical diagnosis of acute/decompensated CHF of coronary origin were examined. Mood was evaluated by the 21-item Hamilton Depression Scale (HAM-D). Four patients met the criteria for major depression. Heart rate variability (HRV) analysis and the levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-4, IL-6 and IL-10 were measured within 24-72 h of admission. A significant positive relationship between score in HAM-D and serum IL-6 levels was detected with a similar trend as far as IL-2 levels. Circulating IL-2 levels were strongly associated with the HRV L/H quotient, an index of increased sympathetic and/or decreased parasympathetic thoracic activity. A negative correlation between vagal activity (as assessed by HRV) and IL-4 occurred. Neither TNF-alpha nor IL-10 were detectable in this group of elderly patients. The results add to the concept that mood and autonomic unbalance are associated with increased systemic inflammation in old patients with decompensated CHF, a potential mechanism for mood-related worsened prognosis of heart failure at an advanced age.
We examined the prevalence, phenomenology, and clinical correlates of delusions in a consecutive ... more We examined the prevalence, phenomenology, and clinical correlates of delusions in a consecutive series of 103 patients with probable Alzheimer's disease (AD). Patients were examined with the Present State Exam and the Dementia-Psychosis Scale. Twenty-one patients (20%) met DSM-III-R criteria for a delusional disorder. The most frequent delusion type was paranoid (71%), followed by hypochondriacal (67%), the Capgras syndrome (29%), house misidentification (29%), and grandiose delusions (29%). Out of the 21 AD patients with delusions, 76% had three or more different types of delusions simultaneously. The frequency of delusions was not significantly associated with age, education, or age at dementia onset, and the type and severity of cognitive impairments was similar for AD patients with and without delusions. However, AD patients with delusions had significantly higher mania and anosognosia scores.
Many reports published during the past 5 years have shown evidence of the beneficial effect of po... more Many reports published during the past 5 years have shown evidence of the beneficial effect of posteroventral pallidotomy (PVP) in large groups of patients for up to 3 years, but none of them have compared patients who underwent surgery with a control group. To compare the evolution of Parkinson's disease symptoms at 1-year follow-up between patients who underwent surgery and those who did not. Ten patients with idiopathic Parkinson's disease refractory to treatment who were included in the Core Assessment for Intracerebral Transplantation program for PVP did not undergo surgery because financial support was lacking. These patients were followed up for 1 year as if they had been operated on and were finally compared with 10 patients having similar characteristics in whom PVP had been performed during the same period of time. There were no significant differences at basal evaluation in the motor section scores of the Unified Parkinson's Disease Rating Scale between those patients who underwent surgery and those who did not, but a significant reduction in Unified Parkinson's Disease Rating Scale motor score in the group who underwent surgery at 1-year evaluation was found (P < 0.006). Dyskinesias, which was nonsignificantly different at basal evaluation, showed, at the 1-year follow-up, a significant reduction in the group who underwent surgery (P < 0.04). Scores from the subsets of the Unified Parkinson's Disease Rating Scale addressing rigidity, tremor, and bradykinesia also proved significantly different at the 1-year follow-up. The slope of the line generated by the two evaluations for each group showed a negative value in the group who underwent surgery (value of -0.21) and a positive value in the group who did not (value of 0.148). At the 1-year follow-up, microelectrode-guided PVP produced significant changes in patient motor status and disease progression versus a comparable group of patients who did not undergo surgery during the same period of time.
Previous studies have linked action recognition with a particular pool of neurons located in the ... more Previous studies have linked action recognition with a particular pool of neurons located in the ventral premotor cortex, the posterior parietal cortex and the superior temporal sulcus (the mirror neuron system). However, it is still unclear if transitive and intransitive gestures share the same neural substrates during action-recognition processes. In the present study, we used event-related functional magnetic resonance imaging (fMRI) to assess the cortical areas active during recognition of pantomimed transitive actions, intransitive gestures, and meaningless control actions. Perception of all types of gestures engaged the right pre-supplementary motor area (pre-SMA), and bilaterally in the posterior superior temporal cortex, the posterior parietal cortex, occipitotemporal regions and visual cortices. Activation of the posterior superior temporal sulcus/superior temporal gyrus region was found in both hemispheres during recognition of transitive and intransitive gestures, and in the right hemisphere during the control condition; the middle temporal gyrus showed activation in the left hemisphere when subjects recognized transitive and intransitive gestures; activation of the left inferior parietal lobe and intraparietal sulcus (IPS) was mainly observed in the left hemisphere during recognition of the three conditions. The most striking finding was the greater activation of the left inferior frontal gyrus (IFG) during recognition of intransitive actions. Results show that a similar neural substrate, albeit, with a distinct engagement underlies the cognitive processing of transitive and intransitive gestures recognition. These findings suggest that selective disruptions in these circuits may lead to distinct clinical deficits.
Depression has been associated with increased mortality among individuals with heart failure, but... more Depression has been associated with increased mortality among individuals with heart failure, but the mechanism for this association is unsettled. Depression is often found to result in autonomic dysfunction which, if present in heart failure, might help explain worsened outcomes. This study was a cross-sectional evaluation of the relationship between depressive symptoms and cardiac autonomic function, as assessed by short-term heart rate variability (HRV) analysis in aged patients with acute/decompensated heart failure of coronary origin (CHF). A 21-item Hamilton Depression score and measures of short-term HRV were obtained in 31 inpatients >or=65 years of age, 24-72 h after admission to the coronary care unit with a diagnosis of CHF. Clinical depression was present in 22.6% of participants. In the sample as a whole, increasing depressive symptoms were associated with decreased low-frequency HRV. These results may be important in light of recent indications that decreased low-frequency HRV is a predictor of mortality in patients with heart failure.
Current concepts regarding the organisation of the motor system indicate the existence of a front... more Current concepts regarding the organisation of the motor system indicate the existence of a frontoparietal circuit involved in prehension and manipulation, whose damage may result in a motor behavioural disorder strongly resembling the one originally described as limb-kinetic apraxia. To determine the specific clinical and kinematic features of this distinctive praxic disorder, 5 patients with corticobasal degeneration (apraxic group), 5 with Parkinson's disease (nonapraxic group), and 10 control subjects were studied by a comprehensive apraxic battery, three-dimensional motion analysis of manipulative movements and motor evoked potentials. A mathematical model [quality of movement coefficient (QMC)] was applied to quantify differential kinematic characteristics between elementary motor deficits and the praxic disorder. Transcranial magnetic stimulation was used to evaluate corticomotoneural projections and cortical inhibition. All five patients in the apraxic group exhibited a unilateral praxic deficit characterised by derangement of fractionated and segmental finger movements. QMC was significantly greater in apraxic than in nonapraxic patients (P < 0.02), revealing a chaotic movement with marked interfinger uncoordination. Conventional transcranial magnetic stimulation parameters were within normal limits in both groups of patients; however, the silent period was significantly shorter in the apraxic limb when compared with control subjects (P < 0.001). Limb-kinetic apraxia is a distinctive disorder affecting the performance of finger and hand postures and movements over and above a corticospinal or basal ganglion deficit. Disruption of the frontoparietal circuit devoted to grasping and manipulation, together with defective cortical inhibition, which would also interfere with the selection and control of hand muscle activity, are the most likely underlying physiopathological mechanisms of limb-kinetic apraxia in patients with corticobasal degeneration.
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Papers by Ramon Leiguarda