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Biomedical subjects

S Starkstein

Publications and source records attributed to S Starkstein.

At least 19 recordsLinked to original sources

Olanzapine as alternative therapy for patients with haloperidol-induced extrapyramidal symptoms: results of a multicenter, collaborative trial in Latin America.

Conventional antipsychotic agents can induce extrapyramidal symptoms (EPS) that may be alleviated by switching patients to novel agents such as olanzapine. Patients with schizophrenia and related disorders (ICD-10) who were taking haloperidol (N = 94; mean dose = 12.7 mg/day) and had EPS (Simpson-Angus Scale [SAS] > 3) were directly switched to 6 weeks of open-label olanzapine treatment (mean dose = 11.4 mg/day). There were significant mean improvements (p <0.001 for all measurements) from baseline to endpoint on the SAS (-9.69+/-5.33; percentage change, 87.2%), the Barnes Akathisia Scale (-1.00+/-1.19; percentage change, 82.5%), and the Abnormal Involuntary Movement Scale (-1.48+/-2.89; percentage change, 81.1%), and anticholinergic use decreased from 47.9% to 12.8% (mean baseline to endpoint change: -1.52+/-1.91-mg equivalents of benztropine; p < 0.001). Significant mean baseline to endpoint improvements (p < 0.001 for all measurements) were observed on the Positive and Negative Syndrome Scale (PANSS; -25.28+/-18.67; percentage change, 30.3%), the PANSS-extracted Brief Psychiatric Rating Scale (0-6 scale, -13.41+/-10.16; percentage change, 54.4%), and the Clinical Global Impressions Severity scale (-1.16+/-1.19; percentage change, 26.4%). Spontaneously reported treatment- emergent adverse events with a greater than 5% incidence were somnolence (16.0%), increased appetite (14.9%), weight gain (11.7%), headache (8.5%), anxiety (7.4%), dizziness (6.4%), and insomnia (5.3%). Criteria for a successful switch were met by 90.5% of patients. Psychotic symptom exacerbation was experienced by 30.9% of patients at any time during the study and by 11.7% of patients at endpoint. Results suggest that a direct switch to olanzapine is a therapeutic option when patients with haloperidol-induced EPS are unable to tolerate a more gradual switch.

Adolescent↗

Bilateral pallidotomy for treatment of Parkinson's disease induced corticobulbar syndrome and psychic akinesia avoidable by globus pallidus lesion combined with contralateral stimulation.

OBJECTIVE: Posteroventral 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. METHODS: A prospective series of patients with severe Parkinson's disease refractory to medical treatment, and severe drug induced dyskinesias, were randomised either to simultaneous bilateral PVP or simultaneous PVP+PVS. All patients were assessed with the core assessment programme for intracerebral transplantation (CAPIT), and a comprehensive neuropsychological and neuropsychiatric battery both before surgery and 3 months later. RESULTS: The severe adverse effects found in the first three patients subjected to bilateral PVP led to discontinuation of the protocol. All three patients developed depression and apathy. Speech, salivation, and swallowing, as well as freezing, walking, and falling, dramatically worsened. By contrast, all three patients undergoing PVP+PVS had a significant motor improvement. CONCLUSION: Bilateral simultaneous lesions within the GPi may produce severe motor and psychiatric complications. On the other hand, a combination of PVP+ PVS significantly improves parkinsonian symptoms not associated with the side effects elicited by bilateral lesions.

Aged↗

Disruption of spatial organization and interjoint coordination in Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy.

Patients with basal ganglia diseases may exhibit ideomotor apraxia. To define the nature of the impairment of the action production system, we studied a repetitive gesture of slicing bread by three-dimensional computergraphic analysis in eight nondemented patients with Parkinson's disease in the "on" state, five with progressive supranuclear palsy and four with multiple system atrophy. Two patients with Parkinson's disease and two with progressive supranuclear palsy showed ideomotor apraxia for transitive movements on standard testing. A Selspott II system was used for kinematic analysis of wrist trajectories and angular motions of the shoulder and elbow joints. Patients with Parkinson's disease, progressive supranuclear palsy, and even some with multiple system atrophy exhibited kinematic deficits in the spatial precision of movement and velocity-curvature relationships; in addition, they failed to maintain proper angle/angle relationships and to apportion their relative joint amplitudes normally. Spatial disruption of wrist trajectories was more severe in patients with ideomotor apraxia. We posit that the basal ganglia are part of the parallel parieto-frontal circuits devoted to sensorimotor integration for object-oriented behavior. The severity and characteristics of spatial abnormalities of a transitive movement would therefore depend on the location and distribution of the pathologic process within these circuits.

Aged↗

Unilateral radiofrequency lesion versus electrostimulation of posteroventral pallidum: a prospective randomized comparison.

Microelectrode-guided posteroventral pallidotomy (PVP) has shown to be an effective method in the treatment of a group of patients with advanced Parkinson's disease. A nonlesioning approach by means of deep brain electrodes connected to a programmable neuropacemaker has also been used to inhibit the internal segment of globus pallidus (posteroventral stimulation [PVS]) reporting comparable clinical efficacy to the one obtained with the ablative method. Nevertheless, no controlled studies have been performed to compare the efficacy of both procedures. A prospective series of 13 patients with a clinical indication for globus pallidus surgery was randomized either to a pallidotomy or stimulator implantation, and comparisons on motor and neuropsychologic measurements were made on a 3-month follow-up basis. Primary measurements of efficacy showed a comparable effect on Unified Parkinson's Disease Rating Scale and activities of daily living score after both procedures. Secondary measurements of efficacy showed that although both techniques improve hand tapping score and dyskinesia score, the bilateral improvement in the former was greater after PVS whereas the latter improved more significantly after PVP. No significant changes in neuropsychologic parameters were observed after either PVP or PVS. Side effects and surgery complications occurred in six of 13 patients (three after PVP and three after PVS): they were mild, transient, and unrelated to optic tract injury. In conclusion, the short-time effect and safety of both procedures is comparable.

Aged↗

Discrimination of facial identity and of emotions in Alzheimer's disease.

OBJECTIVE: To investigate processing of human faces identity and of emotional expressions in patients with Alzheimer's Disease (AD). BACKGROUND: Mechanisms responsible for discriminating facial identity may be dissociated from those involved in discriminating facial expressions. Patients with prosopagnosia often have preserved capacities for processing emotional facial expressions and occasionally, patients with focal lesions may recognize human faces without being able to recognize their facial expression. Such a dissociation has not been clearly shown in groups of AD patients. METHODS: Thirty-one probable AD patients and 14 control subjects were administered tasks of discrimination of faces and of emotions. RESULTS: AD patients were significantly impaired in discriminating facial identities and in naming and pointing to named emotions, but were comparable to controls in discriminating facial expressions of emotion. The deficits of facial discrimination and of identification of emotions were, on the whole, correlated with the MMS and Raven scores. Discrimination of emotions was not correlated to either test, suggesting that this ability is based on cognitive processes different from those underlying the MMS and the PM47. CONCLUSIONS: This dissociation implies two separate systems, one dedicated to discrimination of facial identities and the other to discrimination of emotions. This is compatible with the modular organization of cognitive deficits in AD and may explain the well known experience that nonverbal communication often remains effective even in patients with severe dementia.

Alzheimer Disease↗

Memory and depression in Parkinson's disease.

Disorders of learning and memory are a frequent finding in nondemented Parkinson disease (PD) patients. It is not clear to what extent depression, present in at least half the cases of PD, contributes to these disorders. This paper investigates the possible influence of depression on tests of episodic memory in patients with Parkinson's disease (PD). We studied three groups of 11 subjects each (controls, non-depressed PD, mildly to moderately depressed PD). Neuropsychological tests included tests of short and long-term memory in verbal and non-verbal modalities. The two groups of PD patients performed significantly worse than controls on the memory tests, but there were no differences between the depressed and non-depressed PD patients. This lack of influence of depression on neuropsychological performance is compatible with Starkstein's view that cognitive imnpairment is only found beyond a given threshold of depression severity.Copyright Lippincott-Raven Publishers

Journal Article↗

A randomized, double-blind, placebo-controlled study of methylphenidate in patients with organic amnesia.

We examined the usefulness of methylphenidate (MPH) in the treatment of organic amnesia in a randomized, double-blind, placebo-controlled design. Twenty patients with amnesia due to closed head injuries (n = 10), viral encephalitis (n = 2), stroke lesions (n = 4), or surgical brain resections (n = 4) were assessed with a neuropsychological battery after the intake of MPH (10, 20, 30 or 40 mg), or placebo. We found no significant benefit of MPH for any of the cognitive tests.Copyright Lippincott-Raven Publishers

Journal Article↗

Sleep benefit in Parkinson's disease.

Sleep benefit (SB) In Parkinson's disease (PD) is not well characterized. To determine SB frequency, as well as to characterize and correlate it with other disease variables, we evaluated prospectively a consecutive series of 312 PD patients by means of a structured questionnaire: 55% reported having SB and 35% reported that awakening was their best time of the day. Because of SB, 21% of the entire population were able to skip or delay medication. The mean duration of the phenomenon was 85.4 +/- 67 min. Patients with SB were significantly older (p < 0.0002), had disease longer (p < 0.05), and were often men (chi 2 = 3.5, df 1, p = 0.05). Patients with SB took sleep medication with similar frequency as those without SB. There were no differences in hours of sleep or sleep latency. Sleep problems such as nightmares or somnambulism, but not the number of sleep awakenings, were similar in both groups. In conclusion, SB is a frequent phenomenon, especially in men, elderly patients, and patients with longer disease duration. SB enables the morning L-dopa dose to be postponed in approximately 50% of patients.

Aged↗

Apraxia in Parkinson's disease, progressive supranuclear palsy, multiple system atrophy and neuroleptic-induced parkinsonism.

We studied 45 non-demented patients with Parkinson's disease (PD), 12 with progressive supranuclear palsy (PSP), 10 with multiple system atrophy (MSA) and 12 with neuroleptic-induced parkinsonism (NIP) for the presence of apraxia. Our aim was to determine whether a standard comprehensive assessment of different praxic functions would demonstrate specific types of errors not attributable to bradykinesia, rigidity, tremor or any other abnormal elementary motor deficit. PD patients on chronic levodopa treatment were examined in the 'on' and 'off' (treatment) states. Based on apraxia assessment scores, bilateral ideomotor apraxia for transitive movements was found in eight (75%) and 12 (27%) of PSP and PD patients, respectively. Ideomotor apraxia was mainly characterized by spatial errors (i.e., external and internal configuration, body-part-as-object and trajectory). Four PSP but no PD patients exhibited ideomotor apraxia for intransitive movements. PSP as well as PD patients with ideomotor apraxia also had difficulties in imitating hand and finger postures, but none of them failed on pantomime comprehension and pantomime recognition/discrimination. Some PSP patients exhibited, in addition, a limbkinetic type of apraxia and a minority of them displayed deficits on tasks involving multiple steps. Neither MSA nor NIP patients showed any disturbance of praxic functions. There were no differences in age, disease duration, Mini Mental State Examination (MMSE), Unified Parkinson's disease Rating Scale and Hoehn-Yahr scores between apraxic and non-apraxic PD patients, and ideomotor apraxia scores were similar in the 'on' and 'off' states. A correlation was found between ideomotor apraxia scores in PD patients and deficits in frontal lobe-related neuropsychological tasks such as the Tower of Hanoi, verbal fluency and the Trail Making Test. Furthermore, PD patients with apraxia showed higher Hamilton depression scores than non-apraxic PD patients. In PSP patients, ideomotor apraxia scores correlated significantly with cognitive deficit as measured with MMSE. The presence or absence of cortical involvement, and its severity and distribution might determine the presence and type of apraxia in PD and PSP. Apraxia in these conditions would therefore reflect combined cortico-striatal dysfunction.

Adult↗

Drug-induced parkinsonism in schizophrenic patients: motor response and psychiatric changes after acute challenge with L-Dopa and apomorphine.

Acute single-dose response of drug-induced parkinsonism (DIP) to L-Dopa and apomorphine challenge was evaluated in a double-blind crossover study in 12 schizophrenic patients. There were two noteworthy negative findings. First, neither L-Dopa nor apomorphine produced significant improvements in DIP and second, no changes (neither improvement nor worsening) were found in patients' psychiatric status. Findings suggest that, for a stimulation dose reaching almost 90% of the responsive dose for idiopathic Parkinson's disease, no significant changes may reasonably be expected in the parkinsonism of schizophrenic patients treated with neuroleptic drugs.

Adult↗

Quantified electroencephalographic correlates of relative frontal or parietal hypoperfusion in dementia.

The authors examined the presence of specific quantified electroencephalographic (qEEG) changes in dementia patients with relatively lower frontal or parietal blood perfusion as demonstrated by SPECT. Over all brain regions, patients with relatively lower parietal perfusion showed significantly higher theta relative power than demented patients with relatively lower frontal perfusion or normal control subjects. Dementia patients with relatively lower frontal perfusion showed no differences from age-comparable normal control subjects in qEEG variables. These findings 1) suggest that usefulness of qEEG for the diagnosis of dementia is restricted to a subgroup of patients with the typical SPECT pattern of parietal blood hypoperfusion and 2) demonstrate that the qEEG changes typical of dementia are not related to perfusion deficits in frontal brain areas.

Aged↗

Quantified electroencephalographic changes in depressed patients with and without dementia.

We carried out quantified electroencephalograms (qEEG) in 17 patients with probable Alzheimer's disease (AD), who also met the DSM-III-R criteria for either dysthymia or major depression, and 18 AD patients with comparable intellectual impairment but no depression, 13 patients with depression but no AD, and 10 age-matched normal controls. There was a significant effect for depression in alpha relative power: depressed patients (with or without AD) showed a significantly lower alpha relative power in the right posterior region as compared to nondepressed patients; however, this change was observed over the right hemisphere in depressed non-AD patients, and in left, medial, and right posterior regions in depressed-AD patients. Depressed patients without AD showed a significant global decrease in delta power, whereas depressed patients with AD showed significant increments in delta power in posterior brain areas. In conclusion, AD patients with depression showed qEEG changes that were significantly different from qEEG changes in depressed non-AD patients.

Aged↗

Trial of d-alpha-tocopherol in Huntington's disease.

OBJECTIVE: Evidence suggests that the neuropathology of Huntington's disease, a neuropsychiatric disorder due to a mutation on chromosome 4, results from excessive activation of glutamate-gated ion channels, which kills neurons by oxidative stress. Therefore, the authors hypothesized that alpha-tocopherol, which reduces oxyradical damage to cell membranes, might slow the course of Huntington's disease. METHOD: A prospective, double-blind; placebo-controlled study of high-dose d-alpha-tocopherol treatment was carried out with a cohort of 73 patients with Huntington's disease who were randomly assigned to either d-alpha-tocopherol or placebo. Patients were monitored for changes in neurologic and neuropsychologic symptoms. RESULTS: Treatment with d-alpha-tocopherol had no effect on neurologic and neuropsychiatric symptoms in the treatment group overall. However, post hoc analysis revealed a significant selective therapeutic effect on neurologic symptoms for patients early in the course of the disorder. CONCLUSIONS: Antioxidant therapy may slow the rate of motor decline early in the course of Huntington's disease.

Antioxidants↗

Quantified electroencephalographic correlates of neuropsychological deficits in Alzheimer's disease.

The authors examined relationships between quantified EEG (qEEG) variables and neuropsychological performance in 54 consecutive patients with probable Alzheimer's disease (AD). Patients were studied with qEEG and a neuropsychological battery that assessed memory, attention, verbal functions, set-shifting abilities, and procedural learning. More severe memory, attention, and verbal deficits were significantly correlated with lower alpha relative power, and increased theta relative power was significantly correlated with poor set-shifting abilities. No qEEG variables were significantly correlated with the procedural learning task. These correlations between deficits in specific cognitive domains and qEEG bands suggest that qEEG may have an important role in the investigation of the cognitive deficits in AD.

Aged↗

A randomized, double-blind, placebo-controlled study of bromocriptine in nonfluent aphasia.

We carried out a double-blind and placebo-controlled study of the efficacy of bromocriptine in the treatment of nonfluent aphasia. Seven patients received bromocriptine (up to 60 mg/d) and an identical placebo in a randomized order. End points were the number of content words, content units, and pauses > 3 seconds during the description of a figure; verbal naming; and verbal fluency. There were no significant benefits of bromocriptine over placebo in any of the variables examined.

Adult↗

Extrapyramidalism in Alzheimer's disease: prevalence, psychiatric, and neuropsychological correlates.

The prevalence and clinical correlates of extrapyramidal signs in a consecutive series of 78 patients with Alzheimer's disease attending a neurology clinic, and 20 age comparable normal controls, were examined. Based on the unified Parkinson's disease rating scale (UPDRS) findings, 18 patients (23%) met criteria for parkinsonism, 44 (56%) had isolated extrapyramidal signs, and 16 (21%) had no extrapyramidal signs. Whereas the control group showed a similar prevalence of isolated extrapyramidal signs (57%), none of them showed parkinsonism. No significant differences were found for age, sex, duration of illness, and severity of dementia among the three Alzheimer's disease groups. Patients with Alzheimer's disease-parkinsonism, however, showed a significantly higher frequency of major depression and dysthymia and significantly higher Hamilton depression scores than patients with isolated or no extrapyramidal signs. Patients with Alzheimer's disease-parkinsonism also showed significantly more deficits on frontal lobe related tasks such as the Wisconsin card sorting test, trail making test, and verbal fluency, as well as on tests of constructional praxis and abstract reasoning than patients with Alzheimer's disease but no extrapyramidal signs. In conclusion, the study showed a specific association between Alzheimer's disease and parkinsonism, as well as significant relations between parkinsonism, deficits in executive functions, and depression among patients with Alzheimer's disease.

Aged↗

The nature of apraxia in corticobasal degeneration.

Although apraxia is one of the most frequent signs in corticobasal degeneration, the phenomenology of this disorder has not been formally examined. Hence 10 patients with corticobasal degeneration were studied with a standardised evaluation for different types of apraxia. To minimise the confounding effects of the primary motor disorder, apraxia was assessed in the least affected limb. Whereas none of the patients showed buccofacial apraxia, seven showed deficits on tests of ideomotor apraxia and movement imitation, four on tests of sequential arm movements (all of whom had ideomotor apraxia), and three on tests of ideational apraxia (all of whom had ideomotor apraxia). Ideomotor apraxia significantly correlated with deficit in both the mini mental state examination and in a task sensitive to frontal lobe dysfunction (picture arrangement). Two of the three patients with ideomotor apraxia and ideational apraxia showed severe cognitive impairments. The alien limb behaviour was present only in patients with ideomotor apraxia. In conclusion, ideomotor apraxia is the most frequent type of apraxia in corticobasal degeneration, and may be due to dysfunction of the supplementary motor area. There is a subgroup of patients with corticobasal degeneration who have a severe apraxia (ideomotor and ideational apraxia), which correlates with global cognitive impairment, and may result from additional parietal or diffuse cortical damage.

Aged↗