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Biomedical subjects

J Kulisevsky

Publications and source records attributed to J Kulisevsky.

At least 37 records · Page 2Linked to original sources
PubMed2000

Role of dopamine in learning and memory: implications for the treatment of cognitive dysfunction in patients with Parkinson's disease.

Along with dementia, Parkinson's disease (PD) is associated with subtle but widespread cognitive impairment even in the absence of clinically apparent cognitive decline. Many of the deficits are reminiscent of those observed in patients with lesions of the prefrontal cortex, that is, failure in executive function that involves skills required for anticipation, planning, initiation and monitoring of goal-directed behaviours. This paper reviews the dopaminergic brain circuitry, and preclinical and clinical evidence supporting the regulation of prefrontal cortex activity by dopamine, and the role of dopamine in cognitive impairment in patients with PD. It addresses the need to integrate these facts and the findings of positive, neutral or detrimental frontal cognitive response to dopaminergic drugs in PD which should be viewed mainly in the context of methodological differences for subject selection. The cognitive effect of levodopa does not much depend on a neuropsychological specificity of the drug, the years of evolution of the disease or the severity of the motor signs. Instead, it may be a function of the level of dopamine depletion in different parts of the basal ganglia and prefrontal cortex. Consequently, dopaminergic agents may enhance cognitive functions in some patients and impair them in others. De novo patients tend to improve during the first year of treatment; stable responders to oral levodopa tend to show no changes; and wearing-off responders tend to deteriorate with acute levodopa challenge. Enhancement and impairment of cognitive function with dopaminergic treatment is incomplete and task-specific, suggesting the need to integrate the above dopamine facts with other neurotransmitter systems findings in PD. Meanwhile, such cognitive dissociation can be useful in refining the definition of the cognitive deficit in PD patients without dementia and emphasising the need to develop new and specific strategies for treatment.

Animals↗
PubMed2000

Relationship between cerebral perfusion in frontal-limbic-basal ganglia circuits and neuropsychologic impairment in patients with subclinical hepatic encephalopathy.

UNLABELLED: Early detection of neuropsychologic impairment in cirrhotic patients with subclinical hepatic encephalopathy (SHE) is important for their prognosis and quality of life. Abnormal MRI and MR spectroscopy (MRS) findings have been proposed as early markers of brain damage in these patients, but the role of functional neuroimaging in this field still has to be defined. In this study, the SPECT perfusion pattern in patients with SHE was investigated, and the relationship between regional cerebral blood flow (rCBF) and the MRI, MRS, neuropsychologic evaluation and biochemical data of these patients was assessed. METHODS: Data were obtained from 13 cirrhotic patients with SHE and 13 age-matched healthy volunteers. Fasting venous blood ammonia and manganese sampling and a battery of standardized neuropsychologic tests related to basal ganglia function and sensitive to the effects of liver disease were all performed on the same day. MRI and 99mTc-hexamethyl propyleneamine oxime SPECT were performed within 2 wk. RESULTS: A pattern of decreased prefrontal rCBF was found in patients with SHE compared with healthy volunteers. Basal ganglia and mesial temporal rCBF correlated inversely with performance on motor tasks involving speed (Purdue pegboard test) and frontal premotor function (Luria graphic alternances and Stroop tests). Thalamic rCBF correlated positively with T1-weighted MRI signal hyperintensity in the globus pallidus and with abnormal MRS findings. Neither the MRI signal intensity of the globus pallidus nor MRS correlated with neuropsychologic test results. CONCLUSION: Cirrhotic patients with SHE show a SPECT pattern of impaired prefrontal perfusion that does not seem to account for their neuropsychologic deficits. On the other hand, perfusion in some parts of the limbic system and limbic-connected brain regions, such as the striatum and the mesial temporal regions, increased with neuropsychologic impairment. These findings suggest that brain SPECT may be more sensitive than MRI in delineating cirrhotic patients requiring in-depth clinical testing to reveal basal ganglia-related neuropsychologic alterations.

Basal Ganglia↗
PubMed1999

Pergolide monotherapy in the treatment of early PD: a randomized, controlled study. Pergolide Monotherapy Study Group.

OBJECTIVE: To determine whether pergolide monotherapy provides symptomatic relief in early PD. BACKGROUND: Early treatment with dopamine agonists may reduce the risk of motor fluctuations, which are most likely linked to levodopa therapy. Pergolide, a D1-D2 dopamine agonist, has been studied as "add on" therapy in PD, but no controlled clinical trial studying the efficacy of pergolide monotherapy is available. METHODS: The efficacy and tolerability of pergolide were evaluated in a multicenter, double-blind, randomized, parallel-group, 3-month trial versus placebo. Patients with a diagnosis of idiopathic PD, a modified Hoehn & Yahr score of 1 to 3, and a score greater than 14 points on the Unified Parkinson's Disease Rating Scale (UPDRS) part III at baseline were enrolled in the study (pergolide, n = 53; placebo, n = 52). RESULTS: Patient characteristics at study entry were comparable in the two study groups. The pergolide group showed a significantly greater percent of responders (defined as a -30% decrease in UPDRS part III score at end point) compared with placebo (57% versus 17%; p < 0.001). Pergolide-treated patients experienced a significantly greater improvement than placebo-treated patients (p < 0.001) in UPDRS (overall, part II, and part III) score, Schwab & England score, and Clinical Global Impression improvement score. By the study end the mean dose of pergolide was 2.06 mg/day. Six patients in the pergolide group versus two patients in the placebo group discontinued the study because of treatment emergent side effects. CONCLUSION: This study suggests that pergolide monotherapy may be an efficacious and well-tolerated first-line treatment in patients with early-stage PD.

Aged↗
PubMed1999

Scopolamine prevents tolerance to the effects of caffeine on rotational behavior in 6-hydroxydopamine-denervated rats.

Continuous administration of caffeine has been shown to induce tolerance to its psychostimulant effects. In this study, using unilateral 6-hydroxydopamine nigrostriatal denervated rats, we tested the hypothesis that the muscarinic receptor antagonist, scopolamine, would prevent the tolerance to caffeine-induced contralateral rotational behavior. For that purpose we administered either caffeine (40 mg/kg) plus saline or scopolamine (5, 10 and 20 mg/kg) plus saline, as well as caffeine in combination with the various doses of scopolamine for 7 consecutive days, and measured ipsilateral and contralateral rotational behavior. The results showed that acute injections of scopolamine plus saline produced similar levels of both ipsilateral and contralateral turning, while caffeine produced more contralateral than ipsilateral turning. Tolerance to caffeine-induced contralateral turning was observed as of the second administration, while scopolamine plus saline injections did not produce significant changes in rotational behavior with repeated treatment. Scopolamine co-administered with caffeine significantly attenuated the increased contralateral turning produced by acute injections of caffeine plus saline, but significantly prevented the tolerance effects with repeated administration. These findings strongly suggest that muscarinic cholinergic processes may be involved in tolerance to caffeine-induced contralateral turning. The results are interpreted in terms of the possible interactions between dopamine, adenosine and acetylcholine neurotransmitter systems within the basal ganglia circuitry involved in motor behavior.

Animals↗
PubMed1999

A randomized placebo-controlled comparative trial of gabapentin and propranolol in essential tremor.

BACKGROUND: New medication is needed to treat essential tremor. Preliminary evidence suggests that gabapentin may be effective in the treatment of this disorder. OBJECTIVE: To study the effects of gabapentin in a comparative, double-blind, crossover, placebo-controlled trial of patients who have essential tremor. PATIENTS AND METHODS: 16 patients with essential tremor (6 with a new onset and 10 with a 2-week washout period of previous treatment with propranolol hydrochloride) received gabapentin (Neurontin), 400 mg 3 times daily; propranolol hydrochloride, 40 mg 3 times daily; and placebo for 15 days with a 1-week washout period between treatments. MAJOR OUTCOME MEASURES: Major outcome evaluations consisted of a Tremor Clinical Rating Scale, accelerometric recordings, and a self-reported disability scale obtained before drug intake on study days 1 and 15 of each treatment period. In addition, the initial (day 1) and superimposed (day 15) drug effects were studied before and 2, 4, 6, and 8 hours after drug intake. RESULTS: At day 15, both gabapentin and propranolol demonstrated significant and comparable efficacy in reducing tremor from baseline in all tremor measures. The initial drug effects evaluated through accelerometry revealed no significant changes with the use of a placebo, but gabapentin and propranolol use significantly reduced tremor power. CONCLUSION: Gabapentin may be useful for the treatment of essential tremor.

Acetates↗
PubMed1999

Effects of alprazolam on the acoustic startle response in humans.

In the present study, we assessed the effects of the potent benzodiazepine alprazolam on the human acoustic startle response in healthy volunteers. Eight undergraduate students received single oral doses of placebo and alprazolam 2 mg on 2 separate days, according to a double-blind balanced crossover design. Electromyographic activity of the orbicularis oculi muscle was recorded 5, 7 and 11 h after drug administration. At each recording time, subjects received 21 acoustic stimuli (1 KHz, 116 dB, 50 ms duration) separated by variable intervals (8-30 s, mean 16.5 s). Consistent with previous results obtained for diazepam in humans, alprazolam significantly reduced the amplitude of the startle reflex. A patent increase in onset latency was also observed, this being a novel effect not previously described for benzodiazepines in human studies. Both effects were maximum at 5 h after dosing, the startle response experiencing a recovery as the drug disappeared from systemic circulation. These results indicate a potent inhibitory effect of alprazolam on baseline startle at the dose used, with a robust time-dependent recovery of initial values effectively counteracting between-session habituation.

Adult↗
PubMed1999

Repeated co-administration of caffeine and bromocriptine prevents tolerance to the effects of caffeine in the turning behavior animal model.

The present study examined the effects of repeated co-administrations of caffeine and bromocriptine for 9 consecutive days on contralateral turning in unilateral nigrostriatal 6-hydroxydopamine denervated rats. In agreement with previous data, our results showed that on the first administration, both caffeine and bromocriptine injected plus saline produced a significant increase in contralateral rotational behavior as compared to saline-saline injections. However, with repeated administrations, tolerance was observed to caffeine, but not to bromocriptine. The combination of different doses of bromocriptine (0.1, 0.2, 0.4 and 0.8 mg/kg) with caffeine (40 mg/kg) significantly enhanced the effects of either drug injected with saline on rotational behavior, and no tolerance was observed with repeated treatment. The continuous co-administration of both substances was necessary to maintain elevated levels of rotational behavior, since withdrawing one or the other drug led to decreased contralateral turning. These results demonstrate that when caffeine is administered repeatedly in combination with bromocriptine, tolerance to its psychostimulant effects is not observed, suggesting that caffeine could be used as an adjunctive therapeutic agent with dopamine agonists for the treatment of Parkinson's disease.

Adrenergic Agents↗
PubMed1999

[Parkinson disease and cognition].

Parkinson's Disease patients may have cognitive deficits, which may vary from mild focal specific deficits to global dementia. Executive functions, working memory, visuoespatial functions and internal control of attention are the main affected cognitive areas. The dopaminergic hypothesis suggests that dopaminergic transmission is involved in most altered cognitive processes. However, other neuronal systems are probably implicated, and the improvement of the cognitive function after dopaminergic replacement is incomplete and not seen in all cognitive tasks. The prevalence of dementia in Parkinson's disease is estimated in 15-25%. The pathologic hallmarks may be similar to that seen in Alzheimer's disease. However, in Parkinson's disease patients pure subcortical alterations are able to produce a severe cognitive impairment, such as lost of dopaminergic neurones from substantia nigra to caudate nucleus and frontal areas. Comprehension of the relationship between depression and dementia in Parkinson's disease patients is incomplete. Parkinson's disease patients with depression show poor neuropsychological performance, especially in frontal tasks, but it is unclear whether depression can be considered a risk factor for the development of dementia in Parkinson's disease.

Cognition Disorders↗
PubMed1999

[New treatments in movement disorders].

In recent years there have been considerable advances in the field of movement disorders which have decisively transformed not only the comprehension of the genetics and the pathophysiology of different diseases but have also improved the quality of life of these patients. Examples of these already available advances include the introduction of new treatments for previously untreatable diseases, such as botulinum toxin for dystonia, new therapeutic options or new forms of administration of levodopa for Parkinson disease, such as delayed levodopa, catecol-O-methyl transferase inhibitors and monotherapy with the classical and new dopaminergic agonists or new surgical techniques for previously unapproachable complications, such as dyskinesias in advanced Parkinson's disease. This study reviews the current treatment of Parkinson's disease, essential tremor, dystonia and different forms of choreas and indicates some of the experimental therapies which open renewed perspectives for neurodegenerative diseases, mainly Huntington's chorea and Parkinson's disease, such as the drugs with possible neuroprotective action, glutamatergic transmission reducers, neurotrophic factors and neuronal implants.

Humans↗
PubMed1998

Bipolar disorder in adult patients with Tourette's syndrome: a clinical study.

BACKGROUND: Although recent clinical and epidemiological studies indicate that Tourette's syndrome (TS) is associated with a higher than expected rate of bipolar disorder (BPD), the clinical characteristics of BPD in patients with TS have not been widely investigated. METHODS: Thirty adult TS patients with comorbid BPD were selected from a consecutive series of 90 referred TS patients and examined using structured psychiatric rating scales. RESULTS: The full clinical spectrum of BPD was found, including bipolar I disorder, schizoaffective bipolar disorder, bipolar II disorder, and cyclothymic disorder. Atypical vegetative depressive symptoms, rapid cycling patterns, and seasonal patterns of recurrence were also documented. In the present clinical sample, BPD mainly occurred in patients with mild tic symptoms and was invariably associated with a high lifetime prevalence of general psychopathology, including generalized anxiety disorder, obsessive-compulsive disorder, panic, phobias, eating disorders, self-injurious behavior, attention-deficit hyperactivity disorder, impulse control disorders, and personality disorders. CONCLUSIONS: The results of this clinical study indicate that BPD and nonaffective psychopathology may be prominent comorbid disorders in a subpopulation of patients with TS.

Adult↗
PubMed1998

Unrecognized Tourette syndrome in adult patients referred for psychogenic tremor.

BACKGROUND: The diagnosis of Tourette syndrome may be overlooked in patients with severe psychopathologic disorder but mild motor manifestations of Tourette syndrome. OBJECTIVE: To describe 4 patients with long-lasting general psychopathologic disorder and previously unrecognized mild motor and phonic tics exacerbated during adulthood by the onset of tremor; all of the patients had been referred for the evaluation of psychogenic tremor. SUBJECTS: Four adult patients, with previous psychiatric diagnoses of depression (2 cases), generalized anxiety disorder (3 cases), malingering (1 case), and conversion disorder (3 cases). METHODS: Single case studies. RESULTS: Clinical interviews disclosed that the 4 patients had positive family histories of Tourette syndrome, and all had mild motor and phonic tics that had started before the age of 18 years. On neurologic examination, 2 patients had bilateral postural tremor of the hands that varied in frequency, rhythmicity, and amplitude, and the other 2 had resting tremor mimicking parkinsonism. All 4 patients described involuntary somatic sensations of the affected limbs, which they attempted to alleviate by executing movements. No consistent positive placebo response was observed, but in all patients tremoric movements improved with haloperidol. CONCLUSIONS: These cases illustrate an unusual movement disorder (tremor as a "tic equivalent") in adults with Tourette syndrome and emphasize that cases of the syndrome with mild tics often go unrecognized, precluding adequate treatment.

Adult↗
PubMed1998

Reactivation of posttraumatic stress disorder after minor head injury.

This report describes the reactivation of a posttraumatic stress disorder (PTSD) after a minor head injury in two young women who had recovered from extreme stress caused by sexual abuse during adolescence. Intrusive thoughts, images, dreams, and phobic avoidance bear a direct relationship to the specific circumstances of both head injury and sexual abuse, and were associated with obsessive-compulsive symptoms, generalized anxiety with panic, and depression. These findings suggest that in some individuals minor head injuries may induce not only extreme stress reactions, but also cause the reactivation of symptoms related to previous traumatic experiences.

Adolescent↗
PubMed1998

[Tolcapone: a different, effective approach to improving dopaminergic treatment in Parkinson's disease].

Tolcapone is a potent, selective, reversible inhibitor of COMT. Coadministration of tolcapone with levodopa and a decarboxylase inhibitor prolongs the elimination half-life of levodopa and reduces the formation of 3-0-metildopa in a dose-dependent form. The improvement in the pharmacokinetics of levodopa prolongs the motor effects of levodopa. Clinical studies have shown that the concomitant administration of levodopa and tolcapone is effective on the management of the wearing-off phenomenon. Tolcapone can significantly reduce the off time and increases the total on time while simultaneously reducing levodopa dosage and frequency. Most adverse events are dopaminergic in nature and related to the increase in levodopa bioavailability. Dyskinesias may increase in frequency and severity in patients already having dyskinesias and these may appear for the first time after adding tolcapone in patients at risk. Diarrhoea is the main nondopaminergic adverse event leading to the stop of the drug in less than 10% of cases. Taking into account that tolcapone significantly enhance the action of levodopa, it would be wise to reduce the total daily dose of levodopa at the same time that tolcapone is introduced. No tolerance effect was observed in 12-month studies. Tolcapone can be used with standard or sustained release levodopa, and, when appropriate, in conjunction with dopamine agonists or selegiline.

Antiparkinson Agents↗
PubMed1997

[Initial treatment of Parkinson's disease].

The initial treatment of Parkinson's disease should be addressed to improve symptoms, slow down the progression of the illness and avoid long and short term complications. Drugs currently available for symptomatic treatment are levodopa, dopaminergic agonists, anticholinergics and amantadine. Levodopa is still the goldstandard. Both the standard preparations of carbidopa/levodopa or benserazide/levodopa and the slow release preparations are suitable for initial treatment. However, when to start levodopa remains controversial. Dopaminergic agonists are useful symptomatic drugs. They can be used in monotherapy, but usually require the addition of levodopa to obtain a satisfactory long term therapeutic response. Used as adjuvant treatment to levodopa, they help lowering the dosage of levodopa. Anticholinergic drugs effectively improve symptoms such as tremor and rigidity but their use is limited by their side effects, particularly in older people. Amantadine may be a useful drug for initial treatment of Parkinson's disease when symptoms are not severe. Symptomatic treatment should be considered individually in each patient. If there is only slight disability, treatment may be started with amantadine alone or with a dopaminergic agonist. If there is greater disability, levodopa or the simultaneous use of levodopa and a dopaminergic agonist should be considered. Anticholinergic drugs should be reserved for young patients with tremor as the main symptom. The newer dopamine agonists and inhibitors of catachol-o-methyltransferase (COMT) are coming therapeutic options. Selegiline, a MAOB inhibitor with a possible neuroprotective effect, should also be considered as initial option for Parkinson's disease.

Amantadine↗
PubMed1996

Neuropsychological alterations in patients with computed tomography-detected basal ganglia calcification.

OBJECTIVE: To investigate the cognitive and mental status of patients with basal ganglia calcification on a computed tomographic scan. DESIGN: Eighteen ambulatory patients with basal ganglia calcification and without other radiological findings who were identified from the computed tomography records of a general hospital in a 2-year period and 16 control subjects who were matched for age, education, sex, and premorbid IQ estimation consented to participate. All subjects underwent a neurological evaluation, a comprehensive neuropsychological battery, and tests with psychiatric rating scales. RESULTS: Significant differences for the control group were found in tests that evaluated motor speed and executive, visuospatial, and some memory functions. Four patients (22%) met criteria for organic mood disorder (minor depression, three patients; bipolar depression, one patient) according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, whereas six other patients (33%) met diagnostic criteria for obsessive-compulsive disorder. CONCLUSIONS: These results indicate that patients with basal ganglia calcifications frequently have a subcortical pattern of neuropsychological dysfunction and behavioral changes that are known to be associated with alterations of the frontal-limbic-basal ganglia circuits. The pattern of neuropsychological impairment is consistent with basal ganglia damage. However, poor performance in other neuropsychological tests suggest additional involvement of other connected networks.

Adult↗