Hedonistic homeostatic dysregulation in Parkinson's disease: a short screening questionnaire.
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Behavioral Symptoms↗
Biomedical subjects
C Colosimo
Publications and source records attributed to C Colosimo.
Dihydroergocriptine in Parkinson's disease: clinical efficacy and comparison with other dopamine agonists.
The present paper reviews clinical studies on the use of dihydroergocriptine (DHEC), an ergot derivative with dopamine agonist activity, for the treatment of Parkinson's disease. This compound is a hydrogenated ergot derivative structurally quite similar to bromocriptine, from which it differs because of the hydrogenation in C9 C10 and the lack of bromine in C2. DHEC has a potent D2-like receptor agonist and a partial D1-like receptor agonist activity; because of this biochemical profile, it has been suggested that DHEC may produce fewer side-effects and have clinical efficacy equal to that of a classical dopamine agonist. Several open-label and double-blind studies indicate that DHEC is an efficacious remedy for parkinsonian signs and symptoms. Further studies are necessary to compare DHEC to new dopamine agonists (pergolide, cabergoline, ropinirole, and pramipexole) which have been more recently marketed.
Clinical Trials as Topic↗
Giant prolactinomas in men: efficacy of cabergoline treatment.
OBJECTIVE: The term 'giant prolactinoma' can be used for tumours larger than 4 cm in diameter and/or with massive extrasellar extension. Cabergoline (CAB), a long-lasting dopamine agonist (DA), safe and well tolerated, is effective in normalizing PRL levels and inducing tumour shrinkage in micro- and macroprolactinomas. The purpose of this prospective study was to evaluate the efficacy and safety of CAB also for giant prolactinomas. PATIENTS AND METHODS: Ten men with giant prolactinomas with a median age of 44.8 years were treated with CAB. Before CAB, four patients had previously undergone transsphenoidal surgery without modifying the parasellar extension of the tumour or their visual defects. Pretreatment serum prolactin (PRL) levels ranged between 1230 and 22 916 micro g/l (mean +/- SEM: 5794 +/- 1996) and tumour volume was between 21.8 and 105.5 cm3 (mean +/- SEM: 50.7 +/- 8.8). CAB was administered at an initial low dose of 0.5 mg three times a week and, in five patients who did not achieve serum PRL normalization, the dose was progressively increased up to 10.5 mg/week. The duration of treatment was 13-68 months (mean 38.9). PRL levels and pituitary target organ hormones were assayed before, after 30 days and then every 3 months after the beginning of CAB treatment. Magnetic resonance imaging (MRI) was carried out before, after 1-3 months, after 6 months and then every 10-12 months to evaluate tumour shrinkage. RESULTS: In every patient, a significant PRL decrease (P = 0.0086) of at least 96% of the pretreatment values occurred (from 5794 +/- 1996 to 77 +/- 38, mean +/- SEM); a persistent normalization of PRL levels was achieved in five out of 10 patients (50%) beginning from the first 3-6 months of CAB treatment (only one patient needed 12 months of therapy). A significant tumour shrinkage (P = 0.0003) was achieved after 12 months of therapy in nine out of 10 patients (90%), with a volume reduction greater than 95% in three, of 50% in four and 25% in two patients. Tumour volume decreased from 50.7 +/- 8.8 to 28.6 +/- 9.4 and then to 22.3 +/- 8.8 cm3 (mean +/- SEM) after 6 and 12 months of CAB treatment, respectively. An improvement of visual field defects (VFD) was obtained in six of the seven patients presenting visual impairment before CAB treatment. Among the eight patients presenting libido and potency (L-P) failure, five normalized their PRL levels. In two of these a complete restoration of libido and potency was observed. Three patients with secondary hypoadrenalism and a patient with secondary hypothyroidism were treated with substitutive therapy during all the study time. The drug was well tolerated by all patients and no one discontinued the therapy. CONCLUSIONS: These data suggest that, in giant, aggressive prolactinomas, CAB represents a first-line therapy effective in reducing PRL levels and determining tumour shrinkage.
Adrenal Glands↗
Botulinum toxin type B in blepharospasm and hemifacial spasm.
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Adult↗
Lewy body cortical involvement may not always predict dementia in Parkinson's disease.
BACKGROUND: The presence of Lewy bodies (LB) in the neocortex and limbic system in patients with Parkinson's disease (PD) is commonly thought to be linked with cognitive impairment. The authors present here a series of patients with diagnosis of PD in life and no significant cognitive impairment who, at necropsy, satisfied the current neuropathological criteria for dementia with Lewy bodies (DLB). METHODS: Two hundred and seventy six brains with PD pathology were examined at the Queen Square Brain Bank in London between 1993 and 1999. The neuropathological diagnosis was PD, but 117 patients also had sufficient LB involvement above the brain stem to satisfy the current neuropathological criteria for DLB (50 patients had a neuropathological picture consistent with the limbic category of DLB and 67 with neocortical DLB). Forty eight cases were excluded who developed early cognitive impairment together with motor features of parkinsonism, 12 cases for lack of detailed clinical history, and 19 cases with coexistent features of advanced Alzheimer's disease changes. Thirty eight patients (13.8% of the total with PD pathology and 32.5 % of the total with DLB pathology) were found where there was no or very late cognitive impairment reported in the clinical records. RESULTS: Selected cases were 24 men and 14 women, with a mean (SD) age at onset of parkinsonian symptoms of 60.1 (10.1) years and a mean disease duration of 15.3 (5.5) years. At some time during the evolution of the disease 21 patients developed different degrees of cognitive impairment (after a mean disease duration of 12.2 (4.8) years). Clinical diagnosis at death was PD in 10 cases and PD with dementia in 11. In the remaining 17 patients no history of cognitive impairment was ever recorded in life and all of them had a clinical diagnosis of PD at death; in this subgroup, nine patients later revealed a neuropathological picture consistent with limbic (or transitional) category of DLB and eight with neocortical DLB. Interestingly, in all these patients the parkinsonian features including the response to dopaminergic drugs were indistinguishable from classic brain stem PD. CONCLUSIONS: The authors demonstrate that the classic pathology of DLB can commonly be seen outside the generally accepted clinical spectrum for DLB and that important factors other than the absolute number of LB in the neocortex and limbic system influence the development of cognitive impairment in PD. Furthermore, the pathology of PD may be indistinguishable from that reported in DLB, suggesting that the two clinicopathological syndromes may be attributable to the same biological abnormality.
Adult↗
Magnetic resonance imaging of metastatic disease to the brain with gadobenate dimeglumine.
Seventy-four patients with one to eight proven intraaxial brain metastases received a total cumulative dose of 0.2 mmol/kg bodyweight gadobenate dimeglumine, administered as sequential injections of 0.05, 0.05 and 0.1 m mol/kg over a 20-min period. MR imaging was performed before the first administration (T2- and T1-weighted sequences) and after each injection of contrast agent (T1-weighted sequences only). Quantitative assessment of images revealed significant (P <0.01) dose-related increases in lesion-to-brain (L/B) ratio and percent enhancement of lesion signal intensity. Qualitative assessment by two independent, blinded assessors revealed additional lesions in 22%, 25% and 38% (assessor 1) and 29%, 32% and 34% (assessor 2) of patients after each cumulative dose when compared with combined T1- and T2-weighted pre-contrast images. Significantly more lesions (P < 0.01) were noted by both assessors after the first injection and by one assessor after each subsequent injection. For patients with just one lesion observed on unenhanced T1- and T2-weighted images, additional lesions were noted in 12%, 16% and 28% of patients by assessor 1 following each dose and in 24%, 27% and 30% of patients by assessor 2. Contemporaneously, diagnostic confidence was increased and lesion conspicuity improved over unenhanced MRI. For patients with one lesion observed after an initial dose of 0.05 mmol/kg, additional lesions were noted by assessors 1 and 2 in 9.1% and 11.8% of patients, respectively, after a cumulative dose of 0.1 mmol/kg and in a further 9.1% and 5.9% of patients, respectively, after a cumulative dose of 0.2 mmol/kg. No safety concerns were apparent.
Brain Neoplasms↗
Direct demonstration of long latency cortico-cortical inhibition in normal subjects and in a patient with vascular parkinsonism.
OBJECTIVE: The motor evoked potential to a single suprathreshold transcranial magnetic stimulus (TMS) is suppressed by a preceding stimulus given 100-200 ms before (long latency intracortical inhibition, LICI). The effect is enhanced in patients with Parkinson's disease. Although previous studies have agreed that the effect is cortical, there is disagreement over exactly which cortical mechanisms are involved. The aim of this study was to provide further evidence for cortical involvement in LICI. METHODS: Recordings of corticospinal volleys evoked by the TMS stimulation were made from electrodes inserted into the cervical epidural space of 4 conscious subjects. Three of the patients had received the electrodes for treatment of lumbo-sacral pain; the other patient had vascular parkinsonism, and had the electrode implanted to evaluate its effect on cerebral blood flow. The number and amplitude of the volleys were compared with and without a conditioning stimulus. RESULTS: In 3 pain patients, a conditioning stimulus suppressed the later components of the corticospinal volley (I2 and later waves) when the interval between stimuli was 100-150 ms; at 50 ms the responses were enhanced. Early components of the volley were not affected. Inhibition was much more pronounced and involved all descending volleys except the D wave in the patient with vascular parkinsonism. CONCLUSIONS: LICI, which is conventionally described in EMG recordings, is also evident in recordings of descending corticospinal volleys and appears enhanced in a patient with vascular parkinsonism.
Back Pain↗
The symptomatic treatment of multiple system atrophy.
Multiple system atrophy (MSA) is a neurodegenerative disease of undetermined aetiology that occurs sporadically and manifests itself as a combination of parkinsonian, autonomic, cerebellar and pyramidal signs. Despite the lack of any effective therapy to reverse this condition, some of the symptoms may be, at least temporarily, improved with adequate symptomatic therapies. Medical treatment is largely aimed at mitigating the parkinsonian and autonomic features. The therapeutic results of levodopa therapy in cases of MSA are difficult to interpret because of their variability. Nevertheless, the statement that patients with MSA are non or poorly levodopa-responsive is misleading. Clinical and pathologically proven series document about 40-60% levodopa efficacy in patients with MSA presenting with predominant parkinsonian features. Unfortunately, other antiparkinsonian compounds (dopamine agonists, amantadine) are not more effective than levodopa. Orthostatic hypotension (OH) can be suspected from the patient's history and subsequently documented in the clinic by measuring lying and standing blood pressure. The diagnosis ideally should be confirmed in the laboratory with additional tests to determine the cause and evaluate the functional deficit, so as to aid treatment. A variety of pharmacological agents with different mechanisms of action have been used in MSA to reduce OH when this is symptomatic. OH can also be alleviated by avoiding aggravating factors, such as the effects of food, micturition, exposure to a warm environment and physiological diurnal changes and by using other non-pharmacological strategies. The treatment of the very common genito-urinary symptoms (incontinence, retention, impotence) should also be considered in order to improve the quality of life of these patients.
Autonomic Nervous System Diseases↗
Procerus sign in progressive supranuclear palsy.
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Facial Expression↗
Gadobenate dimeglumine-enhanced magnetic resonance imaging of intracranial metastases: effect of dose on lesion detection and delineation.
Seventy-four patients with one to eight proven intraaxial metastatic lesions to the brain received a total gadobenate dimeglumine dose of 0.3 mmol/kg of body weight, administered as three sequential bolus injections of 0.1 mmol/kg, at 10-minute intervals over a 20-minute period. Quantitative and qualitative assessments of efficacy were performed after each injection and a full evaluation of safety was conducted. Cumulative dosing produced significant (P < 0.01) dose-related increases in lesion-to-brain (L/B) ratio and lesion signal intensity (SI) enhancement. Two independent, blinded assessors noted additional lesions, compared to unenhanced images in 31% and 33%, 49% and 42%, and 50% and 48% of patients after each cumulative dose, respectively. Significantly more lesions were noted after the first injection, compared to unenhanced images (P = 0.002 and P < 0.001; assessors 1 and 2, respectively), and after a second injection, compared to the first (P < 0.001 and P = 0.039; assessors 1 and 2, respectively). Neither assessor noted significantly more lesions after the third injection. For patients with just one lesion observed on unenhanced T1- and T2-weighted images, additional lesions were noted by assessors 1 and 2 for 27% and 26%, 48% and 35%, and 42% and 41% of patients, respectively, following each injection. Contemporaneously, diagnostic confidence was increased and lesion conspicuity improved over unenhanced magnetic resonance imaging (MRI). For patients with one lesion observed after 0.1 mmol/kg of gadobenate dimeglumine, additional lesions were noted for 24% and 17% of patients (assessors 1 and 2, respectively) following a second 0.1 mmol/kg injection. Only assessor 2 noted additional lesions following the third 0.1 mmol/kg injection. The findings of on-site investigators concurred with those of the two off-site assessors. No safety concerns were apparent.
Brain↗
Consensus statement on the role of acute dopaminergic challenge in Parkinson's disease.
Available evidence on the practice of acute pharmacological challenge tests in parkinsonian patients was reviewed by a committee of experts, which achieved a general consensus. The published data deal mainly with the acute administration of levodopa and apomorphine in Parkinson's disease. Such challenge may serve different purposes, e.g., research, diagnosis, or tailoring of treatment. Unique protocols describing the clinical setting and practice parameters are not available. The present paper describes the scientific background and supplies practical guidelines, whenever possible, to perform and evaluate acute challenge tests in parkinsonian syndromes. With the appropriate indication and setting, acute challenge tests are useful in diagnosis and therapy of Parkinson's disease and related disorders.
Apomorphine↗
Dopamine transporter immunoreactivity in peripheral blood lymphocytes in Parkinson's disease.
There is increasing interest in the identification of biological markers for the early diagnosis of Parkinson's disease (PD). Previous studies indicate changes of dopamine content, tyrosine hydroxylase immunoreactivity and dopamine receptors in peripheral blood lymphocytes (PBL) in PD. Here we demonstrate a reduction of dopamine transporter immunoreactivity in PBL in the early clinical stages of the disease. These findings contribute to our understanding of the peripheral dopamine system in PD.
Analysis of Variance↗
Epidemiology of multiple system atrophy. ESGAP Consortium. European Study Group on Atypical Parkinsonisms.
Multiple system atrophy (MSA) is a form of atypical parkinsonism with unknown etiology. The epidemiological studies conducted up to now on this disease are scarce. The incidence rate is about 0.6 cases per 100,000 persons per year. The prevalence rates show 4-5 cases per 100,000 persons. In Italy, about 4,900 prevalent cases have been estimated. The mean onset age is about 54 years; the median survival is 7-9 years. Only one case-control study has been performed on this disease. This study showed an increased risk of MSA associated with occupational exposure to organic solvents, plastic monomers and additives, pesticides and metals. Smoking habits seem to be less frequent in MSA cases (as in Parkinson's disease cases) than in healthy controls. Quinn's clinical criteria and those of the Consensus Conference promoted by the American Academy of Neurology are in fair agreement. We have performed a case-control study on 73 MSA cases, 146 hospital controls and 73 population controls.
Age of Onset↗
Epidemiology of progressive supranuclear palsy. ESGAP Consortium. European Study Group on Atypical Parkinsonisms.
Progressive supranuclear palsy (PSP) is a rare form of parkinsonism. The incidence rates are about 0.3-1.1 cases per 100,000 persons. The only two case-control studies performed up to now show conflictual results as regards education and residence in rural areas. Recently, a cluster of PSP and atypical parkinsonism has been observed in French Antilles. The hypothesis is that a consumption of both tropical fruit and herbal tea may be associated with PSP onset. Some PSP families with a probably autosomal dominant transmission have been described. A high frequency of a tau haplotype (H1/H1) associated with PSP is reported by some authors. The significance of this association is still not clear. We have performed a case-control study on 58 PSP cases, 116 hospital controls and 58 population controls.
Age of Onset↗
Intra-axial dermoid/epidermoid tumors of the brainstem in children.
BACKGROUND: Epidermoid and dermoid cysts are rare intracranial space-occupying lesions, which account for about 1% of all intracranial tumors; they are even rarer in the pediatric age group. Among the various locations, that inside the brain stem is quite exceptional (only 12 cases reported to date in the literature). We report two additional cases occurring in children, underlining their clinical characteristics, the difficulties faced in the diagnostic work-up, and the surgical treatment adopted (which consisted of removal of the cyst contents and partial resection of the cyst membrane, because of its adherence to the surrounding nervous and vascular structures). METHODS: We report two cases of intraaxial dermoid/epidermoid cysts observed within the last 5 years. Both patients complained of cervico-nuchal pain, with a remittent/intermittent character in one of them; this patient also exhibited transient 6th and 7th cranial nerve deficit. One lesion was approached through the floor of the fourth ventricle, the second one through the ventrolateral aspect of the brainstem. RESULTS: Subtotal tumor resection was achieved in both cases. Both patients had a smooth postoperative course without permanent neurological deficits. In the first patient residual tumor remains stable on follow-up MRI. In the second one, early tumor regrowth necessitated a second operation, after which the residual tumor has remained stable. CONCLUSIONS: Based on our experience we suggest that a cautious surgical approach ("conservative" resection) to these lesions is the best choice. In fact, attempts at radical removal carry unacceptably high morbidity and mortality rates.
Adolescent↗
Donepezil in the treatment of progressive supranuclear palsy.
OBJECTIVES: To evaluate the effect of 3 month therapy with donepezil, a centrally acting cholinesterase inhibitor, on cognitive performances, motor function and daily living activities in progressive supranuclear palsy (PSP). MATERIALS AND METHODS: Six patients with a diagnosis of PSP were evaluated at baseline and after 3 months of treatment with donepezil, 10 mg given at bedtime. Cognitive functions, motor symptoms and daily activities were evaluated by means of appropriate rating scales. RESULTS: Donepezil was not effective on cognitive dysfunction and did not change ratings of daily living. Parkinsonian symptoms were unaffected by donepezil treatment. CONCLUSIONS: Cholinergic replacement therapy alone is not likely to improve symptoms in a disorder characterized by a more widespread impairment of monoaminergic systems. Larger studies may be necessary to confirm the lack of effect of donepezil in this disorder.
Aged↗
Detection of intracranial metastases: a multicenter, intrapatient comparison of gadobenate dimeglumine-enhanced MRI with routinely used contrast agents at equal dosage.
RATIONALE AND OBJECTIVES: To compare gadobenate dimeglumine (MultiHance) with other commercially available MRI contrast agents for the detection of intracranial metastases. METHODS: A retrospective assessment was performed on MR images from 22 patients enrolled in a prior phase II clinical trial of gadobenate dimeglumine. Each patient underwent two examinations: a first examination with one of three "comparator" agents (gadopentetate dimeglumine, gadodiamide, and gadoterate meglumine) at a dosage of either 0.1 or 0.2 mmol/kg, and then a similar examination with gadobenate dimeglumine at equal dosage. All images were evaluated randomly for lesion number and location in unpaired and then paired fashion by two independent, masked neuroradiologists. A third assessor performed quantitative assessments on the available complete sets of digitally recorded images (10 cases). RESULTS: The findings for the comparator agents were pooled. Sensitivity for lesion detection with gadobenate dimeglumine (93%-100%) was markedly superior to that of comparator-enhanced examinations (65%-73%). The increase of lesion-to-brain contrast of the main lesion was consistently greater with gadobenate dimeglumine than with comparator agents relative to unenhanced contrast (+43% vs. +27%). CONCLUSIONS: Gadobenate dimeglumine proved to be a more efficacious agent than comparator contrast agents for the detection of intracranial metastatic lesions: superior efficacy was noted by both reviewers for total lesion count as well as for sensitivity and positive predictive value for lesion detection. The higher relaxivity of gadobenate dimeglumine might explain the superior sensitivity of gadobenate dimeglumine-enhanced MRI for the detection of central nervous system metastases.
Brain Neoplasms↗
Surgical treatment of cervical intramedullary spinal cord tumors.
The aim of this study is to determine if radical microsurgical removal of cervical intramedullary spinal cord tumors (CIMSCT) is achievable without causing respiratory, motor and sphincter deficits. Sixteen consecutive patients, who underwent surgical removal of a cervical intramedullary spinal cord tumor between 1988 and 1997, are presented. Surgical findings and results are analyzed. Patients' pre- and postoperative neurological conditions were evaluated using the clinical/functional scale of McCormick et al. The tumor was totally removed in 15 patients (93%). An improvement in sensory and motor functionality was obtained in 10 patients (63%), five patients (31%) remained stable and only one patient (6%), in whom partial removal was performed, presented a worsening of motor and sphincter functions. None of the patients who underwent total removal have shown MR signs of recurrence. The only patient in whom a partial removal was realized, presented a bulbar diffusion of the tumor and died. Microsurgical total removal can be considered the treatment of choice for CIMSCT. An accurate dissection between tumoral mass and normal spinal cord may allow, in the majority of cases, a total removal of tumor with preservation of spinal cord. Potential alterations of the spine stability must be prevented using internal or external stabilization.
Adult↗