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Biomedical subjects

A Antonini

Publications and source records attributed to A Antonini.

At least 19 recordsLinked to original sources
PubMed2006

Clinical correlates and cognitive underpinnings of verbal fluency impairment after chronic subthalamic stimulation in Parkinson's disease.

A decline in verbal fluency is the most consistent neuropsychological sequela of deep brain stimulation (DBS) for Parkinson's disease. We assessed clinical correlates and switching and clustering subcomponents in 26 parkinsonians undergoing subthalamic DBS. Post-surgical motor improvement was accompanied by worsening at both letter and category fluency tasks. Total number of words and switches decreased, while average cluster size was unchanged. Worsening tended to be prominent in patients with baseline poorer cognitive status and more depressed mood. Impairment of shifting suggests prefrontal dysfunction, possibly due to disruption of fronto-striatal circuits along the surgical trajectory and/or to high frequency stimulation itself.

Aged↗
PubMed2006

Comparative analysis of visual and semi-quantitative assessment of striatal [123I]FP-CIT-SPET binding in Parkinson's disease.

We used qualitative visual assessment and semiquantitative measures of striatal DAT binding using [(123)I]FP-CIT-SPET in 85 patients with Parkinson's disease (PD). We compared these two assessments and their correlation with PD clinical progression. SPET imaging was visually classified by a nuclear medicine physician as normal or abnormal pattern grade I, II and III, in relation to a different degree of radioligand reduction uptake. Nineteen patients presented abnormal grade I (group 1), 53 grade II (group 2) and 13 grade III (group 3). The UPDRS III motor score, the H-Y score, the rigidity and bradykinesia subscores were significantly different among the three groups. Post hoc analysis showed that all values of these clinical parameters were higher in group 3 than in 2 and 1. All clinical indices were also significantly higher in group 2 than in group 1. This means that groups 3 and 2 were clinically more severely affected. No significant differences among the 3 groups were observed for age or duration of disease. Values of the mean striatum uptake were also significantly different among the three groups. Post hoc analysis revealed significantly lower values of the mean striatum uptake in group 3 with respect to groups 2 and 1; values were also significantly lower in group 2 than in group 1. We conclude that our findings of good consistency between visual and semi-quantitative assessment may help simplify the evaluation of striatal DAT binding in PD in a clinical routine setting.

Aged↗
PubMed2006

Clinical and neuropsychological follow up at 12 months in patients with complicated Parkinson's disease treated with subcutaneous apomorphine infusion or deep brain stimulation of the subthalamic nucleus.

BACKGROUND: The clinical condition of advanced Parkinson's disease (PD) patients is often complicated by motor fluctuations and dyskinesias which are difficult to control with available oral medications. OBJECTIVE: To compare clinical and neuropsychological 12 month outcome following subcutaneous apomorphine infusion (APO) and chronic deep brain stimulation of the subthalamic nucleus (STN-DBS) in advanced PD patients. METHODS: Patients with advanced PD and medically untreatable fluctuations underwent either APO (13 patients) or STN-DBS (12 patients). All patients were clinically (UPDRS-III, AIMS, 12 h on-off daily) and neuropsychologically (MMSE, Hamilton-17 depression, NPI) evaluated at baseline and at 12 months. APO was discontinued at night. RESULTS: At 12 months APO treatment (74.78+/-24.42 mg/day) resulted in significant reduction in off time (-51%) and no change in AIMS. Levodopa equivalent medication doses were reduced from 665.98+/-215 mg/day at baseline to 470+/-229 mg/day. MMSE, NPI, and Hamilton depression scores were unchanged. At 12 months STN-DBS resulted in significant clinical improvement in terms of reduction in daily off time (-76%) and AIMS (-81%) as well as levodopa equivalent medication doses (980+/-835 to 374+/-284 mg/day). Four out of 12 patients had stopped oral medications. MMSE was unchanged (from 28.6+/-0.3 to 28.4+/-0.6). Hamilton depression was also unchanged, but NPI showed significant worsening (from 6.58+/-9.8 to 18.16+/-10.2; p<0.02). Category fluency also declined. CONCLUSIONS: Both APO and STN-DBS resulted in significant clinical improvement in complicated PD. STN-DBS resulted in greater reduction in dopaminergic medications and provided 24 h motor benefit. However, STN-DBS, unlike APO, appears to be associated with significant worsening on NPI resulting from long term behavioral problems in some patients.

Aged↗
PubMed2005

Parkinson's disease, chronic hydrocarbon exposure and striatal neuronal damage: a 1-H MRS study.

Several patients with Parkinson' s disease (PD) reveal an history of chronic exposure to hydrocarbon-solvents. Chronic exposure to hydrocarbon-solvents has been proposed as a risk factor for more severe forms of PD with earlier onset of symptoms and reduced response to dopaminergic therapy. A direct correlation between disease severity and exposure degree has been previously shown. Seven exposed PD patients (two with low degree exposure and five with high degree exposure), 10 unexposed PD patients matched for sex, age and Hoehn and Yahr scale (=3 in the "on" phase), and 10 unexposed PD patients matched for sex, age and l-dopa daily intake instead of disease severity (Hoehn and Yahr scale=3.5 in the "on" phase) were studied. Twenty normal subjects without previous exposure to hydrocarbon-solvents and matched for age and sex with HPD patients were studied for comparison. The purpose of the study was to assess neuronal degeneration in the striatum of exposed vs unexposed PD patients. The authors investigated whether neuronal damage/loss was detectable in the lentiform nucleus measuring N-acetylaspartate (NAA) levels by 1-H MRS. Multiple single voxel MRS water-suppressed spectra were obtained also from the white matter and the occipital lobe. NAA was normal in the lentiform nucleus of patients with low exposure as well as in patients with no exposure whereas it was decreased in PD patients with high degree exposure. White matter and occipital lobe NAA content was normal both in exposed and unexposed PD patients. Clinical expression is more severe in PD patients with previous high degree solvent exposure because of the associated post-synaptic damage of the nigro-striatal pathway.

Aged↗
PubMed2005

Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes.

OBJECTIVE: To assess the prevalence, nature, and associated phenotypes of PINK1 gene mutations in a large series of patients with early-onset (<50 years) parkinsonism. METHODS: The authors studied 134 patients (116 sporadic and 18 familial; 77% Italian) and 90 Italian controls. The whole PINK1 coding region was sequenced from genomic DNA; cDNA was analyzed in selected cases. RESULTS: Homozygous pathogenic mutations were identified in 4 of 90 Italian sporadic cases, including the novel Gln456Stop mutation; single heterozygous truncating or missense mutations were found in another 4 Italian sporadic cases, including two novel mutations, Pro196Leu and Gln456Stop. Pathogenic mutations were not identified in the familial cases. Novel (Gln115Leu) and known polymorphisms were identified with similar frequency in cases and controls. In cases carrying single heterozygous mutation, cDNA analysis detected no additional mutations, and revealed a major pathogenic effect at mRNA level for the mutant C1366T/Gln456Stop allele. All patients with homozygous mutations had very early disease onset, slow progression, and excellent response to l-dopa, including, in some, symmetric onset, dystonia at onset, and sleep benefit, resembling parkin-related disease. Phenotype in patients with single heterozygous mutation was similar, but onset was later. CONCLUSIONS: PINK1 homozygous mutations are a relevant cause of disease among Italian sporadic patients with early-onset parkinsonism. The role of mutations found in single heterozygous state is difficult to interpret. Our study suggests that, at least in some patients, these mutations are disease causing, in combination with additional, still unknown factors.

Adolescent↗
PubMed2005

Brain SPECT imaging in multiple system atrophy.

Clinical diagnosis of multiple system atrophy (MSA) relays on signs and symptoms that are often difficult to identify particularly at early stage. Indeed neuropathological studies have demonstrated that MSA is the first cause of misdiagnosis in a cohort of patients presenting with parkinsonian features. Dopamine transporter imaging (DAT) shows striatal decrements in both MSA and Parkinson's disease (PD) making it not sensitive for differential diagnosis. Studies of dopamine D2 receptors with IBZM may help revealing striatal degeneration but a large overlap exist particularly if PD patients with advanced disease are included. We have measured brain flow with technetium-99m ethyl cysteinate dimer (ECD-SPECT) in 36 MSA patients and compared it with 43 PD and 39 age-matched controls. Using Statistical Parametric Mapping (SPM99) we found areas of significant reduced perfusion in the striatum, brain stem and cerebellum in MSA compared to the other groups. We believe that ECD-SPECT imaging may offer significant advantages compared to other imaging techniques in the assessment of neuronal degeneration in MSA and may help the clinician in the diagnostic characterization of patients presenting with atypical parkinsonism.

Animals↗
PubMed2005

The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson's disease and originates from a common ancestor.

BACKGROUND: Mutations in the gene Leucine-Rich Repeat Kinase 2 (LRRK2) were recently identified as the cause of PARK8 linked autosomal dominant Parkinson's disease. OBJECTIVE: To study recurrent LRRK2 mutations in a large sample of patients from Italy, including early (<50 years) and late onset familial and sporadic Parkinson's disease. RESULTS: Among 629 probands, 13 (2.1%) were heterozygous carriers of the G2019S mutation. The mutation frequency was higher among familial (5.1%, 9/177) than among sporadic probands (0.9%, 4/452) (p<0.002), and highest among probands with one affected parent (8.7%, 6/69) (p<0.001). There was no difference in the frequency of the G2019S mutation in probands with early v late onset disease. Among 600 probands, one heterozygous R1441C but no R1441G or Y1699C mutations were detected. None of the four mutations was found in Italian controls. Haplotype analysis in families from five countries suggested that the G2019S mutation originated from a single ancient founder. The G2019S mutation was associated with the classical Parkinson's disease phenotype and a broad range of onset age (34 to 73 years). CONCLUSIONS: G2019S is the most common genetic determinant of Parkinson's disease identified so far. It is especially frequent among cases with familial Parkinson's disease of both early and late onset, but less common among sporadic cases. These findings have important implications for diagnosis and genetic counselling in Parkinson's disease.

Adult↗
PubMed2004

Pharmacological and PET studies in patient's with Parkinson's disease and a short duration-motor response: implications in the pathophysiology of motor complications.

Patients with Parkinson's disease (PD) and levodopa-induced motor complications experience a short-duration response (SDR) to levodopa which can be considered the basis of motor fluctuations. The SDR is characterized by reduced response duration, increased magnitude of the response and reduced latency to the peak effect. A short latency and a high magnitude are the most salient pharmacological features of the SDR. Its pathophysiology is not totally understood. The pharmacological characteristics of the motor response to apomorphine and their relationship with 6-[(18)F]fluoro-L-dopa (FDOPA) and [(11)C]raclopride (RACLO) uptake were studied in 9 patients with PD. Latency to peak effect was positively correlated with putaminal FDOPA uptake (p<0.05) and negatively correlated with RACLO uptake (P<0.05). A trend towards significance (p:0.06) between magnitude of the response and FDOPA uptake was found which were negatively correlated. Levodopa-induced dyskinesias were negatively correlated with FDOPA uptake (p<0.05) and a trend towards significance (positive correlation) with RACLO uptake was observed (p:0.07). These results suggest that both pre and postsynaptic mechanisms are involved in the origin of the SDR.

Adult↗
PubMed2004

Continuous apomorphine infusion (CAI) and neuropsychiatric disorders in patients with advanced Parkinson's disease: a follow-up of two years.

This study was performed to assess whether patients with Parkinson's disease (PD)develop cognitive and psychiatric impairments more frequently during therapy with continuous subcutaneous apomorphine infusion (CAI) compared to the standard oral treatment. Thirty consecutive PD patients with severe motor fluctuations were included. Of them, 12 patients received the CAI treatment, while the remaining 18 continued the treatment with oral dopaminergic drugs. The two groups were evaluated with neuropsychological,psychiatric and motor tests at baseline and after two years. The off-awake daily duration and the levodopa dosage were significantly reduced in the patients infused with apomorphine.In comparison with the baseline evaluation, the neuropsychiatric assessment did not change in either of groups at the follow-up, except for a significant improvement of mood in the CAI treated group.

Antiemetics↗
PubMed2004

Deep brain stimulation and its effect on sleep in Parkinson's disease.

Deep Brain Stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor complications whose condition can no longer be improved by adjustment of medical therapy. PD patients often report increased daily somnolence and night sleep abnormalities partially related to dopaminergic treatment. In a survey of 386 consecutive non-demented non-depressed PD patients seen in our clinic over a period of 3 months we found increased daily somnolence to be relatively uncommon in non-demented PD patients, although it may be associated with stable treatment with high dose dopamine agonists. Disease related factors seemed responsible for night sleep abnormalities. Because DBS of the subthalamic nucleus (STN) reduces motor disability, as well as total medication intake, one would expect a similar benefit on sleep abnormalities. Indeed, recent evidence suggests that chronic STN-DBS may improve sleep quality through increased nocturnal mobility and reduction of sleep fragmentation.

Brain↗
PubMed2003

123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in patients with Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy.

We used SPECT and the tracer (123)I-Ioflupane to measure dopamine transporter (DAT) binding in the caudate nucleus and the putamen of 70 patients with Parkinson's disease (PD), 10 with multiple system atrophy (MSA-P type), and 10 with progressive supranuclear palsy (PSP). Data were compared with 12 age-matched control subjects. We found significant reductions in mean striatal values in all three forms of parkinsonism. However, decrements were significantly greater in PSP (0.51+/-0.39, p<0.01) compared with MSA-P (0.70+/-0.33) and PD (0.95+/-0.38). No differences were found between MSA and PD. Putamen/caudate ratios were greater in PSP (0.83+/-0.12, p<0.01) than in PD (0.51+/-0.11), suggesting a more-uniform involvement of dopamine nerve terminals in both caudate nucleus and putamen. Our results confirm that DAT binding can provide an accurate and highly sensitive measure of dopamine degeneration. PSP patients may show a different pattern of neuronal loss compared with MSA and PD.

Aged↗
PubMed2003

Brain flow changes before and after deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) markedly improves motor symptoms and reduces medication needs in Parkinson's disease (PD) patients. However, its effect on brain function has remained unclear. We used SPECT and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the STN in 22 PD patients and 13 healthy controls. PD patients were divided into good and poor responders to DBS, if changes in "off" UPDRS motor scores after surgery were >60% or <40%, respectively. Statistical analysis was performed using the SPM99 software. At baseline, all PD patients showed significant perfusion reductions in cortical areas (premotor frontal, parietal, and occipital). After DBS, changes were normalized only in the good responders, while cortical defects in the poor responders were unchanged. No flow decrements were detected in basal ganglia and thalamus in both groups, suggesting that DBS does not have a "lesion-like" effect. We conclude that good surgery outcome is associated with normalization of cortical flow abnormalities in PD.

Case-Control Studies↗
PubMed2003

Continuous apomorphine infusion and neuropsychiatric disorders: a controlled study in patients with advanced Parkinson's disease.

The aim of this study was to assess whether patients with Parkinson's disease (PD) develop cognitive and psychiatric complications more frequently during prolonged therapy with continuous apomorphine infusion compared with standard oral treatment. Thirty consecutive PD patients with severe motor fluctuations were included in the study. Twelve patients accepted the treatment with subcutaneous continuous apomorphine infusion, while the remaining 18 preferred to continue with oral dopaminergic therapy. The two groups were evaluated with neuropsychological, psychiatric, and motor tests at baseline and after 1 year. The off daily duration and the levodopa dosage were significantly reduced in infused patients. The neuropsychiatric assessment did not change in both groups compared with baseline, except for a significant improvement of mood in the apomorphine group.

Aged↗
PubMed2003

Deep brain stimulation for the treatment of Parkinson's disease: the experience of the Neurosurgical Department in Monza.

deep brain stimulation is a widely accepted surgical therapy for the symptomatic treatment of advanced parkinson's disease; high frequency chronic stimulation of the subthalamic nucleus proved its efficacy to control the major motor symptoms. In the neurosurgical department of Monza we treated 72 parkinsonian patients (November 1998-January 2003). One year follow-up results are: decrease of tremor 90%, hypertonous 56%, bradykinesia 70%, voice impairment amelioration 30%, mean total daily L-dopa intake reduced 58%. Freezing and balance did not ameliorate, some voice impairment and psychic derangement have been observed. Major surgical complications were: haemorrage (1 case - transient hemiparesis), infections (2 cases), pulmonary embolisation (1 case). To optimise the surgical results, careful clinical and instrumental selection of the patients are mandatory before surgery.

Clinical Trials as Topic↗
PubMed2003

MRI indirect stereotactic targeting for deep brain stimulation in Parkinson's disease.

AIM: Stereotactic localisation of brain targets for functional neurosurgery might be obtained with different neuroimaging sources. Magnetic resonance (MR) might be of particular interest for its high definition of the various brain structures; unfortunately, magnetic field distortion and inaccuracy in imaging reproduction constrain the use of MRI in stereotactic surgery. METHODS: We present an experimental work devoted to the utilization of MRI in the targeting of the subthalamic nucleus for deep brain stimulation (DBS) in Parkinsonian patients. RESULTS: Experimental data were obtained after PVC phantom and fixed human brain measurements of the stereotactic coordinates of specific basal ganglia structures. Intrinsic and external sources of error and imaging distortion have been carefully corrected. Afterwards, 36 patients, operated for DBS in the subthalamus for Parkinson's disease (PD), have been investigated. MRI targeting proved to be clinically successful; comparing anatomical and neurophysiological findings, MRI targeting scattered from the neurophysiological targeting in a minority of cases. CONCLUSION: MRI targeting proved to be reliable for functional stereotactic surgery, pending careful and adequate quality control of the distortion and of the sources of error.

Aged↗
PubMed2003

Functional neuroimaging (PET and SPECT) in the selection and assessment of patients with Parkinson's disease undergoing deep brain stimulation.

Deep brain Stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor complications who can no longer be improved by adjustment of medical therapy. Selection of surgery candidates and follow-up after surgery are critical for good outcome. Functional neuroimaging can help in the clinical assessment of these patients. We have used single photon emission computed tomography (SPECT) and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the subthalamic nucleus (STN) in 20 patients with advanced PD. We found a significant increase in the anterior cingulate/supplementary motor cortex in the 12 good responders (change in off unified UPDRS >50%). Conversely, patients with poor response (n=8; change in off UPDRS-III <50% following DBS) revealed a significant worsening of cortical hypoperfusion particularly in the prefrontal areas. No flow decrements were detected in the basal ganglia and in the thalamus in both groups during DBS stimulation suggesting that DBS does not have a "lesion like" effect. If DBS stimulates and does not inactivate STN projection neurons, flow reduction in the poor responders may be secondary to increased inhibitory basal ganglia output.

Cerebrovascular Circulation↗