Antonio Epifanio

Quetiapine and clozapine in parkinsonian patients with dopaminergic psychosis.

ObjectiveThis study aimed to compare the efficacy and safety of quetiapine and clozapine in parkinsonian patients with dopaminergic psychosis in a randomized, open-label, blinded-rater, parallel group trial. MethodsForty-five patients with Parkinson disease (PD) and psychosis induced by antiparkinsonian drugs were randomly assigned to receive either quetiapine or clozapine. The duration of the trial was 12 weeks. Forty patients, 20 in each treatment group, completed the study. The final dose of quetiapine (mean ± SD) was 91 ± 47 mg/d and that of clozapine 26 ± 12 mg/d. The severity of psychosis was assessed using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression Scale–Severity Subscale (CGI-S). The Unified Parkinson’s Disease Rating Scale (UPDRS) III was used to assess motor conditions during the study period. The Abnormal Involuntary Movement Scale (AIMS) was performed to evaluate dyskinesias. ResultsForty patients, 20 on clozapine and 20 on quetiapine, completed the study. The psychopathologic state improved significantly (P < 0.001) from baseline in both treatment groups. No differences were found between clozapine and quetiapine at any assessment time. Motor conditions remained unchanged after clozapine and quetiapine. Dyskinesias decreased significantly (P < 0.05) in both groups. Side effects were mild, generally transient, and well tolerated. ConclusionsQuetiapine and clozapine appear equally efficacious for treatment of dopaminergic psychosis in patients with PD.

Risk of Parkinson disease in women Effect of reproductive characteristics

Objective: To investigate the association between some fertile life characteristics and Parkinson disease (PD) in women. Methods: Women affected by PD and control subjects were matched one to one by age (±2 years). One hundred thirty-one women with idiopathic PD and 131 matched control subjects were interviewed. Controls were randomly selected from the resident list of the same municipality of residence of cases. All subjects had a Mini-Mental State Examination score of ≥24. Cumulative length of pregnancies, age at menarche, age and type of menopause, and estrogen use before and after menopause were investigated in cases and controls through a structured questionnaire. Models of matched pair univariate analysis and conditional logistic regression analyses were used to calculate adjusted odds ratio (OR), 95% CI, and two-tailed p values for the investigated variables. Results: PD was significantly associated with a fertile life length shorter than 36 years (OR 2.07; 95% CI 1.00 to 4.30) and a cumulative length of pregnancies longer than 30 months (OR 2.19; 95% CI 1.22 to 3.91). An inverse association between PD and surgical menopause (adjusted OR 0.30; 95% CI 0.13 to 0.77) was also found. Conclusions: An association between factors reducing estrogen stimulation during life and PD was found. These results support the hypothesis that endogenous estrogens play a role in the development of PD.

Familial hemiplegic migraine type 2 is linked to 0.9Mb region on chromosome 1q23.

Familial hemiplegic migraine (FHM) is a rare autosomal dominant disorder characterized by episodes of transient hemiparesis followed by headache. Two chromosomal loci are associated to FHM: FHM1 on chromosome 19 and FHM2 on chromosome 1q21‐23. Mutations of the α‐1A subunit of the voltage gated calcium channel (CACNA1A) are responsible for FHM1. FHM2 critical region spans 28cM, hence hampering the identification of the responsible gene. Here, we report the FHM2 locus refining by linkage analysis on two large Italian families affected by pure FHM. The new critical region covers a small area of 0.9Mb in 1q23 and renders feasible a positional candidate approach. By mutation analysis, we excluded the calsequestrin and two potassium channel genes mapping within the narrowed FHM2 locus. Ann Neurol 2003

A Case-Control Study on Cigarette, Alcohol, and Coffee Consumption Preceding Parkinson’s Disease

Objective: To investigate the association between cigarette smoking, alcohol drinking, coffee consumption and Parkinson’s disease (PD). Methods: We selected subjects affected by idiopathic PD, with a Mini-Mental State Examination of ≧24, and controls matched 1 to 1 with cases by age (± 2 years) and sex. Controls were randomly selected from the resident list of the same municipality of residence of the cases. We assessed cigarette smoking, alcohol drinking, and coffee consumption preceding the onset of PD or the corresponding time for controls using a structured questionnaire, which also evaluated the duration and dose of exposure. Using conditional logistic regression analysis, we calculated adjusted OR and 95% CI. Results: We interviewed 150 PD patients and 150 matched controls. Cigarette smoking (ever vs. never smokers OR = 0.66, 95% CI = 0.41–1.05, p = 0.08) did not show a statistically significant association with PD. We observed an inverse association between alcohol drinking (ever vs. never OR = 0.61, 95% CI = 0.39–0.97, p = 0.037) and coffee consumption (ever vs. never OR = 0.16, 95% CI 0.05–0.46, p = 0.0001) and PD. These associations remained significant after adjustment for other covariates: OR for ever vs. never alcohol consumption was 0.62 (95% CI = 0.43–0.89, p = 0.009) and that for coffee drinking 0.19 (95% CI = 0.07–0.52, p = 0.001). Heavy coffee consumption confirmed the inverse association between coffee and PD (more than 81 cup/year vs. none: OR = 0.20, 95% CI = 0.08–0.47, p ≤ 0.0001). Conclusions: Consistent with previous studies, our results suggest an inverse association between coffee drinking, alcohol consumption and PD. The multiple inverse association observed may indicate a complex interaction between genetic and environmental factors.

Quetiapine versus clozapine: a preliminary report of comparative effects on dopaminergic psychosis in patients with Parkinson's disease.

Abstract. This study investigated the efficacy and safety of quetiapine versus clozapine in parkinsonian patients with dopaminergic psychosis. All patients fulfilling the inclusion criteria were randomly assigned to receive either quetiapine or clozapine. The duration of the trial was 12 weeks. The severity of psychosis was assessed using the BPRS and the Clinical Global Impression Scale-Severity subscale (CGI-S). The UPDRS III was used to monitor the progression of PD during the study period. Twenty patients, 10 on clozapine, and 10 on quetiapine, completed the study. The psychopathological state, as assessed by the BPRS and by the CGI-S, improved significantly (p<0.001) from baseline in both treatment groups. No differences were found between clozapine and quetiapine at each assessment time. The UPDRS score decreased significantly (p<0.05) in the clozapine group, while was almost unchanged in the quetiapine group.

The parkin gene is not involved in late-onset Parkinson’s disease

Mutations in the parkin gene have been reported in patients with early onset PD. The authors investigated the parkin gene in 118 patients who had an onset of PD after age 45 years: 95 subjects were sporadic patients and 23 subjects were from 18 families with a probable autosomal recessive inheritance. No pathogenetic mutations in the parkin gene were detected either in familial or in sporadic patients. Moreover, no differences were found between patients and 100 age-matched normal controls in the allele and genotype frequencies of four exonic parkin polymorphisms.

Ischaemic Stroke in Young People: A Prospective and Long-Term Follow-Up Study

Background: A few studies have comprehensively assessed the epidemiology, aetiology, prognosis, and secondary prevention of ischaemic stroke in young adults. To gain further information on this field, we have prospectively studied a hospital-based series of young adults with a first-ever episode of cerebral ischaemia (CI). Methods: Sixty consecutive patients aged 17–45 with ischaemic stroke (55 patients) or transient ischaemic attack within 24 h before hospital admission were recruited and investigated by a standardized rigorous protocol. The patients were followed up for ≧1 year after hospital discharge. Arbitrary doses of aspirin 100 mg/d or ticlopidine 250 mg b.i.d. in case of intolerance to aspirin were given for the secondary prevention. Adjusted-dose oral anticoagulation (INR target 2.5) was used in the presence of cardioembolism or hypercoagulable states. Endpoints included the residual disability, rated by modified Rankin Scale (RS) and Barthel Index (BI), and poststroke recurrence. Results: CI was associated with two or more risk factors in 61.6% of patients. Cigarette smoking was more frequently associated with male gender (p < 0.05) and migraine history with female sex (p < 0.05). The atherothrombotic diagnostic subtype and the subtype from ‘other cause’ predominated significantly among patients ≧35 years old (p < 0.05) and <35 years (p < 0.025), respectively. The ‘other cause’ subset was more frequent in female gender (p < 0.05). Transoesophageal echocardiography (TEE) detected potential cardiac sources of emboli (PCSE) at an extent 3 times higher (p < 0.0001) than transthoracic echocardiography. Congenital heart defects were nearly threefold more frequent than acquired ones, with a prevalence of patent foramen ovale. At a mean of 6.1 ± 2.6 years (confidence interval 5.4 to 6.8), follow-up data were available for only 54 patients, since five patients were lost and one died in the acute phase. Poststroke recurrence rate was low (7.4%) and no event was fatal. General handicap was severe to moderately severe (RS>3) in 11% of the patients, slight to moderate (1≧RS≤3) in 59% and absent in 30% (RS = 0). Functional disability was relatively low with 50% of the patients independent (BI ≧95), 38.9% partially dependent (BI 60 to 86), and 11.1% fully dependent (BI <60). Thirty-seven (68.5%) patients returned to work, although adjustments (other job or part-time employment) were necessary for 10 out of them (27%). Conclusions: The present study, though limited by the relatively small number of subjects, suggests that the overall prognosis of ischaemic stroke in young adults is good. We strongly recommend TEE in all patients with ischaemic stroke as an essential tool to increase the detection of PCSE and make the therapeutic approach more efficient.

Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA): Design of a Prospective, Multicenter Trial of Diagnostic Tests

Background and Relevance: Intracranial atherosclerosis is responsible for 70,000 ischemic strokes each year in the USA. Noninvasive testingsuch as transcranial Doppler ultrasound (TCD) and magnetic resonance angiography (MRA) to identify intracranial atherosclerosis is in widespread use, but has not been rigorously validated against the gold standard, catheter angiography. The recently NIH-funded Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial will compare warfarin with aspirin for stroke prevention in patients with intracranial atherosclerosis. WASID requires performance of angiography along with TCD and MRA, providing an opportunity to critically evaluate these noninvasive tests. Main Objective: The purpose of the Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) study is to develop the noninvasive diagnosis of intracranial atherosclerosis. The primary aim of SONIA is to define velocity values on TCD and anatomic abnormalities on MRA that identify severe (50–99%) intracranial stenosis of large, proximal arteries seen on catheter angiography. SONIA will define the criteria, or ‘cutpoints’, for an abnormal TCD or MRA and show that they perform with a reliable positive predictive value (PPV). Study Design: SONIA will be conducted in collaboration with WASID. Study-wide cutpoints defining positive TCD and MRA have been developed and reviewed by the site investigators of WASID. Hard copy angiography, TCD and MRA generated in WASID will be centrally read in SONIA. TCD and MRA cutpoints seek to achieve a target PPV of 80% for the identification of severe intracranial stenosis on angiography. Conclusions: Central readings will be used to validate the cutpoints and to develop measures of negative predictive value, and inter- and intra-observer variability. Sensitivity and specificity will be determined after adjustment for verification bias and employed in receiver-operator characteristic analyses. SONIA will use these techniques to develop TCD and MRA cutpoints that minimize the clinical consequences of test errors occurring in the noninvasive evaluation of patients with suspected intracranial atherosclerosis.

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

Abstract.The aim of this study was to asses 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.

Tumor diagnosis preceding Parkinson's disease: a case-control study.

Lower cancer risk in Parkinsons disease (PD) patients compared to the general population has been reported. However, most of the studies were based on death certificates. We designed a case–control study to estimate the association of tumor preceding PD onset and PD. PD patients were matched by age and gender to PD‐free individuals, randomly selected from the municipalities of residence of cases. Occurrence of tumors preceding PD onset was assessed through a structured questionnaire. Neoplasms were categorized as benign, malignant, or of uncertain classification, and endocrine‐related or not. Odds ratios (OR) were calculated using conditional logistic regression and adjusted for tumor categories and risk factors. We included 222 PD patients. Frequency of cancer was 6.8% for cases, 12.6% for controls. PD patients had a decreased risk for neoplasms (adjusted OR, 0.4; 95% confidence interval [CI], 0.2–0.7). Risk was reduced only for women (adjusted OR, 0.3; 95% CI, 0.1–0.7). PD patients had a decreased risk both for malignant (adjusted OR, 0.6; 95% CI, 0.1–2.5) and nonmalignant neoplasms (adjusted OR, 0.3; 95% CI, 0.1–0.7). Still, risk was decreased for endocrine‐related tumors (adjusted OR, 0.3; 95% CI, 0.1–0.9) and non–endocrine‐related tumors (adjusted OR, 0.4; 95% CI, 0.1–0.9). Our study confirms the inverse association between PD and neoplasms reported in previous epidemiologic studies.