Thrombolysis in elderly stroke patients in Italy (TESPI) trial and updated meta-analysis of randomized controlled trials.

BACKGROUND: Since its approval, the use of alteplase had been limited to patients aged ≤80 years. AIMS: TESPI trial had been designed to evaluate whether alteplase treatment within 3 h in patients with acute ischemic stroke aged >80 years resulted in favorable benefit/risk ratio compared with standard care. The meta-analysis of randomized controlled trials was updated to put findings in the context of all available evidence. METHODS: TESPI was a multicenter, open-label with blinded outcome evaluation, randomized, controlled trial. Main clinical endpoints were 90-day favorable functional outcome (mRS score 0-2) and mortality and symptomatic intracerebral hemorrhage. The trial was prematurely terminated for ethical reasons after publication of IST-3 trial which provided evidence of treatment benefit in elderly. RESULTS: Of the planned 600 patients, 191 (88 assigned to alteplase) were enrolled. Overall, 24/83 (28.9%) alteplase patients had a favorable outcome compared to 22/95 (23.2%) controls (non-significant absolute difference of 5.7% for alteplase; OR 1.35, 95% CI 0.69-2.64, P = 0.381). Rates of death were non-significantly lower in the alteplase patients (18.1% vs. 26.5%); rates of symptomatic intracerebral hemorrhage were similar between the two groups (5.9% vs. 5.1%). The updated meta-analysis showed consistent results with prior estimates and add weights. CONCLUSIONS: The effects of alteplase observed in this interrupted trial did not reach statistical significance, probably for the small numbers, but are consistent with and add weight to the sum total of the randomized evidence demonstrating that alteplase is beneficial in patients with acute ischemic stroke aged over 80 years, particularly if given within 3 h.

Extended release levodopa at bedtime as a treatment for nocturiain Parkinson's disease: An open label study.

BACKGROUND: Bladder dysfunction may cause disabling symptoms in Parkinson's disease (PD) patients. The majority patients' experience symptoms as urinary urgency and nocturia suggest overactive bladder. This seems to be due to an altered brain-bladder relationship because of alteration in fronto-basal ganglia D1-dopaminergic circuit that normally suppresses micturition-reflex. Previous studies demonstrated beneficial effect of D1/D2 dopamine-receptors chronic-stimulation on detrusor overactivity of PD-patients.The present study was aimed to evaluate possible effect of extended-release (ER) Levodopa administered at bed-time on both nocturia and nocturia-related quality-of-life (NQoL) in PD-patients. METHODS: 106 PD-patients (Hoehn and Yahr>1 and < 4, mean age 66 years, 59 females and 47 males) were enrolled by 7 Movement Disorders out-patients clinics. Patients undergo to International Prostatic Symptoms Scale-IPSS, including 1-item about nocturia (item 7), and to Nocturia Quality of Life-NQoL questionnaire, at baseline and after two-months of Extended-Release L-dopa (L-dopa/carbidopa or L-dopa benserazide) treatment at bed-time. RESULTS: Statistical analysis showed significant improvement on both total IPSS, item 7and NQoL scores following two-months ER L-dopa-treatment. ΔIPSS score inversely correlated with disease duration. CONCLUSIONS: This results support previous evidence of pathophysiological involvement of dopaminergic transmission on bladder dysfunction in PD.

Risk factors for impulse control disorders and related behaviors in Parkinson's disease: secondary analyses of the ICARUS study.

Objective: Impulse control disorders and related behaviors (ICDs) are common in patients with Parkinson's disease (PD), yet incidence and predictive factors are not fully understood. We examined the epidemiology of ICDs in PD through secondary and post-hoc analyses of data from the ICARUS (SP0990) study, which enrolled >1000 patients. Methods: Using a modified-Minnesota Impulsive Disorders Interview (mMIDI), ICD incidence was calculated for patients who were ICD-negative at baseline but ICD-positive at year 1, and year 1 and/or 2 (cumulative 2-year ICD incidence). The proportion of "new cases" (ICD-negative at baseline, but ICD-positive at year 1 or 2), and "remitters" (ICD-positive at baseline but ICD-negative at year 1 or 2) was also calculated for the whole ICARUS population. Results: Among 709 patients ICD-negative at baseline, 97 screened ICD-positive (13.7%) at year 1. Among 712 patients who were ICD-negative at baseline, 147 were ICD-positive at ≥1 post-baseline visit (20.6%). Among patients who were ICD-negative at baseline who subsequently experienced an ICD, a higher proportion were male or smokers, younger at baseline, younger at disease/symptom onset, and had longer disease duration. Among the whole population, a similar proportion were "new cases" at years 1 (9.7%) and 2 (8.6%) versus the previous visit. The proportion of "remitters" was slightly higher at year 2 (11.0%) than 1 (9.1%) versus previous visit. Conclusions: The proportion of ICD-remitters approximately matched/exceeded new cases, suggesting patients with ICD are in a state of flux. Current data allow for a conservative estimate of 2-year ICD incidence in ICARUS of ∼21% of patients, not accounting for transient new ICD cases between visits.

Levodopa-induced dyskinesia in Parkinson disease: Sleep matters.

OBJECTIVE: The spectrum of clinical symptom changes during the course of Parkinson disease (PD). Levodopa therapy, while offering remarkable control of classical motor symptoms, causes abnormal involuntary movements as the disease progresses. This levodopa-induced dyskinesia (LID) has been associated with abnormal cortical plasticity. Because slow wave activity (SWA) of nonrapid eye movement (NREM) sleep underlies adjustment of cortical excitability, we sought to elucidate the relationship between this physiological process and LID. METHODS: Thirty-six patients at different stages of PD underwent whole-night video polysomnography-high-density electroencephalography (vPSG-hdEEG), preceded by 1 week of actigraphy. To represent the broad spectrum of the disease, patients were divided into 3 groups by disease stage-(1) de novo (n = 9), (2) advanced (n = 13), and (3) dyskinetic (DYS; n = 14)-were compared to an age-matched control group (n = 12). The SWA-NREM content of the vPSG-hdEEG was then temporally divided into 10 equal parts, from T1 to T10, and power and source analyses were performed. T2-T3-T4 were considered early sleep and were compared to T7-T8-T9, representing late sleep. RESULTS: We found that all groups, except the DYS group, manifested a clear-cut SWA decrease between early and late sleep. INTERPRETATION: Our data demonstrate a strong pathophysiological association between sleep and PD. Given that SWA may be a surrogate for synaptic strength, our data suggest that DYS patients do not have adequate synaptic downscaling. Further analysis is needed to determine the effect of drugs that can enhance cortical SWA in LID. Ann Neurol 2018;84:905-917.

Is there a correlation between urological and cardiovascular dysfunction in Parkinson's disease?

It is well established that non-motor symptoms are a core feature of Parkinson's disease (PD). A dysregulation of the autonomic nervous system seems to be present in PD, supporting the coexistence of urological and cardiovascular non-motor features. We evaluated whether bladder dysfunctions in patients with PD are linked to blood pressure dysregulation. Twenty-eight mild PD patients, previously submitted to a urodynamic evaluation, underwent 24-hour ambulatory blood pressure and heart rate monitoring to allow assessment of their circadian blood pressure profile; the occurrence of postprandial hypotension and orthostatic hypotension was also investigated. No significant differences in blood pressure control were detected between bladder hyperreflexic and normoreflexic subjects. Our findings support different origins of urological and cardiovascular impairments in PD.

Endovascular Stroke Treatment of Acute Tandem Occlusion: A Single-Center Experience.

PURPOSE: To evaluate outcomes and prognostic factors in patients with acute ischemic stroke caused by tandem internal carotid artery/middle cerebral artery occlusion undergoing endovascular treatment. MATERIALS AND METHODS: Characteristics of consecutive patients with tandem occlusion (TO) were extracted from a prospective registry. Collateral vessel quality on pretreatment computed tomographic (CT) angiography was evaluated on a 4-point grading scale, and patients were dichotomized as having poor or good collateral flow. Outcome measures included successful reperfusion according to Thrombolysis In Cerebral Infarction score, good outcome at 3 months defined as a modified Rankin scale score ≤ 2, symptomatic intracranial hemorrhage (ICH; sICH), and mortality. RESULTS: A total of 72 patients with TO (mean age, 65.6 y ± 12.8) were treated. Intravenous thrombolysis was performed in 54.1% of patients, and a carotid stent was inserted in 48.6%. Successful reperfusion was achieved in 64% of patients, and a good outcome was achieved in 32%. sICH occurred in 12.5% of patients, and the overall mortality rate was 32%. Univariate analysis demonstrated that good outcome was associated with good collateral flow (P = .0001), successful reperfusion (P = .001), and lower rate of any ICH (P = .02) and sICH (P = .04). On multivariate analysis, good collateral flow (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.04-0.75; P = .01) and age (OR, 1.08; 95% CI, 1.01-1.15; P = .01) were the only predictors of good outcome. The use of more than one device for thrombectomy was the only predictor of sICH (OR, 10.74; 95% CI, 1.37-84.13; P = .02). CONCLUSIONS: Endovascular treatment for TO resulted in good outcomes. Collateral flow and age were independent predictors of good clinical outcomes at 3 months.

ICARUS study: prevalence and clinical features of impulse control disorders in Parkinson's disease.

BACKGROUND: Impulse control disorders/other compulsive behaviours ('ICD behaviours') occur in Parkinson's disease (PD), but prospective studies are scarce, and prevalence and clinical characteristics of patients are insufficiently defined. OBJECTIVES: To assess the presence of ICD behaviours over a 2-year period, and evaluate patients' clinical characteristics. METHODS: A prospective, non-interventional, multicentre study (ICARUS (Impulse Control disorders And the association of neuRopsychiatric symptoms, cognition and qUality of life in ParkinSon disease); SP0990) in treated Italian PD outpatients. Study visits: baseline, year 1, year 2. Surrogate primary variable: presence of ICD behaviours and five ICD subtypes assessed by modified Minnesota Impulsive Disorder Interview (mMIDI). RESULTS: 1069/1095 (97.6%) patients comprised the Full Analysis Set. Point prevalence of ICD behaviours (mMIDI; primary analysis) was stable across visits: 28.6% (306/1069) at baseline, 29.3% (292/995) at year 1, 26.5% (245/925) at year 2. The most prevalent subtype was compulsive eating, followed by punding, compulsive sexual behaviour, gambling and buying disorder. Patients who were ICD positive at baseline were more likely to be male, younger, younger at PD onset, have longer disease duration, more severe non-motor symptoms (including mood and sexual function), depressive symptoms, sleep impairment and poorer PD-related quality of life. However, they did not differ from the ICD-negative patients in their severity of PD functional disability, motor performance and cognitive function. CONCLUSIONS: Prevalence of ICD behaviours was relatively stable across the 2-year observational period. ICD-positive patients had more severe depression, poorer sleep quality and reduced quality of life.

Rotigotine Effects on Bladder Function in Patients with Parkinson's Disease.

BACKGROUND: The objective of this study was to assess the effect of rotigotine treatment on bladder function in patients with Parkinson's disease (PD) who have urinary urgency. METHODS: in total, 20 patients with PD underwent urodynamic evaluation and completed International Prostate Symptoms questionnaires in off-rotigotine condition and after 3 months of rotigotine patch monotherapy administration. In both sessions, clinical motor condition was evaluated with the Unified Parkinson Disease Rating Scale, Part III (motor part). RESULTS: Rotigotine administration significantly ameliorated the first sensation of bladder filling, the neurogenic detrusor overactive contractions threshold and bladder capacity compared with the off-treatment condition. Moreover, the total score on the International Prostate Symptoms questionnaire revealed a decrease of filling (irritative) symptoms after rotigotine treatment compared with the off-treatment condition. CONCLUSION: The positive effects of rotigotine may be due to its balanced agonism to D1 and D2 receptors and in particular to its stimulation of D1 receptors in the anterior cingulate cortex and insula, which are known as areas involved in bladder-inhibitory functions.

CT angiography-based collateral flow and time to reperfusion are strong predictors of outcome in endovascular treatment of patients with stroke.

BACKGROUND: Collateral flow (CF) is an effective predictor of outcome in acute ischemic stroke (AIS) with potential to sustain the ischemic penumbra. However, the clinical prognostic value of CF in patients with AIS undergoing mechanical thrombectomy has not been clearly established. We evaluated the relationship of CF with clinical outcomes in patients with large artery anterior circulation AIS treated with mechanical thrombectomy. METHODS: Baseline collaterals of patients with AIS (n=135) undergoing mechanical thrombectomy were independently evaluated by CT angiography (CTA) and conventional angiography and dichotomized into poor and good CF. Multivariable analyses were performed to evaluate the predictive effect of CF on outcome and the effect of time to reperfusion on outcome based on adequacy of the collaterals. RESULTS: Evaluation of CF was consistent by both CTA and conventional angiography (p<0.0001). A higher rate of patients with good collaterals had good functional outcome at 3-month follow-up compared with those with poor collaterals (modified Rankin Scale (mRS) 0-2: 60% vs 10%, p=0.0001). Patients with poor collaterals had a significantly higher mortality rate (mRS 6: 45% vs 8%, p=0.0001). Multivariable analyses showed that CF was the strongest predictor of outcome. Time to reperfusion had a clear effect on favorable outcome (mRS ≤2) in patients with good collaterals; in patients with poor collaterals this effect was only seen when mRS ≤3 was considered an acceptable outcome. CONCLUSIONS: CTA is a valid tool for assessing the ability of CF to predict clinical outcome in patients with AIS treated with mechanical thrombectomy. Limiting time to reperfusion is of definite value in patients with good collaterals and also to some extent in those with poor collaterals.

Subthalamic stimulation and levodopa modulate cortical reactivity in Parkinson's patients.

BACKGROUND: The effects of deep brain stimulation of the subthalamic nucleus (DBS-STN) and L-dopa (LD) on cortical activity in Parkinson's disease (PD) are poorly understood. OBJECTIVES: By combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) we explored the effects of STN-DBS, either alone or in combination with L-Dopa (LD), on TMS-evoked cortical activity in a sample of implanted PD patients. METHODS: PD patients were tested in three clinical conditions: i) LD therapy with STN-DBS turned on (ON/ON condition); ii) without LD therapy with STN-DBS turned on (OFF/ON condition); iii) without LD therapy with STN-DBS turned off (OFF/OFF condition). TMS pulses were delivered over left M1 while simultaneously acquiring EEG. Eight age-matched healthy volunteers (HC) were tested as a control group. RESULTS: STN-DBS enhanced early global TMS-evoked activity (∼45-80ms) and high-alpha TMS-evoked oscillations (11-13 Hz) as compared to OFF/OFF condition, independently from concomitant LD therapy. LD intake (ON/ON condition) produced a further increase of late TMS-evoked activity (∼80-130ms) and beta TMS-evoked oscillations (13-30 Hz), as compared to OFF/OFF and OFF/ON conditions, that normalized reactivity as compared to HC range of values. CONCLUSIONS: Our data reveal that bilateral STN-DBS and LD therapy induce a modulation of specific cortical components and specific ranges of frequency. These findings demonstrate that STN-DBS and LD therapy may have synergistic effects on motor cortical activity.

Rotigotine may improve sleep architecture in Parkinson's disease: a double-blind, randomized, placebo-controlled polysomnographic study.

BACKGROUND/OBJECTIVES: Growing evidence demonstrates that in Parkinson's Disease (PD) sleep disturbances are frequent and difficult to treat. Since the efficacy of rotigotine on sleep is corroborated by studies lacking polysomnography (PSG), this study explores the possible rotigotine-mediated impact on PSG parameters in PD patients. METHODS: This is a randomized, double-blind, placebo-controlled, parallel-group study to determine the efficacy of rotigotine vs placebo on PSG parameters in moderately advanced PD patients. An unusual protocol was utilized, since patches were maintained from 18:00 h to awakening, minimizing the possible diurnal impact on motor symptoms. All participants underwent sleep PSG recordings, subjective sleep questionnaires (Parkinson Disease Sleep Scale [PDSS], Pittsburgh Sleep Quality Index [PSQI]), and the assessment of early-morning motor disability. RESULTS: We evaluated 42 PD patients (Hoehn & Yahr stages 2 and 3) with sleep impairment randomly assigned to active branch (N =21) or placebo (N = 21). Rotigotine significantly increased sleep efficiency and reduced both wakefulness after sleep onset and sleep latency compared to placebo. Moreover, the mean change in REM sleep quantity was significantly higher in the rotigotine than placebo group. The improvement of PSG parameters corresponded to the amelioration of PDSS and PSQI scores together with the improvement of patient morning motor symptoms. CONCLUSIONS: This study demonstrated the significant effect of rotigotine on sleep quality and continuity in PD patients by promoting sleep stability and increasing REM. The effectiveness of rotigotine on sleep may be ascribed to its pharmacokinetic/pharmacodynamic profile directly on both D1 and D2 receptors.

Proposal for a Vascular Computed Tomography-Based Grading System in Posterior Circulation Stroke: A Single-Center Experience.

OBJECTIVE: The aim of this study is to investigate the role of a computed tomography angiography (CTA)-based approach in patients undergoing mechanical thrombectomy for vertebrobasilar stroke treatment. METHODS: A CTA and digital subtraction angiography (DSA) retrospective analysis of patients with acute vertebrobasilar stroke treated with thrombectomy was performed. A modified Rankin Scale score of 3 or lower at 3 months was considered as favorable outcome. The posterior circulation ASPECTS (pc-ASPECTS) was evaluated on CTA and vertebrobasilar segments involved in the occlusion were assessed using a 6-point posterior circulation computed tomography angiography (pc-CTA) vascular score aimed at evaluating the posterior circulation vascular pattern including collaterals. The primary end point was the correlation between pc-CTA and outcome; secondary end points included the concordance between CTA-DSA images and the correlation between pc-ASPECTS and outcome. RESULTS: Fifteen patients with vertebrobasilar stroke were retrospectively analyzed. All patients in coma showed a bad outcome (P = .01) and all patients with an alert state showed a good outcome (P = .004). An excellent interobserver agreement for pc-CTA (P = .001) was observed with poor interobserver agreement for pc-ASPECTS (P = .21). No significant correlations between pc-ASPECTS and clinical outcome were observed. Patients with good outcome had a lower pc-CTA (P = .02). The patency of the distal third of the basilar artery and both posterior cerebral arteries was related with good outcome. CONCLUSION: The pc-CTA seems to have prognostic value in patients with vertebrobasilar stroke undergoing mechanical thrombectomy. It may be used as an additional prognostic triage technique in this subgroup of stroke patients.

An investigation of hearing impairment in de-novo Parkinson's disease patients: A preliminary study.

OBJECTIVE: To investigate the peripheral auditory pathway in Parkinson's disease (PD) by using objective, quantitative and non-invasive audiological techniques, transient-evoked (TEOAE) and distortion product (DPOAE) otoacoustic emissions, in order to detect subclinical alterations of cochlear functioning and possible changes after dopaminergic stimulation. METHODS: We enrolled 11 untreated de-novo PD patients and 11 age and sex-matched healthy controls. Subjects underwent a routine audiological evaluation and otoacoustic emission recordings. The patients were then slowly-titrated to a stable dose of 100 mg levodopa four times in a day. A post-treatment assessment was made in order to detect significant changes in audiological responses. Finally, possible associations between clinical data and hearing results were also evaluated. RESULTS: At pure-tone audiometry, higher auditory threshold levels were observed in PD when compared to the controls. Moreover, DPOAE responses in PD patients were found low at almost all tested frequencies, suggesting subclinical cochlear damage. Interestingly, after dopaminergic treatment, a significant increase in DPOAE responses was detected. Notably, DPOAE dysfunction correlated with clinical severity, whereas high hearing thresholds appeared positively related with more prolonged disease duration. CONCLUSIONS: Our findings demonstrate that otoacoustic emission recording and pure-tone audiometry reveal levodopa-sensitive cochlear dysfunction and hearing loss in PD. A parallel improvement in subjective motor symptoms and DPOAE objective responses could help clinicians in monitoring therapeutic responses and dynamic changes during the course of the disease.

Evidence of an association between sleep and levodopa-induced dyskinesia in an animal model of Parkinson's disease.

Levodopa-induced dyskinesia (LID) represents a major challenge for clinicians treating patients affected by Parkinson's disease (PD). Although levodopa is the most effective treatment for PD, the remodeling effects induced by disease progression and the pharmacologic treatment itself cause a narrowing of the therapeutic window because of the development of LID. Although animal models of PD provide strong evidence that striatal plasticity underlies the development of dyskinetic movements, the pathogenesis of LID is not entirely understood. In recent years, slow homeostatic adjustment of intrinsic excitability occurring during sleep has been considered fundamental for network stabilization by gradually modifying plasticity thresholds. So far, how sleep affects on LID has not been investigated. Therefore, we measured synaptic downscaling across sleep episodes in a parkinsonian animal model showing dyskinetic movements similar to LID. Our electrophysiological, molecular, and behavioral results are consistent with an impaired synaptic homeostasis during sleep in animals showing dyskinesia. Accordingly, sleep deprivation causes an anticipation and worsening of LID supporting a link between sleep and the development of LID.

Long-term results of drug-eluting balloon angioplasty for treatment of refractory recurrent carotid in-stent restenosis.

PURPOSE: To evaluate the potential role, safety, and efficacy of paclitaxel-eluting balloon angioplasty for treatment of recurrent carotid in-stent restenosis (ISR). METHODS: Among 856 consecutive patients who underwent carotid artery stenting from May 2002 to January 2008, 41 patients had a significant ISR (>80% stenosis). Of these, 9 patients (7 women; mean age 78.1±5.6 years) had recurrent ISR despite multiple endovascular treatments (3.4±0.9 interventions) within a short period of time (2-5 months). These patients were treated with drug-eluting balloon (DEB) angioplasty for neointimal hyperplasia. Imaging (ultrasound or computed tomographic angiography) was performed at 1, 3, and 6 months and yearly thereafter. RESULTS: Technical success was obtained in 100% of cases, with angiographic stenosis decreasing from 87%±4% to 6%±4% post treatment. Peak systolic velocity decreased significantly from 4.7±1.5 m/s to 0.6.±0.3 m/s after the procedure. Over a mean follow-up of 36.6±2.7 months, ultrasound imaging indicated recurrent ISR in only 3 patients at 18, 25, and 32 months after DEB angioplasty, respectively. The target vessel revascularization rate was 33.3% at 36 months. No neurological or myocardial events were recorded during follow-up. One patient died at 3 months. CONCLUSION: DEB may have a potential role improving outcomes of those patients treated for early recurrent carotid ISR.

Increased common carotid artery wall thickness is associated with rapid progression of asymptomatic carotid stenosis.

BACKGROUND AND PURPOSES: This study aimed to identify clinical and ultrasound imaging predictors of progression of carotid luminal narrowing in subjects with asymptomatic moderate internal carotid artery (ICA) stenosis. METHODS: A total of 571 subjects with asymptomatic moderate (50-69%) ICA stenoses were enrolled. They underwent ultrasound examination at baseline and after 12 months. Demographics, vascular risk factors, medications, plaque characteristics (surface and echogenicity) and common carotid intima-media thickness (IMT) were collected. At the follow-up examination, any change of ICA stenosis was graded in three categories (i) ≥70% to near occlusion, (ii) near occlusion, and (iii) occlusion. Progression of stenosis was defined as an increase in the stenosis degree by at least one category from baseline to follow-up. RESULTS: At 12 months, progression occurred in 142 subjects (prevalence rate 25%). At the multivariable logistic model, pathological IMT values (considered as binary variable: normal: ≤1 mm vs. pathologic: >1 mm) significantly predicted the risk for plaque progression after adjusting the model for possible confounders (OR 2.28, 95% CI 1.18-4.43, P = .014, multivariable logistic model). CONCLUSIONS: Our results confirm the role of carotid wall thickening as a marker of atherosclerosis. Carotid IMT measurement should be considered to implement risk stratification in patients with asymptomatic carotid disease.

Two-year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson's disease.

In a 6-month double-blind, placebo-controlled study of Parkinson's disease patients with motor fluctuations, safinamide 50 and 100 mg/d significantly increased ON-time without increasing dyskinesia. Further long-term safinamide use in these patients was evaluated over an additional 18 months. Patients continued on their randomized placebo, 50, or 100 mg/d safinamide. The primary endpoint was change in Dyskinesia Rating Scale total score during ON-time over 24 months. Other efficacy endpoints included change in ON-time without troublesome dyskinesia, changes in individual diary categories, depressive symptoms, and quality of life measures. Change in Dyskinesia Rating Scale was not significantly different in safinamide versus placebo groups, despite decreased mean total Dyskinesia Rating Scale with safinamide compared with an almost unchanged score in placebo. Ad hoc subgroup analysis of moderate to severe dyskinetic patients at baseline (36% of patients) showed a decrease with safinamide 100 mg/d compared with placebo (P = 0.0317). Improvements in motor function, activities of daily living, depressive symptoms, clinical status, and quality of life at 6 months remained significant at 24 months. Adverse events and discontinuation rates were similar with safinamide and placebo. This 2-year, controlled study of add-on safinamide in mid-to-late Parkinson's disease with motor fluctuations, although not demonstrating an overall difference in dyskinesias between patients and controls, showed improvement in dyskinesia in patients at least moderately dyskinetic at baseline. The study additionally demonstrated significant clinical benefits in ON-time (without troublesome dyskinesia), OFF-time, activities of daily living, motor symptoms, quality of life, and symptoms of depression.

Do CSF levels of t-Tau, p-Tau and ß1₋42 amyloid correlate with dopaminergic system impairment in patients with a clinical diagnosis of Parkinson disease? A ¹²³I-FP-CIT study in the early stages of the disease.

PURPOSE: To investigate the relationships among cerebrospinal fluid (CSF) levels of t-Tau, p-Tau and Aß1₋42 amyloid peptide and (123)I-FP-CIT uptake. METHODS: The study included 58 subjects (31 men and 27 women, age 67 ± 9 years) with a clinical diagnosis of Parkinson disease diagnosed according to the United Kingdom Parkinson Disease Society Brain Bank criteria. All subjects underwent a CSF assay 28 ± 3 days before (123)I-FP-CIT SPECT scanning. The relationships were evaluated by means of linear regression analysis and Pearson correlation. RESULTS: Striatal (123)I-FP-CIT was positively related to both t-Tau and p-Tau CSF values with low levels of t-Tau and p-Tau being related to a low uptake of (123)I-FP-CIT. In particular, differences with higher statistical significance were found for the striatum that is contralateral to theside mainly affected on clinical examination (P<0.001) [corrected].No significant relationships were found between Aß1₋42 amyloid peptide and (123)I-FP-CIT binding. CONCLUSION: The results of our study suggest that the presynaptic dopaminergic system is more involved in Parkinson disease patients with lower t-Tau and p-Tau CSF values while values of Aß1₋42 amyloid peptide seems not to be related to nigrostriatal degeneration in our series.