Cortical metabolic changes and clinical outcome in normal pressure hydrocephalus after ventriculoperitoneal shunt: Our preliminary results. / Cambios metabólicos corticales y resultado clínico en la hidrocefalia normotensiva después de la derivación ventrículo-peritoneal: nuestros resultados preliminares.

INTRODUCTION: Our objective was to evaluate the cortical metabolic changes and clinical outcome in patients affected by idiopathic normal pressure hydrocephalus (iNPH) after a placement of ventriculoperitoneal (VP) shunt. MATERIALS AND METHODS: 10 patients affected by suspected iNPH underwent a CSF hydrodynamics evaluation based on a lumbar infusion test (LIT). The main selection criterion for surgery was based on intracranial elasticity (IE)>0.30. All subjects with an IE>0.30 underwent a PET scan with 18 fluorodeoxiglucose (18F-FDG) at baseline (PET1) and 1 month after surgery (PET2). Furthermore, the same patients were submitted to clinical evaluation before and 1 month after surgery through neuropsychological tests and gait analysis. RESULTS: An overall number of 20 18F-FDG PET scans were performed in all the enrolled patients. As compared to PET1, PET2 showed an increase in glucose consumption in the left frontal and left parietal lobe in PET2 as compared to PET1 (P<.001). All the enrolled patients presented a significant increase in neuropsychological scores (i.e Frontal Assessment Battery and Montreal Cognitive Assessment) and have clinically improved at gait analysis. A significant correlation was found between the increase of cortical glucose consumption in the left parietal area and the cognitive improvement as detectable by neuropsychological assessment. CONCLUSIONS: Improvement in 18F FDG PET glucose metabolism could be considered a useful imaging marker for the assessment of iNPH response to VP shunting.

The coefficient of friction in Parkinson's disease gait.

This study aimed to characterize the coefficient of friction (COF) curves of patients with Parkinson's disease (PD) during barefoot gait and to evaluate the relationships between this variable and functional scales. Twenty-two subjects with PD (ON phase of levodopa) and 22 healthy subjects participated in this study. The participants walked barefoot along a pathway that went over two force plates embedded in the floor of the data collection room. The instantaneous COF was calculated as the ratio between the horizontal and vertical components of the ground reaction forces. Two-sample t-tests applied to every 1% of the support phase of the COF curve were used to compare the groups and to identify the phases in which the two groups were different. Specifically, three COF areas were computed: Area 1 (for the loading response phase), Area 2 (for the midstance phase) and Area 3 (for the terminal stance phase). Pearson's tests were applied to assess the associations between the COF curve areas and the clinical scales. The subjects with PD exhibited lower COF values during the loading response and terminal stance phases and higher COF values during the mid-stance phase compared with the control group. A strong positive correlation was observed between Area 1 and the Timed Up and Go Test (90.3%). In conclusion, the patients' COFs exhibited patterns that were different from those of the control group. Moreover, during the loading response phase, these differences were well-correlated with the Timed Up and Go Test scale data; Timed Up and Go Test data can be used to identify the risk of falls among PD patients.

Robot-assisted gait training versus treadmill training in patients with Parkinson's disease: a kinematic evaluation with gait profile score.

The purpose of this study was to quantitatively compare the effects, on walking performance, of end-effector robotic rehabilitation locomotor training versus intensive training with a treadmill in Parkinson's disease (PD). Fifty patients with PD were randomly divided into two groups: 25 were assigned to the robot-assisted therapy group (RG) and 25 to the intensive treadmill therapy group (IG). They were evaluated with clinical examination and 3D quantitative gait analysis [gait profile score (GPS) and its constituent gait variable scores (GVSs) were calculated from gait analysis data] at the beginning (T0) and at the end (T1) of the treatment. In the RG no differences were found in the GPS, but there were significant improvements in some GVSs (Pelvic Obl and Hip Ab-Add). The IG showed no statistically significant changes in either GPS or GVSs. The end-effector robotic rehabilitation locomotor training improved gait kinematics and seems to be effective for rehabilitation in patients with mild PD.

The Lee Silverman Voice Treatment (LSVT®) speech therapy in progressive supranuclear palsy.

BACKGROUND: The Lee Silverman Voice Treatment (LSVT®) was specifically created and tested to comply with the needs of individuals with Parkinson's disease (PD) and other neurological problems. This is a high effort intensive treatment that aims at increasing vocal intensity through the increase of subglottal air pressure, i.e. respiratory effort, for a better cordal adduction and vibration, following the motto "think loud". AIM: The main goal of this study is to inspect the efficacy of LSVT® treatment in progressive supranuclear palsy (PSP) patients. DESIGN: Longitudinal study. SETTING: Rehabilitative inpatient unit. POPULATION: Sixteen patients with PSP and 23 patients with idiopathic PD as control were enrolled in the study. METHODS: All patients underwent a training consisting in16 sessions of speech therapy following the LSVT® protocol. Initially the two groups of patients had similar voice problems, i.e. low volume and bad articulation of speech. RESULTS: A statistically significant improvement was found among the data collected before and after treatment in the PSP and Parkinson groups. Increase in maximum phonation duration and volume of voice in reading were similar in the two groups. Improvement in quality of voice and articulation were more significant in the PD group as compared to the PSP group. CONCLUSION: These results, along with previous findings, add further support to the generalized therapeutic impact of intensive voice treatment on respiratory and laryngeal functions in individuals with PSP. CLINICAL REHABILITATION IMPACT: The positive results, the absence of dropout and collateral effect following this clinical treatments with LSVT technique encouraged to use this technique in PSP patients.

The relation between Parkinson's disease and ageing. Comparison of the gait patterns of young Parkinson's disease subjects with healthy elderly subjects.

BACKGROUND: The gait of healthy elderly and of subjects with Parkinson's disease (PD) displays some common features, suggesting that PD may be a model of ageing. AIM: The aim of the study was to quantify highlight the differences and similarities between the gait patterns of young PD and healthy elderly, to uncover if PD could be assumed as a model of ageing. DESIGN: An optoelectronic system was used for 3D gait analysis evaluation. POPULATION AND METHODS: We compared the gait parameters of 15 young PD (YPD) with the gait of 32 healthy elderly subjects (ES) and 21 healthy subjects age-matched with the PD subjects. RESULTS. Common features between YPD and ES were majorly found in the parameters that reflect the presence of an unstable, uncertain gait, and of corrective strategies employed to reduce instability. On the other side, typical features were present in the gait patterns of PD subjects. CONCLUSION. Our study helped identifying some typical characteristics of the onset disease, and to unravel the symptoms of ageing from those of PD by comparing young PD subjects to elderly healthy subjects. CLINICAL REHABILITATION IMPACT: This allows a deeper understanding of the mechanisms underlying the gait in ageing and PD.

Symptom relief in Parkinson disease by safinamide: Biochemical and clinical evidence of efficacy beyond MAO-B inhibition.

In an open pilot study, doses of safinamide (100, 150, and 200 mg once a day, higher than previously tested) were administered to 13 parkinsonian patients along with a stable dose of dopamine (DA) agonist, causing a significant progressive improvement in motor performance as evaluated by the Unified Parkinson Disease Rating Scale (UPDRS) part III over an 8-week period (4.2 points; P < 0.001). In association with levodopa, the same doses of safinamide in another group of patients (N = 11) induced a significant decrease in motor fluctuations (UPDRS part IV, 2.1 points; P < 0.001), accompanied by a dose-proportional increase of the levodopa AUC, up to 77% from baseline. Because MAO-B was fully inhibited (95%) at all doses tested, we suggest that these biochemical and symptomatic dose-dependent effects must be related to additional mechanisms of action, such as inhibition of glutamate release, increased dopamine release, or inhibition of dopamine re-uptake. These hypotheses are under investigation and will pursue confirmation in controlled clinical trials.

Combination of two different dopamine agonists in the management of Parkinson's disease.

An alternative approach to the symptomatic treatment of parkinsonian patients with and without motor fluctuations is to use dual dopamine agonists. The aim of this study was to investigate the symptomatic effect of administrating a second dopamine agonist to parkinsonian patients already assuming pramipexole or ropinirole. As the second dopamine agonist we chose cabergoline, a drug with a long half life, whose pharmacological profile differs from that of the newer non-ergot-derived dopamine-receptor agonists. In this pilot study we enrolled 27 patients: 21 patients had motor fluctuations and were receiving levodopa plus a dopamine agonist, and 6 patients without motor fluctuations were receiving a dopamine agonist without levodopa. This open study shows that dual dopamine agonist therapy (cabergoline plus pramipexole or ropinirole) may be used in the symptomatic treatment of patients with Parkinson's disease receiving therapy with or without levodopa.

Modification of respiratory function parameters in patients with severe Parkinson's disease.

Respiratory dysfunction remains one of the most common causes of death in patients with complicated Parkinson's disease (PD). The aim of this study was to investigate pulmonary function in fluctuating PD patients during "on" and "off" states of the disease. We studied 12 fluctuating, non-smoking PD patients (H&Y stages 3-5) without a history of lung or cardiovascular disease; all patients underwent Hoehn and Yahr scale (H&Y) and Unified Parkinson Disease Rating Scale (UPDRS items 18-31) to evaluate extrapyramidal impairment, as well as pulmonary function tests (PFT) and arterial blood gas analyses to assess respiratory function. All evaluations were performed during a stable on state of disease and in an off state produced by 12 hours of therapy withdrawal. A restrictive pattern of flow-volume loop was observed both in on and off states of disease. In the off state, we found a significant worsening in both FEV1 and FVC; the FEV1/FVC ratio was unmodified. These results suggest a restrictive pattern of flow-volume loop in these patients.

Subcutaneous continuous apomorphine infusion in fluctuating patients with Parkinson's disease: long-term results.

Fluctuations in motor disability and dyskinesias are the major problem in the long-term treatment of Parkinson's disease (PD). Many authors and ourselves have shown that by giving patients a continuous infusion of levodopa it is possible to control motor fluctuations. Levodopa can be administered continuously only by intravenous, intragastric or intrajejunal delivery. Continuous dopaminergic stimulation can be achieved more easily by infusing dopamine agonists subcutaneously. Apomorphine is a potent water-soluble dopamine receptor agonist that has been shown to successfully control motor fluctuation when subcutaneously infused in complicated parkinsonian patients. We report the clinical data of 30 PD patients having at least five years of treatment with subcutaneous continuous apomorphine infusion.

Low dose of clozapine in the treatment of dopaminergic psychosis in Parkinson's disease.

Dopaminergic psychosis frequently complicates the pharmacological treatment of Parkinson's disease. Dose reduction of dopaminomimetic therapy or treatment with conventional neuroleptics improves psychosis but worsens parkinsonism. In an open-label 12-month trial, the clinical antipsychotic efficacy of the atypical neuroleptic clozapine was investigated in 36 parkinsonian patients (age range 46-85 years) with symptoms of dopaminergic psychosis including delusions, vivid dreams, hallucinations, frank paranoid delirium, and hypersexuality. Clozapine, given orally at bedtime, was started at a dose of 6.25 mg and titrated upward to the minimal effective dose. In all patients, psychosis responded to very low clozapine doses (mean 10.59 +/- 6.48 mg/day). Clozapine doses correlated with the severity of psychosis. During clozapine treatment, parkinsonian disabilities and levodopa dosage remained statistically unchanged. During the 12-month study, no patient had clozapine-induced agranulocytosis or other severe side effects. These findings indicate that even at low doses, clozapine effectively controls dopaminergic psychosis in Parkinson's disease patients without compromising motor function.

A pharmacological study of cocaine activity in planaria.

Planaria has been proposed as a suitable research model in neurobiology because of its relatively simple organization. Dopaminergic agonists induce in this flatworm typical hyperkinesias that can be antagonized by dopaminergic blocking agents. The neurochemical basis of the effects of cocaine in vertebrates has not been fully elucidated, but the inhibition of catecholamine reuptake at a presynaptic level seems to play an important role. In this study we analyzed the involvement of the dopaminergic system in the mechanism of action of cocaine in planaria. The dose-related effects of cocaine on planaria motility and the response to cocaine treatment associated with the administration of specific D1 or D2 dopamine agonists and antagonists were investigated. The effects of reuptake inhibitors on cocaine activity were also studied. Planaria specimens treated with low doses of cocaine become motionless, whereas high doses induce a typical behavioural response, identical to the response induced by specific D2 agonists. This response is inhibited by a D2 selective blocking agent. Nomifensine, a specific dopamine reuptake inhibitor, induces a mixed D1/D2 response. The results of these experiments are discussed, also in relation with the conservation of dopaminergic receptors during evolution.

[Changes in the nigrostriatal dopamine receptor compartment after continuous dopaminergic infusions in Parkinson disease]. / Modificazioni del compartimento recettoriale dopaminergico nigrostriatale dopo infusione dopaminergica continua nel morbo di Parkinson.

Motor fluctuations often complicate chronic levodopa treatment of Parkinson's disease. Pharmacologically, these phenomena are characterized by a progressive shortening of the duration of action of levodopa and a gradual narrowing of the range of "optimally effective" doses, able to improve parkinsonian akinesia without inducing abnormal involuntary movements. The effects of a continuous intravenous infusion of levodopa lasting 9 +/- 0.3 days on these clinical-pharmacological indices have been studied in 12 parkinsonian patients. Continuous infusion therapy gradually ameliorated motor fluctuations by more than 40%, and this improvement lasted for at least 6 days after resuming standard oral therapy. Moreover, levodopa duration of action was prolonged by about 30%, and the range of "optimally effective" dose was widened by about 50%. The above data suggest the possibility of plastic modifications of the pathogenetic mechanisms underlying motor fluctuations in Parkinson's disease, and a potential deleterious effect of intermittent oral therapy. Consequently, continuous dopaminergic stimulation, when used in the early stages of the disease, might theoretically have a prophylactic role on the development or worsening of motor fluctuations.