Claudio Pacchetti

Active music therapy in Parkinson's disease: an integrative method for motor and emotional rehabilitation.

Background Modern management of Parkinson’s disease (PD) aims to obtain symptom control, to reduce clinical disability, and to improve quality of life. Music acts as a specific stimulus to obtain motor and emotional responses by combining movement and stimulation of different sensory pathways. We explored the efficacy of active music therapy (MT) on motor and emotional functions in patients with PD. Methods This prospective, randomized, controlled, single-blinded study lasted 3 months. It consisted of weekly sessions of MT and physical therapy (PT). Thirty-two patients with PD, all stable responders to levodopa and in Hoehn and Yahr stage 2 or 3, were randomly assigned to two groups of 16 patients each. We assessed severity of PD with the Unified Parkinson’s Disease Rating Scale, emotional functions with the Happiness Measure, and quality of life using the Parkinson’s Disease Quality of Life Questionnaire. MT sessions consisted of choral singing, voice exercise, rhythmic and free body movements, and active music involving collective invention. PT sessions included a series of passive stretching exercises, specific motor tasks, and strategies to improve balance and gait. Results MT had a significant overall effect on bradykinesia as measured by the Unified Parkinson’s Disease Rating Scale ( p < .034). Post–MT session findings were consistent with motor improvement, especially in bradykinesia items (p < .0001). Over time, changes on the Happiness Measure confirmed a beneficial effect of MT on emotional functions (p < .0001). Improvements in activities of daily living and in quality of life were also documented in the MT group (p < .0001). PT improved rigidity (p < .0001). Conclusions MT is effective on motor, affective, and behavioral functions. We propose active MT as a new method for inclusion in PD rehabilitation programs.

Relationship between hallucinations, delusions, and rapid eye movement sleep behavior disorder in Parkinson's disease.

Psychotic symptoms are the main and the most disabling “nonmotor” complications of Parkinsons disease (PD), the pathophysiology of which is poorly recognized. Polysomnographic studies have shown a relationship between visual hallucinations and rapid eye movement (REM) sleep. The objective of this study is to clarify the relationship between psychotic symptoms and REM sleep behavior disorder (RBD) in PD. In a Parkinsons disease outpatient unit, 289 consecutive subjects with idiopathic PD were administered (in the period from January to December 2002) a multiple‐choice questionnaire and structured interview on sleep and mental disorders. RBD was diagnosed in accordance with the minimal diagnostic criteria of the International Classification of Sleep Disorders. Hallucinations and delusional disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders‐IV criteria. The presence or absence of psychotic symptoms, of RBD, and of daytime sleepiness, as well as motor status, cognitive status, and mood were assessed. Approximately 32% (n = 92) of the subjects presented with psychotic disorders; 30% (n = 86) had experienced hallucinations; 2% (n = 6) had delusions without hallucinations. Sixty‐two (72%) hallucinators reported nocturnal hallucinations. A total of 6.6% (n = 19) of the subjects complained of a delusional disorder. There were 26.6% (n = 77) of subjects who presented with RBD: 28 (36%) with onset before and 49 (63%) with onset after PD diagnosis. The presence of RBD was associated with an increased risk of manifesting hallucinations and delusions (odds ratio [OR], 2.73). Other independent clinical factors found to have an effect on psychotic disorders were cognitive impairment (OR, 3.92), disease duration (OR, 2.46), advanced age (OR, 2.34), and severity of motor symptoms (OR, 2.06). These results suggest that RBD is widely associated with psychosis in PD.

Double-blind, placebo-controlled study to evaluate the efficacy and safety of botulinum toxin type A in the treatment of drooling in parkinsonism.

Drooling is a frequent symptom in Parkinsons disease (PD), occurring in almost 75% of all patients. Although it is now well known that drooling in PD is the result of swallowing difficulties rather than excessive saliva production, few treatments have been developed to reduce it. Clinical studies suggest that botulinum toxin A (BTX) injections into salivary glands are effective in decreasing drooling in PD patients. In this double‐blind, placebo‐controlled study, 20 patients with parkinsonism (idiopathic PD or multiple system atrophy), were randomly assigned to receive 450 U of BTX (Dysport; Ipsen, Berkshire, UK) or 2 ml of placebo, injected into the parotids and submandibular glands under ultrasonographic guidance. Treatment efficacy and safety were assessed at baseline, 1 week and 3 months after BTX injections using clinical scales (Drooling Severity and Drooling Frequency scales) and side effects surveillance. After treatment, the average secretion of saliva in the BTX group was significantly lower than in the placebo group, as appraised by clinical measurements. No side effects were observed in either group. BTX injection into parotids and submandibular glands, under ultrasonographic guidance, is an effective and safe treatment for drooling in parkinsonism.

REM sleep behavior disorder, hallucinations, and cognitive impairment in Parkinson's disease

The objective of this study was to evaluate the relationship between REM sleep behavior disorder (RBD), hallucinations, and cognitive impairment in Parkinsons disease (PD). One hundred and ten PD patients, divided into three groups (without RBD or hallucinations; with RBD but no hallucinations; with RBD and hallucinations), were submitted to neuropsychological evaluation. The group without RBD and hallucinations showed normal neuropsychological tests when compared to normal controls. The group with hallucinations was characterized by a more severe cognitive impairment affecting both short‐ and long‐term memory, logical abilities, and frontal functions, while the RBD‐only group presented frontal impairment. The hypothesis that RBD in PD can be considered a risk factor not only of the hallucinations but also of more severe and diffuse cognitive abnormalities needs to be strengthened through a longitudinal evaluation.

Not paralysis, but dystonia causes stridor in multiple system atrophy

Abstract—Electromyography (EMG) was performed in 10 patients with multiple system atrophy, laryngeal or pharyngeal symptoms, or both. In patients with stridor, EMG during quiet breathing revealed persistent tonic activity in both abductor and adductor vocal cord muscles. In patients with dysphagia, the cricopharyngeal muscle showed persistent EMG activity throughout all phases of swallowing. Botulinum toxin injection into the adductor muscle determined subjective improvement and reduced tonic EMG activity. Therefore, the cause of stridor in multiple system atrophy is dystonia of the vocal cords.

A randomised, double-blind, dose-ranging study to evaluate efficacy and safety of three doses of botulinum toxin type A (Botox) for the treatment of spastic foot

Botulinum toxin A (BTX) injections have been used successfully in the treatment of post-stroke foot spasticity, but the optimal dose-response relationship for selected muscles has yet to be established. The aim of this study was to outline beneficial and unwanted effects of three different doses of BTX in the treatment of spastic foot. In this randomised, double-blind, dose-ranging study, 45 spastic feet were randomly allocated to one of three groups, each of which was treated with a different dosage of BTX. The doses were decided on the basis of suggestions in the literature. Outcome measures (Modified Ashworth Scale, Medical Research Council Scale, gait assessment, presence of Achilles tendon clonus, Visual Analogue Scales for Gait Function and Pain, Adverse Effects scale) were applied at baseline, 4 weeks and 4 months after treatment. All the groups showed significant scales scores improvements after treatment with BTX. Group II (mean BTX total dose: 322 U) and Group III (mean BTX total dose: 540 U) showed a greater and more prolonged response than Group I (mean BTX total dose: 167 U). Group III showed the highest rate of adverse effects 4 weeks post-treatment. BTX injections constitute a useful and safe method of improving post-stroke foot spasticity, associated pain, gait speed and function. In particular, the medium BTX dosages (320 UI spread over 2–5 muscles) were found to be both safe and effective in producing long-lasting improvement of spastic foot dysfunction.

Peripheral proteasome and caspase activity in Parkinson disease and Alzheimer disease

Background: Defects of the ubiquitin-proteasome (UP) system, a multicatalytic complex degrading polyubiquitinated proteins, may intervene in the pathogenesis of neurodegenerative disorders characterized by intracellular formation of protein aggregates such as Parkinson disease (PD) and Alzheimer disease (AD) by inducing proapoptotic conditions. Methods: The authors measured the activity of proteolytic UP core, proteasome 20S, and of proapoptotic caspase-3 and -9 in peripheral blood lymphocytes (PBLs) of PD and AD patients to establish whether changes in these systems are detectable peripherally. Results: Proteasome 20S activity was reduced in PBLs of treated PD patients vs healthy controls (mean ± SEM: 1.0 ± 0.1 vs 2.3 ± 0.2 nmol 7-amino-4-methylcoumarin (AMC)/106 cells, p < 0.001), whereas marked increases in caspase-3 activity (1370 ± 153 vs 586 ± 104 pmol AMC/106 cells, p < 0.001) and caspase-9 activity (873 ± 86 vs 304 ± 27 U/106 cells, p < 0.001) were found. Increased caspase-9 activity was also detected in PBLs of untreated PD patients (900 ± 193 U/106 cells). PD duration and severity (Unified Parkinson’s Disease Rating Scale score) were inversely correlated with proteasome 20S activity and directly correlated with caspase-3 activity. An inverse correlation was also observed in PD patients between caspase-3 activity and proteasome 20S activity. No significant changes in proteasome 20S or caspase activity or correlations between biochemical and clinical variables were found in patients with AD. Conclusions: A decrease in proteasome activity, possibly related to caspase activation, is detectable in peripheral blood lymphocytes of patients with Parkinson disease but not patients with Alzheimer disease, suggesting that these variables may be considered for the development of peripheral biomarkers of Parkinson disease.

Hallucinations and sleep-wake cycle in PD A 24-hour continuous polysomnographic study

Twenty-four-hour ambulatory polysomnography was performed in 20 patients with PD who were having visual hallucinations (12 men and 8 women, mean age 70 ± 6 years). Visual hallucinations were clearly related to daytime NREM sleep or nocturnal REM sleep in 33% of the instances. The data reinforce the hypothesis that neural mechanisms implicated in generating sleep and, in particular, in dream imagery play a role in the occurrence of visual hallucinations in PD.

Deep brain stimulation and cognitive functions in Parkinson's disease: A three-year controlled study

There is debate over the cognitive and behavioral effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinsons disease (PD). To evaluate these effects, we performed a prospective, naturalistic controlled, 3‐year follow‐up study. A total of 65 PD patients were enrolled, of whom 32 underwent STN‐DBS (PD‐DBS) and 33, even though eligible for this treatment, declined surgery and chose other therapeutic procedures (PD‐control). Motor and neuropsychological functions were assessed in all the subjects at baseline (T0) and 36 months (T36). The PD‐DBS patients were also evaluated at 1, 6, 12, and 24 months after surgery (T1, T6, T12, and T24). At T1, compared with T0, the PD‐DBS patients recorded worse logical executive function task and verbal fluency (FAS) scores, whereas their performance of memory tasks remained stable. At T12, their cognitive profile had returned within the pre‐DBS range, thereafter remaining stable until T36. FAS scores at T36 were significantly worse in the PD‐DBS compared with the PD‐control patients. This is the first long‐term naturalistic controlled study of cognitive functions in PD patients submitted to STN‐DBS. Our results confirm previous reports of a worsening of verbal fluency after DBS, but show that STN‐DBS seems to be relatively safe from a cognitive standpoint, as the short‐term worsening of frontal‐executive functions was found to be transient.

REM behavior disorder, hallucinations and cognitive impairment in Parkinson's disease: a two-year follow up.

In Parkinsons disease (PD) the presence of REM parasonnias as REM Behaviour Disorder (RBD) or vivid dreams/nightmares, is recognized as largely associated with hallucinations, even if the risk of the development of hallucinations seem not to depend on how long the REM parasomnias had been occurring. The aim of this study was to establish if RBDs occurring earlier than hallucinations in PD are predictive of cognitive impairment development. Three groups of PD patients: i) group 1, without RBD and without hallucinations; ii) group 2, with RBD but without hallucinations; iii) group 3, with RBD and hallucinations have been prospectively investigated at baseline and after two years throughout a clinical and neuropsychological evaluation. After two years, the group 1 continued to present normal neuropsychological tests and did not present either RBDs or hallucinations. In the group 2, the frontal impairment evidenced at baseline was confirmed; the onset of newly hallucinations was reported in a subgroup of 12 patients, who proved to be older, with a more severe executive impairment at baseline and with a more severe motor symptoms progression than those RBD patients who had not manifested hallucinations. The group 3, characterized at baseline by a more severe cognitive impairment presented, after two years, a cognitive worsening and a higher mortality rate. The longitudinal but at preliminary step investigation identified a PD subgroup of patients, in whom a common background disease profile, including the presence of RBD, could represent a “red flag” in developing further cognitive impairment.