Correlation between Quality of Life and severity of Parkinson's Disease by assessing an optimal cut-off point on the Parkinson's Disease questionnaire (PDQ-39) as related to the Hoehn & Yahr (H&Y) scale.

Purpose: Strong evidence shows that symptoms in individuals with Parkinson's Disease (PD) restrict both their independence and social participation, leading to a low Quality of Life (QoL). Conversely, a reduced QoL has a negative impact on symptoms. The aim is to evaluate the correlation between QoL and severity of PD by assessing the presence of an optimal cut-off point on the Parkinson's disease questionnaire (PDQ-39) as related to the Hoehn &Yahr (H&Y) scale in a cohort of Italian adults with PD. Methods: A multicenter, cross-sectional study was performed. This study was conducted on a cohort of consecutive individuals. All participants were evaluated with the PDQ-39, and the severity of PD was recorded according to the H&Y scale by a neurologist. Receiver op-erating characteristic (ROC) curves and coordinates, visually inspected, were used to find cut-off points with optimal sensitivity and specificity. These were in turn used to determine the optimal PDQ-39 cut-off score for identifying disease severity according to H&Y stages. Results: 513 individuals were included in the study. The ROC curve analysis showed that QoL worsened with an increase in disease severity and age. Moreover, QoL was worse in females. Conclusions: The results of this study allowed for the correlation of QoL and disease severity in a cohort of individuals with PD. With this cut-off point, it is now possible to make a determination of QoL of an individual with PD at a certain stage of the disease, in a specific age range, and of a particular gender.

Instrumental Timed Up and Go test discloses abnormalities in patients with Cervical Dystonia.

Background Cervical dystonia is a movement disorder characterized by involuntary and sustained contraction of the neck muscles that determines abnormal posture. The aim of this study was to investigate whether dystonic posture in patients with cervical dystonia affects walking and causes postural changes. Methods Patients with cervical dystonia and a group of age-matched healthy controls underwent an instrumental evaluation of the Timed Up and Go Test. Findings All the spatio-temporal parameters of the sub-phases of the Timed up and go test had a significantly higher duration in cervical dystonia patients compared to the control group while no differences in flection and extension angular amplitudes were observed. Indeed, we found that Cervical Dystonia patients had abnormalities in turning, as well as in standing-up and sitting-down from a chair during the Timed up and go test than healthy controls. Interpretation Impairment in postural control in cervical dystonia patients during walking and postural changes prompts to develop rehabilitation strategies to improve postural stability and reduce the risk of fall in these patients.

The psychosocial impact of assistive device scale: Italian validation in a cohort of nonambulant people with neuromotor disorders.

The importance of adaptive seating system on body structure and function is widely accepted, but its impact on psychosocial aspects needs more consideration by health professionals. This article describes the Italian validation of the Psychosocial Impact of Assistive Device Scale (IT-PIADS) for non-ambulant people with neuromotor disorders.Once agreement has been given by the original authors, the scale was translated and adapted to the Italian culture. The IT-PIADS was administered to different wheelchairs users with heterogeneous diagnosis. The internal consistency and test-retest reliability were examined. Its concurrent validity was evaluated with the Italian version of the WheelCon-M-SF.The IT-PIADS was administered to 87 subjects. Cronbach's α was 0.92 (p < 0.05), and the test-retest reliability (ICC) for competence, adaptability and self-esteem subscales were 0.96, 0.90, 0.93, respectively. The Pearson correlation coefficient of the IT-PIADS with the WheelCon-M-I-SF scores showed significant data for competence and adaptability subscales.Psychosocial perception on assistive devices can be reliably measure. The IT-PIADS showed good psychometric properties and it is possible to confirm its validity for clinical and research purposes. Nevertheless, before using this measure with greater confidence, further psychometric properties tests of the IT-PIADS are recommended.

Corticobasal syndrome: neuroimaging and neurophysiological advances.

Corticobasal degeneration (CBD) is a neurodegenerative condition characterized by 4R tau protein deposition in several brain regions that clinically manifests itself as a heterogeneous atypical parkinsonism typically expressed in adulthood. The prototypical clinical phenotype of CBD is corticobasal syndrome (CBS). Important insights into the pathophysiological mechanisms underlying motor and higher cortical symptoms in CBS have been gained by using advanced neuroimaging and neurophysiological techniques. Structural and functional neuroimaging studies often show asymmetric cortical and subcortical abnormalities, mainly involving perirolandic and parietal regions and basal ganglia structures. Neurophysiological investigations including electroencephalography and somatosensory evoked potentials provide useful information on the origin of myoclonus and on cortical sensory loss. Transcranial magnetic stimulation demonstrates heterogeneous and asymmetric changes in the excitability and plasticity of primary motor cortex and abnormal hemispheric connectivity. Neuroimaging and neurophysiological abnormalities in multiple brain areas reflect asymmetric neurodegeneration, leading to asymmetric motor and higher cortical symptoms in CBS.

Disease progression in blepharospasm: a 5-year longitudinal study.

BACKGROUND AND PURPOSE: The clinical manifestation of dystonic spasms in blepharospasm (BSP) patients may be heterogeneous. Whether the varying phenomenology of eyelid spasms becomes manifest sequentially during the course of the disease or aggregates in separate clusters according to different disease courses is still unclear. For this purpose, the clinical features in BSP patients were evaluated longitudinally over a 5-year period and also the blink reflex recovery cycle was tested in a subgroup of BSP patients. METHODS: Sixty BSP patients were videotaped at time 0 and after approximately 5 years of follow-up. Two experts in movement disorders, who were blinded to the video order, reviewed the videotapes and scored the severity of BSP using the Blepharospasm Severity Rating Scale. Changes in the R2 recovery index were also evaluated in 18 patients twice, i.e. upon enrolment and at the follow-up. RESULTS: The severity of BSP worsened significantly over the 5-year follow-up period owing to the appearance or the increased duration and frequency of prolonged spasms. It was also found that the blink reflex recovery cycle worsened at follow-up in comparison with the baseline. CONCLUSIONS: This study shows that the disease progression of BSP is characterized by the appearance or worsening of prolonged spasms. Prolonged spasms are accompanied by changes in the excitability of brainstem interneurons. Aging-related effects may exacerbate the pathophysiological mechanisms underlying spasms.

Spread of dystonia in patients with idiopathic adult-onset laryngeal dystonia.

BACKGROUND AND PURPOSE: Adult-onset laryngeal dystonia (LD) can be isolated or can be associated with dystonia in other body parts. Combined forms can be segmental at the onset or can result from dystonia spread to or from the larynx. The aim of this study was to identify the main clinical and demographic features of adult-onset idiopathic LD in an Italian population with special focus on dystonia spread. METHODS: Data were obtained from the Italian Dystonia Registry (IDR) produced by 37 Italian institutions. Clinical and demographic data of 71 patients with idiopathic adult-onset LD were extracted from a pool of 1131 subjects included in the IDR. RESULTS: Fifty of 71 patients presented a laryngeal focal onset; the remaining subjects had onset in other body regions and later laryngeal spread. The two groups did not show significant differences of demographic features. 32% of patients with laryngeal onset reported spread to contiguous body regions afterwards and in most cases (12 of 16 subjects) dystonia started to spread within 1 year from the onset. LD patients who remained focal and those who had dystonia spread did not show other differences. CONCLUSIONS: Data from IDR show that dystonic patients with focal laryngeal onset will present spread in almost one-third of cases. Spread from the larynx occurs early and is directed to contiguous body regions showing similarities with clinical progression of blepharospasm. This study gives a new accurate description of LD phenomenology that may contribute to improving the comprehension of dystonia pathophysiology.

Correction to: The Italian Dystonia Registry: rationale, design and preliminary findings.

In the original article, Gina Ferrazzano was affiliated to Department of Neurology and Psychiatry, Neuromed Institute IRCCS, Sapienza University of Rome, Pozzilli, Italy.The corrected affiliation should be: Neuromed Institute IRCCS, Pozzilli, IS, Italy.

Re-emergent tremor in Parkinson's disease: the effect of dopaminergic treatment.

BACKGROUND AND PURPOSE: Patients with Parkinson's disease (PD) with resting tremor may be affected by a tremor that appears after a varying latency while a posture is maintained, a phenomenon referred to as re-emergent tremor (RET). The aim of the study was to evaluate the occurrence and clinical features of RET in patients with PD tested off and on treatment, and to compare the effect of dopaminergic treatment on RET with the effect on resting and action tremor. METHODS: We consecutively enrolled 100 patients with PD. Patients were clinically evaluated 24 h after withdrawal of therapy (off-treatment phase) and 60 min after therapy administration (on-treatment phase). We collected the demographic and clinical data of patients with PD. The severity of the disease was assessed by means of the Hoehn and Yahr scale and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale part III. We evaluated the latency, severity and body side affected both off and on treatment in patients with RET. RESULTS: Re-emergent tremor was present in 24% of the patients with PD off treatment and in 19% of the patients on treatment. Dopaminergic treatment reduced the clinical severity of RET. Dopaminergic treatment increased the number of patients with unilateral RET and reduced the number of those who had bilateral RET. RET and resting tremor responded similarly to dopaminergic treatment, whereas action tremor was less responsive. Patients with RET had milder motor symptoms than patients without RET both off and on treatment. CONCLUSIONS: Dopaminergic treatment modified RET occurrence, severity and body distribution. Dopaminergic depletion plays a role in the pathophysiology of RET.

Clinical heterogeneity in patients with idiopathic blepharospasm: A cluster analysis.

BACKGROUND: Idiopathic blepharospasm is a clinically heterogeneous condition. It is not known whether the various manifestations become manifest sequentially during the course of the disease or aggregate in separate clusters identifying subpopulations of patients. METHODS: Eighty-nine patients with idiopathic blepharospasm were assessed using k-means cluster analysis to identify relatively homogeneous groups on the basis of low-intragroup/high-intergroup differences across a set of selected variables. RESULTS: The results suggest that there may be three groups of patients. Group 1 included patients who had prolonged muscle spasms leading to complete rim closure associated with brief and/or prolonged spasms with incomplete rim closure, the most severe blepharospasm, and a greater tendency to spread to adjacent segments. Group 2 included patients characterized by prolonged spasms with partial rim closure, either alone or associated with brief spasms whereas Group 3 included patients with brief spasms with complete rim closure, the least severe blepharospasm, and the lowest tendency to spread. The severity of Group 2 blepharospasm was between that observed in Group 1 and Group 3, while the tendency to spread was similar to Group 3. The three groups did not differ for disease duration, age of onset, sex and other clinical features. The observation that inhibition of the R2 component of the blink reflex recovery cycle was more abnormal in Groups 1/2 2 than in Group 3 at least in part validates our classification. CONCLUSIONS: The present study suggests that blepharospasm patients may be classified in different subtypes according to the type of spasms, severity of the condition and tendency to spread.

Relationship between pain and motor and non-motor symptoms in Parkinson's disease.

BACKGROUND AND PURPOSE: Although female gender, depressive symptoms and medical conditions predisposing to pain are more common in patients with Parkinson's disease (PD) with pain, no study has yet explored the relationship between pain and other non-motor symptoms (NMS). METHODS: A total of 321 consecutive patients with PD [190 men/131 women aged 68.3 (SD 9.2) years] attending four Italian movement disorder clinics were studied. Demographic/clinical data were obtained by a standardized interview and the NMS scale. The association of pain with motor and NMS was assessed by multivariable logistic regression models. RESULTS: At the time of the study, 180 patients with PD (56%) reported chronic pain that, in most cases, was described as being muscular or arthralgic pain. Pain preceded the onset of motor signs in 36/180 patients. In the main-effect model, factors independently associated with pain were female sex [odds ratio (OR), 2.1; P = 0.01], medical conditions predisposing to pain (OR, 2.9; P < 0.001), Hoehn-Yahr staging (OR, 1.9; P = 0.04), motor complications (OR, 4.7; P = 0.04) and NMS belonging to the sleep/fatigue (OR, 1.6; P = 0.04) and mood/cognition (OR, 1.6; P = 0.03) domains. Most explanatory variables in the multivariable analysis were similarly distributed in patients in whom pain may have been related to PD or to a cause other than PD. CONCLUSIONS: We confirm that pain in PD is more frequent in women and in subjects with medical conditions predisposing to painful symptoms. Moreover, this strengthens the association between pain and motor severity measures and NMS domains, particularly sleep and mood disturbances.

The Italian Dystonia Registry: rationale, design and preliminary findings.

The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.

BDNF and LTP-/LTD-like plasticity of the primary motor cortex in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome (GTS) is characterized by motor and vocal tics and often associated with obsessive-compulsive disorder (OCD). Responses to intermittent/continuous theta-burst stimulation (iTBS/cTBS), which probe long-term potentiation (LTP)-/depression (LTD)-like plasticity in the primary motor cortex (M1), are reduced in GTS. ITBS-/cTBS-induced M1 plasticity can be affected by brain-derived neurotrophic factor (BDNF) polymorphism. We investigated whether the BDNF polymorphism influences iTBS-/cTBS-induced LTP-/LTD-like M1 plasticity in 50 GTS patients and in 50 age- and sex-matched healthy subjects. In GTS patients, motor and psychiatric (OCD) symptom severity was rated using the Yale Global Tic Severity Scale (YGTSS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). We compared M1 iTBS-/cTBS-induced plasticity in healthy subjects and in patients with GTS. We also compared responses to TBS according to BDNF polymorphism (Val/Val vs Met carriers) in patients and controls. Fourteen healthy subjects and 13 GTS patients were Met carriers. When considering the whole group of controls, as expected, iTBS increased whereas cTBS decreased MEPs. Differently, iTBS/cTBS failed to induce LTP-/LTD-like plasticity in patients with GTS. When comparing responses to TBS according to BDNF polymorphism, in healthy subjects, Met carriers showed reduced MEP changes compared with Val/Val individuals. Conversely, in patients with GTS, responses to iTBS/cTBS were comparable in Val/Val individuals and Met carriers. YGTSS and Y-BOCS scores were comparable in Met carriers and in Val/Val subjects. We conclude that iTBS and cTBS failed to induce LTP-/LTD-like plasticity in patients with GTS, and this was not affected by BDNF genotype.

Chiari type 1 malformation in Neurofibromatosis type 1: experience of a center and review of the literature.

OBJECTIVE: To evaluate the possible correlation and the true incidence between Neurofibromatosis type 1 and Arnold-Chiari malformation type I. MATERIALS AND METHODS: We reviewed all clinical charts, neurological consultations and MRI scans of 428 NF1 patients followed by 1994 to 2014 in our Department. NF1 patients in our clinic are seen usually every year by both the dermatologist and the neurologist. All patients also undergo a brain and spinal cord with the same 1.5 Tesla MRI scan. RESULTS: We found a diagnosis of Arnold Chiari malformation type I in 9 of the 428 NF1 cases (2%). CONCLUSION: This frequency is higher than that expected on the basis of a chance association. Therefore we underline the importance of serial MRI studies in patients with NF1 to assess the presence of cranio-cervical anomalies. Future studies should try to better understand what are the pathogenetic mechanisms underlying this close association.

Adherence to anti-Parkinson drug therapy in the "REASON" sample of Italian patients with Parkinson's disease: the linguistic validation of the Italian version of the "Morisky Medical Adherence Scale-8 items".

Information about patients' adherence to therapy represents a primary issue in Parkinson's disease (PD) management. To perform the linguistic validation of the Italian version of the self-rated 8-Item Morisky Medical Adherence Scale (MMAS-8) and to describe in a sample of Italian patients affected by PD the adherence to anti-Parkinson drug therapy and the association between adherence and some socio-demographic and clinical features. MMAS-8 was translated into Italian language by two independent Italian mother-tongue translators. The consensus version was then back-translated by an English mother-tongue translator. This translation process was followed by a consensus meeting between the authors of translation and investigators and then by two comprehension tests. The translated version of the MMAS-8 scale was then administered at the baseline visit of the "REASON" study (Italian Study on the Therapy Management in Parkinson's disease: Motor, Non-Motor, Adherence and Quality Of Life Factors) in a large sample of PD patients. The final version of the MMAS-8 was easily understood. Mean ± SD MMAS-8 score was 6.1 ± 1.2. There were no differences in adherence to therapy in relationship to disease severity, gender, educational level or decision to change therapy. The Italian version of MMAS-8, the key tool of the REASON study to assess the adherence to therapy, has shown to be understandable to patients with PD. Patients enrolled in the REASON study showed medium therapy adherence.

Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease.

OBJECTIVE: To summarize the 2010 EFNS/MDS-ES evidence-based treatment recommendations for the management of Parkinson's disease (PD). This summary includes the treatment recommendations for early and late PD. METHODS: For the 2010 publication, a literature search was undertaken for articles published up to September 2009. For this summary, an additional literature search was undertaken up to December 2010. Classification of scientific evidence and the rating of recommendations were made according to the EFNS guidance. In cases where there was insufficient scientific evidence, a consensus statement ('good practice point') is made. RESULTS AND CONCLUSIONS: For each clinical indication, a list of therapeutic interventions is provided, including classification of evidence.

Somatosensory temporal discrimination threshold may help to differentiate patients with multiple system atrophy from patients with Parkinson's disease.

BACKGROUND AND PURPOSE: Somatosensory temporal discrimination threshold (STDT) is defined as the threshold at which two tactile stimuli applied to the skin are perceived as clearly distinct. The aim of the study was to investigate whether the extent of STDT alterations differs between patients with parkinsonian type multiple system atrophy (MSA-P) and patients with Parkinson's disease (PD). Possible differences between the two groups may help to differentiate MSA-P from PD. METHODS: STDT was investigated in 20 patients with MSA-P, 21 patients with PD and 18 age-matched healthy subjects. The clinical evaluation included the Mini-Mental State Examination, Hoehn and Yahr Scale, Frontal Assessment Battery, Unified Multiple System Atrophy Rating Scale for patients with MSA-P, and Unified Parkinson's Disease Rating Scale for patients with PD. STDT was investigated by delivering paired electrical stimuli starting with an inter-stimulus interval (ISI) of 0 ms (simultaneous pair), and progressively increasing the ISIs in 10-ms steps. RESULTS: Between-group anova showed that STDT statistically differed in MSA-P versus patients with PD and healthy subjects. Post hoc showed that STDT values in patients with MSA-P were significantly higher than those in patients with PD and healthy subjects. Receiver operating characteristic curve analysis showed that STDT testing yielded high diagnostic specificity and sensitivity. CONCLUSIONS: STDT is abnormal in patients with MSA-P and PD. The degree of STDT abnormalities is higher in patients with MSA-P than in patients with PD.

Fatigue in Parkinson's disease: motor or non-motor symptom?

Fatigue is one of the most disabling symptoms in patients with Parkinson's disease (PD), with a significant impact on patients' quality of life. Clinical studies using ad hoc questionnaires showed that in PD fatigue is associated with non-motor as well motor symptoms. Neurophysiological observations suggest that motor mechanisms play a role in the pathophysiology of fatigue but there is no clear correlation between fatigue measured with clinical instruments and fatigue assessed with neurophysiological tests. Neuroimaging studies show that fatigue is associated with an involvement of non-dopaminergic or extrastriatal dopaminergic pathways. It is conceivable that both motor and non-motor mechanisms underlie the pathophysiology of fatigue.

Cutaneous innervation and trigeminal pathway function in a patient with facial pain associated with Parry-Romberg syndrome.

Parry-Romberg syndrome (PRS) is a rare condition manifesting with progressive hemifacial atrophy. Although reported PRS clinical disturbances include facial pain and recent studies raised the possibility that PRS-related pain is a neuropathic pain condition due to the trigeminal nerve damage, no studies have directly investigated cutaneous innervation and trigeminal pathway function in patients with this rare condition. In a 50-year-old woman presenting with a 10-year history of slowly progressive hemifacial atrophy and facial pain, we investigated large myelinated fibres with masticatory muscle electromyography and trigeminal reflexes, and tested small myelinated and unmyelinated fibres with laser-evoked potentials. We also investigated cutaneous innervation by measuring the intraepidermal nerve fibre (IENF) density after skin biopsy of the supraorbital regions. We found that neurophysiological data and IENF density came within normal ranges, with no differences between normal and affected side. Our study showing that the standard reference techniques for assessing cutaneous innervation and trigeminal pathway function disclosed no abnormalities in this patient with PRS suggest that this rare and disabling condition is not associated with trigeminal system damage. These findings indicate that in this patient PRS-related pain is not a neuropathic pain condition, rather it probably arises from the musculoskeletal abnormalities.

Botulinum toxin A modulates afferent fibers in neurogenic detrusor overactivity.

BACKGROUND: Although botulinum toxin (BoNT/A) injected into the detrusor muscle improves overactive bladder symptoms in patients with neurogenic detrusor overactivity, how it does so remains unclear. In this study, we investigated whether BoNT/A improves detrusor overactivity by modulating bladder afferent activity. METHODS: To do so, during urodynamic assessment, we tested the soleus muscle Hoffmann (H) reflex during bladder filling before and after intradetrusor BoNT/A in patients with Parkinson's disease (PD) and in patients with complete chronic spinal cord lesion (SCI) and detrusor overactivity refractory to conventional therapy. Healthy subjects underwent H reflex studies during urodynamic assessment and acted as controls. RESULTS: Our findings show that BoNT/A injected into the detrusor muscle effectively reduces clinical overactive bladder symptoms in patients with PD and SCI. In healthy subjects and patients with PD, bladder filling [at maximum cystometric capacity, (MCC)] significantly decreased the H reflex size, whereas in patients with SCI, it slightly facilitated the H reflex size. At MCC, in patients with PD, BoNT/A significantly reduced the expected H reflex inhibition, whereas in those with SCI, BoNT/A turned the H reflex facilitation at maximum bladder filling into a slight inhibition. CONCLUSIONS: These findings show that BoNT/A injected into the detrusor muscle in patients with PD and SCI modulates bladder afferent activity. Modulation of bladder afferents possibly explains why BoNT/A improves detrusor overactivity.

Pathophysiology of pain and fatigue in Parkinson's disease.

In Parkinson's disease (PD), nigral degeneration determines an altered neuronal ouput from the subthalamic nucleus and globus pallidus, and as a consequence functional changes in the motor circuits linking basal ganglia to the motor cortical areas. Movement slowness, rigidity and tremor are among the principal motor symptoms of PD. Studies of movement execution have shown that PD patients have difficulty in performing simultaneous and sequential movements. In executing sequential movements the abnormalities of PD patients worsen as the sequence progresses. This phenomenon, called sequential effect, may be one of the mechanisms underlying the fatigue of PD patients. Cortical deafferentation is thought to be responsible for the motor disturbances of PD and studies using transcranial magnetic stimulation showed that in PD patients there are abnormalities in cortical plasticity and in cortical connectivity. Sensorimotor integration refers to the processes that link sensory input to motor output to produce appropriate voluntary movements. Sensory information is important for motor preparation and execution in parkinsonian patients, and PD patients have greater difficulty in performing movements when no external cues are provided. Investigating the role of sensory information, several studies provided evidence that PD patients have numerous somatosensory deficits, including tactile temporal discrimination threshold. Neurophysiological testing in PD has also found altered central somatosensory processing. Finally PD patients may experience painful sensations after the onset of the disease and various evidence suggests an abnormal nociceptive input processing in the central nervous system that might predispose PD patients to developing pain.