Showing papers in "Movement Disorders in 2009"
TL;DR: A key role for NMS in the clinical frame of PD is supported and the need to address them specifically in clinical trials using dedicated scales is addressed.
Abstract: We performed a multicenter survey using a semistructured interview in 1,072 consecutive patients with Parkinson's disease (PD) enrolled during 12 months in 55 Italian centers to assess the prevalence of nonmotor symptoms (NMSs), their association with cognitive impairment, and the impact on patients' quality of life (QoL). We found that 98.6% of patients with PD reported the presence of NMSs. The most common were as follows: fatigue (58%), anxiety (56%), leg pain (38%), insomnia (37%), urgency and nocturia (35%), drooling of saliva and difficulties in maintaining concentration (31%). The mean number of NMS per patient was 7.8 (range, 0-32). NMS in the psychiatric domain were the most frequent (67%). Frequency of NMS increased along with the disease duration and severity. Patients with cognitive impairment reported more frequently apathy, attention/memory deficit, and psychiatric symptoms. Apathy was the symptom associated with worse PDQ-39 score but also presence of fatigue, attention/memory, and psychiatric symptoms had a negative impact on QoL. These findings further support a key role for NMS in the clinical frame of PD and the need to address them specifically in clinical trials using dedicated scales.
1,151 citations
TL;DR: The epidemiology, clinical course, diagnosis, and management of some of the most common neuropsychiatric symptoms in Parkinson's disease are discussed: depression, anxiety, apathy, fatigue, and psychotic symptoms.
Abstract: Neuropsychiatric symptoms are common in Parkinson's disease, even at the earliest stages, and have important consequences for quality of life and daily functioning, are associated with increased carer burden and increased risk for nursing home admission. In addition to cognitive impairment, a wide range of neuropsychiatric symptoms have been reported. In this article, the epidemiology, clinical course, diagnosis, and management of some of the most common neuropsychiatric symptoms in PD are discussed: depression, anxiety, apathy, fatigue, and psychotic symptoms. Although much is known regarding the prevalence and course of these symptoms, the empirical evidence for how to manage these symptoms is limited at best. There is thus an urgent need for systematic studies for the pharmacological and non-pharmacological management of these symptoms.
412 citations
TL;DR: Scores on the QUIP appear to be valid as a self‐assessment screening instrument for a range of ICDs and other compulsive behaviors that occur in PD, and a shortened version may perform as well as the full version.
Abstract: As no comprehensive assessment instrument for impulse control disorders (ICDs) in Parkinson's disease (PD) exists, the aim of this study was to design and assess the psychometric properties of a self-administered screening questionnaire for ICDs and other compulsive behaviors in PD. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) has 3 sections: Section 1 assesses four ICDs (involving gambling, sexual, buying, and eating behaviors), Section 2 other compulsive behaviors (punding, hobbyism, and walkabout), and Section 3 compulsive medication use. For validation, a convenience sample of 157 PD patients at 4 movement disorders centers first completed the QUIP, and then was administered a diagnostic interview by a trained rater blinded to the QUIP results. A shortened instrument (QUIP-S) was then explored. The discriminant validity of the QUIP was high for each disorder or behavior (receiver operating characteristic area under the curve [ROC AUC]: gambling = 0.95, sexual behavior = 0.97, buying = 0.87, eating = 0.88, punding = 0.78, hobbyism = 0.93, walkabout = 0.79). On post hoc analysis, the QUIP-S ICD section had similar properties (ROC AUC: gambling = 0.95, sexual behavior = 0.96, buying = 0.87, eating = 0.88). When disorders/behaviors were combined, the sensitivity of the QUIP and QUIP-S to detect an individual with any disorder was 96 and 94%, respectively. Scores on the QUIP appear to be valid as a self-assessment screening instrument for a range of ICDs and other compulsive behaviors that occur in PD, and a shortened version may perform as well as the full version. A positive screen should be followed by a comprehensive, clinical interview to determine the range and severity of symptoms, as well as need for clinical management.
405 citations
TL;DR: A fall risk screen for people with PD using routine clinical measures and an explanatory (physiological) fall risk assessment for guiding fall prevention interventions are devised.
Abstract: The study aims were to devise (1) a fall risk screen for people with PD using routine clinical measures and (2) an explanatory (physiological) fall risk assessment for guiding fall prevention interventions. One hundred thirteen people with PD (age 66 +/- 95% CI 1.6 years) underwent clinical assessments and quantitative tests of sway, gait, strength, reaction time, and lower limb sensation. Participants were then followed up for 12 months to determine fall incidence. In the follow-up year, 51 participants (45%) fell one or more times whereas 62 participants (55%) did not fall. Multivariate analyses of routine clinical measures revealed that a fall in the past year, abnormal axial posture, cognitive impairment, and freezing of gait were independent risk factors for falls and predicted 38/51 fallers (75%) and 45/62 non-fallers (73%). A multivariate model combining clinical and physiological measures that elucidate the pathophysiology of falls identified abnormal posture, freezing of gait, frontal impairment, poor leaning balance, and leg weakness as independent risk factors. This model correctly classified 39/51 fallers (77%) and 51/62 non-fallers (82%). Patients with PD at risk of falls can be identified accurately with routine clinical assessments and quantitative physiological tests. Many of the risk factors identified are amenable to targeted intervention.
354 citations
TL;DR: FOG‐Q was a reliable tool for the assessment of treatment intervention and was best correlated to items of the UPDRS relating to walking, general motor issues, and mobility.
Abstract: To revalidate the Freezing of Gait Questionnaire (FOG-Q), patients with Parkinson's disease (PD) were randomly assigned to receive rasagiline (1 mg/day) (n = 150), entacapone (200 mg with each dose of levodopa) (n = 150), or placebo (n = 154). Patients were assessed at baseline and after 10 weeks using the FOG-Q, Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), and Parkinson's Disease Questionnaire (PDQ-39). FOG-Q dimensionality, test-retest reliability, and internal reliability were examined. Convergent and divergent validities were assessed by correlating FOG-Q with UPDRS, BDI, and PDQ-39. Comparisons between FOG-Q item 3 and UPDRS item 14 were also made. Principal component analysis indicated that FOG-Q measures a single dimension. Test-retest reliability and internal reliability of FOG-Q score was high. FOG-Q was best correlated to items of the UPDRS relating to walking, general motor issues, and mobility. Correlations between baseline and endpoint suggested that FOG-Q item 3 is at least as reliable as UPDRS item 14. At baseline, 85.9% of patients were identified as "Freezers" using FOG-Q item 3 (> or =1) and 44.1% using UPDRS item 14 (> or =1) (P < 0.001). FOG-Q was a reliable tool for the assessment of treatment intervention. FOG-Q item 3 was effective as a screening question for the presence of FOG.
344 citations
TL;DR: This is the first demonstration that a levodopa‐based continuous dopaminergic stimulation is beneficial for NMS and health‐related quality of life in PD in addition to the reduction of motor fluctuations and dyskinesias.
Abstract: Switching from oral medications to continuous infusion of levodopa/carbidopa gel reduces motor complications in advanced Parkinson's disease (PD), but effects on nonmotor symptoms (NMSs) are unknown. In this prospective open-label observational study, we report the effects of intrajejunal levodopa/carbidopa gel infusion on NMS in PD based on standard assessments utilizing the nonmotor symptoms scale (NMSS) along with the unified Parkinson's disease rating scale (UPDRS 3 motor and 4 complications) and quality of life (QoL) using the Parkinson's disease questionnaire (PDQ-8). Twenty-two advanced PD patients (mean age 58.6 years, duration of disease 15.3 years) were followed for 6 months. A statistically significant beneficial effect was shown in six of the nine domains of the NMSS: cardiovascular, sleep/fatigue, attention/memory, gastrointestinal, urinary, and miscellaneous (including pain and dribbling) and for the total score of this scale (NMSST) paralleling improvement of motor symptoms (UPDRS 3 motor and 4 complications in "best on" state) and dyskinesias/motor fluctuations. In addition, significant improvements were found using the Parkinson's disease sleep scale (PDSS) and the PDQ-8 (QoL). The improvement in PDQ-8 scores correlated highly significantly with the changes in NMSST, whereas a moderately strong correlation was observed with UPDRS changes. This is the first demonstration that a levodopa-based continuous dopaminergic stimulation is beneficial for NMS and health-related quality of life in PD in addition to the reduction of motor fluctuations and dyskinesias.
252 citations
TL;DR: The results are consistent with the view that in ET, a network of cerebral areas including brainstem shows oscillatory interactions, which lead to a rhythmic modulation of muscle activity becoming apparent as tremor.
Abstract: Despite the fact that essential tremor (ET) is the most prevalent movement disorder, the underlying pathological mechanisms are not fully understood. There is accumulating evidence that this specific type of tremor is mainly of central origin, in particular involving inferior olive, cerebellum, thalamus, and primary motor cortex. We studied 8 patients with ET recording simultaneously neural activity with a whole-scalp neuromagnetometer and tremor activity with surface electromyography (EMG). Subjects performed an isometric contraction of the left forearm. Tremor frequency of 5 to 7 Hz and its first harmonic were clearly evident in power spectra of EMG recordings. We used the localization technique dynamic imaging of coherent sources (DICS) to identify cerebral areas coherent to the EMG signal at tremor frequency and its first harmonic. All subjects showed coherence to the contralateral primary motor cortex. In a further step, DICS was used to identify areas of significant cerebro-cerebral coherence. The analysis revealed a network of areas consisting of contralateral primary motor cortex, premotor cortex, thalamus, brainstem, and ipsilateral cerebellum. These results are consistent with the view that in ET, a network of cerebral areas including brainstem shows oscillatory interactions, which lead to a rhythmic modulation of muscle activity becoming apparent as tremor.
240 citations
TL;DR: In this study, PD subjects performed the tremor subset of the UPDRS motor section while wearing Kinesia, a wireless system for automated assessment of Parkinson's disease tremor and indicated high clinical acceptance.
Abstract: The objective was to design, build, and assess Kinesia, a wireless system for automated assessment of Parkinson's disease (PD) tremor. The current standard in evaluating PD is the Unified Parkinson's Disease Rating Scale (UPDRS), a qualitative ranking system typically completed during an office visit. Kinesia integrates accelerometers and gyroscopes in a compact patient-worn unit to capture kinematic movement disorder features. Objectively quantifying PD manifestations with increased time resolution should aid in evaluating efficacy of treatment protocols and improve patient management. In this study, PD subjects performed the tremor subset of the UPDRS motor section while wearing Kinesia. Quantitative kinematic features were processed and highly correlated to clinician scores for rest tremor (r(2) = 0.89), postural tremor (r(2) = 0.90), and kinetic tremor (r(2) = 0.69). The quantitative features were used to develop a mathematical model that predicted tremor severity scores for new data with low errors. Finally, PD subjects indicated high clinical acceptance.
234 citations
TL;DR: The prevalence and clinical correlates of all DSM‐IV‐TR anxiety disorder diagnoses in a sample of 127 subjects with idiopathic PD who underwent comprehensive assessments administered by a psychiatrist and neurologist suggest that anxiety in PD is likely underdiagnosed and undertreated and refined characterization of anxiety disorders inPD is needed.
Abstract: Anxiety disorders are common in Parkinson's disease (PD), but are not well characterized. This study determined the prevalence and clinical correlates of all DSM-IV-TR anxiety disorder diagnoses in a sample of 127 subjects with idiopathic PD who underwent comprehensive assessments administered by a psychiatrist and neurologist. A panel of six psychiatrists with expertise in geriatric psychiatry and/or movement disorders established by consensus all psychiatric diagnoses. Current and lifetime prevalence of at least one anxiety disorder diagnosis was 43% (n = 55) and 49% (n = 63), respectively. Anxiety disorder not otherwise specified, a DSM diagnosis used for anxiety disturbances not meeting criteria for defined subtypes, was the most common diagnosis (30% lifetime prevalence, n = 38). Compared with nonanxious subjects, panic disorder (n = 13) was associated with earlier age of PD onset [50.3 (12.2) vs. 61.0 (13.7) years, P < 0.01], higher rates of motor fluctuations [77% (10/13) vs. 39% (25/64), P = 0.01] and morning dystonia [38% (5/13) vs. 13% (8/62), P < 0.03]. This high prevalence of anxiety disorders, including disturbances often not meeting conventional diagnostic criteria, suggests that anxiety in PD is likely underdiagnosed and undertreated and refined characterization of anxiety disorders in PD is needed. In addition, certain anxiety subtypes may be clinically useful markers associated with disease impact in PD.
226 citations
TL;DR: The management of dopaminergic drug‐related compulsive behaviors is discussed in the light of the current understanding of the neurobiological substrate of these disorders.
Abstract: Antiparkinson therapy can be the primary cause of a range of nonmotor symptoms that include a set of complex disinhibitory psychomotor pathologies and are linked by their repetitive, reward or incentive-based natures. These behaviors relate to aberrant or excessive dopamine receptor stimulation and encompass impulse control disorders (ICDs), punding, and the dopamine dysregulation syndrome (DDS). Common ICDs include pathological gambling, hypersexuality, compulsive eating, and compulsive buying. This review focuses on the phenomenology, epidemiology, and methods to identify and rate these disorders. The management of dopaminergic drug-related compulsive behaviors is discussed in the light of the current understanding of the neurobiological substrate of these disorders.
222 citations
TL;DR: A balanced Mediterranean‐like dietary regimen should be recommended before the introduction of levodopa; afterward, patients with advanced disease may benefit considerably from protein redistribution and low‐protein regimens.
Abstract: As with other neurodegenerative diseases, neurologic and nutritional elements may interact affecting each other in Parkinson's disease (PD). However, the long-term effects of such interactions on prognosis and outcome have not been given much attention and are poorly addressed by current research. Factors contributing to the clinical conditions of patients with PD are not only the basic features of PD, progression of disease, and the therapeutic approach but also fiber and nutrient intakes (in terms of both energy and protein content), fluid and micronutrient balance, and pharmaconutrient interactions (protein and levodopa). During the course of PD nutritional requirements frequently change. Accordingly, both body weight gain and loss may occur and, despite controversy, it seems that both changes in energy expenditure and food intake contribute. Nonmotor symptoms play a significant role and dysphagia may be responsible for the impairment of nutritional status and fluid balance. Constipation, gastroparesis, and gastro-oesophageal reflux significantly affect quality of life. Finally, any micronutrient deficiencies should be taken into account. Nutritional assessments should be performed routinely. Optimization of pharmacologic treatment for both motor and nonmotor symptoms is essential, but nutritional interventions and counseling could and should also be planned with regard to nutritional balance designed to prevent weight loss or gain; optimization of levodopa pharmacokinetics and avoidance of interaction with proteins; improvement in gastrointestinal dysfunction (e.g., dysphagia and constipation); prevention and treatment of nutritional deficiencies (micronutrients or vitamins). A balanced Mediterranean-like dietary regimen should be recommended before the introduction of levodopa; afterward, patients with advanced disease may benefit considerably from protein redistribution and low-protein regimens. © 2009 Movement Disorder Society
TL;DR: It is suggested that in nondemented, nondepressed PD patients, apathy may be a predictive factor for dementia and cognitive decline over time.
Abstract: Apathy is usually defined as a lack of motivation. It may occur as part of another disorder (notably depression and dementia) or as an isolated syndrome. In Parkinson's disease (PD), apathy is common and several studies have reported an association between this condition and more severe cognitive symptoms, such as executive dysfunction. However, this association has not been thoroughly investigated. The aim of this study (in nondepressed, nondemented PD patients) was to examine whether or not cognitive decline and/or dementia occurred more frequently in apathetic subjects than in nonapathetic subjects. Forty consecutive PD patients participated in the study (20 with apathy and 20 without). None of the subjects were either demented or depressed at the time of study entry. The patients' cognitive functions were extensively assessed twice: at study entry and after an 18-month follow-up period. At study entry, the apathetic PD patients had significantly lower global cognitive status and executive function scores than the nonapathetic subjects. After a median period of 18 months, the rate of conversion to dementia was found to be significantly higher in the apathetic group than in the nonapathetic group (8 of 20 and 1 of 20, respectively). Even in nondemented patients, the decrease over time in cognitive performance (mainly executive function but also memory impairment) was significantly greater in apathetic subjects than in nonapathetic subjects. These findings suggest that in nondemented, nondepressed PD patients, apathy may be a predictive factor for dementia and cognitive decline over time.
TL;DR: A subclassification of ET is proposed into three categories: hereditary ET, sporadic ET, and senile ET, which it is believed will help researchers resolve many of the controversies in this field.
Abstract: Essential tremor (ET) is a syndrome of tremor in posture and movement, but recent studies have revealed additional cerebellar motor disturbances, cognitive disturbances, personality changes, hearing loss, and olfactory deficits. Even dementia and shortened life expectancy were found in one cohort. Recent postmortem studies have found limited Lewy body pathology in some patients and Purkinje cell loss with torpedoes and Bergmann gliosis in others. These findings have led to the hypothesis that ET is a syndrome produced by at least two neurodegenerative diseases with more widespread clinical consequences than previously appreciated. We review the evidence for and against this hypothesis and conclude that studies purporting to support this hypothesis have failed to control for age-associated comorbidities, depression, medications, and other confounding factors. We propose the alternative hypothesis that abnormal neuronal oscillation is the fundamental abnormality in ET, and the well-documented cerebellar signs and symptoms, the controversial non-motor signs, and even the cerebellar pathology of ET could be caused by this oscillation. A major problem for many studies is the lack of a diagnostic gold standard. Lacking such a standard, we propose a subclassification of ET into three categories: hereditary ET, sporadic ET, and senile ET, which we believe will help researchers resolve many of the controversies in this field.
TL;DR: The results suggest that treadmill training associated with auditory and visual cues might give better results than more conventional treatments, and probably acts as a supplementary external cue.
Abstract: Freezing is a disabling symptom in patients with Parkinson's disease. We investigated the effectiveness of a new rehabilitation strategy based on treadmill training associated with auditory and visual cues. Forty Parkinsonian patients with freezing were randomly assigned to two groups: Group 1 underwent a rehabilitation program based on treadmill training associated with auditory and visual cues, while Group 2 followed a rehabilitation protocol using cues and not associated with treadmill. Functional evaluation was based on the Unified Parkinson's Disease Rating Scale Motor Section (UPDRS III), Freezing of Gait Questionnaire (FOGQ), 6-minute walking test (6MWT), gait speed, and stride cycle. Patients in both the groups had significant improvements in all variables considered by the end of the rehabilitation program (all P = 0.0001). Patients treated with the protocol including treadmill, had more improvement than patients in Group 2 in most functional indicators (P = 0.007, P = 0.0004, P = 0.0126, and P = 0.0263 for FOGQ, 6MWT, gait speed, stride cycle, respectively). The most striking result was obtained for 6MWT, with a mean increase of 130 m in Group 1 compared with 57 m in Group 2. Our results suggest that treadmill training associated with auditory and visual cues might give better results than more conventional treatments. Treadmill training probably acts as a supplementary external cue.
TL;DR: The benefit of high‐frequency rTMS on motor signs in PD was confirmed by the meta‐analysis and lower frequency rT MS had little effect on motorSigns in PD.
Abstract: The objective of this study was to evaluate the effects of repetitive Transcranial Magnetic Stimulation (rTMS) on motor signs in Parkinson's disease (PD). Medline, Embase, CINAHL, Web of Science, Scopus bibliographic, and Google Scholar databases were searched. Relevant controlled clinical trials published between January 1985 and October 2007 were extracted, reviewed, and validated according to the study protocol. The outcome of interest was the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS). We calculated the effect size for the included studies. Sensitivity analysis was performed to further assess factors that may change the results. Ten randomized, controlled clinical trials were included in the meta-analysis. Pooling of the results from these trials yielded an effect size of -0.58 in UPDRS for high-frequency rTMS studies and no significant effects for low-frequency rTMS studies. The benefit of high-frequency rTMS on motor signs in PD was confirmed by the meta-analysis. Lower frequency rTMS had little effect on motor signs in PD.
TL;DR: A brief ataxia rating scale (BARS) for use by movement disorder specialists and general neurologists is developed, valid, reliable, and sufficiently fast and accurate for clinical purposes.
Abstract: To develop a brief ataxia rating scale (BARS) for use by movement disorder specialists and general neurologists. Current ataxia rating scales are cumbersome and not designed for clinical practice. We first modified the International Cooperative Ataxia Rating Scale (ICARS) by adding seven ataxia tests (modified ICARS, or MICARS), and observed only minimally increased scores. We then used the statistics package R to find a five-test subset in MICARS that would correlate best with the total MICARS score. This was accomplished first without constraints and then with the clinical constraint requiring one test each of Gait, Kinetic Function-Arm, Kinetic Function-Leg, Speech, and Eye Movements. We validated these clinical constraints by factor analysis. We then validated the results in a second cohort of patients; evaluated inter-rater reliability in a third cohort; and used the same data set to compare BARS with the Scale for the Assessment and Rating of Ataxia (SARA). Correlation of ICARS with the seven additional tests that when added to ICARS form MICARS was 0.88. There were 31,481 five-test subtests (48% of possible combinations) that had a correlation with total MICARS score of ≥0.90. The strongest correlation of an unconstrained five-test subset was 0.963. The clinically constrained subtest validated by factor analysis, BARS, had a correlation with MICARS-minus-BARS of 0.952. Cronbach alpha for BARS and SARA was 0.90 and 0.92 respectively; and inter-rater reliability (intraclass correlation coefficient) was 0.91 and 0.93 respectively. BARS is valid, reliable, and sufficiently fast and accurate for clinical purposes. © 2009 Movement Disorder Society
TL;DR: Duodenal levodopa infusion seems to be an effective last‐line therapy for motor complications in Parkinson's disease, and technical improvements and earlier introduction should be considered.
Abstract: The studies of duodenal infusion of a levodopa on small groups of parkinsonian patients have reported beneficial effects on motor complications. However, little is known about the patient profile and indications for duodenal levodopa infusion. The purpose of this study is to exhaustively investigate the clinical characteristics of the population and indication, efficacy and tolerability of duodenal levodopa infusion in natural care settings. Of the 102 patients treated with duodenal levodopa infusion since 2003, 91 were enrolled in a multicentre retrospective study. The mean age was 72.7 years, with average disease duration of 17 years. Patients were at advanced stage: 91% had gait disorders, 65% had visual hallucinations, and 50% were demented (MMSE: 23). Duodenal levodopa infusion was the last line of treatment for motor complications in 98% of the patients, due to failure of or contraindication for apomorphine pump and neurosurgical treatments. Long-term treatment was observed by 73% of the population. Of these, >90% reported an improvement in motor fluctuations, quality of life, and autonomy. There were few severe adverse events. Technical problems were commonplace. Duodenal levodopa infusion seems to be an effective last-line therapy for motor complications in Parkinson's disease. Hence, technical improvements and earlier introduction should be considered.
TL;DR: These exploratory data highlight the psychosocial sequelae that swallowing impairment can have in those with IPD and suggest a possible association between swallowing, social function, and depression.
Abstract: Few studies exist in the literature investigating the impact of idiopathic Parkinson's Disease (IPD) on swallow-related quality of life. We therefore aimed in this project to: (1) evaluate swallow-specific quality of life in IPD; (2) delineate potential relationships between IPD duration and severity with swallow-specific quality of life; (3) investigate relationships between swallow-specific quality of life and general health-related quality of life; and (4) investigate relationships between swallow-specific quality of life and depression. Thirty-six patients diagnosed with IPD with and without dysphagia filled out self-report assessments of the SWAL-QOL, Parkinson's Disease Questionnaire-39 (PDQ-39), and Beck Depression Inventory (BDI). A series of Mann Whitney U tests were performed between non-dysphagic and dysphagic groups for the total SWAL-QOL score and the 10 SWAL-QOL domains. Spearman's Rho correlation analyses were performed between the SWAL-QOL and (1) PDQ-39; (2) Hoehn and Yahr stage; (3) PD disease duration; (4) UPDRS "on" score; and (5) the BDI. The dysphagia swallowing group reported significant reductions compared to the non-dysphagic group for the total SWAL-QOL score (P = 0.02), mental health domain score (P = 0.002) and social domain score (P = 0.002). No relationships existed between swallow-specific quality of life and disease duration or severity. Significant relationships existed between swallow-specific quality of life and general health-related quality of life (r(s) =-0.56, P = 0.000) and depression (r(s) = -0.48, P = 0.003). These exploratory data highlight the psychosocial sequelae that swallowing impairment can have in those with IPD and suggest a possible association between swallowing, social function, and depression.
TL;DR: The professional evolution and scientific validation of physical therapy in PD is reviewed, new strategies to improve the organization of allied health care in PD are discussed, making evidence‐based care available to all PD patients.
Abstract: Even with optimal medical management using drugs or neurosurgery, patients with Parkinson's disease (PD) are faced with progressively increasing mobility problems. For this reason, many patients require additional physical therapy. Here, we review the professional evolution and scientific validation of physical therapy in PD, and highlight several future challenges. To gain insight in ongoing, recently completed or published trials and systematic reviews, we performed a structured literature review and contacted experts in the field of physical therapy in PD. Following publication of the first controlled clinical trial in 1981, the quantity and quality of clinical trials evaluating the efficacy of physical therapy in PD has evolved rapidly. In 2004 the first guideline on physical therapy in PD was published, providing recommendations for evidence-based interventions. Current research is aiming to gather additional evidence to support specific intervention strategies such as the prevention of falls, and to evaluate the implementation of evidence into clinical practice. Although research focused on physical therapy for PD is a relatively young field, high-quality supportive evidence is emerging for specific therapeutic strategies. We provide some recommendations for future research, and discuss innovative strategies to improve the organization of allied health care in PD, making evidence-based care available to all PD patients.
TL;DR: Clinopathological and genetic findings in a carrier of the novel K263E TARDBP variation, who developed frontotemporal dementia, supranuclear palsy, and chorea, but no signs of motor neuron disease are described.
Abstract: TDP-43 has been identified as the pathological protein in the majority of cases of frontotemporal lobar degeneration and amyotrophic lateral sclerosis (ALS). TARDBP mutations have so far been uniquely associated with familial and sporadic ALS. We describe clinicopathological and genetic findings in a carrier of the novel K263E TARDBP variation, who developed frontotemporal dementia, supranuclear palsy, and chorea, but no signs of motor neuron disease. Neuropathologic examination revealed neuronal and glial TDP-43-immunoreactive deposits, predominantly in subcortical nuclei and brainstem. This is the first report of a TARDBP variation associated with a neurodegenerative syndrome other than ALS.
TL;DR: Some aspects of dysprosody in Parkinson's disease show characteristic changes over time, but show no clear correlation with general motor impairment as assessed by UPDRS motor score, suggesting that the underlying mechanism could be independent from dopaminergic deficits.
Abstract: Parkinsonian speech or hypokinetic dysarthria results from a multidimensional impairment of phonation, articulation, and prosody. Although the dysprosody in Parkinson's disease (PD) is well described (alterations in speech rate and pause time, speech intensity and pitch variation), little is known about alterations of these single prosodic parameters over a longer time course. The objective of this study is to analyze changes of speech rate and pitch variation in patients with PD over time and to compare these findings with healthy controls. Patients with PD (N = 50; 27 male and 23 female) and n = 50 age-matched healthy controls (25 male, 25 female) were tested and retested after at least 7 months (mean: 25.02; median: 21; SD: 17.44; range: 7–79 months). In the PD group, motor impairment according to UPDRS motor score was similar at first and second visit. The participants had to accomplish a standardized four sentence reading task. The acoustical analysis was performed using a standard head-worn microphone for voice recordings and commercial audio software (WaveLab®). For the determination of intonation based upon fundamental frequency (F0) variation, we used a computer analysis program (Praat®). Articulatory velocity was determined by measurement of syllable rate and pause ratios. In the PD group, total speech rate (syllables per second related to total speech time/TSR) and net speech rate declined from first to second examination, especially in the male patients, but showed no significant differences to the control group. The course of pitch variation revealed some gender particularities. Whereas female patients' pitch variability declined over time, male patients' intonation variability remained relatively stable. F0 variation in male and female patients with PD were significantly reduced compared with the control group in the first examination and the follow up as well. Progression of prosodic impairment over time showed no correlation to disease duration or UPDRS motor score. Some aspects of dysprosody in PD show characteristic changes over time, but show no clear correlation with general motor impairment as assessed by UPDRS motor score. Therefore, we suspect that the underlying mechanism could be independent from dopaminergic deficits. © 2008 Movement Disorder Society
TL;DR: Direct stimulation of the pedunculopontine nucleus can ameliorate some symptoms of Parkinson's disease, as demonstrated in both experimental animals and man.
Abstract: The pedunculopontine nucleus is composed of cholinergic and non-cholinergic neurones and is located in the caudal pontomesencephalic tegmentum. Evidence suggests that the nucleus plays a role in the production and control of movement. The nucleus has dense interconnections with the basal ganglia, as well as with other areas of the brain associated with motor control. Electrical stimulation of the pedunculopontine nucleus in the decerebrate cat or rat produces organized locomotor movements. Physiological studies show that the pedunculopontine nucleus modulates its activity in response to locomotion, as well as voluntary arm and eye movements. Degeneration of the pedunculopontine nucleus is seen in post-mortem brains in humans with Parkinson's disease and Parkinsonian syndromes. In animal models of Parkinson's disease, metabolic changes are seen in the pedunculopontine nucleus, and chemical inhibition or mechanical disruption of the nucleus can produce an akinetic state in animals and man. In this paper we review the literature in support of the suggestion that some of the symptoms of Parkinson's disease are caused by dysfunction of the pedunculopontine nucleus. In accordance with this view, direct stimulation of the nucleus can ameliorate some symptoms of the disease, as demonstrated in both experimental animals and man.
TL;DR: On‐site clinical diagnosis overdiagnosed degenerative parkinsonism at baseline in diagnostically uncertain cases compared with the gold standard clinical diagnosis (at 36 months), the latter giving a sensitivity of 93% and specificity of 46%.
Abstract: Overdiagnosis of Parkinson's disease (PD) is suggested by specialist review of community diagnosis, and in postmortem studies. In specialist centers 4 to 15% of patients entered into clinical trials as early PD do not have functional imaging support for a PD diagnosis. In a European multicenter, prospective, longitudinal study, we compared clinical diagnosis with functional SPECT imaging using [123I]FP-CIT (DaTSCAN, GE Healthcare). Repeat observations were performed over 3 years in patients with tremor and/or parkinsonism in whom there was initial diagnostic uncertainty between degenerative parkinsonism and nondegenerative tremor disorders. Video-recording of clinical features was scored independently of functional imaging results by two blinded clinicians at 36 months (= gold standard clinical diagnosis). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The main endpoint was the sensitivity and specificity of SPECT imaging at baseline compared with the gold standard. In 99 patients completing the three serial assessments, on-site clinical diagnosis overdiagnosed degenerative parkinsonism at baseline in diagnostically uncertain cases compared with the gold standard clinical diagnosis (at 36 months), the latter giving a sensitivity of 93% and specificity of 46%. The corresponding baseline [123I]FP-CIT SPECT results showed a mean sensitivity of 78% and a specificity of 97%. Inter-reader agreement for rating scans as normal or abnormal was high (Cohen's kappa = 0.94-0.97).
TL;DR: The movement strategy group showed improvements on several outcome measures from admission to discharge, including the UPDRS, 10 m walk, 2 minute walk, balance, and PDQ39, however, from discharge to follow up there was significant regression in performance.
Abstract: This randomized controlled clinical trial was conducted to compare the effects of movement rehabilitation strategies and exercise therapy in hospitalized patients with idiopathic Parkinson's disease. Participants were randomly assigned to a group that received movement strategy training or musculoskeletal exercises during 2 consecutive weeks of hospitalization. The primary outcome was disability as measured by the Unified Parkinson's Disease Rating Scale, UPDRS (motor and ADL components). Secondary outcomes were balance, walking speed, endurance, and quality of life. Assessments were carried out by blinded testers at baseline, after the 2 weeks of treatment and 3 months after discharge. The movement strategy group showed improvements on several outcome measures from admission to discharge, including the UPDRS, 10 m walk, 2 minute walk, balance, and PDQ39. However, from discharge to follow up there was significant regression in performance on the 2 minute walk and PDQ39. For the exercise group, quality of life improved significantly during inpatient hospitalization and this was retained at follow-up. Inpatient rehabilitation produces short term reductions in disability and improvements in quality of life in people with Parkinson's disease.
TL;DR: Further research on PD‐specific tools seems mandatory to help establish accurate cut‐off scores for the diagnosis of mild PDD, detect cognitive profiles more prone to the future development of dementia, and allow comparisons between different descriptive or interventional studies.
Abstract: Cognitive impairment (CI) and dementia are frequent and debilitating features associated with Parkinson's disease (PD). Formal neuropsychological examination is required to ascertain the degree and pattern of CI over the course of the disease. The use of different tools may explain heterogeneous data obtained from studies to date. Normative data for extensively used scales [Mattis Dementia Rating Scale (MDRS), Mini-Mental State Examination (MMSE)] is incomplete in PD populations. According to sample characteristics, statistical analyses, and methodological quality, 33 studies using scales not specific to PD (MDRS, MMSE, Cambridge Cognitive Assessment, FAB) or PD-specific scales (Mini-Mental Parkinson, Scales for Outcomes of Parkinson's disease-Cognition, Parkinson's Disease-Cognitive Rating Scale, and Parkinson Neuropsychometric Dementia Assessment) were eligible for the critical analysis of their appropriateness to assess cognition in PD. Of the four scales specifically designed for PD, the SCOPA-COG and the PD-CRS have undergone extensive and rigorous validation processes. While the SCOPA-COG mainly assesses "frontal-subcortical" cognitive defects, the PD-CRS also assesses "instrumental-cortical" functions, allowing better characterization of the different patterns of CI that may be present in PD from the earliest stages. The MMP and PANDA scales were designed as brief screening tests for CI and have not yet been subjected to extensive clinimetric evaluations. Further research on PD-specific tools seems mandatory to help establish accurate cut-off scores for the diagnosis of mild PDD, detect cognitive profiles more prone to the future development of dementia, and allow comparisons between different descriptive or interventional studies.
TL;DR: Findings suggest underlying AD‐pathology in PDD in association with cortical cognitive dysfunction, and that low CSF beta‐amyloid in PDND patients with impaired phonetic fluency can constitute an early marker of cognitive dysfunction.
Abstract: Alzheimer's disease (AD)-pathology may play a role in Parkinson's disease (PD)-related dementia (PDD). The aim of this study was to assess cerebrospinal fluid (CSF) levels of tau, phospho-tau, and beta-amyloid, proposed AD biomarkers, and their relationship with cognitive function in PD. Forty PD patients [20 nondemented (PDND); 20 PDD] and 30 controls underwent CSF tau, phospho-tau, and beta-amyloid analysis using specific ELISA techniques. All PD patients and 15 controls underwent neuropsychological testing of fronto-subcortical (attention, fluency) and neocortical (memory, naming, visuoperceptive) functions. CSF markers levels were compared between groups, and compared and correlated with neuropsychological measures in PDND and PDD separately and as a continuum (PD). CSF tau and phospho-tau were higher in PDD than in PDND and controls (P < 0.05). CSF beta-amyloid ranged from high (controls) to intermediate (PDND) and low (PDD) levels (P < 0.001). In all PD and PDD patients, high CSF tau and phospho-tau were associated with impaired memory and naming. In PDND, CSF beta-amyloid was related with phonetic fluency. These findings suggest underlying AD-pathology in PDD in association with cortical cognitive dysfunction, and that low CSF beta-amyloid in PDND patients with impaired phonetic fluency can constitute an early marker of cognitive dysfunction.
TL;DR: An appreciation of the multiple roles that serotonin (5‐HT) may play in Parkinson's disease has increased, but several unanswered questions remain, and future studies need to focus on correlating changes in 5‐HT neurotransmission in both pathological and in vivo imaging studies with a full clinical phenotype.
Abstract: An appreciation of the multiple roles that serotonin (5-HT) may play in Parkinson's disease (PD) has increased in recent years. Early pathological studies in PD demonstrated nonselective reductions of 5-HT in brain tissue but little correlation to comorbidities such as dyskinesia and mood disturbance. This, combined with treatment failures using serotonergic drugs in comparison to levodopa, meant the field was largely neglected until recently. The multitude of subtypes of 5-HT receptors in the brain and an increased understanding of the potential function 5-HT may play in modulating other neurotransmitter systems, including dopamine, GABA, and glutamate, have meant an expansion in efforts to develop potential serotonergic drugs for both motor and nonmotor symptoms in PD. However, several unanswered questions remain, and future studies need to focus on correlating changes in 5-HT neurotransmission in both pathological and in vivo imaging studies with a full clinical phenotype.
TL;DR: Current knowledge on myoclonus‐dystonia is summarized, with a focus on recent findings, and modified diagnostic criteria and recommendations for clinical management are proposed.
Abstract: Our knowledge of the clinical, neurophysiological, and genetic aspects of myoclonus-dystonia (M-D) has improved markedly in the recent years. Basic research has provided new insights into the complex dysfunctions involved in the pathogenesis of M-D. On the basis of a comprehensive literature search, this review summarizes current knowledge on M-D, with a focus on recent findings. We also propose modified diagnostic criteria and recommendations for clinical management.
TL;DR: The feasibility of a computer based at‐home testing device (AHTD) in early‐stage, unmedicated Parkinson's disease (PD) patients over 6 months is tested, and high patient compliance and satisfaction suggest the feasibility of its incorporation into larger clinical trials, especially when travel is difficult and early changes or frequent data collection are considered important to document.
Abstract: We tested the feasibility of a computer based at-home testing device (AHTD) in early-stage, unmedicated Parkinson's disease (PD) patients over 6 months. We measured compliance, technical reliability, and patient satisfaction to weekly assessments of tremor, small and large muscle bradykinesia, speech, reaction/movement times, and complex motor control. relative to the UPDRS motor score. The AHTD is a 6.5″ × 10″ computerized assessment battery. Data are stored on a USB memory stick and sent by internet to a central data repository as encrypted data packets. Although not designed or powered to measure change, the study collected data to observe patterns relative to UPDRS motor scores. Fifty-two PD patients enrolled, and 50 completed the 6 month trial, 48 remaining without medication. Patients complied with 90.6% of weekly 30-minute assessments, and 98.5% of data packets were successfully transmitted and decrypted. On a 100-point scale, patient satisfaction with the program at study end was 87.2 (range: 80–100). UPDRS motor scores significantly worsened over 6 months, and trends for worsening over time occurred for alternating finger taps (P = 0.08), tremor (P = 0.06) and speech (P = 0.11). Change in tremor was a significant predictor of change in UPDRS (P = 0.047) and was detected in the first month of the study. This new computer-based technology offers a feasible format for assessing PD-related impairment from home. The high patient compliance and satisfaction suggest the feasibility of its incorporation into larger clinical trials, especially when travel is difficult and early changes or frequent data collection are considered important to document. © 2008 Movement Disorder Society
TL;DR: In this paper, the authors conducted a larger multicenter European study to assess medicine-taking behavior for patients with Parkinson's disease taking dopaminergic therapy and found that patients with suboptimal therapy adherence took less than 80% of prescribed doses.
Abstract: Two small studies reported suboptimal therapy adherence in Parkinson's disease. We conducted a larger multicenter European study to assess medicine-taking behavior. Parkinson's disease patients taking dopaminergic therapy were enrolled in 8 centers in 5 countries, and disease severity and demographics recorded. Antiparkinson drug adherence was measured for 4 weeks using electronic monitoring bottles which record the date and time of cap opening (Aardex, Switzerland). One hundred twelve patients, mean age 65 years (standard deviation (SD) 10), with Parkinson's disease for 7.7 (SD 8.2) years completed the study. Total median adherence (doses taken/doses prescribed) was 97.7% (interquartile range [IQ] 90.6-100), days adherence (correct dose days) was 86.2% (IQ 61.1-96.2) and timing adherence (doses taken at correct time intervals) was 24.4% (IQ 5.3-56.5). Fourteen patients (12.5%) took less than 80% of prescribed doses, which was defined as suboptimal adherence. Patients with satisfactory adherence took a median of 8 mg/day (IQ 0-33) less than their prescribed dose of levodopa (P = NS), while suboptimal adherence patients took a median of 481 mg/day (IQ 205-670) less than their prescribed dose (P = 0.0006). The Parkinson motor score was significantly higher in patients with suboptimal adherence at 29 (IQ 20-40), versus those with satisfactory adherence at 19 (IQ 13-26), P = 0.005. Once daily drugs had significantly better adherence when compared with drugs prescribed more frequently (P < 0.0001). Suboptimal therapy adherence is associated with significant deviation from prescribed levodopa doses, despite greater Parkinson's motor severity. Optimizing oral medication intake has a potential role in maximizing the therapy response in Parkinson's disease.