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Janis M Miyasaki,
J Long,
D Mancini,
E Moro,
S H Fox, A E Lang,
C Marras,
R Chen,
A Strafella,
R Arshinoff,
R Ghoche,
J Hui
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ABSTRACT: Palliative care provides a holistic approach to symptom relief using a multidisciplinary team approach to enhance quality of life throughout the entire course of a particular illness. The care team consists of movement disorders neurologist, a palliative care physician, a wound care nurse, a spiritual counselor and a care coordinator. Palliative care concepts were applied to a group of advanced Parkinson disease (PD) patients in a dedicated Palliative Care Clinic. METHODS: A modified Edmonton Symptom Assessment System Scale for PD (ESAS-PD) was developed and applied to 65 PD patients at their initial consultation and following recommended interventions. Scores were compared to those of metastatic cancer patients reported in the palliative care literature. RESULTS: The ESAS-PD scores significantly improved after the interventions (56 and 40 respectively, p = 0.0001). The most improved items were constipation, dysphagia, anxiety, pain and drowsiness. ESAS-PD scores were not significantly different from metastatic cancer patients' ESAS scores. CONCLUSIONS: ESAS-PD is a quick, effective scale for assessment of late stage PD symptoms. Scores are sensitive to intervention, and therefore have potential clinical utility for physicians and other healthcare providers. Advanced PD patients have a similar degree of symptoms as metastatic cancer patients, respond to treatment in a similar way, and therefore should have access to palliative care services.
Parkinsonism & Related Disorders 08/2012; · 3.80 Impact Factor
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ABSTRACT: Parkinsonism, as a gradually progressive disorder, has a prodromal interval during which neurodegeneration has begun but cardinal manifestations have not fully developed. A systematic direct assessment of this interval has never been performed. Since patients with idiopathic REM sleep behaviour disorder are at very high risk of parkinsonism, they provide a unique opportunity to observe directly the development of parkinsonism. Patients with idiopathic REM sleep behaviour disorder in an ongoing cohort study were evaluated annually with several quantitative motor measures, including the Unified Parkinson's Disease Rating Scale, Purdue Pegboard, alternate-tap test and timed up-and-go. Patients who developed parkinsonism were identified from this cohort and matched according to age to normal controls. Their results on motor testing from the preceding years were plotted, and then assessed with regression analysis, to determine when markers first deviated from normal values. Sensitivity and specificity of quantitative motor markers for diagnosing prodromal parkinsonism were assessed. Of 78 patients, 20 developed parkinsonism. On regression analysis, the Unified Parkinson's Disease Rating Scale first intersected normal values at an estimated 4.5 years before diagnosis. Voice and face akinesia intersected earliest (estimated prodromal interval = 9.8 years), followed by rigidity (4.4 years), gait abnormalities (4.4 years) and limb bradykinesia (4.2 years). Quantitative motor tests intersected normal values at longer prodromal intervals than subjective examination (Purdue Pegboard = 8.6 years, alternate-tap = 8.2, timed up-and-go = 6.3). Using Purdue Pegboard and the alternate-tap test, parkinsonism could be detected with 71-82% sensitivity and specificity 3 years before diagnosis, whereas a Unified Parkinson's Disease Rating Scale score >4 identified prodromal parkinsonism with 88% sensitivity and 94% specificity 2 years before diagnosis. Removal of action tremor scores improved sensitivity to 94% and specificity to 97% at 2 years before diagnosis (cut-off >3). Although distinction between conditions was often difficult, prodromal dementia with Lewy bodies appeared to have a slower progression than Parkinson's disease (prodromal interval = 6.0 versus 3.8 years). Using a cut-off of Unified Parkinson's Disease Rating Scale >3 (excluding action tremor), 25% of patients with 'still-idiopathic' REM sleep behaviour disorder demonstrated evidence of possible prodromal parkinsonism. Therefore, using direct assessment of motor examination before parkinsonism in a REM sleep behaviour disorder, we have estimated a prodromal interval of ∼4.5 years on the Unified Parkinson's Disease Rating Scale; other quantitative markers may detect parkinsonism earlier. Simple quantitative motor measures may be capable of reliably detecting parkinsonism, even before a clinical diagnosis can be made by experienced movement disorders neurologists.
Brain 05/2012; 135(Pt 6):1860-70. · 9.46 Impact Factor
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Neurology 03/2012; 78(11):838-9. · 8.31 Impact Factor
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ABSTRACT: To determine the efficacy and safety of pardoprunox in levodopa-treated patients with Parkinson's disease (PD) experiencing motor fluctuations.
Patients were randomized to pardoprunox (up to 42 mg/day, n = 150) or placebo (n = 144). Pardoprunox was titrated to an optimal dose over 7 weeks, followed by a 12-week stable dose period. The primary efficacy variable was the change from baseline to study endpoint in total daily OFF time, based on patient diaries. Secondary analyses included the change in ON time without troublesome dyskinesias, UPDRS-ADL + Motor ON, UPDRS-ADL OFF and PDQ-39. Subgroup analyses explored the impact of pardoprunox on dyskinesias (UPDRS items 32 + 33), depression (Hospital Anxiety Depression Scale) and pain (Visual Analogue Scale).
Pardoprunox significantly reduced OFF time versus placebo (-1.62 h/day versus -0.92 h/day, respectively, p = 0.0215). Compared to placebo, pardoprunox improved ON time without troublesome dyskinesias (p = 0.0386), UPDRS-ADL + Motor ON (p = 0.0003), and UPDRS-ADL OFF (p < 0.0001), while no significant difference was observed on PDQ-39. A high drop-out rate due to adverse events (AEs) (pardoprunox, 37%; placebo, 12%) suggested that the selected dose range may have been too high, and/or titration was too rapid.
Pardoprunox decreased OFF time and increased ON time without troublesome dyskinesias in levodopa-treated PD patients. The high drop-out rate at the selected doses justifies the investigation of lower doses. The impact of pardoprunox on dyskinesias and non-motor symptoms deserves further investigation.
Parkinsonism & Related Disorders 02/2012; 18(4):370-6. · 3.80 Impact Factor
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Movement Disorders 09/2011; 27(2):326. · 4.51 Impact Factor
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C Marras,
B Schüle,
B Schuele,
R P Munhoz,
E Rogaeva,
J W Langston,
M Kasten,
C Meaney,
C Klein,
P M Wadia, [......],
T Steeves,
K M Prakash,
R M A de Bie,
G Adeli,
T Thomsen,
K K Johansen,
H A Teive,
A Asante,
W Reginold, A E Lang
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ABSTRACT: Using a family study design, we describe the motor and nonmotor phenotype in probands with LRRK2 G2019S mutations and family members and compare these individuals to patients with idiopathic Parkinson disease (iPD) and unrelated controls.
Probands with G2019S mutations and their first-degree relatives, subjects with iPD, and unrelated control subjects were identified from 4 movement disorders centers. All underwent neurologic examinations and tests of olfaction, color vision, anxiety, and depression inventories.
Tremor was more often a presenting feature among 25 individuals with LRRK2-associated PD than among 84 individuals with iPD. Subjects with LRRK2-PD had better olfactory identification compared with subjects with iPD, higher Beck Depression Inventory scores, and higher error scores on Farnsworth-Munsell 100-Hue test of color discrimination. Postural or action tremor was more common among 29 nonmanifesting mutation carriers compared with 53 noncarriers within the families. Nonparkinsonian family members had higher Unified Parkinson's Disease Rating Scale motor scores, more constipation, and worse color discrimination than controls, regardless of mutation status.
Although tremor is a more common presenting feature of LRRK2-PD than iPD and some nonmotor features differed in degree, the phenotype is largely overlapping. Postural or action tremor may represent an early sign. Longitudinal evaluation of a large sample of nonmanifesting carriers will be required to describe any premotor phenotype that may allow early diagnosis.
Neurology 07/2011; 77(4):325-33. · 8.31 Impact Factor
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ABSTRACT: To evaluate the perception of patients with Parkinson's disease (PD) regarding dyskinesia.
Multicentre survey.
Tertiary referral centres.
Patients with PD participated in a survey: those not on dopaminergic medications (group I), those on dopaminergic medications without dyskinesia (group II) and those on dopaminergic medications with dyskinesia (group III).
After a short standardised description and explanation of dyskinesia was provided, patients were asked about the nature and source of prior knowledge of dyskinesia. They were then asked about their perceptions of dyskinesia. Patients in group III were also asked about the duration, the severity of dyskinesia and whether their perception of this problem had changed since its appearance.
Level of concern regarding dyskinesia and whether their perception of dyskinesia would have changed their preference of treatment. Results 259 PD patients completed the survey (group I, 52; group II, 102; group III, 105). Patients with dyskinesia were significantly less concerned about dyskinesia than patients without dyskinesia and were more likely to choose dyskinesia over being parkinsonian. Patients who required fewer changes in medications because of dyskinesia were more likely to choose dyskinesia over parkinsonism.
Patients with PD experiencing dyskinesia are less likely to be concerned about dyskinesia and more likely to prefer dyskinesia over parkinsonian symptoms than patients without dyskinesia.
Journal of neurology, neurosurgery, and psychiatry 10/2010; 81(10):1112-5. · 4.87 Impact Factor
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ABSTRACT: Some patients with Parkinson disease (PD) develop pathological gambling when treated with dopamine agonists (DAs). However, little is known about DA-induced changes in neuronal networks that may underpin this drug-induced change in behavior in vulnerable individuals. In this case-control study, we aimed to investigate DA-induced changes in brain activity that may differentiate patients with PD with DA-induced pathological gambling (gamblers) from patients with PD without such a history (controls).
Following overnight withdrawal of antiparkinsonian medication, patients were studied with H₂(15)O PET before and after administration of DA (3 mg apomorphine) to measure changes in regional cerebral blood flow as an index of regional brain activity during a card selection game with probabilistic feedback.
We observed that the direction of DA-related activity change in brain areas that are implicated in impulse control and response inhibition (lateral orbitofrontal cortex, rostral cingulate zone, amygdala, external pallidum) distinguished gamblers from controls. DA significantly increased activity in these areas in controls, while gamblers showed a significant DA-induced reduction of activity.
We propose that in vulnerable patients with PD, DAs produce an abnormal neuronal pattern that resembles those found in nonparkinsonian pathological gambling and drug addiction. DA-induced disruption of inhibitory key functions--outcome monitoring (rostral cingulate zone), acquisition and retention of negative action-outcome associations (amygdala and lateral orbitofrontal cortex)--together with restricted access of those areas to executive control (external pallidum)--may well explain loss of impulse control and response inhibition in vulnerable patients with PD, thereby fostering the development of pathological gambling.
Neurology 10/2010; 75(19):1711-6. · 8.31 Impact Factor
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E Sidransky,
M A Nalls,
J O Aasly,
J Aharon-Peretz,
G Annesi,
E R Barbosa,
A Bar-Shira,
D Berg,
J Bras,
A Brice, [......],
N Tayebi,
T Toda,
A R Troiano,
S Tsuji,
M Wittstock,
T G Wolfsberg,
Y-R Wu,
C P Zabetian,
Y Zhao,
S G Ziegler
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ABSTRACT: Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson's disease.
Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson's disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel-Haenszel procedure used to estimate odds ratios across centers.
All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of patients and 3% of controls, and among non-Ashkenazi Jewish subjects, either mutation was found in 3% of patients and less than 1% of controls. GBA was fully sequenced for 1883 non-Ashkenazi Jewish patients, and mutations were identified in 7%, showing that limited mutation screening can miss half the mutant alleles. The odds ratio for any GBA mutation in patients versus controls was 5.43 across centers. As compared with patients who did not carry a GBA mutation, those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were more likely to have atypical clinical manifestations.
Data collected from 16 centers demonstrate that there is a strong association between GBA mutations and Parkinson's disease.
New England Journal of Medicine 10/2009; 361(17):1651-61. · 53.30 Impact Factor
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ABSTRACT: Pathological gambling is an impulse control disorder reported in association with dopamine agonists used to treat Parkinson's disease. Although impulse control disorders are conceptualized as lying within the spectrum of addictions, little neurobiological evidence exists to support this belief. Functional imaging studies have consistently demonstrated abnormalities of dopaminergic function in patients with drug addictions, but to date no study has specifically evaluated dopaminergic function in Parkinson's disease patients with impulse control disorders. We describe results of a [(11)C] raclopride positron emission tomography (PET) study comparing dopaminergic function during gambling in Parkinson's disease patients, with and without pathological gambling, following dopamine agonists. Patients with pathological gambling demonstrated greater decreases in binding potential in the ventral striatum during gambling (13.9%) than control patients (8.1%), likely reflecting greater dopaminergic release. Ventral striatal bindings at baseline during control task were also lower in patients with pathological gambling. Although prior imaging studies suggest that abnormality in dopaminergic binding and dopamine release may be markers of vulnerability to addiction, this study presents the first evidence of these phenomena in pathological gambling. The emergence of pathological gambling in a number of Parkinson's disease patients may provide a model into the pathophysiology of this disorder.
Brain 05/2009; 132(Pt 5):1376-85. · 9.46 Impact Factor
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ABSTRACT: Intracortical inhibition in the motor cortex may be measured with short interval intracortical inhibition (SICI), likely mediated by GABA(A) receptors, and long interval intracortical inhibition (LICI), likely mediated by GABA(B) receptors. Separate neuronal populations mediate SICI and LICI, and LICI inhibits SICI, likely through GABA(B) mediated presynaptic inhibition. The purpose of this study was to test the hypothesis that cortical presynaptic inhibition in Parkinson disease (PD) is impaired.
Eleven patients with PD were studied at rest both OFF and ON dopaminergic medications and the results were compared to nine healthy, age-matched controls. Motor evoked potentials were recorded from the first dorsal interosseous muscle and a triple-stimulus transcranial magnetic stimulation paradigm was used to evaluate SICI in the presence of LICI. The interstimulus interval (ISI) for SICI was 2 msec and LICI was studied at 100 (LICI(100)) and 150 msec (LICI(150)) ISIs.
There was no difference in SICI between the controls and PD ON and PD OFF groups. LICI(100) was stronger than LICI(150) and both were reduced in the PD ON and OFF groups. LICI(100) led to a much greater reduction in SICI in the control group compared to both the PD OFF and ON groups. LICI(150) caused no significant change in SICI with no significant difference between the controls and PD OFF and PD ON groups.
The inhibitory effect of long interval intracortical inhibition on short interval intracortical inhibition, likely representing presynpatic inhibition in the motor cortex, is decreased in Parkinson disease and may be a nondopaminergic feature of the disease.
Neurology 04/2009; 72(9):842-9. · 8.31 Impact Factor
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V. Voon,
P. Krack, A. E. Lang,
A. M. Lozano,
K. Dujardin,
M. Schuepbach,
S. Thobois,
F. Tamma,
J. Herzog,
J. Samanta,
C. Kubu,
H. Rossignol
European Journal of Endocrinology - EUR J ENDOCRINOLOGY. 01/2009; 132(10).
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E Moro,
J Volkmann,
I R König,
S Winkler,
A Hiller,
S Hassin-Baer,
J Herzog,
A Schnitzler,
K Lohmann,
M O Pinsker,
J Voges,
A Djarmatic,
P Seibler,
A M Lozano,
E Rogaeva, A E Lang,
G Deuschl,
C Klein
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ABSTRACT: To study the frequency of different gene mutations in patients with early-onset parkinsonism and bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and the short- and long-term surgical outcome in mutation-positive (MUT+) and -negative (MUT-) patients.
Eighty patients with disease onset at age <or= 45 years and bilateral STN-DBS were screened for mutations in the Parkin gene and PINK1 gene and for the recurrent p.G2019S mutation in the LRRK2 gene. The Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H-Y) scale were used to compare the on- and off-medication conditions preoperatively and in the off-medication/on-stimulation condition postoperatively.
We identified 12 mutation carriers (11 Parkin [6 with 2 mutated alleles, 5 with 1 mutated allele], 1 homozygous PINK1). There were no clinical differences between the MUT- and MUT+ patients preoperatively, except for more severe H-Y stage and postural and gait scores in the on-medication state in the MUT+ group. During the first year after surgery, MUT- patients showed better clinical improvement (56% motor UPDRS improvement) compared with MUT+ patients (36%). However, in the long-term follow-up (3-6 years), both groups presented with the same degree of clinical improvement (MUT-: 44% vs MUT+: 42%). Although the MUT+ group showed more severe axial signs preoperatively, MUT- patients developed levodopa- and deep brain stimulation-resistant axial signs within the first 3 to 6 years postoperatively, which diminished the initial benefit soon after surgery.
Patients with Parkin or PINK1 mutations benefit from subthalamic nucleus deep brain stimulation. However, the clinical response is not superior to non-mutation carriers and might be limited by more advanced axial motor symptoms at a relatively early disease stage.
Neurology 05/2008; 70(14):1186-91. · 8.31 Impact Factor
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ABSTRACT: Current Health Canada instructions for use of the dopamine agonists (DA), pramipexole and ropinirole, state that Parkinson's disease (PD) patients should be told not to drive. The objective was to assess neurologists' actual clinical practice concerning driving advice they give to PD patients starting a DA.
An online survey was created consisting of 4 items regarding demographics, 5 regarding PD and driving, and 9 regarding DA use and driving. The survey was distributed to 563 neurologists.
In total 96 neurologists (17.9%) responded. 4.4% tell patients with PD not to drive, solely because they are taking a DA. Respondents assess the patient's tendency for excessive daytime sleepiness and sleep attacks after starting a DA more frequently than after starting other dopaminergic drugs (p < 0.001).
A minor proportion of the clinicians responding to our survey advise PD patients not to drive, solely because they use a DA. Such being the case, we propose that current Health Canada guidelines need revision.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 11/2007; 34(4):438-42. · 0.97 Impact Factor
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ABSTRACT: Respiratory myoclonus or diaphragmatic flutter is an unusual movement disorder with abnormal diaphragmatic activity, which may be associated with respiratory symptoms. The effects of distracting maneuvers on diaphragmatic activity have not been investigated.
Two patients with nondisabling abdominal movements of suspected diaphragmatic origin were studied with surface and needle electromyography (EMG).
The abdominal movements resulted from isolated, rhythmic diaphragmatic contractions with variable EMG burst duration, suppressibility with breath-holding and distracting maneuvers, and other attributes of volitional control.
"Respiratory myoclonus" may be a heterogeneous disorder ranging from synchronous movements of the diaphragm and other respiratory muscles associated with respiratory compromise, to diaphragmatic movements under at least some volitional control with no respiratory or functional disability. The latter group could be designated phenomenologically as "isolated diaphragmatic tremor."
Neurology 09/2007; 69(7):689-92. · 8.31 Impact Factor
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ABSTRACT: Ten patients with severe cervical dystonia (CD) unresponsive to medical treatment underwent bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) and were followed for 31.9 +/- 20.9 months. At last follow-up, the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity score improved by 54.8%, the TWSTRS disability score improved by 59.1%, and the TWSTRS pain score improved by 50.4%. Bilateral GPi DBS is an effective long-term therapy in patients with CD.
Neurology 03/2007; 68(6):457-9. · 8.31 Impact Factor
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Neurology 03/2007; 68(9):704-5. · 8.31 Impact Factor
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ABSTRACT: Peripheral sensory stimulation at the wrist inhibits the motor cortex as measured by transcranial magnetic stimulation at interstimulus intervals of approximately 20 ms (short latency afferent inhibition [SAI]) and 200 ms (long latency afferent inhibition [LAI]). Previous studies suggested that reduced SAI in Parkinson disease (PD) reflects adverse effect of dopaminergic medications and reduced LAI may be related to nondopaminergic manifestations of PD. We hypothesize that subthalamic nucleus (STN) deep brain stimulation (DBS) may correct these deficiencies.
We studied the effects of STN DBS on SAI and LAI in seven PD patients and age-matched controls. PD patients were studied in an off medication followed by an on medication session, with the stimulator switched on or off in random order in each session.
In the on medication session, SAI was reduced in the stimulator off condition and was restored by STN DBS. LAI was partially normalized by STN DBS in the medication on condition.
Subthalamic nucleus (STN) stimulation improves short latency afferent inhibition, suggesting that it could normalize pathways that are adversely affected by dopaminergic medications. The effect of STN stimulation on long latency afferent inhibition suggests that it may influence nondopaminergic pathways involved in sensorimotor integration.
Neurology 02/2007; 68(5):356-63. · 8.31 Impact Factor
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ABSTRACT: We surveyed 297 patients with Parkinson disease (PD) with systematic screens and rigorous definitional criteria. Pathologic hypersexuality lifetime prevalence was 2.4%. Compulsive shopping was 0.7%. Combined with our pathologic gambling data, the lifetime prevalence of these behaviors was 6.1% and increases to 13.7% in patients on dopamine agonists.
Neurology 11/2006; 67(7):1254-7. · 8.31 Impact Factor
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Journal of neurology, neurosurgery, and psychiatry 11/2006; 77(10):1194-5. · 4.87 Impact Factor
