Duodenal levodopa/carbidopa infusion therapy in patients with advanced Parkinson’s disease leads to improvement in caregivers’ stress and burden

Background: Continuous duodenal levodopa infusion (DLI) is an effective therapy that improves quality of life (QoL) in advanced Parkinson’s disease (PD). However, the impact of DLI on caregivers’ stress and burden has not been reported. Methods: We evaluated prospectively open‐label seven advanced PD patients (65.7 ± 9.6 years, 71.4% men) treated with DLI. Schwab & England Activities of Daily Living Scale (ADLS), 39‐item Parkinson’s disease QoL Questionnaire Summary Index score (PDQ‐39SI), Zarit Caregiver Burden Interview (ZCBI), and Caregiver Strain Index (CSI) were used. Comparisons were made between scores obtained at baseline and those at a mean follow‐up of 31.4 ± 7.9 months (range, 23–42). Results: In patients, mean ± SD ADLS was increased from 50 ± 8.2 to 80 ± 11.6 (P = 0.014), and mean ± SD PDQ‐39SI was decreased from 53.7 ± 11.9 to 33.6 ± 12.8 (P = 0.018). In caregivers, ZCBI decreased from 43 ± 13.3 to 20.7 ± 12.1 (P = 0.018) and CSI from 6.3 ± 2.5 to 1.6 ± 0.9 (P = 0.018). At baseline, 57.1% of caregivers reported moderate to severe burden (ZCBI 41–88) compared to 28.6% at the end of the follow‐up (P = 0.015); at that time, no caregiver reported high level of stress (CSI ≥ 7) compared to 57.1% at baseline (P = 0.046). There were significant correlations between ZCBI and CSI improvement (r = 0.813, P = 0.026), ZCBI and PDQ‐39SI (r = 0.875, P = 0.01), and ZCBI and ADLS (r = 0.813, P = 0.026). Conclusions: Duodenal levodopa infusion‐related clinical improvement in patients with advanced PD leads to substantial reductions in caregivers’ stress and burden.     

Fluctuating functions related to quality of life in advanced Parkinson disease: effects of duodenal levodopa infusion

Objective – To assess fluctuations in quality of life (QoL) and motor performance in patients with advanced Parkinson disease (PD) treated with continuous daytime duodenal levodopa/carbidopa infusion or conventional therapy. Methods – Of 18 patients completing a 6‐week trial (DIREQT), 12 were followed for up to 6 months and assessed using electronic diaries and the PD Questionnaire‐39 (PDQ‐39). Results – During the trial and follow‐up, major diurnal fluctuations were observed, especially for hyperkinesia, ‘off’ time, ability to walk and depression. Duodenal infusion was associated with significantly more favourable outcomes compared with conventional treatment for satisfaction with overall functioning, ‘off’ time and ability to walk, with improved outcomes with PDQ‐39. Conclusions – Relative to conventional treatment, infusion therapy may stabilize and significantly improve motor function and patient’s QoL. The potential for daily fluctuation in PD symptoms means single measures of treatment effectiveness can result in bias in effect estimates and hence repeated measures are recommended.     

Quality of life in early Parkinson's disease treated with levodopa/carbidopa/entacapone

We aimed to investigate whether treatment with levodopa/carbidopa/entacapone when compared with levodopa/carbidopa improves quality of life in Parkinson's disease (PD) patients with no or minimal, nondisabling motor fluctuations. This is a multicenter, randomized, double‐blind study. One hundred eighty‐four patients on 3 to 4 equal doses of 100/25 to 200/50 mg levodopa/carbidopa or levodopa/benserazide, 0 to 3 hours of nondisabling OFF time over a 48 hour period and no dyskinesia were randomized to levodopa/carbidopa/entacapone or levodopa/carbidopa treatment for 12 weeks. The primary outcome measure was quality of life as assessed by the PDQ‐8. Secondary outcome measures were the UPDRS parts I–IV, and the Wearing Off Card. Treatment with levodopa/carbidopa/entacapone resulted in significantly greater improvements in PDQ‐8 scores compared to treatment with levodopa/carbidopa (mean difference 1.4 points, P = 0.021). Statistically significant improvements were seen predominantly in nonmotor domains (depression, personal relationships, communication, stigma, all P < 0.05; dressing P = 0.056). Patients who were randomly assigned to levodopa/carbidopa/entacapone also showed significantly greater improvement in UPDRS part II scores (P = 0.032) with UPDRS part III scores showing borderline significance. Differences in UPDRS parts I and IV and Wearing Off Card scores were not significant. Treatment with levodopa/carbidopa/entacapone results in improved quality of life compared with levodopa/carbidopa in PD patients with mild or minimal, nondisabling motor fluctuations. © 2007 Movement Disorder Society     

Intrajejunal levodopa infusion in Parkinson's disease: A pilot multicenter study of effects on nonmotor symptoms and quality of life

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. © 2009 Movement Disorder Society     

European neuroborreliosis: quality of life 30 months after treatment

Eikeland R, Mygland Å, Herlofson K, Ljøstad U. European neuroborreliosis: quality of life 30 months after treatment.
Acta Neurol Scand: 2011: 124: 349–354.
© 2011 John Wiley & Sons A/S. Objectives – The prognosis after Lyme neuroborreliosis (LNB) is debated. The aim of this study was to assess health‐related Quality of Life (QoL) and neurological symptoms 30 months after treatment in European patients with LNB. Materials and methods – In a prospective case–control designed study, we investigated 50 well‐characterized patients with LNB who had participated in a treatment trial for LNB 30 months earlier and 50 matched control persons with the health QoL questionnaire Short‐Form 36 (SF‐36), the Fatigue Severity Scale (FSS), the Montgomery and Åsberg Depression Rating Scale (MADRS), the Starkstein Apathy Scale (SAS), and the Mini Mental State (MMS). Clinical and demographic data were collected by semi‐structured interviews and clinical neurological examination. Results – Lyme neuroborreliosis‐treated patients scored lower than control persons in the SF‐36 domains physical component summary (PCS) (44 vs 51 P < 0.001) and mental component summary (MCS) (49 vs 54 P = 0.010). They also scored lower than control persons in all the SF‐36 subscales, except for bodily pain, and on FSS (3.5 vs 2.1 P < 0.001), but not on MMS (28 vs 29 P = 0.106). There was a difference in MADRS (3.1 vs 0. 8 P = 0.003) and SAS (13 vs 11 P = 0.016), but the scores were low in both groups. Fatigue was the most frequently reported symptom among LNB‐treated patients (50%). Patients who reported complete recovery (56%) after LNB had similar QoL scores as the controls. Conclusion – European persons treated for LNB have poorer health‐related QoL and have more fatigue than persons without LNB.     

Activities of daily living and quality of life in persons with newly diagnosed Parkinson’s disease according to subtype of disease,and in comparison to healthy controls

Hariz G‐M, Forsgren L. Activities of daily living and quality of life in persons with newly diagnosed Parkinson’s disease according to subtype of disease, and in comparison to healthy controls.
Acta Neurol Scand: 2011: 123: 20–27.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objective – To describe activity of daily living (ADL) and quality of life (QoL) at first visit to a neurological centre, in patients subsequently diagnosed with Parkinson’s disease (PD), according to subtype of disease and compared to healthy controls. Materials and methods – 99 patients and 31 controls were included. Patients were classified into three groups according to predominant symptoms: 50 Postural instability‐gait difficulties (PIGD), 37 tremor dominant, 12 indeterminate. Evaluations included ADL‐taxonomy, SF‐36, and the Parkinson disease questionnaire (PDQ‐39). Results – Patients experienced early on limitations in ADL and QoL compared to controls. Patients with PIGD subtype had already at first visit a worse status, clinically and in ADL and QoL, than patients with tremor dominant type. Conclusions – Already at first visit to a neurological centre, patients who will eventually receive the diagnosis of PD exhibited restrictions in ADL and QoL. Patients with axial symptoms were affected most.     

Nonmotor symptoms are independently associated with impaired health‐related quality of life in Chinese patients with Parkinson's disease

We performed a cross‐sectional study of 82 Chinese patients with Parkinson's disease (PD) enrolled during an 18‐month period using a clinical interview to assess the prevalence of nonmotor symptoms (NMS), the association with disease severity and motor status, and the impact on patients' health‐related quality of life (Hr‐QoL). The patients' NMS, Hr‐QoL, disease severity, and motor status were assessed by the Nonmotor Symptoms Scale (NMSS), the 39‐item Parkinson's Disease Questionnaire (PDQ‐39), the modified Hoehn and Yahr staging scale (H&Y) and the Unified Parkinson's Disease Rating Scale part III (UPDRS III), respectively. We found that 100% of patients with PD presented with NMS. The NMSS significantly correlated with disease duration (Spearman's r_S = 0.276, P = 0.012), H&Y (r_S = 0.230, P = 0.038), and UPDRS III (r_S = 0.350, P = 0.001). Similarly, the PDQ‐39 SI significantly associated with the disease duration (r_S = 0.258, P = 0.019), H&Y (r_S = 0.340, P = 0.002), and UPDRS III (r_S = 0.453, P < 0.001). NMS domains that influenced the PDQ‐39 SI were sleep/fatigue, mood, gastrointestinal, urinary, and miscellaneous symptoms. This strongly suggested that the five domains played a key role in the manifestation of Hr‐QoL. NMSS explains more of the variability in Hr‐QoL than UPDRS III, when both are the model (stepwise multiple linear regression analysis R² change, 47.8% vs. 5.87%, respectively). Therefore, these findings demonstrate that NMS are independently and negatively associated with Hr‐QoL in PD and that improving NMS should be viewed as an important part in the management of PD. © 2010 Movement Disorder Society     

Non-interventional surveillance study of adverse events in patients with epilepsy

Cruise KE, Bucks RS, Loftus AM, Newton RU, Pegoraro R, Thomas MG. Exercise and Parkinson’s: benefits for cognition and quality of life.
Acta Neurol Scand: 2011: 123: 13–19.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives – The benefits of physical exercise for psychological aspects of quality of life (QoL) are well established in normally ageing adults, yet potential benefits for people with Parkinson’s disease (PD) have received limited attention. This study evaluated the benefits of exercise for cognitive functioning, mood and disease‐specific QoL for people with PD. Methods – Twenty‐eight individuals with PD were allocated to an exercise intervention program (EIP, n = 15) or control group (n = 13). The EIP group undertook a programme of progressive anabolic and aerobic exercise twice weekly for 12 weeks. The control group maintained their usual lifestyle. Results – Exercise was shown to have selective benefits for cognitive functioning by improving frontal lobe based executive function. No significant effects were demonstrated for mood or disease‐specific QoL. Conclusions – These results are consistent with previous research demonstrating selective benefits of exercise for executive function among normal ageing adults and PD.     

Medication dose reductions after pallidal versus subthalamic stimulation in patients with Parkinson's disease

Evidente VGH, Premkumar AP, Adler CH, Caviness JN, Driver‐Dunckley E, Lyons MK. Medication dose reductions after pallidal versus subthalamic stimulation in patients with Parkinson’s disease.
Acta Neurol Scand: 2011: 124: 211–214.
© 2010 John Wiley & Sons A/S. Objective – To compare the medication dose reduction between deep brain stimulation (DBS) of the globus pallidus interna (GPi) vs subthalamic nucleus (STN) in matched patients with Parkinson’s disease (PD). Materials and methods – Records of 12 patients with PD who underwent GPi‐DBS at our institution from 2002 to 2008 were matched by pre‐operative PD medication doses and pre‐operative motor Unified Parkinson’s Disease Rating Scale (UPDRS) scores to 12 cases of STN‐DBS. PD medication doses were converted to levodopa equivalent doses (LEDs). Results – GPi and STN groups had similar mean pre‐operative LEDs and motor UPDRS scores. At 6 months post‐DBS, there was no significant difference in percent reduction in LEDs between the GPi (47.95%) and STN (37.47%) groups (P = 0.52). The mean post‐operative ‘medication off/stimulation on’ motor UPDRS scores did not differ significantly between GPi (15.33) and STN (16.25) groups (P = 0.74). The mean percent reduction in motor UPDRS scores was also similar between GPi (58.44%) and STN (58.98%) patients (P = 0.94). Conclusions – We conclude that in disease‐matched patients with PD undergoing DBS, both GPi and STN may result in similar reduction in PD medication doses.     

The role of apolipoprotein E polymorphisms in levodopa-induced dyskinesia

Molchadski I, Korczyn AD, Cohen OS, Katzav A, Nitzan Z, Chapman J, Hassin‐Baer S. The role of apolipoprotein E polymorphisms in levodopa‐induced dyskinesia.
Acta Neurol Scand: 2011: 123: 117–121.
© 2010 John Wiley & Sons A/S. Objectives – To determine the relationship between apolipoprotein E (APOE) polymorphisms to the time to appearance of levodopa‐induced dyskinesia (LID) in patients with Parkinson’s disease. Methods – The APOE genotype of 155 consecutive patients treated with levodopa was determined and its effect on the time of onset of LID was examined using Cox regression model, controlling for gender, age of disease onset, time to initiation of levodopa treatment and history of smoking. Results – Two patients were homozygous for the APOE ε2 allele, 7 had ε2/ε3, 1 had ε2/ε4, 130 had ε3/ε3, 12 had ε3/ε4 and 3 had ε4/ε4; LID appeared in 57.4% of the patients, appearing 4.1 ± 3.5 years after the initiation of levodopa treatment. The survival curve for LID was not affected by the APOE genotype (P = 0.34). Conclusion – APOE polymorphisms were found not to be associated with either the occurrence or the time to development of LID.     

The impact of treatment of depression on quality of life,disability and relapse in patients with Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disease affecting up to one million individuals in the United States. Depression is found in 40 to 50% of these patients and is associated with a variety of poor outcomes for both patients and their families. Despite this, there are few evidence‐based data to guide clinical care. This was an NIH‐funded, randomized, controlled trial of paroxetine, nortriptyline, and placebo. It included an 8 week acute phase and a 16 week blind extension phase. This report details the impact of depression treatment on quality of life (QoL) and disability in the acute and extension phase of this study. Secondary outcomes included relapse, tolerability, safety, and the impact of depression treatment on PD physical functioning. Patients who had improvement in depression, compared with those who did not, had significant gains in measures of QoL and disability (PDQ‐8, P = 0.0001; SF‐36, P = 0.0001) at 8 weeks and maintained their gains in the extension phase. Patients who were on active drug were significantly less likely to relapse in the extension phase than those on placebo (P = 0.041). Though relatively modest in size, this trial provides the first controlled data on the impact of treatment of depression on QoL and disability in PD. It suggests that successfully treating depression in PD leads to important, sustained improvements in these outcomes and that patients who improve on antidepressants are less likely to relapse than are patients who initially improve on placebo. © 2009 Movement Disorder Society     

The duration of the motor response to apomorphine boluses is conditioned by the length of a prior infusion in Parkinson's disease

“Pulsatile” administration of levodopa has been invocated a relevant factor for motor fluctuations in Parkinson's disease (PD). We studied dopaminergic sensitivity to apomorphine in 10 parkinsonian patients with motor fluctuations. Patients were tested as follows: the minimal effective dose of apomorphine (MED‐1) was administered in the morning to induce an on response. Fifteen minutes after this motor response had disappeared, an apomorphine infusion was initiated and maintained to ensure on periods of three different durations on different days. Infusion lasted for ～30, 60 and 90 minutes. Subsequently, the infusion was stopped, and after 15 minutes in the off state, a second bolus of apomorphine (MED‐2) was given. The mean infusion doses were 49.2 ± 5.4, 108.4 ± 10.3, and 150 ± 8.2 mg. These elicited on periods of 48.2 ± 4.1, 110 ± 4.5, and 195 ± 3.8 minutes. The MED‐2 elicited on responses with a duration of 30 ± 4.5, 18.4 ± 3.2, and 11.2 ± 4.1 minutes. The duration of the on response induced by the apomorphine infusions correlated inversely (P < 0.01) with the on induced by the MED‐2 of apomorphine. Our findings indicate that a continuous dopaminergic stimulus may induce pharmacodynamic changes associated with tolerance in PD patients. © 2009 Movement Disorder Society     

Greater improvement in quality of life following unilateral deep brain stimulation surgery in the globus pallidus as compared to the subthalamic nucleus

While deep brain stimulation (DBS) surgery is a well-accepted treatment for Parkinson disease (PD) that improves overall quality of life (QoL), its effects across different domains of QoL are unclear. The study reported here directly compared the effects of unilateral DBS in subthalamic nucleus (STN) or globus pallidus (GPi) on QoL in 42 non-demented patients with medication-refractory PD. Patients were enrolled in the COMPARE trial, a randomized clinical trial of cognitive and mood effects of STN versus GPi DBS conducted at the University of Florida Movement Disorders Center. Patients underwent motor, mood, verbal fluency and QoL (Parkinson disease questionnaire: PDQ-39) measures before and 6 months following surgery. Groups experienced motor and mood improvements that did not differ by target. Patients with STN DBS evidenced a slight decrement on letter fluency. On average, all patients endorsed better overall QoL after surgery. However, despite similar motor and mood improvements, GPi patients improved more than STN patients (38 vs. 14%, respectively; P = 0.03). Patients reported better QoL on subscales of mobility, activities of daily living (ADLs), emotional well-being, stigma, cognition and discomfort, but not on those of social support and communication. Improvements on the mobility, ADLs, stigma and social support subscales were greater amongst GPi patients. In regression analyses, only depression changes independently predicted changes in overall QoL as well as emotional well-being and social support changes. Within the STN group only, declining category fluency scores correlated with poorer QoL on the communication subscale. Unilateral DBS in both STN and GPi improved QoL overall and in disparate domains 6 months after surgery. Patients receiving GPi DBS reported greater improvements that cannot be explained by differential mood or motor effects; however, verbal fluency changes may have partially contributed to lesser QoL improvements amongst STN patients.     

Depression and quality of life in monogenic compared to idiopathic,early‐onset Parkinson's disease

Quality of life (QoL) is decreased in PD and is linked with depression and anxiety. However, little is known about QoL in monogenic PD. Subjects with mutations in PD genes were recruited from ongoing family and genetic studies (manifesting carriers, n = 23; nonmanifesting carriers, n = 19). For comparison purposes, we included patients with idiopathic PD (IPD; n = 128; early onset, n = 38; late onset, n = 90), healthy controls (n = 127), and data on depressive symptoms of 144 patients with major depression (treated controls). Depression affected 31% of early‐onset PD cases, 21% of late‐onset cases, and 44% of manifesting carriers of mutations in PD genes, but was rare in the nonmanifesting carriers (7%) and healthy controls (5%). Subjects with Parkinson‐associated depression reported fewer feelings of guilt or self‐doubt than treated controls, but the occurrence of suicidal ideation was associated with severity of depression only. Social phobia (P = 0.018) and agoraphobia (P = 0.059) were more common in manifesting carriers than in any other group. QoL was decreased in the Parkinson groups, particularly in the early‐onset cases (P < 0.001), and QoL correlated with depression in all analyses. In our study, monogenic and IPD cases were comparable in QoL and depression characteristics. The QoL and, possibly, overall prognosis of all PD patients can be improved by appropriate attention and treatment for depression, sleep impairments, and anxiety, even if the treatment of the motor problems cannot be further optimized. © 2012 Movement Disorder Society     

Homocysteine‐lowering therapy or antioxidant therapy for bone loss in Parkinson's disease

We investigated whether homocysteine (Hcy)‐ lowering therapy or an antioxidant prevented bone loss in Parkinson's disease (PD) patients taking levodopa. Forty‐two PD patients with low bone mineral density (BMD) taking levodopa were randomly assigned to Hcy‐lowering therapy (5 mg folate and 1500 μg vitamin B₁₂ daily), α‐lipoic acid (α‐LA) therapy (1200 mg daily), or control groups. Primary outcomes were BMD changes from baseline to 12 months. Secondary outcomes were changes in Hcy level, and C‐telopeptide (CTX) levels at 12 months. Forty‐one patients completed the study. Hcy‐lowering therapy resulted in significantly greater BMD changes at the lumbar spine (4.4%), total femur (2.8%), and femur shaft (2.8%) than control (P = 0.005–0.023). BMD changes in the α–LA therapy group were similar to those of the control group, but changes at the trochanter (4.6%) were significantly greater in the α–LA therapy group than in the control group after adjustment for body mass index changes. Hcy concentrations decreased to 35.2% ± 13.4% in the Hcy‐lowering therapy group, but increased in other groups. Serum CTX levels at 12 months tended to be lower in the Hcy‐lowering group (0.442 ± 0.024 ng/mL) than control group (0.628 ± 0.039 ng/mL) (P = 0.159). This small trial suggests that Hcy‐lowering therapy may prevent bone loss in PD patients taking levodopa. © 2009 Movement Disorder Society     

The Creutzfeldt-Jakob disease (CJD) neurological status scale: a new tool for evaluation of disease severity and progression

Cohen OS, Prohovnik I, Korczyn AD, Ephraty L, Nitsan Z, Tsabari R, Appel S, Rosenmann H, Kahana E, Chapman J. The Creutzfeldt–Jakob disease (CJD) neurological status scale: a new tool for evaluation of disease severity and progression.
Acta Neurol Scand: 2011: 124: 368–374.
© 2011 John Wiley & Sons A/S. Objectives – To develop a scale sensitive for the neurological manifestations of Creutzfeldt–Jakob disease (CJD). Methods – A 26‐item CJD neurological status scale (CJD‐NS) was created based on characteristic disease manifestations. Each sign was assigned to one of eight neurological systems to calculate a total scale score (TSS) and a system involvement score (SIS). The scale was administered to 37 CJD patients, 101 healthy first‐degree relatives of the patients and 14 elderly patients with Parkinson’s disease (PD). Results – The mean TSS (±SD) was significantly higher in patients with CJD (13.19 ± 5.63) compared with normal controls (0.41 ± 0.78) and PD patients (9.71 ± 3.05). The mean SIS was also significantly different between the CJD (5.19 ± 1.22) and PD (2.78 ± 1.18 P ≤ 0.01) groups reflecting the disseminated nature of neurological involvement in CJD. Using a cutoff of TSS > 4 yielded a sensitivity of 97% for CJD, and specificity of 100% against healthy controls. All individual items showed excellent specificity against healthy subjects, but sensitivity was highly variable. Repeat assessments of CJD patients over 3–9 months revealed a time‐dependent increase in both the TSS and the SIS reflecting the scale’s ability to track disease progression. Conclusions – The CJD‐NS scale is sensitive to neurological signs and their progression in CJD patients.     

Trial of dextromethorphan/quinidine to treat levodopa‐induced dyskinesia in Parkinson's disease

Background : Nondopaminergic pathways represent potential targets to treat levodopa‐induced dyskinesia in Parkinson's disease (PD). This pilot‐study (NCT01767129) examined the safety/efficacy of the sigma‐1 receptor‐agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa‐induced dyskinesia. Methods : PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2‐week double‐blind, crossover treatment periods, with intervening 2‐week washout. After 14 days, a 2‐hour intravenous levodopa‐infusion was administered. Patient examinations were videotaped before infusion (“off” state) and every 30 minutes during and afterwards until patients returned to “off.” The primary endpoint was dyskinesia‐severity during infusion measured by Unified Dyskinesia Rating Scale part 3 area‐under‐curve scores (blinded expert rated). Additional endpoints included other dyskinesia/motor assessments, global measures of clinical‐change, and adverse‐events. Results : A total of 13 patients were randomized and completed the study (efficacy‐evaluable population). Dyskinesia‐severity was nonsignificantly lower with dextromethorphan/quinidine than placebo during infusion (area‐under‐curve 966.5 vs 1048.8; P = .191 [efficacy‐evaluable patients]), and significantly lower in a post‐hoc sensitivity analysis of the per‐protocol‐population (efficacy‐evaluable patients with ≥ 80% study‐drug‐compliance, n = 12) when measured from infusion start to 4‐hours post–infusion completion (area‐under‐curve 1585.0 vs 1911.3; P = .024). Mean peak dyskinesia decreased significantly from infusion‐start to return to “off” (13.3 vs 14.9; P = .018 [efficacy‐evaluable patients]). A total of 9 patients rated dyskinesia “much/very much improved” on dextromethorphan/quinidine versus 1‐patient on placebo. Dextromethorphan/quinidine did not worsen PD‐motor scores, was generally well tolerated, and was associated with more frequent adverse events. Conclusion : This study provides preliminary evidence of clinical benefit with dextromethorphan/quinidine for treating levodopa‐induced dyskinesia in PD. Larger studies with a longer treatment duration need to corroborate these early findings. © 2017 International Parkinson and Movement Disorder Society     

Psychometric properties of the SCOPA‐AUT Brazilian Portuguese version

Cross‐cultural adaptation and psychometric assessment of the Scales for Outcomes in Parkinson's Disease‐Autonomic questionnaire (SCOPA‐AUT) Brazilian Portuguese version. 150 consecutive Parkinson's disease (PD) patients were evaluated by means of the SCOPA‐motor scale (SCOPA‐M), SCOPA‐cognition (SCOPA‐COG), Hoehn and Yahr staging (H&Y), nonmotor symptoms scale (NMSS), PD questionnaire (PDQ‐39), and SCOPA‐AUT. The following psychometric attributes were explored: acceptability, scaling assumptions, reliability, precision, and construct validity. Patients' age (mean ± standard deviation) was 63.1 ± 11.1 years (56.7% men; duration of disease, 8.7 ± 5.3 years; median H&Y, 2). Mean SCOPA‐AUT was 23.0 ± 11.2. SCOPA‐AUT did not show floor or ceiling effect. As a whole, the SCOPA‐AUT item‐domain correlation was satisfactory, except for items 2 (Saliva), 7 (Faecal incontinence), 16 (Syncope), and 19 (Cold intolerance) (|r_S| = 0.03–0.32). Internal consistency was adequate, except for thermoregulatory and cardiovascular domains (alpha coefficients, 0.56 and 0.63, respectively). Intraclass correlation coefficient for the total score was 0.71, whereas weighted kappa for individual items ranged from 0.15 to 0.71 (only items 4 and 7 were <0.40). Standard error of measurement was 6.04. The SCOPA‐AUT total score correlated closely with the NMSS total score (r_S = 0.65) and PDQ‐39 Summary Index (r_S = 0.61) and at a moderate level with H&Y staging (r_S = 0.35) and SCOPA‐MS total score (r_S = 0.39) (all r_S values, P < 0.0001). Correlation of SCOPA‐AUT with SCOPA‐COG was weak. SCOPA‐AUT significantly increased as the H&Y stage increased (Kruskal‐Wallis, P < 0.0001). The SCOPA‐AUT Brazilian Portuguese version is an acceptable, reliable, and valid questionnaire to evaluate autonomic dysfunction in PD. © 2009 Movement Disorder Society     

Interleukin-2 gene expression in different phases of episodic cluster headache--a pilot study

Kummer A, Scalzo P, Cardoso F, Teixeira AL. Evaluation of fatigue in Parkinson’s disease using the Brazilian version of Parkinson’s Fatigue Scale.
Acta Neurol Scand: 2011: 123: 130–136.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objective – Fatigue is common in Parkinson’s disease (PD). However, factors associated with fatigue in PD are still controversial. This study aimed to translate the Parkinson’s Fatigue Scale (PFS) into Brazilian‐Portuguese, to test its psychometric properties, and to assess the severity of fatigue in PD as well as its relation to demographic and clinical features, depression, anxiety, excessive daytime sleepiness and cognitive performance. Methods – We translated and assessed the internal consistency of the Brazilian version of the PFS. After, we assessed 87 PD patients with several neurological and psychopathological instruments. Results – The Brazilian version of PFS had good internal consistency (Cronbach’s alpha = 0.939). Clinical significant fatigue was present in 36 patients (41.4%). A logistic regression analysis showed that fatigue was better explained by dysthymia (P = 0.006), more severe symptoms of depression as assessed by the Hamilton Depression Rating Scale (P = 0.027), daytime sleepiness (P = 0.022) and female gender (P = 0.031). Conclusions – Fatigue is a common non‐motor symptom in PD and seems to be associated with female gender, dysthymia, severity of depression and daily somnolence.     

Health‐related quality of life in early Parkinson's disease: The impact of nonmotor symptoms

Nonmotor symptoms (NMS) are common in patients with established Parkinson's disease (PD) and have a major impact upon quality of life. We investigated the significance of NMS in relation to health‐related quality of life (HRQoL) in patients with newly diagnosed PD. Patients and healthy controls were recruited as part of the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in Parkinson's Disease Study. Prevalence of NMS was determined with the Non‐Motor Symptom Questionnaire. HRQoL was recorded with the 39‐item Parkinson's Disease Quality of Life Questionnaire (PDQ‐39). Further assessments included measures of motor disability, depression, sleep, and cognition. One hundred and fifty‐eight patients with newly diagnosed PD and 99 controls participated in this cross‐sectional study. Patients reported greater numbers of NMS than controls (mean 8.3 ± 4.3 versus 2.8 ± 2.5 symptoms; P < 0.001). Patients reported lowest HRQoL in the domains assessing bodily discomfort, mobility, and activities of daily living. Motor and nonmotor symptoms impacted negatively upon HRQoL scores. Patients with the postural instability and gait difficulty motor subtype reported worse HRQoL, compared with those with tremor‐dominant disease. Depression (P < 0.001), incomplete bowel emptying (P < 0.001), anxiety (P < 0.001), impaired concentration (P < 0.001), memory complaints (P < 0.001), and insomnia (P = 0.001) had the greatest negative impact upon HRQoL. NMS are common in patients with early PD and represent a significant cause of poorer health‐related quality of life. Cognitive, neuropsychiatric, and sleep disturbances are particularly associated with reduced well‐being. Screening and management of these symptoms should be prioritized at the time of diagnosis. © 2013 International Parkinson and Movement Disorder Society