Levodopa Dose Reduction Research Articles

Lead location as a determinant of motor benefit in subthalamic nucleus deep brain stimulation for Parkinson's disease.

BackgroundSubthalamic nucleus (STN) deep brain stimulation (DBS) is regarded as an effective treatment for patients with advanced Parkinson’s disease (PD). Clinical benefit, however, varies significantly across patients. Lead location has been hypothesized to play a critical role in determining motor outcome and may account for much of the observed variability reported among patients.ObjectiveTo retrospectively evaluate the relationship of lead location to motor outcomes in patients who had been implanted previously at another center by employing a novel visualization technology that more precisely determines the location of the DBS lead and its contacts with respect to each patient’s individually defined STN.MethodsAnatomical models were generated using novel imaging in 40 PD patients who had undergone bilateral STN DBS (80 electrodes) at another center. Patient-specific models of each STN were evaluated to determine DBS electrode contact locations with respect to anterior to posterior and medial to lateral regions of the individualized STNs and compared to the change in the contralateral hemi-body Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) motor score.ResultsThe greatest improvement in hemi-body motor function was found when active contacts were located within the posterolateral portion of the STN (71.5%). Motor benefit was 52 and 36% for central and anterior segments, respectively. Active contacts within the posterolateral portion also demonstrated the greatest reduction in levodopa dosage (77%).ConclusionThe degree of motor benefit was dependent on the location of the stimulating contact within the STN. Although other factors may play a role, we provide further evidence in support of the hypothesis that lead location is a critical factor in determining clinical outcomes in STN DBS.

Combining Device‐Aided Therapies in Parkinson's Disease: A Case Series and a Literature Review

Deep brain stimulation (DBS), levodopa-carbidopa intestinal gel (LCIG) and subcutaneous apomorphine infusion are device-aided therapies (DATs) for advanced Parkinson's disease (PD). We present a case series from the Cretan PD Registry who required 2 DATs for optimal management along with a systematic review of similar studies. From 2009 to 2020, we retrospectively studied all PD patients who were simultaneously treated with 2 DATs. Six patients on DBS required an infusion treatment for persisting or re-emergent fluctuations because of disease progression. Two patients on LCIG infusion received DBS as a levodopa-sparing strategy because of drug-induced complications. Fluctuations and quality of life improved in all patients. We identified 4 case series, 1 prospective and 1 retrospective study that included a total of 50 DBS-treated patients who required an infusion therapy. Improvement in motor outcomes, assessed in different ways, was a constant finding. Selected PD patients on 1 DAT may experience additional benefit from a second DAT, for several reasons along the course of their disease. Although infusion therapies optimize dopaminergic drug delivery in fluctuating DBS-treated patients, DBS added on LCIG treatment has an additive symptomatic effect that allows levodopa dose reduction in patients with drug-induced side effects.

Apraxia of Lid Opening in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease-Frequency, Risk Factors and Response to Treatment.

New-onset apraxia of lid opening (ALO) is reported to occur in Parkinson's disease (PD) patients following Deep Brain Stimulation (DBS). There are only few systematic studies on this uncommon disorder of eyelid movements. We aimed to examine the frequency, temporal evolution, predisposing factors and response to treatment, of new-onset ALO in PD patients who underwent bilateral subthalamic nucleus (STN) DBS. We retrospectively reviewed the data of patients who underwent STN DBS at our centre between 1999 and 2017, with a minimum of 2 years of follow up after surgery. New-onset ALO was seen in 17 (9.1%) of the 187 patients after an average of 16.9 months (Range - 6-36 months). Comparison of the groups with and without ALO revealed that ALO occurred more often in older patients, both at the onset of PD symptoms and at surgery and in those with non-tremor dominant subtypes of PD and freezing of gait at baseline. The extent of levodopa dose reduction after surgery and the pre-operative severity of motor symptoms were not risk factors. Response to adjustments of dopaminergic medications and stimulation parameters was ill-sustained or nil. Botulinum toxin therapy resulted in satisfactory improvement in the majority. New-onset ALO is an uncommon phenomenon that manifests months after STN DBS. Development of ALO is likely to be due to the effects of chronic stimulation of basal ganglia-thalamo-cortical or brain stem circuits controlling lid movements in susceptible patients. Botulinum toxin therapy offers relatively better relief of symptoms than other strategies.

Efficacy of opicapone in patients with Parkinson's disease with levodopa dose reduction: a pooled post-hoc analysis of BIPARK-I and II

Background: Opicapone (OPC), a once-daily catechol-O-methyltransferase inhibitor, was shown to be effective for end-of-dose motor-fluctuations in Parkinson's disease (PD) patients. We evaluated OPC 50 mg as a potential levodopa-sparing agent by assessing its efficacy in patients whose levodopa dose was reduced during the double-blind adjustment periods of BIPARK-I and II.

Rasagiline and safinamide as a dopamine-sparing therapy for Parkinson's disease.

To evaluate whether the prescription of monoamine oxidase B inhibitors (MAOB-I), rasagiline and safinamide, contributes to the reduction of levodopa and/or dopamine agonists (DA) dose in order to minimize adverse effects. A total of 724 patients with Parkinson's disease (PD) have been prospectively included in our database since the year 2000, representing a total of 5124 visits. For each patient and visit, antiparkinsonian treatment was recorded. In the presence of rasagiline and safinamide, we analysed the evolution of levodopa equivalent dose (LED) and LED for DA (LED-DA). The data obtained from the 1664 visits between 2006 and 2010 (321 patients) and the 1709 visits between 2014 and 2018 (403 patients) were analysed in order to assess the impact of the introduction of rasagiline and safinamide, respectively. The annual mean LED remained stable without statistically significant differences. In the first period (impact of rasagiline), the annual mean LED-DA in 2010 was significantly higher than in 2006 (P=0.001). In the second period (impact of safinamide), the annual mean LED-DA in 2018 was significantly lower than in 2014 (P=0.002). A repeated-measure analyses of LED-DA including only patients who had taken safinamide showed a statistically significant decrease in LED-DA (P=0.027). The introduction of MAOB-I in the overall treatment of PD as part of routine clinical practice has not helped to reduce annual mean LED. However, safinamide reduces annual mean LED-DA and may be linked to a reduction in dose-dependent adverse effects in the long term.

A comparative study of stabilising effect and antioxidant activity of different antioxidants on levodopa-loaded liposomes

The aim of this study was to evaluate the stability of levodopa liposomes co-loaded with three different antioxidants (curcumin, ascorbic acid, and superoxide dismutase (SOD)). For this purpose, multilamellar liposomes were prepared. Curcumin was added into the lipid bilayer while ascorbic acid and SOD were placed into the aqueous phase. The influence of preparation technique and surface charge were also investigated. Vesicles were characterised and free radical scavenging potential was determined. From stability study, ascorbic acid showed better stabilising effect. These co-loaded liposomes also exhibited potential radical scavenging activity where ascorbic acid played a key role. From the study of different preparation techniques and charge, we concluded that cationic liposomes made by Thin Layer Evaporation following extrusion offered the best physicochemical and stability properties. A dual mechanism of these liposomes implies the chemical stabilisation of levodopa (dose reduction) and the antioxidant effect, with a preventive effect on Parkinson’s disease.

Focused ultrasound subthalamotomy in patients with asymmetric Parkinson's disease: a pilot study

Ablative neurosurgery has been used to treat Parkinson's disease for many decades. MRI-guided focused ultrasound allows focal lesions to be made in deep brain structures without skull incision. We investigated the safety and preliminary efficacy of unilateral subthalamotomy by focused ultrasound in Parkinson's disease. This prospective, open-label pilot study was done at CINAC (Centro Integral de Neurociencias), University Hospital HM Puerta del Sur in Madrid, Spain. Eligible participants had Parkinson's disease with markedly asymmetric parkinsonism. Patients with severe dyskinesia, history of stereotactic surgery or brain haemorrhage, a diagnosis of an unstable cardiac or psychiatric disease, or a skull density ratio of 0·3 or less were excluded. Enrolled patients underwent focused ultrasound unilateral subthalamotomy. The subthalamic nucleus was targeted by means of brain images acquired with a 3-Tesla MRI apparatus. Several sonications above the definitive ablation temperature of 55°C were delivered and adjusted according to clinical response. The primary outcomes were safety and a change in the motor status of the treated hemibody as assessed with part III of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) in both off-medication and on-medication states at 6 months. Adverse events were monitored up to 48 h after treatment and at scheduled clinic visits at 1, 3, and 6 months after treatment. The study is registered with ClinicalTrials.gov, number NCT02912871. Between April 26 and June 14, 2016, ten patients with markedly asymmetric parkinsonism that was poorly controlled pharmacologically were enrolled for focused ultrasound unilateral subthalamotomy. By 6 months follow-up, 38 incidents of adverse events had been recorded, none of which were serious or severe. Seven adverse events were present at 6 months. Three of these adverse events were directly related to subthalamotomy: off-medication dyskinesia in the treated arm (one patient, almost resolved by 6 months); on-medication dyskinesia in the treated arm (one patient, resolved after levodopa dose reduction); and subjective speech disturbance (one patient). Four of the adverse events present at 6 months were related to medical management (anxiety and fatigue [one patient each] and weight gain [two patients]). The most frequent adverse events were transient gait ataxia (related to subthalamotomy, six patients), transient pin-site head pain (related to the head frame, six patients), and transient high blood pressure (during the procedure, five patients). Transient facial asymmetry (one patient) and moderate impulsivity (two patients) were also recorded. The mean MDS-UPDRS III score in the treated hemibody improved by 53% from baseline to 6 months in the off-medication state (16·6 [SD 2·9] vs 7·5 [3·9]) and by 47% in the on-medication state (11·9 [3·1] vs 5·8 [3·5]). MRI-guided focused ultrasound unilateral subthalamotomy was well tolerated and seemed to improve motor features of Parkinson's disease in patients with noticeably asymmetric parkinsonism. Large randomised controlled trials are necessary to corroborate these preliminary findings and to assess the potential of such an approach to treat Parkinson's disease. Fundación de investigación HM Hospitales and Insightec.

Frameless deep brain stimulation surgery: A community hospital experience

ObjectiveFrame-based stereotaxy has regularly been utilized for deep brain stimulation (DBS) surgery. More recently, frameless neuronavigation has revealed similar outcomes for functional neurosurgical operations. Such comparable outcomes have been described by tertiary referral centers, but whether such excellent surgical outcomes are attainable in a community setting has yet to be reported. MethodsEighteen patients received frameless DBS surgery, 11 with subthalmic nucleus (STN) implantation for Parkinson's disease (PD) and 7 with ventral intermediate nucleus (Vim) implantation for essential tremor (ET). Their data was collected and analyzed, including the Unified Parkinson's Disease Rating Scale (UPDRS) and tremor scores. ResultsThere was a 58% reduction in UPDRS III and a 47% reduction in overall levodopa dose in those with STN DBS (p<0.0001 and p<0.0005, respectively) and those with Vim DBS had a 76% improvement in their overall tremor rating score (p<0.002) at mean follow-up (8.2 and 10.1 months, respectively). No intraoperative complications occurred. Two subjects developed wound dehiscence post-operatively and another had fall-induced lead fracture, all treated with uncomplicated hardware replacement. ConclusionsFrameless DBS for PD and ET can be safely performed in a community setting with similar excellent outcomes as those of larger academic centers as well as clinical results comparable to frame-based surgery. Patients living in community or rural areas may not need to travel across city or even state lines to receive this surgical option, especially if they have the opportunity to receive it closer to home.

17 Rehabilitation improves dyskinesias in Parkinsonian patients: A pilot study comparing two different rehabilitative treatments

Background The present study was devised: (a) to test whether an intensive multidisciplinary rehabilitation treatment (60 h) for Parkinsonian patients is effective in improving dyskinesia and motor performance compared to a control group undergoing a non-intensive non multidisciplinary rehabilitation treatment (30 h) and (b) to verify whether rehabilitation may lead to a reduction in levodopa dosage. Methods Forty Parkinsonian patients suffering from dyskinesias were admitted to study: 20 for an intensive (group-1) and 20 for a standard treatment (group-2). The rating scales used for the clinical evaluation were: Unified Parkinson’s Disease Rating Scales (UPDRS) II, III, IV, Parkinson’s disease disability scale (PDDS), Abnormal Involuntary Movement Scale (AIMS). Results All outcome measurements improved in both groups of patients, but patients group-1 presented better results: UPDRS II was reduced by 33% in group-1 and by 22% in group-2, UPDRS III 29% vs. 22%, UPDRS IV 74% vs. 10%, PDDS 18% vs. 12%, and AIMS 71% vs. 8%. A different behaviour was observed for levodopa dosage at baseline and after treatment: dosage decreased by an average value of 210 mg ( p p = 0.08) in group-2. Conclusion Our findings suggest that a rehabilitation protocol should be considered as a valid non-invasive therapeutic support for patients who show dyskinesias and that there are better results when the treatment is intensive.

Off spells and dyskinesias: Pharmacologic management of motor complications

There are two major causes of disability in patients with Parkinson disease: motor fluctuations that occur when a dose of levodopa becomes ineffective, leading to a "wearing off," and hyperkinetic movements (dyskinesias) caused by excessive levels of dopamine. The utility of continuous levodopa treatment is therefore limited by motor complications. Pharmacologic options to treat wearing off include adding (or increasing the dosage of) levodopa, adding (or increasing the dosage of) a dopamine agonist, or adjunctive treatment with a monoamine oxidase inhibitor or catechol-O-methyltransferase inhibitor. Dyskinesias will respond to a reduction in levodopa dosage at the expense of worsening parkinsonism and an increase in the number of "off" episodes. Continuous dopamine stimulation may overcome the pulsatile stimulation of postsynaptic dopamine receptors produced by standard oral formulations of levodopa that lead to motor complications.

Effect of Bilateral Deep Brain Stimulation of the Subthalamic Nucleus on Freezing of Gait in Parkinson's Disease

A prospective cohort study to evaluate the efficacy of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on freezing of gait (FOG) in patients with advanced Parkinson's disease. Patients (n = 10) with advanced Parkinson's disease were surgically implanted with microelectrodes to facilitate STN-DBS. Evaluations of FOG, motor function, activities of daily living and neuropsychological function were carried out in on-medication and off-medication states (with and without levodopa treatment), before surgery and at 6 and 12 months postoperatively. STN-DBS was associated with significant improvement in FOG score and neuropsychological function at both 6 and 12 months postoperatively, compared with preoperatively. Significant postoperative improvements were also observed in motor function and activities of daily living. Daily levodopa dosage was significantly lower at both 6 and 12 months postoperatively. STN-DBS improved FOG in patients with advanced Parkinson's disease. The significant reduction in levodopa dosage and improvement in neuropsychological function may be the reason for the therapeutic effect seen with STN-DBS.

Intensive Rehabilitation Treatment in Parkinsonian Patients with Dyskinesias: A Preliminary Study with 6-Month Followup

A major adverse effect of levodopa therapy is the development of dyskinesia, which affects 30–40% of chronically treated Parkinsonian patients. We hypothesized that our rehabilitation protocol might allow a reduction in levodopa dosage without worsening motor performances, thus reducing frequency and severity of dyskinesias. Ten Parkinsonian patients underwent a 4-week intensive rehabilitation treatment (IRT). Patients were evaluated at baseline, at the end of the rehabilitation treatment and at 6-month followup. Outcome measures were the Unified Parkinson's Disease Rating Scale Sections II, III, and IV (UPDRS II, III, IV) and the Abnormal Involuntary Movement Scale (AIMS). At the end of the IRT, levodopa dosage was significantly reduced (P = 0.0035), passing from 1016 ± 327 to 777 ± 333 mg/day. All outcome variables improved significantly (P < 0.0005 all) by the end of IRT. At followup, all variables still maintained better values with respect to admission (P < 0.02 all). In particular AIMS score improved passing from 11.90 ± 6.5 at admission to 3.10 ± 2.3 at discharge and to 4.20 ± 2.7 at followup. Our results suggest that it is possible to act on dyskinesias in Parkinsonian patients with properly designed rehabilitation protocols. Intensive rehabilitation treatment, whose acute beneficial effects are maintained over time, might be considered a valid noninvasive therapeutic support for Parkinsonian patients suffering from diskinesia, allowing a reduction in drugs dosage and related adverse effects.

Clinical Data On the prolonged-release Formulation of Ropinirole for Parkinson’s Disease

SUMMARY Ropinirole, a nonergoline dopamine agonist, has been used to treat the motor symptoms of Parkinson’s disease for more than 10 years. Owing to its moderate elimination half-life, the immediate-release formulation is administered three-times daily. Now, a prolonged-release form is also available, and despite administration in the morning, plasma level fluctuations are reduced over 24 h versus the immediate-release formulation, allowing for symptomatic treatment for the entire day with once-daily dosing. The prolonged-release formulation can be up-titrated more rapidly and simply, reaching clinical efficacy as early as the second week of therapy. In clinical studies, higher doses of ropinirole were achieved with the prolonged-release formulation compared with the immediate-release formulation. The results of a randomized, double-blind, head-to-head study of both formulations in patients with advanced Parkinson’s disease demonstrated significantly greater efficacy and a larger levodopa dose reduction for the prolonged-release formulation. A positive effect on night-time motor symptoms and quality of sleep has been established. Due to once-daily administration, compliance and adherence may also be improved.

Bilateral subthalamic nucleus stimulation in the treatment of advanced Parkinson's disease. Five years' personal experience

Background and purposeThe objective of the study was to assess bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) for patients with advanced Parkinson disease (PD). Material and methodsThe study population included 5 patients with bilateral STN DBS who completed a 5-year postoperative follow-up period. In all patients electrodes (Model 3387 or 3389) were stereotactically bilaterally inserted into the STN using a Leksell stereotactic G frame. The clinical rating tests included Unified Parkinson's Disease Rating Scale (UPDRS) and two motor-timed tests derived from CAPIT (rapid movements between two points and stand-walk-sit test). All patients were assessed in off and on condition before implantation and 1, 3 and 5 years in medication on and off condition and stimulation on condition and stimulation off condition. To compare preoperative to postoperative UPDRS scores, only mean values and standard deviations are presented because of the small study population. ResultsThe stimulation effect was noted in the off state, resulting in a 59% improvement in motor scores of UPDRS at 5-year follow-up, when compared to preoperative scores. In the on state the stimulation improved motor scores by 17%. At 5-year follow-up, reduction of daily levodopa dose was 50%. ConclusionsBilateral STN DBS is an effective and safe treatment for patients with advanced PD. Bilateral STN DBS contributes to improvement of parkinsonian symptoms in the off state and levodopa-induced dyskinesia. This can be correlated with a 50% reduction of daily levodopa dose 5 years postoperatively.

Adding a dopamine agonist to preexisting levodopa therapy vs. levodopa therapy alone in advanced Parkinson’s disease: a meta analysis

To perform a meta analysis of randomised placebo-controlled trials evaluating the use of dopamine agonist (DA) or placebo to preexisting levodopa therapy for the treatment of advanced Parkinson's disease (PD). We focused on clinically important efficacy [Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (ADL) and motor scores as well as change in 'off' time and levodopa dose] and safety outcomes (withdrawal because of adverse drug events (ADEs), dyskinesias, hallucinations and mortality). A systematic literature search was performed between January 1990 and July 2007. The primary outcome measures assessed were the reduction in scores of Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (ADL) and motor scores as well as reduction in 'off' time and reductions in levodopa dose from baseline. Safety end-points were also evaluated. A total of 15 trials (n = 4380 subjects) were included in the meta analysis. Adjunctive DA use resulted in greater improvement as measured by the UPDRS ADL [weighted mean difference (WMD) -2.20, 95% confidence interval (CI) -2.64 to -1.76; p < 0.0001] and motor score reduction (WMD -5.56, 95% CI -6.82 to -4.31; p < 0.0001) as well as reduction in 'off' time measured in hours/day (WMD -1.20, 95% CI -1.78 to -0.62; p < 0.0001) and reduction in levodopa dose (WMD -128.5 mg, 95% CI -175.0 to -82.1; p < 0.0001) vs. placebo. Incidence of dyskinesia and hallucinations was higher with DAs [odds ratio (OR) 3.27, 95% CI 2.65-4.03; p < 0.0001] and (OR 3.34, 95% CI 2.44-4.58; p < 0.0001). Non-ergot DAs were qualitatively better, although both ergot and non-ergot DAs showed statistically significant improvements in all UPDRS scores. Adjunctive DA use to levodopa is superior to levodopa alone in reducing PD symptoms in patients not controlled with monotherapy. DAs seem especially useful amongst PD patients with wearing-off phenomenon from levodopa therapy, but can cause some adverse events.

Clinical experience of tolcapone in advanced Parkinson’s disease

We are reporting our clinical experience in 66 patients with advanced Parkinson's disease (PD) who were switched to tolcapone because of persisting off periods despite treatment with entacapone (according to the European Agency for the Evaluation of Medicinal products: EMEA). We used UPDRS II-III-IV in "on" state to monitor tolcapone effectiveness at 6 and 12 months. We found significant reductions in mean off-time duration (UPDRS item 39) and levodopa dose at follow up. Eleven patients dropped out (17%) during the first month of treatment, 2 (3%) because liver enzymes exceeded normal limit. Amongst patients who continued tolcapone, 30/55 (54%) reported "off-time" reduction > or =25% (UPDRS-39 decrement > or =1 point). Our findings indicate that tolcapone widens the levodopa therapeutic window, even in patients who have not benefited from entacapone. We suggest that tolcapone is indicated before patients are referred for more invasive procedures.

Levodopa/DDCI and entacapone is the preferred treatment for Parkinson’s disease patients with motor fluctuations in routine practice: a retrospective, observational analysis of a large French cohort

Levodopa is the gold standard drug for the symptomatic control of Parkinson's disease (PD). However, long-term treatment with conventional formulations [levodopa and a dopa decarboxylase inhibitor (DDCI)], is associated with re-emergence of symptoms because of wearing-off and dyskinesia. Treatment with levodopa/DDCI and entacapone extends the half-life of levodopa, avoiding deep troughs in levodopa plasma levels and providing more continuous delivery of levodopa to the brain. In this open-label, retrospective, observational study we investigated the effects of levodopa/DDCI and entacapone therapy in 800 PD patients with motor fluctuations. Levodopa/DDCI and entacapone treatment was assessed as good/very good in improving motor fluctuations (64%) and activities of daily living (ADL; 62%). The therapeutic utility was considered to be good/very good in 70% of cases. Moreover, there was a reduction in levodopa dose in 20% of patients. Neurologists preferred levodopa/DDCI and entacapone compared with increasing levodopa dosage, dose-fractionation or addition of a dopamine agonist (63%, 29% and 23% of patients respectively). Reasons included achieving more continuous dopaminergic stimulation (40%), reducing motor fluctuations (54%) and improving ADL (41%). This analysis reveals the preference of neurologists for levodopa/DDCI and entacapone over conventional levodopa-modification strategies for the effective treatment of PD motor fluctuations in clinical practice.

Ropinirole 24-hour prolonged release

To evaluate the efficacy of ropinirole 24-hour prolonged release (ropinirole 24-hour) as an adjunct to levodopa in patients with Parkinson disease (PD) and motor fluctuations. In a double-blind, placebo-controlled, 24-week study, 393 subjects with PD were randomized to ropinirole 24-hour (n = 202) or placebo (n = 191). The primary outcome measure was reduction in hours of daily "off" time. At week 24, the mean dose of ropinirole 24-hour was 18.8 mg/day with a mean reduction in daily levodopa of 278 mg. There was a mean reduction in daily "off" time of 2.1 hours in the ropinirole 24-hour group and 0.3 hours with placebo. Secondary outcome measures including change in hours and percent of daily "on" time and "on" time without troublesome dyskinesia, Unified PD Rating Scale motor and activities of daily living subscales, Beck Depression Inventory-II, PDQ-39 subscales of mobility, activities of daily living, emotional well-being, stigma and communication, and PD Sleep Scale were significantly improved at week 24 with ropinirole 24-hour. The most common adverse events (AE) with ropinirole 24-hour were dyskinesia, nausea, dizziness, somnolence, hallucinations, and orthostatic hypotension and AEs led to study withdrawal in 5% of both the active and placebo groups. Ropinirole 24-hour was effective and well tolerated as adjunct therapy in patients with Parkinson disease (PD) not optimally controlled with levodopa. Ropinirole 24-hour demonstrated an improvement in both motor and non-motor PD symptoms, while permitting a reduction in adjunctive levodopa dose.

Efficacy and safety of herbal medicines for idiopathic Parkinson's disease: A systematic review

The objective of this study is to assess the efficacy and safety of herbal medicines (HMs), as a monotherapy or adjunct therapy, compared to placebo or conventional approaches in the treatment of idiopathic Parkinson's disease (PD). We conducted a systematic review of randomized controlled trials from both conventional and alternative medicine sources. Outcome measures were overall improvement, quality of life, reduction of levodopa dose, and adverse events. Nine studies were included, each testing a different HM. Six of the trials had limited internal validity due to major flaws in design, including the lack of proper randomization; insufficient blinding; unclear inclusive criteria in terms of diagnostic criteria, baseline staging, and duration of disease; lack of proper sample size calculation; and insufficient data analysis. Imbalances in gender and ethnicity among the patients in the included trials were observed. No major adverse events emerged, and no specific pattern was detected from the trials describing such data. In addition to major methodological defects, heterogeneity in (1) HM tested, (2) control treatment, and (3) outcome measure hindered in-depth data analysis and synthesis. Current evidence is insufficient to evaluate the efficacy and safety of various HMs. Further studies with improved trial design and reporting, with assessment on cost-effectiveness, quality of life, and qualitative data are warranted.

Parkinsonismo y camptocormia con miopatía focal espinal: descripción de un caso y respuesta al tratamiento

Camptocormia is characterised by extreme flexion of the thoracolumbar spine. It suffered an increase during walking and it is relieved in supine position. Camptocormia has been described in psychogenic disorders, but in other diseases, including Parkinson's disease as well. It has been recently described several cases with focal spinal myopathy, and we present a patient with this clinical association. This 82-year-old man had a 6-year history of parkinsonian symptoms, mostly of rigid-akinetic type. He was in stage 4 on Hoehn & Yahr scale, and he had reached 62 points on Unified Parkinson Disease Rating Scale. Over the past 6-8 months, he developed progressive forward flexion of the trunk with clinical features of camptocormia. He suffered flogotic symptoms and signs on her lower back, and there were no dystonic posture or clinical features. Lumbar computerised tomography showed fat replacement of the paravertebral L3 muscles. A surgical paravertebral muscle examination and biopsy were performed, showing diffuse fat replacement and only a marginal myopathic focus. It was made several therapeutic approaches, with levodopa dose increase, reduction, fractioning, and addition of dopa-agonists. All of these strategies failed. It was determined to try a steroid course, but there were no improvement, so physiotherapy and rehabilitation measures did. He finally was confined to wheelchair. Physiopathologic and therapeutic aspects of camptocormia in Parkinson's disease are unclear. Their relationship could be casual or causal. Patients with clear inflammatory myopathy could benefit from steroid therapy, but patients with end-stage myopathy probably do not so.