Antiparkinsonian Medication Research Articles

Effects of Parkinson disease and antiparkinson medication on central adaptations to repetitive grasping

Cortical activity during motor task performance is attenuated in individuals with Parkinson disease (PD) relative to age-matched adults without PD, and this activity is enhanced with antiparkinson medication. It remains unclear, however, whether the relative change in cortical activity over the duration of the task, i.e., central adaptation, is affected individuals with PD, and if so, whether medication corrects for any unique behaviors. Movement-related cortical potentials (MRCPs) were recorded from scalp electrode sites Cz and C1 during 150 repetitive handgrip contractions at 70% of maximal voluntary contraction, in individuals with PD (n = 10) both ON and OFF of their PD medication, and neurologically normal age- and sex-matched controls (n = 10). Repetitions were divided into two Blocks (Block 1 and 2: repetitions 1–60 and 91–150, respectively), and the composite MRCP slopes were calculated during periods representing movement initiation (−2 s to movement onset) and execution (movement onset to 1 s). No significant interactions were noted for either comparison (PD OFF vs. control; PD OFF vs. PD ON), irrespective of electrode site (Cz or C1) or movement period (initiation or execution). Despite similar MRCP slopes and task performance, PD OFF endorsed greater perceived exertion during task performance than controls. In the present study, we observed attenuated task-related cortical activity among individuals with PD OFF relative to controls, but a similar relative adaptive response to a fatiguing task. Additionally, although antiparkinson medication enhanced cortical activity (PD OFF vs. PD ON), central adaptation was similar.

Efficacy and safety of amantadine for the treatment of L-DOPA-induced dyskinesia.

L-DOPA induced dyskinesias (LIDs) may affect up to 40% of Parkinson's disease (PD) and impact negatively health-related quality of life. Amantadine has demonstrated significant antidyskinetic effects in animal PD models and in randomized double-blind placebo-controlled trials (RCTs) in patients with PD. These effects are thought to be related to the blockade of NMDA receptors modulating cortico-striatal glutamatergic-dopaminergic interactions involved in the genesis of LIDs. There are three pharmaceutical forms of amantadine currently available in the market: an oral immediate-release (IR) formulation, which is widely available; an extended-release (ER) formulation (ADS-5102) which has been recently developed and approved by the FDA; and an intravenous infusion (IV) solution, which is not commonly used in clinical practice. RCTs with amantadine IR or ER, involving more than 650 patients have shown consistent and long-lasting reductions in LIDs. Interestingly, ADS-5102 not only reduced LIDs, but also reduced significantly at the same time the duration of daily OFF-time, a unique finding compared with other antiparkinsonian medications that usually reduce time spent OFF at the cost of worsening of LIDs. Amantadine IR might also have possible effects on other PD symptoms such as apathy or fatigue. The most common adverse reactions with amantadine are constipation, cardiovascular dysfunction including QT prolongation, orthostatic hypotension and edema, neuropsychiatric symptoms such as hallucinations, confusion and delirium, nausea and livedo reticularis. Corneal degeneration is rare but critical. In summary, amantadine immediate and extended-release are effective and safe for the treatment of LIDs.

Subthalamic and Pallidal Deep Brain Stimulation for Parkinson's Disease.

Deep brain stimulation (DBS) is a surgical treatment in which stimulation electrodes are permanently implanted in basal ganglia to treat motor fluctuations and symptoms of Parkinson’s disease (PD). Subthalamic nucleus (STN) and globus pallidus internus (GPi) are the commonly used targets for DBS in PD. Many studies have compared motor and non-motor outcomes of DBS in both targets. However, the selection of PD patients for DBS targets is still poorly studied. Therefore, we performed this narrative review to summarize published studies comparing STN DBS and GPi DBS. GPi DBS is better for patients with problems in speech, mood, or cognition while STN DBS is better from an economic point of view as it allows much reduction in antiparkinson medications and less battery consumption.

Antipsychotic reduction and/or cessation and antipsychotics as specific treatments for tardive dyskinesia.

Since the 1950s antipsychotic medication has been extensively used to treat people with chronic mental illnesses such as schizophrenia. These drugs, however, have also been associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. Various strategies have been examined to reduce a person's cumulative exposure to antipsychotics. These strategies include dose reduction, intermittent dosing strategies such as drug holidays, and antipsychotic cessation. To determine whether a reduction or cessation of antipsychotic drugs is associated with a reduction in TD for people with schizophrenia (or other chronic mental illnesses) who have existing TD. Our secondary objective was to determine whether the use of specific antipsychotics for similar groups of people could be a treatment for TD that was already established. We updated previous searches of Cochrane Schizophrenia's study-based Register of Trials including the registers of clinical trials (16 July 2015 and 26 April 2017). We searched references of all identified studies for further trial citations. We also contacted authors of trials for additional information. We included reports if they assessed people with schizophrenia or other chronic mental illnesses who had established antipsychotic-induced TD, and had been randomly allocated to (a) antipsychotic maintenance versus antipsychotic cessation (placebo or no intervention), (b) antipsychotic maintenance versus antipsychotic reduction (including intermittent strategies), (c) specific antipsychotics for the treatment of TD versus placebo or no intervention, and (d) specific antipsychotics versus other antipsychotics or versus any other drugs for the treatment of TD. We independently extracted data from these trials and estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assumed that people who dropped out had no improvement. We included 13 RCTs with 711 participants; eight of these studies were newly included in this 2017 update. One trial is ongoing.There was low-quality evidence of a clear difference on no clinically important improvement in TD favouring switch to risperidone compared with antipsychotic cessation (with placebo) (1 RCT, 42 people, RR 0.45 CI 0.23 to 0.89, low-quality evidence). Because evidence was of very low quality for antipsychotic dose reduction versus antipsychotic maintenance (2 RCTs, 17 people, RR 0.42 95% CI 0.17 to 1.04, very low-quality evidence), and for switch to a new antipsychotic versus switch to another new antipsychotic (5 comparisons, 5 RCTs, 140 people, no meta-analysis, effects for all comparisons equivocal), we are uncertain about these effects. There was low-quality evidence of a significant difference on extrapyramidal symptoms: use of antiparkinsonism medication favouring switch to quetiapine compared with switch to haloperidol (1 RCT, 45 people, RR 0.45 CI 0.21 to 0.96, low-quality evidence). There was no evidence of a difference for switch to risperidone or haloperidol compared with antipsychotic cessation (with placebo) (RR 1 RCT, 48 people, RR 2.08 95% CI 0.74 to 5.86, low-quality evidence) and switch to risperidone compared with switch to haloperidol (RR 1 RCT, 37 people, RR 0.68 95% CI 0.34 to 1.35, very low-quality evidence).Trials also reported on secondary outcomes such as other TD symptom outcomes, other adverse events outcomes, mental state, and leaving the study early, but the quality of the evidence for all these outcomes was very low due mainly to small sample sizes, very wide 95% CIs, and risk of bias. No trials reported on social confidence, social inclusion, social networks, or personalised quality of life, outcomes that we designated as being important to patients. Limited data from small studies using antipsychotic reduction or specific antipsychotic drugs as treatments for TD did not provide any convincing evidence of the value of these approaches. There is a need for larger trials of a longer duration to fully investigate this area.

A Rare Presentation of Bilateral Vocal Cord Paralysis in Late Stage Parkinson’s Disease

Introduction: Vocal cord paralysis often causes mortality by upper airway obstruction in some neurodegenerative diseases such as Parkinson’s disease and multiple system atrophy. Vocal cord paralysis is uncommon in Parkinson’s disease (PD) on the contrary it is more common in multiple system atrophy (MSA). The pathogenesis of vocal cord paralysis in Parkinson’s disease is not well understood but may involve degeneration of the nucleus ambiguous. In terms of managing patients with bilateral vocal cord paralysis in PD, it can either perform a tracheostomy to relieve the upper airway obstruction or optimize the medical treatment. There are very few available reported cases whereby patients are treated with medical treatment alone.Case Report: We report a case of 65 years old lady who presented with stridor resulting from bilateral vocal cord paralysis and has been diagnosed with Parkinson’s disease for more than 10 years. She had her antiparkinson medication optimized and requiring no surgical intervention to relieve the upper airway obstruction.Conclusion: In conclusion, we would like to emphasize that it is important to recognize bilateral vocal cord paralysis in Parkinson’s disease and early optimization of medical treatment could avoid a need for tracheostomy.

Early occurrence of inspiratory muscle weakness in Parkinson's disease.

IntroductionIn Parkinson’s disease (PD), respiratory insufficiency (including functional and muscle disorders) can impact dysarthria and swallowing. Most studies of this topic have been performed retrospectively in populations of patients with advanced PD. The objective of the present study was to characterize lung function (under off-drug conditions) in early-stage PD patients at baseline and then again two years later.MethodsForty-one early-stage PD patients (mean ± SD age: 61.7 ± 7.7; mean ± SD disease duration: 1.9 ± 1.7 years) were prospectively enrolled and compared with 36 age-matched healthy controls. Neurological evaluations and pulmonary function testing were performed in the off-drug condition at the inclusion visit and then two years later.ResultsPulmonary function testing did not reveal any restrictive or obstructive disorders; at baseline, inspiratory muscle weakness was the only abnormality observed in the PD group (in 53.7% of the patients, vs. 25% in controls; p = 0.0105). The PD patients had a lower mean maximal inspiratory mouth pressure than controls and a lower sniff nasal inspiratory pressure. Two years after the initiation of chronic treatment with antiparkinsonian medications, the maximal inspiratory mouth pressure and the sniff nasal inspiratory pressure tended to be higher. Lastly, overall motor outcomes were not significantly worse in patients with inspiratory muscle weakness than in patients without inspiratory muscle weakness.ConclusionInspiratory muscle weakness seems to be common in patients with early-stage PD, and was seen to be stable over a two-year period. Additional long-term follow-up studies are required to specify the impact of this new feature of PD.

Behavioral addictions in early-onset Parkinson disease are associated with DRD3 variants

BackgroundImpulse control disorders (ICDs) comprise abnormal behaviors frequently found in patients with Parkinson's disease (PD) receiving antiparkinsonian medication. ICDs in PD would develop when dopaminergic treatment overstimulates the dopamine receptor D3 (DR3). Here we studied whether DR3 gene (DRD3) is associated to ICD in PD patients with early-onset (EOPD). MethodsWe performed association analysis of the rs6280 DRD3 single nucleotide variation (SNV) (Ser9Gly) in a clinical sample of 126 non early-onset PD (NEOPD) and 73 EOPD (age at onset < 45). ICD was evaluated using the Questionnaire for Impulsive-Compulsive Disorders (QUIP) in PD. ResultsIn the total sample, we found that a younger onset of PD is linked to ICD traits with a potentially addictive reinforcement (ICDARs, behavioral addictions) (p = .017) and a trend for total ICDs (p = .078) while punding was not associated (p = .75). EOPD sample showed an increase of DRD3 C+ genotype for ICD (p = .022) and ICDARs (p = .043) but not for punding (p = .170). The post-hoc analyses including the time of evolution and Pramipexol or Ropinirole treatments, confirmed the independent effect of the DRD3 upon ICDs (p = .028) and ICDARs (p = .041) as well as the interaction between DRD3 and Pramipexol treatment upon ICDARs (OR = 4.60, 95% CI 1.20–17.632, p = .026). The NEOPD group showed no association between DRD3 and ICDs. ConclusionsWe found that behavioral addictions in PD are associated with an early onset of the disease, the rs6280 DRD3 SNV and the type of dopamine agonist. Further investigation in independent samples is warranted.

Parkinsonism-hyperpyrexia syndrome: A case report and review of literature.

Parkinsonism-hyperpyrexia syndrome (PHS) is a rare but potentially life-threatening complication of the management of Parkinson's disease (PD). Central hypodopaminergic state which results due to abrupt withdrawal of dopaminergic medications in patients with PD is the postulated cause. Clinical manifestations of PHS are very akin to neuroleptic malignant syndrome (NMS). Here, we report a case of a 60-year-old male with 13-year history of PD, who was on Levodopa (300 mg) + Carbidopa (75 mg). On abrupt stoppage of Levodopa (300 mg) + Carbidopa (75 mg), he presented with symptoms akin to NMS, with raised creatine kinase. As soon as the antiparkinsonian medications are reinstituted, the patient recovered completely. Literature in this area is limited to few case reports only. Existing literature recommends prompt reinstitution of antiparkinsonian medications as the mainstay of therapy for patients presenting with PHS.

Clinical Efficacy of Istradefylline for Depression in Parkinson’s Disease

Background: Parkinson’s disease (PD) is a common movement disorder with a wide range of non-motor symptoms. Depression is one of these symptoms; however, its pathomechanism and management remains to be elucidated. We evaluated of istradefylline (ISD), a first selective adenosine A2A receptor antagonist, for the treatment of depression in PD. Method: This was an open-labeled, prospective study that enrolled 15 PD patients (Men 8, Women 7) with motor fluctuations who fully filled UK PD society brain bank clinical diagnostic criteria. We added ISD 20 mg/day for 4 weeks followed with 40 mg/day for next 4 weeks on the preceding anti-parkinsonian medications. We evaluated Patient Health Questionnaire (PHQ-9) and Unified PD Rating Scale (UPDRS) part III (on state) at baseline and 8 weeks follow-up. Results: 14 patients completed the evaluations. PHQ-9 scores improved in 5 patients (responder). PHQ-9 scores of responders at baseline were higher than those of nonresponders; however, there was no significant difference. Furthermore, there were no significant differences in UPDRS part III, age, onset, duration, daily levodopa dose, and levodopa equivalent dose at baseline among both groups. UPDRS part III scores improved in both groups; however, there was also no significant difference between them. Conclusion: ISD could have efficacy to depression in some PD patients.

Vegetative state outcomes improved over the last two decades

ABSTRACTObjective: To describe late outcomes in patients with prolonged unawareness, and factors affecting them.Design: A retrospective study of 154 patients with traumatic brain injury (TBI) and 52 with non-traumatic brain injury (NTBI), admitted for intensive care and consciousness rehabilitation (ICCR), in a vegetative state (VS) lasting over 1 month.Results: Survival rate (67% total) was higher than in past studies carried out at the same facility (p < 0.01). Consciousness recovery rate (54% total) was higher in NTBI VS patients (p < 0.01) than in earlier cohorts, and similar in TBI VS patients, despite their older age than that of earlier cohorts. No meaningful differences were found in characteristics or in outcomes between the TBI and NTBI groups. Age, length of stay in ICCR, and hydrocephalus were found to affect survival (p < 0.001). Younger age, absence of hydrocephalus, and anti-Parkinsonian medication contributed to consciousness recovery after VS (p < 0.05).Conclusions: The present study demonstrated an improvement in survival and recovery of consciousness in VS patients over the last two decades, and similar outcomes for both TBI and NTBI VS. Outcomes suggest that acute medical care and ICCR have contributed to advances in VS care.

Bedtime to morning variation of mobility after nocturnal sleep in Parkinson's disease

Up to 50% of the patients with Parkinson´s disease experience a transient but clinically relevant improvement in mobility on morning awakening, even before taking their habitual antiparkinsonian medications. This phenomenon has been described as Sleep Benefit” (SB). We aimed to evaluate the effect of nocturnal sleep on mobility on morning awakening, compared to the effect of habitual morning dopaminergic medications. Moreover, we explored if this effect varied differently among patients experiencing or not SB and if it was influenced by overall quality of nocturnal sleep macrostructure.

Zuclopenthixol dihydrochloride for schizophrenia.

Zuclopenthixol dihydrochloride, given orally, is commonly used for managing the signs and symptoms of schizophrenia.To determine the effects of zuclopenthixol dhydrochloride for treatment of schizophrenia.We searched the Cochrane Schizophrenia Group's register (December 2004). This register is compiled of methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. To identify further trials we also contacted a pharmaceutical company and authors of relevant studies.We included all randomised controlled trials comparing zuclopenthixol dihydrocodine with antipsychotics or with placebo (or no intervention) for treatment of schizophrenia and/or schizophrenia-like psychoses.We independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed articles and extracted data. For dichotomous data we calculated relative risks (RR) and the 95% confidence intervals (CI) and the number needed to treat (NNT) or number needed to harm statistics. For continuous data we calculated weighted mean differences with 95% CIs for non-skewed data.We included eighteen trials involving 1578 people. Two trials compared zuclopenthixol with placebo and neither reported global or mental state outcomes. People allocated zuclopenthixol did have increased risk of experiencing extraparamydal symptoms compared with placebo (n=64, RR 5.37, CI 1.12 to 29.34 NNH 2 CI 2 to 31). Ten short trials (total n=478) compared zuclopenthixol with other typical antipsychotics. Risk of being unchanged or worse was decreased by allocation to zuclopenthixol (n=357, 7 RCTs, RR 0.72 CI 0.53 to 0.98, NNT 10 CI 6 to 131). No findings suggest any clear difference between zuclopenthixol and other typical antipsycotics across a whole range of adverse effects, including movement disorders (n=280, 6 RCTs, RR needing additional antiparkinsonian medication 1.07 CI 0.86 to 1.33) and general agitation (n=162, 3 RCTs, RR needing treatment with hypnotic/sedative drugs 1.09 CI 0.76 to 1.56). Fewer people allocated zuclopenthixol left in the short term compared with those given other typical antipsychotics (n=424, 22% vs 30%, 8 RCTs, RR 0.70 CI 0.51 to 0.95, NNT 12 CI 7 to 67). Three short trials (total n=233) compared zuclopenthixol with atypical antipsychotics. Zuclopenthixol was associated with no greater risk of being unchanged or worse compared with risperidone (n=98, 1 RCT, RR 1.30 CI 0.80 to 2.11). People allocated zuclopenthixol were prescribed antiparkinsonian medication more frequently compared to those treated with risperidone (n=98, 1 RCT, RR 1.92 CI 1.12 to 3.28, NNH 3 CI 3 to 17). Weight gain was equal for people allocated zuclopenthixol and those given sulpiride (n=61, 1 RCT, WMD 1.60 CI 8.35 to 5.15). Many people left these short studies early (45% zuclopenthixol vs 30% risperidone, n=159, 2 RCTs, RR 1.48 CI 0.98 to 2.22). The two isomers of zuclopenthixol, when compared in four short studies (total n=140), did not result in clearly different outcomes.There is an indication that zuclopenthixol causes movement disorders, perhaps more so than the newer generation of drugs, though no more frequently than the older generation of antipsychotics. There is some suggestion from this review that oral zuclopenthixol may have some clinical advantage, at least in the short term, over other older drugs in terms of global state. If an older drug is going to be prescribed, zuclopenthixol dihydrochloride is a viable option but may be best taken with additional medication to offset movement disorders that occur in about half the people taking this drug. There is no information on service, functional, behavioural outcomes and important outcomes such as relapse, for such a widely used drug this would indicate the need for further studies. We feel that it should remain a choice in the treatment of those for whom older generation drugs are indicated.

Treatment of psychotic symptoms in patients with Parkinson disease.

Persistent psychotic symptoms will develop in up to 60% of patients with Parkinson disease (PD). The initial approach to the management of PD psychosis (PDP) begins with addressing concurrent systemic conditions associated with psychotic behavior, such as delirium, medical conditions (eg, infections), psychiatric disorders (eg, major depression with psychotic symptoms, mania, schizophrenia), and substance misuse or withdrawal. A review of current medications is recommended, and medications that may trigger psychotic symptoms should be eliminated. If possible, antiparkinson medications should be reduced to the minimum therapeutic dose or discontinued in a sequential manner. Generally, dose reduction or discontinuation of anticholinergics is attempted first, followed by that of monoamine oxidase B inhibitors, amantadine, dopamine agonists, catechol-O-methyltransferase inhibitors, and lastly carbidopa/levodopa. The aim of antiparkinson medication dose reduction is to achieve a balance between improving drug-related psychotic symptoms and not significantly worsening the motor symptoms of PD. If additional measures are needed for chronic PDP treatment, the use of second-generation antipsychotics, such as clozapine, pimavanserin, or quetiapine, must be considered. The first-generation antipsychotics (eg, fluphenazine, haloperidol) are not recommended. In the patient with comorbid dementia, the addition of a cholinesterase inhibitor might also be beneficial for PDP. The choice of agent is based on patient-specific parameters, potential benefit, and side effects.

Successful Use of Escitalopram for the Treatment of Visual Hallucinations in Patients With Parkinson Disease

Patients with Parkinson disease (PD) frequently experience visual hallucinations (VH). Visual hallucinations are most often viewed as an adverse effect of antiparkinsonian treatment. Possible treatments for this disturbance include a reduction of antiparkinsonian medications, adding atypical antipsychotics, or cholinesterase inhibitors. Some studies demonstrated that selective serotonin reuptake inhibitors may be an optional treatment for patients experiencing psychosis or agitation in dementia. Currently, there is no standard recommended treatment for VH in patients with PD. We present here our clinical experience with escitalopram (selective serotonin reuptake inhibitor) for treating this disturbance. Thirteen patients with PD (8 men and 5 women; age range 67-83 years) experiencing VH were openly treated with escitalopram 10 or 15 mg/d as add-on. Efficacy was assessed at baseline, then after 4 and 8 weeks of treatment using Clinical Global Impression-Severity and Clinical Global Impression-Improvement. At the end of the 4th week of treatment, of 13 patients, 11 subjects demonstrated improvement, and in only 2 patients were there no changes in their condition. After an additional 4 weeks, 2 of the responders showed very significant improvement, 6 demonstrated much improvement, and 3 patients demonstrated minimal improvement. Only 1 patient showed no change in his condition. One additional patient stopped taking escitalopram after 5 weeks because of an absence of improvement in his state. Escitalopram was well tolerated as treatment of VH in PD patients. This medication could be a promising optional therapy for this disturbance; however, further randomized controlled and bigger studies are necessary.

Persistent oromandibular dystonia and angioedema secondary to haloperidol

We report a case in a young man who developed acute, persistent and painful tongue protrusion followed by swelling for more than 24 hours. He had relapse symptoms of schizophrenia...

Chlorpromazine versus penfluridol for schizophrenia.

The efficacy of chlorpromazine, a benchmark antipsychotic, has not been fully assessed in direct comparison with different individual antipsychotics. Penfluridol is another old antipsychotic with a long half-life so one oral dose may last up to one week. This could confer advantage. To assess the clinical effects of chlorpromazine compared with penfluridol for adults with schizophrenia. On 31 March 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, date, document type, or publication status limitations for inclusion of records in the register. We included all randomised clinical trials focusing on chlorpromazine versus penfluridol for adults with schizophrenia or related disorders. Outcomes of interest were death, service utilisation, global state, mental state, adverse effects and leaving the study early. We included trials meeting our selection criteria and reporting useable data. We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we planned to estimate the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. The review includes three studies with a total of 130 participants. Short-term results for hospital admissions showed no clear difference between chlorpromazine and penfluridol (1 RCT, n = 29, RR 0.19, 95% CI 0.01 to 3.60, low-quality evidence). No clear difference in the incidence of akathisia was found at medium term (2 RCTs, n = 85, RR 0.19, 95% CI 0.04 to 1.06, low-quality evidence), and similar numbers of participants - nearly half - from each treatment group left the study early (3 RCTs, n = 130, RR 1.21, 95% CI 0.83 to 1.77, low-quality evidence). The risk of needing additional antiparkinsonian medication was less in the chlorpromazine group (2 RCTs, n = 74, RR 0.70, 95% CI 0.51 to 0.95). No useable data reported clinically important change in global or mental state. No data were reported for relapse. No deaths were reported by the trials. Only three small studies provided data and the quality of reporting and evidence is low. Limited data indicate the efficacy and adverse effects profiles of chlorpromazine and penfluridol are generally similar. Penfluridol, however, may confer advantage by needing to be given only once per week. Firm conclusions are not possible without good-quality trials, and where these treatments are used, such trials are justified.

Sleepiness and Depression in Parkinson's Disease Patients Treated with Ropinirole and Levodopa.

Objective We aimed to investigate the effect of ropinirole on excessive daytime sleepiness (EDS) and depression in Parkinson’s disease (PD) with a large population.Methods We conducted a cross-sectional observational study at nine hospitals in Korea between April 24, 2013, and April 22, 2015. We analyzed the demographic and clinical features, other medical history, history of antiparkinsonian medication within 6 months, Hoehn and Yahr stage (HY stage), Unified Parkinson’s Disease Rating Scale (UPDRS) part II and III, Epworth Sleepiness Scale (ESS), and 30-item Geriatric Depression Scale (GDS-30).Results Four-hundred-thirteen patients with PD (mean age: 65.2 ± 9.0 years; men: 227 patients) were analyzed. Multivariate logistic regression analysis showed that age at examination, UPDRS II, and GDS-30 were independent risk factors for EDS and that sex, UPDRS II, and ESS were independent risk factors for depression.Conclusion Our large group study did not find any significant associations of ropinirole with EDS and depression in Korean PD patients.

P 83 Parasomnia, parkinsonism, impulse control disorder and bulbar palsy with IgLON5 antibodies: A new case report

Background In 2014 a complex neurological syndrome with parasomnia, sleep breathing dysfunction and variable bulbar symptoms associated with antibodies to IgLON5, a neuronal cell-adhesion protein, was described (Sabater et al., 2016). Postmortal studies revealed tauopathy predominately involving the hypothalamus and tegmentum of the brainstem (Gelpi et al., 2016). To the best of our knowledge, there are 16 published cases so far. Methods (clinical presentation) We report a 72-year-old highly educated male Caucasian patient with a 6 year history of parasomnia with RBD in the beginning, following of multiple falls, parkinsonism, hypomania, frontal lobe disorder and impulse control disorder (ICD; leading to sentence of detention) with aggressive tendencies. By transcranial ultrasound hyperechogenicity of substantia nigra was demonstrated, FDG-PET imaging showed lower 18F-FDG activity in temporal lobes. Thus idiopathic Parkinson’s disease was assumed. Due to neuropsychiatric complications the antiparkinson medication was gradually reduced and eventually discontinued in 2014. Interestingly, there were no relevant changes in symptoms of parkinsonism thereafter. In 2016, after acute coronary syndrome the patient developed a sudden bilateral vocal cord paresis with stridor leading to intubation and following tracheotomy. Subsequently, he showed dysphagia, increasing rigidity, fluctuating level of consciousness with intermittent hypoventilation and hypercapnia, and autonomic dysregulation. Critical decompensation with need of short CPR occurred twice, continuous monitoring with mechanical ventilation was required. Results (workup and treatment, Table 1 ) Brain MRI showed iron accumulation in globus pallidus and dentate nucleus, and a small pineal cyst ( Fig. 1 a). The initial multiple EEGs were normal. Diverse EEGs from 2016 registered generalized slowing with intermittent hyperexcitability; nonconvulsive status epilepticus was captured once ( Fig. 1 b). Laboratory tests displayed neutrophil leukocytosis with MGUS IgG-kappa and -lambda. In serum (1:100) and in CSF (1:10) IgLON5 antibodies (IgG subclass) were detected. HLA-typing revealed HLA-DRB1∗10:01 and HLA-DQB1∗05:01 alleles. Tumor screening (thoracic and abdominal CT, bone marrow examination) did not detect malignancy. Because of suspected IgLON5-syndrome with autoimmune origin an immunosuppressive therapy with initial IV methylprednisolone pulse therapy following oral prednisolone (75 mg/d) and rituximab was initiated. Subsequently, after achieving better vigilance, it was possible to start weaning again. Conclusion Parasomnia, ICD, beginning frontal lobe syndrome with parkinsonism, multiple falls and bulbar symptoms is a new combination in IgLON5 antibody-linked syndrome. A connection to neurodegeneration with brain iron accumulation (NBIA) is possible and requires further investigation.

Prescribing Pattern for Parkinson's Disease in Indian Community before Referral to Tertiary Center.

Several factors determine the choice of medications in patients with Parkinson's disease (PD). We aimed to analyze the pattern of prescription of drugs in patients with PD before attending a tertiary-care center. The study included chart review of 800 PD patients attending the Department of Neurology of the National Institute of Mental Health and Neurosciences in Bangalore, India. The mean age at onset was 51.1±11.8 years. The mean duration of illness was 41.7±43.6 months. At first visit, 79.4% (group 1, n=635) of patients were on medications, 10% (group 2, n=80) were on medications but later discontinued, and 10.6% (group 3, n=85) were drug-naïve. Overall, levodopa was prescribed in 94.8%, trihexyphenidyl in 40.4%, dopamine agonists in 23.2%, and amantadine in 17.2% either as monotherapy or in combination. In group 1, 37.8% were on monotherapy, with levodopa being the most commonly used agent (33.1%), followed by trihexyphenidyl (2.2%), dopamine agonists (1.6%), and amantadine (0.6%). Among those on polytherapy, levodopa plus trihexyphenidyl was the preferred combination (23.9%). In group 2, levodopa monotherapy was also most common (72.5%), followed by trihexyphenidyl monotherapy (7.5%). Levodopa and trihexyphenidyl were the most commonly prescribed drugs in our patients. A higher use of trihexyphenidyl could be due to its easy availability, low cost, and better tolerability in our patients, who were relatively young at the time of onset of their disease. The choice of antiparkinsonian medications at the primary and secondary care levels in India may be inappropriate, and newer guidelines tailored to the Indian context are warranted.

Caffeine; the Forgotten Potential for Parkinson's Disease

Parkinson's disease (PD) is the second most common neurological disorder characterized by loss of dopaminergic fibers in the basal ganglia and presence of Lewy bodies. The literature suggests that caffeine plays multiple roles in PD. Epidemiological studies showed that caffeine intake was associated with less risk of developing PD, especially in genetically susceptible patients. On the level of Lewy bodies' formation, caffeine binds to α-synuclein protein inducing conformational changes and preventing their aggregation. On the level of mitochondrial stress, caffeine acts as an antioxidant that reduces oxidative stress in PD and therefore, slows the progression of the disease. On the level of dopamine release, the literature suggests that caffeine increases dopamine release and the number of dopamine receptors in the striatum via A2a receptor antagonism. As an adjuvant treatment, caffeine interacts with antiparkinsonian medications and can alter levodopa pharmacokinetics, reduce dyskinesia, and improve gait in patients with freezing of gait. In this review, we discussed the potential of caffeine as a possible neuroprotective agent and as an addon therapy for PD.