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Benign esophageal strictures are uncommon and their management remains challenging. Herein, we present a rare both functional and organic esophageal stricture in a patient with Parkinson’s disease and reflux esophagitis. The patient was diagnosed with severe complex stricture in the distal part of the esophagus, requiring surgical treatment. We performed subtotal esophageal resection and Ivor-Lewis gastroesophagoplasty. The successful management of antiparkinsonian drug therapy with adequate parenteral substitution in the early postoperative period is of great importance to avoid any further complications.

Zonisamide has been used as an add-on treatment in order to overcome the deficiencies of the general therapies currently used to resolve the motor complications and non-motor symptoms of Parkinson disease. Various trials have been designed to investigate the mechanism of action and treatment effects of zonisamide in this condition. Most clinical trials of zonisamide in Parkinson disease were from Japan. The vast majority of studies used changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) scores and daily “OFF” time as primary endpoints. Based on adequate randomized controlled trials, zonisamide is considered a safe and efficacious add-on treatment in Parkinson disease. The most convincing proof is available for a dosage of 25–50 mg, which was shown to lead to a significant reduction in the UPDRS III score and daily “OFF” time, without increasing disabling dyskinesia. Furthermore, zonisamide may play a beneficial role in improving non-motor symptoms in PD, including impulsive–compulsive disorder, rapid eye movement sleep behavior disorder, and dementia. Among the various mechanisms reported, inhibition of monoamine oxidase-B, blocking of T-type calcium channels, modulation of the levodopa–dopamine metabolism, modulation of receptor expression, and neuroprotection are the most often cited. The mechanisms underlying neuroprotection, including modulation of dopamine turnover, induction of neurotrophic factor expression, inhibition of oxidative stress and apoptosis, inhibition of neuroinflammation, modulation of synaptic transmission, and modulation of gene expression, have been most extensively studied. This review focuses on structure, pharmacokinetics, mechanisms, therapeutic effectiveness, and safety and tolerability of zonisamide in patients with Parkinson disease.

Subthalamic nucleus deep brain stimulation (STN-DBS) improves motor symptoms in individuals with advanced Parkinson's disease (PD) and enables physicians to reduce doses of antiparkinsonian drugs. We investigated possible predictive factors for the successful reduction of antiparkinsonian drug dosage after STN-DBS. We evaluated 33 PD patients who underwent bilateral STN-DBS. We assessed rates of reduction of the levodopa-equivalent daily dose (LEDD) and levodopa daily dose (LDD) by comparing drug doses before vs. 6-months post-surgery. We used correlation coefficients to measure the strength of the relationships between LEDD and LDD reduction rates and preoperative factors including age, disease duration, preoperative LEDD and LDD, unified Parkinson's Disease Rating Scale part-II and -III, levodopa response rate, Mini-Mental State Examination score, dyskinesia score, Hamilton Rating Scale for depression, and the number of non-motor symptoms. The average LEDD and LDD reduction rates were 61.0% and 70.4%, respectively. Of the variables assessed, only the number of psychiatric/cognitive symptoms was significantly correlated with the LEDD reduction rate. No other preoperative factors were correlated with the LEDD or LDD reduction rate. A wide range of preoperative psychiatric and cognitive symptoms may predict the successful reduction of antiparkinsonian drugs after STN-DBS.

Objective To investigate trends in the incidence of Parkinson’s disease (PD) between 2006 and 2016. Design Cohort study in The Health Improvement Network (THIN): a large UK primary care database. Study participants Individuals actively registered with a practice within THIN aged 50 years and over. Measures of outcome The incidence of Parkinson’s disease between 2006 and 2016 using different case definitions: 1) PD diagnostic Read code; 2) PD diagnostic Read code OR symptom Read code; 3) PD diagnostic Read code OR symptom Read code and OR at least 1 antiparkinsonian drug prescription; 4) PD diagnostic Read code OR symptom Read code plus at least 2 antiparkinsonian drug prescription. The effect of age and sex on these measures were investigated. Results The overall crude incidence of PD for people over 50 years has increased in recent years. The rates increased with increasing age and as expected, higher in men. Using the broadest case definition (3), incidence rate of PD between 2006 and 2016 in men was 190 per 100,000 person years (95% CI 187–193) and in women was 176 per 100,000 person years (95% CI 173–178). Incidence of PD was highest at age 90 (496 per 100,000 95% CI 471–522). Conclusion There is increasing diagnosis of PD in primary care setting.

Hemantane is a novel antiparkinsonian drug that is undergoing clinical trials. Hemantane in the dosage range 10 – 40 mg/kg demonstrated anti-inflammatory activity and decreased statistically significantly the intensity of the exudative reaction in an acetic-acid peritonitis model in mice. Hemantane (10 mg/kg) in a neuro-inflammation model induced by lipopolysaccharide injection in rats prevented loss of body mass, development of forepaw akinesia contralateral to the operation, and smell disturbance.

Interpretation of clinical trials comparing different drug regimens for Parkinson's disease (PD) is complicated by the different dose intensities used: higher doses of levodopa and, possibly, other drugs produce better symptomatic control but more late complications. To address this problem, conversion factors have been calculated for antiparkinsonian drugs that yield a total daily levodopa equivalent dose (LED). LED estimates vary, so we undertook a systematic review of studies reporting LEDs to provide standardized formulae. Electronic database and hand searching of references identified 56 primary reports of LED estimates. Data were extracted and the mean and modal LEDs calculated. This yielded a standardized LED for each drug, providing a useful tool to express dose intensity of different antiparkinsonian drug regimens on a single scale. Using these conversion formulae to report LEDs would improve the consistency of reporting and assist the interpretation of clinical trials comparing different PD medications.

Parkinson's disease is the most common neurodegenerative disorder after Alzheimer's disease. The aim of this study was to investigate the pharmacokinetic parameters of the mGluR4 receptor blocker Rapitalam on rabbits. There was developed the method of the quantitative determination of Rapitalam in the blood plasma of rabbits using high performance liquid chromatography with tandem mass spectrometric detection. The study was performed on 12 rabbits (males, weighing between 3,300 to 3,500 g). In intragastric dosing of the substance was administered using a gastric tube in the form of suspension in water 0.9 mg/ml, 9 mg/ml, and 90 mg/ml at a dose of 0.3 mg/kg, 3 mg/kg and 30 mg/kg. After the administration of the substance blood was sampled through a catheter in a volume of 0.5 ml in polypropylene tubes containing 20 µl of 5% EDTA before and 10, 15, 30, 60, 120, 240, 480, 1440 minutes after administration. The mean absorption time (MAT) of Rapitalam was 268.1 minutes or 4.5 hours. The half-life is longtime and it was 176.4 minutes (2.9 hours) for intravenous and 362.2 minutes (6.0 hours) for intragastric administration. The absolute bioavailability of the intragastric dosing was 26.8%. The main pharmacokinetic parameters of the substance was established on rabbits that allow you to optimize the future use of it's as a potential drug for the treatment of Parkinson's disease.

BACKGROUND There is a move towards treatment of Parkinson's disease (PD) patients in specialized units, however, data on the outcome and on daily antiparkinsonian drug costs are rare. OBJECTIVE The objective of this study was to elucidate relationships between costs of drug treatment and efficacy of drug titration in a PD clinic. SUBJECTS AND METHODS We calculated costs of drug therapy and scored severity of PD of 63 consecutively referred in-patients initially and at the end of their hospital stay under standardized conditions. RESULTS Titration of antiparkinsonian drugs significantly induced a decrease of PD symptoms and an increase of daily drug costs. There were significant correlations between the degree of (i) improvement of the UPDRS score, (ii) increase of dopaminergic agents and (iii) change of corresponding daily antiparkinsonian drug costs. CONCLUSION Our results demonstrate the effectiveness of treatment in PD clinics, which results in increased daily antiparkinsonian drug costs due to elevated dopaminergic substitution.

Parkinson’s disease (PD) is a major worldwide public health problem with a prevalence that is expected to increase dramatically in the coming decades. Because administrative data are useful for epidemiologic and health service studies, we aimed to define procedural algorithms to identify PD patients (on a regional basis) using these data. We built two a priori algorithms, respecting privacy laws, with increasing theoretical specificity for PD including: (1) a hospital discharge diagnosis of PD; (2) PD-specific exemption; (3) a minimum of two separate prescriptions of an antiparkinsonian drug. The two algorithms differed for drugs included. Sensitivities were tested on an opportunistic sample of 319 PD patients from the databases of 5 regional movement disorders clinics. The estimated prevalence of PD in the sample population from Tuscany was 0.49 % for algorithm 1 and 0.28 % for algorithm 2. Algorithm 1 correctly identified 291 PD patients (sensitivity 91.2 %), and algorithm 2 identified 242 PD patients (sensitivity 75.9 %). We developed two reproducible algorithms demonstrating increasing theoretical specificity with good sensitivity in identifying PD patients based on an evaluation of administrative data. This may represent a low-cost strategy to reliably follow up a large number of PD patients as a whole for evaluating the effects of therapies, disease progression and prevalence.

The authors assessed the use and side effects of neuroleptics (especially tardive dyskinesia [TD]) in elderly patients in Japan (N = 73; mean age 76 years, 32 men and 41 women) admitted for the first time to six psychiatric hospitals. The comparison group was 74 elderly patients with dementia admitted to nursing homes or psychiatric hospitals and not treated with neuroleptics. The mean dose of neuroleptics in the Japanese elderly patients was lower than that in Western countries; however, the prevalence of side effects was higher, possibly because of polypharmacy. The total number of psychotropic drugs correlated significantly with the number of side effects. Incidence of dyskinesia in the patients treated with neuroleptics (for a mean of 20 months) was significantly greater (44%) than that in non-neuroleptic-treated patients (14%). A significant risk factor for TD was long-term neuroleptic therapy, whereas age, gender, psychiatric diagnosis, neuroleptic dose, and antiparkinsonian drug use were not risk factors.

International audience; Drug claims databases are increasingly available and provide opportunities to investigate epidemiologic questions. The authors used computerized drug claims databases from a social security system in 5 French districts to predict the probability that a person had Parkinson's disease (PD) based on patterns of antiparkinsonian drug (APD) use. Clinical information for a population-based sample of persons using APDs in 2007 was collected. The authors built a prediction model using demographic variables and APDs as predictors and investigated the additional predictive benefit of including information on dose and regularity of use. Among 1,114 APD users, 320 (29%) had PD and 794 (71%) had another diagnosis as determined by study neurologists. A logistic model including information on cumulative APD dose and regularity of use showed good performance (c statistic = 0.953, sensitivity = 92.5%, specificity = 86.4%). Predicted PD prevalence (among persons aged ≥18 years) was 6.66/1,000; correcting this estimate using sensitivity/specificity led to a similar figure (6.04/1,000). These data demonstrate that drug claims databases can be used to estimate the probability that a person is being treated for PD and that information on APD dose and regularity of use improves models' performances. Similar approaches could be developed for other conditions.

Background: L-dopa is an important antiparkinsonian drug. It is a precursor of dopamine and the other catecholamines. Potentially, administration of L-dopa could lead to increased urinary excretion of catecholamines and their metabolites to abnormal amounts. The current study aimed to determine these excretions in patients with Parkinson's disease (PD) receiving L-dopa compared with suitable controls. This is the first assessment of the effect of exogenous administration of L-dopa on urinary free metadrenalines. Methods: Using one-way analysis of variance (ANOVA), urine catecholamines and metabolites, expressed as mmol per mole creatinine, were compared in: patients with PD who were receiving L-dopa; patients with PD but not receiving L-dopa; and patients without PD who were being investigated for the presence of phaechromocytoma but were found not to have the disease. Results: Significantly higher values for urinary dopamine, homovanillic acid, free normetadrenaline and free metadrenaline were found in patients with PD receiving L-dopa compared with the other two control groups. In all the patients with PD, these four analytes were significantly correlated with daily dose of L-dopa. Conclusion: L-dopa therapy can result in production of false positives for urinary excretion of dopamine, homovanillic acid, free normetadrenaline or free metadrenaline and thereby decrease the diagnostic value of these measurements in identifying phaeochromocytoma and related tumours.

1202 patients suffering from Parkinson’s disease switched from other dopamine agonists to pramipexole under open conditions either abruptly or in an overlapping, gradual manner. Mostly insufficient effectiveness motivated the switch. The investigators gave equal preference to either an abrupt or an overlapping switch to pramipexole in this observational study. There was a tendency in favour of the overlapping switch procedure in those patients who were on a relatively higher dose of a dopamine agonist before the switch. The switch was performed because the investigators expected the effect of pramipexole on tremor, motor functions and depression/anhedonia to be better compared with previous dopamine agonists. The main reasons for switching to pramipexole (anti-tremor effect, anti-depressive/anti-anhedonic effect) as given by the physicians at baseline came up to expectations.

Transdermal delivery of dopamine agonists (DA) is a promising therapeutic concept, which aims to ameliorate frequency and intensity of motor fluctuations in patients with Parkinson’s disease (PD). We treated 8 PD patients with unpredictable on-off phenomena with lisuride patches (release: 2–5/μg lisuride base/cm2/hour in mice) in addition to their preexisting antiparkinsonian drug regime up to a period of 8 days. In order to quantify the intensity and frequency of motor fluctuations, we determined the motor changing rate (MCR), which corresponds to the patient’s self rating of motor function, performed every thirty minutes, divided through the number of scored intervals minus 1. Additional lisuride patch application significantly (p = 0.023) improved the MCR compared to baseline. Relevant side effects were transient skin irritations in four patients. Our observational study demonstrates the safety, tolerability and efficacy of transdermal lisuride delivery in the treatment of motor complications.

In recent years, the antiparkinsonian drug regime has become increasingly complicated. A wide range of antiparkinson agents is meanwhile available. Combination therapies may unfortunately induce interactions up to the point of life-threatening events. The potential of drug-drug interactions must be taken into account before starting a patient on combination treatment. Moreover, the frequent multimorbidity of patients with Parkinson's disease necessitates the application of additional drugs. A general overview is difficult to maintain because of the countless number of possible interactions. Cautious proceeding is certainly indicated in particular cases. The most common interactions will be discussed below. We should bear in mind that many of the interactions related to drug combinations are unknown yet.

Despite clinical experience with levodopa for more than three decades, the role of this agent in the treatment of Parkinson's disease (PD) has not been well defined. Clearly the most effective antiparkinsonian drug, levodopa, is associated with emergence of motor complications, particularly fluctuations and dyskinesias, as well as other side effects. In addition to these limitations, there is an ongoing debate about the potential neurotoxic effects of levodopa, suggested by some in vitro studies. However, there is no support for levodopa-induced neurotoxicity from in vivo studies. This review discusses possible mechanisms of levodopa-related complications and therapeutic strategies for their prevention and management.

A 42-year-old man had suffered from Parkinson's disease for 5 years. Levodopa was effective, but the wearing-off phenomena were severe. Because of relatively low levels of serum copper and ceruloplasmin, D-penicillamine was administered. D-penicillamine increased plasma levodopa concentrations, thereby improving his parkinsonian symptoms. We propose that D-penicillamine facilitates levodopa absorption and, hence, the efficacy of the antiparkinsonian drug.

The authors review management issues in Parkinson’s disease (PD) and provide an overview of the current pharmacological management strategies, with a specific focus on safinamide. Current therapeutic management of PD largely involves strategies to optimize the replacement of deficient dopamine, using levodopa, dopamine agonists, and inhibitors of dopamine-metabolizing enzymes. Currently under investigation for use in the treatment of PD, safinamide has multiple modes of action including monoamine oxidase B inhibition. It is well absorbed orally, has a long plasma half-life, and does not have liver enzyme-inducing or liver enzyme-inhibiting activity. Peak plasma concentration occurs 2–4 hours after single oral doses. Safinamide as monotherapy and as an adjunct to dopamine agonists improves Unified Parkinson’s Disease Rating Scale motor scores. One randomized, placebo-controlled trial involving 168 patients given a median safinamide dose of 70 mg/day (range 40–90 mg/day) significantly increased the proportion of responders – defined as patients improving their Unified Parkinson’s Disease Rating Scale motor scores by 30% or more from baseline – after 3 months (37.5% for safinamide versus 21.4% for placebo; P < 0.05). Safinamide increased “on” time with no or minor dyskinesia compared with the placebo in another trial, but dyskinesia severity was not reduced. Safinamide was well tolerated, with an adverse effect profile similar to that of the placebo. Further Phase III trial data for safinamide efficacy is awaited, and will be of interest in a comparison with other developments in PD therapeutics: modified formulations of available compounds, new drug classes such as adenosine receptor antagonists, and gene-based therapies.

Antiparkinsonian drugs used for 117: chronic schizophrenic patients receiving long-term neuroleptic treatment were withdrawn. Seventy-eight (66.7%) of the 117: patients were without akathisia and/or parkinsonism at least for 6: weeks after the antiparkinsodan drug withdrawal. A double-blind study of clonazepam was carried out for 22: patients and clonazepam was effective on 8: patients (100%) with akathisia and on 3: patients (75%) with parkinsonism. The authors conclude that these data support the need for discontinuous use of antiparkinsonian medication during the long-term neuroleptic therapy of chronic schzophrenic patients and the effectiveness of clonazepam in managing antiparkinsonian drug withdrawal-induced akathisia and parkinsonism.

Many investigators have recently reported marked beneficial effects of L-DOPA in the treatment of Parkinsonism.This author has already reported clinical ex periences with L-DOPA in the treatment of 145 cases of Parkinsonism at St. Barnabas Hospital in N. Y. C., published in the Japanese Journal of Brain and Nerve on December 1970.In this report, following results were stressed. Namely, 80.7% of the patients showed some improvement of symptoms and especially such symptoms as rigidity, bradykinesia, difficulty of speech and ambulation showed moderate or significant improvement, while tremor was unable to get significant relief.This time, the author is reporting clinical experiences with APD-512 (L-DOPA) in the treatment of 14 cases of Parkinsonism, treated at Sapporo District Hospital, Ground Self Defense Force, Japan.The results are summarized as follows: —1. APD-512 was given orally in every case.Initial daily doses started at 500 mg and were increased gradually every couple of days.2. Initial effective daily doses were proved to be 1.5 or 2.0 gm and an average daily maintenance dosage between 2.0 gm and 4.0 gm was sufflcient.3. All 14 cases were responsive to the drug, with apparent improvement of Parkinsonian symptoms.4. Side effects were almost the same as experienced in previous cases, including nausea, vomiting, anorexia, psychic reaction, etc. However, the severity of these complaints was lighter in Japanese cases.5. Marked improvement was noted in such symptoms as rigidity, akinesia, gait and balance and A. D. L., while there was a minimal improvement in tremor.6. The relationship between the severity of the disease and the beneficial effect of APD-512 was very hard to assess in this small series. However, it appears that far advanced cases of the disease show very little marked improvement from the drug so far.These results are almost coincident with other investigators' reports that APD-512 (L-DOPA) is the most useful antiparkinsonian drug ever used.

The potentiation of the anticholinergic effects of one drug by another is frequently overlooked as a cause of acutely developing psychosis. This is not surprising considering that more than 600 drugs with significant anticholinergic properties are currently commercially available (Alpern and Marriot, 1973). This paper defines the central anticholinergic syndrome (CAS), its forms of presentation, etiology, pharmacology, and management.

Movement disorders comprise a large group of neurological conditions characterised by either: (a) slowness and poverty of movement with rigidity, and sometimes rest tremor—the akinetic-rigid syndrome; or (b) abnormal involuntary movements—the dyskinesias. Common causes of these disorders are shown in Tables 5.1 and 5.2.

The results shown are from a survey of unselected patient prescriptions collected from six different hospitals over the years stated. The intervals sampled varied between three and 12 months with a mean period of 5.4 months.

In the years since World War II, the emergency department has grown from a single room where accident cases were taken for first aid into one of the busiest, most complex, labor intensive and sophisticated hospital departments. The reason for this growth has been the unplanned, phenomenal increase in the use of the emergency department, in both Canada and the U.S., documented as being greater than that of any of the other measures of hospital utilization, and well beyond that which could be explained by the population growth (Voineskos, 1981; Krass, 1977; Chaiton, 1975; American Medical Association, 1966; Jenkins and Van de Leuv, 1978; Baltzan, 1972). The increasing utilization of the hospital emergency room has been accompanied by a similar and often greater increase in the percentage of psychiatric emergency visits (Schwartz et al., 1972; Satloff and Worby, 1970; Zonana et al., 1973; Lowy, 1971).

Through the study of the pharmacological and clinical actions of chlozapine, a new drug used in psychiatry, we are questioning one of the traditional statements on the therapeutic action of antipsychotics: the affirmation that those must have, concomitantly, antipsychotic action and intense extrapyramidal effects (druginduced parkinsonism).

Budipine is a new antiparkinsonian drug which has been shown to ameliorate the major parkinsonian symptoms such as tremor, akinesia, and rigidity. It may have some influence on dopamine release and uptake and may also possess anticholinergic properties and exert definite stimulatory effects on the serotonergic receptors (Menge and Brand 1982).

Background The prevalence of smoking in patients with schizophrenia is higher than that in the general population and is an important medical issue. Short-term smoking cessation tends to worsen psychiatric symptoms in patients with schizophrenia but decreases sympathetic nervous system activity and improves plasma cholesterol levels in healthy people. Few studies have assessed the long-term effects of smoking cessation in patients with schizophrenia. Methods Subjects were 70 Japanese patients with schizophrenia (38 smokers, 32 non-smokers). We compared the following clinical parameters between the two groups at baseline (before smoking cessation) and in each group separately between baseline and at three years after smoking cessation: autonomic nervous system activity, plasma cholesterol levels, body weight, drug therapy, and Global Assessment of Functioning scores. We also compared the mean changes in clinical parameters throughout this study between the groups at both time points. Autonomic nervous system activity was assessed by power spectral analysis of heart rate variability. Results Parasympathetic nervous system activity and the doses of antiparkinsonian drugs in smokers were significantly higher than those in non-smokers at baseline. Smoking cessation was associated with significantly decreased sympathetic nervous system activity and decreased doses of antipsychotics and antiparkinsonian drugs at three years after smoking cessation. However, there was no significant difference in the mean change in clinical factors scores, except for Global Assessment of Functioning scores, between smokers and non-smokers at three years after smoking cessation. Conclusions Our results suggest that smoking reduces both autonomic nervous system activity and the effectiveness of drug therapy with antipsychotics and antiparkinsonian drugs in patients with schizophrenia, but that both factors could be ameliorated over the long term by smoking cessation. Taken together with the findings of previous studies, smoking cessation in patients with schizophrenia has many long-term positive physiological effects.

To the Editor.— In the recent article, "Myoclonus in Familial Restless Legs Syndrome" ( Arch Neurol 33:368, 1976), Boghen and Peyronnard refer to symptoms including an unpleasant sensation in the legs and an associated urge to move them, occurring at rest and relieved by walking. I wish to point out the similarity between the clinical manifestations of the familial restlesslegs syndrome and those of phenothiazineinduced akathisia. The latter is characterized by an inability to sit still, intolerance of inactivity, continuous agitation and restless movement, rocking and shifting of weight while standing, and shifting of legs and tapping of feet while sitting. 1 The use of antiparkinsonian drugs has been recommended in the treatment of phenothiazineinduced akathisia. 2 A trial of an antiparkinsonian drug, such as procyclidine, in the treatment of familial restless legs syndrome might be worthwhile.