A preliminary observation of the adverse effects of phenobarbital among patients with convulsive epilepsy in rural West China

BackgroundThis study explored the adverse effect (AE) profile of phenobarbital (PB) among patients with active convulsive epilepsy (ACE) from resource-poor areas.MethodsPatients with ACE were enrolled into an epilepsy management project in rural West China. Information was obtained from monthly follow-up questionnaires. The demographic and clinical features of the patients with AE were firstly described. After that, the occurrence rate was estimated for each subtype of AE at three different severity levels (mild, moderate, and serious). Survival analysis was used to determine the potential risk factors of AEs.ResultsA total of 7231 patients (3780 men) were included in the present cohort. During the follow-up time period (average 33.4 months), the most common AEs were drowsiness (moderate: 4.4%, serious: 0.68%), dizziness (moderate: 3.7%, serious: 0.5%), and headache (moderate: 2.9%, serious: 0.41%). In the confirmed AE groups (moderate and serious severity levels), the symptoms tended to be transient, with durations of less than 3 months. Polytherapy was an independent risk factor for AEs and had an increasing risk when the severity of the AE increased (Hazard Ratio 1.12, 1.55, and 2.52 for mild AE, moderate AE, and serious AE, respectively). Receiving a high dosage of PB (> 180 mg/day) indicated a slightly elevated risk (Hazard Ratio 1.22 and 1.27 for mild AE and moderate AE, respectively).ConclusionPhenobarbital demonstrates overall tolerability, and serious AEs were not common. Patients receiving a high dose of PB or polytherapy are at increased risk of developing AEs.     

Myasthenia gravis Opportunistische Zytomegalievirus-Infektion nach langzeitiger Azathioprin-Therapie

Opportunistic infections after long-term treatment with azathioprine (AZA) have not been noted in patients with myasthenia gravis (MG). We report on a 56-year-old woman with generalized MG who presented with cytomegalovirus infection after being treated with AZA for 17 years. The indication for immunosuppressive treatment in MG should be regularly reconfirmed, particularly since at least 50% of patients can discontinue AZA after two to four years without risk of exacerbation.     

Myasthenia gravis: disease severity and prognosis

Objectives –  To examine myesthenia gravis (MG) severity and long-term prognosis in seronegative, seropositive, and thymoma MG.
Materials and Methods –  Four series of patients were studied retrospectively. Severity and treatment were assessed each year, and muscle antibodies were assayed.
Results –  Seropositive MG patients had a more severe course than seronegative MG patients. MG severity was higher in non-thymectomized compared to thymectomized early-onset MG patients. MG severity did not differ between thymectomized and non-thymectomized late-onset patients. There was no significant difference in MG severity between thymoma and non-thymoma MG patients.
Conclusions –  MG is more severe in seropositive MG patients. With proper treatment, especially early thymectomy, the long-term prognosis is good in seropositive MG patients. The present studies indicate a benefit of thymectomy in early-onset MG, but no dramatic benefit in late-onset MG. Similar MG severity and outcome was seen in thymoma and non-thymoma MG.     

Time course of adverse events most commonly associated with topiramate for migraine prevention

The efficacy, safety and tolerability of topiramate has been demonstrated in three large multicenter, randomized, double-blind, placebo-controlled trials. To characterize the time course of adverse events (AEs) that led to treatment discontinuation in ≥2% of patients who received topiramate 100 mg/day during three pivotal, multicenter, randomized, double-blind, placebo-controlled, and 26-week trials. The pooled population comprised all randomized patients who reported safety data during the double-blind phase (topiramate 100 mg/day, n  = 386; placebo n  = 372), which consisted of a 4-week titration period and a 22-week maintenance period. Incidence, time to onset, and cumulative mean rate of AEs were assessed. Overall, AEs led to treatment discontinuation in 24.9% of patients receiving topiramate 100 mg/day and 11.0% receiving placebo ( P  < 0.001). AEs leading to discontinuation during the double-blind phase in ≥2% of patients included paresthesia (8.0% discontinued), any cognitive symptoms (7.3% discontinued), fatigue (4.7% discontinued), insomnia (3.4% discontinued), nausea (2.3% discontinued), loss of appetite, anxiety, and dizziness (2.1% discontinued because each AE). Most AEs began during the titration period. Paresthesia, any cognitive symptoms, nausea, and loss of appetite occurred at a higher rate in the topiramate group than in the placebo group ( P  < 0.01). AEs leading to discontinuation of topiramate are probably to occur during dose titration. If a patient has not experienced one of these AEs within the first 6 weeks of initiating topiramate 100 mg/day, these AEs are unlikely to occur.     

Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis

Sativex is an endocannabinoid system modulator principally containing Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD). During a 6-week randomised controlled trial, Sativex had a clinically relevant effect on spasticity associated with multiple sclerosis (MS). Patients self-titrated oromucosal Sativex to symptom relief or maximum tolerated dose (maximum of 130 mg THC and 120 mg CBD daily). The primary objective was to evaluate the safety and tolerability of long-term treatment by recording the incidence and severity of adverse events (AEs). Secondary outcomes were to determine evidence of developing tolerance and to assess the long-term dosing profile of Sativex. A validated 11-point Numerical Rating Scale of spasticity severity was used to assess efficacy. A total of 146 patients elected to enter this open-label follow-up safety trial. Mean treatment exposure was 334 days (standard deviation, SD = 209 days), and patients administered on average 7.3 (SD = 4.42) actuations per day. Fifty-two (36 %) patients withdrew from the study in the first year, 14 % due to AEs and 9 % due to lack of efficacy. Most AEs were mild/moderate in severity. Common (>10 %) treatment-related AEs were dizziness (24.7 %) and fatigue (12.3 %). Serious AEs occurred in five patients (3.4 %), with two psychiatric events reported by one patient. No psychoses, psychiatric AE trends, or withdrawal symptoms occurred following abrupt cessation of treatment. Baseline symptoms including spasticity did not deteriorate but were maintained to study completion in those patients who did not withdraw. No new safety concerns were identified with chronic Sativex treatment, and serious AEs were uncommon. There was no evidence of tolerance developing, and patients who remained in the study reported continued benefit.     

MuSK-positive myasthenia gravis is rare in the Polish population

Background and purpose:  MuSK-positive myasthenia gravis (MG) is diagnosed in 0–48% of cases with generalized seronegative MG in different populations. The presence of anti-MuSK antibodies generally relates to a severe course and lack of response to thymectomy. We analyzed for the first time the serology and clinical characteristics of MuSK-positive MG in the Polish population.
Methods:  One hundred and fifty-one patients were tested for the presence of anti-AChR and anti-MuSK antibodies: 62 with seronegative MG, including 14 with ocular seronegative MG, 48 age-matched patients with seropositive MG and 41 controls.
Results: All patients with seropositive MG and the disease controls were MuSK-negative. Anti-MuSK antibodies were detected only in four patients with seronegative MG (8.7% of generalized seronegative cases): three women and one man. All four had predominantly bulbar involvement, and underwent thymectomy, with no apparent benefit. All of them improved clinically after immunosuppressive treatment with remissions lasting up to 7 years.
Conclusion: MuSK-positive MG is rare in Polish population accounting for only 8.7% of seronegative cases with generalized MG. This is consistent with emerging evidence for lower MuSK antibodies at more northerly latitudes.     

Descripción de una serie de pacientes con miastenia gravis refractaria

IntroductionAdvances in the treatment of myasthenia gravis (MG) have improved quality of life and prognosis for the majority of patients. However, 10%-20% of patients present refractory MG, with frequent relapses and significant functional limitations.Patients and methodsPatients with refractory MG were selected from a cohort of patients diagnosed with MG between January 2008 and June 2019. Refractory MG was defined as lack of response to treatment with prednisone and at least 2 immunosuppressants, inability to withdraw treatment without relapse in the last 12 months, or intolerance to treatment with severe adverse reactions.ResultsWe identified 84 patients with MG, 11 of whom (13%) met criteria for refractory MG. Mean (standard deviation) age was 47 (18) years; 64% of patients with refractory MG had early-onset generalised myasthenia (as compared to 22% in the group of patients with MG; P<.01), with a higher proportion of women in this group (P<.01). Disease severity at diagnosis and at the time of data analysis was higher among patients with refractory MG, who presented more relapses during follow-up. Logistic regression analysis revealed an independent association between refractory MG and the number of severe relapses.ConclusionsThe percentage of patients with refractory MG in our series (13%) is similar to those reported in previous studies; these patients were often women and presented early onset, severe forms of onset, and repeated relapses requiring hospital admission during follow-up.     

Successful treatment of refractory generalized myasthenia gravis with rituximab

Objective:  Myasthenia gravis (MG) is an autoimmune neuromuscular disorder for which current therapies carry a high risk of side-effects and may be insufficient in stabilizing the clinical status. Many therapeutic options can be ruled, such as thymectomy, corticosteroids, azathioprine, cyclophosphamide, mycophenolate mofetil, methotrexate, intravenous immunoglobulin (IVIg) or less frequently plasmapheresis must be ruled.
Methods:  We followed prospectively six patients with MG who presented with a poor response to two or three lines of immunosuppressive conventional drugs associated with oral corticosteroids. All but one were acetylcholine receptor negative and three were anti-MuSK positive. IVIg did not improved the neurological status and all patient required high doses of cholinesterase inhibitors.
Results:  Rituximab was introduced with a mean follow-up of 1.5 years (375 mg/m², days 1, 8, 15, 28 during the first month and then one dose every 2 months). After 2 years of follow-up, all patients stopped corticosteroids and tapered off cholinesterase inhibitors from 60 to 180 mg/day without severe infectious events.
Conclusion:  Rituximab, a chimeric IgG k monoclonal antibody that target CD20 is used for the treatment of relapsing/refractory CD20 positive low-grade non-Hodgkin's lymphoma and other autoimmune neuromuscular diseases. Four previous short reports have described a good response of MG associated with lymphoma with rituximab. It appears to be a promising and effective drug for the treatment of MG without lymphoma, with a substantial benefit to the clinical status and good tolerability.     

Safety and effectiveness of levodopa-carbidopa intestinal gel for advanced Parkinson's disease: A large single-center study

BackgroundTreatment with levodopa-carbidopa intestinal gel (LCIG) can effectively relieve motor and non-motor symptoms in advanced Parkinson's disease (PD). However, adverse events (AEs) are frequent.ObjectiveTo describe AEs associated with LCIG treatment and the main reasons for treatment discontinuation. We also looked for factors that were potentially predictive of serious AEs and assessed the effectiveness of and satisfaction with LCIG.MethodWe retrospectively analyzed data on AEs in patients treated with LCIG at a French university medical center. For patients still receiving treatment at last follow-up, effectiveness was assessed according to the Clinical Global Impression (CGI) scale and the Movement Disorders Society – Unified Parkinson's Disease Rating Scale motor score.ResultsOf the 63 patients treated with LCIG for a mean (range) of 19 months (8–47), 57 (90%) experienced at least one AE (340 AEs in total). Most of the AEs (in 69.8% of the patients) were related to percutaneous endoscopic gastrostomy with a jejunal tube (PEG-J) or affected the gastrointestinal tract (granuloma, leakage, or a local infection). Device-related AEs (such as PEG-J removal and device occlusion) were frequent (in 63.5% of patients). Forty-three patients (68%) required at least one additional endoscopic procedure. Dopatherapy-related AEs occurred in 30 patients (48%). Most of the AEs occurred long after treatment initiations, and only a small proportion led to discontinuation. On the CGI scale, 53 patients (84.4%) considered that their condition had improved during LCIG treatment.ConclusionDespite the high frequency of AEs, patients with advanced PD gain clinical benefit from treatment with LCIG. This treatment requires a competent, multidisciplinary team on site.     

Ryanodine receptor antibodies are associated with severe myasthenia gravis

Sera from 32 thymoma patients, 29 of them with myasthenia gravis (MG), were tested for the presence of circulating antibodies to the ryanodine receptor (RyR) in Western blot RyR is a channel protein essential for the excitation-contraction coupling in skeletal muscle. MG severity was scored according to the Osserman classification during 1–17 years of follow-up (mean 7 years). Fifteen patients (14 MG and 1 non-MG) were RyR-antibody positive. RyR-positive patients had a significantly higher frequency of invasive thymomas (p = 0.01), and also a more severe MG than RyR-antibody negative patients (p = 0.04). The use of immunosuppressive drugs at latest follow-up was more frequent in RyR-antibody positive than in RyR-antibody negative patients (p = 0.02). Thus the presence of RyR-antibodies in thymoma patients is associated with a more severe disease and can be used as a prognostic marker.     

Tolerability of selective serotonin reuptake inhibitors in thirty-nine children under age seven: a retrospective chart review

OBJECTIVE: To characterize the adverse effects of treatment with selective serotonin reuptake inhibitors (SSRIs) started in children under age 7 yr. METHODS: We conducted a retrospective review of medical records for all children who had begun treatment with an SSRI under age 7 at an academic psychiatry department in Boston. RESULTS: Thirty-nine children (26 males, 13 females) met the inclusion criteria. Mean age at start of treatment was 5.9 +/- 0.8 yr, and median treatment duration was 5.0 months. The target diagnoses for SSRI treatment were anxiety disorders in 54%, depressive disorders in 23%, and both anxiety and depressive disorders in 20% of patients. There were no reports of suicidal ideation or attempt. No children were medically or psychiatrically hospitalized for adverse effects (AEs). Eleven patients (28%) reported an AE of at least moderate severity; 7 (18%) discontinued the SSRI due to the AE. Six patients discontinued due to behavioral activation and 1 due to gastrointestinal upset. The median time to onset of an AE was 23 days, and median resolution was 19 days from onset. CONCLUSIONS: The high rate of adverse effects, especially activation, in this sample argues for continued caution in using SSRIs in young children. Controlled trials are warranted.     

Swedish natalizumab (Tysabri) multiple sclerosis surveillance study

A post-marketing surveillance program was implemented to monitor the safety and open label efficacy of natalizumab since its launch in Sweden August 2006. Patients are registered in the Swedish multiple sclerosis (MS)-registry that has a nationwide coverage using a standardized follow-up that includes EDSS, MSSS, SDMT, MSIS-29, and recording of adverse events (AEs). As of 31 January, 2010, 1,115 patients had been included, of which 363 were treated ≥24 months. Dropout rate was 10%, mainly due to planned pregnancy. Serious AEs were rare, but included three cases of progressive multifocal leukoencephalopathy (PML), none of which had received previous immunosuppressive therapy. All analyzed clinical outcome parameters showed significant improvements compared to baseline for patients exceeding 24 months of treatment. Our results demonstrate good general tolerability and sustained efficacy of natalizumab for patients with severe MS, though the risk of PML remains a concern.

     

Treatment and outcome of myasthenia gravis: retrospective multi-center analysis of 470 Japanese patients, 1999-2000

To clarify the current status of treatments and outcomes of patients with myasthenia gravis (MG) in Japan, a total of 470 patients (164 men and 306 women; mean age 41 years) were recruited from 19 Japanese tertiary medical centers in 1999-2000. Thymectomy was performed in 319 (68%) of the patients. Patients who received thymectomy were younger (p = 0.01) and had more severe disabilities (p < 0.01) than patients without thymectomy. Irrespective of receiving thymectomy, most of the patients were administered corticosteroids (64%), other immunosuppressive agents (10%), or cholinesterase inhibitors (86%). Of 395 patients followed up for more than 12 months after treatment (mean 8.0 years), 30% (34% of thymectomized and 21% of non-thymectomized patients) were in remission (no symptoms with/without medication), 34% had only ocular symptoms, and the remaining 35% still had weakness of bulbar or limb muscles at the end of follow-up. The prognosis of MG in Japan was generally favorable, but despite the frequent use of thymectomy and immunosuppressive treatments, approximately one-third of patients still had generalized weakness. More effective or intensive treatments are required to improve the prognosis.     

Swedish natalizumab (Tysabri) multiple sclerosis surveillance study

A post-marketing surveillance program was implemented to monitor the safety and open label efficacy of natalizumab since its launch in Sweden August 2006. Patients are registered in the Swedish multiple sclerosis (MS)-registry that has a nationwide coverage using a standardized follow-up that includes EDSS, MSSS, SDMT, MSIS-29, and recording of adverse events (AEs). As of 31 January, 2010, 1,115 patients had been included, of which 363 were treated ≥24 months. Dropout rate was 10%, mainly due to planned pregnancy. Serious AEs were rare, but included three cases of progressive multifocal leukoencephalopathy (PML), none of which had received previous immunosuppressive therapy. All analyzed clinical outcome parameters showed significant improvements compared to baseline for patients exceeding 24 months of treatment. Our results demonstrate good general tolerability and sustained efficacy of natalizumab for patients with severe MS, though the risk of PML remains a concern.     

Clinical and experimental features of MuSK antibody positive MG in Japan

We investigated the presence of antibodies (Abs) against muscle-specific tyrosine kinase (MuSK) in Japanese myasthenia gravis (MG) patients. MuSK Abs were found in 23 (27%) of 85 generalized seronegative MG (SNMG) patients but not in any of the ocular MG patients. MuSK Ab-positive patients were characterized as having female dominance (M:F, 5:18), age range at onset 18 to 72 (median 45) years old, and prominent oculobulbar symptoms (100%) with neck (57%) or respiratory (35%) muscle weakness. Limb muscle weakness was comparatively less severe (52%), thymoma absent. Most patients had good responses to simple plasma exchange and steroid therapy. MuSK IgG from all 18 patients was exclusively the IgG 4 subclass and bound mainly with the MuSK Ig 1–2 domain. Serial studies of 12 individuals showed a close correlation between the variation in MuSK Ab titers and MG clinical severity ( P  = 0.01 by Kruskal–Wallis). MuSK Ab titers were sharply decreased in patients who had a good response to early steroid therapy or simple plasma exchange, but there was no change, or a rapid increase on exacerbation after thymectomy. Measurement of MuSK Ab titers aids in the diagnosis of MG and the monitoring of clinical courses after treatment.     

Long-term effects of combined immunosuppressive treatment on myasthenic crisis

Background and purpose:  We studied the long-term crisis-preventing effect of combined prednisolone-azathioprine (PR-AZA) treatment in myasthenia gravis (MG).
Methods:  Case–control study with a median follow-up of 64 months in the treated group, and 80 months in the non-treated group. Sixty-nine patients with episodes of myasthenic crisis (MC) were treated and followed prospectively in 1990–2004. Twenty-seven patients had MC between 1990 and 1996, and were not treated with immunosuppressants on long-term. Long-term PR-AZA treatment was introduced in another 42 patients, who developed MC in 1997–2004. The difference in the frequency of repeated MCs between the treated and the non-treated group during long-term follow-up was investigated. As secondary end-points, we analyzed the number of admittances to the ICU; the number of mechanical ventilation episodes; the duration of ICU treatment; the characteristics of the applied treatment; and the functional outcome of the patients 1 month after the onset of the crisis.
Results:  Recurrent MCs occurred in 74% of the non-treated and 19% of the treated group ( P  <   0.001). The number of ICU admissions ( P  =   0.005) and mechanical ventilation events ( P  =   0.002) were also reduced. The highly significant MC preventing effect of PR-AZA was evident after 6 months.
Conclusions:  After the initial 6 months of therapy, PR-AZA is effective in preventing MC .     

Azathioprine and interferon beta(1a) in relapsing-remitting multiple sclerosis patients: increasing efficacy of combined treatment

Current treatments of relapsing-remitting multiple sclerosis (RRMS) with immunosuppressive or immunomodulatory drugs have been shown to modify the course of the disease in a significative number of patients. However, in many cases, the response to either interferon beta (IFN-beta) or azathioprine (AZA) treatments was not satisfactory and new therapeutic approaches are needed. We studied clinical and MRI efficacy, safety and tolerance of AZA and IFN-beta(1a) combined therapy in 23 patients with clinically definite RRMS, who had not previously been responsive to either monotherapies. Our cases were divided into three subgroups: 8 previously untreated patients (subgroup A) with at least 2 years of natural course of the disease, 8 patients (subgroup B) previously treated with AZA for 2 years and 7 patients (subgroup C) previously treated with IFN-beta(1a) for 2 years. The baseline Expanded Disability Status Scale (EDSS) ranged from 2 to 4 in all subgroups. All patients completed 2 years of combined treatment with a dose of AZA adjusted to reduce lymphocyte count down to 1,000 +/- 100/microl in association with IFN-beta(1a) at a dose of 6 MIU every other day. The mean number of relapses during the combined treatment period was significantly lower than that observed before combined therapy in all the three subgroups. Also, the mean Delta EDSS score was significantly lower during combined treatment than in monotherapy in subgroups B and C. Moreover, after 2 years of combined treatment, the number of new T(1) hypointense lesions, the number and volume of proton density/T(2) hyperintense lesions and the gadolinium enhancement of T(1) hypointense lesions were significantly lower than before combined treatment. After 2 years of treatment, this combination therapy appears to be safe and well tolerated and no serious side effects were reported. Despite some limitations of our study design, the information regarding efficacy, safety and tolerance of the association of AZA and IFN-beta is most encouraging.     

Does myasthenia gravis provide protection against cancer?

Objectives –  Reports have been made of an altered rate of extrathymic malignancies in patients with myasthenia gravis (MG). This study compared the rate of such malignancies in a group of MG patients with an optimal control group.
Materials and methods –  From the Norwegian Cause of Death Registry, we identified 249 dead MG patients (1951–2001) and a control group of 1,245 individuals (five per patient) dead in the same period, matched for sex and year of birth.
Results –  Patients with MG had a lower occurrence of malignant disease as underlying or contributing cause of death than the controls (8.8% vs 27.2%, P  < 0.001). The main difference was found for colorectal cancer, breast cancer and cancer in the upper digestive tract (esophagus and stomach).
Conclusions –  We report a significantly lower rate of extrathymic malignancies in patients with MG than in controls, and we hypothesize that MG treatment or the immunological mechanisms involved in MG may protect patients with MG from developing an extrathymic malignancy.     

Intravenous immunoglobulin for prophylaxis of acute exacerbation in Myasthenia Gravis

Intravenous immunoglobulin (IVIg) treatment for acute exacerbations of Myasthenia Gravis (MG) was shown in several open-label studies. There are only two studies demonstrating the efficiency of regular intermittent IVIg therapy on MG patients who are not in their acute attack periods. Thirteen patients who had displayed an inadequate clinical response to immunosuppressive treatments, or who were not appropriate for immunosuppressive treatment due to the age factor and thus were given regular IVIg therapy, were retrospectively investigated. Moreover, the pre- and post-treatment attack frequencies were also evaluated. The mean number of attacks was 0.0960 attacks/year before IVIg therapy, and 0.0056 attacks/year after IVIg therapy (p = 0.002). The number and severity of the attacks were decreased in all patients. Eight patients (62 %) had used steroids; among them, steroid was completely stopped in two patients following the regular IVIg therapy, and the dose was decreased by 50 % in the other six patients. The requirement for pyridostigmine did not decrease in four patients, whereas this need decreased by 20–50 % in nine patients. IVIg can produce repeated beneficial effects in patients with MG and may be useful as an adjunct in the management of MG. IVIg has minimal adverse effects and ability to reduce corticosteroid dose. These results suggest that intravenous immunoglobulin maintenance therapy is a valid modality in patients with resistant treatment MG.     

Twelve-month safety of entacapone in patients with Parkinson's disease

The safety of entacapone combined with levodopa and a dopadecarboxylase (DDC) inhibitor was tested in a 12-month double-blind study of 326 patients with idiopathic Parkinson's disease (PD). The study population represented 'typical' PD outpatients, including patients with varying disease severity and with various concomitant medications. Two-thirds of the patients were randomized to receive 200 mg of entacapone with each of 2--10 daily levodopa doses, and one-third to receive placebo. All entacapone patients were included in the safety evaluation of adverse events (AEs), vital signs, ECG, and laboratory parameters. Entacapone was well tolerated with a discontinuation rate due to AEs of 14% compared with 11% with placebo (NS). As expected, due to dopaminergic enhancement, dyskinesia was more frequent as an AE with entacapone than with placebo. Dryness of mouth, urine discoloration and diarrhoea were more frequent non-dopaminergic AEs with entacapone than with placebo. Entacapone had no adverse effects on hepatic enzyme activity, ECG or haemodynamic parameters, and there was no evidence of any toxicity. As an indication of levodopa enhancement with entacapone, patients taking 5--10 doses of levodopa, most likely representing predominantly fluctuating patients, showed a significant decrease in their mean daily levodopa dose of 94 mg in the entacapone group compared with a decrease of 39 mg in the placebo group (P < 0.01). The interval between the first two morning doses of levodopa increased by 17% with entacapone, whereas with placebo no extension was observed (P < 0.05). Despite levodopa dose reduction, efficacy of entacapone was maintained. As further evidence of efficacy, Parkinsonian symptoms markedly worsened in all patients after withdrawal of entacapone. We conclude that entacapone is safe in optimizing levodopa in long-term treatment of idiopathic Parkinson's disease. Monitoring of liver or other safety parameters during entacapone treatment is not required.