Study design: Retrospective study. Objectives: To study the incidence and management of tolerance in patients treated with intrathecal baclofen (ITB) therapy. Setting: Department of neurology and neurosurgery, University Medical Center Groningen, The Netherlands. Methods: Medical records of all patients who had received an implantable ITB pump at our clinic during 1991-2005 were reviewed. Results: A total of 37 patients (representing 116 pump years) were included. Mean follow-up time was 38 months (range 3-120 months). Baclofen dose increased in the first 18 months after implantation (Po0.05), and then stabilized around a mean dose of 350 mg per day. Eight patients (22%) developed tolerance, defined as a dose increase of 4100 mg per year. No predictive factors for development of tolerance could be determined. Three different treatment regimens for tolerant patients were analyzed. Altering the infusion mode from simple to complex continuous (n ¼ 6) had no effect on the development of tolerance. Pulsatile bolus infusion (n ¼ 1) and a drug holiday (n ¼ 2) were both effective in reducing the daily baclofen dose. Patients who needed surgical revision of the pump system because of mechanical failures (n ¼ 11) showed a significant dose decrease during the first month after revision, indicating that the preoperative dose increase most likely had been caused by the pump failure. Pumprelated complications occurred once per 10.5 years of ITB treatment. Drug-related side effects had an annual risk of 13.8%. The reported events were mostly mild. Conclusions: ITB therapy is effective and safe, also in the long term and causes tolerance in only 22% of the treated patients.

BackgroundThe aim of this study is to investigate if early treatment with levodopa has a beneficial disease modifying effect on Parkinson’s disease (PD) symptoms and functional health, improves the ability to (maintain) work, and reduces the use of (informal) care, caregiver burden, and costs. Additionally, cost-effectiveness and cost-utility of early levodopa treatment will be assessed.MethodsTo differentiate between the direct symptomatic effects and possible disease modifying effects of levodopa, we use a randomised delayed-start double-blind placebo-controlled multi-centre trial design. Patients with early stage PD whose functional health does not yet necessitate initiation of PD-medication will be randomised to either 40 weeks of treatment with levodopa/carbidopa 100/25 mg TID including 2 weeks of dose escalation or to 40 weeks placebo TID. Subsequently, all patients receive levodopa/carbidopa 100/25 mg TID for 40 weeks. There are 8 assessments: at baseline and at 4, 22, 40, 44, 56, 68, and 80 weeks. The primary outcome measure is the difference in the mean total Unified Parkinson’s Disease Rating Scale scores between the early- and delayed-start groups at 80 weeks. Secondary outcome measures are rate of progression, the AMC Linear Disability Score, side effects, perceived quality of life with the Parkinson’s Disease Questionnaire-39, the European Quality of Life-5 Dimensions (EQ-5D), ability to (maintain) work, the use of (informal) care, caregiver burden, and costs. 446 newly diagnosed PD patients without impaired functional health need to be recruited in order to detect a minimal clinical relevant difference of 4 points on the total UPDRS at 80 weeks.DiscussionThe LEAP-study will provide insights into the possible disease modifying effects of early levodopa.Trial registrationISRCTN30518857, EudraCT number 2011-000678-72

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Antiparkinsonian Drugs Causing Inappropriate Antidiuretic Hormone SecretionBartter and Schwartz' defined the following criteria for the syndrome of inappropriate secretion of antidiuretic hormone (SIADH): ( 1) hyponatremia with corresponding hypoosmolality of the serum and extracellular fluid; (2) continued renal excretion of sodium; (3) absence of clinical evidence of volume depletion (normal skin turgor and blood pressure); (4) osmolality of the urine greater than appropriate for the concomitant tonicity of the plasma, that is, urine less than maximally diluted; ( 5 ) normal renal function; (6) and normal adrenal function. Making the diagnosis of SIADH is not easy and many pitfalls are known.2 Many causes for SIADH are known: (para)neopIastic (especially in small cell lung ~a n c e r ) ,~ pulmonary infections, central nervous system infections, trauma tumors, hypothyroidism, hypopituitarism, and drugs5 Examples of drugs that can cause SIADH are carbamazepine, cyclophosphamide, tolbutamide, vinblastine, vincristine, oxytocin, and psychotropics like amitriptyline, haloperidol, and fhphena~i n e .~-~ Case ReportIn 1993, the case of a patient with idiopathic Parkinson's disease and hyponatremia after exposure to levodopa @-dopa)-carbidopa and amantadine was described. SIADH could not be proven because of insufficient data." Afterward, treatment with up to 6 mg/day trihexyphenidyl also caused hyponatremia (126 mmol/L) with nausea, vomiting, headache, and cramps in both legs, which improved spontaneously after use of the drug was ceased. Therefore, the same patient was examined again in search of the relationship among L-dopa-carbidopa, trihexyphenidyl, amantadine, and hyponatremia. Our patient was a 70-year-old man who had parkinsonian symptoms since 1992, Hoehn and Yahr stage 111, with a predominant tremor. This was preceded by a coronary-bypass surgery after myocardial infarc-