| 1. |
- af Edholm, Karolina, et al.
(författare)
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Clinical Reasoning : Leg weakness and stiffness at the emergency room
- 2019
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 92:6, s. E622-E625
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A 48-year-old woman from the Maghreb came to the emergency department with insidious gait difficulties, urgency, and constipation starting 6 months prior to the visit. The patient's complaints consisted of weakness, stiffness, and pain in her legs. Her medical history consisted of Hashimoto thyroiditis and breast cancer, with the latter having motivated surgery 4 months prior to admission. Histopathologic examination had demonstrated ductal cancer sensitive to estrogen and mapping with sentinel node biopsy ruled out metastasis. For that reason, the patient was treated with local radiation given weekly over 1 month and treatment with tamoxifen was started. Physical examination upon admission demonstrated weakness and spasticity in both legs. Reflexes were brisk; bilateral nonsustained foot clonus and Babinski sign were also present. Bilateral dorsal flexion was reduced, but vibration and sensation to touch and pinprick were normal. Sphincter tonus was reduced; systemic manifestations such as myalgias, fever, skin rashes, uveitis, sicca, and arthritic joints were absent.
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| 2. |
- Svenningsson, Per, et al.
(författare)
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Eltoprazine counteracts l-DOPA-induced dyskinesias in Parkinson's disease: a dose-finding study.
- 2015
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Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 138:Feb 10, s. 963-973
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Tidskriftsartikel (refereegranskat)abstract
- In advanced stages of Parkinson's disease, serotonergic terminals take up l-DOPA and convert it to dopamine. Abnormally released dopamine may participate in the development of l-DOPA-induced dyskinesias. Simultaneous activation of 5-HT1A and 5-HT1B receptors effectively blocks l-DOPA-induced dyskinesias in animal models of dopamine depletion, justifying a clinical study with eltoprazine, a 5-HT1A/B receptor agonist, against l-DOPA-induced dyskinesias in patients with Parkinson's disease. A double-blind, randomized, placebo-controlled and dose-finding phase I/IIa study was conducted. Single oral treatment with placebo or eltoprazine, at 2.5, 5 and 7.5 mg, was tested in combination with a suprathreshold dose of l-DOPA (Sinemet®) in 22 patients with Parkinson's disease (16 male/six female; 66.6 ± 8.8 years old) with l-DOPA-induced dyskinesias. A Wilcoxon Signed Ranked Test was used to compare each eltoprazine dose level to paired randomized placebo on the prespecified primary efficacy variables; area under the curve scores on Clinical Dyskinesia Rating Scale for 3 h post-dose and maximum change of Unified Parkinson's Disease Rating Scale part III for 3 h post-dose. Secondary objectives included effects on maximum Clinical Dyskinesia Rating Scale score, area under the curve of Rush Dyskinesia Rating Scale score for 3 h post-dose, mood parameters measured by Hospital Anxiety Depression Scale and Montgomery Asberg Depression Rating Scale along with the pharmacokinetics, safety and tolerability profile of eltoprazine. A mixed model repeated measures was used for post hoc analyses of the area under the curve and peak Clinical Dyskinesia Rating Scale scores. It was found that serum concentrations of eltoprazine increased in a dose-proportional manner. Following levodopa challenge, 5 mg eltoprazine caused a significant reduction of l-DOPA-induced dyskinesias on area under the curves of Clinical Dyskinesia Rating Scale [-1.02(1.49); P = 0.004] and Rush Dyskinesia Rating Scale [-0.15(0.23); P = 0.003]; and maximum Clinical Dyskinesia Rating Scale score [-1.14(1.59); P = 0.005]. The post hoc analysis confirmed these results and also showed an antidyskinetic effect of 7.5 mg eltoprazine. Unified Parkinson's Disease Rating Scale part III scores did not differ between the placebo and eltoprazine treatments. The most frequent adverse effects after eltoprazine were nausea and dizziness. It can be concluded that a single dose, oral treatment with eltoprazine has beneficial antidyskinetic effects without altering normal motor responses to l-DOPA. All doses of eltoprazine were well tolerated, with no major adverse effects. Eltoprazine has a favourable risk-benefit and pharmacokinetic profile in patients with Parkinson's disease. The data support further clinical studies with chronic oral eltoprazine to treat l-DOPA-induced-dyskinesias.
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