Behandling av motoriske symptomer ved Parkinsons sykdom

Gjennom de siste årene har nye terapimuligheter og økt kunnskap om gamle metoder ført til endringer i vår behandling av Parkinsons sykdom. Likevel åpner alle tilgjengelige norske og utenlandske terapianbefalinger for ulike og ofte sidestilte alternativer. Basert på de evidensbaserte terapianbefalingene og på våre egne personlige erfaringer og oppfatninger presenterer vi i denne kliniske oversikten et forslag til fremgangsmåte for medisinsk behandling av motoriske symptomer ved Parkinsons sykdom

Pro-arrhythmic effect of escitalopram and citalopram at serum concentrations commonly observed in older patients – a study based on a cohort of 19,742 patients

Background - For a decade, patients have been advised against using high citalopram- and escitalopram-doses due to risk for ventricular arrhythmia and cardiac arrest. Still, these drugs are widely used to treat depression and anxiety especially in older patients. It is unclear why they are cardiotoxic and at what serum concentrations patients are at risk for arrhythmias. Thus, how many patients that are at risk for iatrogenic cardiac arrest is unknown. Methods - We studied the arrhythmogenic effects of citalopram, escitalopram and their metabolites on human cardiomyocytes. Concentrations showing pro-arrhythmic activity were compared with observed drug and metabolite serum concentrations in a cohort of 19,742 patients (age 12–105 years) using escitalopram or citalopram in Norway (2010–2019). As arrhythmia-risk is related to maximum serum concentration, this was simulated for different age-groups from the escitalopram patient material. Findings - Therapeutic concentrations of both citalopram and escitalopram but not their metabolites showed pro-arrhythmic changes in the human cardiac action potential. Due to age-dependent reduction of drug clearance, the proportion of patients above threshold for arrhythmia-risk increased with age. 20% of patients >65 years were predicted to reach potentially pro-arrhythmic concentrations, following intake of 10 mg escitalopram. Interpretation - All patients that are using escitalopram or citalopram and have genetic disposition for acquired long-QT syndrome, are >65 years, are using additional pro-arrhythmic drugs or have predisposition for arrhythmias, should be monitored with therapeutic drug monitoring (TDM) to avoid exposure to potentially cardiotoxic concentrations. Serum concentrations should be kept below 100 nM, to reduce arrhythmia-risk

Genotyping av pasienter behandlet med selektive serotoninreopptakshemmere

BAKGRUNN - Selektive serotoninreopptakshemmere (SSRI) brukes av over 180 000 mennesker i Norge. Enzymene CYP2D6 og CYP2C19 er sentrale i metabolismen av SSRI-antidepressiver. Serotonintransportøren kodet av SLC6A4 kan ha betydning for effekten av medikamentene. MATERIALE OG METODE - Alle pasienter som hadde blitt genotypet for CYP2D6, CYP2C19 og SLC6A4 ved Senter for psykofarmakologi i 2020, uavhengig av indikasjon, ble inkludert. Hos de pasientene der data var tilgjengelige, ble CYP2C19-genotype koblet til serumkonsentrasjonsmåling av escitalopram, som er det mest brukte SSRI-preparatet. RESULTATER - 432 av 3 492 pasienter (12,4 %) hadde en kombinasjon av genotyper av CYP2D6, CYP2C19 og SLC6A4 som anses å gi mest gunstig metabolisme og effekt av SSRI-antidepressiver. Pasienter med manglende CYP2C19-metabolisme hadde mer enn halvert dosebehov for å oppnå samme konsentrasjon av escitalopram som pasienter med normal metabolisme. FORTOLKNING - Våre funn viser lav forekomst av den gunstigste genotypekombinasjonen for respons av SSRI-preparater. Genotypekombinasjoner bidrar sannsynligvis til den store individuelle variasjonen i effekt av disse medikamentene og til at behandlingen ikke gir ønsket utfall hos mange pasienter

Dopamine agonist serum concentrations and impulse control disorders in Parkinson's disease

Background and purpose: Impulse control disorders (ICDs) are common among Parkinson's disease patients using dopamine agonists. We wanted to determine whether ICD patients have higher dopamine agonist serum concentrations than those without any sign of ICD. Methods: Patients who used either pramipexole or ropinirole depot once daily were screened for ICDs using the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease–Rating Scale. Those who scored above the cut-off for one or more of the four defined ICDs (gambling, compulsive sexual behavior, compulsive shopping, and binge-eating) were compared in a case–control study to patients who scored zero points (no evidence of ICD) on the same items. They were examined clinically and evaluated using relevant scales. Three blood samples were taken on the same day: before daily dose, and then 6 and 12 h later. Results: Forty-six patients were included: 19 ICD-positive and 27 controls. Ropinirole serum concentrations 6 h after daily intake (Cmax) were higher in the case group compared to the control group, as was the daily ropinirole dosage. No differences were observed in serum concentrations, dosage or total drug exposure for pramipexole. Disease duration and length of dopamine agonist treatment was significantly longer among ICD patients for ropinirole, but not for pramipexole. Conclusions: The use of pramipexole may in itself confer high ICD risk, whereas ICDs among ropinirole users depend more on serum concentration and drug exposure. The pharmacokinetic properties of ropinirole make it challenging to predict its effects on patients, which supports the need for therapeutic drug monitoring to reduce risk of ICD

Aggravated stuttering following subthalamic deep brain stimulation in Parkinson's disease - two cases

Stuttering is a speech disorder with disruption of verbal fluency which is occasionally present in patients with Parkinson's disease (PD). Long-term medical management of PD is frequently complicated by fluctuating motor functions and dyskinesias. High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment of motor fluctuations and is the most common surgical procedure in PD. Here we report the re-occurrence and aggravation of stuttering following STN-DBS in two male patients treated for advanced PD. In both patients the speech fluency improved considerably when the neurostimulator was turned off, indicating that stuttering aggravation was related to neurostimulation of the STN itself, its afferent or efferent projections and/or to structures localized in the immediate proximity. This report supports previous studies demonstrating that lesions of the basal ganglia-thalamocortical motor circuit, including the STN, is involved in the development of stuttering. In advanced PD STN-DBS is generally an effective and safe treatment. However, patients with PD and stuttering should be informed about the risk of aggravated symptoms following surgical therapy

Lack of Accredited Clinical Training in Movement Disorders in Europe, Egypt, and Tunisia

Background: Little information is available on the official postgraduate and subspecialty training programs in movement disorders (MD) in Europe and North Africa. Objective: To survey the accessible MD clinical training in these regions. Methods: We designed a survey on clinical training in MD in different medical fields, at postgraduate and specialized levels. We assessed the characteristics of the participants and the facilities for MD care in their respective countries. We examined whether there are structured, or even accredited postgraduate, or subspecialty MD training programs in neurology, neurosurgery, internal medicine, geriatrics, neuroradiology, neuropediatrics, and general practice. Participants also shared their suggestions and needs. Results: The survey was completed in 31/49 countries. Structured postgraduate MD programs in neurology exist in 20 countries; structured neurology subspecialty training exists in 14 countries and is being developed in two additional countries. Certified neurology subspecialty training was reported to exist in 7 countries. Recommended reading lists, printed books, and other materials are the most popular educational tools, while courses, lectures, webinars, and case presentations are the most popular learning formats. Mandatory activities and skills to be certified were not defined in 15/31 countries. Most participants expressed their need for a mandatory postgraduate MD program and for certified MD sub-specialization programs in neurology. Conclusion: Certified postgraduate and subspecialty training exists only in a minority of European countries and was not found in the surveyed Egypt and Tunisia. MD training should be improved in many countries.Peer reviewe

Først i verden med dyp hjernestimulering ved Parkinson

Overlege Carl Wilhelm Sem-Jacobsen presenterte i 1962 resultatene fra elektrisk hjernestimulering gjennom innopererte elektroder utført på Gaustad sykehus hos 10 parkinsonpasienter. Sannsynligvis var Sem-Jacobsen den første i verden som foretok dyp hjernestimulering hos denne pasientgruppen