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  • 251.
    Lundström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Spasticity after first-ever stroke2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The prevalence of spasticity after first-ever stroke is approximately 20%, but there are no data on the prevalence of disabling spasticity.The reported prevalence of pain after stroke varies between 19% and 74%, whether pain is associated with spasticity is not known. Until now, there is no health economic analysis of patients with spasticity after stroke.

    Methods: Two groups of patients were studied.

    Cohort I was a cross-sectional survey. A representative sample of 140 patients was investigated 1 year after their first-ever stroke. Spasticity was defined as ≥ 1 score on the modified Ashworth scale, disabling spasticity was defined as spasticity having such an impact that intervention, e.g. intensive physiotherapy, orthoses or pharmacological treatment, should be offered. Pain was assesed with the Visual Analogue Scale. All direct costs during one year were identified and converted into Purchasing Power Parities US dollar (PPP$).

    Cohort II was a prospective cohort study. Forty-nine patients were examined at day 2–10, at one month, and at six months after their first-ever stroke. Assessment and definitions were similar as for cohort I.

    Results: Spasticity occurs within 1 month and disabling spasticity occur within 6 months.

    After one year, the prevalence of spasticity was 17% and that of  disabling spasticity 4%. Disabling spasticity was more frequent in the upper extremity. There was an independent effect of severe upper extremity paresis (OR 22, CI 3.9–125) and age below 65 years (OR 9.5, CI 1.5–60).

    The prevalence of stroke-related pain was 21% after one year. Stroke-related pain was associated with paresis (OR 3.1, 95% CI 1.2–7.7), sensory disturbance (OR 3.1, 95% CI 1.1–8.9) and depression (OR 4.1, 95% CI 1.4–13), but not with spasticity as an independent variable.

    The majority of the direct costs for one year (78%) were associated with hospitalization, whereas 20% was associated with municipality services. Only 1% of all direct costs were related to primary health care and 1% to medication. The mean (median, inter-quartile range) direct cost for stroke patients with spasticity was PPP$ 84 195 (72 116, 53 707) compared to PPP$ 21 842 (12 385, 17 484) for stroke patients without spasticity (P < 0.001).

    List of papers
    1. Prevalence of disabling spasticity 1 year after first-ever stroke
    Open this publication in new window or tab >>Prevalence of disabling spasticity 1 year after first-ever stroke
    2008 (English)In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 15, no 6, p. 533-9Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: To estimate the prevalence of disabling spasticity (DS) 1 year after first-ever stroke. DESIGN: Cross-sectional survey 1 year after first-ever stroke. METHODS: Patients above 18 years from one county with first-ever stroke were identified by use of the national stroke registry. A representative sample of 163 patients was created and 140 of these were followed up. Assessments of motor function and ability with the modified Ashworth Scale, the modified Rankin Scale (mRS), the Barthel Index (BI) and clinical evaluation were performed in order to identify patients with spasticity-related disability. RESULTS: The observed prevalence of any spasticity was 17% and of DS 4%. Patients with DS scored significantly worse than those with no DS on the mRS (P = 0.009) and the BI (P = 0.005). DS was more frequent in the upper extremity, correlated positively with other indices of motor impairment and inversely with age. There was an independent effect of severe upper extremity paresis (OR 22, CI 3.9-125) and age below 65 years (OR 9.5, CI 1.5-60). CONCLUSIONS: The prevalence of DS after first-ever stroke is low but corresponds to a large number of patients and deserves further attention with regards to prevention and treatment.

    Keywords
    disability, prevalence, spasticity, stroke
    National Category
    Medical and Health Sciences
    Research subject
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-103569 (URN)10.1111/j.1468-1331.2008.02114.x (DOI)000255702200007 ()18355307 (PubMedID)
    Available from: 2009-05-20 Created: 2009-05-20 Last updated: 2018-04-15
    2. Risk factors for stroke-related pain 1 year after first-ever stroke
    Open this publication in new window or tab >>Risk factors for stroke-related pain 1 year after first-ever stroke
    2009 (English)In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 16, no 2, p. 188-193Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE:

    To estimate the prevalence of stroke-related pain and to explore its relation to spasticity.

    DESIGN:

    Cross-sectional survey.

    PATIENTS AND METHODS:

    One hundred and forty patients were examined at 1 year after first-ever stroke. Pain was assessed by a structured interview and categorized as stroke-related or not, pain intensity by use of the visual analogue scale (VAS), spasticity by use of the modified Ashworth scale, stroke severity and the presence of specific neurological impairments by use of the National Institute of Health Stroke Scale (NIHSS), and depression by use of the Montgomery-Asberg Depression Scale.

    RESULTS:

    Pain was reported by 68 patients (49%) with a mean VAS of 42 (95% CI 36-47). In 29 patients (21%), pain was categorized as stroke-related pain. Univariate analyses demonstrated correlations between stroke-related pain and total NIHSS score, paresis, sensory disturbance, depression and spasticity respectively. A multiple regression analysis demonstrated an independent association of stroke-related pain with paresis (OR = 3.1, 95% CI 1.2-7.7), sensory disturbance (OR = 3.1, 95% CI 1.1-8.9) and depression (OR = 4.1, 95% CI 1.4-13).

    CONCLUSIONS:

    The estimated prevalence of stroke-related pain was 21%. Stroke-related pain was associated with sensorimotor impairments and depression, but not with spasticity as an independent variable.

    Keywords
    depression, pain, prevalence, sensorimotor impairment, spasticity, stroke, stroke-related pain
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-103416 (URN)10.1111/j.1468-1331.2008.02378.x (DOI)000262468900016 ()19138338 (PubMedID)
    Available from: 2009-05-19 Created: 2009-05-19 Last updated: 2017-12-13Bibliographically approved
    3. Four-fold increase in direct costs of stroke-survivors with spas-ticity compared to stroke-survivors without spasticity: the first year after the event
    Open this publication in new window or tab >>Four-fold increase in direct costs of stroke-survivors with spas-ticity compared to stroke-survivors without spasticity: the first year after the event
    2010 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 41, no 2, p. 319-324Article in journal (Refereed) Published
    Abstract [en]

    Background and Purpose:

    The prevalence of spasticity after first-ever stroke is approximately 20%, but there are no health economic studies on costs associated with spasticity after stroke. The objective of our study was to estimate direct costs of stroke with spasticity for patients surviving up to one year after the stroke event in comparison to costs of stroke without spastic-ity.

    Methods:

    A representative sample of first-ever stroke patients hospitalized at Uppsala University Hospital was eligible for our cross-sectional survey. All direct costs during one year were identified for each patient, includ-ing costs for hospitalization (acute and rehabilitation), primary health care, medication, and costs for municipality services. The Swedish currency (SEK) was converted into Purchasing Power Parities US dollar (PPP$).

    Results:

    Median age (inter-quartile range) was 73 years (18), and the proportion of women was 48%. The majority of the direct costs (78%) were associated with hospitalization, whereas 20% was associated with municipality services during one year after first-ever stroke. Only 1% of all direct costs were related to primary health care and 1% to medication. The level of costs for stroke patients was correlated with the presence of spasticity, as measured with modified Ashworth Scale (rs = 0.524), and with the degree of disability, as measured with modified Rankin Scale (rs = 0.624). The mean (median, inter-quartile range) direct cost for stroke patients with spasticity was PPP$ 84 195 (72 116, 53 707) compared to PPP$ 21 842 (12 385, 17 484) for stroke patients without spasticity (P < 0.001).

    Conclusions:

    Direct costs for stroke patients with spasticity are four times higher than direct costs for non-spasticity stroke patients during the first year after the event.

    Keywords
    stroke, spasticity, cost of illness, medical economics
    National Category
    Neurology
    Research subject
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-107135 (URN)10.1161/STROKEAHA.109.558619 (DOI)000273951600022 ()
    Available from: 2009-07-20 Created: 2009-07-18 Last updated: 2017-12-13Bibliographically approved
    4. Time-course and determinants of spasticity during the first six months following first-ever stroke
    Open this publication in new window or tab >>Time-course and determinants of spasticity during the first six months following first-ever stroke
    2010 (English)In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 42, no 4, p. 296-301Article in journal (Refereed) Published
    Abstract [en]

    Purpose:

    To explore the occurrence of and risk factors for spasticity until six months after first-ever stroke.

    Methods:

    Forty-nine patients were examined at day 2-10, at one month, and at six months. The Modified Ashworth Scale (MAS) was used to assess resistance to passive movements. A comprehensive clinical examination was performed to identify other positive signs of the upper motor neuron syndrome, in accordance with a broader definition of spasticity, and to evaluate if spasticity was disabling. Neurological impairments were determined by use of the National Institutes of Health Stroke Scale and global disability by use of the modified Rankin Scale.

    Results:

    Spasticity was present in two patients (4%) at day 2-10, in 13 patients (27%) at one month, and in 11 patients (23%) at six months. Severe paresis at day 2-10 was associated with a 10-fold higher risk for spasticity at one month (OR=10, 95% CI 2-48). Disabling spasticity was present  in one patient at one month and in 6 patients (13%) at six months.

    Conclusions:

    Spasticity according to MAS usually occurs within one month and disabling spasticity later in a subgroup. Severe paresis of the arm is a risk factor for spasticity.

    Keywords
    stroke, spasticity, incidence, prevalence, prediction
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-107136 (URN)10.2340/16501977-0509 (DOI)000277827500002 ()20461330 (PubMedID)
    Available from: 2009-07-20 Created: 2009-07-18 Last updated: 2017-12-13Bibliographically approved
  • 252.
    Lundström, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Borg, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Four-fold increase in direct costs of stroke-survivors with spas-ticity compared to stroke-survivors without spasticity: the first year after the event2010In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 41, no 2, p. 319-324Article in journal (Refereed)
    Abstract [en]

    Background and Purpose:

    The prevalence of spasticity after first-ever stroke is approximately 20%, but there are no health economic studies on costs associated with spasticity after stroke. The objective of our study was to estimate direct costs of stroke with spasticity for patients surviving up to one year after the stroke event in comparison to costs of stroke without spastic-ity.

    Methods:

    A representative sample of first-ever stroke patients hospitalized at Uppsala University Hospital was eligible for our cross-sectional survey. All direct costs during one year were identified for each patient, includ-ing costs for hospitalization (acute and rehabilitation), primary health care, medication, and costs for municipality services. The Swedish currency (SEK) was converted into Purchasing Power Parities US dollar (PPP$).

    Results:

    Median age (inter-quartile range) was 73 years (18), and the proportion of women was 48%. The majority of the direct costs (78%) were associated with hospitalization, whereas 20% was associated with municipality services during one year after first-ever stroke. Only 1% of all direct costs were related to primary health care and 1% to medication. The level of costs for stroke patients was correlated with the presence of spasticity, as measured with modified Ashworth Scale (rs = 0.524), and with the degree of disability, as measured with modified Rankin Scale (rs = 0.624). The mean (median, inter-quartile range) direct cost for stroke patients with spasticity was PPP$ 84 195 (72 116, 53 707) compared to PPP$ 21 842 (12 385, 17 484) for stroke patients without spasticity (P < 0.001).

    Conclusions:

    Direct costs for stroke patients with spasticity are four times higher than direct costs for non-spasticity stroke patients during the first year after the event.

  • 253.
    Lundström, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Borg, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Risk factors for stroke-related pain 1 year after first-ever stroke2009In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 16, no 2, p. 188-193Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To estimate the prevalence of stroke-related pain and to explore its relation to spasticity.

    DESIGN:

    Cross-sectional survey.

    PATIENTS AND METHODS:

    One hundred and forty patients were examined at 1 year after first-ever stroke. Pain was assessed by a structured interview and categorized as stroke-related or not, pain intensity by use of the visual analogue scale (VAS), spasticity by use of the modified Ashworth scale, stroke severity and the presence of specific neurological impairments by use of the National Institute of Health Stroke Scale (NIHSS), and depression by use of the Montgomery-Asberg Depression Scale.

    RESULTS:

    Pain was reported by 68 patients (49%) with a mean VAS of 42 (95% CI 36-47). In 29 patients (21%), pain was categorized as stroke-related pain. Univariate analyses demonstrated correlations between stroke-related pain and total NIHSS score, paresis, sensory disturbance, depression and spasticity respectively. A multiple regression analysis demonstrated an independent association of stroke-related pain with paresis (OR = 3.1, 95% CI 1.2-7.7), sensory disturbance (OR = 3.1, 95% CI 1.1-8.9) and depression (OR = 4.1, 95% CI 1.4-13).

    CONCLUSIONS:

    The estimated prevalence of stroke-related pain was 21%. Stroke-related pain was associated with sensorimotor impairments and depression, but not with spasticity as an independent variable.

  • 254.
    Lundström, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Borg, Jörgen
    Time-course and determinants of spasticity during the first six months following first-ever stroke2010In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 42, no 4, p. 296-301Article in journal (Refereed)
    Abstract [en]

    Purpose:

    To explore the occurrence of and risk factors for spasticity until six months after first-ever stroke.

    Methods:

    Forty-nine patients were examined at day 2-10, at one month, and at six months. The Modified Ashworth Scale (MAS) was used to assess resistance to passive movements. A comprehensive clinical examination was performed to identify other positive signs of the upper motor neuron syndrome, in accordance with a broader definition of spasticity, and to evaluate if spasticity was disabling. Neurological impairments were determined by use of the National Institutes of Health Stroke Scale and global disability by use of the modified Rankin Scale.

    Results:

    Spasticity was present in two patients (4%) at day 2-10, in 13 patients (27%) at one month, and in 11 patients (23%) at six months. Severe paresis at day 2-10 was associated with a 10-fold higher risk for spasticity at one month (OR=10, 95% CI 2-48). Disabling spasticity was present  in one patient at one month and in 6 patients (13%) at six months.

    Conclusions:

    Spasticity according to MAS usually occurs within one month and disabling spasticity later in a subgroup. Severe paresis of the arm is a risk factor for spasticity.

  • 255.
    Lundström, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Borg, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Prevalence of disabling spasticity 1 year after first-ever stroke2008In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 15, no 6, p. 533-9Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To estimate the prevalence of disabling spasticity (DS) 1 year after first-ever stroke. DESIGN: Cross-sectional survey 1 year after first-ever stroke. METHODS: Patients above 18 years from one county with first-ever stroke were identified by use of the national stroke registry. A representative sample of 163 patients was created and 140 of these were followed up. Assessments of motor function and ability with the modified Ashworth Scale, the modified Rankin Scale (mRS), the Barthel Index (BI) and clinical evaluation were performed in order to identify patients with spasticity-related disability. RESULTS: The observed prevalence of any spasticity was 17% and of DS 4%. Patients with DS scored significantly worse than those with no DS on the mRS (P = 0.009) and the BI (P = 0.005). DS was more frequent in the upper extremity, correlated positively with other indices of motor impairment and inversely with age. There was an independent effect of severe upper extremity paresis (OR 22, CI 3.9-125) and age below 65 years (OR 9.5, CI 1.5-60). CONCLUSIONS: The prevalence of DS after first-ever stroke is low but corresponds to a large number of patients and deserves further attention with regards to prevention and treatment.

  • 256.
    Lundström, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zini, Andrea
    Wahlgren, Nils
    Ahmed, Niaz
    How common is isolated dysphasia among patients with stroke treated with intravenous thrombolysis, and what is their outcome? Results from the SITS-ISTR.2015In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 5, no 11, article id e009109Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To describe the frequency and outcome of isolated dysphasia among patients treated with intravenous thrombolysis (IVT).

    DESIGN: Patients registered in the SITS International Stroke Thrombolysis Register (SITS-ISTR).

    PARTICIPANTS: Patients with stroke (N=58,293) treated with IVT between December 2002 and December 2012.

    SETTING: A multinational, prospective, observational monitoring register.

    MAIN OUTCOME MEASURES: Isolated dysphasia and modified Rankin Scale (mRS).

    METHODS: We identified patients presenting with isolated dysphasia by reviewing items within the baseline National Institutes of Health Stroke Scale (NIHSS). We performed descriptive statistics for baseline and demographic data, and reported patients' characteristics, radiological data and changes in their NIHSS score within 7 days and mRS score at 3 months. We also reported corresponding data from the general SITS-ISTR cohort.

    RESULTS: We found isolated dysphasia at baseline in 1.14% (663/58,293) of all patients treated with IVT patients. Patients with isolated dysphasia had a longer onset to treatment time, lower proportion of visible infarctions on admission imaging scan and atrial fibrillation, and were less often classified as having large vessels causing strokes, in comparison with the rest of the SITS-ISTR. Symptomatic intracerebral haemorrhage occurred in 2.3% of patients per SITS-MOST definition and fatal outcome in 5.5%. At 7 days, 50% of patients with isolated dysphasia recovered completely and at 3 months, 86.3% patients were functionally independent (mRS score 0-2), 71.7% had an excellent outcome (mRS score 0-1) and 45.5% had an mRS score of 0.

    CONCLUSIONS: A low proportion of patients with isolated dysphasia are treated with IVT. Half of these patients were fully recovered at 7 days.

  • 257. Magalhaes, Sandra
    et al.
    Pugliatti, Maura
    Casetta, Ilaria
    Drulovic, Jelena
    Granieri, Enrico
    Holmøy, Trygve
    Kampman, Margitta T
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lauer, Klaus
    Myhr, Kjell-Morten
    Parpinel, Maria
    Pekmezovic, Tatjana
    Riise, Trond
    Wolfson, David
    Zhu, Bin
    Wolfson, Christina
    The EnvIMS Study: Design and Methodology of an International Case-Control Study of Environmental Risk Factors in Multiple Sclerosis2015In: Neuroepidemiology, ISSN 0251-5350, E-ISSN 1423-0208, Vol. 44, no 3, p. 173-181Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Multiple sclerosis (MS) is a chronic disease of the central nervous system, often resulting in significant neurological disability. The causes of MS are not known; however, the incidence of MS is increasing, thereby suggesting that changes in lifestyle and/or environmental factors may be responsible. On this background, the Environmental Risk Factors in MS Study or EnvIMS study was designed to further explore the etiology of MS. The design and methodology are described, providing details to enable investigators to (i) use our experiences to design their own studies; (ii) take advantage of, and build on the methodological work completed for, the EnvIMS study; (iii) become aware of this data source that is available for use by the research community.

    METHODS: EnvIMS is a multinational case-control study, enrolling 2,800 cases with MS and 5,012 population-based controls in Canada, Italy, Norway, Serbia and Sweden. The study was designed to investigate the most commonly implicated risk factors for MS etiology using a self-report questionnaire.

    RESULTS/CONCLUSIONS: The use of a common methodology to study MS etiology across several countries enhances the comparability of results in different geographic regions and research settings, reduces the resources required for study design and enhances the opportunity for data harmonization.

  • 258.
    Mahamud, Z.
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zelano, J.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Risk of epilepsy after a single seizure in multiple sclerosis2018In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 25, no 6, p. 854-860Article in journal (Refereed)
    Abstract [en]

    Background and purposeThe 2014 International League Against Epilepsy clinical definition of epilepsy allows diagnosis after a single unprovoked seizure if the 10-year recurrence risk exceeds 60%. Multiple sclerosis (MS) carries an increased risk of epilepsy, but the risk after a first seizure is unknown. We aimed to investigate the risk of epilepsy in patients with MS who had suffered a first seizure. MethodsWe cross-referenced data from the Swedish MS register with the national patient register for 15810 patients with MS and 43635 controls and included 289 patients with MS and 222 controls with a first diagnosis of seizure or status epilepticus (SE) without prior epilepsy or presumed symptomatic aetiology. Kaplan-Meier curves were used to estimate the risk of epilepsy. ResultsThe 10-year risk of epilepsy was 51.4% [95% confidence interval (CI), 44.0-58.9] for patients with MS and 41.3% (95% CI, 33.5-49.1) for controls. The risk was 46.1% (95% CI, 35.3-56.9) for patients with relapsing-remitting MS and 60.7% (95% CI, 46.6-74.8) for patients with secondary progressive MS. For patients with MS with SE, the 10-year risk of epilepsy was 85.9% (95% CI, 67.9-100). ConclusionsOur data indicate that patients with relapsing-remitting MS have a similar risk as controls of developing epilepsy after a single seizure. Patients with secondary progressive MS could run a greater risk of subsequent epilepsy, but our data do not indicate a risk that, with certainty, exceeds the threshold specified by the International League Against Epilepsy. Patients with SE have a high risk of epilepsy, possibly motivating diagnosis and treatment.

  • 259.
    Malmgren, K.
    et al.
    Gothenburg Univ, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Rydenhag, B.
    Gothenburg Univ, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci & Rehabil, Gothenburg, Sweden..
    Olsson, I.
    Gothenburg Univ, Sahlgrenska Acad, Inst Clin Sci, Dept Paediat, Gothenburg, Sweden..
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Mattsson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Flink, Roland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Epilepsy Surgery Trends In Sweden 1990-20132015In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 56, p. 145-145Article in journal (Other academic)
  • 260. Marrinan, Sarah L
    et al.
    Otiker, Tal
    Vasist, Lakshmi S
    Gibson, Rachel A
    Sarai, Bhopinder K
    Barton, Matthew E
    Richards, Duncan B
    Hellström, Per M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Dukes, George E
    Burn, David J
    A randomized, double-blind, placebo-controlled trial of camicinal in Parkinson's disease.2018In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 33, no 2, p. 329-332Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Delayed gastric emptying may impair l-dopa absorption, contributing to motor fluctuations. We evaluated the effect of camicinal (GSK962040), a gastroprokinetic, on the absorption of l-dopa and symptoms of PD.

    METHODS: Phase II, double-blind, placebo-controlled trial. Participants were randomized to receive camicinal 50 mg once-daily (n = 38) or placebo (n = 20) for 7 to 9 days.

    RESULTS: l-dopa exposure was similar with coadministration of camicinal compared to placebo. Median time to maximum l-dopa concentration was reduced, indicating more rapid absorption of l-dopa. Camicinal resulted in significant reduction in OFF time (-2.31 hours; 95% confidence interval: -3.71, -0.90), significant increase in ON time (+1.88 hours; 95% confidence interval: 0.28, 3.48) per day, and significant decrease in mean total MDS-UPDRS score (-12.5; 95% confidence interval: -19.67, -5.29). Camicinal treatment was generally well tolerated.

    CONCLUSIONS: PD symptom improvement with camicinal occurred in parallel with more rapid absorption of l-dopa. This study provides evidence of an improvement of the motor response to l-dopa in people with PD treated with camicinal 50 mg once-daily compared with placebo, which will require further evaluation.

  • 261.
    Mattsson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Mammography-related breast pain is associated with migraine2009In: Cephalalgia, ISSN 0333-1024, E-ISSN 1468-2982, Vol. 29, no 6, p. 616-623Article in journal (Refereed)
    Abstract [en]

    There is little information about the perception of experimentally inducedextracephalic pain in migraine. This study investigates the associations between mammography-related pain and migraine. A neurologist clinically assessed 630 women aged 40–74 years attending a population-based breast cancer screening programme. Headache criteria proposed by the International Headache Society were used. Mammography-related pain was measured on a 100-mm visualanalogue scale. High levels of mammography-related pain were associated with migraine. This association was related to mammographic examination during the early follicular phase and menopausal status, but unrelated to differences in age, compression pressure, education, current use of hormonal replacement therapy, anxiety, and recent use of analgesics and antimigraine medication. The results of the present study indicate that migraine and compression-induced breast pain are related.

  • 262.
    Mattsson, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lönnstedt, Ingrid
    Nygren, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Physical fitness, but not muscle strength, is a risk factor for death in amyotrophic lateral sclerosis at an early age2012In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 83, no 4, p. 390-394Article in journal (Refereed)
    Abstract [en]

    Background Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder mainly characterised by motor symptoms. Extensive physical activity has been implicated in the aetiology of ALS. Differences in anthropometrics, physical fitness and isometric strength measured at 18-19 years were assessed to determine if they are associated with subsequent death in ALS. Method Data on body weight and height, physical fitness, resting heart rate and isometric strength measured at conscription were linked with data on death certificates in men born in 1951-1965 in Sweden (n=809 789). Physical fitness was assessed as a maximal test on an electrically braked bicycle ergometer. Muscle strength was measured as the maximal isometric strength in handgrip, elbow flexion and knee extension in standardised positions, using a dynamometer. Analyses were based on 684 459 (84.5%) men because of missing data. A matched case control study within this sample was performed. The population was followed until 31 December 2006, and 85 men died from ALS during this period. Results Weight adjusted physical fitness (W/kg), but not physical fitness per se, was a risk factor for ALS (OR 1.98, 95% CI 1.32 to 2.97), whereas resting pulse rate, muscle strength and other variables were not. Conclusions Physical fitness, but not muscle strength, is a risk factor for death at early age in ALS. This may indicate that a common factor underlies both fitness (W/kg) and risk of ALS.

  • 263.
    Mattsson, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Tomson, T
    Eriksson, Ö
    Brännström, L
    Ringbäck Weitoft, G
    Sociodemographic differences in antiepileptic drug prescriptions to adult epilepsy patients2010In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 74, no 4, p. 295-301Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: According to the Swedish Health Care Act, patients should be provided with the health care they need, regardless of sociodemographic status. We investigated whether in Sweden sociodemographic differences are associated with access to expert health care and antiepileptic drug (AED) prescriptions in epilepsy. METHOD: Patients with epilepsy were identified in the National Patient Register. Persons >or=18 years on continuous AED treatment in 2006 were identified in the recently established Swedish Prescribed Drug Register. Data on sociodemographic variables were obtained from several other national registers. We linked data to examine whether epilepsy patients' access to neurologists and the prescription of individual AEDs are related to sex, age, educational level, area of residence, region of birth, or income. We also assessed whether AEDs are prescribed differently to patients with epilepsy by neurologists as compared to non-neurologists. RESULTS: We identified 26,124 epilepsy patients in the register who were on continuous AED treatment (effective sample). Being women, young, highly educated, having high incomes, and residing in a larger city meant being more often treated by a neurologist than by other specialists. The prescriptions of AEDs differed according to gender, age, education, place of residence, and income. Lamotrigine and levetiracetam were prescribed to a larger extent by a neurologist rather than by other specialists. CONCLUSIONS: This nationwide cross-sectional study of epilepsy patients indicates that sociodemographic characteristics are important for access to neurologists and prescriptions of individual antiepileptic drugs. Prospective studies using patient-related outcomes are needed to analyze the consequences of these differences.

  • 264.
    Mattsson, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Tomson, Torbjörn
    Edebol Eeg-Olofsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Brännström, Lars
    Ringbäck Weitoft, Gunilla
    Association between sociodemographic status and antiepileptic drug prescriptions in children with epilepsy2012In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 53, no 12, p. 2149-2155Article in journal (Refereed)
    Abstract [en]

    Purpose: 

    We investigated whether in Sweden sociodemographic differences are associated with access to expert health care and antiepileptic drug (AED) prescriptions in children with epilepsy.

    Methods:

    Data on epilepsy, prescription of AEDs, and sociodemographic variables were obtained from several national administrative registers. We linked individual data to examine whether access by pediatric epilepsy patients to neuropediatricians and the prescription of individual AEDs differed according to gender, age, parental education, place of residence, parental region of birth, and household income. We also assessed whether AEDs are prescribed differently to patients with epilepsy by neuropediatricians as compared to other physicians.

    Key Findings: 

    Of 1,788,382 children aged 1-17 years in 2006, living in the country by the end of 2006, 9,935 had a diagnosis of epilepsy (0.56%). Patients with epilepsy on AED treatment (n = 3,631) comprised 0.24% of the total Swedish population aged 1-17 years. Out of 3631 patients with epilepsy on AED treatment, 2301 (63.4%) received prescriptions from a neuropediatrician. Children with epilepsy aged 1-5 years old-as opposed to older children and adolescents-and children with epilepsy residing in large cities-as opposed to children living in smaller cities and rural areas-were more likely to be treated by a neuropediatrician. Children living in large cities received oxcarbazepine to a greater extent than children living in rural areas. Levetiracetam was prescribed more extensively to children whose parents had higher incomes. Of the five most frequently used AEDs, three (lamotrigine, oxcarbazepine, and levetiracetam) were prescribed to a larger extent by a neuropediatrician rather than by other specialists, and one AED (carbamazepine) was prescribed to a lesser extent.

    Significance: 

    The results of this nationwide cross-sectional study of children with epilepsy are important because they show that universal coverage for medical care does not eliminate inequalities of access to health care services among children and adolescents. No data are available that can guide us as to whether the density of child neurologists is of importance to access to expert health care, but this seems likely. Prescription patterns of AEDs differ between child neurologists and other specialists.

  • 265. McNulty, Paul
    et al.
    Pilcher, Richard
    Ramesh, Raviram
    Necuiniate, Renata
    Hughes, Alis
    Farewell, Daniel
    Holmans, Peter
    Jones, Lesley
    Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study.2018In: Journal of Huntington's disease, ISSN 1879-6400, Vol. 7, no 3, p. 209-222Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: People with Huntington's disease (HD) have been observed to have lower rates of cancers.

    OBJECTIVE: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis.

    METHODS: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects.

    RESULTS: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001).

    CONCLUSIONS: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis.

  • 266. Mead, Gillian E
    et al.
    Dennis, Martin
    Lundström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Murray, Veronica
    Hackett, Maree
    Hankey, Graeme J
    Letter by Mead et al Regarding Article, "Selective Serotonin Reuptake Inhibitors for Stroke: More Trials are Needed"2013In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 44, no 4, p. E40-E41Article in journal (Other academic)
  • 267. Mead, Gillian
    et al.
    Hackett, Maree L
    Lundström, E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Karolinska Univ Hosp, Dept Neurol, Solna, Sweden.
    Murray, Veronica
    Hankey, Graeme J
    Dennis, Martin
    The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: a study protocol for three multicentre randomised controlled trials.2015In: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 16, article id 369Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Several small trials have suggested that fluoxetine improves neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials that aim to determine whether routine administration of fluoxetine (20 mg daily) for 6 months after acute stroke improves patients' functional outcome.

    METHODS/DESIGN: The three trial investigator teams have collaboratively developed a core protocol. Minor variations have been tailored to the national setting in the UK (FOCUS), Australia and New Zealand (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned individual patient data meta-analysis of all three trials will subsequently provide the most precise estimate of the overall effect of fluoxetine after stroke and establish whether any effects differ between trials and subgroups of patients. The trials include patients ≥18 years old with a clinical diagnosis of stroke, persisting focal neurological deficits at randomisation between 2 and 15 days after stroke onset. Patients are randomised centrally via web-based randomisation systems using a common minimisation algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for 6 months. Our primary outcome measure is the modified Rankin scale (mRS) at 6 months. Secondary outcomes include the Stroke Impact Scale, EuroQol (EQ5D-5 L), the vitality subscale of the Short-Form 36, diagnosis of depression, adherence to medication, adverse events and resource use. Outcomes are collected at 6 and 12 months. The methods of collecting these data are tailored to the national setting. If FOCUS, AFFINITY and EFFECTS combined enrol 6000 participants as planned, they would have 90 % power (alpha 5 %) to detect a common odds ratio of 1.16, equivalent to a 3.7 % absolute difference in percentage with mRS 0-2 (44.0 % to 47.7 %). This is based on an ordinal analysis of mRS adjusted for baseline variables included in the minimisation algorithm.

    DISCUSSION: If fluoxetine is safe and effective in promoting functional recovery, it could be rapidly, widely and affordably implemented in routine clinical practice and reduce the burden of disability due to stroke.

    TRIAL REGISTRATION:

    FOCUS: ISRCTN83290762 (23/05/2012), AFFINITY: ACTRN12611000774921 (22/07/2011).

    EFFECTS: ISRCTN13020412 (19/12/2014).

  • 268.
    Melberg, Atle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kretz, Christine
    Kalimo, Hannu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Wallgren-Pettersson, Carina
    Toussaint, Anne
    Böhm, Johann
    Stålberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Laporte, Jocelyn
    Adult course in dynamin 2 dominant centronuclear myopathy with neonatal onset2010In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 20, no 1, p. 53-56Article in journal (Refereed)
    Abstract [en]

    We report a family with autosomal dominant centronuclear (myotubular) myopathy caused by a novel mutation, p.A618D, in dynamin 2 (DNM2). The 64-year-old mother and 26-year-old daughter had neonatal onset with hypotonia and weak suckling, followed by improvement, then slowly progressive muscle weakness and respiratory restriction. Muscle biopsy showed radial sarcoplasmic strands around the frequent central nuclei. Electrophysiology revealed predominantly myopathic patterns without peripheral nerve involvement. Centronuclear myopathy with neonatal onset caused by a DNM2 mutation in the C-terminal part of the pleckstrin homology domain may have a favorable prognosis and follow a course similar to adult-onset centronuclear myopathy. We advise respiratory follow-up in these patients.

  • 269.
    Melberg, Atle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sundblom, Jimmy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    White matter disorders with autosomal dominant heredity2011In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 124, no 1, p. 71-72Article in journal (Refereed)
  • 270. Memedi, Mevludin
    et al.
    Khan, Taha
    Grenholm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Westin, Jerker
    Automatic and Objective Assessment of Alternating Tapping Performance in Parkinson's Disease2013In: Sensors, ISSN 1424-8220, E-ISSN 1424-8220, Vol. 13, no 12, p. 16965-16984Article in journal (Refereed)
    Abstract [en]

    This paper presents the development and evaluation of a method for enabling quantitative and automatic scoring of alternating tapping performance of patients with Parkinson’s disease (PD). Ten healthy elderly subjects and 95 patients in different clinical stages of PD have utilized a touch-pad handheld computer to perform alternate tapping tests in their home environments. First, a neurologist used a web-based system to visually assess impairments in four tapping dimensions (‘speed’, ‘accuracy’, ‘fatigue’ and ‘arrhythmia’) and a global tapping severity (GTS). Second, tapping signals were processed with time series analysis and statistical methods to derive 24 quantitative parameters. Third, principal component analysis was used to reduce the dimensions of these parameters and to obtain scores for the four dimensions. Finally, a logistic regression classifier was trained using a 10-fold stratified cross-validation to map the reduced parameters to the corresponding visually assessed GTS scores. Results showed that the computed scores correlated well to visually assessed scores and were significantly different across Unified Parkinson’s Disease Rating Scale scores of upper limb motor performance. In addition, they had good internal consistency, had good ability to discriminate between healthy elderly and patients in different disease stages, had good sensitivity to treatment interventions and could reflect the natural disease progression over time. In conclusion, the automatic method can be useful to objectively assess the tapping performance of PD patients and can be included in telemedicine tools for remote monitoring of tapping.

  • 271.
    Memedi, Mevludin
    et al.
    Dalarna Univ, Sch Technol & Business Studies, Comp Engn, S-79188 Falun, Sweden..
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Johansson, Anders
    Karolinska Inst, Dept Clin Neurosci, Neurol, S-14186 Huddinge, Sweden..
    Palhagen, Sven
    Karolinska Univ Hosp, Dept Neurol, S-17177 Stockholm, Sweden..
    Willows, Thomas
    Karolinska Univ Hosp, Dept Neurol, S-17177 Stockholm, Sweden..
    Widner, Hakan
    Skane Univ Hosp, Dept Neurol, S-22185 Lund, Sweden..
    Linder, Jan
    Umea Univ, Dept Pharmacol & Clin Neurosci, S-90187 Umea, Sweden..
    Westin, Jerker
    Dalarna Univ, Sch Technol & Business Studies, Comp Engn, S-79188 Falun, Sweden..
    Validity and Responsiveness of At-Home Touch Screen Assessments in Advanced Parkinson's Disease2015In: IEEE journal of biomedical and health informatics, ISSN 2168-2194, E-ISSN 2168-2208, Vol. 19, no 6, p. 1829-1834Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson's disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on unified PD rating scale (UPDRS) and 39-item PD questionnaire (PDQ-39) scales. In LCIG-naive patients, the mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non naive patients, there were no significant changes in the mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS, respectively. The trends of the test scores were similar to the trends of clinical rating scores but the dropout rate was high. Correlations betweenOTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS.

  • 272. Memedi, Mevludin
    et al.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Westin, Jerker
    Combined fine-motor tests and self-assessments for remote detection of motor fluctuations2013In: Recent Patents on Biomedical Engineering, ISSN 1874-7647, Vol. 6, no 2, p. 127-135Article in journal (Refereed)
    Abstract [en]

    A major problem with the clinical management of fluctuating movement disorders, e.g. Parkinson’s disease (PD), is the large variability in manifestation of symptoms among patients. In this condition, frequent measurements which account for both patient-reported and objective assessments are needed in order to capture symptom fluctuations, with the purpose to optimize therapy. The main focus of this paper is to present a mobile-based system for enabling remote monitoring of PD patients from their home environment conditions. The system consists of a patient diary section for collecting patient-based self-assessments, a motor test section for collecting fine motor movements through upper limb motor tests, and a scheduler for restricting operation to a multitude of predetermined limited time intervals. The system processes and compiles time series data into different summary scores representing symptom severity. In addition, the paper presents a review of recent inventions which were filed after year 2000 in the field of telemedicine applications. The review includes a summary of systems and methods which enable remote symptom assessments of patients, not necessarily suffering from movement disorders, through repeated measurements and which take into account their subjective and/or objective health indicators. The findings conclude that there are a small number of inventions which collect subjective and objective health measures in telemedicine settings. Consequently, there is a lack of mechanisms that combine these two types of information into scores to provide a more in-depth assessment of the patient’s general health, their motor and non-motor symptom fluctuations and treatment effects. The paper also provides a discussion concerning different approaches for analyzing and combining subjective and objective measures, and handling data from longitudinal studies.

  • 273. Memedi, Mevludin
    et al.
    Sadikov, Aleksander
    Groznik, Vida
    Zabkar, Jure
    Mozina, Martin
    Bergquist, Filip
    Johansson, Anders
    Haubenberger, Dietrich
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Automatic Spiral Analysis for Objective Assessment of Motor Symptoms in Parkinson's Disease2015In: Sensors, ISSN 1424-8220, E-ISSN 1424-8220, Vol. 15, no 9, p. 23727-23744Article in journal (Refereed)
    Abstract [en]

    A challenge for the clinical management of advanced Parkinson’s disease (PD) patients is the emergence of fluctuations in motor performance, which represents a significant source of disability during activities of daily living of the patients. There is a lack of objective measurement of treatment effects for in-clinic and at-home use that can provide an overview of the treatment response. The objective of this paper was to develop a method for objective quantification of advanced PD motor symptoms related to off episodes and peak dose dyskinesia, using spiral data gathered by a touch screen telemetry device. More specifically, the aim was to objectively characterize motor symptoms (bradykinesia and dyskinesia), to help in automating the process of visual interpretation of movement anomalies in spirals as rated by movement disorder specialists. Digitized upper limb movement data of 65 advanced PD patients and 10 healthy (HE) subjects were recorded as they performed spiral drawing tasks on a touch screen device in their home environment settings. Several spatiotemporal features were extracted from the time series and used as inputs to machine learning methods. The methods were validated against ratings on animated spirals scored by four movement disorder specialists who visually assessed a set of kinematic features and the motor symptom. The ability of the method to discriminate between PD patients and HE subjects and the test-retest reliability of the computed scores were also evaluated. Computed scores correlated well with mean visual ratings of individual kinematic features. The best performing classifier (Multilayer Perceptron) classified the motor symptom (bradykinesia or dyskinesia) with an accuracy of 84% and area under the receiver operating characteristics curve of 0.86 in relation to visual classifications of the raters. In addition, the method provided high discriminating power when distinguishing between PD patients and HE subjects as well as had good test-retest reliability. This study demonstrated the potential of using digital spiral analysis for objective quantification of PD-specific and/or treatment-induced motor symptoms.

  • 274. Memedi, Mevludin
    et al.
    Westin, Jerker
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Spiral drawing during self-rated dyskinesia is more impaired than during self-rated off.2013In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 19, no 5, p. 553-556Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The purpose of this study was to examine repeated measures of fine motor function in relation to self-assessed motor conditions in Parkinson's disease (PD).

    METHODS: One-hundred PD patients, 65 with advanced PD and 35 patients with different disease stages have utilized a test battery in a telemedicine setting. On each test occasion, they initially self-assessed their motor condition (from 'very off' to 'very dyskinetic') and then performed a set of fine motor tests (tapping and spiral drawings).

    RESULTS: The motor tests scores were found to be the best during self-rated On. Self-rated dyskinesias caused more impaired spiral drawing performance (mean = 9.8% worse, P < 0.001) but at the same time tapping speed was faster (mean = 5.0% increase, P < 0.001), compared to scores in self-rated Off.

    CONCLUSIONS: The fine motor tests of the test battery capture different symptoms; the spiral impairment primarily relates to dyskinesias whereas the tapping speed captures the Off symptoms.

  • 275.
    Memedi, Mevludin
    et al.
    Dalarna University.
    Westin, Jerker
    Dalarna University.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Dougherty, Mark
    Dalarna University.
    Groth, Torgny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biomedical Informatics and Engineering.
    A web application for follow-up of results from a mobile device test battery for Parkinson’s disease patients2011In: Computer Methods and Programs in Biomedicine, ISSN 0169-2607, E-ISSN 1872-7565, Vol. 104, no 2, p. 219-226Article in journal (Refereed)
    Abstract [en]

    A test battery consisting of self-assessments and motor tests for patients with Parkinson’s disease (PD) was constructed and implemented on a hand computer with touch screen in a telemedicine setting. In this work, a Web-based system was developed to deliver decision support information to treating clinical staff for assessing PD symptoms in their patients. Test results from the hand unit are transferred to a central server and processed into scores for different symptom dimensions and an “overall test score” reflecting the overall condition of the patient during a test period. The IBM Computer System Usability Questionnaire was administered to assess the users’ satisfaction with the system. Results showed that a majority of users who completed the evaluation were quite satisfied with the usability although a sizeable minority were not.  Response times were tested by simulating up to 100 users accessing the web application at the same time. The average page completion times were in the range of 0.5 seconds indicating fast response. The system was able to summarize the test-battery data and present them in a useful manner. Its main contribution is a novel way to easily access symptom information from the home environment of patients.

  • 276. Morales Drissi, Natasha
    et al.
    Romu, Thobias
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine (IKE), Linköping University, Linköping, Sweden.
    Szakács, Attilla
    Hallböök, Tove
    Darin, Niklas
    Borga, Magnus
    Leinhard, Olof Dahlqvist
    Engström, Maria
    Unexpected Fat Distribution in Adolescents With Narcolepsy.2018In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 9, article id 728Article in journal (Refereed)
    Abstract [en]

    Narcolepsy type 1 is a chronic sleep disorder with significantly higher BMI reported in more than 50% of adolescent patients, putting them at a higher risk for metabolic syndrome in adulthood. Although well-documented, the body fat distribution and mechanisms behind weight gain in narcolepsy are still not fully understood but may be related to the loss of orexin associated with the disease. Orexin has been linked to the regulation of brown adipose tissue (BAT), a metabolically active fat involved in energy homeostasis. Previous studies have used BMI and waist circumference to characterize adipose tissue increases in narcolepsy but none have investigated its specific distribution. Here, we examine adipose tissue distribution in 19 adolescent patients with narcolepsy type 1 and compare them to 17 of their healthy peers using full body magnetic resonance imaging (MRI). In line with previous findings we saw that the narcolepsy patients had more overall fat than the healthy controls, but contrary to our expectations there were no group differences in supraclavicular BAT, suggesting that orexin may have no effect at all on BAT, at least under thermoneutral conditions. Also, in line with previous reports, we observed that patients had more total abdominal adipose tissue (TAAT), however, we found that they had a lower ratio between visceral adipose tissue (VAT) and TAAT indicating a relative increase of subcutaneous abdominal adipose tissue (ASAT). This relationship between VAT and ASAT has been associated with a lower risk for metabolic disease. We conclude that while weight gain in adolescents with narcolepsy matches that of central obesity, the lower VAT ratio may suggest a lower risk of developing metabolic disease.

  • 277. Munro Neville, A
    et al.
    Parsons, Richard W
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Treatment of advanced Parkinson's disease with levodopa/carbidopa intestinal gel is associated with improvements in Hoehn and Yahr stage2012In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 18, no 5, p. 686-687Article in journal (Refereed)
  • 278.
    Niemelä, Valter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Blennow, Kaj
    Zetterberg, Henrik
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Sundblom, Jimmy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Cerebrospinal fluid sCD27 levels indicate active T cell-mediated inflammation in premanifest Huntington's disease2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 2, article id e0193492Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Huntington's disease (HD) is a neurodegenerative disorder, but evidence also suggests neuroinflammation in the pathogenesis. The immune mechanisms involved and the timing of their activation need further clarification.

    METHODS: A clinically well-characterized HD cohort and gene negative controls were enrolled. YKL-40 reflecting innate immunity and sCD27, a marker of adaptive immunity, were measured across disease stages. Comparisons were made with markers of neurodegeneration: neurofilament light (NFL), total-tau (T-tau), and phospho-tau (P-tau).

    RESULTS: 52 cross-sectional cerebrospinal fluid samples and 23 follow-up samples were analyzed. sCD27 was elevated in manifest HD and premanifest gene expansion carriers, whereas controls mostly had undetectable levels. YKL-40 showed a trend toward increase in manifest HD. sCD27 correlated with YKL-40 which in turn was closely associated to all included markers of neurodegeneration. YKL-40, NFL, and both forms of tau could all independently predict HD symptoms, but only NFL levels differed between groups after age-adjustment.

    CONCLUSION: Increased sCD27 in premanifest HD is a sign of T cell-mediated neuroinflammation. This finding is novel since other reports almost exclusively have found early involvement of innate immunity. Validation of sCD27 in a larger HD cohort is needed. The role of adaptive immunity in HD needs further clarification, as it may hasten disease progression.

  • 279.
    Niemelä, Valter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Landtblom, Anne-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Blennow, Kaj
    Univ Gothenburg, Clin Neurochem Lab, Inst Neurosci & Physiol, Sahlgrenska Acad, Molndal Campus, Molndal, Sweden.
    Sundblom, Jimmy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Tau or neurofilament light - Which is the more suitable biomarker for Huntington’s disease?2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 2, article id e0172762Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Previous studies have suggested cerebrospinal fluid (CSF) levels of neurofilament light (NFL) and total tau are elevated in Huntington's disease (HD) and may be used as markers of disease stage. Biomarkers are needed due to the slow disease progression and the limitations of clinical assessment. This study aims to validate the role of NFL and tau as biomarkers in HD.

    METHODS: CSF was obtained from a cohort of HD patients and premanifest HD-mutation carriers. Unified Huntington's Disease Rating Scale (UHDRS) testing was performed on all subjects at the time of sampling. NFL and tau concentrations were determined by ELISA. Spearman correlations were calculated with R version 3.2.3.

    RESULTS: 11 premanifest HD and 12 manifest HD subjects were enrolled. NFL and tau levels were correlated. NFL showed strong correlations with all items included in the clinical assessment (for example the total functional capacity (TFC) (r = - 0.70 p < 0.01) and total motor score (TMS) (r = 0.83p < 0.01). Tau showed slightly weaker correlations (eg. TMS (r = 0.67 p < 0.01); TFC (r = - 0.59 p < 0.01)). NFL was significantly correlated with 5-year probability of disease onset, whereas tau was not.

    CONCLUSION: This study strengthens the case for NFL as a useful biomarker of disease stage. NFL was strongly correlated to all evaluated items in the UHDRS assessment. Tau also has a potential for use as a biomarker but correlations to clinical tests are weaker in this study. We suggest that NFL and possibly tau be used in clinical drug trials as biomarkers of disease progression that are potentially influenced by future disease-modifying therapies.

  • 280.
    Nilsson, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Fasth, Karl Johan
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tedroff, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Hartvig, Per
    Långström, Bengt
    Absorption of L-DOPA from the proximal small intestine studied in the rhesus monkey by positron emission tomography1999In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 7, no 3, p. 185-189Article in journal (Refereed)
    Abstract [en]

    Positron emission tomography (PET) seems to be a valuable method for the understanding of intestinal absorption mechanisms, for simultaneous quantitation of absorption rate and distribution kinetics to the tissues of interest after oral drug delivery. PET was evaluated in three Rhesus monkeys for quantitation of the absorption rate from the gastrointestinal tract and the distribution kinetics into different organs. To obtain optimal standardized conditions for the measurement of absorption the drug was administered via a naso-duodenal catheter directly to the absorption site in the proximal small intestine. l-DOPA was used as study drug given in a suspension together with carbidopa and the radiomarker l-[beta-11C]DOPA. The l-DOPA suspension was given into the duodenum without and after administration of a suspension of six l-amino acids (120 mM) in order to investigate any interaction on the intestinal absorption and distribution of l-DOPA into the liver and brain tissue. Intestinal absorption was in general minor during the first study period and higher together with administered l-amino acids. The somewhat contradictory result with increased absorption when amino acids were present in the intestinal lumen, may be a consequence of increased intestinal motility initiated by the nutrient load.

  • 281. Nilsson, Dag
    et al.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Aquilonius, Sten-Magnus
    Duodenal levodopa infusion in Parkinson’s disease – long-term experience2001In: Acta Neurol Scand, ISSN 1600-0404, Vol. 104, no 6, p. 343-348Article in journal (Refereed)
  • 282. Nordin, N.
    et al.
    Hillert, J.
    Piehl, F.
    Svenningsson, A.
    Lycke, J.
    Fagius, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Walentin, F.
    Martin, C.
    Nilsson, P.
    Feltelius, N.
    Dahle, C.
    Olsson, T.
    The immunomodulation and multiple sclerosis epidemiology (IMSE II) study: a Swedish nationwide pharmaco-epidemiological and genetic study focussed on long-term safety and efficacy of fingolimod (Gilenya (R))2013In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 11, p. 445-446Article in journal (Other academic)
  • 283.
    Novella, Jon Ander
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Emami Khoonsari, Payam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Herman, Stephanie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Whitenack, Daniel
    Capuccini, Marco
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Scientific Computing. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computational Science.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kultima, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Spjuth, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Container-based bioinformatics with Pachyderm2019In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 35, p. 839-846Article in journal (Refereed)
  • 284.
    Nygren, Ingela
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Fagius, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    High resting level and weak response of baroreflex-governed sympathetic outflow in amyotrophic lateral sclerosis2011In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 43, no 3, p. 432-440Article in journal (Refereed)
    Abstract [en]

    Both altered sympathetic function and insulin resistance have been observed in amyotrophic lateral sclerosis (ALS). Insulin is a sympathetic stimulator. We recorded muscle sympathetic nerve activity (MSNA) by microneurography in 9 patients with ALS and 9 healthy controls during rest. We also initiated a number of sympathoexcitatory maneuvers, including intake of 100 g of glucose. Patients showed reduced glucose tolerance and a higher heart rate and higher level of MSNA at rest than controls (61.0 ± 15.2 vs. 41.2 ± 5.8 bursts/min, P = 0.006); baroreflex inhibitory influence was present. In contrast, MSNA in ALS patients responded more weakly to maneuvers. This inverse relationship is interpreted as a "ceiling effect," as ALS patients use nearly maximal MSNA capacity already at rest and do not have sympathetic failure. The increased level of MSNA may be a primary feature of ALS, but insulin stimulation may also contribute. Our findings are assessed in relation to previous, sometimes seemingly contradictory observations.

  • 285.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Duodopa(®) treatment for advanced Parkinson's disease: A review of efficacy and safety2012In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 18, no 8, p. 916-929Article in journal (Refereed)
    Abstract [en]

    Enterally administered levodopa/carbidopa gel (Duodopa(®)) is used for the treatment of advanced Parkinson's disease (PD) in patients with motor fluctuations and dyskinesias. This review summarizes the current efficacy and safety data on this drug. Clinically important differences (CID) have been used to assess whether statistical improvements in symptoms translate into meaningful improvements for the patients. A PubMed search in February 2012 found 23 papers with efficacy data and 33 with safety data. Of 11 studies reporting Unified Parkinson's Disease Rating Scale (UPDRS) III scores, 10 found improvements that met the CID of 10.8 points. Of 7 studies reporting UPDRS IV scores, 5 found improvements meeting the CID of 2.3 points. Quality of life (QoL) was assessed in 6 studies using the 8- or 39-question version of the Parkinson's disease Questionnaire, and all reported improvements meeting the CID (10 points). Due to the nature of the data, it is not possible to give exact numbers for the frequency of adverse events. However, the findings seem to be in line with a previous report stating the majority of adverse events were related to the infusion system or surgical procedure rather than the drug. In conclusion, the large majority of studies have reported that Duodopa(®) is clinically effective in relieving the symptoms of advanced PD and improving QoL in comparison with conventional therapy. High-quality randomized trials with larger patient numbers will yield greater insights into the efficacy and safety of this treatment.

  • 286.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Pharmacotherapy for Parkinson's Disease - Observations and Innovations2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Pharmacotherapy for Parkinson’s disease (PD) is based on levodopa, the most effective dopaminergic drug. The development of motor complications constitutes the major challenge for new or refined therapies.

    To evaluate the impact of levodopa pharmacokinetics on motor function, an observational study in the patients’ home environment was carried out. A high variability in plasma levodopa levels was found in all patients, irrespective of treatment regimen. The impact of levodopa pharmacokinetics was further studied in a crossover trial comparing sustained-release tablets and continuous daytime intestinal infusion. Infusion produced significantly decreased variability in plasma levels of levodopa, resulting in significantly normalised motor function. A permanent system for long-term levodopa infusion has been developed and 28 patients have been followed for 87 patient-years. Motor response was generally preserved during the long-term observation period, implying that there is no development of tolerance to infusion therapy. Levodopa tablets are normally used in multiples of 50 or 100 mg, thus a rough estimate of individual dosage. A new concept for individualising levodopa/carbidopa doses with microtablets of 5/1.25 mg is under development. An electronic drug-dispensing device for administering the microtablets was tested on patients with PD. All were able to handle the dispenser and most were interested in future use of the concept. Self-assessment of symptoms is accurate in PD, but traditional paper diaries are associated with low compliance. A wireless electronic diary was compared with a corresponding paper diary. The time-stamped and thus completely reliable patient compliance was 88% with the electronic diary.

    To conclude, pharmacokinetics of levodopa is the major determinant for motor fluctuations in PD. Every effort to individualise dosage and to smooth out the fluctuations in levodopa concentrations should be made, e.g. by means of microtablets or enteral infusion. Electronic patient diaries for real-time data capture are suitable for PD studies.

    List of papers
    1. Levodopa pharmacokinetics and motor performance during activities of daily living in parkinsonian patients on individual drug combinations
    Open this publication in new window or tab >>Levodopa pharmacokinetics and motor performance during activities of daily living in parkinsonian patients on individual drug combinations
    2002 In: Clin Neuropharmacol, ISSN 0362-5664, Vol. 25, no 2, p. 89-96Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-90199 (URN)
    Available from: 2003-04-10 Created: 2003-04-10 Last updated: 2014-01-29Bibliographically approved
    2. Optimizing levodopa pharmacokinetics: intestinal infusion versus oral sustained-release tablets
    Open this publication in new window or tab >>Optimizing levodopa pharmacokinetics: intestinal infusion versus oral sustained-release tablets
    Show others...
    2003 (English)In: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 26, no 3, p. 156-163Article in journal (Refereed) Published
    Abstract [en]

    Continuous duodenal infusion of carbidopa/levodopa has been shown to control motor fluctuations in advanced Parkinson's disease (PD). The authors compared the pharmacokinetics of levodopa and 3-O-methyldopa in patients with advanced PD after administration of an oral sustained-release levodopa preparation and after continuous intestinal levodopa infusion with a new formulation as a gel suspension. A randomized crossover trial was carried out in 12 patients. Carbidopa/levodopa was administered as an oral sustained-release tablet and by nasoduodenal continuous infusion for 3-week periods for each treatment. Plasma levodopa concentrations and motor performance were evaluated every 30 minutes during 3 test days of each treatment period. The average intraindividual coefficient of variation for the plasma levodopa concentrations after oral therapy was 34% and was significantly lower (14%, p < 0.01) during continuous infusion. Hourly video evaluations showed a significant increase in ON time during infusion and a significant decrease in OFF time and dyskinesia. Continuous intraduodenal delivery of a new carbidopa/levodopa formulation offers a means for markedly improved control of motor fluctuations in late stages of PD.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-90200 (URN)12782919 (PubMedID)
    Available from: 2003-04-10 Created: 2003-04-10 Last updated: 2017-12-14Bibliographically approved
    3. Duodenal levodopa infusion in Parkinson’s disease – long-term experience
    Open this publication in new window or tab >>Duodenal levodopa infusion in Parkinson’s disease – long-term experience
    2001 In: Acta Neurol Scand, ISSN 1600-0404, Vol. 104, no 6, p. 343-348Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-90201 (URN)
    Available from: 2003-04-10 Created: 2003-04-10 Last updated: 2014-01-29Bibliographically approved
    4. An automatic dose dispenser for microtablets: A new concept for individual dosage of drugs in tablet form
    Open this publication in new window or tab >>An automatic dose dispenser for microtablets: A new concept for individual dosage of drugs in tablet form
    2003 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, Vol. 261, no 1-2, p. 137-146Article in journal (Refereed) Published
    Abstract [en]

    A new concept for individualising the dosage of drugs in solid form is presented. The principle is based on the use of standardised units (microtablets), each containing a subtherapeutic amount of the active ingredient. The required dose is fine-tuned by counting out a specific number of these units. The microtablets are counted electronically from the attached cassette by the automatic dispensing device. The individual dose is set and the dispenser counts and delivers the correct number of microtablets. The usefulness of the automatic dispenser concept and acceptability of the apparatus were evaluated in patients with Parkinson’s disease (PD). After initial instruction on use of the dispenser, 20 patients operated it themselves. All patients were generally satisfied with their management of the automatic dispenser and most would be happy to use the device again. Further technical development is required before use in clinical practice, but the current prototype may be acceptable for some patients. It is concluded that the final version of the automatic dose dispenser concept will offer potential for improvement of drug administration for patients with PD or other diseases requiring individual dosage.

    Keywords
    Individual dosage, Drug dispensing device, Parkinson’s disease, Levodopa, Microtablets
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-90434 (URN)10.1016/S0378-5173(03)00294-1 (DOI)000184607500013 ()
    Available from: 2003-04-23 Created: 2003-04-23 Last updated: 2014-01-29Bibliographically approved
    5. Wireless real-time electronic data capture for self-assessment of motor function and quality of life in Parkinson’s disease
    Open this publication in new window or tab >>Wireless real-time electronic data capture for self-assessment of motor function and quality of life in Parkinson’s disease
    In: Article in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-90203 (URN)
    Available from: 2003-04-10 Created: 2003-04-10 Last updated: 2014-01-29Bibliographically approved
  • 287.
    Nyholm, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Update on levodopa/carbidopa intestinal gel infusion2012In: European Neurological Review, ISSN 1758-3837, Vol. 7, no SUPPL.1, p. 13-16Article in journal (Refereed)
    Abstract [en]

    Recent data on levodopa/carbidopa intestinal gel (LCIG) infusion are discussed in this article. LCIG infusion provides improvements in 'off' time and dyskinesia via continuous dopaminergic stimulation (CDS). In the long-term, LCIG infusion appears to maintain efficacy without the need to increase dosages. The growing number of publications on LCIG infusion shows the increasing experience and interest in this therapy. The new data demonstrate the effects of using LCIG infusion in combination with catechol-O-methyl transferase inhibitors, and technical improvements to the pump system (e.g., to the tubing). Despite the invasive nature of LCIG infusion, nearly all patients would recommend this treatment. Furthermore, a number of larger-scale studies on this particular CDS therapy are in progress.

  • 288.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Rörelsestörningar2012In: Neurologi / [ed] Fagius J, Nyholm D, Liber: Liber , 2012Chapter in book (Other (popular science, discussion, etc.))
  • 289.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Stalevo reduction in dyskinesia evaluation in Parkinson's disease results were expected from a pharmacokinetic viewpoint2011In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 69, no 2, p. 424-424Article in journal (Refereed)
  • 290.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Gomes-Trolin, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Knutson, Tina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Nyström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Optimizing levodopa pharmacokinetics: intestinal infusion versus oral sustained-release tablets2003In: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 26, no 3, p. 156-163Article in journal (Refereed)
    Abstract [en]

    Continuous duodenal infusion of carbidopa/levodopa has been shown to control motor fluctuations in advanced Parkinson's disease (PD). The authors compared the pharmacokinetics of levodopa and 3-O-methyldopa in patients with advanced PD after administration of an oral sustained-release levodopa preparation and after continuous intestinal levodopa infusion with a new formulation as a gel suspension. A randomized crossover trial was carried out in 12 patients. Carbidopa/levodopa was administered as an oral sustained-release tablet and by nasoduodenal continuous infusion for 3-week periods for each treatment. Plasma levodopa concentrations and motor performance were evaluated every 30 minutes during 3 test days of each treatment period. The average intraindividual coefficient of variation for the plasma levodopa concentrations after oral therapy was 34% and was significantly lower (14%, p < 0.01) during continuous infusion. Hourly video evaluations showed a significant increase in ON time during infusion and a significant decrease in OFF time and dyskinesia. Continuous intraduodenal delivery of a new carbidopa/levodopa formulation offers a means for markedly improved control of motor fluctuations in late stages of PD.

  • 291.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Constantinescu, R
    Holmberg, B
    Dizdar, N
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Comparison of apomorphine and levodopa infusions in four patients with Parkinson's disease with symptom fluctuations2009In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 119, no 5, p. 345-348Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Motor fluctuations in patients with advanced Parkinson's disease may be successfully treated with subcutaneous apomorphine infusion or intraduodenal levodopa/carbidopa infusion. No comparative trials of these two alternatives were performed. AIMS OF THE STUDY: We present a subanalysis from a randomized crossover clinical trial where levodopa infusion as monotherapy was compared with any other combination of pharmacotherapy in fluctuating patients. Four patients used apomorphine infusion and oral levodopa in the comparator arm. The results of these four patients are presented in detail. METHODS: The duration of the trial was 3 + 3 weeks. Patients were video-recorded half-hourly on two non-consecutive days of both treatment arms. Blinded video ratings were used. Patient self-assessments of motor function and quality-of-life (QoL) parameters were captured using an electronic diary. RESULTS: Ratings in moderate to severe "off" state ranged 0-44% on apomorphine infusion and 0-6% on levodopa infusion. Moderate to severe dyskinesias were not recorded in any of the treatments. QoL was reported to be improved in all patients on duodenal levodopa infusion. CONCLUSIONS: Monotherapy with duodenal infusion of levodopa was more efficacious and brought greater QoL than combination therapy with apomorphine infusion in these fluctuating patients.

  • 292.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Ehrnebo, M
    Lewander, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Trolin, C G
    Bäckström, T
    Panagiotidis, G
    Spira, J
    Nyström, C
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Frequent administration of levodopa/carbidopa microtablets vs levodopa/carbidopa/entacapone in healthy volunteers2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, no 2, p. 124-132Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    An oral dispersible microtablet formulation of levodopa/carbidopa 5/1.25 mg (LC-5) was developed for individualized repeated dosing. The aim was to compare pharmacokinetic profiles of LC-5 and levodopa/carbidopa/entacapone (LCE).

    MATERIALS AND METHODS:

    A randomized, crossover study was carried out in 11 healthy subjects. Plasma concentrations of levodopa, carbidopa and 3-O-methyldopa were determined after intake of 300 mg levodopa during the day, either as three intakes of 100/25/200 mg LCE or as a morning dose of 75/18.25 mg followed by five repeated doses of 45/11.25 mg LC-5.

    RESULTS:

    Repeated dosing (2.4-hourly) with LC-5 microtablets compared to LCE (6-hourly) avoided long periods with low plasma levodopa levels. Time to maximum plasma concentrations was significantly shorter for LC-5. LC-5 showed lower fluctuation index (FI) in plasma compared to LCE (ANOVA P = 0.0028). FI for dose 2-5 was on average 1.26 for levodopa in LC-5, and 2.23 for dose 1-2 of LCE. The ratio between the two mean FI:s is 0.565; that is, LC-5 gave nearly half the FI as compared to LCE.

    CONCLUSIONS:

    Fractionation of levodopa with LC-5 into small, frequent administrations as compared to standard administrations of LCE decreased the FI in plasma for both levodopa and carbidopa by nearly half.

  • 293.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Johansson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Hellquist, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Complexity of Motor Response to Different Doses of Duodenal Levodopa Infusion in Parkinson Disease2012In: Clinical neuropharmacology, ISSN 0362-5664, E-ISSN 1537-162X, Vol. 35, no 1, p. 6-14Article, review/survey (Refereed)
    Abstract [en]

    OBJECTIVE:

    The aim was to elaborately describe individual pharmacokinetic-pharmacodynamic profiles in patients with difficult-to-treat dyskinesias treated with levodopa/carbidopa intestinal gel infusion.

    METHODS:

    A nonrandomized, partly blinded, investigator-initiated trial was conducted in 5 patients with idiopathic Parkinson disease who were difficult to keep in "on" state without dyskinesia. Levodopa/carbidopa intestinal gel (Duodopa) doses of 80% to 120% of individually and clinically optimized dosage were infused during five 4-hour periods. Pharmacokinetic profiling, blinded assessment of video recordings, and objective movement analysis were applied every 20 to 30 minutes.

    RESULTS:

    Individual correlations between plasma levodopa concentrations and corresponding motor scores 20 to 30 minutes after the sampling time were significant in all patients (P < 0.05 and P < 0.001). Motor scores were generally stable during the 4-hour periods. The objective test revealed that motor performance was faster the more dyskinetic the patients were. Mean individual Treatment Response Scale scores were positive in 24 of the 25 steady-state periods. Dystonia was always combined with choreic dyskinesias.

    CONCLUSIONS:

    Motor response from different doses of levodopa/carbidopa intestinal gel is in a broad sense predictable even in dyskinetic patients although major interindividual differences in dose requirement, plasma levels, and motor response are found. That motor performance was faster the more dyskinetic the patients were implies that motor performance may be better with moderate dyskinesia than with mild dyskinesia. This may explain why patients with persistent dyskinesias choose to keep their doses above the dyskinesia threshold. There is no ideal therapeutic window in such patients, but levodopa infusion offers stable motor response.

  • 294.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Johansson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Levodopa infusion combined with entacapone or tolcapone in Parkinson disease: a pilot trial2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no 6, p. 820-826Article in journal (Refereed)
    Abstract [en]

    Background and purpose: 

    Catechol-O-methyltransferase inhibitors may be used to decrease levodopa requirement. The objective was to investigate whether the levodopa/carbidopa intestinal gel infusion dose can be reduced by 20% without worsening of motor fluctuations and levodopa concentration stability when oral catechol-O-methyltransferase inhibitors are added.

    Methods: 

    A short-term, randomized, partly blinded, crossover, investigator-initiated clinical trial was performed, with levodopa/carbidopa intestinal gel combined with oral entacapone and tolcapone on two different days in 10 patients. The primary outcome measure was difference in coefficient of variation of levodopa in plasma between levodopa/carbidopa, levodopa/carbidopa/entacapone, and levodopa/carbidopa/tolcapone. The secondary outcome measures other pharmacokinetic variables, patient-reported outcome, and blinded analysis of motor performance.

    Results:

    Variation of plasma levodopa concentrations did not differ significantly between the treatments. The treatments did not differ regarding motor performance. Levodopa concentrations were significantly higher using tolcapone. Concentrations of the metabolite 3-O-methyldopa decreased gradually during catechol-O-methyltransferase inhibition.

    Conclusions: 

    According to this small, short-term pilot study, oral catechol-O-methyltransferase inhibitors administered in 5-h intervals may be useful in cases where levodopa/carbidopa intestinal gel dose reduction is wanted. Stability of plasma levodopa levels is not significantly altered, and off-time is not increased when decreasing the levodopa/carbidopa intestinal gel dose by 20%. Rather, the dose should probably be decreased more than 20%, especially under tolcapone co-treatment, to avoid increased dyskinesias with time.

  • 295.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Karlsson, E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lundberg, M
    Askmark, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Large differences in levodopa dose requirement in Parkinson's disease: men use higher doses than women2010In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 17, no 2, p. 260-266Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The characteristics of levodopa dosing are not well described in the literature. The aims were to investigate the use of levodopa in a nationwide Swedish survey and to study the characteristics of low-dose and high-dose patients with Parkinson's disease (PD) in a university hospital. METHODS: Patients with >or= 1 and >or= 2 purchases of levodopa during 2007 were selected from the prescribed drug register. Daily levodopa doses were estimated. Records of 504 patients with PD who visited the neurology clinic at Uppsala University Hospital during 2006-2007 were examined to select a low-dose group (< or = 400 mg levodopa daily, n = 21) and a high-dose group (>or= 1200 mg daily, n = 26) with at least 5 years of PD duration. RESULTS: In total, 33 534 levodopa users with > or = 1 levodopa purchase were found. Daily levodopa dose range was large; median daily dose was 465 mg for men and 395 mg for women (P < 0.0001). Almost half (46%) of the patients used < 400 mg levodopa daily. Significantly, more men were treated with doses >or= 1200 mg daily. Dose and age correlated negatively (P < 0.0001). Patients with high dose at 5 years PD duration continuously increased their dosage the following years, whereas low-dose patients did not. The occurrence of dyskinesias was about the same in both groups despite the large difference in levodopa dose. CONCLUSIONS: We conclude that the levodopa requirement in PD ranges considerably, and that men use higher levodopa dose than women. Levodopa requirement is constant during the progression of the disease in low-dose patients but increases in high-dose patients.

  • 296.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Klangemo, K
    Johansson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Levodopa/carbidopa intestinal gel infusion long-term therapy in advanced Parkinson's disease2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no 8, p. 1079-1085Article in journal (Refereed)
    Abstract [en]

    Background:  Infusion of levodopa/carbidopa intestinal gel (Duodopa(®) ; Abbott) was introduced in Sweden in 1991 as an experimental treatment in advanced Parkinson's disease and obtained EU approval in 2004. There is compelling evidence for short-term use of this treatment; however, long-term data are scarce.

    Methods:  A retrospective review of medical records was performed. The primary objective was to assess the duration of treatment for all Swedish patients starting long-term levodopa/carbidopa gel therapy between January 1991 and June 2008. Secondary aims were to study demographics, treatment with anti-Parkinson's disease drugs and other concomitant medications, and reasons for discontinuation of levodopa/carbidopa gel.

    Results:  Of 150 identified patients, 135 were included in the study. On average, patients were 49 years at diagnosis of Parkinson's disease and 63 years when infusion therapy was initiated. The median treatment time on infusion was 3.4 years (range, 0-16 years). The restricted mean treatment time was nearly 8 years; 81 patients were still on treatment at the end of the study. Levodopa was used as monotherapy in a majority of patients. Dosage of the drug was stable over time. Thirty-one patients discontinued infusion prior to the cutoff date and 23 patients died. Device-related problems were the most common reason for discontinuation. Patients were more likely to discontinue infusion therapy before 2000. The year of infusion initiation was significantly earlier in the dropout group compared with a matched group of continuing patients.

    Conclusions:  Levodopa/carbidopa intestinal gel infusion is a long-term treatment alternative in patients with advanced Parkinson's disease.

  • 297.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kowalski, Jan
    Aquilonius, Sten-Magnus
    Wireless real-time electronic data capture for self-assessment of motor function and quality of life in Parkinson’s diseaseIn: Article in journal (Refereed)
  • 298.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Kowalski, Jan
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Wireless real-time electronic data capture for self-assessment of motor function and quality of life in Parkinson's disease2004In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 19, no 4, p. 446-451Article in journal (Refereed)
    Abstract [en]

    Abstract

    Frequent assessment of the symptoms in Parkinson's disease (PD) is important in both clinical and experimental settings, especially when motor fluctuations are present. Patient diaries are increasingly used in studies, allowing patients to stay in their home environments. However, traditional paper diaries may not reflect reality because of a lack in compliance or retrospective data entries. This study presents a comparison between paper diaries and a new method, real-time data capture with a hand-held computer (electronic diary). Twenty patients with PD diagnosed at least 5 years previously were randomly assigned to use either a paper diary or an electronic diary on 8 days during 1 month. Questions were answered every 2 hours over a 12-hour period on each day. Median compliance was 88% with the electronic diary and 98% with the paper diary, although strict compliance to the scheduled times by patients using the paper diary was 78%. Neither age nor earlier experience with computers affected the patient's ability to use the electronic diary. Electronic diaries can be used for self-assessment of PD symptoms. The real-time feature provides fast access to clean data with knowledge of true compliance.

  • 299.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Irregular gastrointestinal drug absorption in Parkinson's disease2008In: Expert Opinion on Drug Metabolism and Toxicology, ISSN 1742-5255, Vol. 4, no 2, p. 193-203Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Symptomatic treatment of Parkinson's disease (PD) is based on the dopamine precursor levodopa. Levodopa is only absorbed in the small intestine, where transit time is approximately 3 h and the plasma elimination half-life is short. Therefore, gastric emptying is a major determining factor for onset of symptom relief. OBJECTIVE: Gastric emptying is delayed in PD, thereby causing motor fluctuations such as 'delayed on'. Factors that further slow gastric emptying should be recognised and eliminated if possible. METHODS: A literature search was performed with the aim to cover the area of irregular gastrointestinal drug absorption in PD. RESULTS/CONCLUSION: Methods for facilitation of pyloric passage or increase of bioavailability are discussed. Development of new drug formulations and alternative routes of administration is ongoing. Transdermal patches and pumps for subcutaneous or intraduodenal infusions are available for patients with severe fluctuations due to erratic gastric emptying.

  • 300.
    Nyholm, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lennernäs, Hans
    Gomes-Trolin, Cecilia
    Aquilonius, Sten-Magnus
    Levodopa pharmacokinetics and motor performance during activities of daily living in parkinsonian patients on individual drug combinations2002In: Clin Neuropharmacol, ISSN 0362-5664, Vol. 25, no 2, p. 89-96Article in journal (Refereed)
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