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1.
Lakartidningen ; 1212024 Apr 26.
Article in Swedish | MEDLINE | ID: mdl-38666665

ABSTRACT

We present a patient with familial amyotrophic lateral sclerosis caused by an aggressive A4S mutation in the SOD1 gene. In 2020, the patient was enrolled in the VALOR SOD1 gene therapy phase-3 trial. At screening, the ALSFRS-R score was 41 (48 is normal) and the level of CSF-neurofilament L (an indicator of ongoing neuronal damage) was 11 000 ng/L (ref <650 ng/L). In the four years following enrollment, the patient received monthly intrathecal treatment with tofersen, an antisense oligonucleotide compound that inhibits SOD1 protein expression and hence lowers the synthesis of toxic SOD1 protein species. Side effects have been minimal and mostly attributed to the spinal taps. The patient remains ambulatory with an active social lifestyle. The ALSFRS-R score has in the past 18 months stabilized around 35-37, CSF-NfL is 1 290 ng/L and plasma-NfL is 12 (reference <13). This is the first documented arresting intervention in a patient with ALS in Sweden.


Subject(s)
Amyotrophic Lateral Sclerosis , Disease Progression , Genetic Therapy , Superoxide Dismutase-1 , Humans , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/drug therapy , Amyotrophic Lateral Sclerosis/therapy , Superoxide Dismutase-1/genetics , Male , Middle Aged , Mutation , Oligonucleotides, Antisense/therapeutic use , Oligonucleotides, Antisense/administration & dosage , Oligonucleotides/therapeutic use , Oligonucleotides/administration & dosage
2.
BMC Oral Health ; 23(1): 381, 2023 06 12.
Article in English | MEDLINE | ID: mdl-37308874

ABSTRACT

BACKGROUND: The difficulties and challenges faced by people with Parkinson's disease (PD) in performing daily orofacial function are not systematically investigated. In this study, specific orofacial non-motor and motor symptoms and functions were systematically examined in PD patients in comparison to a matched control group. METHODS: The clinical case-controlled study was conducted from May 2021 to October 2022 and included persons with PD and age- and gender-matched persons without PD. The participants with PD were outpatients diagnosed with PD at the Department of Neurology at Bispebjerg University Hospital in Copenhagen, Denmark. The participants underwent a systematic clinical and relevant self-assessment of the orofacial function and temporomandibular disorders (TMD). The primary outcomes were objective and subjective assessments of the general orofacial function, mastication, swallowing, xerostomia and drooling. The secondary outcomes were the prevalence of TMD and orofacial pain. The difference in outcome measures between the two groups was analysed using chi-square and Mann-Whitney U test. RESULTS: The study included 20 persons with PD and 20 age- and gender-matched persons without PD. Both objectively and subjectively, persons with PD had poorer orofacial function than the control group. Persons with PD had also a significantly more severe limitation of jaw mobility and jaw function. The objective masticatory function was also significantly reduced for persons with PD compared to the control group, and 60% of persons with PD found it difficult to eat foods with certain consistencies while 0% of the control group reported that problem. Persons with PD could swallow less water per second and the average swallowing event was significantly longer for PD persons. Even though PD persons reported more xerostomia (58% for persons with PD and 20% for control persons), they also reported significantly more drooling than the control group. Additionally, orofacial pain was more prevalent in PD persons. CONCLUSIONS: Persons with PD have a compromised orofacial function. Furthermore, the study indicates a link between PD and orofacial pain. In order to screen and treat persons with PD accordingly, healthcare professionals should be aware of and address these limitations and symptoms. TRIAL REGISTRATION: The trial was approved by the Regional Committee on Research Health Ethics of the Capital Region (H-20,047,464), the Danish Data Protection Agency (514 - 0510/20-3000), and registered at ClinicalTrials.gov (NCT05356845).


Subject(s)
Parkinson Disease , Sialorrhea , Temporomandibular Joint Disorders , Humans , Awareness , Facial Pain
3.
Community Dent Oral Epidemiol ; 51(3): 527-534, 2023 06.
Article in English | MEDLINE | ID: mdl-36317764

ABSTRACT

OBJECTIVES: Persons with Parkinson's disease (PD) have a higher prevalence of oral diseases and orofacial dysfunction, but knowledge about the use of dental care and whether their dental care needs are met is sparse. This study aimed to investigate the dental attendance and usage of dental care services of the total PD population in Denmark and compare it with a control group. METHODS: National registers were used to identify the total PD population in Denmark (n = 6874) and to obtain data on their dental care from 2015 to 2019. These data were compared with a five-fold age-, gender- and geographically matched control group without PD (n = 34 285). Register data on age, gender, civil status, educational level, income, nursing homes status and mortality were also collected and adjusted for in the analyses. The dental attendance was analysed using χ2 -test with Bonferroni correction, and the type of dental care services was analysed using negative binomial regression analysis. RESULTS: A significantly higher proportion of persons with PD were irregular attenders of the dental care system (21.0%), compared with the control group (16.9%). Persons with PD had a significantly higher overall usage of dental cares services. Most prominent was the high usage of treatment services, where persons with PD had a 1.50 times higher incidence rate of tooth extractions and a 1.71 times higher incidence rate of tooth fillings in the five years compared with the control group. CONCLUSION: Persons with PD are more often irregular users of dental care and receive more treatment services than the control group. This indicates a need for high-quality prophylactic initiatives to prevent high filling and tooth extraction rates. Furthermore, this knowledge can be used by clinicians and decision makers to ensure optimal dental care for persons with PD.


Subject(s)
Mouth Diseases , Parkinson Disease , Humans , Parkinson Disease/complications , Parkinson Disease/epidemiology , Parkinson Disease/therapy , Dental Care , Income , Denmark/epidemiology
4.
Parkinsonism Relat Disord ; 96: 74-79, 2022 03.
Article in English | MEDLINE | ID: mdl-35245879

ABSTRACT

AIM: This is a long-term open follow-up of a prospective double-blind crossover study, where electrodes were bilaterally implanted in both the Subthalamic nucleus (STN) and internal pallidum (GPi) in patients with isolated dystonia. METHODS: Patients with isolated dystonia were included to undergo surgery with Deep Brain stimulation (DBS) and after randomization, in a double-blind cross-over study, receiving bilateral stimulation of either STN or GPi for 6 months in each target. Preoperative and postoperative assessments with the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and the 36-item Short Form Health Survey (SF-36) were performed. In this long-term follow-up (LFU), these ratings were repeated, and patients were evaluated with cognitive tests. RESULTS: 21 patients were included in the protocol, 9 patients with generalized dystonia, 12 with a diagnosis of cervical dystonia. The mean duration of disease was 19.3 years, age at time of surgery 50.1 years. Fourteen patients participated in the LFU. At a mean follow-up of 10.2 years (range 4.8-15.4), BFMDRS movement score was improved with a mean of 36% (p < 0.05) compared with baseline. At LFU both a statistically significant improvement of stimulation in STN on BFMDRS movement score (p = 0.029) and Gpi (p = 0.008) was demonstrated, no significant difference was found between the two targets (p = 0.076). SF-36 improved for both targets. CONCLUSION: In this study we performed a long-term follow-up in 14 patients with cervical or generalized dystonia, who received stimulation in GPi, STN or both. The mean follow-up time was more than 10 years. Our data support a long-term effect of both STN-DBS and GPi-DBS in dystonia with equal effect and safety for up to 15 years. STN has been proven a viable safe and effective target and may be used as an alternative to GPi in both adult-onset cervical dystonia and generalized dystonia.


Subject(s)
Deep Brain Stimulation , Dystonic Disorders , Subthalamic Nucleus , Torticollis , Adult , Cross-Over Studies , Deep Brain Stimulation/methods , Dystonic Disorders/therapy , Follow-Up Studies , Globus Pallidus , Heredodegenerative Disorders, Nervous System , Humans , Prospective Studies , Subthalamic Nucleus/surgery , Torticollis/therapy , Treatment Outcome
5.
J Oral Rehabil ; 48(9): 1035-1043, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34129743

ABSTRACT

BACKGROUND: Parkinson's disease (PD) has a negative effect on oral health and orofacial function, but the subjective experience of orofacial symptoms and their impact on the quality of life is not fully investigated. In addition, knowledge of how to improve the subjective oral symptoms is lacking. OBJECTIVES: To assess the self-reported orofacial function and oral health in patients with PD. Furthermore, to investigate the effect of interventions for improvement of oral hygiene and function on oral health-related quality of life (OHRQoL). METHODS: A randomised controlled study with delayed intervention was conducted in 29 patients with moderate to advanced PD. Patients were instructed in a standardised exercise programme for the jaw and orofacial muscles and given an individualised oral hygiene programme. The effect on self-reported orofacial function and OHRQoL was measured after 2 and 4 months using the Nordic Orofacial Test-Screening (NOT-S), the oral health impact profile (OHIP-14), self-reported drooling score and subjective mastication ability. RESULTS: Self-reported oral health and function before the intervention was significantly correlated to the severity and duration of PD. The NOT-S and drooling score were significantly improved by the interventions after 2 months and the OHIP-14 after 4 months. CONCLUSION: The interventions improve the self-reported orofacial function and OHRQoL. These simple interventions can be implemented in the allied multidisciplinary health care surrounding the PD patient.


Subject(s)
Parkinson Disease , Quality of Life , Humans , Oral Health , Oral Hygiene , Parkinson Disease/complications , Surveys and Questionnaires
6.
J Inflamm Res ; 14: 1043-1053, 2021.
Article in English | MEDLINE | ID: mdl-33790619

ABSTRACT

BACKGROUND: The complement system has been suggested to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS), a progressive motor neuron disease. In the present study, we compared levels of selected complement markers to clinical outcome in ALS patients. METHODS: This observational, explorative cohort study included 92 ALS patients, 61 neurological controls (NCs) admitted for suspected aneurysmal subarachnoid haemorrhage, and 96 neurologically healthy controls (NHCs). Peripheral blood and cerebrospinal fluid (CSF) were obtained for the measurement of ficolin-1, -2, and -3; collectin-11, MBL, MASP-3, MAP-1, C4, C3, PTX-3, and complement activation products C4c, C3bc, and sC5b-9. We recorded clinical outcomes of ALS patients for 24 to 48 months after inclusion in order to analyse the effects of the complement markers on survival time. RESULTS: Compared with both control groups, ALS patients exhibited increased collectin-11, C4 and sC5b-9 in plasma, as well as increased ficolin-3 in CSF. Ficolin-2 was significantly decreased in plasma of the ALS patients compared with NHCs, but not with NCs. The concentration of collectin-11, C3 and C3bc correlated negatively with the revised ALS functional rating scale (ALSFRS-R). No association was found between levels of complement markers and survival as estimated by hazard ratios. CONCLUSION: ALS patients exhibit aberrant expression of selected mediators of the lectin complement pathway as well as increased activation of the terminal complement pathway, corroborating the notion that the complement system might be involved in the pathophysiology of ALS.

7.
BMC Neurol ; 21(1): 164, 2021 Apr 17.
Article in English | MEDLINE | ID: mdl-33865343

ABSTRACT

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with great heterogeneity. Biological prognostic markers are needed for the patients to plan future supportive treatment, palliative treatment, and end-of-life decisions. In addition, prognostic markers are greatly needed for the randomization in clinical trials. OBJECTIVE: This study aimed to test the ALS Functional Rating Scale-Revised (ALSFRS-R) progression rate (ΔFS) as a prognostic marker of survival in a Danish ALS cohort. METHODS: The ALSFRS-R score at test date in association with duration of symptoms, from the onset of symptoms until test date, (defined as ΔFS') was calculated for 90 Danish patients diagnosed with either probable or definite sporadic ALS. Median survival time was then estimated from the onset of symptoms until primary endpoint (either death or tracheostomy). ΔFS' was subjected to survival analysis using Cox proportional hazards modelling, log-rank test, and Kaplan-Meier survival analysis. RESULTS AND CONCLUSIONS: Both ΔFS' and age was found to be strong predictors of survival of the Danish ALS cohort. Both variables are easily obtained at the time of diagnosis and could be used by clinicians and ALS patients to plan future supportive and palliative treatment. Furthermore, ΔFS', is a simple, prognostic marker that predicts survival in the early phase of disease as well as at later stages of the disease.


Subject(s)
Amyotrophic Lateral Sclerosis/mortality , Disease Progression , Severity of Illness Index , Adult , Aged , Cohort Studies , Denmark , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis
8.
Mov Disord Clin Pract ; 7(7): 788-796, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33033736

ABSTRACT

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is well established and the most effective treatment for advanced Parkinson's disease (PD). However, little is known of the long-term effects. OBJECTIVES: The aim of this study was to examine the long-term effects of STN-DBS in PD and evaluate the effect of reprogramming after more than 8 years of treatment. METHODS: A total of 82 patients underwent surgery in Copenhagen between 2001 and 2008. Before surgery and at 8 to 15 years follow-up, the patients were rated with the Unified Parkinson's Disease Rating Scale (UPDRS) with and without stimulation and medicine. Furthermore, at long-term follow-up, the patients were offered a systemic reprogramming of the stimulation settings. Data from patients' medical records were collected. The mean (range) age at surgery was 60 (42-78) years, and the duration of disease was 13 (5-25) years. A total of 30 patients completed the long-term follow-up. RESULTS: The mean reduction of the motor UPDRS by medication before surgery was 52%. The improvement of motor UPDRS with stimulation alone compared with motor UPDRS with neither stimulation nor medication was 61% at 1 year and 39% at 8 to 15 years after surgery (before reprogramming). Compared with before surgery, medication was reduced by 55% after 1 year and 44% after 8 to 15 years. After reprogramming, most patients improved. CONCLUSIONS: STN-DBS remains effective in the long run, with a sustained reduction of medication in the 30 of 82 patients available for long-term follow-up. Reprogramming is effective even in the late stages of PD and after many years of treatment.

9.
J Oral Rehabil ; 47(3): 370-376, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31837276

ABSTRACT

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder. It is associated with reduced oral health and impaired oro-facial function, but besides recommendations of dental visits and drooling treatment, there are little documented odontological treatment options. OBJECTIVES: To evaluate the effect of standardised home exercise jaw opening and chewing programmes, as well as home oral hygiene measures instructed and controlled by a trained dentist. METHODS: Twenty-nine patients (median 65 years) with moderate to advanced PD participated in the project after informed consent. They were followed at a Neurology Department, were able to cooperate, and had stable medical treatment and nine also deep brain stimulation. The interventions were individual dental hygiene instruction, training of jaw opening (JawTrainer), and lip and chewing exercises (Ulmer Oral Screen and Proxident Fluoride Gum). The study was performed as a randomised controlled study. The treatment effect was evaluated after 2 and 4 months. The primary outcome was maximum unassisted jaw opening capacity, chewing time of a standardised apple slice, and the Simplified Debris Index. Results were analysed with Wilcoxon matched pairs test and Mann-Whitney U test (significance level P < .05). RESULTS: Jaw opening, chewing time and hygiene were significantly improved 2 months from the start of the invention, respectively, 6%, 49%, and 25%, and the improvement was still significant after 4 months. No significant changes were found after the 2-month control period without intervention. CONCLUSION: The simple measures had a substantial and significant clinical effect which is promising despite the progressive nature of the PD.


Subject(s)
Parkinson Disease , Sialorrhea , Humans , Mastication , Oral Health , Oral Hygiene
11.
Ugeskr Laeger ; 179(7)2017 Feb 13.
Article in Danish | MEDLINE | ID: mdl-28397674

ABSTRACT

Many patients with neurological disorders have symptoms which are difficult to treat with conventional medication. In this case report we present a 40-year-old male patient with primary lateral sclerosis who used cannabidiol oil as therapy. We discuss the evidence of the effects of cannabidiol in the treatment of patients with neurological disease, and we raise the question: "Should patients who use illegal cannabis products as self-medication be diagnosed as drug abusers?"


Subject(s)
Cannabidiol , Motor Neuron Disease/drug therapy , Self Medication , Adult , Cannabidiol/administration & dosage , Cannabidiol/therapeutic use , Humans , Male , Treatment Outcome
12.
J Clin Invest ; 124(7): 3107-20, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24911152

ABSTRACT

Parkinsonism and attention deficit hyperactivity disorder (ADHD) are widespread brain disorders that involve disturbances of dopaminergic signaling. The sodium-coupled dopamine transporter (DAT) controls dopamine homeostasis, but its contribution to disease remains poorly understood. Here, we analyzed a cohort of patients with atypical movement disorder and identified 2 DAT coding variants, DAT-Ile312Phe and a presumed de novo mutant DAT-Asp421Asn, in an adult male with early-onset parkinsonism and ADHD. According to DAT single-photon emission computed tomography (DAT-SPECT) scans and a fluoro-deoxy-glucose-PET/MRI (FDG-PET/MRI) scan, the patient suffered from progressive dopaminergic neurodegeneration. In heterologous cells, both DAT variants exhibited markedly reduced dopamine uptake capacity but preserved membrane targeting, consistent with impaired catalytic activity. Computational simulations and uptake experiments suggested that the disrupted function of the DAT-Asp421Asn mutant is the result of compromised sodium binding, in agreement with Asp421 coordinating sodium at the second sodium site. For DAT-Asp421Asn, substrate efflux experiments revealed a constitutive, anomalous efflux of dopamine, and electrophysiological analyses identified a large cation leak that might further perturb dopaminergic neurotransmission. Our results link specific DAT missense mutations to neurodegenerative early-onset parkinsonism. Moreover, the neuropsychiatric comorbidity provides additional support for the idea that DAT missense mutations are an ADHD risk factor and suggests that complex DAT genotype and phenotype correlations contribute to different dopaminergic pathologies.


Subject(s)
Attention Deficit Disorder with Hyperactivity/genetics , Attention Deficit Disorder with Hyperactivity/metabolism , Dopamine Plasma Membrane Transport Proteins/genetics , Dopamine Plasma Membrane Transport Proteins/metabolism , Mutant Proteins/genetics , Mutant Proteins/metabolism , Mutation, Missense , Parkinsonian Disorders/genetics , Parkinsonian Disorders/metabolism , Adult , Amino Acid Sequence , Amino Acid Substitution , Animals , Attention Deficit Disorder with Hyperactivity/complications , Brain/diagnostic imaging , Brain/metabolism , Cohort Studies , DNA Mutational Analysis , Dopamine/metabolism , Dopamine Plasma Membrane Transport Proteins/chemistry , Female , HEK293 Cells , Humans , Male , Models, Molecular , Molecular Sequence Data , Mutant Proteins/chemistry , Oocytes/metabolism , Parkinsonian Disorders/complications , Pedigree , Positron-Emission Tomography , Protein Conformation , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Sequence Homology, Amino Acid , Sodium/metabolism , Tomography, Emission-Computed, Single-Photon , Xenopus
13.
J Neurosurg ; 119(6): 1537-45, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24116723

ABSTRACT

OBJECT: The authors' aim was to compare the subthalamic nucleus (STN) with the globus pallidus internus (GPi) as a stimulation target for deep brain stimulation (DBS) for medically refractory dystonia. METHODS: In a prospective double-blind crossover study, electrodes were bilaterally implanted in the STN and GPi of 12 patients with focal, multifocal, or generalized dystonia. Each patient was randomly selected to undergo initial bilateral stimulation of either the STN or the GPi for 6 months, followed by bilateral stimulation of the other nucleus for another 6 months. Preoperative and postoperative ratings were assessed by using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and video recordings. Quality of life was evaluated by using questionnaires (36-item Short Form Health Survey). Supplemental Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores were assessed for patients with focal dystonia (torticollis) by examining the video recordings. RESULTS: On average for all patients, DBS improved the BFMDRS movement scores (p < 0.05) and quality of life physical scores (p < 0.01). After stimulation of the STN, the mean 6-month improvement in BFMDRS movement score was 13.8 points; after stimulation of the GPi, this improvement was 9.1 points (p = 0.08). Quality of life did not differ significantly regardless of which nucleus was stimulated. All 12 patients accepted 6 months of stimulation of the STN, but only 7 accepted 6 months of stimulation of the GPi. Among those who rejected stimulation of the GPi, 3 accepted concomitant stimulation of both the STN and GPi for 6 months, resulting in improved quality of life physical and mental scores and BFMDRS movement scores. Among the 4 patients who were rated according to TWSTRS, after 6 months of stimulation of both the STN and GPi, TWSTRS scores improved by 4.7% after stimulation of the GPi and 50.8% after stimulation of the STN (p = 0.08). CONCLUSIONS: The STN seems to be a well-accepted, safe, and promising stimulation target in the treatment of dystonia, but further studies are necessary before the optimal target can be concluded. Simultaneous stimulation of the STN and GPi should be further investigated. Clinical trial registration no.: KF 01-110/01 (Committees on Biomedical Research Ethics of the Capital Region of Denmark).


Subject(s)
Deep Brain Stimulation/methods , Dystonia/therapy , Globus Pallidus/physiopathology , Subthalamic Nucleus/physiopathology , Adult , Age of Onset , Aged , Cross-Over Studies , Deep Brain Stimulation/instrumentation , Double-Blind Method , Dystonia/physiopathology , Dystonia/surgery , Electrodes, Implanted/statistics & numerical data , Globus Pallidus/surgery , Humans , Middle Aged , Prospective Studies , Quality of Life , Severity of Illness Index , Subthalamic Nucleus/surgery , Torticollis/physiopathology , Torticollis/therapy , Treatment Outcome
14.
J Nucl Med ; 54(7): 1072-6, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23637201

ABSTRACT

UNLABELLED: Patients who have dementia with Lewy bodies (DLB) show both clinical and histopathologic overlap with Alzheimer disease patients and Parkinson disease patients. In this study, we correlated the core features of DLB (dementia, parkinsonism, hallucinations, and fluctuations) with striatal dopamine transporter (DAT) availability as assessed with SPECT and (123)I-N-(3-iodoprop-2E-enyl)-2-ß-carbomethoxy-3ß-(4-methylphenyl) nortropane ((123)I-PE2I) in patients with newly diagnosed DLB. METHODS: Two hundred eighty-eight patients were consecutively included in the study as they were referred for diagnostic SPECT scanning of DAT with (123)I-PE2I. Of those patients, 51 had, on the basis of clinical guideline criteria, a probable-DLB diagnosis at follow-up 16 ± 11.6 mo later. Before or on the day of the SPECT scan, DLB patients had a routine neurologic examination including Hoehn and Yahr grading and were cognitively evaluated with the Mini Mental State Examination. RESULTS: There was no correlation between Mini Mental State Examination, Hoehn and Yahr score, fluctuations or hallucinations, and striatal DAT availability as measured with (123)I-PE2I and SPECT. CONCLUSION: In patients with newly diagnosed DLB, symptoms are not associated with a reduction in striatal DAT despite its firm involvement in DLB pathology.


Subject(s)
Brain/metabolism , Corpus Striatum/metabolism , Dopamine Plasma Membrane Transport Proteins/metabolism , Lewy Body Disease/epidemiology , Lewy Body Disease/metabolism , Nortropanes/pharmacokinetics , Aged , Biomarkers/metabolism , Brain/diagnostic imaging , Corpus Striatum/diagnostic imaging , Denmark/epidemiology , Female , Humans , Lewy Body Disease/diagnostic imaging , Male , Prevalence , Protein Binding , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Reproducibility of Results , Risk Assessment , Sensitivity and Specificity , Severity of Illness Index , Statistics as Topic
15.
Eur J Nucl Med Mol Imaging ; 39(2): 242-50, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22095050

ABSTRACT

PURPOSE: To examine the diagnostic sensitivity and specificity of dopamine transporter SPECT imaging with a highly dopamine transporter selective radioligand. The study included consecutively enrolled, drug-naive patients with an average short history of parkinsonian motor symptoms, referred for diagnostic scanning. METHODS: The study group comprised 288 patients naive to antiparkinson treatment who were enrolled as they were admitted for a diagnostic SPECT scan with the radioligand [(123)I]-N-(3-iodoprop-2E-enyl)-2-ß-carbomethoxy-3ß-(4-methylphenyl)nortropane ((123)I-PE2I). After the diagnostic scanning, patients were followed clinically with an average follow-up of 19.7 ± 12.5 months. RESULTS: A diagnosis could be clinically settled in 189 patients and among these patients, a dopamine transporter scan had a sensitivity of 88% and a specificity of 91% for discrimination between patients with and without striatal neurodegeneration. In cognitively impaired patients (Mini Mental State Examination <27) the specificity was 75% and the sensitivity 95%. A striatal anterior-posterior ratio (APR) of >2 differentiated between idiopathic Parkinson's disease and atypical parkinsonian syndromes with a specificity of 84% and a sensitivity of 63%. CONCLUSION: In drug-naive patients with subtle clinical parkinsonian motor symptoms, dopamine transporter scan using (123)I-PE21 has a high sensitivity and specificity in distinguishing between patients with and without striatal neurodegeneration. The specificity is lower in patients who are also cognitively impaired. Calculation of the striatal APR can assist in differentiating between idiopathic Parkinson's disease and atypical parkinsonian syndromes.


Subject(s)
Parkinson Disease/metabolism , Tomography, Emission-Computed, Single-Photon/methods , Adult , Aged , Aged, 80 and over , Dopamine Plasma Membrane Transport Proteins/metabolism , Female , Humans , Iodine Radioisotopes/pharmacology , Male , Middle Aged , Neurodegenerative Diseases/metabolism , Nortropanes/pharmacology , Predictive Value of Tests , Sensitivity and Specificity
16.
Acta Odontol Scand ; 69(3): 151-7, 2011 May.
Article in English | MEDLINE | ID: mdl-21198339

ABSTRACT

OBJECTIVE: Drooling in neurodegenerative diseases is associated with social impediment. Previous treatments of drooling have little effect or are effective but with severe side effects. Therefore, there is a need to test new methods such as the use of botulinum toxin type A (BTX-A). MATERIAL AND METHODS: This open, prospective study deals with treatment of drooling in 12 patients with amyotrophic lateral sclerosis and three with Parkinson's disease. Injections of BTX-A (Botox) were given into the parotid (25-40 units) and submandibular (15-30 units) glands with ultrasonographic guidance. After BTX-A treatment, the patients were followed for 2 months with evaluations every second week by means of self-assessed rating scales for drooling intensity, discomfort and treatment effect, and determination of unstimulated whole saliva (UWS) flow rate, and inorganic and organic UWS composition. The treatment was repeated up to four times, but seven patients dropped out shortly after the first treatment due to marked worsening of their disease-related condition. RESULTS: Drooling and flow were reduced (P < 0.05) 2 weeks after treatment, without side-effects. The maximal reductions during the observation period were 40% for drooling and 30% for flow. There was a systematic variation in flow during the observation period, with an initial decrease and then an increase followed by a second decrease. Amylase activity and total protein concentration generally increased with decreasing flow (P ≤ 0.03). CONCLUSION: Inhibition of acetylcholine release from postganglionic parasympathetic nerve endings by injection of BTX-A into salivary glands seemed useful for secondary sialorrhoea, although cyclic variations in flow may occur, possibly due to transitory sprouting and regeneration.


Subject(s)
Amyotrophic Lateral Sclerosis/complications , Botulinum Toxins, Type A/therapeutic use , Neuromuscular Agents/therapeutic use , Parkinson Disease/complications , Sialorrhea/drug therapy , Acetylcholine/metabolism , Aged , Algorithms , Botulinum Toxins, Type A/administration & dosage , Botulinum Toxins, Type A/pharmacology , Female , Humans , Injections , Male , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/pharmacology , Parotid Gland/drug effects , Prospective Studies , Saliva/chemistry , Saliva/metabolism , Salivation/drug effects , Secretory Rate/drug effects , Sialorrhea/etiology , Submandibular Gland/drug effects , Ultrasonography, Interventional
17.
Eur J Oral Sci ; 119(1): 27-32, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21244508

ABSTRACT

No comprehensive study has previously been published on orofacial function in patients with well-defined Parkinson's disease (PD). Therefore, the aim of this study was to perform an overall assessment of orofacial function and oral health in patients, and to compare the findings with matched control subjects. Fifteen outpatients (nine women and six men, 61-82 yr of age; Hoehn & Yahr Stages 2-4; and with motor impairment ranging from 17 to 61 according to the Unified Parkinson's Disease Rating Scale, Objective Motor Part III) were examined in their 'on' state together with 15 age- and gender-matched controls. Orofacial function and oral health were assessed using the Nordic Orofacial Test, masticatory ability, performance and efficiency, oral stereognosis, jaw opening, jaw muscle tenderness, the Oral Health Impact Profile-49, number of natural teeth, and oral hygiene. Orofacial dysfunction was more prevalent, mastication and jaw opening poorer, and impact of oral health on daily life more negative, in patients with PD than in controls. The results indicate that mastication and orofacial function are impaired in moderate to advanced PD, and with progression of the disease both orofacial and dental problems become more marked. It is suggested that greater awareness of the special needs in PD patients and frequent dental visits are desirable to prevent dental diseases and decay and to support masticatory function.


Subject(s)
Jaw/physiopathology , Mastication , Masticatory Muscles/physiopathology , Oral Health , Parkinson Disease/physiopathology , Aged , Aged, 80 and over , Bite Force , Case-Control Studies , Deglutition Disorders/etiology , Facial Expression , Female , Humans , Male , Middle Aged , Oral Hygiene , Parkinson Disease/complications , Sialorrhea/etiology , Sickness Impact Profile , Speech Disorders/etiology , Statistics, Nonparametric , Stereognosis , Surveys and Questionnaires , Xerostomia/etiology
18.
Dan Med Bull ; 57(6): A4155, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20515603

ABSTRACT

INTRODUCTION: Patients with advanced Parkinson's disease (PD) often develop motor complications including fluctuations and involuntary movements (dyskinesias). In Denmark, treatment has comprised Deep Brain Stimulation (DBS) since the late 1990s, and as from 2002 use of a subcutaneous apomorphine pump. Monotherapy with continuous intestinal levodopa infusion to the duodenum (Duodopa) was introduced in 2004. MATERIAL AND METHODS: A total of 14 PD patients were assessed for Duodopa pump therapy in the 2004-2008 period. After an initial test week, 12 of the patients had a permanent percutaneous endoscopic gastrostomy (PEG) tube inserted containing a smaller intestinal tube terminating in the duodenum. Before and after treatment initiation, we evaluated the patients using clinical rating scales and video recordings. RESULTS: Objectively, all 12 patients experienced a significant reduction in fluctuations and dyskinesias while achieving a better gait function. Three patients received Duodopa as 24-hour treatment with good effect on severe nocturnal dystonic pain. One patient suffered a severe complication (peritonitis). CONCLUSION: Duodopa has a symptom-relieving and stabilizing effect without side effects, but entails a risk of surgical complications (peritonitis).


Subject(s)
Antiparkinson Agents/administration & dosage , Infusion Pumps , Levodopa/administration & dosage , Parkinson Disease/drug therapy , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
20.
Sleep Med ; 8(7-8): 768-72, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17825613

ABSTRACT

BACKGROUND: Restless legs syndrome (RLS) is a neurological movement disorder, which often causes sleep problems. However, the comorbidity of this disorder is not well known. This study aimed to document the prevalence of RLS in the general population of Sweden and to identify factors associated with this condition. METHODS: A cross-sectional study was performed in Sweden. One thousand subjects aged 18-90 years old underwent telephone interviews. The questionnaire assessed such factors as sleep variables, depressive mood, treatment of diabetes mellitus, and treatment with drugs for depression during the previous four-week period. RLS was diagnosed based on the minimal criteria provided by the International RLS Study Group. RESULTS: The prevalence of RLS was 5% (5.7% in women, 3.5% in men). Severe or very severe RLS symptoms during the previous week were noted by 64% of the RLS subjects. Factors associated with RLS were insomnia, excessive daytime sleepiness, periodic limb movements in sleep, and depressed mood. Those affected by RLS were not more often consumers of drugs for depression than non-RLS subjects. CONCLUSIONS: RLS is prevalent in the general population in Sweden. RLS negatively influenced sleep and was associated with depressed mood. Antidepressive drug treatment was not associated with RLS.


Subject(s)
Diabetes Mellitus/epidemiology , Disorders of Excessive Somnolence/epidemiology , Restless Legs Syndrome/epidemiology , Sleep Initiation and Maintenance Disorders/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Comorbidity , Cross-Sectional Studies , Disorders of Excessive Somnolence/diagnosis , Female , Humans , Male , Middle Aged , Polysomnography , Prevalence , Restless Legs Syndrome/diagnosis , Severity of Illness Index , Sleep Initiation and Maintenance Disorders/diagnosis , Sweden/epidemiology
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