Publications by authors named "Wolfgang H Jost"

101 Publications

Use of Botulinum Neurotoxin in Parkinson's Disease: A Critical Appraisal.

Authors:
Wolfgang H Jost

Toxins (Basel) 2021 Jan 25;13(2). Epub 2021 Jan 25.

Parkinson-Klinik Ortenau, Kreuzbergstr. 12, 77709 Wolfach, Germany.

For well over 30 years, the botulinum neurotoxin (BoNT) has been used for a large number of indications, some of which however have not been licensed. Admittedly, approval varies in many countries and this permits a large spectrum for evaluation. Thus, BoNT is used for patients with Parkinson's disease (PD) and other Parkinson's syndromes (PS) in varying degrees of frequency. We have to distinguish between (1) indications that are either approved or (2) those not approved, (3) indications that might be a result of PS and (4) finally those which appear independent of PS. The most important indication for BoNT in PS patients is probably sialorrhea, for which approval has been granted in the majority of countries. Cervical dystonia is a frequent symptom in PS, with anterocollis as a specific entity. A further indication is blepharospasm in the different forms, especially the inhibition of eyelid opening in atypical PS. The use of BoNT in cases of camptocormia, the Pisa syndrome and neck rigidity is still a matter of debate. In dystonia of the extremities BoNT can be recommended, especially in dystonia of the feet. One well-known indication, for which however sufficient data are still lacking, involves treating tremor with BoNT. As to autonomic symptoms: Focal hyperhidrosis and detrusor hyperactivity can be mentioned, in this last case BoNT has already been approved. A number of further but rare indications such as freezing-of-gait, dyskinesia, and dysphagia will be discussed and evaluated.
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http://dx.doi.org/10.3390/toxins13020087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910947PMC
January 2021

Dose per muscle in cervical dystonia: pooled data from seven movement disorder centres.

Neurol Neurochir Pol 2021 Jan 20. Epub 2021 Jan 20.

Department of Neurological-Psychiatric Nursing, Medical University of Gdańsk, Dpt. of Neurology, St. Adalbert Hospital, Gdańsk, Poland.

Aim Of Study: Botulinum neurotoxin type A (BoNT/A) injections are the established treatment in cervical dystonia (CD). But clinical practice regarding the choice of muscles into which injections are made varies between centres. Until now, there have been no dose-per-muscle recommendations based on 'searching the dose' clinical trial data.

Clinical Rationale For Study: We therefore examined the dosages under real world conditions at seven international movement disorders centres, using an identical clinical approach.

Results: We examined 305 patients with CD (55.6 ± 13.2 years, 204 female). The most commonly injected muscles were the splenius capitis (84.9%), sternocleidomastoid (80.3%), trapezius (59.7%), levator scapulae (49.8%), semispinalis capitis (39%), and obliquus capitis inferior (36.7%). The mean total dose per treatment session with aboBoNT/A was 652.5 (SD = 285.5), with onaBoNT/A it was 159.5 (SD = 62.4), and with incoBoNT/A it was 173.4 (SD = 99.2) units. The doses injected into each muscle in the ona- or incoBoNT/A groups were between 19.7 and 48.2 units, with the highest dose for the splenius capitis with 49.2 ± 26.0 units. The doses in the aboBoNT/A group were between 69.6 and 146.4 units, and the highest dose being injected into the splenius capitis (139.6 ± 80.7 units).

Conclusions And Clinical Implications: In clinical trials the doses per muscle are based on an arbitrary decision. In our study, the doses were lower than in other studies, which may be due to the number of muscles per session, the use of ultrasound guidance (and therefore more precise injections), as well as the use of the Col-Cap concept. Our results exemplify everyday practice, and may help as the basis for recommendations and further investigations.
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http://dx.doi.org/10.5603/PJNNS.a2021.0005DOI Listing
January 2021

Spasticity in practice (SPACE): an international non-interventional study of botulinum neurotoxin type A in treatment-naïve subjects with spasticity.

Neurol Neurochir Pol 2021 Jan 12. Epub 2021 Jan 12.

Parkinson-Klinik Ortenau, Wolfach, Germany.

Aim Of The Study: SPACE, a prospective, non-interventional, open-label, multinational study, investigated physicians' and subjects' assessment of safety, efficacy, and health-related quality of life (HRQoL) following botulinum neurotoxin type A (BoNT-A) treatment to understand real-world clinical usage for the management of focal and multifocal spasticity.

Clinical Rationale For The Study: Treatment guidelines recommend the use of BoNT-A for the management of spasticity in adults. This study assessed how physicians use BoNT-A therapy in real-world clinical practice, and provided evidence on long-term safety and efficacy over a period of up to 2 years.

Materials And Methods: BoNT treatment-naïve adults with spasticity of any aetiology received any BoNT-A formulation at their physician's discretion, and were observed for ≤ 8 treatment cycles (≤ 2 years). Daily practice information, physician's global assessments of tolerability and efficacy, and HRQoL were documented. Incidences of adverse drug reactions or all adverse events were documented for non-Mexican subjects and for Mexican subjects, respectively, due to protocol differences based on local regulatory requirements.

Results: A total of 701 subjects were enrolled (safety population; nine countries). Physicians rated the tolerability of BoNT-A as 'very good' or 'good' for 88.2-97.4% of subjects throughout the study (subject numbers declined throughout this non-interventional study). Adverse drug reactions were reported for 16/600 (2.7%) of the non-Mexican subjects, with two considered to be 'definitely related' to treatment (injection-site haematoma, n = 1; botulism, n = 1). For 687 subjects, efficacy was rated 'very good' or 'good' by most physicians and subjects. Improvements in HRQoL were observed.

Conclusions And Clinical Implications: Throughout this 2-year study, BoNT-A treatment was generally well-tolerated, effective, and associated with an improved HRQoL. This study makes a valuable contribution to the broader understanding of how physicians use BoNT-A therapy to manage spasticity in real-world clinical practice.
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http://dx.doi.org/10.5603/PJNNS.a2021.0001DOI Listing
January 2021

Differential diagnosis of parkinsonism: a head-to-head comparison of FDG PET and MIBG scintigraphy.

NPJ Parkinsons Dis 2020 Dec 11;6(1):39. Epub 2020 Dec 11.

Faculty of Medicine, Department of Nuclear Medicine, Medical Center-University of Freiburg, University of Freiburg, Freiburg im Breisgau, Germany.

[F]fluorodeoxyglucose (FDG) PET and [I]metaiodobenzylguanidine (MIBG) scintigraphy may contribute to the differential diagnosis of neurodegenerative parkinsonism. To identify the superior method, we retrospectively evaluated 54 patients with suspected neurodegenerative parkinsonism, who were referred for FDG PET and MIBG scintigraphy. Two investigators visually assessed FDG PET scans using an ordinal 6-step score for disease-specific patterns of Lewy body diseases (LBD) or atypical parkinsonism (APS) and assigned the latter to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome. Regions-of-interest analysis on anterior planar MIBG images served to calculate the heart-to-mediastinum ratio. Movement disorder specialists blinded to imaging results established clinical follow-up diagnosis by means of guideline-derived case vignettes. Clinical follow-up (1.7 ± 2.3 years) revealed the following diagnoses: n = 19 LBD (n = 17 Parkinson's disease [PD], n = 1 PD dementia, and n = 1 dementia with Lewy bodies), n = 31 APS (n = 28 MSA, n = 3 PSP), n = 3 non-neurodegenerative parkinsonism; n = 1 patient could not be diagnosed and was excluded. Receiver operating characteristic analyses for discriminating LBD vs. non-LBD revealed a larger area under the curve for FDG PET than for MIBG scintigraphy at statistical trend level for consensus rating (0.82 vs. 0.69, p = 0.06; significant for investigator #1: 0.83 vs. 0.69, p = 0.04). The analysis of PD vs. MSA showed a similar difference (0.82 vs. 0.69, p = 0.11; rater #1: 0.83 vs. 0.69, p = 0.07). Albeit the notable differences in diagnostic performance did not attain statistical significance, the authors consider this finding clinically relevant and suggest that FDG PET, which also allows for subgrouping of APS, should be preferred.
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http://dx.doi.org/10.1038/s41531-020-00141-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733458PMC
December 2020

Long-Term Observational Results from the ASPIRE Study: OnabotulinumtoxinA Treatment for Adult Lower Limb Spasticity.

PM R 2020 Nov 5. Epub 2020 Nov 5.

University of Texas Health Science Center McGovern Medical School and TIRR Memorial Hermann, Houston, TX, USA.

Introduction: OnabotulinumtoxinA treatment for spasticity varies according to numerous factors and is individualized to meet treatment goals.

Objective: To explore real-world onabotulinumtoxinA utilization and effectiveness in patients with lower limb spasticity from the Adult Spasticity International Registry (ASPIRE) study.

Design: Two-year, multicenter, prospective, observational registry (NCT01930786).

Setting: Fifty-four international clinical sites.

Patients: Adults (naïve or non-naïve to botulinum toxin[s] treatment for spasticity, across multiple etiologies) with lower limb spasticity related to upper motor neuron syndrome.

Interventions: OnabotulinumtoxinA administered at the clinician's discretion.

Main Outcome Measures: OnabotulinumtoxinA treatment utilization, clinician- and patient-reported satisfaction.

Results: In ASPIRE, 530 patients received ≥1 onabotulinumtoxinA treatment for lower limb spasticity (mean age, 52 years; stroke, 49.4%; multiple sclerosis, 20.4%). Equinovarus foot was treated most often (80.9% of patients), followed by flexed knee (26.0%), stiff extended knee (22.5%), and flexed toes (22.3%). OnabotulinumtoxinA doses ranged between 10 and 1100 U across all presentations. Electromyography (EMG) was most commonly used for injection localization (≥41.1% of treatment sessions). Despite low patient response on the satisfaction questionnaire, clinicians (94.6% of treatment sessions) and patients (84.5%) reported satisfaction/extreme satisfaction that treatment helped manage spasticity, and clinicians (98.3%) and patients (91.6%) would probably/definitely continue onabotulinumtoxinA treatment. These data should be interpreted with care. Twenty-one adverse events (AEs) in 18 patients (3.4%) were considered treatment-related. Sixty-seven patients (12.6%) reported 138 serious AEs; 3 serious AEs in two patients (0.4%) were considered treatment-related. No new safety signals were identified.

Conclusions: ASPIRE provides long-term observational data on the treatment of lower limb spasticity with onabotulinumtoxinA. Real-world data from this primary analysis can help to guide the clinical use of onabotulinumtoxinA to improve spasticity management.
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http://dx.doi.org/10.1002/pmrj.12517DOI Listing
November 2020

Impact of early intervention with onabotulinumtoxinA treatment in adult patients with post-stroke lower limb spasticity: results from the double-blind, placebo-controlled, phase 3 REFLEX study.

J Neural Transm (Vienna) 2020 Dec 27;127(12):1619-1629. Epub 2020 Oct 27.

Allergan Plc, Irvine, CA, USA.

The aim of this study in patients with post-stroke lower limb spasticity (PSLLS) was to evaluate the relationship between time of onabotulinumtoxinA treatment relative to stroke and efficacy outcomes. This was a phase 3, international, multicenter, randomized, 12-week, double-blind study, followed by a repeated treatment, open-label extension. Patients were aged 18-85 years with PSLLS (Modified Ashworth Scale [MAS] ≥ 3) of the ankle with the most recent stroke occurring ≥ 3 months before screening. Patients (double-blind phase) were randomized (n = 468) to onabotulinumtoxinA 300-400 U (300 U, mandatory ankle muscles (gastrocnemius, soleus, tibialis posterior); and ≤ 100 U, optional lower limb muscles (flexor digitorum longus, flexor hallucis longus, flexor digitorum brevis, extensor hallucis, and rectus femoris]) or placebo. Primary endpoint: MAS change from baseline (average score of weeks 4 and 6). Secondary endpoints: physician-assessed Clinical Global Impression of Change (CGI) average score of weeks 4 and 6 and physician-assessed Goal Attainment Scale (GAS; active and passive, weeks 8 and 12). When stratified by time since stroke (≤ 24 months, n = 153; > 24 months, n = 315, post hoc), patients treated ≤ 24 months post-stroke experienced greater improvements from baseline versus placebo in MAS (- 0.31 vs - 0.17), CGI (0.49 vs 0.12), and passive GAS scores (week 12, 0.37 vs 0.26). A ≥  - 1-point improvement in active (week 12; p = 0.04) and passive (week 8; p = 0.02) GAS scores versus placebo was achieved by more patients treated ≤ 24 months post-stroke; in patients treated > 24 months post-stroke, improvements were only observed in active scores (week 8; p = 0.04). OnabotulinumtoxinA 300-400 U was well tolerated, with no new safety findings.
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http://dx.doi.org/10.1007/s00702-020-02251-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666298PMC
December 2020

A European Observational Study to Evaluate the Safety and the Effectiveness of Safinamide in Routine Clinical Practice: The SYNAPSES Trial.

J Parkinsons Dis 2021 ;11(1):187-198

Parkinson-Klinik Ortenau, University of Freiburg, Wolfach, Germany.

Background: Safinamide modulates both dopaminergic and glutamatergic systems with positive effects on motor and non-motor symptoms of Parkinson's disease (PD). The drug utilization study SYNAPSES was designed to investigate the use of safinamide in routine clinical practice, as recommended by the European Medicines Agency.

Objective: To describe the occurrence of adverse events in PD patients treated with safinamide in real-life conditions.

Methods: The SYNAPSES trial is an observational, European, multicenter, retrospective-prospective cohort study. Patients were followed up to 12 months with analyses performed in the overall population and in patients aged >75 years, with relevant comorbidities and with psychiatric conditions.

Results: Of the 1610 patients included, 82.4% were evaluable after 12 months with 25.1% of patients >75 years, 70.8% with relevant comorbidities and 42.4% with psychiatric conditions. During observation 45.8% patients experienced adverse events, 27.7% patients had adverse drug reactions and 9.2% patients had serious adverse events. The adverse events were those already described in the patients' information leaflet. The majority were mild or moderate and completely resolved and no differences were detected between the subgroup of patients. Clinically significant improvements were seen in the UPDRS motor score and in the UPDRS total score in ≥40% of patients, according to the criteria developed by Shulman et al.Conclusion:The SYNAPSES study confirms the good safety profile of safinamide even in special groups of patients. Motor complications and motor scores improved with clinically significant results in the UPDRS scale maintained in the long-term.
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http://dx.doi.org/10.3233/JPD-202224DOI Listing
January 2021

Is It Meanwhile Biomedical Sciences or Still "Ars Medica"?

Authors:
Wolfgang H Jost

Cells 2020 10 17;9(10). Epub 2020 Oct 17.

Parkinson-Klinik Ortenau, Center for Movement Disorders, 77709 Wolfach, Germany.

Scientific work is usually quite time-intensive and frequently replete with frustrations [...].
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http://dx.doi.org/10.3390/cells9102313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602963PMC
October 2020

Reply to: Sudden Death In Parkinson´s Disease: Treating Hypertension In The Elderly.

Authors:
Wolfgang H Jost

Expert Opin Pharmacother 2020 Oct 12:1-2. Epub 2020 Oct 12.

Parkinson-Klinik , Wolfach, Germany.

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http://dx.doi.org/10.1080/14656566.2021.1833606DOI Listing
October 2020

High clinician- and patient-reported satisfaction with individualized onabotulinumtoxinA treatment for spasticity across several etiologies from the ASPIRE study.

Toxicon X 2020 Sep 6;7:100040. Epub 2020 Jun 6.

MossRehab Gait and Motion Analysis Laboratory, Elkins Park, PA, USA.

Etiology-specific onabotulinumtoxinA utilization to manage spasticity is largely unknown. In this 1-year interim analysis, we evaluated real-world onabotulinumtoxinA utilization and effectiveness across several etiologies from the Adult Spasticity International Registry (ASPIRE) study. ASPIRE is a multicenter, prospective, observational registry (NCT01930786) examining stroke, multiple sclerosis [MS], cerebral palsy [CP], traumatic brain injury [TBI], and spinal cord injury [SCI] patients with spasticity treated with onabotulinumtoxinA at the clinician's discretion. Assessments included onabotulinumtoxinA utilization (each session), clinician (subsequent session)/patient (5±1 weeks post-treatment) satisfaction, and the Disability Assessment Scale (DAS; subsequent session). 730 patients received ≥1 onabotulinumtoxinA treatment, with 37% naïve to botulinum toxin(s) for spasticity. The most common etiology was stroke (n=411, 56%), followed by MS (N=119, 16%), CP (N=77, 11%), TBI (N=45, 6%), and SCI (N=42, 6%). The total body mean cumulative dose (±SD) of onabotulinumtoxinA per session ranged from 296 U (±145) in CP to 406 U (±152) in TBI. The most commonly treated upper limb presentations were clenched fist (stroke, MS, and SCI), flexed wrist (CP), and flexed elbow (TBI). Equinovarus foot was the most commonly treated lower limb presentation in all etiologies. Stroke patients showed improved DAS scores for nearly all subscales in both limbs, indicative of improved global function. All etiologies showed improved lower limb mobility DAS scores. Across all sessions, clinicians (range: 87.4% [SCI]-94.2% [CP]) and patients (range: 67.6% [TBI]-89.7% [SCI]) reported extreme satisfaction/satisfaction that onabotulinumtoxinA helped manage spasticity, and clinicians (range: 94.6% [TBI]-98.8% [CP]) and patients (range: 88.4% [stroke]-91.2% [TBI]) would definitely/probably continue treatment. Treatment-related adverse events (TRAEs) and treatment-related serious adverse events (TRSAEs) were reported as follows: stroke: 10 TRAEs (2.2% patients), 3 TRSAEs (0.5%); MS: 5 TRAEs (4.2%), 0 TRSAEs; CP: 0 TRAEs, 0 TRSAEs; TBI: 1 TRAEs (2.2%), 0 TRSAEs; SCI: 0 TRAEs, 0 TRSAEs. No new safety signals were identified. High clinician- and patient-reported satisfaction were observed following individualized onabotulinumtoxinA treatment, as well as improved global function. Interim results from ASPIRE demonstrate etiology-specific similarities and differences in clinical approaches to manage spasticity.
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http://dx.doi.org/10.1016/j.toxcx.2020.100040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452133PMC
September 2020

Tremor in Idiopathic Cervical Dystonia - Possible Implications for Botulinum Toxin Treatment Considering the Col-Cap Classification.

Tremor Other Hyperkinet Mov (N Y) 2020 07 7;10:13. Epub 2020 Jul 7.

Parkinson-Klinik Ortenau, Kreuzbergstr, Wolfach, DE.

Background: Tremor is an important phenotypic feature of dystonia. Using the new concept (Col-Cap) of classification we examined the frequency of tremor in cervical dystonia (CD) patients, their main subtypes and muscles injected.

Methods: In this large study conducted at multiple movement disorder centres in Europe and India, between January and June 2019, we examined 293 patients with idiopathic CD who were all treated with botulinum toxin (BTX).

Results: The dystonic head tremor (DHT+) was present in 57.6 % of CD patients and they had a significantly longer duration of symptoms than patients without head tremor (DHT-). In DHT+ patients torticaput was the most common subtype and the majority (63.3%) had one or two subtypes only. There was no significant difference between the number of unilateral injections for any of the muscles in the DHT+ and DHT- groups, while the number of patients receiving bilateral injections in splenius capitis (78 vs 25; p = 0.00001), sternocleidomastoid (31 vs 6; p = 0.0005), trapezius (28 vs 9; p = 0.01), and obliquus capitis inferior (15 vs 2; p = 0.008) were significantly more in the DHT+ group. The mean doses of all three types of BTX/A were not significantly different between the two groups.

Conclusions: The frequency of head tremor was 57.6% in our CD patients and torticaput was the most common dystonic subtype associated with tremor. Simple forms of CD seemed more likely associated with head tremor, than complex forms of CD. Most of the DHT+ patients received bilateral injections. The use of 'Col-Cap' classification was helpful in the identification of muscles likely to be involved in tremor in CD patients.
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http://dx.doi.org/10.5334/tohm.63DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394191PMC
July 2020

Management of Pain in Parkinson's Disease.

J Parkinsons Dis 2020 ;10(s1):S37-S48

Parkinson-Klinik Ortenau, Wolfach, Germany.

Pain is a very frequent symptom with influence on the quality of life in Parkinson's disease (PD), but is still underdiagnosed and commonly treated only unsystematically. Pain etiology and pain character are often complex and multi-causal, and data regarding treatment recommendations are limited. Pain can be primarily related to PD but frequently it is associated with secondary diseases, such as arthrosis of the spine or joints. However, even basically PD-unrelated pain often is amplified by motor- or non-motor PD symptoms, such as akinesia or depression. Beyond an optimization of anti-parkinsonian treatment, additional pain treatment strategies are usually needed to properly address pain in PD. A careful pain history and diagnostic work-up is essential to rate the underlying pain pathophysiology and to develop a targeted therapeutic concept. This review gives an overview on how pain is treated in PD patients and how patients assess the effectiveness of these therapies; here, the manuscript focuses on pathophysiology-driven suggestions for a multimodal pain management in clinical practice.
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http://dx.doi.org/10.3233/JPD-202069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592654PMC
January 2020

[New Therapeutic Options for the Individualised Titration of Levodopa].

Fortschr Neurol Psychiatr 2021 Jan 27;89(1-02):23-28. Epub 2020 May 27.

Neurologische Klinik der Ruhr-Universität Bochum, St. Josef-Hospital, Bochum.

Levodopa is the most effective medication in the treatment of Parkinson's disease. In the course of the disease the storage facility of dopaminergic neurones deteriorates, so that the duration of the half-life period likewise converges. This results in fluctuations in performance, and also in dyskinesias as a further consequence of the narrowing therapeutic window. Therapeutically, this in turn leads to further fractioning of the levodopa dosage and a reduction of single-dose levels. There is, however, only limited scope for doing this with the conventional levodopa formulations. For this reason, the introduction of water-soluble microtablets à 5 / 1.25 mg levodopa / carbidopa can be regarded as a beneficial extension permitting for fine titration of the dopaminergic stimulation. Here we present this new therapeutic principle, the available data and concepts for clinical use.
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http://dx.doi.org/10.1055/a-1158-9281DOI Listing
January 2021

[Structure and efferences of the substantia nigra pars compacta in Parkinson's disease].

Fortschr Neurol Psychiatr 2020 Sep 12;88(9):591-599. Epub 2020 May 12.

Krankenhaus Lindenbrunn, Coppenbrügge.

There is consensus that the neuropathological characteristic of Parkinson's disease (PD) is the neuronal cell loss of the substantia nigra pars compacta (SNc) in connection with a Lewy pathology. The transsynaptic spread of Lewy pathology is considered essential in PD pathogenesis. Therefore, the knowledge of pre-existing neuroanatomical connections of the SNc is essential. We describe recent animal experiments on the afferent and efferent projections of the SNc and discuss the evidence for and against the sequential transsynaptic spread of Lewy pathology in the pathogenesis of PD.
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http://dx.doi.org/10.1055/a-1149-9280DOI Listing
September 2020

Cervical dystonia - improving the effectiveness of botulinum toxin therapy.

Neurol Neurochir Pol 2020 14;54(3):232-242. Epub 2020 Apr 14.

Department of Neurological-Psychiatric Nursing, Medical University of Gdańsk, Poland.

Introduction: Cervical dystonia is the most frequent form of focal dystonia. It is characterised by involuntary muscular contractions resulting in abnormal head/neck and shoulder movements and postures, which can be associated with tremor and pain. Local intramuscular injections of botulinum toxin type A (BoNT-A) is the treatment of choice, being both effective and well-tolerated. However, a considerable number (c. 30%) of patients discontinue this treatment. The aim of this review was to analyse the factors possibly responsible for treatment failures of cervical dystonia (CD), with special regard to the new classification known as the 'Col-Cap' concept and non-motor symptoms.

Clinical Implications: Several factors analysed in this review are responsible for effective treatment: proper diagnosis of dystonia and exclusion of pseudodystonias, correct recognition of dystonia pattern and identification of new patterns according to the Col-Cap concept, muscle selection and precise injections under electromyography (EMG) and/or ultrasonography (US) guidance. Furthermore, concomitant diagnosis and treatment of non-motor symptoms such as depression, anxiety, fatigue, sleep problems, phobias and stigmatisation are crucial in obtaining the best overall effect of the treatment. Primary and secondary immunisation and non-responsiveness seem to be marginal problems nowadays due to a low potential of new BoNT-A formulations to produce neutralising antibodies.

Future Directions: There is a need for new and relevant scales combining the Col-Cap concept patterns with non-motor symptoms and quality of life. There is also a lack of specific rehabilitation protocols which could enhance BoNT-A treatment results.
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http://dx.doi.org/10.5603/PJNNS.a2020.0021DOI Listing
August 2020

Preferred muscles in cervical dystonia.

Neurol Neurochir Pol 2020 30;54(3):277-279. Epub 2020 Mar 30.

Department of Neuromuscular Diseases and Department of Anatomy. CHRU Besançon, University of Franche-Comté, Besançon, France Abstract.

The classification of abnormal posture and the assessment of the affected muscles in cervical dystonia (CD) have changed in recent years. To determine the frequency of injected muscles, we studied 306 patients with CD. The mean age was 55.5 ± 13.1 years (range 21-90), 67% were female. Splenius capitis was the most commonly injected muscle (83%), followed by sternocleidomastoid (79.1%), and trapezius muscles (58.5%). The three next most common were the levator scapulae, semispinalis capitis, and obliquus capitis inferior muscles. The study shows that the most commonly injected muscles have remained unchanged over the past few decades, although the concept has changed. However, several new muscles have been added that were previously never, or hardly ever, considered.
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http://dx.doi.org/10.5603/PJNNS.a2020.0022DOI Listing
August 2020

Influence of levodopa on orthostatic hypotension in Parkinson's Disease.

Neurol Neurochir Pol 2020 27;54(2):200-203. Epub 2020 Mar 27.

Parkinson-Klinik Ortenau, Wolfach, Germany.

Aim Of The Study: Orthostatic hypotension presents in all phases of Parkinson's Disease (PD) and occurs in about 80% of patients. There is some debate in the literature as to the relationship of orthostasis to the standard drug treatments. A distinct tendency towards hypotension has been found, especially for treatment with levodopa (LD). We therefore wanted to investigate the influence of LD on blood pressure response in PD patients.

Methods: We examined prospectively PD patients using lying-to-standing orthostatic tests (the modified Schellong test). The patients underwent measurements on two consecutive days, starting in the morning after a 12-hour period of restriction of food and medication. The second measurement ensued under the same condition of food restriction but consecutive to their usual LD dosage. Measurements were performed every minute for 10 minutes after rising. Measurements compared the maximum drop in blood pressure to the average resting blood pressure (after a 10-minute period of lying recumbent).

Results: We examined 99 PD patients (72 male, 27 female) with a mean age of 74 years (SD = 7.8; range 52-88). The duration of the disease (i.e. time from first diagnosis to date of examination) was on average seven years (SD = 4.4, range 0-19 years). The drop in blood pressure after orthostasis without levodopa medication reached on average 45.46 mmHg (SD = 23.76; SEM = 2.39), and the average drop after levodopa medication was 43.75 (SD = 17.88; SEM = 1.8). There was no significant statistical difference (t[98] = 0.91; p = 0.37). Subdivision into patient groups with (n = 32) or without (n = 67) antihypertensives revealed a similar result for these subgroups, i.e. no statistically significant difference in blood pressure drop in conditions with or without levodopa administration. There was no significant correlation of Hoehn & Yahr stage with drop in blood pressure.

Conclusion: Orthostatic hypotension frequently occurs in patients with PD, occasionally with serious consequences. LD has often been viewed as essentially causing this state. Our study did not confirm this supposition, but rather revealed merely a minor association in individual cases.
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http://dx.doi.org/10.5603/PJNNS.a2020.0019DOI Listing
July 2020

What are the considerations for anti-hypertensive treatment in patients with Parkinson's disease?

Authors:
Wolfgang H Jost

Expert Opin Pharmacother 2020 07 20;21(10):1127-1130. Epub 2020 Mar 20.

Parkinson-Klinik Ortenau , Wolfach, Germany.

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http://dx.doi.org/10.1080/14656566.2020.1744565DOI Listing
July 2020

Tau Imaging in the 4-Repeat-Tauopathies Progressive Supranuclear Palsy and Corticobasal Syndrome: A 11C-Pyridinyl-Butadienyl-Benzothiazole 3 PET Pilot Study.

Clin Nucl Med 2020 Apr;45(4):283-287

Department of Nuclear Medicine.

Background And Objectives: To evaluate tau PET using C-pyridinyl-butadienyl-benzothiazole 3 (C-PBB3) in the 4-repeat (4R)-tauopathies progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS).

Methods: Retrospective analysis of C-PBB3 PET in 2, 7, and 2 patients with CBS, PSP, and Alzheimer dementia (AD), respectively. Normalized C-PBB3 uptake in clusters with significant hypometabolism on F-FDG-PET and corresponding atlas-based volumes of interest was compared between diagnostic groups.

Results: In accordance with visually appreciable group differences, C-PBB3 uptake was significantly higher in dorsolateral frontal and motor cortex in CBS patients and frontal and temporal cortices in AD patients as compared with PSP patients. Patients with PSP showed mildly but significantly higher uptake in midbrain compared with AD patients.

Conclusions: In line with known neuropathological changes, the spatial pattern and magnitude of C-PBB3 tau binding differ between CBS, PSP, and AD, which may be of diagnostic utility. Thus, C-PBB3 offers a promising lead structure for development of ligands for tau imaging, including 4R-tauopathies.
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http://dx.doi.org/10.1097/RLU.0000000000002949DOI Listing
April 2020

Individualized OnabotulinumtoxinA Treatment for Upper Limb Spasticity Resulted in High Clinician- and Patient-Reported Satisfaction: Long-Term Observational Results from the ASPIRE Study.

PM R 2020 11 27;12(11):1120-1133. Epub 2020 Feb 27.

MossRehab Gait and Motion Analysis Laboratory, Elkins Park, PA.

Introduction: OnabotulinumtoxinA treatment for spasticity is dependent on numerous factors and varies according to selected treatment goals.

Objective: To examine real-world onabotulinumtoxinA treatment utilization and effectiveness in patients with upper limb spasticity over 2 years from the Adult Spasticity International Registry (ASPIRE) study.

Design: Multicenter, prospective, observational registry (NCT01930786).

Setting: Fifty-four international clinical sites in North America, Europe, and Asia.

Patients: Adults (naïve or non-naïve to botulinum toxins for spasticity) with upper limb focal spasticity related to upper motor neuron syndrome across multiple etiologies.

Interventions: OnabotulinumtoxinA administered at clinician's discretion.

Main Outcome Measures: OnabotulinumtoxinA utilization, clinician and patient satisfaction.

Results: Four hundred eighty-four patients received ≥1 treatment of onabotulinumtoxinA for upper limb spasticity. Patients were on average 55.1 years old, 50.8% male, predominantly Caucasian (72.3%), and 38.6% were naïve to botulinum toxins. Stroke was the most frequently reported underlying etiology (74.0%). Most patients (81.2%) had moderate to severe spasticity at baseline. The most commonly treated upper limb clinical presentation was clenched fist (79.1% of patients). Across all presentations, onabotulinumtoxinA doses ranged between 5-600U. Electromyography (EMG) was most often utilized to localize muscles (≥57.0% of treatment sessions). Clinicians (92.9% of treatment sessions) and patients (85.7%) reported being extremely satisfied/satisfied that treatment helped manage spasticity, and clinicians (98.6%) and patients (92.2%) would definitely/probably continue onabotulinumtoxinA treatment. One hundred seventy-nine patients (37.0%) reported 563 adverse events (AEs); 15 AEs in 14 patients (2.9%) were considered treatment related. Sixty-nine patients (14.3%) reported 137 serious AEs; 3 serious AEs in 2 patients (0.4%) were considered treatment related. No new safety signals were identified.

Conclusions: ASPIRE captured the real-world individualized nature of onabotulinumtoxinA utilization for upper limb spasticity over 2 years, with consistently high clinician- and patient-reported satisfaction. Data in this primary analysis will guide clinical use of onabotulinumtoxinA, as well as provide insights to improve educational programs on spasticity management.
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http://dx.doi.org/10.1002/pmrj.12328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687094PMC
November 2020

Injection into the Longus Colli Muscle via the Thyroid Gland.

Tremor Other Hyperkinet Mov (N Y) 2019 6;9. Epub 2019 Dec 6.

Parkinson-Klinik Ortenau, Wolfach, DE.

Background: Anterior forms of cervical dystonia are considered to be the most difficult to treat because of the deep cervical muscles that can be involved.

Case Report: We report the case of a woman with cervical dystonia who presented with anterior sagittal shift, which required injections through the longus colli muscle to obtain a satisfactory outcome. The approach via the thyroid gland was chosen.

Discussion: The longus colli muscle can be injected under electromyography (EMG), computed tomography (CT), ultrasonography (US), or endoscopy guidance. We recommend using both ultrasonography and electromyography guidance as excellent complementary techniques for injection at the C5-C6 level.
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http://dx.doi.org/10.7916/tohm.v0.718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898894PMC
September 2020

Frequency of different subtypes of cervical dystonia: a prospective multicenter study according to Col-Cap concept.

J Neural Transm (Vienna) 2020 01 11;127(1):45-50. Epub 2019 Dec 11.

Service de Neurologie et Pathologie du Mouvement, CHRU de Lille, Lille, France.

Patients with cervical dystonia (CD) may present with head and/or neck movements in the coronal, sagittal or transverse plane. According to the Col-Cap concept, CD postures are classified in torti-, latero-, ante- and retrocollis/caput patterns. The frequency of these different subtypes has to be evaluated. Between January and June 2019, we examined 306 patients (55.5 ± 13.1 years, 67% female) with CD according to the Col-Cap concept. They were all treated with botulinum toxin. This prospective study took place in seven different movement disorder centers. The most common primary form was torticaput (49%), the second most common was laterocaput (16.7%). All other subtypes were less than 10% of the study population. Pure forms were observed in 16.3% of patients only. Torticaput was combined in 46% with laterocaput, and in 20.7% with retrocaput. Laterocaput was combined mainly with torticaput (45.1%), laterocollis (33.2%) or retrocaput (23.5%). Shift forms were found in 14.7%, but diagnosed only in 3.9%. On average, the patients had 2.51 (± SD 1.09) subtypes each. Tremor was observed in 55.6%. The mean number of injected muscles was 4.4 (SD 1.6). The most often injected muscles were splenius capitis (83%), sternocleidomatoideus (79.1%), and upper trapezius (58.5%). This is the first multicenter study to examine the frequency of different subtypes of CD according to the Col-Cap concept. The caput subforms are more common than the cervical types, with torticaput as the most common one. Shift forms were diagnosed less often than described. Pure forms are very rare, combinations of 2-6 subtypes are common (83.7%). Sternocleidomatoideus, splenius capitis and trapezius muscles were still injected most often, but the muscles rarely injected in the past such as levator scapulae (48.7%), obliquus capitis inferior (35.3%) and longissimus (16.7%) were considered quite often. Since optimal therapy results depend on the injection of the right muscles, the correct classification should optimize the treatment outcome.
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http://dx.doi.org/10.1007/s00702-019-02116-7DOI Listing
January 2020

Long-term incobotulinumtoxinA treatment for chronic sialorrhea: Efficacy and safety over 64 weeks.

Parkinsonism Relat Disord 2020 01 26;70:23-30. Epub 2019 Nov 26.

Department of Otolaryngology/Head and Neck Surgery, Columbia University College of Physicians and Surgeons, New York, NY, USA; Department of Neurology, Icahn School of Medicine at Mt. Sinai, New York, NY, USA; NY Center for Voice and Swallowing Disorders, New York, NY, USA. Electronic address:

Background: Botulinum neurotoxin (BoNT) is an effective treatment for chronic sialorrhea; however, reliable and robust evidence supporting long-term efficacy and safety is lacking. This study investigated the efficacy and safety of repeated incobotulinumtoxinA injections for chronic sialorrhea over 64 weeks.

Methods: Adults with sialorrhea were randomized (2:2:1) to incobotulinumtoxinA 75 U, incobotulinumtoxinA 100 U (n = 74 each), or placebo (n = 36) in the double-blind, placebo-controlled main period (NCT02091739). Eligible subjects entered the extension period and received dose-blinded incobotulinumtoxinA 75 or 100 U in three further 16±2-week injection cycles. Efficacy and safety assessments in subjects who received incobotulinumtoxinA throughout the study included unstimulated salivary flow rate (uSFR), subjects' Global Impression of Change Scale (GICS), Drooling Severity and Frequency Scale (DSFS), modified Radboud Oral Motor Inventory for Parkinson's Disease (mROMP) drooling, speech, and swallowing symptom scores, and incidence of adverse events (AEs).

Results: In total, 173/184 subjects (94%) completed the main period and entered the extension period; 141 subjects received incobotulinumtoxinA 75 U (n = 69) or 100 U (n = 72) in both periods. Mean uSFR decreased consistently with repeated incobotulinumtoxinA 75 and 100 U treatment and by -0.16 and -0.17, respectively, at the end-of-study visit. Subjects' GICS, DSFS, and mROMP drooling scores also improved at all assessments. mROMP speech and swallowing scores remained stable. The most common treatment-related AEs during the extension period were dry mouth (4.4% and 11.1%) and dysphagia (1.5% and 4.2%).

Conclusions: Data support long-term efficacy and safety of repeated incobotulinumtoxinA treatment for sialorrhea, with no additional safety concerns reported over 64 weeks.
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http://dx.doi.org/10.1016/j.parkreldis.2019.11.024DOI Listing
January 2020

Long-Term Efficacy of Safinamide on Symptoms Severity and Quality of Life in Fluctuating Parkinson's Disease Patients.

J Parkinsons Dis 2020 ;10(1):89-97

Department of Clinical Science and Community, Section of Medical Statistics and Biometry "GA Maccacaro", University of Milan, Milan, Italy.

Background: Parkinson's disease (PD) is characterized by a wide range of motor and non-motor symptoms. Levodopa is still the most effective drug; however, its long-term use is associated with motor complications which may deteriorate patient's quality of life. Safinamide is a unique treatment modulating both dopaminergic and glutamatergic systems. Previous results from two six months, double-blind, placebo-controlled studies demonstrated that safinamide has positive effects on both motor functions and quality of life in PD patients.

Objective: To investigate the effects of safinamide 100 mg/day over two-year treatment on PD symptoms severity and quality of life, using data from the study 018.

Methods: Data from 352 patients were analyzed to evaluate the effects of safinamide on OFF time and ON time (with no or non-troublesome dyskinesia) in the overall population and in subgroups of patients (receiving levodopa monotherapy or with other anti-Parkinson therapies), and the effects of safinamide on motor symptoms/clinical fluctuations (by means of UPDRS III and IV) and on health-related quality of life (using UPDRS II and PDQ-39 summary index score).

Results: Safinamide, administered as add-on to standard therapy in fluctuating PD patients, significantly improved motor symptoms and clinical fluctuations in the overall population and in some subgroups of patients. Additionally, safinamide improved quality of life and activities of daily living, maintaining the efficacy in the long-term.

Conclusions: The findings of these analyses suggest that safinamide may be considered an appropriate adjunct therapy in patient not sufficiently controlled. Further investigations are desirable to confirm these results in usual care setting.
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http://dx.doi.org/10.3233/JPD-191765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029312PMC
January 2020

Therapy of Sialorrhea with Botulinum Neurotoxin.

Neurol Ther 2019 Dec 21;8(2):273-288. Epub 2019 Sep 21.

Walton Centre NHS Foundation Trust, Liverpool, UK.

Botulinum neurotoxin (BoNT) is considered the treatment of choice for various symptoms and diseases such as focal dystonia and focal spasticity. The effects of BoNT on the salivary glands have also been known for years, but their use was limited because of a lack of approval studies. Now the indication of sialorrhea is approved in some countries for incobotulinumtoxinA, such as the USA and Europe, and therapy could also become the treatment of choice. According to the pivotal study, a dose of 100 units of incobotulinumtoxinA, which is divided into the parotid and submandibular glands, is recommended. RimabotulinumtoxinB is approved in the USA only. To define the value of this therapy, we must consider anatomy, physiology, and available therapies. Therapy includes conservative measures such as functional dysphagia therapy, oral or transdermal application of anticholinergics, and, in selected cases, radiotherapy and surgical procedures. A combination of different approaches is optional. On the basis of the evidence and clinical experience, BoNT injections will be the first line of pharmacotherapy for chronic sialorrhea.
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http://dx.doi.org/10.1007/s40120-019-00155-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858891PMC
December 2019

Torticaput versus Torticollis: Clinical Effects with Modified Classification and Muscle Selection.

Authors:
Wolfgang H Jost

Tremor Other Hyperkinet Mov (N Y) 2019 12;9. Epub 2019 Jul 12.

Parkinson-Klinik Ortenau, Wolfach, DE.

Background: Several different subtypes are distinguished in cervical dystonia, depending on their different levels of movement. In simple rotation, classified as torticollis spasmodicus, we now differentiate between torticollis and torticaput dependent on whether only the head or the neck is turned. The new classification system permits for different injection schemes.

Case Reports: In a retrospective study of 22 patients, we examined whether modifying the injected muscles leads to improvement in the results as evaluated in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). The results showed that both injection schemes do in fact lead to improvements while differentiating between caput and collum has significantly better effects.

Discussion: Due to our results we recommend the classification differentiating between torticollis and torticaput type.
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http://dx.doi.org/10.7916/tohm.v0.647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691609PMC
January 2020

[Therapy of sialorrhea with botulinum toxin].

Fortschr Neurol Psychiatr 2019 Oct 25;87(10):554-563. Epub 2019 Jul 25.

Krankenhaus Rummelsberg, Schwarzenbruck.

The most important salivary glands are the paired parotid and submandibular glands. Adults produce 1 to 1.5 liters of saliva which are then regularly swallowed. When the act of swallowing is disturbed, salivation occurs. More rarely, the cause can be found in increased saliva production, for example, when caused through medication. Sialorrhea impairs the quality of life substantially and is frequently often socially stigmatizing. Therapy includes conservative measures such as functional dysphagia therapy, oral or transdermal application of anticholinergics, as well as, in selected cases, radiation and surgical measures. Over the last 20 years local injection of botulinum toxin has been successfully applied in the treatment of this condition. With approval of this therapy by the European agencies, this measure will become the therapy of choice for pronounced therapy-resistant sialorrhea.
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http://dx.doi.org/10.1055/a-0958-2417DOI Listing
October 2019

Imaging cardiac sympathetic innervation with MIBG: linear conversion of the heart-to-mediastinum ratio between different collimators.

EJNMMI Phys 2019 Jul 23;6(1):12. Epub 2019 Jul 23.

Department of Nuclear Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Hugstetter Straße 55, 79106, Freiburg im Breisgau, Germany.

Background: The heart-to-mediastinum (H/M) ratio is a commonly used parameter to measure cardiac I-123 metaiodobenzylguanidine (MIBG) uptake. Since the H/M ratio is substantially influenced by the collimator type, we investigated whether an empirical linear conversion of H/M ratios between camera systems with low-energy (LE) and medium-energy (ME) collimator is possible.

Methods: We included 18 patients with parkinsonism who were referred to one of the two participating molecular imaging facilities for the evaluation of cardiac sympathetic innervation by MIBG scintigraphy. Two consecutive planar image datasets were acquired with LE and ME collimators at 4 h after MIBG administration. Linear regression analyses were performed to describe the association between the H/M ratios gained with both collimator settings, and the accuracy of a linear transfer of the H/M ratio between collimators and across centers was assessed using a leave-one-out procedure.

Results: H/M ratios acquired with LE and ME collimators showed a strong linear relationship both within each imaging facility (R = 0.99, p < 0.001 and R = 0.90, p < 0.001) and across centers (H/M-LE = 0.41 × H/M-ME + 0.63, R = 0.97, p < 0.001). A linear conversion of H/M ratios between collimators and across centers was estimated to be very accurate (mean absolute error 0.05 ± 0.04; mean relative absolute error 3.2 ± 2.6%).

Conclusions: The present study demonstrates that a simple linear conversion of H/M ratios acquired with different collimators is possible with high accuracy. This should greatly facilitate the exchange of normative data between settings and pooling of data from different institutions.
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http://dx.doi.org/10.1186/s40658-019-0250-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650508PMC
July 2019

The challenge of pain in the pharmacological management of Parkinson's disease.

Expert Opin Pharmacother 2019 Oct 10;20(15):1847-1854. Epub 2019 Jul 10.

Department of Neurology, Center for Clinical Neurosciences, University Medical Center , Hamburg , Germany.

: Pain is a common symptom in Parkinson's disease (PD), impairing quality of life. The clinical appearance and the underlying etiologies are diverse. Different subtypes of pain may occur, with musculoskeletal pain considered to be the most frequent. Often there is also a combination of different causes of pain. There is a lack of controlled studies addressing pain therapy in PD. : In this review the authors analyzed the currently available data, taking into account the available publications in the databases, especially PubMed. The authors further provided their expert perspectives on the challenges of treating pain in PD patients. : There is both nociceptive and neuropathic pain and in patients with PD, some PD-related pain and some unrelated. Diagnosis requires a thorough and differentiated history and examination, and targeted diagnostics. Therapeutically, many drugs are used, but the data is unfortunately limited and not specific. Medications used include Parkinson-related, mainly dopaminergic drugs, as well as opioids and non-opioid analgetics, anticonvulsives, antidepressants, and more recently cannabinoids. Currently, therapy is performed nonspecifically, without taking into account the special requirements of PD. Unfortunately, in many cases, pain is resistant to these therapies. In the future, both diagnostic and therapeutic efforts should be made to address this issue.
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http://dx.doi.org/10.1080/14656566.2019.1639672DOI Listing
October 2019

Dyskinesia in multiple system atrophy and progressive supranuclear palsy.

J Neural Transm (Vienna) 2019 07 13;126(7):925-932. Epub 2019 May 13.

UCL Institute of Neurology, London, UK.

In the differential diagnosis of Parkinson syndromes, the response to L-Dopa is an essential criterion for the diagnosis of idiopathic Parkinson's syndrome (IPS), and the presence of L-Dopa-induced dyskinesia (LID) is considered a supportive criterion. This implies that in the presence of LID an atypical Parkinson-syndrome (APS) is unlikely. However, dyskinesia, and in particular LID, can also be present in APS such as MSA and PSP, although less frequently, and with varying clinical appearance. We conclude that whilst presence of dyskinesia provides support for a diagnosis of IPD, they do not allow reliable differentiation from APS.
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http://dx.doi.org/10.1007/s00702-019-02012-0DOI Listing
July 2019