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BMC Medicine Aug 2022Medical cannabinoids differ in their pharmacology and may have different treatment effects. We aimed to conduct a pharmacology-based systematic review (SR) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Medical cannabinoids differ in their pharmacology and may have different treatment effects. We aimed to conduct a pharmacology-based systematic review (SR) and meta-analyses of medical cannabinoids for efficacy, retention and adverse events.
METHODS
We systematically reviewed (registered at PROSPERO: CRD42021229932) eight databases for randomized controlled trials (RCTs) of dronabinol, nabilone, cannabidiol and nabiximols for chronic pain, spasticity, nausea /vomiting, appetite, ALS, irritable bowel syndrome, MS, Chorea Huntington, epilepsy, dystonia, Parkinsonism, glaucoma, ADHD, anorexia nervosa, anxiety, dementia, depression, schizophrenia, PTSD, sleeping disorders, SUD and Tourette. Main outcomes and measures included patient-relevant/disease-specific outcomes, retention and adverse events. Data were calculated as standardized mean difference (SMD) and ORs with confidence intervals (CI) via random effects. Evidence quality was assessed by the Cochrane Risk of Bias and GRADE tools.
RESULTS
In total, 152 RCTs (12,123 participants) were analysed according to the type of the cannabinoid, outcome and comparator used, resulting in 84 comparisons. Significant therapeutic effects of medical cannabinoids show a large variability in the grade of evidence that depends on the type of cannabinoid. CBD has a significant therapeutic effect for epilepsy (SMD - 0.5[CI - 0.62, - 0.38] high grade) and Parkinsonism (- 0.41[CI - 0.75, - 0.08] moderate grade). There is moderate evidence for dronabinol for chronic pain (- 0.31[CI - 0.46, - 0.15]), appetite (- 0.51[CI - 0.87, - 0.15]) and Tourette (- 1.01[CI - 1.58, - 0.44]) and moderate evidence for nabiximols on chronic pain (- 0.25[- 0.37, - 0.14]), spasticity (- 0.36[CI - 0.54, - 0.19]), sleep (- 0.24[CI - 0.35, - 0.14]) and SUDs (- 0.48[CI - 0.92, - 0.04]). All other significant therapeutic effects have either low, very low, or even no grade of evidence. Cannabinoids produce different adverse events, and there is low to moderate grade of evidence for this conclusion depending on the type of cannabinoid.
CONCLUSIONS
Cannabinoids are effective therapeutics for several medical indications if their specific pharmacological properties are considered. We suggest that future systematic studies in the cannabinoid field should be based upon their specific pharmacology.
Topics: Cannabinoids; Chronic Pain; Dronabinol; Humans; Nausea; Vomiting
PubMed: 35982439
DOI: 10.1186/s12916-022-02459-1 -
Movement Disorders Clinical Practice Mar 2023There is overlap between movement disorders and neuroendocrine abnormalities. (Review)
Review
BACKGROUND
There is overlap between movement disorders and neuroendocrine abnormalities.
OBJECTIVES AND METHODS
To provide a systematic review on the association of thyroid dysfunction and movement disorders. Thyroid physiological function and classical thyroid disorders highlighting typical and atypical manifestations including movement disorders, as well as diagnostic procedures, and treatments are discussed.
RESULTS
Hypothyroidism may be associated with hypokinetic and hyperkinetic disorders. There is debate whether their concomitance reflects a causal link, is coincidence, or the result of one unmasking the other. Hypothyroidism-associated parkinsonism may resemble idiopathic Parkinson's disease. Hypothyroidism-associated hyperkinetic disorders mainly occur in the context of steroid-responsive encephalopathy with autoimmune thyroiditis, that is, Hashimoto disease, mostly manifesting with tremor, myoclonus, and ataxia present in 28-80%, 42-65% and 33-65% in larger series. Congenital hypothyroidism manifesting with movement disorders, mostly chorea and dystonia, due to Mendelian genetic disease are rare.Hyperthyroidism on the other hand mostly manifests with hyperkinetic movement disorders, typically tremor (present in three quarters of patients). Chorea (present in about 2% of hyperthyroid patients), dystonia, myoclonus, ataxia and paroxysmal movement disorders, as well as parkinsonism have also been reported, with correlation between movement intensity and thyroid hormone levels.On a group level, studies on the role of thyroid dysfunction as a risk factor for the development of PD remain non-conclusive.
CONCLUSIONS
In view of the treatability of movement disorders associated with thyroid disease, accurate diagnosis is important. The pathophysiology remains poorly understood. More detailed case documentation and systematic studies, along with experimental studies are needed.
PubMed: 36949803
DOI: 10.1002/mdc3.13656 -
Toxins Nov 2022Physiotherapy is mentioned as an adjunctive treatment to improve the symptoms of cervical dystonia in terms of pain, function and quality of life. However, botulinum... (Review)
Review
Physiotherapy is mentioned as an adjunctive treatment to improve the symptoms of cervical dystonia in terms of pain, function and quality of life. However, botulinum neurotoxin injection remains the treatment of choice. This systematic review emphasizes physical therapy and evaluates it by including six studies. The methodology is based on a previous systematic review on this topic to provide better comparability and actuality. For this purpose, two databases were searched using the previously published keywords. This time, only randomised controlled trials were evaluated to increase the power. In conclusion, additional physical therapy and active home exercise programs appear to be useful. Further research should focus on the dose-response principle to emphasize physical therapy treatment modalities.
Topics: Humans; Torticollis; Quality of Life; Physical Therapy Modalities; Botulinum Toxins; Exercise Therapy
PubMed: 36422957
DOI: 10.3390/toxins14110784 -
Chiropractic & Manual Therapies Jun 2020To investigate for congenital muscular torticollis (CMT) and positional plagiocephaly (PP) the effectiveness and safety of manual therapy, repositioning and helmet...
The effectiveness and safety of conservative interventions for positional plagiocephaly and congenital muscular torticollis: a synthesis of systematic reviews and guidance.
AIM
To investigate for congenital muscular torticollis (CMT) and positional plagiocephaly (PP) the effectiveness and safety of manual therapy, repositioning and helmet therapy (PP only) using a systematic review of systematic reviews and national guidelines.
METHODS
We searched four major relevant databases: PubMed, Embase, Cochrane and MANTIS for research studies published between the period 1999-2019. Inclusion criteria were systematic reviews that analysed results from multiple studies and guidelines that used evidence and expert opinion to recommend treatment and care approaches. Three reviewers independently selected articles by title, abstract and full paper review, and extracted data. Selected studies were described by two authors and assessed for quality. Where possible meta-analysed data for change in outcomes (range of movement and head shape) were extracted and qualitative conclusions were assessed.
RESULTS
We found 10 systematic reviews for PP and 4 for CMT. One national guideline was found for each PP and CMT. For PP, manual therapy was found to be more effective than repositioning including tummy time (moderate to high evidence) but not better than helmet therapy (low evidence). Helmet therapy was better than usual care or repositioning (low evidence); and repositioning better than usual care (moderate to high evidence). The results for CMT showed that manual therapy in the form of practitioner-led stretching had moderate favourable evidence for increased range of movement. Advice, guidance and parental support was recommended in all the guidance to reassure parents of the favourable trajectory and nature of these conditions over time.
CONCLUSIONS
Distinguishing between superiority of treatments was difficult due to the lack of standardised measurement systems, the variety of outcomes and limited high quality studies. More well powered effectiveness and efficacy studies are needed. However overall, advice and guidance on repositioning (including tummy-time) and practitioner-led stretching were low risk, potentially helpful and inexpensive interventions for parents to consider.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO 2019 CRD42019139074.
Topics: Head Protective Devices; Humans; Musculoskeletal Manipulations; Plagiocephaly, Nonsynostotic; Systematic Reviews as Topic; Torticollis
PubMed: 32522230
DOI: 10.1186/s12998-020-00321-w -
Developmental Medicine and Child... Sep 2021To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and... (Meta-Analysis)
Meta-Analysis
AIM
To update a systematic review of evidence published up to December 2015 for pharmacological/neurosurgical interventions among individuals with cerebral palsy (CP) and dystonia.
METHOD
Searches were updated (January 2016 to May 2020) for oral baclofen, trihexyphenidyl, benzodiazepines, clonidine, gabapentin, levodopa, botulinum neurotoxin (BoNT), intrathecal baclofen (ITB), and deep brain stimulation (DBS), and from database inception for medical cannabis. Eligible studies included at least five individuals with CP and dystonia and reported on dystonia, goal achievement, motor function, pain/comfort, ease of caregiving, quality of life (QoL), or adverse events. Evidence certainty was evaluated using GRADE.
RESULTS
Nineteen new studies met inclusion criteria (two trihexyphenidyl, one clonidine, two BoNT, nine ITB, six DBS), giving a total of 46 studies (four randomized, 42 non-randomized) comprising 915 participants when combined with those from the original systematic review. Very low certainty evidence supported improved dystonia (clonidine, ITB, DBS) and goal achievement (clonidine, BoNT, ITB, DBS). Low to very low certainty evidence supported improved motor function (DBS), pain/comfort (clonidine, BoNT, ITB, DBS), ease of caregiving (clonidine, BoNT, ITB), and QoL (ITB, DBS). Trihexyphenidyl, clonidine, BoNT, ITB, and DBS may increase adverse events. No studies were identified for benzodiazepines, gabapentin, oral baclofen, and medical cannabis.
INTERPRETATION
Evidence evaluating the use of pharmacological and neurosurgical management options for individuals with CP and dystonia is limited to between low and very low certainty. What this paper adds Meta-analysis suggests that intrathecal baclofen (ITB) and deep brain stimulation (DBS) may improve dystonia and pain. Meta-analysis suggests that DBS may improve motor function. Clonidine, botulinum neurotoxin, ITB, and DBS may improve achievement of individualized goals. ITB and DBS may improve quality of life. No direct evidence is available for oral baclofen, benzodiazepines, gabapentin, or medical cannabis.
Topics: Baclofen; Botulinum Toxins; Cerebral Palsy; Clonidine; Deep Brain Stimulation; Dystonia; Humans; Injections, Spinal; Levodopa; Neurosurgical Procedures; Trihexyphenidyl
PubMed: 33772789
DOI: 10.1111/dmcn.14874 -
Journal of Neurology, Neurosurgery, and... Jun 2020We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on...
OBJECTIVES
We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes.
METHODS
A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group.
RESULTS
Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years).
CONCLUSIONS
There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population.
Topics: Humans; Nervous System Diseases; Outcome Assessment, Health Care
PubMed: 32111637
DOI: 10.1136/jnnp-2019-322180 -
Pediatric Physical Therapy : the... Apr 2023To systematically review current evidence on the physical therapy assessment, intervention, and prognosis of congenital muscular torticollis (CMT) to inform the update...
PURPOSE
To systematically review current evidence on the physical therapy assessment, intervention, and prognosis of congenital muscular torticollis (CMT) to inform the update to the 2018 CMT Clinical Practice Guideline (CPG).
METHODS
Six databases were searched for studies that informed assessment, intervention, and prognosis for physical therapy management of infants with CMT.
RESULTS
Fifteen studies were included. Four studies investigated the psychometric properties of new and established assessments. Six studies informed the feasibility and efficacy of first-choice and supplemental interventions including traditional Chinese medicine and neural and visceral manipulation. One qualitative study found that parents of infants with mild and severe CMT had different concerns. Five studies informed prognosis, including factors associated with treatment duration, clinical outcomes, and use of supplemental interventions.
CONCLUSION
Newer evidence reaffirms 5 of 17 recommendations of the 2018 CMT CPG and could increase the recommendation strength to strong for neck passive range of motion.
Topics: Infant; Humans; Torticollis; Muscular Diseases; Neck; Physical Therapy Modalities
PubMed: 36637442
DOI: 10.1097/PEP.0000000000000993 -
Movement Disorders Clinical Practice Jan 2022Early evidence suggests good response to pallidal deep brain stimulation (DBS) in DYT-. (Review)
Review
BACKGROUND
Early evidence suggests good response to pallidal deep brain stimulation (DBS) in DYT-.
OBJECTIVES
We aimed to conduct a systematic review and meta-analysis to assess outcomes and identify predictors of good outcome following GPi-DBS in DYT-.
METHODS
We searched MEDLINE, Cochrane and MDS-abstracts databases using the MeSH terms " and DYT28". We included studies that reported objective outcomes following GPi-DBS in DYT-. The BFMDRS-M (Burke-Fahn-Marsden Dystonia Rating Scale- Movement) total scores pre- and post-surgery were used to quantify outcomes. We calculated pooled effects using a random effects meta-analysis and used meta-regression to identify potential effect modifiers. Multiple linear regression using individual patient data was used to identify predictors of good outcome (>50% improvement from baseline on BFMDRS-M).
RESULTS
Initial searches screened 132 abstracts of which 34 full-text articles were identified to be of potential interest. Ten studies reporting 42 individual patients, met the inclusion/exclusion criteria and were included in the final review. The mean age at onset was 6.4 ± 5.7 years and 40% were male. The median follow-up was 12 months (range: 1-264 months). GPi-DBS resulted in median BFMDRS-M improvement of 42.7% (range: -103.5% to 95.9%) postoperatively. Pooled proportion of patients experiencing clinical improvement >50% on BFMDRS-M was 41% (95% CI: 27%-57%). Male gender [β: 22.6, 95% CI: 8.0-37.3, = 0.004), and higher pre-operative BFMDRS-M score [β: 0.62, 95% CI: 0.36-0.87, < 0.001) were independently associated with better outcome.
CONCLUSION
-associated dystonia responds effectively to pallidal stimulation. The outcome is better in males and those with more severe dystonia at baseline.
PubMed: 35005062
DOI: 10.1002/mdc3.13374 -
Movement Disorders : Official Journal... Feb 2022Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive... (Review)
Review
BACKGROUND
Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive dystonia (DRD). Diagnosis and treatment are often delayed due to high between- and within-group variability.
OBJECTIVES
Comprehensively analyzed individual genotype, phenotype, treatment response, and biochemistry information.
METHODS
734 DRD patients and 151 asymptomatic GCH1 mutation carriers were included using an MDSGene systematic literature review and an automated classification approach to distinguish between different forms of monogenic DRDs.
RESULTS
Whereas dystonia, L-Dopa responsiveness, early age at onset, and diurnal fluctuations were identified as red flags, parkinsonism without dystonia was rarely reported (11%) and combined with dystonia in only 18% of patients. While sex was equally distributed in autosomal recessive DRD, there was female predominance in autosomal dominant DYT/PARK-GCH1 patients accompanied by a lower median age at onset and more dystonia in females compared to males. Accordingly, the majority of asymptomatic heterozygous GCH1 mutation carriers (>8 years of age) were males. Multiple other subgroup-specific characteristics were identified, showing high accuracy in the automated classification approach: Seizures and microcephaly were mostly seen in DYT/PARK-PTS, autonomic symptoms appeared commonly in DYT/PARK-TH and DYT/PARK-PTS, and sleep disorders and oculogyric crises in DYT/PARK-SPR. Biochemically, homovanillic acid and 5-hydroxyindoleacetic acid in CSF were reduced in most DRDs, but neopterin and biopterin were increased only in DYT/PARK-PTS and DYT/PARK-SPR. Hyperphenylalaninemia was seen in DYT/PARK-PTS, DYT/PARK-QDPR, and rarely reported in autosomal recessive DYT/PARK-GCH1.
CONCLUSIONS
Our indicators will help to specify diagnosis and accelerate start of treatment. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Dystonia; Dystonic Disorders; Female; GTP Cyclohydrolase; Genotype; Humans; Male; Phenotype
PubMed: 34908184
DOI: 10.1002/mds.28874 -
Movement Disorders : Official Journal... Mar 2021Stereotactic lesioning of the bilateral globus pallidus (GPi) was one of the first surgical treatments for medication-refractory dystonia but has largely been abandoned... (Review)
Review
Stereotactic lesioning of the bilateral globus pallidus (GPi) was one of the first surgical treatments for medication-refractory dystonia but has largely been abandoned in clinical practice after the introduction of deep brain stimulation (DBS). However, some patients with dystonia are not eligible for DBS. Therefore, we reviewed the efficacy, safety, and sustainability of bilateral pallidotomy by conducting a systematic review of individual patient data (IPD). Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and IPD were followed. In May 2020, Medline, Embase, Web of Science, and Cochrane Library were searched for studies reporting on outcome of bilateral pallidotomy for dystonia. If available, IPD were collected. In this systematic review, 100 patients from 33 articles were evaluated. Adverse events were reported in 20 patients (20%), of which 8 were permanent (8%). Pre-and postoperative Burke-Fahn-Marsden Dystonia Rating Movement Scale scores were available for 53 patients. A clinically relevant improvement (>20%) of this score was found in 42 of 53 patients (79%). Twenty-five patients with status dystonicus (SD) were described. In all but 2 the SD resolved after bilateral pallidotomy. Seven patients experienced a relapse of SD. Median-reported follow-up was 12 months (n = 83; range: 2-180 months). Based on the current literature, bilateral pallidotomy is an effective and relatively safe procedure for certain types of dystonia, particularly in medication-refractory SD. Although due to publication bias the underreporting of negative outcomes is very likely, bilateral pallidotomy is a reasonable alternative to DBS in selected dystonia patients. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Deep Brain Stimulation; Dystonia; Dystonic Disorders; Globus Pallidus; Humans; Movement Disorders; Pallidotomy; Treatment Outcome
PubMed: 33215750
DOI: 10.1002/mds.28384