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Translational Psychiatry Jun 2024Mapping brain-behaviour associations is paramount to understand and treat psychiatric disorders. Standard approaches involve investigating the association between one... (Review)
Review
Mapping brain-behaviour associations is paramount to understand and treat psychiatric disorders. Standard approaches involve investigating the association between one brain and one behavioural variable (univariate) or multiple variables against one brain/behaviour feature ('single' multivariate). Recently, large multimodal datasets have propelled a new wave of studies that leverage on 'doubly' multivariate approaches capable of parsing the multifaceted nature of both brain and behaviour simultaneously. Within this movement, canonical correlation analysis (CCA) and partial least squares (PLS) emerge as the most popular techniques. Both seek to capture shared information between brain and behaviour in the form of latent variables. We provide an overview of these methods, review the literature in psychiatric disorders, and discuss the main challenges from a predictive modelling perspective. We identified 39 studies across four diagnostic groups: attention deficit and hyperactive disorder (ADHD, k = 4, N = 569), autism spectrum disorders (ASD, k = 6, N = 1731), major depressive disorder (MDD, k = 5, N = 938), psychosis spectrum disorders (PSD, k = 13, N = 1150) and one transdiagnostic group (TD, k = 11, N = 5731). Most studies (67%) used CCA and focused on the association between either brain morphology, resting-state functional connectivity or fractional anisotropy against symptoms and/or cognition. There were three main findings. First, most diagnoses shared a link between clinical/cognitive symptoms and two brain measures, namely frontal morphology/brain activity and white matter association fibres (tracts between cortical areas in the same hemisphere). Second, typically less investigated behavioural variables in multivariate models such as physical health (e.g., BMI, drug use) and clinical history (e.g., childhood trauma) were identified as important features. Finally, most studies were at risk of bias due to low sample size/feature ratio and/or in-sample testing only. We highlight the importance of carefully mitigating these sources of bias with an exemplar application of CCA.
Topics: Humans; Brain; Mental Disorders; Autism Spectrum Disorder; Depressive Disorder, Major; Canonical Correlation Analysis; Attention Deficit Disorder with Hyperactivity; Least-Squares Analysis
PubMed: 38824172
DOI: 10.1038/s41398-024-02954-4 -
Neurosurgery Sep 2023Focused ultrasound (FUS-T) and stereotactic radiosurgery thalamotomy (SRS-T) targeting the ventral intermediate nucleus are effective incisionless surgeries for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Focused ultrasound (FUS-T) and stereotactic radiosurgery thalamotomy (SRS-T) targeting the ventral intermediate nucleus are effective incisionless surgeries for essential tremor (ET). However, their efficacy for tremor reduction and, importantly, adverse event incidence have not been directly compared.
OBJECTIVE
To present a comprehensive systematic review with network meta-analysis examining both efficacy and adverse events (AEs) of FUS-T vs SRS-T for treating medically refractory ET.
METHODS
We conducted a systematic review and network meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using the PubMed and Embase databases. We included all primary FUS-T/SRS-T studies with approximately 1-year follow-up, with unilateral Fahn-Tolosa-Marin Tremor Rating Scale or Clinical Rating Scale for Tremor scores prethalamotomy/post-thalamotomy and/or AEs. The primary efficacy outcome was Fahn-Tolosa-Marin Tremor Rating Scale A+B score reduction. AEs were reported as an estimated incidence.
RESULTS
Fifteen studies of 464 patients and 3 studies of 62 patients met inclusion criteria for FUS-T/SRS-T efficacy comparison, respectively. Network meta-analysis demonstrated similar tremor reduction between modalities (absolute tremor reduction: FUS-T: -11.6 (95% CI: -13.3, -9.9); SRS-T: -10.3 (95% CI: -14.2, -6.0). FUS-T had a greater 1-year adverse event rate, particularly imbalance and gait disturbances (10.5%) and sensory disturbances (8.3%). Contralateral hemiparesis (2.7%) often accompanied by speech impairment (2.4%) were most common after SRS-T. There was no correlation between efficacy and lesion volume.
CONCLUSION
Our systematic review found similar efficacy between FUS-T and SRS-T for ET, with trend toward higher efficacy yet greater adverse event incidence with FUS-T. Smaller lesion volumes could mitigate FUS-T off-target effects for greater safety.
Topics: Humans; Essential Tremor; Magnetic Resonance Imaging; Radiosurgery; Thalamus; Treatment Outcome; Tremor; Ultrasonic Surgical Procedures; Network Meta-Analysis
PubMed: 37010324
DOI: 10.1227/neu.0000000000002462 -
Tremor and Other Hyperkinetic Movements... 2023Movement disorders, particularly chorea, are uncommon in inborn errors of metabolism, but their identification is essential for improved clinical outcomes. In this... (Review)
Review
BACKGROUND
Movement disorders, particularly chorea, are uncommon in inborn errors of metabolism, but their identification is essential for improved clinical outcomes. In this context, comprehensive descriptions of movement disorders are limited and primarily derived from single cases or small patient series, highlighting the need for increased awareness and additional research in this field.
METHODS
A systematic review was conducted using the MEDLINE database and GeneReviews. The search included studies on inborn errors of metabolism associated with chorea, athetosis, or ballismus. The review adhered to PRISMA guidelines.
RESULTS
The systematic review analyzed 76 studies out of 2350 records, encompassing the period from 1964 to 2022. Chorea was observed in 90.1% of the 173 patients, followed by athetosis in 5.7%. Various inborn errors of metabolism showed an association with chorea, with trace elements and metals being the most frequent. Cognitive and developmental abnormalities were common in the cohort. Frequent neurological features included seizures, dysarthria, and optic atrophy, whereas non-neurological features included, among others, facial dysmorphia and failure to thrive. Neuroimaging and biochemical testing played crucial roles in aiding diagnosis, revealing abnormal findings in 34.1% and 47.9% of patients, respectively. However, symptomatic treatment efficacy for movement disorders was limited.
DISCUSSION
This study emphasizes the complexities of chorea in inborn errors of metabolism. A systematic approach with red flags, biochemical testing, and neuroimaging is required for diagnosis. Collaboration between neurologists, geneticists, and metabolic specialists is crucial for improving early detection and individualized treatment. Utilizing genetic testing technologies and potential therapeutic avenues can aid in the improvement of patient outcomes.
Topics: Humans; Chorea; Athetosis; Metabolism, Inborn Errors; Movement Disorders; Dyskinesias
PubMed: 37810989
DOI: 10.5334/tohm.801 -
European Journal of Neurology Oct 2023Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While... (Review)
Review
BACKGROUND
Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein-IgG associated disease (MOGAD) represent major and well-defined differential diagnoses, non-demyelinating NMOSD mimics remain poorly characterized.
METHODS
We conducted a systematic review on PubMed/MEDLINE to identify reports of patients with non-demyelinating disorders that mimicked or were misdiagnosed as NMOSD. Three novel cases seen at the authors' institutions were also included. The characteristics of NMOSD mimics were analyzed and red flags associated with misdiagnosis identified.
RESULTS
A total of 68 patients were included; 35 (52%) were female. Median age at symptoms onset was 44 (range, 1-78) years. Fifty-six (82%) patients did not fulfil the 2015 NMOSD diagnostic criteria. The clinical syndromes misinterpreted for NMOSD were myelopathy (41%), myelopathy + optic neuropathy (41%), optic neuropathy (6%), or other (12%). Alternative etiologies included genetic/metabolic disorders, neoplasms, infections, vascular disorders, spondylosis, and other immune-mediated disorders. Common red flags associated with misdiagnosis were lack of cerebrospinal fluid (CSF) pleocytosis (57%), lack of response to immunotherapy (55%), progressive disease course (54%), and lack of magnetic resonance imaging gadolinium enhancement (31%). Aquaporin-4-IgG positivity was detected in five patients by enzyme-linked immunosorbent assay (n = 2), cell-based assay (n = 2: serum, 1; CSF, 1), and non-specified assay (n = 1).
CONCLUSIONS
The spectrum of NMOSD mimics is broad. Misdiagnosis frequently results from incorrect application of diagnostic criteria, in patients with multiple identifiable red flags. False aquaporin-4-IgG positivity, generally from nonspecific testing assays, may rarely contribute to misdiagnosis.
Topics: Humans; Female; Male; Neuromyelitis Optica; Contrast Media; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Gadolinium; Aquaporin 4; Spinal Cord Diseases; Immunoglobulin G
PubMed: 37433584
DOI: 10.1111/ene.15983 -
Journal of Personalized Medicine Feb 2024Although the reported frequency of diplopia is between 10 to 40% of patients with Parkinson's disease (PD) and other movement disorders, it remains one of the most... (Review)
Review
INTRODUCTION
Although the reported frequency of diplopia is between 10 to 40% of patients with Parkinson's disease (PD) and other movement disorders, it remains one of the most undiagnosed non-motor symptoms. Furthermore, it has a major impact on the quality of life of these patients. The aim of this study is to systematically review the literature regarding the frequency, causes, and implications of diplopia in movement disorders.
METHODOLOGY
An electronic search was conducted in March and June 2023 using the PubMed database in order to identify appropriate studies. Studies that were written in English, that represented observational, analytical studies, and case reports, and that provided information regarding diplopia in movement disorders were included in the systematic review.
RESULTS
A total of 686 articles were identified out of which 43 met the inclusion criteria. The studies included in the systematic review ranged from descriptive studies (case reports and case series) to analytical-observational studies (cross-sectional studies, prospective and retrospective cohort studies, and case-control studies). In Parkinson's disease, the incidence of diplopia ranged from 10 to 38%. In these patients, diplopia was linked to the presence of visual hallucinations and cognitive decline but also to convergence insufficiency and the presence of motor fluctuations. Cases of diplopia secondary to deep brain stimulation were also reported. Diplopia was associated with longer disease duration and worse motor and non-motor scores. Diplopia was also reported in other movement disorders such as multiple system atrophy (frequency as high as 18%) and progressive supranuclear palsy (frequency as high as 39%) and was associated with increased mortality and shorter duration in life span.
CONCLUSIONS
Diplopia occurs in up to 38% of patients with movement disorders and has a negative impact on their health-related quality of life. Treating physicians should actively ask about diplopia and other ophthalmological symptoms, as many patients do not spontaneously report them. The pathophysiology of diplopia is complex, and it involves heterogeneous peripheral and central mechanisms. The management of these patients should involve a multidisciplinary team of health professionals in order to provide appropriate, tailored management.
PubMed: 38541012
DOI: 10.3390/jpm14030270 -
American Journal of Epidemiology Jul 2023Metal exposure has been suggested as a possible environmental risk factor for Parkinson disease (PD). We searched the PubMed, EMBASE, and Cochrane databases to... (Meta-Analysis)
Meta-Analysis
Metal exposure has been suggested as a possible environmental risk factor for Parkinson disease (PD). We searched the PubMed, EMBASE, and Cochrane databases to systematically review the literature on the relationship between metal exposure and PD risk and to examine the overall quality of each study and the exposure assessment method. A total of 83 case-control studies and 5 cohort studies published during the period 1963-July 2021 were included, of which 73 were graded as being of low or moderate overall quality. Investigators in 69 studies adopted self-reported exposure and biomonitoring after disease diagnosis for exposure assessment approaches. The meta-analyses showed that concentrations of copper and iron in serum and concentrations of zinc in either serum or plasma were lower, while concentrations of magnesium in CSF and zinc in hair were higher, among PD cases as compared with controls. Cumulative lead levels in bone were found to be associated with increased risk of PD. We did not find associations between other metals and PD. The current level of evidence for associations between metals and PD risk is limited, as biases from methodological limitations cannot be ruled out. High-quality studies assessing metal levels before disease onset are needed to improve our understanding of the role of metals in the etiology of PD.
Topics: Humans; Cohort Studies; Copper; Lead; Parkinson Disease; Zinc; Metals
PubMed: 37022311
DOI: 10.1093/aje/kwad082 -
Frontiers in Neurology 2023Past research indicates a higher prevalence, incidence, and severe clinical manifestations of alpha-synucleinopathies in men, leading to a suggestion of neuroprotective...
BACKGROUND
Past research indicates a higher prevalence, incidence, and severe clinical manifestations of alpha-synucleinopathies in men, leading to a suggestion of neuroprotective properties of female sex hormones (especially estrogen). The potential pathomechanisms of any such effect on alpha-synucleinopathies, however, are far from understood. With that aim, we undertook to systematically review, and to critically assess, contemporary evidence on sex and gender differences in alpha-synucleinopathies using a bench-to-bedside approach.
METHODS
In this systematic review, studies investigating sex and gender differences in alpha-synucleinopathies (Rapid Eye Movement (REM) Behavior Disorder (RBD), Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) from 2012 to 2022 were identified using electronic database searches of PubMed, Embase and Ovid.
RESULTS
One hundred sixty-two studies were included; 5 RBD, 6 MSA, 20 DLB and 131 PD studies. Overall, there is conclusive evidence to suggest sex-and gender-specific manifestation in demographics, biomarkers, genetics, clinical features, interventions, and quality of life in alpha-synucleinopathies. Only limited data exists on the effects of distinct sex hormones, with majority of studies concentrating on estrogen and its speculated neuroprotective effects.
CONCLUSION
Future studies disentangling the underlying sex-specific mechanisms of alpha-synucleinopathies are urgently needed in order to enable novel sex-specific therapeutics.
PubMed: 37545736
DOI: 10.3389/fneur.2023.1204104 -
International Journal of Molecular... Dec 2023Inborn errors of metabolism (IEMs) comprise a diverse group of monogenic disorders caused by enzyme deficiencies that result either in a toxic accumulation of metabolic... (Meta-Analysis)
Meta-Analysis Review
Inborn errors of metabolism (IEMs) comprise a diverse group of monogenic disorders caused by enzyme deficiencies that result either in a toxic accumulation of metabolic intermediates or a shortage of essential end-products. Certain IEMs, like phenylketonuria (PKU), necessitate stringent dietary intervention that could lead to microbiome dysbiosis, thereby exacerbating the clinical phenotype. The objective of this systematic review was to examine the impact of PKU therapies on the intestinal microbiota. This research was conducted following the PRISMA Statement, with data from PubMed, Scopus, ScienceDirect, and Web of Science. A total of 18 articles meeting the inclusion criteria were published from 2011 to 2022. Significant reductions in several taxonomic groups in individuals with PKU when compared to the control group were detected in a quantitative analysis conducted across seven studies. The meta-analysis synthesis indicates a contrast in biodiversity between PKU subjects and the control population. Additionally, the meta-regression results, derived from the Bacillota/Bacteroidota ratio data, suggest a potential influence of diet in adult PKU populations ( = 0.004). It is worth noting that the limited number of studies calls for further research and analysis in this area. Our findings indicate the necessity of enhancing understanding of microbiota variability in reaction to treatments among PKU subjects to design tailored therapeutic and nutritional interventions to prevent complications resulting from microbiota disruption.
Topics: Adult; Humans; Phenylketonurias; Diet; Gastrointestinal Microbiome
PubMed: 38139256
DOI: 10.3390/ijms242417428 -
Psychopharmacology Feb 2024Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce dopaminergic transmission but have limited activity at postsynaptic receptors and so may have antipsychotic activity with lower risk of tardive dyskinesia.
METHODS
We conducted a systematic database search from inception to September 2022 for articles describing the use of VMAT-2 inhibitors in psychosis. Inclusion criteria were as follows: Population: adults diagnosed with psychosis or schizophrenia; Intervention: treatment with tetrabenazine, deutetrabenazine or valbenazine; Comparison: comparison with placebo or/and antipsychotic drug; Outcomes: with efficacy outcomes (e.g. Brief Psychiatric Rating Scale (BPRS) change or clinician assessment) and adverse effects ratings (e.g. rating scale or clinician assessment or dropouts); and Studies: in randomised controlled trials and non-randomised studies.
RESULTS
We identified 4892 records relating to VMAT-2 inhibitor use of which 5 (173 participants) met our a priori meta-analysis inclusion criteria. VMAT-2 inhibitors were more effective than placebo for the outcome 'slight improvement' (risk ratio (RR) = 1.77 (95% CI 1.03, 3.04)) but not for 'moderate improvement' (RR 2.81 (95% CI 0.27, 29.17). VMAT-2 inhibitors were as effective as active comparators on both measures for-'slight improvement' (RR 1.05 (95% CI 0.6, 1.81)) and 'moderate improvement' (RR 1.11 (95% CI 0.51, 2.42). Antipsychotic efficacy was also suggested by a narrative review of 37 studies excluded from the meta-analysis.
CONCLUSIONS
VMAT-2 inhibitors may have antipsychotic activity and may offer promise for treatment of psychosis with the potential for a reduced risk of TD.
Topics: Adult; Humans; Antipsychotic Agents; Psychotic Disorders; Schizophrenia; Tardive Dyskinesia; Tetrabenazine; Vesicular Monoamine Transport Proteins
PubMed: 38238580
DOI: 10.1007/s00213-023-06488-3 -
Parkinsonism & Related Disorders Mar 2024Numerous smartphone and tablet applications (apps) are available to monitor movement disorders, but an overview of their purpose and stage of development is missing. (Review)
Review
BACKGROUND
Numerous smartphone and tablet applications (apps) are available to monitor movement disorders, but an overview of their purpose and stage of development is missing.
OBJECTIVES
To systematically review published literature and classify smartphone and tablet apps with objective measurement capabilities for the diagnosis, monitoring, assessment, or treatment of movement disorders.
METHODS
We systematically searched for publications covering smartphone or tablet apps to monitor movement disorders until November 22nd 2023. We reviewed the target population, measured domains, purpose, and technology readiness level (TRL) of the proposed app and checked their availability in common app stores.
RESULTS
We identified 113 apps. Most apps were developed for Parkinson's disease specifically (n = 82; 73%) or for movement disorders in general (n = 17; 15%). Apps were either designed to momentarily assess symptoms (n = 65; 58%), support treatment (n = 22; 19%), aid in diagnosis (n = 16; 14%), or passively track symptoms (n = 11; 10%). Commonly assessed domains across movement disorders included fine motor skills (n = 34; 30%), gait (n = 36; 32%), and tremor (n = 32; 28%) for the motor domain and cognition (n = 16; 14%) for the non-motor domain. Twenty-six (23%) apps were proof-of-concepts (TRL 1-3), while most apps were tested in a controlled setting (TRL 4-6; n = 63; 56%). Twenty-four apps were tested in their target setting (TRL 7-9) of which 10 were accessible in common app stores or as Android Package.
CONCLUSIONS
The development of apps strongly gravitates towards Parkinson's disease and a selection of motor symptoms. Collaboration, re-use and further development of existing apps is encouraged to avoid reinventions of the wheel.
Topics: Humans; Mobile Applications; Smartphone; Parkinson Disease; Tremor
PubMed: 38184466
DOI: 10.1016/j.parkreldis.2023.105988