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Tremor and Other Hyperkinetic Movements... 2024Opsoclonus is a rare disorder characterized by conjugate multidirectional, horizontal, vertical, and torsional saccadic oscillations, without intersaccadic interval,...
BACKGROUND
Opsoclonus is a rare disorder characterized by conjugate multidirectional, horizontal, vertical, and torsional saccadic oscillations, without intersaccadic interval, resulting from dysfunction within complex neuronal pathways in the brainstem and cerebellum. While most cases of opsoclonus are associated with autoimmune or paraneoplastic disorders, infectious agents, trauma, or remain idiopathic, opsoclonus can also be caused by medications affecting neurotransmission. This review was prompted by a case of opsoclonus occurring in a patient with Multiple System Atrophy, where amantadine, an NMDA-receptor antagonist, appeared to induce opsoclonus.
METHODS
Case report of a single patient and systematized review of toxic/drug-induced opsoclonus, selecting articles based on predefined criteria and assessing the quality of included studies.
RESULTS
The review included 30 articles encompassing 158 cases of toxic/drug-induced opsoclonus. 74% of cases were attributed to bark scorpion poisoning, followed by 9% of cases associated with chlordecone intoxication. The remaining cases were due to various toxics/drugs, highlighting the involvement of various neurotransmitters, including acetylcholine, glutamate, GABA, dopamine, glycine, and sodium channels, in the development of opsoclonus.
CONCLUSION
Toxic/drug-induced opsoclonus is very rare. The diversity of toxics/drugs impacting different neurotransmitter systems makes it challenging to define a unifying mechanism, given the intricate neuronal pathways underlying eye movement physiology and opsoclonus pathophysiology.
Topics: Humans; Male; Amantadine; Multiple System Atrophy; Ocular Motility Disorders; Aged
PubMed: 38737300
DOI: 10.5334/tohm.832 -
Journal of Neurology Jun 2024We conducted a systematic review to identify existing ICD-10 coding validation studies in progressive supranuclear palsy and corticobasal syndrome [PSP/CBS]) and, in a...
Accuracy of routinely collected hospital administrative discharge data and death certificate ICD-10 diagnostic coding in progressive supranuclear palsy and corticobasal syndrome: a systematic review and validation study.
BACKGROUND
We conducted a systematic review to identify existing ICD-10 coding validation studies in progressive supranuclear palsy and corticobasal syndrome [PSP/CBS]) and, in a new study, evaluated the accuracy of ICD-10 diagnostic codes for PSP/CBS in Scottish hospital inpatient and death certificate data.
METHODS
Original studies that assessed the accuracy of specific ICD-10 diagnostic codes in PSP/CBS were sought. Separately, we estimated the positive predictive value (PPV) of specific codes for PSP/CBS in inpatient hospital data (SMR01, SMR04) compared to clinical diagnosis in four regions. Sensitivity was assessed in one region due to a concurrent prevalence study. For PSP, the consistency of the G23.1 code in inpatient and death certificate coding was evaluated across Scotland.
RESULTS
No previous ICD-10 validation studies were identified. 14,767 records (SMR01) and 1497 records (SMR04) were assigned the candidate ICD-10 diagnostic codes between February 2011 and July 2019. The best PPV was achieved with G23.1 (1.00, 95% CI 0.93-1.00) in PSP and G23.9 in CBS (0.20, 95% CI 0.04-0.62). The sensitivity of G23.1 for PSP was 0.52 (95% CI 0.33-0.70) and G31.8 for CBS was 0.17 (95% CI 0.05-0.45). Only 38.1% of deceased G23.1 hospital-coded cases also had this coding on their death certificate: the majority (49.0%) erroneously assigned the G12.2 code.
DISCUSSION
The high G23.1 PPV in inpatient data shows it is a useful tool for PSP case ascertainment, but death certificate coding is inaccurate. The PPV and sensitivity of existing ICD-10 codes for CBS are poor due to a lack of a specific code.
Topics: Humans; Supranuclear Palsy, Progressive; International Classification of Diseases; Death Certificates; Patient Discharge; Basal Ganglia Diseases; Clinical Coding
PubMed: 38609666
DOI: 10.1007/s00415-024-12280-w -
Brain Injury Jun 2024Mild traumatic brain injury (mTBI) can cause persistent symptoms suggestive of oculomotor deficits. This research synthesized evidence on restitutive interventions for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mild traumatic brain injury (mTBI) can cause persistent symptoms suggestive of oculomotor deficits. This research synthesized evidence on restitutive interventions for reducing oculomotor deficits in adults with mTBI to understand if these interventions have clinical utility for improving recovery.
METHODS
Medline, EMBASE, CINHAL, PsychInfo, and Scopus, databases were searched for experimental studies published in English. We rated risk of bias (RoB) using recommended tools, and the certainty of the evidence according to GRADE guidelines. We conducted meta-analyses for similar outcomes reported in at least two studies.
RESULTS
Out of 5,328 citations, 12 studies (seven case series and five crossover design), with a combined sample size of 354 participants; (43% males) met the inclusion criteria and were analyzed. The analysis revealed a trend toward improvement of oculomotor deficits and visual tasks in response to restitutive intervention. None of the studies addressed sex or gender effects. All studies had high RoB, suggesting low certainty in the reported results.
DISCUSSION
Restitutive interventions may be beneficial for adults with oculomotor deficits after mTBI, however overall certainty of the evidence remains low. Future efforts must include enhancing attention to study methodology and reporting, sex and gender analyses, and reaching a consensus on outcome measures.
PROSPERO REGISTRATION NUMBER
CRD42022352276.
Topics: Humans; Brain Concussion; Ocular Motility Disorders; Adult; Treatment Outcome; Male
PubMed: 38433498
DOI: 10.1080/02699052.2024.2320163 -
BMC Oral Health Feb 2024Moebius syndrome (MS) is a rare, non-progressive, neuromuscular, congenic disease involving the oral maxillofacial region. The present study aimed to describe the oral...
BACKGROUND
Moebius syndrome (MS) is a rare, non-progressive, neuromuscular, congenic disease involving the oral maxillofacial region. The present study aimed to describe the oral and extraoral findings in MS patients and their comprehensive dental management.
METHODS
A digital search was carried out in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar, restricted to articles in English from Jan 01, 2000, to Apr 02, 2023, following PRISMA guidelines. The methodological quality of the studies was evaluated following the JBI guidelines. Qualitative analysis was carried out on the overall result, extraoral and intraoral manifestations, considering dental management as appropriate.
RESULTS
Twenty-three studies were included, and a total of 124 cases of patients with MS were analyzed. The 82% of patients with MS were younger than 15 years of age. The most frequent extraoral manifestations were blinking and visual problems (78,22%), malformations of the upper and lower limbs (58,22%), bilateral facial paralysis (12,90%), lack of facial expression (12.09%), and unilateral facial paralysis (6,45%). On the other hand, the most frequent oral manifestations were tongue deformities (78,22%), micrognathia (37,90%), labial incompetence (36,29%), cleft palate (22,87%), gothic palate (16,12%), microstomia (15,32%), anterior open bite (15,32%), dental caries (8,87%), and periodontal disease (8,06%). The majority of MS patients were treated by pediatric dentistry (60,86%), using a surgical approach (56,52%), and orthodontic and orthopedic maxillary (43,47%) followed by restorative (39,13%), and periodontal treatments (21,73%).
CONCLUSIONS
This systematic review demonstrates that patients with MS present a wide variety of oral and extraoral manifestations, for which dental treatments are planned and tailored to each patient in accordance with oral manifestations. These treatments encompass problem resolution and oral health maintenance, incorporating recent techniques in managing and treating patients with MS.
Topics: Child; Humans; Mobius Syndrome; Facial Paralysis; Dental Caries; Cleft Palate; Dental Care
PubMed: 38321523
DOI: 10.1186/s12903-024-03968-6 -
Epilepsia Mar 2024KCTD7-related progressive myoclonic epilepsy (PME) is a rare autosomal-recessive disorder. This study aimed to describe the clinical details and genetic variants in a...
OBJECTIVE
KCTD7-related progressive myoclonic epilepsy (PME) is a rare autosomal-recessive disorder. This study aimed to describe the clinical details and genetic variants in a large international cohort.
METHODS
Families with molecularly confirmed diagnoses of KCTD7-related PME were identified through international collaboration. Furthermore, a systematic review was done to identify previously reported cases. Salient demographic, epilepsy, treatment, genetic testing, electroencephalographic (EEG), and imaging-related variables were collected and summarized.
RESULTS
Forty-two patients (36 families) were included. The median age at first seizure was 14 months (interquartile range = 11.75-22.5). Myoclonic seizures were frequently the first seizure type noted (n = 18, 43.9%). EEG and brain magnetic resonance imaging findings were variable. Many patients exhibited delayed development with subsequent progressive regression (n = 16, 38.1%). Twenty-one cases with genetic testing available (55%) had previously reported variants in KCTD7, and 17 cases (45%) had novel variants in KCTD7 gene. Six patients died in the cohort (age range = 1.5-21 years). The systematic review identified 23 eligible studies and further identified 59 previously reported cases of KCTD7-related disorders from the literature. The phenotype for the majority of the reported cases was consistent with a PME (n = 52, 88%). Other reported phenotypes in the literature included opsoclonus myoclonus ataxia syndrome (n = 2), myoclonus dystonia (n = 2), and neuronal ceroid lipofuscinosis (n = 3). Eight published cases died over time (14%, age range = 3-18 years).
SIGNIFICANCE
This study cohort and systematic review consolidated the phenotypic spectrum and natural history of KCTD7-related disorders. Early onset drug-resistant epilepsy, relentless neuroregression, and severe neurological sequalae were common. Better understanding of the natural history may help future clinical trials.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Young Adult; Electroencephalography; Epilepsies, Myoclonic; Myoclonic Epilepsies, Progressive; Potassium Channels; Seizures; Unverricht-Lundborg Syndrome
PubMed: 38231304
DOI: 10.1111/epi.17880 -
Optometry and Vision Science : Official... Dec 2023Eye tracking is a promising method for objectively assessing functional visual capabilities, but its suitability remains unclear when assessing the vision of people with...
BACKGROUND
Eye tracking is a promising method for objectively assessing functional visual capabilities, but its suitability remains unclear when assessing the vision of people with vision impairment. In particular, accurate eye tracking typically relies on a stable and reliable image of the pupil and cornea, which may be compromised by abnormalities associated with vision impairment (e.g., nystagmus, aniridia).
OBJECTIVES
This study aimed to establish the degree to which video-based eye tracking can be used to assess visual function in the presence of vision impairment.
DATA SOURCES
A systematic review was conducted using PubMed, EMBASE, and Web of Science databases, encompassing literature from inception to July 2022.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
Studies included in the review used video-based eye tracking, included individuals with vision impairment, and used screen-based tasks unrelated to practiced skills such as reading or driving.
STUDY APPRAISAL AND SYNTHESIS METHODS
The included studies were assessed for quality using the Strengthening the Reporting of Observational Studies in Epidemiology assessment tool. Data extraction and synthesis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
Our analysis revealed that five common tests of visual function were used: (i) fixation stability, (ii) smooth pursuit, (iii) saccades, (iv) free viewing, and (v) visual search. The studies reported considerable success when testing individuals with vision impairment, yielding usable data from 96.5% of participants.
LIMITATIONS
There was an overrepresentation of conditions affecting the optic nerve or macula and an underrepresentation of conditions affecting the anterior segment or peripheral retina.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
The results offer promise for the use of eye tracking to assess the visual function of a considerable proportion of those with vision impairment. Based on the findings, we outline a framework for how eye tracking can be used to test visual function in the presence of vision impairment.
Topics: Humans; Eye-Tracking Technology; Nystagmus, Pathologic; Retina; Pursuit, Smooth
PubMed: 38165789
DOI: 10.1097/OPX.0000000000002088 -
The British Journal of Ophthalmology Jun 2024Recent work has called into question the ability of visual acuity (VA) to accurately represent changes in visual function in infantile nystagmus (IN). This systematic...
BACKGROUND/AIMS
Recent work has called into question the ability of visual acuity (VA) to accurately represent changes in visual function in infantile nystagmus (IN). This systematic review investigated factors affecting visual performance in IN, to guide development of suitable alternatives to VA.
METHODS
Included studies used an experimental manipulation to assess changes in visual function in people with IN. Interventional studies, case series and case studies were excluded. Six databases were searched in August 2023. Selection, detection, attrition and measurement bias were assessed. Due to heterogeneous methodologies, narrative synthesis was undertaken.
RESULTS
Eighteen relevant papers were identified, 11 of which complied with the review criteria. Articles were grouped according to the factor manipulated to evoke within-participant changes in performance (motion blur, psychological state, gaze angle or visual crowding). Optotype, image, grating and moving stimuli have been employed under varying lighting conditions and exposure duration.
CONCLUSION
Several factors affecting visual performance should be considered when assessing visual function in IN. While maximum VA is a useful metric, its measurement deliberately minimises nystagmus-specific factors such as changes in visual performance with gaze angle and the 'slow to see' phenomenon. Maximum VA can be measured using the null zone, providing unlimited viewing time, reducing stress/mental load and minimising visual crowding. Gaze-dependent functional vision space is a promising measure which quantifies the impact of the null zone but does not consider temporal vision. Although no complete measurement technique has yet been proven, this review provides insights to guide future work towards development of appropriate methods.
Topics: Humans; Visual Acuity; Nystagmus, Congenital; Eye Movements
PubMed: 38164583
DOI: 10.1136/bjo-2023-324254 -
Cells Dec 2023Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by four-repeat tau deposition in various cell types and anatomical regions, and can... (Review)
Review
Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by four-repeat tau deposition in various cell types and anatomical regions, and can manifest as several clinical phenotypes, including the most common phenotype, Richardson's syndrome. The limited availability of biomarkers for PSP relates to the overlap of clinical features with other neurodegenerative disorders, but identification of a growing number of biomarkers from imaging is underway. One way to increase the reliability of imaging biomarkers is to combine different modalities for multimodal imaging. This review aimed to provide an overview of the current state of PSP hybrid imaging by combinations of positron emission tomography (PET) and magnetic resonance imaging (MRI). Specifically, combined PET and MRI studies in PSP highlight the potential of [18F]AV-1451 to detect tau, but also the challenge in differentiating PSP from other neurodegenerative diseases. Studies over the last years showed a reduced synaptic density in [11C]UCB-J PET, linked [11C]PK11195 and [18F]AV-1451 markers to disease progression, and suggested the potential role of [18F]RO948 PET for identifying tau pathology in subcortical regions. The integration of quantitative global and regional gray matter analysis by MRI may further guide the assessment of reduced cortical thickness or volume alterations, and diffusion MRI could provide insight into microstructural changes and structural connectivity in PSP. Challenges in radiopharmaceutical biomarkers and hybrid imaging require further research targeting markers for comprehensive PSP diagnosis.
Topics: Humans; Supranuclear Palsy, Progressive; Radiopharmaceuticals; Neurodegenerative Diseases; Reproducibility of Results; Multimodal Imaging; Biomarkers
PubMed: 38132096
DOI: 10.3390/cells12242776 -
Journal of Neurology Apr 2024Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS), exhibit overlapping early-stage symptoms, complicating definitive diagnosis despite heterogeneous cellular and regional pathophysiology. Additionally, the progression and the eventual conversion of prodromal conditions such as REM behavior disorder (RBD) to PD, MSA, or DLB remain challenging to predict. Extracellular vesicles (EVs) are small, membrane-enclosed structures released by cells, playing a vital role in communicating cell-state-specific messages. Due to their ability to cross the blood-brain barrier into the peripheral circulation, measuring biomarkers in blood-isolated speculative CNS enriched EVs has become a popular diagnostic approach. However, replication and independent validation remain challenging in this field. Here, we aimed to evaluate the diagnostic accuracy of speculative CNS-enriched EVs for parkinsonian disorders.
METHODS
We conducted a PRISMA-guided systematic review and meta-analysis, covering 18 studies with a total of 1695 patients with PD, 253 with MSA, 21 with DLB, 172 with PSP, 152 with CBS, 189 with RBD, and 1288 HCs, employing either hierarchical bivariate models or univariate models based on study size.
RESULTS
Diagnostic accuracy was moderate for differentiating patients with PD from HCs, but revealed high heterogeneity and significant publication bias, suggesting an inflation of the perceived diagnostic effectiveness. The bias observed indicates that studies with non-significant or lower effect sizes were less likely to be published. Although results for differentiating patients with PD from those with MSA or PSP and CBS appeared promising, their validity is limited due to the small number of involved studies coming from the same research group. Despite initial reports, our analyses suggest that using speculative CNS-enriched EV biomarkers may not reliably differentiate patients with MSA from HCs or patients with RBD from HCs, due to their lesser accuracy and substantial variability among the studies, further complicated by substantial publication bias.
CONCLUSION
Our findings underscore the moderate, yet unreliable diagnostic accuracy of biomarkers in speculative CNS-enriched EVs in differentiating parkinsonian disorders, highlighting the presence of substantial heterogeneity and significant publication bias. These observations reinforce the need for larger, more standardized, and unbiased studies to validate the utility of these biomarkers but also call for the development of better biomarkers for parkinsonian disorders.
Topics: Humans; Parkinsonian Disorders; Parkinson Disease; Multiple System Atrophy; Supranuclear Palsy, Progressive; REM Sleep Behavior Disorder; Biomarkers; Extracellular Vesicles; Diagnosis, Differential
PubMed: 38103086
DOI: 10.1007/s00415-023-12093-3 -
The Cochrane Database of Systematic... Nov 2023Dizziness is a common reason for people to seek medical care. Acute vestibular syndrome (AVS) is a specific type of dizziness, which can include severe vertigo, nausea... (Review)
Review
BACKGROUND
Dizziness is a common reason for people to seek medical care. Acute vestibular syndrome (AVS) is a specific type of dizziness, which can include severe vertigo, nausea and vomiting, nystagmus, or unsteadiness. Acute vestibular syndrome can be due to peripheral or central causes. It is important to determine the cause, as the intervention and outcomes differ if it is from a peripheral or central cause. Clinicians can assess for the cause using risk factors, patient history, examination findings, or advanced imaging, such as a magnetic resonance imaging (MRI). The head impulse, nystagmus, test of skew (HINTS) examination is a three-part examination performed by clinicians to determine if AVS is due to a peripheral or central cause. This includes assessing how the eyes move in response to rapidly turning a person's head (head impulse), assessing the direction of involuntary eye movements (nystagmus), and assessing whether the eyes are aligned or misaligned (test of skew). The HINTS Plus examination includes an additional assessment of auditory function.
OBJECTIVES
To assess the diagnostic accuracy of the HINTS and HINTS Plus examinations, with or without video assistance, for identifying a central etiology for AVS.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, Google Scholar, the International HTA database, and two trials registers to September 2022.
SELECTION CRITERIA
We included all retrospective and prospective diagnostic test accuracy studies that evaluated the HINTS or HINTS Plus test used in a primary care clinic, an urgent care clinic, the emergency department, or during inpatient hospitalization against a final diagnosis of a central etiology of AVS, as defined by the reference standard of advanced imaging or final diagnosis by a neurologist.
DATA COLLECTION AND ANALYSIS
Two review authors independently determined eligibility of each study according to eligibility criteria, extracted data, assessed the risk of bias, and determined the certainty of evidence. Disagreements were adjudicated by consensus or a third review author if needed. The primary outcome was the diagnostic accuracy of the HINTS and HINTS Plus examinations for identifying a central etiology for AVS, conducted clinically (clinician visual assessment) or with video assistance (e.g. video recording with goggles); we independently assessed the clinical and video-assisted examinations. Subgroup analyses were performed by provider type (e.g. physicians, non-physicians), time from symptom onset to presentation (e.g. less than 24 hours, longer than 24 hours), reference standard (e.g. advanced imaging, discharge diagnosis), underlying etiology (e.g. ischemic stroke, alternative etiologies [hemorrhagic stroke, intracranial mass]), study setting (e.g. outpatient [outpatient clinic, urgent care clinic, emergency department], inpatient), physician level of training (e.g. resident, fellow/attending), physician specialty (e.g. otolaryngology, emergency medicine, neurology, and neurologic subspecialist [e.g. neuro-ophthalmology, neuro-otology]), and individual diagnostic accuracy of each component of the examination (e.g. head impulse, direction-changing nystagmus, test of skew). We created 2 x 2 tables of the true positives, true negatives, false positives, and false negatives and used these data to calculate the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio with 95% confidence intervals (95% CI) for each outcome.
MAIN RESULTS
We included 16 studies with a total of 2024 participants (981 women and 1043 men) with a mean age of 60 years. Twelve studies assessed the HINTS examination; five assessed the HINTS Plus examination. Thirteen studies were performed in the emergency department; half were performed by neurologists. The clinical HINTS examination (12 studies, 1890 participants) was 94.0% (95% confidence interval [CI] 82.0% to 98.2%) sensitive, and 86.9% (95% CI 75.3% to 93.6%) specific (low-certainty evidence). The video-assisted HINTS examination (3 studies, 199 participants) was 85.0% to 100% sensitive (low-certainty evidence), and 38.9% to 100% specific (very low-certainty evidence). The clinical HINTS Plus examination (5 studies, 451 participants) was 95.3% (95% CI 78.4% to 99.1%) sensitive, and 72.9% (95% CI 44.4% to 90.1%) specific (low-certainty evidence). The video-assisted HINTS Plus examination (2 studies, 163 participants) was 85.0% to 93.8% sensitive, and 28.6% to 38.9% specific (moderate-certainty evidence). Subgroup analyses were limited, as most studies were conducted in the emergency department, by physicians, and with MRI as a reference standard. Time from symptom onset to presentation varied across studies. Three studies were at high risk of bias and three studies were at unclear risk of bias for participant selection. Three studies were at unclear risk of bias for the index test. Four studies were at unclear risk of bias for the reference standard. Two studies were at unclear risk of bias for flow and timing. One study had unclear applicability concerns for participant selection. Two studies had high applicability concerns for the index test and two studies had unclear applicability concerns for the index test. No studies had applicability concerns for the reference standard.
AUTHORS' CONCLUSIONS
The HINTS and HINTS Plus examinations had good sensitivity and reasonable specificity for diagnosing a central cause for AVS in the emergency department when performed by trained clinicians. Overall, the evidence was of low certainty. There were limited data for the role of video-assistance or specific subgroups. Future research should include more high-quality studies of the HINTS and HINTS Plus examination; assessment of inter-rater reliability across users; accuracy across different providers, specialties, and experience; and direct comparison with no HINTS or MRI to assess the effect on clinical care.
Topics: Male; Humans; Female; Middle Aged; Dizziness; Retrospective Studies; Prospective Studies; Reproducibility of Results; Vertigo; Vomiting; Nausea; Nystagmus, Pathologic
PubMed: 37916744
DOI: 10.1002/14651858.CD015089.pub2