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Practical Neurology Oct 2021Treating patients with progressive supranuclear palsy (PSP) is both effective and rewarding. This review aims to share our experience in the proactive management of PSP,... (Review)
Review
Treating patients with progressive supranuclear palsy (PSP) is both effective and rewarding. This review aims to share our experience in the proactive management of PSP, considering the patient, the family and the medical context in which the illness unfolds. There are many opportunities to assist your patients, ameliorate their symptoms, reduce their risks and harm, and guide them through the complex medical, social and legal minefield that characterises life with chronic neurological illness. We summarise the challenges of early diagnosis, consider PSP mimics and the role of investigations in excluding these, and discuss the available pharmacological and non-pharmacological treatment strategies to tackle the common and challenging symptoms of PSP. The best treatment will be patient centred and as part of a multidisciplinary team.
Topics: Diagnosis, Differential; Humans; Supranuclear Palsy, Progressive
PubMed: 34215700
DOI: 10.1136/practneurol-2020-002794 -
Parkinsonism & Related Disorders Apr 2020Progressive supranuclear palsy (PSP) is a complex clinicopathologic disease with no current cure or disease modulating therapies that can only be definitively confirmed... (Review)
Review
Progressive supranuclear palsy (PSP) is a complex clinicopathologic disease with no current cure or disease modulating therapies that can only be definitively confirmed at autopsy. Growing understanding of the phenotypic diversity of PSP has led to expanded clinical criteria and new insights into etiopathogenesis that coupled with improved in vivo biomarkers makes increased access to current clinical trials possible. Current standard-of-care treatment of PSP is multidisciplinary, supportive and symptomatic, and several trials of potentially disease modulating agents have already been completed with disappointing results. Current ongoing clinical trials target the abnormal aggregation of tau through a variety of mechanisms including immunotherapy and gene therapy offer a more direct method of treatment. Here we review PSP clinicopathologic correlations, in vivo biomarkers including MRI, PET, and CSF biomarkers. We additionally review current pharmacologic and non-pharmacologic methods of treatment, prior and ongoing clinical trials in PSP. Newly expanded clinical criteria and improved specific biomarkers will aid in identifying patients with PSP earlier and more accurately and expand access to these potentially beneficial clinical trials.
Topics: Drug Therapy; Genetic Therapy; Humans; Immunotherapy; Supranuclear Palsy, Progressive
PubMed: 32487421
DOI: 10.1016/j.parkreldis.2020.04.014 -
Neurology(R) Neuroimmunology &... May 2022Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare disorder of the nervous system that classically presents with a combination of characteristic eye movement disorder... (Review)
Review
BACKGROUND AND OBJECTIVES
Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare disorder of the nervous system that classically presents with a combination of characteristic eye movement disorder and myoclonus, in addition to ataxia, irritability, and sleep disturbance. There is good evidence that OMAS is an immune-mediated condition that may be paraneoplastic in the context of neuroblastoma. This syndrome may be associated with long-term cognitive impairment, yet it remains unclear how this is influenced by disease course and treatment. Treatment is largely predicated on immune suppression, but there is limited evidence to indicate an optimal regimen.
METHODS
Following an international multiprofessional workshop in 2004, a body of clinicians and scientists comprising the International OMS Study group continued to meet biennially in a joint professionals and family workshop focusing on pediatric OMAS. Seventeen years after publication of the first report, a writing group was convened to provide a clinical update on the definitions and clinical presentation of OMAS, biomarkers and the role of investigations in a child presenting with OMAS, treatment and management strategies including identification and support of long-term sequelae.
RESULTS
The clinical criteria for diagnosis were reviewed, with a proposed approach to laboratory and radiologic investigation of a child presenting with possible OMAS. The evidence for an upfront vs escalating treatment regimen was reviewed, and a treatment algorithm proposed to recognize both these approaches. Importantly, recommendations on monitoring of immunotherapy response and longer-term follow-up based on an expert consensus are provided.
DISCUSSION
OMAS is a rare neurologic condition that can be associated with poor cognitive outcomes. This report proposes an approach to investigation and treatment of children presenting with OMAS, based on expert international opinion recognizing the limited data available.
Topics: Ataxia; Child; Disease Progression; Humans; Internationality; Neuroblastoma; Ocular Motility Disorders; Opsoclonus-Myoclonus Syndrome
PubMed: 35260471
DOI: 10.1212/NXI.0000000000001153 -
Handbook of Clinical Neurology 2023Progressive external ophthalmoplegia (PEO), characterized by ptosis and impaired eye movements, is a clinical syndrome with an expanding number of etiologically distinct... (Review)
Review
Progressive external ophthalmoplegia (PEO), characterized by ptosis and impaired eye movements, is a clinical syndrome with an expanding number of etiologically distinct subtypes. Advances in molecular genetics have revealed numerous pathogenic causes of PEO, originally heralded in 1988 by the detection of single large-scale deletions of mitochondrial DNA (mtDNA) in skeletal muscle of people with PEO and Kearns-Sayre syndrome. Since then, multiple point variants of mtDNA and nuclear genes have been identified to cause mitochondrial PEO and PEO-plus syndromes, including mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and sensory ataxic neuropathy dysarthria ophthalmoplegia (SANDO). Intriguingly, many of those nuclear DNA pathogenic variants impair maintenance of the mitochondrial genome causing downstream mtDNA multiple deletions and depletion. In addition, numerous genetic causes of nonmitochondrial PEO have been identified.
Topics: Humans; Ophthalmoplegia, Chronic Progressive External; DNA, Mitochondrial; Ophthalmoplegia; Muscle, Skeletal; Syndrome
PubMed: 36813323
DOI: 10.1016/B978-0-12-821751-1.00018-X -
The Cochrane Database of Systematic... Sep 2021The clinical management of intermittent exotropia (X(T)) has been discussed extensively in the literature, yet there remains a lack of clarity regarding indications for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The clinical management of intermittent exotropia (X(T)) has been discussed extensively in the literature, yet there remains a lack of clarity regarding indications for intervention, the most effective form of treatment, and whether there is an optimal time in the evolution of the disease at which any given treatment should be carried out.
OBJECTIVES
The objective of this review was to analyze the effects of various surgical and non-surgical treatments in randomized controlled trials (RCTs) of participants with intermittent exotropia, and to report intervention criteria and determine whether the treatment effect varies by age and subtype of X(T).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 1), which contains the Cochrane Eyes and Vision Trials Register; Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Science Information database (LILACS); the ISRCTN registry; ClinicalTrials.gov, and the WHO ICTRP. The date of the search was 20 January 2021. We performed manual searches of the British Orthoptic Journal up to 2002, and the proceedings of the European Strabismological Association (ESA), International Strabismological Association (ISA), and American Association for Pediatric Ophthalmology and Strabismus meeting (AAPOS) up to 2001.
SELECTION CRITERIA
We included RCTs of any surgical or non-surgical treatment for intermittent exotropia.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology.
MAIN RESULTS
We included six RCTs, four of which took place in the United States, and the remaining two in Asia (Turkey, India). A total of 890 participants with basic or distance X(T) were included, most of whom were children aged 12 months to 10 years. Three of these six studies were from the 2013 version of this review. Overall, the included studies had a high risk of performance bias as masking of participants and personnel administering treatment was not possible. Two RCTs compared bilateral lateral rectus recession versus unilateral lateral rectus recession with medial rectus resection, but only one RCT (n = 197) reported on the primary outcomes of this review. Bilateral lateral rectus recession likely results in little difference in motor alignment at near (MD 1.00, 95% CI -2.69 to 4.69) and distance (MD 2.00, 95% CI -1.22 to 5.22) fixation as measured in pupillary distance using PACT (moderate-certainty evidence). Bilateral lateral rectus recession may result in little to no difference in stereoacuity at near fixation (risk ratio (RR) 0.77, 95% CI 0.35 to 1.71), adverse events (RR 7.36, 95% CI 0.39 to 140.65), or quality of life measures (low-certainty evidence). We conducted a meta-analysis of two RCTs comparing patching (n = 249) with active observation (n = 252), but were unable to conduct further meta-analyses due to the clinical and methodological heterogeneity in the remaining trials. We found evidence that patching was clinically more effective than active observation in improving motor alignment at near (mean difference (MD) -2.23, 95% confidence interval (CI) -4.02 to -0.44) and distance (MD -2.00, 95% CI -3.40 to -0.61) fixation as measured by prism and alternate cover test (PACT) at six months (high-certainty evidence). The evidence suggests that patching results in little to no difference in stereoacuity at near fixation (MD 0.00, 95% CI -0.07 to 0.07) (low-certainty evidence). Stereoacuity at distance, motor fusion test, and quality of life measures were not reported. Adverse events were also not reported, but study authors explained that they were not anticipated due to the non-surgical nature of patching. One RCT (n = 38) compared prism adaptation test with eye muscle surgery versus eye muscle surgery alone. No review outcomes were reported. One RCT (n = 60) compared lateral rectus recession and medial rectus plication versus lateral rectus recession and medial rectus resection. Lateral rectus recession and medial rectus plication may not improve motor alignment at distance (MD 0.66, 95% CI -1.06 to 2.38) (low-certainty evidence). The evidence for the effect of lateral rectus recession and medial rectus plication on motor fusion test performance is very uncertain (RR 0.92, 95% CI 0.48 to 1.74) (very low-certainty evidence).
AUTHORS' CONCLUSIONS
Patching confers a clinical benefit in children aged 12 months to 10 years of age with basic- or distance-type X(T) compared with active observation. There is insufficient evidence to determine whether interventions such as bilateral lateral rectus recession versus unilateral lateral rectus recession with medial rectus resection; lateral rectus recession and medial rectus plication versus lateral rectus recession and medial rectus resection; and prism adaptation test prior to eye muscle surgery versus eye muscle surgery alone may confer any benefit.
Topics: Asia; Child; Exotropia; Humans; Oculomotor Muscles; Strabismus; Visual Acuity
PubMed: 34516656
DOI: 10.1002/14651858.CD003737.pub4 -
Journal of Optometry 2022Convergence insufficiency (CI) is a common binocular vision (BV) disorder characterized by difficulty in maintaining motor fusion at near, which affects approximately... (Review)
Review
Convergence insufficiency (CI) is a common binocular vision (BV) disorder characterized by difficulty in maintaining motor fusion at near, which affects approximately 7.5 percent of the population. Diagnostic criteria for the disorder are inconsistent, ranging from one to many clinical signs. Methodology for clinical tests is inconsistent in measurement technique, visual targets, required repetitions, and normative values. This manuscript demonstrates the inconsistencies amongst published studies, and highlights the importance of consistent clinical diagnostic signs, measurement techniques, visual targets, and cut-off criteria. For each clinical sign, the recommended methodology for the procedure is described. Several studies do not take age into account when diagnosing CI in their cohorts. As such, the review emphasizes changes in diagnostic signs with age. This manuscript highlights the need for consistent and clear procedures and diagnostic criteria amongst clinicians and provides the basis for future studies in terms of diagnostic testing required for CI of varying age groups.
Topics: Accommodation, Ocular; Convergence, Ocular; Humans; Ocular Motility Disorders; Vision Disorders; Vision, Binocular
PubMed: 34963569
DOI: 10.1016/j.optom.2021.11.002 -
Ugeskrift For Laeger Jan 2023Strabismus is a common condition affecting both children and adults. Strabismus patients may experience double vision, abnormal head position and loss of stereovision....
Strabismus is a common condition affecting both children and adults. Strabismus patients may experience double vision, abnormal head position and loss of stereovision. The psychosocial negative impact of strabismus may be severe, affect self-esteem, social relationships, and job opportunities. Strabismus is a congenital condition or a result of an illness in later life and surgical treatment should be considered as reconstructive surgery and not downrated as just »a cosmetic procedure«. Strabismus surgery is safe, effective and addresses functional as well as psychosocial problems.
Topics: Adult; Child; Humans; Strabismus; Oculomotor Muscles; Plastic Surgery Procedures; Interpersonal Relations
PubMed: 36760141
DOI: No ID Found -
The Cochrane Database of Systematic... Dec 2020Convergence insufficiency is a common binocular vision disorder in which the eyes have a strong tendency to drift outward (exophoria) with difficulty turning the eyes... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Convergence insufficiency is a common binocular vision disorder in which the eyes have a strong tendency to drift outward (exophoria) with difficulty turning the eyes inward when reading or doing close work.
OBJECTIVES
To assess the comparative effectiveness and relative ranking of non-surgical interventions for convergence insufficiency through a systematic review and network meta-analysis (NMA).
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, PubMed and three trials registers up to 20 September 2019.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) examining any form of non-surgical intervention versus placebo, no treatment, sham treatment, or other non-surgical interventions. Participants were children and adults with symptomatic convergence insufficiency.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. We performed NMAs separately for children and adults.
MAIN RESULTS
We included 12 trials (six in children and six in adults) with a total of 1289 participants. Trials evaluated seven interventions: 1) office-based vergence/accommodative therapy with home reinforcement; 2) home-based pencil/target push-ups; 3) home-based computer vergence/accommodative therapy; 4) office-based vergence/accommodative therapy alone; 5) placebo vergence/accommodative therapy or other placebo intervention; 6) prism reading glasses; and 7) placebo reading glasses. Six RCTs in the pediatric population randomized 968 participants. Of these, the Convergence Insufficiency Treatment Trial (CITT) Investigator Group completed four RCTs with 737 participants. All four CITT RCTs were rated at low risk of bias. Diagnostic criteria and outcome measures were identical or similar among these trials. The four CITT RCTs contributed data to the pediatric NMA, incorporating interventions 1, 2, 3 and 5. When treatment success was defined by a composite outcome requiring both clinical measures of convergence to be normal, and also show a pre-specified magnitude of improvement, we found high-certainty evidence that office-based vergence/accommodative therapy with home reinforcement increases the chance of a successful outcome, compared with home-based computer vergence/accommodative therapy (risk ratio (RR) 1.96, 95% confidence interval (CI) 1.32 to 2.94), home-based pencil/target push-ups (RR 2.86, 95% CI 1.82 to 4.35); and placebo (RR 3.04, 95% CI 2.32 to 3.98). However, there may be no evidence of any treatment difference between home-based computer vergence/accommodative therapy and home-based pencil/target push-ups (RR 1.44, 95% CI 0.93 to 2.24; low-certainty evidence), or between either of the two home-based therapies and placebo therapy, for the outcome of treatment success. When treatment success was defined as the composite convergence and symptom success outcome, we found moderate-certainty evidence that participants who received office-based vergence/accommodative therapy with home reinforcement were 5.12 (95% CI 2.01 to 13.07) times more likely to achieve treatment success than those who received placebo therapy. We found low-certainty evidence that participants who received office-based vergence/accommodative therapy with home reinforcement might be 4.41 (95% CI 1.26 to 15.38) times more likely to achieve treatment success than those who received home-based pencil push-ups, and 4.65 (95% CI 1.23 to 17.54) times more likely than those who received home-based computer vergence/accommodative therapy. There was no evidence of any treatment difference between home-based pencil push-ups and home-based computer vergence/accommodative therapy, or between either of the two home-based therapies and placebo therapy. One RCT evaluated the effectiveness of base-in prism reading glasses in children. When base-in prism reading glasses were compared with placebo reading glasses, investigators found no evidence of a difference in the three outcome measures of near point convergence (NPC), positive fusional vergence (PFV), or symptom scores measured by the Convergence Insufficiency Symptom Survey (CISS). Six RCTs in the adult population randomized 321 participants. We rated only one RCT at low risk of bias. Because not all studies of adults included composite success data, we could not conduct NMAs for treatment success. We thus were limited to comparing the mean difference (MD) between interventions for improving NPC, PFV, and CISS scores individually using data from three RCTs (107 participants; interventions 1, 2, 4 and 5). Compared with placebo treatment, office-based vergence accommodative therapy was relatively more effective in improving PFV (MD 16.73, 95% CI 6.96 to 26.60), but there was no evidence of a difference for NPC or the CISS score. There was no evidence of difference for any other comparisons for any outcomes. One trial evaluated base-in prism glasses prescribed for near-work activities and found that the prism glasses group had fewer symptoms compared with the placebo glasses group at three months (MD -8.9, 95% CI -11.6 to -6.3). The trial found no evidence of a difference with this intervention in NPC or PFV. No adverse effects related to study treatments were reported for any of the included studies. Excellent adherence was reported for office-based vergence/accommodative therapy (96.6% or higher) in two trials. Reported adherence with home-based therapy was less consistent, with one study reporting decreasing adherence over time (weeks 7 to 12) and lower completion rates with home-based pencil/target push-ups.
AUTHORS' CONCLUSIONS
Current research suggests that office-based vergence/accommodative therapy with home reinforcement is more effective than home-based pencil/target push-ups or home-based computer vergence/accommodative therapy for children. In adults, evidence of the effectiveness of various non-surgical interventions is less clear.
Topics: Adult; Bias; Child; Exotropia; Eyeglasses; Humans; Network Meta-Analysis; Ocular Motility Disorders; Orthoptics; Randomized Controlled Trials as Topic
PubMed: 33263359
DOI: 10.1002/14651858.CD006768.pub3 -
Developmental Medicine and Child... Dec 2021Aicardi-Goutières syndrome (AGS) is a rare genetic neuroinflammatory disorder caused by abnormal upregulation of type 1 interferon signalling. Opsoclonus-myoclonus...
Aicardi-Goutières syndrome (AGS) is a rare genetic neuroinflammatory disorder caused by abnormal upregulation of type 1 interferon signalling. Opsoclonus-myoclonus syndrome is a rare autoimmune phenotype demonstrating a disturbance in the humoral immune response mostly seen in the context of paraneoplastic or postinfectious states, although its pathophysiology is incompletely understood. We report the first three children described with AGS demonstrating transient opsoclonus and myoclonus after irritability and/or developmental regression, suggesting a pathological association. We describe the presentation, clinical features, progress, cerebrospinal fluid (CSF) inflammatory markers, electroencephalogram (EEG), and magnetic resonance imaging (MRI) findings in these children. Two patients had developmental regression but demonstrated a positive response to JAK1/2 inhibition clinically and on serial examination of CSF inflammatory markers. These findings suggest that AGS should be considered in children presenting with opsoclonus-myoclonus, and that the association between AGS and opsoclonus-myoclonus further supports the role of immune dysregulation as causal in the rare neurological phenomenon opsoclonus and myoclonus. What this paper adds There is a phenotypic association between opsoclonus-myoclonus syndrome and Aicardi-Goutières syndrome. There is clinical evidence of immune dysregulation in the pathogenesis of opsoclonus and myoclonus.
Topics: Autoimmune Diseases of the Nervous System; Biomarkers; Brain; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Neopterin; Nervous System Malformations; Opsoclonus-Myoclonus Syndrome; White Matter
PubMed: 34155623
DOI: 10.1111/dmcn.14969 -
Journal of Binocular Vision and Ocular... 2019Amblyopia is a neurodevelopmental disorder of the visual system, as a result of discordant visual experience during infancy or early childhood. Because amblyopia is... (Review)
Review
Amblyopia is a neurodevelopmental disorder of the visual system, as a result of discordant visual experience during infancy or early childhood. Because amblyopia is typically defined as monocularly reduced visual acuity accompanied by one or more known amblyogenic factors, it is often assumed that the fellow eye is normal and sufficient for tasks like reading and eye-hand coordination. Recent scientific evidence of ocular motor, visual, and visuomotor deficits that are present with fellow eye monocular viewing and with binocular viewing calls this assumption into question. This clinical update reviews the research that has revealed fellow ocular motor and visual deficits and the effect that these deficits have on an amblyopic child's visuomotor and visuocognitive skills. We need to understand how to prevent and rehabilitate the effects of amblyopia not only on the nonpreferred eye but also on the fellow eye.
Topics: Amblyopia; Child; Diagnostic Techniques, Ophthalmological; Humans; Ocular Motility Disorders; Perceptual Disorders; Physical Examination; Psychomotor Performance; Vision, Binocular; Visual Acuity
PubMed: 31161888
DOI: 10.1080/2576117X.2019.1624440