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The Journal of Headache and Pain Aug 2023It is unknown whether new daily persistent headache (NDPH) is a single disorder or heterogenous group of disorders, and whether it is a unique disorder from chronic...
BACKGROUND
It is unknown whether new daily persistent headache (NDPH) is a single disorder or heterogenous group of disorders, and whether it is a unique disorder from chronic migraine and chronic tension-type headache. We describe a large group of patients with primary NDPH, compare its phenotype to transformed chronic daily headache (T-CDH), and use cluster analysis to reveal potential sub-phenotypes in the NDPH group.
METHODS
We performed a case-control study using prospectively collected clinical data in patients with primary NDPH and T-CDH (encompassing chronic migraine and chronic tension-type headache). We used logistic regression with propensity score matching to compare demographics, phenotype, comorbidities, and treatment responses between NDPH and T-CDH. We used K-means cluster analysis with Gower distance to identify sub-clusters in the NDPH group based on a combination of demographics, phenotype, and comorbidities.
RESULTS
We identified 366 patients with NDPH and 696 with T-CDH who met inclusion criteria. Patients with NDPH were less likely to be female (62.6% vs. 73.3%, p < 0.001). Nausea, vomiting, photophobia, phonophobia, motion sensitivity, vertigo, and cranial autonomic symptoms were all significantly less frequent in NDPH than T-CDH (p value for all < 0.001). Acute treatments appeared less effective in NDPH than T-CDH, and medication overuse was less common (16% vs. 42%, p < 0.001). Response to most classes of oral preventive treatments was poor in both groups. The most effective treatment in NDPH was doselupin in 45.7% patients (95% CI 34.8-56.5%). Cluster analysis identified three subgroups of NDPH. Cluster 1 was older, had a high proportion of male patients, and less severe headaches. Cluster 2 was predominantly female, had severe headaches, and few associated symptoms. Cluster 3 was predominantly female with a high prevalence of migrainous symptoms and headache triggers.
CONCLUSIONS
Whilst there is overlap in the phenotype of NDPH and T-CDH, the differences in migrainous, cranial autonomic symptoms, and vulnerability to medication overuse suggest that they are not the same disorder. NDPH may be fractionated into three sub-phenotypes, which require further investigation.
Topics: Female; Male; Humans; Tension-Type Headache; Case-Control Studies; Headache Disorders; Headache; Migraine Disorders; Phenotype
PubMed: 37587430
DOI: 10.1186/s10194-023-01639-5 -
Eye (London, England) Feb 2024The prevalence of myopia is increasing across the world. Controlling myopia progression would be beneficial to reduce adverse outcomes such as retinal detachment and... (Review)
Review
The prevalence of myopia is increasing across the world. Controlling myopia progression would be beneficial to reduce adverse outcomes such as retinal detachment and myopic maculopathy which are associated with increased axial length. Pharmacological control of myopia progression with atropine has been investigated since the 19th century and the benefits of slowing myopia progression are considered against the side-effects of near blur and photophobia. More recently, randomised trials have focused on determining the optimum concentration of atropine leading to low-concentration atropine being used to manage myopia progression by practitioners across the world. Currently, in the United Kingdom, there is no licensed pharmacological intervention for myopia management. The aim of this review is to interpret the available data to inform clinical practice. We conducted a narrative review of the literature and identified peer-reviewed randomised controlled trials using the search terms 'myopia' and 'atropine', limited to the English language. We identified two key studies, which were the Atropine in the Treatment Of Myopia (ATOM) and Low-concentration Atropine for Myopia Progression (LAMP). Further studies were identified using the above search terms and the references from the identified literature. Atropine 0.01% has a modest effect on controlling axial length progression. Atropine 0.05% appears to be superior to atropine 0.01% in managing myopia progression. There is a dose-dependent rebound effect when treatment is stopped. Atropine is a well-tolerated, safe, and effective intervention. Treatment would be needed for several years and into adolescence, until axial length progression is stable.
Topics: Humans; Atropine; Ophthalmic Solutions; Myopia; Prevalence; United Kingdom; Disease Progression; Refraction, Ocular; Mydriatics
PubMed: 37717107
DOI: 10.1038/s41433-023-02718-2 -
BioEssays : News and Reviews in... Sep 2023The photocycle of visual opsins is essential to maintain the light sensitivity of the retina. The early physical observations of the rhodopsin photocycle by Böll and... (Review)
Review
The photocycle of visual opsins is essential to maintain the light sensitivity of the retina. The early physical observations of the rhodopsin photocycle by Böll and Kühne in the 1870s inspired over a century's worth of investigations on rhodopsin biochemistry. A single photon isomerizes the Schiff-base linked 11-cis-retinylidene chromophore of rhodopsin, converting it to the all-trans agonist to elicit phototransduction through photoactivated rhodopsin (Rho*). Schiff base hydrolysis of the agonist is a key step in the photocycle, not only diminishing ongoing phototransduction but also allowing for entry and binding of fresh 11-cis chromophore to regenerate the rhodopsin pigment and maintain light sensitivity. Many challenges have been encountered in measuring the rate of this hydrolysis, but recent advancements have facilitated studies of the hydrolysis within the native membrane environment of rhodopsin. These techniques can now be applied to study hydrolysis of agonist in other opsin proteins that mediate phototransduction or chromophore turnover. In this review, we discuss the progress that has been made in characterizing the rhodopsin photocycle and the journey to characterize the hydrolysis of its all-trans-retinylidene agonist.
Topics: Humans; Rhodopsin; Photophobia; Retinaldehyde; Retina
PubMed: 37454357
DOI: 10.1002/bies.202300068 -
Current Opinion in Neurology Jun 2024Visual snow syndrome (VSS) is a disorder characterized by persistent visual disturbances, including the visual snow phenomenon, palinopsia, heightened perception of... (Review)
Review
PURPOSE OF REVIEW
Visual snow syndrome (VSS) is a disorder characterized by persistent visual disturbances, including the visual snow phenomenon, palinopsia, heightened perception of entoptic phenomena, impaired night vision, and photophobia. The purpose of this review is to provide an update on recent findings over the past 18 months in VSS research and to summarize the current state of treatment approaches.
RECENT FINDINGS
Electrophysiological studies have revealed cortical hyperresponsivity in visual brain areas, imaging studies demonstrated microstructural and functional connectivity alterations in multiple cortical and thalamic regions and investigated glutamatergic and serotoninergic neurotransmission. These findings suggest that VSS might be a network disorder.Only few treatment studies are currently available demonstrating limited response to medication and even worsening or triggering of visual symptoms by certain antidepressants. Promising nonpharmacological treatments include mindfulness-based cognitive therapy, the use of chromatic filters, and research on visual noise adaption and neuro-optometric visual rehabilitation therapy (NORT). However, the level of evidence is still low and further research is needed including larger trials and involving objective measures of individual dysfunction.
SUMMARY
Although there has been recent progress, we still have not fully understood the nature of VSS. Further research is needed on a clinical and pathophysiological level to successfully treat the condition.
Topics: Humans; Vision Disorders; Syndrome; Perceptual Disorders
PubMed: 38465699
DOI: 10.1097/WCO.0000000000001258 -
Joint Bone Spine Feb 2024Spondyloarthritis (SpA) encompasses a group of chronic inflammatory disorders of the joints frequently associated with uveitis in almost a quarter of cases. SpA-related...
Spondyloarthritis (SpA) encompasses a group of chronic inflammatory disorders of the joints frequently associated with uveitis in almost a quarter of cases. SpA-related uveitis typically affects the eye anterior chamber with sudden onset, causing pain, redness, photophobia, and blurred vision. Ophthalmologists will describe an acute anterior unilateral uveitis. Most patients present with episodic acute anterior non-granulomatous uveitis and retain excellent visual acuity. However, systemic treatments are recommended in the event of frequent relapses (2-3/year) or in rare cases of sight-threatening with ocular complications. The improved understanding of the pathogenesis of SpA has led to the management of this disease by biologics. Here, we review the main data regarding the opportunity to target specific components in inflammatory pathways for the treatment of SpA-related uveitis. These therapies are recommended for long-term control when uveitis relapses occur too frequently despite conventional systemic treatments. Significant benefits have been obtained with the tumor necrosis factor-α inhibitors (TNFis), particularly infliximab and adalimumab. Paradoxically, a high number of uveitis occurrences have been shown on etanercept. Mixed results have been demonstrated with interleukin-17 antagonists (secukinumab) and interleukin-12/interleukin-23 antagonists (ustekinumab) in cases of failure of TNFis. JAK inhibitors seem to be a valuable class of medications for these patients in the future. Although SpA-related uveitis is typically managed with conventional local and/or systemic treatments, these biological/targeted therapies may provide avenues to control both the underlying SpA and uveitis manifestations. Thus, a close collaboration between patients, rheumatologists, internists, and ophthalmologists is needed to optimally manage ocular inflammation in SpA.
PubMed: 38309516
DOI: 10.1016/j.jbspin.2024.105697 -
Open Forum Infectious Diseases Nov 2023Neurological opportunistic infections cause significant morbidity and mortality in people with human immunodeficiency virus (HIV) but are difficult to diagnose.
BACKGROUND
Neurological opportunistic infections cause significant morbidity and mortality in people with human immunodeficiency virus (HIV) but are difficult to diagnose.
METHODS
One hundred forty people with HIV with acute neurological symptoms from Iquitos, Peru, were evaluated for cerebral toxoplasmosis with quantitative polymerase chain reaction (qPCR) of cerebrospinal fluid (CSF) and for cryptococcal meningitis with cryptococcal antigen test (CrAg) in serum or CSF. Differences between groups were assessed with standard statistical methods. A subset of samples was evaluated by metagenomic next-generation sequencing (mNGS) of CSF to compare standard diagnostics and identify additional diagnoses.
RESULTS
Twenty-seven participants were diagnosed with cerebral toxoplasmosis by qPCR and 13 with cryptococcal meningitis by CrAg. Compared to participants without cerebral toxoplasmosis, abnormal Glasgow Coma Scale score ( = .05), unilateral focal motor signs ( = .01), positive Babinski reflex ( = .01), and multiple lesions on head computed tomography (CT) ( = .002) were associated with cerebral toxoplasmosis. Photophobia ( = .03) and absence of lesions on head CT ( = .02) were associated with cryptococcal meningitis. mNGS of 42 samples identified 8 cases of cerebral toxoplasmosis, 7 cases of cryptococcal meningitis, 5 possible cases of tuberculous meningitis, and incidental detections of hepatitis B virus (n = 1) and pegivirus (n = 1). mNGS had a positive percentage agreement of 71% and a negative percentage agreement of 91% with qPCR for . mNGS had a sensitivity of 78% and specificity of 100% for diagnosis.
CONCLUSIONS
An infection was diagnosed by any method in only 34% of participants, demonstrating the challenges of diagnosing neurological opportunistic infections in this population and highlighting the need for broader, more sensitive diagnostic tests for central nervous system infections.
PubMed: 37965640
DOI: 10.1093/ofid/ofad515 -
PloS One 2023Recently, the most bothersome symptom has been recommended as a co-primary endpoint in clinical trials on the acute treatment of migraine. Probable migraine is a subtype...
Recently, the most bothersome symptom has been recommended as a co-primary endpoint in clinical trials on the acute treatment of migraine. Probable migraine is a subtype of migraine that fulfills all but one criterion for migraine diagnosis. We aimed to compare the most bothersome symptom between probable migraine and migraine. This study analyzed data from a nationwide study conducted in Korea, and the most bothersome symptom was assessed by requesting the participants to select one of the four typical accompanying symptoms of migraine. Responses to acute treatment were evaluated using the migraine Treatment Optimization Questionnaire-6. Nausea was the most bothersome symptom, followed by phonophobia and vomiting in the migraine group (nausea, 61.8%; phonophobia, 25.3%; vomiting, 10.0%; and photophobia, 2.9%) and the probable migraine group (nausea, 82.2%; phonophobia, 9.5%; vomiting, 5.6%; and photophobia, 2.7%). In participants with migraine, vomiting (adjusted odds ratio = 6.513; 95% confidence interval, 1.763-24.057) and phonophobia (adjusted odds ratio = 0.437; 95% confidence interval, 0.206-0.929) were significantly associated with severe headache intensity and nausea was significantly associated with >3 headache days per 30 days (adjusted odds ratio = 0.441; 95% confidence, 0.210-0.927). Different patterns of associations were observed in probable migraine.
Topics: Humans; Photophobia; Hyperacusis; Migraine Disorders; Nausea; Vomiting; Headache; Surveys and Questionnaires; Double-Blind Method
PubMed: 38019845
DOI: 10.1371/journal.pone.0289729 -
BMJ Case Reports Mar 2024Clozapine is an antipsychotic used for treatment-resistant schizophrenia with a significant side effect profile, including agranulocytosis, myocarditis and fever....
Clozapine is an antipsychotic used for treatment-resistant schizophrenia with a significant side effect profile, including agranulocytosis, myocarditis and fever. Clozapine-induced fever often occurs in the first 2 weeks of treatment and settle after a few days. We report a case of a woman in her mid-30s who developed fever and infective symptoms suggestive of an atypical pneumonia while on clozapine titration. She was on clozapine for 16 days before developing high-grade fever, dry cough, diarrhoea, headache and photophobia with a very high CRP. We performed an extensive infection workup that returned negative results except for bilateral upper lobe ground glass changes of the lungs on CT. Despite antibiotic therapy, which would cover an atypical pneumonia, her CRP remained elevated and her fever persisted. Focus was directed to clozapine-induced pneumonitis as the cause for her symptoms. Her antibiotics were ceased, and clozapine was downtitrated. With the adjustment of her clozapine dose, her fevers and associated symptoms resolved, and CRP downtrended. Her fevers did not return when clozapine was uptitrated in the community subsequently. Clozapine-induced fever or other immune-allergic reactions should be systematically considered when patients develop fever during the initiation phase of clozapine therapy. Ruling out infective causes is desirable prior to attributing fevers to clozapine especially when they are accompanied by infective symptoms and high inflammatory markers. Careful downtitration of clozapine should be considered rather than abrupt cessation in managing clozapine-induced fevers and subsequent slow uptitration could be considered.
Topics: Female; Humans; Clozapine; Antipsychotic Agents; Fever; Pneumonia, Mycoplasma
PubMed: 38531554
DOI: 10.1136/bcr-2023-259154 -
Medicine Sep 2023The last few decades have witnessed an appalling rise in several emerging and re-emerging viral and zoonotic outbreaks. Amongst those emerging zoonosis, one of the...
BACKGROUND
The last few decades have witnessed an appalling rise in several emerging and re-emerging viral and zoonotic outbreaks. Amongst those emerging zoonosis, one of the diseases which is gaining popularity these days and has been declared as public health emergency of international concern by the world health organization, is human monkeypox virus (HMPX). Proper understanding of the clinical spectrum of the disease is of paramount importance for early diagnosis and treatment. In this review, we aimed to study and quantify the neurological manifestations of HMPX virus infection.
METHODS
Any study, released prior to April 13, 2023, that reported neurological manifestations in patients infected by HMPX virus were reviewed systematically on PubMed, Scopus, Google Scholar, and Cochrane Library using the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) statement.
RESULTS
Our systematic review included data from 22 eligible studies: 10 cohort studies, 3 cross sectional studies, one retrospective study, 5 case series, and 2 case reports. The most commonly reported neurological manifestations of HMPX were headache (48.84%), myalgia (27.50%), fatigue (17.73%), and photophobia (4.43%). Uncommonly, HMPX can also present with visual deficit (0.57%), seizure (0.34%), encephalitis (0.8%), dizziness (0.34%), encephalomyelitis (0.23%), coma (0.11%), and transverse myelitis (0.11%).
DISCUSSIONS
Monkeypox virus usually presents with self-limiting painful rash, lymphadenitis, and fever, complications like secondary skin infection, eye problems and pneumonia can be life threatening, carrying a case fatality rate of 1% to 10%. Neurological manifestations are not uncommon and can further add-on to morbidity and mortality.
Topics: Humans; Coinfection; Cross-Sectional Studies; Mpox (monkeypox); Monkeypox virus; Public Health; Retrospective Studies
PubMed: 37657009
DOI: 10.1097/MD.0000000000034664 -
Ophthalmology and Therapy Apr 2024Corneal neuropathic pain (CNP) is a debilitating condition characterized by pain in the absence of a noxious stimulus. Symptoms such as ocular stinging, burning,...
Corneal neuropathic pain (CNP) is a debilitating condition characterized by pain in the absence of a noxious stimulus. Symptoms such as ocular stinging, burning, photophobia, irritation, and a deep aching pain can be severe despite a seemingly normal ocular surface on examination. CNP may develop due to either peripheral or central sensitization. Peripheral sensitization develops due to aberrant regeneration of corneal nociceptors and nerve fibers as a result of corneal injury or disease of peripheral corneal nerves. Whereas, central sensitization develops due to upregulation of excitatory neurotransmitters as a result of chronic inflammation, which leads to amplification of neuronal response to stimuli. Unfortunately, due to the disparity in severity of symptomology and the observable signs on examination, patients' symptoms are commonly thought to be "psychological" or "functional", and patients report feeling ignored and neglected. Additionally, diagnosis is often delayed which adversely affects patient outcomes. Research to date has focused on the scientific aspects of corneal neuropathic pain: its pathophysiology, epidemiology, investigations, and management. Research into the patient personal experience and the challenges faced by individual patients and their clinicians is lacking. We present the patient and physician perspective on the journey of both patients in order to provide insights into the challenges faced by patients and physicians in the diagnosis, assessment, and management of corneal neuropathic pain.
PubMed: 38363459
DOI: 10.1007/s40123-024-00897-z