Lack of a direct link between macular cones function and photophobia in interictal migraine.

BACKGROUND: It is still debatable whether the mechanisms underlying photophobia are related to altered visual cortex excitability or specific abnormalities of colour-related focal macular retino-thalamic information processing. METHODS: This cross-sectional study examined Ganzfeld blue-red (B-R) and blue-yellow (B-Y) focal macular cone flash ERG (ffERG) and focal-flash visual evoked potentials (ffVEPs) simultaneously in a group of migraine patients with (n = 18) and without (n = 19) aura during the interictal phase, in comparison to a group of healthy volunteers (HVs) (n = 20). We correlate the resulting retinal and cortical electrophysiological responses with subjective discomfort from exposure to bright light verified on a numerical scale. RESULTS: Compared to HVs, the amplitude and phase of the first and second harmonic of ffERG and ffVEPs were non-significantly different in migraine patients without aura and migraine patients with aura for both the B-R and the B-Y focal stimuli. Pearson's correlation test did not disclose correlations between clinical variables, including the photophobia scale and electrophysiological variables. CONCLUSIONS: These results do not favour interictal functional abnormalities in L-M- and S-cone opponent visual pathways in patients with migraine. They also suggest that the discomfort resulting from exposure to bright light is not related to focal macular retinal-to-visual cortex pathway.

Quantifying sensory thresholds along the migraine cycle: An exploratory longitudinal study.

BACKGROUND: To date, a number of studies on migraine have cross-sectionally evaluated sensory sensitivity with aversion thresholds/scores along the migraine cycle, reporting a decreased tolerance to sensory stimuli in different sensory modalities. Our hypothesis was that patients with migraine would exhibit heightened sensitivity to sound, light, touch and smell on days where they reported greater headache intensity. METHODS: This is an exploratory, longitudinal study, carried out over the course of 27 days. Aversion thresholds or scores to sound, light, touch and smell were quantified in six patients with migraine (11.33 ± 6.53 headache days/month). RESULTS: Patients reported an increased sensitivity to light (padj = 0.0297), touch (padj = 0.0077), and smell (padj = 0.0201) on days with higher headache intensity. However, a greater sensitivity to sound on days with higher headache intensity was only reported when anxiety levels were high (padj = 1.4e-06). Interestingly, variable levels of tolerance to bothersome light over time can also influence the correlation between light sensitivity and headache intensity (padj = 1.4e-06). CONCLUSIONS: Based on the present findings, future longitudinal studies evaluating sensory threshold changes along the migraine cycle in patients with migraine should account for the increased tolerance to bothersome light over time as well as the effect of anxiety on auditory sensitivity.

A study to investigate the prevalence of headache disorders and migraine conducted using medical claims data and linked results from online surveys: post-hoc analysis of other headache disorders.

BACKGROUND: Surveys using questionnaires to collect epidemiologic data may be subject to misclassification. Here, we analyzed a headache questionnaire to evaluate which questions led to a classification other than migraine. METHODS: Anonymized surveys coupled with medical claims data from individuals 19-74 years old were obtained from DeSC Healthcare Inc. to examine proportions of patients with primary headache disorders (i.e.; migraine, tension-type headache, cluster headache, and "other headache disorders"). Six criteria that determined migraine were used to explore how people with other headache disorders responded to these questions. RESULTS: Among the 21480 respondents, 7331 (34.0%) reported having headaches. 691 (3.2%) respondents reported migraine, 1441 (6.7%) had tension-type headache, 21 (0.1%) had cluster headache, and 5208 (24.2%) reported other headache disorders. Responses of participants with other headache disorders were analyzed, and the top 3 criteria combined with "Symptoms associated with headache" were "Site of pain" (7.3%), "Headache changes in severity during daily activities" (6.4%), and the 3 criteria combined (8.8%). The symptoms associated with headache were "Stiff shoulders" (13.6%), "Stiff neck" (9.4%), or "Nausea or vomiting" (8.7%), Photophobia" (3.3%) and "Phonophobia" (2.5%). CONCLUSIONS: Prevalence of migraine as diagnosed by questionnaire was much lower than expected while the prevalence of "other headache" was higher than expected. We believe the reason for this observation was due to misclassification, and resulted from the failure of the questionnaire to identify some features of migraine that would have been revealed by clinical history taking. Questionnaires should, therefore, be carefully designed, and doctors should be educated, on how to ask questions and record information when conducting semi-structured interviews with patients, to obtain more precise information about their symptoms, including photophobia and phonophobia.

Hyperactivity of the medial thalamus in patients with photophobia-associated migraine.

OBJECTIVE: To examine cerebral functional alterations associated with sensory processing in patients with migraine and constant photophobia. BACKGROUND: Migraine is a common headache disorder that presents with photophobia in many patients during attacks. Furthermore, some patients with migraine experience constant photophobia, even during headache-free intervals, leading to a compromised quality of life. METHODS: This prospective, case-control study included 40 patients with migraine (18 male and 22 female) who were recruited at an eye hospital and eye clinic. The patients were divided into two groups: migraine with photophobia group, consisting of 22 patients (10 male and 12 female) with constant photophobia, and migraine without photophobia group, consisting of 18 patients (eight male and 10 female) without constant photophobia. We used 18F-fluorodeoxyglucose and positron emission tomography to compare cerebral glucose metabolism between the two patient groups and 42 healthy participants (16 men and 26 women). RESULTS: Compared with the healthy group, both the migraine with photophobia and migraine without photophobia groups showed cerebral glucose hypermetabolism in the bilateral thalamus (p < 0.05, family-wise error-corrected). Moreover, the contrast of migraine with photophobia minus migraine without photophobia patients showed glucose hypermetabolism in the bilateral medial thalamus (p < 0.05, family-wise error-corrected). CONCLUSIONS: The medial thalamus may be associated with the development of continuous photophobia in patients with migraine.

Clinical course of two siblings with potassium voltage-gated channel modifier subfamily V member 2 (KCNV2)-associated retinopathy.

BACKGROUND: KCNV2-associated retinopathy causes a phenotype reported as "cone dystrophy with nyctalopia and supernormal rod responses (CDSRR; OMIM# 610356)," featuring pathognomonic findings on electroretinography (ERG). Here, we report the clinical courses of two siblings with CDSRR. CASE REPORTS: Patient 1: A 3-year-old boy with intermittent exophoria was referred to our hospital. The patient's decimal best-corrected visual acuity (BCVA) at age 6 was 0.7 and 0.7 in the right and left eyes, respectively. Photophobia and night blindness were also observed. Because the ERG showed a delayed and supernormal b-wave with a "squaring (trough-flattened)" a-wave in the DA-30 ERG, and CDSRR was diagnosed. The patient's vision gradually worsened, and faint bilateral bull's eye maculopathy was observed at the age of 27 years, although the fundi were initially unremarkable. Genetic examination revealed a homozygous missense variant, c.529T > C (p.Cys177Arg), in the KCNV2 gene. Patient 2: The second patient was Patient 1's younger sister, who was brought to our hospital at 3 years of age. The patient presented with exotropia, mild nystagmus, photophobia, night blindness, and color vision abnormalities. The patients' decimal BCVA at age 13 was 0.6 and 0.4 in the right and left eyes, respectively, and BCVA gradually decreased until the age of 24 years. The fundi were unremarkable. The siblings had similar ERG findings and the same homozygous missense variant in the KCNV2 gene. CONCLUSIONS: The siblings had clinical findings typical of CDSRR. High-intense flash ERG is recommended for identifying pathognomonic "squaring" a-waves in patients with CDSRR.

Visual snow syndrome in patients with migraine: widening the clinical spectrum of the syndrome with permanent and episodic manifestations.

PURPOSE: Migraine is the comorbidity most frequently associated with visual snow syndrome (VSS), but the prevalence of VSS in patients with migraine (PWM) has not been studied. Our objective was to evaluate the frequency of VSS in PWM and to analyze if symptoms of VSS happened in a permanent or episodic manner (eVSS) in this population. METHODS: We conducted a multicenter observational cross-sectional study. PWM was recruited from headache units, and a survey about the presence of visual snow symptoms was administered. The frequency and characteristics of patients that met current VSS criteria were analyzed. Demographic and clinical features of patients with VSS, eVSS, and PWM with no visual snow were compared. RESULTS: A total of 217 PWM were included. Seventeen patients (7.8%) met the VSS criteria. VSS patients had visual aura more frequently (58.8% vs. 31%; p = 0.019) and a higher MIDAS score (96.6 vs. 47.7; p = 0.014). Fifty-eight PWM (26.7%) showed visual snow and associated features in an episodic way and were classified as eVSS. Patients with VSS showed a tendency towards a higher frequency of visual symptoms than patients with eVSS (p > 0.05). No statistically significant differences in sociodemographic characteristics and comorbid conditions were found between VSS and eVSS. CONCLUSION: The prevalence of VSS in PWM may be higher than that described for the general population. Some PWM may present similar visual symptoms to patients with VSS but in an episodic manner. Our study reinforces the observation that the clinical spectrum of visual snow is likely to be broader than previously described.

Individualized spectral filters alleviate persistent photophobia, headaches and migraines in active duty military and Veterans following brain trauma.

PURPOSE: Consistent with association between photophobia and headache, growing evidence suggests an underlying causal relationship between light sensitivity and central pain. We investigated whether an intervention to regulate light sensitivity by filtering only wavelengths causing difficulties for the specific individual could alleviate headaches/migraines resulting from traumatic brain injury (TBI). METHODS: Secondary data analysis of a clinical database including N = 392 military personnel (97% men, 3% women), ranging in age from 20 to 51 years, diagnosed with TBI, persistent headaches/migraines, and light sensitivity. The average elapsed time from TBI diagnosis to intervention was 3 years. Headache/migraine severity, frequency, medication use, and difficulties related to daily functioning were assessed pre and 4-12 weeks post-intervention with individualized spectral filters. RESULTS: Monthly migraine frequency decreased significantly from an average of 14.8 to 1.9, with 74% reporting no migraines post-intervention. Prescription and over-the-counter medication use decreased by more than 70%. Individuals also reported significant improvement in light sensitivity, headaches/migraine severity, and physical and perceptual symptoms. CONCLUSIONS: Wearing individualized spectral filters was associated with symptom relief, increased subjective quality of reported health and well-being, and decreased objective medication use for TBI-related persistent headaches/migraines. These results support a suggested relationship between dysregulated light sensitivity and central regulation of pain.

Hypersensitivity of Intrinsically Photosensitive Retinal Ganglion Cells in Migraine Induces Cortical Spreading Depression.

Migraine is a complex disorder characterized by episodes of moderate-to-severe, often unilateral headaches and generally accompanied by nausea, vomiting, and increased sensitivity to light (photophobia), sound (phonophobia), and smell (hyperosmia). Photophobia is considered the most bothersome symptom of migraine attacks. Although the underlying mechanism remains unclear, the intrinsically photosensitive retinal ganglion cells (ipRGCs) are considered to be involved in photophobia associated with migraine. In this study, we investigated the association between the sensitivity of ipRGCs and migraines and cortical spreading depression (CSD), which may trigger migraine attacks. The pupillary responses closely associated with the function of ipRGCs in patients with migraine who were irradiated with lights were evaluated. Blue (486 nm) light irradiation elicited a response from ipRGCs; however, red light (560 nm) had no such effect. Melanopsin, a photosensitive protein, phototransduces in ipRGCs following blue light stimulation. Hypersensitivity of ipRGCs was observed in patients with migraine. CSD was more easily induced with blue light than with incandescent light using a mouse CSD model. Moreover, CSD was suppressed, even in the presence of blue light, after injecting opsinamide, a melanopsin inhibitor. The hypersensitivity of ipRGCs in patients with migraine may induce CSD, resulting in migraine attacks.

Photophobia is associated with lower sleep quality in individuals with migraine: results from the American Registry for Migraine Research (ARMR).

BACKGROUND: Patients with migraine often have poor sleep quality between and during migraine attacks. Furthermore, extensive research has identified photophobia as the most common and most bothersome symptom in individuals with migraine, second only to headache. Seeking the comfort of darkness is a common strategy for managing pain during an attack and preventing its recurrence between episodes. Given the well-established effects of daily light exposure on circadian activity rhythms and sleep quality, this study aimed to investigate the relationship between photophobia symptoms and sleep quality in a cohort of patients with migraine. METHODS: A cross-sectional observational study was conducted using existing data extracted from the American Registry for Migraine Research (ARMR). Participants with a migraine diagnosis who had completed the baseline questionnaires (Photosensitivity Assessment Questionnaire (PAQ), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-2 (PHQ-2)), and selected questions of the ARMR Sleep questionnaire were included. Models were created to describe the relationship of photophobia and photophilia with various sleep facets, including sleep quality (SQ), sleep disturbance (SDis), sleep onset latency (SOL), sleep-related impairments (SRI), and insomnia. Each model was controlled for age, sex, headache frequency, anxiety, and depression. RESULTS: A total of 852 patients meeting the inclusion criteria were included in the analysis (mean age (SD) = 49.8 (13.9), 86.6% (n = 738) female). Those with photophobia exhibited significantly poorer sleep quality compared to patients without photophobia (p < 0.001). Photophobia scores were associated with SQ (p < 0.001), SDis (p < 0.001), SOL (p = 0.011), SRI (p = 0.020), and insomnia (p = 0.005) after controlling for age, sex, headache frequency, depression, and anxiety, signifying that higher levels of photophobia were associated with worse sleep-related outcomes. Conversely, photophilia scores were associated with better sleep-related outcomes for SQ (p < 0.007), SOL (p = 0.010), and insomnia (p = 0.014). CONCLUSION: Results suggest that photophobia is a significant predictor of poor sleep quality and sleep disturbances in migraine. These results underscore the necessity for comprehensive and systematic investigations into the intricate interplay between photophobia and sleep to enhance our understanding and develop tailored solutions for individuals with migraine.

Psychometric Properties of the Persian Translation of the 12-Item Utah Photophobia Symptom Impact Scale Questionnaire.

To translate the the Utah Photophobia Symptom Impact Scale-12 questionnaire into Persian and assess the psychometric aspects to check its validity and reliability based on the Rasch modelling method. Translation and cultural adjustment of the English language UPSIS-12 questionnaire to Persian was undertaken. A total of 61 patients with complaints of photophobia participated in evaluating validity and reliability aspects. All the participants were asked to complete the Persian translation of the UPSIS-12 questionnaire. Rasch analyses of the survey items were conducted using WINSTEPS. All items fit the Rasch model. Point-measure correlation values varied from 0.41 to 0.77, providing a preliminary indication of adequate construct validity. All factor loadings were found more than 0.4. All items obtained infit and outfit mean square (MnSq) values of < 2.0. All participants except 5 had normal outfit values. Patients' abilities relative to the items' difficulty were analysed. Item difficulty was estimated and item characteristic curves were included. Sufficient unidimensionality, hierarchical order, and equal interval scoring were obtained. In conclusion, the Persian UPSIS-10 questionnaire has excellent psychometric properties and it will be valuable in both clinical practice and research. It will help Persian practitioners to assess their patients' photophobia.

Mutations in SREBF1, Encoding Sterol Regulatory Element Binding Transcription Factor 1, Cause Autosomal-Dominant IFAP Syndrome.

IFAP syndrome is a rare genetic disorder characterized by ichthyosis follicularis, atrichia, and photophobia. Previous research found that mutations in MBTPS2, encoding site-2-protease (S2P), underlie X-linked IFAP syndrome. The present report describes the identification via whole-exome sequencing of three heterozygous mutations in SREBF1 in 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. SREBF1 encodes sterol regulatory element-binding protein 1 (SREBP1), which promotes the transcription of lipogenes involved in the biosynthesis of fatty acids and cholesterols. This process requires cleavage of SREBP1 by site-1-protease (S1P) and S2P and subsequent translocation into the nucleus where it binds to sterol regulatory elements (SRE). The three detected SREBF1 mutations caused substitution or deletion of residues 527, 528, and 530, which are crucial for S1P cleavage. In vitro investigation of SREBP1 variants demonstrated impaired S1P cleavage, which prohibited nuclear translocation of the transcriptionally active form of SREBP1. As a result, SREBP1 variants exhibited significantly lower transcriptional activity compared to the wild-type, as demonstrated via luciferase reporter assay. RNA sequencing of the scalp skin from IFAP-affected individuals revealed a dramatic reduction in transcript levels of low-density lipoprotein receptor (LDLR) and of keratin genes known to be expressed in the outer root sheath of hair follicles. An increased rate of in situ keratinocyte apoptosis, which might contribute to skin hyperkeratosis and hypotrichosis, was also detected in scalp samples from affected individuals. Together with previous research, the present findings suggest that SREBP signaling plays an essential role in epidermal differentiation, skin barrier formation, hair growth, and eye function.

Impact of anti-CGRP monoclonal antibodies on migraine attack accompanying symptoms: A real-world evidence study.

BACKGROUND: Clinical trials on anti-calcitonin gene-related peptide monoclonal antibodies poorly investigated their impact on migraine accompanying symptoms. OBJECTIVE: To evaluate the impact of basal accompanying symptoms on anti-CGRP monoclonal antibodies treatment response and their evolution after six months of treatment in migraine patients. METHODS: Patients with migraine diagnosis seen in the Headache Clinic and treated with erenumab, galcanezumab or fremanezumab were prospectively recruited. They completed a daily eDiary which provided data on headache frequency and the following accompanying symptoms of each day: photophobia, phonophobia, nausea, dizziness, and aura. Patients were classified as responders or non-responders based on 50% or greater reduction in headache days per month at month 6 (≥50% response rate). Accompanying symptoms ratios based on headache days per month were assessed per patient at baseline and after three and six months. Comparisons for basal characteristics, basal accompanying symptoms ratios and their evolution after six months between responders and non-responders were performed. RESULTS: One hundred and fifty-eight patients were included, 44% (69/158) showed ≥50% response rate after six months. A significant reduction in headache days per month in both groups was found at month 6 (-9.4 days/month in ≥50% response rate group; p < 0.001, -2.2 days/month in <50% response rate group; p = 0.004). Additionally, significant decreases in photophobia (-19.5%, p < 0.001), phonophobia (-12.1%, p = 0.010) and aura ratios (-25.1%, p = 0.008) were found in ≥50% response rate group. No statistically significant reductions were found in nausea and dizziness in any group since their reduction was correlated with the decrease in headache days per month. Higher photophobia ratios at baseline were predictive of an increased response between months 3 and 6 (Incidence Risk Ratio = 0.928, p = 0.040). CONCLUSIONS: The days per month with photophobia, phonophobia and aura decreased at a higher rate than headache days per month after six months in the ≥50% response group. Higher photophobia ratios were associated with higher response rates between three and six months. It could indicate an involvement of peripheral CGRP in photophobia as well as a central modulation of migraine through these treatments which mainly act on the periphery.

Photobehaviours guided by simple photoreceptor systems.

Light provides a widely abundant energy source and valuable sensory cue in nature. Most animals exposed to light have photoreceptor cells and in addition to eyes, there are many extraocular strategies for light sensing. Here, we review how these simpler forms of detecting light can mediate rapid behavioural responses in animals. Examples of these behaviours include photophobic (light avoidance) or scotophobic (shadow) responses, photokinesis, phototaxis and wavelength discrimination. We review the cells and response mechanisms in these forms of elementary light detection, focusing on aquatic invertebrates with some protist and terrestrial examples to illustrate the general principles. Light cues can be used very efficiently by these simple photosensitive systems to effectively guide animal behaviours without investment in complex and energetically expensive visual structures.

Neural correlates of photophobia in prodromal and mild dementia with Lewy bodies.

BACKGROUND AND OBJECTIVES: Photophobia is a sensory disturbance provoked by light. Little is known about the association between photophobia and dementia with Lewy bodies (DLB). In this study, we aimed to identify the frequency and the neural basis of photophobia in prodromal and mild DLB. METHODS: One hundred and thirteen DLB patients, 53 Alzheimer's disease (AD) patients, 20 AD and DLB patients, 31 patients with other neurocognitive diseases (including prodromal and mild demented patients), and 31 healthy elderly controls were included in this case-control study. Photophobia was systematically looked for and compared between groups. Among a selection of 77 DLB patients, we used voxel-based morphometry (VBM) to compare those with and those without photophobia (gray matter volume; SPM12, XjView, and Matlab R2021b software). RESULTS: The frequency of photophobia was higher in the DLB group (47.3%) than in the other groups (p = 0.002). The photophobia questionnaire score was higher in the DLB group than in the AD group (p = 0.001). Comparison between DLB patients with and those without photophobia showed decreased gray matter in the photophobia subgroup, in the right precentral cortex, in the eyelid motor region of Penfield's homunculus (p = 0.007, family-wise error [FWE] corrected). CONCLUSIONS: Photophobia is a quite frequent symptom of prodromal and mild DLB. The neural basis of photophobia in DLB involves the right precentral cortex, which could have a role in the decrease of cerebral excitability, but also the motricity of the eyelids.

Validation of the Utah Photophobia Symptom Impact Scale (version 2) as a headache-specific photophobia assessment tool.

OBJECTIVE: To present an updated version of the Utah Photophobia Symptom Impact Scale version 2 (UPSIS2), providing robust clinical and psychometric validation, to improve headache-specific evaluation of light sensitivity and headache-related photophobia. BACKGROUND: The original UPSIS filled a gap in available tools for assessment of headache-associated light sensitivity by providing patient-reported evaluation of the impact of light sensitivity on activities of daily living (ADLs). We have since revised the original questionnaire to provide a more robust item construct and refined validation approach. METHODS: We conducted a psychometric validation of the UPSIS2 through a primary analysis of an online survey of volunteers with recurrent headaches recruited from the University of Utah clinics and surrounding community. Volunteers completed the original UPSIS and UPSIS2 questionnaire versions in addition to measures of headache impact, disability, and frequency. The UPSIS2 now includes a pre-defined recall period and a 1-4 Likert scale with standardized response anchors to improve clarity. Internal construct validity, external construct validity, and test-retest reliability, were evaluated. RESULTS: Responses were obtained from 163 volunteers, with UPSIS2 scores ranging from 15 to 57 (out of a possible 15-60) with a mean (standard deviation) of 32.4 (8.80). Construct validity was satisfactory, as evidenced by sufficient unidimensionality, monotonicity, and local independence. Reliability was excellent, with Rasch test reliability = 0.90 and Cronbach's alpha = 0.92, and an intraclass correlation of 0.79 (95% confidence interval 0.65-0.88) for participants who took the test twice. UPSIS2 correlates well with other headache measures (Spearman's correlations >0.50), as well as the original UPSIS (Spearman's correlation = 0.87), indicating good convergent validity. UPSIS2 scores differ significantly across International Classification of Headache Disorders (third edition) groups, indicating good known group validity. CONCLUSION: The UPSIS2 provides a well-validated headache-specific outcome measure for the assessment of photophobia impact on ADLs.

Perceived severity of Visual Snow Syndrome is associated with visual allodynia.

OBJECTIVE: To investigate whether sensory sensitivity is associated with the perceived severity of Visual Snow Syndrome (VSS) symptoms. BACKGROUND: Visual Snow (VS) is a perceptual anomaly which manifests as flashing pinpricks of light throughout the visual field. VSS has an estimated population prevalence of 2.2% and is thought to be at least moderately debilitating for all who experience it. However, some people who meet the criteria for VSS have no awareness of it. This may be because they have lower sensory sensitivity, allowing them to ignore their visual phenomena. METHOD: Our study used a cross-sectional design. We recruited two distinct samples of people with VSS: a sample of people with confirmed VSS; and a sample of people who met the criteria for the condition but had no prior knowledge of it (latent VSS). The latter group was recruited and screened for symptoms via an online crowd-sourcing platform. In total, 100 participants with VSS (49 with confirmed VSS, 51 with latent VSS) completed the Visual Snow Handicap Index and three measures of sensory hypersensitivity. RESULTS: The 100 participants (52 female, 47 male, 1 non-binary) had a mean age of 35.1 years (SD = 12.2). Leiden Visual Sensitivity Scale scores were associated with both the perceived severity of VSS, ß = 0.35, p = 0.003, and the number of VSS symptoms endorsed, ß = 0.45, p < 0.001. On average, participants with VSS experienced elevated sensory hypersensitivity across all measures. Furthermore, longer duration of VSS was associated with lower perceived severity, F(1, 98) = 11.37, p = 0.001, R2  = 0.103. CONCLUSIONS: Our results suggest that sensory hypersensitivity may be prevalent in people with VSS and indicate that visual allodynia is associated with increased severity of VSS. Additionally, our findings indicate that inclusion of cases of latent VSS in future research may be important for researchers to develop a more complete understanding of the perceptual experiences of people with VSS.

Sensory hypersensitivities are associated with post-traumatic headache-related disability.

OBJECTIVE: To examine whether sensory hypersensitivity contributes to headache-related disability in a secondary analysis of patients with post-traumatic headache. BACKGROUND: Up to one-third of individuals with traumatic brain injuries report persistent headache 3 months post-injury. High rates of allodynia and photophobia have been observed in clinical studies and animal models of post-traumatic headache, but we do not fully understand how sensory amplifications impact post-traumatic headache-related disability. METHODS: We identified a cross-sectional sample of patients from the American Registry for Migraine Research database with new or worsening headaches post-head injury from 2016 to 2020 and performed a secondary analysis of those data. We modeled the relationship between sensory sensitivity and Migraine Disability Assessment scores using questionnaires. Candidate variables included data collection features (study site and year), headache-related and general clinical features (headache frequency, migraine diagnosis, abuse history, sex, age, cognitive and affective symptom scores), and sensory symptoms (related to light, sound, and touch sensitivity). RESULTS: The final sample included 193 patients (median age 46, IQR 22; 161/193, 83.4% female). Migraine Disability Assessment scores ranged from 0 to 260 (median 47, IQR 87). The final model included allodynia, hyperacusis, photosensitivity, headache days per month, abuse history, anxiety and depression, cognitive dysfunction, and age (R2 = 0.43). An increase of one point in allodynia score corresponded to a 3% increase in headache disability (95% CI: 0%-7%; p = 0.027), an increase of one-tenth of a point in the photosensitivity score corresponded to a 12% increase (95% CI: 3%-25%; p = 0.002), and an increase of one point in the hyperacusis score corresponded to a 2% increase (95% CI: 0%-4%; p = 0.016). CONCLUSIONS: Increased photosensitivity, allodynia, and hyperacusis were associated with increased headache-related disability in this sample of patients with post-traumatic headache. Symptoms of sensory amplification likely contribute to post-traumatic headache-related disability and merit an ongoing investigation into their potential as disease markers and treatment targets.

Selective amplification of ipRGC signals accounts for interictal photophobia in migraine.

Second only to headache, photophobia is the most debilitating symptom reported by people with migraine. While the melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to play a role, how cone and melanopsin signals are integrated in this pathway to produce visual discomfort is poorly understood. We studied 60 people: 20 without headache and 20 each with interictal photophobia from migraine with or without visual aura. Participants viewed pulses of spectral change that selectively targeted melanopsin, the cones, or both and rated the degree of visual discomfort produced by these stimuli while we recorded pupil responses. We examined the data within a model that describes how cone and melanopsin signals are weighted and combined at the level of the retina and how this combined signal is transformed into a rating of discomfort or pupil response. Our results indicate that people with migraine do not differ from headache-free controls in the manner in which melanopsin and cone signals are combined. Instead, people with migraine demonstrate an enhanced response to integrated ipRGC signals for discomfort. This effect of migraine is selective for ratings of visual discomfort, in that an enhancement of pupil responses was not seen in the migraine group, nor were group differences found in surveys of other behaviors putatively linked to ipRGC function (chronotype, seasonal sensitivity, presence of a photic sneeze reflex). By revealing a dissociation in the amplification of discomfort vs. pupil response, our findings suggest a postretinal alteration in processing of ipRGC signals for photophobia in migraine.

Keratitis-ichthyosis-deafness syndrome: A comprehensive review of cutaneous and systemic manifestations.

Keratitis-ichthyosis-deafness syndrome is a rare genetic disease presenting with cutaneous, ocular, and otic defects. This comprehensive review provides insight into the clinical presentations, highlighting the cutaneous manifestations including histopathology and treatment options.

Blue Light-Ocular and Systemic Damaging Effects: A Narrative Review.

Light is a fundamental aspect of our lives, being involved in the regulation of numerous processes in our body. While blue light has always existed in nature, with the ever-growing number of electronic devices that make use of short wavelength (blue) light, the human retina has seen increased exposure to it. Because it is at the high-energy end of the visible spectrum, many authors have investigated the theoretical harmful effects that it poses to the human retina and, more recently, the human body, given the discovery and characterization of the intrinsically photosensitive retinal ganglion cells. Many approaches have been explored, with the focus shifting throughout the years from examining classic ophthalmological parameters, such as visual acuity, and contrast sensitivity to more complex ones seen on electrophysiological assays and optical coherence tomographies. The current study aims to gather the most recent relevant data, reveal encountered pitfalls, and suggest future directions for studies regarding local and/or systemic effects of blue light retinal exposures.