Utility of iPhone-Based Pupillometry in Comparing Pupillary Dynamics Between Sport Concussed Subjects With Photosensitivity and Healthy Controls.

BACKGROUND: To compare the pupillary dynamics using an iPhone-based pupillometry technique in subjects with sports concussion with photosensitivity and aged-matched controls. METHODS: Fifty subjects with sports concussion were compared with 50 aged-matched healthy controls. Athletes with persistent concussive symptoms for 1 year or more after the initial injury were included. All the subjects underwent a Post-Concussion Symptom Scale (PCSS) administration followed by pupillary dynamics measurement using an iPhone-based application (Reflex-Pro PLR analyzer). RESULTS: The mean age was 27 ± 4 years in the concussed group and 26 ± 5 years in the control group. In subjects with concussion, there was a significant decrease in the mean of the following parameters: average constriction speed (1.10 ± 0.15 vs 1.78 ± 0.12 mm/s; P < 0.001), maximum constriction speed (2.05 ± 0.26 vs 3.84 ± 0.28 mm/s; P < 0.001), average diameter (3.64 ± 0.12 vs 0.36 ± 0.05 mm; P < 0.001), maximum diameter (4.75 ± 0.17 vs 5.23 ± 0.16 mm; P < 0.001), and minimum diameter (2.75 ± 0.17 vs 3.64 ± 0.11 mm; P < 0.001). An increase in the following parameters was noted in concussion vs age-matched controls: dilation release amplitude (0.54 ± 0.96 vs 0.36 ± 0.05 mm; P < 0.001) and latency (0.25 ± 0.05 vs 0.21 ± 0.02 s; P < 0.001). Subjects with concussion with photosensitivity exhibited increased dilation release amplitudes ( P < 0.001). CONCLUSIONS: Individuals with sport concussion had impairment in pupillary constriction velocities, latency, and diameter in more than 1 year after concussion. The increase in dilation release amplitude among subjects with concussion might serve as a biomarker in diagnosing the underlying symptom of photosensitivity. The iPhone-based pupillometry could serve as a convenient and diagnostic tool in diagnosing these symptoms.

Interrater agreement of classification of photoparoxysmal electroencephalographic response.

Our goal was to assess the interrater agreement (IRA) of photoparoxysmal response (PPR) using the classification proposed by a task force of the International League Against Epilepsy (ILAE), and a simplified classification system proposed by our group. In addition, we evaluated IRA of epileptiform discharges (EDs) and the diagnostic significance of the electroencephalographic (EEG) abnormalities. We used EEG recordings from the European Reference Network (EpiCARE) and Standardized Computer-based Organized Reporting of EEG (SCORE). Six raters independently scored EEG recordings from 30 patients. We calculated the agreement coefficient (AC) for each feature. IRA of PPR using the classification proposed by the ILAE task force was only fair (AC = 0.38). This improved to a moderate agreement by using the simplified classification (AC = 0.56; P = .004). IRA of EDs was almost perfect (AC = 0.98), and IRA of scoring the diagnostic significance was moderate (AC = 0.51). Our results suggest that the simplified classification of the PPR is suitable for implementation in clinical practice.

A study of the significance of photoparoxysmal responses and spontaneous epileptiform discharges in the EEG in childhood epilepsy.

AIM: In clinical practice, there is a prevailing notion that photosensitivity mostly occurs in children with epilepsy (CWE) with idiopathic generalized epilepsy. We investigated the distribution of epilepsy types and etiology in photosensitive children and the associations with specific clinical and electroencephalogram (EEG) variables. METHODS: In this retrospective cohort study, clinical data were acquired from all children that showed photosensitivity during systematic intermittent photic stimulation (IPS), over a 10-year interval at a tertiary level Children's Hospital, Winnipeg. Patient demographics, EEG findings, and clinical data and symptoms during IPS were abstracted. Classification of diagnoses using the International League Against Epilepsy (ILAE) 2017 guidelines was done by an expert panel. RESULTS: Seventy-eight photosensitive children were identified. Forty (51.3%) had generalized epilepsy (idiopathic: 27, structural: 2, other: 11) compared with 19 (24.4%) focal (idiopathic: 1, structural: 2, other: 16), 8 (10.3%) combined focal and generalized (structural: 4, other: 4), and 11 (14.1%) unknown epilepsy (other: 11); (χ2 (3) = 32.1, p = .000). Self-sustaining or outlasting photoparoxysmal responses (PPRs) occurred in association with all epilepsy types; however, the EEGs of focal CWE without treatment comprised almost solely of PPRs which outlasted the stimulus (8/10), in contrast to only 8/17 of focal CWE with treatment and to 13/26 of generalized epilepsy without treatment. Most frequency intervals in individual patients were less under treatment: a decrease in standardized photosensitivity range (SPR) was seen in 5 CWE, an increase in 2, and no change in 1 during treatment. Both CWE with focal and generalized epilepsy showed abnormal activity on EEG during hyperventilation (40% vs 65.7%). Thirteen out of 14 CWE with clinical signs during IPS had independent spontaneous epileptiform discharges (SEDs) in the EEG recording. CONCLUSION: Photosensitivity occurs in all types of epilepsy rather than in idiopathic generalized epilepsy alone. Surprisingly, there is a tendency for focal epilepsy to be associated with self-sustaining PPRs, especially when no treatment is used. Treatment tends to make the PPR more self-limiting and decrease the SPR. There is a tendency that clinical signs during IPS occur in EEGs in individuals with SEDs.

Evaluation of the minimal erythema dose for UVB and UVA in context of skin phototype and nature of photodermatosis.

BACKGROUND: Phototesting is part of the standard procedure for the evaluation of patients with photosensitivity disorders. The response of patients to targeted UVB or UVA radiation helps to find out more about the nature of photodermatosis. Nevertheless, there are no default values of the minimal erythema dose (MED). METHODS: This study evaluated data of 203 patients (131 female, 72 male, mean age 52 years) who were referred for phototesting to the University Hospital Zurich between 2012 and 2017. We retrospectively analyzed the demographic data, medical history, skin phototype, reaction to UVB and UVA radiation, and, if present, the diagnosis of photodermatosis. In patients who did not develop erythema at the highest tested UV doses, the next logical increment was taken for analysis. In case of UVA, the two periphery doses could not be evaluated due to technical issues, so the closest reliable UVA doses were used. RESULTS: The MED-UVB correlated with the skin type and increased with a higher phototype. No such correlation could be seen for MED-UVA. However, the MED-UVA was significantly reduced in patients with photodermatosis without significant differences between the subgroups of photodermatosis. More than half of the patients did not show a reduced MED despite a diagnosed photodermatosis. CONCLUSION: We showed, how different skin types with and without photodermatosis react to UV radiation. Based on the results, we suggested threshold doses that can be chosen for phototesting, presented which doses can be considered pathologic and showed the probability of a pathologic MED in correlation with a diagnosed photodermatosis.

Assessment of Predictors of Sun Sensitivity as Defined by Fitzpatrick Skin Phototype in an Ecuadorian Population and Its Correlation with Skin Damage.

BACKGROUND: The Fitzpatrick skin phototype scale (FSPTS) is a widely used instrument to assess skin type. METHODS: A cross-sectional survey collected responses from 254 subjects from Quito regarding self-reported FSPTS, gender, age, education, and tobacco and alcohol consumption. Univariate and multivariate logistic regression analyses were performed to determine if ethnicity, hair color, and eye color significantly predict FSPTS. In addition, we studied the correlation between FSPTS and the SCINEXA scale with Pearson's correlation coefficient. RESULTS: Ethnicity, eye color, and hair color are significant independent predictors of FSPTS (p < 0.0001). CONCLUSIONS: Patient self-reported race and pigmentary phenotypes are inaccurate predictors of sun sensitivity as defined by Fitzpatrick skin phototype. Our study does not fully represent the population of the country. There are limitations to using patient-reported race and appearance in predicting individual sunburn risk.

Functional and clinical relevance of novel mutations in a large cohort of patients with Cockayne syndrome.

BACKGROUND: Cockayne syndrome (CS) is a rare, autosomal recessive multisystem disorder characterised by prenatal or postnatal growth failure, progressive neurological dysfunction, ocular and skeletal abnormalities and premature ageing. About half of the patients with symptoms diagnostic for CS show cutaneous photosensitivity and an abnormal cellular response to UV light due to mutations in either the ERCC8/CSA or ERCC6/CSB gene. Studies performed thus far have failed to delineate clear genotype-phenotype relationships. We have carried out a four-centre clinical, molecular and cellular analysis of 124 patients with CS. METHODS AND RESULTS: We assigned 39 patients to the ERCC8/CSA and 85 to the ERCC6/CSB genes. Most of the genetic variants were truncations. The missense variants were distributed non-randomly with concentrations in relatively short regions of the respective proteins. Our analyses revealed several hotspots and founder mutations in ERCC6/CSB. Although no unequivocal genotype-phenotype relationships could be made, patients were more likely to have severe clinical features if the mutation was downstream of the PiggyBac insertion in intron 5 of ERCC6/CSB than if it was upstream. Also a higher proportion of severely affected patients was found with mutations in ERCC6/CSB than in ERCC8/CSA. CONCLUSION: By identifying >70 novel homozygous or compound heterozygous genetic variants in 124 patients with CS with different disease severity and ethnic backgrounds, we considerably broaden the CSA and CSB mutation spectrum responsible for CS. Besides providing information relevant for diagnosis of and genetic counselling for this devastating disorder, this study improves the definition of the puzzling genotype-phenotype relationships in patients with CS.

Clinical and immunological profile in patients with mixed connective tissue disease.

Mixed connective tissue disease (MCTD) is a rare disease and presents with varied overlapping symptoms of different connective tissue disorders. Many patients evolve into other connective tissue disorders with the passage of time. The case series included 20 patients with the diagnosis of MCTD, registered at the Rheumatology Clinic of Jinnah Postgraduate Medical Centre (JPMC), Karachi, from June 2010 to May 2015. Of these, 16 (80.0%) were female and 4 (20.0%) patients were male. The mean age was 30.5±8.9 years and the mean duration of illness was 4.5±2 years. Commonest presenting symptom was arthralgia in 17 (85%) patients. All the patients had positive ANA and anti-RNP antibodies. Over the disease course of 6 years, 2 (10%) patients evolved into Systemic lupus erythematosus (SLE); One each (5%) into Sjogren's syndrome, Scleroderma and Rheumatoid arthritis.

Photodermatoses in the Pigmented Skin.

Skin colour (specifically in relation to its melanin content and composition) has a marked influence on its interaction with ultraviolet light. Eumelanin has mainly photoprotective properties while pheomelanin has the ability to cause formation of reactive oxygen species. This difference is responsible for the difference in incidence and presentation of various idiopathic photodermatoses in dark skinned patients compared to those with lighter skin types. Certain conditions are peculiar to darker skins including pin point popular variant of polymorphous light eruption. These differences are discussed in this chapter while also highlighting the challenges faced in performing phototesting in patients with dark skin.

Skin equivalents: skin from reconstructions as models to study skin development and diseases.

While skin is readily available for sampling and direct studies of its constituents, an important intermediate step is to design in vitro and/or in vivo models to address scientific or medical questions in dermatology and skin biology. Pioneered more than 30 years ago, human skin equivalents (HSEs) have been refined with better cell culture techniques and media, together with sophisticated cell biology tools including genetic engineering and cell reprogramming. HSEs mimic key elements of human skin biology and have been instrumental in demonstrating the importance of cell-cell interactions in skin homeostasis and the role of a complex cellular microenvironment to coordinate epidermal proliferation, differentiation and pigmentation. HSEs have a wide field of applications from cell biology to dermocosmetics, modelling diseases, drug development, skin ageing, pathophysiology and regenerative medicine. In this article we critically review the major current approaches used to reconstruct organotypic skin models and their application with a particular emphasis on skin biology and pathophysiology of skin disorders.

Overactive visuomotor connections underlie the photoparoxysmal response. A TMS study.

OBJECTIVE: The photoparoxysmal response (PPR) involves rapid spread of epileptic activity from visual to parietal and frontal areas. We used a transcranial magnetic stimulation (TMS) technique to assess the physiologic connections between primary visual (V1) and motor (M1) areas in patients with idiopathic generalized epilepsy (IGE). We hypothesized that in PPR-positive patients, M1 would respond excessively to inputs from V1. METHODS: Eleven photosensitive patients with IGE who had a PPR at the time of the study were compared with 10 similar patients without a PPR, and with 11 healthy subjects of similar age and sex. The connection between V1 and M1 was assessed in resting participants by delivering a conditioning stimulus (CS) over the phosphene hotspot of the visual cortex (intensity 90% phosphene threshold, PT) followed at random interstimulus intervals (ISIs; 15, 18, 21, 24, 27, 30, 35 and 40 msec) by a test stimulus (TS) over the left motor cortex to elicit a motor evoked potential (MEP) of ~1 mV from the right first dorsal interosseous muscle. RESULTS: In healthy subjects, a CS over V1 suppressed M1 at ISIs between 18 and 40 msec. Similar effects occurred in IGE patients without a PPR. This was not true in PPR-positive IGE patients, in whom this type of physiologic inhibition was significantly (p < 0.05) reduced. SIGNIFICANCE: IGE patients with a PPR have an overactive functional response of M1 to inputs traveling from V1. This may represent one core factor for the anterior spread of the PPR itself and for the origin of the abnormal epileptic motor phenomenon, such as myoclonus.

Cortical Thickness Changes Associated with Photoparoxysmal Response.

Photoparoxysmal response (PPR) is an EEG trait of spike and spike-wave discharges in response to photic stimulation that is closely linked to idiopathic generalized epilepsy (IGE). In our previous studies we showed that PPR is associated with functional alterations in the occipital and frontal cortices. The aim of the present study was to determine structural changes associated with PPR. For this purpose we analysed the cortical thickness as derived from T1 MRI images in PPR-positive-subjects (n = 12; 15.5 ± 8.6 years; 4 males), PPR-positive-IGE-patients (n = 12; 14.9 ± 2.7 years; 4 males) and compared these groups with a group of PPR-negative-healthy-controls (HC, n = 17; 15.3 ± 3.6 years; 6 males). Our results revealed an increase of cortical thickness in the occipital, frontal and parietal cortices bilaterally in PPR-positive-subjects in comparison to HC. Moreover PPR-positive-subjects presented a significant decrease of cortical thickness in the temporal cortex in the same group contrast. IGE patients exhibited lower cortical thickness in the temporal lobe bilaterally and in the right paracentral region in comparison to PPR-positive-subjects. Our study demonstrates structural changes in the occipital lobe, frontoparietal regions and temporal lobe, which also show functional changes associated with PPR. Patients with epilepsy present changes in the temporal lobe and supplementary motor area.

Actinic Prurigo.

Actinic prurigo is an idiopathic photodermatosis that affects the skin, as well as the labial and conjunctival mucosa in indigenous and mestizo populations of Latin America. It starts predominantly in childhood, has a chronic course, and is exacerbated with solar exposure. Little is known of its pathophysiology, including the known mechanisms of the participation of HLA-DR4 and an abnormal immunologic response with increase of T CD4+ lymphocytes. The presence of IgE, eosinophils, and mast cells suggests that it is a hypersensitivity reaction (likely type IVa or b). The diagnosis is clinical, and the presence of lymphoid follicles in the mucosal histopathologic study of mucosa is pathognomonic. The best available treatment to date is thalidomide, despite its secondary effects.

[Aged skin and skin care]. / Altershaut und Hautpflege.

BACKGROUND: Aged skin is the sum of chronological und UV-induced aging. Light-exposed skin is unattractive, with irregular pigmentation, roughness und scaliness. The skin is often dry and itches. METHODS: The present paper provides an overview of diseases of aging skin and describes how to prevent or reduce disease by prophylactic and therapeutic skin care. RESULTS: Aged skin can develop into several skin diseases, e.g., different types of eczema and skin cancer. In the body folds we often find an irritant contact eczema caused by friction from skin to skin, sweating, and urinary and fecal incontinence. In the bedridden, bed sores can also develop. Furthermore, there is a delay in wound healing owing to old age. Use of adequate creams and ointments is very helpful in preventing and improving most skin diseases of mature skin. However, the knowledge of aged people and healthcare professionals about the importance of skin care is low. Older people are often unable to care for their skin because they are lacking the physical and mental ability. CONCLUSION: Healthcare professionals are not sufficiently trained about the value of proper skin care. Adequate studies on the role of skin care and selection of the correct preparation in various aged-related diseases are lacking.

Evidence and conjecture about mechanisms of cutaneous disease in photodermatology.

Photosensitivity disorders are caused by a variety of mechanisms. Three common themes are as follows: excess chromophore allowing visible light energy to cause photodynamic damage, reduced DNA repair capacity to UV-induced DNA damage, and enhanced sensitivity to light-induced allergens mediated immunologically. Although the cause of each condition may be known, the precise pathogenesis underlying the photosensitivity has taken longer to understand. By focussing on three clinical disorders under each of these themes, we have explored the following: why erythropoietic protoporphyria differs so markedly from the other cutaneous porphyrias; how a DNA repair defect was eventually revealed to be the underlying cause of the vitamin B3 deficiency disorder of pellagra; an immunological explanation for the over reactivity to photoallergens in chronic actinic dermatitis.

Caspase-14 protects against epidermal UVB photodamage and water loss.

Caspase-14 belongs to a conserved family of aspartate-specific proteinases. Its expression is restricted almost exclusively to the suprabasal layers of the epidermis and the hair follicles. Moreover, the proteolytic activation of caspase-14 is associated with stratum corneum formation, implicating caspase-14 in terminal keratinocyte differentiation and cornification. Here, we show that the skin of caspase-14-deficient mice was shiny and lichenified, indicating an altered stratum-corneum composition. Caspase-14-deficient epidermis contained significantly more alveolar keratohyalin F-granules, the profilaggrin stores. Accordingly, caspase-14-deficient epidermis is characterized by an altered profilaggrin processing pattern and we show that recombinant caspase-14 can directly cleave profilaggrin in vitro. Caspase-14-deficient epidermis is characterized by reduced skin-hydration levels and increased water loss. In view of the important role of filaggrin in the structure and moisturization of the skin, the knockout phenotype could be explained by an aberrant processing of filaggrin. Importantly, the skin of caspase-14-deficient mice was highly sensitive to the formation of cyclobutane pyrimidine dimers after UVB irradiation, leading to increased levels of UVB-induced apoptosis. Removal of the stratum corneum indicate that caspase-14 controls the UVB scavenging capacity of the stratum corneum.

Comparison of photodermatoses in African-Americans and Caucasians: a follow-up study.

BACKGROUND/PURPOSE: Only a few studies have compared frequencies of photodermatoses among different races and skin types. This is an extension of a study performed by Kerr and Lim and evaluates the frequency of photodermatoses in African-Americans compared with Caucasians in the same institution during an 8-year period. METHODS: Retrospective chart review was performed, including dermatology clinic charts from October 2004 to August 2012 with International Classification of Diseases, Ninth Revision diagnostic codes related to photodermatoses. RESULTS: We identified 229 patients with photodermatoses. Of these, 138 (46.6%) were African-American and 63 (42.2%) were Caucasian. Statistically significant differences in the distribution of photodermatoses in African-Americans and Caucasians, respectively, were as follows: phototoxic drug eruption (0.7% and 15.9%, P < 0.0001), phytophotodermatitis (0% and 6.3%, P = 0.009), polymorphous light eruption (PMLE) (86.2% and 54%, P < 0.0001) and porphyrias (0% and 7.9%, P = 0.003). CONCLUSION: Combined with data from Kerr and Lim, this is the largest study of photodermatoses in African-Americans to date. Congruent to former studies, photodermatoses do occur regularly in dark-skinned individuals. Overall, the frequency of photodermatoses in African-Americans and Caucasians are similar; however, PMLE occurs more commonly in African-Americans, and porphyias and phototoxicity occur more commonly in Caucasians.

Photosensitivity in mild traumatic brain injury (mTBI): a retrospective analysis.

PRIMARY OBJECTIVE: To determine whether photosensitivity (PS) changes over time and, if so, what factors may be related to the change; furthermore, to determine whether tint density changes over time, all in mild traumatic brain injury (mTBI). DESIGN AND METHODS: A retrospective analysis of 62 patient records (aged 18-40 years) with mTBI and PS was conducted. All charts were obtained from the SUNY/College of Optometry clinics from 2004-2011. RESULTS: Fifty per cent demonstrated reduced PS over time, with most occurring after year 1 post-injury (40%). Promotion of PS reduction appears to be associated with the lack of spectacle tint usage (p = 0.01) and the use of contact lenses (p = 0.03). Inhibition of PS reduction appears to be associated with tinted lenses (p = 0.06), hyperacusis (p = 0.03), dry eye (p = 0.04), migraines (p = 0.03) and loss of consciousness at the time of injury (p = 0.05). Concerning tint density changes over time, 71% (p = 0.002) maintained the same degree over time, while 27% (p = 0.002) reduced and 2% waxed and waned. CONCLUSION: Neural adaptation to PS appears to be a long-term process. Tint usage may act to inhibit this adaptive process, while the use of contact lenses may act to promote it. These findings may provide guidance in the clinical management of photosensitivity in the mTBI population.

Study of idiopathic, exogenous photodermatoses. Part 1: pathophysiology and technical aspects of photobiologic studies.

Photodermatoses are skin conditions that are induced or exacerbated by electromagnetic radiation (including visible light, UV light, and infrared radiation) from the sun or artificial light sources. In Part 1 of this series we review current understanding of the pathophysiology of these processes and their classification. We also discuss technical aspects and the basic physics of photobiology and describe the equipment required for photobiologic testing and calibration (light sources and measurement instruments).

Photosensitivity and self-induction in patients aged 50 and older.

OBJECTIVE: Photosensitivity is known to occur predominantly in children and adolescents and with a clear female predominance. Little is known on the prevalence of photosensitivity in older patients (50+) and its phenotypical appearance. METHODS: A retrospective observational study was performed investigating the prevalence of a photoparoxysmal EEG response (PPR) on at least one EEG during the period 2015-2021. Data were gathered from patients aged 50 years and older by retrieving clinical and EEG characteristics from existing medical records. Data on photosensitivity-related symptoms in daily life were gathered with telephone interviewing. RESULTS: In 248 patients a PPR had been elicited, of whom 16 patients (6.5%) were 50 years or older. In older patients, photosensitivity was a persistent feature of childhood-onset epilepsy (n = 8), of adult-onset epilepsy (n = 7), or an incidental finding (n = 1). In the 50+ group, 56% of photosensitive patients was female, whereas 72% in the total PPR-group. In six of 16 older patients, eye closure sensitivity was observed; two of these patients reported self-induction. Symptoms of photosensitivity in daily life were present in eight out of nine patients who consented in a telephone interview. For seven of these patients, wearing sunglasses was helpful. SIGNIFICANCE: Female preponderance for photosensitivity was not found in epilepsy patients of 50 years and older. In 44% of the older photosensitive patients in this series, the PPR was a feature of adult-onset epilepsy. Symptoms of photosensitivity in daily life in older patients with epilepsy seem comparable to those in younger patients, and thus worthwhile to diagnose and treat them equally.