Photophobia and allodynia in persistent post-traumatic headache are associated with higher disease burden.

OBJECTIVE: To assess photophobia and allodynia in subjects with post-traumatic headache and examine how these sensory hypersensitivities associate with clinical measures of disease burden. BACKGROUND: Post-traumatic headache is the most frequent and disabling long-term consequence of mild traumatic brain injury. There is evidence of sensory dysfunction in acute post-traumatic headache, and it is known from other headache conditions that sensory amplifications correlate with more severe disease. However, systematic studies in post-traumatic headache are surprisingly scarce. METHODS: We tested light and tactile sensitivity, along with measures of disease burden, in 30 persistent post-traumatic headache subjects and 35 controls. RESULTS: In all, 79% of post-traumatic headache subjects exhibited sensory hypersensitivity based on psychophysical assessment. Of those exhibiting hypersensitivity, 54% exhibited both light and tactile sensitivity. Finally, sensory thresholds were correlated across modalities, as well as with headache attack frequency. CONCLUSIONS: In this study, post-traumatic headache subjects with both light and tactile sensitivity had significantly higher headache frequencies and lower sensitivity thresholds to both modalities, compared to those with single or no sensory hypersensitivity. This pattern suggests that hypersensitivity across multiple modalities may be functionally synergistic, reflect a higher disease burden, and may serve as candidate markers of disease.

Traits related to bipolar disorder are associated with an increased post-illumination pupil response.

Mood states in bipolar disorder appear to be closely linked to changes in sleep and circadian function. It has been suggested that hypersensitivity of the circadian system to light may be a trait vulnerability for bipolar disorder. Healthy persons with emotional-behavioural traits associated with bipolar disorder also appear to exhibit problems with circadian rhythms, which may be associated with individual differences in light sensitivity. This study investigated the melanopsin-driven post-illumination pupil response (PIPR) in relation to emotional-behavioural traits associated with bipolar disorder (measured with the General Behavior Inventory) in a non-clinical group (n = 61). An increased PIPR was associated with increased bipolar disorder-related traits. Specifically, the hypomania scale of the General Behavior Inventory was associated with an increased post-blue PIPR. Further, both the full hypomania and shortened '7 Up' scales were significantly predicted by PIPR, after age, sex and depressive traits were controlled. These findings suggest that increased sensitivity to light may be a risk factor for mood problems in the general population, and support the idea that hypersensitivity to light is a trait vulnerability for, rather than symptom of, bipolar disorder.

Sensory Sensitivity in TBI: Implications for Chronic Disability.

PURPOSE OF REVIEW: This review investigates the relationship between sensory sensitivity and traumatic brain injury (TBI), and the role sensory sensitivity plays in chronic disability. RECENT FINDINGS: TBI is a significant cause of disability with a range of physical, cognitive, and mental health consequences. Sensory sensitivities (e.g., noise and light) are among the most frequently reported, yet least outwardly recognizable symptoms following TBI. Clinicians and scientists alike have yet to identify consistent nomenclature for defining noise and light sensitivity, making it difficult to accurately and reliably assess their influence. Noise and light sensitivity can profoundly affect critical aspects of independent function including communication, productivity, socialization, cognition, sleep, and mental health. Research examining the prevalence of sensory sensitivity and evidence for the association of sensory sensitivity with TBI is inconclusive. Evidence-based interventions for sensory sensitivity, particularly following TBI, are lacking.

Sex differences in light sensitivity impact on brightness perception, vigilant attention and sleep in humans.

Artificial light endows a "round-the-clock", 24-h/7-d society. Chronic exposure to light at night contributes to health hazards for humans, including disorders of sleep. Yet the influence of inter-individual traits, such as sex-differences, on light sensitivity remains to be established. Here we investigated potential sex-differences to evening light exposure of 40 lx at 6500 K (blue-enriched) or at 2500 K (non-blue-enriched), and their impact on brightness perception, vigilant attention and sleep physiology. In contrast to women, men had higher brightness perception and faster reaction times in a sustained attention task during blue-enriched light than non-blue-enriched. After blue-enriched light exposure, men had significantly higher all-night frontal NREM sleep slow-wave activity (SWA: 2-4 Hz), than women, particularly during the beginning of the sleep episode. Furthermore, brightness perception during blue-enriched light significantly predicted men's improved sustained attention performance and increased frontal NREM SWA. Our data indicate that, in contrast to women, men show a stronger response to blue-enriched light in the late evening even at very low light levels (40lux), as indexed by increased vigilant attention and sleep EEG hallmarks. Collectively, the data indicate that sex differences in light sensitivity might play a key role for ensuring the success of individually-targeted light interventions.

Colored Glasses to Mitigate Photophobia Symptoms Posttraumatic Brain Injury.

CONTEXT: After a concussion or mild traumatic brain injury (mTBI), patients often suffer from light sensitivity, or photophobia, which contributes to decreased quality of life post-mTBI. Whereas sunglasses may provide some relief from photophobia, they are not practical indoors or in low light. A light-mitigation strategy can be easily used indoors as needed to optimize the relief. We have found that many photophobic patients experience relief using colored sunglasses. OBJECTIVE: To provide the athletic trainer with a means and method to assess whether an athlete is suffering from photophobia after concussion and to determine if colored glasses provide relief. DESIGN: Cross-sectional study. SETTING: Rehabilitation clinic. PATIENTS OR OTHER PARTICIPANTS: Fifty-one patients being treated after concussion. INTERVENTION(S): We assessed postconcussion patients for visual symptoms including photophobia and photosensitivity. Off-the-shelf glasses were used to determine whether specific colors provided relief from photophobia. Screening was done using a penlight and multiple pairs of colored glasses. MAIN OUTCOME MEASURE(S): Self-reported mitigation of photophobia symptoms and the specific color frequency that reduced symptoms in each individual. RESULTS: Of the 39 patients studied who had visual symptoms, 76% complained of photophobia. Using glasses of 1 or more colors, symptoms were relieved in 85% of patients reporting photophobia. The colors that provided the most relief were blue, green, red, and purple. No adverse events were reported. CONCLUSIONS: An empirical assessment of frequency-specific photophobia is easy to perform. A traditional penlight is used to elicit photophobia and then the colored glasses are tested for optimal relief. Frequency-specific photophobia can be reduced with a strategy of light-mitigation therapy, including colored glasses, sunglasses, hats, and light avoidance. This, we believe, helps to improve the patient's quality of life and may aid in the recovery process. More work is needed to identify the best colors and methods of mitigating frequency-specific photophobia.

Induction of Migraine-Like Photophobic Behavior in Mice by Both Peripheral and Central CGRP Mechanisms.

The neuropeptide calcitonin gene-related peptide (CGRP) is a key player in migraine. Although migraine can be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain unknown. To address the role of CGRP both within and outside the CNS, we used CGRP-induced light-aversive behavior in mice as a measure of migraine-associated photophobia. Peripheral (intraperitoneal) injection of CGRP resulted in light-aversive behavior in wild-type CD1 mice similar to aversion seen previously after central (intracerebroventricular) injection. The phenotype was also observed in C57BL/6J mice, although to a lesser degree and with more variability. After intraperitoneal CGRP, motility was decreased in the dark only, similar to motility changes after intracerebroventricular CGRP. In addition, as with intracerebroventricular CGRP, there was no general increase in anxiety as measured in an open-field assay after intraperitoneal CGRP. Importantly, two clinically effective migraine drugs, the 5-HT1B/D agonist sumatriptan and a CGRP-blocking monoclonal antibody, attenuated the peripheral CGRP-induced light aversion and motility behaviors. To begin to address the mechanism of peripheral CGRP action, we used transgenic CGRP-sensitized mice that have elevated levels of the CGRP receptor hRAMP1 subunit in nervous tissue (nestin/hRAMP1). Surprisingly, sensitivity to low light was not seen after intraperitoneal CGRP injection, but was seen after intracerebroventricular CGRP injection. These results suggest that CGRP can act in both the periphery and the brain by distinct mechanisms and that CGRP actions may be transmitted to the CNS via indirect sensitization of peripheral nerves. SIGNIFICANCE STATEMENT: The neuropeptide calcitonin gene-related peptide (CGRP) is a central player in migraine pathogenesis, yet its site(s) of action remains unknown. Some preclinical studies have pointed to central sites in the brain and brainstem. However, a peripheral site of action is indicated by the ability of intravenous CGRP to trigger migraine in humans and the efficacy of CGRP receptor antagonists that evidently do no penetrate the CNS in effective amounts. Resolving this issue is particularly important given recent clinical trials showing that anti-CGRP monoclonal antibodies can reduce and even prevent migraine attacks. In this study, we report that CGRP can act in both the brain and the periphery of the mouse to cause migraine-like photophobia by apparently distinct mechanisms.

Photophobia in primary headaches, in essential blepharospasm and in major depression.

OBJECTIVES: Although photophobia is a well-known symptom in various disorders, it has rarely been studied explicitly and its definition in a clinical setting can be somewhat elusive. Here, we assessed photophobia with a common psychometric tool in different conditions, in which light intolerance is considered part of the syndrome. PATIENTS AND METHODS: A prospective study was undertaken in patients with migraine (MH), cluster headache (CH), tension-type headache (TH), essential blepharospasm (BS) and major depression (MD). Photophobia was assessed by the photophobia questionnaire (range 0-8). Symptom severity was measured in each patient group with appropriate scales. Finally, depression was assessed explicitly in each condition. RESULTS: Hundred and six subjects met the inclusion criteria (MH: 27, CH: 21, TH: 20, BS: 18, MD: 20). Photophobia scores differed between patient groups, with migraineurs showing the highest (6.63) and TH patients the lowest (2.10) scores (ranking: MH, BS, CH, MD and TH). Symptom severity as well as depression had little, if any, influence on the degree of photophobia. DISCUSSION: Photophobia is a core symptom of migraine but also constitutes a feature of other neurological conditions. The relative independence from other, disease-specific features, suggests that photophobia is a rather autonomous symptom.

Infusion of low dose glyceryl trinitrate has no consistent effect on burrowing behavior, running wheel activity and light sensitivity in female rats.

INTRODUCTION: Glyceryl trinitrate induces headache during infusion to man and migraine patients develop an additional migraine attack a few hours after the infusion. Recently, we have moved this model into rat with the intention of developing an animal model predictive of migraine therapy. In the current paper we have studied the effect of glyceryl trinitrate infusion on three different rat behaviors. METHODS: The stability of burrowing behavior, running wheel activity and light sensitivity towards repeated testing was evaluated also with respect to estrous cycle. Finally, the effect of glyceryl trinitrate on these behaviors in female rats was observed. RESULTS: Burrowing behavior and running wheel activity were stable in the individual rat between experiments. The burrowing behavior was significantly affected by the stage of estrous cycle. The other assays were stable throughout the cycle. None of the three behavioral tests were altered by glyceryl trinitrate infusion. In the light-dark box, some batches of rats showed light sensitivity after treatment with glyceryl trinitrate but it could not be repeated in other batches of rats. DISCUSSION: We have investigated the stability towards repeated testing and the effect of i.v. glyceryl trinitrate infusion to awake rats in three behavioral assays. Of the assays evaluated, only light sensitivity was capable of detecting changes after glyceryl trinitrate infusion but, this was not repeatable. Thus, the infusion of a low dose glyceryl trinitrate to concious rats together with the chosen behavioral tests is not a robust setup for studying immediate GTN induced headache behavior in rats.

[Influence of combined vitamin deficiency on unconditioned reflexes and learning in growing rats].

The aim of this study was to investigate the effect of combined deficiency of all vitamins on the manifestation of unconditioned reflex and learning (in response to an electric current) in growing Wistar rats with initial body weight 53.4 ± 1.2 g (45.5-62.0 g). 20 of 46 tested male rats (latent period of transition from the illuminated chamber to the dark compartment did not exceed 60 s) were included in the experiment. Rats were randomly divided into 2 groups (control and experimental) for the duration of the latent period and body mass. Within 23 days the rats of the control group received a complete semisynthetic diet. Combined vitamin deficiency in tested rats was caused by 5-fold diet decrease of the amount of vitamin mixture without vitamin E. On the 12th day the second phase of testing was performed, during which the rat received electrocutaneous irritation on paws (current 0.4 mA, 8 seconds) after transition to the dark compartment of the chamber. Preservation of the conducted reflex was performed 24 h and 9 days after training. On the 23rd day pre-anesthetized with ether rats were taken out from the experiment by decapitation. The content of vitamin A (retinol and retinol palmitate) and E (tocopherols) in plasma and liver and in the sunflower oil was analyzed by HPLC, the level of vitamins B1 and B2 in liver and casein by fluorimetric method, blood serum malondialdehyde content--by spectrophotometric method. Reducing of vitamin mixture amount of the diet lead to significant reduction in liver vitamin A, E, B1, and B2 level and in blood plasma vitamin A and E concentration by the end of the experiment, but had no effect on blood plasma MDA concentration. On the 12th day of vitamin deficiency in rats manifestation of unconditioned reflex (photophobia) has been deteriorated, as evidenced by the significant 3,2-fold increase of latent period of transition to the dark compartment compared with animals fed a complete diet (47.8 ± 15.8 vs 14.8 ± 3.6 sec), but their ability to learn hadn't been effected. Based on the data that vitamin deficiency, especially of vitamin-antioxidants, causes oxidative stress, and that increase of corticosterone level in hippocampus during aging significantly inhibits the function of the brain, we can assume that increasing of corticosterone level may be one of the cause of the detected cognitive impairment, as isolated vitamin A deficiency in rats increases tissue corticosterone levels.

Seeing double: sertraline and diplopia: a case report.

OBJECTIVE: To describe the first case of sertraline-induced diplopia. METHOD: Medline and PubMed data search using the words sertraline, Zoloft, diplopia, double vision. A case summary of a patient who developed diplopia from sertraline. RESULT: This case describes a 34-year-old man who developed diplopia after treatment with sertraline. The diplopia resolved after discontinuation of sertraline and redeveloped upon rechallenge. CONCLUSION: Although incidences of diplopia caused by citalopram, another SSRI, have been described, to the best of our knowledge, this is the first reported case of sertraline-induced diplopia. More studies are needed to describe the full mechanism of action of sertraline-induced diplopia.

Modulation of CGRP-induced light aversion in wild-type mice by a 5-HT(1B/D) agonist.

The neuropeptide calcitonin gene-related peptide (CGRP) plays a critical role in the pathophysiology of migraine. We have focused on the role of CGRP in photophobia, which is a common migraine symptom. We previously used an operant-based assay to show that CGRP-sensitized transgenic (nestin/hRAMP1), but not control, mice exhibited light aversion in response to an intracerebroventricular CGRP injection. A key question was whether the transgenic phenotype was due to overexpression of the CGRP receptor at endogenous or novel expression sites. We reasoned that if endogenous receptor sites were sufficient for light-aversive behavior, then wild-type mice should also show the phenotype when given a sufficiently strong stimulus. In this study, we report that mice with normal levels of endogenous CGRP receptors demonstrate light avoidance following CGRP administration. This phenotype required the combination of two factors: higher light intensity and habituation to the testing chamber. Control tests confirmed that light aversion was dependent on coincident exposure to CGRP and light and cannot be fully explained by increased anxiety. Furthermore, CGRP reduced locomotion only in the dark, not in the light. Coadministration of rizatriptan, a 5-HT(1B/D) agonist anti-migraine drug, attenuated the effects of exogenous CGRP on light aversion and motility. This suggests that triptans can act by mechanisms that are distinct from inhibition of CGRP release. Thus, we demonstrate that activation of endogenous CGRP receptors is sufficient to elicit light aversion in mice, which can be modulated by a drug commonly used to treat migraine.

Seeing the light.

Seeing the light is an expression that usually connotes a conceptual grasp of meaning in all its complexity, while the perception of light is not the issue. In this paper, the authors present a patient with an exquisite light sensitivity that disturbs her sleep; she is "seeing the light" in a symptomatic, concrete way. Light itself has become a compliant and collusive element onto which an aspect of conflict is displaced in the service of self-deception. Ironically, the analysis and deconstruction of the symptom eventually led to the kind of insight that the expression seeing the light conveys.

Migraine strikes study: factors in patients' decision to treat early.

To describe factors associated with early treatment of migraine, and to examine reasons patients do not treat early, this cross-sectional observational study email-recruited migraineurs >or= 18-years-old who were currently prescribed acute migraine medication. Within 24 h of migraine resolution, eligible patients completed an online migraine strikes questionnaire which addressed pain severity, associated symptoms, and other variables including reasons for not treating early. Results reported were descriptive. Among 1,044 evaluable patients, early treatment was significantly associated with several factors such as leisure activity at onset (OR 1.32, P=0.010), photophobia (OR 1.39, P=0.013), diagnosis of migraine with aura (OR 1.36, P=0.004), and other factors. Among 840 patients who reported wanting to treat earlier desire to reserve medication for a severe migraine was the most common reason given for not doing so (51.2%). Overcoming these factors may facilitate earlier migraine treatment.

Photosensitivity in panic disorder.

BACKGROUND: The objective of this study is to evaluate abnormal light-related behavior in patients with panic disorder (PD). METHODS: We administered the Photosensitivity Assessment Questionnaire to 30 subjects with PD and to 40 healthy subjects. The Photosensitivity Assessment Questionnaire is a self-report questionnaire that evaluates two dimensions of photosensitivity: photophilia and photophobia. RESULTS: Compared to healthy controls, PD subjects reported significantly higher scores on the photophobia (P<.003) and significantly lower scores on the photophilia (P<.001) questions. CONCLUSIONS: Subjects with PD indicated that they tolerate and seek light to a significantly lower degree than normal controls.

The "sunglasses sign" predicts nonorganic visual loss in neuro-ophthalmologic practice.

OBJECTIVE: The aim of our study was to evaluate whether wearing sunglasses (the "sunglasses sign") can be used by neuro-ophthalmologists to predict nonorganic visual loss (NOVL) in their patients. METHODS: We prospectively collected information on all new patients seen by us over 13 months. We included all patients who ultimately received a diagnosis of NOVL, and all patients wearing sunglasses in our clinic. We recorded demographics, iris color, number of positive review of systems, ocular examination, precipitating event or trauma, workers' compensation claims, disability and lawsuit related to the visual loss, and the reason for wearing sunglasses. RESULTS: Among the 1,377 consecutive new patients seen in our clinic during the study, 34 patients wore sunglasses, among whom 7 (20.6%) had organic visual loss. During the study period, 59 patients were diagnosed with NOVL, among whom 27 (45.8%) wore sunglasses. The sensitivity of wearing sunglasses for NOVL was 0.46 (95% CI 0.33 to 0.59). The probability that a patient walking into our clinic had NOVL was 0.043 (95% CI 0.033 to 0.055); it increased to 0.79 (95% CI 0.62 to 0.91) in sunglasses patients. The specificity of sunglasses for the diagnosis of NOVL was 0.995 (95% CI 0.989 to 0.998). At least one of the following characteristics (highly positive review of systems, workers' compensation claim, disability, and lawsuit) was found in 26 of 27 (96.3%) of NOVL patients wearing sunglasses and in none of the sunglasses patients with organic neuro-ophthalmic disorders. All 7 sunglasses patients with organic neuro-ophthalmic disorders had reasonable ophthalmic explanations for wearing sunglasses. CONCLUSION: The "sunglasses sign" in a patient without an obvious ophthalmic reason to wear sunglasses is highly suggestive of nonorganic visual loss.

Clinicians' ratings and self-reports of basic symptoms.

A sample of 34 paranoid or undifferentiated schizophrenic outpatients were given the Rome Basic Disorders Scale, a self-rating questionnaire aimed to the assessment of basic symptoms, as defined by the Bonn Scale. These patients were then interviewed on the same 54 basic symptoms explored with the scale, by two independent clinicians blind to the outpatients' data. Self-ratings compared with clinicians' ratings by Student t for dependent samples yielded only one significant difference (p< .01) for the item measuring hypersensitivity to light. Present findings suggest that the Rome Basic Disorders Scale may be safely self-rated even by collaborative schizophrenic patients.

Successful cognitive-behavioral habituation training toward photophobia in photogenic partial seizures.

We report on the cognitive-behavioral treatment of a 12-year-old boy with photogenic partial seizures with secondary generalization who had developed phobic avoidant behavior toward all kinds of situations with potential photostimulation, leading to serious impairments of life quality. Based on a behavioral analysis of seizure and anxiety reaction, a habituation training (systematic desensitization procedure) was developed and performed, while maintaining protection against seizures with antiepileptic pharmacotherapy. The treatment was to gradually increase exposure to computer monitor and television screen photostimulation, closely adjusted to the level of subjective distress and tolerance. In addition to exercising control of photogenic input by regulating the monitor control button, rapid relaxation and imagery techniques were taught and applied as countermeasures at the onset of seizure precipitants. The treatment resulted in complete remission of phobic anxieties and responses and may also have facilitated ongoing seizure control after termination of antiepileptic medication.