Blepharospasm With Photophobia Secondary to Midbrain Tuberculoma and Thalamic Infarct.

INTRODUCTION: Blepharospasm is a type of focal dystonia and categorized into primary and secondary forms, based on whether or not a cause can be established. Secondary blepharospasm is uncommon and can be associated with underlying brain lesions. Photophobia is a prominent complaint in blepharospasm patients. We are reporting a case of secondary blepharospasm with photophobia in a patient who had underlying midbrain tuberculoma and thalamic infarcts. This type of presentation has not been reported to the best of our knowledge. CASE REPORT: A 26-year-old man presented to us with the complaint of increased blinking and involuntary closure of both eyes for 1 year. He had a past history of tubercular meningitis 16 years back when he presented with bilateral ptosis, left up gaze palsy and right hemiparesis suggestive of Weber syndrome. His magnetic resonance images of the brain were suggestive of multiple intracranial tuberculomas, thalamic infarcts, and noncommunicating hydrocephalus. Following treatment he recovered significantly with no residual neurological deficit except mild bilateral ptosis. His recent magnetic resonance images of the brain was suggestive of calcified granuloma in the midbrain and chronic left thalamic lacunar infarcts. He was treated with injection Onabotulinum toxin and his symptoms improved significantly. CONCLUSIONS: Our patient had tuberculoma in the midbrain and chronic infarcts in the thalamus, and both lesions may cause blepharospasm and photophobia independently, so it is difficult to ascertain the causative lesion in our patient. However, it is possible that these heterogenous lesions are all part of a single functionally connected brain network and further studies are required to confirm this hypothesis.

The American Registry for Migraine Research: Research Methods and Baseline Data for an Initial Patient Cohort.

BACKGROUND: The American Registry for Migraine Research (ARMR) is a multicenter, prospective, longitudinal patient registry, biorepository, and neuroimaging repository that collects clinical data, electronic health record (EHR) data, blood samples, and brain imaging data from individuals with migraine or other headache types. In this manuscript, we outline ARMR research methods and report baseline data describing an initial cohort of ARMR participants. METHODS: Adults with any International Classification of Headache Disorders (ICHD) diagnosis were prospectively enrolled from one of the 8 participating headache specialty centers. At baseline, ARMR participants complete web-based questionnaires, clinicians enter the participant's ICHD diagnoses, an optional blood specimen is collected, and neuroimaging data are uploaded to the ARMR neuroimaging repository. Participants maintain the ARMR daily headache diary longitudinally and follow-up questionnaires are completed by participants every 3 months. EHR data are integrated into the ARMR database from a subset of ARMR sites. Herein, we describe the ARMR methodology and report the summary data from ARMR participants who had, from February 2016 to May 2019, completed at least 1 baseline questionnaire from which data are reported in this manuscript. Descriptive statistics are used to provide an overview of patient's sociodemographics, headache diagnoses, headache characteristics, most bothersome symptoms other than headache, headache-related disability, comorbidities, and treatments. RESULTS: Data were available from 996 ARMR participants, enrolled from Mayo Clinic Arizona, Dartmouth-Hitchcock Medical Center, University of Utah, University of Colorado, Thomas Jefferson University, University of Texas Health Science Center at Houston, Georgetown University Medical Center, and DENT Neurological Institute. Among ARMR participants, 86.7% (n = 864) were female and the mean age at the time of enrollment was 48.6 years (±13.9; range 18-84). The most common provider-reported diagnosis was chronic migraine (n = 622), followed by migraine without aura (n = 327), migraine with aura (n = 196), and medication overuse headache (n = 65). Average headache frequency was 19.1 ± 9.2 days per month (n = 751), with 68% reporting at least 15 headache days per month. Sensitivity to light was the most frequent (n = 222) most bothersome symptom overall, other than headache, but when present, cognitive dysfunction was most frequently (n = 157) the most bothersome symptom other than headache. Average migraine disability assessment (MIDAS) score was 52 ± 49 (n = 760), (very severe headache-related disability); however, 17% of the ARMR population had MIDAS scores suggesting "no" or "mild" disability. The most common non-headache health issues were allergies (n = 364), back pain (n = 296), neck pain (n = 296), depression (n = 292), and anxiety (n = 278). Nearly 85% (n = 695) of patients were using preventive medications and 24.7% were using non-medication preventive therapy (eg, vitamins and neuromodulation). The most common preventive medication classes were neurotoxins, anticonvulsants, antidepressants, vitamins/supplements, and anticalcitonin gene-related peptide ligand or receptor-targeted monoclonal antibodies. Nearly 90% (n = 734) of ARMR participants was taking medications to treat migraine attacks, with the most common classes being triptans, non-steroidal anti-inflammatory drugs, antiemetics, acetaminophen, and combination analgesics. CONCLUSIONS: ARMR is a source of real-world patient data, biospecimens, and brain neuroimaging data that provides comprehensive insight into patients with migraine and other headache types being seen in headache specialty clinics in the United States. ARMR data will allow for longitudinal and advanced analytics that are expected to lead to a better characterization of patient heterogeneity, healthcare resource utilization, identification of endophenotypes, factors that predict treatment outcomes and clinical course, and ultimately advance the field toward precision headache medicine.

Current understanding of premonitory networks in migraine: A window to attack generation.

AIM: To describe neuronal networks underlying commonly reported migraine premonitory symptoms and to discuss how these might precipitate migraine pain. BACKGROUND: Migraine headache is frequently preceded by a distinct and well characterized premonitory phase including symptoms like yawning, sleep disturbances, alterations in appetite and food intake and hypersensitivity to certain external stimuli. Recent neuroimaging studies strongly suggest the hypothalamus as the key mediator of the premonitory phase and also suggested alterations in hypothalamic networks as a mechanism of migraine attack generation. When looking at the vast evidence from basic research within the last decades, hypothalamic and thalamic networks are most likely to integrate peripheral influences with central mechanisms, facilitating the precipitation of migraine headaches. These networks include sleep, feeding and stress modulating centers within the hypothalamus, thalamic pathways and brainstem centers closely involved in trigeminal pain processing such as the spinal trigeminal nucleus and the rostral ventromedial medulla, all of which are closely interconnected. CONCLUSION: Taken together, these networks represent the pathophysiological basis for migraine premonitory symptoms as well as a possible integration site of peripheral so-called "triggers" with central attack facilitating processes.

Neurobiology of Photophobia.

BACKGROUND: Photophobia is commonly associated with migraine, meningitis, concussion, and a variety of ocular diseases. Advances in our ability to trace multiple brain pathways through which light information is processed have paved the way to a better understanding of the neurobiology of photophobia and the complexity of the symptoms triggered by light. PURPOSE: The purpose of this review is to summarize recent anatomical and physiological studies on the neurobiology of photophobia with emphasis on migraine. RECENT FINDINGS: Observations made in blind and seeing migraine patients, and in a variety of animal models, have led to the discovery of a novel retino-thalamo-cortical pathway that carries photic signal from melanopsinergic and nonmelanopsinergic retinal ganglion cells (RGCs) to thalamic neurons. Activity of these neurons is driven by migraine and their axonal projections convey signals about headache and light to multiple cortical areas involved in the generation of common migraine symptoms. Novel projections of RGCs into previously unidentified hypothalamic neurons that regulate parasympathetic and sympathetic functions have also been discovered. Finally, recent work has led to a novel understanding of color preference in migraine-type photophobia and of the roles played by the retina, thalamus, and cortex. SUMMARY: The findings provide a neural substrate for understanding the complexity of aversion to light in patients with migraine and neuro-ophthalmologic other disorders.

Current understanding of thalamic structure and function in migraine.

OBJECTIVE: To review and discuss the literature on the role of thalamic structure and function in migraine. DISCUSSION: The thalamus holds an important position in our understanding of allodynia, central sensitization and photophobia in migraine. Structural and functional findings suggest abnormal functional connectivity between the thalamus and various cortical regions pointing towards an altered pain processing in migraine. Pharmacological nociceptive modulation suggests that the thalamus is a potential drug target. CONCLUSION: A critical role for the thalamus in migraine-related allodynia and photophobia is well established. Additionally, the thalamus is most likely involved in the dysfunctional pain modulation and processing in migraine, but further research is needed to clarify the exact clinical implications of these findings.

Current understanding of photophobia, visual networks and headaches.

OBJECTIVE: To review clinical and pre-clinical evidence supporting the role of visual pathways, from the eye to the cortex, in the development of photophobia in headache disorders. BACKGROUND: Photophobia is a poorly understood light-induced phenomenon that emerges in a variety of neurological and ophthalmological conditions. Over the years, multiple mechanisms have been proposed to explain its causes; however, scarce research and lack of systematic assessment of photophobia in patients has made the search for answers quite challenging. In the field of headaches, significant progress has been made recently on how specific visual networks contribute to photophobia features such as light-induced intensification of headache, increased perception of brightness and visual discomfort, which are frequently experienced by migraineurs. Such progress improved our understanding of the phenomenon and points to abnormal processing of light by both cone/rod-mediated image-forming and melanopsin-mediated non-image-forming visual pathways, and the consequential transfer of photic signals to multiple brain regions involved in sensory, autonomic and emotional regulation. CONCLUSION: Photophobia phenotype is diverse, and the relative contribution of visual, trigeminal and autonomic systems may depend on the disease it emerges from. In migraine, photophobia could result from photic activation of retina-driven pathways involved in the regulation of homeostasis, making its association with headache more complex than previously thought.

Noninvasive Electrical Stimulation for the Treatment of Chronic Ocular Pain and Photophobia.

INTRODUCTION: "Dry eye" or "keratoconjunctivitis sicca" is a multifactorial disease estimated to have a worldwide prevalence of 5-33%. Conventional therapies targeting the ocular surface with artificial tears, anti-inflammatories, punctal closure, eyelid hygiene, and antibiotics do not provide relief in all patients, especially those with neuropathic-like ocular complaints (wind hyperalgesia and photophobia). We anticipated that ocular transcutaneous electrical nerve stimulation (TENS) would alleviate symptoms of ocular pain, photophobia, and dryness in these latter individuals. METHODS: All individuals who received electrical stimulation between May 10, 2016 and April 6, 2017 for the treatment of chronic ocular pain at the oculofacial pain clinic of the Miami Veterans Administration Hospital were included in this retrospective review. All patients had symptoms of dryness along with other neuropathic-like symptoms (e.g., photophobia) and minimal signs of tear dysfunction. Ocular pain intensity, symptoms of dryness, and light sensitivity were compared pre-treatment and five min post-treatment via a two-tailed paired Student's t-test. RESULTS: The use of TENS significantly reduced the mean pain intensity in both the right and left eyes five min after treatment compared to prior to treatment (p < 0.05, paired t-test). The use of TENS significantly decreased light sensitivity in both eyes (p < 0.05). The findings for symptoms of dryness, however, were equivocal with a significant decrease in the left eye but not the right (p < 0.05, paired t-test). DISCUSSION: Our data indicate that TENS may similarly provide analgesia in patients with dry eye symptoms as it does for many other chronic pain conditions. Furthermore, the noted effect on symptoms of photophobia and dryness suggest that all may be linked by similar trigeminal-thalamic-cortical pathways. Prospective studies with electrical stimulation of dry eye are needed to further elucidate its benefit and mechanism of action.

Updated strategies for the management, pathogenesis and molecular genetics of different forms of ichthyosis syndromes with prominent hair abnormalities.

Syndromic ichthyosis is rare inherited disorders of cornification with varied disease complications. This disorder appears in seventeen subtypes associated with severe systematic manifestations along with medical, cosmetic and social problems. Syndromic ichthyosis with prominent hair abnormalities covers five major subtypes: Netherton syndrome, trichothiodystrophy, ichthyosis hypotrichosis syndrome, ichthyosis hypotrichosis sclerosing cholangitis and ichthyosis follicularis atrichia photophobia syndrome. These syndromes mostly prevail in high consanguinity states, with distinctive clinical features. The known pathogenic molecules involved in ichthyosis syndromes with prominent hair abnormalities include SPINK5, ERCC2, ERCC3, GTF2H5, MPLKIP, ST14, CLDN1 and MBTPS2. Despite underlying genetic origin, most of the health professionals solely rely on phenotypic expression of these disorders that leads to improper management of patients, hence making these patients living an orphanage life. After dermal features, association of other systems such as nervous system, skeletal system, hair abnormalities or liver problems may sometimes give clues for diagnosis but still leaving place for molecular screening for efficient diagnosis. In this paper, we have presented a review of ichthyosis syndrome with prominent hair abnormalities, with special emphasis on their updated genetic consequences and disease management. Additionally, we aim to update health professionals about the practice of molecular screening in ichthyosis syndromes for appropriate diagnosis and treatment.

Migraine photophobia originating in cone-driven retinal pathways.

Migraine headache is uniquely exacerbated by light. Using psychophysical assessments in patients with normal eyesight we found that green light exacerbates migraine headache significantly less than white, blue, amber or red lights. To delineate mechanisms, we used electroretinography and visual evoked potential recording in patients, and multi-unit recording of dura- and light-sensitive thalamic neurons in rats to show that green activates cone-driven retinal pathways to a lesser extent than white, blue and red; that thalamic neurons are most responsive to blue and least responsive to green; and that cortical responses to green are significantly smaller than those generated by blue, amber and red lights. These findings suggest that patients' experience with colour and migraine photophobia could originate in cone-driven retinal pathways, fine-tuned in relay thalamic neurons outside the main visual pathway, and preserved by the cortex. Additionally, the findings provide substrate for the soothing effects of green light.

Effect of manual therapy techniques on headache disability in patients with tension-type headache. Randomized controlled trial.

BACKGROUND: Tension-type headache (TTH) is the most common type of primary headache however there is no clear evidence as to which specific treatment is most effective or whether combined treatment is more effective than individual treatments. AIM: To assess the effectiveness of manual therapy techniques, applied to the suboccipital region, on aspects of disability in a sample of patients with tension-type headache. DESIGN: Randomized Controlled Trial. SETTING: Specialized centre for headache treatment. POPULATION: Seventy-six (62 women) patients (age: 39.9 ± 10.9 years) with episodic chronic TTH. METHODS: Patients were randomly divided into four treatment groups: 1) suboccipital soft tissue inhibition; 2) occiput-atlas-axis manipulation; 3) combined treatment of both techniques; 4) control. Four sessions were applied over 4 weeks and disability was assessed before and after treatment using the Headache Disability Inventory (HDI). Headache frequency, severity and the functional and emotional subscales of the questionnaire were assessed. Photophobia, phonophobia and pericranial tenderness were also monitored. RESULTS: Headache frequency was significantly reduced with the manipulative and combined treatment (P<0.05), and the severity and functional subscale of the HDI changed in all three treatment groups (P<0.05). Manipulation treatment also reduced the score on the emotional subscale of the HDI (P<0.05). The combined intervention showed a greater effect at reducing the overall HDI score compared to the group that received suboccipital soft tissue inhibition and to the control group (both P<0.05). In addition, photophobia, phonophobia and pericranial tenderness only improved in the group receiving combined therapy (P<0.05). CONCLUSION: When given individually, suboccipital soft tissue inhibition and occiput-atlas-axis manipulation resulted in changes in different parameters related to the disability caused by TTH. However, when the two treatments were combined, effectiveness was noted for all aspects of disability and other symptoms including photophobia, phonophobia and pericranial tenderness. CLINICAL REHABILITATION IMPACT: Although individual manual therapy treatments showed a positive change in headache features, measures of photophobia, photophobia and pericranial tenderness only improved in the group that received the combined treatment suggesting that combined treatment is the most appropriate for symptomatic relief of TTH.

Migraine, vertigo and migrainous vertigo: Links between vestibular and pain mechanisms.

This review develops the hypothesis that co-morbid balance disorders and migraine can be understood as additive effects of processing afferent vestibular and pain information in pre-parabrachial and pre-thalamic pathways, that have consequences on cortical mechanisms influencing perception, interoception and affect. There are remarkable parallel neurochemical phenotypes for inner ear and trigeminal ganglion cells and these afferent channels appear to converge in shared central pathways for vestibular and nociceptive information processing. These pathways share expression of receptors targeted by anti-migraine drugs. New evidence is also presented regarding the distribution of serotonin receptors in the planum semilunatum of the primate cristae ampullaris, which may indicate involvement of inner ear ionic homeostatic mechanisms in audiovestibular symptoms that can accompany migraine.

Migraine variants and beyond.

Migraine is amongst the oldest of diseases known to mankind. Migraine is a heterogenous entity, usually characterised by periodic attacks of headache on one or both sides of the head. These may be accompanied by nausea, vomiting, increased sensitivity of the eyes to light (photophobia), increased sensitivity to sound (phonophobia), dizziness, blurred vision, cognitive disturbances, and other symptoms. Migraines are not always preceded by an aura and some migraines may not include headache. If migraine does not manifest itself in the form of headache but in some other form such as paroxysmal episodes of prolonged visual auras, atypical sensory, motor, or visual aura, confusion, dysarthria, focal neurologic deficits with or without a headache, it is labelled a Migraine Variant (MV). MV is therefore diagnosed by the history of paroxysmal symptoms with or without cephalgia and a prior history of migraine with aura, in the absence of other medical disorders that may contribute to the symptoms. Many of the MVs have been included and redefined in the revised edition of The International Classification of Headache Disorders (ICHD-II) 2004 classification. These include hemiplegic migraine, basilar migraine, childhood periodic syndromes, retinal migraine, complicated migraine and ophthalmoplegic migraine. Even though conditions such as vertiginous migraine, acute confusional migraine of childhood and nocturnal migraine are well recognized entities, they have not yet been included in IHCD-II, but will be discussed here in brief because they are relatively common conditions.

Photophobia in essential blepharospasm--a positron emission tomographic study.

To localize regional alterations in cerebral glucose metabolism in essential blepharospasm (EB) patients with photophobia. We have studied 22 EB patients by performing positron emission tomography and [(18)F]-fluorodeoxyglucose analysis. The patients were classified into two subgroups, namely, EB with photophobia (P group) and EB without photophobia (NP group), and compared with a healthy control group (n = 44). There were no significant differences between the two patient groups with respect to the severity of motor symptoms or the duration for which the condition persisted. The FDG-PET images were analyzed using the statistical parametric mapping software. As compared to the control group, the P group exhibited significant hypermetabolism in the thalamus (P = 0.002), while the NP group exhibited significant hypometabolism in the dorsal midbrain, especially, in the superior colliculus (P = 0.005). The P group exhibited significant hypermetabolism in the thalamus and the dorsal midbrain as compared to the NP group (P < 0.001). These findings suggest that photophobia in EB patients may be associated with abnormal hyperactivity in the thalamus. Either hyperactivity of the thalamus or hypoactivity of the superior colliculus, or both may be associated with excessive blinking in these patients.

[The eye and anorexia nervosa. A case report]. / Oeil et anorexie mentale. A propos d'un cas.

INTRODUCTION: Vitamin A deficiency occurs in the poor in developing countries and is one of the main causes of blindness by perforative corneal complications. It is a rare pathology in industrialized countries and it is associated with an absorption syndrome. The authors report the first case of hypovitaminosis A in a patient suffering from chronic and severe anorexia nervosa. CASE REPORT: The patient suffered from epiphora, photophobia, and hesperanopia. The ophthalmologic findings were keratoconjunctival xerosis with bilateral corneal ulcerations. The visual field showed a concentric bilateral restriction of isopters with tubular central vision, a similar aspect to retinitis pigmentosa. The ERG was modified with a b2 reduction and normal photopic and impaired scotopic responses. The fluorescein angiography was normal. The serum concentration of retinol confirmed the diagnosis of hypovitaminosis A. Corneoconjunctival improvement was obtained with vitamin supplementation, but no campimetric improvement was observed. DISCUSSION: The corneoconjunctival signs result from direct destruction of goblet cells, whereas the campimetric deficit is explained by a dysfunction of rod cells. Rhodopsin, necessary to the survival of the cell, cannot be renewed if retinol is not present, which causes a permanent bright light stimulation that is lethal for the photoreceptor. CONCLUSION: Vitamin A deficiency is rarely caused by psychiatric disease. Even if the main clinical finding is xerophthalmia with a high risk of keratomalacia, the visual prognosis can also be engaged by dysfunction of photoreceptors.

[Comparative action of melatonin and bilobil on light perception and psychophysiological indices in patients with cerebral trauma anamnesis].

Pineal hormone melatonin (melaxen preparation) and a typical cognitive enhancer Ginkgo biloba (bilobil preparation) decreased the retinal light sensitivity thresholds upon two-week administration in young (aged 19-23) patients with cerebral trauma anamnesis. This effect was more significant in evening than in the morning hours. Both drugs also attenuated the reactive anxiety (bilobil was slightly superior to melaxen in this respect) and insignificantly increased the volume of acoustic memory. The observed similarity of the psychotropic effect of two preparations allows melatonin to be classified into nootropic agents.

Visual perception during phacoemulsification cataract surgery under subtenons anaesthesia.

AIM: The aim of this study was to record the subjective visual experience of patients during phacoemulsification and intraocular lens implantation under subtenons anaesthesia. METHODS: Prospective, nonrandomised, cohort, postoperative questionnaire based study. Patients selected underwent routine phacoemulsification and intraocular lens implantation under regional subtenons anaesthesia. chi(2) and Fisher's exact tests (two-tail) were used to evaluate the data. RESULTS: A total of 104 patients were selected, 38 (36.5%) were male and 66 (63.5%) were female. The mean age of patients was 74.0+/-8.8 years. In all, 87.5% saw light during the operation with 9.6% finding this painful. Photophobia was highest among younger patients (P=0.002). Coloured lights were seen by 56.7% and 13.5% found the visual experience frightening. Frightening visual experiences were significantly associated with the perception of colour (P=0.005) and photophobia (P=0.003). A volume of anaesthetic greater than 4 m was associated with a significant reduction in anxiety as a result of the visual experience (P=0.003). None of the other visual phenomena recorded were associated with a frightening visual experience. CONCLUSIONS: Patients undergoing regional anaesthesia experience a wide variety of visual sensations during cataract surgery. Perception of colour and volumes of anaesthetic less than 4 m appear to be associated with the visual experience being more frightening. Detailed preoperative counselling is mandatory. It should include comprehensive information about visual perception during the procedure relieving the patients from unnecessary distress.

Macular infarction after transpupillary thermotherapy for subfoveal choroidal neovascularization in age-related macular degeneration.

PURPOSE: To report the complication of macular infarction after transpupillary thermotherapy (TTT) for the treatment of subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). DESIGN: Interventional case reports. METHODS: Among 107 consecutive patients with subfoveal CNV due to AMD, a 73-year-old woman with recurrent subfoveal classic choroidal neovascularization and a 76-year-old man with subfoveal occult choroidal neovascularization with adjacent areas of geographic retinal pigment epithelium atrophy noted a severe decrease in visual acuity and photopsias within hours of undergoing TTT. RESULTS: Both patients had marked whitening of the macula clinically and closure of the perifoveal capillaries on fluorescein angiography. Immediately after treatment their visual acuity decreased from 20/200 to 6/200 and from 20/400 to 2/200, respectively. Several months later, all exudation had resolved and their visual acuity had stabilized at 20/100 and 20/200, respectively. CONCLUSIONS: Macular infarction is a rare complication that occurred in two of 107 patients undergoing TTT for subfoveal CNV due to AMD. The presence of geographic retinal pigment epithelium atrophy or a previous laser treatment scar in the macular region may predispose patients to this complication.

Management of thyroid eye disease.

Thyroid eye disease (TED) is the most frequent extrathyroidal manifestation of Graves' disease. In most instances it is mild and non-progressive, but in 3%-5% of cases it is severe. Non-severe TED requires only supportive measures, such as eye ointments, sunglasses and prisms. By contrast, severe TED requires aggressive treatment, either medical (high-dose glucocorticoids, orbital radiotherapy) or surgical (orbital decompression). The choice of treatment relies on the assessment of both TED severity and activity. Removal of controllable risk factors, especially cigarette smoking, is important to improve the course and the therapeutic outcome. A coordinated approach to the treatment of hyperthyroidism and TED is also required. Novel promising treatments, to be verified in large series of patients, include somatostatin analogues and cytokine antagonists.