Lacrimal Neuralgia: A Case Report and Comprehensive Review of the Literature.

PURPOSE OF REVIEW: Lacrimal neuralgia is a rare periorbital neuralgia. To date, only nine cases have been reported in the literature. Herein, we report a case and a comprehensive overview of the entity with a focus on the differential diagnosis of lacrimal neuralgia. Additionally, we propose putative diagnostic criteria for this rare neuralgia based on cases that have been reported. RECENT FINDINGS: Among the ten cases of lacrimal neuralgia reported (including the one in this review), seven out of ten were idiopathic, and the other three were considered secondary. Most patients reported stabbing and shooting pain that was either paroxysmal or continuous. The most effective therapy was nerve block for seven patients and pregabalin for three patients. The most important clues to differentiate lacrimal neuralgia from other causes of periorbital pain include pain topography and pain with features suggestive of neuralgia. The core feature of lacrimal neuralgia is neuralgic pain located in the area supplied by the lacrimal nerve, and the etiology could be primary or secondary. Responsiveness to anesthetic blockade might better serve as a confirmational, rather than mandatory, criterion for diagnosis.

Visual Snow: Updates and Narrative Review.

PURPOSE OF REVIEW: Visual snow (VS) involves visualization of innumerable dots throughout the visual field, sometimes resembling "TV static." Patients who experience this symptom may also have additional visual symptoms (e.g., photophobia, palinopsia, floaters, and nyctalopia) with a pattern now defined as visual snow syndrome (VSS). This manuscript describes both VS and VSS in detail and provides an updated review on the clinical features, pathophysiology, and optimal management strategies for these symptoms. RECENT FINDINGS: VS/VSS may be primary or secondary to a variety of etiologies, including ophthalmologic or brain disorders, systemic disease, and medication/hallucinogen exposure. Evaluation involves ruling out secondary causes and mimics of VS. Increasing evidence suggests that VSS is a widespread process extending beyond the visual system. Pathophysiology may involve cortical hyperexcitability or dysfunctional connectivity of thalamocortical or attention/salience networks. VSS is typically a benign, non-progressive syndrome and can be managed with non-medicine strategies. Though no medication provides complete relief, some may provide partial improvement in severity of VS.

GADD45A is a mediator of mitochondrial loss, atrophy, and weakness in skeletal muscle.

Aging and many illnesses and injuries impair skeletal muscle mass and function, but the molecular mechanisms are not well understood. To better understand the mechanisms, we generated and studied transgenic mice with skeletal muscle-specific expression of growth arrest and DNA damage inducible α (GADD45A), a signaling protein whose expression in skeletal muscle rises during aging and a wide range of illnesses and injuries. We found that GADD45A induced several cellular changes that are characteristic of skeletal muscle atrophy, including a reduction in skeletal muscle mitochondria and oxidative capacity, selective atrophy of glycolytic muscle fibers, and paradoxical expression of oxidative myosin heavy chains despite mitochondrial loss. These cellular changes were at least partly mediated by MAP kinase kinase kinase 4, a protein kinase that is directly activated by GADD45A. By inducing these changes, GADD45A decreased the mass of muscles that are enriched in glycolytic fibers, and it impaired strength, specific force, and endurance exercise capacity. Furthermore, as predicted by data from mouse models, we found that GADD45A expression in skeletal muscle was associated with muscle weakness in humans. Collectively, these findings identify GADD45A as a mediator of mitochondrial loss, atrophy, and weakness in mouse skeletal muscle and a potential target for muscle weakness in humans.

Migraine Patient Care Model Preferences in a Community Practice.

Background and Objectives: Developing high-value care models with limited resources for large populations of individuals with migraine requires advanced understanding of patient preferences for care delivery methods. In this study, we aimed to inform the development of migraine care models by assessing patient preferences for types of care delivery and determining differences based on migraine frequency and disability. Methods: We analyzed unpublished data from a cross-sectional survey of 516 randomly selected individuals with migraine within a community practice associated with Mayo Clinic, Rochester, MN. Results: Individuals with chronic migraine, compared with those with episodic migraine, were more likely to prefer a visit with a neurologist (p = 0.0005), synchronous telephone conference with primary care provider (PCP) and neurologist (p = 0.0102), and a written migraine action plan in the medical record (p = 0.0343). Compared with those with mild/no disability, individuals with moderate-to-severe disability were more likely to prefer a visit with a neurologist (p < 0.0001), synchronous video or telephone conference with PCP and neurologist (p < 0.0001), PCP communication with neurologist (p = 0.0099), electronic message to primary care team with access to neurologist (p = 0.0216), and written action plan in the medical record (p = 0.0011). Collectively, individuals most preferred telephone follow-up and least preferred communications with a nurse or pharmacist or generalized education (all p < 0.001). Discussion: We observed differences in migraine care delivery preferences between migraine frequency and level of migraine disability. Observations support development of care pathways that include a written migraine action plan, primary care-neurology collaboration including nontraditional interactions, and prioritization of traditional neurology consultation for the most disabled patients.

The transcription regulator ATF4 is a mediator of skeletal muscle aging.

Aging slowly erodes skeletal muscle strength and mass, eventually leading to profound functional deficits and muscle atrophy. The molecular mechanisms of skeletal muscle aging are not well understood. To better understand mechanisms of muscle aging, we investigated the potential role of ATF4, a transcription regulatory protein that can rapidly promote skeletal muscle atrophy in young animals deprived of adequate nutrition or activity. To test the hypothesis that ATF4 may be involved in skeletal muscle aging, we studied fed and active muscle-specific ATF4 knockout mice (ATF4 mKO mice) at 6 months of age, when wild-type mice have achieved peak muscle mass and function, and at 22 months of age, when wild-type mice have begun to manifest age-related muscle atrophy and weakness. We found that 6-month-old ATF4 mKO mice develop normally and are phenotypically indistinguishable from 6-month-old littermate control mice. However, as ATF4 mKO mice become older, they exhibit significant protection from age-related declines in strength, muscle quality, exercise capacity, and muscle mass. Furthermore, ATF4 mKO muscles are protected from some of the transcriptional changes characteristic of normal muscle aging (repression of certain anabolic mRNAs and induction of certain senescence-associated mRNAs), and ATF4 mKO muscles exhibit altered turnover of several proteins with important roles in skeletal muscle structure and metabolism. Collectively, these data suggest ATF4 as an essential mediator of skeletal muscle aging and provide new insight into a degenerative process that impairs the health and quality of life of many older adults.

Narrative review of migraine management in patients with renal or hepatic disease.

OBJECTIVES/BACKGROUND: Treatment of migraine in the setting of either renal or hepatic disease can be daunting for clinicians. Not only does the method of metabolism have to be considered, but also the method of elimination/excretion of the parent drug and any active or toxic metabolites. Furthermore, it is difficult to think about liver or kidney disease in isolation, as liver disease can sometimes contribute to impaired renal function and renal disease can sometimes impair hepatic metabolism, through the cytochrome P450 system. METHODS: A detailed search for terms related to liver disease, renal disease, and migraine management was performed in PubMed, Ovid Medline, Embase, and the Cochrane Library.For each medication, product labels were retrieved and reviewed using the US FDA website, with additional review of IBM Micromedex, LiverTox, and the Renal Drug Handbook. RESULTS: This manuscript provides an overview of migraine drug metabolism and how it can be affected by liver and renal impairment. It reviews the standard terminology recommended by the US Food and Drug Administration for the different stages of hepatic and renal failure. The available evidence regarding the use of abortive and preventative medicines in the setting of organ failure is discussed in detail, including more recent therapies such as lasmiditan, gepants, and calcitonin gene-related peptide antibodies. CONCLUSIONS: For acute therapy, the use of NSAIDS should be limited, as these carry risk for both severe hepatic and renal disease. Triptans can be selectively used, often with dose guideline adjustments. Ubrogepant may be used in severe hepatic disease with dose adjustment and lasmiditan can be used in end stage renal disease. Though non-medicine strategies may be the most reasonable initial approach, many preventative medications can be used in the setting of hepatic and renal disease, often with dose adjustment. This review provides tables of guidelines, including reduced dosing recommendations, for the use of abortive and preventative migraine medications in hepatic and renal failure.

Narrative review of peripheral nerve blocks for the management of headache.

OBJECTIVE: To provide an overview of the current available literature on peripheral nerve blocks for the management of migraine and other headache disorders in adults. BACKGROUND: Peripheral nerve blocks have been commonly performed in the headache practice for migraine, cluster headache, occipital neuralgia, and other headache disorders, despite a paucity of evidence supporting their use historically. In the past decade, there has been an effort to explore the efficacy and safety of peripheral nerve blocks for the management of headache, with the greatest interest centered around greater occipital blocks. DESIGN: We performed a search in PubMed using key words including "occipital nerve blocks," "peripheral nerve blocks," "occipital nerve," "migraine," "cluster headache," and "neuralgia." We reviewed the randomized controlled trials (RCTs), observational studies, and case series, and summarized the anatomy, techniques, and the evidence for the use of peripheral nerve blocks in different headache disorders, with particular focus on available RCTs. Case reports were included for a detail review of adverse events. RESULTS: Of 12 RCTs examining the use of greater occipital nerve blocks for migraine, all but one demonstrate efficacy with reduction in headache frequency, intensity, and/or duration compared to placebo. Studies have not demonstrated a difference in clinical outcomes with the use of corticosteroids for nerve blocks compared to blocks with local anesthetic in the treatment of migraine. There are two RCTs supporting the use of greater occipital blockade for cluster headache, both showing benefit of suboccipitally injected corticosteroid. One RCT suggests benefit of greater occipital nerve blocks for cervicogenic headache. Observational studies and case series/reports show that greater occipital nerve block may be effective in prolonged migraine aura, status migrainosus, post-dural puncture headache, and occipital neuralgia. Overall, peripheral nerve blocks are well tolerated. Serious side effects are rare but have been reported, including acute cerebellar syndrome and infection. CONCLUSIONS: Peripheral nerve blocks, especially occipital nerve blocks, are a viable treatment option for migraine and may be helpful in cluster headache as a transitional therapy or rescue therapy. Additional prospective studies are needed to investigate the efficacy and safety of occipital nerve blocks for long-term migraine prevention, as well as for other headache disorders, such as occipital neuralgia.

Real-World Patient Experience of CGRP-Targeting Therapy for Migraine: a Narrative Review.

PURPOSE OF REVIEW: To summarize available calcitonin gene-related peptide (CGRP)-targeting therapies for migraine and discuss their use in real-world populations. BACKGROUND: CGRP has long been a topic of interest in migraine pathophysiology, with new therapies targeting CGRP since 2018 for both the preventive and acute treatment of migraine. METHODS: We searched PubMed using keywords including "migraine," "CGRP," "real-world," "erenumab," "galcanezumab," "fremanezumab," "eptinezumab," "ubrogepant," "rimegepant," and "atogepant." We reviewed all pertinent studies and summarized main findings. We also compiled detailed patient characteristics (e.g., migraine diagnoses, medication overuse, prior treatment failures) and treatment outcome measures, such as 50% responder rates, reduction in migraine days, and adverse event rates in several tables. Overall, studies reporting real-world patient experiences of CGRP-targeting therapies suggested meaningful effectiveness for migraine treatment with response rates comparable to the numbers reported in clinical trials. Furthermore, studies suggested benefit in patients with multiple prior unsuccessful treatment trials, medication overuse, and complex medical comorbidities. In some studies, adverse event rates have been notably higher than reported in clinical trials. Additional long-term data is needed to further evaluate sustained efficacy, predictors of treatment response, and adverse events.

Biology of Activating Transcription Factor 4 (ATF4) and Its Role in Skeletal Muscle Atrophy.

Activating transcription factor 4 (ATF4) is a multifunctional transcription regulatory protein in the basic leucine zipper superfamily. ATF4 can be expressed in most if not all mammalian cell types, and it can participate in a variety of cellular responses to specific environmental stresses, intracellular derangements, or growth factors. Because ATF4 is involved in a wide range of biological processes, its roles in human health and disease are not yet fully understood. Much of our current knowledge about ATF4 comes from investigations in cultured cell models, where ATF4 was originally characterized and where further investigations continue to provide new insights. ATF4 is also an increasingly prominent topic of in vivo investigations in fully differentiated mammalian cell types, where our current understanding of ATF4 is less complete. Here, we review some important high-level concepts and questions concerning the basic biology of ATF4. We then discuss current knowledge and emerging questions about the in vivo role of ATF4 in one fully differentiated cell type, mammalian skeletal muscle fibers.

Chemotherapy in the treatment of malignant gliomas.

Malignant gliomas are one of the most difficult tumors to treat, with only modest advances being made in the past few decades. Surgery and radiation have had the greatest impact, increasing survival. Chemotherapy modestly increases survival. The use of chemotherapy in the treatment of malignant gliomas is the focus of this paper and the more commonly used agents at diagnosis and relapse are reviewed. Since most patients fail first-, second- and even third-line agents that are commercially available, some of the more relevant new biological compounds will also be discussed. As treatments for brain tumors evolve, it is likely that optimal therapies will come from combination therapies that incorporate target-specific and chemotherapeutic agents.

Primary central nervous system lymphoma.

Primary central nervous system lymphoma is a stage 1E non-Hodgkin's lymphoma confined to the nervous system. It is seen in immunocompetent and immunodeficient populations, the latter group associated with the Epstein-Barr virus. Primary central nervous system lymphoma can affect the brain, leptomeninges, spinal cord or eyes. The institution of high-dose methotrexate-based regimens and whole-brain radiation therapy has significantly increased survival, but neurotoxicity is high in patients over 60 years of age. Despite these advances, 50% of patients initially treated will relapse. Recent investigations include the use of rituximab (immunotherapy) and stem-cell transplantation, as well as regimens without whole-brain radiation therapy in the elderly. The optimal treatment regimen is yet to been determined.