Radiological features of patients with headache as a presenting symptom of neurosarcoidosis.

OBJECTIVE: To describe the radiological features of patients with headache as a presenting symptom of neurosarcoidosis. BACKGROUND: Neurologic complications occur in approximately 5%-10% of patients with sarcoidosis, and approximately 50% of these patients have neurologic deficits at the time sarcoidosis is first diagnosed. A wide spectrum of central and peripheral nervous system clinical manifestations may be observed, including cranial nerve palsies, sensory and/or motor deficits, and headache. Magnetic resonance imaging (MRI) results in patients with neurosarcoidosis may include abnormal contrast enhancement, structural masses, and demyelinating lesions. METHODS: This single-center retrospective cohort study assessed patients who were diagnosed with neurosarcoidosis in an urban tertiary care center between 1995 and 2016. We included patients who had MRI results at the time of diagnosis. Patients were divided into two groups based on the presence or absence of headache as a presenting symptom. The MRI result of meningeal contrast enhancement was reviewed. RESULTS: Of the 110 patients analyzed, 30 (27.3%) had an initial presenting symptom of headache while 80 (72.7%) did not. Patients with headache had a higher proportion of meningeal contrast enhancement on MRI (66.7% [20/30] vs. 25.0% [20/80]; p < 0.001) and leptomeningeal involvement (53.3% [16/30] vs. 7.5% [6/80], p < 0.001) compared to patients with no headache. However, those with headache had a lower proportion of spinal cord localization (13.8% [4/29] vs. 34.2% [26/76], p = 0.038) and intraparenchymal central nervous system involvement (16.7% [5/30] vs. 51.3% [41/80], p = 0.001) compared to patients with no headache. CONCLUSION: Patients with neurosarcoidosis who presented with headache as an initial symptom had a higher proportion of meningeal contrast enhancement seen by MRI than patients who presented with other neurological symptoms. This suggests a clinico-radiologic link between headache and meningeal disruption in patients with neurosarcoidosis.

Clinical Features and Headache Diagnoses in Patients With Chief Complaint of Craniofacial Pain.

OBJECTIVES: Investigate the use of nasal endoscopy, sinus imaging, and neurologic evaluation in patients presenting to a rhinologist primarily for craniofacial pain. METHODS: This was a retrospective analysis of consecutive outpatients presenting to a rhinologist between 2016 and 2019 with chief complaints of craniofacial pain with or without other sinonasal symptoms, who were then referred to and evaluated by headache specialists. Data analyzed included sinusitis symptoms, Sino-Nasal Outcome Test (SNOT-22) scores (and facial pain subscores), pain location, nasal endoscopy, computed tomography (CT) findings, and headache diagnoses made by headache specialists. RESULTS: Of the 134 patients with prominent craniofacial pain, the majority of patients were diagnosed with migraine (50%) or tension-type (22%) headache, followed by multiple other non-sinogenic headache disorders. Approximately 5% of patients had headaches attributed to sinusitis. Amongst all patients, 90% had negative nasal endoscopies. Patients with negative endoscopies were significantly less likely to report smell loss (P = .003) compared to those with positive endoscopies. Poor agreement was demonstrated between self-reported pain locations and sinus findings on CT (kappa values < 0.20). Negative nasal endoscopy showed high concurrence with negative CT findings (80%-97%). CONCLUSIONS: Patients presenting with chief complaints of craniofacial pain generally met criteria for various non-sinogenic headache disorders. Nasal endoscopy was negative in 90% of patients, and CT demonstrated poor agreement with pain locations. Nasal endoscopy and CT shared high concurrence rates for negative sinus findings. The value of nasal endoscopy over sinus imaging in craniofacial pain evaluation should be explored in future studies.

The role of urgent care centers in headache management: a quality improvement project.

BACKGROUND: Patients with headache often seek urgent medical care to treat pain and associated symptoms that do not respond to therapeutic options at home. Urgent Cares (UCs) may be suitable for the evaluation and treatment of such patients but there is little data on how headache is evaluated in UC settings and what types of treatments are available. We conducted a study to evaluate the types of care available for patients with headache presenting to UCs. DESIGN: Cross-Sectional. METHODS: Headache specialists across the United States contacted UCs to collect data on a questionnaire. Questions asked about UC staffing (e.g. number and backgrounds of staff, hours of operation), average length of UC visits for headache, treatments and tests available for patients presenting with headache, and disposition including to the ED. RESULTS: Data from 10 UC programs comprised of 61 individual UC sites revealed: The vast majority (8/10; 80%) had diagnostic testing onsite for headache evaluation. A small majority (6/10; 60%) had the American Headache Society recommended intravenous medications for acute migraine available. Half (5/10) had a headache protocol in place. The majority (6/10; 60%) had no follow up policy after UC discharge. CONCLUSIONS: UCs have the potential to provide expedited care for patients presenting for evaluation and treatment of headache. However, considerable variability exists amongst UCs in their abilities to manage headaches. This study reveals many opportunities for future research including the development of protocols and professional partnerships to help guide the evaluation, triage, and treatment of patients with headache in UC settings.

Headache as the Presenting Symptom in 2 Patients With COVID-19 and a History of Migraine: 2 Case Reports.

The coronavirus disease 2019 (COVID-19) pandemic has now affected more than 5 million people globally. Typical symptoms include fever, cough, and shortness of breath. Patients with underlying medical comorbidities such as cardiovascular disease and diabetes are more likely to become severely ill. To date there is limited information on how COVID-19 affects patients with a history migraine. Here, we present the cases of 2 women with a history of migraine whose first symptom of COVID-19 was a severe persistent headache.

Delay in OnabotulinumtoxinA Treatment During the COVID-19 Pandemic-Perspectives from a Virus Hotspot.

The COVID-19 pandemic has undoubtedly changed our practice of medicine. With our collective resources and attention focused on caring for those afflicted with the disease, other medical conditions have temporarily but understandably faced constraint. For migraine patients who often require in-person visits for infusions and procedures, this has become particularly challenging. Here, we share our experience in navigating this exigency amidst a local surge of COVID-19.

Coining the Pablo Picasso Syndrome.

BACKGROUND: The Alice in Wonderland Syndrome has been well described in the literature. Along with sensory disturbances, patients notably experience metamorphopsias, or distortions in size (micropsia/macropsia) and distance (teleopsia), particularly of body parts. Some migraineurs, however, report dislocation and disorientation of body parts, which are common features found in paintings of Pablo Picasso. METHODS: A 60-year-old female with a 20-year history of chronic migraine presented for evaluation of frequent headaches and visual disturbances. In between her attacks of migraine, she would occasionally notice alterations which she describes as a "Picasso" painting. When looking at people, she would note their ear on top of their head, or their right arm would be short and attached to the face. This would occur 1-2 times per week and would last 5 to 10 minutes. Inanimate objects, however, would not appear distorted. RESULTS: The available literature, including published works and biographies, suggests Picasso did not suffer from migraine. Nonetheless, careful descriptions taken from migraineurs with visual disturbances may uncover features that resemble his paintings, be it dislocation of limbs with hints of cubism, as reported above, or illusory splitting as has been previously reported. CONCLUSION: Dislocation or disorientation of body parts as a migraine-related visual phenomenon is rare and only sparsely reported in the medical literature. Coining of a "Pablo Picasso Syndrome" may better describe this occurrence.

New Daily Persistent Headache and OnabotulinumtoxinA Therapy.

OBJECTIVE: The aim of the study was to determine whether onabotulinumtoxinA therapy is effective in the treatment of new daily persistent headache (NDPH). BACKGROUND: New daily persistent headache is a difficult to treat headache syndrome resistant to both conventional and unconventional headache therapies. New daily persistent headache was excluded in the registration trials for onabotunlinumtoxinA (onabot) in chronic migraine. Apart from case reports supporting its benefit, little is known about its therapeutic value in NDPH. DESIGN AND METHODS: We performed a single-center, retrospective chart review of patients with a diagnosis of NDPH who received onabot treatment for a 30-month period at the Cleveland Clinic Headache Center. Measures of interest were headache frequency and headache severity. All patients had received the Food and Drug Administration-approved PREEMPT Protocol. RESULTS: A decrease in headache frequency was noted in 8 (50.0%) of 16 patients at 6 months and 7 (63.6%) of 11 patients at 12 months. Headache severity improved in 5 (50.0%) of 10 patients at 6 months and in 7 (77.8%) of 9 patients at 12 months. CONCLUSIONS: Most therapies are unable to break the unremitting course of NDPH. In our investigation, at 1 year (3-4 cycles of onabot treatment), approximately half of the patients treated showed a reduction in headache frequency and approximately 75% demonstrated some improvement in headache severity. Evidence from this small-scale retrospective study suggests that onabot shows strong promise for the treatment of NDPH, which currently is resistant to most therapies, but a randomized controlled study should be the next step in confirmation of this therapy.

Triaging Patients with Multiple Sclerosis in the Emergency Department: Room for Improvement.

BACKGROUND: Patients with multiple sclerosis (MS) present to the emergency department (ED) for various reasons. Although true relapse is rarely the underlying culprit, ED visits commonly result in new magnetic resonance imaging (MRI) and neurology admissions. We studied ED visits in patients with MS and evaluated decision making regarding diagnostic/therapeutic interventions and visit outcomes. We identified potential areas for improvement and used the data to propose a triaging algorithm for patients with MS in the ED. METHODS: We reviewed the medical records from 176 ED visits for patients with MS in 2014. RESULTS: Ninety-seven visits in 75 patients were MS related (66.6% female; mean ± SD age, 52.6 ± 13.8 years; mean ± SD disease duration, 18.5 ± 10.5 years). Thirty-three visits were for new neurologic symptoms (category 1), 29 for worsening preexisting symptoms (category 2), and 35 for MS-related complications (category 3). Eighty-nine visits (91.8%) resulted in hospital admission (42.7% to neurology). Only 39% of ordered MRIs showed radiographic activity. New relapses were determined in 27.8% of the visits and were more prevalent in category 1 compared with category 2 (P = .003); however, the two categories had similar rates of ordered MRIs and neurology admissions. CONCLUSIONS: New relapse is a rare cause of ED visits in MS. Unnecessary MRIs and neurology admissions can be avoided by developing a triaging system for patients with MS based on symptom stratification.

Migraine With Neurological Features in a Scuba Diver With a Patent Foramen Ovale.

Neurologic complications of decompression sickness have been observed for over half of a century. Little is known, however, about the risk of diving in patients that suffer from migraine with aura (MWA). We report the case of a pediatric patient with a history of migraine with aura, who was later found to have a PFO, who developed headache with neurological symptoms during a scuba diving lesson.

The role of cancer stem cells and miRNAs in defining the complexities of brain metastasis.

Researchers and clinicians have been challenged with the development of therapies for the treatment of cancer patients whose tumors metastasized to the brain. Among the most lethal weapons known today, current management of brain metastases involves multiple therapeutic modalities that provide little, if any, for improving the quality of life and overall survival. Recently the role of cancer stem cells (CSCs) in the development of cancer has been studied extensively, and thus its role in the prognosis, diagnosis, and treatment is now being investigated even in the realm of brain metastasis (BM). Recognizing the molecular make-up of CSCs as well as understanding the role of these cells in resistance to treatment modalities is expected to benefit cancer patients. Additionally, past decade has witnessed an increase in awareness and understanding of the role of microRNAs (miRNAs) in various cancer types, and the deregulation miRNAs are critically important for the regulation of genes during the development and progression of human malignancies. The role miRNAs in BM is being investigated, and has also shown tremendous promise for future research. In this review, we discuss the problem and lethality of brain metastases and the current state of management, and further provide insight into novel avenues that are worth considering including the biological complexities of CSCs and miRNAs for designing novel therapies.

3,3'-Diindolylmethane enhances taxotere-induced growth inhibition of breast cancer cells through downregulation of FoxM1.

Emerging evidence suggests that the transcription factor Forkhead Box M1 (FoxM1) is associated with aggressive human carcinomas, including breast cancer. Because elevated expression of FoxM1 has been observed in human breast cancers, FoxM1 has attracted much attention in recent years as a potential target for the prevention and/or therapeutic intervention in breast cancer. However, no information is currently available regarding how downregulation of FoxM1 could be achieved for breast cancer prevention and therapy. Here, we report for the first time that 3,3'-diindolylmethane (DIM), a nontoxic dietary chemopreventive agent could effectively downregulate FoxM1 in various breast cancer cell lines. Using gene transfection, real-time reverse transcription-PCR, Western blotting, invasion and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, we found that DIM could enhance Taxotere-induced growth inhibition of breast cancer cells, and decreased invasive capacity of breast cancer cells was observed after either treatment alone or the combination. These effects were associated with downregulation of FoxM1. We also found that knock down of FoxM1 expression by small interfering RNA (siRNA) transfection increased DIM-induced cell growth inhibition, whereas over-expression of FoxM1 by cDNA transfection attenuated DIM-induced cell growth inhibition, suggesting the mechanistic role of FoxM1. Most importantly, the combination treatment significantly inhibited tumor growth in severe combined immunodeficiency (SCID) mice, and the results were correlated with the downregulation of FoxM1 in tumor remnants. We conclude that inactivation of FoxM1 and its target genes by DIM could enhance the therapeutic efficacy of Taxotere in breast cancer, which could be a useful strategy for the prevention and/or treatment of breast cancer.

Exploitation of protein kinase C: a useful target for cancer therapy.

Protein kinase C is a family of serine/threonine kinases. The PKC family is made up of at least 12 isozymes, which have a role in cell proliferation, differentiation, angiogenesis, and apoptosis. Activation of PKC isozyme is dependent on tyrosine-kinase receptors and G-protein-coupled receptors. PKC isozymes regulate multiple signaling pathways including PI3-K/Akt, MAPK, and GSK-3beta. PKC isozymes have variable roles in tumor biology which in part depend on the cell type and intracellular localization. PKC isozymes are commonly dysregulated in the cancer of the prostate, breast, colon, pancreatic, liver, and kidney. Currently, several classes of PKC inhibitors are being evaluated in clinical trials and several challenges in targeting PKC isozymes have been recently identified. In conclusion, PKC remains a promising target for cancer prevention and therapy.

A novel copper complex of 3-benzoyl-alpha methyl benzene acetic acid with antitumor activity mediated via cyclooxygenase pathway.

Pancreatic cancer (PC) is characterized as one of the deadliest malignancies and its treatment is a great challenge to clinical oncologists. Expression of COX-2 is detectable in 75% of PCs among which 50% showed overexpression, suggesting the importance of COX-2 enzyme and its metabolic product prostaglandin E2 (PGE(2)) in PC. Here the authors report the synthesis and biological activity of a novel COX-2 inhibitor, FPA-306, and its effects on PC cells with different levels of COX-2 expression. Using MTT assay, the authors found a significant growth inhibition of BxPC-3 cells treated by FPA-306 with an IC(50) of 10 micromol/L, which was lower than that of ketoprofen (IC(50) = 35.4 micromol/L) and celecoxib (IC(50) > 100 micromol/L). There was no such effect found in MIAPaCa cell line, which does not express COX-2. The authors also found dose dependent reduction in cell survival and induction of apoptosis by FPA-306 treatment in BxPC-3 cells but not in MIAPaCa cells. These results were correlated with apoptosis data and secreted PGE(2) levels. The molecular modeling of FPA-306 in the COX-2 active site showed that FPA-306 is potentially able to inhibit the activity of enzyme by blocking the active site, thereby resulting in decreased PGE(2) production. The authors also found a significant reduction of COX-2 at the mRNA and protein levels together with downregulation of NF-kappaB DNA binding activity and its downstream genes, Bcl-2 and survivin. These results suggest that FPA-306 is an effective and potent agent in inhibiting the growth of PC cells.