Persistent Headache Research Articles

Gamma-aminobutyric acid and glutamate/glutamine levels in the dentate nucleus and periaqueductal gray in new daily persistent headache: a magnetic resonance spectroscopy study

BackgroundMagnetic resonance spectroscopy (MRS) studies have indicated that the imbalance between gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels was the potential cause of migraine development. However, the changes in the GABA and Glx levels in patients with New daily persistent headache (NDPH) remain unclear. This study aimed to investigate the changes in GABA and Glx levels in the periaqueductal gray (PAG) and dentate nucleus (DN) in patients with NDPH using the MEGA-PRESS sequence.MethodsTwenty-one NDPH patients and 22 age- and sex-matched healthy controls (HCs) were included and underwent a 3.0T MRI examination, using the MEGA-PRESS sequence to analyze GABA and Glx levels of PAG and DN. The correlations between these neurotransmitter levels and clinical characteristics were also analyzed.ResultsThere were no significant differences in the GABA+/Water, GABA+/Cr, Glx/Water, and Glx/Cr levels in both PAG and DN between the two groups (all p > 0.05). Moderate-severe NDPH patients had lower levels of Glx/Water (p = 0.034) and Glx/Cr (p = 0.012) in DN than minimal-mild NDPH patients. In patients with NDPH, higher Glx/Water levels in the PAG (r=-0.471, p = 0.031, n = 21) and DN (r=-0.501, p = 0.021, n = 21) and higher Glx/Cr levels in DN (r=-0.483, p = 0.026, n = 21) were found to be correlated with lower Visual Analogue Scale scores. Additionally, a positive correlation was observed between the GABA+/Cr levels in the DN and the Generalized Anxiety Disorder-7 scores (r = 0.519, p = 0.039, n = 16).ConclusionsThe results of this study indicated that the GABA and Glx levels in the PAG and DN may not be the primary contributor to the development of NDPH. The correlations between certain clinical scales and the neurotransmitter levels may be derived from the NDPH related symptoms.

Prevalence and Risk Factors of Headache Associated with COVID-19.

Background: Headache is a prevalent and disabling non-respiratory symptom of COVID-19, posing a persistent challenge in post-COVID syndrome. This study aimed to determine the prevalence, phenotypes, risk factors and biomarkers associated with COVID-related headaches. Methods: A retrospective analysis of 634 hospitalized COVID-19 patients was conducted, with 295 participants being followed up 12-15 months post-discharge via telephone call. Initial laboratory workups, including complete blood count and various biochemical parameters, were compared between headache and non-headache groups. Results: One-third of hospitalized patients experienced headaches, predominantly younger individuals (p < 0.001) and women (p = 0.002). Non-dominant headaches were characterized as dull (56.9%) and holocranial (26.5%), while dominant headaches were unilateral (31.3%) with photophobia (34.3%) and nausea (56.3%). Persistent headaches were unilateral (40%) and pulsating (38%) with phonophobia (74%). Decreased CD4 T cells independently predicted COVID-associated headaches, with elevated IL-6 levels noted in the dominant-headache group (p = 0.040). Remarkably, 50% of patients reported persistent headaches 12-15 months post-infection. Dexamethasone administration significantly reduced the likelihood of long-COVID headaches (52% vs. 73%, p = 0.029). Conclusions: Headache was present in one-third of patients with heterogenous phenotypes: tension headache in the non-dominant group, and migraine in the dominant and persistent headache groups. Persistent headache remains a challenge, with dexamethasone showing potential in reducing its incidence, emphasizing the need for tailored approaches in managing long-COVID headaches.

Cerebellar abscess secondary to metastatic lung adenocarcinoma: a case report

BackgroundCerebellar abscesses are rare, life-threatening infections often originating from bacterial sources, while metastatic brain lesions from lung adenocarcinoma are relatively common. However, the coexistence of a cerebellar abscess secondary to metastatic lung adenocarcinoma is exceedingly rare and presents unique diagnostic and management challenges.Case PresentationWe report a case of a 35 year-old Pakistani female patient with persistent headaches, nausea, and vertigo, who was found to have a large cerebellar mass with features suggestive of metastatic lung adenocarcinoma. Further investigation revealed a concomitant cerebellar abscess. Surgical excision and broad-spectrum antibiotics were initiated, resulting in a favorable outcome.ConclusionThis case showcases the rarity and complexity of cerebellar abscesses due to metastatic lung adenocarcinoma. Timely intervention, including surgery and targeted therapy, is crucial for successful management. Further research is needed to enhance treatment strategies.

Virtual reality: a game-changer in the diagnosis and surgical planning of astrocytoma grade III: a case report

BackgroundIn the dynamic realm of modern medicine, the advent of virtual reality technology heralds a transformative era, reshaping the contours of diagnosis and surgical planning with its immersive prowess. This study delves into the groundbreaking application of virtual reality in the intricate dance of neurosurgery, particularly spotlighting its role in the management of astrocytoma grade III—a cerebral challenge of significant complexity.Case presentationA 30-year-old Middle Eastern man from Syria grappled with the invisible tendrils of pain, manifesting as persistent headaches and a numbing sensation that crept into his neck and extremities. For two relentless months, the morning sun brought not hope but an intensification of his agony, rendering him unable to partake in the daily dance of life. The usual sentinels of relief, analgesic drugs, stood defeated, offering no respite. The neurological examination was normal, there were no pathological findings on sensory and motor examination, and he exhibited normal reflexes and neither meningeal nor cerebellar signs. He showed a family history of breast cancer. The initial foray into the enigmatic depths of his brain via computed tomography and magnetic resonance imaging imaging unveiled a finding in the right temporal lobe, a lesion that suggested something more sinister. Previous medical interventions included analgesic medications prescribed for persistent headaches, but they offered no relief. No other therapeutic interventions were administered prior to the current diagnosis. It was here that virtual reality technology emerged not as a mere tool but as a beacon of precision, casting a three-dimensional light on the shadowy intruder. This technological marvel allowed for meticulous measurement 21.8 × 14.5 mm and localization within the temporal theater, setting the stage for what was to come. With the path laid clear, the patient embarked on a surgical odyssey, a quest to excise the unwelcome guest. The operation was a triumph, a testament to human ingenuity and the symbiotic relationship between flesh and machine. The postoperative verdict was delivered through the lens of histopathology, confirming the presence of an astrocytoma grade III, a cerebral interloper known for its rapid proliferation. The battle, however, was far from over. Complementary radiotherapy and chemotherapy were enlisted as allies in this ongoing war, their potent forces working in concert to stave off the cellular insurgence. The patient’s journey through the healing arts was charted by periodic clinical and neurological examinations, with laboratory tests and the vigilant gaze of brain magnetic resonance imaging ensuring a watchful eye was kept on any potential resurgence.ConclusionsIn this narrative of resilience and technological prowess, we witness the harmonious fusion of human touch and digital precision, a partnership that redefines the boundaries of medicine and the art of healing, by use of virtual reality technology in the diagnosis of astrocytoma and enhancing the accuracy, effectiveness, and safety of neurosurgical procedures, which can ultimately benefit patients with brain tumors.

Enlarged Breast Size (Macromastia) and Associated Neurologic Risks: A Scoping Review.

Symptomatic macromastia (enlarged breasts) is a syndrome of persistent headache, neck and shoulder pain, thoracic kyphosis, painful shoulder grooving from bra straps, inframammary rash, backache, and upper extremity paresthesias. Up to 89% of the 100,000 US women undergoing breast reduction surgery (reduction mammoplasty) annually report headache preoperatively with many endorsing postoperative headache improvement. Headache is one insurance indication to cover surgical reduction, and peak prevalence of migraine matches the average age of women with macromastia at time of surgery. Little is known about the influence of macromastia on headache. The goal of our narrative review is to understand the evidence for and potential mechanisms underlying macromastia-related headache. A literature search was performed in PubMed Medline using concepts "breast hypertrophy," "macromastia," "headache," "migraine," "breast reduction," and "reduction mammoplasty" excluding limits on age, language, publication date, or study type. Supplemental literature searches were performed to provide a comprehensive understanding of potential mechanisms underlying macromastia-related headache. We identified 25 studies describing macromastia-associated headache in the setting of reduction mammoplasty, with 23 original research studies (retrospective, n = 12, prospective, n = 11) totaling 3,799 patients, 1 systematic review, and 1 meta-analysis. Most (24/25) were published in Plastic Surgery, one in Internal Medicine, and none in Neurology. Wide ranges were identified for preoperative headache prevalence (2%-89%) and postoperative headache improvement (34%-100%). Studies described headache as "myofascial" or "tension-type" without detailing headache definitions, chronicity, headache screening method, or neurologic examination. Potential pathophysiologic mechanisms of macromastia-associated headache include structural, mechanical, psychosocial, and hormonal. No studies on macromastia-associated headache and reduction mammoplasty are published in Neurology. This important women's health topic remains unexplored in fields outside Plastic Surgery. Many questions remain unanswered that are important for neurologists to understand, including which headache type(s) women with macromastia experience and which headache type(s) respond to surgical intervention.

Protein-losing enteropathy as a new phenotype in atypical hemolytic uremic syndrome caused by CD46 gene mutation.

Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy. Genetic defects in the alternative complement (AP) pathway have been identified in 60-70% of individuals. Eculizumab is recommended as a first-line therapy. We collected the clinical data of a pediatric patient with aHUS accompanied by protein-losing enteropathy (PLE). Genetic testing was performed. Related literature on aHUS combined with PLE was reviewed. A 15-year-old Chinese girl was diagnosed with aHUS at 3.7years of age and experienced five episodes; her symptoms completely resolved with plasma treatment. Severe gastrointestinal symptoms and hypoalbuminemia presented after the first episode, and PLE was diagnosed. A novel homozygous CD46 variant was identified, and FACS revealed significantly decreased CD46 expression. She presented at a recent relapse with persistent GI symptoms and headache and progressed to chronic kidney failure; peritoneal dialysis was initiated. Eculizumab was given 8months after the last recurrence. Surprisingly, PLE was cured. Afterward, dialysis was discontinued, and eGFR recovered to 44.8ml/min/1.73 m2. A review of the literature indicated that PLE with thrombosis was caused by CD55 variants via hyperactivation of the AP system. We report an aHUS patient with PLE caused by CD46 variants. Symptoms of both PLE and aHUS were significantly alleviated in our patient and patients with CD55 variants treated with eculizumab, indicating that PLE was a new symptom of aHUS in our patient with a CD46 variant. Our case expands the phenotype of aHUS caused by a CD46 mutation and provides evidence of the efficacy of eculizumab after a long phase of chronic kidney failure.

Beyond movement: Headache in patients with functional movement disorders.

To evaluate headache comorbidity in a cohort of patients with functional movement disorders by assessing the prevalence, clinical characteristics, and temporal relationship of headache with the onset of functional symptoms. Functional movement disorders are common and potentially treatable. Although headache is frequent in these patients, few studies have evaluated their headache features. This observational cohort study included consecutive patients with functional movement disorders evaluated in our Functional Movement Disorders Unit between October 2021 and November 2022. Clinical and demographic features from clinical charts were reviewed, and patients completed a self-administered questionnaire designed by the authors that included headache characteristics, disease duration, treatments received, and the Headache Impact Test-6. Headache type was classified as per the Classification of Headache Disorders, third edition (ICHD-3). A total of 51 patients with functional movement disorders were included. Of those, 40 (78%) reported having recurrent headache. Headache intensity was moderate-severe in 33/40 (83%), and about two-thirds experienced headache >9 days/month. Disability secondary to headache was high (median [interquartile range] Headache Impact Test-6 score 62 [49-66]). Based on the ICHD-3, 23/40 (58%) of patients with headache met the criteria for migraine or probable migraine, 11/40 (27%) for tension-type headache, two of 40 (5%) for new daily persistent headache, and one of 40 (3%) for primary exercise headache, while three of 40 (7%) were unclassifiable. The onset of headache occurred before the functional movement disorder in 28/40 (70%), after the functional movement disorder in five of 40 (12%), and simultaneously in six of 40 (15%). In this last group, four of the six (67%) patients described a daily headache from the onset, and two met the criteria for new daily persistent headache. Headache is a frequent condition in patients with functional movement disorders and an additional burden of disability beyond their motor symptoms. We found that, besides migraine and tension-type headache, new daily persistent headache may be a comorbid phenotype in patients with functional movement disorders and should be further studied in larger prospective studies.

Dural venous sinus angioplasty and stenting for treatment of idiopathic intracranial hypertension: a single-center experience with 20 consecutive cases

Background: Dural venous sinus stenosis has been shown to be a potential cause or aggravating factor of idiopathic intracranial hypertension (IIH). Endovascular therapy for angioplasty of venous sinus stenosis is emerging as a potential alternative to treat IIH. Objective: This article aims to present the results of a cases series representing the experience of a single center in treating this disease. Materials and Methods: We retrospectively reviewed the angiographic and manometric data of patients undergoing angioplasty and stenting for the treatment of IIH with venous sinus stenosis on magnetic resonance angiography. All patients had failed conventional medical treatment. Data on demographic features, clinical and radiologic presentation, and outcomes were collected retrospectively. Results: 20 female patients, with persistent headache and papilledema, underwent venous sinus angioplasty and stenting. Mean age was 35.9 (SD, 10) years. Eighteen patients (90%) had clinical improvement after the procedure. Of these, all showed resolution (17 patients, 94%) or partial improvement (1 patient, 6%) of papilledema within 6 months. Two patients had persistent moderate-to-severe headache (intensity &gt; 6 on a 10-point pain scale), with continued papilledema despite stable visual acuity on visual field testing. The mean pre-procedure lumbar puncture opening pressure was 30.1 (SD, 4) mm Hg, decreasing to 16.2 (SD, 4) mm Hg after the procedure. Only 4 patients experienced complications directly or indirectly related to the procedure, with no impact on outcome. Conclusion: Angioplasty and stenting of the stenotic segment may effectively and safely treat IIH associated with focal venous sinus stenosis, with a high technical success rate and an acceptable complication rate.

Diagnostic and therapeutic insights in individuals with persistent post-dural puncture headache: A cross-sectional study.

Post-dural puncture headache (PDPH) is a frequent complication following lumbar puncture, epidural analgesia, or neuraxial anesthesia. The International Classification of Headache Disorders, third edition categorizes PDPH as a self-limiting condition; however, emerging evidence, including our findings, suggests that PDPH can have a prolonged course, challenging this traditional view. To elucidate the diagnostic characteristics and treatment outcomes of persistent PDPH (pPDPH), offering insights into its demographic profiles and diagnostic features. We executed an anonymous, web-based survey targeting individuals aged ≥18 years diagnosed with or suspected of having pPDPH. Recruitment occurred through self-help groups on Facebook. The survey comprised questions regarding diagnostic procedures, treatment regimens, outcomes, and healthcare consultation. The survey achieved a response rate of 179/347 (51.6%) individuals completing the questionnaire. Cerebrospinal fluid (CSF) leaks were confirmed in nine of 179 (5.0%) cases. Signs of intracranial hypotension without a CSF leak were observed in 70/179 (39.1%) individuals. All participants underwent magnetic resonance imaging scans of the brain and spine, with computed tomography myelography performed in 113/179 (63.1%) cases. Medications, including analgesics, theophylline, and gabapentin, provided minimal short-term relief. Epidural blood patch treatments resulted in slight-to-moderate short-term improvement in 136/179 (76.0%), significant improvement in 22/179 (12.3%), and complete effectiveness in eight of 179 (4.5%) individuals. For long-term outcomes, slight-to-moderate improvement was reported by 118/179 (66.0%) individuals. Surgical interventions were carried out in 42/179 (23.5%) patients, revealing pseudomeningoceles intraoperatively in 20/42 (47.6%) individuals. After surgery, 21/42 (50.0%) of the participants experienced slight-to-moderate improvement, 12/42 (28.6%) showed more pronounced improvement, and five of the 42 (11.9%) achieved complete effectiveness. This study underscores the complexities of managing pPDPH. The delay in diagnosis can impact the effectiveness of treatments, including epidural blood patch and surgical interventions, resulting in ongoing symptoms. This underscores the importance of tailored and adaptable treatment strategies. The findings advocate for additional research to deepen the understanding of pPDPH and improve long-term patient outcomes.

A COVID-19 Case: Isolated and Persistent Headache

COVID-19 effects many systems such as respiratory, nervous, renal and hematologic system. Third of patients have experienced neurological symptoms such as headache, anosmia, ageusia, and dizziness. Headache has been reported as the most common neurological manifestation but cases just headache are extremely rare. This case is a Covid-19 case with no symptoms other than sudden onset headache. The result of the nasal swab PCR sampling was negative however local infiltration areas with ground glass density in the periphery of the middle lobe, lateral segment of the both lungs were detected in the thorax CT.

Diffuse pulmonary arteriovenous malformation presenting with secondary polycythemia and headaches: a case report

BackgroundPulmonary arteriovenous malformations are a relatively uncommon medical condition, affecting roughly 1 in every 2500 individuals. Of those suffering from pulmonary arteriovenous malformations, 80% have an underlying genetic condition: hereditary hemorrhagic telangiectasia.Case presentationWe present the case of a 20-year-old Pakistani male with a history of persistent slower-onset frontal headaches that increased in severity within the course of the day. His hemoglobin was 18 g/dl, indicating polycythemia, for which he had undergone seven venesections in a month previously. His physical examination was unremarkable. His computed tomography scan depicted multiple dilated tortuous vessels with branching linear opacities in the right lower lobe of the lungs. The multiple feeding arteries were supplied by the right main pulmonary artery, and the large draining veins led to the right inferior pulmonary vein. This was identified as a diffuse pulmonary arteriovenous malformation. He was recommended for a right pulmonary artery angiogram. It showed multiple tortuous vessels with a nidus and large draining veins—features of a diffuse arteriovenous malformation in the right lower lobe of the lung consistent with the computed tomography scan. Embolization of two of these vessels feeding the arteriovenous malformation was conducted, using Amplatzer Vascular plug 2, whereas multiple pushable coils (five coils) were used for embolizing the third feeding vessel. This achieved 70–80% successful embolization of right pulmonary AVM; however, some residual flow was still seen in the arteriovenous malformation given the complexity of the lesion. Immediately after, his oxygen saturation improved from 78% to 96%.ConclusionDiffuse pulmonary arteriovenous malformations, as seen in this patient, are rare, accounting for less than 5% of total pulmonary arteriovenous malformations diagnosed. The patient presented with a complaint of progressive frontal headaches, which can be attributed to low oxygen saturation or the presence of a cerebral arteriovenous malformation. There was no history of hereditary hemorrhagic telangiectasia in the patient’s family. Furthermore, although most patients with hereditary hemorrhagic telangiectasia and hence pulmonary arteriovenous malformation have complaints of iron-deficiency anemia, our patient in contrast was suffering from polycythemia. This can be explained as a compensatory mechanism in hypoxemic conditions. Moreover, the patient had no complaint of hemoptysis or epistaxis, giving a varied presentation in comparison with a typical pulmonary arteriovenous malformation.

White matter and cortical gray matter microstructural abnormalities in new daily persistent headache: a NODDI study

BackgroundNew daily persistent headache (NDPH) is a rare primary headache with unclear pathogenesis. Neuroimaging studies of NDPH are limited, and controversy still exists. Diffusion tensor imaging (DTI) is commonly used to study the white matter. However, lacking specificity, the potential pathological mechanisms of white matter microstructural changes remain poorly understood. In addition, the intricacy of gray matter structures impedes the application of the DTI model. Here, we applied an advanced diffusion model of neurite orientation dispersion and density imaging (NODDI) to study the white matter and cortical gray matter microstructure in patients with NDPH.MethodsThis study assessed brain microstructure, including 27 patients with NDPH, and matched 28 healthy controls (HCs) by NODDI. The differences between the two groups were assessed by tract-based spatial statistics (TBSS) and surface-based analysis (SBA), focusing on the NODDI metrics (neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF)). Furthermore, we performed Pearson’s correlation analysis between the NODDI indicators and clinical characteristics.ResultsCompared to HCs, patients with NDPH had a reduction of density and complexity in several fiber tracts. For robust results, the fiber tracts were defined as comprising more than 100 voxels, including bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), as well as right corticospinal tract (CST). Moreover, the reduction of neurite density was uncovered in the left superior and middle frontal cortex, left precentral cortex, and right lateral orbitofrontal cortex and insula. There was no correlation between the NODDI metrics of these brain regions and clinical variables or scales of relevance after the Bonferroni correction.ConclusionsOur research indicated that neurite loss was detected in both white matter and cortical gray matter of patients with NDPH.

Persistent headache and chronic daily headache after COVID-19: a prospective cohort study.

Little is known about the frequency and impact of the persistent headache and about the incidence of chronic daily headache (CDH) after coronavirus disease 2019 (COVID-19). The aim of this prospective cohort study was to assess the incidence, risk factors, characteristics, and impact of CDH in patients with COVID-19. In the first stage, 288 patients were interviewed by telephone after the acute phase of COVID-19. Subsequently, 199 patients who presented headache were reinterviewed at least one year after COVID-19. Headaches that persisted beyond the acute phase of COVID-19 for three or more months and presented frequency ≥ 45 days over the first three months were considered to be CDH. One hundred and twenty-three patients were included, 56% were females; median age: 50 years (25th and 75th percentile: 41;58). The headache persisted beyond the acute phase of COVID-19 in 52%, and 20.3% had CDH (95% confidence interval: 13.6-28.2). Individuals who previously had headaches and who had headaches of greater intensity during the acute phase were at higher risk of developing CDH. The group with CDH included more females, greater impact of headache, more persistence of headache beyond the 120th day of COVID-19 and less throbbing headache than did the other individuals whose headache persisted. Patients who had COVID-19 had a high incidence of CDH. Previous headache and greater intensity of headache were associated with higher risk of CDH.

Hepatitis colestásica por sífilis secundaria en paciente con VIH: a propósito de un caso

Syphilis is a sexually transmitted disease caused by Treponema pallidum, and presents a variety of symptoms. Liver involvement in secondary syphilis is uncommon (1%), and can reach up to 3% in patients with HIV infection. We present the case of a 49-year-old man with the diagnosis of HIV on treatment with TARGA and an undetectable viral load, who attended the health center for jaundice, persistent headache, and hyperpigmented papular lesions on palms and soles. After laboratory tests and a cholangiopancreatography, the patient was diagnosed with cholestatic hepatitis due to secondary syphilis. The patient was treated with intravenous penicillin G sodium 3 million IU every 4 hours for 14 days, with a favorable clinical evolution and improvement of cholestasis.

Monoclonal antibody therapy for refractory chronic migraine-like headache related Lyme disease: a case report

IntroductionLyme disease, caused by Borrelia burgdorferi, can lead to diverse neurological manifestations, including headache. While most Lyme-associated headaches resolve with antibiotics, some may evolve into a refractory chronic migraine-like syndrome. We present a case of post-Lyme chronic migraine-like headache responsive to galcanezumab, a calcitonin gene-related peptide (CGRP) monoclonal antibody.Case ReportA 42-year-old woman developed chronic migraine-like headaches following treatment for Lyme neuroborreliosis. The headaches were refractory to standard preventive therapies and only partially responsive to onabotulinumtoxinA. Administration of galcanezumab resulted in significant reduction of headache frequency, intensity, and impact on daily activities.CommentThis case highlights the potential of CGRP-targeted therapies for persistent migraine-like headaches following Lyme neuroborreliosis. The favorable response to galcanezumab suggests a role for CGRP in the pathophysiology of post-Lyme headache. While further research is needed to establish efficacy and safety, clinicians should consider CGRP monoclonal antibodies for chronic migraine-like headaches refractory to standard treatments in the post-infectious phase of Lyme disease. The emergence of chronic migraine-like headaches following Lyme neuroborreliosis and the response to a CGRP monoclonal antibody in this case underscore the importance of considering targeted migraine therapies in the management of persistent headaches after antibiotic treatment. This report contributes to the understanding of Lyme disease sequelae and potential treatment options, warranting further investigation into the utility of CGRP-targeted therapies in this context.

A single-center experience of the upright proton therapy for skull-base chordomas and chondrosarcomas: Updated results

AimTo access efficacy and safety of the upright proton therapy for the skull-base chordomas and chondrosarcomas. Materials and methodsThe study encompasses single-center experience of proton therapy in chordomas (CA) and chondrosarcomas (CSA) of skull-base localization. We evaluate overall survival, local control and toxicity. Tumor response was assessed in accordance with RANO criteria. Treatment-related toxicity was evaluated with the help of CTCAE v 5.0 scale. ResultsProton therapy in the upright position was utilized for 51pts (patients) with CA-CSA (40 pts with chordoma and 11pts with chondrosarcoma) at the A. Tsyb Medical Radiological Research Center in 2016–2023. Median tumor volume constituted 30 cm3 (IQR (interquartile range) 15–41 cm3). Median total dose was 70 GyRBE. Median number of fractions was 35. Overall survival (OS) at 1-, 2- and 3-year rates reached 98.0 %, 88.6 % and 82.7 %, respectively. Median follow-up time was 36 months. The 1-, 2- and 3-year local control (LC) rates constituted, respectively, 98 %, 78.6 % and 66.3 %. Prior surgery showed statistically significant association with better prognosis (p = 0.023). Brainstem-to-tumor dose coverage compromise became the major pattern of LC failure (p = 0.03). The late radiation toxicity reactions included temporal lobe necrosis grade 2 in 2 pts, xerostomia grade 1 in 1pt, radiation cataract grade 2 in 1pt and persistent headache grade 2 in 4 pts. Severe late toxicity reactions were observed in 2 cases (4 %): 1 myelitis grade 3 and brainstem damage grade 5 in 1pt. ConclusionLocal control was achieved in the majority of patients receiving the scanning-beam upright proton therapy for skull-base CA-CSA. The LC rates after a surgery-radiotherapy combination treatment were higher compared with irradiation alone. Pattern of failure is mostly brainstem-tumor dose compromise. The high OS and LC rates were accompanied by low toxicity incidence. Even in complex case of the skull base CA-CSA upright proton therapy shows promising clinical outcomes.

Relato de caso e breve revisão da literatura sobre o sarcoma de alto grau em calota craniana

O sarcoma de alto grau na calota craniana é uma neoplasia rara, afetando adultos entre 30 e 60 anos, sem predileção de gênero. Fatores genéticos e exposição a radiações ionizantes podem estar associados ao seu desenvolvimento. Apresenta perfil histológico maligno, com células pouco diferenciadas, crescimento rápido e invasão local agressiva. Esse artigo visa descrever detalhadamente o caso de um paciente de 22 anos, sem comorbidades previstas, que sofreu trauma na região frontal da cabeça. Após o incidente, desenvolveu cefaleia persistente e diária, levando à realização de exames de imagem. Foram realizadas tomografia computadorizada e ressonância magnética do crânio, evidenciando o sarcoma, que foi prontamente abordado. Em janeiro de 2023, o paciente retornou com recorrência tumoral, evidenciando a necessidade de uma segunda abordagem cirúrgica. O paciente foi encaminhado para quimioterapia e radioterapia posteriormente como parte do plano de tratamento.

Hypersensitivity to BKCa channel opening in persistent post-traumatic headache

BackgroundLarge conductance calcium-activated potassium (BKCa) channels have been implicated in the neurobiological underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to examine whether MaxiPost (a BKCa channel opener) could induce migraine-like headache in persons with PPTH.MethodsThis is a randomized double-blind, placebo-controlled, two-way crossover study from September 2023 to December 2023. Eligible participants were adults with PPTH after mild traumatic brain injury who reported having no personal history of migraine. The randomized participants received a single dose of either MaxiPost (0.05 mg/min) or placebo (isotonic saline) that was infused intravenously over 20 minutes. The two experiment sessions were scheduled at least one week apart to avoid potential carryover effects. The primary endpoint was the induction of migraine-like headache after MaxiPost as compared to placebo within 12 hours of drug administration. The secondary endpoint was the area under the curve (AUC) values for headache intensity scores between MaxiPost and placebo over the same 12-hour observation period.ResultsTwenty-one adult participants (comprising 14 females and 7 males) with PPTH were enrolled and completed both experiment sessions. The proportion of participants who developed migraine-like headache was 11 (52%) of 21 participants after MaxiPost infusion, in contrast to four (19%) participants following placebo (P = .02). Furthermore, the median headache intensity scores, represented by AUC values, were higher following MaxiPost than after placebo (P < .001).ConclusionsOur results indicate that BKCa channel opening can elicit migraine-like headache in persons with PPTH. Thus, pharmacologic blockade of BKCa channels might present a novel avenue for drug discovery. Additional investigations are nonetheless needed to confirm these insights and explore the therapeutic prospects of BKCa channel blockers in managing PPTH.ClinicalTrials.gov IdentifierNCT05378074.

Neurological manifestations among Egyptian children with familial Mediterranean fever

BackgroundFamilial Mediterranean fever (FMF) is an auto-inflammatory periodic disorder resulting from mutations in the Mediterranean fever gene. Although it is considered a polyserositis disease, neurological-associated symptoms were also reported among different populations.Aim of the workTo detect the frequency of neurological manifestations among Egyptian children with FMF and to investigate its association with various disease characteristics and various FMF gene mutations.Patients and methodsThis is an analytical cross-sectional study that enrolled 300 FMF children. Neurological manifestations such as headache, paresthesia, convulsions, tremors, breath-holding attacks, and syncope were reported. The dose, duration, and compliance with colchicine and the international severity scoring system for FMF (ISSF) were recorded. Serum amyloid A and gene mutations were recorded from patients’ files.ResultsThe mean age of the patients was 10.35 ± 2.89 years; 158 (52.7%) were females, and 142 (47.3%) were males (F:M, 1.1:1), age at onset 4.67 ± 2.35 years and disease duration 3.28 ± 1.31 years. Genetic testing revealed positive MEFV gene mutation in 89.3%. Serum amyloid A was elevated in 33.7%. All patients were treated with colchicine, and 81.3% were compliant. Neurological manifestations were detected in 160 (53.3%) patients. Headache was the most common symptom in 136 (45.3%), followed by paraesthesia in 76 (25.3%). Epilepsy was present in 7 (2.3%) cases. Headaches were most frequent among patients with compound heterozygous mutation, severe ISSF scores, and poor compliance with colchicine.ConclusionEgyptian children with FMF present with various neurological manifestations. Headache and paresthesia were the most frequent, especially with the compound heterozygous mutations, severe ISSF score, and among colchicine non-compliant patients. Rheumatologists and neurologists should be aware of these manifestations and address the importance of disease control and adherence to colchicine to avoid or decrease these manifestations. Persistent unexplained headache or other neurological manifestations, in the presence of other symptoms suggestive of FMF or high serum amyloid A, should raise suspicion of FMF, and genetic testing should be requested. A multidisciplinary approach must be considered when managing these children.

Neurocognitive and Neuropsychiatric Sequelae in Long COVID-19 Infection.

Objective: To characterize the cognitive profile of long COVID-19 subjects and its possible association with clinical symptoms, emotional disturbance, biomarkers, and disease severity. Methods: We performed a single-center cross-sectional cohort study. Subjects between 20 and 60 years old with confirmed COVID-19 infection were included. The assessment was performed 6 months following hospital or ambulatory discharge. Excluded were those with prior neurocognitive impairment and severe neurological/neuropsychiatric disorders. Demographic and laboratory data were extracted from medical records. Results: Altogether, 108 participants were included, 64 were male (59.25%), and the mean age was 49.10 years. The patients were classified into four groups: non-hospitalized (NH, n = 10), hospitalized without Intensive Care Unit (ICU) or oxygen therapy (HOSPI, n = 21), hospitalized without ICU but with oxygen therapy (OXY, n = 56), and ICU (ICU, n = 21) patients. In total, 38 (35.18%) reported Subjective Cognitive Complaints (SCC). No differences were found considering illness severity between groups. Females had more persistent clinical symptoms and SCC than males. Persistent dyspnea and headache were associated with higher scores in anxiety and depression. Persistent fatigue, anxiety, and depression were associated with worse overall cognition. Conclusions: No cognitive impairment was found regarding the severity of post-COVID-19 infection. SCC was not associated with a worse cognitive performance, but with higher anxiety and depression. Persistent clinical symptoms were frequent independent of illness severity. Fatigue, anxiety, and depression were linked to poorer cognitive function. Tests for attention, processing speed, and executive function were the most sensitive in detecting cognitive changes in these patients.