Recurrent Headache Research Articles

AYURVEDIC MANAGEMENT OF PARTIAL EMPTY SELLA SYNDROME: A CASE REPORT

Empty Sella Syndrome is a disorder that involves the presence of Cerebro-spinal fluid in Sella turcica in an excess amount. In empty Sella syndrome the Sella turcica is either partially filled with cerebrospinal fluid and an atrophied pituitary gland lying in the floor of the Sella (Partial Empty Sella Syndrome) or filled with cerebrospinal fluid which pushes the pituitary gland into a side of Sella turcica resulting in non-visualization of the gland. (Completely empty Sella). A 37-year-old female diagnosed with partial empty Sella syndrome was managed with Pathyakshadhatryadi kashayam 15 ml twice daily in empty stomach with 45 ml lukewarm water, Rasnadi choornam tailam application, mahatraiphala ghritam 10 ml at night after food, Kshirabala 7 Avarti tailam pratimarsha nasyam. After completion of the treatment, there was considerable relief in the primary complaint of the patient which was a recurrent headache and the follow up MRI showed a marked change in the condition. This case report highlights the role of Ayurveda in the management of partial empty Sella syndrome and sheds light for further study on the same.

Can the neck contribute to persistent symptoms post concussion? Long-term follow up from a prospective descriptive case series

ABSTRACT Objective: To describe individual long-term outcomes of people with persistent symptoms following a concussion who received neck treatment as part of multidisciplinary concussion care. A secondary objective is to report on how participants describe the outcomes of neck treatmentMethods: Long-term follow-up for a subgroup of participants in a prospective case series (n = 11). Data were collected at initial assessment, completion of neck treatment, 6 and 12 months including standard questionnaires (Rivermead post-concussion symptoms questionnaire, neck disability index, dizziness handicap inventory); patient-reported measures of headache, dizziness and neck pain and participant descriptions of the effects of neck treatmentResults: Grouped measures of post-concussion symptoms were further improved or sustained at 6 and 12 months. Ten of the 11 participants reported neck treatment as a beneficial part of their care and described the effects on the neck, multiple symptoms and their overall recovery. However, seven participants experienced recurrent headache, neck pain or dizziness at 6- or 12-month follow-up.Conclusion: Long-term follow-up of individuals receiving neck treatment shows improvement across a range of patient reported outcomes, yet highlights frequent recurrence of symptoms. Neck treatment can play a valuable role in people’s recovery that extends beyond local effects on the neck.

Detecting Abnormal Neuronal Activity in a Chronic Migraine Model by Egr1-EGFP Transgenic Mice

Chronic migraine (CM) is a highly disabling neurological disorder characterized by recurrent headache accompanied by a variety of sensory and/or emotional symptoms. However, the mechanisms of migraine onset and its chronicity have not been elucidated. The present study was designed to search for brain regions and neurons that were abnormally activated by CM and might be related to its pathogenesis and different concomitant symptoms. CM models were established here by repeated intraperitoneal injection of nitroglycerin (NTG) every other day for 9 days to early growth response gene 1 (Egr1)-enhanced green fluorescent protein (EGFP) transgenic mice, which allowed monitoring of neuronal activities in the whole brain. CM-related behaviors were recorded through head grooming test and light aversion assay. Elevation of Egr1 expression signals was detected in trigeminal nucleus caudalis (TNC), primary somatosensory cortex (SSp), lateral amygdala nucleus (LA), primary visual area (VISp), and temporal association areas (TEa) 2 h after the last injection of NTG by immunofluorescence and digital slice scanning technology. Meanwhile, no change of Egr1 expression was found in auditory areas (AUD), CA1, ectorhinal area (ECT), piriform (PIR), and anterior cingulate area (ACC). Furthermore, with the strongest support by evidence-based medicine among the current limited oral treatments of CM, topiramate was administrated every day for 11 days from 2 days before the first NTG injection. The results showed that topiramate partially improved the photophobia behavior of CM models in the short-term with gradually weakened efficacy as the course of the disease prolonged. Meanwhile, NTG-induced increase in Egr1 expression was completely reversed in TNC, SSp, and VISp and partially reduced in LA and TEa by topiramate at the same time point mentioned above. In conclusion, the current results suggested that the abnormal hyperactivities in TNC, SSp and VISp were associated with the pathogenesis of CM.

Clinical, neuroradiological and genetic findings in a cohort of patients with multiple Cerebral Cavernous Malformations.

Cerebral cavernous malformations (CCM) consist of clusters of irregular dilated capillaries and represent the second most common type of vascular malformation affecting the central nervous system. CCM might be asymptomatic or cause cerebral hemorrhage, seizures, recurrent headaches and focal neurologic deficits. Causative mutations underlining CCM have been reported in three genes: KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3. Therapeutic avenues are limited to surgery. Here we present clinical, neuroradiological and molecular findings in a cohort of familial and sporadic CCM patients. Thirty subjects underwent full clinical and radiological assessment. Molecular analysis was performed by direct sequencing and MLPA analysis. Twenty-eight of 30 subjects (93%) experienced one or more typical CCM disturbances with cerebral/spinal hemorrhage being the most common (43%) presenting symptom. A molecular diagnosis was achieved in 87% of cases, with three novel mutations identified. KRIT1/CCM1 patients displayed higher risk of de novo CCMs appearance and bleedings. Magnetic Resonance Imaging (MRI) showed that infratentorial region was more frequently affected in mutated subjects while brainstem was often spared in patients with negative genetic testing.

Reversible Cerebral Vasoconstriction Syndrome Following Exposure to Oleoresin Capsicum “Pepper Spray”

ObjectivesTo report a case associating the use of Oleoresin Capsicum Pepper Spray (OCPS) during law enforcement training with development of Reversible Cerebral Vasoconstriction Syndrome (RCVS). Materials and MethodsRCVS is radiographically characterized by multifocal smooth narrowing of cerebral arteries heralded by clinical manifestations of recurrent thunderclap headaches. 70% of cases with RCVS have a clear precipitating factor and agents commonly implicated were cannabis, selective serotonin reuptake inhibitors, nasal decongestants, cocaine, postpartum state, eclampsia and strenuous physical/sexual activity.1 Results24-year-old female police officer with no past medical history who presented with thunderclap headaches after exposure to pepper spray to her face during work training. Neurological examination was unremarkable. CT angiogram (CTA) of the head and neck and subsequent conventional angiogram revealed multifocal mild arterial narrowing of bilateral middle cerebral arteries (MCA), bilateral posterior cerebral arteries (PCA) and left anterior cerebral artery (ACA) concerning for RCVS. Eight weeks later, she had a repeat MRA head and neck demonstrating complete resolution of the previously noted narrowing of her cerebral arteries. ConclusionsOCPS is widely used in law enforcement training as well as by general population as a self- defense tool. It is generally assumed to be safe, although the consequences of its use can never be predicted with certainty.2 As our case highlights, use of OCPS may be associated with development of RCVS and awareness needs to be raised regarding this rare but serious complication.

Social Impact of Prophylactic Migraine Treatments in Germany: A State-Transition and Open Cohort Approach

ObjectivesMigraine is a highly prevalent neurological disorder. The most characteristic symptom of migraine is moderate to severe recurrent headache along with other neurological symptoms. In this study, we modeled the potential reduction in migraine days and corresponding avoided productivity losses if erenumab was prescribed to the patient population indicated for prophylactic migraine treatment (≥ 4 monthly migraine days [MMDs]) in Germany from 2020 to the end of 2027. MethodsWe simulated the incremental benefits of erenumab against the standard of care. Response rates, transition probabilities, discontinuation rates, and productivity estimates were derived from the erenumab clinical trial program. Patients had a probability of residing in 1 of 7 states, given the MMDs in addition to the probability of death. Based on accrued MMDs in every cycle, days of absenteeism and presenteeism for paid and unpaid work were derived. Paid work was monetized according to gross value added using the human capital approach, whereas unpaid work was valuated according to the proxy good method. In addition, downstream macroeconomic effects were captured using value-added multipliers. Direct medical costs were concomitantly calculated. ResultsOur results show that prescribing erenumab for the indicated population in Germany could lead to a reduction of 166 million migraine days annually and reduce productivity losses in the range of €27 billion. This includes €13.1 billion from direct productivity and €13.5 billion from economic value chain effects. ConclusionsThis study highlights the macroeconomic effects of a systematic introduction of novel inhibitors of the calcitonin gene-related peptide pathway for migraine in Germany.

Next-generation sequencing combined with serological tests based pathogen analysis for a neurocysticercosis patient with a 20-year history:a case report

BackgroundNeurocysticercosis (NCC) is the most common helminthic infection of the central nervous system (CNS) caused by the larval stage of Taenia solium. Accurate and early diagnosis of NCC remains challenging due to its heterogeneous clinical manifestations, neuroimaging deficits, variable sensitivity, and specificity of serological tests. Next-generation sequencing (NGS)-based pathogen analysis in patient’s cerebrospinal fluid (CSF) with NCC infection has recently been reported indicating its diagnostic efficacy. In this case study, we report the diagnosis of a NCC patient with a symptomatic history of over 20 years using NGS analysis and further confirmation of the pathology by immunological tests.Case presentationThis study reports the clinical imaging and immunological features of a patient with a recurrent headache for more than 20 years, which worsened gradually with the symptom of fever for more than 7 years and paroxysmal amaurosis for more than 1 year. By utilizing NGS technique, the pathogen was detected in patient’s CSF, and the presence of Taenia solium-DNA was confirmed by a positive immunological reaction to cysticercus IgG antibody in CSF and serum samples. The symptoms of the patient were alleviated, and the CSF condition was improved substantially after the anti-helminthic treatment.ConclusionsThis study suggests that combining CSF NGS with cysticercus IgG testing may be a highly promising approach for diagnosing the challenging cases of NCC. Further studies are needed to evaluate the parasitic DNA load in patients’ CSF for the diagnosis of disease severity, stage, and monitoring of therapeutic responses.

The prevalence and burden of recurrent headache in Australian adolescents: findings from the longitudinal study of Australian children

BackgroundHeadache disorders are highly prevalent worldwide, but not well investigated in adolescents. Few studies have included representative nationwide samples. This study aimed to present the prevalence and burden of recurrent headache in Australian adolescents.MethodsThe prevalence of recurrent headache, headache characteristics (severity and frequency) and burden on health-related quality of life in Australian children aged 10–17 years were presented, using nationally representative data from the Longitudinal Study of Australian children (LSAC). The LSAC, commencing in 2004, collects data every 2 years from a sample of Australian children of two different age cohorts: B ‘baby’ cohort, aged 0–1 years and K ‘kindergarten’ cohort, aged 4–5 years at the commencement of the study. Face-to-face interviews and self-complete questionnaires have been conducted with the study child and parents of the study child (carer-reported data) at each data collection wave, with seven waves of data available at the time of the current study. Wave 7 of the LSAC was conducted in 2016, with B cohort children aged 12–13 years and K cohort children aged 16–17 years. For the current study, data were accessed for four out of seven waves of available data (Wave 4–7) and presented cross-sectionally for the two cohorts of Australian children, for the included age groups (10–11 years, 12–13 years, 14–15 years and 16–17 years). All available carer-reported questionnaire data pertaining to headache prevalence, severity and frequency, general health and health-related quality of life, for the two cohorts, were included in the study, and presented for male and female adolescents. Carer-reported general health status of the study child and health-related quality of life scores, using the parent proxy-report of the Paediatric Quality of Life Inventory™ 4.0, were compared for male and female adolescents with recurrent headache and compared with a healthy group. Finally, health-related quality of life scores were compared based on headache frequency and severity.ResultsThe LSAC study initially recruited 10,090 Australian children (B cohort n = 5107, K cohort n = 4983), and 64.1% of the initial sample responded at wave 7. Attrition rates across the included waves ranged from 26.3% to 33.8% (wave 6 and 7) for the B cohort, and 16.3% to 38.0% (wave 4–7) for the K cohort. Recurrent headache was more common in females, increasing from 6.6% in 10–11 years old females to 13.2% in 16–17 years old females. The prevalence of headache in males ranged from 4.3% to 6.4% across the age groups. Health-related quality of life scores were lower for all functional domains in adolescents with recurrent headache, for both sexes. Headache frequency, but not severity, was significantly associated with lower health-related quality of life scores, in both males and females.ConclusionsRecurrent headache was common among Australian adolescents and increased in prevalence for females, across the age groups. Frequent recurrent headache is burdensome for both male and female adolescents. This study provides information regarding the prevalence and burden of recurrent headache in the adolescent population based on findings from the Longitudinal Study of Australian Children.

A Comparative Analysis of Amytripiline, Flunnarazine and Topiramate in the treatment of Primary Headache

Introduction 
 Primary headache disorder, characterized by recurrent headache is the most
 prevalent disease leading to widespread ill health and impaired quality of life.
 In Nepal headache is one of the most common cause of patient attending neurology
 clinic. Amitriptyline, Flunarizine and Topiramate are common drugs in the
 treatment of primary headache. We conducted this study to compare the efficacy of drugs namely Amitriptyline, Flunarizine and Topiramate in the treatment of primary headache
 Materials and Methods
 This is the retrospective data analysis of primary headache patient treated with
 amitriptyline, flunarizine and topiramate. On their first, second and
 third subsequent visits, Headache Impact Test 6 Scoring was done by a medical
 person. Patient were treated clinically. After third follow up data were
 analyzed using SPSS version 20.0. Categorical variables were compared by
 chi-square test, paired sample t-test, ANOVA test and Welch test.
 Results
 A total of 142 patient data was analyzed. The most common age group were
 between 20 to 39 years (56.34%) followed by 40 to 59 years (33.80%). Female were
 predominant in the group 124 (87.32%). All three medication Amitriptyline,
 Flunarizine and Topiramate were able to significantly lower Headache impact test 
 -17.23 ± 6.643, -14.06 ± 7.155, -15.82 ± 5.907 respectively (P- <0.001).
 Amitriptyline was found to be better than other two drugs in reducing Headache
 Impact Test.
 Conclusion 
 All three drugs namely Amitriptyline, Flunarizine and Topiramate, are significantly
 effective in the treatment of primary headache. Though tension type of headache is the most common type of headache, amitriptyline seems to be equally effective in treatment with other primary headaches.

EFFECTS OF TRIGGER POINT DRY NEEDLING ON NECK PAIN AND CERVICAL RANGE OF MOTION (ROM) IN PATIENTS WITH CERVICOGENIC HEADACHE: A CASE SERIES

Musculoskeletal headaches are a common complaint with impaired postures. About 15% to 20% of chronic and recurrent headaches are diagnosed as cervicogenic headaches and are related to musculoskeletal impairments (4). Often associated with tension in posterior cervical muscles and pain at the attachment of the cervical extensors, at the cervico-thoracic junction, and/or radiating across the top, side, or back of the scalp

Other Primary Headache Disorders.

This article provides an overview of a diverse group of primary headache disorders that are categorized in the International Classification of Headache Disorders, 3rd Edition (ICHD-3), as "other primary headache disorders." This article provides clinicians with a distilled understanding of the diagnoses and their epidemiology, pathophysiology, and management. Cough-induced headache requires neuroimaging to exclude posterior fossa pathology and recently has been reported as a common symptom in patients with CSF-venous fistula. Clinical overlap is observed between patients with primary exercise headache and primary headache associated with sexual activity. Patients with recurrent thunderclap headache associated with sexual activity should be presumed to have reversible cerebral vasoconstriction syndrome until proven otherwise. De novo external-pressure headache is a common sequela among health care workers using personal protective equipment during the COVID-19 pandemic. New daily persistent headache is an important mimicker of chronic migraine or chronic tension-type headache and is distinguished by a daily-from-onset progression of persistent headache; a treatment-refractory course is often observed, and early involvement of a multidisciplinary team, including a psychotherapist, is advised. Patients with primary headache disorders that are classified as "other primary headache disorders" have presentations with unique diagnostic and management considerations. The disorders are highly recognizable, and an appreciation of the diagnoses will aid clinicians in providing safe and effective care for patients presenting with headache.

Headache in Children and Adolescents.

This article reviews the approach to a child or adolescent with headache, the criteria for common diagnoses, and the evidence base for treatments. The guidelines for acute and preventive treatment of migraine were updated in 2019. These guidelines summarize the available evidence and outline the questions that should be addressed in future research. The US Food and Drug Administration (FDA) approval of several new classes of drugs and devices to treat adult migraine in the past few years has resulted in ongoing or planned pediatric trials. Headache is a common symptom in children, and it is important to take a detailed history and perform a thorough physical examination to make the diagnosis. Nearly 1 in 10 children experience recurrent headaches due to migraine, which cause significant impairment in school performance and quality of life. The acute and preventive treatments that are currently available will help at least two-thirds of children with migraine, and several trials of new therapies offer hope for the future.

Findings of Brain Magnetic Resonance Imaging in Girls with Central Precocious Puberty Compared with Girls with Chronic or Recurrent Headache.

In the present study, the results of brain magnetic resonance imaging (MRI) in girls with central precocious puberty (CPP) were compared those in with girls evaluated for headaches. A total of 295 girls with CPP who underwent sellar MRI were enrolled. A total of 205 age-matched girls with chronic or recurrent headaches without neurological abnormality who had brain MRI were included as controls. The positive MRI findings were categorized as incidental non-hypothalamic–pituitary (H–P), incidental H–P, or pathological. Positive MRI findings were observed in 39 girls (13.2%) with CPP; 8 (2.7%) were classified as incidental non-H–P lesions, 30 (10.2%) as incidental H–P lesions, and 1 (0.3%) as a pathological lesion (tuber cinereum hamartoma). The prevalence of positive MRI findings in girls with CPP did not differ from girls with headaches (13.2% vs. 12.2%, p = 0.74). The prevalence of incidental H–P lesions in girls with CPP <6 years of age, 6–6.9 years of age, and 7–7.9 years of age was 21.2%, 13.5%, and 9.6%, respectively (p = 0.21). Known pathological lesions were detected in only one (3.0%) girl with CPP aged <6 years and in no girls with CPP aged 6–7.9 years. Microadenomas were detected in no girls with CPP aged <6 years and in 5 (1.9%) girls with CPP aged of 6–7.9 years. Our findings call into question the routine use of brain MRI in girls with CPP, especially in girls 6 years or older. Current guidelines recommend a follow-up MRI in cases of microadenoma, but few data exist to support this recommendation for children.

When Your Thyroid Causes Muscle Paralysis

Background: Periodic paralysis represents a spectrum of disorders characterized by ion channel dysfunction, mainly Na-K-ATPase channels. Thyrotoxic periodic paralysis (TTP) is defined by the presence of hypokalemia and diffuse muscular paralysis in a pre-existing hyperthyroid state. Diagnosis can be challenging, especially in cases of undiagnosed hyperthyroidism due to the non-specific presentation of this illness. We present a case of a young male who presented with recurrent, spontaneous paralysis found to have Graves’ disease. Clinical Case: A 38-year-old Asian male presented with sudden onset diffuse weakness, numbness, and tingling. The weakness was so severe that he could barely walk more than a few steps. However, his symptoms resolved in less than 24 hours without any intervention. Five months later, the patient experienced a recurrent episode of this similar constellation of diffuse muscle weakness and paresthesia. The patient was taken to a nearby hospital, where he was provided with intravenous fluid resuscitation. Initial laboratory workup was notable for hypokalemia to 1.4 mmol/L (n: 3.6 - 5.3 mmol/L), hypophosphatemia to 0.6 mmol/L (n: 2.4 – 4.8 mmol/L), and elevated creatinine kinase to 807 U/L (n: 22 – 198 U/L). Additionally, TSH was <0.001 mU/L (n: 0.45 – 4.5 mU/L) along with free T4 3.4 ng/dL (n: 0.80 – 1.70 ng/dL. The patient denied any other symptoms or a family history of similar symptoms. Lumbar puncture and brain/spine MRIs were unremarkable. Symptoms gradually improved throughout hospitalization with fluid and electrolyte repletion. Hyperthyroidism was treated with methimazole 5mg twice daily, later changed to PTU 50mg every eight hours due to recurrent headaches. Thyroid uptake scan showed diffuse bilateral uptake to 39.11% at 4 hours and 61.8% at 24 hours. Follow up labs revealed: TSH 0.3 mU/L, free T4 1.44 ng/dL, free T3 3.5 pg/mL (n: 2.3 – 4.1 pg/mL). Patient denied recurrent episodes of weakness or paresthesia. Definitive hyperthyroidism treatment with RAI was planned. Conclusions: The prevalence of TPP is higher in Asian males compared to other ethnic groups. TPP manifests as a sporadic onset of muscle weakness ranging from mild weakness to flaccid paralysis. It has been described that thyroid hormone itself augments the activity of the Na-K-ATPase channel and increases its responsiveness to beta-adrenergic stimulation. In addition, hyperthyroidism is associated with insulin resistance leading to hyperinsulinemia. Both beta-agonism and insulin promote potassium to be driven into cells resulting in hypokalemia. As such, activities which increase beta adrenergic stimulation, like stress and exercise, and promote the secretion of insulin, such as heavy carbohydrate intake, are well described triggers of TPP. Treatment revolves around acutely treating hypokalemia followed by preventing subsequent attacks via regulation of the altered thyroid state.

Clinical Reasoning: A 29-Year-Old Woman Presenting with Recurrent Headache and Fever

Clinical Reasoning: A 29-Year-Old Woman Presenting with Recurrent Headache and Fever

Socioeconomic inequality in noncommunicable diseases: Results from a baseline Persian cohort study.

Background: Contrary to health indices advancement during recent years, health inequalities are still a global challenge. This study aimed to determine socioeconomic factors for noncommunicable diseases using concentration indices (CI). Methods: This cross-sectional study was conducted on the baseline data from a cohort study in Fasa (southern Iran). Principle component analysis was used to measure asset index. Moreover, socioeconomic inequalities were calculated by CI. Analysis was done at 95% confidence level using STATA software. Results: A total of 7990 individuals were included in the study. The highest negative CIs were significantly found for epilepsy (-0.334), paramnesia (-0.255), and learning disabilities (-0.063), respectively, and the lowest were significantly found for chronic headaches (-0.046), recurrent headaches (-0.03), infertility (-0.028) and hypertension (-0.057). This index was positive for breast cancer (0.298). Furthermore, it was not Significant for diabetes, thyroid disorders, depression, and chronic lung diseases. Conclusion: The findings showed a significant inequality in the most of the noncommunicable diseases in the region, which are more concentrated among the poorest population. Policymakers in the health system and city planners should consider these results to decrease the burden of noncommunicable diseases in the society by identifying vulnerable subcategories.

Riscos biomecânicos e ocupacionais em uma central de materiais e esterilização

INTRODUÇÃO: Os profissionais que atuam na central de material e esterilização (CME) possuem a função de recepcionar, limpar, esterilizar, embalar e armazenar utensílios utilizados em cirurgias no hospital. Trata-se assim, de uma profissão de grande exigência física e mental, com alta carga de trabalho e estresse. OBJETIVO: analisar os riscos biomecânicos e os sintomas osteomioarticulares de servidores da CME de um complexo hospitalar público. Materiais e MÉTODOS: um estudo observacional, prospectivo que foi desenvolvido em um hospital público do sul do país. Participaram 20 profissionais, tais como auxiliares, técnicos e enfermeiros. Os critérios de inclusão foram que o indivíduo atuasse na CME, ser auxiliar, técnico ou enfermeiro da CME ao menos a 6 meses, idade igual ou maior que 18 anos, de ambos os sexos e exercer qualquer função. Os critérios de exclusão, foram estar em período de férias ou licença saúde/capacitação no período de coleta de dados, trabalhar no setor a menos de 6 meses. Instrumentos de coleta: questionário sociodemográfico, internacional de atividade física (IPAQ) - versão curta e o Nórdico de Sintomas Osteomusculares. Resultados: Verificou-se que 85% dos profissionais são do sexo feminino; a idade média foi de 47 anos; 70% são auxiliares de enfermagem; 85% dos profissionais possuem filhos; 35% apresentaram dores em pescoço, punhos/mãos e quadril/coxas; 85% sentem dores de cabeça recorrentes; 50% já sofreram algum acidente de trabalho, sendo 80% com perfurocortantes. CONCLUSÃO: conclui-se que os servidores de CME tem riscos biomecânicos e ocupacionais, medidas preventivas devem ser adotadas para minimizar riscos à saúde física e mental dos mesmos.

Homozygous variant p. Arg90His in NCF1 is associated with early-onset Interferonopathy: a case report

BackgroundBiallelic loss-of-function variants in NCF1 lead to reactive oxygen species deficiency and chronic granulomatous disease (CGD). Heterozygosity for the p.Arg90His variant in NCF1 has been associated with susceptibility to systemic lupus erythematosus, rheumatoid arthritis, and Sjögren’s syndrome in adult patients. This study demonstrates the association of the homozygous p.Arg90His variant with interferonopathy with features of autoinflammation and autoimmunity in a pediatric patient.Case presentationA 5-year old female of Indian ancestry with early-onset recurrent fever and headache, and persistently elevated antinuclear, anti-Ro, and anti-La antibodies was found to carry the homozygous p.Arg90His variant in NCF1 through exome sequencing. Her unaffected parents and three other siblings were carriers for the mutant allele. Because the presence of two NCF1 pseudogenes, this variant was confirmed by independent genotyping methods. Her intracellular neutrophil oxidative burst and NCF1 expression levels were normal, and no clinical features of CGD were apparent. Gene expression analysis in peripheral blood detected an interferon gene expression signature, which was further supported by cytokine analyses of supernatants of cultured patient’s cells. These findings suggested that her inflammatory disease is at least in part mediated by type I interferons. While her fever episodes responded well to systemic steroids, treatment with the JAK inhibitor tofacitinib resulted in decreased serum ferritin levels and reduced frequency of fevers.ConclusionHomozygosity for p.Arg90His in NCF1 should be considered contributory in young patients with an atypical systemic inflammatory antecedent phenotype that may evolve into autoimmunity later in life. The complex genomic organization of NCF1 poses a difficulty for high-throughput genotyping techniques and variants in this gene should be carefully evaluated when using the next generation and Sanger sequencing technologies. The p.Arg90His variant is found at a variable allele frequency in different populations, and is higher in people of South East Asian ancestry. In complex genetic diseases such as SLE, other rare and common susceptibility alleles might be necessary for the full disease expressivity.

Reversible cerebral vasoconstriction syndrome (RCVS): an interesting case report

BackgroundReversible Cerebral Vasoconstriction Syndrome is a condition of transient cerebral vascular spasms, which usually presents with recurrent thunderclap headaches and recovers within 3 months. Several probable triggers and underlying factors, such as sex hormones, vasoactive drugs, head trauma or surgery, and tumors, have been implicated.Case presentationIn this paper, we present a 53-year-old woman with thunderclap headaches and normal lab tests who was radio-clinically diagnosed with reversible cerebral vasoconstriction syndrome and treated accordingly. Then, she experienced the recurrence of RCVS after about 2 years and headaches after 1 year in association with high blood pressure, high blood sugar, hypothyroidism, hyperlipidemia, and a urine metanephrine level of 5 times higher than the normal limit, suggesting a diagnosis of pheochromocytoma. After confirmation of the diagnosis with further imaging studies, surgical removal of the tumor resolved all the signs and symptoms.ConclusionOften underdiagnosed, pheochromocytoma could be an important condition associated with RCVS. It is important for clinicians to bear this diagnosis in mind while dealing with similar cases of recurrent thunderclap headaches.

New Management of Cluster Headache

Galcanezumab, a CGRP monoclonal antibody drug, has been approved by the U.S. Food and Drug Administration (FDA) for the prevention of recurrent cluster headaches. This was done after a randomized, double-blind, placebo-controlled trial found it to be effective and safe. Similarly sphenopalatine ganglion stimulation has been found to be effective and safe in a randomized, controlled trial as an acute treatment for chronic cluster headache. This article reviews the mechanisms of action of these therapies and their clinical trial results, clinical uses, and prospects in Japan.