Reported Adverse Events in a Multicenter Cohort of Patients Ages 6-18 Years with Cystic Fibrosis and at Least One F508del Allele Receiving Elexacaftor/Tezacaftor/Ivacaftor.

OBJECTIVE: The objective of this study was to describe reported adverse events (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI) in a pediatric sample with cystic fibrosis (CF) aged 6-18 years, with at least one F508del variant, followed at multiple Italian CF centers. STUDY DESIGN: This was a retrospective, multicenter, observational study. All children receiving ETI therapy from October 2019 to December 2023 were included. We assessed the prevalence and type of any reported potential drug-related AEs, regardless of discontinuation necessity. Persistent AEs were defined as those continuing at the end of the observation period. RESULTS: Among 608 patients on ETI, 109 (17.9%) reported at least 1 AE. The majority (n = 85, 77.9%) were temporary, with a median duration of 11 days (range 1-441 days). Only 7 (1.1%) patients permanently discontinued treatment, suggesting good overall safety of ETI. The most common AEs leading to discontinuation were transaminase elevations (temporary 14.1%, persistent 25.9%) and urticaria (temporary 41.2%, persistent 7.4%). Creatinine phosphokinase elevation was uncommon. No significant differences in AEs were observed based on sex, age groups (6-11 vs 12-18 years), or genotype. Pre-existing CF-related liver disease was associated with an increased risk of transaminase elevations. We identified significant variability in the percentage of reported AEs (ANOVA P value .026). CONCLUSIONS: This real-world study highlights significant variability in reported AEs. Our findings suggest that ETI is a safe and well-tolerated therapy in children and adolescents with CF. However, further long-term safety and effectiveness investigations are warranted.

Lower thoracic schwannoma presenting as pseudotumor cerebri: a case report.

Primary Spinal tumors presenting as increased intracranial pressure is a rare and intradural extramedullary (IDEM) spinal schwannoma with unique presentation of pseudotumour cerebri (PTC) is extremely rare. Here, we describe a case of 48 years old male patient who presented to us with six months' history of headache and visual disturbances and was found to have bilateral papilledema. CT scan of brain was normal and CSF opening pressure on Lumbar puncture (LP) was 30 cm of H2O with raised protein level. His headache and visual symptoms settled down after LP (Lumbo-peritoneal) shunt was performed. Three days postoperatively, patient complained of hypoesthesia and weakness of left leg that became an established complain after 2 weeks. A Lumbosacral MRI was performed with concerns of any postoperative complications of LP Shunt, which revealed IDEM spinal tumour at D11-D12 level. Patient underwent second surgery for excision of tumor. We reviewed the relevant literatures and discuss the possible mechanism of such atypical presentation of spinal tumors.

[Papilledema as a sign of intracranial hypertension]. / Zastoinyi disk zritel'nogo nerva kak priznak vnutricherepnoi gipertenzii.

Papilledema (choked disk) is a sign of intracranial hypertension (ICH) - condition that presents danger not only for patient's vision, but also for their life. Despite the fact that ICH is usually a neurosurgical pathology, sometimes an ophthalmologist is the first doctor such patients visit, most often in a primary healthcare clinic. At the same time, as practice shows, not all ophthalmologists are well aware about in this pathology; difficulties occur in differential diagnosis of papilledema against similar changes of the optic nerve head seen during ophthalmoscopic examination. This article reviews scientific literature on ICH, including benign ICH, diagnosis and differential diagnosis of papilledema. The authors also share their decades-long experience of working in a neurosurgical facility.

Infectious and inflammatory disorders might increase the risk of developing idiopathic intracranial hypertension - a national case-control study.

OBJECTIVE: To investigate whether conditions causing inflammatory activation are associated with increased risk of idiopathic intracranial hypertension. METHODS: All newly diagnosed idiopathic intracranial hypertension patients (cases) in Sweden between 2000-2016 were identified using pre-determined algorithms (n = 902) and matched with five controls from the general population and five individuals with an obesity diagnosis (n = 4510) for age, sex, region, and vital status. National health registers provided information on infections, inflammatory disorders and dispensed medications. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals. RESULTS: Compared to general population controls, the cases had fourfold increased odds of having an infection (odds ratio = 4.3, 95% confidence interval 3.3-5.6), and threefold increased odds of an inflammatory disorder the year prior to idiopathic intracranial hypertension diagnosis (odds ratio = 3.2, 95% confidence interval 2.4-4.3). Organ specific analyses showed that odds were increased for the study diseases in the respiratory organ, kidney organ and gastrointestinal tract, but not for female genital infections. Similar results were found when comparing idiopathic intracranial hypertension with obese controls though the odds ratios were of lower magnitude. Sub-analyses on exposure to anti-infectious and anti-inflammatory drugs confirmed the increased odds ratios for idiopathic intracranial hypertension patients. CONCLUSIONS: These findings suggest that major inflammatory activation may be a risk factor in idiopathic intracranial hypertension development.

Benign intracranial hypertension in a patient treated with ustekinumab for psoriasis.

Ustekinumab is a monoclonal antibody, which binds the p40 subunit of IL-12 and IL-23 so they are unable to bind to their receptors, ultimately reducing T-cell-mediated inflammation in psoriasis. Studies and cases have focused on the risk of infection and malignancy associated with the use of biologics medications; however, there have been limited data available on the potential neurological adverse effects of biologics. We report the case of a 44-year-old female with a longstanding history of psoriasis who developed benign intracranial hypertension while on ustekinumab for her psoriasis.

Pediatric otitic hydrocephalus: Report of two unusual cases and literature review.

Otitic hydrocephalus (OH) comprises a form of benign intracranial hypertension, which is secondary to otogenic lateral sinus thrombosis (LST). Only a small percentage of the patients with otogenic LST go into developing OH, and this may be associated with the multiplicity of anatomic variations of the cerebral venous drainage pathways. We present two pediatric cases of OH, along with a comprehensive review of the relevant literature. Both cases discussed in this article had concomitantly a rather rare anatomical variation; a high-riding, dehiscent jugular bulb, which might have played a role in the development of their clinical syndrome. The pediatric population with this particular imaging finding should receive special attention. Clinical implications of this concurrence are fitly discussed.

Visual failure and sinus thrombosis following depressed skull fracture: management with single session lumboperitoneal shunt and sinus decompression -case report.

Elevation of a depressed skull fracture (DSF) overlying a venous sinus is generally avoided due to risk of sinus injury. Rarely, the sinus may be compressed by the fractured segment, causing intracranial hypertension (IH) or encephalopathy and can only be diagnosed with cerebral angiography or MR imaging techniques. The posterior third of the superior sagittal sinus (SSS) was found involved in all the reported cases. There is no consensus on its management, but most patients did not have any sinus thrombosis and improved after elevation of the compressing DSF alone. There are isolated reports of improvement with serial lumbar punctures or ventriculoperitoneal shunt.We report for the first time, a single session lumboperitoneal shunt and DSF elevation for a patient with thrombosis of the posterior part of SSS due to an overlying DSF, causing florid papilledema and impending blindness. Elevation of the DSF alone would not have achieved patency of the thrombosed sinus immediately to save his vision. Hence a lumboperitoneal shunt was done for immediate relief of IH. This CSF diversion alone was insufficient to achieve patency of the thrombosed sinus in the presence of significant external compression by the DSF; even if anticoagulants were used. Hence we elevated the DSF after craniotomy using a technical modification; by making a wide gutter circumferentially around the DSF with a high speed drill, to avoid sinus injury; prior to its elevation. The patient's vision improved in 48 hours and anticoagulants were used till 2 months when sinuses were found normal on MRI. Serial CT &MR images showing progression to thrombosis and recovery after decompression are presented. Both CSF diversion and DSF elevation are necessary when vision is threatened by IH due to sinus thrombosis with an overlying DSF.

Idiopathic intracranial hypertension and bariatric surgery: a literature review and a presentation of two cases.

OBJECTIVE: There is paucity of data concerning the impact of bariatric surgery on idiopathic intracranial hypertension (IIH). We therefore present the clinical course of two cases that were managed at our centre, which is a regional referral centre for bariatric surgery and present a literature review of patients with IIH who underwent bariatric surgery for the treatment of obesity. METHOD: Two patients were referred for bariatric surgery who were both morbidly obese and were diagnosed with IIH. One patient underwent bariatric surgery; the other patient's weight was managed conservatively. We followed up both patients for 2 years. PubMed was searched for published studies of patients with IIH undergoing bariatric surgery. RESULTS: The patient that underwent weight loss surgery achieved sustained weight loss from 108kg to 87kg and gross resolution of their symptoms. The patient whose weight was managed conservatively lost weight initially and then put the weight back on. Her IIH symptoms persisted despite CSF shunt therapy. The literature review identified 12 original studies, containing 51 patients. Weight loss after bariatric surgery was reported for 84% of patients and improvement or resolution of IIH symptoms was reported for 84% of patients. CONCLUSION: In light of the literature review and our experience, bariatric surgery appears to be a potential treatment option for IIH alongside the comorbidities associated with obesity. However, more robust studies are needed.

Bibliometric analysis of the top-cited articles on idiopathic intracranial hypertension.

OBJECTIVE: To identify and characterize the top-cited articles on idiopathic intracranial hypertension. METHODS: We used "Web of Science database" to identify the top-cited articles published between the years of 1975-2017. The articles were evaluated using citation count and other factors that have an effect on the citation count. RESULTS: The search yielded a total of 2,141 articles and the most frequently cited articles received between 58-476 citations. Most articles were published between the years 1990-1999. The most popular study design involved natural history studies. USA ranked first in productivity with 72 articles and the leading institution was University of Iowa. The journal "Neurology" published the greatest number of articles. In assessing the specialties, neurology contributed to 32% of top 100 articles. There was no correlation between the citation count and number of references, years since publication, number of authors, authors' H-index, and number of institutions that had collaborated. There were positive correlations between the citation count and journal impact factor, Scimago journal rank and journal source-normalized impact per paper values. While descriptive keywords were more frequent between 1980s and 1990s, keywords describing surgical management options such as "nerve sheath decompression" and "cerebrospinal-fluid diversion" were top-listed keywords after the year 2000. CONCLUSIONS: Our study can help researchers identify the most significant and impactful articles on idiopathic intracranial hypertension, as well as to provide insight into the most noteworthy scientific trends and to visualize future research needs of the topic.

An Up to Date Review of Pseudotumor Cerebri Syndrome.

PURPOSE OF REVIEW: Idiopathic intracranial hypertension (IIH), pseudotumor cerebri syndrome (PTCS), and benign intracranial hypertension are all terms that have been used for a neurologic syndrome consisting of elevated intracranial pressure (ICP), headache and vision loss without mass lesion or underlying infection or malignancy. In this review article, categorization, diagnostic criteria, symptom management strategies, and disease treatment options for pseudotumor cerebri syndrome will be discussed. RECENT FINDINGS: The Idiopathic Intracranial Hypertension Treatment Trial has now proven that acetazolamide should be the first line therapy in primary PTCS, but other treatment options exist in patients who cannot tolerate acetazolamide or in selected cases, which requires surgical intervention for PTCS which acutely threatens vision. Headache has also been shown to require focused treatment beyond therapies that lower ICP, specifically targeting coexistent primary headache disorders and medication overuse. Advances in treatment and diagnostic modalities have improved understanding of PTCS types and their treatment. The pathophysiology of primary PTCS, however, remains incompletely understood, but continued evaluation of cerebrospinal fluid flow dynamics, aquaporins, hormones, natriuretic peptides, and the link with female gender and obesity may lead to future answers.

Giant arachnoid granulation in a child with benign intracranial hypertension: an unusual case.

CASE PRESENTATION: A 6-year-old girl complained of diplopia and headache over a 2-week period after sustaining a minor head injury. Her neurological examinations were normal, but visual examination identified bilateral papilledema. Magnetic resonance imaging of the brain revealed a protruding nodular lesion causing compression within the anterior superior sagittal sinus in the midline, showing high signal intensity on T2-weighted imaging (T2WI) and low signal intensity on T1WI, similar to that of cerebrospinal fluid. Enhanced T1WI showed irregular narrowing of the anterior superior sagittal sinus adjacent to this lesion. The cortical vein drained to the frontal pole of the arachnoid granulation lesion and into the superior sagittal sinus. No other parenchymal abnormality was noted. A lumbar puncture showed increased opening pressure (30 mmHg), and the laboratory findings were normal. Based on the imaging and clinical findings, benign intracranial venous hypertension with giant arachnoid granulation was diagnosed. The patient's symptoms were reduced satisfactorily following daily treatment with 750 mg acetazolamide. CONCLUSION: We report a case of giant arachnoid granulation involving the anterior superior sagittal sinus in a 6-year-old girl who presented with benign intracranial hypertension. Clinicians should be aware of this rare anatomic variant to avoid unnecessary invasive procedures or examinations in children with benign intracranial hypertension.

Pseudotumor cerebri in kaposiform lymphangiomatosis: a case report and pathogenetic hypothesis.

CASE REPORT: A 4-year-old boy with kaposiform lymphangiomatosis (KLA) developed progressive headaches and papilloedema and was diagnosed with pseudotumor cerebri initially treated with acetazolamide. Clinical deterioration prompted placement of a ventriculoperitoneal shunt. After the surgery, the child's condition has markedly improved. DISCUSSION AND CONCLUSIONS: A network of intracranial lymphatics is presently being investigated. Neuroimaging excluded KLA infiltration of the skull and/or meninges, leaving as the most plausible explanation for the child's pseudotumor cerebri the existence of an increase in intracranial venous pressure by venous compression at the thorax. To our knowledge, our case constitutes the first report of pseudotumor cerebri occurring in the context of KLA.

Understanding the complex pathophysiology of idiopathic intracranial hypertension and the evolving role of venous sinus stenting: a comprehensive review of the literature.

Idiopathic intracranial hypertension (IIH) is a disease defined by elevated intracranial pressure without established etiology. Although there is now consensus on the definition of the disorder, its complex pathophysiology remains elusive. The most common clinical symptoms of IIH include headache and visual complaints. Many current theories regarding the etiology of IIH focus on increased secretion or decreased absorption of cerebrospinal fluid (CSF) and on cerebral venous outflow obstruction due to venous sinus stenosis. In addition, it has been postulated that obesity plays a role, given its prevalence in this population of patients. Several treatments, including optic nerve sheath fenestration, CSF diversion with ventriculoperitoneal or lumboperitoneal shunts, and more recently venous sinus stenting, have been described for medically refractory IIH. Despite the availability of these treatments, no guidelines or standard management algorithms exist for the treatment of this disorder. In this paper, the authors provide a review of the literature on IIH, its clinical presentation, pathophysiology, and evidence supporting treatment strategies, with a specific focus on the role of venous sinus stenting.

Idiopathic intracranial hypertension.

BACKGROUND: Idiopathic intracranial hypertension or pseudotumour cerebri is primarily a disorder of young obese women characterised by symptoms and signs associated with raised intracranial pressure in the absence of a space-occupying lesion or other identifiable cause. SUMMARY: The overall incidence of idiopathic intracranial hypertension is approximately two per 100,000, but is considerably higher among obese individuals and, given the global obesity epidemic, is likely to rise further. The pathophysiology of this condition is poorly understood, but most theories focus on the presence of intracranial venous hypertension and/or increased cerebrospinal fluid outflow resistance and how this relates to obesity. A lack of randomised clinical trials has resulted in unsatisfactory treatment guidelines and although weight loss is important, especially when used in conjunction with drugs that reduce cerebrospinal fluid production, resistant cases remain difficult to manage and patients invariably undergo neurosurgical shunting procedures. The use of transverse cerebral sinus stenting remains contentious and long-term benefits are yet to be determined. CONCLUSION: An understanding of the clinical features, diagnostic work-up and therapeutic options available for patients with idiopathic intracranial hypertension is important both for neurologists and ophthalmologists as visual loss maybe permanent if untreated.

Treatment of idiopathic intracranial hypertension with gastric bypass surgery.

Idiopathic intracranial hypertension (IIH) is defined by elevated intracranial pressure and associated headaches, changes in vision and pulsatile tinnitus, among other symptoms. It occurs most frequently in young, obese women. Gastric bypass surgery has been used to treat morbid obesity and its comorbidities, and IIH has recently been considered among these indications. We present a case report of a 29-year-old female with a maximum BMI of 50.3 and a 5-year history of severe headaches and moderate papilledema due to IIH. She also developed migraine headaches. After a waxing and waning course and various medical treatments, the patient underwent laparoscopic Roux-en-Y gastric bypass surgery with anterior repair of hiatal hernia. Dramatic improvement in IIH headaches occurred by 4 months postprocedure and was maintained at 1 year, when she reached her weight plateau with a BMI of 35. Presurgery migraines persisted. This adds to the small number of case reports and retrospective analyses of the successful treatment of IIH with gastric bypass surgery, and brings this data from the surgical literature into the neurological domain. It offers insight into an early time course for symptom resolution, and explores the impact of weight-loss surgery on migraine headaches. This treatment modality should be further investigated prospectively to analyze the rate of headache improvement with weight loss, the amount of weight loss needed for clinical improvement, and the possible correlation with improvement in papilledema.

Fifteen-minute consultation: the child with idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is a rare condition where intracranial hypertension is found in the context of normal brain parenchyma and no mass lesion, ventriculomegaly, underlying infection, or malignancy. Our understanding of this condition has greatly improved in the recent years with neuroimaging features and normal values for lumbar puncture opening pressure now well defined. This article provides a review of IIH in children and revised diagnostic criteria based on recent evidence and published opinion. We have also presented an algorithmic approach to the child with possible IIH.

The Pseudotumor Cerebri Syndrome: A Unifying Pathophysiological Concept for Patients with Isolated Intracranial Hypertension with Neither Mass Lesion Nor Ventriculomegaly.

In 1991 we proposed that while the syndrome of isolated intracranial hypertension might have many definite and probable causes, it has nonetheless a single unifying pathophysiological mechanism: namely, impairment of cerebrospinal fluid (CSF) reabsorption. For that reason, we also proposed then that it is best described by a single, unifying, inclusive term, namely, pseudotumor cerebri syndrome. Although it appears that there is, as far as nomenclature is concerned, now international agreement, there is as yet no agreement on pathophysiology and classification. Herein we outline our views on these matters and give our reasons.

A Rare Case Report of Benign Intracranial Hypertension Caused by Hypervitaminosis A.

Benign intracranial hypertension (BIH) in children is recognized as elevated intracranial pressure without hydrocephalus or intracranial mass. It manifests differently in adults, with no apparent predilection for sex or weight. Headache, papilledema, and possibly sixth nerve palsy with visual field defects are the typical symptoms of this syndrome. Vitamin A toxicity is a rare cause of BIH. We report the case of a previously healthy 13-year-old girl presenting with photophobia, a frontal headache, and vomiting. She had bilateral papilledema discovered by fundoscopy. Both magnetic resonance imaging and brain CT were normal. At admission, a lumbar puncture (LP) revealed an opening pressure of 26 cm H2O with normal cerebrospinal fluid (CSF) analysis. The diagnosis of BIH was established, and treatment with acetazolamide was started, with good clinical results. Regular eye evaluations showed a regression of papilledema. Elevated serum vitamin A levels were the only positive findings. Within two weeks, the patient was discharged without any symptoms. This study aims to attract the attention of clinicians to the importance of evaluating vitamin A toxicity in the context of papilledema and oculomotor problems in a child who has undergone normal neuroradiological investigations.