OBJECTIVE: 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.
METHODS: 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 one 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 0·026).
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.

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.

OBJECTIVE: Patients with Chiari malformation (CM) are prone to a variety of neurological sequelae, including benign intracranial hypertension (BIH). In these patients, BIH is attributed to impaired cerebrospinal fluid (CSF) flow due to anatomical abnormalities of the posterior fossa. Occasionally, patients with CM may require growth hormone therapy (GHT), which can increase the production of CSF. It is thought that patients with CM who undergo GHT are at high risk of BIH-associated symptoms (BIHAS). We describe the incidence of neurological symptoms in 34 patients with CM before and during GHT.
METHODS: The database of a pediatric endocrinology center was queried for patients with CM who received GHT from 2010-22. Records were reviewed for adverse events. Demographic and radiological data were collected and analyzed. Patients with neoplastic disease, active inflammation, or acute trauma were excluded. CM diagnoses were independently assigned by a neuroradiology department. Patients were grouped based on the presence and nature of symptoms before and during GHT. Relationships between starting dose/BMI and occurrence of BIHAS/all GHT-associated symptoms were evaluated.
RESULTS: GHT was not associated with new-onset or worsening of preexisting BIHAS in 33 out of 34 patients with CM. Five complex patients continued to have preexisting BIHAS, which did not worsen. Of the four patients who developed new-onset BIHAS during GHT, three patients\' symptoms were attributed to other medical conditions. No patient permanently discontinued GHT due to BIHAS.
CONCLUSIONS: Growth hormone therapy is likely a safe treatment in patients with Chiari malformation and is unlikely to cause BIHAS.

UNASSIGNED: Increased intracranial pressure is a potential cause of spontaneous cerebrospinal fluid (sCSF) leak. Associated neuro-ophthalmic features have not been well studied, particularly relationships with idiopathic intracranial hypertension (IIH). We hypothesized that neuro-ophthalmic features routinely used in evaluations for IIH can be useful in the investigation of a causal relationship between IIH and sCSF leak. We reviewed the neuro-ophthalmic examination and office-based ophthalmic imaging data of all consecutive patients with sCSF leaks and at least one repair to investigate the clinical and neuro-ophthalmic features of increased intracranial pressure.
UNASSIGNED: We conducted a retrospective longitudinal study at a single institution by querying the electronic medical record system for CSF leak Current Procedural Terminology (CPT) codes (G96.00 and G96.01) from June 1, 2019, to July 31, 2022. For patients with a confirmed diagnosis of sCSF leak, demographic information, eye examination results, and ophthalmic imaging details for both eyes were collected.
UNASSIGNED: A total of 189 patients with CSF leaks were identified through CPT coding; 159 had iatrogenic or traumatic CSF leaks, and 30 individuals (3 male, 27 female) had confirmed sCSF leaks. The mean age of patients with sCSF leaks was 46 years (range: 29 - 81), with a mean body mass index of 35.2 kg/m2 (range: 18.2 - 54.1). Only 11 of 30 underwent eye examinations (8 before surgical repair and 10 after). The mean pre-repair and post-repair best-corrected visual acuity were 20/30 (range: 20/20 - 20/55) and 20/25 (range: 20/20 - 20/40), respectively (P = 0.188). The mean retinal nerve fiber layer thickness was 99 µm (range: 96 - 104) pre-repair and 97 µm (range: 84 - 103) post-repair (P = 0.195). The mean ganglion cell complex thickness was 84 µm (range: 72 - 94) pre-repair and 82 µm (range: 71 - 94) post-repair (P = 0.500). Humphrey visual field average mean deviation was -5.1 (range: -12.4 - -1.8) pre-repair and -1.0 (range: -10.1 - 2.1) post-repair (P = 0.063).
UNASSIGNED: Serial neuro-ophthalmic examinations are recommended for patients with sCSF leaks to screen for signs of current or prior increased intracranial pressure. Larger studies are required to clarify the longitudinal changes in neuro-ophthalmic features, to investigate the incidence of IIH in cases of sCSF leak development or recurrence after surgical repair, and to explore potential causal relationships to guide post-repair management and prevent recurrent leaks. A multicenter consortium is also suggested to develop a standard clinical protocol for comprehensive management of sCSF leaks.

OBJECTIVE: The purpose of this study was to evaluate the prevalence of idiopathic intracranial hypertension (IIH) in fibromyalgia (FMS) patients by utilizing ultrasound to measure the optic nerve sheath diameter (ONSD), a marker of elevated intracranial pressure and also to investigate the relationship with function, fatigue, quality of life (QOL), central sensitization (CS) and neuropathic pain.
METHODS: The study encompassed 80 female FMS patients and 75 healthy controls. Ultrasound was employed to measure the average ONSD in both groups. Conditions potentially elevating intracranial pressure were ruled out following neurological assessments. Pain (via visual analog scale, VAS), function (revised Fibromyalgia Impact Questionnaire, r-FIQ), QOL (Short Form-36, SF-36), fatigue (fatigue severity scale, FACIT), CS (Central Sensitization Scale), and neuropathic pain (Douleur Neuropathique-4) were evaluated.
RESULTS: The average ONSD was significantly higher in the patient group than the control group. Patients with ONSD >5.5 mm consistent with IIH were categorized as Group 1 (n = 54, 67.5%), while those with a diameter of 5.5 mm and below-formed Group 2. VAS pain (p = .033) and FIQ-R scores (p = .033) were significantly higher in Group 1 than Group 2. Headache was found more common in Group 1.
CONCLUSIONS: This study unveils a substantial occurrence (67.5%) of IIH in FMS patients, suggesting shared pathophysiological mechanisms contributing to symptoms like fatigue, headache, and cognitive dysfunction. Additionally, these findings implicate heightened functional impairment, CS, headache, and fatigue in FMS patients with IIH.

BACKGROUND: Pseudotumor cerebri (PC) in prepubertal patients displays certain characteristics that differentiate it from its presentation at the postpubertal stage. The aim of this study is to describe the characteristics of paediatric patients diagnosed with PC at our centre and to compare them according to their pubertal status.
METHODS: We included patients aged between 1 and 18 years who were diagnosed with PC in a tertiary-level hospital between 2006 and 2019 and who met the updated diagnostic criteria for PC. They were classified according to body weight and pubertal status. Subsequently, we analysed results from lumbar punctures, neuroimaging studies, ophthalmological assessments, and treatments received during follow-up.
RESULTS: We included 28 patients, of whom 22 were of prepubertal age and 6 were of postpubertal age. The mean age (standard deviation) was 9.04 (2.86) years. Among the postpubertal patients, 83.3% were boys, 66.7% of whom presented overweight/obesity. In the group of prepubertal patients, 27% were boys, 31.8% of whom were overweight. The most frequent symptoms were headache (89.9%) and blurred vision (42.9%). All patients presented papilloedema, and 21.4% manifested sixth nerve palsy. Possible triggers were identified in 28.6% of cases. Nineteen percent of patients presented clinical recurrence, all of whom were prepubertal patients. Complete clinical resolution was achieved in 55.6% of patients.
CONCLUSIONS: Prepubertal patients with PC show lower prevalence of obesity, higher prevalence of secondary aetiologies, and higher recurrence rates than postpubertal patients.

Sarcoidosis is an immune-mediated disease that can involve multiple systems. Sarcoidosis of the nervous system or neurosarcoidosis may present as cranial mononeuropathy, hypothalamic involvement, aseptic meningitis, granulomatous inflammation in the brain parenchyma or spinal cord, peripheral neuropathy, and, in rare cases, as myopathy and benign intracranial hypertension. The most common cranial nerve involvement is the facial nerve, which can present as unilateral or bilateral facial nerve palsy, often with recurrent episodes. Involvement of other cranial nerves such as the second and eighth cranial nerves has also been reported. Granulomatous inflammation in the spinal cord presents as myelopathy or radiculopathy. Peripheral neuropathy can manifest as mononeuropathy, mononeuritis multiplex, or generalized sensory-motor neuropathy. Carpal tunnel syndrome is more common in patients with sarcoidosis compared to the general population. Here, we describe the case of a 40-year-old female who presented with heaviness of the head and blurred vision, with a prior history of left-sided Bell\'s palsy. Bilateral papilledema was observed during the fundus examination. MRI of the brain revealed signs suggestive of benign intracranial hypertension. The cerebrospinal fluid (CSF) opening pressure was measured at 40 cmH2O. Biopsy of bilateral hilar lymphadenopathy indicated granulomatous inflammation consistent with sarcoidosis. The patient was started on steroids and acetazolamide, and she had a dramatic improvement in symptoms.

暂无摘要。

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.
Застойный диск зрительного нерва (ЗДЗН) является признаком внутричерепной гипертензии (ВЧГ) — состояния, угрожающего не только зрению, но и жизни пациента. Несмотря на то что ВЧГ — это, как правило, нейрохирургическая патология, нередко офтальмолог может стать первым врачом, к которому обращается пациент. Чаще всего это врачи первичного звена. В то же время, как показывает практика, далеко не все офтальмологи ориентируются в этой патологии; трудности представляет дифференциальная диагностика ЗДЗН с подобными по офтальмоскопической картине изменениями диска зрительного нерва. Настоящий обзор представляет данные научной литературы, касающиеся ВЧГ, в том числе и доброкачественной ВЧГ, диагностики и дифференциальной диагностики ЗДЗН. Авторы также делятся собственным опытом, который накоплен за десятилетия работы в нейрохирургическом учреждении.

Idiopathic intracranial hypertension (IIH) is a neurological disease characterized by symptoms and signs of increased intracranial pressure (ICP) of unknown cause. Most attention has been given to the role of cerebrospinal fluid (CSF) disturbance and intracranial venous hypertension caused by sinus vein stenosis. We previously proposed that key pathophysiological processes take place within the brain at the glia-neuro-vascular interface. However, the relative importance of the proposed mechanisms in IIH disease remains unknown. Modern treatment regimens aim to reduce intracranial CSF and venous pressures, but a substantial proportion of patients experience lasting complaints. In 2010, the first author established a database for the prospective collection of information from individuals being assessed for IIH. The database incorporates clinical, imaging, physiological, and biological data, and information about treatment/outcome. This study retrieved information from the database, asking the following research questions: In IIH subjects responding to shunt surgery, what is the occurrence of signs of CSF disturbance, sinus vein stenosis, intracranial hypertension, and microscopic evidence of structural abnormalities at the glia-neuro-vascular interface? Secondarily, do semi-quantitative measures of abnormal ultrastructure at the glia-neurovascular differ between subjects with definite IIH and non-IIH (reference) subjects? The study included 13 patients with IIH who fulfilled the diagnostic criteria and who improved following shunt surgery, i.e., patients with definite IIH. Comparisons were done regarding magnetic resonance imaging (MRI) findings, pulsatile and static ICP scores, and immune-histochemistry microscopy. Among these 13 IIH subjects, 6/13 (46%) of patients presented with magnetic resonance imaging (MRI) signs of CSF disturbance (empty sella and/or distended perioptic subarachnoid spaces), 0/13 (0%) of patients with IIH had MRI signs of sinus vein stenosis, 13/13 (100%) of patients with IIH presented with abnormal preoperative pulsatile ICP [overnight mean ICP wave amplitude (MWA) above thresholds], 3/13 (23%) patients showed abnormal static ICP (overnight mean ICP above threshold), and 12/13 (92%) of patients with IIH showed abnormal structural changes at the glia-neuro-vascular interface. Comparisons of semi-quantitative structural variables between IIH and aged- and gender-matched reference (REF) subjects showed IIH abnormalities in glial cells, neurons, and capillaries. The present data suggest a key role of disease processes affecting the glia-neuro-vascular interface.