Airway Closure and Expiratory Flow Limitation in Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is mostly characterized by the loss of aerated lung volume associated with an increase in lung tissue and intense and complex lung inflammation. ARDS has long been associated with the histological pattern of diffuse alveolar damage (DAD). However, DAD is not the unique pathological figure in ARDS and it can also be observed in settings other than ARDS. In the coronavirus disease 2019 (COVID-19) related ARDS, the impairment of lung microvasculature has been pointed out. The airways, and of notice the small peripheral airways, may contribute to the loss of aeration observed in ARDS. High-resolution lung imaging techniques found that in specific experimental conditions small airway closure was a reality. Furthermore, low-volume ventilator-induced lung injury, also called as atelectrauma, should involve the airways. Atelectrauma is one of the basic tenet subtending the use of positive end-expiratory pressure (PEEP) set at the ventilator in ARDS. Recent data revisited the role of airways in humans with ARDS and provided findings consistent with the expiratory flow limitation and airway closure in a substantial number of patients with ARDS. We discussed the pattern of airway opening pressure disclosed in the inspiratory volume-pressure curves in COVID-19 and in non-COVID-19 related ARDS. In addition, we discussed the functional interplay between airway opening pressure and expiratory flow limitation displayed in the flow-volume curves. We discussed the individualization of the PEEP setting based on these findings.

Infantile idiopathic intracranial hypertension: case report and review of the literature

Background Idiopathic intracranial hypertension is an infrequent condition of childhood, and is extremely rare in infants, with only 26 cases described. The etiology is still unknown. Typical clinical manifestations change with age, and symptoms are atypical in infants, thus the diagnosis could be late. This is based on increased opening pressure at lumbar puncture, papilloedema and normal cerebral MRI. The measurement of cerebrospinal fluid opening pressure in infants is an issue because many factors may affect it, and data about normal values are scanty. The mainstay of treatment is acetazolamide, which allows to relieve symptoms and to avoid permanent visual loss if promptly administered. Case presentation We report the case of an 8-month-old infant admitted because of vomit, loss of appetite and irritability; later, also bulging anterior fontanel was observed. Cerebral MRI and cerebrospinal fluid analysis resulted negative and after two lumbar punctures he experienced initial symptom relief. Once the diagnosis of idiopathic intracranial hypertension was made, he received oral acetazolamide, and corticosteroids, with progressive symptom resolution. Conclusions Infantile idiopathic intracranial hypertension is extremely rare, and not well described yet. Bulging anterior fontanel in otherwise healthy infants with normal neuroimaging should be always considered suggestive, but can be a late sign, while irritability and anorexia, especially if associated with vomiting, may represent an early sign. In such cases, lumbar puncture should be always done, hopefully with cerebrospinal fluid opening pressure measurement, which is among coded diagnostic criteria, but whose threshold is controversial in infants. Early diagnosis, timely treatment and strict follow-up help to prevent vision loss or death of affected infants.

Clinical Manifestations, Neuroimaging Findings, and Treatment of Idiopathic Intracranial Hypertension in a Nepalese Tertiary Centre

Introduction: Idiopathic Intracranial Hypertension is characterized by headache, visual impairment, papilledema, and increased cerebrospinal fluid opening pressure. We aim to evaluate clinical manifestations, neuroimaging findings, and treatment of Idiopathic Intracranial Hypertension in a Nepalese tertiary center. Materials and Methods: We retrospectively included patients with the diagnosis of Idiopathic Intracranial Hypertension who were admitted to the Neurology department of Tribhuvan University Teaching Hospital from 2019 June to 2021 May and presented to the Neuro-ophthalmology outpatient clinic of the hospital for follow-up. Results: Out of 16 Idiopathic Intracranial Hypertension patients, 12(75%) patients had either headache or ocular pain. Reduced visual acuity and progressive visual loss were found in 44% of patients. Normal CSF opening pressure was found in 19%, 44% had CSF opening pressure at a range of 20-30 cm H20 and > 30 cm H20 in 37.5%. 15 Idiopathic Intracranial Hypertension patients (93.7%) were subtyped as Typical and 1 patient was diagnosed as Fulminant Idiopathic Intracranial Hypertension. Acetazolamide was used for treatment in 15 patients and 1 patient needed ventriculoperitoneal shunting. 56% Seven patients (44%) had some abnormal findings: partial empty sella (44%), and tortuous optic nerve (31%), flattened posterior eyeball (31%), and hypoplastic transverse sinus (19%). Conclusions: Idiopathic Intracranial Hypertension is an uncommon diagnosis but should be suspected in patients with chronic headaches with visual impairment. In low-resource settings, proper history along with neurological and ophthalmological examinations can even detect the early features and timely referral can save the vision and disability of Idiopathic Intracranial Hypertension patients.

Idiopathic intracranial hypertension leading to bilateral optic atrophy in a patient with recent COVID-19 infection: a case report

Neurologic complications are common in patients hospitalised with COVID-19 infection. Most common complications are myalgias, headaches, encephalopathy and dizziness. Uncommon complications are stroke, motor and sensory deficits, seizures, ataxia and movement disorders. Multiple neuro-ophthalmological manifestations have also been reported in association with COVID-19. These complications may be the result of a range of pathophysiological mechanisms like hypoxic neuronal injury during active COVID-19 infection, RAS dysfunction, immune dysfunction and direct injury by the virus etc throughout the course of the disease. Here we reported a case of neuro-ophthalmic complication of Idiopathic intracranial hypertension (IIH) followed by bilateral optic atrophy in a middle-aged man with recent COVID-19 infection. He presented to the emergency with complaints of headache, dizziness and sudden painless bilateral diminution of vision for 3 days. His fundus examination was suggestive of bilateral papilledema, his MRI brain was normal and opening pressure of CSF was raised on lumbar puncture. His MRV was normal, there was no evidence of CSVT. He was started on steroids and acetazolamide. His headache improved but there was no improvement in visual acuity. Repeat fundus showed pale disc and MRI orbit was suggestive of bilateral optic atrophy.

Use of non-invasive sensor to assess intracranial compliance in the management of migraine patients: case report

The objective of this study is to report the use of a non-invasive sensor to assess intracranial compliance (ICC) in patients complaining of migraine. This case report presents a 34-year-old, female patient that was treated for idiopathic intracranial hypertension (IIH) by placing a non-adjustable lumboperitoneal shunt. After one year, she presented with headache and signs of overdrainage. Non-invasive monitoring of ICC was done, suggesting a reduction in the ICC, but no change in the opening pressure of the valve. A diagnosis of migraine was made, with improvement after brain monitoring, leading treatment without any new surgical intervention. With this case, we conclude that the use of non-invasive sensor helped the medical team to understand the information obtained by the ICP curve in the office, and in the management of patients with headache complaints, supporting clinical decision making, improving the quality of care, correlated with underlying diseases and procedural and patient safety.

Neuroimaging Features of Intracranial Hypertension in Pediatric Patients With New-Onset Idiopathic Seizures, a Comparison With Patients with Confirmed Diagnosis of Idiopathic Intracranial Hypertension: A Preliminary Study

Seizures have been reported in association with idiopathic intracranial hypertension in pediatric patients. Magnetic resonance imaging (MRI) signs of intracranial hypertension have not been investigated before in pediatric patients with new-onset idiopathic seizures. MRI scans of 182 pediatric patients were retrospectively analyzed for imaging findings of intracranial hypertension, including 46 patients with new-onset idiopathic seizures and elevated cerebrospinal fluid opening pressure, 40 patients with new-onset idiopathic seizures and normal opening pressure, 56 patients with confirmed idiopathic intracranial hypertension, and 40 age- and sex-matched controls. The optic nerve sheath diameter is significantly larger in the group with new-onset idiopathic seizures and elevated opening pressure (mean diameter of 6.02 ± 0.45 mm) compared to patients with new-onset idiopathic seizures and normal opening pressure (mean diameter of 5.24 ± 0.50 mm) ( P value <.001). The cutoff value of 6.0 mm for optic nerve sheath diameter showed 63% sensitivity and 88% specificity to differentiate pediatric patients with seizures and elevated opening pressure from those with seizures and normal opening pressure. Conclusion A cutoff value of 6.0 mm for optic nerve sheath dilation may be used as a screening imaging marker to suspect elevated opening pressure with specificity of 88% in pediatric patients with new-onset idiopathic seizures.

Intrathecal Chemotherapy As a Potential Alternative Treatment for Steroid-Refractory Immune Effector Cell-Associated Neurotoxicity Syndrome

Introduction Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigm for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and other hematologic malignancies. However, its use is associated with serious adverse effects including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Severe ICANS can present with aphasia, mutism, somnolence, seizures, signs of increased intracranial pressure and rarely cerebral edema. Corticosteroids (CS) and IL-6 inhibitors are first line treatment for CRS and ICANS. Prolonged CS use has been associated with decreased over-all survival in CAR T-cell treated patients. Data on effective treatments for CART T-cell induced neurotoxicity is limited, especially in steroid-refractory ICANS. Blood-brain barrier (BBB) disruption and infiltration of myeloid and immune effector cells into the central nervous system are implicated in the pathogenesis of ICANS. This likely explains the role of intrathecal chemotherapy, which has been described in literature for treatment of steroid-refractory ICANS. Here, we report the outcomes of two patients with refractory DLBCL who developed severe ICANS after receiving axicabtagene ciloleucel (axi cel) and treated with intrathecal (IT) chemotherapy. Case Presentation Our first case is of a 66 year old male with diagnosis of R/R DLBCL, who was treated with R-CHOP, followed by R-GemOx, with no response then received axi cel. Patient developed grade 2 CRS and grade 1 ICANS (National Cancer Institute Common Terminology Criteria for Adverse Effects v4.03) on day +2 post infusion, treated with tocilizumab and dexamethasone with good response initially. While tapering dexamethasone on day +5, he developed grade 3 CRS and grade 3 ICANS. Brain MRI did not show any intracranial abnormality and EEG showed no seizure activity. Lumbar puncture (LP) was done on day +7 and showed opening pressure of 32 cm H2O, and 12 lymphocytes. He was started on IV solumedrol and tocilizumab was resumed. CRS improved while neurotoxicity progressed to grade 4 prompting intubation and mechanical ventilation on day +8. On day +9, patient received intrathecal methotrexate 12 mg and hydrocortisone 50 mg. On day +12, neurotoxicity improved to grade 1 and patient was extubated on day +13. Steroid taper stopped on +17. Despite disease response, patient remained hospitalized at day +45 for deconditioning and vocal cord paralysis related to a lengthy hospital stay and intubation. He was eventually discharged, however passed away on day +49 from complications of prolonged hospitalization. Our second case is of a 69 year old female with a diagnosis of R/R DLBCL with CNS involvement, treated with RCHOP x6 followed by salvage chemotherapy with refractory disease, She then received axi cel. Patient developed grade 1 CRS on day +4, treated with tocilizumab and dexamethasone, and patient responded well. On day +9, she developed grade 2 CRS and grade 3 ICANS. At that time, dexamethasone was switched to pulse dose solumedrol and tocilizumab was continued. CT head showed no acute intracranial abnormality and EEG did not show any epileptiform activity. LP showed opening pressure of 21, and 84 lymphocytes. On day +11, patient's CRS resolved, however ICANS developed to grade 4 and patient received 12 mg intrathecal methotrexate and hydrocortisone 50 mg for steroid-refractory ICANS. The very next day, patient showed significant neurological improvement. Steroid taper was initiated and patient's ICANS resolved on day +16. MRI brain showed decrease in size of nodular enhancement along periventricular white matter and left occipital area corresponding to treatment response. She was discharged on day +28 and continues to do well one year out of axi cel infusion Conclusion Our abstract adds to the sparse literature about the use IT chemotherapy in cases with severe ICANS. It also highlights its importance as an alternative potential therapy to high doses and prolonged courses of corticosteroids which is associated with increased morbidity and mortality. Steroid-refractory ICANS has limited treatment options and further evaluation of the use of IT chemotherapy in large scale studies is warranted. Disclosures Kahn: Abbvie: Research Funding, Speakers Bureau; Astrazeneca: Research Funding, Speakers Bureau; Beigene: Research Funding, Speakers Bureau; Epizyme: Research Funding, Speakers Bureau; Genetech: Research Funding, Speakers Bureau; GSK: Speakers Bureau; Karyopharm: Speakers Bureau; Kite: Speakers Bureau; Morphosys: Speakers Bureau; Sanofi: Speakers Bureau; SeaGen: Speakers Bureau. Fazal: Agios: Consultancy, Honoraria, Speakers Bureau; AMGEN: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; Glaxo Smith Kline: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Janssen Oncology: Consultancy, Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Karyopharm Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Sanofi Genzyme: Consultancy, Honoraria, Speakers Bureau; Stemline Therapeutics: Consultancy, Honoraria, Speakers Bureau; Taiho Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau. Lister: Oncology Analytics: Other: Academic Board.