Defining the Phenotype and Prognosis of People With Idiopathic Intracranial Hypertension After Cerebrospinal Fluid Diversion Surgery.

PURPOSE: To characterize the phenotype of patients with idiopathic intracranial hypertension (IIH) who received cerebrospinal (CSF) diversion surgery and to detail the trajectory of recovery. DESIGN: Prospective cohort registry study. METHODS: Patients with IIH with sight-threatening papilledema presenting to a single United Kingdom neuroscience center between 2019 and 2021 were included. Outcomes consisted of perimetric mean deviation (PMD) and optical coherence tomography measures of papilledema (retinal nerve fiber layer [RNFL]) and macular ganglion cell layer (GCL) in both eyes. Headache outcomes included monthly headache days (MHD). Logistic regression methods were used to model long-term outcomes. RESULTS: Fifty-one patients without previous surgical interventions were included (92% female, mean age 28.1 years [SD 8.4], body mass index 37.4 kg/m2 [SD 9.7], mean days of follow-up 330 [SD 209]). Measurements before surgery showed mean PMD -11.4 dB (SD 9.7), RNFL 364 µm (SD 128), Frisén grade papilledema 4.3 (SD 0.9). and MHD 23 (SD 10.6). At 1 month postoperatively, RNFL and PMD had improved by 38% and 4%, respectively. At 4 months postoperatively, papilledema had resolved. GCL declined by 13% over 12 months. MHD reduced by 75% 3 months postoperatively before returning to baseline levels by 12 months. Five patients (9.8%) required revision surgeries. CONCLUSIONS: Detailed characteristics of patients with sight-threatening IIH who received CSF diversion surgery and their typical postoperative recovery are presented. These parameters should guide physicians as to when patients with IIH may require surgery and enable the early identification of outliers who fail to respond. Papilledema and PMD recovered but GCL atrophy continued for 12 months. The implication of this delayed atrophy is unknown.

The idiopathic intracranial hypertension prospective cohort study: evaluation of prognostic factors and outcomes.

BACKGROUND: There are limited longitudinal data evaluating outcomes in idiopathic intracranial hypertension (IIH). We aimed to evaluate the long-term outcomes in a real-world cohort of patients with IIH and sought to establish the prognostic factors. METHODS: A longitudinal prospective cohort study was conducted over 9 years (2012-2021). Data included demographics and disease status. All consenting patients with IIH were recruited. Visual outcomes included visual acuity, Humphrey visual field and optical coherence tomography (OCT) imaging measurements. Headache frequency, severity, and impact were noted. We analysed the key variables impacting visual and headache outcomes. RESULTS: The cohort contained 490 patients with a confirmed IIH diagnosis. 98% were female with a mean body mass index (BMI) of 38 kg/m2. Those with the highest OCT retinal nerve fibre layer had the worst visual outcomes. We noted a delayed decline, in the visual field and OCT ganglion cell layer after 12 months. In the medically managed cohort (n = 426), we found that disease duration and change in BMI had the greatest influence on visual outcomes. There was a high burden of headache, with a daily headache at presentation and prior migraine history influencing long-term headache prognosis. CONCLUSIONS: There is a delayed decline in visual outcomes in those with the most severe papilloedema. Disease duration and change in BMI were the key visual prognostic factors, therefore those with the more acute disease may require closer monitoring. Improving prognosis in IIH should focus on the potentially modifiable factor of weight management.

An update on the clinical approach to giant cell arteritis.

Recent national and international guidance from rheumatology societies have reflected the advances in evidence for both the investigation and management of giant cell arteritis. Cranial ultrasound reduces diagnostic delay and improves clinical outcomes. Immediate high-dose glucocorticoids remain the standard treatment for giant cell arteritis. Randomised controlled trial evidence using tocilizumab, an interleukin-6 receptor antagonist, has been shown to have good clinical efficacy with glucocorticoid sparing effects. Overall patient outcomes appear to be improved by formalising pathways for diagnosis to include clinical experts' opinion early in decision making.

Diagnosis and treatment of diaphragmatic endometriosis: results of an international patient survey.

OBJECTIVES: To quantify the delays associated with the diagnosis and treatment of diaphragmatic endometriosis (DE), and to evaluate patient-reported postoperative outcomes. STUDY DESIGN: An anonymous survey was designed to collect data regarding demographics, duration and nature of DE symptoms, type of surgery and postoperative outcomes. Members of endometriosis patient associations in 14 countries were invited to complete the survey if they had been diagnosed with DE. Factors associated with postoperative outcomes were analyzed using Mann-Whitney U and Fisher's exact tests. RESULTS: Data was available from 136 respondents (median age 34 years). 98 % of respondents were from Europe, North America or Oceania. The most frequently reported symptoms of DE were moderate-severe pain in the upper abdomen (68 %), chest (64 %) and shoulder (54 %). Pain was right-sided in 54 %, left-sided in 11 % and bilateral in 35 %. Of 122 respondents who initially consulted a primary care physician, a gynaecology referral occurred after a median of five consultations (range 1-100). The median time between first primary care consultation and diagnosis of DE was two years (range 0-23). 31 % were diagnosed >1 year after their first gynaecology consultation (range 1-13 years), and 30 % required two or more laparoscopies before diagnosis. 116 respondents underwent surgical treatment. Postoperative data was available for 113 respondents, and 65 % reported either a significant improvement or complete resolution of symptoms. There was no significant difference in age (P = 0.19), timing of diagnosis (P = 0.59) or type of procedure (excision or ablation) (P = 0.13) between respondents who did and did not experience symptomatic relief after surgery. 61 % reported long-lasting symptomatic relief after a median of 1 year, whilst 39 % reported ongoing moderate-severe pain or have undergone further surgery for recurrent symptoms. CONCLUSION: The diagnosis and treatment of diaphragmatic endometriosis is often delayed, due to lack of awareness by patients and healthcare professionals. The diagnosis of DE requires a high index of suspicion and involvement of surgeons trained in laparoscopic liver mobilization. Recurrent symptoms are common following surgical treatment, and international collaborative studies are required to determine the long-term outcomes of this condition.

The nuclear envelope: LINCing tissue mechanics to genome regulation in cardiac and skeletal muscle.

Regulation of the genome is viewed through the prism of gene expression, DNA replication and DNA repair as controlled through transcription, chromatin compartmentalisation and recruitment of repair factors by enzymes such as DNA polymerases, ligases, acetylases, methylases and cyclin-dependent kinases. However, recent advances in the field of muscle cell physiology have also shown a compelling role for 'outside-in' biophysical control of genomic material through mechanotransduction. The crucial hub that transduces these biophysical signals is called the Linker of Nucleoskeleton and Cytoskeleton (LINC). This complex is embedded across the nuclear envelope, which separates the nucleus from the cytoplasm. How the LINC complex operates to mechanically regulate the many functions of DNA is becoming increasingly clear, and recent advances have provided exciting insight into how this occurs in cells from mechanically activated tissues such as skeletal and cardiac muscle. Nevertheless, there are still some notable shortcomings in our understanding of these processes and resolving these will likely help us understand how muscle diseases manifest at the level of the genome.