Outcomes of Pulsatile Tinnitus after Cerebral Venous Sinus Stenting: Systematic Review and Pooled Analysis of 616 Patients.

BACKGROUND: Pulsatile tinnitus (PT) is a debilitating condition with substantial morbidity related to quality of life. Cerebral venous sinus stenosis has recently emerged as a non-infrequent cause of PT, either in the setting of concurrent idiopathic intracranial hypertension (IIH) or due to primary venous stenosis. Venous sinus stenting (VSS) is an endovascular technique that can be used to treat venous stenosis. However, it is unclear if outcomes are different between patients with primary venogenic PT and IIH associated PT. METHODS: A systematic literature review and pooled analysis was completed to evaluate the clinical outcomes of PT in patients undergoing cerebral VSS. Outcome measures included: Improved PT, complete resolution of PT, PT recurrence at follow up. Subgroup analysis between patients with IIH and primary PT was completed. RESULTS: In total, 28 studies were identified with 616 patients. The proportion of improved PT symptoms after VSS had an overall pooled rate of 91.7% (CI:88.1%-95.2%; I2=65%) and no difference between subgroups (P=0.12). Complete resolution after VSS had an overall pooled rate of 88.6% (CI:84.0%-93.3%; I2=68%) and no significant difference between subgroups (P=0.35). Recurrent PT after stenting occurred in 6.5% of cases (CI:1.7%-11.3%; I2=62%). Furthermore, subgroup analysis demonstrated that IIH patients had a significantly higher recurrence rate (10.6%; CI:5.2%-16.1%; I2=26%) compared to patients treated with venous stenting for PT as the primary indication (2.0%; CI:0.8%-4.7%; I2=0%) (P<0.0001). CONCLUSION: Venous stenting in patients with pulsatile tinnitus results in a substantial decrease and often complete resolution of symptoms. PT is more likely to recur in patients with IIH-associated PT.

Total brain volume is associated with severity of transverse sinus stenosis in idiopathic intracranial hypertension.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a complex neurological condition characterized by symptoms of increased intracranial pressure of unclear etiology. While transverse sinus stenosis (TSS) is often present in patients with IIH, how and why it occurs remains unclear. METHODS: IIH patients and a set of age-matched normal controls were identified from our single-center tertiary care institution from 2016 to 2024. Brain MRIs before treatment were computationally segmented and parcellated using FreeSurfer software. Extent of TSS on MR venograms was graded using the Farb scoring system. Relationship between normalized brain volume, normalized brain-to-CSF volume, and TSS was investigated. Multiple linear regression was conducted to investigate the association between continuous variables, accounting for the covariates body mass index, sex, and age. RESULTS: In total, 84 IIH patients (mean age, 29.8 years; 87% female) and 15 normal controls (mean age, 28.1 years) were included. Overall, increasing/worsening TSS was found to be significantly associated with normalized total brain volume (p=0.018, R=0.179) and brain-to-CSF ratio volume (p=0.026, R=0.184). Additionally, there was a significant difference between controls and IIH patients with mild and severe stenosis regarding normalized total brain volume (ANCOVA, p=0.023) and brain-to-CSF ratio volume (ANCOVA, p=0.034). Likewise, IIH patients with severe TSS had a significantly higher brain-to-CSF volume compared with controls (p=0.038) and compared with IIH patients with mild TSS (p=0.038). CONCLUSIONS: These findings suggest that total brain volume is associated with extent of TSS, which may reflect extramural venous compression due to enlarged brain and/or venous hypertension with associated cerebral congestion/swelling.

Large bladder diverticulum causing direct extrinsic compression of the left ureter.

Bladder diverticula are herniations of the bladder mucosa through the muscular layer and can be congenital or acquired. Acquired bladder diverticula are almost always associated with bladder outlet obstruction. Bladder diverticula are uncommon and often asymptomatic, however, can present with non-specific lower urinary tract symptoms, haematuria, or urinary tract infection. We report a rare case of a large bladder diverticulum causing extrinsic left ureteric compression in a 37-year-old male with a high bladder neck presenting as left flank pain and hydronephrosis. A bladder neck incision successfully resolved voiding symptoms and decompressed the diverticulum leading to resolution of ureteric obstruction.

Advancement in perioperative management of pituitary adenomas-Current concepts and best practices.

Pituitary adenomas are very common representing 18.1% of all brain tumors and are the second most common brain pathology. Transsphenoidal surgery is the mainstay of treatment for all pituitary adenomas except for prolactinomas which are primarily treated medically with dopamine agonists. A thorough endocrine evaluation of pituitary adenoma preoperatively is crucial to identify hormonal compromise caused by the large sellar mass, identifying prolactin-producing tumors and comorbidities associated with Cushing and acromegaly to improve patient care and outcome. Transsphenoidal surgery is relatively safe in the hands of experienced surgeons, but still carries a substantial risk of causing hypopituitarism that required close follow-up in the immediate postoperative period to decrease mortality. A multidisciplinary team approach with endocrinologists, ophthalmologists, and neurosurgeons is the cornerstone in the perioperative management of pituitary adenomas.

Prostate cancer recurrence in the urethra with low PSA.

When localised prostate cancer recurs after treatment, it occurs predictably in sites such as the prostatic bed, pelvic lymph nodes, spine, lung, and liver. Urethral metastasis of prostate cancer is exceedingly rare. We report a case of urethral recurrence of prostate cancer presenting as new lower urinary tract symptoms in an 82-year-old male 10 years after robotic radical prostatectomy with a very low PSA level of 0.05µg/L. This rare case highlights the need to maintain a degree of suspicion for prostate cancer recurrence in patients with a late onset of or changing lower urinary tract symptoms after radical prostatectomy.

Decreasing the blood flow of non-compressible intra-abdominal organs with non-invasive transcutaneous electrical stimulation.

Non-invasive neuromodulation of non-compressible internal organs has significant potential for internal organ bleeding and blood-shift in aero/space medicine. The present study aims to investigate the potential influences of the non-invasive transcutaneous electrical nerve stimulation (TENS) on multiple non-compressible internal organs' blood flow. Porcine animal model (n = 8) was randomized for a total of 48 neuromodulation sessions with two different TENS stimulation frequencies (80 Hz, 10 Hz) and a placebo stimulation. A combination of two different electrode configurations (Abdominal-only or Abdominal and hind limb) were also performed. Intraarterial blood flow measurements were taken during pre and post-stimulation periods at the left renal artery, common hepatic artery, and left coronary artery. Intracranial, and extracranial arterial blood flows were also assessed with digital subtraction angiography. TENS with abdominal-only electrode configurations at 10 Hz demonstrated significant reductions in average peak blood flow velocity (APV) of the common hepatic artery (p = 0.0233) and renal arteries (p = 0.0493). Arterial pressures (p = 0.0221) were also significantly lower when renal APV was reduced. The outcome of the present study emphasises the potential use of TENS in decreasing the blood flow of non-compressible internal organs when the correct combination of electrodes configuration and frequency is used.

The potential for senotherapy as a novel approach to extend life quality in veterinary medicine.

Cellular senescence, a condition where cells undergo arrest and can assume an inflammatory phenotype, has been associated with initiation and perpetuation of inflammation driving multiple disease processes in rodent models and humans. Senescent cells secrete inflammatory cytokines, proteins, and matrix metalloproteinases, termed the senescence associated secretory phenotype (SASP), which accelerates the aging processes. In preclinical models, drug interventions termed "senotherapeutics" selectively clear senescent cells and represent a promising strategy to prevent or treat multiple age-related conditions in humans and veterinary species. In this review, we summarize the current available literature describing in vitro evidence for senotheraputic activity, preclinical models of disease, ongoing human clinical trials, and potential clinical applications in veterinary medicine. These promising data to date provide further justification for future studies identifying the most active senotherapeutic combinations, dosages, and routes of administration for use in veterinary medicine.

Evaluation of stem-cell therapies in companion animal disease models: a concise review (2015-2023).

Companion animals in veterinary medicine develop multiple naturally occurring diseases analogous to human conditions. We previously reported a comprehensive review on the feasibility, safety, and biologic activity of using novel stem cell therapies to treat a variety of inflammatory conditions in dogs and cats (2008-2015) [Hoffman AM, Dow SW. Concise review: stem cell trials using companion animal disease models. Stem Cells. 2016;34(7):1709-1729. https://doi.org/10.1002/stem.2377]. The purpose of this review is to provide an updated summary of current studies in companion animal disease models that have evaluated stem cell therapeutics that are relevant to human disease. Here we have reviewed the literature from 2015 to 2023 for publications on stem cell therapies that have been evaluated in companion animals, including dogs, cats, and horses. The review excluded case reports or studies performed in experimentally induced models of disease, studies involving cancer, or studies in purpose-bred laboratory species such as rodents. We identified 45 manuscripts meeting these criteria, an increase from 19 that were described in the previous review [Hoffman AM, Dow SW. Concise review: stem cell trials using companion animal disease models. Stem Cells. 2016;34(7):1709-1729. https://doi.org/10.1002/stem.2377]. The majority of studies were performed in dogs (n = 28), with additional studies in horses (n = 9) and cats (n = 8). Disease models included those related to musculoskeletal disease (osteoarthritis and tendon/ligament injury), neurologic disease (canine cognitive dysfunction, intervertebral disc disease, spinal cord injury) gingival/dental disease (gingivostomatitis), dermatologic disease (atopic dermatitis), chronic multi-drug resistant infections, ophthalmic disease (keratoconjunctivitis sicca, eosinophilic keratitis, immune-mediated keratitis), cardiopulmonary disease (asthma, degenerative valve disease, dilated cardiomyopathy), gastrointestinal disease (inflammatory bowel disease, chronic enteropathy), and renal disease (chronic kidney disease). The majority of studies reported beneficial responses to stem cell treatment, with the exception of those related to more chronic processes such as spinal cord injury and chronic kidney disease. However, it should also be noted that 22 studies were open-label, baseline-controlled trials and only 12 studies were randomized and controlled, making overall study interpretation difficult. As noted in the previous review, improved regulatory oversight and consistency in manufacturing of stem cell therapies are needed. Enhanced understanding of the temporal course of disease processes using advanced-omics approaches may further inform mechanisms of action and help define appropriate timing of interventions. Future directions of stem-cell-based therapies could include use of stem-cell-derived extracellular vesicles, or cell conditioning approaches to direct cells to specific pathways that are tailored to individual disease processes and stages of illness.

Do microbes play a role in Alzheimer's disease?

Alzheimer's disease is a complex and progressive condition that affects essential neurological functions such as memory and reasoning. In the brain, neuronal loss, synaptic dysfunction, proteinopathy, neurofibrillary tangles, and neuroinflammation are the hallmarks of Alzheimer's disease pathophysiology. In addition, recent evidence has highlighted that microbes, whether commensal or pathogenic, also have the ability to interact with their host and to regulate its immune system, therefore participating in the exchanges that lead to peripheral inflammation and neuropathology. Because of this intimate relationship, bacteria, viruses, fungi, and protozoa have been implicated in the development of Alzheimer's disease. Here, we bring together current and most recent evidence of the role of microbes in Alzheimer's disease, raising burning questions that need to be addressed to guide therapeutic approaches and potential prophylactic strategies.

A dual-targeting succinate dehydrogenase and F1Fo-ATP synthase inhibitor rapidly sterilizes replicating and non-replicating Mycobacterium tuberculosis.

Mycobacterial bioenergetics is a validated target space for antitubercular drug development. Here, we identify BB2-50F, a 6-substituted 5-(N,N-hexamethylene)amiloride derivative as a potent, multi-targeting bioenergetic inhibitor of Mycobacterium tuberculosis. We show that BB2-50F rapidly sterilizes both replicating and non-replicating cultures of M. tuberculosis and synergizes with several tuberculosis drugs. Target identification experiments, supported by docking studies, showed that BB2-50F targets the membrane-embedded c-ring of the F1Fo-ATP synthase and the catalytic subunit (substrate-binding site) of succinate dehydrogenase. Biochemical assays and metabolomic profiling showed that BB2-50F inhibits succinate oxidation, decreases the activity of the tricarboxylic acid (TCA) cycle, and results in succinate secretion from M. tuberculosis. Moreover, we show that the lethality of BB2-50F under aerobic conditions involves the accumulation of reactive oxygen species. Overall, this study identifies BB2-50F as an effective inhibitor of M. tuberculosis and highlights that targeting multiple components of the mycobacterial respiratory chain can produce fast-acting antimicrobials.

Opinion article: Neurosurgical treatment for neuro-ophthalmologic conditions.

A significant role of the neuro-ophthalmologist is to counsel patients on appropriate management and anticipated visual prognosis for conditions affecting the afferent and efferent visual systems, including those requiring neurosurgical treatment. However, the literature regarding anticipated neuro- ophthalmologic prognosis after neurosurgical intervention for cerebral aneurysms, sellar lesions, optic pathway tumors, and elevated intracranial pressure is limited with many key questions unanswered. For example, if a cerebral aneurysm is equally amenable to clipping or endovascular coiling, is there a preferred approach in terms of visual prognosis based on aneurysm location? Is dural venous sinus stenting (VSS) for idiopathic intracranial hypertension (IIH) superior, equivalent or inferior to shunting in terms of visual recovery and safety profile? Landmark studies on pituitary tumors using pre-operative optical coherence tomography (OCT) imaging of the optic nerve head to predict visual recovery after surgical decompression of the optic chiasm have changed neuro-ophthalmologic practice and enabled patients to be better informed regarding expected visual outcomes. 1,2 In order to optimize an interdisciplinary team approach to patient care, further studies of visual outcomes for neuro- ophthalmologic conditions requiring neurosurgical intervention are needed.

A novel endovascular treatment for true ophthalmic aneurysms: A case report.

Introduction: Cerebral aneurysms located along the internal carotid artery at the origin of the ophthalmic artery can be treated through open surgery or endovascular technique. The former affords more certainty of aneurysm obliteration, while the latter poses less risk to vision. Flow diversion is an increasingly accepted treatment for side-wall carotid aneurysms, although location at the branch point of the ophthalmic artery is known to moderate occlusion outcomes. Case presentation: We present a case of a middle-aged female patient with a morphologically irregular 4-mm ophthalmic artery aneurysm (OphA) and a smaller superior hypophyseal artery (SHA) aneurysm whose successful and uncomplicated obliteration by flow diversion with adjunctive coiling was predicted via a balloon test occlusion (BTO). BTO was employed prior to stent placement to confirm a) ophthalmic artery distal collateralization with external carotid artery (ECA) branches and b) preserved arterial flow in the retina visualized via fundoscopy. At 1 year following angiography, the patient had no postoperative deficits and benefitted from complete occlusion of the OphA and SHA. Conclusion: OphAs constitute a complex surgical disease that is historically associated with high visual morbidity. We present a novel advanced endovascular technique of BTO followed by flow diversion with adjunctive coiling that successfully obliterated an OphA while preserving vision.