Rebekah M. Ahmed

Transverse Sinus Stenting for Idiopathic Intracranial Hypertension: A Review of 52 Patients and of Model Predictions

Current thinking is that transverse sinus stenosis with significant pressure gradient across the narrowing may play a role in pseudotumor cerebri and that treatment may improve symptoms. Here, the authors review their experience with 52 patients who were clinically followed for 2–8 months after stenting. During this time all pressure gradients improved and symptoms were abolished. Symptom relapse occurred in 6 patients and all showed sinus restenosis. At the end of the study period, 49 of 52 patients were cured of their headaches and the authors concluded that transverse sinus stenting is beneficial in this clinical setting. BACKGROUND AND PURPOSE: Transverse sinus stenosis is common in patients with IIH. While the role of transverse sinus stenosis in IIH pathogenesis remains controversial, modeling studies suggest that stent placement within a transverse sinus stenosis with a significant pressure gradient should decrease cerebral venous pressure, improve CSF resorption in the venous system, and thereby reduce intracranial (CSF) pressure, improving the symptoms of IIH and reducing papilledema. We aimed to determine if IIH could be reliably treated by stent placement in transverse sinus stenosis. MATERIALS AND METHODS: We reviewed the clinical, venographic, and intracranial pressure data before and after stent placement in transverse sinus stenosis in 52 of our own patients with IIH unresponsive to maximum acceptable medical treatment, treated since 2001 and followed between 2 months and 9 years. RESULTS: Before stent placement, the mean superior sagittal sinus pressure was 34 mm Hg (462 mm H20) with a mean transverse sinus stenosis gradient of 20 mm Hg. The mean lumbar CSF pressure before stent placement was 322 mm H2O. In all 52 patients, stent placement immediately eliminated the TSS pressure gradient, rapidly improved IIH symptoms, and abolished papilledema. In 6 patients, symptom relapse (headache) was associated with increased venous pressure and recurrent stenosis adjacent to the previous stent. In these cases, placement of another stent again removed the transverse sinus stenosis pressure gradient and improved symptoms. Of the 52 patients, 49 have been cured of all IIH symptoms. CONCLUSIONS: These findings indicate a role for transverse sinus stent placement in the management of selected patients with IIH.

Gentamicin ototoxicity: a 23-year selected case series of 103 patients

Objective: To review patients with severe bilateral vestibular loss associated with gentamicin treatment in hospital.

Biomarkers in dementia: clinical utility and new directions

Imaging, cerebrospinal fluid (CSF) and blood-based biomarkers have the potential to improve the accuracy by which specific causes of dementia can be diagnosed in vivo, provide insights into the underlying pathophysiology, and may be used as inclusion criteria and outcome measures for clinical trials. While a number of imaging and CSF biomarkers are currently used for each of these purposes, this is an evolving field, with numerous potential biomarkers in varying stages of research and development. We review the currently available biomarkers for the three most common forms of neurodegenerative dementia, and give an overview of research techniques that may in due course make their way into the clinic.

Stenting of the transverse sinuses in idiopathic intracranial hypertension

Although the mechanism of idiopathic intracranial hypertension (IIH) is uncertain, the cerebral venous system has been implicated since the 1930s. Dandy (1) hypothesized that the volume of cerebrospinal fluid (CSF) or cerebral blood might be increased. Others postulated that the cerebral microvasculature was the source of cerebral edema in this condition (2–4). Intracranial venous hypertension was subsequently proposed as a unifying mechanism or final common pathway of IIH. Johnston and Paterson (5) first suggested that increased sagittal sinus pressure causing decreased CSF absorption was the underlying cause of IIH. A syndrome clinically identical to IIH is produced by cerebral venous sinus thrombosis (6–8). Interest in the dural venous sinuses as the source of increased intracranial pressure (ICP) in IIH was heightened in the 1990s, with studies of direct venous manometry in IIH patients and studies performed in IIH patients undergoing bariatric surgery. Intracranial and central systemic venography and manometry were performed in 10 patients with increased ICP associated with various disorders (1 congenital stenosis, 2 idiopathic, 5 morbid obesity, 1 tumor compressing the dural sinus, 1 craniodiaphyseal dysplasia, and bony overgrowth of the skull) (9). All patients had CSF pressures above 200 mm H2O and had no ventriculomegaly. No venous outflow obstruction was found in the obese patients, but some degree of stenosis or occlusion was seen in the other 5 patients (including those with congenital stenosis and tumor). Superior sagittal sinus pressure was elevated in all 7 patients in whom it was measured, including the 5 obese patients. The mean increase was small (1.8 mm Hg above normal) in patients without obstruction, and it is uncertain whether the elevation was statistically significant. Central venous pressure was measured in 6 of the 7 patients who had venous sinus manometry and was abnormal in 5 patients. Patients with venous sinus occlusion were treated with angioplasty/thrombolysis or shunting. The patient with the tumor underwent a CSF diversion procedure (shunt), and the patients with IIH were treated with a combination of shunt, optic nerve sheath fenestration, or gastric stapling. None of the manometric measurements was repeated following treatment.

Amyotrophic lateral sclerosis and frontotemporal dementia: distinct and overlapping changes in eating behaviour and metabolism

Metabolic changes incorporating fluctuations in weight, insulin resistance, and cholesterol concentrations have been identified in several neurodegenerative disorders. Whether these changes result from the neurodegenerative process affecting brain regions necessary for metabolic regulation or whether they drive the degenerative process is unknown. Emerging evidence from epidemiological, clinical, pathological, and experimental studies emphasises a range of changes in eating behaviours and metabolism in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In ALS, metabolic changes have been linked to disease progression and prognosis. Furthermore, changes in eating behaviour that affect metabolism have been incorporated into the diagnostic criteria for FTD, which has some clinical and pathological overlap with ALS. Whether the distinct and shared metabolic and eating changes represent a component of the proposed spectrum of the two diseases is an intriguing possibility. Moreover, future research should aim to unravel the complex connections between eating, metabolism, and neurodegeneration in ALS and FTD, and aim to understand the potential for targeting modifiable risk factors in disease development and progression.

Quantifying the Eating Abnormalities in Frontotemporal Dementia

IMPORTANCE Presence of eating abnormalities is one of the core criteria for the diagnosis of behavioral variant frontotemporal dementia (bvFTD), yet their occurrence in other subtypes of frontotemporal dementia (FTD) and effect on metabolic health is not known. OBJECTIVE To define and quantify patterns of eating behavior and energy, sugar, carbohydrate, protein, and fat intake, as well as indices of metabolic health in patients with bvFTD and semantic dementia (SD) compared with patients with Alzheimer disease (AD) and healthy control participants. DESIGN, SETTING, AND PARTICIPANTS Prospective case-controlled study involving patient and caregiver completion of surveys. Seventy-five participants with dementia (21 with bvFTD, 26 with SD, and 28 with AD) and 18 age- and education-matched healthy controls were recruited from FRONTIER, the FTD research clinic at Neuroscience Research Australia in Sydney. MAIN OUTCOMES AND MEASURES Caregivers of patients with FTD and AD completed validated questionnaires on appetite, eating behaviors, energy consumption, and dietary macronutrient composition. All participants completed surveys on hunger and satiety. Body mass index and weight measurements were prospectively collected. RESULTS The bvFTD group had significant abnormalities in the domains of appetite (U = 111.0, z = 2.7, P = .007), eating habits (U = 69.5, z = 3.8, P = .001), food preferences (U = 57.0, z = 4.1, P = .001), swallowing (U = 109.0, z = 3.0, P = .003), and other oral behaviors (U = 141.0, z = 2.6, P = .009) compared with the AD group. The bvFTD and SD groups tended to have increased energy consumption. Compared with controls, the bvFTD group had significantly increased carbohydrate intake (251 vs 170 g/d; P = .05) and the SD group had significantly increased sugar intake (114 vs 76 g/d; P = .049). No significant differences in total fat or protein intake between the groups were found. Despite similar energy intake, the SD group had lower hunger and satiety scores compared with the bvFTD group. In contrast, hunger and satiety scores did not differ between the bvFTD group and controls. The abnormal eating behavior was found in the 2 groups (bvFTD and SD) with the highest body mass index (F = 4.2, P = .008) and waist circumference (F = 6.4, P = .001). CONCLUSIONS AND RELEVANCE Abnormal eating behaviors are prominent in patients with bvFTD and those with SD and are not limited to increased appetite. The observed higher intake of sugar and carbohydrates was found in patients with the FTD subtypes and those with higher body mass index and waist circumference and was not explained simply by increased hunger or lower satiety.

Neuronal network disintegration: common pathways linking neurodegenerative diseases

Neurodegeneration refers to a heterogeneous group of brain disorders that progressively evolve. It has been increasingly appreciated that many neurodegenerative conditions overlap at multiple levels and therefore traditional clinicopathological correlation approaches to better classify a disease have met with limited success. Neuronal network disintegration is fundamental to neurodegeneration, and concepts based around such a concept may better explain the overlap between their clinical and pathological phenotypes. In this Review, promoters of overlap in neurodegeneration incorporating behavioural, cognitive, metabolic, motor, and extrapyramidal presentations will be critically appraised. In addition, evidence that may support the existence of large-scale networks that might be contributing to phenotypic differentiation will be considered across a neurodegenerative spectrum. Disintegration of neuronal networks through different pathological processes, such as prion-like spread, may provide a better paradigm of disease and thereby facilitate the identification of novel therapies for neurodegeneration.

Neuro-ophthalmology of invasive fungal sinusitis: 14 consecutive patients and a review of the literature

Invasive fungal sinusitis is a rare condition that usually occurs in immunocompromised patients and often presents as an orbital apex syndrome. It is frequently misdiagnosed on presentation and is almost always lethal without early treatment.

Eating behavior in frontotemporal dementia Peripheral hormones vs hypothalamic pathology

Objective: To contrast the relationships of hormonal eating peptides and hypothalamic volumes to eating behavior and metabolic changes (body mass index [BMI]) in behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA). Methods: Seventy-five patients with dementia (19 bvFTD, 26 svPPA, and 30 Alzheimer disease dementia) and 23 controls underwent fasting blood analyses of leptin, ghrelin, cholecystokinin, peptide tyrosine tyrosine (PYY), and agouti-related peptide (AgRP) levels. On brain MRI anterior, posterior, and total hypothalamic volumes were measured. Relationships between endocrine measures, hypothalamic volumes, eating behaviors, and BMI were investigated. Results: Levels of AgRP were higher in patients with bvFTD (69 ± 89 pg/mL) and svPPA (62 ± 81 pg/mL) compared with controls (23 ± 19 pg/mL, p < 0.01). No differences were found for leptin, oxytocin, cholecystokinin, ghrelin, and PYY levels. Patients with bvFTD and svPPA had higher scores on questionnaires measuring eating behaviors. Atrophy of the posterior and total hypothalamus was observed in the bvFTD group only. Linear regression modeling revealed that leptin and AgRP levels predicted BMI. Conclusion: Eating abnormalities are multifactorial in FTD. In bvFTD, they are in part related to hypothalamic degeneration, with potential disintegration of the network connections between the hypothalamus and orbitofrontal cortex/reward pathways. In svPPA, although hypothalamic volumes are preserved, this group experiences elevated AgRP levels similar to bvFTD, which predicts BMI in both groups. This finding highlights the potential key role of AgRP in eating and metabolic changes and provides a potential target for treatment to modify disease progression.

Transverse Sinus Stenting for Pseudotumor Cerebri: A Cost Comparison with CSF Shunting

BACKGROUND AND PURPOSE: Transverse sinus venous stent placement has been shown to lower intracranial pressure in patients with venogenic pseudotumor cerebri and to reverse, or at least stabilize, its symptoms and signs. There have been no studies comparing the cost of venous stenting with the time-honored treatment for pseudotumor cerebri–CSF shunting. The purpose of this study was to compare the cost of trasverse sinus stenting versus CSF shunting for the treatment of pseudotumor cerebri. MATERIALS AND METHODS: This work was a retrospective cost analysis of individual resource use in 86 adults who were stented for pseudotumor cerebri during a 12-year period compared with resource use in 110 children who were shunted for hydrocephalus during a 3-year period. RESULTS: There was no significant difference between the cost of inserting an initial venous stent (