Senescent changes in cerebrospinal fluid circulatory physiology and their role in the pathogenesis of normal-tension glaucoma

Authors: Wostyn P, De Groot V, Van Dam D, Audenaert K, De Deyn PP.

PURPOSE: To evaluate the evidence supporting a role for senescent changes in cerebrospinal fluid (CSF) circulatory physiology in the pathogenesis of normal-tension glaucoma (NTG).
DESIGN: Literature review and personal perspective of the authors.
METHODS: Analysis of selected articles in the peer-reviewed literature with interpretation and perspective.
RESULTS: Recent studies have reported that intracranial pressure is lower in patients with NTG when compared with patients with primary open-angle glaucoma and nonglaucomatous control subjects. It has been suggested that a low intracranial pressure in patients with normal intraocular pressure could lead to glaucomatous damage. This low intracranial pressure, leading to an abnormally high trans-lamina cribrosa pressure difference, could result in barotraumatically induced optic nerve damage at the lamina cribrosa. However, several experimental studies do not support the speculation that low intracranial pressure and the resulting pressure-dependent effects cause bowing back of the lamina cribrosa and optic disc cupping. On the other hand, CSF production and turnover have been shown to be decreased in aging and in pathologic conditions, such as Alzheimer disease and normal pressure hydrocephalus. Interestingly, recent studies have revealed that both Alzheimer disease patients and patients with normal pressure hydrocephalus may have a higher risk of developing glaucoma. Therefore, we believe that CSF circulatory failure, ultimately resulting in reduced neurotoxin clearance along the optic nerves, could be an alternative explanation as to why glaucoma develops in patients with low intracranial pressure.
CONCLUSIONS: On the basis of the evidence available from the peer-reviewed literature, our tentative conclusion is that age-related changes in CSF circulatory physiology and the subsequent decrease in CSF turnover, with diminished clearance of toxic substances, can account for, at least in part, the pathogenesis of NTG. It should be stressed that for the moment at least, the present hypothesis remains unproven. Further research will be necessary to determine the possible role of CSF circulatory dysfunction in NTG. If confirmed, this hypothesis could provide new, important insights into the pathogenesis of NTG.

Management of increased intracranial pressure

Authors: Sandsmark DK, Sheth KN.


After brain injury, neurologic intensive care focuses on the detection and treatment of secondary brain insults that may compound the initial injury. Increased intracranial pressure (ICP) contributes to secondary brain injury by causing brain ischemia, hypoxia, and metabolic dysfunction. Because ICP is easily measured at the bedside, it is the target of numerous pharmacologic and surgical interventions in efforts to improve brain physiology and limit secondary injury. However, ICP may not adequately reflect the metabolic health of the underlying brain tissue, particularly in cases of focal brain injury. As a result, ICP control alone may be insufficient to impact patients' long-term recovery. Further studies are needed to better understand the combination of cerebral, hemodynamic, and metabolic markers that are best utilized to ensure optimal brain and systemic recovery and overall patient outcome after brain injury.

Intracranial hypotension syndrome in a patient due to suboccipital craniectomy secondary to Chiari type malformation

Authors: Dora B, Nikolaos B, Stylianos G, Damianos S.

Intracranial hypotension syndrome (IHS) is a rare disorder characterized by a decrease in cerebrospinal fluid pressure to less than 60 mm H2O. The syndrome is associated with occipital headache radiating to the frontal and temporal zones. The current clinical case describes the manifestation of IHS in a twenty-five year old female with a history of suboccipital craniectomy due to Chiari I malformation nine years earlier. The patient was admitted to the hospital complaining about postural, mainly occipital, headache during the last three months, aggravated by being in an upright position. The magnetic resonance imaging (MRI) revealed engorgement of the dural venous sinuses, significant enlargement of the pituitary gland and download displacement or sagging of the brain with effacement of the perichiasmatic cisterns and the prepontine cistern, while the spinal T2W MRI revealed a 7 mm × 2.5 mm dural defect with an extradural cerebrospinal fluid collection at the dorsal soft tissues of the cervical spine. The previous imaging did not reveal subdural effusions.

Intraocular pressure is not associated with acute mountain sickness

Authors: Cushing T, Paterson R, Haukoos J, Harris NS.

Intraocular pressure is not associated with acute mountain sickness. High Alt Med Biol 14:342-345, 2013.-Objective: Acute mountain sickness (AMS) is common at high altitude and may lead to high altitude cerebral edema (HACE) if not properly recognized. Previous studies have suggested that AMS is associated with increases in intracranial pressure (ICP). Increased ICP has been associated with increased intra-ocular pressure (IOP). This study was designed to determine the association between IOP and AMS. Methods: Subjects were recruited from a convenience sample of travelers in the Khumbu region of Nepal, elevation 14,410 ft (4392 m). Study participation involved completion of a questionnaire to assess for AMS by the Lake Louise Score (LLS), followed by three IOP measurements in each eye. Investigators were blinded to the LLS. Subjects with a history of ocular surgery were excluded. Three IOP measurements per eye were made using an applanation tonometer (Tono-Pen XL(®), Reichart Technologies) and averaged across both eyes. Multivariable logistic regression analysis was used to estimate the association between IOP and AMS while adjusting for age, ascent or descent, and use of acetazolamide. IOP and blood O2 saturation were compared using a Spearman correlation coefficient. Results: 161 subjects were enrolled with a median age of 36 (IQR: 29-45) years; 60% were male, 75% were ascending, and 64% were taking acetazolamide; additionally, 38%, (95% CI: 31%-47%) were diagnosed with AMS (LLS ≥3). The median IOP was 21 (IQR 18-24) mmHg. The logistic regression model demonstrated no association between IOP and AMS as measured by LLS (odds ratio 1.0, 95% CI: 0.9-1.1),age (OR 1.0, 95% CI: 0.9-1.0) or with use of acetazolamide (OR 1.4, 95% CI: 0.6-2.6). Ascent (OR 0.4, 95% CI: 0.2-0.9) was negatively associated with IOP but not significantly so. IOP and O2 saturation were not correlated (p=0.93). Conclusions: IOP measured at high altitude is not associated with the diagnosis of AMS. Other approaches to diagnose AMS easily and accurately are needed.

Recurrent syncope due to refractory cerebral venous sinus thrombosis and transient elevations of intracranial pressure

Authors: Larimer P, McDermott MW, Scott BJ, Shih TT, Poisson SN.

Chronic paroxysmal intracranial hypertension leading to syncope is a phenomenon not reported previously in patients with refractory cerebral venous sinus thrombosis. We report a case of paroxysmal intracranial hypertension leading to syncopal episodes in a patient with idiopathic autoimmune hemolytic anemia and venous sinus thrombosis. This case demonstrates that intermittent elevations in intracranial pressure can lead to syncope in patients with venous sinus thrombosis and emphasizes the importance of considering this potentially treatable etiology of syncopal episodes.

Blood-brain barrier and traumatic brain injury

Author: Alves JL.

The blood-brain barrier (BBB) is an anatomical microstructural unit, with several different components playing key roles in normal brain physiological regulation. Formed by tightly connected cerebrovascular endothelial cells, its normal function depends on paracrine interactions between endothelium and closely related glia, with several recent reports stressing the need to consider the entire gliovascular unit in order to explain the underlying cellular and molecular mechanisms. Despite that, with regard to traumatic brain injury (TBI) and significant events in incidence and potential clinical consequences in pediatric and adult ages, little is known about the actual role of BBB disruption in its diverse pathological pathways. This Mini-Review addresses the current literature on possible factors affecting gliovascular units and contributing to posttraumatic BBB dysfunction, including neuroinflammation and disturbed transport mechanisms along with altered permeability and consequent posttraumatic edema. Key mechanisms and its components are described, and promising lines of basic and clinical research are identified, because further knowledge on BBB pathological interference should play a key role in understanding TBI and provide a basis for possible therapeutic targets in the near future, whether through restoration of normal BBB function after injury or delivering drugs in an increased permeability context, preventing secondary damage and improving functional outcome. © 2013 Wiley Periodicals, Inc.


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