Impaired perfusion modifies the relationship between blood pressure and stroke risk in major cerebral artery disease

Authors: Yamauchi H, Higashi T, Kagawa S, Kishibe Y, Takahashi M.

OBJECTIVE: Blood pressure (BP) lowering may increase stroke risk in patients with symptomatic major cerebral artery disease and impaired perfusion. To investigate the relationships among BP, impaired perfusion and stroke risk.
METHODS: We retrospectively analysed data from 130 non-disabled, medically treated patients with either symptomatic extracranial carotid occlusion or intracranial stenosis or occlusion of the carotid artery or middle cerebral arteries. All patients had baseline haemodynamic measurements with 15O-gas positron emission tomography and were followed for 2 years or until stroke recurrence or death.
RESULTS: There was a negative linear relationship between systolic BP (SBP) and risk of stroke in the territory of the diseased artery. The 2-year incidence of ischaemic stroke in the territory in patients with normal SBP (<130 mm Hg, 5/32 patients) was significantly higher than in patients with high SBP (2/98, p<0.005). Multivariate analysis revealed that normal SBP and impaired perfusion were independently associated with increased risk of stroke in the previously affected territory, while risk of stroke elsewhere was positively correlated with SBP. Overall, high total stroke risk was observed at lower BP in patients with impaired perfusion and at higher BPs in patients without (interaction, p<0.01). Overall, the relationship between SBP and total stroke recurrence was J-shaped.
CONCLUSIONS: Impaired perfusion modified the relationship between blood pressure and stroke risk, although this study had limitations including the retrospective analysis, the potentially biased sample, the small number of critical events and the fact that BP was measured only as a snapshot in clinic.

Does the treatment of normal pressure hydrocephalus put the retinal ganglion cells at risk? A brief literature review and novel hypothesis

Authors: Bokhari RF, Baeesa SS.

Normal pressure hydrocephalus (NPH) is a poorly understood entity as well as a source of continuous controversy in the neuroscientific community. The surgical management of this disease requires that intracranial pressure (ICP), also referred to as the cerebrospinal fluid pressure (CSFP), be lowered using a cerebrospinal fluid (CSF) diversion procedure. Numerous complications are linked with this procedure; we believe that new evidence suggests that the induction or acceleration of glaucomatous optic neuropathy are possible sequelae that warrant further investigation. We also suggest potential solutions derived from the increased understanding of the disease's pathophysiology and new advances in imaging of the optic nerve head complex. The recent inclusion of the translaminar gradient (TLG) (the difference between the intraocular pressure (IOP) and the ICP/CSFP across the thickness of the lamina cribrosa in the optic nerve head complex) in the pathogenesis of normal tension glaucoma (NTG) suggests that the disease may be a complication encountered during the treatment of NPH with CSF diversion procedures. The significant decrease in CSFP required to treat NPH increases this gradient. In addition, there have been recent observations of an increased prevalence of NTG, as well as other forms of glaucoma, among patients with NPH, thought to be due to inherently fragile neurons in these patients. This new data suggest that patients who undergo ICP lowering therapy for their NPH may be at a higher risk of developing or accelerating already present NTG. We present the clinical and theoretical basis for our hypothesis after reviewing the relevant literature linking the two entities. We also propose a possible solution, as we believe that treatment guidelines for NPH should take the TLG into account. Indeed, recent advances in the imaging of the optic nerve head complex may provide an opportunity to detect the mechanical sequelae of an increased TLG in the preclinical stage, i.e., prior to optic nerve damage. If we are able to determine safe parameters for the TLG in this population, we may be able to recommend the initiation of prophylactic glaucoma therapy for selected patients.

Decreased risk of acute kidney injury with intracranial pressure monitoring in patients with moderate or severe brain injury

Authors: Zeng J, Tong W, Zheng P.

Object The authors undertook this study to evaluate the effects of continuous intracranial pressure (ICP) monitoring-directed mannitol treatment on kidney function in patients with moderate or severe traumatic brain injury (TBI). Methods One hundred sixty-eight patients with TBI were prospectively assigned to an ICP monitoring group or a conventional treatment control group based on the Brain Trauma Foundation guidelines. Clinical data included the dynamic changes of patients' blood concentrations of cystatin C, creatinine (Cr), and blood urea nitrogen (BUN); mannitol use; and 6-month Glasgow Outcome Scale (GOS) scores. Results There were no statistically significant differences with respect to hospitalized injury, age, or sex distribution between the 2 groups. The incidence of acute kidney injury (AKI) was higher in the control group than in the ICP monitoring group (p < 0.05). The mean mannitol dosage in the ICP monitoring group (443 ± 133 g) was significantly lower than in the control group (820 ± 412 g) (p < 0.01), and the period of mannitol use in the ICP monitoring group (3 ± 3.8 days) was significantly shorter than in the control group (7 ± 2.3 days) (p < 0.01). The 6-month GOS scores in the ICP monitoring group were significantly better than in the control group (p < 0.05). On the 7th, 14th, and 21st days after injury, the plasma cystatin C and Cr concentrations in the ICP-monitoring group were significantly higher than the control group (p < 0.05). Conclusions In patients with moderate and severe TBI, ICP-directed mannitol treatment demonstrated a beneficial effect on reducing the incidence of AKI compared with treatment directed by neurological signs and physiological indicators.

Methodology and Evaluation of Intracranial Pressure Response in Rats Exposed to Complex Shock Waves

Authors: Dal Cengio Leonardi A, Keane NJ, Hay K, Ryan AG, Bir CA, Vandevord PJ.

Studies on blast neurotrauma have focused on investigating the effects of exposure to free-field blast representing the simplest form of blast threat scenario without considering any reflecting surfaces. However, in reality personnel are often located within enclosures or nearby reflecting walls causing a complex blast environment, that is, involving shock reflections and/or compound waves from different directions. The purpose of this study was to design a complex wave testing system and perform a preliminary investigation of the intracranial pressure (ICP) response of rats exposed to a complex blast wave environment (CBWE). The effects of head orientation in the same environment were also explored. Furthermore, since it is hypothesized that exposure to a CBWE would be more injurious as compared to a free-field blast wave environment (FFBWE), a histological comparison of hippocampal injury (cleaved caspase-3 and glial fibrillary acidic protein (GFAP)) was conducted in both environments. Results demonstrated that, regardless of orientation, peak ICP values were significantly elevated over the peak static air overpressure. Qualitative differences could be noticed compared to the ICP response in rats exposed to simulated FFBWE. In the CBWE scenario, after the initial loading the skull/brain system was not allowed to return to rest and was loaded again reaching high ICP values. Furthermore, results indicated consistent and distinct ICP-time profiles according to orientation, as well as distinctive values of impulse associated with each orientation. Histologically, cleaved caspase-3 positive cells were significantly increased in the CBWE as compared to the FFBWE. Overall, these findings suggest that the geometry of the skull and the way sutures are distributed in the rats are responsible for the difference in the stresses observed. Moreover, this increase stress contributes to correlation of increased injury in the CBWE.

Low-pressure hydrocephalus: indication for custom-made catheters? Technical report

Authors: Galbarriatu L, Rivero-Garvía M, Olivares M, Miranda D, Pomposo I, Márquez-Rivas J.

BACKGROUND: Low-pressure hydrocephalus (LPH) is characterized by ventriculomegaly with persistent low intracranial pressure (ICP). Sub-zero drainage is needed for its management and multiple solutions have been described. Our aim is to report our experience with custom-made peritoneal catheters with larger inner diameter as an alternative treatment option.
METHODS: We made a retrospective review of all patients diagnosed with LPH and treated with custom-made peritoneal catheters at the Virgen del Rocío Pediatric Neurosurgical Unit. Catheters were coated with antibiotic or silver. The inner diameter of ventricular catheters was 1.4 mm; peritoneal catheters were larger than usual (1.9 mm inner diameter).
RESULTS: We identified four patients in whom five custom-made peritoneal catheters were used over a 3-year period. There were two males and the mean age was 10 years (6 months-17 years). In all patients, placement of an EVD was necessary for sub-zero drainage, with maximum negative pressure of -8 cm H20. The mean time of maintenance of EVD was 102 days (10 days-1 year). Finally, three ventriculoperitoneal (VP) valveless systems, one with antigravitation device, and one Pro-GAV VP shunt were placed, all of them with larger custom-made peritoneal catheters. After a mean follow-up period of 2.3 years (6 months-3 years), two patients are completely recovered, one patient is partially dependent for daily activities with good cognitive status, and the last one is a child who died due to his brain tumor.
CONCLUSION: The custom-made peritoneal catheters with larger inner diameter could be a good option for the management of this complex pathology.

The size, burden and cost of disorders of the brain in the UK

Authors: Naomi A Fineberg, Peter M Haddad, Lewis Carpenter, Brenda Gannon, Rachel Sharpe, Allan H Young, Eileen Joyce, James Rowe, David Wellsted, David Nutt, Barbara J Sahakian

Aim: The aim of this paper is to increase awareness of the prevalence and cost of psychiatric and neurological disorders (brain disorders) in the UK.
Method: UK data for 18 brain disorders were extracted from a systematic review of European epidemiological data and prevalence rates and the costs of each disorder were summarized (2010 values).
Results: There were approximately 45 million cases of brain disorders in the UK, with a cost of €134 billion per annum. The most prevalent were headache, anxiety disorders, sleep disorders, mood disorders and somatoform disorders. However, the five most costly disorders (€ million) were: dementia: €22,164; psychotic disorders: €16,717; mood disorders: €19,238; addiction: €11,719; anxiety disorders: €11,687. Apart from psychosis, these five disorders ranked amongst those with the lowest direct medical expenditure per subject (<€3000). The approximate breakdown of costs was: 50% indirect costs, 25% direct non-medical and 25% direct healthcare costs.
Discussion: The prevalence and cost of UK brain disorders is likely to increase given the ageing population. Translational neurosciences research has the potential to develop more effective treatments but is underfunded. Addressing the clinical and economic challenges posed by brain disorders requires a coordinated effort at an EU and national level to transform the current scientific, healthcare and educational agenda.

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