Differences in the Calculated Transvenous Pressure Drop between Chronic Hydrocephalus and Idiopathic Intracranial Hypertension.

BACKGROUND AND PURPOSE: Chronic hydrocephalus is associated with dilated ventricles despite a normal intracranial pressure. In idiopathic intracranial hypertension, the ventricles are normal despite an elevated intracranial pressure. This apparent paradox has largely remained unexplained. It is suggested that a pressure difference between the superficial and deep venous territories of the brain could account for the variation between the 2 diseases. The purpose of this paper is to investigate the cause of this pressure difference. MATERIALS AND METHODS: Using MR phase-contrast imaging, we calculated the hydraulic diameters of the sagittal and straight sinuses in 21 patients with hydrocephalus, 20 patients with idiopathic intracranial hypertension, and 20 age-matched controls. The outflow resistance of each sinus was estimated using the Poiseuille equation. The outflow pressure was estimated using the flow data. A smaller subset of the patients with hydrocephalus had these studies repeated after successful shunt insertion. RESULTS: In hydrocephalus, the sagittal sinuses were 21% smaller than those in controls (P < .001); the straight sinuses were not significantly different. In idiopathic intracranial hypertension, both sinuses were not significantly different from those of controls. The pressure drop from the sagittal sinus to the end of the straight sinus was elevated by 1.2 mm Hg in hydrocephalus (P = .001) but not significantly different from that in controls in idiopathic intracranial hypertension. Shunt insertion dilated the sagittal sinuses in hydrocephalus, leaving them 18% larger than normal and eliminating the transvenous pressure change. CONCLUSIONS: There is a transvenous pressure difference in hydrocephalus that is absent in idiopathic intracranial hypertension. This difference is eliminated by shunt insertion. The findings may have a bearing on ventricular dilation.

Acute ischemic stroke: imaging-guided tenecteplase treatment in an extended time window.

BACKGROUND: Tenecteplase is a modified tissue plasminogen activator with a longer half-life and higher fibrin specificity than alteplase. METHODS: We conducted a prospective, nonrandomized, pilot study of 0.1 mg/kg IV tenecteplase given 3 to 6 hours after ischemic stroke onset. For a control group, we used patients contemporaneously treated with sub-3-hour 0.9 mg/kg IV alteplase following standard selection criteria. All patients underwent pretreatment and 24-hour perfusion/angiographic imaging with CT or MRI. Eligibility criteria for tenecteplase (but not alteplase) treatment included a perfusion lesion at least 20% greater than the infarct core, with an associated vessel occlusion. Primary outcomes, assessed blind to treatment group, were reperfusion (reduction in baseline-24-hour mean transit time lesion) and major vessel recanalization. RESULTS: Fifteen patients received tenecteplase, and 35 patients received alteplase. The tenecteplase group had greater reperfusion (mean 74% vs 44% in the alteplase group, p = 0.01) and major vessel recanalization (10/15 tenecteplase vs 7/29 alteplase, p = 0.01). Despite later time to treatment, more tenecteplase patients (10/15 vs 7/35 alteplase, p = 0.001) had major neurologic improvement at 24 hours (NIH Stroke Scale reduction > or = 8). Four of the alteplase patients and none of the tenecteplase patients had parenchymal hematoma at 24 hours. CONCLUSIONS: Tenecteplase 0.1 mg/kg, using advanced imaging guidance in an extended time window, may have significant biologic efficacy in acute ischemic stroke. The imaging selection differences between the tenecteplase and alteplase groups prevent a conclusive efficacy comparison. Nonetheless, these results lend support for randomized trials comparing tenecteplase with alteplase, preferably incorporating penumbral/angiographic imaging selection.

The pathophysiology of idiopathic normal pressure hydrocephalus: cerebral ischemia or altered venous hemodynamics?

BACKGROUND AND PURPOSE: Many theories of normal pressure hydrocephalus (NPH) stress the importance of ischemia in the deep white matter. Alternate theories stress a reduction in superficial venous compliance and changes in pulse-wave propagation. An overlap in the cerebral blood flow volumes measured between NPH and controls suggests that ischemia may not be a prerequisite for this condition. This study sought to compare blood flow and compliance measures in a cohort of patients with NPH selected for having arterial inflows above the normal range to see if deep brain ischemia or superficial hemodynamic changes contribute to the pathophysiology of NPH. MATERIALS AND METHODS: Twenty patients with NPH and arterial inflows above the normal range were selected. They underwent MR imaging with flow quantification measuring the total blood inflow, sagittal/straight sinus outflow, aqueduct stroke volume, and arteriovenous delay (AVD). Patients were compared with 12 age-matched controls. RESULTS: The deep outflow volumes were normal. The superficial venous outflow was reduced as a percentage of the inflow by 9% (P = .04). The sagittal sinus compliance as measured by the AVD was reduced by 50% (P = .0001), and the aqueduct stroke volume was elevated by 192% (P = .02). CONCLUSION: Ischemia in the deep venous territory is not a prerequisite for NPH. Patients with high-inflow NPH show alterations in superficial venous compliance and a reduction in the blood flow returning via the sagittal sinus. These changes together suggest that an elevation in superficial venous pressure may occur in NPH.

Can MR measurement of intracranial hydrodynamics and compliance differentiate which patient with idiopathic normal pressure hydrocephalus will improve following shunt insertion?

BACKGROUND: Between 10 and 90% of patients with normal pressure hydrocephalus (NPH) treated with a shunt will improve but they risk significant morbidity/mortality from this procedure. NPH is treated hydrodynamically and it has been assumed that a hydrodynamic difference must exist to differentiate which patient will respond. The purpose of this study is to see whether MRI hydrodynamics can differentiate which patients will improve post shunting. METHOD: Thirty-two patients with NPH underwent MRI with flow quantification measuring the degree of ventricular enlargement, sulcal compression, white matter disease, total blood inflow, sagittal sinus outflow, aqueduct stroke volume, relative compliance ratio and arteriovenous delay. Patients were followed up after shunt insertion to gauge the degree of improvement and were compared with 12 age-matched controls and 12 patients with Alzheimer's disease. FINDINGS: 63% of patients improved with insertion. The responders were identical to the non-responders in all variables. The NPH patients were significantly different to the controls (e.g. Total blood inflow reduced 20%, sagittal sinus outflow reduced 35%, aqueduct stroke volume increased 210%, relative compliance ratio reduced 60% and arteriovenous delay reduced 57% with p = 0.007, 0.03, 0.04, 0.0002 and 0.0003 respectively. The patient's with Alzheimer's disease values were midway between the NPH and control patients. CONCLUSIONS: Significant hydrodynamic differences were noted between NPH and controls but these were unable to differentiate the responders from non-responders. The hydrodynamics of Alzheimer's disease makes exclusion of comorbidity from this disease difficult.

Identification of the penumbra and infarct core on hyperacute noncontrast and perfusion CT.

OBJECTIVES: To correlate the two types of early ischemic change on noncontrast CT (NCCT) (parenchymal hypoattenuation [PH] and isolated focal swelling [IFS]) with concurrent assessment of cerebral perfusion and to compare their rates of progression to infarction. METHODS: We assessed cortical regions on NCCT for early ischemic change. Quantitative perfusion values were calculated for cortical regions from acute CT perfusion (CTP) maps of cerebral blood volume (CBV), blood flow (CBF), and mean transit time (MTT). Reperfusion and presence of infarction were determined from follow-up MRI. RESULTS: We studied 40 patients with sub-6 hour anterior circulation ischemic stroke; 19 received IV recombinant tissue plasminogen activator. Of the 202 regions acutely hypoperfused on CTP, 123 were normal on NCCT, 58 had PH, and 21 had IFS. Acute CBV was low in PH regions, and elevated in IFS regions. Acute CBF was reduced in IFS regions, but more so in PH regions. Progression to infarction occurred in virtually all PH regions, but IFS regions had much lower rates of infarction with major reperfusion. Acute CBV in hypoperfused normal NCCT regions ranged from reduced to elevated, with substantially differing risk of infarction. CONCLUSIONS: Isolated focal swelling identifies penumbral tissue and parenchymal hypoattenuation identifies infarct core. Although this has prognostic implications when assessing patient suitability for thrombolytic therapy, the majority of acutely hypoperfused regions appear normal on noncontrast CT. Perfusion CT can stratify the level of risk of subsequent infarction for normal-appearing regions on noncontrast CT.

The reversibility of reduced cortical vein compliance in normal-pressure hydrocephalus following shunt insertion.

Superficial cortical venous compression secondary to alterations in craniospinal compliance is implicated in the pathogenesis of normal pressure hydrocephalus (NPH). A reduction in the pulsation in the outflow of the cortical veins would be expected to occur following compression of these veins and this has been shown in NPH. If cortical vein compression is a causative factor in NPH, it would be expected that cortical vein compliance as measured by pulsatility would be significantly altered by a curative procedure i.e. shunt tube insertion. My purpose is to compare the blood flow pulsatility characteristics in a group of patients with NPH before and after shunt tube insertion. I initially studied 18 subjects without pathology with MRI flow quantification studies of the cerebral arteries and veins to define the range of normality. The main study involved 18 patients with idiopathic dementia and mild leukoaraiosis who served as controls and seven patients with NPH studied before and after shunt insertion. Arterial, superior sagittal and straight sinus pulsatility was not significantly different between the patients with idiopathic dementia and those NPH patients before or after shunting. Cortical vein pulsatility before shunting in the patients with NPH was 43% lower than in those with idiopathic dementia ( P=0.006). Following shunting, cortical vein pulsatility increased by 186% ( P=0.007). There is thus reduced compliance in cortical veins in NPH which is significantly increased in patients who respond to insertion of a shunt tube. These findings suggest that reversible elevation in cortical vein pressure and reversal of the normal absorption pathway for cerebrospinal fluid may be behind the pathophysiology of NPH.

Pulse-wave encephalopathy: a comparative study of the hydrodynamics of leukoaraiosis and normal-pressure hydrocephalus.

There is a strong association between the occurrence of leukoaraiosis and normal-pressure hydrocephalus (NPH). Venous compression secondary to alterations in craniospinal compliance is implicated in the pathogenesis of NPH, and venous pathology has also been implicated in leukoaraiosis. The purpose of this paper is to compare and contrast the blood-flow and fluid-pulsatility characteristics of these conditions. I initially studied 18 subjects without pathology, with MRI flow-quantification studies of the cerebral arteries and veins, to define the range of normality. The main study involved 10 patients with idiopathic dementia but no leukoaraiosis who served as controls, 50 with idiopathic dementia with varying degrees of leukoaraiosis and 18 with NPH. I compared blood-flow volumes, vascular pulse-wave amplitudes and velocities. There was no significant difference in blood flow across the dementia patients. In patients with moderate leukoaraiosis, arterial pulsatility was 69%, cerebrospinal fluid (CSF) pulsation 104%, sagittal sinus pulsatility 48% and cortical vein pulsatility 34% higher than in demented patients without leukoaraiosis. Patients with NPH showed similar results with arterial pulsatility increased by 56% and sagittal sinus pulsatility by 70%. By contrast, the NPH patients' CSF pulse was 42% and the pulse wave delay at the sagittal sinus 50% less than in moderate leukoaraiosis. Thus, leukoaraiosis and NPH share increased arterial and sinus pulsatility. In leukoaraiosis cortical vein compliance is initially increased but in severe leukoaraiosis and NPH it is reduced.

Vascular compliance in normal pressure hydrocephalus.

BACKGROUND AND PURPOSE: Normal pressure hydrocephalus (NPH) is considered to be a combination of altered CSF resorption and a reversible form of cerebral ischemia. The hypothesis tested in this study was that a reduction in venous compliance in the territory drained by the superior sagittal sinus (SSS) is associated with NPH and cerebral ischemia. METHODS: This prospective study involved 27 patients without evidence of hydrocephalus. This group was subdivided into those with normal MR findings and those with evidence of ischemia or atrophy. Ten patients with NPH then underwent MR flow quantification studies of the cerebral vessels. Five of these patients had the same studies performed after CSF drainage. Vascular compliance was measured in the SSS and straight sinus territory by use of MR flow quantification with net systolic pulse volume (NSPV) and arteriovenous delay (AVD) as markers. RESULTS: Vascular compliance of patients with ischemia or atrophy was significantly higher than that of healthy subjects (mean NSPV in the SSS, 417 microL and 274 microL, respectively). Patients with NPH showed lower compliance than that of the healthy subjects in the SSS (mean NSPV, 212 microL and 274 microL, respectively; mean AVD, 42 ms and 89 ms, respectively). After intervention, the NPH group showed compliance approximating the group with ischemia/atrophy. CONCLUSION: Vascular compliance is significantly different in the brains of healthy subjects as compared with that in patients with ischemia/atrophy or NPH.