Utility of CSF pressure monitoring to identify idiopathic intracranial hypertension without papilledema in patients with chronic daily headache.

The aim of the present study was to report on the utility of continuous Pcsf monitoring in establishing the diagnosis of idiopathic intracranial hypertension without papilledema (IIHWOP) in chronic daily headache (CDH) patients. We report a series of patients (n = 10) with refractory headaches and suspected IIHWOP referred to us for continuous Pcsf monitoring between 1991 and 2000. Pcsf was measured via a lumbar catheter and analysed for mean, peak, highest pulse amplitude and abnormal waveforms. A 1-2 day trial of continuous controlled CSF drainage (10 cc/ h) followed Pcsf monitoring. Response to CSF drainage was defined as improvement in headache symptoms. Patients with abnormal waveforms underwent a ventriculoperitoneal (VPS) or lumboperitoneal (LPS) shunt insertion. All patients had normal resting Pcsf (8 +/- 1 mmHg) defined as ICP < 15 mmHg. During sleep, all patients had B-waves and 90% had plateau waves or near plateau waves. All patients underwent either a VPS or LPS procedure. All reported improvement of their headache after surgery. Demonstration of pathological Pcsf patterns by continuous Pcsf monitoring was essential in confirming the diagnosis of IIHWOP, and provided objective evidence to support the decision for shunt surgery. Increased Pcsf was seen mostly during sleep and was intermittent, suggesting that Pcsf elevation may be missed by a single spot-check LP measurement. The similarity between IIHWOP and CDH suggests that continuous Pcsf monitoring in CDH patients may have an important diagnostic role that should be further investigated.

Effect of age on cerebral blood flow velocity and incidence of vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Current transcranial Doppler criteria for vasospasm after aneurysmal subarachnoid hemorrhage are not age specific. We analyzed the effect of age on cerebral blood flow velocity changes after subarachnoid hemorrhage and constructed an age-adjusted predictive model of cerebral blood flow velocity in subarachnoid hemorrhage patients. METHODS: We identified patients with aneurysmal subarachnoid hemorrhage admitted between 1991 and 1999 with a prospective transcranial Doppler database. Eighty-one patients, with complete medical records and transcranial Doppler examinations of the vessels of interest, were included. Patients were subdivided into 2 groups by age: younger, <68 years of age (n=47) and older, >/=68 years of age (n=34). Maximum mean flow velocity and incidence of symptomatic vasospasm were reported. Linear and nonlinear regression analyses were performed. RESULTS: Middle cerebral artery and internal carotid artery mean flow velocity were lower in older patients (median 76 versus 114 cm/s and 76 versus 126 cm/s, respectively; P<0.003). Incidence of symptomatic vasospasm was lower in older patients (44% versus 66%; P=0.05). Older patients developed symptomatic vasospasm at lower middle cerebral artery (median 57 versus 103 cm/s; P=0.04) and internal carotid artery (median 54 versus 81 cm/s, P=0.02) mean flow velocity. Relationship between middle cerebral artery and internal carotid artery mean flow velocity and age was quadratic (ANOVA, P<0.0001). CONCLUSIONS: Older patients have a lower incidence of symptomatic vasospasm, and such vasospasm develops at lower cerebral blood flow velocity than younger patients. A quadratic relationship was found between age and cerebral blood flow velocity. This model could be used to create an age-adjusted nomogram that might improve diagnostic capabilities of transcranial Doppler.

Effect of adenosine on cerebral blood flow velocity.

BACKGROUND AND PURPOSE: Evidence suggests that adenosine (ADN) is a potent vasodilator of cerebral vessels. However, the feasibility of manipulating human cerebral vascular resistance with ADN has not been assessed by means of TCD. The purpose of this study was to quantitatively estimate the change in middle cerebral artery cerebral blood flow velocity (CBFV) in response to intravenous ADN infusion in humans. METHODS: Eleven patients with subacute cerebrovascular events (ischemic stroke, transient ischemic attack, or hemorrhage) undergoing adenosine-thallium stress testing were studied before, during, and after ADN infusion to evaluate the effect of ADN on cerebral blood flow velocity. Continuous blood pressure (BP), heart rate (HR), respiration rate (RR), end-tidal CO2 (ET-CO2), and transcranial Doppler ultrasonography monitoring of CBFV and pulsatility index (PI) in both middle cerebral arteries were performed. RESULTS: The mean CBFVs were 65.4 +/- 19.2 cm/s before, 55.4 +/- 18.1 cm/s during, and 64.1 +/- 22.5 cm/s after ADN infusion, which represents a statistically significant decrease during ADN test compared with both baseline (P = .007) and posttest levels (P = .017). The PI was increased during the test (0.91 +/- 0.2) when compared with baseline (0.71 +/- 0.1) (P = .007). During ADN injection, mean HR increased (P = .004) and mean ET-CO2 levels decreased significantly (P = .003). Mean BP and RR did not change significantly. CONCLUSIONS: The authors hypothesize that any direct vasodilatory effect of ADN on the distal cerebral peripheral vasculature may be negated by an effect of ADN on depth of respiration resulting in hypocapnia and secondary distal vasoconstriction.

Cerebral vasculitis: diagnosis and follow-up with transcranial Doppler ultrasonography.

The authors report a patient with postpartum intracerebral hemorrhage associated with cerebral vasculitis. Cerebral circulation was assessed with transcranial Doppler (TCD) ultrasonography, magnetic resonance angiography, and conventional cerebral angiography. Initial TCD studies demonstrated bilateral patchy increased cerebral blood flow velocity (CBFV) in the anterior circulation with complete normalization during remission. This case report provides evidence that cerebral vasculitis leads to relevant CBFV changes and that the TCD technique may assist in diagnosis and follow-up of these patients.

Diagnostic impact of early transcranial Doppler ultrasonography on the TOAST classification subtype in acute cerebral ischemia.

OBJECTIVE: The impact of early transcranial Doppler ultrasonography (TCD) upon stroke subtype diagnosis is unknown and may affect therapeutic strategies. In this study, the diagnostic usefulness of TCD in stroke subtype diagnosis according to the criteria of the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) study was investigated in patients with acute cerebral ischemia. METHODS: TCD examination within 24 h of symptom onset was performed in 50 consecutive patients with acute cerebral ischemia. Of these 54% were female. Sixty percent of patients were black, 36% white, and 4% Asian. Initial TOAST stroke subtype diagnosis (ITSSD) was based upon clinical presentation and initial brain imaging studies. Modified TOAST stroke subtype diagnosis was determined subsequently after additional review of the TCD examination. Final TOAST stroke subtype diagnosis was determined at hospital discharge, incorporating all diagnostic studies. Using final TOAST stroke subtype diagnosis as the 'gold standard' ITSSD and modified TOAST stroke subtype diagnosis were compared in order to determine additional benefit from the information obtained by TCD. Data were collected retrospectively by a single investigator. RESULTS: ITSSD classified 23 of 50 (46%) patients correctly. After TCD, 30 of 50 (60%) patients were classified correctly, for an absolute benefit of 14% and a relative benefit of 30% (p = 0.018). Most benefit from TCD was observed in the TOAST stroke subtype category large-artery atherosclerosis, in particular in patients with intracranial vascular disease. In this category, ITSSD had a sensitivity of 27% which increased to 64% after TCD (p = 0.002). CONCLUSION: TCD within 24 h of symptom onset improves the accuracy of early stroke subtype diagnosis in patients with acute cerebral ischemia due to large-artery atherosclerosis. This may have clinical implications for early therapeutic interventions.

Cerebral hemodynamics changes during retrograde brain perfusion in dogs.

The objective of this study was to examine cerebral hemodynamics changes during hypothermic circulatory arrest (HCA) with and without retrograde cerebral perfusion (RCP). Thirteen colony-bred hound dogs were placed on cardiopulmonary bypass (CPB) and cooled to 18 degrees C. Five dogs underwent 2 hours of HCA without RCP and 8 with RCP. The animals were then rewarmed on CPB until normothermic and weaned. Cerebral blood flow velocity (CBFV) and Gosling Pulsatility Index (PI) in the middle cerebral artery (MCA) were studied using trans-cranial Doppler ultrasound (TCD). At baseline and during pre- and postarrest CPB, there was anterograde direction of blood flow in the MCA. During HCA with RCP, there was retrograde direction of blood flow in the MCA. There was no difference in CBFV between pre-, during, and postarrest CPB in the group with RCP; however, there was significantly increased CBFV during postarrest CPB in the group without RCP compared to the dogs with RCP. Later, at 3 hours after postarrest CPB, there was decreased CBFV in all animals accompanied by increased PI (2.4 +/- 0.4 and 2.2 +/- 0.6 for animals with RCP and without RCP, respectively) and abnormal TCD waveform changes including decreased diastolic compartment and sharp systolic peak. During hypothermic circulatory arrest, RCP provides CBFV in the MCA comparable to MCA CBFV during CPB. HCA dogs without RCP showed immediate hyperemia on reperfusion. The decreased CBFV and increased PI at 1 hour after postarrest CPB could be an indicator of progressive ischemic injury due to the increased intracranial pressure despite the implementation of RCP.

Early identification of patients at risk for symptomatic vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To develop a scheme for early identification of individuals at risk for symptomatic vasospasm after subarachnoid hemorrhage (SAH). DESIGN: Analysis of prospectively collected data from the placebo-treated group in a multicenter clinical trial. SETTINGS: Fifty-four neurosurgical centers in North America. MEASUREMENTS AND MAIN RESULTS: We identified independent predictors of symptomatic vasospasm using stepwise logistic regression analysis from demographic, clinical, laboratory, and neuroimaging characteristics of the participants. We developed a scoring system (symptomatic vasospasm risk index) based on a combination of these predictors. Out of 283 patients in the analysis (all treated with oral nimodipine), 93 (33%) developed symptomatic vasospasm within 14 days after SAH. There were four independent predictors of symptomatic vasospasm: thickness of subarachnoid clot on computed tomographic scan (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.8-10.0); early rise in middle cerebral artery mean flow velocity (MCA-MFV), defined as a value > or =110 cm/sec recorded on or before post-SAH day 5 (OR, 1.9; 95% CI, 1.1-3.3), Glasgow Coma Scale score <14 (OR, 1.8; 95% CI, 1.1-3.1); and rupture of anterior cerebral or internal carotid artery aneurysm (OR, 1.9; 95% CI, 1.0-3.4). The probability of identifying patients who would develop symptomatic vasospasm (percentage of area under receiver operating characteristics curve +/- SEM) was higher with symptomatic vasospasm risk index (68%+/-8%) compared with thickness of clot (62%+/-8%; p = .08) or MCA-MFV (45%+/-7%, p < .05) criteria alone. CONCLUSIONS: Patients at high risk for symptomatic vasospasm can be identified early in the course of SAH using a risk index. A risk index based on a combination of variables may represent a predictive paradigm superior to conventionally used criteria based on clot thickness or MCA-MFV criteria.

TCD, MRA and MRI in acute cerebral ischemia.

OBJECTIVES: The aim of this study was to determine accuracy of transcranial Doppler ultrasound (TCD) and compare efficacy of three non-invasive tests [TCD, magnetic resonance angiography (MRA), and magnetic resonance imaging (MRI)] in patients with acute cerebral ischemia. MATERIAL AND METHODS: This prospective study involved 30 patients. MRI, MRA, and TCD were performed within 24 h after onset of ictus. The 2nd MRI was repeated at 48-72 h and was used as the standard for the evaluation of sensitivity and specificity of MRA, TCD, and initial MRI. RESULTS: TCD showed a sensitivity of 96% and a specificity of 33% for recognizing abnormal cerebral blood flow velocities. MRA showed a sensitivity of 46% and a specificity of 75% for assessing intracranial vascular anatomy, while initial MRI revealed a sensitivity of 84% and a specificity of 100% for evaluation of ischemic parenchymal changes. CONCLUSION: Our results revealed that TCD is an accurate indicator of blood flow status and correlated well with MRI, MRA abnormalities in acute stroke.

A new optical immunoassay for detection of S-100B protein in whole blood.

BACKGROUND: S-100B is a protein mainly found in astroglial cells and only detected to a low level in blood. Serum levels of S-100B increase in patients with acute brain injuries. The aim of this study was to establish feasibility of a new Optical ImmunoAssay ([OIA], Bio-Star, Inc, Boulder, CO) test for determination of S-100B in blood. METHODS: We have developed a new, rapid, and sensitive OIA test to identify elevated levels of S-100B in whole blood. The OIA test for S-100B combines monoclonal antibodies specific for the B-subunit of S-100 with OIA thin film technology. Each sample was tested for S-100B by the OIA method and a commercially available immunoluminometric assay. Blood samples were drawn serially from 9 patients undergoing coronary artery bypass graft surgery and during the early postoperative period. RESULTS: The OIA test determination of S-100B protein correlated with immunoluminometric assay data (r = 0.8) with a detection limit of 0.25 ng/mL. CONCLUSIONS: The sensitivity and feasibility of this rapid assay may be suitable for rapid evaluation of S-100B in urgent care settings (surgery, intensive care units, or emergency room).

Comparison of Pcsf monitoring and controlled CSF drainage diagnose normal pressure hydrocephalus.

We evaluated 86 patients for possible normal pressure hydrocephalus (NPH) by: 1) CSF pressure (Pcsf) monitoring and analysis for percent of time with A or B-waves, and 2) controlled CSF drainage for 3 days via a lumbar subarachnoid catheter. Clinical outcome after CSF drainage and shunt surgery was assessed as change of clinical exam, with grades of none, minor, moderate, or marked change. For outcome analysis in 47 patients after shunt surgery, NPH was defined as moderate or marked clinical improvement. We assessed the diagnostic discrimination of percent-of-time thresholds of A and B-waves for 38 patients. At 10%, sensitivity for NPH is 91%, specificity is 13%, positive predictive value (PPV) is 62%, and the false positive rate is 38%. At the 25% threshold, sensitivity is 78%, specificity is 40%, PPV is 67%, false positive rate is 33%, and the false negative rate is 22%. For CSF drainage (threshold of minor improvement or better), the sensitivity is 97%, specificity is 60%, PPV is 84%, negative predictive value (NPV) is 90%, and the false negative rate is 3%. We conclude: 1) clinical response to controlled CSF drainage accurately predicts the outcome after shunt surgery in patients suspected of having NPH, and 2) A or B-waves poorly predict which patients will respond to shunt surgery. Three days of CSF drainage seems to encompass critical thresholds of CSF volume removal or duration of Pcsf reduction necessary for neuronal function to begin returning and symptoms to begin resolving in patients with NPH.

Magnetic resonance imaging, unstable intracranial pressure and clinical outcome in patients with normal pressure hydrocephalus.

To identify features on magnetic resonance imaging (MRI) scans that are associated with unstable intracranial pressure (ICP) and outcome after CSF shunting in patients with NPH, we reviewed MRI scans of 17 patients who had continuous ICP monitoring performed prior to ventriculo-peritoneal shunt insertion. We evaluated the association between periventricular/deep white matter lesion burden, focal impingement of the corpus callosum, aqueductal CSF flow void, and B-waves with outcome after shunting. The change in neurological function between pre- and post CSF shunting evaluation was scored according to a standard scale (range -3 or +3). Patients were divided into those with clinical improvement (score > 0) or without improvement (score < or = 0) after shunt surgery. Focal impingement of the corpus callosum was more frequent in patients who improved after CSF shunting compared to those without improvement (8 of 13 vs 0 of 4, p = 0.05). Patients with focal impingement of corpus callosum had more B-wave time than those without impingement (60.5% vs 24.7%, p = 0.02). Focal impingement of corpus callosum on MRI may be associated with unstable intracranial pressure in patients with NPH and may be useful in identifying patients who will benefit from CSF shunting.

Evaluation of shunt function in patients who are never better, or better than worse after shunt surgery for NPH.

We investigated the cause of poor outcome in patients with normal pressure hydrocephalus (NPH) who did not respond as expected after shunt surgery. Two methods were used to evaluate shunts: radionuclide shunt patency study, or continuous ICP monitoring. 33/52 shunted patients (64%) from 1989 to 1995 had poor outcome, and 28/52 (54%) were investigated. Of those investigated, 9/28 (32%) were never better, and 19/28 (68%) were initially better then worse. Of 9 patients who were never better, ineffective shunt function was seen in 7; 5 had shunt revision (2 declined), and 1 improved. Of 19 patients who were initially better then worse, 15 had ineffective shunts; 15 underwent shunt revision, and 13 improved. Poor clinical outcome occurred in two-thirds of all patients after shunt surgery for NPH, but a potentially treatable cause (i.e. obstruction of the shunt or a shunt system that was patent but did not adequately correct the CSF circulatory disorder) was found in nearly 80% (22/28) of those investigated. The predominant cause of ineffective shunt function was obstruction of the peritoneal catheter. Clinical recovery occurred in 70% (14/20) of patients who had shunt revision surgery. We conclude that ineffective shunt function is a frequent cause of poor outcome after shunt surgery to treat NPH that should be sought and treated. These results have implications for longitudinal studies of the diagnosis and treatment of NPH. The effect of unrecognized shunt ineffectiveness on prior studies is unknown. Future studies should be designed to confirm that shunts are functioning before the diagnosis of NPH is considered incorrect.

Validation of transcranial Doppler ultrasound with a stereotactic neurosurgical technique.

Vessel identification during a transcranial Doppler (TCD) ultrasound examination is usually based on well-established inferential criteria without confirmation by imaging. Part of a routine study involves taking measurements from the M1 segment of the middle cerebral artery (MCA) and the A1 segment of the anterior cerebral artery (ACA) at the points of maximum mean linear blood flow velocity (LBFV). The authors tested the hypothesis that insonation is from the midpoints of the M1 and A1 segments during clinical TCD examinations. Conventional hand-held TCD examinations were performed on five volunteers. The points of maximum mean LBFV of the M1 and A1 segments of the MCA and ACA were located. Measurements were also taken from the midpoints of the M1 and A1 segments using a magnetic resonance (MR) imaging-guided stereotactic TCD technique. Values for depths of insonation and maximum mean LBFV obtained with the two techniques were compared. There was no significant difference between the two techniques for the measured values of depth of insonation of either the individual vessels (p > 0.11) or the aggregate (p = 0.46). There was a significant difference between the aggregate maximum mean LBFV measurements (p = 0.0022). The hand-held technique systematically produced higher maximum mean LBFV than the MR-guided stereotactic technique. The authors conclude that when using traditional criteria for TCD examination of the ACA and MCA, the points of insonation approximate the middle of the A1 and M1 segments.

Intracranial pressure measurement/cranial vault mechanics: clinical and experimental observations.

The absolute value of intracranial pressure (ICP) should be considered in conjunction with evaluation of a patient's clinical condition. In addition, other aspects of cranial vault mechanics may be important in multiple disease states. Among the important physiological measures of cranial vault sufficiency are hydrodynamic interaction between brain tissue, blood and cerebrospinal fluid (CSF)--volume-pressure relation, CSF dynamics--CSF outflow resistance, CSF production rate, sagittal sinus pressure, and appearance of ICP waves. Clinical and experimental studies brought together in this review provide an insight into the dynamics of ICP and the cranial vault.

Venous and cerebrospinal fluid outflow in patients with brain swelling and oedema.

67 patients with benign intracranial hypertension (BIH) and 44 with normal pressure hydrocephalus (NPH) were examined by employment of infusion tests. Brain swelling (decrease of ventricular size with normal or increased brain tissue density) was a characteristic feature of BIH. It may result from venous outflow disturbances leading to vascular engorgement. But later, the process appears to be independent from the increase of the dural sinus pressure. This was normal in patients with BIH and NPH. Despite absorption disturbances there was a strong positive correlation in NPH between cerebrospinal fluid- and dural sinus pressure, while in BIH such a correlation was absent. The data confirm a pathogenesis of brain swelling in BIH as an obstacle to venous outflow at the level of the bridging veins and venous lacunae, however, not at the level of the dural sinuses.