Shahan Momjian

Cerebrospinal fluid dynamics.

Hydrocephalus is far more complicated than a simple disorder of CSF circulation. Historically, it has been diagnosed using clinical and psychomotor assessment plus brain imaging. The role of physiological measurement to aid diagnosis becomes more appreciated in current clinical practice. This has been reflected by recently formulated guidelines for the management of normal pressure hydrocephalus. Clinical measurement in hydrocephalus is mainly related to intracranial pressure (ICP) and cerebral blood flow. This review lists and discusses most common forms of the methods: CSF infusion study, overnight ICP monitoring, assessment of slow ICP waves, testing pressure reactivity, cerebral autoregulation, CO2 reactivity and PET-CBF studies combined with MRI co-registration. The basics of CSF dynamics modelling are presented and the principles of the assessment of functioning of the implanted hydrocephalus shunts are also discussed. The descriptions of multiple forms of measurement along with clinical illustrations are mainly based on in-house experience of a multidisciplinary group of scientists and clinicians from Cambridge, UK.

Normal pressure hydrocephalus and cerebral blood flow: a PET study of baseline values

Regional cerebral blood flow (CBF) was studied with O15-water positron emission tomography and anatomic region-of-interest analysis on coregistered magnetic resonance in patients with idiopathic (n = 12) and secondary (n = 5) normal pressure hydrocephalus (NPH). Mean CBF was compared with values obtained from healthy volunteers (n = 12) and with clinical parameters. Mean CBF was significantly decreased in the cerebrum and cerebellum of patients with NPH. The regional analysis demonstrated that CBF was reduced in the basal ganglia and the thalamus but not in white matter regions. The results suggest that the role of the basal ganglia and thalamus in NPH may be more prominent than currently appreciated. The implications for theories regarding the pathogenesis of NPH are discussed.

Changes in Cerebral Blood Flow during Cerebrospinal Fluid Pressure Manipulation in Patients with Normal Pressure Hydrocephalus: A Methodological Study:

The combination of cerebral blood flow measurement using 15O-water positron emission tomography with magnetic resonance coregistration and CSF infusion studies was used to study the global and regional changes in CBF with changes in CSF pressure in 15 patients with normal pressure hydrocephalus. With increases in CSF pressure, there was a variable increase in arterial blood pressure between individuals and global CBF was reduced, including in the cerebellum. Regionally, mean CBF decreased in the thalamus and basal ganglia, as well as in white matter regions. These reductions in CBF were significantly correlated with changes in the CSF pressure and with proximity to the ventricles. A three-dimensional finite-element analysis was used to analyze the effects on ventricular size and the distribution of stress during infusion. To study regional cerebral autoregulation in patients with possible normal pressure hydrocephalus, a sensitive CBF technique is required that provides absolute, not relative normalized, values for regional CBF and an adequate change in cerebral perfusion pressure must be provoked.

Link between vasogenic waves of intracranial pressure and cerebrospinal fluid outflow resistance in normal pressure hydrocephalus.

Recent studies on normal pressure hydrocephalus (NPH) have pointed to a possible link between the disturbance in CSF circulation and cerebrovascular factors. We investigated the quantitative relationship between the resistance to CSF outflow (Rcsf) and vasogenic waves of ICP in patients with normal pressure hydrocephalus. Forty-five patients with NPH were investigated by an infusion study. The magnitudes of vasogenic ICP components: pulse, respiratory and slow vasogenic waves were assessed, and compared with Rcsf. Both baseline respiratory and slow waves of ICP were positively correlated with Rcsf. The respiratory wave at baseline was a single independent predictor of Rcsf (r = 0.66, p < 0.0002). All vasogenic components increased significantly during the infusion test. The magnitude of the increase was positively correlated with Rcsf. The vasogenic ICP waves, notably the respiratory wave of ICP, correlate with the resistance to CSF outflow.

Intracranial baroreflex yielding an early Cushing response in human

The Cushing response is a pre-terminal sympatho-adrenal systemic response to very high ICP. Animal studies have demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response. Infusion studies are routine procedures to investigate, by infusing CSF space with saline, the cerebrospinal fluid (CSF) biophysics in patients suspected of hydrocephalus. Our study aims at assessing systemic and cerebral haemodynamic changes during moderate rise of ICP in human. Infusion studies were performed in 34 patients. This is a routine test perform in patients presenting with symptoms of NPH during their pre-shunting assessment. Arterial blood pressure (ABP) and cerebral blood flow velocity (FV) were non-invasively monitored with photoplethysmography and transcranial Doppler. The rise in ICP (8.2 +/- 5.1 mmHg to 25 +/- 8.3 mmHg) was followed by a significant rise in ABP (106.6 +/- 29.7 mmHg to 115.2 +/- 30.1 mmHg), drop in CPP (98.3 +/- 29 mmHg to 90.2 +/- 30.7 mmHg) and decrease in FV (55.6 +/- 17 cm/s to 51.1 +/- 16.3 cm/s). Increasing ICP did not alter heart rate (70.4 +/- 10.4/min to 70.3 +/- 9.1/min) but augmented the heart rate variance (0.046 +/- 0.058 to 0.067 +/- 0.075/min). In a population suspected of hydrocephalus, our study demonstrated that a moderate rise of ICP yields a reversible pressure-mediated systemic response, demonstrating an early Cushing response in human and a putative intracranial baroreflex.

Hysteresis of the cerebrospinal pressure-volume curve in hydrocephalus.

The objective was to study the displacement of the cerebrospinal fluid pressure-volume curve during the descent relative to the ascent of intracranial pressure recorded during the cerebrospinal fluid constant rate infusion test. This phenomenon can be interpreted as the hysteresis of the pressure-volume curve. The cerebrospinal fluid dynamics were tested in fifty-eight patients with clinical symptoms of hydrocephalus. After finished infusion, ICP was recorded until it returned to steady state level. Pressure-volume curves were plotted separately for ascending and descending phases of the test. The parameters of CSF compensation were estimated on the basis of mathematical mono-exponential model of CSF circulation. The pressure-volume curve post-infusion was visibly shifted upward in 69% of tests. Those who demonstrated the upward shift of the pressure-volume curve had greater an elastance coefficient of the cerebrospinal space (with shift: E1 = 0.26 +/- 0.14; without shift: E1 = 0.17 +/- 0.06; p < 0.05). Magnitude of the shift was positively correlated with pulse amplitude of ICP (r = -0.763; p < 0.0001). The accuracy of clinical examination of the pressure-volume compensatory reserve, which take into account both compression and decompression phase of the study, may be affected by this phenomenon.

Pulse amplitude of intracranial pressure waveform in hydrocephalus

BACKGROUND There is increasing interest in evaluation of the pulse amplitude of intracranial pressure (AMP) in explaining dynamic aspects of hydrocephalus. We reviewed a large number of ICP recordings in a group of hydrocephalic patients to assess utility of AMP. MATERIALS AND METHODS From a database including approximately 2,100 cases of infusion studies (either lumbar or intraventricular) and overnight ICP monitoring in patients suffering from hydrocephalus of various types (both communicating and non-communicating), etiology and stage of management (non-shunted or shunted) pressure recordings were evaluated. For subgroup analysis we selected 60 patients with idiopathic NPH with full follow-up after shunting. In 29 patients we compared pulse amplitude during an infusion study performed before and after shunting with a properly functioning shunt. Amplitude was calculated from ICP waveforms using spectral analysis methodology. FINDINGS A large amplitude was associated with good outcome after shunting (positive predictive value of clinical improvement for AMP above 2.5 mmHg was 95%). However, low amplitude did not predict poor outcome (for AMP below 2.5 mmHg 52% of patients improved). Correlations of AMP with ICP and Rcsf were positive and statistically significant (N = 131 with idiopathic NPH; R = 0.21 for correlation with mean ICP and 0.22 with Rcsf; p< 0.01). Correlation with the brain elastance coefficient (or PVI) was not significant. There was also no significant correlation between pulse amplitude and width of the ventricles. The pulse amplitude decreased (p < 0.005) after shunting. CONCLUSIONS Interpretation of the ICP pulse waveform may be clinically useful in patients suffering from hydrocephalus. Elevated amplitude seems to be a positive predictor for clinical improvement after shunting. A properly functioning shunt reduces the pulse amplitude.

Calculation of the resistance to CSF outflow

We read the paper by Kahlon et al with great interest.1 Comparative studies about the use of different diagnostic techniques to predict the response to shunting in hydrocephalus are of great value as they are likely to form a landmark for future clinical practice. Therefore, it is of paramount importance that the procedures taken for comparison are methodologically sound. Unfortunately, the interpretation of the lumbar infusion study given by the authors raises our concern. For unknown reasons, the authors have taken into account only the end equilibrium pressure obtained during a constant rate lumbar infusion and neglected the baseline CSF pressure. The authors presumed that this pressure was the same in everybody and equal to the value resulting from the mean taken from the whole cohort (11 mm Hg). Interpretation of the infusion study can be based only partially on the resistance to CSF outflow (Rcsf), with other parameters describing CSF dynamics like the baseline pressure, elasticity, etc, taken into account.2–4 The resistance to CSF outflow is, undoubtedly the most important parameter, about which a number of independent studies have been conducted in the past,2,5 including a quite recent multicentre Dutch trial.6 The proper way to calculate Rcsf results from the well known Davson’s formula2: \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\mathit{ICP}_{\mathit{baseline}}\mathit{=Rcsf{\times}Formation\ of\ CSF+Pss;}\ (where\ \mathit{Pss}\ is\ sagittal\ sinus\ pressure).\] \end{document} ICP reached during infusion is equal …

Pattern of regional white matter CBF in normal pressure hydrocephalus during infusion test

Materials and Methods Ten patients with idiopathic NPH (mean age 69 years) underwent a CSF infusion study via a previously implanted right frontal ventricular catheter connected to a subcutaneous reservoir. CBF was measured by H215O PET at baseline and then during the steady-state plateau of raised ICP. The PET images were co-registered to 3D structural T1-weighted MR images. In 10 healthy normal volunteers (mean age 45 years) image acquisition and reconstruction were accomplished in the same manner, except that only a baseline CBF determination was performed.