Cerebrospinal Fluid Infusion Studies: Current View and Concepts in Assessment of Post-Traumatic Hydrocephalus

By: Gunes A. Aygok, M.D.,Ph.D., Harold F. Young, M.D. and Anthony Marmarou, Ph.D. (posthumously)

Due to the heterogeneous nature of the traumatic brain injury (TBI), the difference in mechanism and management of direct and indirect pathologies of head injury reinforces the importance of classifying the brain damage as primary and secondary. Primary damage occurs as a result of the direct impact and mechanical damage to the blood vessels, axons, neurons and glial cells. Most variables of primary damage relate to physical destruction and cannot be manipulated once the injury is sustained. Secondary damage such as increased intracranial pressure (ICP), decreased cerebral blood flow (CBF), hypotension/hypoxia, brain swelling, post-traumatic hydrocephalus (PTH) and infection occur late after the primary injury and can lead to further disruption of cell function4.

Among these, the incidence of post-traumatic hydrocephalus varies greatly from 0.7% 3 - 45%17. The term hydrocephalus derived from the Greek words "hydro" meaning water and "cephalous" meaning head, more specifically implies excessive accumulation of cerebrospinal fluid (CSF) within the ventricles. However, this definition has limitations in understanding the pathophysiology and treatment of hydrocephalus. Most recently, in Crete, where the 5th International Hydrocephalus Workshop was held, Rekate proposed a definition as a starting point to develop a consensus statement defining hydrocephalus: "Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of cerebrospinal fluid from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation."20. It was also clearly indicated that clinical symptoms together with static brain imaging could not distinguish this active process whether the etiology of hydrocephalus is primary or secondary. Therefore, CSF dynamic studies and supplementary tests have been conducted to describe the CSF biomechanical characteristics in identifying the hydrocephalic patients.

Historically, the first mathematical model of CSF pressure–volume which provides much of the basis for understanding the CSF dynamics was introduced by Marmarou and verified experimentally in his work 13, 16.  Using this model, the author described the pressure-volume index (PVI) as the volume required to increase ICP tenfold, in other words as the compliance which is  the ability of the craniospinal system to accommodate the change in volume per unit change in pressure (dV/dP) over the whole physiological range of ICP 19.  Marmarou’s model also allowed the identification of CSF outflow resistance (Ro) which is considered to be the impedance of flow offered by the CSF absorption pathways. Absorption of CSF fluid into the venous compartment takes place predominantly (in humans)through arachnoid granulations adjacent to the walls of the sagittal sinus. The nature of the CSF absorption is proportional to the pressure gradient between the CSF sideof the granulation and the sagittal sinus 12, 18. To date, several methods have been used to measure the Ro. The bolus CSF infusion method used in our clinical setting involves injecting a known volume, usually 4 ml, into the lumbar subarachnoid space at a rate of 1 ml/s. Recording the baseline pressure just before injection (P0), the maximum pressure immediately after injection (Pp), and the pressureafter a time (t) from the injection (Pt) determines the Ro which is calculated from the following equation : R0 = P0/PVI x log [(Pt/Pp) x (Pp - P0)/(Pt - P0)] and the PVI which is also calculated using the equation: PVI = dv/log (P0/Pp) 15.  On the other hand, in the constant rate infusion test described by Katzman et al. 8, the Ro is the difference in the final steady-state pressure reached and the initial pressure divided by the infused flow rate. Later, this method was modified using the computerized infusion test 5. Other techniques include the constant-pressuremethod and the ventriculocisternal method 6. The basic similarity between different methods is the principle which examines the pressure response from an active infusion or withdrawal of CSF and use the pressure and flow relationship to characterize the parameters such as Ro and PVI 9. To eliminate this invasive nature of CSF infusion tests, Alperin developed a non-invasive MRI based method which needs further validation 1

By utilizing CSF infusion tests, there has been an improvement in diagnosing PTH patients. The distinction whether post-traumatic ventriculomegaly is related to atrophy or true hydrocephalus becomes more evident. While most investigators combined primary and secondary hydrocephalus in their CSF analysis, few studied PTH cases only. Among those, Marmarou et al 15 described a systematic classification of PTH in a prospective clinical study of 75 severely head injured patient. Based on changes in ventricular size, presence of atrophy, and CSF infusion study using the bolus method, the patients were separated in to five groups. Group 1 (normal group, 41.3%) demonstrated normal ventricular size and normal ICP. Group 2 (benign intracranial hypertension group, 14.7%) showed normal ventricular size and elevated ICP. Group 3 (atrophy group, 24%) had ventriculomegaly, normal ICP and normal R0. Group 4 (normal-pressure hydrocephalus group, 9.3%) had ventriculomegaly, normal ICP, high R0 together with a progressively decreasing PVI. Group 5 (high-pressure hydrocephalus group, 10.7%) showed ventriculomegaly and elevated ICP with variable R0. More than 70% of those patients who developed PTH also demonstrated SAH and/or IVH on their admission CT scan. Interestingly, in hydrocephalic patients (group 4 and 5); outcomes were similar among those with and without SAH.

In conclusion, according to current literature and our clinical experience, we suggest the following algorithm for management of PTH patients: If the patient’s neurological condition deteriorate and/or brain imaging indicates ventriculomegaly using the frontal horn index or Evans’ ratio demonstrated by Kosteljanetz and Ingstrup 10,  then the CSF infusion studies should be performed via lumbar puncture in order to assess the baseline ICP, Ro and PVI values. These could be coupled with large volume CSF tap test (30 to50 ml) or extended lumbar drainage 7, 14. Once the etiology is identified, the shunt procedure would be recommended to patients with high pressure and normal pressure hydrocephalus 2, 15. If these patients are left untreated, the GOS score would be expected as worse. Moreover, not only the insertion of a shunt but also the timing of the CSF infusion test and the shunt placement plays a major role in clinical management. Marmarou et al.15 found that patients who have had clinical symptoms of hydrocephalus for less than 6 months have a better prognosis. In one study of 98 patients with PTH, Licata et al11 reported favorable outcome in more than 50 % of their patients treated with internal shunts immediately after diagnosis despite severe preoperative conditions. The possible explanation could be the onset of hydrocephalus which was immediate after trauma in 14%, whereas a delayed onset was observed within 30 days in 45%, between one-four months in 31% and between four-six months in 10% 11. Data from Mazzina’s study 17 also showed a recovery in hypoperfusion of temporal and frontal lobes of PTH patients after surgery which suggests a reversible process can occur within the first 6 months post injury. It is our recommendation that a prospective evaluation of PTH patients, diagnosed and shunted before and after 6 months post TBI will show promise as a means of studying the effect of timing for surgery and understanding the underlying pathophysiology.


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