Umeå University Medical Dissertations

BACKGROUND: Idiopathic normal pressure hydrocephalus (INPH) is still a syndrome generating more questions than answers. Research today focuses mainly on two areas: understanding the pathophysiology and finding better methods to select patients benefiting from a shunt operation. Even though the background of the disease remains unclear, there is wide agreement that there are two pillars of the disease concerning its pathophysiology: firstly, dysfunctional hydrodynamics of the CSF system and secondly, a periventricular chronic ischemia. Unfortunately, the causal effect between these entities remains unsolved, the solution most likely being the key to finally understand the disorder. This thesis targets the aspect of finding better selection methods by investigating the measurability of intracranial pressure via lumbar space, and determining if intraparenchymal measurement of long-term ICP-oscillations (B-waves) could be replaced by short-term measurements of CSF pulse pressure waves via lumbar space. Furthermore, I look into the interaction between the CSF system and the parenchyma itself by investigating how the brain changes its cortical activity after long-term CSF drainage, and if there is any regress in the suggested ischemia after this intervention. Finally, I examine if the neuronal integrity in the INPH brain is impaired, and if this feature is relevant for the likeliness of improvement after CSF diversion. METHODS: The comparisons of intracranial and lumbar pressure were made over a vast pressure interval using our unique CSF infusion technique, and it included ten INPH patients. Pressure was measured via lumbar space and in brain tissue, and the pressures were compared using a general linear model. Short-term lumbar pressure waves were quantified by determining the slope between CSF pulse pressure and mean pressure, defined as the relative pulse pressure coefficient (RPPC). The correlation between RPPC, B-waves, and CSF outflow resistance was investigated. In a prospective study, functional MRI assessed brain activity before and after longterm drainage of 400 ml of CSF in eleven INPH patients. The functionalities tested included finger movement, memory, and attention. The results were benchmarked against the activity in ten healthy controls to identify the brain areas improving after drainage. The ischemia (Lactate) and neuronal integrity (NAA and Choline) were measured in a similar manner in 16 patients and 10 controls using proton MR