Theoretical considerations on the pathophysiology of normal pressure hydrocephalus (NPH) and NPH-related dementia.

Normal pressure hydrocephalus (NPH) is considered to be an example of reversible dementia although clinical improvement after shunting varies from subject to subject, and recent studies have pointed to a possible link with other dementia. The authors consider that the craniospinal compartment is a partially closed sphere with control device systems represented by the spinal axis and the sagittal sinus-arachnoid villi complex which interact with each other in the clinical patient setting. We hypothesise that changing spinal compliance by altering the flow process and CSF dynamics lead to hydrocephalus. Therefore four NPH types have been distinguished according to the alterations in spinal compliance, decrease in CSF absorption at the sagittal sinus or both occurrences. The authors consider that NPH and NPH-related diseases (NPH-RD) are initiated by the same common final pathway and demonstrate that NPH could represent an initial stage of NPH-RD. Progression of clinical signs can be explained as damage to the cerebral tissue by both intermittent increased intracranial pressure and pulse pressure waves leading to periventricular ischaemia. In addition, they believe that both volume equilibrium and spinal compliance are restored in patients who improve after CSF shunt, whereas in patients whose condition does not improve, only volume equilibrium is restored and not spinal compliance, which was the underlying cause of hydrocephalus in such cases. They therefore wonder whether cervical decompression should not be indicated in patients who show no improvement. Although attractive, this analysis warrants confirmation from clinical, radiological, and hydrodynamic studies.

Idiopathic normal pressure hydrocephalus: theoretical concept of a spinal etiology.

Normal pressure hydrocephalus (NPH) is an adult syndrome characterised by a combination of gait disturbance, varying degrees of cognitive decline, urinary incontinence, ventricular enlargement and normal mean intracranial pressure. Since this syndrome was first described, its pathophysiology has been a matter of great debate, although it is now considered that NPH could be divided into two groups: cases with unknown etiology (idiopathic normal pressure hydrocephalus, or INPH) and those which develop from several known causes (such as trauma, meningitis or subarachnoid haemorrhage). The pathophysiology of INPH is still unclear and a matter of debate. In this manuscript, the current pathophysiological conditions of INPH are analysed and the authors put forward the theory that the disease is a dynamic syndrome which occurs in patients who have suffered a significant loss of spinal compliance over time. Consequently, intracranial pressure increases more during systole in INPH patients because it cannot be compensated for by the escape of CSF into the spinal canal as effectively, due to the reduced volume or lack of distension of the spinal canal. This leads to an increase in ventricular size and causes cumulative brain damage over a long period of time and accounts for the slow, progressive nature of NPH. The loss of spinal compliance with age is fundamental to the proposed theory which provides a theoretical justification for studying the spinal canal in INPH and investigating the relationship between the progressive narrowing of the spinal canal and the compensating ability of the craniospinal system.

Pathophysiology of capillary haemangioma growth after birth.

Capillary haemangiomas (CHs) are the most common soft tissue tumours of infancy. It is generally believed that the primary defect in CHs is intrinsic to endothelial cells, but their pathogenesis is yet poorly understood. The relatively low oxygen environment, in which the human foeto-placental unit develops, during the first trimester, is necessary to induce vasculo-angiogenesis via embryonic endothelial cells proliferation, since these cells are sensitive to hypoxia and acidosis. In newborn infants with haemangioma, persistent embryonic primitive endothelial cells trapped in the intimae underneath the developing vessels, and representing "leader" endothelial cells, can stabilise the labile vascular endothelial growth factor mRNA (VEGF mRNA), produce other angiogenic factors, degrade the underlying basement membrane and invade into the stroma of the neighbouring tissue. With bearing down, the transition from intra- to extra-uterine life is accompanied by more or less pronounced hypoxia. Consequently, in babies with haemangioma, hypoxia can act as a switch to activate these "leader" endothelial cells and thereby initiate a cascade of reactions leading to CH proliferation. As they are regulated by embryonic cells, the haemangioma growth mechanisms pursue the pathway of embryonic angiogenesis and it will stop at the end of the embryonic endothelial cell cycle. Addressing this mechanism in vivo has partly been done (the angiogenic peptide bFGF varies with haemangioma growth). Thus, early treatment seems necessary in infants with haemangioma, before the endothelial cells achieve their proliferative stage. The use of an antibody to interfere with VEGF receptors provides a particular attractive strategy.

Hypothesis about the physiopathology of acute deterioration and sudden death caused by colloid cysts of the third ventricle.

In this paper, the authors review the mechanisms of acute deterioration and sudden death caused by colloid cysts (CCs). These dreaded events are widely recognized complications of CC, however the mechanism(s) in cause has been subject to controversy. Increased intracranial pressure (ICP) is a common event associated with many cerebral disorders, including colloid cysts, though compensatory mechanisms may allow ICP to remain at normal levels. However, a compensated system might decompensate for many factors such as intracranial haemorrhage, acute hydrocephalus, brain oedema, or an increase in sagittal sinus pressure (SSP). The sagittal sinus in adults with brain tumours appears to respond unpredictably when ICP increases and in some patients, when ICP increased the SSP increased too due to the fact that their sinuses collapse. We therefore speculate that the mechanism of acute deterioration and sudden death is a multifactorial and dynamic process, in which the increase in sagittal sinus pressure would appear to be an important element. It seems possible that acute deterioration is initiated by an increase in sagittal sinus pressure, which provokes acute brain swelling, with a series of often-irreversible events, leading to sudden death. Since the majority of cases of acute deterioration and death are due to CCs of the third ventricle, the authors suggest that surgical resection should be carried out on diagnosed CCs measuring over 1 cm, because sudden death has not been reported as having been caused by colloid cysts measuring less than this dimension.