Vascular risk factors implicated in normal pressure hydrocephalus

Researchers have found that vascular risk factors are associated with idiopathic normal pressure hydrocephalus (iNPH) and could be a possible target for intervention.

From a pooled sample of 1235 people older than 70 years from four population-based studies, the researchers identified 55 showing hydrocephalic ventricle enlargement on computerised tomography scans and, of these, 26 fulfilled the international guideline criteria for probable iNPH.

These 81 patients were each matched with five individuals with no radiological or clinical signs of iNPH based on age, gender and study cohort.

The results, published in Neurology, show that patients with radiological evidence of hydrocephalic ventricle enlargement had a significant 6.5 times greater odds of having moderate-to-severe white matter lesions (WMLs), compared with controls, while patients with suspected iNPH had a 5.2 times greater odds.

Hydrocephalic ventricle enlargement was also significantly associated with an increased risk of hypertension and diabetes mellitus, the team reports, at odds ratios of 2.7 and 4.3, respectively. Moreover, these associations were independent of WMLs and are therefore likely to increase the risk of iNPH through other mechanisms.

“Our results suggest that vascular risk factors are involved in the disease mechanism of this disorder”, report lead researcher Daniel Jaraj (University of Gothenburg, Sweden) and colleagues.

“Our findings may also have implications for prevention, as these risk factors are modifiable.”

This statement was echoed in a related editorial by Neill Graff-Radford (Mayo Clinic, Jacksonville, Florida, USA), who says that “early effective intervention treating vascular risk factors may reduce the incidence of NPH.”

He also points out that many NPH patients with normal cerebrospinal fluid absorption still improve with shunt surgery, suggesting an important role for other factors; potentially vascular risk factors. So whether NPH patients with normal cerebrospinal fluid absorption but vascular risk factors may improve with such surgery is an important question.

Jaraj et al suggest that hypertension and diabetes may affect ventricle size by affecting their ability to expand during systole, which in turn increases pulse pressure, puts more mechanical force on the brain parenchyma and leads to distension of the ventricles.

“Our findings should be seen in light of reports that patients with iNPH and concurrent hypertension or [diabetes mellitus] have more severe symptoms than those without”, the researchers comment.

Graff-Radford concludes that the next steps should be to confirm whether the association between vascular risk factors and iNPH is a causative one.

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