Normal Pressure Hydrocephalus (NPH) and Missing White Matter

By SWA

Normal Pressure Hydrocephalus (NPH) is a neurological condition marked by an abnormal buildup of cerebrospinal fluid (CSF) in the brain's ventricles. Unlike other forms of hydrocephalus, NPH does not lead to a significant increase in intracranial pressure. Instead, the ventricles gradually enlarge, causing pressure on surrounding brain tissue, particularly in regions responsible for motor function, cognition, and bladder control.

What Causes NPH?

The exact cause of NPH is often unclear, but it is generally divided into two categories:

Primary (Idiopathic) NPH

This form appears without any identifiable trigger. The leading hypothesis is impaired CSF resorption—meaning the brain’s natural system for reabsorbing fluid into the bloodstream is dysfunctional. The resulting fluid buildup gradually distends the ventricles.

Secondary NPH

Secondary NPH arises as a result of other medical conditions or events that disrupt the flow or absorption of CSF. Common causes include:

  • Brain hemorrhages, which may lead to scarring and blockages in CSF pathways.

  • Infections such as meningitis, which can inflame and damage the CSF circulation system.

  • Head trauma, potentially disturbing the brain’s internal drainage mechanisms.

  • Brain tumors, which may obstruct CSF flow directly.

Treatment for NPH typically involves the surgical insertion of a ventriculoperitoneal (VP) shunt, a device that diverts excess CSF from the brain into the abdominal cavity to relieve pressure and prevent further damage.

Is NPH Related to White Matter Loss?

Yes—NPH is strongly associated with a reduction in white matter, especially in the periventricular region, the area surrounding the fluid-filled ventricles. This phenomenon, often described as “missing white matter,” is not simply incidental but central to understanding the symptoms and progression of the disease.

1. Periventricular White Matter Lesions

NPH is frequently accompanied by lesions in the white matter, including signs of demyelination—a process where the protective myelin sheath surrounding nerve fibers breaks down. This impairs communication between different parts of the brain and is closely linked to cognitive decline and gait disturbance, both hallmarks of NPH.

2. Mechanical Pressure from Enlarged Ventricles

As the ventricles expand, they exert mechanical pressure on surrounding brain tissue. This compression can physically damage the white matter, reducing its volume and function over time.

3. Abnormal CSF Dynamics

Disruption in normal CSF flow can lead to CSF seepage into brain tissue, particularly into the white matter. This leakage can cause localized swelling (edema), which further degrades white matter structure and function.

4. Impaired Cerebral Blood Flow

Studies have shown that cerebral blood flow (CBF) is often diminished in the white matter regions affected by NPH. This lack of adequate blood supply limits oxygen and nutrient delivery, compounding the damage caused by fluid buildup and pressure.

5. Distinct Pathological Pattern

It’s important to note that the pattern of white matter damage seen in NPH differs from other neurodegenerative conditions, such as Binswanger’s disease or age-related white matter degeneration. While those disorders are primarily vascular in nature, NPH-related white matter loss appears to stem from a complex interplay of mechanical, fluid dynamic, and metabolic factors.

In Summary

Normal Pressure Hydrocephalus is more than just a problem of fluid accumulation. It significantly impacts brain structure, particularly the white matter, which plays a critical role in communication between brain regions. The loss or damage of white matter in NPH—driven by ventricular enlargement, disrupted CSF flow, and poor blood supply—contributes directly to its classic triad of symptoms: gait disturbance, cognitive decline, and urinary incontinence.

Understanding the relationship between NPH and white matter damage offers valuable insight into its diagnosis, treatment, and ongoing research efforts. As imaging and biomarker technologies improve, so too does the potential for earlier detection and more targeted therapies aimed at preserving brain function.

References:

After Stroke to Binswanger Encephalopathy: The Role of White Matter Hyperintensities https://swaresearch.blogspot.com/2025/05/after-stroke-to-binswanger.html

Neuropathological findings in possible normal pressure hydro-cephalus: A post-mortem study of 29 cases with lifelines
https://pmc.ncbi.nlm.nih.gov/articles/PMC10210004/

Normal pressure hydrocephalus, or Hakim syndrome: review and update
https://journals.viamedica.pl/neurologia_neurochirurgia_polska/article/view/97343/78807

 

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742

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