What are the causes of normal pressure hydrocephalus (NPH)?

Causes of Normal Pressure Hydrocephalus (NPH)

Normal pressure hydrocephalus can result from trauma, intracranial hemorrhage, meningitis (infectious or non-infectious), venous sinus thrombosis, or vasculitis, with idiopathic cases accounting for approximately half of all NPH diagnoses. 1

Primary Causes (Secondary NPH)

• Traumatic Brain Injury: Head trauma can disrupt normal CSF flow patterns and absorption mechanisms 1
• Intracranial Hemorrhage: Subarachnoid hemorrhage or other forms of intracranial bleeding can impair CSF circulation 1
• Meningitis: Both infectious and non-infectious forms of meningitis can lead to NPH through inflammation of the meninges 1
• Venous Sinus Thrombosis: Blockage of venous drainage can alter CSF dynamics 1
• Vasculitis: Inflammation of blood vessels can affect CSF production and absorption 1

Pathophysiological Mechanisms

• CSF Circulation Disruption: Initially raised CSF pressure followed by ventricular enlargement and decreased absorption of CSF at the transcapillary or transvenular level 1
• Interstitial Edema: Fluid accumulation in brain tissue contributes to white matter damage 1
• Ischemic Damage: White matter damage occurs due to compromised blood flow 1
• Inflammatory Processes: Neuroinflammation is typically more intense when there is more interstitial edema 1

Associated Conditions

• Systemic Lupus Erythematosus (SLE): Evidence shows a link between NPH and SLE, where inflammatory processes in meningeal tissues (with deposition of IgG, IgA, IgM, C3, and C1q on dural vessels) or vasculitis can increase CSF volume 1
• Alzheimer's Disease: Approximately 20-57% of NPH patients have comorbid Alzheimer's disease, which can affect response to treatment 2
• Other Neurodegenerative Disorders: About 75% of NPH patients requiring treatment also have another neurodegenerative disorder 3

Idiopathic NPH

• Unknown Etiology: Approximately 50% of NPH cases have no identifiable cause and are classified as idiopathic 4
• Age-Related Factors: More common in elderly people, possibly related to increased incidence of cerebrovascular disease 4
• Vascular Risk Factors: Conditions affecting cerebral blood flow may contribute to idiopathic NPH 5

Pathophysiological Progression

1. Initial Phase: Disruption of normal CSF absorption pathways 1
2. Middle Phase: Ventricular enlargement with normal or only mildly elevated CSF pressure 3
3. Late Phase: Development of the classic triad of symptoms (gait disturbance, cognitive impairment, urinary incontinence) 6, 7

Clinical Implications

• Early identification of the underlying cause is crucial for treatment planning 3
• Patients with NPH and moderate to severe Alzheimer's disease burden are significantly less likely to respond to shunting 1
• Understanding the etiology helps predict treatment outcomes and long-term prognosis 5

Diagnostic Considerations

• MRI without IV contrast is the preferred imaging modality for diagnosing NPH 2
• Key radiological findings include ventriculomegaly, narrowed posterior callosal angle, effaced sulci, widened sylvian fissures, and periventricular white matter changes 2
• Semi-invasive diagnostic procedures may be necessary to establish surgical indications when clinical and imaging findings are inconclusive 3

Understanding the specific cause of NPH is essential for appropriate management and for predicting response to CSF diversion procedures, which can significantly improve outcomes in carefully selected patients.