Ongoing search for diagnostic biomarkers in idiopathic normal pressure hydrocephalus

http://www.futuremedicine.com/doi/abs/10.2217/bmm.09.37

Idiopathic normal pressure hydrocephalus is a syndrome, which typically has a clinical presentation of gait/balance disturbance, often accompanied by cognitive decline and/or urinary incontinence. Its diagnosis is based on relevant history and clinical examination, appropriate imaging findings and physiological testing. The clinical picture of idiopathic normal pressure hydrocephalus may occasionally be difficult to distinguish from that of Alzheimer’s dementia, subcortical ischemic vascular dementia and Parkinson’s disease. The aim of this article is to systematically review the literature from the last 29 years in order to identify cerebrospinal fluid (CSF) or imaging biomarkers that may aid in the diagnosis of the syndrome. The authors concluded that no CSF or imaging biomarker is currently fulfilling the criteria required to aid in the diagnosis of the condition. However, a few studies have revealed promising CSF and imaging markers that need to be verified by independent groups. The reasons that the progress in this field has been slow so far is also commented on, as well as steps required to apply the current evidence in the design of future studies within the field.

Normal pressure hydrocephalus: a reversible cause of dementia

Laurence D Watkins, Andrew Tarnaris and Ahmed Toma

Send response to journal: Re: Normal pressure hydrocephalus: a reversible cause of dementia

We read with interest the review by Burns and Iliffe (BMJ 2009; 338:b75) with its very timely focus on dementia and its various causes। However, we were concerned that Normal Pressure Hydrocephalus (NPH) was mentioned only briefly। This condition perhaps deserves much greater emphasis, since it is a potentially reversible condition and may be a contributory factor in up to 5% of the dementia population.1 Normal pressure (or chronic adult) hydrocephalus affects the ageing population (usually over 60 years old) and typically has a clinical presentation of gait/balance disturbance, often accompanied by cognitive decline and/or urinary incontinence. CSF pressure appears “normal” and brain imaging shows ventriculomegaly. Symptoms may be improved by surgical CSF diversion, especially if picked up early.2

Recent population-based studies have estimated the prevalence of NPH to be about 0।5% in those over 65 years old, with an incidence of about 5.5/100,000/year.3,4 Quality of life of patients treated by shunt insertion can improve substantially and the improvement can be long-lasting.5,6 Yet, less than 350 shunt insertion surgeries operations are performed in the UK for normal pressure hydrocephalus each year, representing a fraction of about 10% of the expected incidence (UK shunt registry, personal communication).

The authors mentioned that NPH should be excluded via neurocognitive assessment and (if available) computed tomogragraphy। Although CT scan of the brain is essential to establish ventriculomegaly as a prerequisite for the diagnosis of NPH,7 the sensitivity of neuropsychological assessment and brain imaging are low in diagnosing this condition and referral to specialized neurosurgical centre to conduct further testing by either lumbar drainage or assessment of CSF dynamics is essential.8

We certainly welcome the current expansion of services aimed at improving provision for dementia patients and would encourage inclusion of NPH in all diagnostic algorithms. It is important to consider the possible diagnosis if there is ventriculomegaly and the patient is fit enough to be a surgical candidate. If the diagnosis is being considered, then it should not be excluded except by invasive testing (such as extended lumbar drainage), which generally will mean referral to a specialist unit.9
References:
1. Silverberg G, Mayo M, Saul T, Fellmann J, McGuire D. Elevated cerebrospinal fluid pressure in patients with Alzheimer’s disease. Cerebrospinal Fluid Research 2006;3:7.
2. Relkin N, Marmarou A, Klinge P, Bergsneider M, Black PM. Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery 2005;57(3 Suppl):S4-16
3. Tanaka N, Yamaguchi S, Ishikawa H, Ishii H, Meguro K. Prevalence of Possible Idiopathic Normal-Pressure Hydrocephalus in Japan: The Osaki-Tajiri Project. Neuroepidemiology 2008;32(3):171-5.
4. Brean A, Eide PK. Prevalence of probable idiopathic normal pressure hydrocephalus in a Norwegian population. Acta Neurologica Scandinavica 2008;118(1):48-53.
5. Stein SC, Burnett MG, Sonnad SS. Shunts in normal-pressure hydrocephalus: do we place too many or too few? J Neurosurg 2006;105(6):815-22.
6. Pujari S, Kharkar S, Metellus P, Shuck J, Williams MA, Rigamonti D. Normal Pressure Hydrocephalus: Very long term outcome after shunt surgery. J Neurol Neurosurg Psychiatry 2008;79(11):1282-6
7. Tarnaris A, Kitchen ND, Watkins LD. Noninvasive biomarkers in normal pressure hydrocephalus: evidence for the role of neuroimaging. J Neurosurg. [Epub ahead of print] JNS, November 7, 2008; http://thejns.org/doi/abs/10.3171/2007.9.17572.
8. Marmarou A, Bergsneider M, Klinge P, Relkin N, Black PM. The value of supplemental prognostic tests for the preoperative assessment of idiopathic normal-pressure hydrocephalus. Neurosurgery 2005;57(3 Suppl):S17-28.
9. Batra S, Rigamonti D. Idiopathic normal pressure hydrocephalus: the benefits and problems of shunting. Nat Clin Pract Neurol. 2009; 5(2):80-1.
Competing interests: The Clinical Research Fellow at Victor Horsley department of Neurosurgery at the National Hospital for Neurology and Neurosurgery salary is supported by a grant from B. Braun Medical Ltd

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