When it really is NPH

Text: Carsten Wikkelsø, Professor of Neurology at the Sahlgrenska Academy and Consultant at the Sahlgrenska University Hospital in Gothenburg

The medical history of a good friend and colleague provides the introduction to this article on normal-pressure hydrocephalus (NPH), an important differential diagnosis for cognitive and motor deficiency that may otherwise be diagnosed as, for example, Parkinson's disease. Professor Emeritus of Hepatology Harold O. Conn, MD, FACP of the Yale University School of Medicine developed symptoms of problems with gait at age 68 years, immediately after retiring. The symptoms became slowly more pronounced in the following years. He was diagnosed by colleagues in neurology at Yale with "Parkinson's disease-like syndrome", based on observed cerebral atrophy (Figure 1).

Figure 1 (Two MR sections, T2-weighted, on illness debut)
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His wife noticed that he gradually lost his intellectual focus and sense of humour, and developed double incontinence. Three newly consulted neurologists gave a diagnosis of a variant of Parkinson's disease (PD), and after a follow up of 5 years predicted that the cerebral atrophy would continue and the condition was untreatable. Nine years after the debut of the disease, the patient had stopped his various hobbies, and applied for an electrical wheelchair, since he could barely walk to the garage. The application was refused, and he was referred by his colleagues in endocrinology to a younger neurologist in another state. Here, he was diagnosed with idiopathic NPH (iNPH, or NPH without known cause). After experiencing immediate improvement following the tapping of 60 ml cerebrospinal fluid, he elected to undergo shunt surgery, and this led to permanent improvement, after 10 years of disease (1).

Professor Conn relinquished his interest for liver disease and devoted the life he had regained to "making NPH a familiar term for physicians and lay people alike". Eight years have now passed, and this period has given articles about the disease and the deficient knowledge of it among doctors. An investigation carried out by questionnaires distributed in association with "Hydrocephalus 2006" in Gothenburg revealed that a majority of district doctors in western Sweden considered themselves to have poor knowledge about the most common symptoms of NPH. The doctors saw an average of 1.3 patients with suspected NPH per year.

NPH is characterised by disturbances of gait and balance, intellectual deficiency and continence problems. The gait is slow and wide-based, with foot dragging, and outwardly rotated feet. Motion in the joints is reduced and arm swing can sometimes be emphasised (shuffling gait). Falls are common, normally backwards, and sometimes occur early in the progression. What is objectively noticed is the patient appears to be pulled backwards, and this is sometime compensated by a forward-leaning posture of the trunk (2). The cognitive difficulties are usually "subcortical", and thus not totally different from those seen in Parkinson's disease, with reduced mental and fine motor speed, impaired memory of recent events, and a difficulty is starting and carrying out actions in a focused manner. It is also common to be affected by reduced wakefulness and an increase in the need for sleep, emotional shallowness, loss of initiative and loss of motivation (3). The problems with continence are usually the last symptom to become apparent, with sudden urgency and incontinence.

It is usually easy to recognise NPH, but the symptoms may be less typical due to symptoms of other concomitant disease (such as vascular disease, Alzheimer's disease or frontotemporal degeneration). There is a significant vascular concomitant disease among patients with NPH (hypertension, diabetes and high concentrations of blood lipids are common).

NPH is caused by a reduced absorption of cerebrospinal fluid to the blood. By definition, the intracranial pressure (ICP) is normal, and the ventricular system dilated due to the cerebrospinal fluid excess. The dilation of the ventricular system in typical cases includes not only the temporal horns but also the 3rd and 4th ventricles. Flattening of the furrows at the brain's highest point is seen, and a corpus callosum angle of less than 90º (Figure 2).

Figure 2, Typical MR changes seen in iNPH
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The diagnostic and predictive value of these MR changes and of measurement of cerebrospinal fluid dynamics are extensively described in "Guidelines for idiopathic NPH" (4). Our colleague, who was misdiagnosed for 9 years, is an example of how difficult it can be to determine whether the dilated ventricles seen by MR (or CT) are a consequence of cerebral atrophy or a disturbance in cerebrospinal fluid dynamics. It is not possible, either, to eliminate the suspicion of NPH in a patient with symptoms by referring to changes in the MR that are consistent with atrophy (5). The opposite is also found: changes typical for NPH that are seen in CT/MR are accidentally discovered in people without any symptom, or with a completely different degenerative disease. The most important differential diagnoses are Binswanger's disease (cerebral small-vessel disease), PD, multiple system atrophy and progressive supranuclear palsy.

The investigation of patients with symptom and with MR/CT-verified dilation of ventricles is intended to confirm the diagnosis of NPH and to predict the outcome of surgery, if undertaken. Currently, more than 80% of those undergoing surgery experience improvement, but since the frequency of complications is relatively high, surgery on patients that does not have an effect should be avoided.

Neurological, neurospsychological, physiotherapy-based observations, MR/CT, and blood and cerebrospinal fluid examinations are important investigations for the diagnosis and prediction. Two methods for the prediction of treatment effect have achieved widespread international use: the measurement of cerebrospinal fluid dynamics (often its resistance to outflow into the blood, Rout) (6), and the effect of cerebrospinal fluid tapping (7).

Swedish scientists have been active in this development and one result (among others) is the development of a new methodology for standardised measurements of cerebrospinal fluid dynamics (CELDA®, Likvor AB) in Umeå, where a highly successful group in hydrocephalus research has been active for many years. The resistance that arises when artificial cerebrospinal fluid is added is measured. The greater the resistance, the stronger are the indications for treatment.

The effects of the tapping of 50 ml cerebrospinal fluid are measured by examining the effects on motor functions and cognitive functions. The greater the effect, the better the result of shunt surgery is expected to be.

The treatment of NPH involves the establishment of a new flow pathway for cerebrospinal fluid from the subarachnoidal cavity to the peritoneum ("ventriculoperitoneal shunt") or to the right atrium of the heart ("ventriculoatrial shunt") through a subcutaneous catheter system (Figure 3). In modern systems the opening pressure of the valve can be manually adjusted, and thus adapted to the individual needs of the user, with the aid of a magnet.

Figure 3
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The shunt system consists of four parts that are all X-ray-opaque and are located in the following order:

1.  ventricular catheter - a silicone tube that opens out into the ventricular system of the brain
2.  the Rickham reservoir - which consists of a silicone upper part and a metal bottom, and is located in the drilled hole
3.  valve housing
4.  a distal silicone tube - opens out into the peritoneum or the right atrium.

When lecturing about NPH, it is common to meet the ideas that this is a very unusual condition and that the results of treatment are so poor that it is hardly worth investigating the case. Both ideas are erroneous.

The prevalence of iNPH, which constitutes approximately half of all NPH, in the Nordic region is approximately 22/100,000 and the incidence is 5.5/100,000, while much higher figures have been reported in Japan, with a prevalence of between 0.5% and 2.9% of all people aged 65 years or older, approximately corresponding to 120-600/100,000. The effects of treatment are good, both in the short-term (80% experience short-term improvement) and in the long-term (up to 60% experience long-term improvement). The survival duration for this group of patients is shorter than that of healthy individuals. This is, however, not a result of the NPH itself, rather of co-morbidity.

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