Background (Physicians)
Normal pressure hydrocephalus (NPH) is a clinical syndrome characterised by the gradual onset of worsening gait apraxia, dementia and incontinence, referred to as the classical symptom triad. NPH was first described by Solomon Hakim in 1964 (1), and gained popular medical acceptance with its description in the New England Journal in 1969 (2).
The symptomology can be variable, and there may often be only one or two of the classical triad of symptoms. NPH may also present with more overt psychiatric symptoms such as mania or depression, and other neurological features such as speech impairment or drop attacks (see Publications - Case Reports). Essentially NPH should be a serious consideration in any patient who presents with one or more of gait disorder, dementia or incontinence, or any other unexplainable, gradual onset of neurological or psychiatric dysfunction.
The first stage of investigation should be a CT or MRI scan. These studies commonly show increased ventricular size, and a reduction of both periventricular white matter, and cortical grey matter. Patients with symptoms, and these radiological findings should be referred to a Neurosurgeon with experience in NPH for further evaluation. Furthermore patients with the classical triad of symptoms and an apparently normal CT or MRI should also be evaluated fully for the possibility of NPH. The differential diagnoses are Alzheimer's disease, Binswangers disease, neurosyphilis, hypothyroidism, chronic subdural hematoma, intracranial neoplasia, alcoholic dementia and chronic electrolyte disturbances.
Alzhemier's disease, Binswanger's disease and NPH may all present with dementia and dilated cerebral ventricles. It is almost impossible to distinguish from normal CT or MRI, whether ventricles are dilated primarily because of cerebral atrophy (Alzheimer's and Binswanger's) or because of NPH. However the clinical course of illness may provide important clues. In Alzheimer's disease the course of symptom onset may have been very gradual, over years; memory impairment is usually the first sign, and gait disturbance with incontinence only occurs in the very late stages of disease. Binswanger's disease (arteriosclerotic dementia) has a similar course to Alzheimer's and there may a history of either risk factors for atherosclerotic disease, and/or stroke and transient ischemic attacks. NPH however may show gait disturbance and incontinence with only very mild cognitive disturbance, and the onset of symptoms, although gradual is usually of the order of months, rather than years. NPH may also occur after subarachnoid hemorhage, infection, CNS trauma, and neoplasia. When there is no antecedent factor it is "idiopathic" NPH.
The pathological cause of NPH is not currently known. Several possibilities have been discussed in the literature. Certainly there have been reports of diminished cerebral blood flow, altered cerebral autoregulation (3), and reductions in the cerebral metabolic rate of glucose use (4). However it is difficult to understand whether these findings are the cause of NPH or simply a result of disordered neural function. There are clearly abnormalities in the flow and/or absorption of CSF. This has been demonstrated using CSF pressure dynamics studies, in which the most common finding is an abnormality of CSF absorption (5), and also with CSF flow studies (most recently using MRI), where CSF flow through the aqueduct appears to be increased (6). Abnormalities of CSF production are not commonly found.
The leading theory for the cause of NPH is therefore an abnormal CSF absorption pathway. However it is difficult to understand why this increase in CSF volume occurs in the absence of a rising ICP. It has been suggested that very early in the disease, ICP may rise, and the ventricular dilation is a compensatory mechanism to reduce the ICP. It is equally possible that the changes occur so slowly that ICP never acutely rises, but rather "erodes" aging cerebral tissue, in order to compensate for the increased CSF volume. An erosive process such as this may be enhanced by areas of low CBF, and indeed there is a strong association between NPH and cardiovascular disease, diabetes mellitus and hypertension (7). Furthermore these features predict a poorer response to treatment (8).
Whilst attractive, this hypothesis is weakened by the fact that patients may dramatically improve over a matter of days if a volume of CSF is removed. Therefore the clinical symptoms must relate in part, to a reversible neuronal dysfunction, as opposed to a frank destruction of tissue. It has been postulated that the gait apraxia and incontinence are caused by compression of long-tracts. This presupposes some degree of pressure gradient within the cranial vault, which is not measurable as an ICP change per se. Shunting may improve symptoms either by regulation of ICP to the opening pressure of the shunt valve, or by actually removing a volume of CSF.
References:
(1) Hakim S.Some observations on CSF pressure: Hydrocephalic syndrome in adults with "Normal" CSF pressure. Thesis No. 957. Javeriana University School of Medicine, Bogota, Colombia, March 10, 1964.
(2) Adams RD, Fisher CM, Hakim S, Ojemann RG, Sweet WH: Symptomatic occult hydrocephalus with "normal" cerebrospinal fluid pressure. A treatable syndrome. The New England Journal of Medicine, 273 (3): 117-126, July 1965.
(3) Tanaka A. Kimura M. Nakayama Y. Yoshinaga S. Tomonaga M. Cerebral blood flow and autoregulation in normal pressure hydrocephalus. Neurosurgery. 40(6):1161-5; discussion 1165-7, 1997 Jun.
(4) Tedeschi E. Hasselbalch SG. Waldemar G. Juhler M. Hogh P. Holm S. Garde L. Knudsen LL. Klinken L. Gjerris F. et al. Heterogeneous cerebral glucose metabolism in normal pressure hydrocephalus. Journal of Neurology, Neurosurgery & Psychiatry. 59(6):608-15, 1995 Dec.
(5) Borgesen SE, Gjerris F (1982) The predictive value of conductance to outflow of CSF in normal pressure hydrocephalus. Brain 105: 65-86.
(6) Gideon P. Stahlberg F. Thomsen C. Gjerris F. Sorensen PS. Henriksen O. Cerebrospinal fluid flow and production in patients with normal pressure hydrocephalus studied by MRI. Neuroradiology. 36(3):210-5, 1994 Apr.
(7) Casmiro M. D'Alessandro R. Cacciatore FM. Daidone R. Calbucci F. Lugaresi E. Risk factors for the syndrome of ventricular enlargement with gait apraxia (idiopathic normal pressure hydrocephalus): a case-control study. Journal of Neurology, Neurosurgery & Psychiatry. 52(7):847-52, 1989 Jul.
(8) Boon AJ. Tans JT. Delwel EJ. Egeler-Peerdeman SM. Hanlo PW. Wurzer HA. Hermans J. Dutch Normal-Pressure Hydrocephalus Study: the role of cerebrovascular disease. Journal of Neurosurgery. 90(2):221-6, 1999 Feb.