What occurance results from obstruction within the ventricles of the brain or inadequate reabsorption of cerebrospinal fluid?

Normal pressure hydrocephalus (NPH) is increasingly recognized as a treatable cause of gait disturbance, cognitive decline, and urinary incontinence in the aging population. The impact of treatment on both improved quality of life and decreased need for institutional care is potentially very great, and will only increase as the population ages. This article provides a state-of-the-art review of the presentation, diagnosis, surgical treatment, and clinical management of idiopathic normal pressure hydrocephalus (iNPH). In particular, new clinical guidelines and recently developed programmable valve technology that makes the diagnosis more sure and the safer treatment are detailed.

Prevalence, Prognosis, and Definition

Normal pressure hydrocephalus is a relatively rare disorder characterized by enlargement of the ventricles, a gait disorder, incontinence, and cognitive impairment. Although some studies have suggested that up to 5% of patients with dementia have normal pressure hydrocephalus, other studies have found the prevalence to be closer to 1%, which is consistent with our experience of patients referred to a memory disorders clinic (for a review see Tanaka et al., 2009). It may, however, be underdiagnosed in the general population; one study showed that 5.9% of individuals 80 years and older met criteria for normal pressure hydrocephalus (Jaraj et al., 2014).

II.J.3 Normal Pressure Hydrocephalus

Normal pressure hydrocephalus (NPH) was first described in 1965 and generated substantial enthusiasm because it was thought to represent a dementia syndrome that could be treated successfully with shunting procedures. The clinical features of NPH include dementia, gait disorder, and incontinence, reflecting primary involvement of the subfrontal white matter. The disorder sometimes follows TBI, infection, or subarachnoid hemorrhage but is frequently idiopathic. Although undoubtedly some cases exist that have been successfully reversed with a shunt, these cases are disappointingly rare; moreover, complications of the shunt procedure are common. Nevertheless, NPH is a good example of dementia due to potentially reversible structural involvement of the cerebral white matter.

Variant

Normal pressure hydrocephalus (NPH), affecting mainly the elderly in their sixth or seventh decade of life, is marked by ventricle enlargement without an apparent increase in CSF pressure. NPH exhibits the classic triad of symptoms (popularly known as the Hakim’s or Adam’s triad)—urinary incontinence, gait disturbance, and dementia (commonly referred to as wet, wobbly, wacky). NPH is caused by an increase in ICP due to an abnormal accumulation of CSF in the ventricles of the brain, which can cause the ventricles to enlarge. The ICP gradually falls but still remains slightly elevated compared with baseline measurements. The enlarged ventricles exert pressure on the adjacent cortical tissues, causing the symptoms. NPH may be idiopathic or secondary. Secondary NPH can be due to a subarachnoid hemorrhage, head trauma, tumor, infection in the central nervous system, or a complication of cranial surgery.

Hydrocephalus ex vacuo is a compensatory enlargement of the CSF spaces in response to brain parenchyma loss (as occurs in cerebral atrophy or post trauma) and is not the result of increased CSF pressure.

Normal-Pressure Hydrocephalus

NPH is a quintessential correctable cause of dementia. Most cases of NPH are idiopathic, but meningitis or subarachnoid hemorrhage often precedes it. In those cases, inflammatory material or blood probably clogs the arachnoid villi overlying the brain and impairs reabsorption of CSF. As CSF production continues despite inadequate reabsorption, excessive CSF accumulates in the ventricles and expands them to the point of producing hydrocephalus (Fig. 7-9).

NPH is essentially a syndrome of three elements: dementia, urinary incontinence, and gait apraxia. The dementia conforms to the subcortical classification because it entails slowing of thought and gait, but spares language skills. Although the dementia may bring the patient to a psychiatrist's attention, gait apraxia is generally the initial, most consistent, and most prominent feature of NPH (Fig. 7-10). It is also the first to improve with treatment (see later). Urinary incontinence consists of urgency and frequency that progress to incontinence, and it also improves with treatment. The physical features of NPH easily separate it from Alzheimer disease and other dementia-producing illnesses.

In NPH, CT and MRI show ventricular dilation, particularly of the temporal horns (see Figs 20-7 and 20-19), and sometimes signs of CSF reabsorption across ventricular surfaces. They show minimal or no cerebral atrophy. Nevertheless, diagnosing NPH exclusively by CT and MRI is unreliable because the findings are nonspecific, particularly because they resemble cerebral atrophy with resultant hydrocephalus (hydrocephalus ex vacuo, see Fig. 20-3). The CSF pressure and its protein and glucose concentrations are normal.

One worthwhile test is simply to withdraw large volumes (30–60 mL) of CSF by LP or to perform a series of three LPs. Following the removal of large volumes of CSF, which presumably reduces hydrocephalus, improvement in the patient's gait – not necessarily the dementia – indicates NPH and predicts a benefit from permanent CSF drainage. A negative test, however, does not preclude the diagnosis.

NPH can be relieved by a neurosurgeon inserting a shunt into a lateral ventricle to drain CSF into the chest or abdominal cavity. However, a clinically beneficial response occurs inconsistently and neurosurgical complications, which can be devastating, occur in up to 30% of cases.

Normal pressure hydrocephalus

Normal pressure hydrocephalus (NPH) should be considered in the differential diagnosis of all patients with progressive gait disturbance and other parkinsonian features (Curran and Lang, 1994; Vanneste, 2000; Palm et al., 2009). Since the CSF pressure is not always normal and the disorder seems to be quite heterogeneous in terms of age at onset and clinical presentation, the term chronic hydrocephalus has been proposed (Bret et al., 2002). The gait and parkinsonian features associated with NPH include short steps, wide base, stiff legs, start hesitation, and freezing (“magnetic gait”). In contrast to other parkinsonian disorders associated with freezing, the gait of patients with NPH usually does not improve with visual clues (Lai and Jankovic, 1995). In addition to the characteristic gait disturbance, the NPH patients frequently exhibit bradykinesia, flexed posture, and loss of postural reflexes as well as cognitive decline and urinary incontinence. In contrast to PD, patients with NPH have near normal leg function in supine and sitting positions, and they tend to have less tremor. Some patients with NPH may later develop PD (Curran and Lang, 1994). Shunting may be considered for patients with NPH in whom gait disturbance precedes mental impairment and the mental impairment is of recent origin and mild. Other predictors of favorable outcome after shunting include a known cause of NPH, absence of white matter lesions on MRI, a substantial clinical improvement after CSF tap, 50% occurrence of B-wave on intracranial pressure recording, and resistance to CSF outflow of at least 18 mmHg per minute during CSF infusion test.

Patients with short history, a known cause of hydrocephalus, predominant gait disorder, and imaging studies suggestive of hydrodynamic hydrocephalus without cortical atrophy and without white matter involvement, are considered the best candidates for shunting, and 50–70% experience substantial improvement after surgery (Vanneste, 2000). In one study of 55 patients treated with shunting for NPH, the improvement was sustained during the mean follow-up of 5.9 ± 2.5 years, with gait and cognitive function improving the most (Pujari et al., 2008). NPH is sometimes difficult to differentiate from vascular parkinsonism or subcortical arteriosclerotic encephalopathy (SAE). The CSF sulfatide concentration was markedly increased in patients with arteriosclerotic encephalopathy (mean: 766 nmol/L, range: 300–3800 nmol/L) and this test distinguished between patients with arteriosclerotic encephalopathy and those with NPH with a sensitivity of 74% and a specificity of 94%, making it an important diagnostic marker (Tullberg et al., 2000). Obstructive hydrocephalus, with or without aqueductal stenosis, can also result in parkinsonism that may respond to levodopa (Jankovic et al., 1986; Zeidler et al., 1998; Racette et al., 2004). Most patients with disabling symptoms of hydrocephalus-associated parkinsonism require ventriculoperitoneal shunting. Despite aggressive marketing directly to patients by various companies promoting their shunting devices (e.g., Codman), NPH is actually quite uncommon and even well-selected patients do not always obtain satisfactory results from shunting (http://www.ninds.nih.gov/disorders/normal_pressure_hydrocephalus/normal_pressure_hydrocephalus.htm).

Normal Pressure Hydrocephalus

Normal pressure hydrocephalus (NPH) often presents with the classical triad of cognitive impairment, urinary incontinence, and gait apraxia with associated significant ventricular enlargement out of proportion with cortical atrophy on imaging studies. The cognitive profile is one of marked slowing, and the apraxia is virtually confined to gait with the characteristic glued-to-the-floor ‘magnetic’ gait. The etiology in many cases is unclear, although some are secondary to head injury, subarachnoid hemorrhage, or meningitis. Although many patients with NPH respond to removal of cerebrospinal fluid at lumbar puncture, predicting which patients will respond to ventricular shunting procedures is far from reliable with MRI, and intracranial pressure monitoring fails to reliably predict outcome.

PATHOGENESIS AND PATHOPHYSIOLOGY

Normal‐pressure hydrocephalus (NPH) is the result of an imbalance between production and resorption of the CSF, usually around the brain convexities. Whereas there is full communication between the ventricles and the subarachnoid space (communicating hydrocephalus), the communication between the subarachnoid space and the arachnoid villi and granulations is not intact, so fluid is not transferred efficiently to the superior sagittal sinus. Subarachnoid hemorrhage, meningitis, head trauma, and elevated levels of CSF protein all cause thickening of the arachnoid or obstruction of the subarachnoid space. A relatively large number of patients do not have an identifiable cause for hydrocephalus, and, pathophysiologically, their lesion best fits with reduced resorption of CSF, based on studies of increased resistance to CSF outflow.48 Less frequently, intracranial tumors, stenosis of the aqueduct of Sylvius, and arachnoid cysts (causes mainly discussed in the previous section) can cause NPH due to obstruction within the ventricular system, and normal pressure is maintained as a result of apparent compensations.

In spite of its name, it appears that intracranial pressure in NPH is not always normal. Physiological experiments suggest that a transient elevation of pressure may increase ventricular size and a new fluid balance is reached with normal pressure but with a higher force, based on Pascal's law of pressure in fluids. Other mechanisms may include abnormal ventricular distensibility, increased CSF pulse amplitude, and increased transmantle pressure gradients between the intraventricular and subdural spaces that lead to expansion of the ventricles.

EPIDEMIOLOGY AND RISK FACTORS

NPH has its highest prevalence in the late middle‐aged and elderly groups, and is rare in patients younger than 60 years of age. On the other hand, neonates, infants, children, adolescents, and young adults can develop primary or secondary NPH. It accounts for 5% of patients with dementia in the older age group, but its prevalence in the general population is unknown.

CLINICAL FINDINGS AND ASSOCIATED DISORDERS

The triad of progressive dementia, gait disturbance, and urinary incontinence was originally described by Adams and colleagues.49 In most instances, gait disturbance is the first sign, followed by dementia, and, later, urinary dysfunction. The gait is slow, unsteady, and wide‐based (Video 54, Normal‐Pressure Hydrocephalus). Steps are usually short, and patients have difficulty picking their feet off the ground to ambulate (so‐called magnetic gait). Turning is difficult and takes several steps. On examination, there is bradykinesia, and the legs may be spastic with increased reflexes. Patients may have difficulty in handwriting and dressing, and may appear to be mildly parkinsonian, but their tremor, if present, is usually postural, not resting. One particular feature is the discrepancy between leg function during walking and simulated walking when sitting. Patients can usually move their legs well and imitate walking while in a chair, but they become awkward and severely impaired as soon as they attempt to walk. This dyspraxia for gait eliminates a pyramidal lesion.

Cognitive decline is clinically multidimensioned and involves impaired attention, poor memory, and poor executive function.50 Apathy and bradyphrenia are common, whereas aphasia and upper extremity limb dyspraxia are uncommon.

Neuroanatomically, the gait dysfunction and urinary impairment are believed to relate to the stretched fibers innervating the legs and sphincters that project through the vicinity of the frontal horns of the ventricular system. Compromised microcirculation due to increased intraparenchymal pressure may contribute to the cognitive impairment. Positron‐emission tomography (PET) data suggest that glucose utilization defects are widespread in NPH and involve subcortical and cortical regions.

EVALUATION AND DIFFERENTIAL DIAGNOSIS

Because the clinical picture of NPH is not specific, especially in the younger patient, several diagnostic tests play a crucial diagnostic role. CT or MRI scans are important to establish the presence of hydrocephalus. The diagnosis of NPH is supported when the anterior ventricular horns measure greater than 30% of the diameter of the cranial cavity and the inferior horns are wider than 2 mm. On T2‐weighted MRI, increased signal in the periventricular areas occurs due to presumed transependymal exudation of CSF. Other findings can suggest alternate diagnoses: for example, a normal‐sized fourth ventricle with dilated third and lateral ventricles usually indicates aqueductal stenosis.

Clinically, dementing illnesses of all types must be differentiated from NPH. Alzheimer's disease is not associated with marked gait dysfunction, and a patient with multi‐infarct dementia or Binswanger's disease may have a similar clinical presentation to a patient with NPH but has MRI signs of multiple strokes. In younger patients, in whom the classic clinical triad may not be met, the differential diagnosis is wider.

A lumbar puncture usually reveals normal CSF pressure. Furthermore, removal of 20 to 50 mL of CSF may cause clinical improvement in cognitive and gait dysfunction supporting the diagnosis of NPH. Intermittent pressure B‐waves detected by intracranial monitoring devices suggest decreased brain compliance and NPH. Radioisotope cisternography is used most often but is not particularly specific. Whereas in normal subjects isotope injected intrathecally can be seen around the brain convexity within 48 hours, reflux into the ventricles and stasis beyond 48 hours are often seen with NPH. However, this finding has relatively low predictive accuracy in the diagnosis of NPH and the response to therapy by shunting procedures.51

MANAGEMENT AND PROGNOSIS

The primary treatment is large‐volume lumbar puncture and eventual ventricular shunting. However, selection of patients for shunting is controversial; most reports agree that dementia of less than 2 years' duration and typical gait and urinary dysfunction should be considered for shunting as long as there is no evidence for a multi‐infarct state on MRI scans. Medical management can include acetazolamide or digoxin to decrease CSF production. The rate of complications of CSF‐diverting procedures is approximately 30%, with 5% being serious with long‐term sequelae.52 Subdural hematomas, intracranial infections, stroke, and failure of the shunt are the major complications. The proportion of patients who experience long‐term benefit from this treatment range from 25% to 80%.

SYNDROMES OF ALTERED CSF DYNAMICS

Several syndromes occur when the normal production or flow of CSF is altered. Those syndromes related to obstruction of the ventricular system, either the foramen leaving the lateral ventricles or the third or fourth ventricle cause “obstructive hydrocephalus,” discussed primarily in Chapter 1 because altered level of consciousness is the usual overriding symptom. Another condition, normal pressure hydrocephalus, as a syndrome, is discussed in this chapter and further details are available in various Chapters in Part Three dealing with specific etiologies associated with this clinical picture.

Normal-pressure hydrocephalus

NPH was first described by Hakim and Adams in 1965 (Adams et al., 1965). At that time, the cause was not known, i.e., the disease was considered “idiopathic.” Since that time, patients with known causes of chronic communicating hydrocephalus have also been included as part of NPH. These known cases tend to be younger and respond better to shunting than the idiopathic variety, possibly because of poor historic selection criteria for the latter.

When an elderly patient presents with a gait disturbance and dementia suggestive of NPH, the first diagnostic test is usually an MRI looking for ventricular dilatation out of proportion to any sulcal enlargement, i.e., the pattern of communicating hydrocephalus rather than atrophy (Fig. 28.1). The amount of interstitial edema surrounding the lateral ventricles should be minimal to absent (which goes along with the normal mean intraventricular pressure). There is frequently associated evidence of deep white-matter ischemia (DWMI), a.k.a. small-vessel ischemia (Fig. 28.1), a.k.a. leukoaraiosis (Bradley et al., 1991a). The third ventricle is often bowed out and may have a prominent CSF flow void which extends down through the aqueduct to the obex of the fourth ventricle (Figs 28.1 and 28.2).

The CSF flow void is indicative of hyperdynamic CSF flow similar to the flow voids seen in arteries on MRI. The extent of the CSF flow void on conventional proton density-weighted spin-echo images in the past (Fig. 28.1) was found to correlate with successful response to ventriculoperitoneal shunting for NPH (Bradley et al., 1991b). Unfortunately, the more modern MRI techniques such as fast/turbo spin echo are much more intrinsically flow-compensated, thus the flow void is less conspicuous now than in the early days of MRI; however, when present it means the flow is extremely hyperdynamic (Fig. 28.2). This led to the development of more sophisticated phase-contrast (PC) MRI techniques to evaluate CSF flow for the selection of appropriately symptomatic patients for possible ventriculoperitoneal shunting for NPH (Nitz et al., 1992).

F. Normal-Pressure Hydrocephalus

Normal-pressure hydrocephalus is often idiopathic, but has also been associated with many neurological diseases. The classic triad of symptoms includes frontal dementia, urinary incontinence, and gait disorder with unsteadiness. It is associated with enlargement of the cerebral ventricles on CT or MRI and a cerebrospinal fluid pressure of 180 mm H2O or less. A dynamic test is necessary to confirm the diagnosis of true (opposed to ex vacuo) hydrocephalus (Borgesen and Gjerris, 1982). The removal and 50 ml of cerebrospinal fluid may improve the symptoms of gait disorder (Sudarsky and Simon, 1987). Mental dysfunction improves less than gait after a shunt. The patient walks wide-based with small steps, feet “glued to the floor,” marked imbalance, and difficulty initiating walking. Postural instability with frequent falling may occur. Clinical signs may include hyperreflexia, extensor plantar responses and extrapyramidal signs, including hypokinesia and freezing during walking. Diagnosing normal-pressure hydrocephalus may be difficult since the three cardinal symptoms are common in the elderly. Moreover, gait disorder may precede other symptoms for several years and can be the only symptom for a long period. Normal-pressure hydrocephalus is a common cause of gait disorders in the elderly, while in dementia it accounts for only 0–5% of persons with dementia (Fisher, 1982). It should account for 4–6.7% of the gait disorders in the elderly (Sudarsky and Ronthal, 1983; and Sudarsky, 1997).