Dutch normal pressure hydrocephalus study: baseline characteristics with emphasis on clinical findings

We present the baseline characteristics of 101 patients with normal pressure hydrocephalus (NPH), entering a study that evaluates the diagnostic reliability of CSF outflow resistance. Patients were assessed by a gait scale consisting of 10 features of walking and the number of steps and seconds necessary for 10 m, a dementia scale comprising the 10 word test, trail making, digit span and finger tapping, the modified Mini Mental State Examination (3MSE) and the modified Rankin scale (MRS). Inclusion criteria were a gait and dementia scale ≥ 12 (range 2–40), a MRS ≥ 2 and a communicating hydrocephalus on CT. Gait disorder and dementia varied from mild to severe leading to MRS 2 in 17%, MRS 3 in 34%, MRS 4 in 21%, MRS 5 in 16% and MRS 6, including akinetic mutism, in 12%. Only one patient showed both normal tandem walking and turning. Small steps, reduced foot floor clearance and wide base were also frequently seen in the 67 patients walking independently; 34 needed assistance or could not walk at all. Applying the 3MSE, 64% were demented; the remaining 36% exhibited a milder cognitive deficit. The 10 word test and trail making decreased with increasing dementia. Digit span and finger tapping declined in the most demented patients. This group of elderly patients with NPH, mostly of the idiopathic type, proved to be vulnerable because of considerable disability and comorbidity.     

Two elderly patients with idiopathic normal pressure hydrocephalus diagnosed by head MRI and tap test

Dementia, gait disturbance and urinary incontinence were noted in two elderly patients, and diagnosed as idiopathic normal pressure hydrocephalus (iNPH). Case 1 was a 79‐year‐old man in whom dementia symptoms appeared 2 years ago. Gait disturbance and urge incontinence of urine developed later, and the patient visited our hospital. Walking was wide‐based and frozen gait was noted at the time of visiting our hospital. The mini‐mental state examination (MMSE) score was 11. A head MRI detected expansion of the cerebral ventricles and sylvian fissures, and narrowing of the cerebral fissures and the subarachnoid space in the higher convexity region. The diagnosis of iNPH was made based on the clinical symptoms and imaging findings, and a shunt operation (cerebrospinal fluid shunt) was performed in the neurosurgery department. Gait disturbance and cognitive function slightly improved after the operation. Case 2 was an 81‐year‐old woman who had had brachybasia for 1 year, and swayed from side to side while walking. Since disorientation and urge incontinence transiently occurred, the patient visited our hospital. The MMSE score was 24. Head MRI findings were similar to those in case 1. The cerebrospinal tap test was performed, and walking improved in the 1‐week course observation. iNPH is not very well recognized, compared to secondary NPH, and is likely to be overlooked because differentiation from Alzheimer's disease and vascular dementia based on symptoms and imaging is difficult in elderly patients. As iNPH is treatable by accurate diagnosis and therapy, the accumulation of cases indicated for shunt operation may be necessary.     

Motor evoked potentials in the preoperative and postoperative assessment of normal pressure hydrocephalus.

Motor evoked potentials and central motor conduction time (CMCT) were examined from both upper and lower limbs in patients with normal pressure hydrocephalus to find a predictor for the success of shunting procedures. The hypotheses that walking disturbances are due to pyramidal tract compression as well as the possibility that the upper limbs are affected subclinically in these patients were also studied. The study suggests that the walking disturbances are not the result of a major pyramidal tract dysfunction but probably involve the sensorimotor integration leading to normal gait. Furthermore, CMCT measured with electromagnetic motor stimulation can help in selecting the patients that will benefit from shunting. The study does not provide electrophysiological evidence of upper limb involvement in normal pressure hydrocephalus.     

Normal pressure hydrocephalus in geriatric medicine: a challenge

Normal pressure hydrocephalus (NPH) in elderly patients is reviewed. Since the clinical signs that characterize NPH--incontinence, difficulty walking, and dementia--occur frequently in the elderly in association with a wide variety of disorders, attention is paid to the differential diagnosis of NPH on the basis of both clinical findings and laboratory tests. Success rates for treatment of NPH using surgical shunting are discussed, as are mortality rates and complication rates for this type of surgery in the elderly. Factors that may be of value in predicting which NPH patients are most likely to benefit from surgical intervention are reviewed, and the need for the development of pharmacological alternatives to surgery for elderly NPH patients is emphasized. As one of the most treatable causes of dementia in the elderly, NPH should be considered in the diagnosis of demented elderly patients with continence and gait disturbances, and it merits further research.     

Hydrocephalus as a cause of disturbances of gait in the elderly

To investigate the possible role of symptomatic normal-pressure hydrocephalus (NPH) in unexplained walking difficulties of the elderly, we used CT to measure lateral ventricular size. We compared data in 50 patients over the age of 60 with a disturbance of gait and 80 control subjects of similar age who walked well and were mentally sound. Forty-six of the 50 gait patients (92%) had a ventricular span of more than 12 mm, whereas only 5 of the 80 controls (6.3%) had ventricles of that size. There was a narrow zone of overlap. Seventeen of the gait patients later improved after surgical shunting or test withdrawal of lumbar CSF. These findings demonstrate that hydrocephalus is an important cause of disturbances of walking in the elderly. The validity of the study, the clinical picture in NPH, and the nature of NPH are discussed.     

Gait in ageing and associated dementias; its relationship with cognition

The focus of this review is on the close relationship between gait and cognition in ageing and associated dementias. This close relationship is supported by epidemiological studies, clinical studies of older people with and without dementia that focused on the intensity of the physical activity, clinical studies with older persons without dementia examining a relationship between gait and specific cognitive processes, and human and animal experimental studies examining a neural basis for such a relationship. Despite these findings, most studies with patients with dementia focus exclusively on the relationship between cognition and dementia, with relatively few addressing the relationship between gait and dementia. However, subtle disturbances in gait can be observed in ageing and in (preclinical) subtypes of dementia that are not known for prominent motor disturbances, i.e. Mild Cognitive Impairment, Alzheimer's Disease, vascular Cognitive Impairment No Dementia, Subcortical Ischaemic Vascular Dementia, Frontotemporal Mild Cognitive Impairment, and Frontotemporal Dementia, supporting a close relationship between gait and cognition. The relationship between gait and cognition is weakened by the few available intervention studies that examine the effects of walking on cognition in patients with (preclinical) dementia. These studies report equivocal results, which will be discussed. Finally, suggestions for future research will be made.     

Monosymptomatic clinical course of posttraumatic normal pressure hydrocephalus

Triad of Hakim--Adams is well known for normal pressure hydrocephalus (NPH): dementia, gait disturbances and urinary incontinence. Variability of intensity of these symptoms is obvious. However in clinical practice all classic signs are present. We describe a case of posttraumatic NPH producing only gait impairment with intact intellect and memory and bladder function. Such reports were not found in literature.     

Idiopathic normal pressure hydrocephalus]

Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by gait disturbance, dementia, and/or urinary incontinence without causative disorders, and ventricular enlargement due to disturbed CSF circulation. The diagnosis of iNPH in the elderly remains a substantial issue, and the treatment is not always adequately provided. Many patients with possibly curable INPH often are misdiagnosed as having AD or vascular dementia. Recognition of INPH in those patients is of great importance. Here, some key clinical and neuroimaging features distinctive from other dementia are discussed. Also reviewed are the results of the recently completed prospective cohort study of iNPH (Study of iNPH on Neurological Improvement: SINPHONI). In SINPHONI, the MRI-based diagnosis (dilated ventricles associated with narrow dorsal subarrachnoid space) and ventriculoperitoneal shunt with Codman Hakim programmable valve shunt system were validated against 1-year post-surgery outcome.     

Variables predicting surgical outcome in symptomatic hydrocephalus in the elderly

We prospectively studied 30 older patients who had shunt surgery for symptomatic hydrocephalus and measured outcome using serial videotaping of gait, neuropsychological testing, and the Katz index of activities of daily living. Twenty-three patients improved and 7 did not. Using univariate analysis and the Fisher exact test, we found that the following variables were significantly related to outcome: (1) time B-waves present on 24-hour CSF pressure record; (2) anterior/posterior ratio on slice 4 of regional cerebral blood flow study; (3) duration of dementia prior to surgery; and (4) gait abnormality preceding dementia. The following variables showed a trend towards significance: (1) time CSF pressure greater than 15 mm Hg; and (2) scoring either pass or fail on the Multilingual Visual Naming Test. We conclude that several variables are significantly associated with surgical outcome in symptomatic hydrocephalus in the elderly and can be used in deciding whether to recommend surgery.     

Lumboperitoneal shunt and normal pressure hydrocephalus in elderly subjects

Forty six patients who had normal pressure hydrocephalus (NPH) and who presented 2 or more of the 5 following preoperative signs: dementia with gait disturbances and urinary incontinence, gait disturbance as first sign, known etiology, positive lumbar puncture withdrawal test, presence of periventricular hypodensity on CT and absence of visible cerebral sulci, were treated by lumboperitoneal shunt. Postoperative results were evaluated at 1 month, 6 months and 1 year with 60.6 p. 100 of good results. Complications of LP shunts (26 p. 100) were mild and did not compromise the outcome. We emphasize the necessity of clinical selecting criteria before surgery and the value of LP shunt in the treatment of NPH.     

Positron emission tomography with [18F]fluorodeoxyglucose differentiates normal pressure hydrocephalus from Alzheimer-type dementia.

Because diagnostic criteria for normal pressure hydrocephalus have not been clearly determined, it is often difficult to differentiate patients with this potentially treatable condition from those with Alzheimer-type dementia. We have studied three patients with normal pressure hydrocephalus, 17 patients with Alzheimer-type dementia, and seven healthy elderly controls using positron emission tomography and [18F]Fluorodeoxyglucose (FDG). Both Alzheimer-type dementia and normal pressure hydrocephalus groups showed lower cortical rates of FDG utilisation than controls. However, the patterns of metabolic abnormality were distinctly different in the two dementia groups, with Alzheimer-type dementia subjects demonstrating bilateral temporoparietal hypometabolism while normal pressure hydrocephalus subjects showed globally diminished glucose use.     

Hippocampal atrophy correlates with severe cognitive impairment in elderly patients with suspected normal pressure hydrocephalus.

Measurements of hippocampal formation atrophy using MRI have been useful in distinguishing demented patients with a diagnosis of probable Alzheimer's disease from cognitively normal controls. To determine whether there is a similar relationship between hippocampal size and dementia in elderly patients suspected of normal pressure hydrocephalus (NPH), the authors obtained mini-mental status examination (MMSE) scores and MRI measurements of hippocampal size and CSF volume on 16 elderly patients whose severe ventriculomegaly and unexplained gait impairment made NPH a probable diagnosis. Hippocampal size correlated strongly with MMSE score (r = 0.75, p < 0.001); no significant MMSE correlation was found for ventricular CSF volume or extra-ventricular/ventricular CSF ratio. It was concluded that hippocampal atrophy is associated with severe cognitive dysfunction in many elderly patients with a diagnosis of NPH. As a hypothesis for further investigation, the detection of such atrophy may help identify cases where the presence of a pathology of Alzheimer's disease complicates the diagnosis of NPH.     

Outcome of shunt operation on urinary incontinence in normal pressure hydrocephalus predicted by lumbar puncture.

Bladder function in four patients with normal pressure hydrocephalus, one with dementia of Alzheimer type and five patients with multi-infarct dementia was studied by history and urodynamic tests (cystometry and Bor's ice water test). The bladder hyperactivity could be temporarily improved by a lumbar puncture and removal of 50 ml CSF and later abolished by a shunt operation in patients with normal pressure hydrocephalus while no changes occurred in the other patients. Urodynamic testing in connection with a lumbar puncture may be a reliable way to predict the outcome of a shunt operation in cases of normal pressure hydrocephalus.     

Gait disturbance in patients with low pressure hydrocephalus.

Using criteria of the classification recently described by Nutt et al., we examined gait disorder in five patients with normal pressure hydrocephalus (NPH). Their cerebrospinal fluid (CSF) pressures were in the normal range, and trials of CSF removal produced temporary improvement of symptoms. Surgical procedures to relieve hydrocephalus improved gait disorders in all patients. No patient showed spasticity, sensory ataxia, cerebellar ataxia, extrapyramidal signs, or limb apraxia. All walked slowly with a wide base and a short stride. The arm swing normally associated with walking was preserved. In standing, patients were unsteady and fell easily when pushed. Four patients showed hesitation in initiating walking and in turning. These clinical features fit Nutt's criteria for frontal gait disorder and frontal disequilibrium. Unlike findings in Parkinson's disease, where similar gait disorders may occur, other extrapyramidal signs, Myerson's sign, and upper limb dysfunction were absent in NPH, and arm swing while walking was preserved. We suspect that ventricular dilatation disturbs neuronal connections between the supplementary motor area and the globus pallidus in NPH patients.     

Dementia associated mental and behavioural disturbances in elderly people in the community: findings from the first Nakayama study

OBJECTIVE: To determine the prevalence of mental and behavioural disturbances associated with dementia in elderly people living in the Japanese community of Nakayama. METHODS: A door to door three phase population survey was carried out on all persons aged 65 years and older living at home. The study included a psychiatric interview, neurological and neuropsychological examination, and cranial computed tomography. Participants with dementia were rated on the neuropsychiatric inventory. RESULTS: Of 1438 inhabitants, 1162 (81.0%) completed the protocol. The prevalence of dementia was 4.8%. Of the 60 participants with dementia (Alzheimer's disease 35%, vascular dementia 47%, and dementia from other causes 17%), 53 (88.3%) had shown one or more mental and behavioural disturbances. Apathy/indifference (56.7%), followed by agitation/aggression (35%), aberrant motor behaviour (31.7%), and irritability (31.7%) were the common symptoms. More productive (positive) symptoms such as delusions and aberrant motor behaviour were found in the Alzheimer group than in the vascular dementia group. CONCLUSIONS: A wide range of dementia associated mental and behavioural disturbances developed in the majority of community dwelling individuals with dementia. The findings suggest that a screening programme focusing on identifying these symptoms should be included in the physician's diagnostic tools for dementia.     

Subcortical arteriosclerotic encephalopathy (Binswanger's disease). Computed tomographic, nuclear magnetic resonance, and clinical correlations

Twenty-three elderly patients were found to have a consistent pattern of leukoencephalopathy by computed tomography and nuclear magnetic resonance imaging. Eight patients presented with vague, nonspecific symptoms and had no neurologic deficits. The other 15 patients had neurologic deficits that presented in one of three ways: stroke, seven patients; slowly progressive dementia and gait disturbance, five patients; or slowly progressive dementia alone, three patients. Risk factors for arteriosclerosis (hypertension, diabetes) were present in 18 patients (78%). The necropsy of one patient revealed arteriosclerotic vasculopathy characteristic of subcortical arteriosclerotic encephalopathy (SAE) or Binswanger's disease. Subcortical arteriosclerotic encephalopathy may be a relatively common affliction of elderly patients, most of whom have risk factors for arteriosclerosis. The modes of presentation and associated clinical signs are variable, and more than one third may have no neurologic deficit. In some cases SAE overlaps with normal pressure hydrocephalus by clinical and neuroimaging criteria. Some patients with normal pressure hydrocephalus who do not respond to ventricular shunting may actually have SAE.     

Ventriculomegaly and balance disturbances in patients with TIA

Israelsson H, Birgander R, Ambarki K, Eklund A, Malm J. Ventriculomegaly and balance disturbances in patients with TIA.
Acta Neurol Scand: 2012: 125: 163–170.
© 2011 John Wiley & Sons A/S. Objectives – Dilated ventricles and gait disturbances are common in the elderly, and these are also features of the treatable syndrome idiopathic normal pressure hydrocephalus (INPH). Many studies report an association between hypertension, vascular disease and INPH. The objective of this study was to study the frequency of ventriculomegaly, with or without hydrocephalic symptoms, in patients who had suffered from a transitory ischaemic attack (TIA). Methods – Gait, Romberg sign, tandem standing and one‐leg stance were consecutively evaluated in elderly >24 h after a TIA. Ventricular size, white matter lesions and atrophy were assessed on computed tomography scans. Exclusion criteria were conditions possibly influencing the balance tests. Results – Seventy‐six patients with TIA out of 105 were included. Ventriculomegaly [Evans Index (EI) > 0.30] was observed in 19.7% and very large ventricles (EI > 0.33) in 7.9%. Ventriculomegaly was found in 58% of the patients with a previous ‘history of balance or gait disturbance’, but only in 12% of those without any prior disturbance (chi‐square test; P = 0.0009). Three out of 76 patients with TIA (3.9%) fulfilled both radiological and clinical criteria for ‘possible INPH’. Conclusion – Ventriculomegaly is a common finding in elderly. One out of 20 patients with TIA may suffer from INPH, existing before and independent of the TIA diagnosis. Therefore, patients presenting with ventriculomegaly and gait/balance disturbances not attributable to other causes should be referred to a hydrocephalus centre or a neurologist with special interest in INPH.     

Cerebral amyloid angiopathy in senile dementia--a comparison between senile dementia and Alzheimer disease

The brain was examined neuropathologically in 16 elderly patients with severe dementia (8 cases of senile dementia, 5 of vascular dementia and 3 of combined senile-vascular dementia), focussing an attention on amyloid angiopathy and and other senile changes. The findings were compared with the results obtained in 10 cases of Alzheimer disease described previously. Amyloid angiopathy was noted in all cases of senile dementia and its distribution was similar to that of Alzheimer disease. The frequency of cerebral amyloid angiopathy in elderly patients with severe dementia was more closely related to disease than to age. One patient each with senile dementia and combined senile-vascular dementia showed markedly advanced amyloid angiopathy. The cases who showed other senile changes (e. g., senile plaque, Alzheimer neurofibrillary tangle, nerve cell deciduation) were frequently seen in patients with Alzheimer disease than in those with senile dementia. Further, there was a tendency that the brain weight was lighter in patients with Alzheimer disease than in those with senile dementia.     

Differential circadian rhythm disturbances in men with Alzheimer disease and frontotemporal degeneration

BACKGROUND: Caregiver exhaustion is a frequent consequence of sleep disturbance and rest-activity rhythm disruption that occurs in dementia. This exhaustion is the causal factor most frequently cited by caregivers in making the decision to institutionalize patients with dementia. Recent studies have implicated dysfunction of the circadian pacemaker in the etiology of these disturbances in dementia. METHODS: We studied the activity and core-body temperature rhythms in a cohort of 38 male patients with a clinical diagnosis of probable Alzheimer disease (AD) approximately 2 years before death. These patients were later given a confirmed diagnosis of AD (n = 23), frontotemporal degeneration (FTD) (n = 9), or diffuse Lewy body disease (DLB) with mixed AD or FTD pathologies (n = 6) after autopsy and neuropathological examination. Physiological rhythms of patients with AD and FTD were then compared with a group of normal, elderly men (n = 8) from the community. RESULTS: Alzheimer patients showed increased nocturnal activity and a significant phase-delay in their rhythms of core-body temperature and activity compared with patients with FTD and controls. The activity rhythm of FTD patients was highly fragmented and phase-advanced in comparison with controls and apparently uncoupled from the rhythm of core-body temperature. CONCLUSIONS: Patients with AD and patients with FTD show different disturbances in their rhythms of activity and temperature compared with each other and with normal elderly patients.     

Dementia: characteristics of a referral population and factors associated with progression

We evaluated in a standard fashion 375 patients presenting with complaints of memory loss. Etiology of memory loss included senile dementia of the Alzheimer type (SDAT)-70%, vascular dementia-5%, mixed dementia (SDAT + vascular)-9%, and other etiologies-16%. Incontinence, transient symptoms, and gait disturbances occurred more frequently in vascular dementia than in SDAT. A history of cardiovascular disease and stroke was more common in vascular dementia than SDAT. Disturbances of gait, bradykinesia, and pyramidal tract findings were commonly seen in vascular dementia. Advanced technology aided diagnosis in only 6% of patients and CT was the most useful of such tests. An earlier age of onset was noted in those with a positive family history of SDAT. Duration of symptoms at presentation for SDAT patients varied inversely with the rate of progression of dementia 15 to 55 months later, suggesting that individuals who progress more slowly require more time to elapse before the family or patient realizes the need for medical attention.