Normal Pressure Hydrocephalus Syndrome Research Articles

Proposal for a normal pressure hydrocephalus syndrome center of excellence

Normal pressure hydrocephalus syndrome, characterized by ventriculomegaly and the classic triad of symmetric gait disturbance, cognitive decline, and urinary incontinence, is the most common cause of hydrocephalus in the adult population and a significant cause of reversible dementia among older adults. The only effective treatment for this syndrome, to date, is a cerebrospinal fluid shunting procedure, commonly a ventriculoperitoneal, ventriculoatrial, or lumboperitoneal shunt. The shunting success rate ranges between 73 and 96%. Hence, early identification, proper diagnosis, and treatment are paramount.We designed a protocol-based program supported on the best available evidence for an integral approach of patients with normal pressure hydrocephalus syndrome. The protocol consists of a series of patient-centered tests and interventions performed on adults with clinical suspicion, leading to optimized and sustainable outcomes for patients living with this condition.The program obtained the recognition of the Joint Commission International as an accredited center of excellence. The objectives of our center are increasing awareness and knowledge of normal pressure hydrocephalus syndrome within the community, delivering optimized interdisciplinary care, mitigating risks, improving quality of life to patients and their families, and ultimately saving from oblivion a significant number of patients who would be otherwise condemned.

Poroelastic Mechanical Properties of the Brain Tissue of Normal Pressure Hydrocephalus Patients During Lumbar Drain Treatment Using Intrinsic Actuation MR Elastography

Hydrocephalus (HC) is caused by accumulating cerebrospinal fluid resulting in enlarged ventricles and neurological symptoms. HC can be treated via a shunt in a subset of patients; identifying which individuals will respond through noninvasive imaging would avoid complications from unsuccessful treatments. This preliminary work is a longitudinal study applying MR Elastography (MRE) to HC patients with a focus on normal pressure hydrocephalus (NPH). Twenty-two ventriculomegaly patients were imaged and subsequently received a lumbar drain placement for cerebrospinal fluid (CSF) drainage. NPH lumbar drain responders and NPH syndrome nonresponders were categorized by clinical presentation. Displacement images were acquired using intrinsic activation (IA) MRE and poroelastic inversion recovered shear stiffness and hydraulic conductivity values. A stable IA-MRE inversion protocol was developed to produce unique solutions for both recovered properties, independent of initial estimates. Property images showed significantly increased shear modulus (p = 0.003 in periventricular region, p = 0.005 in remaining cerebral tissue) and hydraulic conductivity (p = 0.04 in periventricular region) in ventriculomegaly patients compared to healthy volunteers. Baseline MRE imaging did not detect significant differences between NPH lumbar drain responders and NPH syndrome nonresponders; however, MRE time series analysis demonstrated consistent trends in average poroelastic shear modulus values over the course of the lumbar drain process in responders (initial increase, followed by a later decrease) which did not occur in nonresponders. These findings are indicative of acute mechanical changes in the brain resulting from CSF drainage in NPH patients.

Does aqueductal stenosis influence the lumbar infusion test in normal-pressure hydrocephalus?

Late-onset idiopathic aqueductal stenosis may present with clinical features indistinct from idiopathic normal-pressure hydrocephalus (NPH). Moreover, aqueductal stenosis (AS) is not always detected by conventional magnetic resonance imaging (MRI). The aim of this study was to compare the hydrodynamic pattern among NPH patients according to the patency of the aqueduct. Fifty-six consecutive lumbar infusion tests were performed in patients with NPH syndrome. Precipitating causes of hydrocephalus were excluded, and aqueductal patency was examined through high-resolution, T2-weighted 3D MRI. Patients were classified into two groups: non-patent aqueduct and patent aqueduct. Mean values of pressure and pulse amplitude were obtained from basal and plateau stages of infusion studies. Twelve of 56 patients with NPH-like symptoms presented with morphological AS (21.4%). Patent aqueduct and non-patent aqueduct groups had similar values of mean opening lumbar pressure (8.2 vs. 8.1mmHg), and mean opening pulse amplitude (3.1 vs. 2.9mmHg). Mean pressure in the plateau stage (28.6 vs. 23.2mmHg), and mean pulse amplitude in the plateau stage (12.5 vs. 10.6mmHg) were higher in the patent aqueduct group. These differences were not statistically significant. Only Rout was significantly higher in the patent aqueduct group (13.6 vs. 10.1mmHg/ml/min). One-third of NPH patients with AS presented Rout >12mmHg/ml/min. No differences in mean pressure or pulse amplitude during basal and plateau epochs of the lumbar infusion test in NPH patients were detected, regardless of aqueductal patency. However, Rout was significantly higher in patients with patent aqueduct.

Profile of cognitive dysfunction and relation with gait disturbance in Normal Pressure Hydrocephalus

ObjectivesAlthough dementia is one of the most relevant symptoms of the idiopathic Normal-Pressure Hydrocephalus (iNPH) syndrome, some doubts remain about the nature of cognitive deficits in this disease. We aimed to determine the neuropsychological profile in iNPH and its relation with ventricular size, white matter vascular lesions (WML) and gait dysfunction. MethodsSeventeen iNPH patients and a control group (n=14) were assessed with a battery of neuropsychological tests and a timed walk test. We calculated measures of frontal horn, occipital horn and third ventricle sizes and assessed white matter lesion (WML) load with a validated visual scale. ResultsPatients differed significantly from controls in all cognitive tests, but did worse on the Rey Complex Figure test. We found no significant correlations between cognitive and imaging results in iNPH. Cognitive function was related to gait in controls, but not in iNPH patients. ConclusionsPatients presented widespread cognitive dysfunction with a predominance of visuo-spatial deficits. Dissociation between gait and cognitive dysfunction in iNPH patients suggests the existence of different pathophysiological mechanisms.

The Anterior Ventriculo-Cisternostomy: The Pioneers' Work Revisited

There is no satisfactory medical treatment for hydrocephalus and most often surgical treatment is necessary, including shunting or endoscopic third ventriculostomy (ETV), both with their well-known advantages and drawbacks. The objective of this study is to describe a contemporary series of anterior ventriculocisternostomy. Twenty-two patients with hydrocephalus treated at two institutions between 2005 and 2009 were presented. The authors employed a technique called anterior ventriculocisternostomy to treat selected cases. This technique includes supraciliary incision, small craniotomy, and fenestration of the lamina terminalis and Liliquist membrane. Hydrocephalus was secondary to hemorrhage from arteriovenous malformation (3 cases), spontaneous subarachnoid hemorrhage (2 cases), posterior fossa tumors (4 cases), head injury (1 case), basilar aneurysm (1 case), and posterior fossa hemorrhage (1 case). Eight patients had a normal-pressure hydrocephalus syndrome and one patient a slit ventricle syndrome. Aqueduct obstruction was noticed in one patient. Patients were followed up for 20.2 months (range: 10 to 46 months). No hemorrhagic complications or parenchymal injury were observed. One cerebrospinal fluid leakage occurred. No infection, mortality, and neurological morbidity were reported. Improvements were noticed in 18 cases. Eighty-two percent of the patients remained independent of shunt. Anterior ventriculocisternostomy integrates old views of open ventriculocisternostomy with contemporary concepts of minimally invasive neurosurgery. It provides the most straightforward anatomical and physiological alternative to treat many types of hydrocephalus with no significant morbidity. Compared with conventional procedures, it has several advantages. This procedure is an important option to manage hydrocephalus and constitutes a safe, effective, and relatively inexpensive alternative to ETV and shunts.

Normal pressure hydrocephalus or neuroborreliosis?

An 80-year-old woman presented with progressive cognitive decline and with a 6-month history of gait ataxia. Brain MRI depicted enlarged ventricles and periventricular lesions. Clinical improvement after CSF spinal tap test suggested a normal pressure hydrocephalus syndrome. But CSF pleocytosis with activated lymphocytes and plasma cells and intrathecal Borrelia burgdorferi specific antibody production led to the diagnosis of active Lyme neuroborreliosis. Clinical symptoms of NPH resolved after a course of ceftriaxone. Neurological examination, MMSE, brain MRI, lumbar puncture, spinal tap test. Dementia due Borrelia burgdorferi infection with chronic meningitis was reversible after treatment with iv.2 g ceftriaxone per day for 4 weeks. Rare but treatable dementias must be diagnosed promptly to slow down or even reverse cognitive decline.

Correlates of local cerebral blood flow (CBF) in normal pressure hydrocephalus patients before and after shunting—A retrospective analysis of [ 15O]H 2O PET-CBF studies in 65 patients

Objectives Findings in local cerebral blood flow (rCBF) in Normal pressure hydrocephalus (NPH) have always been challenged by the variable and inconsistent relation to clinical symptoms before and after shunt treatment. [ 15O]H 2O PET data from a consecutive cohort of 65 idiopathic NPH patients were retrospectively analyzed questioning whether the functional status before and after shunt treatment might correlate with local blood flow. Patients and methods Using statistical parametric mapping (SPM99, Wellcome Department of Cognitive Neurology, London), the [ 15O]H 2O uptake was correlated with the preoperative clinical scores, graded according to a modified Stein and Langfitt score. Furthermore, differences in the uptake in the pre-and post-shunt treatment study after seven to 10 days in patients with and without clinical improvement were studied. Results A higher clinical score significantly correlated with a reduced tracer uptake in mesial frontal ( k = 1239 voxel, Z = 4.41) and anterior temporal ( k = 469, Z = 4.07) areas. In the mesial frontal areas, tracer uptake showed significant reciprocal changes in the clinically improved vs. the unimproved patients. Conclusion Matched with the existing literature, the regional blood flow alterations are suggested relevant to the NPH syndrome and to post-treatment functional changes. The present rCBF findings warrant prospective studies on the accuracy of neuroimaging studies as they may provide a more specific insight into disease mechanisms.

INTRA-ABDOMINAL PRESSURE

In the selection of a ventriculoperitoneal cerebrospinal fluid shunt, the intra-abdominal pressure (IAP) is traditionally neglected as a result of the idea that its value is close to 0 mmHg. Our aim was to explore the relationship between body mass index (BMI) and IAP with the goal of providing clinically relevant data that could help neurosurgeons to estimate IAP and select the appropriate shunt for patients with hydrocephalus and especially those with normal-pressure hydrocephalus syndrome. Sixty patients requiring the placement of a ventriculoperitoneal shunt were included in the study. We determined weight, BMI, and IAP. IAP was measured through an intraperitoneal catheter during the shunt surgery. To determine whether a linear relationship existed between quantitative variables, linear regression analysis was used. BMI was 28.1 +/- 4.8 kg/m2. Eighteen patients (30%) had normal weight, 21 (35%) were moderately overweight, and 21 (35%) were obese. IAP was related to patient BMI. A significant positive linear correlation was identified between BMI and IAP (r = 0.52; P = 0.018) with a slope of 0.31 (P < 0.001) and an intercept of -5.5. In our study, we determined that IAP had a strong positive linear relationship with BMI. This correlation was independent of sex. An IAP of 0 mmHg can, therefore, only be assumed for patients with a normal BMI who are recumbent. In obese or overweight patients, neurosurgeons should take IAP into account when selecting both the most adequate differential pressure valve to be implanted and in which distal cavity to place the distal catheter to avoid shunt underdrainage induced by high IAP.

Continuous intraventricular pressure monitoring for diagnosis of normal-pressure hydrocephalus

Normal-pressure hydrocephalus (NPH) syndrome is treatable by implantation of a cerebrospinal fluid (CSF) shunt. However, diagnosis of NPH by clinical and radiological findings alone is unreliable, and co-existing structural dementia can contribute to low success rates after shunt implantation. The aim of our study was to investigate whether long-term results after shunt implantation in NPH improve when surgical candidates are selected by continuous intraventricular pressure monitoring (CIPM). Ninety-two consecutive patients who were admitted with suspected NPH received CIPM for 48 h including an intraventricular steady-state infusion test to determine the resistance outflow. With positive CIPM, shunt implantation was performed and the patients were prospectively followed up for 1 to 10 years (median 6.5 years). CIPM was negative in 37 patients. Fifty-five patients had a positive CIPM and received CSF shunt. 96.1% of them improved from gait disturbance, 77.1% from cognitive impairment and 75.7% from urinary dysfunction. Clinical improvement remained during long-term follow-up in all but 3 patients who showed a decline at 4, 5 and 7 years, respectively. CIPM-related complications (ventriculitis) occurred in only one patient. CIPM is a safe and valuable tool to establish a reliable diagnosis of NPH and to identify promising surgical candidates.

Orthostatic myoclonus

We encountered 15 patients with a newly recognized clinical phenomenon that we term orthostatic myoclonus. We conducted a retrospective chart review to better understand the clinical context and importance of this phenomenon. To describe the clinical picture of orthostatic myoclonus. The Mayo Clinic Rochester Movement Disorders Laboratory database was searched for all patients diagnosed electrophysiologically with orthostatic myoclonus (2002 through 2006). Medical records and laboratory data of all patients were retrospectively reviewed. Fifteen patients with orthostatic myoclonus were identified, all seniors (64 to 81 years). Seven of the patients had a CNS degenerative disorder and two had a systemic illness known to be associated with myoclonus. In the remaining six patients no known CNS disorder contributed to the phenomenon. The onset of orthostatic myoclonus was accompanied by complaints of leg jerking or observed leg jerking in 13 of 15 patients during upright posture. An insidious deterioration of gait that was often described as "apraxia" or "gait initiation difficulty" accompanied the myoclonus in 13 of 15 patients. Clinicians frequently suspected normal pressure hydrocephalus or orthostatic tremor syndrome. Surface EMG studies revealed short duration myoclonic bursts that occurred predominately with the assumption of an upright posture. Some patients improved on clonazepam. Orthostatic myoclonus is a unique clinical and physiologic phenomenon that accompanies a slowly progressive and eventually disabling gait disorder in the elderly. This phenomenon often arises in the company of more widespread CNS disease.

Poor Prognosis/Good Outcome in Patients with NPH

Object. The authors set out to describe the outcome in a subgroup of patients with normal-pressure hydrocephalus (NPH) in whom prognostic factors were poor. This subgroup of patients who had received shunts was selected according to strict criteria. Methods. From a cohort of 56 patients with NPH in whom shunts were placed, the authors selected a subgroup with four of the factors traditionally considered to indicate poor prognosis: idiopathic type, cortical atrophy, longstanding symptoms, and presence of dementia in addition to old age. Twelve patients met the inclusion criteria. After receiving shunts, 92% of the patients showed clinical improvement on the NPH scale; gait improved in 100% of patients, sphincter control in 90%, and dementia in 33%. Improvement was significant for gait and sphincter control, general NPH score, and most daily life activity scales. No significant differences regarding clinical, cognitive, or functional changes following surgery were found in comparison with the rest of patients (the good prognosis subgroup). Conclusions. The clinical condition of patients with NPH who present with traditionally accepted markers of poor prognosis can improve after surgery, especially as regards gait and sphincter control. The authors assert that the presence of these markers should not be considered to be an absolute criterion for ruling out shunt surgery in cases of NPH syndrome.

Poor Prognosis/Good Outcome in Patients with NPH

Object. The authors set out to describe the outcome in a subgroup of patients with normal-pressure hydrocephalus (NPH) in whom prognostic factors were poor. This subgroup of patients who had received shunts was selected according to strict criteria. Methods. From a cohort of 56 patients with NPH in whom shunts were placed, the authors selected a subgroup with four of the factors traditionally considered to indicate poor prognosis: idiopathic type, cortical atrophy, longstanding symptoms, and presence of dementia in addition to old age. Twelve patients met the inclusion criteria. After receiving shunts, 92% of the patients showed clinical improvement on the NPH scale; gait improved in 100% of patients, sphincter control in 90%, and dementia in 33%. Improvement was significant for gait and sphincter control, general NPH score, and most daily life activity scales. No significant differences regarding clinical, cognitive, or functional changes following surgery were found in comparison with the rest of patients (the good prognosis subgroup). Conclusions. The clinical condition of patients with NPH who present with traditionally accepted markers of poor prognosis can improve after surgery, especially as regards gait and sphincter control. The authors assert that the presence of these markers should not be considered to be an absolute criterion for ruling out shunt surgery in cases of NPH syndrome.

Voxel-based assessment of spinal tap test-induced regional cerebral blood flow changes in normal pressure hydrocephalus

Normal pressure hydrocephalus (NPH) is a cause of dementia that may be amended by medical intervention. Its diagnosis is therefore of major importance and the establishment of response criteria to cerebrospinal fluid (CSF) shunting is essential. One of these criteria is the clinical response to spinal tap. The accuracy of the spinal tap test could potentially be improved by adding neuroimaging of regional cerebral blood flow (rCBF) changes to the response criteria. Statistical parametric mapping (SPM) is a voxel-based method of image analysis that may be used to statistically assess the significance of rCBF changes. The objective of this study was to evaluate, by SPM, spinal tap test-induced rCBF changes in patients with NPH syndrome. Forty patients with NPH syndrome underwent hexamethylpropylene amine oxime (HMPAO) brain single photon emission computed tomography (SPECT) before and after a spinal tap test (1-day split-dose protocol). The differences in rCBF between these pairs of scans were analysed by SPM in the whole group and between subgroups divided according to gait improvement at the spinal tap test. In the whole group of patients, there was no statistical difference between pre- and post-spinal tap SPECT images. SPM analysis of patients grouped as a function of their clinical response to the spinal tap test revealed a significant post-spinal tap rCBF increase in the bilateral dorsolateral frontal and left mesiotemporal cortex in clinically responding compared with non-responding patients. According to SPM analysis, gait improvement at the spinal tap test in patients with NPH syndrome is associated with an rCBF increase localized in the bilateral dorsolateral frontal and left mesiotemporal cortex.

Good outcome in patients with normal-pressure hydrocephalus and factors indicating poor prognosis

The authors set out to describe the outcome in a subgroup of patients with normal-pressure hydrocephalus (NPH) in whom prognostic factors were poor. This subgroup of patients who had received shunts was selected according to strict criteria. From a cohort of 56 patients with NPH in whom shunts were placed, the authors selected a subgroup with four of the factors traditionally considered to indicate poor prognosis: idiopathic type, cortical atrophy, longstanding symptoms, and presence of dementia in addition to old age. Twelve patients met the inclusion criteria. After receiving shunts, 92% of the patients showed clinical improvement on the NPH scale; gait improved in 100% of patients, sphincter control in 90%, and dementia in 33%. Improvement was significant for gait and sphincter control, general NPH score, and most daily life activity scales. No significant differences regarding clinical, cognitive, or functional changes following surgery were found in comparison with the rest of patients (the good prognosis subgroup). The clinical condition of patients with NPH who present with traditionally accepted markers of poor prognosis can improve after surgery, especially as regards gait and sphincter control. The authors assert that the presence of these markers should not be considered to be an absolute criterion for ruling out shunt surgery in cases of NPH syndrome.

The prognostic value of clinical characteristics and parameters of cerebrospinal fluid hydrodynamics in shunting for idiopathic normal pressure hydrocephalus

It is difficult to predict which patients with symptoms and radiological signs of normal pressure hydrocephalus (NPH) will benefit from a shunting procedure and which patients will not. Risk of this procedure is also higher in patients with NPH than in the overall population of hydrocephalic patients. The aim of this study is to investigate which clinical characteristics, CT parameters and parameters of cerebrospinal fluid dynamics could predict improvement after shunting. Eighty-three consecutive patients with symptoms and radiological signs of NPH were included in a prospective study. Parameters of the cerebrospinal fluid dynamics were measured by calculation of computerised data obtained by a constant-flow lumbar infusion test. Sixty-six patients considered candidates for surgery were treated with a medium-pressure Spitz-Holter valve; in seventeen patients a shunting procedure was not considered indicated. Clinical and radiological follow-up was performed for at least one year postoperatively. The odds ratio, the sensitivity and specificity as well as the positive and negative predictive value of individual and combinations of measured parameters did not show a statistically significant relation to clinical improvement after shunting. We conclude that neither individual parameters nor combinations of measured parameters show any statistically significant relation to clinical improvement following shunting procedures in patients suspected of NPH. We suggest restricting the term normal pressure hydrocephalus to cases that improve after shunting and using the term normal pressure hydrocephalus syndrome for patients suspected of NPH and for patients not improving after implantation of a proven well-functioning shunt.

Angiotensin I converting enzyme polymorphism effects in patients with normal pressure hydrocephalus syndrome before and after surgery

Previous reports have suggested an association between the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE), cardiovascular disease, and cognitive performance. Normal pressure hydrocephalus (NPH) is considered to be an example of reversible dementia although the clinical improvement after shunting varies from subject to subject. An association has been suggested between vascular risk factors and the development of NPH. The ACE plays a major role in vascular pathology and physiology. In the present study we investigated the distribution of an ACE gene insertion/deletion polymorphism in 112 patients diagnosed with NPH and in 124 controls. We also evaluated the role of this genetic polymorphism in cognitive functioning before and following surgery in a subgroup of 72 patients. No differences in genetic or allele distributions were found between patients and healthy subjects, but among patients, carriers of D/D or D/I genotypes obtained less cognitive benefit following shunt surgery, especially on measures of memory and frontal function. Our data support previous findings in other conditions indicating that possession of at least one D allele is associated with poorer cognitive performance.

Is the placement of shunts in patients with idiopathic normal-pressure hydrocephalus worth the risk? Results of a study based on continuous monitoring of intracranial pressure.

Data from many studies have demonstrated that shunt insertion in patients with idiopathic normal-pressure hydrocephalus (NPH) is associated with high morbidity and a lack of significant improvement; however, the use of strict diagnostic and treatment protocols can improve the results of surgery in these patients. The primary aim in this prospective study was to analyze the results of shunt placement in 43 patients with idiopathic NPH. A secondary aim was to determine the relationship between several clinical and neuroimaging factors, and patient outcome after surgery. Thirty men and 13 women with a mean age of 71.1 +/- 6.9 years participated in this study. All patients underwent clinical, neuropsychological, and radiological assessment before and 6 months after surgery. In all patients continuous monitoring of intracranial pressure was performed using a fiberoptic extradural sensor. In 31 patients cerebrospinal fluid dynamics were also determined. Eighty-six percent of patients showed clinical improvement after shunt insertion, 11.6% showed no change, and 2.3% exhibited some worsening. Gait improved in 81.4% of the patients, sphincter control in 69.8%, and cognitive dysfunction in 39.5%. There was no treatment-related death. Early or late postsurgical complications occurred in six patients (14%), although all of these complications were minor or were satisfactorily resolved. The complete clinical triad, cortical sulci size, and periventricular lucencies were related to outcome, whereas patient age, symptom duration, ventricular dilation, and the degree of presurgical dementia were unrelated to outcome. Given the correct diagnosis, shunt insertion can produce marked improvement in patients with idiopathic NPH syndrome, causing few deaths and few clinically relevant complications.

Shunt related changes in somatostatin, neuropeptide Y, and corticotropin releasing factor concentrations in patients with normal pressure hydrocephalus

OBJECTIVESRecent data indicate that alterations in brain neuropeptides may play a pathogenic role in dementia. Neuropeptide Y (NPY), somastostatin (SOM), and corticotropin releasing factor (CRF) are neuropeptides involved in cognitive...

Reduction of cerebral cortical [ 3H]ouabain binding site (Na +,K +-ATPase) density in dementia as evaluated in fresh human cerebral cortical biopsies

Na +,K +-ATPase density in human cerebral cortex was for the first time studied by vanadate facilitated [ 3H]ouabain binding to intact samples. Fresh human cerebral cortical biopsies were obtained as a result of diagnostic frontal lobe biopsy from patients with normal pressure hydrocephalus (NPH) syndrome and associated dementia. For control measurements post-mortem samples were obtained from patients without clinically observed dementia. [ 3H]ouabain binding kinetics were evaluated: when incubating samples in 1 μM [ 3H]ouabain binding equilibrium was obtained after 6 h of incubation, non-specific uptake and retention amounted to only 2.3% of total uptake and retention of [ 3H]ouabain and release of specifically bound [ 3H]ouabain during washout in the cold occurred only slowly ( T 1 2 = 37 h ). Evaluation of receptor affinity for ouabain was in agreement with a heterogeneous population of [ 3H]ouabain binding sites. [ 3H]ouabain binding was significantly reduced after frozen storage of samples before measurements. Post-mortem degradation of cerebral [ 3H]ouabain binding sites occurred only slowly ( T 1 2 = 75 h ). No significant variation in [ 3H]ouabain binding site density was observed between the cerebral lobes with occipital, parietal and temporal values (means ± S.E.M., n = 5) amounting to 10 281 ± 649, 11 267 ± 1011 and 9263 ± 615 pmol/g wet wt., respectively. [ 3H]Ouabain binding measured in frontal cortical samples gave values of (means ± S.E.M., n = 5) 4274 ± 1020 and 11 397 ± 976 pmol/g wet wt. (▴ % = 62; P < 0.·05) in patients with dementia and controls, respectively. Human cerebral cortical capacity for active K + uptake was around 37- and 16-fold greater than in skeletal muscular and myocardial tissue, respectively.

Heterogeneous cerebral glucose metabolism in normal pressure hydrocephalus.

The regional cerebral metabolic rate for glucose (rCMRglu) has never been investigated in large consecutive groups of patients with normal pressure hydrocephalus (NPH), a potentially treatable form of dementia with an unpredictable outcome after shunt surgery. Using PET and 18F-2-fluorodeoxyglucose, rCMRglu was studied in 18 patients who fulfilled hydrodynamic criteria for NPH and in whom a biopsy of the frontal cortex was obtained. When compared with an age matched group of 11 healthy subjects, the patients with NPH showed a significant rCMRglu reduction in all cortical and subcortical regions of interest. Individual metabolic patterns, however, disclosed a large topographical heterogeneity. Furthermore, histopathological examination identified Alzheimer's disease or cerebrovascular disease in six cases, and no parenchymal disease or non-specific degenerative processes in the remaining 12. After separating the patients according to the histological diagnosis, the rCMRglu patterns were still heterogeneous, the abnormalities ranging from focal to diffuse in both subgroups. After shunt operation, 11 patients did not improve or worsened clinically. Six patients improved; of those, two had Alzheimer changes and two cerebrovascular changes in their biopsy. The metabolic pattern of these six patients did not differ from the rest of the NPH group. The results indicate that the NPH syndrome may be non-specifically associated with different degenerative disorders. The metabolic heterogeneity, together with the heterogeneous histopathological findings, indicate the necessity of reevaluating the pathogenesis of the NPH syndrome, and may account for the high variability in the success rate of shunt surgery series.