No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Preoperative and postoperative H-1-MR spectroscopy changes in frontal deep white matter and the thalamus in idiopathic normal pressure hydrocephalus
Abstract
Background In a previous study we found significantly decreased N-acetyl aspartate (NAA) and total N-acetyl (tNA) groups in the thalamus of patients with idiopathic normal pressure hydrocephalus (iNPH) compared with healthy individuals (HI). No significant difference between the groups could be found in the frontal deep white matter (FDWM).
Objective The primary aim of this study was to investigate if these metabolites in the thalamus were normalised after shunt surgery. The secondary aim was to investigate postoperative metabolic changes in FDWM.
Subjects and methods Fourteen patients with iNPH, mean age 74 years, and 15 HI, also mean age 74 years, were examined. Assessment of a motor score (MOSs) was performed before and after shunt surgery. Absolute quantitative 1H-MR spectroscopy (1.5 T, volumes of interest 2.5–3 ml) was performed on the patients in the FDWM and in the thalamus, before and 3 months after shunt surgery, and also once on the HI. The following metabolites were analysed: tNA, NAA, total creatine, total choline (tCho), myo-inositol (mIns), glutamate and lactate concentrations. MRI volumetric calculations of the lateral ventricles were also performed.
Results At 3 months postoperatively, we found no significant changes of tNA or NAA in the thalamus. In contrast, in the FDWM, there was a significant increase of tCho (p=0.01) and a borderline significant decrease of mIns (p=0.06). 12/14 patients were shunt responders (motor function). Median reduction of the lateral ventricle was 16%. A weak correlation between MOS and ventricular reduction was seen.
Conclusions Normalisation of thalamic tNA and NAA could not be detected postoperatively. The increased tCho and decreased mIns in the FDWM postoperatively might relate to clinical improvement.
... Postoperatively, a greater decrease in NFL correlated to a larger reduction in PVH and a more significant clinical improvement [106]. Using MR spectroscopy postoperatively, increased total choline and decreased myo-inositol in the frontal DWM was found, which could be correlated with clinical improvement [107]. ...
Idiopathic bormal pressure hydrocephalus (iNPH) is a neurological syndrome that clinically presents with Hakim’s triad, namely cognitive impairment, gait disturbances, and urinary incontinence. The fact that iNPH is potentially reversible makes its accurate and early diagnosis of paramount importance. Its main imaging characteristic is the dilation of the brain’s ventricular system and the imaging parameters are also included in its diagnostic criteria along with clinical data. There is a variety of different modalities used and a great number of imaging markers that have been described while assessing iNPH patients. The present literature review attempts to describe the most important of these imaging markers and to shed some light on their role in diagnosis, differential diagnosis, and possibly prognosis of this potentially reversible neurological syndrome.
... It was found that communicating hydrocephalus showed enlargement and continuous development of lateral ventricle on cistern imaging, with less or no distribution of radiation on convex surface of brain, while obstructive hydrocephalus showed slow migration of radiation to sagittal sinus and delayed development of convex surface of brain, The lateral ventricle does not develop all the time, which is similar to the research results of Guan Feng et al. [25] MRS can quantitatively analyze a series of specific nuclei such as material metabolism in living brain tissue and other compounds by using the phenomenon of nuclear magnetic resonance and chemical displacement. Lundin f et al. [26] performed MRS examination on 14 patients with hydrocephalus before operation and 3 months after operation. It was found that the total nacetylaspartic acid and n-acetylaspartic acid in thalamus before and after shunt were significantly lower than those in healthy individuals, while the spectral analysis of deep brain white matter before shunt was not significantly different from that in normal people. ...
Hydrocephalus is a common neurological disease caused by imbalance in the production and absorption of cerebrospinal fluid (CSF) or obstruction of its circulation pathways. The etiology of the disease is complex, often accompanied by a variety of complication. In recent years, hydrocephalus has been intensively studied. In this paper, the etiology, epidemiology, diagnosis and treatment of hydrocephalus in study on traditional Chinese and western medicine treatment were reviewed in order to provide reference for clinical diagnosis and treatment of hydrocephalus in the future.
... It has been reported that proton magnetic resonance spectroscopy shows significant decrease in the N-acetylaspartate/creatine (NAA/Cr) ratio in the frontal lobe white matter and thalamus 136,137) and a peak in lactate is seen in the cerebral ventricles in iNPH. 138) Although the NAA/Cr ratio reportedly increases after surgery and correlates with improvement in cognitive function, 58) there are also negative reports, 139,140) and its diagnostic value has not been established. ...
Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming of great importance. The first edition of these guidelines for management of iNPH was published in 2004, and the second edition in 2012, to provide a series of timely, evidence-based recommendations related to iNPH. Since the last edition, clinical awareness of iNPH has risen dramatically, and clinical and basic research efforts on iNPH have increased significantly. This third edition of the guidelines was made to share these ideas with the international community and to promote international research on iNPH. The revision of the guidelines was undertaken by a multidisciplinary expert working group of the Japanese Society of Normal Pressure Hydrocephalus in conjunction with the Japanese Ministry of Health, Labour and Welfare research project. This revision proposes a new classification for NPH. The category of iNPH is clearly distinguished from NPH with congenital/developmental and acquired etiologies. Additionally, the essential role of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) in the imaging diagnosis and decision for further management of iNPH is discussed in this edition. We created an algorithm for diagnosis and decision for shunt management. Diagnosis by biomarkers that distinguish prognosis has been also initiated. Therefore, diagnosis and treatment of iNPH have entered a new phase. We hope that this third edition of the guidelines will help patients, their families, and healthcare professionals involved in treating iNPH.
... 25,26 Moreover, changes in the interstitial fluid pressure by CSF removal could decrease edema in the periventricular tissue, 24,41 thereby improving the clearance of vasoactive and/or neurotoxic metabolites. Both the improved vascular autoregulation and the enhanced capacity for metabolic clearance may be the pathophysiological substrates of delayed walking improvement in the first days after LP. 21 However, the current study was not designed to adequately address the relationship between brain structure and function in iNPH. Future investigations using neuroimaging and neurophysiological measurements in parallel are required to directly address these pathophysiological mechanisms. ...
OBJECTIVE
The determination of gait improvement after lumbar puncture (LP) in idiopathic normal-pressure hydrocephalus (iNPH) is crucial, but the best time for such an assessment is unclear. The authors determined the time course of improvement in walking after LP for single-task and dual-task walking in iNPH.
METHODS
In patients with iNPH, sequential recordings of gait velocity were obtained prior to LP (time point [TP]0), 1–8 hours after LP (TP1), 24 hours after LP (TP2), 48 hours after LP (TP3), and 72 hours after LP (TP4). Gait analysis was performed using a pressure-sensitive carpet (GAITRite) under 4 conditions: walking at preferred velocity (STPS), walking at maximal velocity (STMS), walking while performing serial 7 subtractions (dual-task walking with serial 7 [DTS7]), and walking while performing verbal fluency tasks (dual-task walking with verbal fluency [DTVF]).
RESULTS
Twenty-four patients with a mean age of 76.1 ± 7.8 years were included in this study. Objective responder status moderately coincided with the self-estimation of the patients with subjective high false-positive results (83%). The extent of improvement was greater for single-task walking than for dual-task walking (p < 0.05). Significant increases in walking speed were found at TP2 for STPS (p = 0.042) and DTVF (p = 0.046) and at TP3 for STPS (p = 0.035), DTS7 (p = 0.042), and DTVF (p = 0.044). Enlargement of the ventricles (Evans Index) positively correlated with early improvement. Gait improvement at TP3 correlated with the shunt response in 18 patients.
CONCLUSIONS
Quantitative gait assessment in iNPH is important due to the poor self-evaluation of the patients. The maximal increase in gait velocity can be observed 24–48 hours after the LP. This time point is also best to predict the response to shunting. For dual-task paradigms, maximal improvement appears to occur later (48 to 72 hours). Assessment of gait should be performed at Day 2 or 3 after LP.
... 45 Cerebral blood flow represents an important marker that can be assessed with a variety of techniques, including PET, 98 SPECT, and MRI. 19,40,74 Standardization of techniques is also critical for multiple centers to correlate various outcome measures. ...
Building on previous National Institutes of Health-sponsored symposia on hydrocephalus research, "Opportunities for Hydrocephalus Research: Pathways to Better Outcomes" was held in Seattle, Washington, July 9-11, 2012. Plenary sessions were organized into four major themes, each with two subtopics: Causes of Hydrocephalus (Genetics and Pathophysiological Modifications); Diagnosis of Hydrocephalus (Biomarkers and Neuroimaging); Treatment of Hydrocephalus (Bioengineering Advances and Surgical Treatments); and Outcome in Hydrocephalus (Neuropsychological and Neurological). International experts gave plenary talks, and extensive group discussions were held for each of the major themes. The conference emphasized patient-centered care and translational research, with the main objective to arrive at a consensus on priorities in hydrocephalus that have the potential to impact patient care in the next 5 years. The current state of hydrocephalus research and treatment was presented, and the following priorities for research were recommended for each theme. 1) Causes of Hydrocephalus-CSF absorption, production, and related drug therapies; pathogenesis of human hydrocephalus; improved animal and in vitro models of hydrocephalus; developmental and macromolecular transport mechanisms; biomechanical changes in hydrocephalus; and age-dependent mechanisms in the development of hydrocephalus. 2) Diagnosis of Hydrocephalus-implementation of a standardized set of protocols and a shared repository of technical information; prospective studies of multimodal techniques including MRI and CSF biomarkers to test potential pharmacological treatments; and quantitative and cost-effective CSF assessment techniques. 3) Treatment of Hydrocephalus-improved bioengineering efforts to reduce proximal catheter and overall shunt failure; external or implantable diagnostics and support for the biological infrastructure research that informs these efforts; and evidence-based surgical standardization with longitudinal metrics to validate or refute implemented practices, procedures, or tests. 4) Outcome in Hydrocephalus-development of specific, reliable batteries with metrics focused on the hydrocephalic patient; measurements of neurocognitive outcome and quality-of-life measures that are adaptable, trackable across the growth spectrum, and applicable cross-culturally; development of comparison metrics against normal aging and sensitive screening tools to diagnose idiopathic normal pressure hydrocephalus against appropriate normative age-based data; better understanding of the incidence and prevalence of hydrocephalus within both pediatric and adult populations; and comparisons of aging patterns in adults with hydrocephalus against normal aging patterns.
... 45 Cerebral blood flow represents an important marker that can be assessed with a variety of techniques, including PET, 98 SPECT, and MRI. 19,40,74 Standardization of techniques is also critical for multiple centers to correlate various outcome measures. ...
Object:
Shunt survival may improve when ventricular catheters are placed into the frontal horn or trigone of the lateral ventricle. However, techniques for accurate catheter placement have not been developed. The authors recently reported a prospective study designed to test the accuracy of catheter placement with the assistance of intraoperative ultrasound, but the results were poor (accurate placement in 59%). A major reason for the poor accurate placement rate was catheter movement that occurred between the time of the intraoperative ultrasound image and the first postoperative scan (33% of cases). The control group of non-ultrasound using surgeons also had a low rate of accurate placement (accurate placement in 49%). The authors conducted an exploratory post hoc analysis of patients in their ultrasound study to identify factors associated with either catheter movement or poor catheter placement so that improved surgical techniques for catheter insertion could be developed.
Methods:
The authors investigated the following risk factors for catheter movement and poor catheter placement: age, ventricular size, cortical mantle thickness, surgeon experience, surgeon experience with ultrasound prior to trial, shunt entry site, shunt hardware at entry site, ventricular catheter length, and use of an ultrasound probe guide for catheter insertion. Univariate analysis followed by multivariate logistic regression models were used to determine which factors were independent risk factors for either catheter movement or inaccurate catheter location.
Results:
In the univariate analyses, only age < 6 months was associated with catheter movement (p = 0.021); cortical mantle thickness < 1 cm was near-significant (p = 0.066). In a multivariate model, age remained significant after adjusting for cortical mantle thickness (OR 8.35, exact 95% CI 1.20-infinity). Univariate analyses of factors associated with inaccurate catheter placement showed that age < 6 months (p = 0.001) and a posterior shunt entry site (p = 0.021) were both associated with poor catheter placement. In a multivariate model, both age < 6 months and a posterior shunt entry site were independent risk factors for poor catheter placement (OR 4.54, 95% CI 1.80-11.42, and OR 2.59, 95% CI 1.14-5.89, respectively).
Conclusions:
Catheter movement and inaccurate catheter placement are both more likely to occur in young patients (< 6 months). Inaccurate catheter placement is also more likely to occur in cases involving a posterior shunt entry site than those involving an anterior shunt entry site. Future clinical studies aimed at improving shunt placement techniques must consider the effects of young age and choice of entry site on catheter location.
Idiopathic normal pressure hydrocephalus (iNPH), the most common type of adult‐onset hydrocephalus, is a potentially reversible neuropsychiatric entity characterized by dilated ventricles, cognitive deficit, gait apraxia, and urinary incontinence. Despite its relatively typical imaging features and clinical symptoms, the pathogenesis and pathophysiology of iNPH remain unclear. In this review, we summarize current pathogenetic conceptions of iNPH and its pathophysiological features that lead to neurological deficits. The common consensus is that ventriculomegaly resulting from cerebrospinal fluid (CSF) dynamics could initiate a vicious cycle of neurological damages in iNPH. Pathophysiological factors including hypoperfusion, glymphatic impairment, disturbance of metabolism, astrogliosis, neuroinflammation, and blood‐brain barrier disruption jointly cause white matter and gray matter lesions, and eventually lead to various iNPH symptoms. Also, we review the current treatment options and discuss the prospective treatment strategies for iNPH. CSF diversion with ventriculoperitoneal or lumboperitonealshunts remains as the standard therapy, while its complications prompt attempts to refine shunt insertion and develop new therapeutic procedures. Recent progress on advanced biomaterials and improved understanding of pathogenesis offers new avenues to treat iNPH.
OBJECTIVE
The relationship of the white matter tracts to the lateral ventricles is important when planning surgical approaches to the ventricles and in understanding the symptoms of hydrocephalus. The authors' aim was to explore the relationship of the white matter tracts of the cerebrum to the lateral ventricles using fiber dissection technique and MR tractography and to discuss these findings in relation to approaches to ventricular lesions.
METHODS
Forty adult human formalin-fixed cadaveric hemispheres (20 brains) and 3 whole heads were examined using fiber dissection technique. The dissections were performed from lateral to medial, medial to lateral, superior to inferior, and inferior to superior. MR tractography showing the lateral ventricles aided in the understanding of the 3D relationships of the white matter tracts with the lateral ventricles.
RESULTS
The relationship between the lateral ventricles and the superior longitudinal I, II, and III, arcuate, vertical occipital, middle longitudinal, inferior longitudinal, inferior frontooccipital, uncinate, sledge runner, and lingular amygdaloidal fasciculi; and the anterior commissure fibers, optic radiations, internal capsule, corona radiata, thalamic radiations, cingulum, corpus callosum, fornix, caudate nucleus, thalamus, stria terminalis, and stria medullaris thalami were defined anatomically and radiologically. These fibers and structures have a consistent relationship to the lateral ventricles.
CONCLUSIONS
Knowledge of the relationship of the white matter tracts of the cerebrum to the lateral ventricles should aid in planning more accurate surgery for lesions within the lateral ventricles.
The Image Foresting Transform (IFT) is a framework for image partitioning, commonly used for interactive segmentation. Given
an image where a subset of the image elements (seed-points) have been assigned user-defined labels, the IFT completes the
labeling by computing minimal cost paths from all image elements to the seed-points. Each image element is then given the
same label as the closest seed-point. In its original form, the IFT produces crisp segmentations, i.e., each image element
is assigned the label of exactly one seed-point. Here, we propose a modified version of the IFT that computes region boundaries
with sub-pixel precision by allowing mixed labels at region boundaries. We demonstrate that the proposed sub-pixel IFT allows
properties of the segmented object to be measured with higher precision.
Patients with idiopathic normal pressure hydrocephalus (INPH) frequently have a reduction in cerebral blood flow in the subcortical frontal lobe/basal ganglia/thalamic areas. With magnetic resonance spectroscopy, the metabolism in the brain can be examined. The aim of this study was to investigate if there was a compromised metabolism in the thalamus and in the subcortical frontal areas in INPH patients. This was done by measuring total creatine, myo-inositol, total choline, N-acetylaspartate (NAA), total N-acetylaspartate (tNA), glutamate and lactate levels. A comparison was made with healthy individuals (HI).
16 patients (nine males, seven females, mean age 74 years, range 49-83) diagnosed as INPH and 15 HI (nine males, six females, mean age 74 years, range 62-89) were examined. (1)H magnetic resonance spectroscopy (1.5 T, point-resolved spectroscopy, echo time/relaxation time 30/3000 ms, volume of interest 2.5-3 ml) was performed in frontal deep white matter and in the thalamus. Absolute quantification with internal water as a reference was used.
INPH patients had lower NAA (p=0.02) and lower tNA (p=0.05) concentrations in the thalamus compared with HI. NAA and tNA in the frontal deep white matter did not differ between patients and HI. The absolute metabolic concentrations of total creatine, myo-inositol total choline, tNA, lactate and Cr ratios in frontal deep white matter and in the thalamus were similar in INPH patients and HI.
Reduced thalamic NAA and tNA in INPH patients suggest a compromised metabolic neuronal function in these regions. Thus, the thalamus might have an important role in the pathogenesis of INPH.
The differentiation of idiopathic normal-pressure hydrocephalus (INPH) from other types of dementia is a clinical challenge. The aim of this prospective study was to evaluate the role of proton MR spectroscopy (MRS) and white matter hyperintensities (WMH) in the diagnosis of INPH, predicting response to therapy and differentiating INPH from other dementias. The study included 18 patients with INPH (Group 1), 11 patients with other types of dementia (Group 2) and 20 control patients (Group 3). The value of WMH scores and MRS findings in diagnosis, evaluation of response to therapy and in the differentiation of INPH from other dementias was statistically evaluated. The level of statistical significance was set at p<0.05 (Kruskal-Wallis and Mann-Whitney U-test). In both Groups 1 and 2, N-acetylaspartate (NAA)/choline-NAA/creatine ratios were significantly less than in the control group (p<0.05). The WMH and MRS findings of Groups 1 and 2 demonstrated no statistically significant correlation (p>0.05). No correlation was found between the outcome of shunt operations and WMH and MRS findings (p>0.05). In conclusion, neither WMH nor MRS were useful in differentiating INPH from other types of dementia. WMH and MRS showed no additional benefit in identifying INPH patients who will better respond to shunt therapy.
The clinical impact of Alzheimer's disease pathology at biopsy was investigated in 56 cognitively impaired patients undergoing shunt surgery for idiopathic normal pressure hydrocephalus (NPH). Cognition was measured by means of the global deterioration scale (GDS), the mini mental status examination (MMSE) and a battery of six psychometric tests. Gait was assessed using objective measurements of velocity and the ambulatory index (AI). The prevalence of cases exhibiting neuritic plaques (positive biopsies) increased in parallel with dementia severity from 18% for patients with GDS 3 to 75% for patients with GDS scores > or =6. Patients with positive biopsies were more cognitively impaired (higher GDS and lower MMSE scores) as well as more gait impaired (higher AI scores and slower velocities) than patients with negative biopsies. After surgery, gait velocity and AI scores improved significantly and to a comparable degree for patients with and without positive biopsies. Similar proportions of positive and negative biopsy patients also had improved gait as assessed by means of subjective video tape comparisons. There were no significant differences between the biopsy groups in the magnitude of postoperative psychometric change or in the proportion of cases exhibiting improved urinary control. Alzheimer's disease pathology is a common source of comorbidity in older patients with idiopathic NPH where it contributes to the clinical impairment associated with this disorder. For patients accurately diagnosed with NPH, concomitant Alzheimer's disease pathology does not strongly influence the clinical response to shunt surgery.
The syndrome of normal-pressure hydrocephalus (NPH) refers to the clinical triad of gait disturbance, dementia, and urinary incontinence in association with idiopathic ventriculomegaly and normal intracranial pressure. Ventriculoperitoneal (VP) shunt placement often yields significant clinical improvements, sometimes without apparent reduction of ventricular size. The authors hypothesized that careful volumetric measurements would show a decrease in ventricular volume in these patients.
Twenty consecutive patients with NPH underwent placement of VP shunts equipped with programmable valves. In 11 patients pre- and postoperative neuroimaging was performed, which allowed volumetric analysis. Volumetric measurements of the lateral ventricles were calculated in triplicate by National Institutes of Health image-processing software to assess standard computerized tomography (CT) scans (eight patients) or magnetic resonance (MR) images (three patients) obtained before and after shunt placement. Ventricular volumes were also assessed by an independent neuroradiologist. Postoperative studies were performed at a time of clinical improvement, between 1 and 9 months postsurgery (mean 5 months). Preoperative and postoperative Unified Parkinson's Disease Rating Scale evaluations were performed in four patients. Significant clinical improvement occurred in all patients after shunt placement (mean follow-up period 17.5 months). Although 10 (91%) of 11 patients demonstrated a calculable decrease in volume in the lateral ventricles (mean decrease 39%), formal interpretation of neuroimages indicated a definite decrease in lateral ventricular volume in only three (27%) of 11 patients.
Volumetric measurements obtained to compare preoperative and postoperative CT or MR studies obtained in patients with NPH in whom clinical improvement was seen after shunt placement surgery show a demonstrable decrease in ventricular size. Volumetric measurements may be helpful in clinical assessment postoperatively and in guiding programmable valve pressure settings.
No single neuroprotective agent has been shown to influence outcome after acute stroke. Citicoline has been studied worldwide in many clinical trials with positive findings, but only 1 trial has obtained significant results in the primary efficacy variables. Our objective was to evaluate the effects of oral citicoline in patients with acute ischemic stroke by a data pooling analysis of clinical trials. The primary efficacy end point chosen was the common evaluation of recovery, combining National Institutes of Health Stroke Scale </=1, modified Rankin Scale score </=1, and Barthel Index >/=95 at 3 months using the generalized estimating equations analysis.
A systematic search of all prospective, randomized, placebo-controlled, double-blind clinical trials with oral citicoline (MEDLINE, Cochrane, and Ferrer Group bibliographic databases) was undertaken. Individual patient data were extracted from each study and pooled in a single data file. The main inclusion criteria included compatible neuroimaging with ischemic stroke, National Institutes of Health Stroke Scale >/=8, and prior modified Rankin Scale score </=1. Four clinical trials using various doses of oral citicoline (500, 1000, and 2000 mg) were identified.
Of 1652 randomized patients, 1372 fulfilled the inclusion criteria (583 received placebo, 789 received citicoline). Recovery at 3 months was 25.2% in citicoline-treated patients and 20.2% in placebo-treated patients (odds ratio [OR], 1.33; 95% CI, 1.10 to 1.62; P=0.0034). The dose showing the largest difference with placebo was 2000 mg, with 27.9% of patients achieving recovery (OR, 1.38; 95% CI, 1.10 to 1.72; P=0.0043). The overall safety of citicoline was similar to placebo.
Treatment with oral citicoline within the first 24 hours after onset in patients with moderate to severe stroke increases the probability of complete recovery at 3 months.
Normal pressure hydrocephalus (NPH) is considered to be a treatable form of dementia, because cerebrospinal fluid (CSF) shunting can lessen symptoms. However, neuroimaging has failed to predict when shunting will be effective.
To investigate whether 1H (proton) magnetic resonance (MR) spectroscopy could predict functional outcome in patients after shunting.
Neurological state including Hasegawa's dementia scale, gait, continence, and the modified Rankin scale were evaluated in 21 patients with secondary NPH who underwent ventriculo-peritoneal shunting. Outcomes were measured postoperatively at one and 12 months and were classified as excellent, fair, or poor. MR spectra were obtained from left hemispheric white matter.
Significant preoperative differences in N-acetyl aspartate (NAA)/creatine (Cr) and NAA/choline (Cho) were noted between patients with excellent and poor outcome at one month (p = 0.0014 and 0.0036, respectively). Multiple regression analysis linked higher preoperative NAA/Cr ratio, gait score, and modified Rankin scale to better one month outcome. Predictive value, sensitivity, and specificity for excellent outcome following shunting were 95.2%, 100%, and 87.5%. Multiple regression analysis indicated that NAA/Cho had the best predictive value for one year outcome (p = 0.0032); predictive value, sensitivity, and specificity were 89.5%, 90.0%, and 88.9%.
MR spectroscopy predicted long term post-shunting outcomes in patients with secondary NPH, and it would be a useful assessment tool before lumbar drainage.
The neurophysiological basis of cognition is relatively unexplained, with most studies reporting weak relationships between cognition and measures of brain function, such as event-related potentials, brain size and cerebral blood flow. Magnetic resonance spectroscopy (MRS) is an in vivo method used to detect neurochemicals within the brain that are relevant to certain brain processes. The most widely used methods are 1H-MRS and 31P-MRS, which detect compounds that contain hydrogen and phosphorus, respectively. Recent studies have shown that the absolute concentrations or ratios of these neurochemicals, in particular N-acetyl aspartate (NAA), which is associated with neuronal viability, correlate with performance on neuropsychological tests or other measures of cognitive function in normal subjects. Many studies in adults and children have shown a relationship between neurometabolite values and cognitive status or extent of cognitive dysfunction in various neurological and neuropsychiatric disorders. We review these studies and conclude that MRS has potential applications for the study of cognitive processes in health and disease and may be used clinically for differential diagnosis, the early detection of pathology and the examination of longitudinal change.
Adult normal pressure hydrocephalus (NPH) is one of the few potentially treatable causes of dementia. Some morphological and functional abnormalities attributed to hydrocephalus improve following treatment.
We focused on analysis of changes in cerebral metabolites using proton magnetic resonance spectroscopy (1H-MRS) after NPH treatment, and its clinical and cognitive correlation.
1H-MRS, neuropsychological and clinical status examinations were performed before and 6 months after shunting in 12 adults with idiopathic NPH. We obtained N-acetyl-aspartate (NAA), choline (Cho), myoinositol (MI) and creatine (Cr) values.
After surgery, NAA/Cr was significantly increased. Moreover, NAA/Cr values were related to cognitive deterioration.
MRS could be a marker of neuronal dysfunction in NPH.
While much work has concentrated on focal white matter (WM) lesions in multiple sclerosis, there is growing evidence to suggest that normal‐appearing WM (NAWM) and grey matter (GM) are also involved in the disease process. This study investigated multiple sclerosis disease effects on NAWM and cortical GM (CGM) metabolite concentrations, and the relationships between these metabolite concentrations and clinical impairment. Proton magnetic resonance spectroscopic imaging (1H‐MRSI) data acquired using point resolved spectroscopic (PRESS) localization (echo time 30 ms, repetition time 3000 ms, nominal voxel volume 2.3 ml) from 27 relapsing–remitting multiple sclerosis and 29 normal control (NC) subjects were processed using LCModel to estimate metabolite concentrations in millimoles per litre. 1H‐MRSI voxel tissue contents were estimated using SPM99 tissue and semi‐automatic lesion segmentations of three‐dimensional fast spoiled gradient recall scans acquired during the same scanning session. NAWM and CGM metabolite concentrations estimated were: choline‐containing compounds (Cho); creatine and phosphocreatine (Cr); myo‐inositol (Ins); N ‐acetyl‐aspartate plus N ‐acetyl‐aspartyl‐glutamate (tNAA); and glutamate plus glutamine (Glx). CGM data came from 24 of the multiple sclerosis (mean age 35.2 years, mean disease duration 1.7 years) and 25 of the NC (mean age 34.9 years) subjects. NAWM data came from 25 of the multiple sclerosis (mean age 35.0 years, mean disease duration 1.7 years) and 28 of the NC (mean age 36.7 years) subjects. Metabolite concentrations were compared between multiple sclerosis and NC subjects using multiple (linear) regression models allowing for age, gender, 1H‐MRSI voxel tissue and CSF contents, and brain parenchymal volume. At a significance level of P < 0.05, CGM Cho, CGM and NAWM tNAA, and CGM Glx were all significantly reduced, and NAWM Ins was significantly elevated. Spearman correlations of multiple sclerosis functional composite scores with tissue metabolite concentrations were significant for the following: CGM Cr ( r s = 0.524, P = 0.009), CGM Glx ( r s = 0.580, P = 0.003) and NAWM Ins ( r s = –0.559, P = 0.004). These results indicate that metabolite changes in NAWM and CGM can be detected early in the clinical course of multiple sclerosis, and that some of these changes relate to clinical status. The correlation of clinical impairment with CGM Cr and Glx but not tNAA suggests that it is more closely associated with neuronal metabolic dysfunction rather than loss in clinically early relapsing–remitting multiple sclerosis. The correlation of clinical impairment with a raised NAWM Ins may indicate that glial proliferation also relates to function at this stage of the disease.
Citicoline (CDP-choline or cytidine 5'-diphosphocholine) has been used as a therapeutic agent in combination with levodopa in the treatment of Parkinson's disease (PD). The present study examines the effects of citicoline by using validated in vivo and in vitro models. Citicoline reduces the cytotoxic effect of 6-hydroxydopamine (6-OHDA)-treated human dopaminergic SH-SY5Y neuroblastoma cells as measured cellular redox activity with 3-[4.5-dimethylthiazol-2-yl]-2.5-diphenyltetrazolium bromide (MTT) and increases the levels of reduced glutathione (GSH), a major antioxidant agent. Moreover, citicoline (500 mg/kg i.p.) administered for 7 days ameliorates functional behaviour by significantly reducing the number of apomorphine-induced contralateral rotations in 6-OHDA rats. Finally, citicoline significantly attenuates substantia nigra (SN) dopaminergic cell dropout and tyrosine hydroxylase immunoreactivity in the ipsilateral striatum in rats injected intrastriatally with 6-hydroxydopamine (6-OHDA).
The LCModel method analyzes an in vivo spectrum as a Linear Combination of Model in vitro spectra from individual metabolite solutions. Complete model spectra, rather than individual resonances, are used in order to incorporate maximum prior information into the analysis. A nearly model‐free constrained regularization method automatically accounts for the baseline and lineshape in vivo without imposing a restrictive parameterized form on them. LCModel is automatic (non‐interactive) with no subjective input. Approximately maximum‐likelihood estimates of the metabolite concentrations and their uncertainties (Cramér‐Rao lower bounds) are obtained. LCModel analyses of spectra from users with fields from 1.5 to 9.4 T and a wide range of sequences, particularly with short TE , are used here to illustrate the capabilities and limitations of LCModel and proton MRS. Copyright © 2001 John Wiley & Sons, Ltd.
Abbreviations used
Ala alanine
Asp aspartate
Cr creatine
GABA γ‐aminobutyric acid
Glc glucose
Gln glutamine
Glu glutamate
GPC glycerophosphocholine
GSH glutathione
Ins myo ‐inositol
Lac lactate
NAA N ‐acetylaspartate
NAAG N ‐acetylaspartylglutamate
PC phosphocholine
PCr phosphocreatine
PE phosphoethanolamine
Scyllo scyllo ‐inositol
S/N signal‐to‐noise ratio
Tau taurine.
The reliability of a single-voxel, localized proton magnetic resonance spectroscopy protocol suitable for clinical studies was investigated by means of in vitro, single-subject in vivo and multi-subject in vivo examinations of healthy adults aged from 19 to 67 years. The study was performed at 1.5 T using a standard quadrature head coil and a single voxel PRESS sequence (in vitroTR/TE = 1500/30 ms, in vivoTR/TE=2000/35 ms). Eighty-four in vitro and 30 single-subject examinations were statistically evaluated after quantification, including the calculation of the coefficients of variations (CV) for choline (Cho), creatine (Cr), myo-inositol (mI), lactate (Lac), N-acetyl-aspartate (NAA) and unresolved glutamine, glutamate and GABA (Glx). The CVs for absolute concentrations of the main metabolites Cho, Cr and NAA, ranged from 3.3% (3.8) to 4.0% (6.4%) (the in vivo results are given in brackets). Multi-subject CVs of absolute concentrations for Cho, Cr and NAA ranged from 7.6% to 15.0%. CVs of relative in vivo concentrations were found to be higher than CVs of absolute concentrations. Due to the better reproducibility of intra-individual absolute in vivo concentrations, cross-over studies using institutional units are recommended. Copyright © 2000 John Wiley & Sons, Ltd.
Neuropsychological dysfunction is common in patients with idiopathic normal pressure hydrocephalus (iNPH). Shunt treatment is beneficial, some patients reaching complete or almost complete recovery, while others show only minor improvement. We aimed to assess the efficacy of a small selection of well characterized and sensitive neuropsychological tests in the context of the European multicentre study on iNPH (Eu-INPH).
One hundred and forty-two iNPH patients included in Eu-iNPH were tested with the Rey Auditory Verbal Learning Test (RAVLT), the Grooved Pegboard and the Stroop test before and after three and twelve months of treatment with a ventriculoperitoneal shunt. Their performance was compared to that of 108 healthy individuals (HI).
INPH patients performed significantly worse than HI on all of the neuropsychological measures at entry. The discriminative capacities of the eight variables were similar, with areas under the curve (AUC; ROC analysis) ranging between .86 (Delayed Recall) and .95 (Grooved Pegboard). The most usable test was RAVLT (Learning and Delayed Recall), administered to ≥90% of the patients at all occasions. However, the Grooved Pegboard and the Stroop test were more sensitive to treatment effects.
The three neuropsychological tests used in the Eu-iNPH are expedient, highly diagnostically discriminative, and well suited to evaluate changes following shunt treatment.
The cerebrospinal fluid tap test (TT) is a diagnostic tool used to select patients with idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery. The procedure and the evaluation of the TT vary between centres. We aimed to describe the evaluation time after the TT, to assess the variability between repeated measurements, the interrater agreement of the gait tests chosen and finally to investigate whether pain affects the gait performance post-TT.
Forty patients (21 men and 19 women) under evaluation for iNPH underwent a TT. Standardized gait analyses were performed before and 2, 4, 6, 8 and 24 h after the TT and repeated twice on every occasion. Independent of each other, two investigators evaluated the quality of gait. At each assessment time, the patients graded headache and back pain on a visual analogue scale.
Twenty-seven patients (15 men and 12 women) responded to TT. Improvements in gait speed and number of steps were significant at every assessment time post-TT. The variability between two measurements was low (Intra class correlation coefficient=0.97), and the inter-rater agreement was good with a κ=0.74. Pain correlated negatively with improvement in gait speed (r=-0.40, P<0.05).
We suggest that the TT can be evaluated at any time within the first 24 h and should be repeated if the patient does not initially improve. Gait analysis appears reliable between two evaluators. Further, it is indicated that post-lumbar puncture pain negatively affects the gait and should be minimized.
Patients with idiopathic normal pressure hydrocephalus (iNPH) often present with impaired gait and cognition together with ventricular enlargement and normal intracranial pressure. Many have vascular risk factors as well as periventricular and deep white matter changes on MR imaging. Abnormal CSF dynamics, that is, high resistance to outflow or improvement after CSF drainage, indicate good effects of shunt surgery. The authors examined whether the worst-case iNPH patients with extensive vascular white matter disease and normal CSF dynamics would benefit from shunt surgery. These patients also fulfilled the criteria for Binswanger disease. Therefore, a randomized controlled double-blind study was performed.
Fourteen consecutive patients fulfilling the above criteria were randomized to receive either open or closed shunts. At 3 months after surgery, the patients with initially ligated shunts had their shunts opened. Clinical evaluation consisting of 7 quantitative psychometric and 6 continuous gait tests was performed preoperatively and 3 and 6 months after surgery.
Patients randomized to receive open shunts had improved motor (30% increase) and psychometric (23% increase) scores 3 months after shunt placement. There were no significant changes between the 3- and 6-month follow-up in these same patients. Conversely, those with initially ligated shunts were unchanged during the first 3-month period, although they improved in both motor (28%) and cognitive (18%) functions following removal of the ligature.
Patients with enlarged ventricles, hydrocephalic symptoms, and extensive vascular white matter changes benefit from shunt surgery.
To prospectively evaluate the effects of shunting on the neuropsychological performance of patients with idiopathic normal pressure hydrocephalus (INPH), to compare their performance with that of healthy individuals, and to estimate the predictive utility of putatively important factors.
A consecutive series of 47 patients with INPH underwent neurological, radiological, and neuropsychological examinations before and 3 months after shunt surgery. The same neuropsychological tests, measuring simple and target reaction times, dexterity, memory and learning, working memory, and aspects of executive functioning, were also administered to 159 healthy individuals.
Performance on all neuropsychological tests, except Simple Reaction Time and Digit Span, significantly improved after surgery, with more severe functional deficits showing greatest improvement. Age, education, duration, vascular comorbidity, sex, and onset symptom all failed to predict the neuropsychological effects of treatment. Despite improvement 3 months after shunt surgery, INPH patients were still outperformed by healthy individuals.
Most of the wide range of neuropsychological functions that are affected by INPH are markedly improved by shunt treatment, but not completely restored.
This study evaluated a modified, timed version of the "Get-Up and Go" Test (Mathias et al, 1986) in 60 patients referred to a Geriatric Day Hospital (mean age 79.5 years). The patient is observed and timed while he rises from an arm chair, walks 3 meters, turns, walks back, and sits down again. The results indicate that the time score is (1) reliable (inter-rater and intra-rater); (2) correlates well with log-transformed scores on the Berg Balance Scale (r = -0.81), gait speed (r = -0.61) and Barthel Index of ADL (r = -0.78); and (3) appears to predict the patient's ability to go outside alone safely. These data suggest that the timed "Up & Go" test is a reliable and valid test for quantifying functional mobility that may also be useful in following clinical change over time. The test is quick, requires no special equipment or training, and is easily included as part of the routine medical examination.
In a series of personally observed cases, three of which are reported in detail, the authors have noted that a state of symptomatic hydrocephalus may exist in the presence of normal CSF pressure. The patients had exhibited mental dullness, inattentiveness, psychomotor retardation, unsteadiness of gait, and incontinence of urine, a syndrome which may be mistakenly ascribed to a degenerative or traumatic vascular disease of the cerebrum. Ventriculo-atrial shunt corrected this condition and permitted recovery by lowering the CSF pressure 20 or more mm of water. An important factor, heretofore overlooked, in explaining this symptomatic hydrocephalus with relatively normal CSF pressure is that the force exerted on the ventricular wall represents a product of pressure times surface area. A given pressure exerts a greater force in a large ventricular system than in a small one. A pressure of 170 or 180 mm H2O in ventricles that are three times normal size may produce symptoms, whereas it would not do so in a normal-sized ventricular system. This hydraulic press hypothesis must be applied in all cases of hydrocephalus. Without some knowledge of ventricular size in this condition, the CSF pressure cannot be accurately evaluated. This physical principle applies not only to adult hydrocephalus but also to infantile hydrocephalus, where the cranium expands, and to certain types of porencephaly and postoperative meningeal cysts and possibly syringomyelia.
We examined CSF levels of markers of neuronal degeneration and astrogliosis-the light subunit of the neurofilament triplet protein (NFL) and the glial fibrillary acidic protein (GFAP)-in 65 patients with normal pressure hydrocephalus (NPH). NFL was increased sixfold (864 +/- 1,538 [mean +/- SD] versus 156 +/- 81 ng/L; p < or = 0.001) and GFAP twofold (1,116 +/- 1,085 versus 637 +/- 295 ng/L; p < or = 0.01) in NPH patients compared with neurologically healthy age-matched controls. No correlation was found between any particular symptom or sign and GFAP levels in CSF. The levels of NFL, on the other hand, were higher in patients with severe symptoms compared with those with moderate or no symptoms. Furthermore, there was a correlation between a high level of NFL and gait disturbance, incontinence, psychometric incapability, and social dysfunction. A high preoperative NFL level was associated with favorable outcome after shunt surgery. This indicates that NFL is a marker of ongoing and possibly still-reversible axonal damage in NPH.
The reliability of a single-voxel, localized proton magnetic resonance spectroscopy protocol suitable for clinical studies was investigated by means of in vitro, single-subject in vivo and multi-subject in vivo examinations of healthy adults aged from 19 to 67 years. The study was performed at 1.5 T using a standard quadrature head coil and a single voxel PRESS sequence (in vitro TR/TE = 1500/30 ms, in vivo TR/TE=2000/35 ms). Eighty-four in vitro and 30 single-subject examinations were statistically evaluated after quantification, including the calculation of the coefficients of variations (CV) for choline (Cho), creatine (Cr), myo-inositol (mI), lactate (Lac), N-acetyl-aspartate (NAA) and unresolved glutamine, glutamate and GABA (Glx). The CVs for absolute concentrations of the main metabolites Cho, Cr and NAA, ranged from 3.3% (3.8) to 4.0% (6.4%) (the in vivo results are given in brackets). Multi-subject CVs of absolute concentrations for Cho, Cr and NAA ranged from 7.6% to 15.0%. CVs of relative in vivo concentrations were found to be higher than CVs of absolute concentrations. Due to the better reproducibility of intra-individual absolute in vivo concentrations, cross-over studies using institutional units are recommended.
Proton NMR chemical shift and J-coupling values are presented for 35 metabolites that can be detected by in vivo or in vitro NMR studies of mammalian brain. Measurements were obtained using high-field NMR spectra of metabolites in solution, under conditions typical for normal physiological temperature and pH. This information is presented with an accuracy that is suitable for computer simulation of metabolite spectra to be used as basis functions of a parametric spectral analysis procedure. This procedure is verified by the analysis of a rat brain extract spectrum, using the measured spectral parameters. In addition, the metabolite structures and example spectra are presented, and clinical applications and MR spectroscopic measurements of these metabolites are reviewed.
The LCModel method analyzes an in vivo spectrum as a Linear Combination of Model in vitro spectra from individual metabolite solutions. Complete model spectra, rather than individual resonances, are used in order to incorporate maximum prior information into the analysis. A nearly model-free constrained regularization method automatically accounts for the baseline and lineshape in vivo without imposing a restrictive parameterized form on them. LCModel is automatic (non-interactive) with no subjective input. Approximately maximum-likelihood estimates of the metabolite concentrations and their uncertainties (Cramér-Rao lower bounds) are obtained. LCModel analyses of spectra from users with fields from 1.5 to 9.4 T and a wide range of sequences, particularly with short TE, are used here to illustrate the capabilities and limitations of LCModel and proton MRS.
The thalamus has long been thought to convey subcortical information to the cortex. Indeed, models of basal ganglia function attribute the primary role for the thalamus to a simple relay of information processed in the basal ganglia to the cortex. The thalamic nuclear groups that are associated primarily with this function are the ventral anterior and ventral lateral nuclei and the mediodorsal thalamic nucleus. However, recent studies have shown that the corticothalamic projection is important for the dynamics of the thalamocortical processing. Furthermore, the relay nuclei that carry basal ganglia output to the cortex have recently been shown to project back to the basal ganglia directly. These two recent developments indicate a more dynamic role for the thalamus in basal ganglia information processing than a passive relay.
Normal pressure hydrocephalus is a neurological disease which poses both diagnostic and therapeutic problems for the clinician. The measurement and characterisation of cerebral blood flow has been proposed as a tool for resolving such problems as well as elucidating its pathophysiology. We review the results of studies in which this tool has been applied to normal pressure hydrocephalus patients and consider the merits of the techniques that have been utilised. Finally, consideration is given to feasible future studies and the methods that could be employed in the study of cerebral blood flow and metabolism in patients with normal pressure hydrocephalus.
While much work has concentrated on focal white matter (WM) lesions in multiple sclerosis, there is growing evidence to suggest that normal-appearing WM (NAWM) and grey matter (GM) are also involved in the disease process. This study investigated multiple sclerosis disease effects on NAWM and cortical GM (CGM) metabolite concentrations, and the relationships between these metabolite concentrations and clinical impairment. Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) data acquired using point resolved spectroscopic (PRESS) localization (echo time 30 ms, repetition time 3000 ms, nominal voxel volume 2.3 ml) from 27 relapsing-remitting multiple sclerosis and 29 normal control (NC) subjects were processed using LCModel to estimate metabolite concentrations in millimoles per litre. (1)H-MRSI voxel tissue contents were estimated using SPM99 tissue and semi-automatic lesion segmentations of three-dimensional fast spoiled gradient recall scans acquired during the same scanning session. NAWM and CGM metabolite concentrations estimated were: choline-containing compounds (Cho); creatine and phosphocreatine (Cr); myo-inositol (Ins); N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (tNAA); and glutamate plus glutamine (Glx). CGM data came from 24 of the multiple sclerosis (mean age 35.2 years, mean disease duration 1.7 years) and 25 of the NC (mean age 34.9 years) subjects. NAWM data came from 25 of the multiple sclerosis (mean age 35.0 years, mean disease duration 1.7 years) and 28 of the NC (mean age 36.7 years) subjects. Metabolite concentrations were compared between multiple sclerosis and NC subjects using multiple (linear) regression models allowing for age, gender, (1)H-MRSI voxel tissue and CSF contents, and brain parenchymal volume. At a significance level of P < 0.05, CGM Cho, CGM and NAWM tNAA, and CGM Glx were all significantly reduced, and NAWM Ins was significantly elevated. Spearman correlations of multiple sclerosis functional composite scores with tissue metabolite concentrations were significant for the following: CGM Cr (r(s) = 0.524, P = 0.009), CGM Glx (r(s) = 0.580, P = 0.003) and NAWM Ins (r(s) = -0.559, P = 0.004). These results indicate that metabolite changes in NAWM and CGM can be detected early in the clinical course of multiple sclerosis, and that some of these changes relate to clinical status. The correlation of clinical impairment with CGM Cr and Glx but not tNAA suggests that it is more closely associated with neuronal metabolic dysfunction rather than loss in clinically early relapsing-remitting multiple sclerosis. The correlation of clinical impairment with a raised NAWM Ins may indicate that glial proliferation also relates to function at this stage of the disease.
Our aim was to determine if the resonance intensity of choline-containing compounds (Cho) measured using proton magnetic resonance spectroscopy (MRS) was increased in pre-lesional normal appearing white matter (NAWM) in patients with multiple sclerosis (MS) relative to NAWM that remained stable in subsequent scans.
The Cho peak in MR spectra is associated with membrane phospholipids and increases in acute MS plaques, possibly even before the appearance of MRI-visible MS lesions.
Three combined proton MRI and MRS imaging examinations of the corpus callosum and adjacent periventricular white matter were performed on 12 MS patients at intervals of 6 months. Proton density (PD) images were visually matched across 3 time points and the lesion volume in each voxel of the volume of interest was determined. The voxels were subdivided into four groups based on the presence or absence of lesion at baseline and change or no change in lesion volume on the subsequent scan.
We found a significantly higher baseline Cho/Creatine (Cr) ratio in NAWM voxels that displayed MRI visible lesions 6 months later than NAWM voxels that remained unchanged (1.57 +/- 0.30 and 1.37 +/- 0.33, respectively, p < 0.001). The 12-month interval data revealed similar pre-lesional elevated Cho/Cr, (1.51 +/- 0.29 versus 1.39 +/- 0.32, p = 0.009). Voxels that contained lesion at baseline and increased in lesion volume at 6 months also showed a significantly higher Cho/Cr ratio than those whose lesion volume did not change (1.60 +/- 0.32 and 1.49 +/- 0.36, respectively, p = 0.043).
The results of this study are consistent with focal pre-lesional myelin membrane pathology in the NAWM at least 12 months before lesions become visible on conventional MRI. This could reflect altered myelin chemistry or the presence of inflammation as seen in experimental allergic encephalomyelitis.
In patients with communicating or normal-pressure hydrocephalus, ventricular volume decreases following implantation of differential pressure valves. We implanted hydrostatic (Miethke dual-switch) valves in 60 patients with normal-pressure hydrocephalus (NPH) between September 1997 and December 2001. The patients underwent CT 1 year after operation, and we measured the Evans index. Although 83% of the patients showed no change in ventricular volume as assessed by this index, 72% nevertheless showed good to excellent and 16% satisfactory clinical improvement, while 12% showed no improvement. Moderate or marked reduction in ventricular size was observed in 17%, of whom 40% of these patients showed good to excellent and 20% satisfactory clinical improvement; 40% showed unsatisfactory improvement. The favourable outcome following implantation of a hydrostatic shunt thus did not correlate with decreased ventricular volume 1 year after operation, better outcomes being observed in patients with little or no alteration in ventricular size than in those with a marked decrease. Postoperative change in ventricular volume in NPH thus does not have the same significance as in patients with high-pressure hydrocephalus.
Regional cerebral blood flow (CBF) was studied with O(15)-water positron emission tomography and anatomic region-of-interest analysis on co-registered magnetic resonance in patients with idiopathic (n = 12) and secondary (n = 5) normal pressure hydrocephalus (NPH). Mean CBF was compared with values obtained from healthy volunteers (n = 12) and with clinical parameters. Mean CBF was significantly decreased in the cerebrum and cerebellum of patients with NPH. The regional analysis demonstrated that CBF was reduced in the basal ganglia and the thalamus but not in white matter regions. The results suggest that the role of the basal ganglia and thalamus in NPH may be more prominent than currently appreciated. The implications for theories regarding the pathogenesis of NPH are discussed.
The precise incidence and prevalence of idiopathic normal-pressure hydrocephalus (INPH) is not known, and evidence-based clinical diagnostic criteria have not been developed previously. This report contains evidence-based guidelines for clinical diagnosis of INPH that are intended to facilitate future epidemiological studies of INPH, promote earlier and more accurate diagnosis, and ultimately improve treatment outcome.
The criteria for the diagnosis of INPH are based on evidence from the medical literature, supplemented as necessary by expert opinion. From 1966 to 2003, 653 publications on "normal-pressure hydrocephalus" were cited in MEDLINE, including 29 articles that met the more stringent criteria of including "idiopathic normal-pressure hydrocephalus" in their title. Additional studies were considered that explicitly identified INPH cases and/or specified the criteria for a diagnosis of INPH. Studies were graded according to the class of evidence and results summarized in evidentiary tables. For issues of clinical relevance that lacked substantive evidence from the medical literature, the opinions of consulting experts were considered and contributed to "Options."
Evidence-based guidelines for the clinical diagnosis of INPH have been developed. A detailed understanding of the range of clinical manifestations of this disorder and adherence to practice guidelines should improve the timely and accurate recognition of this disorder.
It is recommended that INPH be classified into probable, possible, and unlikely categories. We hope that these criteria will be widely applied in clinical practice and will promote greater consistency in patient selection in future clinical investigations involving INPH.
To compare the neuropsychological performance of patients with idiopathic normal pressure hydrocephalus (INPH) with that of healthy individuals and to examine its relation to neurological signs, vascular comorbidity, and background factors.
A consecutive series of 58 patients with INPH underwent neurological, neuroradiological, and neuropsychological examinations. The neuropsychological tests, measuring vigilance, fine movements of the hands, learning, working memory, and aspects of executive functioning, were also administered to 108 healthy individuals.
Patients performed worse than healthy individuals on all included tests. Significant correlations between test results were more frequent and stronger among patients and the degree of neuropsychological impairment was related to the severity of other signs of INPH. Patients with vascular risk factors performed worse than those without.
The neuropsychological deficits in INPH are widely distributed, interrelated, associated with neurological signs, and aggravated by vascular comorbidity.
The clinical condition normal pressure hydrocephalus (NPH) is one of the few conditions with dementia that can be successfully treated. Even though NPH was described more than 40 years ago, information on prevalence and incidence of this disease is scarce. The objective of this study was to obtain information about prevalence of iNPH in a Norwegian population.
In a stable population of 220,000 inhabitants, structured and intensive efforts were directed towards the public via local newspapers, radio and television channels, and directed towards the healthcare professionals via personal letters and lectures, to recruit patients with idiopathic NPH (iNPH) investigation during a 12-month period. This population is served by only one neurological department and one neurosurgical department, thus avoiding any leakage of patients during the investigation period. We determined those patients fulfilling the diagnostic criteria of probable iNPH.
Eighty-six patients were referred, of whom 48 patients fulfilled the diagnostic criteria of probable iNPH. This equals a minimum prevalence of iNPH in our population of 21.9/100,000. Most importantly, the prevalence was increasing with age. When excluding patients who had symptoms for more than 1 year, we found an incidence of 5.5/100,000/year.
In this Norwegian population of 220,000 inhabitants, we found a prevalence of probable iNPH of 21.9/100,000 and an incidence of 5.5/100,000. The numbers should be regarded as minimum estimates.
This study uses proton magnetic resonance spectroscopy to investigate whether or not idiopathic normal pressure hydrocephalus is associated with neuronal dysfunction or ischemia in the brain. We evaluate whether or not proton magnetic resonance spectroscopy is useful for predicting improvement after long-term external lumbar drainage (ELD) of cerebrospinal fluid.
Eighteen patients (mean age, 73 yr; six women) and 10 matching controls participated. Participants were characterized by clinical features, cognitive and motor function tests, and cerebrospinal fluid hydrodynamics (patients only). Signals from N-acetyl-aspartate (NAA), choline, lactate, and creatine (Cr) (reference) were sampled once in controls and twice in patients (before and after a 3-day ELD of approximately 135 mL/24 h) by proton magnetic resonance spectroscopy (1.5 T) from a 7.2-mL volume in the frontal white matter. Improvement was defined by video recordings of the patients' gait.
Sixteen patients finished the ELD (one patient had meningitis, and one patient had catheter insertion failure) with a mean drain volume of 395 mL. NAA/Cr ratios were lower in patients than in controls (1.60 versus 1.84, P = 0.02), but no difference was found for choline/Cr ratios. No lactate signals were detected. Fifty percent of patients improved after ELD. They had higher NAA/Cr ratios than nonimproved patients (1.70 versus 1.51, P = 0.01), but no differences were found in choline/Cr ratios or drain volume.
NAA/Cr ratios were decreased in patients with idiopathic normal pressure hydrocephalus, which is consistent with neuronal dysfunction in the frontal white matter. Improved patients had NAA/Cr ratios close to normal, indicating that enough functional neurons are a prerequisite for the cerebrospinal fluid drainage to have an effect.
Present data support the concept that (1)H magnetic resonance spectroscopy ((1)H MRS) may become an adjunct to clinical evaluation for differential diagnosis of dementia in the future. The value of (1)H MRS in monitoring the disease progression in dementia is expected to be in areas where group effects are sought such as monitoring effectiveness of therapies in drug trials. Elevation of myoinositol to creatine (mI/Cr) and choline to creatine (Cho/Cr) and reduction in the neuronal integrity marker N-acetylaspartate to creatine (NAA/Cr) levels in individuals with mild cognitive impairment and pre-symptomatic Alzheimer's disease suggests that (1)H MRS may also be valuable in predicting future development of dementia and monitoring early disease progression for preventive therapies. Investigations of in vivo (1)H MRS as a marker for differential diagnosis and progression of dementia, however, has been limited to clinically confirmed cohorts and remains to be validated by histopathology at autopsy. Overall, MRS is a promising investigational technique in ageing and dementia at this time. The potential clinical application of MRS in ageing and dementia, however, is growing with technical advances in the field.
In localized brain proton MR spectroscopy ((1)H-MRS), metabolites' levels are often expressed as ratios, rather than as absolute concentrations. Frequently, their denominator is the creatine [Cr], which level is explicitly assumed to be stable in normal as well as in many pathologic states. The rationale is that ratios self-correct for imager and localization method differences, gain instabilities, regional susceptibility variations and partial volume effects. The implicit assumption is that these benefits are worth their cost(w)-(w) propagation of the individual variation of each of the ratio's components. To test this hypothesis, absolute levels of N-acetylaspartate [NAA], choline [Cho] and [Cr] were quantified in various regions of the brains of 8 volunteers, using 3-dimensional (3D) (1)H-MRS at 1.5 T. The results show that in over 50% of approximately 2000 voxels examined, [NAA]/[Cr] and [Cho]/[Cr] exhibited higher coefficients of variations (CV) than [NAA] and [Cho] individually. Furthermore, in approximately 33% of these voxels, the ratios' CVs exceeded even the combined constituents' CVs. Consequently, basing metabolite quantification on ratios and assuming stable [Cr] introduces more variability into (1)H-MRS than it prevents. Therefore, its cost exceeds the benefit.