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BACKGROUND AND PURPOSE: CSF loss in spontaneous intracranial hypotension disrupts a well-regulated equilibrium. We aimed to evaluate the volume shift between intracranial compartments in patients with spontaneous intracranial hypotension before and after surgical closure of the underlying spinal dural breach. MATERIALS AND METHODS: In total, 19 patients with spontaneous intracranial hypotension with a proved spinal CSF leak investigated at our institution between July 2014 and March 2017 (mean age, 41.8 years; 13 women) were included. Brain MR imaging–based volumetry at baseline and after surgery was performed with FreeSurfer. In addition, the spontaneous intracranial hypotension score, ranging from 0 to 9, with 0 indicating very low and 9 very high probability of spinal CSF loss, was calculated. RESULTS: Total mean ventricular CSF volume significantly increased from baseline (15.3 mL) to posttreatment MR imaging (18.0 mL), resulting in a mean absolute and relative difference, +2.7 mL and +18.8% (95% CI, +1.2 to +3.9 mL; P

Meningitis patient can present with various manifestation including hydrocephalus due to multiple reason. Diagnosis of meningitis mainly rely on CSF analysis which is usually obtained from lumbar puncture. In case of hydrocephalus CSF can be obtain from ventricles during VP shunt operation. Sometimes ventricular CSF can be normal in meningitis patient while lumbar CSF shows abnormality. Possible mechanisms behind this phenomenon are discussed here. Patients who present with hydrocephalus and have normal Ventricular CSF should investigated with lumbar CSF analysis in a view of delay in diagnosis and treatment.

Cerebrospinal fluid (CSF) T 2 mapping can potentially be used to investigate CSF composition. A previously proposed CSF T 2–mapping method reported a T 2 difference between peripheral and ventricular CSF, and suggested that this reflected different CSF compositions. We studied the performance of this method at 7 T and evaluated the influence of partial volume and B 1 and B 0 inhomogeneity. T 2-preparation-based CSF T 2-mapping was performed in seven healthy volunteers at 7 and 3 T, and was compared with a single echo spin-echo sequence with various echo times. The influence of partial volume was assessed by our analyzing the longest echo times only. B 1 and B 0 maps were acquired. B 1 and B 0 dependency of the sequences was tested with a phantom. T 2,CSF was shorter at 7 T compared with 3 T. At 3 T, but not at 7 T, peripheral T 2,CSF was significantly shorter than ventricular T 2,CSF. Partial volume contributed to this T 2 difference, but could not fully explain it. B 1 and B 0 inhomogeneity had only a very limited effect. T 2,CSF did not depend on the voxel size, probably because of the used method to select of the regions of interest. CSF T 2 mapping is feasible at 7 T. The shorter peripheral T 2,CSF is likely a combined effect of partial volume and CSF composition.

Purpose To develop a quantitative susceptibility mapping (QSM) method with a consistent zero reference using minimal variation in cerebrospinal fluid (CSF) susceptibility. Theory and methods The ventricular CSF was automatically segmented on the R2* map. An L2 -regularization was used to enforce CSF susceptibility homogeneity within the segmented region, with the averaged CSF susceptibility as the zero reference. This regularization for CSF homogeneity was added to the model used in a prior QSM method (morphology enabled dipole inversion [MEDI]). Therefore, the proposed method was referred to as MEDI+0 and compared with MEDI in a numerical simulation, in multiple sclerosis (MS) lesions, and in a reproducibility study in healthy subjects. Results In both the numerical simulations and in vivo experiments, MEDI+0 not only decreased the susceptibility variation within the ventricular CSF, but also suppressed the artifact near the lateral ventricles. In the simulation, MEDI+0 also provided more accurate quantification compared to MEDI in the globus pallidus, substantia nigra, corpus callosum, and internal capsule. MEDI+0 measurements of MS lesion susceptibility were in good agreement with those obtained by MEDI. Finally, both MEDI+0 and MEDI showed good and similar intrasubject reproducibility. Conclusion QSM with a minimal variation in ventricular CSF is viable to provide a consistent zero reference while improving image quality. Magn Reson Med 79:2795-2803, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Background and purpose Cerebrospinal fluid (CSF) in the brain can be compartmentalized into two main divisions: ventricular CSF and subarachnoid space (sulcal CSF). Changes in CSF volumetry are seen in many neurological conditions including multiple sclerosis (MS) and found to correlate with clinical outcomes. We aimed to test the relation between the volumetry of sulcal and ventricular CSF and cognitive impairment (CI) based on the minimal assessment of cognitive function in MS (MACFIMS) in patients with MS. Material and methods Forty-six patients with MS underwent the MACFIMS battery and classified as nonimpaired (MSNI) (n = 10) and cognitively impaired (MSCI) (n = 30) and borderline (MSBD) MS patients (n = 6). Volumes of sulcal and ventricular CSF along with global gray and white matter volumes and cortical thickness were obtained by diffusion tensor imaging (DTI) and T1-weighted (T1w)-based segmentation. These measures were statistically analyzed for associations with CI after adjusting for the age, education in years, lesion load, and disease duration. Results Sulcal CSF showed the strongest correlation with CI (r = .51, P = .001) in our cohort, whereas ventricular CSF (P = .28, P = .19) along with cortical thickness and gray matter volume failed to show a significant correlation. Group analyses unadjusted for multiple comparisons showed significant difference in volumes of sulcal CSF and ventricular CSF between MSNI and MSCI groups (P Conclusion Sulcal CSF correlates with CI in patients with MS, possibly explained by cortical atrophy. DTI/T1w-based sulcal CSF segmentation method might be used as an indirect and simple neuroimaging marker to monitor CI in MS patients.

Background Aneurysmal subarachnoid hemorrhage (aSAH) is often complicated by the occurrence of delayed ischemic neurologic deficits (DIND), which impairs the clinical outcome of patients. The release of oxyhemoglobin (oxyHb) from lysing erythrocytes into cerebrospinal fluid (CSF) may critically contribute to the development of DIND. Methods Ventricular CSF of 18 high-grade (Fisher 3 and 4) aSAH patients was sampled daily from external ventricular drains between days 0 and 14 after bleeding. CSF was spectrophotometrically analyzed with precise quantification of cell-free oxyHb levels. Results OxyHb levels in CSF showed a delayed peak reaching the highest levels in the high-risk period for developing of DIND between days 3 and 14 after aneurysm rupture. Patients with DIND had a significantly higher cumulative oxyHb exposure within the first week after bleeding. Conclusions OxyHb levels in CSF may be useful as a biomarker to predict DIND in aSAH patients. The contribution of oxyHb in CSF to the pathogenesis of DIND should be further investigated as a potential therapeutic target.

In this chapter we describe in detail the surgical and imaging techniques employed for the study of the anatomical routes of drainage of cerebrospinal fluid (CSF) and interstitial fluid (ISF) from the brain. The types of tracers, sites of injection, and volumes injected are crucial. For example, when testing the drainage of ISF from the parenchyma, volumes larger than 0.5 μL result in spillage of ISF into the ventricular CSF.

The human brain lateral ventricular (LV) cerebrospinal fluid (CSF) volume has been used as a neuroimaging marker of brain changes in health and disease. The LV CSF diffusivity may offer a useful quality assurance measure and become a potential noninvasive marker of deep brain temperature. In this work we sought to validate a method for human brain lateral ventricular (LV) cerebrospinal fluid (CSF) using diffusion tensor imaging (DTI) contrast to provide LV volume and corresponding DTI metrics. We compared LV volume obtained using DTI with that obtained using validated segmentations of the LV on T1-weighted data. DTI and T1-weighted data were acquired at 3 T on 49 healthy males and 56 age-matched females aged 18–59 years. We showed histogram distributions of LV DTI metrics to establish quality assurance measures. We also analyzed the age and gender effects of LV volume and diffusivity. LV volumes estimated using both T1-weighted and DTI correlated strongly in males and females (ICC=0.99; median Dice index ~80%). The LV-to-intracranial volume percentage increased significantly with age only in males, using the DTI-based approach (r=0.39; p=0.005). LV CSF Mean diffusivity was greater in males than females ((~1.2%; p=0.03). Mean diffusivity of lateral ventricular CSF decreased significantly with age in healthy adults (r=−0.30; p=0.02). Our results highlight the importance of age and gender-based analyses and the potential of LV diffusivity measures as a quantitative marker.

The equilibrium between the ventricular and lumbar cerebrospinal fluid (CSF) compartments may be disturbed (in terms of flow and biochemistry) in patients with chronic hydrocephalus (CH). Using flow magnetic resonance imaging (MRI) and CSF assays, we sought to determine whether changes in CSF were associated with biochemical alterations. Nine elderly patients with CH underwent phase-contrast MRI. An index of CSF dynamics (Idyn) was defined as the product of the lumbar and ventricular CSF flows. During surgery, samples of CSF were collected from the lumbar and ventricular compartments and assayed for chloride, glucose and total protein. The lumbar/ventricular (L/V) ratio was calculated for each analyte. The ratio between measured and expected levels (Ibioch) was calculated for each analyte and compared with Idyn. Idyn varied from 0 to 100.10(3)μl(2).s(2). In contrast to the L/V ratios for chloride and glucose, the L/V ratio for total protein varied markedly from one patient to another (mean ± standard deviation (SD): 2.63 ± 1.24). The Ibioch for total protein was strongly correlated with the corresponding Idyn (Spearman's R: 0.98; p5 × 10(-5)).We observed correlated alterations in CSF flow and biochemical parameters in patients with CH. Our findings also highlight the value of dynamic flow analysis in the interpretation of data on CSF biochemistry.

Object The authors undertook this study to determine white blood cell (WBC) counts in CSF obtained from lateral ventricles and myelomeningoceles (MMCs) in infants in a developing country at the time of their initial presentation for medical evaluation. Methods CSF was aspirated from the lateral ventricles and from MMC sacs of 100 consecutive infants at Kijabe Hospital, Kijabe, Kenya. Peripheral blood WBC counts and CSF WBC counts were determined in the laboratory. CSF with WBC counts of 5 cells/mm3 or greater was cultured. Results The mean WBC count in ventricular CSF was 16 cells/mm3, with a median and mode of 0 cells/mm3. The mean WBC count of CSF in MMC sacs was 141 cells/mm3 (median 15 cells/mm3). No child had both a positive culture from ventricular CSF and a negative culture from MMC CSF. There was no correlation between age at presentation and WBC counts in the MMCs. Infants younger than 8 days old were as likely to have high WBC counts in CSF from their MMC sacs as were older children; 7 of 12 infants with 500 WBCs or more in CSF from their MMCs were younger than 8 days old. Only 5 of 58 CSF specimens from MMC sacs with 5 or more WBCs/mm3 had positive bacterial cultures, which may be a reflection of CSF specimen processing rather than of true culture negativity. Conclusions CSF from ventricular fluid of infants presenting with MMCs infrequently has high WBC counts, so infrequently that it does not need to be evaluated routinely. CSF in MMC sacs often has high WBC counts that suggest the presence of bacterial infection. In developing countries where culture reliability is questionable, intravenous administration of antibiotics before MMC closure for infants with high MMC WBC counts may diminish postoperative meningitis/ventriculitis.

SUMMARY The author discusses several experiments in tracing the bulk movement of cerebrospinal fluid in animals and in human subjects by the injection of radio-active isotopes.

The origins of excessive daytime sleepiness in Parkinson disease (PD) are unclear. The authors hypothesize that orexin neurons, a recently identified wake promoting system, could contribute to its pathophysiology. They measured orexin-A/hypocretin-1 concentration in ventricular CSF in 19 parkinsonian patients and compared it with neurologic controls. Orexin levels were lower in patients and decreased with the severity of the disease. The authors suggest that orexin neurons contribute to daytime sleepiness in late stage PD.

Objectives This study establishes reference data for human lumbar CSF butyrylcholinesterase (E.C.3.1.1.8.) activity and investigates the enzyme activity in ventricular CSF. We comment on the relationship between CSF butyrylcholinesterase activity and other laboratory parameters. Subjects and methods We investigated 64 lumbar CSF samples obtained from a clinically healthy population and 169 ventricular CSF samples collected from 90 neurosurgical patients. Results The reference range we recommend for lumbar CSF butyrylcholinesterase activity is 5.4 to 17.0 nmol/min x ml. The majority of ventricular butyrylcholinesterase activities in our patient subset ranged up to 5 nmol/min x ml. Conclusions We established the relative influence of serum and CNS components on total CSF butyrylcholinesterase activity. The CNS fraction predominates the total butyrylcholinesterase activity in normal lumbar CSF. In ventricular CSF enzyme influx from serum outweighs the CNS component.

We studied the nycterohemeral variations of homovanillic acid (HVA) in ventricular cerebrospinal fluid (CSF) in 24 patients undergoing monitoring of intracranial pressure as part of the normotensive hydrocephalus (NTH) work-up. CSF samples were obtained every 4 h in each patient. The mean individual values of HVA in the ventricular CSF ranged from 133 to 421 ng/ml, and they could not be correlated to any clinical feature. The intraindividual levels of HVA were stable throughout 24 hours, with a variation coefficient inferior to 10% in 63% of cases, and inferior to 20% in all the patients.

Protein concentration, leukocyte density, and lactate concentration were studied in 41 pairs of ventricular and lumbar CSF drawn at an interval of less than 24 hours from patients with suspected bacterial CNS infections. The ventriculo-lumbar ratios ranged from 0.003 to 10.2 (median = 0.42) for protein and from 0.002 to 53.5 (median = 0.17) for leukocytes. The uneven distribution of leukocytes and proteins in the CSF space may produce findings that fail to indicate bacterial CNS infections. Lactate was distributed more homogeneously in the CSF space than protein and leukocytes (ventriculo-lumbar ratio 0.52 to 1.66 [median = 0.81]).

Objective Patients with Parkinson’s disease frequently complain of sleep disturbances and loss of muscle atonia during rapid-eye-movement (REM) sleep is not rare. The orexin-A (hypocretin-1) hypothalamic system plays a central role in controlling REM sleep. Loss of orexin neurons results in narcolepsy-cataplexy, a condition characterized by diurnal sleepiness and REM sleep without atonia. Alterations in the orexin-A system have been also documented in Parkinson’s disease, but whether these alterations have clinical consequences remains unknown. Methods Here, we measured orexin-A levels in ventricular cerebrospinal fluid from eight patients with Parkinson’s disease (four males and four females) who underwent ventriculography during deep brain-stimulation surgery and performed full-night polysomnography before surgery. Results Our results showed a positive correlation between orexin-A levels and REM sleep without muscle atonia. Conclusion Our results suggest that high levels of orexin-A in Parkinson’s disease may be associated with loss of REM muscle atonia.

This is the first report of the presence of free D-amino acids in lumbar and ventricular human cerebrospinal fluid (CSF) of individuals with Alzheimer disease (AD) compared with CSF of normal control subjects and with individuals affected by multiple sclerosis, as an unrelated neurologic disorder. Free D-amino acids are present at significantly higher levels in AD CSF than normal CSF, whereas in the CSF of patients affected by multiple sclerosis, D-amino acids occurs at the same level as in the normal controls. The total D-amino acid content in ventricular CSF was 1.48 times higher in the AD than controls (26.4 vs 17.9 nmol/mL, p = 0.025). The total D-amino acid content was 1.43 times higher in AD lumbar CSF than controls (1.89 vs 1.32 nmol/mL, p = 0.001). D-Aspartate in particular was 2.74 times higher in AD ventricular CSF compared to normal ventricular CSF (3.34 vs 1.22 nmol/mL, p = 0.029). In lumbar CSF, D-aspartate was 1.5 times higher in AD than controls (0.054 vs 0.036 nmol/mL, p = 0.041). Previously we reported that D-amino acids are elevated in AD brain proteins associated with neurofibrillary tangles compared to normal brain proteins (D'Aniello et al., 1992c; Fisher et al., 1992a,b). Thus, the D-amino acids present in CSF may originate from degradation of brain proteins.

In 1900, Ernst Overton found that the entry of anilin dyes through the cell membranes of living cells depended on the lipophilicity of the dyes. The brain is surrounded by barriers consisting of lipid layers that possess several inward and outward active transport systems. In the absence of meningeal inflammation, the cerebrospinal fluid (CSF) penetration of anti-infectives in humans estimated by the ratio of the area under the concentration-time curve (AUC) in CSF (AUC CSF ) to that in serum (AUC CSF /AUC S ) correlated positively with the lipid-water partition coefficient at pH 7.0 (log D ) (Spearman's rank correlation coefficient r S = 0.40; P = 0.01) and negatively with the molecular mass (MM) ( r S = −0.33; P = 0.04). The ratio of AUC CSF to the AUC of the fraction in serum that was not bound (AUC CSF /AUC S,free ) strongly correlated with log D ( r S = 0.67; P < 0.0001). In the presence of meningeal inflammation, AUC CSF /AUC S also correlated positively with log D ( r S = 0.46; P = 0.002) and negatively with the MM ( r S = −0.37; P = 0.01). The correlation of AUC CSF /AUC S,free with log D ( r S = 0.66; P < 0.0001) was as strong as in the absence of meningeal inflammation. Despite these clear correlations, Overton's rule was able to explain only part of the differences in CSF penetration of the individual compounds. The site of CSF withdrawal (lumbar versus ventricular CSF), age of the patients, underlying diseases, active transport, and alterations in the pharmacokinetics by comedications also appeared to strongly influence the CSF penetration of the drugs studied.

Background. The standard procedure for the diagnosis of central nervous system (CNS) infections consists of cerebrospinal fluid (CSF) sampling, which is usually accomplished by a lumbar puncture. However, in some patients presenting with acute hydrocephalus submitted to immediate CSF drainage, the fluid is customarily obtained from the placed draining system. In addition, the CSF obtained from the ventricular and lumbar spaces in some cases may show unusual differences, both in physiological and pathological conditions. Illustrative cases. We report two children who presented with confounding results in the initial studies of their ventricular and lumbar CSF who were subsequently diagnosed with tuberculous meningitis, causing delay in diagnosis and treatment. Aim. By reporting these cases, we wanted to alert the treating physician about the possibility of this discrepancy to avoid the delayed diagnosis and management of the affected patients. Discussion. We comment on the possible pathophysiological mechanisms that may result in this dissociation in ventricular and lumbar CSF composition. Conclusions. Normal results in CSF studies, especially those of the ventricular fluid, do not always rule out the presence of tuberculous meningitis. We suggest obtaining a CSF sample from the lumbar subarachnoid space in doubtful, or suspicious, cases of CNS infection even in the presence of a normal ventricular CSF. Antecedentes. El procedimiento habitual para el diagnóstico de infección del sistema nervioso central (CNS) consiste en el estudio del liquido cefalorraquídeo (LCR) mediante la realización de una punción lumbar. Sin embargo, en pacientes que debutan con un cuadro de hidrocefalia aguda que son tratados de urgencia mediante la inserción de un sistema de drenaje de LCR, el líquido es rutinariamente obtenido desde el sistema derivativo implantado. Pero, en ciertos casos, el LCR ventricular y lumbar analizados pueden mostrar diferencias significativas, tanto en condiciones fisiológicas como patológicas. Casos ilustrativos. Se describen los casos de dos niños que presentaron resultados dispares en los estudios iniciales del LCR ventricular y lumbar, en los que se demostró posteriormente que padecían una hidrocefalia por meningitis tuberculosa, lo que motivó un considerable retraso en su diagnóstico y tratamiento. Objetivo. Al describir estos dos casos, pretendemos alertar al médico responsable sobre la posibilidad de esta discrepancia, para evitar retrasos en el diagnóstico y tratamiento de estos pacientes. Discusión. Se comentan los posibles mecanismos patogénicos que pueden producir esta disociación en la composición del LCR ventricular y lumbar. Conclusiones. Un resultado normal del LCR, especialmente del líquido ventricular, no descarta siempre la presencia de una meningitis tuberculosa. Sugerimos la obtención de una muestra de LCR a partir del espacio subaracnoideo lumbar en casos dudosos o sospechosos de infección del SNC, incluso ante la presencia de un LCR ventricular normal.

Antecedentes. El procedimiento habitual para el diagnostico de infeccion del sistema nervioso central (CNS) consiste en el estudio del liquido cefalorraquideo (LCR) mediante la realizacion de una puncion lumbar. Sin embargo, en pacientes que debutan con un cuadro de hidrocefalia aguda que son tratados de urgencia mediante la insercion de un sistema de drenaje de LCR, el liquido es rutinariamente obtenido desde el sistema derivativo implantado. Pero, en ciertos casos, el LCR ventricular y lumbar analizados pueden mostrar diferencias significativas, tanto en condiciones fisiologicas como patologicas. Casos ilustrativos. Se describen los casos de dos ninos que presentaron resultados dispares en los estudios iniciales del LCR ventricular y lumbar, en los que se demostro posteriormente que padecian una hidrocefalia por meningitis tuberculosa, lo que motivo un considerable retraso en su diagnostico y tratamiento. Objetivo. Al describir estos dos casos, pretendemos alertar al medico responsable sobre la posibilidad de esta discrepancia, para evitar retrasos en el diagnostico y tratamiento de estos pacientes. Discusion. Se comentan los posibles mecanismos patogenicos que pueden producir esta disociacion en la composicion del LCR ventricular y lumbar. Conclusiones. Un resultado normal del LCR, especialmente del liquido ventricular, no descarta siempre la presencia de una meningitis tuberculosa. Sugerimos la obtencion de una muestra de LCR a partir del espacio subaracnoideo lumbar en casos dudosos o sospechosos de infeccion del SNC, incluso ante la presencia de un LCR ventricular normal.

Background: Blood contamination is commonly observed in ventricular cerebrospinal fluid (CSF) samples from patients with extraventricular drainage systems. Because the introduction of blood may interfere with the white blood cell count as a useful marker for the diagnosis of an infection, correction for blood content would be desirable. Methods: In a retrospective study, we analysed the use of correction formulas in 724 blood-contaminated ventricular CSF samples. Results: Using a standard correction method the white blood cell count was not normalised in most CSF samples, with pleocytosis indicating an inflammatory stimulus set by the blood itself or by the foreign body. When correcting white blood cell counts in the CSF of culture-positive patients, some samples were normalised or overcorrected. In addition, correction of the CSF white blood cell count did not increase sensitivity and specificity for the detection of culture-positive CSF samples. Conclusions: Correction is not necessary when using the white blood cell count as a parameter to predict CSF infection in ventricular CSF samples.

Ventricular CSF shunt infections due to Corynebacterium jeikeium are rare. Such infections may become manifest weeks to months after surgery. They are difficult to eradicate and often recur. We report three cases of C. jeikeium ventricular CSF shunt infections, all of which occurred in patients who received long-term prophylactic therapy with antibiotics and had protracted hospitalizations. Two patients had multiple recurrences, and all patients required shunt revision. Additional therapy with intrathecal vancomycin for 6-10 days after surgery was effective for this unusual cause of ventricular CSF shunt infection. On the basis of our experience and a review of six previously published case reports, we recommend CSF sterilization with intravenous and intrathecal vancomycin, followed by replacement of shunt hardware.

Objective: The goal of this study was to compare brain volumes of alcoholic and nonalcoholic men and women and determine if the magnitudes of differences in brain volumes between alcoholic women and nonalcoholic women are greater than the magnitudes of the differences between alcoholic men and nonalcoholic men. Method: The study group included 118 subjects: 79 inpatients 30–60 years of age who were alcohol dependent but had no clinically apparent cognitive impairment or medical illness (43 men and 36 women) and 39 healthy comparison subjects of similar age who were not alcoholic (20 men and 19 women). The volume of intracranial contents was segmented into gray matter, white matter, sulcal CSF, and ventricular CSF from a T1-weighted magnetic resonance image obtained after the alcoholic subjects had attained 3 weeks of sobriety. Results: Alcoholic women had significantly smaller volumes of gray and white matter as well as greater volumes of sulcal and ventricular CSF than nonalcoholic women. The differences in gray and white matter volumes between alcoholic and nonalcoholic men were significant, but the significance of these differences was of a smaller magnitude than the significance of the differences between alcoholic and nonalcoholic women. Direct comparisons of alcoholic men and women showed that the proportion of intracranial contents occupied by gray matter was smaller in alcoholic women than in alcoholic men. The magnitudes of differences in brain volumes adjusted for intracranial size between alcoholic women and nonalcoholic women were greater than the magnitudes of the adjusted differences between alcoholic men and nonalcoholic men. Conclusions: These results are consistent with greater sensitivity to alcohol neurotoxicity among women.

Differential diagnosis of NPH and brain atrophy is sometimes difficult. Recently, a new method using MRI was introduced as a noninvasive, direct technique for the measurement of intracranial CSF volume. Using this new technique, we measured the intracranial and ventricle CSF volume in patients with enlarged ventricles in order to differentiate between NPH and brain atrophy. Ten healthy volunteers (control group) and 21 patients with enlarged ventricles were enrolled in this study. Eleven out of 21 patients were clinically diagnosed as having NPH (shunted group) and the remaining 10 patients were considered to have cerebral atrophy (non-shunted group). Intracranial and ventricular CSF volume in each case were measured by 3D FASE (Fast Asymmetric Spine-Echo) MR imaging sequence with region growing method. Ventricular/intracranial CSF volume ratio was also calculated. Ten out of 11 patients showed improvement in clinical symptoms and/or dementia scale after shunting. Our results clearly indicate that the ventricular volume in the shunted group was enlarged and that the ventricular/intracranial CSF ratio was significantly high. Thus we concluded that enlarged ventricle with high ventricular/intracranial CSF volume ratio strongly suggests NPH.

We report the impact of diagnostic ventricular CSF removal (VCR) on the gait disturbance in 24 patients with suspected normal pressure hydrocephalus (NPH) who had an intraventricular catheter for studies of CSF dynamics in order to select patients for shunt surgery. There were no complications related to removal of 24 ml CSF over a period of 6 hours in four instances or to the removal of 15-18 ml at one time in twenty instances. Seventeen out of 24 patients were diagnosed as having NPH. Two of those patients who had relatively mild symptoms had a prolonged amelioration of their gait disturbance after diagnostic VCR. Thirteen patients underwent subsequent shunt operations. Eleven of them had good functional and symptomatic improvement on follow-up. In those six patients who had a marked amelioration of their gait disturbance after diagnostic VCR, not only improvement of the gait disturbance was observed after shunting, but a consistent overall improvement as well. The predictive value of VCR was more variable in those six patients who had only a moderate response to VCR. No change of the gait disturbance after VCR was noted in seven patients in whom the diagnosis of NPH was not confirmed. Diagnostic VCR might be a valuable ancillary test in specialized centers which routinely use intraventricular CSF monitoring in the selection of patients for shunt surgery.

Objective: To investigate the validity of the Penney Burden of Pathology (BOP) score (Age X [CAG length-35.5]) (Penney et al, 1997) as a measure of disease severity in premanifest HD (preHD). We also compare the BOP9s utility with other preHD burden measures, namely the Aylward (Aylward et al, 2004) and Langbehn (Langbehn et al, 2010) years-to-onset (YTO) estimates. Background Although developed in 1997 from post-mortem analysis of striatal atrophy in 89 Huntington9s patients, the BOP has never been validated as a useful preHD burden measure. Despite this, a number of recent preHD studies have used this score for inclusion criteria for subjects in clinical trials. Design/Methods: 37 preHD subjects (mean age 41.2, mean CAG repeat length 42.3) underwent 1.5T T1-weighted structural imaging. Automated segmentation methods (Stoffers et al, 2010; Majid et al, in press) were used to determine normalized volumes for the whole brain, gray matter, white matter, cerebrospinal fluid, subcortical nuclei (caudate and putamen), and various cortical regions. These measures were then correlated with the BOP, in addition to Aylward and Langbehn YTO estimates. Results: BOP correlated with total brain (R=-.36, p=.03), gray matter (R=-.38, p=.02), ventricular CSF (R=.52, p=.001), and putamen (R=-.39, p=.02) volumes but not significantly with either caudate (R=-.30, p=.07) or cortical volumes. Correlations with the Langbehn YTO estimate were similar. By contrast, the Aylward YTO more strongly predicted atrophy in all the above regions, in addition to the caudate (R=.53, p=.001) and also a number of specific cortical areas. Conclusions: Comparison of various preHD burden measures suggests that the Aylward YTO estimate may be a better predictor of structural atrophy, possibly because of the addition of "parental age-of-onset", which may comprise genetic and environmental factors unaccounted for by CAG repeat length alone. Caution should be exercised in selecting preHD subjects for clinical trials solely on the basis of BOP score. Supported by: CHDI. Disclosure: Dr. Majid has nothing to disclose. Dr. Stoffers has nothing to disclose. Dr. Anders has received personal compensation for activities with CorTech Labs. Dr. Anders holds stock and/or stock options in CorTechs Labs, Inc. Dr. Goldstein has nothing to disclose. Dr. Aron has nothing to disclose. Dr. Corey-Bloom has received personal compensation for activities with Isis Pharmaceuticals as a consultant. Dr. Corey-Bloom has received research support from Medivation, Pfizer Inc, Elan Corporation, Forest Laboratories, Inc., Teva Neuroscience, NeuroSearch, and CHDI.

A serial measurement of endothelin-1(ET-1) levels in plasma, cisternal and ventricular cerebrospinal fluid(CSF) was performed in 16 patients with subarachnoid haemorrhage (SAH). The patients were classified as grade III or IV according to the clinical grade of Hunt and Hess, and computerised tomography(CT) was classified as Fisher's CT group 3. Cisternal and ventricular CSF and plasma were obtained from the patients on the day of operation days 0-3, days 5-8 and days 14-18 after SAH. ET-I concentration in each sample was quantified by sandwich-enzyme immunoassay. ET-I levels in plasma and CSF were the highest between days 0-3 and then decreased. The ET-I levels in the cisternal CSF were significantly higher during days 0-3(p

The relationship between olfactory identification ability and MRI volumetric indices of specific cortical and subcortical brain regions was investigated in 36 recently detoxified male alcoholics. The results of correlational analyses between MRI indices and score on the University of Pennsylvania Smell Identification Test (UPSIT) revealed that impairment in olfactory identification was associated with elevated cortical and ventricular CSF volumes as well as with reduced tissue volumes in the cortical and subcortical grey matter. The volume of the thalamus was found to be a significant unique predictor of UPSIT score, even after accounting for variance shared with other MRI indices. These findings provide the first empirical support for existing hypotheses that olfactory loss in alcoholic subjects may be mediated by both cortical and subcortical structures.

Cisternal fluid (CF) tryptophan (TRP), 5-hydroxyindole-3-acetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were measured from 40 adult cadavers. They were divided into 4 groups (n = 10 in each group), with samples taken 2, 4, 10 and 24 h after death. The CF concentrations of TRP and all determined biogenic amine metabolites were distinctly higher than in lumbar CSF during life, and concentrations of 5-HIAA were also higher in post-mortem samples than in cisternal or ventricular CSF in living humans. The means of the samples of 5-HIAA, DOPAC, HVA and MHPG were not statistically significantly different over time, but some trends were evident. TRP concentrations in CF increased linearly with time (from 4.6 to 23.6 mumol/l, P less than 0.001). CF DOPAC and HVA concentrations were dependent on agonal time and dopamine infusions. Our results imply that both ante-mortem and post-mortem conditions may influence monoamine metabolite and TRP concentrations in CF. These conditions should be accounted for in studies using post-mortem samples to study differences between patient groups in CNS neurochemistry.

The pH of third ventricular CSF was altered by infusing acidic or alkaline solution of artificial cerebrospinal fluid (aCSF) through chronically implanted stainless steel cannula. In two separate group of rats (n=18 each) water and food consumptions were recorded 30 min, 1 hr, and 24 hr after intraventricular infusions of the modified aCSF solutions having pH 6.0, 8.0 and 7.4 (control). On raising the CSF pH, water intake increased in all three observations. Feeding was not affected in the observations taken after 30 min and 1 hr, but significantly reduced food consumption was observed 24 hr after the infusions. Lowering of pH had no effect either on dipsogenic or feeding response. The CSF pH correlated positively with drinking in all three observations. Since dipsogenic and feeding responses are centrally regulated by ion sensitive cells, it may be presumed that altered CSF pH influenced the activities of the sensors by altering ionic conductance across their membranes.