Plasma and cerebrospinal fluid concentrations of neurofilament light protein correlate in patients with idiopathic normal pressure hydrocephalus.

BACKGROUND: Neurofilament light chain protein (NFL), a marker of neuronal axonal degeneration, is increased in cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH). Assays for analysis of NFL in plasma are now widely available but plasma NFL has not been reported in iNPH patients. Our aim was to examine plasma NFL in iNPH patients and to evaluate the correlation between plasma and CSF levels, and whether NFL levels are associated with clinical symptoms and outcome after shunt surgery. METHODS: Fifty iNPH patients with median age 73 who had their symptoms assessed with the iNPH scale and plasma and CSF NFL sampled pre- and median 9 months post-operatively. CSF plasma was compared with 50 healthy controls (HC) matched for age and gender. Concentrations of NFL were determined in plasma using an in-house Simoa method and in CSF using a commercially available ELISA method. RESULTS: Plasma NFL was elevated in patients with iNPH compared to HC (iNPH: 45 (30-64) pg/mL; HC: 33 (26-50) (median; Q1-Q3), p = 0.029). Plasma and CSF NFL concentrations correlated in iNPH patients both pre- and postoperatively (r = 0.67 and 0.72, p < 0.001). We found only weak correlations between plasma or CSF NFL and clinical symptoms and no associations with outcome. A postoperative NFL increase was seen in CSF but not in plasma. CONCLUSIONS: Plasma NFL is increased in iNPH patients and concentrations correlate with CSF NFL implying that plasma NFL can be used to assess evidence of axonal degeneration in iNPH. This finding opens a window for plasma samples to be used in future studies of other biomarkers in iNPH. NFL is probably not a very useful marker of symptomatology or for prediction of outcome in iNPH.

Absence of Disproportionately Enlarged Subarachnoid Space Hydrocephalus, a Sharp Callosal Angle, or Other Morphologic MRI Markers Should Not Be Used to Exclude Patients with Idiopathic Normal Pressure Hydrocephalus from Shunt Surgery.

BACKGROUND AND PURPOSE: Several studies have evaluated the use of MR imaging markers for the prediction of outcome after shunt surgery in idiopathic normal pressure hydrocephalus with conflicting results. Our aim was to investigate the predictive value of a number of earlier proposed morphologic MR imaging markers in a large group of patients with idiopathic normal pressure hydrocephalus. MATERIALS AND METHODS: One hundred sixty-eight patients (mean age, 70 ± 9.3 years) with idiopathic normal pressure hydrocephalus, subjected to standardized quantification of clinical symptoms before and after shunt surgery, were included in the study. Outcome was calculated using a composite score. Preoperative T1, FLAIR, and flow-sensitive images were analyzed regarding the presence of 13 different morphologic MR imaging markers. RESULTS: The median Evans index was 0.41 (interquartile range, 0.37-0.44). All patients had an aqueductal flow void sign present and white matter hyperintensities. The median callosal angle was 68.8° (interquartile range, 57.7°-80.8°). Dilated Sylvian fissures were found in 69%; focally dilated sulci, in 25%; and widening of the interhemispheric fissure, in 55%. Obliteration of the sulci at the convexity was found in 36%, and 36% of patients were characterized as having disproportionately enlarged subarachnoid space hydrocephalus. Sixty-eight percent of patients improved after surgery. None of the investigated MR imaging markers were significant predictors of improvement after shunt surgery. CONCLUSIONS: Disproportionately enlarged subarachnoid space hydrocephalus, a small callosal angle, and the other MR imaging markers evaluated in this study should not be used to exclude patients from shunt surgery. These markers, though they may be indicative of idiopathic normal pressure hydrocephalus, do not seem to be a part of the mechanisms connected to the reversibility of the syndrome.

Estimated ventricle size using Evans index: reference values from a population-based sample.

BACKGROUND AND PURPOSE: Evans index is an estimate of ventricular size used in the diagnosis of idiopathic normal-pressure hydrocephalus (iNPH). Values >0.3 are considered pathological and are required by guidelines for the diagnosis of iNPH. However, there are no previous epidemiological studies on Evans index, and normal values in adults are thus not precisely known. We examined a representative sample to obtain reference values and descriptive data on Evans index. METHODS: A population-based sample (n = 1235) of men and women aged ≥70 years was examined. The sample comprised people living in private households and residential care, systematically selected from the Swedish population register. Neuropsychiatric examinations, including head computed tomography, were performed between 1986 and 2000. RESULTS: Evans index ranged from 0.11 to 0.46. The mean value in the total sample was 0.28 (SD, 0.04) and 20.6% (n = 255) had values >0.3. Among men aged ≥80 years, the mean value of Evans index was 0.3 (SD, 0.03). Individuals with dementia had a mean value of Evans index of 0.31 (SD, 0.05) and those with radiological signs of iNPH had a mean value of 0.36 (SD, 0.04). CONCLUSIONS: A substantial number of subjects had ventricular enlargement according to current criteria. Clinicians and researchers need to be aware of the range of values among older individuals.

Amyloid mis-metabolism in idiopathic normal pressure hydrocephalus.

BACKGROUND: Patients with idiopathic normal pressure hydrocephalus (iNPH) have reduced cerebrospinal fluid (CSF) concentrations of amyloid-ß (Aß) and α- and ß-cleaved soluble forms of amyloid precursor protein (sAPPα and sAPPß). The aims of this study were to examine if changes could also be seen in the CSF for secreted metabolites of APP-like protein 1 (APLP1) and to explore the prognostic value of amyloid-related CSF biomarkers, as well as markers of neuronal injury and astroglial activation, as regards to clinical outcome after shunt surgery. METHODS: Twenty patients diagnosed with iNPH, 10 improved and 10 unchanged by shunt surgery, and 20 neurologically healthy controls were included. All patients were examined clinically prior to surgery and at 6-month follow-up after surgery using the iNPH scale. Lumbar puncture was performed pre-operatively. CSF samples were analyzed for neurofilament light (NFL), Aß isoforms Aß38, Aß40 and Aß42, sAPPα, sAPPß, APLP1 ß-derived peptides APL1ß25, APL1ß 27 and APL1ß 28 and YKL40 by immunochemical methods. RESULTS: The concentrations of all soluble forms of APP, all Aß isoforms and APL1ß28 were lower, whilst APL1ß25 and APL1ß27 were higher in the CSF of iNPH patients compared to controls. There was no difference in biomarker concentrations between patients who improved after surgery and those who remained unchanged. CONCLUSIONS: The reduced CSF concentrations of Aß38, Aß40, Aß42, sAPPα and sAPPß suggest that APP expression could be downregulated in iNPH. In contrast, APLP1 concentration in the CSF seems relatively unchanged. The increase of APL1ß25 and APL1ß27 in combination with a slight decreased APL1ß28 could be caused by more available γ-secretase due to reduced availability of its primary substrate, APP. The data did not support the use of these markers as indicators of shunt responsiveness.

Serum IGF-1 is higher in patients with idiopathic normal pressure hydrocephalus than in the population.

BACKGROUND: Hypopituitarism has been reported in patients with idiopathic normal pressure hydrocephalus (iNPH), which could enhance characteristic symptoms like impaired wakefulness, gait, body balance, and subcortical cognitive deterioration. PURPOSE: To compare basal serum levels of pituitary and sex hormones and serum insulin-like growth factor-1 (S-IGF-1) in patients with iNPH and an age-matched control population, and to correlate the preoperative hormone levels with symptoms and signs pre-operatively and three months after surgery. METHODS: A cross-sectional case control design was used. Patients diagnosed with iNPH, n=108 (65 men and 43 women, mean age 72.3 years), were consecutively included during 2006-2011 at Sahlgrenska University Hospital, Gothenburg, Sweden. S-TSH, S-free T4, S-FSH, S-LH, S-prolactin, plasma ACTH, S-testosterone, S-oestradiol and S-IGF-1 were examined. Symptoms and signs were scored using the iNPH scale score. Population controls, n=146, were recruited from the WHO MONICA project, Gothenburg in 2008. RESULTS: Men and women with iNPH had higher S-IGF-1 than controls (p<0.001). Women with iNPH had lower S-TSH (p=0.016) than controls, but the frequency of levothyroxine substitution was similar. Among men, a higher level of S-IGF-1 was associated with milder symptoms, while higher levels of S-FSH and S-LH were associated with more severe symptoms. CONCLUSIONS: Patients with iNPH did not have lower levels of pituitary or sex hormones but presented with higher levels of S-IGF-1, compared with healthy, age-matched controls. Higher S-IGF-1 in men was related to milder mental and physical symptoms and signs.

Postural function in idiopathic normal pressure hydrocephalus before and after shunt surgery: a controlled study using computerized dynamic posturography (EquiTest).

INTRODUCTION: Postural dysfunction is one of the major features of idiopathic normal pressure hydrocephalus (iNPH). With computerized dynamic posturography (CDP) balance can be assessed objectively. The primary aim of this study was to describe the postural function in iNPH patients pre- and post-operatively in comparison with healthy individuals (HI) using CDP. SUBJECTS AND METHODS: Thirty-five patients (16 M, 19 F) with a mean age of 73 (range 49-81) with iNPH, and sixteen HI (7 M, 9 F) aged 73 (62-89) were included. iNPH patients were operated on with a ventriculo-peritoneal shunt. Patients and HI were tested regarding motor function, balance and cognition. CDP, EquiTest (NeuroCom International, Clackamas, OR), was performed before and three months after shunt surgery and twice in HI, with a three-month interval. RESULTS: Pre-operatively, the 35 patients had poorer balance measured with the Sensory Organizing Test (SOT) score in every condition (p=0.01 in SOT 1 and p<0.001 in SOT 2-6) compared to the HI. The greatest difference was in test conditions measuring mainly vestibular function, where loss of balance (LOB) was frequent. Twenty patients were evaluated three months after shunt surgery and 18/20 (90%) of them were considered shunt responders, with a mean improvement of motor score of 26% (range 5-67%). There was an improvement post-operatively in the weighted composite SOT score (p<0.05) but no significant change in any of the SOT conditions. LOB was not significantly reduced in any of the test conditions. CONCLUSION: CDP showed that the patients had a poorer balance than the HI. The greatest difference was in SOT 5-6, indicating that the postural disturbance is of primarily central vestibular origin. There was a slight improvement of balance post-operatively.

How active are patients with idiopathic normal pressure hydrocephalus and does activity improve after shunt surgery? A controlled actigraphic study.

INTRODUCTION: Actigraphy allows long-time evaluation of physical activity and resting behaviour in a normal environment. The aim of this study was, by use of actigraphy, to measure motor function, energy expenditure and resting/sleeping time in idiopathic normal pressure hydrocephalus (iNPH) patients before and after surgery, and compare the results with healthy individuals (HI). SUBJECTS AND METHODS: 33 patients (mean 73 year) and 17 HI (mean 73 year) participated. Actigraphy with SenseWear (BodyMedia Inc., Pittsburgh, PA, USA) was recorded in the iNPH patients before and three months postoperatively and twice in the HI with a three-month interval. In addition, gait speed, timed up and Go (TUG) and MMSE were registered pre- and post-operatively. RESULTS: During daytime the patients took fewer steps (p < 0.001) and their total energy expenditure (TEE) was lower (p < 0.01) than in the HI. Twenty patients were evaluated pre- and post-operatively and no change in either the number of steps, TEE, or time spent lying/sleeping after surgery could be detected. iNPH patients had lower gait speed, worse TUG and MMSE compared to the HI. Gait and TUG improved after surgery. CONCLUSION: Actigraphy in iNPH patients indicated reduced ambulatory activity and lower energy expenditure compared to HI preoperatively. This did not change postoperatively in spite of improved TUG and gait speed.

One-year outcome in the European multicentre study on iNPH.

OBJECTIVES: To assess the 1-year outcome after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: Patients (n = 142) were prospectively included in the European multicentre study by 13 centres. Diagnoses were based solely on clinical and radiological findings. All received a programmable ventriculoperitoneal shunt. Re-examinations, 12 months after surgery, were performed in 115 patients, and the outcome was assessed by the modified Rankin scale (mRs) and a new iNPH grading scale. Improvement was defined as ≥1 step on the mRs and ≥5 points on the iNPH scale. RESULTS: The scores on both scales were significantly improved after 1 year of shunt treatment (Ps < 0.001). Sixty-nine per cent of the patients were improved according to the mRs and 84% according to the iNPH scale. The proportion able to live independently (scores 0-2 on the mRs) was increased from 53% before to 82% 12 months after surgery (P < 0.001). Neither classification (typical or questionable) nor comorbidity affected the level of improvement. Patients not completing the study were worse off with regard to their clinical condition at entry than completers. Twenty-eight per cent of the patients experienced complications and were either conservatively (13%) or surgically (15%) treated. CONCLUSION: The results of this prospective multicentre study on patients with iNPH diagnosed solely on clinical and radiological criteria support shunt surgery in patients presenting with symptoms and signs and MRI findings suggestive of iNPH.

A new scale for assessment of severity and outcome in iNPH.

OBJECTIVE: To present a new, continuous, calibrated and norm-based scale for the grading of severity and assessment of treatment outcome in idiopathic normal pressure hydrocephalus (iNPH). PATIENTS AND METHODS: A scale designed for the assessment of the four domains, gait, neuropsychology, balance and continence, using ordinal ratings and continuous measures, was developed. Data from a series of 181 consecutive iNPH patients were used to calibrate the continuous parts of the scale and to describe the distributional properties of the ordinal ratings. Data from normative studies were used to determine the limits for normal scores. RESULTS: The construction of the scale made it well equipped to separate iNPH patients at baseline, and the total scores assumed a bell-shaped, approximately normal distribution. All four domain scores correlated significantly with each other, underscoring the well-known syndromatic nature of iNPH, and justifying the use of a total score to describe the patients. Reliability [Cronbach's α for the total score = 0.74, and for the domains of gait and neuropsychology, 0.86 and 0.89, respectively) and validity estimates (convergent validity evaluated by Spearman rank correlations for the scale and the modified Rankin scale (ρ = -0.61) and the mini mental state examination (ρ = 0.57)] are satisfying. CONCLUSION: The iNPH scale covers the four most important symptom domains and the full range of severity of the iNPH syndrome. The scale is sensitive, reliable, valid and feasible. We recommend that it should be used in future iNPH research.

Spinal cerebrospinal fluid volume in healthy elderly individuals.

The amount of spinal cerebrospinal fluid (CSF) could be of importance for the understanding of CSF dynamics, CSF biomarker analyses as well as for the amount and effect of anaesthesia using intrathecally administered drugs. However, knowledge of spinal CSF volumes is scarce. The main purpose of this article is to present data on spinal CSF volumes. In total, 22 healthy individuals aged between 64 and 76 years underwent MR imaging with a 3D balanced turbo field echo pulse sequence, which provided high contrast between spinal cord, CSF and the extradural surroundings. The entire spinal CSF volume, the cervical, thoracic, and lumbosacral CSF volumes and the spinal cord volume were calculated. The total spinal CSF volume was 81 ± 13 ml (range 52-103 ml). The amount of CSF in the cervical region was 19 ± 4 ml, in the thoracic region 38 ± 8 and in the lumbosacral region 25 ± 7 ml. There was no difference between genders nor was there any correlation with height. The volume of the spinal cord was 20 ± 3 ml. The results present new magnetic resonance imaging-based data on the spinal CSF volume in healthy elderly individuals.

Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled 1H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification.

INTRODUCTION: 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). SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Ventricular cerebrospinal fluid neurofilament protein levels decrease in parallel with white matter pathology after shunt surgery in normal pressure hydrocephalus.

Normal pressure hydrocephalus (NPH) is characterized by disturbed cerebrospinal fluid (CSF) dynamics and white matter lesions (WML). Although the morphology of these lesions is described, little is known about the biochemistry. Our aim was to explore the relationship between ventricular CSF markers, periventricular WML and postoperative clinical outcome in patients with NPH. We analysed lumbar and ventricular concentrations of 10 CSF markers, 12 clinical symptoms and signs, magnetic resonance imaging (MRI) periventricular white matter hyperintensities (PVH) and ventricular size before and 3 months after shunt surgery in 35 patients with NPH. Higher ventricular CSF neurofilament protein (NFL), an axonal marker, correlated with more extensive PVH. A larger postoperative reduction in NFL correlated with larger reduction in PVH and a more pronounced overall improvement. Albumin ratio, HMPG, NPY, VIP and GD3 increased postoperatively whereas NFL, tau and HVA decreased. Variations in ventricular size were not associated with CSF concentrations of any marker. We conclude that NPH is characterized by an ongoing periventricular neuronal dysfunction seen on MRI as PVH. Clinical improvement after shunt surgery is associated with CSF changes indicating a restitution of axonal function. Other biochemical effects of shunting may include increased monoaminergic and peptidergic neurotransmission, breakdown of blood brain barrier function, and gliosis.

Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injury.

OBJECTIVE: We investigated if tau, microtubular binding protein, in serum and ventricular CSF (vCSF) in patients with severe traumatic brain injury (TBI) during the initial posttraumatic days correlated to 1-year outcome. METHODS: Patients with severe TBI (n = 39, Glasgow Coma Scale score 2,126 pg/mL on days 2 to 3 discriminated between dead and alive (sensitivity of 100% and a specificity of 81%). A vCSF total tau level of >702 pg/mL on days 2 to 3 discriminated between bad (GOSE 1 to 4) and good (GOSE 5 to 8) outcome (sensitivity of 83% and a specificity of 69%). Patients with GOSE 1 (dead) had higher vCSF total tau levels on days 2 to 3 (p < 0.001) vs both surviving patients (GOSE 2 to 8) and those with NPH. Total tau was not detected in serum throughout the study. CONCLUSION: The increase in ventricular CSF (vCSF) total tau probably reflects axonal damage, known to be a central pathologic mechanism in traumatic brain injury (TBI). These results suggest that vCSF total tau may be an important early biochemical neuromarker for predicting long-term outcome in patients with a severe TBI.

Long-term outcome in 109 adult patients operated on for hydrocephalus.

To examine the long-term effects of surgery in adult hydrocephalus we conducted a cross-sectional questionnaire study assessing both the patients' sense of well-being, and changes in gait, living conditions, daily need of sleep and bladder function. One-hundred-and-nine consecutive patients operated for non-communicating hydrocephalus (N-CH) (22) and communicating normal pressure hydrocephalus (NPH), both idiopathic (38) and secondary (49) were included. For survival analyses, three reference groups were selected from the general population and from the Northern Sweden MONICA Project. At long-term follow-up, 29 (27%) patients had died. Sixty-eight patients (62%) returned the questionnaire, while 12 (11%) patients did not reply. The median follow-up time was 4.2 years (range 2.3 - 6.2 years). Fifty-four (79%) of these patients reported that they still felt improved and 60% had persisting observable improvement of gait, living conditions, bladder function and need of sleep. Intention-to-treat analyses revealed that 54 (50%) of the patients still felt better and 37% remained functionally improved. The standardized mortality ratio (observed/expected) was 3.01 (CI: 2.01 - 4.32).

National and regional incidence of surgery for adult hydrocephalus in Sweden.

In Sweden, the annual incidence of surgery for hydrocephalus was 3.4 per 100,000 adults between the years 1996 and 1998. The most common indication for surgery was normal pressure hydrocephalus (NPH; 47%), followed by high-pressure hydrocephalus (27%). Seventy-three percent of the patients had communicating hydrocephalus, of which 63% had NPH. Twenty percent of the patients had non-communicating hydrocephalus, of which half resulted from aqueduct stenosis. The annual incidence of operations varied between regional clinics from 2.3 to 6.3 per 100,000 inhabitants.

Objective B wave analysis in 55 patients with non-communicating and communicating hydrocephalus.

BACKGROUND: B waves, slow and rhythmic oscillations in intracranial pressure (ICP), are claimed to be one of the best predictors of outcome after surgery for normal pressure hydrocephalus (NPH). OBJECT: To determine the relation between the percentage of B waves and outcome in patients with hydrocephalus, and also the diurnal variation of B waves. METHODS: ICP and patient behaviour were recorded overnight (17 to 26 hours) in 29 patients with non-communicating hydrocephalus and 26 with NPH. The B wave activity, measured with an amplitude threshold of 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, and 5.0 mm Hg, was estimated as the percentage of total monitoring time (% B waves) using a computer algorithm, and correlated with postoperative outcome, defined as changes in 12 standardised symptoms and signs. RESULTS: There was no linear correlation between improvement after surgery in the 55 patients and total % B waves, but a correlation was found between improvement and % B waves during sleep (r = 0.39, p = 0.04). The percentage of B waves was the same during sleep and wakefulness, and patients with NPH had the same proportion of B waves as the non-communicating patients. CONCLUSIONS: B waves are commonly observed in patients with both communicating and non-communicating hydrocephalus, but are only weakly related to the degree of postsurgical improvement.

Impaired wakefulness is associated with reduced anterior cingulate CBF in patients with normal pressure hydrocephalus.

OBJECTIVE: To evaluate if impaired wakefulness (IW) in normal pressure hydrocephalus (NPH) is associated with reduced blood flow in regions associated with the brain arousal system. METHOD: NPH (n = 28) patients were studied before and after surgery. Wakefulness was assessed using a new developed scale. Relative regional cerebral blood flow (rrCBF) was quantified using SPECT and rectangular regions of interest analysis. RESULTS: Sixteen patients presented with IW at baseline and in 14 of these, IW vanished after surgery. Patients presenting with IW had reduced rrCBF in the anterior cingulate cortex compared with those without. After surgery, rrCBF increased significantly in thalamic, frontal and hippocampal grey matter regions. Increased hippocampal rrCBF correlated with increased basal frontal rrCBF (r = 0.64). In patients where IW vanished after surgery, rrCBF increased in the mesencephalon, hippocampus and the frontal association cortex. The postoperative increase in wakefulness correlated with increased rrCBF in frontal (r = 0.74) and parietal (r = 0.65) association cortex areas. CONCLUSION: IW in NPH is associated with reduced rrCBF in the anterior cingulate cortex. Improved wakefulness following surgery corresponds to rrCBF increments in the frontal association cortex. This study provides support for a functional coupling between frontal, hippocampal, thalamic and mesencephalic rrCBF in NPH at large.

Differences in cerebrospinal fluid dynamics do not affect the levels of biochemical markers in ventricular CSF from patients with aqueductal stenosis and idiopathic normal pressure hydrocephalus.

To compare levels of biochemical markers in ventricular cerebrospinal fluid (vCSF) between patients with aqueductal stenosis (AS) and idiopathic normal pressure hydrocephalus (INPH) and relate these results to clinical outcome after surgery. Neurofilament light protein, tau protein, sulfatide, vasoactive intestinal peptide (VIP), neuropeptide PYY (NPY) and CSF/serum albumin ratio were measured in vCSF from 18 consecutive AS and 19 consecutive INPH patients. Clinical outcome was evaluated after surgery by standardized indices. The levels of markers were related to clinical outcome. No differences in any of the markers were found between AS and INPH patients. The concentration of sulfatide and albumin ratio correlated inversely with psychometric improvement, whilst VIP and NPY correlated inversely with improvement in alertness. The similar levels of biochemical markers in vCSF from AS and INPH patients indicate similarities in pathophysiology and turnover rate of vCSF despite differences in CSF dynamics. High albumin ratio and sulfatide concentrations in vCSF in hydrocephalus patients have negative implications for surgical outcome and might indicate concomitant cerebrovascular disorder.

Normal pressure hydrocephalus triggers intrathecal production of TNF-alpha.

Normal pressure hydrocephalus (NPH) is associated with periventricular white matter lesions and demyelination. The aim of the present study was to examine the cerebrospinal fluid (CSF) levels of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine mediating myelin damage, in patients with NPH. TNF-alpha levels were analyzed by ELISA and measured before and after shunt operation in 35 patients with NPH. The levels of this cytokine were related to the symptomatology and to magnetic resonance imaging (MRI) verified white matter lesions. They were also related to intrathecal levels of sulfatide, a marker for white matter degradation and to levels of neurofilament, a marker for neuronal degeneration. The preoperative levels of TNF-alpha were increased in the CSF of NPH patients compared to controls, and correlated to the levels of sulfatide. The intrathecal TNF-alpha levels were higher in NPH patients with impairment of wakefulness than in those without this symptom. The preoperative TNF-alpha levels were significantly correlated to the improvement of psychometrical test scores, and of wakefulness and to the overall improvement of the patients following shunt operation. Importantly, shunt operation led to complete disappearance of intrathecal TNF-alpha. We conclude that NPH is correlated with intrathecal TNF-alpha production being reversed following shunt operation in parallel with the clinical improvement. The positive correlation between preoperative TNF-alpha and sulfatide levels in the CSF suggest that intrathecal TNF-alpha may contribute to the damage of the white matter known to occur in patients with NPH.

Neurological symptoms and signs in adult aqueductal stenosis.

OBJECTIVE: To comprehensively describe and compare prospectively (pre/postoperatively) the symptomatology in aqueductal stenosis (AS) vs idiopathic normal pressure hydrocephalus (INPH). METHODS: Twenty-seven patients with AS and 39 patients with INPH were consecutively included. Postural functions, gait, wakefulness, cognitive functions, urinary continence and headache were examined before and 3 months after treatment with shunt operation or endoscopic ventriculostomy. RESULTS: The AS patients had better postural functions, walked faster, performed better cognitively and had a higher wakefulness than INPH patients, but these differences were explained by age differences between groups. The frequency of incontinence was similar in the two patients groups. Headache occurred more frequently in AS, but independently of the other symptoms. Most symptoms and signs improved after surgery. CONCLUSION: Patients with AS had a higher frequency of headaches than INPH patients, but otherwise the symptomology of the two groups was not found to differ after correcting for age differences.