Biomedical subjects

C Wikkelsö

Publications and source records attributed to C Wikkelsö.

At least 19 recordsLinked to original sources

PubMed2006

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.

Adolescent↗

PubMed2006

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).

Adolescent↗

PubMed2005

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.

Adult↗

PubMed2004

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.

Adult↗

PubMed2003

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.

Adult↗

PubMed2003

Correlation between intrathecal sulfatide and TNF-alpha levels in patients with vascular dementia.

OBJECTIVES: Subcortical vascular dementia (SVD) is associated with white matter lesions and demyelination. The aim of the present study was to examine the cerebrospinal fluid (CSF) levels of TNF-alpha, a proinflammatory cytokine mediating myelin damage, in SVD patients. The intrathecal TNF-alpha levels were related to the clinical symptoms of dementia, as well as to intrathecal levels of sulfatide, a marker of white matter degradation, and of neurofilament, a marker of neuronal degeneration. METHODS: CSF levels of TNF-a, sulfatide and neurofilament were all analyzed by immunoenzymatic procedures in 17 patients with SVD and in 26 healthy controls. RESULTS: The intrathecal concentration of TNF-alpha was significantly increased in SVD patients compared to healthy controls (p = 0.0001). The intrathecal levels of TNF-alpha were significantly correlated (r = 0.6, p = 0.02) to the levels of sulfatide, but not to the levels of neurofilament, (r = 0.08, NS). CONCLUSIONS: We have demonstrated intrathecal production of TNF-alpha in SVD patients. The correlation between TNF-a and sulfatide levels in the CSF suggests that this apoptosis-inducing cytokine leads to the death of oligodendrocytes, thereby contributing to white matter degeneration, a hallmark of SVD.

Aged↗

PubMed2001

Regional cerebral blood flow in normal individuals aged 40, 75 and 88 years studied by 99Tc(m)-d,l-HMPAO SPET.

Age-related changes in cerebral blood flow (CBF) were examined with [99Tc(m)]-d,l-hexamethylpropylene amine oxime (HMPAO), using a single photon emission tomography (SPET) gamma camera system equipped with a high resolution collimator, in 33 normal individuals in three age groups: 40 years old (n = 11), 75 years old (n = 9) and 88 years old (n = 13). A standard activity of 1000 MBq [99Tc(m)]-d,l-HMPAO was administered. Regional CBF (rCBF) (relative to cerebellar counts) was quantified in 28 grey and white matter regions. The mean rCBF of all the regions was 0.80 (95% confidence interval [CI] 0.77-0.83) in 40 year olds, 0.77 (0.74-0.80) in 75 year olds and 0.76 (0.73-0.78) in 88 year olds. rCBF in the hippocampus, angular and cingular gyri, and frontal association and motor cortices was 5-10% lower in the 75 and 88 year olds than in the middle-aged subjects (P < 0.05). The annual reduction in rCBF was 0.10% between the ages of 40 and 75 years and 0.13% between the ages of 75 and 88 years. The reduction in rCBF in the hippocampus rose from 0.14% between the ages of 40 and 75 years to 0.33% between the ages of 75 and 88 years. The mean rCBF in all 33 individuals showed no sex-related differences.

Adult↗

PubMed2000

Reduced regional cerebral blood flow in non-psychotic violent offenders.

The present study was designed to replicate previously reported findings of abnormal frontal and/or temporal cerebral blood flow in violent offenders and to control for the influence of major mental disorder (MMD), substance abuse, and current medication. HMPAO-SPECT-CBF and MRI scans from pretrial forensic psychiatric investigations of 21 subjects convicted of impulsive violent crimes were retrospectively re-evaluated. In 16/21 subjects, visual assessment of SPECT scans showed some hypoperfusion in the temporal and/or frontal lobes. MRI showed no corresponding structural damage. Quantified regional cerebral blood flow (rCBF) in defined regions of interest was compared between index cases and 11 healthy control subjects. Index subjects had significant reductions in the right angular gyrus and the right medial temporal gyrus, bilaterally in the hippocampus, and in the left white frontal matter, but they had significantly increased rCBF in the parietal association cortex bilaterally. The aberrations were as frequent and severe among the subjects without MMD, substance abuse, and current medication (n=7) as in the entire group of index subjects.

Adolescent↗

PubMed2000

Postural disturbance in patients with normal pressure hydrocephalus.

The postural function in 52 patients with normal pressure hydrocephalus (NPH) and in 19 patients with subcortical arteriosclerotic encephalopathy (SAE) was analysed bedside and in 17 of the NPH, 10 of the SAE and 23 healthy individuals (HI) also examined with a force platform. At the bedside examination, no differences in postural functions between NPH and SAE patients were found. The NPH patients improved more in the postural than in motor functions after shunt surgery. The NPH patients had a larger sway area and a higher backward directed velocity of centre of pressure than HI. The direction of the inclination in the sagittal plane was neutral or forward in the NPH and the SAE patients while it was backward in HI. The postural function was better in positions with open eyes in all 3 groups, but significantly less in the NPH patients, indicating a misinterpretation of afferent visual stimuli in the brainstem postural centre.

Aged↗

PubMed2000

Dual-window scatter correction and energy window setting in cerebral blood flow SPECT: a Monte Carlo study.

The image quality in SPECT studies of the regional cerebral blood flow (rCBF) performed with 99mTc-HMPAO is degraded by scattered photons. The finite energy resolution of the gamma camera makes the detection of scattered photons unavoidable, and this is observed in the image as an impaired contrast between grey and white matter structures. In this work, a Monte Carlo simulated SPECT study of a realistic voxel-based brain phantom was used to evaluate the resulting contrast-to-noise ratio for a number of energy window settings, with and without the dual-window scatter correction. Values of the scaling factor k, used to obtain the fraction of scattered photons in the photopeak window, were estimated for each energy window. The use of a narrower, asymmetric, energy discrimination window improved the contrast, with a subsequent increase in statistical noise due to the lower number of counts. The photopeak-window setting giving the best contrast-to-noise ratio was found to be the same whether or not scatter correction was applied. Its value was 17% centred at 142 keV. At the optimum photopeak-window setting, the contrast was improved by using scatter correction, but the contrast-to-noise ratio was made worse.

Brain↗

PubMed2000

Attenuation correction in quantitative SPECT of cerebral blood flow: a Monte Carlo study.

Monte Carlo simulation has been used to produce projections from a voxel-based brain phantom, simulating a 99mTc-HMPAO single photon emission computed tomography (SPECT) brain investigation. For comparison, projections free from the effects of attenuation and scattering were also simulated, giving ideal transaxial images after reconstruction. Three methods of attenuation correction were studied: (a) a pre-processing method, (b) a post-processing uniform method and (c) a post-processing non-uniform method using a density map. The accuracy of these methods was estimated by comparison of the reconstructed images with the ideal images using the normalized mean square error, NMSE, and quantitative values of the regional cerebral blood flow, rCBF. A minimum NMSE was achieved for the effective linear attenuation coefficient mu(eff) = 0.07 (0.09) cm(-1) for the uniform(pre) method, the effective mass attenuation coefficient mu(eff)/rho = 0.08 (0.10) cm2 g(-1) for the uniform(post) method and mu(eff)/rho = 0.12 (0.13) cm2 g(-1) for the non-uniform(post) method. Values in parentheses represent the case of dual-window scatter correction. The non-uniform(post) method performed better, as measured by the NMSE, both with and without scatter correction. Furthermore, the non-uniform(post) method gave, on average, more accurate rCBF values. Although the difference in rCBF accuracy was small between the various methods, the same method should be used for patient studies as for the reference material.

Humans↗

PubMed2000

How effective is endoscopic third ventriculostomy in treating adult hydrocephalus caused by primary aqueductal stenosis?

OBJECTIVE: To evaluate the long-term efficacy of third ventriculostomies for adult patients with hydrocephalus caused by primary aqueductal stenosis. METHODS: Eighteen of 64 patients who underwent endoscopic third ventriculostomies (ETVs) between June 1991 and July 1995 were treated because of primary aqueductal stenosis. All of these patients accepted follow-up investigations, which were performed 3 months to 5 years after surgery. If hydrocephalic symptoms persisted, the patency of the ventriculostomy was investigated; in cases of open ventriculostomies, the patients were offered shunt surgery. The effects of the shunt surgery were evaluated after 3 months. RESULTS: After ETV, nine of the patients exhibited excellent improvements, two exhibited slight improvements, one displayed no change, and six demonstrated temporary improvements. The ventriculostomies were patent in all nine patients who experienced less than excellent results. Subsequent ventriculoperitoneal shunt placement produced improvements for all seven patients who accepted the surgery. CONCLUSION: In our experience, the long-term effectiveness of ETVs for adult patients with noncommunicating hydrocephalus was sufficient in only 50% of the cases. One-third of the patients exhibited temporary improvements, lasting 1 to 12 months (average duration, 5 mo) after the ETVs, and then demonstrated deterioration to even worse clinical conditions, despite patent ventriculostomies. All patients who did not exhibit permanent improvements after the ETVs benefited from shunt surgery. Efforts should be made to establish methods for the selection of patients for ETV or ventriculoperitoneal shunt surgery.

Adolescent↗

PubMed1998

CSF neurofilament and glial fibrillary acidic protein in normal pressure hydrocephalus.

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.

Adult↗

PubMed1997

Intrathecal release of pro- and anti-inflammatory cytokines during stroke.

A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of ischaemic brain damage. We have recently demonstrated that stroke patients display an intrathecal production of proinflammatory cytokines, such as IL-1beta and IL-6 already within the first 24 h after the beginning of symptoms (Tarkowski et al., 1995). The aim of the present study was to investigate patterns of local inflammatory responses as a consequence of acute stroke. Thirty stroke patients were studied prospectively on days 0-3, 7-9, 21-26 and after day 90 with clinical evaluations, radiological assessments and analysis of cerebrospinal fluid (CSF) cytokine levels. In addition, 15 healthy control CSF samples were used. Significantly increased CSF levels of IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-10 were observed early during the stroke with a peak on day 2 for the proinflammatory cytokines IL-8 and GM-CSF, and on day 3 for the immunoregulatory cytokine IL-10. Patients with a brain infarct predominantly located in the white matter showed significantly higher levels of IL-8 in CSF than patients with an infarct mainly located in the grey matter. Also, high levels of intrathecal tumour necrosis factor-alpha (TNF-alpha) were associated with the presence of white matter disease. Our study demonstrates an intrathecal production of proinflammatory and immunoregulatory cytokines in patients with stroke, supporting the notion of localized immune response to the acute brain lesion. A better understanding of the inflammatory response in stroke may lead to new treatment strategies.

Adult↗

PubMed1997

Selection of collimator for rCBF studies and evaluation of triple-headed SPET using noise-resolution plots.

We investigated the effect of collimator selection on image quality in regional cerebral blood flow (rCBF) studies of the brain performed with 99Tc(m)-HMPAO. A triple-headed SPET system (GE/CGR Neurocam) was used, together with three sets of parallel-hole collimators - general-purpose (GP), high-resolution (HR) and ultra-high-resolution (UHR). Two image quality parameters were used to describe the image quality, namely, noise and resolution. Noise was measured in experimental and Monte-Carlo simulated SPET studies of a cylinder phantom of uniform activity as the pixel root mean square error (RMS) and as the coefficient of variation (CV) of quantitative rCBF values. Resolution was measured as full-width at half-maximum in experimental SPET studies of a line-source. Plots of noise versus resolution for the different collimators were obtained by varying the cut-off frequency of the Hanning filter applied in the reconstruction of transaxial slices. From these noise-resolution plots, we were able to determine which collimator gave the best resolution for a specific noise level. A lowest reasonable noise level may be established by comparison with the inter-observer CV of the quantification method.

Brain↗

PubMed1997

A new set of fiducial markers for MRI, CT and SPET alignment.

A set of fiducial markers for use in the alignment of MR, CT and SPET images is presented. The marker system consists of individually produced imprints of the external auditory meatus, a pair of plastic spectacle frames and three fiducial markers. The markers are filled with a suitable contrast agent, fixed into the imprints and screwed onto the spectacle frame just before examination. The reproducibility in positioning the marker system on the patient was evaluated by repeated MRI examinations of a volunteer. The fiducial markers could be repositioned with an accuracy of less than +/- 1.6 mm in the left-right and anterio-posterior directions and +/- 1.9 mm in the cranio-caudal direction (95% confidence interval). The marker system is inexpensive and easy to produce, taking less than 20 min to produce on the ward. Only a few minutes are required to fix the system prior to examination. It is comfortable for the patient, even during long examinations. In cases lacking visible intrinsic structures and external contours, fiducial markers provide a good means of alignment for image fusion. The marker system described here for the alignment of SPET, CT and MR images can be used on a routine basis without the invasive fixation of fiducial markers.

Brain↗

PubMed1997

Cerebrospinal fluid proteins in subclinical and overt hypothyroidism.

PATIENTS AND METHODS: We analysed cerebrospinal fluid (CSF) albumin and immunoglobulin G (IgG) concentrations and psychometric performance in subclinical (n = 6) and overt hypothyroidism (n = 9) before and after 6 months with L-thyroxine. RESULTS: In overt hypothyroidism, CSF albumin and IgG concentrations were increased before therapy [mean(SD): 328(156) mg/l and 69(27) mg/l], but within the reference interval [198(48) mg/l and 39(11) mg/l], P < 0.05, after therapy. In contrast, in subclinical hypothyroidism CSF protein concentrations were within the reference intervals before and after therapy. Psychometric testing indicated an improvement in performance in both groups. CONCLUSION: The increase in CSF proteins in overt hypothyroidism does not appear to be related to thyroid autoimmune disease per se, since we found no increase in CSF proteins in individuals with subclinical hypothyroidism and presence of thyroid antibodies. The increase might rather be caused by a blood-brain barrier dysfunction related to low thyroid hormone concentrations.

Adult↗

PubMed1996

Immunoglobulin M in cerebrospinal fluid: reference values derived from 111 healthy individuals 18-88 years of age.

The importance of immunoglobulin M (IgM) determination in cerebrospinal fluid (CSF) has increased parallel to the need for early diagnosis of infectious and inflammatory disorders of the central nervous system. Current reference values are based on analysis of CSF from 'reference groups' consisting of patients with psychiatric and/or neurological symptoms but without positive clinical findings. Therefore, accurate reference values for CSF IgM are of utmost importance. The present study presents reference values for IgM in CSF in a large sample (n = 111) of healthy individuals with an age span of 18-88 years. The upper reference limit, calculated as the 0.95 fractile, was 0.36 mg/l for CSF IgM, 0.40 for CSF/serum IgM ratio, and 0.045 for the IgM index. These parameters showed no significant difference between sexes nor any significant correlations with age. The correlations between CSF/serum albumin ratio and CSF/S IgM ratio were linear and statistically highly significant, suggesting that the IgM index values do not depend on the blood-CSF barrier function within the normal range of the CSF/serum albumin ratio.

Adolescent↗