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L Rosengren

Publications and source records attributed to L Rosengren.

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

CSF -neurofilament correlates with outcome after aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating event. Following the bleeding, a number of pathophysiological changes and clinical factors determine outcome. Not surprisingly, attempts to predict outcome based on a single factor have failed. The neurological status graded at admission to hospital and distributions of the blood on CT are the strongest predictors. There is evidence that cerebrospinal fluid (CSF) proteins may serve as markers of the extent of brain damage. The present study is focused on the light unit of neurofilament protein (NFL), previously not evaluated in aSAH. Lumbar puncture (LP), neurological grading according to World Federation of Neurological Surgeons (WFNS) and neurological examination according to the National Institute of Health Stroke Scale (NIHSS) were performed in 48 consecutive patients with aSAH 10-14 days after the hemorrhage. CSF-NFL concentrations were analyzed using an ELISA. Outcome was assessed after 1 year and categorised according to the extended Glasgow Outcome Scale (GOSE). A significant correlation between CSF-NFL and GOSE was detected at follow up after 1 year. CSF-NFL also correlated with WFNS and NIHSS on the day of the lumbar puncture. CSF-NFL is a biochemical marker of brain damage correlating to neurological status and long-term outcome after aneurysmal subarachnoid hemorrhage.

Adult↗
PubMed2005

Increased serum-GFAP in patients with severe traumatic brain injury is related to outcome.

OBJECTIVES: Several studies have established the relevance of S-100 in blood as a marker of brain damage after traumatic brain injury. However, a more specific marker is required and glial fibrillary acidic protein (GFAP) is considered to be a good candidate. METHODS: In order to assess the increase of GFAP in serum (s-GFAP) after a severe traumatic brain injury (TBI) we collected daily serum samples from 59 patients with severe TBI starting on the day of the trauma. S-GFAP was measured using a sandwich ELISA. The Glasgow outcome scale (GOS) assessed outcome after 1 year. RESULTS: All but one patient had maximal s-GFAP values above the laboratory reference value (median increased 10-fold). The highest detected levels were seen during the first days after TBI and then decreased gradually. Patients with unfavourable outcome had significantly (p<0.001) higher maximal s-GFAP values in the acute phase compared with patients with favourable outcome. All patients (n=5) with s-GFAP>15.04 microg /L died (reference level<0.15 microg/L). We found no significant difference in the maximal s-GFAP levels of patients with isolated brain injury in comparison with patients with multiple traumas. CONCLUSION: Serum-GFAP is increased during the first days after a severe traumatic brain injury and related to clinical outcome.

Adolescent↗
PubMed2005

Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults.

OBJECTIVES: To study the occurrence of relapse of herpes simplex encephalitis (HSE) and to find out whether soluble activity markers in cerebrospinal fluid (CSF) indicate direct viral or immune- mediated events. METHODS: A consecutive series of 32 adult survivors of HSE were followed to determine the incidence of clinical relapse of HSE. Four patients had neurological deterioration interpreted as relapsing HSE. Four non-relapsing HSE cases were selected as matched controls. Fifty nine batched, paired CSF and serum samples from the eight HSE patients were analysed for soluble activity markers, predominantly cytokines and mediators (interferon-gamma, soluble CD8, tumour necrosis factor-alpha, and interleukin-10), amount of HSV-DNA and markers of glial and neuronal destruction (neurofilament protein, glial fibrillary acidic protein, S-100-beta, and neuron specific enolase). RESULTS: Relapse of HSE was diagnosed in 3 of 26 (12 %) acyclovir-treated patients (5 episodes during 6.1 years of followup) and in 1 of 6 vidarabine-recipients. All relapses occurred from 1 to 4 months after acute HSE, except for a second relapse after 3.3 years in one patient. Computer tomography at relapses revealed few abnormalities apart from those found during the primary disease. Intravenous acyclovir and corticosteroids were given for 7-21 days in all the relapse patients. All relapse patients seemed to recover to the pre-relapse condition. HSV-DNA was demonstrated in CSF in all patients during the acute stage but not in any of 13 CSF samples taken during relapse phases. The HSV viral load during the acute stage of HSE was not higher or of longer duration in the relapsing patients than in the non-relapsing HSE controls. The levels of sCD8 were increased in nearly all CSF samples tested with peaks of sCD8 at one month of acute HSE. In all episodes of relapse, sCD8 peaks were detected during the first week at high levels. CSF levels of neuron-specific enolase, S-100 and glial fibrillary acidic protein were markedly lower at relapse than at the acute stage of HSV-1 encephalitis. CONCLUSION: The lack of demonstrable HSV DNA in CSF, the lack of acute CSF signs and the lack of signs of neural and glia cells destruction indicate that a direct viral cytotoxicity is not the major pathogenic mechanism in relapse. Instead, the pronounced CSF proinflammatory immunological response and the relative lack of CSF anti-inflammatory cytokine IL-10 response suggest immunologically-mediated pathogenicity.

Adolescent↗
PubMed2005

Increased levels of GFAP in the cerebrospinal fluid in three subtypes of genetically confirmed Alexander disease.

GFAP levels in the CSF were highly elevated in three genetically confirmed cases of Alexander disease clinically conforming with infantile, early and late juvenile forms. No other CSF abnormalities were detected. Assay of CSF-GFAP may prove to be a rapid and cost-effective screening test in clinical variants of Alexander disease and an indicator of GFAP gene mutations.

Adult↗
PubMed2004

Neurofilament and glial fibrillary acidic protein in multiple sclerosis.

OBJECTIVE: To evaluate levels of neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) in CSF from patients with multiple sclerosis (MS) in relation to clinical progress of the disease. METHODS: CSF levels of NFL and GFAP were determined by sensitive ELISAs in 99 patients with different subtypes of MS, classified in terms of "ongoing relapse" or "clinically stable disease," and 25 control subjects. Levels were compared with paraclinical data such as immunoglobulin G index and inflammatory cell count in the CSF, and the levels were related to Expanded Disability Status Scale score and progression index at clinical follow-up evaluations later in the disease course. RESULTS: NFL and GFAP levels were elevated in MS patients as compared with control subjects (p < 0.001). The NFL levels were higher at relapses, whereas GFAP levels were unaffected. High NFL levels correlated with progression in patients with an active relapse (r = 0.49; p < 0.01) and in clinically stable patients (r = 0.29; p < 0.05). GFAP correlated to progression in the total patient cohort (r = 0.24; p < 0.05). Moreover, a strong correlation between NFL levels and inflammatory cell counts was evident in the group of patients with an ongoing relapse (r = 0.52; p = 0.001). CONCLUSIONS: CSF levels of neurofilament light and glial fibrillary acidic protein may have prognostic value in multiple sclerosis.

Adult↗
PubMed2004

CSF levels of neurofilament is a valuable predictor of long-term outcome after cardiac arrest.

AIMS: Prognostication of brain damage after cardiac arrest mainly relies on clinical observations. Recently, it has been shown that biochemical markers of brain damage measured in serum aid in this process. In the present study, we wanted to test the usefulness of CSF determinations of a neuronal protein, the neurofilament protein (NFL). METHODS AND RESULTS: Lumbar punctures were performed during week 2 or 3 in 22 patients surviving cardiac arrests. CSF NFL concentrations were analysed using an ELISA. Levels were increased in cardiac arrest patients. Patients with poor outcome according to the Glasgow outcome scale (GOS), low performance at a mini mental state examination (MMSE) and dependent according to Katz at 1 year follow up had the highest NFL levels. The NFL levels correlated well with anoxia time and coma depth. High positive and negative predictive values, particularly for poor outcome according to GOS were observed. CONCLUSIONS: Levels of CSF NFL give a reliable measure of the brain damage following cardiac arrest and the levels are highly predictive of poor outcome. This observation urges the development of sensitive serum assays of this marker to be used in the clinical setting.

Adult↗
PubMed2004

Cerebrospinal fluid markers in MS patients and their healthy siblings.

In a previous study we found that nine of 47 siblings to multiple sclerosis (MS) patients with a normal neurological examination carry an intrathecal oligoclonal immunopathy with limited specificity, a condition we termed MS immunopathic trait. The purpose of this study is to further characterize the MS immunopathic trait phenotype. We found that the neurofilament light protein (NFL) and glial fibrillary acidic protein (GFAp) concentrations were increased in the group of patients with clinically definite MS (n = 47) in latent or slowly progressive phases. There was no increase in GFAp and NFL in cerebrospinal fluid in the healthy siblings of MS patients (n = 47), nor in the subgroup of these siblings with MS immunopathic trait (n = 9) compared with a group of healthy control subjects (n = 50). Thus, there was no indication of presymptomatic CNS parenchymal involvement in MS immunopathic trait.

Adult↗
PubMed2003

Neurofilament light protein and glial fibrillary acidic protein as biological markers in MS.

OBJECTIVE: To determine if CNS-derived proteins present in the CSF of multiple sclerosis (MS) patients reflect different pathologic processes of MS and if these proteins could be useful as biologic markers of disease activity. METHODS: Concentrations of the neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), S100B, and the neuron-specific enolase protein (NSE) were determined in the CSF of 66 MS patients and 50 healthy control subjects with immunoassays. RESULTS: The mean levels of the NFL were increased during all stages of MS compared with controls (p < 0.001), peaking almost 10 times higher during acute relapses. The highest levels of GFAP were found during the secondary progressive course (p < 0.001) with a strong correlation with neurologic deficits (Expanded Disability Status Scale score, r = 0.73, p < 0.001). No increase of S100B or NSE protein was found in the CSF of MS patients compared with control subjects. CONCLUSIONS: Increased level of NFL is a general feature of MS, indicating continuous axonal damage during the entire course of the disease with the most profound damage during acute relapses. GFAP may serve as a biomarker for disease progression, probably reflecting the increasing rate of astrogliosis.

Acute Disease↗
PubMed2002

Bradycardic response during submersion in infant swimming.

UNLABELLED: The diving response involves reflex bradycardia, apnoea and peripheral vasoconstriction and is known to exist in human infants. The response diminishes with increasing age and has been reported to disappear by the age of 6 mo. This study was performed to analyse the physiological events during natural diving of full-term healthy infants and describe how these events alter with maturation. Thirty-six infants were studied during diving exercises in infant swimming. All of the infants who participated showed an immediate decrease in heart rate when submerged. On average, the heart rate decreased by 25% (range -5.0% to -50.7%, p <0.0001). The bradycardia was sustained during the dive and for some seconds afterwards. The response was often followed by a tachycardia as the bradycardia ceased. A decline of reflex bradycardia was observed with increasing age (p = 0.03), but the response was still clearly evident in infants over the age of 6 mo. CONCLUSION: This study demonstrates the existence of a diving response in infants, which includes an immediate bradycardic response, suggesting vagal mediation. Although the bradycardic response gradually decreases, the study shows that a clear-cut response exists in children older than has previously been reported.

Adaptation, Physiological↗
PubMed2001

Neurofilament protein in cerebrospinal fluid: a marker of white matter changes.

The objective of this study was to compare cerebrospinal fluid (CSF) levels of the light subtype of the neurofilament proteins (NFL), tau, and beta-amyloid42 (Abeta42) in individuals with moderate or severe white matter changes (WMC) and in those with mild or no WMC. Twenty-two patients with Alzheimer's disease (AD), nine patients with subcortical vascular dementia (SVD), and 20 normal controls were included in the study. The occurrence of WMC was evaluated by a neuroradiologist using the Blennow-Wallin scale. Thirty-seven subjects had no or only punctate WMC; 14 had moderate to severe WMC. Both diagnostic group and WMC, but not gender or apolipoproteinE E4 inheritance, contributed to the variance in the CSF levels of tau, NFL, and Abeta42. In patients with moderate to severe WMC, CSF NFL (P < 0.01), but not CSF tau or CSF Abeta42, was increased also after correction for age, gender, and degree of cognitive impairment. A comparison between patients and controls with any signs of WMC and those without such signs yielded a similar result: CSF NFL (P < 0.001) was increased in the group with signs of WMC. As in numerous previous studies, we found that CSF tau was increased in AD (P < 0.001) compared with controls. Furthermore, CSF NFL was increased in both AD and SVD compared with controls (P < 0.001 for both). Although diagnostic group seems to be a stronger predictor of the variance found in CSF NFL, a clear association between the presence of WMC and increased CSF NFL was found. Because NFL is located mainly in large myelinated axons, increased CSF NFL in individuals with WMC probably reflects axonal degeneration.

Aged↗
PubMed2001

Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke.

An increase in cerebrospinal fluid (CSF)-total-tau, and recently also in CSF-phospho-tau, has been found in Alzheimer's disease (AD). However, the mechanisms for these changes are not known. We examined longitudinal CSF samples from nine patients with acute stroke. As compared with baseline levels (day 0-1), CSF-total-tau showed an increase at day 2-3 (179%; P=0.018), day 7-9 (257%; P=0.003), and after 3 weeks (425%; P=0.002) and returned to normal levels after 3-5 months (140%; NS). In contrast, there was no significant change in CSF-phospho-tau. These findings suggest that total tau and phospho-tau in CSF reflect different pathogenic processes in the brain; total-tau the degree of neuronal damage and phospho-tau the phosphorylation state of tau and thus possibly the formation of neurofibrillary tangles.

Aged↗
PubMed2001

Serum levels of the brain-derived proteins S-100 and NSE predict long-term outcome after cardiac arrest.

BACKGROUND AND PURPOSE: patients with cardiac arrest have a high mortality and the long-term outcome is doubtful. The prognosis is mainly dependent on clinical parameters. S-100 and neurone specific enolase (NSE) are established biochemical markers of central nervous system (CNS) injury. The purpose of this study was to validate the use of serum determinations of S-100 and NSE with neurological investigations in regard to brain damage and long-term outcome after cardiac arrest. METHODS: neurological examinations were performed on 66 patients after cardiac arrest. Serum levels of S-100 and NSE were determined during the first 3 days of post arrest, using commercial luminescent immunoassays (LIAs). The main outcome variable was the Glasgow Outcome Scale (GOS), while secondary variables were the activity of daily living (ADL) index and mini mental state examination (MMSE). Outcome was determined at 1 year. RESULTS: the serum levels of S-100 and NSE were increased during the first 3 days after the arrest and were related to coma depth, time of anoxia and abnormal brain stem reflexes. High levels predicted a poor outcome, according to the GOS (death, vegetative state and severe disability). The prognostic value of the brain damage markers was comparable with that of traditional clinical parameters. None of the secondary outcome variables (ADL and MMSE) was strongly associated with S-100 or NSE. DISCUSSION: the serum levels of S-100 and NSE increased after cardiac arrest due to the anoxic brain damage. The determination of S-100 and NSE can be used as an adjunct to predict long-term outcome after cardiac arrest.

Activities of Daily Living↗
PubMed2001

CSF-neurofilament and levodopa tests combined with discriminant analysis may contribute to the differential diagnosis of Parkinsonian syndromes.

The differentiation between Parkinson's disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is important for prognostic and therapeutic purposes. In order to evaluate the diagnostic capability of two tests reflecting these items, patients fulfilling strict clinical criteria for PD (n=35), MSA (n=36) and PSP (n=14), were consecutively included. An analysis of neurofilament protein (NFL), a marker of axonal degeneration in the cerebrospinal fluid (CSF) and a levodopa test, recorded with optoelectronic technique were performed. Using discriminant analyses, the test's abilities to predict the clinical PD or non-PD (MSA and PSP) diagnoses were compared. Whereas the CSF-NFL and levodopa tests predicted 79 and 85% correct diagnoses respectively, the combined test predicted 90% correct diagnoses. We conclude that the CSF-NFL and levodopa tests provide detailed information of clinical variables on which the clinical diagnostic criteria are based. As they are pathologically unrelated, the diagnostic precision increases compared to clinical diagnoses when they are combined.

Adult↗
PubMed2001

Antisense inhibition of BCL-2 expression induces retinoic acid-mediated cell death during differentiation of human NT2N neurons.

Changes in expression of the proto-oncogene Bcl-2 are well known in the developing brain, with a high expression level in young post-mitotic neurons that are beginning the outgrowth of processes. The physiological significance of the Bcl-2 up-regulation in these neurons is not fully understood. We used a differentiation model for human CNS neurons to study the expression and function of Bcl-2. NT2/D1 human neuronal precursor cells differentiated into a neuronal phenotype in the presence of 10 microM retinoic acid for 3-5 weeks. This concentration of retinoic acid was not toxic to undifferentiated NT2/D1 cells but was sufficient to up-regulate the BCL-2 protein in 6 days. The BCL-2 levels increased further after 3 weeks, i.e. when the cells started to show neuronal morphology. Inhibition of the accumulation of endogenous BCL-2 with vectors expressing the antisense mRNA of Bcl-2 caused extensive apoptosis after 3 weeks of the retinoic acid treatment. The loss of neuron-like cells from differentiating cultures indicated that the dead cells were those committed to neuronal differentiation. Death was related to the presence of retinoic acid since withdrawal of retinoic acid after 16 days of treatment dramatically increased cell surviving. The ability of BCL-2 to prevent retinoic acid-induced cell death was also confirmed in undifferentiated NT2/D1 cells that were transfected with a vector containing Bcl-2 cDNA in sense orientation and exposed to toxic doses (40-80 microM) of retinoic acid. Furthermore, down-regulation of BCL-2 levels by an antisense oligonucleotide in neuronally differentiated NT2/D1 cells increased their susceptibility to retinoic acid-induced apoptosis. These results indicate that one function of the up-regulation of endogenous BCL-2 during neuronal differentiation is to regulate the sensitivity of young post-mitotic neurons to retinoic acid-mediated apoptosis.

Apoptosis↗
PubMed2001

Glial fibrillary acidic protein and neurofilament in children with cerebral white matter abnormalities.

Glial fibrillary acidic protein (GFAP) is the major structural protein of the intermediate filaments found in glial cells. Increased levels in the cerebrospinal fluid (CSF) have been found to indicate gliosis. Neurofilament (NFL) is a structural element of neurons, mainly found in large myelinated axons. Its presence in the CSF has been suggested to reflect destruction of axons. The aim of this study was to see if GFAP and NFL in the CSF of children with neurological disabilities and an abnormal signal on magnetic resonance imaging (MRI) of the cerebral white matter could be used to clarify the underlying neuropathology. The potential of GFAP and NFL to differentiate a progressive disease from a stationary disorder was investigated, as was the correlation with disability and clinical findings. CSF from 26 children, eleven with progressive and 15 with non-progressive disorders, was analysed. GFAP was increased in all, interpreted to reflect gliosis. NFL was elevated in seven and considered to indicate ongoing neuroaxonal damage as all but one patient were found to have a progressive disease. GFAP did not differentiate between progressive and non-progressive disorders, although low levels were found in stationary and high levels in progressive disorders. The severity of the disability correlated with the NFL levels, but not with the concentration of GFAP.

Adolescent↗
PubMed2001

Brain-specific proteins in the cerebrospinal fluid of severely asphyxiated newborn infants.

UNLABELLED: Upcoming trials of neuroprotective strategies in severely asphyxiated newborn infants emphasize the need for early and objective markers of both good and bad long-term prognosis. Traditional markers such as neurological depression and seizures are not specific. AIM: To study whether measurement in the cerebrospinal fluid of some proteins known to be specific to the central nervous system was in covariance with the clinical course and long-term prognosis. METHODS: Twenty-two asphyxiated infants were included in the study and compared with a control group of 8 infants without signs of perinatal asphyxia. Cerebrospinal fluid (CSF) was collected during the first 4 d of life and analysed for neurofilament protein (NFp), glial fibrillary acidic protein (GFAp), protein S-100 and neuron-specific enolase (NSE). RESULTS: The concentrations of all four proteins were significantly increased in the CSF of asphyxiated infants. The concentrations correlated significantly with other indicators of long-term prognosis and to neurological impairment at I y of age, or death before that time. Specifically, concentrations were excessively high in the five infants who died. CONCLUSIONS: High concentrations of brain-specific proteins are released into the CSF of asphyxiated infants. It might therefore be useful to measure these concentrations when excluding patients with the gravest prognosis from neuroprotective trials.

Asphyxia Neonatorum↗