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Publications (60) View all
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Article: Neuron-specific enolase correlates with other prognostic markers after cardiac arrest.
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ABSTRACT: Therapeutic hypothermia (TH) is a recommended treatment for survivors of cardiac arrest. Prognostication is complicated since sedation and muscle relaxation are used and established indicators of a poor prognosis are lacking. This prospective, observational study describes the pattern of commonly used prognostic markers in a hypothermia-treated cohort of cardiac arrest patients with prolonged coma. Among 111 consecutive patients, 19 died, 58 recovered, and 34 were in coma 3 days after normothermia (4.5 days after cardiac arrest), defined as prolonged coma. All patients were monitored with continuous amplitude-integrated EEG and repeated samples of neuron-specific enolase (NSE) were collected. In patients with prolonged coma, somatosensory evoked potentials (SSEP) and brain MRI were performed. A postmortem brain investigation was undertaken in patients who died. Six of the 17 patients (35%) with NSE levels <33 μg/L at 48 hours regained the capacity to obey verbal commands. By contrast, all 17 patients with NSE levels >33 failed to recover consciousness. In the >33 NSE group, all 10 studied with MRI had extensive brain injury on diffusion-weighted images, 12/16 lacked cortical responses on SSEP, and all 6 who underwent autopsy had extensive severe histologic damage. NSE levels also correlated with EEG pattern, but less uniformly, since 11/17 with NSE <33 had an electrographic status epilepticus (ESE), only one of whom recovered. A continuous EEG pattern correlated to NSE <33 and awakening. NSE correlates well with other markers of ischemic brain injury. In patients with no other signs of brain injury, postanoxic ESE may explain a poor outcome.Neurology 08/2011; 77(7):623-30. · 8.31 Impact Factor -
Article: Cause of death in patients with dementia disorders.
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ABSTRACT: Investigations on cause of death may provide valuable information about life expectancy and on conditions of terminal dementia care, which perhaps can be ameliorated. The autopsy reports were studied on all patients (n = 524; 55.3% females; median age 80 years) with a clinically and neuropathologically diagnosed dementia disorder who underwent a complete autopsy at the University Hospital in Lund, Sweden, during 1974-2004. The two most common causes of death were bronchopneumonia (38.4%) and ischaemic heart disease (23.1%), whilst neoplastic diseases were uncommon (3.8%). In a general population of elderly studied for comparison, bronchopneumonia accounted for 2.8%, ischaemic heart disease for 22.0%, and neoplasm for 21.3% of the deaths. Amongst the demented patients, circulatory and respiratory system diseases were the causes of death in 23.2% and 55.5% of the Alzheimer patients, respectively, whilst the corresponding figures were 54.8% and 33.1% for the patients with vascular dementia. In patients with dementia, pneumonia as the immediate cause of death may reflect a terminal stage in which patient care and feeding is difficult to manage well. Knowledge about what actually causes death is of value in the terminal care of patients with dementia disorders.European Journal of Neurology 02/2009; 16(4):488-92. · 3.69 Impact Factor -
Article: Genetic intratumour heterogeneity in high-grade brain tumours is associated with telomere-dependent mitotic instability.
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ABSTRACT: Glioblastoma multiforme (GBM) and other high-grade brain tumours are typically characterized by complex chromosome abnormalities and extensive intratumour cytogenetic heterogeneity. The mechanisms behind this diversity have been little explored. In this study, we analysed the pattern of chromosome segregation at mitosis in 20 brain tumours. We found an abnormal segregation of chromatids at mitosis through anaphase bridging (10-25% of anaphase cells) in all 10 GBMs. Anaphase bridging was also found in two medulloblastomas (7-15%), one anaplastic astrocytoma (17%) and one oligodendroglioma (6%). These tumours showed a relatively high degree of cytogenetic complexity and heterogeneity. In contrast, cell division abnormalities were not found in low-grade brain tumours with less complex karyotypes, including two pilocytic astrocytomas and two ependymomas. Further analysis of two GBMs by fluorescence in situ hybridization with telomeric repeat probes revealed excessive shortening of TTAGGG repeats, indicating dysfunctional protection of chromosome ends. In xenografts established from these GBMs, there was a gradual reduction in cytogenetic heterogeneity through successive passages as the proportion of abnormally short telomeres was reduced and the frequency of anaphase bridges decreased from >25% to 0. However, bridging could be reintroduced in late-passage xenograft cells by pharmacological induction of telomere shortening, using a small-molecule telomerase inhibitor. Telomere-dependent abnormal segregation of chromosomes at mitosis is thus a common phenomenon in high-grade brain tumours and may be one important factor behind cytogenetic intratumour diversity in GBM.Neuropathology and Applied Neurobiology 09/2007; 33(4):440-54. · 3.80 Impact Factor -
Article: Dynamic susceptibility contrast-enhanced perfusion magnetic resonance (MR) imaging combined with contrast-enhanced MR imaging in the follow-up of immunogene-treated glioblastoma multiforme.
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ABSTRACT: To assess the value of the combined use of dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging (MRI) and conventional contrast-enhanced MRI for the follow-up of treatment of glioblastoma multiforme (GBM). 79 examinations were performed in six surgically and immunogene-treated patients and two surgically treated patients. Ratios of the relative cerebral blood volume (rCBV) in lesions and in the contralateral normal-appearing white matter were calculated. The regions with elevated rCBV were compared with those with contrast enhancement. Tissue specimens from surgical biopsies and autopsies were studied histopathologically. The lesion-to-normal rCBV ratios were high in the tumors prior to operation (7.3 to 18.2) as well as in the recurrent tumors (1.6 to 13.2). The volumes of the regions with elevated rCBV were similar to those with contrast enhancement in 63 of the 79 examinations. However, in 11 of 79 examinations, the regions with high rCBV were smaller than the regions with contrast enhancement ("mismatch"). In two samples from the immunogene-treated patients this was correlated with the histopathological finding of malignant tumor with numerous proliferating GBM vessels with multiple minimal lumina, sometimes thrombotized or ruptured. These vessels may have increased permeability with contrast enhancement not accompanied by increased microvascular volume. 1) Elevated rCBV on perfusion MRI corresponding to the contrast-enhancing lesion supports the diagnosis of recurrent malignant tumor. 2) A mismatch showing a volume of rCBV elevation smaller than that of contrast enhancement can be seen in particularly aggressive tumor growth and is thus not always a sign of reactive non-tumor changes. 3) The combination of perfusion MRI and conventional contrast MRI provides useful information in the follow-up of glioblastoma multiforme treatment.Acta Radiologica 11/2006; 47(8):852-61. · 1.37 Impact Factor -
Article: Tumor extension in high-grade gliomas assessed with diffusion magnetic resonance imaging: values and lesion-to-brain ratios of apparent diffusion coefficient and fractional anisotropy.
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ABSTRACT: To determine whether the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) can distinguish tumor-infiltrated edema in gliomas from pure edema in meningiomas and metastases. Thirty patients were studied: 18 WHO grade III or IV gliomas, 7 meningiomas, and 5 metastatic lesions. ADC and FA were determined from ROIs placed in peritumoral areas with T2-signal changes, adjacent normal appearing white matter (NAWM), and corresponding areas in the contralateral healthy brain. Values and lesion-to-brain ratios from gliomas were compared to those from meningiomas and metastases. Values and lesion-to-brain ratios of ADC and FA in peritumoral areas with T2-signal changes did not differ between gliomas, meningiomas, and metastases (P = 0.40, P = 0.40, P = 0.61, P = 0.34). Values of ADC and FA and the lesion-to-brain ratio of FA in the adjacent NAWM did not differ between tumor types (P = 0.74, P = 0.25, and P = 0.31). The lesion-to-brain ratio of ADC in the adjacent NAWM was higher in gliomas than in meningiomas and metastases (P = 0.004), but overlapped between tumor types. Values and lesion-to-brain ratios of ADC and FA in areas with T2-signal changes surrounding intracranial tumors and adjacent NAWM were not helpful for distinguishing pure edema from tumor-infiltrated edema when data from gliomas, meningiomas, and metastases were compared.Acta Radiologica 05/2006; 47(3):311-9. · 1.37 Impact Factor
