PI3K-regulated system xc(-) activity is not only involved in the stress resistance of neuronal cells and in cell growth by increasing the cysteine supply and glutathione synthesis, but also plays a role in the pathophysiology of tumor- and non-tumor-associated epilepsy by up-regulating extracellular cerebral glutamate.

Ischemic stroke in patients with cancer is thought to be associated with a worse prognosis and might be the initial symptom of an unknown malignancy. However, diagnostic algorithms to reliably identify cancer-associated stroke have not been developed. In this retrospective single-centre analysis, 68 patients with ischemic stroke and an active solid malignancy were identified. Neurological assessment and outcome, cardiovascular risk factors, neuroimaging studies as well as laboratory findings were compared to 68 age- and sex-matched control subjects with ischemic stroke without diagnosis of cancer. Lung, pancreatic and renal cancer showed increased prevalences compared to those of the general population in Germany. Diagnosis of cancer was most often made within the 12 months preceding (32.4%) or during the diagnostic work-up for stroke (17.7%). Cancer-associated stroke was characterized by a more severe clinical deficit, frequent clinical deterioration (13.2 vs. 1.5%) or death (25 vs. 4.4%). Ischemic lesions often involved multiple territories (51.6 vs. 12.7%), more often with co-existing subacute and acute infarctions in imaging studies (54.8 vs. 11.1%). Patients with cancer had significantly higher levels of C-reactive protein, relative granulocytosis and serum lactate dehydrogenase activity. Using receiver operating characteristics-based multiple analysis, we developed a model using these parameters which detected cancer-associated stroke with a sensitivity of 75% and specificity of 95%. Our analysis suggests that a multiple algorithm combining the number of territories involved and laboratory signs of inflammation and cell turnover might identify patients with stroke suffering from previously unknown malignancy.

No abstract

BackgroundThere is an ongoing debate whether primary lateral sclerosis (PLS) should be regarded as an independent disease entity separate from amyotrophic lateral sclerosis (ALS) or as a slowly progressive variant of ALS.ObjectiveThe study was designed to investigate specific white matter alterations in diffusion tensor imaging (DTI) data from PLS patients by a hypothesis-guided tract-of-interest-based approach compared with ‘classical’ ALS patients and healthy controls, in order to identify microstructural changes according to the neuropathologically defined ALS affectation pattern in vivo.MethodsDTI-based white matter mapping was performed both by an unbiased voxelwise statistical comparison and by a hypothesis-guided tractwise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 50 PLS and 50 ALS patients vs 50 matched controls.ResultsThe analysis of white matter integrity by regional FA reductions demonstrated the characteristic alteration patterns along the CST and also in frontal and prefrontal brain areas in PLS patients and ALS patients. In the tract-specific analysis according to the ALS-staging pattern, PLS and ALS affectation patterns showed identical significant alterations of ALS-related tract systems when compared with controls and no differences when compared with each other.ConclusionsThis DTI study showed the same microstructural affectation patterns in PLS patients as in ALS, in support of the hypothesis that PLS is a phenotypical variant of ALS.

BackgroundAfter the demonstration of a corticoefferent propagation pattern in amyotrophic lateral sclerosis (ALS) by neuropathological studies, this concept has been used for in vivo staging of individual patients by diffusion tensor imaging (DTI) techniques, both in `classical` ALS and in restricted phenotypes such as primary lateral sclerosis (PLS).ObjectiveThe study was designed to investigate that microstructural changes according to the neuropathologically defined ALS alteration pattern in PLS patients could be confirmed to be identical to ´classical´ ALS patients. The novelty in this approach is that the results were independent of the subject samples and the data acquisition parameters (as was validated in two samples from two different centres). That way, reproducibility across (international) centres in addition to harmonisation/standardisation of data analysis has been addressed, for the possible use of MRI-based staging to stratify patients in clinical trials.MethodsTractwise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern was applied to DTI data (pooled from two ALS centres) of 88 PLS patients and 88 ALS patients with a ‘classical’ phenotype in comparison to 88 matched controls in order to identify white matter integrity alterations.ResultsIn the tract-specific analysis, alterations were identical for PLS and ALS in the tract systems corresponding to the ALS staging pattern, independent of the subject samples and the data acquisition parameters. The individual categorisation into ALS stages did not differ between PLS and ALS patients.ConclusionsThis DTI study in a two-centre setting demonstrated that the neuropathological stages can be mapped in vivo in PLS with high reproducibility and that PLS-associated cerebral propagation, although showing the same corticofugal patterns as ALS, might have a different time course of neuropathology, in analogy to its much slower clinical progression rates.