Idiopathic generalised epilepsy: a pilot study of memory and neuronal dysfunction in the temporal lobes, assessed by magnetic resonance spectroscopy.

BACKGROUND: The memory deficits in patients with temporal lobe epilepsy (TLE) are associated with epileptogenic lesions of the temporal lobes, especially hippocampal sclerosis. Memory deficits have been extensively studied in TLE, but the presence of pre-existing temporal lobe abnormality has confounded studies on the relationship between memory dysfunction and seizure activity. Idiopathic generalised epilepsy (IGE) is characterised by primary generalised seizures and is found to occur in the absence of any macroscopic brain abnormalities. IGE is therefore ideal for investigations on the effects of seizure activity on memory and cognition. AIM AND METHODS: Magnetic resonance spectroscopy (MRS) and neuropsychological testing were used to investigate the relationship between epileptic seizures, memory performance and neuronal dysfunction in the temporal lobes of a group of patients with IGE. 30 patients and 15 healthy controls participated in the study. RESULTS: Patients with IGE were found to perform worse than controls on tests of speed of information processing, general cognitive performance and a range of memory tests, including face recognition, word recognition, verbal recall and complex figure recall. The performance of the patient group on the visual recognition and verbal recall sections of the Doors and People Test was found to correlate with MRS ratios of N-acetyl aspartate:choline and N-acetyl aspartate:creatine in the temporal lobes. CONCLUSION: This result supports the hypothesis that memory deficits in epilepsy may be due to neuronal dysfunction secondary to epileptic activity itself in the absence of any macroscopic lesions in the temporal lobes.

Longitudinal study of chemokine receptor expression on peripheral lymphocytes in multiple sclerosis: CXCR3 upregulation is associated with relapse.

The interaction between chemokines and their receptors leads to selective recruitment of cells to foci of inflammation. Cross-sectional studies have reported significantly different expression of chemokine receptors CXCR3, CCR5 and CCR2 on peripheral blood lymphocytes in multiple sclerosis (MS) compared with controls. Cells expressing these receptors are likely to play a pathogenic role as suggested by studies of experimental autoimmune encephalomyelitis. Also, immunogenetic studies of nonfunctional CCR5 receptors in MS patients, due to 32delta deletion, demonstrated a delay in time to next relapse. The aims of this study were to detect any changes in the serial expression of chemokine receptors CCR2, CCR3, CCR5 and CXCR3 on peripheral blood CD4+ lymphocytes from patients with MS and to correlate the changes with relapses. Upregulation of CXCR3 expression on peripheral blood CD4+ lymphocytes was associated with all relapses and CCR5 expression was significantly affected with all relapses. Clinical recovery, with or without intravenous methylprednisolone treatment, coincided with the return of CXCR3 towards baseline in all but one case. Fluctuation in the expression of CXCR3 and CCR5 was also significantly greater in clinically stable patients with MS compared with controls, which may be due to subclinical disease activity. These findings provide further support for the view that CXCR3 and CCR5 antagonists could have a therapeutic value in MS.

Expression of chemokines in cerebrospinal fluid and serum of patients with chronic inflammatory demyelinating polyneuropathy.

Chemokines are likely to contribute to the pathogenesis of chronic inflammatory demyelinating polyneuropathy (CIDP), as evidenced by data from experimental autoimmune neuritis. The alpha and beta chemokines in the cerebrospinal fluid (CSF) and serum from patients with CIDP were analysed using an enzyme linked immunosorbent assay. CXCL9, CXCL10, and CCL3 were raised in the CSF in CIDP compared with controls and non-demyelinating neuropathies (p < 0.001). Although the CSF levels of CCL2 were significantly higher than the serum levels for all groups, the difference between groups was not significant. CXCL9, CXCL10, and CCL3 may contribute to the pathogenesis of CIDP by recruiting inflammatory T cells and monocytes to spinal nerve roots, while CCL2 is likely to play a physiological role.

Expression of chemokines in the CSF and correlation with clinical disease activity in patients with multiple sclerosis.

OBJECTIVE: To define the chemokine profile in the CSF of patients with multiple sclerosis (MS) and compare it with three control groups; patients with benign headache (headache), non-inflammatory neurological diseases (NIND), and other inflammatory neurological diseases (IND). In addition, the correlations of CSF chemokine concentrations with chemokine receptor expression on CSF CD4(+) T cells and with clinical disease activity were assessed. METHODS: Forty three patients with MS, 24 with IND, 44 with NIND, and 12 with benign headache undergoing diagnostic or therapeutic lumbar puncture were included. Supernatant fluid from CSF was analysed for four beta (CCL2, CCL3, CCL4, CCL5) and two alpha (CXCL9, CXCL10)chemokines by enzyme linked immunosorbent assay (ELISA). Chemokine receptors CCR3, CCR5, and CXCR3 on CD4(+) T cells from eight patients with MS were analysed using directly conjugated fluorescent labelled monoclonal antibodies and flow cytometry. RESULTS: CXCL10, formerly interferon-gamma inducible protein-10 (IP-10), was significantly increased and CCL2, formerly monocyte chemoattractant protein-1 (MCP-1), was significantly reduced in the CSF of patients with MS and IND compared with those with benign headache and NIND. Concentrations of CXCL10 were significantly greater in patients with relapsing-remitting compared with secondary progressive MS and correlated significantly with CXCR3 expression on CSF CD4(+) T cells from patients with MS. Concentrations of CXCL10 decreased and CCL2 concentrations increased as time from the last relapse increased in patients with MS. CONCLUSION: Increased CXCL10 and decreased CCL2 concentrations in the CSF are associated with relapses in MS. Although serial values from individual patients were not available, this study suggests that CXCL10 and CCL2 may return towards baseline concentrations after a relapse. Correlation of CXCL10 with CD4(+) T cell expression of CXCR3 was consistent with its chemoattractant role for activated lymphocytes. Thus CXCL10 neutralising agents and CXCR3 receptor antagonists may be therapeutic targets in MS.