First case of anti-ganglioside GM1-positive Guillain-Barré syndrome due to hepatitis E virus infection.

A 51-year-old previously healthy woman presented with Guillain-Barré syndrome (GBS) and elevated liver enzymes. Further diagnostic investigations showed the presence of an acute hepatitis E infection associated with anti-ganglioside GM1 antibodies. After treatment with intravenous immunoglobulins, the patient made a rapid recovery. Here, we report the first case of GBS due to acute hepatitis E virus (HEV) infection associated with the presence of anti-ganglioside GM1 antibodies. We also review available literature on the association between acute HEV infection and GBS.

A case of aseptic meningitis due to Japanese encephalitis virus in a traveller returning from the Philippines.

We here report the case of Japanese encephalitis virus (JEV) meningitis in a previously healthy young women returning from a trip to the Philippines. JEV is a mosquito-borne encephalitic flavivirus pathogen, which is endemic in South East and Eastern Asia. Our patient presented with aseptic meningitis and recovered well under supportive therapy. Although the chance of a traveller getting symptomatic JEV infection is extremely low, clinicians and microbiologist should be aware of patients contracting this emerging infectious disease, especially in the light of the increasing international travel.

Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma.

BACKGROUND: To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with recurrent high-grade glioma (HGG) after failure of surgery, radiation therapy, and chemotherapy. PATIENTS AND METHODS: In this two-arm, open-label, phase II study patients were stratified according to their epidermal growth factor receptor (EGFR) gene amplification status. Cetuximab was administered intravenously at a dose of 400 mg/m(2) on week 1 followed by weekly dose of 250 mg/m(2). The primary end point for this study was the response rate in both study arms separately. RESULTS: Fifty-five eligible patients (28 with and 27 without EGFR amplification) tolerated cetuximab well. Three patients (5.5%) had a partial response and 16 patients (29.6%) had stable disease. The median time to progression was 1.9 months [95% confidence interval (CI) 1.6-2.2 months]. Whereas the progression-free survival (PFS) was <6 months in the majority (n = 50/55) of patients, five patients (9.2%) had a PFS on cetuximab of >9 months. Median overall survival was 5.0 months (95% CI 4.2-5.9 months). No significant correlation was found between response, survival and EGFR amplification. CONCLUSIONS: Cetuximab was well tolerated but had limited activity in this patient population with progressive HGG. A minority of patients may derive a more durable benefit but were not prospectively identified by EGFR gene copy number.

MGMT promoter hypermethylation correlates with a survival benefit from temozolomide in patients with recurrent anaplastic astrocytoma but not glioblastoma.

AIMS: To investigate the correlation between O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and benefit from temozolomide in patients with recurrent high-grade glioma. PATIENTS AND METHODS: A real-time, quantitative, methylation-specific PCR assay was performed on archival tissue blocks from patients treated with temozolomide at the first recurrence. RESULTS: A subgroup of 38 patients who were chemotherapy-naive at recurrence was analysed (22 glioblastoma, 12 anaplastic astrocytoma [AA] and 4 anaplastic oligoastrocytoma [AOA]); none had 1p/19q loss. Among 10 (26%) patients with a hypermethylated MGMT promoter, none experienced disease progression within the first two treatment cycles compared with 12 of 28 (43%) patients with an unmethylated promoter (p=0.016). By Cox multivariate analysis, tumour grade and MGMT promoter methylation correlated with time to progression (p<0.05); MGMT promoter methylation correlated with superior overall survival in AA/AOA but not in glioblastoma. CONCLUSIONS: MGMT promoter methylation predicted a survival benefit in patients with 1p/19q intact AA/AOA treated with temozolomide at recurrence.

Long-term follow up of glatiramer acetate compassionate use in Belgium.

Between June 1995 and November 1998, 228 patients with relapsing-remitting Multiple Sclerosis started treatment with glatiramer acetate (Copaxone) 20 mg once daily in the frame of a "compassionate use" protocol in 15 Belgian centers. Following an average treatment period of 5.8 years, treating neurologists were requested to fill in follow-up forms indicating neurological disability status and side effects during the previous 6 months. These data were available for 134 patients. In this group, the Expanded Disability Status Scale (EDSS) improved in 26.3% of patients. An additional 36.8% of patients remained neurologically stable. The Ambulation Index (AI) showed similar results: 12.5% of patients improved, 50% of patients remained stable, and 37.5% worsened. Only 10% of patients dropped out due to several reasons. The adverse events occurring in the period preceding the follow-up survey were non-serious and consistent with the current product information of glatiramer acetate. Among the 94 patients no longer followed-up in the compassionate program, reasons for lost to follow-up were obtained for 63; most of them (41) had stopped GA treatment or switched to another disease-modifying treatment. Overall these results are very similar to the ones reported in the extension study of the pivotal trial (Johnson et al., 2000), and indicate that patients treated with glatiramer acetate have a better outcome than expected on the basis of the natural course of the disease. Despite limitations of the study design, this report confirms the sustained efficacy of glatiramer acetate in reducing the disease progression in patients with relapsing-remitting multiple sclerosis treated in day-to-day clinical practice.

Intravenous loading with arginine-hydrochloride and ornithine-aspartate in siblings of two families, presenting a familial neurological syndrome associated with cystinuria.

1. Arginine-hydrochloride and ornithine-aspartate solutions have been infused intravenously to children of two families. Three children of the WOL. family are affected with hyperargininemia and hyperammonemia, due to a lack of arginase. They present a secondary cystine-lysinuria. The three WIL. siblings are suffering from muscular hypotonia, dwarfism, incomplete renal tubular acidosis and primary cystinuria. 2. The aim was to verify how and to what extent the artificial rise of one serum amino acid could influence the serum concentrations and the urinary losses of the other amino acids. The results found for the serum have been submitted to a statistical analysis of variance. 3. The variations observed for the amino acids of the urea cycle can be interpreted as being the reflections of known metabolic pathways. 4. Additional remarks are made on a paradox in the lysinemia-lysinuria relation after arginine infusion, with a simultaneous rise of this essential amino acid in serum and urine.