Neuropsychological Findings: Myoclonic Astatic Epilepsy (MAE) and Lennox-Gastaut Syndrome (LGS)

Summary:  Purpose: To identify a specific neuropsychological profile associated with myoclonic astatic epilepsy (MAE) and Lennox-Gastaut syndrome (LGS).
Methods: Seven patients diagnosed with MAE and four patients diagnosed with LGS were selected from patients referred to our Child Neurology Unit. The patients were assessed both clinically (awake, sleep, Holter EEG, seizures frequency, and semiology) and neuropsychologically (IQ, language, attention, visuospatial and visuomotor abilities, and behavior). One representative case of each syndrome is presented here.
Results: The clinical picture of the MAE patient resembled that of an MAE condition associated with transitory epileptic encephalopathy. The neuropsychological findings suggest that electroclinical anomalies can temporarily affect cognitive and behavioral functioning. Early effective antiepileptic drug (AED) treatment was found to improve cognitive outcome. In contrast, LGS was associated with mental retardation, which persisted after seizure control.
Conclusions: At present, it remains difficult to delineate a precise neuropsychological profile associated with MAE and LGS. The cognitive outcome of MAE is variable and depends on the clinical pattern. With regard to LGS, the hypothesis of a genetic predisposition underlying both the epilepsy and the mental retardation is still valid. Alternatively, exposure to subclinical electrophysiological anomalies during a critical period of cerebral development may be responsible for the mental retardation. At the time the clinical manifestations appear, drug treatment, even if effective, would have only limited impact on cognitive outcome. However, early multidisciplinary intervention may help to improve behavior and communicative abilities, enhancing the quality of life of these children and their families.     

Stable preference for high ethanol concentrations after ethanol deprivation in Sardinian alcohol-preferring (sP) rats.

Results of a recent study have demonstrated that exposure to multiple ethanol concentrations and repeated ethanol deprivation periods in Indiana ethanol-preferring (P) rats resulted in the development of an alcohol deprivation effect (ADE; the temporary increase in voluntary ethanol intake after a period of deprivation from ethanol) characterized by consumption of intoxicating amounts of ethanol. The current study was designed to possibly extend these results to Sardinian alcohol-preferring (sP) rats, generated with the same selective program previously used for P rats. To this aim, ethanol-naive sP rats were exposed initially to the home cage four-bottle choice [10%, 20%, and 30% (vol./vol.) ethanol solutions and water] for eight consecutive weeks. Subsequently, rats were divided into two groups: The first group had continuous access to the four-bottle regimen (nondeprived rats), and the second group was exposed to five cycles of 14-day periods of deprivation from ethanol and 14-day periods of reexposure to the four-bottle regimen. An ADE developed after each deprivation period. However, the extra intake of ethanol was limited to the first hour of each reaccess period. Magnitude of ADE did not change with repeated periods of deprivation. However, a shift in preference toward the two highest concentrations of ethanol solutions was evident from the first reexposure to ethanol and was maintained throughout the study. These results provide further evidence on the heterogeneity of ethanol-drinking behavior among rat lines selectively bred for high ethanol preference and consumption.     

Poly(2,6-Dimethyl-1,4-Phenylene oxide)/crosslinked polystyrene semi-interpenetrating networks: Synthesis and properties

Semi-interpenetrating networks (semi-IPN's) based on linear poly(phenylene ether)s and crosslinked polystyrene can be prepared by reactive moulding of crosslinkable polymeric mixtures. These materials show thermomechanical properties which strongly depend on both the ratio of the two polymeric matrices and the degree of crosslinking in the polystyrene network. Samples based on a 50/50 weight ratio of poly(2,6-dimethyl-1,4-phenylene oxide)/crosslinked polystyrene show glass transition temperatures (T_g) which are very dependent on the degree of crosslinking. It is therefore possible to obtain materials with desired T_g, ranging from the T_g of the corresponding linear blend to that of poly(2,6-dimethyl-1,4-phenylene oxide) alone.     

Selecting antibodies to detect HER2 overexpression by immunohistochemistry in invasive mammary carcinomas.

There is an increasing clinical demand for HER2 analysis in breast cancer, especially since the release of trastuzumab. The authors assessed the ability of immunohistochemistry to detect HER2 overexpression in invasive mammary carcinomas (IMC) using five antibodies. Paraffin-embedded samples of 86 IMCs (T2N0) were used to compare the immunohistochemical overexpression of HER2 using two polyclonal antibodies (HercepTest [DAKO] and A0485 [DAKO]) and three monoclonal antibodies (CB11 from two different laboratories, Biogenex and Novocastra, and 4D5 [Genentech]). All immunostainings were scored according to the FDA-approved HercepTest recommendations. The HercepTest-positive cases were compared with gene amplification by FISH (Oncor Inform, Ventana). The HercepTest was positive in 31 of the 86 cases (36.1%). The DAKO antibody A0485 was positive in 25 of the 66 (37.8%). Monoclonal antibody 4D5 was positive in only 15 of the 86 cases (17.4%). There was almost total agreement in results between the two CB11 antibodies: 25 of the 86 positive cases (29.1%). All cases positive for CB11 or 4D5 were HercepTest positive. Most of the HercepTest 2+ cases were negative when using either monoclonal antibody. FISH was positive in 19 of the 20 HercepTest 3+ cases and negative in 5 HercepTest 2+ cases. Three CB11-2+ cases showed no amplification by FISH. In three FISH-positive cases the immunohistochemistry showed no overexpression by all antibodies used. These findings suggest that immunohistochemistry may be used reliably as a primary methodology for evaluating HER2; however, the use of polyclonal antibodies may not be adequate to assess HER2 overexpression. CB11, regardless of the manufacturer (Biogenex or Novocastra), showed better concordance with FISH (kappa=0.83) than did the polyclonal antibodies.     

M-2 protocol for melphalan-resistant and relapsing multiple myeloma

33 patients with advanced refractory multiple myeloma received a combination of vincristine, cyclophosphamide, carmustine, melphalan and steroids (M-2 protocol). 20 of them had failed prior chemotherapy with alkylating agents and the remaining 13 patients had relapsed after a response to these drugs. An objective tumour cell mass reduction (greater than or equal to 50%) was achieved in 17% of the patients (6% of previously nonresponders and 33% of previously relapsing), while 9 additional patients improved (30-50% tumour reduction), for an overall response rate of 47% (39% for previously nonresponders and 58% for previously relapsing). The median duration of response was 7 months. Thrombocytopenia was the most common toxicity encountered in the study (39% of cases). Our findings indicate that M-2 protocol is an effective salvage treatment for patients who relapse from previous chemotherapy with alkylating agents. In contrast, results in patients who are primarily resistant to these drugs justify the search for different treatment programmes which can produce greater degrees of tumour reduction.     

B-B10 (anti-CD25)-saporin immunotoxin--a possible tool in graft-versus-host disease treatment.

An immunotoxin containing the B-B10 MoAb, directed against the CD25 determinant, and the ribosome-inactivating protein saporin, inhibits 3H-TdR incorporation in phytohemagglutin, allogeneic-stimulated lymphocytes (primary and secondary mixed-lymphocyte reaction), and in an alloreactive T cell clone. A lower degree of inhibition was obtained with the B-B10 MoAb, which is known to inhibit IL-2 activity, as well as with the unconjugated compounds. These results suggest that the in vivo administration of the conjugate might be a more effective tool in the treatment of patients affected by graft-versus-host disease than B-B10 alone, by inducing an efficient killing of allogeneic-reacting T lymphocytes.     

Profile of in Vitro Binding Affinities of Neuroleptics at Different Rat Brain Receptors: Cluster Analysis Comparison with Pharmacological and Clinical Profiles

A series of 21 neuroleptics with different chemical structures (phenothiazines, thioxanthenes, dibenzodiazepines, butyrophenones, benzamides, etc.) was examined for their in vitro interactions with 12 neurotransmitter binding sites in the rat brain (alpha- and beta-noradrenergic, dopaminergic, muscarinic, serotoninergic, histaminic, and opioid receptors, calcium channels, and serotonin uptake binding sites). The biochemical profile obtained from the binding data was compared with reported pharmacological and clinical profiles for this class of compounds by cluster analysis. Cluster analysis on binding data classified the compounds in three main subgroups: benzamides, compounds with an affinity mainly for DA2 and 5-HT2 receptors and inactive at muscarinic receptors, and compounds with a high affinity for alpha 1-adrenergic receptors and muscarinic receptors. The main subgroups resulting from cluster analysis of previously published pharmacological and clinical data for neuroleptics contain compounds common to the present study, with some correlations. The results extend previous observations that a complete binding profile corresponds to the pharmacological and clinical profile of this class of compounds.     

Identification of a Promiscuous T-Cell Epitope in Mycobacterium tuberculosis Mce Proteins

The characterization of Mycobacterium tuberculosis antigens inducing CD4(+) T-cell responses could critically contribute to the development of subunit vaccines for M. tuberculosis. Here we performed computational analysis by using T-cell epitope prediction software (known as TEPITOPE) to predict promiscuous HLA-DR ligands in the products of the mce genes of M. tuberculosis. The analysis of the proliferative responses of CD4(+) T cells from patients with pulmonary tuberculosis to selected peptides displaying promiscuous binding to HLA-DR in vitro led us to the identification of a peptide that induced proliferation of CD4(+) cells from 50% of the tested subjects. This study demonstrates that a systematic computational approach can be used to identify T-cell epitopes in proteins expressed by an intracellular pathogen.