Juvenile myoclonic epilepsy

CONCLUSION: We conclude that despite inevitable variability the clinical picture of JME is characteristic. It is easy to diagnose JME if one thinks of it while the history should be thoroughly analyzed. An EEG recording during sleep confirms the diagnosis. An early diagnosis of JME permits adequate prognosis of the subsequent course of epilepsy, and adequate therapy brings remission in most of the patients. If treatment starts following the large number of severe GTC seizures, the response to therapy is incomplete. The persistency of the illness throughout the life, the need for continuous medication and therapeutic unresponsiveness in cases with late diagnosis, do not justify the increasing misconception that JME is of benign nature. Diagnosis of JME is rare because of insufficient familiarily of physicians with the illness. BACKGROUND: Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epileptic syndrome characterized with the combination of myoclonic, generalized tonic-clonic (GTC) and absence seizures that are readily provoked by sleep deprivation. PATIENTS: Forty-three patients, aged from 14 to 51 years, participated in a 5-year follow-up study. Diagnosis was made according to the criteria (Table 1) for diagnosis of JME set by Panayiotopoulos et al. (1994). Nineteen patients made their first contact with a neurologist at the Institute of Neurology and were diagnosed as JME, while the remaining 24 were referred to from other medical institutions with a diagnosis of therapy resistant to focal epilepsy. All patients underwent a somatic and neurological examination, "mini mental test," EEG in waking and CT scan of the brain. Some patients had EEG performed during sleep and some had MRI of the head. RESULTS: JME began between 9 and 26 (average 17) years. All patients had myoclonic seizures, 98% had GTC and 23% absence seizures. The first myoclonic seizure occurred between 9 and 24 years while the frst GTC seizure occurred between 10 and 32 years. Myoclonic seizures (83% of patients) and GTC seizures (70% of patients) occurred most often immediately after awaking. The most frequent provocative factors were insufficient sleep, alcohol abuse and tiredness. Epilepsy in the family was present in 39%, focal neurological deficiency in 9% and pathological findings on of CT and MRI in 7% of patients. Waking EEG was pathological in 77% of patients; it included generalized spike-wave discharges in 73%, multiple spike-wave complexes in 33% and focal discharges in 12% of patients, respectively. In all 26 patients tested, sleep EEG was pathological most often with multiple spike-wave complexes in 85% and 3-4 Hz spike-wave complexes in 57% of patients. The correct diagnosis of JME following a comprehensive examination was made in 24 (56%) patients after a delay of 1 to 35 years. In 24 patients with delayed diagnosis of JME the replacement of earlier medication with valproic acid (VPA) induced remission in 18 patients (75%) while 1 patient (4%) experienced a reduction in the number of seizures. Five patients (21%) did not respond to VPA medication: 2 due to a weak compliance, another 2 due to inefficient medication and 1 because of the preexistent malabsorption syndrome. In 19 patients (44%) with initial diagnosis of JME, VPA was introduced immediately upon diagnosis. Of them, 15 (79%) had excellent response to VPA, 1 refused therapy and for 3 patients there is no information. In 2 patients VPA was substituted due to side effects (hepatotoxicity and alopetia) with lamotrigine (low doses), which brought about decrease in frequency and mitigation in myoclonic seizures.     

Net interaction between different forms of short-term synaptic plasticity and slow-IPSPs in the hippocampus and auditory cortex

Paired-pulse plasticity is typically used to study the mechanisms underlying synaptic transmission and modulation. An important question relates to whether, under physiological conditions in which various opposing synaptic properties are acting in parallel, the net effect is facilitatory or depressive, that is, whether cells further or closer to threshold. For example, does the net sum of paired-pulse facilitation (PPF) of excitatory postsynaptic potentials (EPSPs), paired-pulse depression (PPD) of inhibitory postsynaptic potentials (IPSPs), and the hyperpolarizing slow IPSP result in depression or facilitation? Here we examine how different time-dependent properties act in parallel and examine the contribution of gamma-aminobutyric acid-B (GABAB) receptors that mediate two opposing processes, the slow IPSP and PPD of the fast IPSP. Using intracellular recordings from rat CA3 hippocampal neurons and L-II/III auditory cortex neurons, we examined the postsynaptic responses to paired-pulse stimulation (with intervals between 50 and 400 ms) of the Schaffer collaterals and white matter, respectively. Changes in the amplitude, time-to-peak (TTP), and slope of each EPSP were analyzed before and after application of the GABAB antagonist CGP-55845. In both CA3 and L-II/III neurons the peak amplitude of the second EPSP was generally depressed (further from threshold) compared with the first at the longer intervals; however, these EPSPs were generally broader and exhibited a longer TTP that could result in facilitation by enhancing temporal summation. At the short intervals CA3 neurons exhibited facilitation of the peak EPSP amplitude in the absence and presence of CGP-55845. In contrast, on average L-II/III cells did not exhibit facilitation at any interval, in the absence or presence of CGP-55845. CGP-55845 generally "erased" short-term plasticity, equalizing the peak amplitude and TTP of the first and second EPSPs at longer intervals in the hippocampus and auditory cortex. These results show that it is necessary to consider all time-dependent properties to determine whether facilitation or depression will dominate under intact pharmacological conditions. Furthermore our results suggest that GABAB-dependent properties may be the major contributor to short-term plasticity on the time scale of a few hundred milliseconds and are consistent with the hypothesis that the balance of different time-dependent processes can modulate the state of networks in a complex manner and could contribute to the generation of temporally sensitive neural responses.     

Ethanol-induced gastrointestinal damage. Influence of endogenous antioxidant components and gender

This study compared the effects of undiluted and 8% ethanol administered orally on gastrointestinal antioxidant components of male and female rats. Eight percent ethanol increased the activities of duodenal glutathione peroxide (29% in males, 14% in females) and superoxide dismutase in female gastric (24%) and male duodenal (15%) mucosa. This dose of ethanol also increased the glutathione content of gastric mucosa (12% in males, 13% in females). Undiluted ethanol decreased glutathione levels in gastric mucosa (22% in males, 11% in females) and increased glutathione peroxide activity in gastric mucosa (14% in males, 9% in females). Undiluted alcohol also produced decreases in the activity of glutathione reductase in stomach (14% in males, 9% in females) and duodenum (16% in males, 12% in females). Undiluted ethanol caused mucosal damage in the body of the stomach in both genders, accompanied by an increase in luminal pH and fluid accumulation in the stomach; these changes were absent in rats given 8% ethanol. The increase in gastrointestinal antioxidant capacity associated with the administration of 8% ethanol may be a factor in the reported cytoprotective effect of lower doses of ethanol.     

Stomach implant for long-term erythropoietin expression in rats

Caveolae are small microdomains of the plasma membrane that are thought to play important roles in signal transduction processes. In this work, we have investigated the association of Rho proteins with caveolae-enriched membrane domains isolated from cultured endothelial cells. Fractionation of ECV304 cells by sucrose gradient density centrifugation in the absence of detergent resulted in the co-sedimentation of a significant proportion of RhoA and Cdc42 with known caveolae marker proteins, including caveolin, but not with other non-caveolae membrane proteins such as the angiotensin-converting enzyme. Immunoprecipitation experiments carried on crude endothelial cell lysates as well as with solubilized caveolae-enriched membrane domains showed the coimmunoprecipitation of caveolin with RhoA but not with Cdc42. Incubation of endothelial cell lysates with a glutathione-S-transferase (GST)-RhoA fusion protein resulted in the specific precipitation of caveolin, while addition of GST-caveolin-1 to the lysates promoted the precipitation of RhoA. Moreover, incubation of bacterially expressed RhoA with GST-caveolin-1 resulted in the precipitation of RhoA, indicating that RhoA directly interacts with caveolin-1. This interaction was found to be nucleotide-independent and was not affected by prior modification of RhoA with the C3 exoenzyme from C. botulinium or with the cytotoxic necrotinizing factor from E. coli. Taken together, these results suggest the association of RhoA with endothelial caveolae-enriched membrane domains, likely through physical interaction with caveolin-1. These findings may provide new insights into the functions played by Rho proteins and caveolae in signal transduction events.     

The clinical complexity of splenic vein thrombosis

Upper gastrointestinal hemorrhage secondary to splenic vein thrombosis is a curable form of localized portal hypertension when treated with splenectomy. A high index of suspicion is necessary in order to promptly diagnose and treat this underrecognized condition that is most commonly caused by inflammation or neoplasm of the pancreas. The triad of isolated gastric varices, splenomegaly, and normal hepatic function is classic; it is not uncommon, however, for patients to have only some or even none of these conditions. Mesenteric angiography with venous phase imaging is the gold standard of diagnosis. Ultrasound and CT may identify splenic vein thrombosis, but are most helpful in delineating concomitant upper abdominal pathology. Early recognition and intervention allow associated underlying conditions to be treated under the same anesthetic with minimal morbidity and mortality.     

Transport is the primary determinant of glycine content in retinal neurons

This study demonstrates that in mammalian and nonmammalian species it is possible to deplete selectively and reversibly retinal glycinergic neurons of their content of glycine by exposure to sarcosine, a competitive inhibitor of glycine transporter 1 (glyt-1). This observation was used as a tool to test the hypothesis that uptake of glycine rather than de novo synthesis is the main determinant of glycine content in retinal neurons. Isolated retinae were depleted of immunocytochemically detectable pools of glycine. Thereafter retinae were exposed either to physiological medium containing glycine or to medium lacking glycine but containing precursors for the synthesis of glycine. Retinae exposed to glycine-containing medium rapidly recovered their content of glycine, whereas retinae exposed to medium lacking glycine but containing serine, a substrate for synthesis of glycine, showed only a slow recovery of immunoreactivity for glycine in a few amacrine cells. These data indicate that uptake of glycine is the primary determinant of glycine content in most retinal glycinergic neurons. The origins of the extracellular pools of glycine remain to be identified; however, it is suggested that such glycine may be derived from the vitreous humor and that in turn this glycine may be derived from the peripheral circulation.     

B lymphocytes are critical antigen-presenting cells for the initiation of T cell-mediated autoimmune diabetes in nonobese diabetic mice

Nonobese diabetic (NOD) mice genetically deficient in B lymphocytes (NODJg mu(null)) are resistant to T cell-mediated autoimmune insulin-dependent diabetes mellitus (IDDM). Ig infusions from diabetic NOD donors did not abrogate IDDM resistance in NODJg mu(null) mice. However, T cell responses to the candidate pancreatic beta cell autoantigen glutamic acid decarboxylase (GAD), but not the control Ag keyhole limpet hemocyanin, were eliminated in NODJg mu(null) mice. To initially test whether they contribute to IDDM as APC, NOD B lymphocytes were transferred into NODJg mu(null) recipients. B lymphocytes transferred into unmanipulated NODJg mu(null) recipients were rejected by MHC class I-restricted T cells. Stable T and B lymphocyte repopulation was achieved in irradiated NODJg mu(null) mice reconstituted with syngeneic bone marrow admixed with NOD B lymphocytes. IDDM susceptibility was restored in NODJg mu(null) mice reconstituted with syngeneic marrow plus B lymphocytes, but not with syngeneic marrow only. T cell responses to GAD were restored only in NODJg mu(null) mice reconstituted with syngeneic marrow plus B lymphocytes. Hence, B lymphocytes appear to contribute to IDDM in NOD mice as APC with a preferential ability to present certain beta cell Ags such as GAD to autoreactive T cells.