[Tall R waves in the right precordial leads as a possible expression of left septal fascicular block]. / Ampie onde R nelle derivazioni precordiali destre quale possibile espressione di un blocco del fascicolo settale della branca sinistra.

Histological, physiological and pathophysiological studies have shown that the left bundle branch mainly divides into three fascicles, and a septal (middle) fascicle is present in over half of human hearts. Electrocardiographic criteria for the diagnosis of the block of this fascicle have been suggested by some authors: tall R waves in lead V2 and sometimes in V1 in the absence of a right bundle branch block pattern or a well evident jump of R waves from V1 to V2, absence of initial septal q waves and/or possible small q waves in the right precordial leads, normal QRS duration and normal QRS axis. At present, this intraventricular block can only be suspected but not diagnosed with certainty even after clinical/instrumental exclusion of pathological situations associated with tall R waves in leads V1 and V2 (right ventricular hypertrophy, lateral infarction, severe septal hypertrophy) because of the marked variability of normal ECG and the potential presence of confounding diseases.

Intermittent isolated anterior displacement of QRS complex - Differential diagnosis.

BACKGROUND: The proposed criteria for diagnosis of left septal (middle) fascicular block (LSFB) appear to be conflicting. Moreover, it has been claimed that isolated anterior displacement (AD) of QRS complex could be a manifestation of a conduction delay of the right bundle branch, besides of LSFB. The purpose of the present study was to better define the etiology of AD through an analysis of the case reports dealing with intermittent AD, published up to now. METHODS: PubMed search was performed to include all case reports dealing with intermittent AD occurring spontaneously, with an available 12­lead electrocardiographic recording. Pertinent data were extracted from the papers for further analysis. RESULTS: Eighteen case reports were found in the literature; in all cases intermittent AD was attributed to LSFB. In all cases AD was associated to changes of initial QRS forces, characterized by disappearance of septal q waves (in I and V6) and/or appearance of a small q wave in leads V1-V3. Morphology of terminal QRS forces, analysed for the first time, was unchanged in 90% of cases. Some Isolated ADs observed during induction of premature atrial extra-stimuli and recorded by vectorcardiographic tracing and some electrocardiographic leads were attributed to a conduction delay of the right bundle branch. In this case, initial QRS forces did not change and terminal QRS forces shifted to the right. CONCLUSIONS: In the presence of intermittent isolated AD, a differential diagnosis between LSFB and a conduction delay of the right bundle branch appears to be possible by the analysis of initial and terminal QRS forces. Instead, the diagnosis of permanent LSFB remains a challenge.

Hippocampal NPY Y2 receptors modulate memory depending on emotional valence and time.

Posttraumatic stress disorder is characterized by contextually inappropriate, dys-regulated and generalized fear expression and often resistant to therapy. The hippocampus integrates contextual information into spatial and emotional memories, but how diverse modulatory neurotransmitters are shaping this process is not known. Neuropeptide Y is a peptide-neurotransmitter, which modulates hippocampal excitability by activating several G-protein-coupled receptors. Postsynaptic Y1 receptors create strong anxiolytic and fear-suppressing behavior, while pre-synaptic Y2 receptors (Y2R) are mainly anxiogenic. The role of Y2Rs in spatial compared to emotional learning is, however, still controversial. Here we show that deletion of Y2Rs increased recall, but delayed extinction of contextual fear. Interestingly, spatial memory in the Barnes maze was enhanced during early and late testing, suggesting that Y2Rs suppress learning by hippocampal and extra-hippocampal mechanisms. To demonstrate sufficiency of hippocampal Y2Rs we performed viral vector-mediated, locally restricted re-expression of Y2Rs in the hippocampus of Y2KO mice. This treatment reduced spatial memory to the level of wildtype mice only during early, but not late recall. Furthermore, contextual fear was reduced, while induction of fear extinction appeared earlier. Our results suggest that hippocampal Y2R signaling inhibits learning in a time- and content-specific way, resulting in an early reduction of spatial memory and in a specific suppression of fear, by reducing fear recall and promoting fear extinction. We thus propose that reduction of hippocampal excitability through pre-synaptic Y2Rs may control the integration of contextual information into developing memories.

Calcium-binding proteins in focal cortical dysplasia.

OBJECTIVE: Alterations in γ-aminobutyric acid (GABA)-ergic cortical neurons have been reported in focal cortical dysplasia (FCD)Ia/IIIa, a malformation of cortical development associated with drug-resistant epilepsy. We compared numbers of neurons containing calcium-binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR) and densities of respective fibers in lateral temporal lobe surgical specimens of 17 patients with FCD with 19 patients who underwent anterior temporal lobe resection due to nonlesional temporal lobe epilepsy (non-FCD) as well as with 7 postmortem controls. METHODS: PV-, CB-, and CR-immunoreactive (IR) neurons were quantitatively investigated with use of two-dimensional cell counting and densitometry (reflecting mainly IR fibers) in cortical layers II, IV, and V. RESULTS: Numbers of PV-IR neurons, ratios of PV-containing to Nissl-stained neurons (correcting for eventual cell loss), and densities of PV-IR were higher in layer II of the cortex of FCD compared to non-FCD patients. Similarly, densities of CB-IR and CR-IR were also higher in layers II and V, respectively, of FCD than of non-FCD patients. Comparison with postmortem controls revealed significant higher cell numbers and fiber labeling for all three calcium-binding proteins in FCD cortex, whereas numbers of Nissl-stained neurons did not vary between FCD, non-FCD, and postmortem controls. In non-FCD versus postmortem controls, ratios of calcium-binding protein-IR cells to Nissl-stained neurons were unchanged in most instances except for increased CB/Nissl ratios and CB-IR densities in all cortical layers. SIGNIFICANCE: Increased numbers of PV neurons and fiber labeling in FCD compared to nondysplastic epileptic temporal neocortex and postmortem controls may be related to cortical malformation, whereas an increased number of CB-IR neurons and fiber labeling both in FCD and non-FCD specimens compared with postmortem controls may be associated with ongoing seizure activity. The observed changes may represent increased expression of calcium-binding proteins and thus compensatory mechanisms for seizures and neuronal loss in drug-resistant epilepsy.

Somatostatin and neuropeptide Y neurons undergo different plasticity in parahippocampal regions in kainic acid-induced epilepsy.

Parahippocampal brain areas including the subiculum, presubiculum and parasubiculum, and entorhinal cortex give rise to major input and output neurons of the hippocampus and exert increased excitability in animal models and human temporal lobe epilepsy. Using immunohistochemistry and in situ hybridization for somatostatin and neuropeptide Y, we investigated plastic morphologic and neurochemical changes in parahippocampal neurons in the kainic acid (KA) model of temporal lobe epilepsy. Although constitutively contained in similar subclasses of γ-aminobutyric acid (GABA)-ergic neurons, both neuropeptide systems undergo distinctly different changes in their expression. Somatostatin messenger RNA (mRNA) is rapidly but transiently expressed de novo in pyramidal neurons of the subiculum and entorhinal cortex 24 hours after KA. Surviving somatostatin interneurons display increased mRNA levels at late intervals (3 months) after KA and increased labeling of their terminals in the outer molecular layer of the subiculum; the labeling correlates with the number of spontaneous seizures, suggesting that the seizures may trigger somatostatin expression. In contrast, neuropeptide Y mRNA is consistently expressed in principal neurons of the proximal subiculum and the lateral entorhinal cortex and labeling for the peptide persistently increased in virtually all major excitatory pathways of the hippocampal formation. The pronounced plastic changes differentially involving both neuropeptide systems indicate marked rearrangement of parahippocampal areas, presumably aiming at endogenous seizure protection. Their receptors may be targets for anticonvulsive drug therapy.

Glutamate decarboxylase 67 is expressed in hippocampal mossy fibers of temporal lobe epilepsy patients.

Recently, expression of glutamate decarboxylase-67 (GAD67), a key enzyme of GABA synthesis, was detected in the otherwise glutamatergic mossy fibers of the rat hippocampus. Synthesis of the enzyme was markedly enhanced after experimentally induced status epilepticus. Here, we investigated the expression of GAD67 protein and mRNA in 44 hippocampal specimens from patients with mesial temporal lobe epilepsy (TLE) using double immunofluorescence histochemistry, immunoblotting, and in situ hybridization. Both in specimens with (n = 37) and without (n = 7) hippocampal sclerosis, GAD67 was highly coexpressed with dynorphin in terminal areas of mossy fibers, including the dentate hilus and the stratum lucidum of sector CA3. In the cases with Ammon's horn sclerosis, also the inner molecular layer of the dentate gyrus contained strong staining for GAD67 immunoreactivity, indicating labeling of mossy fiber terminals that specifically sprout into this area. Double immunofluorescence revealed the colocalization of GAD67 immunoreactivity with the mossy fiber marker dynorphin. The extent of colabeling correlated with the number of seizures experienced by the patients. Furthermore, GAD67 mRNA was found in granule cells of the dentate gyrus. Levels, both of GAD67 mRNA and of GAD67 immunoreactivity were similar in sclerotic and nonsclerotic specimens and appeared to be increased compared to post mortem controls. Provided that the strong expression of GAD67 results in synthesis of GABA in hippocampal mossy fibers this may represent a self-protecting mechanism in TLE. In addition GAD67 expression also may result in conversion of excessive intracellular glutamate to nontoxic GABA within mossy fiber terminals.