Traumatic Brain Injury as a Trigger of Neurodegeneration.

Although millions of individuals suffer a traumatic brain injury (TBI) worldwide each year, it is only recently that TBI has been recognized as a major public health problem. Beyond the acute clinical manifestations, there is growing recognition that a single severe TBI (sTBI) or repeated mild TBIs (rTBI) can also induce insidious neurodegenerative processes, which may be associated with early dementia, in particular chronic traumatic encephalopathy (CTE). Identified at autopsy examination in individuals with histories of exposure to sTBI or rTBI, CTE is recognized as a complex pathology featuring both macroscopic and microscopic abnormalities. These include cavum septum pellucidum, brain atrophy and ventricular dilation, together with pathologies in tau, TDP-43, and amyloid-ß. However, the establishment and characterization of CTE as a distinct disease entity is in its infancy. Moreover, the relative "dose" of TBI, such as the frequency and severity of injury, associated with risk of CTE remains unknown. As such, there is a clear and pressing need to improve the recognition and diagnosis of CTE and to identify mechanistic links between TBI and chronic neurodegeneration.

Transcranial ultrasound to detect elevated intracranial pressure: comparison of septum pellucidum undulations and optic nerve sheath diameter.

Two ultrasound tests that can be used to assess increased intracranial pressure (ICP) at the bedside are described. In outpatients receiving lumbar puncture and in intensive care patients with invasive ICP monitoring, we measured the optic nerve sheath diameter (ONSD) with transbulbar B-mode sonography and septum pellucidum undulation (SPU) induced by repeated passive head rotation with transtemporal M-mode sonography. We assessed the sensitivity and specificity of ONSD and SPU in the prediction of ICP >20 cm H2O. For ONSD, sensitivity was 53% and specificity 100% (n = 35, p < 0.001). The sensitivity of the SPU test was 75% and the specificity 100% (n = 32, p < 0.001). Although the SPU test may not feasible in some patients, it has high sensitivity and specificity comparable to those of ONSD measurement. The SPU test and ONSD may be useful alternatives to fundoscopy in clinical routine, preferably in combination.

The relationship between large cavum septum pellucidum and antisocial behavior, callous-unemotional traits and psychopathy in adolescents.

BACKGROUND: The presence of a large cavum septum pellucidum (CSP) has been previously associated with antisocial behavior/psychopathic traits in an adult community sample. AIMS: The current study investigated the relationship between a large CSP and symptom severity in disruptive behavior disorders (DBD; conduct disorder and oppositional defiant disorder). METHOD: Structural MRI scans of youth with DBDs (N = 32) and healthy comparison youth (N = 27) were examined for the presence of a large CSP and if this was related to symptom severity. RESULTS: Replicating previous results, a large CSP was associated with DBD diagnosis, proactive aggression, and level of psychopathic traits in youth. However, the presence of a large CSP was unrelated to aggression or psychopathic traits within the DBD sample. CONCLUSIONS: Early brain mal-development may increase the risk of a DBD diagnosis, but does not mark a particularly severe form of DBD within patients receiving these diagnoses.

Septohippocampal pathways contribute to system consolidation of a spatial memory: sequential implication of GABAergic and cholinergic neurons.

Studies of the neuropharmacological substrates of spatial memory formation have focused on the contribution of septohippocampal pathways. Although these pathways include, among others, cholinergic and GABAergic fibers innervating the hippocampus, research has essentially been oriented towards the role of their cholinergic component. Recently, a few studies investigated the role of GABAergic septohippocampal projections. These only focused on almost immediate or recent memory and yielded discrepant results. GABAergic lesions impaired learning or had no effects. Given the role of the hippocampus in memory consolidation and the potential modulatory influence of the septum on hippocampal function, it is relevant to study the role of the septohippocampal interface in memory stabilization. We performed investigations with relatively selective lesions of GABAergic (using oxerin-saporin) or/and cholinergic (using 192 IgG-saporin) medial septum/vertical limb of the diagonal band of Broca (MS/vDBB) neurons in rats, and assessed acquisition of a spatial memory and its subsequent recall in the water maze. Following a 6-day training phase during which all groups improved performance to comparable levels, retention was tested 1, 5, or 25 days later. At the 1-day delay, all groups performed above chance and did not differ significantly among each other. At the 5-day delay, only rats with GABAergic or combined lesions exhibited a retention deficit. At the 25-day delay, all three lesion groups performed at chance level; in these groups, performance was significantly lower than that found in sham-operated rats. Immunochemical and histochemical verifications of the lesion extent/selectivity showed extensive GABAergic damage after intraseptal orexin-saporin infusions or cholinergic damage after 192 IgG-saporin infusions, with relatively limited damage to the other neurotransmitter system. Our data show that GABAergic and cholinergic septohippocampal neurons both contribute to memory stabilization, and could do so in a sequential way: GABAergic processes could be engaged at an earlier stage than cholinergic ones during system consolidation of a spatial memory.

Septo-optic dysplasia.

Septo-optic dysplasia is a rare disorder characterized by optic nerve hypoplasia; midline developmental defects including agenesis of the septum pellucidum, thinning or absence of the corpus callosum, or both; and deficiencies of pituitary hormones. The majority of cases are sporadic but rare familial cases occur. The clinical manifestations include poor visual function in one or both eyes, developmental delay, seizures, sleep disturbances, and precocious puberty. A life-long multidisciplinary approach is crucial in the management of these patients to optimize their growth and development and to help them lead as normal lives as possible.

Septo-hippocampal networks in chronic epilepsy.

The medial septum inhibits the appearance of interictal spikes and seizures through theta rhythm generation. We have determined that medial septal neurons increase their firing rates during chronic epilepsy and that the GABAergic neurons from both medial and lateral septal regions are highly and selectively vulnerable to the epilepsy process. Since the lateral septal region receives a strong projection from the hippocampus and its neurons are vulnerable to epilepsy, their functional properties are probably altered by this disorder. Using the pilocarpine model of temporal lobe epilepsy we examined the pilocarpine-induced functional alterations of lateral septal neurons and provided additional observations on the pilocarpine-induced functional alterations of medial septal neurons. Simultaneous extracellular recordings of septal neurons and hippocampal field potentials were obtained from chronic epileptic rats under urethane anesthesia. Our results show that: (1) the firing rates of lateral septal neurons were chronically decreased by epilepsy, (2) a subset of lateral septal neurons increased their firing rates before and during hippocampal interictal spikes, (3) the discharges of those lateral septal neurons were well correlated to the hippocampal interictal spikes, (4) in contrast, the discharges of medial septal neurons were not correlated with the hippocampal interictal spikes. We conclude that epilepsy creates dysfunctional and uncoupled septo-hippocampal networks. The elucidation of the roles of altered septo-hippocampal neuronal populations and networks during temporal lobe epilepsy will help design new and effective interventions dedicated to reduce or suppress epileptic activity.

Neuroendoscopic management of symptomatic septum pellucidum cavum vergae cyst using a high-definition flexible endoscopic system.

A 24-year-old man, who had an asymptomatic septum pellucidum cyst incidentally found one year previously, presented with severe headache and right abducens nerve palsy caused by expansion of the midline cyst. Preoperative magnetic resonance (MR) imaging revealed obstructive hydrocephalus due to the enlarged midline cyst. Neuroendoscopic fenestration of the septum pellucidum cyst was successfully performed via a right frontal approach using a high-resolution flexible neuroendoscopic system without complication. Communication between the cyst cavity and bilateral lateral ventricles was constructed via a single trajectory. The entire inner cyst wall could be inspected from the cyst cavity by manipulating the flexible neuroendoscopic system, which excluded the presence of neoplasm. His symptoms were completely relieved after surgery, and postoperative MR imaging showed significant improvement of hydrocephalus and shrinkage of the midline cyst. Septum pellucidum cavum vergae cyst may expand and become symptomatic, so fenestration using a flexible neuroendoscope system may be the optimal method for constructing communication to the bilateral lateral ventricles with minimal invasion.

The Probst bundle associated with anomalies of the precommissural separated fornix in an acallosal brain

Dissection of the brain disclosed a unique form of the Probst bundle and a rare variation of the precommissural fornix. The latter showed an unusual size, branches and path on the medial surface of hemisphere. Its posterior branch continued to curve parallel with the posterior commissural fornix to follow an abnormal path and end in the hypothalamus. The Probst bundle was intermingled with the separated fornix in an anteroposterior direction as well as in the anterior and posterior parts in an atypical way. Focusing on such morphological abnormalities may help to gain a better understanding of the pathophysiology of brain disorders (AU)

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Cavum septum pellucidum in subjects at ultra-high risk for psychosis: compared with first-degree relatives of patients with schizophrenia and healthy volunteers.

OBJECTIVE: The cavum septum pellucidum (CSP) is a space between the two leaflets of the septum pellucidum, and is a putative marker of disturbance in early brain development. We examined whether CSP was present more frequently in subjects at ultra-high risk (UHR) for psychosis compared to first-degree relatives of patients with schizophrenia (genetic high risk, GHR) and healthy controls (HC). METHODS: We evaluated CSP in 87 subjects (30 UHR, 23 GHR, and 34 HC) according to a published grading system using high-resolution magnetic resonance imaging (MRI) with 0.45-mm slice thickness. We also assessed two other criteria: presence of CSP on at least one MRI slice, and abnormally large CSP (i.e., > or =6 mm in length). Correlational analysis between CSP measures and clinical symptoms was also examined. RESULTS: Based on the grading scale, the UHR group exhibited a significantly higher incidence of abnormal CSP (grades 2, 3, and 4) compared to the HC group, but there were no significant differences in the incidence of abnormal CSP between the UHR and GHR or the GHR and HC groups. There were no significant differences among the groups in the presence of CSP on at least one MRI slice or abnormally large CSP based on the length of CSP. In addition, no significant correlations between CSP measures and clinical symptoms were found. CONCLUSION: These findings suggest that abnormal CSP might be associated with susceptibility to psychosis, although the CSP itself might be a normal anatomical variant. Further studies using a larger sample are needed to clarify issues on neurodevelopmental perspective in subjects at high risk for psychosis.

Psychopharmacological treatment in borderline personality disorder.

Borderline personality disorder is a disorder with important social and clinical repercussions, which has been treated mainly by psychotherapy. In recent years, the syndromic analysis of this disorder has allowed us to identify different symptoms capable of being improved with psychopharmacology treatment. Thus, its complex symptomatology could be included in four clinical dimensions: impulsive-aggressive, affective instability, cognitive- perceptive and anxiety-inhibition. Antidepressants, mood stabilizers, antipsychotics, anxiolytics, or more recently omega-3 fatty acids have shown efficacy in the treatment of symptomatic dimensions of this disease. We have reviewed scientific articles (reviews, clinical trials or clinical guidelines) published over the last ten years and have proposed therapeutic algorithms for psychopharmacology management in these patients.

Age-related changes in memory and in acetylcholine functions in the hippocampus in the Ts65Dn mouse, a model of Down syndrome.

Spatial working memory and the ability of a cholinesterase inhibitor to enhance memory were assessed at 4, 10, and 16 months of ages in control and Ts65Dn mice, a partial trisomy model of Down syndrome, with possibly significant relationships to Alzheimer's disease as well. In addition, ACh release during memory testing was measured in samples collected from the hippocampus using in vivo microdialysis at 4, 10, and 22-25 months of age. When tested on a four-arm spontaneous alternation task, the Ts65Dn mice exhibited impaired memory scores at both 4 and 10 months. At 16 months, control performance had declined toward that of the Ts65Dn mice and the difference in scores across genotypes was not significant. Physostigmine (50 microg/kg) fully reversed memory deficits in the Ts65Dn mice in the 4-month-old group but not in older mice. Ts65Dn and control mice exhibited comparable baseline levels of ACh release at all ages tested; these levels did not decline significantly across age in either genotype. ACh release increased significantly during alternation testing only in the young Ts65Dn and control mice. However, the increase in ACh release during alternation testing was significantly greater in control than Ts65Dn mice at this age. The controls exhibited a significant age-related decline in the testing-related increase in ACh release. With only a small increase during testing in young Ts65Dn mice, the age-related decline in responsiveness of ACh release to testing was not significant in these mice. Overall, these results suggest that diminished responsiveness of ACh release in the hippocampus to behavioral testing may contribute memory impairments in Ts65Dn mice.

Cavum septum pellucidum in schizophrenia: a case report.

Different structural alterations of the central nervous system (CNS), such as an increase in ventricular size, decrease in hippocampus and amygdala volume, and other abnormalities that are probably secondary to a loss of neuronal mass and neuropili (axons and dendrite ramifications) linked to a precocious alteration in neurodevelopment are described in patients with schizophrenia in greater proportion than in the general population. The cavum septum pellucidum is among the alterations whose role in the disease is more unknown, since the cavity between the two septum laminae draws attention in very few cases. According to several studies, this alteration is more frequent in patients with schizophrenia than in healthy subjects and currently its association to the disease is being studied. In the following, we present the case of a 37 year old patient with no outstanding background, who was admitted to our psychiatry department due to psychotic symptoms.

Spontaneous regression of a cystic cavum septum pellucidum.

A persistent cavum septum pellucidum (CSP) is present in approximately 0.73% of adults, although its incidence ranges from 0.14 to 18.9% depending on the detection method. Cystic CSP is even rarer. A cyst causing mass within the CSP can obstruct the intraventricular foramen, leading to blockage of CSF flow and possible hydrocephalus, often justifying surgical intervention. We describe spontaneous decompression of a cystic CSP in a 36-year-old man. Initial MRI showed a cystic CSP with lateral bowing of the septal walls to 1.9 cm. Follow-up MRI 15 months later demonstrated no lateral bowing, and the septal wall width was 1.0 cm. This spontaneous decompression was not explained by the one previously described case report of cystic CSP regression.

Neuroprotective effects of behavioural training and nicotine on age-related deficits in spatial learning.

Studies in humans and animals show a clear decline in spatial memory with age and several approaches have been adopted to alleviate this impairment. The purpose of our review is to assess the studies that have suggested the possible neuroprotective actions of behavioural training and nicotine-applied both independently and in conjunction-on age-related deficits in spatial learning. Both spatial pretraining and nonspatial experiences influence an animal's performance in spatial tasks. In aged rats, the experience of training in the water maze task increases the number of newly generated neurons in the hippocampus. The neuroprotective effects of nicotine have been demonstrated in both in-vitro and in-vivo models, although the molecular mechanisms underlying these actions are not yet fully understood. It had been concluded in different studies that nicotine can improve, impair or have no effect on performance in the water maze. Neurobiological data also suggest an interaction between nicotine and prior experience in complex tasks, although few studies have raised the question of whether nicotine treatment and training in spatial tasks may contribute in an interactive manner to alleviate spatial cognition impairment associated with the ageing process. Different findings suggest that past experience could be a confounding variable in longitudinal studies that aim to evaluate the neuroprotective effects of nicotine on age-related deficits in spatial learning.

The quest of cavum septi pellucidi: obscure chance event discovery or the result of some encoded disturbance? Developmental cerebral dysplasias, cavum septi pellucidi and epilepsy: clinical, MRI and electrophysiological study.

OBJECTIVES: Developmental cerebral dysplasias are frequent causes of epilepsy. The early stage of gestation, mainly the period of neural crest separation and neuroblast migration (disturbance of midline structures, heterotopias, cortical dysplasias and disturbance of the ventricular and vascular formation), may be considered as a cause of serious cerebral dysplasia. The aim of the study was focused on frequent simultaneous occurrences of epileptic seizures and the defect or abnormality of the ventricular system - cavum septi pellucidi (CSP). MATERIAL AND METHOD: In our study the clinical symptoms, EEG and somatosensory evoked potentials (SEP's) following median nerve stimulation and MRI pictures in the group of patients with CSP (n= 35), were analyzed. In the SEP analysis, a control group of normal, healthy volunteers (n = 40) and a group of age matched patients with epileptic seizures of different origin, without structural lesions evident on MRI (n=21), were used. RESULTS: Analysis of the patient population with CSP (CSP was confirmed by MRI) showed that approximately in 2/3 cases, different types of cranio-cerebral dysplasias were evident on MRI. More than 2/3 of the patients with CSP showed epilepsy and an abnormal EEG record, however, focal EEG changes were seen more frequently in the group of patients with epilepsy without CSP, than in patients with CSP. The SEP's in patients with CSP showed a statistically significant prolongation of latency of thalamic P15 waves, however these changes were not present in the group of patients with epilepsy of a different origin. CONCLUSIONS: In a group of patients with CSP, dysplastic MRI changes, together with the prolongation of thalamic wave latencies according SEP, were examined. These clinical symptoms may be considered the result of disturbances of early gestation and of lesions of midline structures. CSP became an interesting model opportunity for us, and allowed for the clinical, MRI and electrophysiological examination of developmental cerebral dysplasias. We believe that there is an important role for septal and diencephalic midline structures in cerebral electrogenesis, and possibly in the origin of epileptic seizures too.

[Neuronal septal activity during hippocampal seizure discharges generation in acute model of epilepsy].

The activity of the neurones of the medial septal region (MS) and the hippocampal EEG in control and during the appearance of seizure discharges provoked by electrical stimulation of the perforant path were investigated in the awake rabbit. During afterdischarge generation in the hippocampus the dense neuronal bursts separated by periods of inhibition were recorded in the MS. In one group of neurons the bursts of spikes coincided with the discharges in the hippocampus, in other group-occured during inhibitory periods. When the afterdischarge stopped, in the septal neurons with theta activity the disruption of theta pattern was recorded, which have been correlated with the occurrence of low amplitude high frequency (20-25 Hz) waves in the hippocampal EEG. As a rule, the neuronal activivity of the MS recovered much quickly than EEG of the hippocampus; in some cases the increasing of the theta regularity was observed. The definite accordance of the electrical activity of the hippocampus and MS during seizure discharges suggests that the septohippocampal system operate as integral nervous circuit in these conditions. Diverse in the temporal interrelations between the discharges of MS neurones and ictal discharges in the hippocampus in the different cells possible indicate that various groups of the septal nervous elements have different participation in the seizure development. Appearance of the high frequency bursts in the MS is a possible "precursor" of the seizure onsets.

Cavum septi pellucidi in first-episode schizophrenia and first-episode affective psychosis: an MRI study.

A high prevalence of abnormal cavum septi pellucidi (CSP) in schizophrenia may reflect neurodevelopmental abnormalities in midline structures of the brain. The relationship, however, between abnormal CSP and clinical symptoms, and with abnormalities in other limbic structures remains unclear, as does the question of whether a similar abnormality is present in affective psychosis. Seventy-four patients at their first hospitalization, 33 with schizophrenia and 41 with affective (mainly manic) psychosis, and 56 healthy control subjects underwent high-spatial-resolution magnetic resonance imaging (MRI). CSP on six slices or more on 0.9375-mm resampled coronal images was categorized as abnormal. The prevalence of abnormal CSP in both schizophrenic patients (26.1%) and affective psychosis patients (18.2%) was significantly higher than was observed in control subjects (8.2%). In schizophrenic patients only, larger CSP was significantly associated with more severe thinking disturbance and smaller left parahippocampal gyrus gray matter volumes. While the relationships between CSP ratings and clinical symptoms did not significantly differ between the two psychosis groups as assessed by the comparison of regression slopes, the association with limbic volumes appeared to be specific to schizophrenic patients. These results suggest that psychosis associated with schizophrenia and affective disorder share, at least to some extent, neurodevelopmental abnormalities involving midline structures and associated psychopathological consequences. However, the association between abnormal CSP and limbic systems may be more specific to schizophrenia.

[Visual analysis of EEG in children with a cavum of the septum pellucidum]. / Wzrokowa analiza zapisów EEG u dzieci z torbiela przegrody przezroczystej.

HYPOTHESIS: It is possible that bioelectric activity of the both brain hemispheres is changed in children with a cavum of the spectrum pellucidum (CSP), a marker of brain dysgenesis. It could be connected probably with neuropsychological impairment in children with CSP. MATERIAL: Visual analysis of EEG was done in 41 children with CSP aged 2 months to 17 years and in 32 children without CSP aged 3 months to 17 years. It induced 8 EEG curve pairs from each child, that means 328 pairs in CSP and 256 pairs without CSP children. METHODS: EEG pattern was analysed by two physicians with an electro-encephalography license and data are a mean value of both analysis. Analysed were 40 minute EEG patterns, registered by 16 channels MedtronicDantec EEG PL-270 Video Option Aparat. RESULTS: Brain bioelectric activity was significantly more often immature and basic activity irregular in children with CSP than in the group without CSP. Asymmetry of frequency and amplitude and slow activity were also significantly more often observed in children with CSP. Abnormal graphoelements were also significantly more often disclosed in children with CSP. CONCLUSIONS: Visual analysis disclosed significant differences of EEG pattern in children with and without CSP. For identification of EEG from patient with CSP the quantitative method of analysis is necessary.

[Quantitative analysis of bioelectric activity of both brain hemispheres in children with a cavum of the septum pellucidum]. / Ilosciowa ocena czynnosci bioelektrycznej pólkul mózgowych u dzieci z torbiela przegrody przezroczystej.

BACKGROUND: Visual EEG analysis in children with a cavum of the septum pellucidum (CSP) disclosed asymmetry and immaturity in the majority of them. In this project authors try to determine significance of difference in quantification of bioelectric activity of both hemispheres in the brain of children with CSP and in control group. MATERIAL: 41 children with CSP and 32 without CSP were examined. Analyzed were 328 pairs of EEG (curves from left and right hemispheres) in children with CSP and additional 256 in the control group. 7 seconds fragments of EEG were analyzed, which were selected by two physicians with an electroencephalography license. METHODS: Mathematic and statistic evaluation of EEG pattern, with Fourier transform, was done. RESULTS: It is impossible to differentiate of EEG in children with and without CSP by partial (frequency, statistic) methods. Recursive-adaptative discrete Fourier transform with m measure is able to identify EEG pattern in child with CSP.