Comparison of anticonvulsant effects of valproic acid entrapped in positively and negatively charged liposomes in amygdaloid-kindled rats

Intraperitoneal injection of free valproic acid (VPA) suppressed amygdaloid-kindled seizure 1 h after injection in rats, but had no effect at 24 h. VPA entrapped in positively charged liposomes showed a prolonged anticonvulsant effect lasting for 2 days, while the effect evaluated at 1 h was not different from that with free VPA. VPA entrapped in negatively charged liposomes exerted a significantly stronger effect at 1 h than did free VPA, while it had no significant effect at 24 h. These results suggest that surface charges on liposomes play an important role in modifying the anticonvulsant effect of VPA.     

Seizures with Onset in the Sensorimotor Face Area: Clinical Patterns and Results of Surgical Treatment in 20 Patients

Summary: It is not generally appreciated that intractable seizures involving the face area are amenable to surgical treatment. Twenty patients with onset of sensorimotor seizures in the face area of the pre- and postcentral gyri have been studied and surgically treated since 1948. Seizures started in the face, tongue, or throat, followed by diverse patterns depending on spread of seizure activity. Two patients had epilepsia partialis continua; 6 had either tonic or atonic drop attacks. All patients had pre- and postcentral face area resections, 12 in the dominant hemisphere. In addition, 3 had more extensive postcentral removal, 7 had temporal lobe, and 4 had small separate or contiguous frontal or parietal resection. Because the seizures were not sufficiently reduced by the first operation, 6 required reoperation; 4 of these patients had residual epileptiform activity on electrocorticogram (ECoG) after the first resection. Three patients had new neurologic signs that did not return to the preoperative level, but in 2 of them the deficit related mainly to higher resection in the central area. All but 2 of these 20 patients had at least moderate seizure reduction. Corticectomy can be performed for treatment of seizures arising in the lower central area and usually does not lead to significant permanent neurologic deficit.     

Stress during gestation alters postpartum maternal care and the development of the offspring in a rodent model.

BACKGROUND: Epidemiological studies suggest that environmental adversity can alter parental care and thus influence child development. We addressed the question of whether stressors can directly affect parental behavior using a rodent model of stable, individual differences in maternal behavior. METHODS: Lactating rat mothers were characterized as high or low in pup-directed licking/grooming (LG) behavior, rebred, and subjected to 7 days of intermittent stress or control conditions during gestation. Female rats were mated a third time without any subsequent intervention. Maternal behavior, oxytocin receptor (OTR) binding, and offspring behavior were examined. RESULTS: Stress reduced OTR levels and pup LG of high LG mothers to levels comparable with those of low LG mothers. The adult offspring of the gestational stress/high LG mothers resembled those of low LG mothers on behavioral measures of anxiety and maternal behavior, as well as OTR levels. The results of the third mating revealed an enduring effect of gestational stress on both mother and offspring maternal LG. CONCLUSIONS: These findings suggest that stress can directly alter maternal care through the neuroendocrine systems that normally regulate this behavior. Thus, the effects of environmental adversity can be transmitted across generations through a nongenomic mechanism involving maternal care.     

In vivo mapping of drug-induced seizures with voltage-sensitive dye

The voltage-sensitive dye diO-C2-5 was used to produce an in vivo map of the membrane potential in two types of seizures. Mild limbic seizures were induced in rats with kainic acid; clonic convulsive seizures were induced with bicuculline. Kainic acid animals showed various levels of neural depolarization during their seizures in limbic, thalamic, cortical, and brainstem sites. The bicuculline animals showed uniformly greater levels of neural depolarization during their seizures. The magnitude of these changes relative to controls varied across seizure models and reflected the different underlying neural mechanisms for each model. The ability of the technique to capture local electrical events provides a new tool in which to explore brain activity.     

Serotonin reduction in the mouse neostriatum during hyperthermia-induced convulsions studied by immunohistochemistry

Summary Changes occurring in serotonin neurons during hyperthermia-induced convulsions were examined by means of a modified immunohistochemical method. All mice (8–12 weeks of age) exposed to the temperature of 50°C had convulsions, showing a generalized tonic and/or clonic pattern. Immediately after the convulsions, the animals were perfused transcardially with a fixative. A significant reduction in serotonin immunoreactivity was observed in the neostratum (caudate-putamen complex) of the mice which had hyperthermia-induced seizures, while the serotonin immunoreactivity remained unchanged in the neocortex and paleostriatum. These results suggest that serotonin may be an important mediator in the mechanism of hyperthermia-induced convulsions or that the susceptibility of serotonin neurons to a convulsive state is greatest in the neostriatum.Supported in part by Grant No. 86-05 from the National Center for Nervous, Mental and Muscular Disorders (NCNMMD) of the Ministry of Health and Welfare and Grant No. 62770677 from the Ministry of Education, Science and Culture, Japan     

Frontal lobe epilepsy presented as ictal aggression

Abstract Aggressive behaviour is rarely observed as an ictal semiology. Ictal aggression can occur in lesions of frontal and limbic structures. In limbic structure lesions, the main mechanism of aggressive behaviour is hyperactivity; whereas frontal lesions may cause aggressive behaviour with an indirect mechanism in which the suppression on limbic system is lost. Here we present a patient with ictal aggression. In this case a right frontoparietal epileptiform focus was detected during the postictal period. Magnetic resonance imaging showed cortical dysplasia on the right inferior frontal gyrus. The seizures disappeared completely after pharmacological treatment.     

Predictors of punding in Parkinson's disease: results from a questionnaire survey.

Dopamine replacement therapy (DRT) for Parkinson's disease (PD) has recently been linked to the development of a number of nonmotor behavioral control problems. Punding, one of these nonmotor problems, is a term used to describe complex, purposeless stereotyped behaviors such as the repetitive handling or sorting of objects. A self-report questionnaire was adapted to assess punding in the context of dysfunctional hobby-related activities. We report the results of a survey of PD outpatients from a PD research clinic (n = 141) and non-PD controls (n = 103); conducted to identify clinical and psychological factors predictive of punding behaviors. The PD group reported hobbies and activities, which scored significantly higher on the Punding Scale than controls. Higher impulsivity, poorer disease-related quality of life, younger age of disease onset, and concomitant daily medication dosage from dopamine receptor agonists were independently predictive of higher Punding Scale scores in the PD group. These findings are similar to those seen in dopamine dysregulation syndrome, and provide further evidence for the role of impulsivity and age at disease onset in DRT-related nonmotor behavioral problems in PD.     

Functional MRI Studies of Animal Models in Epilepsy

Summary:  Functional magnetic resonance imaging (fMRI) has become a widely used imaging modality in the past decade in both human studies and animal models. Epilepsy presents unique challenges for neuroimaging due to subject movement during seizures, and the need to correlate the timing of often unpredictable seizure events with fMRI data acquisition. These challenges can readily be overcome in animal models of epilepsy. Animal models also provide an opportunity to investigate the fundamental relationships between fMRI signals and brain electrical activity through invasive studies not possible in humans. fMRI studies in animal models of epilepsy can enable us to correctly interpret fMRI signal increases and decreases in human studies, ultimately elucidating specific networks that will be targeted for improved treatment of epilepsy.     

Thrombophilic risk factors and unusual clinical features in three Italian CADASIL patients

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically transmitted cerebrovascular disease. Typically, the first clinical manifestation is migraine and the full clinical spectrum of the disease with recurrent strokes of the subcortical type, cognitive, and mood disorders is seen during the fourth and fifth decades of life. Vascular risk factors are usually absent in CADASIL patients and the diagnosis of the disease is particularly suspected in young adults with cerebrovascular events of unknown cause, diffuse leukoencephalopathy on computed tomography or magnetic resonance imaging, and a history of cerebrovascular diseases or dementia in many family members. We describe three Italian CADASIL patients who presented to medical attention for cerebrovascular events occurred after the age of 55 and had, in addition to hypertension and hyperlipidemia, thrombophilic risk factors such as hyperhomocysteinemia, elevated levels of lipoprotein(a), and antiphospholipid antibodies. Symptoms possibly related to cortical involvement, such as dysphasia and visual field deficits, were reported by two of these patients. We conclude that a diagnosis of CADASIL should not be disregarded in patients with vascular risk factors and presenting with symptoms not immediately referable to subcortical damage at ages more advanced than commonly reported.     

Digital computer analysis of dermatoscopical images of 260 melanocytic skin lesions; perimeter/area ratio for the differentiation between malignant melanomas and melanocytic nevi

BACKGROUND: Digital computer analysis of dermatoscopical images has been reported to facilitate the differential diagnosis of pigmented skin lesions in recent years. OBJECTIVE: The aim of our study was to perform digital computer analysis of a set of different melanocytic lesions and compare the objective results. METHODS: The set of 260 melanocytic lesions (150 excised difficult cases (46 melanomas, 47 atypical nevi, 57 common nevi and 110 unexcised common nevi) was automatically analysed by the digital dermatoscopical system microDERM. We searched for differences in asymmetry, size, compactness and colour distribution. Perimeter/area ratio was calculated. RESULTS: The perimeter/area ratio was detected as the most important criterion for differentiation between malignant and benign melanocytic lesions (sensitivity 91.3% and specificity 90.7% for malignant melanomas vs. all benign nevi; sensitivity 91.3% and specificity 80.8% for melanomas vs. clinically atypical nevi). Differences in size of the lesion, shape and asymmetry of colour were found and statistically verified. Using step-wise logistic regression the formula for calculation of probability of malignant nature of every analysed lesion was constructed. CONCLUSION: The perimeter/area ratio is a simple parameter for the differential diagnosis of melanocytic skin lesions.