Ewa Nagańska

Risk factors for depression in patients with epilepsy.

PURPOSE Symptoms of depression are present in 40 to 60 percent of patients with epilepsy. Prior research indicated significant correlation between the incidence and frequency of focal seizures and clinical depression, especially in patients with temporal lobe epilepsy. Anticonvulsive drugs and psychosocial factors contribute to the occurrence of depression as well. The aim of the study was to determine the major depression risk factors in patients with epilepsy. METHODS The research was conducted on 203 patients with epilepsy (117 females and 86 males), aged 18 to 50 years, with total time of illness ranging from 60 to 580 months. All subjects underwent the same research protocol, which was applied interictally. Interictal depression was diagnosed according to ICD-10 diagnostic criteria for affective and delusional disorders. The diagnosis was supported by Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAM-D) and Montgomery-Asberg Depression Rating Scale (MADRS). Statistical analysis included chi2 test, Fishers exact test and stepwise logical regression model analysis. RESULTS In our study 100 patients with epilepsy out of 203 suffered from concurrent depression (49.2%); 76 of them had severe depression (37.4%) and 24 patients had mild depression (11.8%). Complex partial seizures and absence of secondary generalized tonic-clonic seizures were found to be the risk factors for depression. Treatment with clonazepam, frequent hospitalizations (drug-resistancy) and lack of occupational activity were revealed to be additional significant contributing factors. CONCLUSIONS Depression in patients with epilepsy is a serious medical and social problem since it afflicts almost one half of all patients treated in epilepsy referral centers. It seems to be correlated with certain types of epileptic seizures, with high frequency of seizures, sub-optimal pharmacologic treatment and lack of occupational and social activity.

Hypersexuality in two patients with epilepsy treated with lamotrigine

PURPOSE Lamotrigine (LTG) is a novel anticonvulsant drug that exerts an antiepileptic effect by decreasing glutamate release through inhibition of voltage-sensitive sodium channels. LTG has no effect on serum levels of most female reproductive hormones, but its effect on male reproductive hormones still remains unclear. Improvement in sexual function after LTG treatment has been reported, and could have been caused by reduction of seizures, inhibition of focal discharges, or an unknown effect of LTG on reproductive hormones and protein levels. CASES Two male patients exhibited acute hypersexuality while taking lamotrigine as add-on therapy: one patient on carbamazepine and one on oxcarbazepine. Neither prior history of psychiatric illness nor brain damage predisposed them to such a response to treatment, and in both patients, the hypersexuality was not a part of hypomania or a more diffuse psychiatric disturbance. In the first case, sexual hyperactivity resolved after discontinuation of LTG therapy without any concomitant treatment. In the second case, a reduction in the dose of LTG decreased the intensity of the hypersexuality and contributed to the patients increased satisfaction with his sex life. CONCLUSIONS Lamotrigine may cause drug-related hypersexuality by an unclear underlying mechanism.

Autophagic Degeneration of Motor Neurons in a Model of Slow Glutamate Excitotoxicity in Vitro

There is increasing evidence that so-called “autophagic cell death” participates in cell degeneration in certain pathological conditions. Autophagy might be involved in some neurodegenerative processes, including lateral amyotrophic sclerosis (SLA). The exact mechanism leading to progressive motor neuron (MN) loss remains unclear, but glutamate-mediated mechanism is thought to be responsible. Previous ultrastructural studies by the authors performed on a model of SLA in vitro, based on chronic glutamate excitotoxicity, revealed a subset of morphological features characteristic to different modes of neuronal death, including autophagic degeneration. The contribution of this pathway of MNs death is evaluated in organotypic cultures of rat lumbar spinal cord chronically exposed to specific glutamate uptake blockers: DL-threo-β-hydroxyaspartate (THA) and L-transpyrrolidine-2,4-dicarboxylate (PDC). The study documents the various steps of authophagy in slowly evolving process of MN neurodegeneration. The cells undergoing autophagy usually exhibited sequestration of some parts of cytoplasm with normal and/or degenerated organelles, whereas other parts of cytoplasm as well as neuronal nucleus remained unchanged. The advanced autophagic changes were often associated with other modes of MN death, especially with apoptosis. Numerous MNs revealed apoptotic nuclear features with typical peripheral margination of nuclear chromatin, accompanied by severe autophagic or autophagic-necrotic degeneration of the cytoplasm. These results support the opinion of unclear distinction between different modes of cell death and indicate the involvement of autophagey in MNs neurodegeneration in vitro.

The protective effect of ZnCl2 pretreatment on the development of postanoxic neuronal damage in organotypic rat hippocampal cultures.

Zinc is one of the trace elements playing an important role in many fundamental biological processes. However, it is also one of the possible etiological agents involved in nerve cell damage in certain human neurodegenerative disorders. The precise mechanism of neuroprotective ability of Zn against neurotoxicity evidenced in various pathological conditions remains unclear, especially concerning the intrinsic potential toxicity of this metal. This ultrastructural study was undertaken to determine the effect of zinc on the evolution of anoxia-induced neuronal injury in the organotypic cultures of rat hippocampus. The in vitro model of oxygen deprivation was produced by maintaining the cultures in a pure nitrogen atmosphere in flask adapted for permanent gas flow for 20 min. The selected cultures were pretreated with micromolar concentration of ZnCl 2 (25-500 µM) at 30 min prior anoxia. The ultrastructural findings documented that Zn exhibited dose-dependent ability to reduce anoxia-induced neuronal changes in hippocampal neurons in vitro. Zn at a concentration of 100 µM was able to significantly protect the hippocampal formation against the development of late apoptotic changes, whereas the early necrotic anoxia-induced neuronal injury was not so efficiently reduced.

Ganglion cell tumours in the sella turcica in close morphological connection with pituitary adenomas.

Ganglion cell tumours in the sellar region are uncommon. They are usually associated with pituitary adenomas, while isolated ganglion cell neoplasms are extremely rare. We report the clinicopathological studies of five cases diagnosed as ganglion cell tumours located in the intrasellar region: four mixed/collision tumours composed of gangliocytoma and pituitary adenoma, and one isolated ganglioglioma unrelated to adenoma. Clinically, two patients presented with acromegaly, while three others were initially diagnosed as non-functioning adenomas. In four cases, the histopathological examination of surgical specimens revealed intermixed lesions composed of pituitary adenoma and ganglion cell elements. The adenomas appeared to secrete growth hormone. Electron microscopy enabled identification of the sparsely granulated somatotroph cells. Neoplastic neuronal lesions were composed of mature ganglion cells, including binucleate or multinucleate cells. In all cases, boundaries between adenomatous and gangliocytic components were not clearly demarcated, and numerous gangliocytic cells were closely intermingled with adenomatous tissue. One case lacked endocrine symptoms, and no pituitary adenoma was identified in the surgically excised material; it was finally diagnosed as low-grade ganglioglioma. The etiopathogenesis of ganglion cell neoplasms in the sellar region is not clearly defined. Our study revealed that if ganglion cell neoplasms were combined with adenoma, both neoplastic components were closely related to each other, and numerous neuronal elements were strictly intermingled with adenoma cells. Such a tissue pattern indicates that these neoplastic changes, including their common respective etiopathogeneses, are closely related. The identification of both components in sellar regions may have some nosological implications.

Differentiating Stroke and Seizure in Acute Setting-Perfusion Computed Tomography?

BACKGROUND Perfusion computed tomography (PCT) is part of acute stroke protocol in many hospitals; however, its clinical utility is still being disputed. Beyond its use in core and penumbra estimation, there is also a question about PCT role in stroke mimics diagnosis. Case series or small, retrospective studies showed equivocal results. This is the first published prospective, comparative study on PCT in differentiating stroke and seizure in acute setting. METHODS Patients with acute focal neurologic deficits and without acute ischemic lesions on routine CT underwent PCT and electroencephalography (EEG) within 12 hours after symptom onset. Perfusion parameters were set up as asymmetry indices for corresponding regions of brain hemispheres. EEG findings were assigned to 1 of 5 classes. Neurologic examination was performed using the National Institutes of Health Stroke Scale (NIHSS). Follow-up noncontrast computed tomography was performed on the third day after symptom onset. If no CT changes appeared, magnetic resonance diffusion-weighted imaging was conducted. RESULTS Final diagnosis was hemispheric ischemic stroke in 17 patients and focal neurologic deficits in the course of seizures (post- and intraictally) in 12 patients. Those groups were significantly different only in one single PCT parameter-time to peak (TTP)-in the lateral part of the middle cerebral artery territory. Analyzed groups were not significantly different in the NIHSS scores and the EEG evaluation. CONCLUSIONS TTP may stay relatively when seizure is a cause of focal neurologic deficits, but not stroke. Further, large, prospective studies are necessary to verify the results.