Outcome prediction of initial lamotrigine monotherapy in adult patients with newly diagnosed localization related epilepsies.

OBJECTIVE: To develop and test model to predict outcome of treatment with initial lamotrigine monotherapy in adult patients with newly diagnosed localization - related epilepsy, using data available at the time of diagnosis. METHODS: Prospective longitudinal study included consecutive series of adult patients with newly diagnosed localization - related epilepsy started of lamotrigine monotherapy. Logistic regression analysis using backward procedure was performed with treatment failure as the outcome variable. We evaluated both calibration and discrimination of the model. Internal validation of the model was performed with bootstrapping techniques. RESULTS: A total of 159 patients on lamotrigine monotherapy have been included in final analysis. Among them 78 (49.06%) patients had persistent seizures. Finally fitted multivariate model included: 1) age at therapy start, 2) presence of complex partial seizures, 3) aetiology of epilepsy and 4) interaction of age and epilepsy aetiology. Estimated odds ratio for seizure relapse in old patients with symptomatic epilepsy is lower than for the old patients with cryptogenic epilepsy, despite strong positive covariate effect of epilepsy aetiology. The model correctly classified 69.23% patients with seizure relapses and 81.48% of patients with seizure freedom, with estimated c - statistic of 0.80. Testing practical application we observed threefold increase or reduction of odds for the seizure relapse after model's positive or negative prediction respectively. CONCLUSION: Standard clinical data were modesty adequate to predict response to the initial trial of lamotrigine in adult patients with localization related epilepsy. Better markers of antiepileptic failure are required to guide optimal patient counselling and clinical decisions. Formal interaction analysis of variables improves outcome prediction and may be a key to correct interpretation of data.

Idiopathic intracranial hypertension from the perspective of headache center.

Idiopathic intracranial hypertension (IIH) is a pathological state defined as an increase of intracranial pressure in the absence of a causative pathological process. The aim of this study was to evaluate the clinical features of the patients with IIH diagnosed in our Headache Center according to the current knowledge of this disorder. In the retrospective and cross-sectional analysis of 3395 patients we present 12 newly diagnosed IIH patients, ten women and two men, aged from 19 to 51, with obtained values of cerebrospinal fluid pressure between 250 and 680 mm of water. The symptoms of IIH clinical presentation have been headache, reported by 92% of patients; papilledema, noted in 67%; and cranial nerve impairment (25%). The results obtained from presented patients confirmed the presence of headache features that are included in criteria for headache attributed with IIH in majority of them: progressive, daily, diffuse, non-pulsatile headache with aggravation by coughing or straining. Decrease of pain intensity after lumbar puncture was noted in all patients. We notice the relatively small proportion of patients with headache attributed to IIH among the patients treated in our Headache Center. The prevalence of IIH is not low and headache is the most frequent presenting symptom; therefore, we could only conclude that some chronic headache patients refractory for treatment are patients with IIH.

Artificial neural networks based early clinical prediction of mortality after spontaneous intracerebral hemorrhage.

Numerous outcome prediction models have been developed for mortality and functional outcome after spontaneous intracerebral haemorrhage (ICH). However, no outcome prediction model for ICH has considered the impact of care restriction. To develop and compare results of the artificial neural networks (ANN) and logistic regression (LR) models, based on initial clinical parameters, for prediction of mortality after spontaneous ICH. Analysis has been conducted on consecutive dataset of patients with spontaneous ICH, over 5-year period in tertiary care academic hospital. Patients older than 18 years were eligible for inclusion if they had been presented within 6 h from the start of symptoms and had evidence of spontaneous supratentorial ICH on initial brain computed tomography within 24 h. Initial clinical parameters have been used to develop LR and ANN prediction models for hospital mortality as outcome measure. Models have been accessed for discrimination and calibration abilities. We have analyzed 411 patients (199 males and 212 females) with spontaneous ICH, medically treated and not withdrawn from therapy, with average age of 67.35 years. From them, 256 (62.29%) patients died during hospital treatment and 155 (37.71%) patients survived. In the observed dataset, ANN model overall correctly classified outcome in 93.55% of patients, compared with 79.32% of correct classification for the LR model. Discrimination and calibration parameters indicate that both models show an adequate fit of expected and observed values, with superiority of ANN model. Our results favour the ANN model for prediction of mortality after spontaneous ICH. Further studies of the strengths and limitations of this method are needed with larger prospective samples.

[Syringomyelia in demyelinating disease of the central nervous system: report of two cases].

INTRODUCTION: Syringomyelia is a cavitary extension inside the spinal cord which can be either symptomatic or congenitally-idiopathic. Syringomyelia during the course of the disease in patients presenting with clinically definite multiple sclerosis was described earlier. Syringomyelia in patients presenting with a clinically isolated syndrome suggestive of multiple sclerosis is unusual. CASE OUTLINE: We present two patients presenting with demyelinating disease of the central nervous system with syringomyelia in the cervical and thoracic spinal cord. We did not find classical clinical signs of syringomyelia in our patients, but we disclosed syringomyelia incidentally during magnetic resonance exploration. Magnetic resonance exploration using the gadolinium contrast revealed the signs of active demyelinating lesions in the spinal cord in one patient but not in the other. CONCLUSION: Syringomyelia in demyelinating disease of the central nervous system opens the question whether it is a coincidental finding or a part of clinical features of the disease. Differentiation of the significance of syringomyelia finding in these patients plays a role in the choice of treatment concept in such patients.

[Epileptic seizure as the first sign of hypoparathyroidism].

BACKGROUND: Hypoparathyroidism refers to a group of disorders in which extracellular calcium levels cannot be maintained within the normal range due to relative or absolute deficiency of parathyroid hormone (PTH). The clinical features of hypoparathyroidism are consistent with hypocalcaemia and, predominantly, neuromuscular dysfunction. Although hypocalcaemia-induced seizures are well documented hypoparathyroidism-induced epilepsy is often misdiagnosed as idiopathic epilepsy. CASE REPORT: We reported a 57-year-old woman with new-onset seizure due to hypoparathyroidism. At first, diagnosis of epilepsy was established and the antiepileptic therapy was initiated with gradual increase of the dose. Computerized tomography scan of the head revealed bilateral basal ganglia and cerebellar calcification and many punctiform calcifications between cortical and subcortical parts. During hospitalization, laboratory tests showed hypocalcemia, hyperphosphatemia and low PTH level. Once the diagnosis of hypoparathyroidism was established, a proper treatment with calcium and vitamin D was started, and the patient was discharged from hospital with full seizure control. CONCLUSION: Standard evaluation of serum calcium levels in patients with new-onset epileptic seizures should be obligatory part of a diagnostic algoritam to avoid misdiagnosis of idiopathic epilepsy.

A case of complex arteriovenous malformation with skull destruction presented in sixth decade of life.

Intracranial AVMs are typically diagnosed before the patient has reached the age of 40 years, and a few cases have been reported of AVM with skull destruction. We described a rare case of a complex cerebral AVM with skull destruction, presented de novo in 52-year-old woman with epileptic seizures. Neuroimaging investigations revealed complex AVM in right hemisphere as well as extracranially, with signs of skull destructions, likely caused by significant involvement of feeders from external carotid artery. Neurosurgery treatment was not recommended due to morphological characteristics and drainage patterns of the AVM. EEG investigation showed discrete specific activity in correspondent area and pharmacology treatment for seizures was initiated. One year after the initial presentation patient had survived rebleeding episode witch left permanent neurology deficit. This patient considered as a rare case of complex AVM with skull destruction, presented de novo in sixth decade of life.

[Gender difference in hipolipemic and anti-inflammatory effects of statins in diabetics with coronary artery disease].

BACKGROUND/AIM: Statins produce hipolipemic and pleotropic effects on markers of inflammation with stabilization of atheromatous plaque. The aim of this paper was to examine gender difference in hipolipemic and antiinflammatory effects of statins in patients with diabetes mellitus (DM) type 2 with coronary artery disease (CAD). METHODS: Sixty dyslipidemic patients with DM type 2 were analyzed. Lifestyle modification and hipolipemic diet were applied in all patients divided into two groups: 30 patients with statins therapy (20 mg of simvastatin or equivalent dose of some other statins, during 3 months) and 30 patients without statins therapy. Estimation of obesity, quality of glicoregulation, and determination of inflammatory parameters: C-reactive protein (CRP), fibrinogen, total and differential leukocyte count, intracellular adhesive molecules (ICAM-1), vascular adhesive molecule-(VCAM-1) and lipid profile (total cholesterol--TC, LDL-C, HDL-C, triglicerides--TG) were done. RESULTS: Women with DM type 2 were more obese and had significant disturbances in lipid profiles, glicoregulation and inflammatory markers compared to men. Statins therapy significantly improved all lipid parameters and quality of glicoregulation in women, while there were only significant reduction of LDL-C and nonHDL-C in males. There were more significant reductions of inflammatory markers in women as compared to men with statins therapy. In the group without statins there was not such significant reduction. Concentration of ICAM-1 was the lowest in men on statins therapy, while there were no significant variability of VCAM-1 values between groups and genders. CONCLUSION: Women with DM type 2 and CAD have more prominent lipoprotein disorders and impaired glicoregulation with expression of enhanced proinflammatory state which could not be seen in men. Statins therapy exerts more favorable effects in women leading to stabilization of lipoprotein profiles, improvement of glicoregulation and reduction of inflammatory markers. More superior antiinflammatory effects of statins therapy in men were registered only in significant ICAM-1 reduction.

Epileptic seizures due to multiple cerebral cavernomatosis.

BACKGROUND: Cavernous angiomas are angiographically occult vascular malformations that are present in 0.4-0.9% of people, and represent around 5% of all cerebrovascular malformations. They can be single or multiple, and sporadic or familial. The presence of multiple lesions is more frequent in familial cavernomatosis. Ten to 30% are associated with familial clustering. CASE REPORT: We presented the case of a 43-year-old man, admitted to the Emergency Department due to unprovoked seizure during the wide awake and everyday activities. Neurological examination was with no focal signs. A 32-channel standard digital EEG was without any significant changes of normal baseline activity. After sleep deprivation EEG showed multifocal, bilateral and asymmetric polyspikes and sharpwaves activity. Hyperventilation induced generalized epileptiform discharges. MRI scan demonstrated multiple small cavernous angiomas. Neuropsychological testing demonstrated a delayed memory impairment. Neurosurgery treatment was not recommended, and the therapy with valproate 1 250 mg/day had an excellent efficacy with no singnificant adverse effects. CONCLUSION: This patient considered as a rare case with multiple cavernomatosis highlights the importance of neuroradiological examination in adult patients with the first epileptic seizure but with no focal neurological signs.

[Cessation of epileptic seizures series using peroral valproate in an adult patient with partial epilepsy].

INTRODUCTION: Golden rule for the initiation of antiepileptic therapy in the majority of epileptic syndromes is "start low and go slow", a principle after the second unprovoked seizure. There are certain clinical situations however when fast titration of antiepileptic medication is needed. CASE REPORT: We present a case of the 48-year-old man referred for further management of uncontrolled partial seizures. At the age of 37 years, he had subarachnoid haemorrhage, due to aneurysm rupture of the left internal carotid artery, with consecutive vasospasm and right haemiparesis. Since that time he had received phenobarbital 100 mg nocte. On examination he had a right sided upper motor neuron weakness affecting the arm more than the leg, and mild dysarthria, EEG investigation showed frequent transitory spikewaves discharges above the left hemisphere with the fast contralateral propagation with generalised discharges and CT showed old infarction in distribution of left medial cerebral artery. Valproate therapy was initiated with the retard form in the loading dose of 2000 mg. Seizures stopped in 7th hours after the treatment initiation. Laboratory parameters (liver function tests, blood count, level of antiepileptic drugs) were monitored every day. No further seizures were recorded. The patient was discharged from the hospital after 15 days in excellent condition. CONCLUSION: In selected clinical conditions it is possible to apply the protocol for valproate loading and switch-off from the previous antiepileptic drugs to valproate monotherapy. Adverse effects are rare and mild but potentially serious, and close monitoring of clinical and laboratory parameters is necessary. Hence, a rapid switch to valproate monotherapy can be done safely only in an inpatient setting.

Peripheral nerve conduction study in workers exposed to a mixture of organic solvents in paint and lacquer industry.

AIM: To compare levels of combined exposure to white spirit, toluene, butyl acetate, ethyl acetate, and xylene in the manufacturing of paint, cartridge, drying, and top-coat sections of paint and lacquer industry, and peripheral nerve conduction parameters in the exposed workers. METHODS: The exposed group comprised 120 workers while the control group included 110 workers who had never been exposed to the above listed organic solvents. Nerve conduction studies of the radial and tibial anterior nerve were performed in both groups. RESULTS: Motor and sensitive conduction velocity, as well as terminal latency of the radial and tibial anterior nerve showed significant changes in exposed workers in comparison to those of the control group (p<0.001). These parameters were significantly changed in workers with long length exposure to the toxic agents. In early stages of exposure, neural conduction parameters of the radial nerve were the most sensitive parameters in detecting subclinical peripheral nerve changes (p<0.001). There was significant correlation between the nerve conduction changes and urinary levels of hippuric and methyl-hippuric acids (p<0.01). CONCLUSION: The results of the study suggest neurotoxic effects of the mixture of white spirit, toluene, butyl acetate, ethyl acetate, and xylene detected in paint and lacquer industry. Standard measurement of the urinary levels of hippuric and methyl-hippuric acids could be a useful indicator of need for nerve conduction studies and the subclinical peripheral neuropathy screening in exposed workers.