A comparison of monotherapy with lamotrigine or carbamazepine in patients with newly diagnosed partial epilepsy.

Monotherapy with lamotrigine or carbamazepine was evaluated in a multicentre open trial of patients aged 2 years and above with newly diagnosed partial epilepsy. A total of 417 patients were randomised to treatment with lamotrigine, while 201 patients received carbamazepine. Following a dose escalation period of 6 weeks, maintenance therapy (Weeks 7-24) was adjusted according to response. Efficacy was similar with both treatments (65% with lamotrigine, 73% with carbamazepine, P=0.085). Efficacy was assessed by the proportion of patients seizure free during the last 16 weeks of treatment; all subjects who remained in the study for at least 18 weeks after the week 4 visit were included in the analysis. More patients receiving lamotrigine completed the study (81%), compared with those receiving carbamazepine (77%). This difference was primarily due to discontinuation as a result of adverse events, reported by 34 (8%) of those treated with lamotrigine but 26 (13%) of those treated with carbamazepine. The proportion of patients who experienced adverse events in the lamotrigine group was lower (218 patients, 52%) compared with the carbamazepine group (120 patients, 60%). The proportion of patients with adverse events considered to be drug related was lower in the lamotrigine group (132 patients, 32%) compared with the carbamazepine group (83 patients, 41%). Somnolence was the only adverse event reported at an incidence of greater than 5% and where there was a difference of 5% or more between treatment groups (4% lamotrigine, 11% carbamazepine patients). The small subsets of elderly patients (aged 65 years or over) and paediatric patients (aged 2-12 years) also showed better tolerability to lamotrigine than to carbamazepine. In conclusion, monotherapy with lamotrigine is as effective as carbamazepine in patients with newly diagnosed partial epilepsy. Patients were able to tolerate lamotrigine better than carbamazepine, so more patients receiving lamotrigine were able to remain on therapy.

A double-blind controlled clinical trial: oxcarbazepine versus sodium valproate in adults with newly diagnosed epilepsy.

Oxcarbazepine (OXC) has been licensed as monotherapy and add-on treatment in epilepsy patients with partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS). Its use as monotherapy in adults with newly diagnosed epilepsy was investigated in a double-blind, randomized, parallel-group comparison with sodium valproate (VPA). Two-hundred and forty-nine patients with either PS or generalized seizures aged 15-65 years were randomized. After a retrospective baseline, patients were randomized to VPA or OXC in a 1:1 ratio. The double-blind treatment phase was divided into two periods, flexible titration and maintenance. The titration period was 8 weeks followed by 48 weeks of individualized, maintenance treatment given three times a day. Three primary analyses were used to assess efficacy, tolerability, and the association between the two. In the efficacy analyses comprising 212 patients who had at least one seizure assessment during the maintenance period, no statistically significant difference at the 5% level was found between the treatment groups. Sixty patients (56.6%) in the OXC group and 57 patients (53.8%) in the VPA group were seizure free during maintenance treatment. Fifty-two patients in the OXC group discontinued treatment prematurely (15 because of tolerability reasons) compared to 41 patients in the VPA group (ten due to tolerability reasons). There was no statistically significant difference between the treatment groups with respect to the total number of premature discontinuations or those due to adverse experiences. This trial provides support for the efficacy and safety of OXC as first-line treatment in adults with PS and GTCS.

Liver failure in erythropoietic protoporphyria associated with choledocholithiasis and severe post-transplantation polyneuropathy.

In a 58-year-old woman with erythropoietic protoporphyria, asymptomatic liver involvement had been diagnosed 12 years earlier. For more than 20 years the patient had been known to have symptomatic gallstones. A mild polyneuropathy of the lower limbs had been diagnosed several years ago. In December 1992, she presented with colicky upper abdominal pain, dyspepsia and mild jaundice. Diagnosis of beginning cholestasis in erythrohepatic protoporphyria and coincidental choledocholithiasis was made. A causal relation between choledocholithiasis and deterioration of liver function was assumed. Endoscopic extraction of the bile duct stones, however, could not prevent the development of terminal hepatic failure. Biochemically, an excessive protoporphyrinemia and coproporphyrinuria were found. Five weeks after presentation, the patient underwent orthotopic liver transplantation. Immediately after the operation she developed a severe axonal neuropathy with cranial nerve involvement. One year after transplantation, her general condition has markedly improved, but there is still a disabling polyneuropathy. Recently, there were single reports on patients with very similar neurological symptoms following liver transplantation in erythropoietic protoporphyria. This case supports the assumption of a distinct protoporphyrin-induced neural damage in severe hepatic failure.

The optimal immunosuppressant after liver transplantation according to diagnosis: cyclosporine A or FK506?

Since we may soon be able to choose between primarily CsA- or FK506-based immunosuppression, it is important to establish the superior immunosuppressive agent for the individual patient. In the present study, 121 patients, 61 randomly assigned to FK506- and 60 assigned to CsA-based immunosuppression, were analyzed according to the primary diagnosis for liver transplantation. One-year patient survival was similar in all groups. However, the incidence and severity of acute rejection within the 1st year after transplantation was significantly higher in patients transplanted due to HCV disease who were receiving FK506 (58.8%) compared with those patients receiving CsA (27.8%; p < or = 0.05). Furthermore, the incidence of moderate and severe neurotoxicity was significantly higher during the 1st month after LTX in patients transplanted owing to HCV disease treated with FK506 (35.3%) compared with those patients receiving CsA (16.7%; p < or = 0.05). Irrespective of the immunosuppressive regimen, the incidence of early postoperative neurotoxicity was significantly lower in patients transplanted owing to HBV disease, alcoholic cirrhosis and various other liver diseases summarized than in patients transplanted due to HCV disease receiving FK506 therapy. During the 1st year, the incidence and severity of rejection in patients transplanted due to alcoholic cirrhosis and PBC was significantly lower in patients treated with FK506 (11.1% for both groups) compared with those patients receiving CsA (54.5% and 60.0%, respectively; p < or = 0.05. Furthermore, this was accompanied by a lower incidence of toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurotoxicity after orthotopic liver transplantation. A comparison between cyclosporine and FK506.

Neurotoxicity represents a serious complication following orthotopic liver transplantation. Neurotoxicity may be evoked by various perioperative factors or develop due to drug-specific toxicity of immunosuppression. We evaluated the incidence of neurotoxicity in 121 patients, 61 randomly assigned to FK506 and 60 to CsA-based immunosuppression. The incidence of moderate or severe neurotoxicity was markedly higher in patients treated with FK506 in the early postoperative period (21.3% vs. 11.7% in patients receiving CsA), after retransplantation (100% vs. 0% in patients receiving CsA), and late (8 of 10 patients; P < or = 0.05 vs. CsA). Furthermore late neurotoxicity was highly associated with severe infections and MOFS, which had a lethal outcome in more than 50% of the patients. Patients who subsequently died developed neurologic symptoms in 67% of the cases. These patients also experienced moderate or severe neurotoxicity significantly more often in the early postoperative period compared with patients with a successful outcome (50% vs. 17.3%; P < or = 0.01). However, various blood and serum parameters, including ALT, bilirubin, urea, creatinine and glucose, when analyzed alone or in multivariate fashion, also correlated significantly with the incidence and severity of early postoperative neurotoxicity, indicating that neurotoxicity following LTX may be caused by various factors and is not exclusively a drug-specific side effect of immunosuppression.

Neurotoxicity after orthotopic liver transplantation in cyclosporin A- and FK 506-treated patients.

Neurotoxicity is a serious complication following orthotopic liver transplantation leading to increased morbidity and mortality. Neurotoxicity may be evoked by various perioperative factors, or may be due to drug-specific toxicity of immunosuppression. In the present study we evaluated the incidence of central nervous system (CNS) toxicity occurring within the early postoperative period of 121 patients, 61 randomly assigned to FK 506- and 60 to CsA-based immunosuppression as part of a multicentre study. The incidence of moderate or severe CNS toxicity was higher in patients treated with FK 506 (21.3%) than in patients receiving CsA (11.7%). The duration of symptoms was also greater in patients treated with FK 506 than in patients receiving CsA. The incidence of moderate or severe neurotoxicity after retransplantation was markedly greater in patients treated with FK 506 (100% of the patients).

[Border-area cerebral ischemia--3D-SPECT for the imaging of the regional cerebral blood flow]. / Zerebrale Grenzzonenischämie--3D-SPECT zur Darstellung des regionalen zerebralen Blutflusses.

15 patients with suspected cerebral ischaemia were examined using 99mTc-HM-PAO-SPECT to assess cerebral blood flow. Results obtained from SPECT were correlated with CT and Doppler ultrasound findings. A 3D-display algorithm is proposed to enhance the lesion to non-lesion contrast compared to the standard 2D-image interpretation. In all cases contrast was superior on 3D-display to 2D-display (-0.38 versus -0.09). 3D-display of SPECT-data enhances lesion contrast due to postreconstructive data processing and may improve exact interpretation of cerebral blood flow studies.

Focal epilepsies: HM-PAO SPECT compared with CT, MR, and EEG.

Regional cerebral blood flow (rCBF) was evaluated quantitatively by 99mTc hexamethyl propyleneamine oxime and single photon emission CT (SPECT) during the interictal phase in 52 patients with focal epilepsy. The results were compared with those obtained by electroencephalography (EEG), CT, and magnetic resonance (MR) imaging. Twenty-four of the 52 patients had one area of local hypoperfusion whereas 7 patients showed an area of local hyperperfusion. In 20 of the 52 patients, both reduced and elevated rCBF values were found. One patient had a normal perfusion pattern. The SPECT findings correlated well with the foci shown by EEG, both with regard to the sides affected and the locations of the regions of altered perfusion. The MR images showed focal lesions in only approximately one-half of the patients examined, and CT in even fewer.

Epidemiologic survey of epilepsy among Army draftees in Lombardy, Italy.

We conducted an epidemiological survey of epilepsy among males born in 1967 who were called for selection for military service from the Lombardy region in northern Italy. Of 54,520 subjects, 258 had active epilepsy (prevalence, 0.47%). Idiopathic partial epilepsy was most common (29.1%), and generalized idiopathic and/or symptomatic epilepsy was least common (3.8%). In the year preceding the interview, 66.9% of the subjects had been free of generalized tonic-clonic seizures, 57.6% had been free of minor seizures, and 36.9% were seizure-free. Case histories revealed a background of febrile convulsions in 18.9% of subjects, status epilepticus in 11.3%, and a family history of epilepsy in 18.9%. Physical and mental development was normal in 75.5% of the subjects. Education level of subjects was lower than a control group, and the unemployment rate was the same as the local rate.

Subacute and chronic cerebral infarctions: SPECT and gadolinium-DTPA enhanced MR imaging.

Single photon emission computed tomography (SPECT) examinations of regional cerebral blood flow (rCBF) and regional cerebral blood volume (rCBV) were carried out in 23 patients with 19 subacute and 7 chronic cerebral infarctions. Corresponding magnetic resonance (MR) examinations (unenhanced and contrast enhanced scans) were done within a time interval of 2 days. Although all subacute lesions showed an increased rCBV, the rCBF could be either increased or decreased. Contrast enhancement in MR was associated with increased rCBV but not with increased rCBF. In all chronic lesions rCBV and rCBF were decreased and there was no contrast enhancement detectable in MR. The application of Gd-diethylenetriamine pentaacetic acid as contrast agent in MR demonstrates blood-brain barrier disruption as focal or gyral contrast enhancement in cerebral infarction. The SPECT examinations revealed an increased rCBV indicating a vasodilation or vasoparalysis. The rCBF was either increased or decreased depending on the collateral formation or recanalization of occluded vessels.

[Aciclovir against Herpes simplex encephalitis]. / Aciclovir gegen Herpes-simplex-Enzephalitis.

Four patients with typical manifestations of herpes simplex encephalitis were treated with Aciclovir. Infection with herpes simplex virus was confirmed in three of the four cases. Complete cure was achieved in each of the patients despite severe initial disease patterns. In view of these results in the treatment of a disease that had so far been partly lethal or produced severely defective states, the specific use of Aciclovir is emphasised.

[Comparison of 133xenon and 123I-isopropylamphetamine for measuring regional cerebral circulation]. / Vergleich von 133Xenon und 123J-Isopropyl-Amphetamin zur Messung der regionalen Hirndurchblutung.

In 26 patients the regional cerebral blood flow was measured using 123I-isopropyl-amphetamine. The measurement was performed with a dynamic single photon emission tomograph. In 16 patients we compared the findings with the results of the tomographic 133Xe-Clearance. Both methods seem to be suitable for the measurement of the effective perfusion and gave similar results. In the case of the tomographic 133Xe-clearance we need a more specialized technical equipment whereas the permanent costs are lower and the performance less complicated. Besides the applicability of this method is more universal. On the contrary the use of 123I-isopropyl-amphetamine makes a higher resolution possible depending on the available equipment and does not need an ability to cooperation of the patient. With the presently disposable radionuclides the hope was not yet adequately accomplished, to get a tomographic in-vivo-information of cerebral metabolic and receptor-functions by means of SPECT.

An attempt to quantitate the contribution of antidiuretic hormone to the diuresis of left atrial distension in conscious dogs.

In order to quantitate the contribution of the antidiuretic hormone (ADH) to the diuresis of left atrial distension 52 experiments have been performed in 12 conscious, chronically instrumented beagle dogs. Left atrial pressure was increased by a reversible mitral stenosis by about 10 cm H2O (1.0 kPa) for 60 min. Plasma ADH concentration (range between 1.3 and 6.0 pg . ml-1) (radioimmunoassay) decreased in every experiment, the average decrease being about 50%. An i.v. infusion of vasopressin (0.05 mU . min-1 . kg-1) abolished the diuretic effect of left atrial distension or decreased the urine volume below control values; natriuresis was not affected. The magnitude of the vasopressin effect was dependent on the concurrent sodium excretion: when sodium excretion was low during left atrial distension, vasopressin was more effective in reducing the urine volume than when sodium excretion was high. It is concluded that the diuresis of left atrial distension is mediated (a) by a suppression of ADH and (b) by factors controlling sodium excretion, the contribution of these two mechanisms being dependent on the concurrent sodium excretion.