Postictal psychosis in temporal lobe epilepsy: a case-control study.

BACKGROUND AND PURPOSE: To investigate the prevalence of postictal psychosis (PP) in patients with temporal lobe epilepsy (TLE) and to estimate the predictive value of various variables for the development of PP. METHODS: By retrospectively reviewing the charts of all patients evaluated with video-electroencephalogram (EEG)-monitoring at our unit between January 1995 and February 2012, we identified 684 patients with TLE, of which 48 patients had a history of PP. Patients with TLE and PP were compared with 200 controls (patients with TLE without a psychotic history) on demographic, clinical, EEG and magnetic resonance imaging (MRI) variables. RESULTS: The prevalence of PP in our TLE sample was 7.0%. Aggressive behaviour during PP was present in 22.9% of the sample. Univariate analysis revealed that PP was significantly associated with early age at epilepsy onset (P = 0.007), longer duration of epilepsy (P = 0.002), presence of ictal fear (P = 0.005), impaired intellectual function (P = 0.045), and bilateral ictal and interictal epileptiform activity (both P < 0.0001). Using logistic regression analysis, ictal fear [odds ratio (OR) 2.88; P = 0.015] and bilateral interictal EEG activity (OR 6.40; P < 0.0001) were predictive of PP development. No association of PP with MRI pathology or epilepsy-relevant aetiological factors was found. CONCLUSIONS: PP is a frequent and potentially dangerous complication within the course of TLE. Bilateral or widespread functional central nervous system disturbances rather than distinct structural brain alterations or certain predisposing aetiologies of epilepsy appear to be a risk factor for the development of PP. Ictal fear may be a predictive clinical variable of PP in TLE.

The effect of early prednisolone treatment on the generalization rate in ocular myasthenia gravis.

BACKGROUND AND PURPOSE: Several small retrospective studies have observed that patients with a purely ocular manifestation of myasthenia gravis (MG) are significantly less likely to convert to a generalized disease when treated early on with corticosteroids. However, given the limited number of reported patients in the literature these findings still remain controversial. METHODS: In order to increase the number of published cases, we performed a retrospective analysis on 44 patients with newly diagnosed ocular MG who were subsequently either treated with corticosteroids or received no immunosuppressive therapy at all. The generalization rate was assessed at the end of a 2-year follow-up period. RESULTS: Whereas none of 17 treated patients generalized, 11 of 27 (41%) untreated patients developed generalized symptoms. The difference between the groups was significant (P=0.003). CONCLUSIONS: Our results agree well with previous studies on this issue. Taken together, published data indicate risk ratios for generalization of below 0.32 under corticosteroid treatment in comparison to untreated patients.

Prenatal magnetic resonance imaging: towards optimized patient information.

OBJECTIVES: To investigate the perception of fetal magnetic resonance imaging (MRI) by women confronted with the necessity of a targeted prenatal examination because of suspicion of an abnormality, in order to develop a pre-scan information leaflet tailored to the information requirements of these women. METHODS: Sixty-two women were assessed by qualitative interview immediately before and after scanning. Data were analyzed by means of a qualitative content analysis. The transcribed interviews were coded within established categories, including knowledge of the purpose of the exam, understanding of the procedure, expectation of the baby's reaction, satisfaction with pre-information, experience of fetal MRI, distressing conditions during scanning, anxiety and suggestions for improvement of the scanning procedure. RESULTS: Pre-scan interviews indicated 66% of our sample to be well-informed about the purpose of fetal MRI. A realistic, detailed description of the examination was given by 37%. Only 32% expected the scanning to be safe for their baby. Despite the overall good tolerance of fetal MRI (63%), post-scan interviews revealed that 58% of women had experienced anxiety during MRI, which was partly due to the fearful perception of intensified fetal body movements during scanning. The quality of the pre-information leaflet was rated as sufficiently informative by 68% of the women. Suggestions for improvement were centered on physical conditions, the presence of the partner during scanning, and the availability of pre-scan briefings. CONCLUSIONS: Based on women's needs, detailed information about the fetal MRI procedure should be provided, containing clear-cut explanations about the purpose, course, method and possible distressing conditions. A leaflet describing these details should be given to women by the referring physician well in advance of the examination, and the woman given the opportunity to discuss unclear points.

A novel mutation in the MFSD8 gene in late infantile neuronal ceroid lipofuscinosis.

Neuronal ceroid lipofuscinoses (NCL) are lysosomal storage disorders and constitute the most common group of progressive neurodegenerative diseases in childhood. Most NCLs are inherited in a recessive manner and are clinically characterised by a variable age at onset, epileptic seizures, psychomotor decline, visual impairment and premature death. To date, eight causative genes have been identified to underlie various clinical forms of NCL. We performed a genome-wide linkage analysis followed by sequencing the recently described NCL gene MFSD8 in three affected and three unaffected members of a consanguineous Egyptian family with an autosomal recessively inherited progressive neurodegenerative disorder. The clinical picture of the patients was compatible with a late infantile NCL (LINCL); however, impairment of the visual system was not a cardinal symptom in the respective family. By linkage analysis, we identified two putative loci on chromosome 1p36.11-p35.1 and 4q28.1-q28.2. The latter locus (4q28.1-q28.2) contained the MFSD8 gene, comprising a novel homozygous missense mutation in exon 5 (c.362a>g /p.Tyr121Cys), which segregated with the disease in the three affected sibs. We describe a novel mutation in the previously identified MFSD8 gene in a family with a common phenotype of LINCL, but no clinical report of vision loss. Our results enlarge the mutational and perhaps the nosological spectrum of one of the recently identified subtypes of NCL, called CLN7.

Inclusive K(S);(0)K(S);(0) resonance production in ep collisions at HERA.

Inclusive K_{S};{0}K_{S};{0} production in ep collisions at the DESY ep collider HERA was studied with the ZEUS detector using an integrated luminosity of 0.5 fb;{-1}. Enhancements in the mass spectrum were observed and are attributed to the production of f_{2}(1270)/a_{2};{0}(1320), f_{2};{'}(1525) and f_{0}(1710). Masses and widths were obtained using a fit which takes into account theoretical predictions based on SU(3) symmetry arguments, and are consistent with the Particle Data Group values. The f_{0}(1710) state, which has a mass consistent with a glueball candidate, was observed with a statistical significance of 5 standard deviations. However, if this state is the same as that seen in gammagamma-->K_{S};{0}K_{S};{0}, it is unlikely to be a pure glueball state.

Idiopathic generalized epilepsy phenotypes associated with different EFHC1 mutations.

We sequenced 61 patients with various idiopathic generalized epilepsy (IGE) syndromes for mutations in the EFHC1 gene. We detected three novel heterozygous missense mutations (I174V, C259Y, A394S) and one possibly pathogenic variant in the 3' UTR (2014t>c). The mutation I174V was also detected in 1 of 372 screened patients with temporal lobe epilepsy. We conclude that mutations in the EFHC1 gene may underlie different types of epilepsy syndromes.

Mutations in the CLCN2 gene are a rare cause of idiopathic generalized epilepsy syndromes.

Mutations in the chloride channel gene CLCN2 have been reported in families with generalized and focal epilepsy syndromes. To evaluate the contribution of mutations in the CLCN2 gene to the etiology of epilepsies in our population, we screened 96 patients with different epilepsy syndromes and a putative genetic background. No definite mutations were found in our study population. We conclude that mutations in the CLCN2 gene are only a rare cause of idiopathic generalized epilepsy.

Postictal paresis in focal epilepsies--incidence, duration, and causes: a video-EEG monitoring study.

BACKGROUND: Although familiar to every neurologist, postictal paresis (PP) has only rarely been analyzed systematically. OBJECTIVE: To describe the frequency and duration of PP in patients undergoing video-EEG monitoring, the semiology characteristics of seizures preceding PP, and the pattern of associated symptoms and signs. METHODS: The records of 513 consecutive patients who underwent prolonged video-EEG monitoring during presurgical epilepsy evaluation were reviewed for postictal motor deficit. Three hundred twenty-eight patients fulfilled the inclusion criteria. The videotapes of patients with PP were subsequently analyzed with a careful analysis of ictal motor phenomena at the side of the PP. RESULTS: PP was found in 44 patients (13.4%). PP was always unilateral and always contralateral to the seizure focus and had a median duration of 173.5 seconds (range 11 seconds to 22 minutes). Of all seizures with PP, 77.8% were accompanied by evident and 9.7% by very slight ictal motor phenomena ipsilateral to the side of PP, whereas 9.7% of the seizures showed no motor signs (two seizures [2.8%] could not be evaluated for motor phenomena). The most common ictal lateralizing sign was unilateral clonic activity in 55.6% of all seizures. Concomitant dystonic posturing was found in 47.9% and ictal limb immobility in 24.6% of the seizures. PP was of longer duration if ictal clonic activity was present and after tonic-clonic seizures. CONCLUSIONS: PP is relatively frequent (13.4%), is easy to detect, and has a high lateralizing value. The high incidences of dystonic posturing and of ictal limb immobility in our patients with PP may indicate that an active inhibitory process is involved in its pathogenesis.

Affective state of women following a prenatal diagnosis: predictors of a negative psychological outcome.

OBJECTIVE: The benefits of prenatal diagnostic procedures are well documented. However, the investigation of psychological consequences related to these procedures has remained a surprisingly neglected area of research. The main aim of the present study was to investigate the potential relationship between psychological outcome and associated (socio-demographic, psychological and obstetric) variables in women attending a tertiary referral center for prenatal diagnosis and therapy for ultrasound scanning (due to the suspicion of a fetal malformation raised by the gynecologist in private practice), amniocentesis or chorionic villus sampling. METHODS: Affective state was assessed by means of standardized measures of anxiety and depression (State-Trait Anxiety Inventory; Mood Scale) in 77 consecutive, unselected women. A follow-up investigation, including an additional assessment of coping mechanisms, took place 6 months after the first contact. Given the considerable number of intervening and correlating factors, a path analysis was undertaken. RESULTS: We found that all women in our sample experienced acute distress, not only those with proven fetal malformations, genetic disorders or intrauterine fetal death, but also those with the diagnosis of a sonographic sign. At baseline (i.e. immediately after the diagnostic procedure), mood and anxiety scores in our sample were found to be comparable to those of patients with a major depressive episode. A high trait anxiety level, implementation of negative coping strategies and loss of the child during pregnancy were found to be predictive of a negative psychological outcome at follow-up. Socio-demographic variables did not have a significant predictive function for the psychological outcome. CONCLUSIONS: We assume that a considerable number of women undergoing prenatal diagnostic procedures experience psychological distress, which may be underestimated by workers in prenatal care. Establishment of interdisciplinary treatment settings, in which access to psychological support is facilitated, may be extremely beneficial for women following a prenatal diagnosis.

Context-Oriented Model Development in Psychotherapy Planning ('COMEPP'): a useful adjunct to diagnosis and therapy of severe personality disorders.

OBJECTIVE: Pathogenous interpersonal (e.g. interfamilial) relationships and reference styles can compromise treatment efforts in severely disturbed (i.e. psychotic or borderline) patients. The integration of family- and individual-centred starting points may be useful in establishing interdisciplinary treatment concepts in these patients. Context-Oriented Model Development in Psychotherapy Planning (COMEPP) represents a diagnostic and therapy planning process, integrating both systemic and psychoanalytic conceptualizations. METHOD: COMEPP is exemplified by the case of a young man with psychotic personality disorder who had previously been unresponsive to pharmacological and psychological treatment. RESULTS: After psycho-dynamical conflicts (i.e. primitive projective processes from the patient's mother to her son) had been elucidated during the COMEPP process, a sufficient treatment setting could be established. CONCLUSION: COMEPP provides a psychotherapeutical approach to treatment planning on case-specific premises and may serve as an adjunct to concomitant pharmacological and psychological treatment strategies in so-called 'therapy refractory' patients.

A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is associated with DSM-IV depression subtypes in seasonal affective disorder.

Serotonergic mechanisms are thought to play an important role in the pathogenesis of seasonal affective disorder (SAD). The expression of the serotonin transporter (5-HTT) is regulated in part by an insertion/deletion polymorphism in the serotonin transporter gene promoter region (5-HTTLPR). The 5-HTTLPR short allele (s) has been associated with anxiety-related personality traits and depression, and one study observed an association between the 5-HTTLPR s-allele and SAD and the trait of seasonality. We genotyped 138 SAD patients and 146 healthy volunteers with low seasonality for 5-HTTLPR. No difference between patients and controls was found for genotype distribution and s-allele frequency. However, genotype distribution and allele frequencies were strongly associated with DSM-IV depression subtypes. Melancholic depression was associated with the 5-HTTLPR long (l) allele and atypical depression with the 5-HTTLPR s-allele (two-sided Fisher's exact test: genotype distribution: P=0.0038; allele frequencies: P=0.007). Our data are compatible with the hypothesis of a disease process that is not causally related to 5-HTTLPR, but involves 5-HT neurotransmission and 5-HTTLPR somewhere on its way to phenotypic disease expression.

[Seasonal affective depression in 2 German speaking university centers: Bonn, Vienna. Clinical and demographic characteristics]. / Saisonal abhängige Depression in zwei deutschsprachigen Universitätszentren: Bonn, Wien. Klinische und demographische Charakteristika.

Six hundred ten patients with seasonal affective disorder (SAD) were diagnosed and treated at the university hospitals for psychiatry in Bonn, Germany (1989-1992) and Vienna, Austria (1993-2001). The aim of this study was to compare our sample with other SAD populations in the literature and to investigate differences between the two study locations. We found female:male sex ratios of 5.0:1.0 in unipolar depressives and 1.5:1.0 in patients with bipolar affective disorder. Of our patients, 21.7% suffered from bipolar II disorder, and 1.3% were diagnosed as having bipolar I. Our patients obtained a mean global seasonality score (GSS) of 15.4. Women had a higher GSS than men (t = 2.127, P = 0.035), and Viennese patients had higher scores than patients in Bonn (t = 3.104, P = 0.002). Totals of 66.3% of all patients suffered from atypical depression and 17.8% from melancholic depression. Patients with atypical depression were more frequent in Vienna, whereas patients with melancholic depression predominated in Bonn (chi 2 = 54.952, df = 2, P < 0.001). The demographic and clinical characteristics of the patients described in this article confirm the findings of other epidemiological investigations obtained in non-German-speaking samples.

Changes of clinical pattern in seasonal affective disorder (SAD) over time in a German-speaking sample.

OBJECTIVE: The goals of this study are to provide estimates of clinical and demographic variables of patients with seasonal affective disorder (SAD) in Germany and Austria, to compare our results with those of previously published SAD studies, and to find out whether the clinical pattern of SAD remained stable over several years. METHOD: We investigated 610 SAD patients from the outpatient clinics in Bonn (n = 190) and Vienna (n = 420). Patients in Bonn were recruited in the fall-winter season of the years 1989-1992, those in Vienna in the years 1993-2001. RESULTS: We observed a change in the clinical pattern in our patients: patients from Bonn, who were diagnosed and treated about 5 years earlier, were more likely to suffer from melancholic depression, whereas Viennese patients rather suffered from atypical depression (chi(2) = 54.952, df = 2, p < 0.001). The symptoms of hypersomnia, daytime fatigue, increased eating and carbohydrate-craving were more frequent in the Viennese sample, anxiety and deterioration of patients' capacity to perform at work predominated in Bonn. In addition, patients from Vienna obtained a higher GSS (global seasonality score, measured by the SPAQ - Seasonal Pattern Assessment Questionnaire) than those from Bonn (15.7 +/- 3.3 and 14.6 +/- 4.1 respectively; t = 3.104, p = 0.002). Taken together, our results were in good accordance to other published SAD materials, but we were able to demonstrate that our patients reported "feeling worst" (measured by item 13H of the SPAQ) in November and December, whereas SAD patients in the USA clearly had their worst months in January and February. CONCLUSIONS: We suggest that an increase in awareness of fall-winter depression in the last decade by both doctors, who referred patients, as well as patients or the entire population must have caused patients to sign up for light therapy at the Viennese SAD clinic because of having heard about the atypical symptom profile. This increased awareness of SAD can also be measured by a statistically significant reduction in the diagnostic latency (from the age of onset to the diagnosis of SAD) when comparing the two study locations.

[Atypical antipsychotics in the treatment of bipolar affective disorders]. / Atypische Antipsychotika in der Therapie der bipolaren affektiven Störung.

Antipsychotics are commonly used in the treatment of bipolar affective disorder. The use of conventional antipsychotic agents, though effective as antimanic agents, is associated with a number of limitations such as their acute side effect profile and their unsufficient mood stabilizing activity. In addition, exposure to conventional neuroleptics poses a risk for the development of tardive dyskinesia, especially in mood disorder patients. Growing evidence suggests that the novel, so-called atypical neuroleptics may offer a number of advantages in the treatment of bipolar disorder, including their thymoleptic activity and minimal risk for acute and long-term extraypyramidal symptoms. Clinical experience with clozapine and olanzapine as mood stabilizers suggests greater antimanic than antidepressant properties, while risperidone may have greater antidepressant properties with some liability for triggering or exacerbating mania. The mood stabilizing properties of further atypical drugs are currently under investigation. This review focuses on the use of atypical antipsychotics in the treatment of bipolar disorder. We also present an overview concerning potential pharmakokinetic interactions based on the cytochrome P450 enzyme system when antipsychotics are combined with other mood stabilizing compounds. In conclusion, atypical antipsychotics should come to play an increasingly important role in the acute and long-term management of bipolar disorder, but there is a clear need for further controlled trials in this indication.

[Pharmacotherapy of seasonal depression]. / Die Pharmakotherapie der saisonal abhängigen Depression.

Seasonal affective disorder (SAD), first described in 1984, is a condition characterized by recurring depressive episodes in fall and winter alternating with nondepressive episodes in spring and summer. Various neurotransmitters have been implicated in the etiology of SAD, with the strongest evidence for an involvement of serotonin. Moreover, researchers have focused on the development of treatment modalities for SAD. Despite the proven efficacy of light therapy in SAD, some patients do not experience sufficient relief of depressive symptoms with light, and a number of them feel unable to comply because of logistical difficulties in administering bright light therapy. Comparatively few studies have examined the role of pharmacotherapy in the treatment of SAD. So far, selective serotonin reuptake inhibitors and possibly compounds with a distinct noradrenergic mechanism of action seem to be the treatment of choice for seasonal depression. There is, however, a clear need for further placebo-controlled studies to evaluate pharmacological treatment options for SAD.

[Depressive pseudodementia]. / Depressive Pseudodemenzen.

Elderly depressive patients complaining about cognitive symptoms are at particular risk of being labelled as demented. It is well documented that depressive disorders frequently cause mild cognitive deficits which manifest in psychometric procedures. A wide spectrum of potentially reversible cognitive deficits related to a depressive syndrome are summarized under the term of "Depressive Pseudodementia (DPD)". Most depressive patients who are referred to "DPD" suffer from cognitive dysfunctions outside the range of dementia. The clinical interface between depression and dementia is complex. There is some evidence that depression may be a risk factor for the expression of Alzheimer's disease in later life and that depression may occur as a prodrome for Alzheimer dementia. Moreover, depression often complicates the course of dementing disorders. However, there is no evidence that depressive disorders cause dementia without coexisting depressive symptoms. It is essential to search for depressive symptoms even after cognitive symptoms have been found.

The effect of orlistat on plasma levels of psychotropic drugs in patients with long-term psychopharmacotherapy.

Weight gain induced by long-term psychopharmacotherapy has emerged as a relevant clinical issue because it is a major problem affecting compliance and long-term outcome. The novel antiobesity drug orlistat inhibits gastrointestinal lipases, thus lowering the absorption of dietary fat and raising the possibility of decreased absorption of fat-soluble vitamins and certain concomitantly administered drugs in some individuals. We monitored plasma levels of several psychotropic agents in eight psychiatric patients receiving orlistat to determine the potential influence of orlistat on the bioavailability of these drugs. We found no clinically relevant changes in plasma concentrations of haloperidol, clozapine, clomipramine, desipramine, or carbamazepine over an 8-week period in orlistat recipients. We therefore consider orlistat to be compatible with use during long-term pharmacotherapy. Our preliminary findings suggest that orlistat may offer a pharmacological treatment option to support dietary efforts in obese and overweight psychiatric patients. However, so far no data about the potential influence of orlistat on pharmacokinetics of psychotropics have been published; therefore, plasma level monitoring is recommended.

Intravenous mirtazapine in the treatment of depressed inpatients.

Mirtazapine is a novel antidepressant with a noradrenergic and specific serotonergic mode of action. So far, mirtazapine has been administered orally. This naturalistic study evaluates the antidepressant efficacy, safety, and tolerability of mirtazapine 15 mg/day administered intravenously to 27 inpatients with moderate to severe major depression. Compared with baseline, we found a significant decrease of the Hamilton Depressive Rating Scale (HDRS) total score (P<0.001). Side effects were mild and transient. Altogether, the results of this preliminary study show that intravenous mirtazapine is an effective, safe and well tolerated treatment for depressed inpatients.

Dopamine transporter availability in symptomatic depressed patients with seasonal affective disorder and healthy controls.

BACKGROUND: During recent years hypotheses about the pathophysiology of seasonal affective disorder/winter type (SAD) have focused monoaminergic mechanisms. There is substantial evidence that serotonergic systems play an important role. The potential role of catecholaminergic pathways has not been fully explored. METHODS: Eleven drug-free, symptomatic depressed patients with SAD and 11 healthy age- and gender-matched healthy controls were invited to participate in a 123Ibeta-CIT single photon emission computed tomography (SPECT) study to assess striatal density of dopamine transporters (DATs). The cerebellum was used as reference region. Ratios were calculated between mean counts in left and right striatum and cerebellum. These ratios minus I represent specific/non-displaceable binding and are assumed to be directly related to DAT availability at the time of binding equilibrium. RESULTS: Displaceable 153Ibeta-CIT binding in the area corresponding to the left striatum was significantly reduced in SAD patients compared to healthy controls (10.49+/-0.91 v. 1195+/-1.54, respectively; 2-tailed P = 0.017, Mann-Whitney U test). CONCLUSIONS: These data suggest reductions in the availability of striatal DAT binding sites in untreated symptomatic depressed SAD patients. It remains unclear whether these reductions represent a primary defect or an attempt to overcome a state of possible lowered dopamine availability in the synaptic cleft during a depressive episode of SAD. However, these findings provide evidence that brain dopaminergic systems may be involved in the pathophysiology of SAD.

In vivo (123)I IBZM SPECT imaging of striatal dopamine 2 receptor occupancy in schizophrenic patients.

RATIONALE: Single photon emission computed tomography (SPECT) using (123)I iodobenzamide (IBZM) as tracer substance has been shown to be a useful tool to visualize dopamine 2 (D2) receptor occupancy. OBJECTIVES: We investigated the striatal D2 receptor occupancy of zotepine which is referred to the class of atypical antipsychotic drugs. METHODS: (123)I IBZM and SPECT were used to visualize striatal dopamine 2 (D2) receptor occupancy in zotepine-treated schizophrenic patients. Two groups of schizophrenic patients receiving either 150 mg/day zotepine (n=6) or 300 mg/day (n=6) underwent examination. For the quantification of striatal D2 receptor occupancy, striatal IBZM binding in patients treated with antipsychotics was compared to untreated healthy controls (n=8) reported earlier. RESULTS: Zotepine led to a mean overall striatal D2 receptor occupancy of 73%. Patients with 150 mg daily showed a significantly lower occupancy (65.8%, SD=6.2) than patients with 300 mg/day (77.8%, SD=10.7; P<0.05). No clinically relevant extrapyramidal side effects occurred during treatment with zotepine. CONCLUSIONS: There was no correlation between the degree of striatal D2 receptor occupancy and clinical improvement.