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.

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.

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.

[123I]-beta-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder.

BACKGROUND: Numerous findings indicate alterations in brain serotonin systems in seasonal affective disorder (SAD). [(123)I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([(123)I]-beta-CIT) labels serotonin transporters (5-HTTs) in the midbrain. We performed a [(123)I]-beta-CIT single photon emission computer tomography (SPECT) study under the hypothesis of lower [(123)I]-beta-CIT binding reflecting reduced central 5-HTT availability in depressed SAD patients. METHODS: Depressed SAD patients and healthy control subjects were investigated using [(123)I]-beta-CIT SPECT 4 hours and again 24 hours after tracer injection. Subjects had either never used psychotropic medication or had been drug-free for at least 6 months prior to the investigation. Specific-to-nondisplaceable partition coefficient (V(3)") was calculated for the thalamus-hypothalamus and the midbrain-pons; the cerebellum served as a reference region. RESULTS: Patients showed a reduction in V(3)" in thalamus-hypothalamus (2.41+/-0.3 vs. 2.84+/-0.4; p = .026) 24 hours post tracer injection (p.i.). No difference between patients and control subjects was found in midbrain-pons (1.31+/-0.2 vs. 1.42+/-0.2; p = .39). No differences were detected in the SPECT acquisitions 4 hours p.i. CONCLUSIONS: Depressed SAD patients showed lower specific-to-nondisplaceable [(123)I]-beta-CIT binding in the region of interest (ROI) thalamus-hypothalamus. The small size of the midbrain-pons ROI may have contributed to the failure to show a difference in this ROI as well. Similar to reduced midbrain 5-HTT availability in nonseasonal depression, depression in SAD seems to be associated with reduced 5-HTT availability to the thalamus-hypothalamus.

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.

Reboxetine in seasonal affective disorder: an open trial.

Seasonal affective disorder (SAD), winter type, is a condition characterized by the annual recurrence of depressive episodes during fall/winter, alternating with spring/summer euthymia or hypomania. Various neurotransmitters have been implicated in the etiology of SAD, the strongest evidence involving serotonin. Recently, increasing attention has been paid to the potential role of catecholaminergic pathways in the pathophysiology of SAD. We investigated the efficacy and tolerability of reboxetine, a selective noradrenaline inhibitor, in patients with SAD. Eleven out of sixteen patients who were included in a 6-week drug surveillance during winter season experienced full remission of depressive symptoms. Nine patients reported a rapid relief of preexistent severe atypical depressive symptoms within the first treatment week. Reboxetine might therefore be an effective and well-tolerated treatment option for SAD patients. In conclusion, our preliminary results are in line with evidence from recent studies suggesting that catecholaminergic systems might also be involved in the pathophysiology of SAD.

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.

Prevalence of premenstrual dysphoric disorder in female patients with seasonal affective disorder.

BACKGROUND: Both seasonal affective disorder/winter type (SAD) and premenstrual dysphoric disorder (PMDD) are cyclical disorders characterized by so-called atypical depressive symptoms. In the present study we compared the point prevalence rates of PMDD between a sample of premenopausal female patients suffering from SAD and healthy female controls. METHODS: Forty-six female patients with SAD and 46 healthy controls were included in our study. All subjects underwent a semistructured clinical interview according to DSM IV criteria and completed the Seasonal Pattern Assessment Questionnaire. PMDD was diagnosed in a self-rating interview for PMDD according to DSM IV criteria. To verify the diagnosis of PMDD, all patients were followed up in stable summer remission using daily self-rating scales for two full menstrual cycles. RESULTS: Patients with SAD fulfilled significantly more often the diagnostic criteria for PMDD than female healthy controls (46% vs. 2%, respectively; chi-square: P<0.001). CONCLUSIONS: These results provide preliminary evidence for a high point prevalence rate of PMDD in premenopausal females with SAD. CLINICAL IMPLICATIONS: It would be worthwhile to investigate whether an additional diagnosis of PMDD has an impact on the clinical outcome and the response to bright light therapy in female patients with SAD.

Reboxetine: the first selective noradrenaline re-uptake inhibitor.

Several treatment approaches are available for treatment of depression. However, reboxetine is the first selective noradrenaline re-uptake inhibitor. Whereas formerly only noradrenaline re-uptake inhibitors with a mixed mechanism of action were available. These included action not only at noradrenergic, but also at serotonergic and other neurotransmitter-sites. Thus, reboxetine represents the first of a new class of antidepressant agents with specificity for the noradrenergic system. Reboxetine has been shown to be an effective first-line treatment for patients with all grades of depression, to be effective in the prevention of relapse and recurrence and to offer significant benefits in terms of relieving the impaired social functioning associated with depressive disorders. Reboxetine was significantly superior to the serotonergic compound fluoxetine in improvement of social functioning in both the general depressed population and in those patients who achieved symptomatic remission, indicating a superior quality of remission. Altogether reboxetine was well tolerated during the acute and long-term treatment phase; side-effects such as increased sweating, constipation and dry mouth were the most prominent to be reported. The availability of reboxetine represents a significant addition to the currently available pharmacologic armamentarium for the treatment of depression.

[Atypical neuroleptics: new approaches to drug therapy of schizophrenic disorders]. / Atypische Neuroleptika: Neue Wege in der Pharmakotherapie schizophrener Störungen.

The introduction of conventional antipsychotics revolutionized the management of psychotic disorders in the 1950s. The use of these agents has been marked by several shortcomings, including their association with severe motor disturbances and their limited efficacy in treating the negative and cognitive symptoms of schizophrenia. Patients noncompliance has largely been the result of subjectively distressing extrapyramidal motor side-effects (EPMS). It was therefore necessary to develop antipsychotic drugs with selective pharmacological profiles, e.g. limbic selectivity. A defining characteristic of atypical neuroleptics is a higher ratio of serotonin receptor blockade to D2 receptor blockade. Their primary advantage is their superior side-effect profile. The implications of EPMS reduction touch several domains of pathology in schizophrenia such as short- and long-term movement disorders, noncompliance, relapse rate, negative symptoms and cognitive dysfunction. Novel antipsychotics may represent the second pharmacological revolution in the treatment of psychotic disorders. There is, however, still a need for a critical evaluation of the risk-benefit-ratio of differing atypical agents.

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.

[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.

[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.

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.

[Therapeutic sleep deprivation and phototherapy]. / Therapeutischer Schlafentzug und Lichttherapie.

Since ancient times the influence of chronobiological factors on the pathogenesis, course, and treatment of depression has been well known. Amongst antidepressive treatment strategies two are based on chronobiological knowledge: therapeutic sleep deprivation, which exerts a rapid and dramatic, albeit usually short-lasting, improvement of mood in the majority of patients with major depressive disorder, and light therapy with full-spectrum bright light. About sixty percent of all depressed patients improve after a single night of total or partial sleep deprivation. It has been shown that a combination of pharmacotherapy with antidepressants and sleep deprivation is superior to pharmacotherapy alone. Moreover, sleep deprivation has proved to hasten the onset of action of antidepressant medication and repeated sleep deprivation can also be an efficient treatment strategy in drug refractory depression. Light therapy with bright artificial light is especially beneficial in patients with a fall/winter pattern of depressive symptomatology that has been termed seasonal affective disorder. Similar to sleep deprivation, bright light therapy is characterized by a fast onset of antidepressant action and by the exertion of additive properties to antidepressive medication. Bright light therapy, beginning in the morning after partial sleep deprivation, is able to prevent the depressive relapse after the next night of sleep in sleep deprivation responders.

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.