Autism traits outweigh alexithymia traits in the explanation of mentalising performance in adults with autism but not in adults with rejected autism diagnosis.

BACKGROUND: Pronounced alexithymia traits have been found in autism spectrum disorder (ASD) and recent research has been carving out the impact alexithymia traits might have on mentalising deficits associated with ASD. METHOD: In this cross-sectional study, a large representative referral population for diagnostic examination for possible ASD (n = 400) was screened for clinical alexithymia with a German version of the Reading the Mind in the Eyes test (RME). In contrast to previous attempts to carve out the impact of alexithymia traits on mentalising deficits though, we employed dominance analysis to account for the correlation between predictors. The relative relationship between alexithymia traits and autism traits with RME performance was investigated in the group of individuals with confirmed ASD diagnosis (N = 281) and compared to the clinical referral sample in which ASD was ruled out (N = 119). RESULTS: Dominance analysis revealed autism traits to be the strongest predictor for reduced mentalising skills in the ASD sample, whereas alexithymia contributed significantly less. In the sample of individuals with ruled out diagnosis, autism traits were the strongest predictor, but alexithymia traits were in sum equally associated to mentalising, with the External-Oriented Thinking subscale as an important predictor of this association. LIMITATIONS: It needs to be considered that the cross-sectional study design does not allow for causal inference. Furthermore, mentalising is a highly facetted capacity and measurements need to reduce this complexity into simple quantities which limits the generalizability of results. DISCUSSION: While alexithymia traits should be considered for their mental health importance, they do not dominate the explanation of reduced mentalising skills in individuals with ASD, but they might do to a larger degree in individuals with ruled out ASD.

Alexithymia traits outweigh autism traits in the explanation of depression in adults with autism.

When contemplating the alarming depression rates in adults with autism spectrum disorder (ASD), there is a need to find factors explaining heightened symptoms of depression. Beyond the impact of autism traits, markedly increased levels of alexithymia traits should be considered as a candidate for explaining why individuals with ASD report higher levels of depressive symptoms. Here, we aim to identify the extent to which autism or alexithymia traits indicate depressive symptoms in ASD and whether the pattern of association are specific to ASD. Data of a large (N = 400) representative clinical population of adults referred to autism diagnostics have been investigated and split by cases with a confirmed ASD diagnosis (N = 281) and cases with a ruled out ASD diagnosis (N = 119). Dominance analysis revealed the alexithymia factor, difficulties in identifying feelings, as the strongest predictor for depressive symptomatology in ASD, outweighing autism traits and other alexithymia factors. This pattern of prediction was not specific to ASD and was shared by clinical controls from the referral population with a ruled out ASD diagnosis. Thus, the association of alexithymia traits with depression is not unique to ASD and may constitute a general psychopathological mechanism in clinical samples.

Successful Treatment of Super-Refractory Status Epilepticus with High-Intensity Electroconvulsive Therapy - A Case Report and Review of the Current Literature.

Status epilepticus (SE) is a severe neurological condition in which epileptic activity is prolonged or recurring, and the likelihood of spontaneous seizure cessation decreases over time. Evidence on the appropriate treatment regimen in therapy-refractory cases is still sparse. Electroconvulsive therapy (ECT) is known as a last resort treatment for SE due its anticonvulsant properties mediated by an increase in seizure threshold during the course of a treatment series. We examined the effects of ECT in a 61-year-old male patient with new-onset super-refractory SE (SRSE), for whom previous extensive efforts to achieve seizure control had failed. To achieve reliable seizure inductions in ECT concomitantly with an extended anticonvulsant treatment, we established a high-intensity ECT protocol: bitemporal ECT was conducted at a double-dosage setting (200% stimulation energy; equivalent to a mean charge of 1,031 mC) including three seizure stimulations during each treatment session on consecutive days until SRSE termination. After the first course of ECT, temporary seizure cessation was reached but lasted for only several days. A second course of ECT was then initiated, using the identical regimen but followed by tapering sessions every other day. Again, the SRSE terminated and after regaining consciousness the patient could be transferred to an acute rehabilitation facility. SRSE cessation can successfully be achieved by means of high-intensity ECT even after six weeks of prolonged SE and exhausted anticonvulsant pharmacotherapeutic strategies. As controlled clinical trials in the area of SRSE are still lacking, the relative significance of a high-intensity ECT protocol in this clinical setting has yet to be determined.

In-depth analysis of cost structure for electroconvulsive therapy in a performance-based hospital budget.

OBJECTIVE: New medical guideline recommendations for the treatment of major depressive disorders and regulative changes in the payment system of the German mental health care system warrant a revision of the framework in which electroconvulsive therapies (ECT) are offered. METHODS: A cost structure analysis of the clinical resources essential for the ECT procedure was conducted and economically validated, exemplified at a German inpatient ECT treatment center. RESULTS: The identification of directly attributable costs to the ECT intervention presupposes an accurate assessment of personnel engagement time and material consumption as well as an inclusion of overhead costs for the operational readiness of the hospital. CONCLUSION: The increasing importance of ECT in the clinical portfolio of therapy options demands an adequate refunding to support the expansion of this highly effective treatment. For the calculation of an appropriate reimbursement for ECT and ascertaining an acceptable contribution, a detailed knowledge of personnel costs and infrastructure settings of the respective hospitals is required.

Sex-Related Cognitive Profile in Autism Spectrum Disorders Diagnosed Late in Life: Implications for the Female Autistic Phenotype.

Females with high-functioning ASD are known to camouflage their autistic symptoms better than their male counterparts, making them prone to being under-ascertained and delayed in diagnostic assessment. Thus far the underlying cognitive processes that enable such successful socio-communicative adaptation are not well understood. The current results show sex-related differences in the cognitive profile of ASD individuals, which were diagnosed late in life exclusively. Higher verbal abilities were found in males (n = 69) as opposed to higher processing speed and better executive functions in females with ASD (n = 38). Since both sexes remained unidentified during childhood and adolescence, these results are suggestive for sex-distinctive cognitive strategies as an alternative to typically-developed reciprocal social behavior and social mimicry in high functioning ASD.

The investigation and differential diagnosis of Asperger syndrome in adults.

BACKGROUND: As a result of the increased public interest in autism spectrum disorders (ASD), certain core manifestations of ASD--impaired social interaction and communication, bizarre interests--are now commonly recognized as being typical of autism, not only in children, but in adults as well. More often than before, general practitioners, neurologists, and psychiatrists find themselves being asked whether a patient is suffering from previously unrecognized Asperger syndrome (AS). The prevalence of ASD is estimated at 1%, and the ratio of diagnosed to undiagnosed cases at about 3:2. Little is known about the diagnostic evaluation of AS in adulthood. METHOD: We selectively searched the Medline database for pertinent literature, paying special attention to diagnostic manuals and to the guideline of the United Kingdom's National Institute for Health and Care Excellence (NICE). RESULTS: Centrally important aspects of the diagnosis of AS include an assessment of the patient's ability to assume the emotional perspectives of others, non-verbal modes of expression, repetitive behavior patterns, and childhood social behavioral history. The autism quotient (AQ) is now established as a simple but nonspecific screening test. Up to 70% of all affected adults have comorbid disturbances, most often depression and anxiety disorders. The differential diagnosis includes personality disorders, anxiety disorders, obsessive-compulsive disorder, and attention deficit-hyperactivity disorder. The diagnostic assessment should proceed in stepwise fashion, starting from simple screening in primary care and then moving on to evaluation of the suspected diagnosis by a mental health care specialist, followed by extensive further investigation in an outpatient clinic specifically devoted to patients with autism spectrum disorders. CONCLUSION: The diagnostic assessment of autism in adults requires knowledge of the core and accompanying manifestations of autism and of their differential diagnoses. More research is needed for the development of further screening tests and the precise determination of diagnosis rates, differential diagnoses, nd comorbidities.

Prediction of malignant middle cerebral artery infarction by magnetic resonance imaging within 6 hours of symptom onset: A prospective multicenter observational study.

OBJECTIVE: Early identification of patients at risk of space-occupying "malignant" middle cerebral artery (MCA) infarction (MMI) is needed to enable timely decision for potentially life-saving treatment such as decompressive hemicraniectomy. We tested the hypothesis that acute stroke magnetic resonance imaging (MRI) predicts MMI within 6 hours of stroke onset. METHODS: In a prospective, multicenter, observational cohort study patients with acute ischemic stroke and MCA main stem occlusion were studied by MRI including diffusion-weighted imaging (DWI), perfusion imaging (PI), and MR-angiography within 6 hours of symptom onset. Multivariate regression analysis was used to identify clinical and imaging predictors of MMI. RESULTS: Of 140 patients included, 27 (19.3%) developed MMI. The following parameters were identified as independent predictors of MMI: larger acute DWI lesion volume (per 1 ml odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.06; p < 0.001), combined MCA + internal carotid artery occlusion (5.38, 1.55-18.68; p = 0.008), and severity of neurological deficit on admission assessed by the National Institutes of Health Stroke Scale score (per 1 point 1.16, 1.00-1.35; p = 0.053). The prespecified threshold of a DWI lesion volume >82 ml predicted MMI with high specificity (0.98, 95% CI 0.94-1.00), negative predictive value (0.90, 0.83-0.94), and positive predictive value (0.88, 0.62-0.98), but sensitivity was low (0.52, 0.32-0.71). INTERPRETATION: Stroke MRI on admission predicts malignant course in severe MCA stroke with high positive and negative predictive value and may help in guiding treatment decisions, such as decompressive surgery. In a subset of patients with small initial DWI lesion volumes, repeated diagnostic tests are required.

Altered cerebral glucose metabolism in a family with clinical features resembling mitochondrial neurogastrointestinal encephalomyopathy syndrome in association with multiple mitochondrial DNA deletions.

OBJECTIVE: To determine the involvement of cerebral metabolism in 2 siblings with mitochondrial neurogastrointestinal encephalomyopathy syndrome (MNGIE)-like disease with multiple mitochondrial DNA (mtDNA) deletions. DESIGN: Case report. SETTING: Department of Neurology at a university medical center. PATIENTS: Two siblings with MNGIE-like disease with multiple mtDNA deletions. MAIN OUTCOME MEASURES: Clinical, biochemical, genetic, and imaging findings, including cerebral magnetic resonance imaging, proton magnetic resonance spectroscopy, and positron emission tomography with fluorine 18-labeled deoxyglucose (FDG-PET). RESULTS: Genetic analysis of muscle DNA revealed multiple mtDNA deletions, while no mutations were detected in ECGF1, POLG1, ANT1, or Twinkle. Cerebral magnetic resonance imaging and proton magnetic resonance spectroscopy findings were unremarkable. Reduced regional glucose metabolism was found in a patchy and asymmetrical pattern predominantly in the frontotemporal region in both siblings by means of FDG-PET. CONCLUSIONS: The discrepancy between absence of clinical signs of cerebral involvement and the substantial impairment of glucose metabolism reflects a chronic subclinical encephalopathy. To our knowledge, the predominantly frontotemporal distribution has not been described previously in mitochondrial disorders.

Dissociation between key processes of social cognition in autism: impaired mentalizing but intact sense of agency.

Deficits in social cognition and interaction, such as in mentalizing and imitation behavior, are hallmark features of autism spectrum disorders. Both imitation and mentalizing are at the core of the sense of agency, the awareness that we are the initiators of our own behavior. Little evidence exists regarding the sense of agency in autism. Thus, we compared high-functioning adults with autism to healthy control subjects using an action monitoring and attribution task. Subjects with autism did not show deficits in this task, yet they showed significant mentalizing deficits. Our findings indicate a dissociation between the sense of agency and ascription of mental states in autism. We propose that social-cognitive deficits in autism may arise on a higher level than that of action monitoring and awareness.

Metabolic differences between primary and recurrent human brain tumors: a 1H NMR spectroscopic investigation.

High-resolution proton magnetic resonance spectroscopy was performed on tissue specimens from 33 patients with astrocytic tumors (22 astrocytomas, 11 glioblastomas) and 13 patients with meningiomas. For all patients, samples of primary tumors and their first recurrences were examined. Increased anaplasia, with respect to malignant transformation, resulting in a higher malignancy grade, was present in 11 recurrences of 22 astrocytoma patients. Spectroscopic features of tumor types, as determined on samples of the primary occurrences, were in good agreement with previous studies. Compared with the respective primary astrocytomas, characteristic features of glioblastomas were significantly increased concentrations of alanine (Ala) (p = 0.005), increased metabolite ratios of glycine (Gly)/total creatine (tCr) (p = 0.0001) and glutamate (Glu)/glutamine (Gln) (p = 0.004). Meningiomas showed increased Ala (p = 0.02) and metabolite ratios [Gly, total choline (tCho), Ala] over tCr (p = 0.001) relative to astrocytomas, and N-acetylaspartate and myo-inositol were absent. Metabolic changes of an evolving tumor were observed in recurrent astrocytomas: owing to their consecutive assessments, more indicators of malignant degeneration were detected in astrocytoma recurrences (e.g. Gly, p = 0.029; tCho, p = 0.034; Glu, p = 0.015; tCho/tCr, p = 0.001) in contrast to the comparison of primary astrocytomas with primary glioblastomas. The present investigation demonstrated a correlation of the tCho-signal with tumor progression. Significantly elevated concentrations of Ala (p = 0.037) and Glu (p = 0.003) and metabolite ratio tCho/tCr (p = 0.005) were even found in recurrent low-grade astrocytomas with unchanged histopathological grading (n = 11). This may be related to an early stage of malignant transformation, not yet detectable morphologically, and emphasizes the high sensitivity of 1H NMR spectroscopy in elucidating characteristics of brain tumor metabolism.

Value of gradient-echo magnetic resonance imaging in the diagnosis of familial cerebral cavernous malformation.

BACKGROUND: Cerebral cavernous malformations (CCMs) are congenital vascular anomalies that can cause seizures, intracranial hemorrhages, focal neurological deficits, and migrainelike headaches. Magnetic resonance (MR) imaging has substantially facilitated diagnosis of CCM. It is now widely accepted that familial clustering with an autosomal dominant inheritance pattern should be suspected in cases of multiple lesions. OBJECTIVE: To determine by MR imaging the penetrance of cavernous malformations in a 3-generation family that included 5 members with typical clinical signs and diagnostic findings. METHODS: All family members underwent routine MR T1-weighted and T2-weighted spin-echo sequences in addition to MR T2-weighted gradient-echo sequences. RESULTS: Four family members had been symptomatic with either brainstem bleeding, headaches, or focal neurological signs. The gradient-echo sequences yielded a dramatically higher sensitivity with regard to lesion number and distribution. As in previous reports of familial CCM, an increase in lesion number with increasing age, changes in lesion characteristics, de novo occurrence in serial MR imaging over time, and the phenomenon of anticipation could be confirmed in this family. CONCLUSION: Magnetic resonance gradient-echo sequences should be considered the method of choice for diagnosis of familial CCM.

Does the mismatch match the penumbra? Magnetic resonance imaging and positron emission tomography in early ischemic stroke.

BACKGROUND AND PURPOSE: In ischemic stroke, diffusion-weighted (DW) and perfusion-weighted (PW) magnet resonance imaging (MRI) is used to define the mismatch as the therapeutic target. With positron emission tomography (PET), we characterized the metabolic patterns of tissue compartments identified by MRI and compared the volumes of mismatch to those of PET-defined penumbra. METHODS: In 6 acute (median, 5.2 hours) and 7 chronic (median, 10 days) stroke patients in whom a mismatch was defined by PW/DW MRI, PET was performed (median, 120-minute delay). Cerebral blood flow (CBF), oxygen metabolism (CMRO2), and oxygen extraction fraction (OEF) was determined in the areas of DWI lesion, mismatch, and oligemia. Then, the mismatch volume was compared with the volume of penumbra. RESULTS: DWI lesions showed impaired tissue integrity (low CMRO2 and low OEF). Mismatch areas were viable (normal CMRO2) but showed largely varying OEF. Oligemic areas had metabolic patterns comparable to normal tissue. A mismatch volume was found in all 13 patients. However, only 8 of 13 had a corresponding penumbra volume that covered only a part of the mismatch. CONCLUSIONS: Our comparative PET/MRI study confirmed the current pathophysiological hypothesis for the DWI lesion and for the oligemic areas. However, the mismatch area did not reliably detect elevated OEF and overestimated the penumbra defined by PET.

Probability of cortical infarction predicted by flumazenil binding and diffusion-weighted imaging signal intensity: a comparative positron emission tomography/magnetic resonance imaging study in early ischemic stroke.

BACKGROUND AND PURPOSE: The differentiation of reversible from irreversible ischemic damage is essential for identifying patients with acute ischemic deficits who may benefit from therapeutic interventions. Diffusion-weighted imaging (DWI) has become the method of choice to detect ischemic lesions. Positron emission tomography (PET) of the central benzodiazepine receptor ligand 11C flumazenil (FMZ) has been shown to be a reliable marker of neuronal integrity. These 2 imaging parameters were compared with respect to the probability to predict cortical infarction in early ischemic stroke. METHODS: In 12 patients with acute stroke, results from DWI (median, 6.5 hours after symptom onset) and FMZ-PET (interval, 85 minutes between DWI and PET) were compared with infarct extension 24 to 48 hours after onset of stroke on T2-weighted magnetic resonance imaging (T2-MRI). Probability curves predictive of eventual infarction were computed using respective DWI, FMZ, and apparent diffusion coefficient (ADC) values for voxels of interest (VOI) later classified as representing infarcted or noninfarcted tissue. RESULTS: Ninety-five percent limits predictive of cortical infarction were determined for relative FMZ binding (< or =3.2), DWI signal intensity (> or =1.18), and ADC values (< or =0.83). Cortical regions with values beyond these 95% limits did not necessarily overlap with nor were fully congruous with final cortical infarct volumes. The respective median volumes for these regions were FMZ median 10.9, range 0 to 99.7 cm3; DWI median 15.2, range 0 to 116.0 cm3; ADC median 12.4, range 0 to 112.7 cm3; and final infarct median 14.9, range 0 to 114.7 cm(3). Overall, 83.5% of the final infarct, on average, was predicted by decreased FMZ binding, 84.7% by increased DWI signal intensity, and 70.9% by a decreased ADC value. The portions of the final infarct not predicted in the early investigation (false-negatives) were 4.8 cm3 (median) for FMZ, 3.7 cm3 for DWI, and 6.0 cm3 for ADC. The false-positive volumes not included in the final infarct were 0 cm3 (median) for FMZ, 5.1 cm3 for DWI, and 3.6 cm3 for ADC. CONCLUSIONS: These results indicate that FMZ-PET and DWI are comparable in the prediction of probability of ischemic cortical infarction, but FMZ-PET carries a lower probability of false-positive prediction. The final infarcts include tissue not identified by these imaging modalities; at the time of the study, these tissue compartments are viable and could benefit from treatment. The discrepancy in predictive probability could be related to the fundamental difference of the measured variables: benzodiazepine receptor activity is a reliable marker of neuronal integrity in the cortex, and movement of water molecules in the extracellular space might be a more variable indicator of tissue damage.

Extracellular concentrations of non-transmitter amino acids in peri-infarct tissue of patients predict malignant middle cerebral artery infarction.

BACKGROUND AND PURPOSE: Space-occupying brain edema is a life-threatening complication in patients with large middle cerebral artery (MCA) infarction. To determine predictors of this detrimental process, we investigated alterations of extracellular non-transmitter amino acid concentrations in peri-infarct tissue. METHODS: Thirty-one patients with infarctions covering >50% of the MCA territory in early cranial CT scans were included in the study. Probes for microdialysis, intracranial pressure, and tissue oxygen pressure were placed into the noninfarcted ipsilateral frontal lobe. Positron emission tomography imaging was performed in 16 of these patients to measure cerebral blood flow in the tissue around the neuromonitoring probes. RESULTS: Fourteen of the 31 patients developed a malignant MCA infarction, and 17 did not. The patients in the malignant group had significantly lower extracellular concentrations of non-transmitter amino acids than those in the benign group in the first 12 hours of neuromonitoring. At this time, CBF values determined in regions of interest around the probes by positron emission tomography and tissue oxygen pressure showed that the monitored tissues were not yet infarcted, and no differences in transmitter amino acids concentrations were found between the 2 groups. Furthermore, extracellular concentrations of non-transmitter amino acids were negatively correlated with size of infarction. CONCLUSIONS: We assume that reduction of non-transmitter amino acid concentrations reflects an expansion of the extracellular space by vasogenic edema formation in peri-infarct tissue of patients with malignant MCA infarction. Our findings facilitate early prediction of malignant edema formation and may help to increase knowledge of the pathophysiology of the peri-infarct zone of large MCA infarction.