Cognitive Performance After Facial Botulinum Toxin Treatment in a Cohort of Neurologic Patients: An Exploratory Study.

OBJECTIVE: To investigate higher cognitive functions after mimicry changes after facial botulinum toxin (BTX) injections, we tested verbal and nonverbal reasoning in patients with blepharospasm or hemifacial spasm before and after their long-term botulinum toxin treatment. DESIGN: Explorative, nonrandomized, clinical trial. SETTING: Patients receiving ambulatory care and control participants from the general community. PARTICIPANTS: Volunteer sample (N=84) of patients (n=21) with blepharospasm or hemifacial spasm who received facial BTX injections. Control participants included patients (n=30) with cervical dystonia who received cervical BTX injections and individuals without neurological disorders (n=33). INTERVENTIONS: The 2 groups receiving injections were tested before and 3 weeks after their treatment. The group without neurological disorders received no injections. MAIN OUTCOME MEASURES: Verbal and nonverbal reasoning scores. RESULTS: The key unexpected finding was that patients who received facial BTX injections perform significantly worse in nonverbal reasoning tasks, when compared with those who did not receive injections (P=.022). There was no significant difference in the baseline reasoning scores and at follow-up for verbal reasoning between the 3 groups. There was no correlation between toxin dose and reasoning scores (verbal: P=.132; nonverbal: P=.294). CONCLUSIONS: Because of potential confounders, the results do not yet allow any conclusion on causality. Further research is needed to confirm our findings.

Cognitive and affective Theory of Mind in adolescence: developmental aspects and associated neuropsychological variables.

Theory of Mind (ToM) is the ability to represent and attribute mental states to oneself and others. So far, research regarding ToM processing across adolescence is scarce. Existing studies either yield inconsistent results or did not or not thoroughly investigate aspects like higher order ToM and associated neuropsychological variables which the current study tried to address. 643 typically developing early, middle, and late adolescents (age groups 13-14; 15-16; 17-18) performed cognitive and affective ToM tasks as well as neuropsychological tasks tapping the cognitive or affective domain. Regarding both ToM types, 15- to 16-year-olds and 17- to 18-year-olds outperformed 13- to 14-year-olds, whereas females were superior regarding cognitive ToM. Across adolescence, cognitive and affective ToM correlated with attention and affective intelligence, whereas working memory, language comprehension, and figural intelligence additionally correlated with cognitive ToM. In early adolescence, attention correlated with both ToM types, whereas cognitive ToM further correlated with language comprehension and affective ToM with verbal intelligence, verbal fluency, and verbal flexibility. In middle and late adolescence, affective intelligence correlated with both ToM types, whereas cognitive ToM additionally correlated with working memory, language comprehension, and figural intelligence. The current study shows a developmental step regarding cognitive and affective ToM in middle adolescence as well as gender differences in cognitive ToM processing. Associations between neuropsychological variables and ToM processing were shown across adolescence and within age groups. Results give new insights into social cognition in adolescence and are well supported by neuroscientific and neurobiological studies regarding ToM and the integration of cognitive and affective processes.

Subjective emotional arousal: an explorative study on the role of gender, age, intensity, emotion regulation difficulties, depression and anxiety symptoms, and meta-emotion.

Subjective emotional arousal in typically developing adults was investigated in an explorative study. 177 participants (20-70 years) rated facial expressions and words for self-experienced arousal and perceived intensity, and completed the Difficulties in Emotion Regulation scale and the Hospital Anxiety and Depression scale (HADS-D). Exclusion criteria were psychiatric or neurological diseases, or clinically relevant scores in the HADS-D. Arousal regarding faces and words was significantly predicted by emotional clarity. Separate analyses showed following significant results: arousal regarding faces and arousal regarding words constantly predicted each other; negative faces were predicted by age and intensity; neutral faces by gender and impulse control; positive faces by gender and intensity; negative words by emotional clarity; and neutral words by gender. Males showed higher arousal scores than females regarding neutral faces and neutral words; for the other arousal scores, no explicit group differences were shown. Cluster analysis yielded three distinguished emotional characteristics groups: "emotional difficulties disposition group" (mainly females; highest emotion regulation difficulties, depression and anxiety scores; by trend highest arousal), "low emotional awareness group" (exclusively males; lowest awareness regarding currently experienced emotions; by trend intermediate arousal), and a "low emotional difficulties group" (exclusively females; lowest values throughout). No age effect was shown. Results suggest that arousal elicited by facial expressions and words are specialized parts of a greater emotional processing system and that typically developing adults show some kind of stable, modality-unspecific dispositional baseline of emotional arousal. Emotional awareness and clarity, and impulse control probably are trait aspects of emotion regulation that influence emotional arousal in typically developing adults and can be regarded as aspects of meta-emotion. Different emotional personality styles were shown between as well as within gender groups.

Developmental Steps in Metaphorical Language Abilities: The Influence of Age, Gender, Cognitive Flexibility, Information Processing Speed, and Analogical Reasoning.

PURPOSE: Metaphor is a specific type of figurative language that is used in various important fields such as in the work with children in clinical or teaching contexts. The aim of the study was to investigate the developmental course, developmental steps, and possible cognitive predictors regarding metaphor processing in childhood and early adolescence. METHOD: One hundred sixty-four typically developing children (7-year-olds, 9-year-olds) and early adolescents (11-year-olds) were tested for metaphor identification, comprehension, comprehension quality, and preference by the Metaphoric Triads Task as well as for analogical reasoning, information processing speed, cognitive flexibility under time pressure, and cognitive flexibility without time pressure. RESULTS: Metaphor identification and comprehension consecutively increased with age. Eleven-year-olds showed significantly higher metaphor comprehension quality and preference scores than seven- and nine-year-olds, whilst these younger age groups did not differ. Age, cognitive flexibility under time pressure, information processing speed, analogical reasoning, and cognitive flexibility without time pressure significantly predicted metaphor comprehension. CONCLUSIONS: Metaphorical language ability shows an ongoing development and seemingly changes qualitatively at the beginning of early adolescence. These results can possibly be explained by a greater synaptic reorganization in early adolescents. Furthermore, cognitive flexibility under time pressure and information processing speed possibly facilitate the ability to adapt metaphor processing strategies in a flexible, quick, and appropriate way.

Wanted: a better cut-off value for the Epworth Sleepiness Scale.

BACKGROUND: Excessive daytime sleepiness (EDS) is the main complaint in many neurological sleep disorders, such as idiopathic hypersomnia, narcolepsy, or obstructive sleep apnea/hypopnea syndrome (OSAS). The validity of the Epworth Sleepiness Scale (ESS) as a screening tool for EDS remains controversial. We therefore investigated (1) the interrelation of the ESS total score and the mean sleep latency (MSL) during the multiple sleep latency test (MSLT) and (2) the diagnostic accuracy of the ESS total score to detect EDS in patients with the chief complaint of subjective EDS. METHODS: A total of 94 patients (48 males) with subjective EDS were included in this study. Regression analyses and ROC curve analyses were carried out to assess the predictive value of the ESS score for MSL. RESULTS: The ESS score significantly predicted a shortened MSL (p = 0.01, ß = -0.29). After dichotomizing into two groups, the ESS score predicted MSL only in patients with hypersomnia or narcolepsy (p = 0.01, ß = -0.33), but not in patients with other clinical diagnoses (e. g. OSAS; p = 0.36, ß = -0.15). The ROC curve analyses indicated an optimal ESS cut-off value of 16 with a sensitivity of 70%; however, specificity remained unsatisfactory (55.6%). CONCLUSIONS: Our results suggest that the predictive value of the ESS score in patients with subjective EDS is low and patient subgroup-specific (superior in hypersomnia/narcolepsy vs. other diagnoses) and that the commonly used cut-off of 11 points may be insufficient for clinical practice.

Manifestations of neurological symptoms and thromboembolism in adults with MTHFR-deficiency.

BACKGROUND: Methylenetetrahydrofolate-reductase (MTHFR) deficiency is a rare autosomal recessive disorder affecting intracellular folate metabolism with affection of different organ systems and clinical manifestation usually in childhood. OBJECTIVE: We report on four adult members of a family with MTHFR deficiency presenting with neurological and thromboembolic complications in adulthood. METHODS: Extensive diagnostic work-up including genetic testing was performed in four adult members. RESULTS: The male siblings aged 42 and 32years presented with various neurological symptoms, and a recent history of deep vein thrombosis. Extensive diagnostic work-up revealed total homocysteine (tHcy) plasma concentrations of 135µmol/L and 231µmol/L. and compound heterozygosity for two novel MTHFR gene mutations in exon 2 (c.202C>G, p.Arg68Gly) and intron 10 (c.1632+2T>G), and the known polymorphic variant MTHFR c.665C>T (p.Ala222Val, MTHFR 677C>T). Their mother was heterozygous for MTHFR c.1632+2T>G and c.665C>T, and a paternal relative was heterozygous for MTHFR c.202.C>G and MTHFR c.665C>T mutation. Both brothers showed partial response to therapy with betaine and multivitamins with clinical improvement. MTHFR activity was determined in fibroblast extracts and was around 4% of the mean control. Cell culture analysis indicated a re-methylation defect due to MTHFR deficiency. CONCLUSION: Severe hyperhomocysteinemia due to two mutations of the MTHFR gene resulted in severe neurological symptoms in adulthood. Vitamin and methionine supplementation stabilize tHcy plasma levels. Severity of clinical manifestation varied greatly between the siblings. Damages to the nervous system may be present for years before becoming clinically manifest.

Task-dependent variability of Essential Tremor.

INTRODUCTION: In Essential Tremor (ET), tremor characteristics and the impairment caused by tremor may vary from task to task. A variability of tremor frequency between postural and kinetic tasks has been proposed in ET, suggesting either multiple central oscillating networks, or peripheral or proprioceptive feedback-mechanisms. This electrophysiological study aimed to assess tremor frequencies and amplitudes in tasks involving postural and kinetic tremor, and compare findings within and across tasks, to delineate physiological differences underlying individually affected manual tasks in ET. METHODS: 40 ET patients were included in the study. Tremor was characterized clinically, as well as electrophysiologically using accelerometry and digitizing tablet tasks. Tremor amplitude measures and frequencies were extracted for tasks involving kinetic (digital spiral drawing, handwriting), as well as postural tremor. Tremor was compared between and within tasks. RESULTS: Digital spiral tremor frequencies were significantly higher compared to postural tremor frequencies, as measured by accelerometry, with a mean difference of >2 Hz (p < 0.001). Within-task variability of repeated digital spirals revealed a significant amplitude reduction over time in both hands (p < 0.001), with an up to 32% reduction compared to the first spiral. CONCLUSION: ET exhibited a frequency variability, which was dependent on activation condition, suggesting neurophysiologically distinct pathways between postural and kinetic tremor. The reduction of tremor amplitudes observed in repeated digital spiral drawing may be explained by a learning effect or adaptation, and should be considered as non-random factor of variability when using spirals in ET to assess effects of interventions.

Iodinated contrast agents in patients with myasthenia gravis: a retrospective cohort study.

Currently, it has not been satisfactorily established, whether modern low-osmolality iodinated contrast agents (ICAs) used in computed tomography (CT) studies are a risk factor for exacerbation of myasthenic symptoms. The rate of acute adverse events as well as delayed clinical worsening up to 30 days were analyzed in 73 patients with confirmed myasthenia gravis (MG) who underwent contrast-enhanced CT studies and compared to 52 patients who underwent unenhanced CT studies. One acute adverse event was documented. 12.3% of MG patients experienced a delayed exacerbation of symptoms after ICA administration. The rate of delayed severe exacerbation was higher in the contrast-enhanced group. Alternative causes for the exacerbation of MG-related symptoms were more likely than ICA administration in all cases. ICA administration for CT studies in MG patients should not be withheld if indicated, but patients particularly those with concomitant acute diseases should be carefully monitored for exacerbation of symptoms.

Screening for Specific Language Impairment in Preschool Children: Evaluating a Screening Procedure Including the Token Test.

Specific language impairment (SLI) comprises impairments in receptive and/or expressive language. Aim of this study was to evaluate a screening for SLI. 61 children with SLI (SLI-children, age-range 4-6 years) and 61 matched typically developing controls were tested for receptive language ability (Token Test-TT) and for intelligence (Wechsler Preschool-and-Primary-Scale-of-Intelligence-WPPSI). Group differences were analyzed using t tests, as well as direct and stepwise discriminant analyses. The predictive value of the WPPSI with respect to TT performance was analyzed using regression analyses. SLI-children performed significantly worse on both TT and WPPSI ([Formula: see text]). The TT alone yielded an overall classification rate of 79%, the TT and the WPPSI together yielded an overall classification rate of 80%. TT performance was significantly predicted by verbal intelligence in SLI-children and nonverbal intelligence in controls whilst WPPSI subtest arithmetic was predictive in both groups. Without further research, the Token Test cannot be seen as a valid and sufficient tool for the screening of SLI in preschool children but rather as a tool for the assessment of more general intellectual capacities. SLI-children at this age already show impairments typically associated with SLI which indicates the necessity of early developmental support or training. Token Test performance is possibly an indicator for a more general developmental factor rather than an exclusive indicator for language difficulties.

Assessment of individual cognitive changes after deep brain stimulation surgery in Parkinson's disease using the Neuropsychological Test Battery Vienna short version.

Long-term therapy of Parkinson's disease with L­DOPA is associated with a high risk of developing motor fluctuations and dyskinesia. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can improve these motor complications. Although the positive effect on motor symptoms has been proven, postoperative cognitive decline has been documented. To tackle the impact of DBS on cognition, 18 DBS patients were compared to 25 best medically treated Parkinson's patients, 24 patients with mild cognitive impairment (MCI) and 12 healthy controls using the Neuropsychological Test Battery Vienna short version (NTBV-short) for cognitive outcome 12 months after the first examination. Reliable change index methodology was used. Roughly 10% of DBS patients showed cognitive decline mainly affecting the domains attention and executive functioning (phonemic fluency). Further research is needed to identify the mechanisms that lead to improvement or deterioration of cognitive functions in individual cases.

Lateralization of language function in epilepsy patients: A high-density scalp-derived event-related potentials (ERP) study.

OBJECTIVES: Language functional magnetic resonance imaging (fMRI) represents the clinical standard for language lateralization assessment in presurgical epilepsy evaluation, but still many patients experience postoperative language deficits. Event-related potentials (ERPs), especially the negative component around and after 400ms, are related to language processing and could therefore represent a complementary method of language lateralization assessment. METHODS: Scalp EEG was recorded from 64 locations in 36 epilepsy patients and 37 controls during three visually presented language tasks: A short-term language memory task (differentiation memorized vs. unknown words), a phonological task (detection of rhymes in word pairs), and a semantic decision task (differentiation words vs. pseudowords). ERPs were analyzed in the 300ms-800ms epoch. Language fMRI was routinely obtained in patients. RESULTS: ERPs were significantly more negative over the left compared to the right hemisphere in all three tasks in patients and controls. Laterality indices showed highest concordance with fMRI for the Word/Pseudoword Task. CONCLUSIONS: ERPs of language processing were lateralized to the left hemisphere in the majority of epilepsy patients and controls. In patients, single-subject laterality indices showed high concordance with fMRI results. SIGNIFICANCE: Results indicate that scalp-derived ERPs are a promising tool to investigate lateralization of language function in epilepsy patients.

Cognitive and emotional demands of black humour processing: the role of intelligence, aggressiveness and mood.

Humour processing is a complex information-processing task that is dependent on cognitive and emotional aspects which presumably influence frame-shifting and conceptual blending, mental operations that underlie humour processing. The aim of the current study was to find distinctive groups of subjects with respect to black humour processing, intellectual capacities, mood disturbance and aggressiveness. A total of 156 adults rated black humour cartoons and conducted measurements of verbal and nonverbal intelligence, mood disturbance and aggressiveness. Cluster analysis yields three groups comprising following properties: (1) moderate black humour preference and moderate comprehension; average nonverbal and verbal intelligence; low mood disturbance and moderate aggressiveness; (2) low black humour preference and moderate comprehension; average nonverbal and verbal intelligence, high mood disturbance and high aggressiveness; and (3) high black humour preference and high comprehension; high nonverbal and verbal intelligence; no mood disturbance and low aggressiveness. Age and gender do not differ significantly, differences in education level can be found. Black humour preference and comprehension are positively associated with higher verbal and nonverbal intelligence as well as higher levels of education. Emotional instability and higher aggressiveness apparently lead to decreased levels of pleasure when dealing with black humour. These results support the hypothesis that humour processing involves cognitive as well as affective components and suggest that these variables influence the execution of frame-shifting and conceptual blending in the course of humour processing.

Early dysfunctions of fronto-parietal praxis networks in Parkinson's disease.

In Parkinson's disease (PD) the prevalence of apraxia increases with disease severity implying that patients in early stages may already have subclinical deficits. The aim of this exploratory fMRI study was to investigate if subclinical aberrations of the praxis network are already present in patients with early PD. In previous functional imaging literature only data on basal motor functions in PD exists. Thirteen patients with mild parkinsonian symptoms and without clinically diagnosed apraxia and 14 healthy controls entered this study. During fMRI participants performed a pantomime task in which they imitated the use of visually presented objects. Patients were measured ON and OFF dopaminergic therapy to evaluate a potential medication effect on praxis abilities and related brain functions. Although none of the patients was apraxic according to De Renzi ideomotor scores (range 62-72), patients OFF showed significantly lower praxis scores than controls. Patients exhibited significant hyperactivation in left fronto-parietal core areas of the praxis network. Frontal activations were clearly dominant in patients and were correlated with lower individual praxis scores. We conclude that early PD patients already show characteristic signs of praxis network dysfunctions and rely on specific hyperactivations to avoid clinically evident apraxic symptoms. Subclinical apraxic deficits were shown to correlate with an activation shift from left parietal to left frontal areas implying a prospective individual imaging marker for incipient apraxia.

Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging.

In multiple sclerosis (MS), iron accumulates inside activated microglia/macrophages at edges of some chronic demyelinated lesions, forming rims. In susceptibility-based magnetic resonance imaging at 7 T, iron-laden microglia/macrophages induce a rim of decreased signal at lesion edges and have been associated with slowly expanding lesions. We aimed to determine (1) what lesion types and stages are associated with iron accumulation at their edges, (2) what cells at the lesion edges accumulate iron and what is their activation status, (3) how reliably can iron accumulation at the lesion edge be detected by 7 T magnetic resonance imaging (MRI), and (4) if lesions with rims enlarge over time in vivo, when compared to lesions without rims. Double-hemispheric brain sections of 28 MS cases were stained for iron, myelin, and microglia/macrophages. Prior to histology, 4 of these 28 cases were imaged at 7 T using post-mortem susceptibility-weighted imaging. In vivo, seven MS patients underwent annual neurological examinations and 7 T MRI for 3.5 years, using a fluid attenuated inversion recovery/susceptibility-weighted imaging fusion sequence. Pathologically, we found iron rims around slowly expanding and some inactive lesions but hardly around remyelinated shadow plaques. Iron in rims was mainly present in microglia/macrophages with a pro-inflammatory activation status, but only very rarely in astrocytes. Histological validation of post-mortem susceptibility-weighted imaging revealed a quantitative threshold of iron-laden microglia when a rim was visible. Slowly expanding lesions significantly exceeded this threshold, when compared with inactive lesions (p = 0.003). We show for the first time that rim lesions significantly expanded in vivo after 3.5 years, compared to lesions without rims (p = 0.003). Thus, slow expansion of MS lesions with rims, which reflects chronic lesion activity, may, in the future, become an MRI marker for disease activity in MS.

Self-reported and informant-reported memory functioning and awareness in patients with mild cognitive impairment and Alzheimer´s disease.

BACKGROUND: Awareness of subjective memory is an important factor for adequate treatment of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). This study served to find out whether awareness of subjective memory complies with objective performance, if differences in awareness are observed longitudinally and whether decrease of awareness can serve as a predictor of AD in MCI patients. METHODS: Thirty-four patients with MCI seeking help in a memory outpatient clinic were included. All participants underwent thorough neuropsychological examination. Awareness of subjective memory was obtained by calculating difference scores between patient and informant ratings on a 16-item questionnaire concerning complaints about loss of memory in every-day life. Retesting was performed after a mean follow-up period of 24 months. RESULTS: Whole group analyses showed that awareness remained relatively stable across time. Self-reported memory complaints correlated with episodic memory at baseline and with performance on a language task at follow-up. Retests displayed decrease of awareness. At group level differences in awareness between both times of assessment were not significant for MCI and MCI patients converting to mild AD at follow-up. The predictive value of awareness was low. CONCLUSIONS: Awareness of subjective memory deficit is linked to episodic memory function and decreases with decline of cognitive ability. Further studies evaluating predictive power of awareness of subjective memory should include a larger patient sample.

Between- and within-site variability of fMRI localizations.

This study provides first data about the spatial variability of fMRI sensorimotor localizations when investigating the same subjects at different fMRI sites. Results are comparable to a previous patient study. We found a median between-site variability of about 6 mm independent of task (motor or sensory) and experimental standardization (high or low). An intraclass correlation coefficient analysis using data quality measures indicated a major influence of the fMRI site on variability. In accordance with this, within-site localization variability was considerably lower (about 3 mm). We conclude that the fMRI site is a considerable confound for localization of brain activity. However, when performed by experienced clinical fMRI experts, brain pathology does not seem to have a relevant impact on the reliability of fMRI localizations. Hum Brain Mapp 37:2151-2160, 2016. © 2016 Wiley Periodicals, Inc.

Gaucher cells are not associated with α-synuclein neuropathology in infants.

A link between Gaucher disease (GD) and Parkinson disease (PD) has been suggested by many studies. Lewy-body-like α-synuclein inclusions have been shown in older GD patients who developed Parkinsonism. It has been proposed that decreased levels of glucocerebrosidase mediate impaired α-synuclein degradation and hence its accumulation. Nevertheless, this phenomenon is less investigated in the infantile form of GD. The aim of the study was to evaluate α-synuclein and τ-pathology in the brain and non-neural tissues (liver, spleen, pancreas, myocardial muscle, and lung) of 5 infants (age range from 1 month to 4 years) with GD. Our immunohistochemical study did not provide evidence that pathological α-synuclein or τ-accumulates early in tissues where Gaucher cells are already prominently present. Although recent finding of altered plasma α-synuclein levels in infantile GD patients suggest an early imbalance of α-synuclein homeostasis, our findings indicate that this does not inevitably coincide with α-synuclein pathology in the brain. Understanding this temporal variance of plasma levels and brain accumulation of α-synuclein might also be important when interpreting blood-based α-synuclein assays for the diagnosis of PD.

Activities of Daily Living and Depressive Symptoms in Patients with Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease.

BACKGROUND: Subjective cognitive decline (SCD) may be an early indicator for an increased risk of dementia. The exact definition of SCD remains unclear and has recently become a major research interest. OBJECTIVES: To determine impairments in activities of daily living (ADL) and depressive symptoms in elderly individuals with SCD, mild cognitive impairment (MCI), and Alzheimer's disease (AD). METHODS: We included 752 consecutive patients suffering from SCD, non-amnestic (naMCI) or amnestic MCI (aMCI), AD, and 343 healthy controls into this prospective cohort study. A neuropsychological test battery, B-ADL and BDI-II was performed. RESULTS: SCD patients showed a decreased performance in ADL compared to controls. Performance in ADL declined concurrently with cognitive abilities along the controls-SCD-naMCI-aMCI-AD continuum. Individuals with cognitive complains, no matter if SCD, MCI, or AD patients, reported more often depressive symptoms compared to healthy controls without complaints. Within all five cognitive subgroups, patients with depressive symptoms reported more difficulties in ADL in comparison to patients without depressive symptoms. Adjusting for depressive symptoms, there was no significant group difference between the control versus the SCD group (OR 1.1, CI 0.6-1.7). CONCLUSIONS: SCD is a heterogeneous clinical condition. Specific features such as slightly impaired ADL and depressive symptoms are associated with SCD. Clinical markers may serve as an indicator for preclinical AD and in combination with biomarkers guide to an early diagnosis of a progressive neurodegenerative disease.