Post-COVID-19 Syndrome is Rarely Associated with Damage of the Nervous System: Findings from a Prospective Observational Cohort Study in 171 Patients.

INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect multiple organs. Reports of persistent or newly emergent symptoms, including those related to the nervous system, have increased over the course of the pandemic, leading to the introduction of post-COVID-19 syndrome. However, this novel syndrome is still ill-defined and structured objectification of complaints is scarce. Therefore, we performed a prospective observational cohort study to better define and validate subjective neurological disturbances in patients with post-COVID-19 syndrome. METHODS: A total of 171 patients fulfilling the post-COVID-19 WHO Delphi consensus criteria underwent a comprehensive neurological diagnostic work-up including neurovascular, electrophysiological, and blood analysis. In addition, magnetic resonance imaging (MRI) and lumbar puncture were conducted in subgroups of patients. Furthermore, patients underwent neuropsychological, psychosomatic, and fatigue assessment. RESULTS: Patients were predominantly female, middle-aged, and had incurred mostly mild-to-moderate acute COVID-19. The most frequent post-COVID-19 complaints included fatigue, difficulties in concentration, and memory deficits. In most patients (85.8%), in-depth neurological assessment yielded no pathological findings. In 97.7% of the cases, either no diagnosis other than post COVID-19 syndrome, or no diagnosis likely related to preceding acute COVID-19 could be established. Sensory or motor complaints were more often associated with a neurological diagnosis other than post-COVID-19 syndrome. Previous psychiatric conditions were identified as a risk factor for developing post-COVID-19 syndrome. We found high somatization scores in our patient group that correlated with cognitive deficits and the extent of fatigue. CONCLUSIONS: Albeit frequently reported by patients, objectifiable affection of the nervous system is rare in post-COVID-19 syndrome. Instead, elevated levels of somatization point towards a pathogenesis potentially involving psychosomatic factors. However, thorough neurological assessment is important in this patient group in order to not miss neurological diseases other than post-COVID-19.

Cognitive Impairment in Adult Patients with 5q-Associated Spinal Muscular Atrophy.

In previous studies, a below-average, average, or above-average intelligence quotient (IQ) in children with SMA was detected but, aside from a severe physical disability, the cognitive performance of adult SMA patients has not yet been evaluated. The intelligence test used in this study, the Wechsler Adult Intelligence Scale, fourth edition (WAIS-IV), was used to measure major intelligence components of adult SMA patients. The WAIS-IV determines four index scores representing verbal comprehension, perceptual reasoning, working memory, and processing speed. Due to time-dependent demands on motor function, the processing speed index score was excluded. IQ index scores of 33 adult SMA patients did not differ from IQ index scores of the normal population. In SMA type-3 patients, the index scores for verbal comprehension, perceptual reasoning, and working memory did not differ from the normal population but showed a trend of IQ scores towards lower points. Patients with SMA type 2 had lower IQ index scores for working memory (90.33 ± 12.95; p = 0.012) and perceptual reasoning (90.73 ± 12.58; p = 0.013) than the normal population. This study provided further evidence that SMA is a multi-systemic disease and may refute the widespread hypothesis that SMA patients might improve their cognitive skills to compensate for their physical impairment.

Cognitive Function After Lung Transplantation.

Cognitive functioning after transplantation, which could influence medication compliance and independence, has not been well studied. This study investigated cognitive impairment after lung transplantation. Patients undergoing bilateral transplant between March 2013 and October 2015 underwent comprehensive neuropsychological assessment at 60.1 ± 44.1 months post-transplantation: verbal memory (Auditory-Verbal Learning Test, digit span forward), visual memory (Corsi Block-Tapping Test forward, Benton Visual Retention Test), concentration/speed of processing/attention (D2 Test of Attention, Trail Making Test (TMT) A, Grooved Pegboard), and executive functioning (TMT B, Stroop Color-Word Test, semantic and phonematic verbal fluency, digit span backward, Corsi Block-Tapping Test backward). Mean scores were compared with a normative dataset using a one-sample t-test. A cognitive domain was judged impaired if the score on two or more domain-specific tests was greater than one standard deviation below the normative dataset age range mean. Of 124 lung transplant recipients (51% male, 54.3 ± 9.0 years), 70% showed cognitive impairment in one or more domains. Executive function was most often impaired (78% of recipients not within the age range) followed by verbal memory impairment (72% not within the age range). Cognitive function reductions were largely independent of age, gender, education, immunosuppressive medications, and time since transplantation. The findings show that cognitive impairment is common after lung transplantation and should be subject to rehabilitation and psychological resilience strategies.

Impairments in learning by monetary rewards and alcohol-associated rewards in detoxified alcoholic patients.

BACKGROUND: Excessive alcohol consumption has been linked to structural and functional brain changes associated with cognitive, emotional, and behavioral impairments. It has been suggested that neural processing in the reward system is also affected by alcoholism. The present study aimed at further investigating reward-based associative learning and reversal learning in detoxified alcohol-dependent patients. METHODS: Twenty-one detoxified alcohol-dependent patients and 26 healthy control subjects participated in a probabilistic learning task using monetary and alcohol-associated rewards as feedback stimuli indicating correct responses. Performance during acquisition and reversal learning in the different feedback conditions was analyzed. RESULTS: Alcohol-dependent patients and healthy control subjects showed an increase in learning performance over learning blocks during acquisition, with learning performance being significantly lower in alcohol-dependent patients. After changing the contingencies, alcohol-dependent patients exhibited impaired reversal learning and showed, in contrast to healthy controls, different learning curves for different types of rewards with no increase in performance for high monetary and alcohol-associated feedback. CONCLUSIONS: The present findings provide evidence that dysfunctional processing in the reward system in alcohol-dependent patients leads to alterations in reward-based learning resulting in a generally reduced performance. In addition, the results suggest that alcohol-dependent patients are, in particular, more impaired in changing an established behavior originally reinforced by high rewards.

Pallidal deep brain stimulation relieves camptocormia in primary dystonia.

Camptocormia, characterised by a forward flexion of the thoracolumbar spine may occur in various movement disorders, mainly in Parkinson's disease or in primary dystonia. In severe cases, patients with camptocormia are unable to walk. While treatment options are limited, deep brain stimulation (DBS) with bilateral stimulation of the subthalamic nucleus or globus pallidus internus (GPi) has been proposed as a therapeutic option in refractory cases of Parkinson's disease. Here we present two patients with severe camptocormia as an isolated form of dystonia and as part of generalised dystonia, respectively, which were both treated with bilateral stimulation of the GPi. Symptoms of dystonia were assessed using the Burke-Fahn-Marsden dystonia rating scale (BFM) before and during deep brain stimulation. In both patients there was a significant functional improvement following long-term bilateral GPi stimulation and both patients gained ability to walk. In the first patient with an isolated dystonic camptocormia the BFM motor subscore for the truncal flexion improved by 75 %. The total BFM motor score in the second patient with a camptocormia in generalised dystonia improved by 45 %, while the BFM score for truncal flexion improved by 87 %. In both patients the effect of the bilateral GPi stimulation on camptocormia was substantial, independent of generalisation of dystonia. Therefore, GPi DBS is a possible treatment option for this rare disease.

Cognitive function after transapical aortic valve implantation: a single-centre study with 3-month follow-up.

OBJECTIVES: Reports on adverse neurological events following transcatheter aortic valve implantation (TAVI) have focused on strokes, while more subtle postoperative cognitive decline has not yet been systematically investigated. In this study, we prospectively examined neurological and cognitive outcomes in patients undergoing transapical (TA) and surgical aortic valve replacement (AVR). METHODS: A total of 64 patients with severe symptomatic aortic stenosis were investigated between January 2008 and July 2009. Clinical neurological examination and comprehensive neuropsychological testing were performed before and after the procedure, at discharge and at 3-month follow-up. Diffusion-weighted magnetic resonance imaging (DW-MRI) was applied to detect morphological brain injury. RESULTS: TA-TAVI patients (n = 27) were older and at higher surgical risk compared with surgical AVR patients (n = 37; mean age 82.2 ± 4.7 vs 67.5 ± 8.9 years; log EuroSCORE 36.4 ± 13.2 vs 2.6 ± 8.5%, both P <0.001). There was one stroke in each group (3.7 vs 2.7%, P = 0.49), both classified as embolic based on imaging characteristics. After TA-TAVI, cognitive tests showed no decline during follow-up, while, after AVR, 7 of 11 tests showed a decline early after surgery. Similarly, with-in patient analysis showed that the rate of individuals with clinically relevant cognitive decline was increased early after AVR (TA-TAVI vs AVR: 18 vs 46% at discharge [P = 0.03]; 28 vs 6% at 3 months [P = 0.04]). New focal ischaemic cerebral lesions were detected on DW-MRI in 58% (7 of 12) of patients after TA-TAVI vs 34% (12 of 35) after AVR (P = 0.13). The number of brain lesions per patient and cumulative embolic load per patient were similar between groups. An association between postoperative cerebral ischaemia and cognitive dysfunction was not found (odds ratio 2.37, 95% confidence interval 0.05-113.75, P = 0.66). CONCLUSIONS: Cognitive function was only mildly impaired after TA-TAVI when compared with a marked, albeit transient, decline after surgical AVR. Focal embolic brain injury tended to occur more frequently after TA-TAVI, but this was not related to cognitive decline during the 3-month follow-up.

Evaluation-related frontocentral negativity evoked by correct responses and errors.

An event-related potential (ERP) with frontocentral negativity is known to be evoked by error responses, but may also occur on correct response trials. The error-related negativity (ERN) is thought to be generated in the anterior cingulate cortex (ACC). The current study aimed to further elucidate its functional significance as well as its neuronal correlates by directly comparing its amplitude and time course on correct and error trials in a continuous performance task (CPT). Results yielded a frontocentral positive potential preceding correct responses and a high amplitude post-response frontocentral negative potential during conditions involving response competition. To remove potential no-confounding effects of the positive component preceding the motor response, a second experiment was conducted where a red fixation cross served as a cue for potential response competition tendencies. Again, results yielded highest post-response amplitudes on correct trials involving response competition. The positive pre-response potential was eliminated by the visual cue. Interestingly, the cue led to an enhancement of the negative post-response component on trials without response competition. Taken together, the frontocentral post-response negativity might reflect evaluative rather than error-related processing.

Modulation of gamma and alpha activity during a working memory task engaging the dorsal or ventral stream.

Despite extensive experimental work in both animals and humans, the actual role of oscillatory brain activity for working memory maintenance remains elusive. Gamma band activity (30-100 Hz) has been hypothesized to reflect either the maintenance of neuronal representations or changing demands in attention. Regarding posterior alpha activity (8-13 Hz), it is under debate whether it reflects functional inhibition or neuronal processing required for the task. The aim of the present study was to further elucidate the role of oscillatory brain activity in humans using a working memory task engaging either the dorsal or ventral visual stream. We recorded brain activity using magnetoencephalography from subjects performing a delayed-match-to-sample task. Subjects were instructed to remember either the identity or the spatial orientation of shortly presented faces. The analysis revealed stronger alpha power around the parieto-occipital sulcus during retention of face identities (ventral stream) compared with the retention of face orientations (dorsal stream). In contrast, successful retention of face orientations was associated with an increase in gamma power in the occipital lobe relative to the face identity condition. We propose that gamma activity reflects the actual neuronal maintenance of visual representations, whereas the alpha increase is a result of functional inhibition.

Self recognition versus recognition of others by biological motion: viewpoint-dependent effects.

We investigated the influence of viewing angle on performance in recognising the identity of one's own person and familiar individuals such as friends or colleagues from walking patterns. Viewpoint-dependent recognition performance was tested in two groups of twelve persons who knew each other very well. Participants' motion data were acquired by recording their walking patterns in three-dimensional space with the use of a motion capture system. Size-normalised point-light displays of biological motion of these walking patterns, including one's own, were presented to the same group members on a computer screen in frontal view, half-profile view, and profile view. Observers were requested to assign the person's name to the individual gait pattern. No feedback was given. Whereas recognition performance of one's own walking patterns was viewpoint independent, recognition rate for other familiar individuals was better for frontal and half-profile view than for profile view. These findings are discussed in the context of the theory of common coding of motor and visual body representations.

Differential involvement of the cerebellum in biological and coherent motion perception.

Perception of biological motion (BM) is a fundamental property of the human visual system. It is as yet unclear which role the cerebellum plays with respect to the perceptual analysis of BM represented as point-light displays. Imaging studies investigating BM perception revealed inconsistent results concerning cerebellar contribution. The present study aimed to explore the role of the cerebellum in the perception of BM by testing the performance of BM perception in patients suffering from circumscribed cerebellar lesions and comparing their performance with an age-matched control group. Perceptual performance was investigated in an experimental task testing the threshold to detect BM masked by scrambled motion and a control task testing the detection of motion direction of coherent motion masked by random noise. Results show clear evidence for a differential contribution of the cerebellum to the perceptual analysis of coherent motion compared with BM. Whereas the ability to detect BM masked by scrambled motion was unaffected in the patient group, their ability to discriminate the direction of coherent motion in random noise was substantially affected. We conclude that intact cerebellar function is not a prerequisite for a preserved ability to detect BM. Because the dorsal motion pathway as well as the ventral form pathway contribute to the visual perception of BM, the question of whether cerebellar dysfunction affecting the dorsal pathway is compensated for by the unaffected ventral pathway or whether perceptual analysis of BM is performed completely without cerebellar contribution remains to be determined.

Structural encoding and recognition of biological motion: evidence from event-related potentials and source analysis.

In the present study, we investigated how different processing stages involved in the perceptual analysis of biological motion (BM) are reflected by modulations in event-related potentials (ERP) in order to elucidate the time course and location of neural processing of BM. Data analysis was carried out using conventional averaging techniques as well as source localization with low resolution brain electromagnetic tomography (LORETA). ERPs were recorded in response to point-light displays of a walking person, an inverted walking person and displays of scrambled motion. Analysis yielded a pronounced negativity with a peak at 180 ms after stimulus onset which was more pronounced for upright walkers than for inverted walkers and scrambled motion. A later negative component between 230 and 360 ms after stimulus onset had a larger amplitude for upright and inverted walkers as compared to scrambled walkers. In the later component, negativity was more pronounced in the right hemisphere revealing asymmetries in BM perception. LORETA analysis yielded evidence for sources specific to BM within the right fusiform gyrus and the right superior temporal gyrus for the second component, whereas sources for BM in the early component were located in areas associated with attentional aspects of visual processing. The early component might reflect the pop-out effect of a moving dot pattern representing the highly familiar form of a human figure, whereas the later component might be associated with the specific analysis of motion patterns providing biologically relevant information.

Biological motion as a cue for the perception of size.

Animals as well as humans adjust their gait patterns in order to minimize energy required for their locomotion. A particularly important factor is the constant force of earth's gravity. In many dynamic systems, gravity defines a relation between temporal and spatial parameters. The stride frequency of an animal that moves efficiently in terms of energy consumption depends on its size. In two psychophysical experiments, we investigated whether human observers can employ this relation in order to retrieve size information from point-light displays of dogs moving with varying stride frequencies across the screen. In Experiment 1, observers had to adjust the apparent size of a walking point-light dog by placing it at different depths in a three-dimensional depiction of a complex landscape. In Experiment 2, the size of the dog could be adjusted directly. Results show that displays with high stride frequencies are perceived to be smaller than displays with low stride frequencies and that this correlation perfectly reflects the predicted inverse quadratic relation between stride frequency and size. We conclude that biological motion can serve as a cue to retrieve the size of an animal and, therefore, to scale the visual environment.