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The integrity of cortical motor networks and their descending effector-pathway (the corticospinal tract; CST) is a major determinant motor recovery after stroke. However, this view neglects the importance of ascending tracts and their modulatory effects on cortical physiology. Here, we explore the role of such a tract that connects dopaminergic ventral tegmental midbrain nuclei to motor cortex (the VTMC-tract) for post-stroke recovery.Lesion data and diffusivity parameters (fractional anisotropy) of the ipsi- and contralesional VTMC-tract and CST were obtained from 133 patients (63.9±13.4 years, 45 female) during acute and chronic stage after first-ever ischemic stroke in the middle cerebral artery territory. Degeneration of VTMC-tract and CST was quantified and related to clinical outcome parameters (National Institute of Health Stroke Scale [NIHSS] with motor and cortical-symptom subscores; modified Fugl-Meyer upper extremity score [mFMMS]; modified Ranking Scale [mRS]).A significant post-stroke degeneration occurred in both tracts, but only VTMC-degeneration was associated with lesion size. Using multiple regression models, we dissected the impact of particular tracts on recovery: Changes in VTMC-tract integrity were stronger associated with independence in daily activities (mRS), upper limb motor impairment (mFMMS) and cortical symptoms (aphasia, neglect) captured by NIHSS compared to CST. Changes in CST-integrity merely were associated with the degree of hemiparesis (NIHSS motor subscale).Post-stroke outcome is influenced by ascending (VTMC) and descending (CST) fiber tracts. Favourable outcome regarding independence (mRS), upper limb motor function (mFMMS) and cortical symptoms (aphasia, neglect) was stronger related to the ascending than descending tract. This article is protected by copyright. All rights reserved.

The anatomical relationship between speech apraxia (SA) and oral apraxia (OA) is still unclear. To shed light on this matter we studied 137 patients with acute ischaemic left-hemisphere stroke and performed support vector regression-based, multivariate lesion–symptom mapping. Thirty-three patients presented with either SA or OA. These two symptoms mostly co-occurred (n = 28), except for few patients with isolated SA (n = 2) or OA (n = 3). All patient with either SA or OA presented with aphasia (p p

ZusammenfassungDie COVID-19-Pandemie hat erhebliche Auswirkungen auf die psychische Gesundheit. Neben Ängsten um die ökonomische Situation, die eigene Gesundheit und die Gesundheit anderer Menschen können auch Maßnahmen der Pandemiekontrolle wie Distanzierung und die dadurch bedingte Isolation psychosoziale Folgen haben. Schließlich kann die Infektion selbst im Rahmen einer systemischen Manifestation zu psychiatrischen und neuropsychiatrischen Symptomen führen. In dieser Arbeit werden unterschiedliche Mechanismen dargestellt, die mittelbar oder unmittelbar zu neuropsychologischen und psychopathologischen Symptomen im Kontext der COVID-19-Pandemie führen können.

Apraxia is frequently described after left hemisphere stroke and results from lesions to a complex network for motor cognition with dorso-dorsal, ventro-dorsal and ventral processing streams. Apraxia also occurs after right hemisphere stroke, but lesion correlates and underlying mechanisms remain to be elucidated. To clarify the role of the right hemisphere in apraxic deficits and the influence of neglect, we prospectively examined apraxia (imitation of meaningless postures and pantomime of tool use) and neglect in 138 acute right hemisphere stroke patients with first-ever ischemic stroke in the middle cerebral artery territory and identified corresponding lesion correlates using voxel-based lesion-symptom mapping. Imitation of meaningless postures was impaired as frequently as after left hemisphere stroke (38.4%) and was significantly associated with neglect. Imitation of meaningless postures was related to temporal (middle temporal gyrus, temporoparietal junction, superior temporal gyrus and sulcus), parietal (angular gyrus, parieto-occpitpial sulcus), secondary sensorimotor cortex and (peri-)insular lesions. Presence of neglect dichotomized the results: a lesion correlate for isolated imitation without neglect was found in the right parieto-occipital cortex, while imitation deficits, when co-occurring with neglect, were related to lateral occipito-temporal, superior temporal sulcus and (peri-)insular lesions. Pantomime of tool use deficits, typical for apraxia after left hemisphere lesions, were found in only 5 cases (3.6%) and only in the context of neglect, and were associated with occipital lobe, ventral and anterior temporal lobe, and inferior frontal (areas 45/47) lesions. The syndrome of apraxia after right hemisphere stroke differs from apraxia after left hemisphere stroke. Imitation deficits are found in both hemispheres after dorso-dorsal stream lesions. Neglect also leads to and explains deficits in imitation and pantomime in patients with right ventral stream lesions. Therefore, in right hemisphere lesions, apraxia can either be explained as impaired visuomotor transformation or as a result of visuospatial deficits.

While neuropathological examinations in patients who died from COVID-19 revealed inflammatory changes in cerebral white matter, cerebral MRI frequently fails to detect abnormalities even in the presence of neurological symptoms. Application of multi-compartment diffusion microstructure imaging (DMI), that detects even small volume shifts between the compartments (intra-axonal, extra-axonal and free water/CSF) of a white matter model, is a promising approach to overcome this discrepancy. In this monocentric prospective study, a cohort of 20 COVID-19 inpatients (57.3 ± 17.1 years) with neurological symptoms (e.g. delirium, cranial nerve palsies) and cognitive impairments measured by the Montreal Cognitive Assessment (MoCA test; 22.4 ± 4.9; 70% below the cut-off value In summary, DMI in subacute COVID-19 patients revealed widespread volume shifts compatible with vasogenic oedema, affecting various supratentorial white matter tracts. These changes were associated with cognitive impairment and COVID-19 related changes in 18F-FDG PET imaging.

Irrespective of the great impact stroke exerts on the society as a whole and far-reaching advances in acute treatment and rehabilitation of stroke, so far outpatient services for post-stroke care have not been established on a national level in Germany.Against the background of this contemporary lack of care, in May 2020 the German Stroke Society (DSG) established the stroke aftercare commission. This position paper discusses structural models of future services addressing outpatient post-stroke care.The specialized care by a neurologist should be central to a multidisciplinary, interprofessional and transsectoral treatment. Structural concepts of post-stroke care must take regional differences but also effective strategies for quality control into account. Certification processes and appropriate financing of follow-up registries at state and federal levels may pave the way for improvement over the medium term. Structured outpatient post-stroke care services should be open to all subgroups of stroke patients. Additionally, innovative technologies can make an important contribution to post-stroke care; however, the implementation of specialized services demands adequate funding as well as separate financial incentives for the providers. The solution must carefully balance the advantages and disadvantages of the specific care and financing models. Currently the discussion of new models of post-stroke care is gaining new momentum, which opens up perspectives for the advancement of the otherwise still insufficient contemporary care structures.HINTERGRUND: Ungeachtet der großen gesamtgesellschaftlichen Bedeutung des Schlaganfalls sowie der Fortschritte in der Akutversorgung und Rehabilitation konnten bisher keine flächendeckenden Versorgungsstrukturen zur strukturierten ambulanten Nachsorge in Deutschland etabliert werden.Vor dem Hintergrund der bestehenden Versorgungslücken wurde im Mai 2020 die Kommission Schlaganfallnachsorge der Deutschen Schlaganfall-Gesellschaft (DSG) gegründet. Das Positionspapier diskutiert strukturelle Konzepte für zukünftige Versorgungsformen der Schlaganfallnachsorge.Eine neurologische Betreuung sollte zentraler Bestandteil einer multidisziplinären, interprofessionellen und sektorenübergreifenden Behandlungsplanung sein. Strukturelle Konzepte zur Schlaganfallnachsorge müssen sowohl regionale Strukturunterschiede als auch den Aspekt der Qualitätssicherung berücksichtigen. Zertifizierungsprozesse und die angemessene Finanzierung von Nachsorgeregistern auf Landes- und Bundesebene können den Weg hierhin mittelfristig ebnen. Das Angebot zur strukturierten Schlaganfallnachsorge sollte allen Subgruppen von Schlaganfallpatienten offenstehen. Auch innovative Technologien können einen wichtigen Beitrag zur Schlaganfallnachsorge leisten. Die Einführung und Umsetzung einer strukturierten Schlaganfallnachsorge bedarf in jedem Fall einer ausreichenden Finanzierung und eigener finanzieller Anreize für die Leistungsträger. Die Vor- und Nachteile der spezifischen Versorgungs- und Finanzierungsmodelle müssen dabei kritisch gegeneinander abgewogen werden. Die Diskussion neuer Versorgungsformen zur Schlaganfallnachsorge erfährt gegenwärtig ein neues Momentum und eröffnet Perspektiven für eine Verbesserung der aktuell noch unzureichenden Versorgungslösung.

During the Corona Virus Disease 2019 (COVID-19) pandemic, Long COVID-syndrome, which impairs patients through cognitive deficits, fatigue, and exhaustion, has become increasingly relevant. Its underlying pathophysiology, however, is unknown. In this study, we assessed cognitive profiles and regional cerebral glucose metabolism as a biomarker of neuronal function in outpatients suffering from long-term neurocognitive symptoms after COVID-19. Methods: Outpatients seeking neurological counseling with neurocognitive symptoms persisting for more than three months after polymerase chain reaction (PCR)-confirmed COVID-19 were included prospectively between June 16, 2020, and January 29, 2021. Patients (n = 31, 54±2.0 years) in the long-term phase after COVID-19 (202±58 days after positive PCR) were assessed with a neuropsychological test battery. Cerebral 18F-FDG PET imaging was performed in 14/31 patients. Results: Patients self-reported impaired attention, memory, and multitasking abilities (31/31), word-finding difficulties (27/31), and fatigue (24/31). Twelve of 31 patients could not return to the previous level of independence/employment. For all cognitive domains, average group results of the neuropsychological test-battery showed no impairment, but deficits (z-score

The COVID-19 pandemic has a significant impact on mental health. On the one hand, fears about one's economic situation, own health and the health of others can lead to psychosocial consequences. On the other hand, social isolation through physical distancing can affect mental health. Finally, the infection itself can lead to psychiatric and neuropsychiatric symptoms as part of a systemic manifestation. In this paper, different mechanisms are presented, which can lead directly or indirectly to neuropsychological and psychopathological symptoms in the context of the COVID-19 pandemic.Die COVID-19-Pandemie hat erhebliche Auswirkungen auf die psychische Gesundheit. Neben Ängsten um die ökonomische Situation, die eigene Gesundheit und die Gesundheit anderer Menschen können auch Maßnahmen der Pandemiekontrolle wie Distanzierung und die dadurch bedingte Isolation psychosoziale Folgen haben. Schließlich kann die Infektion selbst im Rahmen einer systemischen Manifestation zu psychiatrischen und neuropsychiatrischen Symptomen führen. In dieser Arbeit werden unterschiedliche Mechanismen dargestellt, die mittelbar oder unmittelbar zu neuropsychologischen und psychopathologischen Symptomen im Kontext der COVID-19-Pandemie führen können.

Ziel/Aim Given the rapid spread of SARS-CoV-2 and emerging evidence of neurological symptoms particularly in hospitalized COVID-19 patients, we examined the impact of COVID-19 on the CNS in inpatients at the subacute stage by F-18-FDG PET. Methodik/Methods We assessed neurological and neuropsychological symptoms (MoCA) and F-18-FDG PET scans in 15 COVID-19 inpatients (once patients were no longer infectious). All scans were visually read using a 3-step rating scale (normal, mildly and severely abnormal). Principal components analysis (PCA;avoiding the need of a currently unknown reference region) was employed to explore whether a spatial covariance pattern exists in COVID-19 (compared to 45 control patients without somatic CNS disease). Exploratory, we assessed mean normalized F-18-FDG uptake (lean body weight- and plasma glucose-adjusted standardized uptake value, SUV) in 10 % voxels with highest covariance weights (positive and negative). Ergebnisse/Results Visual reads indicated pathological results in 10/15 patients (mainly frontotemporal hypometabolism). We detected a highly significant (p .39] in 10 % voxels with most negative and positive weights, respectively). Schlussfolgerungen/Conclusions Neocortical dysfunction accompanied by cognitive impairment was detected in two-thirds of inpatients with subacute COVID-19. A clear indication of regional hypermetabolism (suggesting inflammation) was not found. Follow-up studies are currently underway.

Cognitive impairment is a frequent complaint in coronavirus disease-19 (COVID-19) and can be related to cortical hypometabolism on 18F-FDG PET at the subacute stage. However, it is unclear if these changes are reversible. Methods: We prospectively assessed Montreal Cognitive Assessment (MoCA) and 18F-FDG PET scans in 8 COVID-19 patients at the subacute (as no longer infectious) and chronic stages (approximately six months after symptom onset). The expression of the previously established COVID-19-related covariance pattern was analyzed at both stages to examine the time course of post-COVID-19 cognitive impairment. For further validation, we also conducted a conventional group analysis. Results: Follow-up 18F-FDG PET revealed a significant reduction of initial frontoparietal and, to a lesser extent, temporal glucose hypometabolism that was accompanied by a significant improvement in cognition. The expression of the previously established COVID-19-related pattern was significantly lower at follow-up and correlated inversely with MoCA performance. However, both 18F-FDG PET and cognitive assessment suggest a residual impairment. Conclusions: Although a significant recovery of regional neuronal function and cognition can be clearly stated, residuals are still measurable in some patients six months after the manifestation of COVID-19. Given the current pandemic situation and tremendous uncertainty concerning the long-term effects of COVID-19, the present study provides novel insights of highest medical and socioeconomic relevance.

Objective This study investigates the clinical course of recovery of apraxia after left-hemisphere stroke and the underlying neuroanatomical correlates for persisting or recovering deficits in relation to the major processing streams in the network for motor cognition. Methods 90 patients were examined during the acute (4.74 ± 2.73 days) and chronic (14.3 ± 15.39 months) stage after left-hemisphere stroke for deficits in meaningless imitation, as well as production and conceptual errors in tool use pantomime. Lesion correlates for persisting or recovering deficits were analyzed with an extension of the non-parametric Brunner-Munzel rank-order test for multi-factorial designs (two-way repeated-measures ANOVA) using acute images. Results Meaningless imitation and tool use production deficits persisted into the chronic stage. Conceptual errors in tool use pantomime showed an almost complete recovery. Imitation errors persisted after occipitotemporal and superior temporal lesions in the dorso-dorsal stream. Chronic pantomime production errors were related to the supramarginal gyrus, the key structure of the ventro-dorsal stream. More anterior lesions in the ventro-dorsal stream (ventral premotor cortex) were additionally associated with poor recovery of production errors in pantomime. Conceptual errors in pantomime after temporal and supramarginal gyrus lesions persisted into the chronic stage. However, they resolved completely when related to angular gyrus or insular lesions. Conclusion The diverging courses of recovery in different apraxia tasks can be related to different mechanisms. Critical lesions to key structures of the network or entrance areas of the processing streams lead to persisting deficits in the corresponding tasks. Contrary, lesions located outside the core network but inducing a temporary network dysfunction allow good recovery e.g., of conceptual errors in pantomime. The identification of lesion correlates for different long-term recovery patterns in apraxia might also allow early clinical prediction of the course of recovery.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age > 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with ≥2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.

ZusammenfassungObwohl Aphasien nach ischämischen Schlaganfällen oder Hirnblutungen häufig auftreten, hat sich weder die medizinische Wissenschaft noch die obergerichtliche Rechtsprechung intensiver mit der praktisch bedeutsamen Frage beschäftigt, welche Auswirkungen diese Störung auf die Geschäftsfähigkeit hat.Mit Hilfe moderner Bildgebungsstudien ist eine differenzierte Betrachtung der unterliegenden Pathologien der erworbenen Sprachstörungen, der daraus resultierenden unterschiedlichen klinischen Bilder der Aphasie sowie dem Erholungsverlauf möglich. Auf der Basis dieser Befunde sowie dem Konzept der „Inneren Sprache“ wird untersucht, inwieweit Aphasien die Geschäftsfähigkeit beeinträchtigen könnten und ein Phasenmodell zur Beurteilung der Geschäftsfähigkeit bei Aphasie vorgeschlagen, welches die grundsätzlichen Möglichkeiten der Erholung im Rahmen neuronaler Reorganisation berücksichtigt.Die gutachtliche Beurteilung der Voraussetzungen zur Annahme einer Geschäftsfähigkeit oder -unfähigkeit bei Aphasie erfordert eine interdisziplinäre Zusammenarbeit von Neurologen, Psychiatern und Sprachtherapeuten. Da Gutachten zur Geschäftsunfähigkeit häufig ex-post erstellt werden müssen, ist der Gutachter auf eine detaillierte Befunddokumentation von Fähigkeiten und Defiziten bei Vorliegen einer Aphasie angewiesen. Um die bisherigen Limitationen in der Begutachtung der Geschäftsfähigkeit von Patienten mit Aphasien zu verbessern, wäre eine standardisierte Beschreibung der Aphasie und assoziierter neuropsychologischer Symptome als obligater Bestandteil eines Arztbriefes nach einer neurologischen Akut- und Rehabilitationsbehandlung wünschenswert.

Pure alexia is a deficit of reading affecting the ability to process a word’s letters in parallel. Instead, a slow, effortful letter-by-letter reading strategy is employed. It has been claimed that a visual impairment caused the reading impairment. The present study compares visual processing and word reading of a patient with severe visuospatial deficits due to probable posterior cortical atrophy (PCA) to two patients with pure alexia. A double dissociation emerged between visual processing and word reading: The participant with PCA was severely impaired in all visual tasks but read fluently while the patients with pure alexia read slowly but exhibited better preserved visual processing. It is concluded that a visual impairment does not inevitably lead to pure alexia, and that this syndrome is more plausibly conceived of as an orthographic deficit. In addition, the PCA patient’s hypometabolism was assessed, and the interaction of the dorsal and ventral visual stream in word reading is discussed.

We report a case of successful intravenous thrombolysis for a distal middle cerebral artery occlusion shortly after traumatic cardiopulmonary resuscitation due to an episode of ventricular tachycardia. A high prevalence of fatal cardiac arrhythmias in acute stroke patients raises the question of safety when administrating thrombolytic therapy after traumatic cardiopulmonary resuscitation; guidelines do not provide a satisfactory statement about this. Our case suggests that intravenous tissue-type plasminogen activator for acute ischemic stroke can be administered after a thorough risk-to-benefit evaluation without major adverse effects in patients after traumatic cardiopulmonary resuscitation, as bleeding complications seem rare and can be monitored and treated.

Verbal fluency for semantic categories and phonological letters is frequently applied to studies of language and executive functions. Despite its popularity, it is still debated whether measures of semantic and phonological fluency reflect the same or distinct sets of cognitive processes. Word generation in the two task variants is believed to involve different types of search processes. Findings from the lesion and neuroimaging literature further suggest a stronger reliance of phonological and semantic fluency on frontal and temporal brain areas, respectively. This evidence for differential cognitive and neural contributions is, however, strongly challenged by findings from factor analyses, which have consistently yielded only one explanatory factor. As all previous factor-analytical approaches were based on very small item sets, this apparent discrepancy may be due to methodological limitations. In this study, we therefore applied a German version of the verbal fluency task with 8 semantic (i.e. categories) and 8 phonological items (i.e. letters). An exploratory factor analysis with oblique rotation in N=69 healthy young adults indeed revealed a two-factor solution with markedly different loadings for semantic and phonological items. This pattern was corroborated by a confirmatory factor analysis in a sample of N=174 stroke patients. As results from both samples also revealed a substantial portion of common variance between the semantic and phonological factor, the present data further demonstrate that semantic and phonological verbal fluency are based on clearly distinct but also on shared sets of cognitive processes.

Visual neglect and extinction are two distinct visuospatial attention deficits that frequently occur after right hemisphere cerebral stroke. However, their different lesion profiles remain a matter of debate. In the left hemisphere, a domain-general dual-loop model with distinct computational abilities onto which several cognitive functions may project, has been proposed: a dorsal stream for sensori-motor mapping in time and space and a ventral stream for comprehension and representation of concepts. We wondered whether such a distinction may apply to visual extinction and neglect in left hemisphere lesions. Of 165 prospectively studied patients with acute left hemispheric ischemic stroke with a single lesion on MRI, 122 had no visuospatial attention deficit, 10 had extinction, 31 neglect and 2 had both, visual extinction and neglect. Voxel-based-lesion-symptom mapping (VLSM, FDR

Background Osmotic demyelination syndrome (ODS), which embraces central pontine myelinolysis (CPM) and extrapontine myelinosis (EPM), is often underdiagnosed in clinical practice, but can be fatal. In this article, we review the etiology, patho- physiology, clinical features, diagnosis, treatment, and prognosis of ODS. Methods Pertinent publications from the years 1959 to 2018 were retrieved by a selective search in PubMed. Results The most common cause of ODS is hyponatremia; particular groups of patients, e.g., liver transplant recipients, are also at risk of developing ODS. The pathophysiology of ODS consists of cerebral apoptosis and loss of myelin due to osmotic stress. Accordingly, brain areas that are rich in oligodendrocytes and myelin tend to be the most frequently affected. Patients with ODS often have a biphasic course, the first phase reflecting the underlying predisposing illness and the second phase reflecting ODS itself, with pontine dysfunction, impaired vigilance, and movement disorders, among other neurological abnormalities. The diagnostic modality of choice is magnetic resonance imaging (MRI) of the brain, which can also be used to detect oligosymptomatic ODS. The current mainstay of management is prevention; treatment strategies for manifest ODS are still experimental. The prognosis has improved as a result of MRI-based diagnosis, but ODS can still be fatal (33% to 55% of patients either die or remain permanently dependent on nursing care). Conclusion ODS is a secondary neurological illness resulting from a foregoing primary disease. Though rare overall, it occurs with greater frequency in certain groups of patients. Clinicians of all specialties should therefore be familiar with the risk constellations, clinical presentation, and prevention of ODS. The treatment of ODS is still experimental at present, as no evidence-based treatment is yet available.

Aphasia is a frequent cognitive disorder after stroke. Despite a high prevalence, there is comparatively little medical literature or high court jurisdiction concerning the question if aphasia impairs patients in their legal capacity.Imaging studies allow a detailed understanding of the underlying pathology of aphasia, the resulting clinical pictures and potential mechanisms of recovery. Based on functional-anatomical models of language and associated concepts of inner speech, the impact of language disorders on legal capacity is evaluated. A phase model for the assessment of patients with aphasia is proposed, accounting for different stages of potential recovery after stroke.In practice, evaluation of the prerequisites for legal capacity or incapacity in patients with aphasia requires an interdisciplinary cooperation between neurologists, psychiatrists and speech language therapists. In cases of ex-post assessment, the evaluation of legal incapacity at a specific date, however, relies on a detailed documentation of the patient's language impairment and its recovery. To overcome the current limitations standardized and test-based assessment of neuropsychiatric and language capacities after acute hospital treatment and rehabilitation treatment is desirable.Obwohl Aphasien nach ischämischen Schlaganfällen oder Hirnblutungen häufig auftreten, hat sich weder die medizinische Wissenschaft noch die obergerichtliche Rechtsprechung intensiver mit der praktisch bedeutsamen Frage beschäftigt, welche Auswirkungen diese Störung auf die Geschäftsfähigkeit hat.Mit Hilfe moderner Bildgebungsstudien ist eine differenzierte Betrachtung der unterliegenden Pathologien der erworbenen Sprachstörungen, der daraus resultierenden unterschiedlichen klinischen Bilder der Aphasie sowie dem Erholungsverlauf möglich. Auf der Basis dieser Befunde sowie dem Konzept der „Inneren Sprache“ wird untersucht, inwieweit Aphasien die Geschäftsfähigkeit beeinträchtigen könnten und ein Phasenmodell zur Beurteilung der Geschäftsfähigkeit bei Aphasie vorgeschlagen, welches die grundsätzlichen Möglichkeiten der Erholung im Rahmen neuronaler Reorganisation berücksichtigt.Die gutachtliche Beurteilung der Voraussetzungen zur Annahme einer Geschäftsfähigkeit oder -unfähigkeit bei Aphasie erfordert eine interdisziplinäre Zusammenarbeit von Neurologen, Psychiatern und Sprachtherapeuten. Da Gutachten zur Geschäftsunfähigkeit häufig ex-post erstellt werden müssen, ist der Gutachter auf eine detaillierte Befunddokumentation von Fähigkeiten und Defiziten bei Vorliegen einer Aphasie angewiesen. Um die bisherigen Limitationen in der Begutachtung der Geschäftsfähigkeit von Patienten mit Aphasien zu verbessern, wäre eine standardisierte Beschreibung der Aphasie und assoziierter neuropsychologischer Symptome als obligater Bestandteil eines Arztbriefes nach einer neurologischen Akut- und Rehabilitationsbehandlung wünschenswert.

Previous lesion studies suggest that semantic and phonological fluency are differentially subserved by distinct brain regions in the left temporal and the left frontal cortex, respectively. However, as of yet, this often implied double dissociation has not been explicitly investigated due to mainly two reasons: (i) the lack of sufficiently large samples of brain-lesioned patients that underwent assessment of the two fluency variants and (ii) the lack of tools to assess interactions in factorial analyses of non-normally distributed behavioral data. In addition, previous studies did not control for task resource artifacts potentially introduced by the generally higher task difficulty of phonological compared to semantic fluency.We addressed these issues by task-difficulty adjusted assessment of semantic and phonological fluency in 85 chronic patients with ischemic stroke of the left middle cerebral artery. For classical region-based lesion-behavior mapping patients were grouped with respect to their primary lesion location. Building on the extension of the non-parametric Brunner-Munzel rank-order test to multi-factorial designs, ANOVA-type analyses revealed a significant two-way interaction for cue type (semantic vs. phonological) by lesion location (left temporal vs. left frontal vs. other as stroke control group). Subsequent contrast analyses further confirmed the proposed double dissociation by demonstrating that (i) compared to stroke controls, left temporal lesions led to significant impairments in semantic but not in phonological fluency, whereas left frontal lesions led to significant impairments in phonological but not in semantic fluency, and that (ii) patients with frontal lesions showed significantly poorer performance in phonological than in semantic fluency, whereas patients with temporal lesions showed significantly poorer performance in semantic than in phonological fluency.The anatomical specificity of these findings was further assessed in voxel-based lesion-behavior mapping analyses using the multi-factorial extension of the Brunner-Munzel test. Voxel-wise ANOVA-type analyses identified circumscribed parts of left inferior frontal gyrus and left superior and middle temporal gyrus that significantly double-dissociated with respect to their differential contribution to phonological and semantic fluency, respectively. Furthermore, a main effect of lesion with significant impairments in both fluency types was found in left inferior frontal regions adjacent to but not overlapping with those showing the differential effect for phonological fluency.The present study hence not only provides first explicit evidence for the anatomical double dissociation in verbal fluency at the group level but also clearly underlines that its formulation constitutes an oversimplification as parts of left frontal cortex appear to contribute to both semantic and phonological fluency. Keywords: Verbal fluency, Brain lesion, Frontal lobe, Temporal lobe, Double dissociation

Behavioral deficits after stroke like apraxia can be related to structural lesions and to a functional state of the underlying network – three factors, reciprocally influencing each other. Combining lesion data, behavioral performance and passive functional activation of the network-of-interest, this study aims to disentangle those mutual influences and to identify 1) activation patterns associated with the presence or absence of acute apraxia in tool-associated actions and 2) the specific impact of lesion location on those activation patterns. Brain activity of 48 patients (63.31 ± 13.68 years, 35 male) was assessed in a fMRI paradigm with observation of tool-related actions during the acute phase after first-ever left-hemispheric stroke (4.83 ± 2.04 days). Behavioral assessment of apraxia in tool-related tasks was obtained independently. Brain activation was compared between patients versus healthy controls and between patient with versus without apraxia. Interaction effects of lesion location (frontal vs parietal) and behavioral performance (apraxia vs no apraxia) were assessed in a 2 × 2 factorial design. Action observation activated the ventro-dorsal parts of the network for cognitive motor function; activation was globally downregulated after stroke. Apraxic compared to non-apraxic patients showed relatively increased activity in bilateral posterior middle temporal gyrus and middle frontal gyrus/superior frontal sulcus. Altered activation occurred in regions for tool-related cognition, corroborating known functions of the ventro-dorsal and ventral streams for praxis, and comprised domain-general areas, functionally related to cognitive control. The interaction analyses revealed different levels of activation in the left anterior middle temporal gyrus in the ventral stream in apraxic patients with frontal compared to parietal lesions, suggesting a modulation of network activation in relation to behavioral performance and lesion location as separate factors. By detecting apraxia-specific activation patterns modulated by lesion location, this study underlines the necessity to combine structural lesion information, behavioral parameters and functional activation to comprehensively examine cognitive functions in acute stroke patients.

Apraxia is a debilitating cognitive motor disorder that frequently occurs after left hemisphere stroke and affects tool-associated and imitative skills. However, the severity of the apraxic deficits varies even across patients with similar lesions. This variability raises the question whether regions outside the left hemisphere network typically associated with cognitive motor tasks in healthy subjects are of additional functional relevance. To investigate this hypothesis, we explored regions where functional magnetic resonance imaging activity is associated with better cognitive motor performance in patients with left hemisphere ischaemic stroke. Thirty-six patients with chronic (>6 months) large left hemisphere infarcts (age ± standard deviation, 60 ± 12 years, 29 male) and 29 control subjects (age ± standard deviation, 72 ± 7, 15 male) were first assessed behaviourally outside the scanner with tests for actual tool use, pantomime and imitation of tool-use gestures, as well as for meaningless gesture imitation. Second, functional magnetic resonance imaging activity was registered during the passive observation of videos showing tool-associated actions. Voxel-wise linear regression analyses were used to identify areas where behavioural performance was correlated with functional magnetic resonance imaging activity. Furthermore, lesions were delineated on the magnetic resonance imaging scans for voxel-based lesion–symptom mapping. The analyses revealed two sets of regions where functional magnetic resonance imaging activity was associated with better performance in the clinical tasks. First, activity in left hemisphere areas thought to mediate cognitive motor functions in healthy individuals (i.e. activity within the putative ‘healthy’ network) was correlated with better scores. Within this network, tool-associated tasks were mainly related to activity in supramarginal gyrus and ventral premotor cortex, while meaningless gesture imitation depended more on the anterior intraparietal sulcus and superior parietal lobule. Second, repeating the regression analyses with total left hemisphere lesion volume as additional covariate demonstrated that tool-related skills were further supported by right premotor, right inferior frontal and left anterior temporal areas, while meaningless gesture imitation was also driven by the left dorso-lateral prefrontal cortex. In summary, tool-related and imitative skills in left hemisphere stroke patients depend on the activation of spared left hemisphere regions that support these abilities in healthy individuals. In addition, cognitive motor functions rely on the activation of ipsi- and contralesional areas that are situated outside this ‘healthy’ network. This activity may explain why some patients perform surprisingly well despite large left brain lesions, while others are severely impaired. * Abbreviations : ATL = : anterior temporal lobe BOLD = : blood oxygen level-dependant IFG = : inferior frontal gyrus IPL = : inferior parietal lobule MCA = : middle cerebral artery PFC = : prefrontal cortex PMC = : premotor cortex SMG = : supramarginal gyrus SPL = : superior parietal lobule VLSM = : voxel-based lesion–symptom mapping

The ability to recognize and respond to actions performed by others is fundamental for a wide range of activities involving social interactions. However, despite an enormous number of functional imaging studies, a precise delineation of the brain regions crucial for distinct aspects of action recognition has remained elusive. Moreover, the degree of overlap between regions involved in active action performance is controversial. To elucidate these issues, 98 acute stroke patients (68 male, age mean ± SD, 65 ± 13 years) were examined in the acute period after stroke (mean ± SD 4.4 ± 2 days after symptom onset). First, action recognition was assessed with a newly designed test which required patients to distinguish between correctly and incorrectly performed tool-associated actions depicted in short videos. Errors categories comprised conceptual (e.g., spreading jam on toast with a paint brush), and spatio-temporal errors (orientation of the tool, hand configuration, and movement kinematics). Second, actual use of tools was probed using an established test which, in analogy to the error categories for action recognition, included separate measures for the ability to match tools and recipients (e.g., hammer – nail; conceptual score), and for the quality of the executed action (e.g., hammering; spatio-temporal score). Lesions were delineated on diffusion-weighted scans for voxel-based lesion-symptom mapping. Impaired recognition of conceptual errors was associated mainly with lesions to the anterior middle temporal gyrus as well as to the caudal middle frontal gyrus. Conversely, the detection of spatio-temporal errors depended on the posterior superior temporal gyrus and sulcus, inferior parietal lobule (IPL) and ventral premotor cortex (vPMC). Analyses for distinct spatio-temporal error subcategories revealed that superior temporal lesions specifically affected the recognition of kinematic and tool orientation errors, while inferior parietal and premotor damage selectively impaired the discrimination of hand configurations. Lastly, compared to the recognition of conceptual and spatio-temporal errors, both active tool-recipient matching and action execution, respectively, were more dependent on the IPL and vPMC; conversely, action recognition deficits were more strongly associated with occipito-temporal and superior temporal lesions. The results demonstrate that action recognition is enabled by a network of dissociable regions that are specialized for the processing of distinct action features. While the decoding of conceptual action aspects relies mainly on anterior temporal regions, IPL and vPMC mediate the recognition of hand configurations, and the posterior superior temporal lobe is crucial for the processing of movement kinematics and tool orientation. Our findings show that, with the exception of the hand configuration, action recognition does not rely on the fronto-parietal regions that subserve the performance of actual tool use.

Imitation of tool-use gestures (transitive; e.g., hammering) and communicative emblems (intransitive; e.g., waving goodbye) is frequently impaired after left-hemispheric lesions. We aimed 1) to identify lesions related to deficient transitive or intransitive gestures, 2) to delineate regions associated with distinct error types (e.g., hand configuration, kinematics), and 3) to compare imitation to previous data on pantomimed and actual tool use. Of note, 156 patients (64.3 ± 14.6 years; 56 female) with first-ever left-hemispheric ischemic stroke were prospectively examined 4.8 ± 2.0 days after symptom onset. Lesions were delineated on magnetic resonance imaging scans for voxel-based lesion-symptom mapping. First, while inferior-parietal lesions affected both gesture types, specific associations emerged between intransitive gesture deficits and anterior temporal damage and between transitive gesture deficits and premotor and occipito-parietal lesions. Second, impaired hand configurations were related to anterior intraparietal damage, hand/wrist-orientation errors to premotor lesions, and kinematic errors to inferior-parietal/occipito-temporal lesions. Third, premotor lesions impacted more on transitive imitation compared with actual tool use, pantomimed and actual tool use were more susceptible to lesioned insular cortex and subjacent white matter. In summary, transitive and intransitive gestures differentially rely on ventro-dorsal and ventral streams due to higher demands on temporo-spatial processing (transitive) or stronger reliance on semantic information (intransitive), respectively.

The study aimed to elucidate areas involved in recognizing tool-associated actions, and to characterize the relationship between recognition and active performance of tool use.We performed voxel-based lesion-symptom mapping in a prospective cohort of 98 acute left-hemisphere ischemic stroke patients (68 male, age mean ± standard deviation, 65 ± 13 years; examination 4.4 ± 2 days post-stroke). In a video-based test, patients distinguished correct tool-related actions from actions with spatio-temporal (incorrect grip, kinematics, or tool orientation) or conceptual errors (incorrect tool-recipient matching, e.g., spreading jam on toast with a paintbrush). Moreover, spatio-temporal and conceptual errors were determined during actual tool use.Deficient spatio-temporal error discrimination followed lesions within a dorsal network in which the inferior parietal lobule (IPL) and the lateral temporal cortex (sLTC) were specifically relevant for assessing functional hand postures and kinematics, respectively. Conversely, impaired recognition of conceptual errors resulted from damage to ventral stream regions including anterior temporal lobe. Furthermore, LTC and IPL lesions impacted differently on action recognition and active tool use, respectively.In summary, recognition of tool-associated actions relies on a componential network. Our study particularly highlights the dissociable roles of LTC and IPL for the recognition of action kinematics and functional hand postures, respectively.

Impaired tool use despite preserved basic motor functions occurs after stroke in the context of apraxia, a cognitive motor disorder. To elucidate the neuroanatomical underpinnings of different tool use deficits, prospective behavioral assessments of 136 acute left-hemisphere stroke patients were combined with lesion delineation on magnetic resonance imaging (MRI) images for voxel-based lesion-symptom mapping. Deficits affecting both the selection of the appropriate recipient for a given tool (ToolSelect, e.g., choosing the nail for the hammer), and the performance of the typical tool-associated action (ToolUse, e.g., hammering in the nail) were associated with ventro-dorsal stream lesions, particularly within inferior parietal lobule. However, ToolSelect compared with ToolUse deficits were specifically related to damage within ventral stream regions including anterior temporal lobe. Additional retrospective error dichotomization based on the videotaped performances of ToolUse revealed that spatio-temporal errors (movement errors) were mainly caused by inferior parietal damage adjacent to the intraparietal sulcus while content errors, that is, perplexity, unrecognizable, or semantically incorrect movements, resulted from lesions within supramarginal gyrus and superior temporal lobe. In summary, our results suggest that in the use of tools, conceptual and production-related aspects can be differentiated and are implemented in anatomically distinct streams.

Background Meaningful gestures are one of the key features of social interaction and comprise both object-associated transitive movements (e.g. hammering) as well as intransitive movements referring to a communicative content (e.g. waving goodbye). The ability to imitate meaningful gestures is frequently impaired in apraxia due to left-hemispheric stroke. However, the pathophysiology behind these deficits so far remained unresolved. A dual stream-model for a dichotomized organisation of higher cognitive functions such as language or praxis has been proposed, with a dorsal stream involved in sensorimotor processing and a ventral stream for content and imagery. Aim of the study was to elucidate the role of the dual stream-model in imitation of meaningful movements using voxel-based lesion-symptom mapping (VLSM). Methods We performed VLSM in a sample of 136 left-hemispheric stroke patients (mean age ± SD 65 years ± 15, 83 male). Neuropsychological testing and MR-imaging were carried out in the acute phase after ischemic stroke (5.1 ± 1.9 days after symptom onset) to avoid interference with brain reorganization. Imitation deficits were assessed with a block of ten object-related movements and a block of ten communicative gestures presented by the examiner, patients were instructed to imitate the movement. Lesions were mapped on the diffusion-weighted image (if not available on Flair- image), statistical analysis with Brunner–Munzel Test was performed using non-parametric statistics implemented in MRIcron. Results Deficits in both, imitation of transitive and intransitive movements were associated with lesions in areas of the dorsal stream involved in motor control and action representations, such as the inferior parietal lobule, and the supramarginal gyrus. In addition to these common areas, deficits in imitation of intransitive movements showed a specific association with the superior and middle temporal lobe, whereas deficient transitive movements were also related to lesions within the ventral premotor cortex without involvement of temporal structures. Conclusion Deficits affecting imitation of transitive and intransitive gestures result from different and characteristic neuroanatomical lesion patterns. Our data suggest that imitation of transitive gestures depicting common tool-associated actions mainly involves stored motor programs and, thus, is mainly based on the dorsal stream. Conversely, imitation of intransitive communicative gestures additionally relies on the ventral stream, probably due to the higher semantic content, given the often symbolic character of intransitive gestures.

Background Apraxia, a disorder of higher motor control, frequently leads to impaired tool use or imitation capacities due to left hemispheric lesions. However, despite similar lesion size or location, patients present with different apraxic deficits thus different early reorganization mechanism may be assumed. To understand the impaired praxis network after stroke on a functional level, we correlated behavioral performance in imitation and tool use tasks with activation patterns in fMRI of 47 acute left-hemispheric stroke patients. Methods A cohort of 47 acute stroke patients (mean age 63.5 years ± SD 13.6; 13 female) with first ever embolic stroke in the left arteria cerebri media territory were tested for deficits in imitation of meaningless hand and finger postures and tool associated actions (pantomime of tool use, imitation of tool use, actual tool use). Testing was performed mean 4.8 days ± SD 2.9 post stroke. FMRI was acquired during presentation of video sequences of tool-associated actions viewed from a first-person perspective. Voxel wise linear regression analyses for task scores only and with lesion volume as covariate as well as group differences for categorized behavioral performance (deficit vs. no deficit) were calculated to analyze activity associated with behavioral performance in tool use and meaningless imitation. Analyses were performed using GLMflex. Results are presented on a p Results Intact imitation of meaningless postures was associated with activation in the left middle occipital gyrus as well as in the left superior temporal lobe in linear regression analyses and categorical group differences (deficit vs. no deficit). Tool associated tasks correlated with activation in the left supramarginal gyrus and superior temporal lobe without occipital activation. For group differences in pantomime of tool use (deficit vs. no deficit) an additional activation for patients with low behavioral performance could be found in the posterior middle temporal gyrus. Conclusion For intact imitation of meaningless postures and tool associated actions, specific left hemispheric activation patterns in the acute phase after stroke could be determined. These areas are commonly associated to the left hemispheric praxis network. While intact imitation of meaningless gestures seems to rely on intact left middle occipital gyrus for visual analysis of the presented movement tool associated actions rather seem to rely on integrity of the supramarginal gyrus, known to store movement engrams. Patients with deficits in pantomime of tool use additionally show activation of posterior middle temporal gyrus for semantic movement information. These mechanisms possibly can be interpreted as early compensatory effort.