Florian Brugger

Do executive dysfunction and freezing of gait in Parkinson's disease share the same neuroanatomical correlates?

Current hypotheses postulate a relationship between executive dysfunction and freezing of gait (FOG) in Parkinsons disease (PD). Hitherto, most evidence comes from entirely clinical approaches, while knowledge about this relationship on the morphological level is sparse. The aim of this study was therefore to assess the overlap of gray matter atrophy associated with FOG and executive dysfunction in PD. We included 18 PD patients with FOG and 20 without FOG in our analysis. A voxel-based morphometry approach was used to reveal voxel clusters in the gray matter which were associated with FOG and executive dysfunction as measured by the Frontal Assessment Battery, respectively. Conjunction analysis was applied to detect overlaps of the associated patterns. FOG correlated with different cortical clusters in the frontal and parietal lobes, whereas those associated with the FAB scores were, although widespread, widely confined to the frontal lobe. Conjunction analysis revealed a significant cluster of gray matter loss in the right dorsolateral prefrontal cortex. We could show that the patterns of neurodegeneration associated with FOG and executive dysfunction (as measured by the FAB) share atrophic changes in the same cortical areas. However, there is also a considerable number of cortical areas where neurodegenerative changes are only unique for either sign. Particularly, the involvement of parietal lobe areas seems to be more specific for FOG.

Impaired eye blink classical conditioning distinguishes dystonic patients with and without tremor

INTRODUCTION Tremor is frequently associated with dystonia, but its pathophysiology is still unclear. Dysfunctions of cerebellar circuits are known to play a role in the pathophysiology of action-induced tremors, and cerebellar impairment has frequently been associated to dystonia. However, a link between dystonic tremor and cerebellar abnormalities has not been demonstrated so far. METHODS Twenty-five patients with idiopathic isolated cervical dystonia, with and without tremor, were enrolled. We studied the excitability of inhibitory circuits in the brainstem by measuring the R2 blink reflex recovery cycle (BRC) and implicit learning mediated by the cerebellum by means of eyeblink classical conditioning (EBCC). Results were compared with those obtained in a group of age-matched healthy subjects (HS). RESULTS Statistical analysis did not disclose any significant clinical differences among dystonic patients with and without tremor. Patients with dystonia (regardless of the presence of tremor) showed decreased inhibition of R2 blink reflex by conditioning pulses compared with HS. Patients with dystonic tremor showed a decreased number of conditioned responses in the EBCC paradigm compared to HS and dystonic patients without tremor. CONCLUSION The present data show that cerebellar impairment segregates with the presence of tremor in patients with dystonia, suggesting that the cerebellum might have a role in the occurrence of dystonic tremor.

Neuroanatomical correlates of tube dependency and impaired oral intake after hemispheric stroke.

Acute stroke patients with severely impaired oral intake are at risk of malnutrition and dehydration. Rapid identification of these patients is necessary to establish early enteral tube feeding. Whether specific lesion location predicts early tube dependency was analysed, and the neural correlates of impaired oral intake after hemispheric ischaemic stroke were assessed.

Why is there motor deterioration in Parkinson’s disease during systemic infections-a hypothetical view

Clinicians are well aware of the fact that patients with Parkinson’s disease may significantly deteriorate following a systemic infection or, in its most severe case, may even develop an akinetic crisis. Although this phenomenon is widely observed and has a major impact on the patients’ condition, the knowledge about the underlying mechanisms behind is still sparse. Possible explanations encompass changes in the pharmacodynamics of the dopaminergic drugs, altered dopamine metabolism in the brain, alterations in the dopaminergic transmission in the striatum or an enhancement of neurodegeneration due to remote effects of peripheral inflammatory processes or circulating bacterial toxins. This article provides possible explanatory concepts and may hence support formulating hypothesis for future studies in this field.

Early Ataxia and Subsequent Parkinsonism: PLA2G6 Mutations Cause a Continuum Rather Than Three Discrete Phenotypes

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Supplementary Motor Complex and Disturbed Motor Control – a Retrospective Clinical and Lesion Analysis of Patients after Anterior Cerebral Artery Stroke

Background Both the supplementary motor complex (SMC), consisting of the supplementary motor area (SMA) proper, the pre-SMA, and the supplementary eye field, and the rostral cingulate cortex are supplied by the anterior cerebral artery (ACA) and are involved in higher motor control. The Bereitschaftspotential (BP) originates from the SMC and reflects cognitive preparation processes before volitional movements. ACA strokes may lead to impaired motor control in the absence of limb weakness and evoke an alien hand syndrome (AHS) in its extreme form. Aim To characterize the clinical spectrum of disturbed motor control after ACA strokes, including signs attributable to AHS and to identify the underlying neuroanatomical correlates. Methods A clinical assessment focusing on signs of disturbed motor control including intermanual conflict (i.e., bilateral hand movements directed at opposite purposes), lack of self-initiated movements, exaggerated grasping, motor perseverations, mirror movements, and gait apraxia was performed. Symptoms were grouped into (A) AHS-specific and (B) non-AHS-specific signs of upper limbs, and (C) gait apraxia. Lesion summation mapping was applied to the patients’ MRI or CT scans to reveal associated lesion patterns. The BP was recorded in two patients. Results Ten patients with ACA strokes (nine unilateral, one bilateral; mean age: 74.2 years; median NIH-SS at admission: 13.0) were included in this case series. In the acute stage, all cases had marked difficulties to perform volitional hand movements, while movements in response to external stimuli were preserved. In the chronic stage (median follow-up: 83.5 days) initiation of voluntary movements improved, although all patients showed persistent signs of disturbed motor control. Impaired motor control is predominantly associated with damaged voxels within the SMC and the anterior and medial cingulate cortex, while lesions within the pre-SMA are specifically related to AHS. No BP was detected over the damaged hemisphere. Conclusion ACA strokes involving the premotor cortices, particularly the pre-SMA, are associated with AHS-specific signs. In the acute phase, motor behavior is characterized by the inability to carry out self-initiated movements. Motor control deficits may persist to a variable degree beyond the acute phase. Alterations of the BP point to an underlying SMC dysfunction in AHS.

Diverging lesion and connectivity patterns influence early and late swallowing recovery after hemispheric stroke

Knowledge about the recovery of oral intake after hemispheric stroke is important to guide therapeutic decisions, including the administration of enteral tube feeding and the choice of the appropriate feeding route. They aimed to determine the localization and connectivity of lesions in impaired recovery versus recovered swallowing after initially dysphagic stroke. Sixty‐two acute ischemic hemispheric stroke patients with impaired oral intake were included in a prospective observational cohort study. Voxel‐based lesion‐symptom mapping and probabilistic tractography were used to determine the association of lesion location and connectivity with impaired recovery of oral intake ≥7 days (indication for early tube feeding) and ≥4 weeks (indication for percutaneous endoscopic gastrostomy feeding) after stroke. Two distinct patterns influencing recovery of swallowing were recognized. Firstly, impaired recovery of oral intake after ≥7 days was significantly associated with lesions of the superior corona radiata (65% of statistical map, P < 0.05). The affected fibers were connected with the thalamus, primary motor, and supplemental motor areas and the basal ganglia. Secondly, impaired recovery of oral intake after ≥4 weeks significantly correlated with lesions of the anterior insula (54% of statistical map, P < 0.05), which was connected to adjacent operculo‐insular areas of deglutition. These findings indicate that early swallowing recovery is influenced by white matter lesions disrupting thalamic and corticobulbar projection fibers. Late recovery is determined by specific cortical lesions affecting association fibers. This knowledge may help clinicians to identify patients at risk of prolonged swallowing problems that would benefit from enteral tube feeding. Hum Brain Mapp 38:2165–2176, 2017.

Diverging lesion and connectivity patterns influence early and late swallowing recovery after hemispheric stroke: Lesion Patterns in Swallowing Recovery

Knowledge about the recovery of oral intake after hemispheric stroke is important to guide therapeutic decisions, including the administration of enteral tube feeding and the choice of the appropriate feeding route. They aimed to determine the localization and connectivity of lesions in impaired recovery versus recovered swallowing after initially dysphagic stroke. Sixty‐two acute ischemic hemispheric stroke patients with impaired oral intake were included in a prospective observational cohort study. Voxel‐based lesion‐symptom mapping and probabilistic tractography were used to determine the association of lesion location and connectivity with impaired recovery of oral intake ≥7 days (indication for early tube feeding) and ≥4 weeks (indication for percutaneous endoscopic gastrostomy feeding) after stroke. Two distinct patterns influencing recovery of swallowing were recognized. Firstly, impaired recovery of oral intake after ≥7 days was significantly associated with lesions of the superior corona radiata (65% of statistical map, P < 0.05). The affected fibers were connected with the thalamus, primary motor, and supplemental motor areas and the basal ganglia. Secondly, impaired recovery of oral intake after ≥4 weeks significantly correlated with lesions of the anterior insula (54% of statistical map, P < 0.05), which was connected to adjacent operculo‐insular areas of deglutition. These findings indicate that early swallowing recovery is influenced by white matter lesions disrupting thalamic and corticobulbar projection fibers. Late recovery is determined by specific cortical lesions affecting association fibers. This knowledge may help clinicians to identify patients at risk of prolonged swallowing problems that would benefit from enteral tube feeding. Hum Brain Mapp 38:2165–2176, 2017.

Endophenotyping in idiopathic adult onset cervical dystonia

OBJECTIVE Idiopathic adult onset cervical dystonia (IAOCD) is considered to be a partially penetrant autosomal dominant genetic condition. Dystonia may result from genetic and environmental factors. In this view, part of the physiology should be an endophenotype stemming from the genetic background. We assessed the most discriminative test to separate patients with IAOCD and healthy controls for further endophenotyping in non-affected 1st degree relatives. METHODS We included patients with IAOCD, their 1st degree relatives and healthy controls. Tests performed: (1) Sensory temporal discrimination (visual, tactile, visuo-tactile), (2) Paired pulse paradigms using transcranial magnetic stimulation (TMS), (3) Mental rotation paradigms. RESULTS 45 patients with IAOCD, 23 healthy controls and 14 non-affected 1st degree relatives were recruited. Visuo-tactile temporal discrimination separated best between controls and patients as well as between controls and 1st degree relatives. 36% of the latter had an abnormal visuo-tactile temporal discrimination. No difference between patients and healthy controls was found for the other paradigms. CONCLUSIONS Visuo-tactile temporal discrimination separates controls from patients with IAOCD and its 1st degree relatives. 36% of the latter had abnormal visuo-tactile thresholds supporting the role of visuo-tactile temporal discrimination as an endophenotype for IAOCD. SIGNIFICANCE Even though the study was of exploratory design, our findings expand the understanding of endophenotypes in IAOCD.

Bilateral MR imaging-guided high intensity focused ultrasound for the treatment of tremor-dominant Parkinson’s disease: first experience with 9 months follow up

MR imaging-guided high intensity focused ultrasound (MRIgFUS) is a novel, noninvasive technique for the treatment of functional brain disorders through the intact human skull at millimeter precision. The ExAblate 4000 transcranial MRIgFUS system (InSightec, Haifa, Israel) uses a 1024-element phased array transducer, which is attached to the patient’s head via a standard stereotactic frame situated inside a 3T MRI scanner, and is CE certified for interventions in the thalamus, subthalamus and pallidum.