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BACKGROUND Acute disseminated encephalomyelitis (ADEM) is a rare, acquired demyelination syndrome that causes cognitive impairment and
focal neurological deficits and may be fatal. The potentially reversible disease mainly affects children, often after vaccination or viral infection, but may
be seen rarely in adults.
OBSERVATIONS A 50-year-old woman presented with loss of visual acuity of the left eye. Magnetic resonance imaging (MRI) revealed an intra- and
suprasellar mass, which was removed successfully. On postoperative day 1, MRI showed gross total resection of the lesion and no surgery-related
complications. On postoperative day 2, the patient presented with a progressive left-sided hemiparesis, hemineglect, and decline of cognitive
performance. MRI showed white matter edema in both hemispheres. Cerebrospinal fluid analysis revealed mixed pleocytosis (355/mL) without further
evidence of infection. In synopsis of the findings, ADEM was diagnosed and treated with intravenous immunoglobulins. Shortly thereafter, the patient
recovered, and no sensorimotor deficits were detected in the follow-up examination.
LESSONS Pituitary gland pathologies are commonly treated by transsphenoidal surgery, with only minor risks for complications. A case of ADEM after
craniopharyngioma resection has not been published before and should be considered in case of progressive neurological deterioration with multiple
white matter lesions.
Background
Understanding how SARS-CoV-2 affects respiratory centres in the brainstem may help to preclude assisted ventilation for patients in intensive care setting. Viral invasion appears unlikely, although autoimmunity has been implicated, the responsible antigens remain unknown. We previously predicted the involvement of three epitopes within distinct brainstem proteins: disabled homolog 1 (DAB1), apoptosis-inducing-factor-1 (AIFM1), and surfeit-locus-protein-1 (SURF1).
Methods
Here, we used microarrays to screen serum from COVID-19 patients admitted to intensive care and compared those with controls who experienced mild course of the disease.
Findings
The results confirm the occurrence of IgG and IgM antibodies against the hypothesised epitopes in COVID-19 patients. Importantly, while IgM levels were similar in both groups, IgG levels were significantly elevated in severely ill patients compared to controls, suggesting a pathogenic role of IgG.
Interpretation
The newly discovered anti-neuronal antibodies might be promising markers of severe disease and the targeted peptide epitopes might be used for targeted immunomodulation. Further work is needed to determine whether these antibodies may play a role in long-COVID.
Funding
AF, CF and PR received support from the German Research Foundation (grants FL 379/22-1, 327654276-SFB 1315, FR 4479/1-1, PR 1274/8-1). SH, DR, and DB received support from the Ministry of Economy, State of Mecklenburg Western Pomerania, Germany (grant COVIDPROTECT: “Optimisation of diagnostic and therapeutic pathways for COVID-19 patients in MV”). SH received support from the Research Group Molecular Medicine University of Greifswald (FVMM, seed funding FOVB-2021-01). AV received support from the Else Kröner Fresenius Foundation and the Alzheimer Research Initiative.
Background
Neuroinflammation and maladaptive neuroplasticity play pivotal roles in migraine (MIG), trigeminal autonomic cephalalgias (TAC), and complex regional pain syndrome (CRPS). Notably, CRPS shares connections with calcitonin gene-related peptide (CGRP) in its pathophysiology. This study aims to assess if the documented links between CRPS and MIG/TAC in literature align with clinical phenotypes and disease progressions. This assessment may bolster the hypothesis of shared pathophysiological mechanisms.
Methods
Patients with CRPS (n = 184) and an age-/gender-matched control group with trauma but without CRPS (n = 148) participated in this case–control study. Participant answered well-established questionnaires for the definition of CRPS symptoms, any headache complaints, headache entity, and clinical management.
Results
Patients with CRPS were significantly more likely to suffer from migraine (OR: 3.23, 95% CI 1.82–5.85), TAC (OR: 8.07, 95% CI 1.33–154.79), or non-classified headaches (OR: 3.68, 95% CI 1.88–7.49) compared to the control group. Patients with MIG/TAC developed CRPS earlier in life (37.2 ± 11.1 vs 46.8 ± 13.5 years), had more often a central CRPS phenotype (60.6% vs. 37.0% overall) and were three times more likely to report allodynia compared to CRPS patients with other types of headaches. Additionally, these patients experienced higher pain levels and more severe CRPS, which intensified with an increasing number of headache days. Patients receiving monoclonal antibody treatment targeting the CGRP pathway for headaches reported positive effects on CRPS symptoms.
Conclusion
This study identified clinically relevant associations of MIG/TAC and CRPS not explained by chance. Further longitudinal investigations exploring potentially mutual pathomechanisms may improve the clinical management of both CRPS and primary headache disorders.
Trial registration
German Clinical Trials Register (DRKS00022961).
Objectives: The significance of pre-motor (PMC) corticospinal projections in a frontoparietal motor network remains elusive. Temporal activation patterns can provide valuable information about a region's engagement in a hierarchical network. Navigated transcranial magnetic stimulation (nTMS)-induced virtual lesions provide an excellent method to study cortical physiology by disrupting ongoing activity at high temporal resolution and anatomical precision. We use nTMS-induced virtual lesions applied during an established behavioral task demanding pre-motor activation to clarify the temporal activation pattern of pre-motor corticospinal projections.
Materials and Methods: Ten healthy volunteers participated in the experiment (4 female, mean age 24 ± 2 years, 1 left-handed). NTMS was used to map Brodmann areae 4 and 6 for primary motor (M1) and PMC corticospinal projections. We then determined the stimulator output intensity required to elicit a 1 mV motor evoked potential (1 mV-MT) through M1 nTMS. TMS pulse were randomly delivered at distinct time intervals (40, 60, 80, 100, 120, and 140 ms) at 1 mV-MT intensity to M1, PMC and the DLPFC (dorsolateral pre-frontal cortex; control condition) before participants had to perform major changes of their trajectory of movement during a tracing task. Each participant performed six trials (20 runs per trial). Task performance and contribution of regions under investigation was quantified through calculating the tracing error induced by the stimulation.
Results: A pre-motor stimulation hotspot could be identified in all participants (16.3 ± 1.7 mm medial, 18.6 ± 1.4 mm anterior to the M1 hotspot). NTMS over studied regions significantly affected task performance at discrete time intervals (F(10, 80) = 3.25, p = 0.001). NTMS applied over PMC 120 and 140 ms before changes in movement trajectory impaired task performance significantly more than when applied over M1 (p = 0.021 and p = 0.003) or DLPFC (p = 0.017 and p < 0.001). Stimulation intensity did not account for error size (β = −0.0074, p = 1).
Conclusions: We provide novel evidence that the role of pre-motor corticospinal projections extends beyond that of simple corticospinal motor output. Their activation is crucial for task performance early in the stage of motor preparation suggesting a significant role in shaping voluntary movement. Temporal patterns of human pre-motor activation are similar to that observed in intracortical electrophysiological studies in primates.
Neuroinflammatory mechanisms and maladaptive neuroplasticity underlie the progression of complex regional pain syndrome (CRPS), which is prototypical of central neuropathic pain conditions. While cortical maladaptive alterations are well described, little is known about the contribution of the brainstem to the pathophysiology. This study investigates the role of pain-modulatory brainstem pathways in CRPS using the nociceptive blink reflex (nBR), which not only provides a direct read-out of brainstem excitability and habituation to painful stimuli but may also be suitable for use as a diagnostic biomarker for CRPS. Thirteen patients with CRPS and thirteen healthy controls (HCs) participated in this prospective case-control study investigating the polysynaptic trigemino-cervical (R2) nBR response. The R2 area and its habituation were assessed following repeated supraorbital electrical stimulation. Between-group comparisons included evaluations of diagnostic characteristics as a potential biomarker for the disease. Patients with CRPS showed a substantial decrease in habituation on the stimulated (Cohen’s d: 1.3; p = 0.012) and the non-stimulated side (Cohen’s d: 1.1; p = 0.04). This is the first study to reveal altered nBR habituation as a pathophysiological mechanism and potential diagnostic biomarker in CRPS. We confirmed previous findings of altered nBR excitability, but the diagnostic accuracy was inferior. Future studies should investigate the nBR as a marker of progression to central mechanisms in CRPS and as a biomarker to predict treatment response or prognosis.
Objectives: Navigated transcranial magnetic stimulation (nTMS) provides significant benefits over classic TMS. Yet, the acquisition of individual structural magnetic resonance images (MRIindividual) is a time-consuming, expensive, and not feasible prerequisite in all subjects for spatial tracking and anatomical guidance in nTMS studies. We hypothesize that spatial transformation can be used to adjust MRI templates to individual head shapes (MRIwarped) and that TMS parameters do not differ between nTMS using MRIindividual or MRIwarped.
Materials and Methods: Twenty identical TMS sessions, each including four different navigation conditions, were conducted in 10 healthy subjects (one female, 27.4 ± 3.8 years), i.e., twice per subject by two researchers to additionally assess interrater reliabilities. MRIindividual were acquired for all subjects. MRIwarped were obtained through the spatial transformation of a template MRI following a 5-, 9-and 36-point head surface registration (MRIwarped_5, MRIwarped_9, MRIwarped_36). Stimulation hotspot locations, resting motor threshold (RMT), 500 μV motor threshold (500 μV-MT), and mean absolute motor evoked potential difference (MAD) of primary motor cortex (M1) examinations were compared between nTMS using either MRIwarped variants or MRIindividual and non-navigated TMS.
Results: M1 hotspots were spatially consistent between MRIindividual and MRIwarped_36 (insignificant deviation by 4.79 ± 2.62 mm). MEP thresholds and variance were also equivalent between MRIindividual and MRIwarped_36 with mean differences of RMT by −0.05 ± 2.28% maximum stimulator output (%MSO; t(19) = −0.09, p = 0.923), 500 μV-MT by −0.15 ± 1.63%MSO (t(19) = −0.41, p = 0.686) and MAD by 70.5 ± 214.38 μV (t(19) = 1.47, p = 0.158). Intraclass correlations (ICC) of motor thresholds were between 0.88 and 0.97.
Conclusions: NTMS examinations of M1 yield equivalent topographical and functional results using MRIindividual and MRIwarped if a sufficient number of registration points are used.
Background and Objective: Transcranial random noise stimulation (tRNS) is an emerging non-invasive brain stimulation technique to modulate brain function, with previous studies highlighting its considerable benefits in therapeutic stimulation of the motor system. However, high variability of results and bidirectional task-dependent effects limit more widespread clinical application. Task dependency largely results from a lack of understanding of the interaction between externally applied tRNS and the endogenous state of neural activity during stimulation. Hence, the aim of this study was to investigate the task dependency of tRNS-induced neuromodulation in the motor system using a finger-tapping task (FT) versus a go/no-go task (GNG). We hypothesized that the tasks would modulate tRNS’ effects on corticospinal excitability (CSE) and task performance in opposite directions.
Methods: Thirty healthy subjects received 10 min of tRNS of the dominant primary motor cortex in a double-blind, sham-controlled study design. tRNS was applied during two well-established tasks tied to diverging brain states. Accordingly, participants were randomly assigned to two equally-sized groups: the first group performed a simple motor training task (FT task), known primarily to increase CSE, while the second group performed an inhibitory control task (go/no-go task) associated with inhibition of CSE. To establish task-dependent effects of tRNS, CSE was evaluated prior to- and after stimulation with navigated transcranial magnetic stimulation.
Results: In an ‘activating’ motor task, tRNS during FT significantly facilitated CSE. FT task performance improvements, shown by training-related reductions in intertap intervals and increased number of finger taps, were similar for both tRNS and sham stimulation. In an ‘inhibitory’ motor task, tRNS during GNG left CSE unchanged while inhibitory control was enhanced as shown by slowed reaction times and enhanced task accuracy during and after stimulation.
Conclusion: We provide evidence that tRNS-induced neuromodulatory effects are task-dependent and that resulting enhancements are specific to the underlying task-dependent brain state. While mechanisms underlying this effect require further investigation, these findings highlight the potential of tRNS in enhancing task-dependent brain states to modulate human behavior.
Introduction
A substantial number of patients diagnosed with COVID-19 experience long-term persistent symptoms. First evidence suggests that long-term symptoms develop largely independently of disease severity and include, among others, cognitive impairment. For these symptoms, there are currently no validated therapeutic approaches available. Cognitive training interventions are a promising approach to counteract cognitive impairment. Combining training with concurrent transcranial direct current stimulation (tDCS) may further increase and sustain behavioural training effects. Here, we aim to examine the effects of cognitive training alone or in combination with tDCS on cognitive performance, quality of life and mental health in patients with post-COVID-19 subjective or objective cognitive impairments.
Methods and analysis
This study protocol describes a prospective randomised open endpoint-blinded trial. Patients with post-COVID-19 cognitive impairment will either participate in a 3-week cognitive training or in a defined muscle relaxation training (open-label interventions). Irrespective of their primary intervention, half of the cognitive training group will additionally receive anodal tDCS, all other patients will receive sham tDCS (double-blinded, secondary intervention). The primary outcome will be improvement of working memory performance, operationalised by an n-back task, at the postintervention assessment. Secondary outcomes will include performance on trained and untrained tasks and measures of health-related quality of life at postassessment and follow-up assessments (1 month after the end of the trainings).
Ethics and dissemination
Ethical approval was granted by the Ethics Committee of the University Medicine Greifswald (number: BB 066/21). Results will be available through publications in peer-reviewed journals and presentations at national and international conferences.
Trial registration number NCT04944147.