As of 8 April 2021, a total of 2.9 million people have died with or from the coronavirus infection causing COVID-19 (Corona Virus Disease 2019). On 29 January 2021, the European Medicines Agency ...(EMA) approved a COVID-19 vaccine developed by Oxford University and AstraZeneca (AZD1222, ChAdOx1 nCoV-19, COVID-19 vaccine AstraZeneca, Vaxzevria, Covishield). While the vaccine prevents severe course of and death from COVID-19, the observation of pulmonary, abdominal, and intracranial venous thromboembolic events has raised concerns.
To describe the clinical manifestations and the concerning management of patients with cranial venous sinus thrombosis following first exposure to the "COVID-19 vaccine AstraZeneca".
Patient files, laboratory findings, and diagnostic imaging results, and endovascular interventions of three concerning patients were evaluated in retrospect.
Three women with intracranial venous sinus thrombosis after their first vaccination with "COVID-19 vaccine AstraZeneca" were encountered. Patient #1 was 22 years old and developed headaches four days after the vaccination. On day 7, she experienced a generalized epileptic seizure. Patient #2 was 46 years old. She presented with severe headaches, hemianopia to the right, and mild aphasia 13 days after the vaccination. MRI showed a left occipital intracerebral hemorrhage. Patient #3 was 36 years old and presented 17 days after the vaccination with acute somnolence and right-hand hemiparesis. The three patients were diagnosed with extensive venous sinus thrombosis. They were managed by heparinization and endovascular recanalization of their venous sinuses. They shared similar findings: elevated levels of D-dimers, platelet factor 4 antiplatelet antibodies, corona spike protein antibodies, combined with thrombocytopenia. Under treatment with low-molecular-weight heparin, platelet counts normalized within several days.
Early observations insinuate that the exposure to the "COVID-19 vaccine AstraZeneca" might trigger the expression of antiplatelet antibodies, resulting in a condition with thrombocytopenia and venous thrombotic events (e.g., intracranial venous sinus thrombosis). These patients' treatment should address the thrombo-embolic manifestations, the coagulation disorder, and the underlying immunological phenomena.
Co-expression modules are groups of genes with highly correlated expression patterns. In cancer, differences in module activity potentially represent the heterogeneity of phenotypes important in ...carcinogenesis, progression, or treatment response. To find gene expression modules active in breast cancer subpopulations, we assembled 72 breast cancer-related gene expression datasets containing ∼5,700 samples altogether. Per dataset, we identified genes with bimodal expression and used mixture-model clustering to ultimately define 11 modules of genes that are consistently co-regulated across multiple datasets. Functionally, these modules reflected estrogen signaling, development/differentiation, immune signaling, histone modification, ERBB2 signaling, the extracellular matrix (ECM) and stroma, and cell proliferation. The Tcell/Bcell immune modules appeared tumor-extrinsic, with coherent expression in tumors but not cell lines; whereas most other modules, interferon and ECM included, appeared intrinsic. Only four of the eleven modules were represented in the PAM50 intrinsic subtype classifier and other well-established prognostic signatures; although the immune modules were highly correlated to previously published immune signatures. As expected, the proliferation module was highly associated with decreased recurrence-free survival (RFS). Interestingly, the immune modules appeared associated with RFS even after adjustment for receptor subtype and proliferation; and in a multivariate analysis, the combination of Tcell/Bcell immune module down-regulation and proliferation module upregulation strongly associated with decreased RFS. Immune modules are unusual in that their upregulation is associated with a good prognosis without chemotherapy and a good response to chemotherapy, suggesting the paradox of high immune patients who respond to chemotherapy but would do well without it. Other findings concern the ECM/stromal modules, which despite common themes were associated with different sites of metastasis, possibly relating to the "seed and soil" hypothesis of cancer dissemination. Overall, co-expression modules provide a high-level functional view of breast cancer that complements the "cancer hallmarks" and may form the basis for improved predictors and treatments.
Functional stereotactic neurosurgery including deep brain stimulation (DBS) and radiofrequency lesioning is well established and widely used for treatment of movement disorders and various other ...neurological and psychiatric diseases. Although functional stereotactic neurosurgery procedures are considered relatively safe, intracranial hemorrhage resulting in permanent neurological deficits may occur in 1%-3% of patients. Microelectrode recording (MER) has been recognized as a valuable tool for refining the final target in functional stereotactic neurosurgery. Moreover, MER provides insight into the underlying neurophysiological pathomechanisms of movement disorders and other diseases. Nevertheless, there is an ongoing controversy on whether MER increases the risk for hemorrhage. The authors aimed to compare the risk of hemorrhage in functional stereotactic neurosurgical procedures with regard to the use of MER.
The authors performed a comparative analysis on a consecutive series of 645 functional neurosurgery procedures, including 624 DBS surgeries and 21 radiofrequency lesionings, to evaluate whether the use of MER would increase the risk for hemorrhage. MER was performed in 396 procedures, while no MER was used in 249 cases. The MER technique involved the use of a guiding cannula and a single trajectory when feasible. Postoperative CT scans were obtained within 24 hours after surgery in all patients and screened for the presence of hemorrhage.
Twenty-one intracranial hemorrhages were detected on the postoperative CT scans (3.2%). Of the 21 intracranial hemorrhages, 14 were asymptomatic and 7 were symptomatic. Symptoms were transient except in 1 case. There was no statistically significant correlation between hemorrhage and the use of MER at any site (subdural, ventricle, trajectory, target, whether asymptomatic or symptomatic). There were 4 cases of symptomatic hemorrhage in the MER group (1%) and 3 cases in those without MER (1.2%).
Intraoperative MER did not increase the overall risk of hemorrhage in the authors' experience using primarily a single MER trajectory and a guiding cannula.
Background
Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has become an accepted treatment for severe cervical dystonia (CD). Assessment of therapeutic efficacy of DBS mostly ...focused on head position at rest but hardly on limitations of head and neck mobility, which represent a functionally important impairment in CD.
Objective
We aimed to determine prospectively head and neck range of motion (ROM) preoperatively and during chronic bilateral GPi DBS in a series of 11 patients with idiopathic CD or segmental dystonia with prominent CD using a computerized motion analysis.
Methods
Maximum horizontal rotation of the head in the transverse plane and lateral inclination in the frontal plane were measured preoperatively and at a median of 7 months of chronic GPi DBS, using an ultrasound-based three-dimensional measuring system combined with surface electromyography of cervical muscles.
Results
Horizontal rotation of the head increased from 78.8° ± 31.5° (mean ± SD) preoperatively to 100.7° ± 24.7° with GPi DBS (
p
< 0.01), thereby improvement of head rotation to the anti-dystonic side (+ 14,2° ± 12,2°) was greater than to the pro-dystonic side (+ 7,8° ± 9,2°;
p
< 0.05). Movement-related agonistic-antagonistic EMG modulation during head rotation was enhanced with GPi DBS in both sternocleidomastoid (modulation index (MI) 35.8% ± 26.7% preoperatively vs. 67.3% ± 16.9% with GPi DBS,
p
< 0.01), and splenius capitis muscles (MI 1.9% ± 24.5% preoperatively vs. 44.8% ± 11.6% with GPi DBS,
p
< 0.01).
Conclusion
Chronic bilateral GPi DBS significantly improves head ROM in CD, likely due to enhanced agonist–antagonist EMG activity with reduced co-contraction. Computerized motion analysis provides an objective measurement to assess the improvement of head and neck mobility in CD.
Tardive dystonia/dyskinesia (TDD) occurs as a side effect of anti-dopaminergic drugs, including metoclopramide, and is often refractory to medication. While pallidal deep brain stimulation (DBS) has ...become an accepted treatment for TDD secondary to neuroleptic medication, there is much less knowledge about its effects on metoclopramide-induced TDD.
We present the case of a woman with metoclopramide-induced TDD, whose symptoms were initially misjudged as "functional." After 8 years of ineffective medical treatments, she received bilateral implantation of quadripolar electrodes into the posteroventral lateral globus pallidus internus (GPi).
GPi DBS led to significant symptom reduction Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score 24/44 at admission and 7/44 at discharge. Chronic stimulation led to full recovery from TDD symptoms 9 years after surgery. The BFMDRS motor score decreased to 0.5 (98% improvement).
Pallidal DBS may result in sustained improvement of TDD secondary to chronic metoclopramide intake in the long term.
Dystonia-choreoathetosis is common in patients with cerebral palsy, and medical treatment is mostly unsatisfactory. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has shown some ...effect, but there is still a need to optimize treatment strategies. We aimed to assess whether the thalamic ventral intermediate nucleus (Vim) might be an alternative DBS target in dystonia-choreoathetosis.
Three patients with cerebral palsy and dystonia-choreoathetosis underwent implantation of DBS electrodes concurrently in the GPi and Vim. Final selection of stimulation site and switches during follow-up with corresponding clinical outcomes were assessed.
One patient with initial GPi stimulation was switched to Vim, but likewise did not improve significantly (BFM: pre-OP 142, GPi 140, Vim 134) and stimulation was discontinued. In one patient Vim was chosen as initial target for chronic DBS. Since clinical benefit was not yet satisfying, stimulation was switched to GPi resulting in further mild clinical improvement (BFM: pre-OP 99.5, Vim 82.5, GPi 82). In one patient GPi was selected and kept on follow-up due to some therapeutic effect (BFM: pre-OP 135, GPi DBS 121).
The GPi still represents the most convenient DBS target in patients with dystonia-choreoathetosis. Vim DBS did not show a relevant long-term advantage in everyday life in our patients. Further alternative DBS targets need to be considered in acquired dystonia.
•First study to compare different DBS targets in cerebral palsy with dystonia-choreoathetosis.•Improvement with GPi DBS was better than with Vim DBS.•GPi was used for longterm stimulation.
OBJECTIVE:To investigate possible leptomeningeal contrast enhancement using postcontrast fluid-attenuated inversion recovery (FLAIR) MRI as an additional marker of inflammation in patients with ...multiple sclerosis (MS).
METHODS:A cohort of 112 patients (73 women) with clinically definitive MS or a clinically isolated syndrome suggestive of CNS demyelination were included. A pathologic control group of 5 stroke patients was also examined. MRI was performed on a 3T system including FLAIR, T2-weighted, T1-weighted–contrast injection, followed by T1-weighted and FLAIR.
RESULTS:Of the 112 patients, 39 had an acute relapse at the time of MRI. In total, 96 contrast-enhancing lesions were identified on postcontrast T1-weighted images. The pathologic control group demonstrated the sensitivity of postcontrast FLAIR images demonstrating leptomeningeal enhancement in all cases. In contrast, only 1 out of 112 examined patients with MS showed a single area of abnormal leptomeningeal contrast enhancement.
CONCLUSIONS:In contrast to intraparenchymal blood–brain barrier (BBB) dysfunction that is frequently seen in patients with MS, BBB dysfunction of leptomeningeal vessels is usually not detectable in patients with early MS.
Introduction: The treatment of neuropathic and central pain still remains a major challenge. Thalamic deep brain stimulation (DBS) involving various target structures is a therapeutic option which ...has received increased re-interest. Beneficial results have been reported in several more recent smaller studies, however, there is a lack of prospective studies on larger series providing long term outcomes. Methods: Forty patients with refractory neuropathic and central pain syndromes underwent stereotactic bifocal implantation of DBS electrodes in the centromedian–parafascicular (CM–Pf) and the ventroposterolateral (VPL) or ventroposteromedial (VPM) nucleus contralateral to the side of pain. Electrodes were externalized for test stimulation for several days. Outcome was assessed with five specific VAS pain scores (maximum, minimum, average pain, pain at presentation, allodynia). Results: The mean age at surgery was 53.5 years, and the mean duration of pain was 8.2 years. During test stimulation significant reductions of all five pain scores was achieved with either CM–Pf or VPL/VPM stimulation. Pacemakers were implanted in 33/40 patients for chronic stimulation for whom a mean follow-up of 62.8 months (range 3–180 months) was available. Of these, 18 patients had a follow-up beyond four years. Hardware related complications requiring secondary surgeries occurred in 11/33 patients. The VAS maximum pain score was improved by ≥50% in 8/18, and by ≥30% in 11/18 on long term follow-up beyond four years, and the VAS average pain score by ≥50% in 10/18, and by ≥30% in 16/18. On a group level, changes in pain scores remained statistically significant over time, however, there was no difference when comparing the efficacy of CM–Pf versus VPL/VPM stimulation. The best results were achieved in patients with facial pain, poststroke/central pain (except thalamic pain), or brachial plexus injury, while patients with thalamic lesions had the least benefit. Conclusion: Thalamic DBS is a useful treatment option in selected patients with severe and medically refractory pain.
Changes in cerebral perfusion during migraine with aura (MA) have been assessed mainly using dynamic susceptibility contrast (DSC) magnetic resonance perfusion imaging. A contrast agent-free method ...to assess these changes would be desirable. We assessed changes in cerebral perfusion during MA using arterial spin labeling (ASL) perfusion magnetic resonance imaging.
We investigated 4 patients with a standardized protocol including ASL perfusion imaging during MA (n = 2) or early headache phase (n = 2) and asymptomatic follow-up. Semiquantitative evaluation was done using a region of interest (ROI) within hypoperfused or hyperperfused areas and corresponding ROIs in the contralateral hemisphere. Relative ratios of mean perfusion in the corresponding ROIs were calculated. DSC imaging was done at initial time points and compared visually with ASL findings.
In all patients, regional perfusion changes were detected in the acute phase. These abnormalities did not respect the boundaries of major cerebral vascular territories but overlapped onto adjoining regions. During MA, adjacent hypoperfused and hyperperfused areas were found, whereas during headache, regional hyperperfusion only was observed. Perfusion abnormalities normalized on follow-up.
ASL perfusion imaging is a contrast agent-free method suitable for assessment of reversible perfusion changes during or immediately after MA.
Our aim was to analyze an important subgroup represented by young adult patients (19–45 years) with acute ischemic stroke according to stroke classification (including the novel ASCO score), infarct ...types and risk factors. All patients up to 45 years of age with an acute ischemic stroke confirmed by MRI and treated in our stroke unit from 2006 to 2009 were recruited for this study. Patients were neurologically examined and underwent thorough stroke work-up. One hundred four patients (58 women, 46 men) with a mean age of 38 ± 6.9 years were evaluated. The mean NIHSS score (±SD) was 3 ± 5 on admission and 1 ± 4 on discharge. The classification using TOAST/ASCO (grade 1) was as follows: Macroangiopathic 10.6%/8.7%, cardiac origin 21.2%/10.6%, microangiopathic 9.6%/9.6%, other causes 19.2%/13.5% and undetermined 39.4%/19.2% (for A0S0C0O0). The most common risk factors were smoking (55.2%), hypertension (31.4%) and hyperlipidemia (27.6%). Twenty nine of 74 patients with TEE (39.2%) had a patent foramen ovale (PFO). Hypoplastic posterior circulation (21.9%) and migraine (21.0%) were also quite common. Young adult ischemic stroke patients share many of the characteristic risk factors with the general elderly ischemic stroke population. If regular work-up includes TEE, a high percentage of young patients reveal comorbidities with PFO, hypoplasia of the posterior circulation and migraine. The ASCO classification should be favored for a better classification of coexisting stroke subtypes and lower number of undetermined etiologies in this patient group.
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