Background
Comprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far.
Objective
To analyze systematically the CSF profile in COVID-19.
Methods
Retrospective analysis of 150 lumbar punctures in 127 patients with PCR-proven COVID-19 and neurological symptoms seen at 17 European university centers
Results
The most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72–50.8]), which was present in 58/116 (50%) samples from patients without pre-/coexisting CNS diseases (group I). QAlb remained elevated > 14d (47.6%) and even > 30d (55.6%) after neurological onset. CSF total protein was elevated in 54/118 (45.8%) samples (median 65.35 mg/dl [45.3–240.4]) and strongly correlated with QAlb. The CSF white cell count (WCC) was increased in 14/128 (11%) samples (mostly lympho-monocytic; median 10 cells/µl, > 100 in only 4). An albuminocytological dissociation (ACD) was found in 43/115 (37.4%) samples. CSF l-lactate was increased in 26/109 (24%; median 3.04 mmol/l [2.2–4]). CSF-IgG was elevated in 50/100 (50%), but was of peripheral origin, since QIgG was normal in almost all cases, as were QIgA and QIgM. In 58/103 samples (56%) pattern 4 oligoclonal bands (OCB) compatible with systemic inflammation were present, while CSF-restricted OCB were found in only 2/103 (1.9%). SARS-CoV-2-CSF-PCR was negative in 76/76 samples. Routine CSF findings were normal in 35%. Cytokine levels were frequently elevated in the CSF (often associated with BCB dysfunction) and serum, partly remaining positive at high levels for weeks/months (939 tests). Of note, a positive SARS-CoV-2-IgG-antibody index (AI) was found in 2/19 (10.5%) patients which was associated with unusually high WCC in both of them and a strongly increased interleukin-6 (IL-6) index in one (not tested in the other). Anti-neuronal/anti-glial autoantibodies were mostly absent in the CSF and serum (1509 tests). In samples from patients with pre-/coexisting CNS disorders (group II [N = 19]; including multiple sclerosis, JC-virus-associated immune reconstitution inflammatory syndrome, HSV/VZV encephalitis/meningitis, CNS lymphoma, anti-Yo syndrome, subarachnoid hemorrhage), CSF findings were mostly representative of the respective disease.
Conclusions
The CSF profile in COVID-19 with neurological symptoms is mainly characterized by BCB disruption in the absence of intrathecal inflammation, compatible with cerebrospinal endotheliopathy. Persistent BCB dysfunction and elevated cytokine levels may contribute to both acute symptoms and ‘long COVID’. Direct infection of the CNS with SARS-CoV-2, if occurring at all, seems to be rare. Broad differential diagnostic considerations are recommended to avoid misinterpretation of treatable coexisting neurological disorders as complications of COVID-19.
Monitoring of renal oxygen metabolism allows early prediction of AKI in infants after cardiac surgery. In contrast, renal resistive index does not allow prediction of AKI after neonatal palliation with aortopulmonary shunt establishment.
OBJECTIVES: Cerebral protection is a major issue in the treatment of infants with complex congenital heart disease. We tested a new device combining tissue spectrometry and laser Doppler flowmetry for non-invasive determination of cerebral oxygen metabolism following cardiac surgery in infants.
METHODS:We prospectively measured regional cerebral oxygen saturation cSO 2 and microperfusion (rcFlow) in 43 infants 12-24 h following corrective (n = 30) or palliative surgery (n = 13) of congenital heart defects. For comparison, cerebral blood flow (CBF) was determined by colour duplex sonography of the extracranial cerebral arteries. Cerebral fractional tissue oxygen extraction, approximated cerebral metabolic rate of oxygen (aCMRO 2 ) and cerebral metabolic rate of oxygen (CMRO 2 ) were calculated. CONCLUSIONS: According to our experience, combined photospectrometry and laser Doppler flowmetry enable non-invasive assessment of cerebral oxygen metabolism. The method promises new insights into perioperative cerebral perfusion following palliation or corrective surgery in infancy.
Background
Eslicarbazepine acetate (ESL), a novel sodium channel blocker, is approved for mono and adjunctive treatment of partial epileptic seizures with or without secondary generalization. Its efficacy in primary generalized seizures has not yet been evaluated.
Objective
To evaluate the efficacy and safety of ESL in primary generalized tonic-clonic seizures (PGTCS) in an observational study.
Methods
The data were collected from a prospective population-based register. Effectiveness was measured as relative reduction in standardized seizure frequency (SSF), responder rate (≥ 50% reduction in SSF), and seizure freedom rate at 6 and 12 months after initiation of ESL. Safety and tolerability were evaluated using patients’ diaries.
Results
Fifty-six adult patients with PGTCS were treated with ESL as adjunctive therapy. Of these, 30.4% (
n
= 17) had myoclonic seizures in addition to PGTCS. The retention rate after 12 months was 80.4% (
n
= 45). After initiating ESL therapy, reduction in SSF for PGTCS on ESL was 56.0% after 6 months and 56.9% after 12 months (
p
< 0.01), whereas myoclonic seizures did not show any significant improvement in frequency. The responder rate for PGTCS was 64.3% after 6 months and 66.1% after 12 months, and seizure freedom was achieved in 32.1% and 35.7%, respectively. Forty-three patients (73.2%) reported no side effects. Among the reported side effects of ESL therapy, headache (7.1%), dizziness (8.9%), tiredness (7.1%), nausea (5.4%), and hyponatremia (5.4%) were the most prevalent.
Conclusions
Our data suggest that ESL may provide additional benefits in the treatment of patients with PGTCS and motivate randomized controlled trials in this indication.
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