Korrelation und Quantifizierung von Magnetresonanz-Parametern mit klinischen Symptomen bei Patienten mit Idiopathischer intrakranieller Hypertension vor und nach Liquorpunktion

Einführung: Die Liquorpunktion (LP) stellt ein wichtiges diagnostisches Verfahren bei der Beurteilung der Idiopathischen intrakraniellen Hypertension (IIH) dar. Zur Erforschung des Zusammenhangs von makroskopischen Veränderungen und mikrostrukturellen Parametern, welche mit einer intrakraniellen Druckerhöhung einhergehen, ist die Magnetresonanztomographie (MRT) bei Patienten mit IIH entscheidend. Studien zu Pathologien des retrolaminaren Anteils des Sehnerven (ON) oder des Geruchsempfindens sind, vor allem in Zusammenhang mit dem Kurzzeiteffekt der Normalisierung des Hirndruckes auf diese Veränderungen, rar. Ziel der Arbeit war es, strukturelle und klinische Verbesserungen durch eine Liquordrainage zu identifizieren. Material und Methoden: Bei allen eingeschlossenen Patienten wurde eine Idiopathisch intrakranielle Hypertension diagnostiziert. Sie wurden einer hochauflösenden MRT, einer Diffusions-Tensor-Imaging (DTI)-Messung sowie klinischen Tests zu Kopfschmerzen, Geruchs- und visuellem Empfinden unterzogen. Die Daten aller Studienteilnehmer wurden hinsichtlich epidemiologischer Parameter, zeitlicher Verläufe und des klinischen Erscheinungsbildes ausgewertet. Es wurde die Korrelation zwischen den Resultaten und dem Liquoröffnungsdruck untersucht. Ergebnisse: Nach Normalisierung des intrakraniellen Druckes (ICP) blieben die morphometrischen MRT-Untersuchungen unverändert. Die DTI-Messung zeigte, als Ausdruck einer Reduktion des Papillenödems nach LP, eine Verringerung der fraktionellen Anisotropie (FA). Korrespondierend verbesserten sich das Riechvermögen, die Kopfschmerzen und die Begleitsymptome deutlich. Insgesamt zeigte die Riechtestung in allen Untersuchungen eine signifikante Verbesserung (je p < 0,003). Der Liquoröffnungsdruck korrelierte signifikant mit einem Anstieg der Punktzahl im Schwellenwert- (T), Diskriminierungs- (D) und Geruchsidentifikations- (I) Test nach der Drainage der Cerebrospinalflüssigkeit (CSF) (r = 0,609; p = 0,021). Schlussfolgerung: Die Analyse der Daten zeigt, dass die IIH mit klinischen und mikrostrukturellen Veränderungen einhergeht. Diese können als direkte Folge eines chronisch erhöhten Hirndruckes auftreten. Die Ergebnisse stützen die Hypothese, dass eine Kompression des ON den axoplasmatischen Fluss verschlechtert und dadurch ein prälaminares Papillenödem verursacht. Die klinischen Symptome besserten sich innerhalb von Stunden nach der Normalisierung des ICP.Introduction: Lumbal puncture (LP) is an important diagnostic procedure for the assessment of Idiopathic intracranial hypertension (IIH). To investigate the correlation of macroscopic changes and microstructural parameters with intracranial pressure (ICP), cranial magnetic resonance imaging (MRI) of patients with IIH is crucial. Studies on possible pathologies of the retrolaminar area of the optic nerve (ON) or the sense of smell and the short-term effect of normalization of intracranial pressure on these alterations are rare. The aim of the studies was to identify structural and clinical improvements attained in patients with IIH through cerebrospinal fluid (CSF) drainage. Material and methods: Idiopathic intracranial hypertension was diagnosed in all included patients. They underwent high-resolution MRI, diffusion tensor imaging (DTI) measurement, and clinical tests on headache as well as olfactory and visual senses. All study participants were evaluated with regards to epidemiological parameters, disease progression, and clinical appearance. The correlation between the results and the CSF opening pressure was evaluated. Results: After normalization of the ICP, the morphometric MRI examinations remained unchanged. The DTI measurement showed a reduction in fractional anisotropy (FA), which indicates an expression of a reduction in papillary edema after LP. In accordance with this, there were significant improvements in clinical symptoms, both in the smell test and in the questionnaires on headaches and their accompanying symptoms. Overall, the smell tests showed a significant improvement (p < 0.003) in all examinations. The CSF opening pressure correlated significantly with an improvement of the threshold (T) value, the discrimination (D) and the scent identification (I) score after CSF drainage (r = 0.609; p = 0.021). Conclusion: The analyses indicate that IIH is associated with clinical and microstructural changes. These can be a direct result of the chronically increased intracranial pressure. The data supports the hypothesis that compression of the ON deteriorates the axoplasmic flow and thereby causes the prelaminar papilla edema. Clinical symptoms improved within hours of ICP normalization

The effect of CSF drain on the optic nerve in idiopathic intracranial hypertension

Background: Elevation of intracranial pressure in idiopathic intracranial hypertension induces an edema of the prelaminar section of the optic nerve (papilledema). Beside the commonly observed optic nerve sheath distention, information on a potential pathology of the retrolaminar section of the optic nerve and the short-term effect of normalization of intracranial pressure on these abnormalities remains scarce. Methods: In this exploratory study 8 patients diagnosed with idiopathic intracranial hypertension underwent a MRI scan (T2 mapping) as well as a diffusion tensor imaging analysis (fractional anisotropy and mean diffusivity). In addition, the clinical presentation of headache and its accompanying symptoms were assessed. Intracranial pressure was then normalized by lumbar puncture and the initial parameters (MRI and clinical features) were re-assessed within 26 h. Results: After normalization of CSF pressure, the morphometric MRI scans of the optic nerve and optic nerve sheath remained unchanged. In the diffusion tensor imaging, the fractional anisotropy value was reduced suggesting a tissue decompression of the optic nerve after lumbar puncture. In line with these finding, headache and most of the accompanying symptoms also improved or remitted within that short time frame. Conclusion: The findings support the hypothesis that the elevation of intracranial pressure induces a microstructural compression of the optic nerve impairing axoplasmic flow and thereby causing the prelaminar papilledema. The microstructural compression of the optic nerve as well as the clinical symptoms improve within hours of normalization of intracranial pressure

Metabolic imbalance of T cells in COVID-19 is hallmarked by basigin and mitigated by dexamethasone

Metabolic pathways regulate immune responses and disrupted metabolism leads to immune dysfunction and disease. Coronavirus disease 2019 (COVID-19) is driven by imbalanced immune responses, yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 87 patients with confirmed SARS-CoV-2 infection, 6 critically ill non–COVID-19 patients, and 47 uninfected controls, we found an immunometabolic dysregulation in patients with progressed COVID-19. Specifically, T cells, monocytes, and granulocytes exhibited increased mitochondrial mass, yet only T cells accumulated intracellular reactive oxygen species (ROS), were metabolically quiescent, and showed a disrupted mitochondrial architecture. During recovery, T cell ROS decreased to match the uninfected controls. Transcriptionally, T cells from severe/critical COVID-19 patients showed an induction of ROS-responsive genes as well as genes related to mitochondrial function and the basigin network. Basigin (CD147) ligands cyclophilin A and the SARS-CoV-2 spike protein triggered ROS production in T cells in vitro. In line with this, only PCR-positive patients showed increased ROS levels. Dexamethasone treatment resulted in a downregulation of ROS in vitro and T cells from dexamethasone-treated patients exhibited low ROS and basigin levels. This was reflected by changes in the transcriptional landscape. Our findings provide evidence of an immunometabolic dysregulation in COVID-19 that can be mitigated by dexamethasone treatment