Neurological symptoms might be associated with a Covid-19 infection. There are frequent reports in the last weeks. The neurological symptoms range from harmless side effects of a viral infection to meningoencephalitis and acute haemorrhagic necrotizing encephalopathy. Our patient reported burning headache and paresthesia as the initial symptoms mainly without other signs of viral infection like cough or fever. Such an initial neurological presentation seems to be rare. Most cases have neurological symptoms which can be expected after severe systemic viral infections like fever associated headache. Many COVID-19 patients with mild disease are at home and the further course is unknown. Our case shows, that neurological symptoms can be the first manifestation of an COVID-19 disease. While restricted paraesthesia has been reported in SARS-CoV-2 infections, hemisymptoms have not been described as initial symptoms.

Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischeria and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats following focal cerebral ischemla. To ascertain directly the role of SOD in the protection against superoxide radical-induced injury, we measured infarct size and water content 24 hr following focal cerebral ischemia in nontransgenic mice and in transgeic mice bearing the human SODI gene. These transgenic mice have 3.1-fold higher cellular CuZn-SOD activity in the brain than do their nontransgenic littermates. We also'measured antioxidant levels (reduced glutathione and reduced ascorbate) of contralateral cortex, infarct cortex, surrounding cortex, and striatum. Infarct size and brain edema were s ntly decreased in trenic mice compared with nontransgenic mice. Reduced glutathione and reduced ascorbate levels decreased in the ischemlc hemisphere, -but levels-in surrounding cortex and striaturm were gficantly higher in trasgenic'mice than in nontransgenic mice. These rEsults indicate that increased endogenous SOD activity in brain reduces the level of ischemic damage and support the concept that superoxide radicals play an important role in the-pathogenesis of infarction and edema following focal cerebral ischemia.The role of oxygen free radicals in the pathogenesis of infarction and edema following cerebral ischemia has been intensively investigated since the report of Flamm et al. (1).Because of technical 4ffficulties in the measurement of free radicals'in brain tissues the part played by free radicals in the pathogenesis of cerebral ischemia still remains unclear (2, 3). However, reports of decreased levels of lipid-soluble and water-soluble endogenous antioxidants and of increased levels ofconjugated dienes and lipid peroxidation (4-10) support the notion that free radicals are involved in ischemic brain injury.Indirect methods using specific antioxidants [e.g., superoxide dismutase (SOD) and catalase] have traditionally been used to implicate oxygen free radicals in physiological or pathological processes. Unfortunately, the half-life of CuZn-SOD in circulating blood is extremely short (6 min), and it is unable to pass the blood-brain barrier. Therefore, use has been made of chemically modified enzymes for work on cerebral injury (11), and it has been found that polyethylene glycol-conjugated CuZn-SOD (PEG-SOD) and PEG-catalase reduce the degree of cortical infarction resulting from focal cerebral ischemia (12). Similarly, CuZn-SOD conjugated with divinyl ether/maleic acid copolymer ameliorated delayed hippocampal neuronal death after global cerebral ischemia in the gerbil brain (13). Liposome-entrapped CuZn-SOD, which has a half life of 4.2 hr (11), reduces the severity of traumatic and ischemic injuries (14,15).Although these studies provide potential therapeutic precedents for the management of brain in...

Background and Purpose-To clarify the effect of superoxide dismutase (SOD) on vasospasm after subarachnoid hemorrhage (SAH), we investigated sequential changes in arterial diameter after SAH in transgenic mice overexpressing CuZn-SOD (SOD-1). Methods-SOD-transgenic mice and nontransgenic littermates (35 to 40 g) were subjected to SAH produced by endovascular perforation of left anterior cerebral artery. At 4 hours and 1, 3, 7, and 14 days after SAH, the mice were perfused with 10% formalin and consequently with a mixture of carbon black and 10% gelatin to cast all vessels. Vasospasm was evaluated by measuring the diameter of the left middle cerebral artery (MCA) with a microscope. Results-In nontransgenic mice, the diameter of the MCA on day 3 after SAH (110.5Ϯ20.5 m [meanϮSD]; nϭ16) was significantly reduced compared with that without SAH (138.5Ϯ14.5 m; nϭ12) (PϽ0.01). Moreover, on day 3 after SAH, the diameter of the MCA in SOD-transgenic mice (127.9Ϯ20.2 m; nϭ20) was significantly larger than that in nontransgenic mice (110.5Ϯ20.5 m; nϭ16) (PϽ0.05). Conclusions-These results suggest that SOD is effective on the amelioration of vasospasm after SAH and that oxygen free radicals, particularly superoxide, play an important role in the pathogenesis of vasospasm after SAH. (Stroke. 1999;30:867-872.)Key Words: free radicals Ⅲ mice, transgenic Ⅲ subarachnoid hemorrhage Ⅲ superoxide dismutase Ⅲ vasospasm E rythrocytes are essential for causing vasospasm, and oxyhemoglobin released from erythrocytes in the subarachnoid clot is believed to be a most potent trigger of vasospasm. 1,2 However, the pathophysiology of cerebral vasospasm after subarachnoid hemorrhage (SAH) still remains unclear. Recently, 2 major derangements in the cerebral artery have been indicated as a cause for cerebral vasospasm after SAH. One is augmentation of contraction, which is protein kinase C (PKC) dependent, and the other is suppression of dilation, which is mediated by endothelium-derived relaxing factor/nitric oxide (NO). 3 Oxygen free radicals are involved in both systems; active oxygens can activate the PKC system and lead to lipid peroxidation through activation of phospholipase A 2 , 4 and superoxide (O 2 Ϫ ) is known to inactivate NO, 5 resulting in the occurrence of vasospasm after SAH. Therefore, superoxide dismutase (SOD), an enzyme converting O 2 Ϫ to hydrogen peroxide (H 2 O 2 ), could prevent contraction of the cerebral artery after SAH. Experiments in vivo, however, have not always proven the efficacy of SOD in preventing vasospasm after SAH. Kamiyama et al 6 See Editorial Comment, page 872initially showed that SOD is effective against vasospasm induced by oxyhemoglobin in cats. In addition, intracisternal injection of SOD reduced endothelial injury and prevented the occurrence of vasospasm in a rabbit SAH model. 7 However, intrathecal administration of both SOD and catalase failed to protect against oxyhemoglobin-induced vasospasm in monkeys. 8 The discrepancy in the effect of SOD on vasospasm after SAH may result from difference...

Summary:The endoplasmic reticulum (ER), which plays important roles in apoptosis, is susceptible to oxidative stress. Because reactive oxygen species (ROS) are robustly produced in the ischemic brain, ER damage by ROS may be implicated in ischemic neuronal cell death. We induced global brain ischemia on wild-type and copper/zinc superoxide dismutase (SOD1) transgenic rats and compared ER stress and neuronal damage. Phosphorylated forms of eukaryotic initiation factor 2␣ (eIF2␣) and RNA-dependent protein kinase-like ER eIF2␣ kinase (PERK), both of which play active roles in apoptosis, were increased in hippocampal CA1 neurons after ischemia but to a lesser degree in the transgenic animals. This finding, together with the finding that the transgenic animals showed decreased neuronal degeneration, indicates that oxidative ER damage is involved in ischemic neuronal cell death. To elucidate the mechanisms of ER damage by ROS, we analyzed glucose-regulated protein 78 (GRP78) binding with PERK and oxidative ER protein modification. The proteins were oxidatively modified and stagnated in the ER lumen, and GRP78 was detached from PERK by ischemia, all of which were attenuated by SOD1 overexpression. We propose that ROS attack and modify ER proteins and elicit ER stress response, which results in neuronal cell death.

Oxygen free radicals have been implicated in the pathogenesis of brain injury induced by ischemia/reperfusion. We studied the role of endogenous reduced glutathione (GSH) in brain infarction associated with focal cerebral ischemia caused by permanent ligation of the right middle cerebral artery (MCA) and the right common carotid artery (CCA) plus temporary occlusion of the left CCA. GSH levels in the ischemic side of cortex decreased with time after ischemia and preceded cortical infarction estimated by the staining of mitochondrial respiratory enzymes with 2,3,5-triphenyltetrazolium chloride. GSH levels in the contralateral cortex were unchanged through the experimental periods. The extent of decrease of GSH levels and the severity of infarction in the ischemic cortex at 24 h after ischemia depended on the duration of occlusion of the left CCA. Depletion of brain GSH with buthionine sulfoximine, a selective inhibitor for gamma-glutamylcysteine synthetase, exacerbated cortical infarction and edema after ischemia. These results suggest that the endogenous brain GSH is an important determinant in the defense mechanisms against lesion formation after ischemia and support the possible role of oxygen radicals in the pathogenesis of ischemic brain injury.

Preconditioning (PC) using a preceding sublethal ischemic insult is an attractive strategy for protecting neurons by inducing ischemic tolerance in the brain. Although the underlying molecular mechanisms have been extensively studied, almost all studies have focused on neurons. Here, using a middle cerebral artery occlusion model in mice, we show that astrocytes play an essential role in the induction of brain ischemic tolerance. PC caused activation of glial cells without producing any noticeable brain damage. The spatiotemporal pattern of astrocytic, but not microglial, activation correlated well with that of ischemic tolerance. Interestingly, such activation in astrocytes lasted at least 8 weeks. Importantly, inhibiting astrocytes with fluorocitrate abolished the induction of ischemic tolerance. To investigate the underlying mechanisms, we focused on the P2X7 receptor as a key molecule in astrocyte-mediated ischemic tolerance. P2X7 receptors were dramatically upregulated in activated astrocytes. PC-induced ischemic tolerance was abolished in P2X7 receptor knock-out mice. Moreover, our results suggest that hypoxia-inducible factor-1␣, a well known mediator of ischemic tolerance, is involved in P2X7 receptor-mediated ischemic tolerance. Unlike previous reports focusing on neuron-based mechanisms, our results show that astrocytes play indispensable roles in inducing ischemic tolerance, and that upregulation of P2X7 receptors in astrocytes is essential.

If computerized tomography scanning shows SAH predominantly in the posterior fossa and no abnormalities are found on intracranial four-vessel angiographic study, proximal vertebral angiography should be performed to detect dural AVS at the craniocervical junction. The results of surgical intervention for this disease are quite satisfactory.

BACKGROUND AND PURPOSE:Spontaneous intracranial hypotension (SIH) presents with orthostatic headache, and the diagnosis is made on the basis of low CSF pressure and brain MR imaging findings characteristic of the disorder. However, a broad spectrum of symptoms and MR imaging findings of SIH is recognized, and some cases have no typical MR imaging abnormalities. SIH is believed to be caused by CSF leakage from the spinal dural sac, whereas the usefulness of MR imaging of the spine remains unclear. Our aim was to elucidate the diagnostic value of brain and spinal MR imaging