Anosmia, stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, and seizures are some of the neurological complications in patients with coronavirus disease-19 (COVID-19) which is caused by acute respiratory syndrome coronavirus 2 (SARS-Cov2). There remains a challenge to determine the extent to which neurological abnormalities in COVID-19 are caused by SARS-Cov2 itself, the exaggerated cytokine response it triggers, and/or the resulting hypercoagulapathy and formation of blood clots in blood vessels throughout the body and the brain. In this article, we review the reports that address neurological manifestations in patients with COVID-19 who may present with acute neurological symptoms (e.g., stroke), even without typical respiratory symptoms such as fever, cough, or shortness of breath. Next, we discuss the different neurobiological processes and mechanisms that may underlie the link between SARS-Cov2 and COVID-19 in the brain, cranial nerves, peripheral nerves, and muscles. Finally, we propose a basic "NeuroCovid" classification scheme that integrates these concepts and highlights some of the short-term challenges for the practice of neurology today and the longterm sequalae of COVID-19 such as depression, OCD, insomnia, cognitive decline, accelerated aging, Parkinson's disease, or Alzheimer's disease in the future. In doing so, we intend to provide a basis from which to build on future hypotheses and investigations regarding SARS-Cov2 and the nervous system.

We concluded that early-life seizures, without causing overt cellular injury, predispose the brain to the damaging effect of seizures later in life.

The hippocampus is especially vulnerable to seizure-induced damage and excitotoxic neuronal injury. This study examined the time course of neuronal death in relationship to seizure duration and the pharmacological mechanisms underlying seizure-induced cell death using low magnesium (Mg 2+ ) induced continuous high frequency epileptiform discharges (in vitro status epilepticus) in hippocampal neuronal cultures. Neuronal death was assessed using cell morphology and Fluorescein diacetate-Propidium iodide staining. Effects of low Mg 2+ and various receptor antagonists on spike frequency were assessed using patch clamp electrophysiology. We observed a linear and timedependent increase in neuronal death with increasing durations of status epilepticus. This cell death was dependent upon extracellular calcium that entered primarily through the N-methyl-D-aspartate (NMDA) glutamate receptor channel subtype. Neuronal death was significantly decreased by coincubation with the NMDA receptor antagonists and was also inhibited by reduction of extracellular calcium (Ca 2+ ) during status epilepticus. In contrast, neuronal death from in vitro status epilepticus was not significantly prevented by inhibition of other glutamate receptor subtypes or voltage-gated Ca 2+ channels. Interestingly this NMDA-Ca 2+ dependent neuronal death was much more gradual in onset compared to cell death from excitotoxic glutamate exposure. The results provide evidence that in vitro status epilepticus results in increased activation of the NMDA-Ca 2+ transduction pathway leading to neuronal death in a time dependent fashion. The results also indicate that there is a significant window of opportunity during the initial time of continuous seizure activity to be able to intervene, protect neurons and decrease the high morbidity and mortality associated with status epilepticus. KeywordsLow Mg 2+ model of status epilepticus; Neuronal death; NMDA-Ca 2+ pathway

SummaryIt is established that the majority but not all of the seizure-induced cell death is associated with status epilepticus while spontaneous recurrent seizures associated with epilepsy do not cause neuronal death. Extracellular effects and compensatory changes in brain physiology complicate assessment of neuronal death in vivo as the result of seizures. In this study we utilized a well-characterized in vitro hippocampal neuronal culture model of both continuous high-frequency epileptiform discharges (status epilepticus) and spontaneous recurrent epileptiform discharges (acquired epilepsy) to investigate the direct effects of continuous and episodic electrographic epileptiform discharges on cell death in a carefully controlled extracellular environment. The results from this study indicate that continuous high-frequency epileptiform discharges can cause neuronal death in a time-dependent manner. Episodic epileptiform seizure activity occurring for the life of the neurons in culture was not associated with increased neuronal cell death. Our data confirm observations from clinical and some animal studies that spontaneous recurrent seizures do not initiate cell death. The hippocampal neuronal culture model provides a powerful in vitro tool for carefully evaluating the effects of seizure activity alone on neuronal viability in the absence of various confounding factors and may provide new insights into the development of novel therapeutic agents to prevent neuronal injury during status epilepticus.

Meckel’s cave is a dural recess in the posteromedial portion of the middle cranial fossa that acts as a conduit for the trigeminal nerve between the prepontine cistern and the cavernous sinus, and houses the Gasserian ganglion and proximal rootlets of the trigeminal nerve. It serves as a major pathway in perineural spread of pathologies such as head and neck neoplasms, automatically upstaging tumours, and is a key structure to assess in cases of trigeminal neuralgia. The purpose of this pictorial review is threefold: (1) to review the normal anatomy of Meckel’s cave; (2) to describe imaging findings that identify disease involving Meckel’s cave; (3) to present case examples of trigeminal and non-trigeminal processes affecting Meckel’s cave.Teaching points• Meckel’s cave contains the trigeminal nerve between prepontine cistern and cavernous sinus.• Assessment is essential for perineural spread of disease and trigeminal neuralgia.• Key imaging: neural enhancement, enlargement, perineural fat/CSF effacement, skull base foraminal changes.

The inter-arterial watershed zone in neonates is a geographic area without discernible anatomic boundaries and difficult to demarcate and usually not featured in atlases. Schematics currently used to depict the areas are not based on any prior anatomic mapping, compared to adults. Magnetic resonance imaging (MRI) of neonates in the acute to subacute phase with suspected hypoxic-ischaemic injury (HII) can demonstrate signal abnormality and restricted diffusion in the cortical and subcortical parenchyma of the watershed regions. In the chronic stage of partial-prolonged hypoxic-ischaemic injury, atrophy and ulegyria can make the watershed zone more conspicuous as a region. Our aim is to use images extracted from a sizable medicolegal database (approximately 2000 cases), of delayed MRI scans in children with cerebral palsy, to demonstrate the watershed region. To achieve this, we have selected cases diagnosed on imaging as having sustained a term pattern of partial-prolonged HII affecting the hemispheric cortex, based on the presence of bilateral, symmetric atrophy with ulegyria. From these, we have identified those patients demonstrating injury along the whole watershed continuum as well as those demonstrating selective anterior or posterior watershed predominant injury for demonstration. Recognition of this zone is essential for diagnosing partial-prolonged hypoxic-ischaemic injury sustained in term neonates. The images presented in this pictorial review provide a template for identifying the cortical watershed distribution when there is milder regional (anterior, parasagittal, peri-Sylvian and posterior) watershed injury and for more severe injury where multiple regions are injured in combination or as a continuum.Lack of clear anatomic structural demarcation of the inter-arterial watershed makes appreciation difficult in normal brains. Recognition of this zone and its potential involvement is essential for diagnosing partialprolonged hypoxic-ischaemic injury in term neonates.Watershed injury at any stage should be distinguished from arterial territory involvement. In the chronic phase, watershed injury must be distinguished from generalised atrophy of the brain. This pictorial review provides a template for identifying the cortical watershed distribution in milder regional or wider more severe injury in a continuum.

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