Summary Background The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome epidemics, cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be expected to be rare. Recent developments A growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barre syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 2–6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin. Where next? Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease (eg, hypoxic encephalopathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barre syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base.

Neurological Associations of COVID-19

Background: The COVID-19 pandemic, caused by SARS-CoV-2, is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. Based on knowledge of other coronaviruses, especially those that caused the SARS and MERS epidemics, we might expect to see rare cases of central nervous system (CNS) and peripheral nervous system (PNS) disease caused by SARS-CoV-2.

Recent developments: A growing number of case reports and series describe a wide array of neurological manifestations, but many lack detail, reflecting the challenge of studying such patients. Encephalopathy is relatively common, being reported for 93 patients in total, including 16 (7.5%) of 214 hospitalised COVID-19 patients in Wuhan, China, and 40 (69%) of 58 in intensive care with COVID-19 in France. Encephalitis has been described in 8 patients to date, and Guillain-Barre syndrome in 19 patients. SARS-CoV-2 is detected in the cerebrospinal fluid of some patients. Anosmia and ageusia are common and may occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 1.6-6% of hospitalised COVID-19 cases. So far, 88 patients have been described, mostly with ischaemic stroke, who frequently have vascular events in the context of a pro-inflammatory hypercoagulable state with elevated CRP, D-dimer, and ferritin.

Where next?: Careful clinical, diagnostic and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease, such as hypoxic encephalopathy and critical care neuropathy, from those caused directly or indirectly by the virus; these include infectious, para- and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barre syndrome. Recognising SARS-CoV-2 neurological disease in patients whose respiratory infection is mild or asymptomatic may prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will remain small. However, these patients may be left with severe neurological sequelae. With so much of the population infected, the overall number of neurological patients, and their associated health, social and economic costs, may be large. Healthcare planners and policymakers must prepare for this eventuality. The many ongoing studies investigating the neurological association will increase our knowledge base.

/pdf/neurological-associations-of-covid-19-o39p8yig6g.pdf

Cerebral venous thrombosis is a relatively uncommon but serious neurologic disorder that is potentially reversible with prompt diagnosis and appropriate medical care. Because the possible causal factors and clinical manifestations of this disorder are many and varied, imaging plays a primary role in the diagnosis. Magnetic resonance (MR) imaging, unenhanced computed tomography (CT), unenhanced time-of-flight MR venography, and contrast material-enhanced MR venography and CT venography are particularly useful techniques for detecting cerebral venous and brain parenchymal changes that may be related to thrombosis. To achieve an accurate diagnosis, it is important to have a detailed knowledge of the normal venous anatomy and variants, the spectrum of findings (venous sinus thrombi and recanalization, parenchymal diffusion or perfusion changes or hemorrhage), other potentially relevant conditions (deep venous occlusion, isolated cortical venous thrombosis, idiopathic intracranial hypertension), and potential pitfalls in image interpretation.

Imaging of cerebral venous thrombosis : Current techniques, spectrum of findings, and diagnostic pitfalls. Commentary and Authors' reply

[Whipple's disease].

Summary Background Structural retinal imaging biomarkers are important for early recognition and monitoring of inflammation and neurodegeneration in multiple sclerosis. With the introduction of spectral domain optical coherence tomography (SD-OCT), supervised automated segmentation of individual retinal layers is possible. We aimed to investigate which retinal layers show atrophy associated with neurodegeneration in multiple sclerosis when measured with SD-OCT. Methods In this systematic review and meta-analysis, we searched for studies in which SD-OCT was used to look at the retina in people with multiple sclerosis with or without optic neuritis in PubMed, Web of Science, and Google Scholar between Nov 22, 1991, and April 19, 2016. Data were taken from cross-sectional cohorts and from one timepoint from longitudinal studies (at least 3 months after onset in studies of optic neuritis). We classified data on eyes into healthy controls, multiple-sclerosis-associated optic neuritis (MSON), and multiple sclerosis without optic neuritis (MSNON). We assessed thickness of the retinal layers and we rated individual layer segmentation performance by random effects meta-analysis for MSON eyes versus control eyes, MSNON eyes versus control eyes, and MSNON eyes versus MSON eyes. We excluded relevant sources of bias by funnel plots. Findings Of 25 497 records identified, 110 articles were eligible and 40 reported data (in total 5776 eyes from patients with multiple sclerosis [1667 MSON eyes and 4109 MSNON eyes] and 1697 eyes from healthy controls) that met published OCT quality control criteria and were suitable for meta-analysis. Compared with control eyes, the peripapillary retinal nerve fibre layer (RNFL) showed thinning in MSON eyes (mean difference −20·10 μm, 95% CI −22·76 to −17·44; p Interpretation The largest and most robust differences between the eyes of people with multiple sclerosis and control eyes were found in the peripapillary RNFL and macular GCIPL. Inflammatory disease activity might be captured by the INL. Because of the consistency, robustness, and large effect size, we recommend inclusion of the peripapillary RNFL and macular GCIPL for diagnosis, monitoring, and research. Funding None.

/pdf/retinal-layer-segmentation-in-multiple-sclerosis-a-543rjgpwlw.pdf

Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis

Neurologic complications of COVID-19 are not well described. We report 2 patients who were diagnosed with COVID-19 after presenting with diplopia and ophthalmoparesis.

https://n.neurology.org/content/neurology/early/2020/04/28/WNL.0000000000009700.full.pdf

COVID-19 presenting with ophthalmoparesis from cranial nerve palsy.

Background:Our goal was to evaluate the safety and efficacy of stenting of venous sinus stenosis (VSS) in patients with medically-refractory, medically-intolerant or fulminant idiopathic intracranial hypertension (IIH) in a prospective, observational study.Methods:Thirteen patients with IIH who were

Venous Sinus Stenting in Idiopathic Intracranial Hypertension: Results of a Prospective Trial.

Degeneration of neuron and axons following injury to cells with which they synapse is termed trans-synaptic degeneration. This phenomenon may be seen in postsynaptic neurons (anterograde) or in presynaptic neurons (retrograde). Retrograde trans-synaptic degeneration (RTSD) of the retinal ganglion cells and retinal nerve fiber layer following injury to the occipital lobe has been well documented histologically in animal studies, but its occurrence in the human retina was, for many years, felt to be limited to cases of neonatal injury during a critical period of neuronal development. Over the last decade, imaging techniques such as MRI and optical coherence tomography have allowed us to visualize and quantify RTSD and analyze its time course and relationship to degree of vision loss and age of cortical injury. A deeper understanding of RTSD in the human visual system may allow us to interfere with its occurrence, potentially allowing for greater recovery following visual cortex injury.

Trans-synaptic Retrograde Degeneration in the Human Visual System: Slow, Silent, and Real

Aims We report the cerebrospinal fluid opening pressure (CSF-OP) measurements obtained before and after venous sinus stenting (VSS) in 50 patients with idiopathic intracranial hypertension. Methods The CSF-OP was measured with a spinal tap 3 months before and 3 months after treatment. All data were prospectively collected and included patient demographics, weight (kg), body mass index (BMI), acetazolamide daily dosage (mg), procedural details, complications, venous sinus pressures (mm Hg), trans-stenotic pressure gradient (mm Hg), transverse sinus symmetry, and type of venous sinus stenosis. Results The average pretreatment CSF-OP was 37 cm H 2 O (range 25–77) and the average post-treatment CSF-OP was 20.2 cm H 2 O (range 10–36), with an average reduction of 16.8 cm H 2 O (P 2 O in 40/50 patients. The average acetazolamide daily dose decreased from 950 mg to 300 mg at the time of 3-month follow-up (P Conclusions We provide evidence that there is a significant decrease in CSF-OP in patients with idiopathic intracranial hypertension 3 months after VSS, independent of acetazolamide usage or weight loss.

https://jnis.bmj.com/content/neurintsurg/11/2/175.full.pdf

Marc Dinkin

Papers

COVID-19 presenting with ophthalmoparesis from cranial nerve palsy.

Venous Sinus Stenting in Idiopathic Intracranial Hypertension: Results of a Prospective Trial.

Trans-synaptic Retrograde Degeneration in the Human Visual System: Slow, Silent, and Real

Venous sinus stenting lowers the intracranial pressure in patients with idiopathic intracranial hypertension.

Venous Sinus Stenting for Idiopathic Intracranial Hypertension: Where Are We Now?