Neuropsychiatric aspects of long COVID: A comprehensive review

Although some patients have persistent symptoms or develop new symptoms following coronavirus disease 2019 (COVID-19) infection, neuropsychiatric aspects of long COVID are not well known. This review summarizes and provides an update on the neuropsychiatric dimensions of long COVID. Its neuropsychiatric manifestations commonly include fatigue, cognitive impairment, sleep disorders, depression, anxiety, and post-traumatic stress disorder. There are no specific tests for long COVID, but some characteristic findings such as hypometabolism on positron emission tomography have been reported. The possible mechanisms of long COVID include inflammation, ischemic effects, direct viral invasion, and social and environmental changes. Some patient characteristics and the severity and complications of acute COVID-19 infection may be associated with an increased risk of neuropsychiatric symptoms. Long COVID may resolve spontaneously or persist, depending on the type of neuropsychiatric symptoms. Although established treatments are lacking, various psychological and pharmacological treatments have been attempted. Vaccination against COVID-19 infection plays a key role in the prevention of long coronavirus disease. With differences among the SARS-CoV-2 variants, including the omicron variant, the aspects of long COVID are likely to change in the future. Further studies clarifying the aspects of long COVID to develop effective treatments are warranted.     

Reversible cerebral vasoconstriction following carotid endarterectomy

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by the triad of severe "thunderclap" headaches, neurological symptoms and transient segmental cerebral arterial vasoconstriction. We report a patient with RCVS following carotid endarterectomy and review the literature on RCVS following carotid revascularisation.     

Reversible Cerebral Vasoconstriction Syndrome in Patients with Coronavirus Disease: A Multicenter Case Series

Background and objectivesRCVS (Reversible Cerebral Vasoconstrictive Syndrome) is a condition associated with vasoactive agents that alter endothelial function. There is growing evidence that endothelial inflammation contributes to cerebrovascular disease in patients with coronavirus disease 2019 (COVID-19). In our study, we describe the clinical features, risk factors, and outcomes of RCVS in a multicenter case series of patients with COVID-19.Materials and methodsMulticenter retrospective case series. We collected clinical characteristics, imaging, and outcomes of patients with RCVS and COVID-19 identified at each participating site.ResultsTen patients were identified, 7 women, ages 21 – 62 years. Risk factors included use of vasoconstrictive agents in 7 and history of migraine in 2. Presenting symptoms included thunderclap headache in 5 patients with recurrent headaches in 4. Eight were hypertensive on arrival to the hospital. Symptoms of COVID-19 included fever in 2, respiratory symptoms in 8, and gastrointestinal symptoms in 1. One patient did not have systemic COVID-19 symptoms. MRI showed subarachnoid hemorrhage in 3 cases, intraparenchymal hemorrhage in 2, acute ischemic stroke in 4, FLAIR hyperintensities in 2, and no abnormalities in 1 case. Neurovascular imaging showed focal segment irregularity and narrowing concerning for vasospasm of the left MCA in 4 cases and diffuse, multifocal narrowing of the intracranial vasculature in 6 cases. Outcomes varied, with 2 deaths, 2 remaining in the ICU, and 6 surviving to discharge with modified Rankin scale (mRS) scores of 0 (n=3), 2 (n=2), and 3 (n=1).ConclusionsOur series suggests that patients with COVID-19 may be at risk for RCVS, particularly in the setting of additional risk factors such as exposure to vasoactive agents. There was variability in the symptoms and severity of COVID-19, clinical characteristics, abnormalities on imaging, and mRS scores. However, a larger study is needed to validate a causal relationship between RCVS and COVID-19.     

Reversible cerebral vasoconstriction syndrome and dissection in the setting of COVID-19 infection

The current COVID-19 pandemic has recently brought to attention the myriad of neuro- logic sequelae associated with Coronavirus infection including the predilection for stroke, particularly in young patients. Reversible cerebral vasoconstriction syndrome (RCVS) is a well-described clinical syndrome leading to vasoconstriction in the intracra- nial vessels, and has been associated with convexity subarachnoid hemorrhage and oc- casionally cervical artery dissection. It is usually reported in the context of a trigger such as medications, recreational drugs, or the postpartum state; however, it has not been described in COVID-19 infection. We report a case of both cervical vertebral ar- tery dissection as well as convexity subarachnoid hemorrhage due to RCVS, in a pa- tient with COVID-19 infection and no other triggers.     

Management and Outcomes of COVID – 19 Associated Cerebral Venous Sinus Thrombosis

BackgroundSystemic hyper-coagulabilty leading to micro and macro thrombosis is a known complication of Coronavirus disease – 2019(COVID -19). The postulated mechanism appears to be the viral activation of endothelium, triggering the coagulation pathways. Thrombosis of the cerebral veins and sinuses (CVT), a potentially serious condition, has been increasingly reported with COVID – 19 infection. In this clinical study we attempt to describe the clinical profile, investigations and outcomes of patients with COVID- 19 associated CVT.MethodsThis is a single center prospective observational study from South India. The study included patients (aged >18 years) with concomitant COVID infection and CVT. The clinical, laboratory, imaging characteristics, management and outcomes were described and compared with COVID negative CVT patients.ResultsOut of 97 cases of CVT treated at our center during the first and second waves of the COVID pandemic 11/97 (11%) were COVID related CVT. Among these 11 patients, 9 (81%) had presented with only CVT related symptoms and signs and were tested positive for COVID - 19 infection during the pre-hospitalization screening. Respiratory symptoms were absent in 90% of the patients. Headache (100%) and seizures (90%) were the common presenting symptoms. The median time to diagnosis was 6 hours, from presentation to the emergency department. Transverse sinus was involved 10/11 (90%) and majority of them (9/11) had Haemorrhagic Venous Infarction (HVI). Acute inflammatory markers were elevated in comparison with non COVID CVT patients, with the mean serum D-dimer being 2462.75 ng/ml and the C-reactive protein was 64.5 mg/dl. Three patients (30%) underwent decompressive hemicraniectomy (DHC) because of large hemispheric HVI. All patients survived in the COVID CVT group while the mortality in the non COVID group was 4%. At 6 months follow up excellent outcome (modified Rankin Scale (mRS) score of 0–2) was noted equally in both groups.ConclusionsSymptoms and signs of CVT may be the only presentation of COVID-19 infection. Prompt recognition and aggressive medical management including DHC offers excellent outcomes.     

Reversible cerebral vasoconstriction syndrome or primary angiitis of the central nervous system?

BACKGROUND: Reversible Cerebral Vasoconstriction Syndrome (RCVS) may present as thunderclap headache (TCH), accompanied by reversible cerebral vasospasm and focal neurological deficits, often without a clear precipitant. RCVS may be mistaken for Primary Angiitis of the Central Nervous System (PACNS) due to the presence of similar angiographic features of segmental narrowing of cerebral arteries. We discuss the clinical features of a young female migraine patient who developed TCH and was found to have RCVS following initial treatment with corticosteroids for PACNS, in the context of a systematic review of the available medical literature. METHODS: A Medline search was performed to identify all case reports since 1966 describing RCVS and PACNS that provide sufficient clinical detail to permit diagnostic classification according to published criteria. RCVS included case studies in which there was angiographic or transcranial Doppler ultrasound evidence of near-to-complete resolution of cerebral vasoconstriction in the absence of a well-recognized secondary cause. PACNS included reports of histologically confirmed PACNS either through biopsy or necropsy. RESULTS: Reversible Cerebral Vasoconstriction Syndrome occurs primarily in females and is characterized by sudden, severe headache at onset, normal CSF analysis, vasoconstriction involving the Circle of Willis and its immediate branches, and angiographic or TCD ultrasound evidence of near-to-complete vasospastic resolution within 1-4 weeks. It occurs typically in the context of vasoconstrictive drug use, the peripartum period, bathing, and physical exertion. CONCLUSION: Initial and follow-up (within 4 weeks) non-invasive angiographic studies are indicated in patients who present with TCH or who have clinical presentations that could be consistent with RCVS or PACNS in the absence of a well-recognized secondary cause, such as subarachnoid haemorrhage. Early reversibility of cerebral vasospasm is the key neuroradiological feature that supports the clinical diagnosis of RCVS.     

Postvaricella acute transverse myelitis in a previously vaccinated child

We describe a 14-year-old boy with acute transverse myelitis after breakthrough varicella infection, despite immunization with the Varicella zoster virus vaccine 8 years earlier. He recovered fully after treatment with intravenous corticosteroids and acyclovir. To our knowledge, there are no previously reported cases of postvaricella acute transverse myelitis in vaccinated individuals. Our report emphasizes that the Varicella zoster virus booster vaccine may be necessary to prevent not only acute varicella, but also its postinfectious neurologic complications.     

Isolated thunderclap headache during sex: Orgasmic headache or reversible cerebral vasoconstriction syndrome?

Orgasmic headache (OH) is an “explosive” headache that occurs at orgasm. Historically, it was considered benign with no treatment needed. Reversible cerebral vasoconstriction syndrome (RCVS) refers to a group of disorders characterized by recurrent thunderclap headache (TCH) and multifocal vasoconstriction. Patients who have RCVS often recover completely, but some may have persistent neurological deficits. We report a 34-year-old woman who presented with isolated and recurrent TCH at orgasm, which fulfilled the diagnosis of OH. However, she was post-partum and had recent exposure to ecstasy, making her symptoms highly suggestive of RCVS. Brain magnetic resonance angiography showed segmental vasoconstriction. We concluded that she could be considered to have either OH or RCVS. This patient suggests the theory that OH could be a presentation of RCVS. Given that RCVS is potentially treatable, early recognition by clinicians is vital in order to prevent devastating complications.     

COVID-19 Associated Reversible Cerebral Vasoconstriction Syndrome Successfully Treated with Nimodipine and Aspirin

There have been limited cases linking SARS-CoV-2 infection with the development of reversible cerebral vasoconstriction syndrome (RCVS). We hereby report a rare case of RCVS in the setting of mild SARS-CoV-2 respiratory infection successfully treated with nimodipine and aspirin. SARS-CoV-2 attacks the ACE2-receptors, which are expressed in various body organs including the lungs, kidneys, and blood vessels. Vasoconstriction can result from down-regulation of the ACE2-receptors that can lead to sympathetic hypertonia of the cerebral blood vessel walls and/or over-activation of the renin-angiotensin axis.     

Reversible cerebral vasoconstriction syndrome combined with posterior reversible encephalopathy syndrome after heart transplantation

Reversible cerebral vasoconstriction syndrome (RCVS) combined with posterior reversible encephalopathy syndrome (PRES) is a rare complication in patients treated with immunosuppressants. A 52-year-old male patient presented with seizures after heart transplantation. The patient was suspected of having PRES on brain images. Despite the strict blood pressure control, the patient presented with altered mentality and the brain images showed a newly developed large acute infarction. Digital subtraction angiography (DSA) revealed the classic “sausage on a string” appearance of the cerebral arteries – potential feature of RCVS. To our knowledge, this is the first case report to describe RCVS combined with PRES after heart transplantation.     

Stroke care during the COVID‐19 pandemic: experience from three large European countries

In order to cope with the exponentially increasing number of patients infected with SARS‐CoV‐2, European countries made enormous efforts to reorganize medical assistance and several diseases, including stroke, were particularly impacted. We report the experience of stroke neurologists from three European countries (Italy, France and Germany) that faced the pandemic at diverse time points and with different approaches, depending on their resources and healthcare system organization. Pre‐hospital and in‐hospital acute stroke pathways were reorganized to prioritize COVID‐19 management and, in severely affected regions of Italy and France, stroke care was centralized to a limited number of centers, whereas the remaining stroke units were dedicated to patients with COVID‐19. Access to acute stroke diagnostics and time‐dependent therapies was limited or delayed because of reduced capacities of emergency services due to the burden of patients with COVID‐19. A marked reduction in the number of patients presenting with transient ischaemic attack and stroke was noted in the emergency departments of all three countries. Although we only have preliminary data, these conditions may have affected stroke outcome. These indirect effects of the COVID‐19 pandemic could negate the efforts of stroke neurologists over the last few years to improve outcome and reduce mortality of stroke patients. Although the SARS‐CoV‐2 infection rate is slowing down in Europe, the effects of ending lockdown in the next months are unpredictable. It is important for the European and world stroke community to share what has been learned so far to be plan strategies to ensure stroke care in the future and upcoming challenging times.     

Did the COVID‐19 pandemic silence the needs of people with epilepsy?

Aims. The COVID‐19 pandemic shook European healthcare systems, with unavoidable gaps in the management of patients with chronic diseases. We describe the impact of the pandemic on epilepsy care in three tertiary epilepsy centres from Spain and Italy, the most affected European countries. Methods. The three epilepsy centres, members of the European EpiCARE network, manage more than 5,700 people with epilepsy. In Bologna and Barcelona, the hospitals housing the epilepsy centres were fully converted into COVID‐19 units. We describe the reorganization of the clinics and report on the frequency of SARS‐CoV‐2 in people with epilepsy as well as the frequency of seizures in patients admitted to the COVID units. Finally, we elaborate on critical issues regarding the second phase of the pandemic. Results. The activities related to epilepsy care were reduced to less than 10% and were deprioritized. Discharges were expedited and elective epilepsy surgeries, including vagal nerve stimulator implantations, cancelled. Hospitalizations and EEG examinations were limited to emergencies. The outpatient visits for new patients were postponed, and follow‐up visits mostly managed by telehealth. Antiseizure medication weaning plans and changes in vagal nerve stimulator settings were halted. Among the 5,700 people with epilepsy managed in our centres, only 14 tested positive for SARS‐CoV‐2, without obvious impact on their epilepsy. None of the 2,122 patients admitted to COVID units experienced seizures among the early symptoms. Conclusion. Epilepsy care was negatively impacted by the pandemic, irrespective of COVID‐19 epidemiology or conversion of the hospital into a COVID‐19 centre. The pandemic did not silence the needs of people with epilepsy, and this must be considered in the planning of the second phase.     

Reversible cerebral vasoconstriction syndrome identification of prognostic factors

Object

: Reversible cerebral vasoconstriction syndrome (RCVS) is described as a clinical and radiological entity characterized by thunderclap headaches, a reversible segmental or multifocal vasoconstriction of cerebral arteries with or without focal neurological deficits or seizures. The purpose of this study is to determine risk factors of poor outcome in patients presented a RCVS.

Methods

A retrospective multi-center review of invasive and non-invasive neurovascular imaging between January 2006 and January 2011 has identified 10 patients with criterion of reversible segmental vasoconstriction syndrome. Demographics data, vascular risks and evolution of each of these patients were analyzed.

Results

Seven of the ten patients were females with a mean age of 46 years. In four patients, we did not found any causative factors. Two cases presented RCVS in post-partum period between their first and their third week after delivery. The other three cases were drug-induced RCVS, mainly vaso-active drugs. Cannabis was found as the causative factor in two patient, Sumatriptan identified in one patient while cyclosporine was the causative agent in also one patient. The mean duration of clinical follow-up was 10.2 months (range: 0–28 months). Two patients had neurological sequelae: one patient kept a dysphasia and the other had a homonymous lateral hemianopia. We could not find any significant difference of the evolution between secondary RCVS and idiopathic RCVS. The only two factors, which could be correlated to the clinical outcome were the neurological status at admission and the presence of intraparenchymal abnormalities (ischemic stroke, hematoma) in brain imaging.

Conclusions

Fulminant vasoconstriction resulting in progressive symptoms or death has been reported in exceptional frequency. Physicians had to remember that such evolution could happen and predict them by identifying all factors of poor prognosis (neurological status at admission, the presence of intraparenchymal abnormalities).     

Bilateral facial nerve palsy associated with COVID‐19 and Epstein–Barr virus co‐infection

COVID‐19 can occasionally be associated with cranial nerve involvement, but facial palsy, particularly if bilateral, is exceptional. We here report a patient who presented with severe bilateral facial palsy and evidence of SARS‐CoV‐2 infection preceded by upper respiratory symptoms. He also had serological evidence of coinfection with Epstein‐Barr virus, which could have also played a role in his neurological manifestations. PCR in the cerebrospinal fluid was negative for both EBV and SARS‐CoV‐2, which suggests an indirect, immune‐mediated mechanism rather than direct, viral‐induced damage. The patient was treated with prednisone 60 mg/24h with a tapering schedule and had a favorable outcome, with an almost complete recovery in 3 weeks. SARS‐CoV‐2 adds to the list of infectious agents causative of bilateral facial palsy. Coinfection with SARS‐CoV‐2 is not rare and should be considered in the differential diagnosis.     

External carotid artery branches involvement in reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by segmental vasoconstriction and dilatation of intracranial arteries, usually revealed by headaches, which spontaneously resolve in few weeks. We report a patient with RCVS, revealed by thunderclap headaches, involving both internal and external carotid artery (ECA). She received fluoxetin for depression and took a great amount of cannabis in the last months. While angio-MR, transcranial Doppler and CSF analysis were normal, cerebral angiography disclosed stenoses and dilatations of the middle cerebral artery. It also showed an involvement of maxillary arteries. Fluoxetin and cannabis were stopped. After few days, she had no more headaches. At 8th week, angiography was normalized confirming the RCVS. ECA angiogram may help reaching a diagnosis in patients with suspected RCVS when intracerebral abnormalities are minor or absent.     

Reversible Vasoconstriction Syndrome with Bilateral Basal Ganglia Hemorrhages

Reversible cerebral vasoconstriction syndrome (RCVS) is an increasingly recognized acute cerebrovascular condition that may produce myriad transient and sustained neurologic deficits as well as a host of radiologic features. We report the case of a woman with RCVS and a severe clinical syndrome with bilateral basal ganglia hemorrhages, cerebral infarctions, and marked vascular abnormalities. The patient made a near complete clinical recovery, representing an extreme and illustrative form of RCVS.     

Invited Review: The spectrum of neuropathology in COVID‐19

There is increasing evidence that patients with Coronavirus disease 19 (COVID‐19) present with neurological and psychiatric symptoms. Anosmia, hypogeusia, headache, nausea and altered consciousness are commonly described, although there are emerging clinical reports of more serious and specific conditions such as acute cerebrovascular accident, encephalitis and demyelinating disease. Whether these presentations are directly due to viral invasion of the central nervous system (CNS) or caused by indirect mechanisms has yet to be established. Neuropathological examination of brain tissue at autopsy will be essential to establish the neuro‐invasive potential of the SARS‐CoV‐2 virus but, to date, there have been few detailed studies. The pathological changes in the brain probably represent a combination of direct cytopathic effects mediated by SARS‐CoV‐2 replication or indirect effects due to respiratory failure, injurious cytokine reaction, reduced immune response and cerebrovascular accidents induced by viral infection. Further large‐scale molecular and cellular investigations are warranted to clarify the neuropathological correlates of the neurological and psychiatric features seen clinically in COVID‐19. In this review, we summarize the current reports of neuropathological examination in COVID‐19 patients, in addition to our own experience, and discuss their contribution to the understanding of CNS involvement in this disease.     

Fulminant Guillain-Barr�� Syndrome Mimicking Cerebral Death Following Acute Viral Hepatitis A

A 32-year-old man was transferred to an intensive care unit due to respiratory difficulties with a 4-day history of progressive areflexic quadriparesis following acute hepatitis A. A nerve-conduction study revealed inexcitability of most nerves. The cerebrospinal fluid showed albuminocytologic dissociation, suggesting Guillain-Barré syndrome (GBS). The patient appeared brain dead on day 4, showing absent brainstem reflexes, respiratory failure, and fully dilated and fixed pupils. This case is an example of how GBS can evolve and simulate a brain-dead state from fulminant deafferentation following acute hepatitis A.     

PRES and RCVS: Two Distinct Entities or a Spectrum of the Same Disease?

ObjectivesTo report a case of a patient with overlapping posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), and review the existing literature emphasizing the pathophysiological overlap of these two entities.Materials and MethodsWe conducted a literature search in electronic database PubMed identifying studies reporting the overlap of PRES and RCVS.ResultsPRES and RCVS are two increasingly recognized entities that share similar clinical and imaging features. PRES is characterized by vasogenic edema predominantly in the parieto-occipital regions, associated with acute onset of neurological symptoms including encephalopathy, seizures, headaches, and visual disturbances. RCVS is characterized by reversible segmental and multifocal vasoconstriction of the cerebral arteries and classically presents with thunderclap headache, with or without associated focal neurological deficits and seizures. PRES is frequently associated with uncontrolled hypertension but can also be seen in the setting of renal failure, exposure to cytotoxic agents, or pre-eclampsia. RCVS is often triggered by exposure to vasoactive agents, postpartum state, or immunosuppression. We report a case of a patient presenting with vision changes and hemiparesis, and found to have extensive cytotoxic and vasogenic edema involving the cortex and subcortical white matter on brain imaging. These changes were primarily noted in the parieto-occipital and brainstem regions, along with features of reversible vasculopathy on vascular imaging suggestive of coexisting PRES and RCVS.ConclusionsPRES and RCVS share precipitating factors, clinical and radiological features, and frequently co-exist, suggesting a common pathophysiological mechanism related to reversible dysregulation of cerebral vasculature, endothelial dysfunction, and breakdown of the blood-brain barrier.     

Bilateral facial palsy with paresthesias,variant of Guillain-Barré syndrome following COVID-19 vaccine: A case series of 9 patients

Several cases of Guillain-Barré Syndrome (GBS) associated with COVID-19 vaccination have been reported, including the rare subtype known as Bilateral Facial Palsy with paresthesias (BFP). To date, it is not known whether a causal relationship may exist between the two. We report 9 cases of BFP in patients vaccinated against COVID-19 in the previous month. Nerve conduction studies revealed demyelinating polyneuropathy in 4 patients, and 5 presented bilateral, focal facial nerve involvement, exclusively. Ganglioside antibody panel was positive in 4 patients (anti-GM1=2, anti-GD1a=1 and anti-sulfatide=1). Seven patients received intravenous immunoglobulin treatment, one plasma exchange, and one patient died from sudden cardiac arrest following arrhythmia before treatment could be administered. Rates of BFP following COVID-19 vaccination, did not differ from those reported in previous series. Epidemiological studies are essential to determine whether a causal relationship may exist between this rare form of GBS and COVID-19 vaccination.