Disorders of Consciousness Associated With COVID-19: A Prospective Multimodal Study of Recovery and Brain Connectivity.

BACKGROUND AND OBJECTIVES: In patients with severe coronavirus disease 2019 (COVID-19), disorders of consciousness (DoC) have emerged as a serious complication. The prognosis and pathophysiology of COVID-DoC remain unclear, complicating decisions about continuing life-sustaining treatment. We describe the natural history of COVID-DoC and investigate its associated brain connectivity profile. METHODS: In a prospective longitudinal study, we screened consecutive patients with COVID-19 at our institution. We enrolled critically ill adult patients with a DoC unexplained by sedation or structural brain injury and who were planned to undergo a brain MRI. We performed resting-state fMRI and diffusion MRI to evaluate functional and structural connectivity compared to healthy controls and patients with DoC resulting from severe traumatic brain injury (TBI). We assessed the recovery of consciousness (command following) and functional outcomes (Glasgow Outcome Scale Extended [GOSE] and the Disability Rating Scale [DRS]) at hospital discharge and 3 and 6 months after discharge. We also explored whether clinical variables were associated with recovery from COVID-DoC. RESULTS: After screening 1,105 patients with COVID-19, we enrolled 12 with COVID-DoC. The median age was 63.5 years (interquartile range 55-76.3 years). After the exclusion of 1 patient who died shortly after enrollment, all of the remaining 11 patients recovered consciousness 0 to 25 days (median 7 [5-14.5] days) after the cessation of continuous IV sedation. At discharge, all surviving patients remained dependent: median GOSE score 3 (1-3) and median DRS score 23 (16-30). Ultimately, however, except for 2 patients with severe polyneuropathy, all returned home with normal cognition and minimal disability: at 3 months, median GOSE score 3 (3-3) and median DRS score 7 (5-13); at 6 months, median GOSE score 4 (4-5), median DRS score 3 (3-5). Ten patients with COVID-DoC underwent advanced neuroimaging; functional and structural brain connectivity in those with COVID-DoC was diminished compared to healthy controls, and structural connectivity was comparable to that in patients with severe TBI. DISCUSSION: Patients who survived invariably recovered consciousness after COVID-DoC. Although disability was common after hospitalization, functional status improved over the ensuing months. While future research is necessary, these prospective findings inform the prognosis and pathophysiology of COVID-DoC. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier: NCT04476589.

Clinical course of SARS-CoV-2 infection in patients with severe acquired brain injury and a disorder of consciousness: an observational study.

Purpose: SARS-CoV-2 infection can cause the coronavirus disease (COVID), ranging from flu-like symptoms to interstitial pneumonia. Mortality is high in COVID pneumonia and it is the highest among the frailest. COVID could be particularly serious in patients with severe acquired brain injury (SABI), such as those with a disorder of consciousness. We here describe a cohort of patients with a disorder of consciousness exposed to SARS-CoV-2 early after their SABI.Materials and methods: The full cohort of 11 patients with SABI hospitalized in March 2020 in the IRCCS Fondazione Don Gnocchi rehabilitation (Milan, Italy) was recruited. Participants received SARS-CoV-2 testing and different clinical and laboratory data were collected.Results: Six patients contracted SARS-CoV-2 and four of them developed the COVID. Of these, one patient had ground-glass opacities on the chest CT scan, while the remaining three developed consolidations. No patient died and the overall respiratory involvement was mild, requiring in the worst cases low-flow oxygen.Conclusions: Here we report the clinical course of a cohort of patients with SABI exposed to SARS-CoV-2. The infection spread among patients and caused COVID in some of them. Unexpectedly, COVID was moderate, caused at most mild respiratory distress and did not result in fatalities.

Alteración del nivel de conciencia puerperal: ¿puede el COVID-19 ser causa de síndrome de encefalopatía posterior reversible? / Postpartum consciousness disturbance: can covid-19 cause posterior reversible encephalopathy syndrome?

Describimos el caso de una gestante de 24 años de edad, sin enfermedades previas, que fue ingresada con diagnóstico de neumonía bilateral por el nuevo coronavirus 2. Por empeoramiento clínico precisó cesárea urgente con anestesia general e intubación orotraqueal por intolerancia al decúbito. Tras la extubación desarrolló un cuadro de obnubilación que obligó al diagnóstico diferencial de encefalitis/meningitis por SARS-CoV-2, con tomografía computarizada (TC) y angioTC normales, bioquímica del líquido cefalorraquídeo (LCR) inespecífica y resonancia magnética informada como «síndrome de encefalopatía posterior reversible» (al presentar características radiológicas sugestivas de edema vasogénico con alteraciones en la sustancia blanca de localización parieto-temporo-occipital, junto con alteración de nivel de conciencia) secundaria a cuadro hipertensivo del embarazo. La paciente 11 días después de la cesárea comenzó a desarrollar un cuadro hipertensivo que requirió tratamiento. La encefalopatía posterior reversible (PRES) asocia un conjunto de características clínicas (cefalea, alteración del nivel de conciencia, alteraciones visuales y convulsiones) y radiológicas (alteraciones reversibles en la sustancia blanca fundamentalmente en regiones parieto-temporo-occipitales) sugestivas de edema vasogénico. En pacientes gestantes SARS-CoV-2, el diagnóstico diferencial de la patología hipertensiva y las alteraciones de nivel de conciencia puede ser extremadamente complicado, al encontrarnos pruebas complementarias normales y ausencia de hipertensión arterial (HTA) en el periparto inmediato. Tal vez la secuenciación del genoma del SARS-CoV-2 en el LCR nos hubiera permitido un diagnóstico de certeza, aunque el tratamiento no hubiera variado

We describe the case of a 24-year-old pregnant woman with no history of note who was admitted with a diagnosis of bilateral pneumonia caused by the new coronavirus. Due to clinical worsening, she required urgent cesarean section with general anaesthesia and intubation for decubitus intolerance. After extubation, she presented altered mental state that required a differential diagnosis of encephalitis/meningitis secondary to SARS-CoV-2. CT and CT-angiography were normal, spinal fluid tests were non-specific, and magnetic resonance imaging reported posterior reversible encephalopathy syndrome (PRES) (due to radiological features suggestive of white matter vasogenic edema affecting the parietal, temporal and occipital lobes, along with altered mental state) secondary to gestational hypertension. Eleven days after the cesarean section the patient began to develop hypertension that required treatment. PRES is associated with certain clinical (headache, altered mental state, visual disturbances and convulsions) and radiological (reversible changes in white substance mainly affecting the parietal, temporal, and occipital lobes) characteristics suggestive of vasogenic oedema In pregnant SARS-CoV-2 patients, the differential diagnosis of hypertension and altered mental state is often extremely complicated because complementary tests can be normal and there is no immediate sign of peripartum hypertension. SARS-CoV-2 genome sequencing in spinal fluid could have provided a definitive diagnosis, but the treatment would not have differed

[Epidemic of rubella encephalitis]. / Encéphalite rubéolique : observation récente d'une fréquence inhabituelle.

Rubella is a mild viral illness in children. Rubella encephalitis is an extremely uncommon complication of rubella affecting unvaccinated children, aged between 5 and 14 years. From May to June 2011, we observed 9 cases of rubella encephalitis diagnosed during an epidemic of rubella. All were previously healthy (8 boys and 1 girl). None of them had received rubella vaccine. The mean age was 11.6 years. The onset of neurological symptoms occurred within 1-5 days after the typical rush and was associated with seizures and altered consciousness in all cases. The presence of serum immunoglobulin M antibody against rubella virus was demonstrated in all patients. EEGs showed slow wave activity in all patients and brain MRI was normal in the 9 cases. Full recovery was obtained in all patients. However, 4 of them required intensive care unit referral. Acute encephalitis is an extremely rare complication of rubella. The main neurological findings are headache, ataxia, and hemiplegia. Epileptic seizure and altered consciousness are rarely observed. Rubella encephalitis is generally self-limiting with about 80% recovery rate with no sequelae. However, severe courses have been reported. These cases illustrated the potential severity of rubella and they should be prevented by encouraging widespread early childhood vaccination. In Tunisia, rubella encephalitis has been reported once previously and vaccination against rubella virus has only recently been included in the national vaccination program, prescribed only for adolescent females. Following this rubella epidemic, vaccination strategies in Tunisia have been revised.

Viral encephalitis in the ICU.

Viral encephalitis causes an altered level of consciousness, which may be associated with fever, seizures, focal deficits, CSF pleocytosis, and abnormal neuroimaging. Potential pathogens include HSV, VZV, enterovirus, and in some regions, arboviruses. Autoimmune (eg, anti-NMDA receptor) and paraneoplastic encephalitis are responsible for some cases where no pathogen is identified. Indications for ICU admission include coma, status epilepticus and respiratory failure. Timely initiation of anti-viral therapy is crucial while relevant molecular and serological test results are being performed. Supportive care should be directed at the prevention and treatment of cerebral edema and other physiological derangements which may contribute to secondary neurological injury.

Classification of acute encephalopathy in respiratory syncytial virus infection.

Infection with respiratory syncytial virus (RSV) is known to be associated with central nervous system symptoms such as convulsions. We investigated cytokines, nitrogen oxide (NO)( x ), and the viral genome in cerebrospinal fluid (CSF) obtained from children with RSV infection-related convulsions or central nervous symptoms and compared the data with type of encephalopathy. Of nine patients enrolled (six boys and three girls; aged 10 days-3 years), one metabolic error, five excitotoxicity, one cytokine storm, and two hypoxia cases were found. The patients presented with unilateral convulsions, generalized convulsions, and convulsions following cardiopulmonary arrest, apnea, and nuchal rigidity. In all patients, a rapid check for RSV of nasal fluid was positive. The RSV genome (subgroup A) was detected in the CSF of five of the nine patients; two patients with hypoxic encephalopathy were negative for the RSV genome. The CSF interleukin (IL)-6 levels were high only in patients with the excitotoxicity and cytokine storm type of encephalopathy. NO( x ) levels were high in all the subject cases. In the excitotoxicity type, NO( x ) levels were significantly higher than those in the control and other groups. NO( x ) level may become an important parameter for the diagnosis and classification of acute encephalopathy in RSV. Strategies to treat each type of encephalopathy, targeting cytokines and free radicals, should be established.

Midbrain and spinal cord magnetic resonance imaging (MRI) changes in poliomyelitis.

Poliomyelitis, though eradicated from most parts of the world, continues to occur in India. There is paucity of data on the magnetic resonance imaging (MRI) changes in poliomyelitis. We report a 3(1/2)-year-old boy who presented with subacute onset flaccid paralysis and altered sensorium. Stool culture was positive for wild polio virus type 3. Magnetic resonance imaging revealed signal changes in bilateral substantia nigra and anterior horns of the spinal cord. These MRI changes may be of potential diagnostic significance in a child with poliomyelitis.

Herpes zoster with progression to acute varicella zoster virus-meningoencephalitis.

BACKGROUND: Acute meningoencephalitis (ME) from varicella zoster virus (VZV) reactivation is a rare and serious complication of herpes zoster (HZ). OBJECTIVES AND METHODS: As early diagnostic detection is mandatory to prevent long-term sequelae, any clinical indication is helpful to identify patients that are at higher risk of the development of VZV-ME. In order to find such risk factors, the clinical data of 38 patients consecutively hospitalized for the treatment of HZ over a 1-year period were analyzed. RESULTS: Four of the 38 patients with HZ developed ME. Of these, three had involvement of the trigeminal nerve branch, one including an ophthalmic affection, and one presented with disseminated HZ. All were women with an average age of 83.5 years, in comparison with patients with HZ but without ME who had an average age of 69.3 years and a female preponderance of 60%. The first clinical signs of ME were rapidly progressing somnolence and meningism. Patients with HZ-ME were treated with intravenous acyclovir, oral glucocorticosteroids, and antiseizure therapy, and recovered almost completely without major residual symptoms. CONCLUSION: Progression of HZ to ME seems to occur more often than normally believed. Female patients above 80 years of age with either ophthalmic involvement or disseminated HZ are at a potentially high risk of the development of ME. The general recommendation of starting oral glucocorticosteroids from day 1 of antiviral treatment in older patients must be questioned, as it may stimulate VZV replication and dissemination.

Reactivation and centripetal spread of herpes simplex virus complicating acoustic neuroma resection.

BACKGROUND: Herpes simplex is a common human pathogen that has rare but severe manifestations including encephalitis. CASE DESCRIPTION: A 44-year-old man underwent uneventful resection of an acoustic neuroma. Postoperatively, he developed swinging pyrexia, vomiting, and episodic confusion. Analysis of cerebrospinal fluid showed a lymphocytosis, and polymerase chain reaction revealed herpes simplex DNA. After treatment of herpes encephalitis with acyclovir, the patient made a good recovery. CONCLUSION: Herpes encephalitis is a rare complication of neurosurgical procedures, and the most likely etiology is reactivation of latent infection from manipulation of cranial nerves.

Neurologic complications associated with novel influenza A (H1N1) virus infection in children - Dallas, Texas, May 2009.

Neurologic complications, including seizures, encephalitis, encephalopathy, Reye syndrome, and other neurologic disorders, have been described previously in association with respiratory tract infection with seasonal influenza A or B viruses, but not with novel influenza A (H1N1) virus. On May 28, 2009, the Dallas County Department of Health and Human Services (DCHHS) notified CDC of four children with neurologic complications associated with novel influenza A (H1N1) virus infection admitted to hospitals in Dallas County, Texas, during May 18-28. This report summarizes the clinical characteristics of those four cases. Patients were aged 7-17 years and were admitted with signs of influenza-like illness (ILI) and seizures or altered mental status. Three of the four patients had abnormal electroencephalograms (EEGs). In all four patients, novel influenza A (H1N1) viral RNA was detected in nasopharyngeal specimens but not in cerebrospinal fluid (CSF). Antiviral therapy included oseltamivir (four patients) and rimantadine (three patients). All four patients recovered fully and had no neurologic sequelae at discharge. These findings indicate that, as with seasonal influenza, neurologic complications can occur after respiratory tract infection with novel influenza A (H1N1) virus. For children who have ILI accompanied by unexplained seizures or mental status changes, clinicians should consider acute seasonal influenza or novel influenza A (H1N1) virus infection in the differential diagnosis, send respiratory specimens for appropriate diagnostic testing, and promptly initiate empirical antiviral treatment, especially in hospitalized patients.

Neurologic manifestations of pediatric chikungunya infection.

Chikungunya virus, a mosquito-borne arbovirus, was responsible for a massive epidemic in La Réunion Island during 2005 to 2006. The disease is usually benign, but neurologic involvement, with sometimes fatal outcome, has been described. We report a retrospective hospital-based pediatric series of 30 children (23 boys and 7 girls) who presented neurologic manifestations of chikungunya such as encephalitis (n = 12), febrile seizures (n = 10), meningeal syndrome (n = 4), and acute encephalopathy (n = 4). Cerebrospinal fluid biological and cytological analyses (n = 23) were unremarkable except for 1 case of acute disseminated encephalomyelitis. The presence of viral genome in cerebrospinal fluid was inconstantly positive. Brain magnetic resonance imaging (MRI) scans (n = 14) were abnormal in 5 cases. Electroencephalography was nonspecific. Two patients died. At discharge and 6 months later, 5 children had neurologic sequelae. Patients with initial severe neurologic presentation and having pathological brain MRI had more sequelae or fatal disease.

Febrile seizures associated with influenza A.

To clarify the clinical impact of influenza A on the development of febrile seizures (FS), consecutive FS patients brought to our hospital between October 2003 and September 2004 were prospectively surveyed. Patients infected with influenza A (influenza A patients) and those uninfected with influenza (non-influenza patients) were compared with regard to clinical characteristics of FS. Influenza infection was determined by rapid antigen test and/or serologically. Associations of influenza A with atypical findings of FS, including partial seizures, prolonged seizures, multiple seizures during the same illness, and 30-min or longer prolonged postictal impairment of consciousness (PPIC), were analyzed by multiple logistic regression. A total of 215 patients (47 influenza A and 168 non-influenza patients) were enrolled in the study. Age was significantly higher in the influenza A group (39.85+/-22.16 months vs. 27.51+/-17.14 months, P<0.001). Of 42 patients aged 48 months or older, which corresponded to the 80th percentile for age, 15 (35.7%) were influenza A patients, with a significantly higher incidence of such patients than in the subgroup of patients aged 47 months or younger (32/173, 18.5%) (P=0.015). On multiple logistic regression analysis, influenza A was independently associated with PPIC (odds ratio: 4.44, 95% confidence interval: 1.52-12.95, P=0.006), but not with other atypical findings. The positive association of influenza A with PPIC suggests that influenza may affect state of consciousness at the same time that it induces seizures with fever.

Herpes simplex encephalitis: some interesting presentations.

Herpes Simplex Encephalitis (HSE) is the most common cause of fatal viral encephalitis. A high index of suspicion is mandatory for early diagnosis and successful therapy to restrict morbidity and mortality. We report 4 patients of HSE, with interesting presentations, viz. brainstem involvement in an immunosuppressed patient, Kluver-Bucy Syndrome-a consequence of untreated HSE, HSE in the postpartum period mistaken as cortical venous thrombosis, and response to inadequate treatment. They demonstrate the wide spectrum of clinical features, pitfalls in diagnosis, and a variable response to therapy in HSE.

West Nile virus infection in 2002: morbidity and mortality among patients admitted to hospital in southcentral Ontario.

BACKGROUND: In August and September 2002 an outbreak of West Nile virus (WNV) infection occurred in southern Ontario. We encountered a number of seriously ill patients at our hospitals. In this article we document the clinical characteristics of these cases. METHODS: We conducted a retrospective chart review of patients who came to the attention of infectious disease or neurology consultants or the microbiology laboratories at 7 hospitals in the municipalities of Toronto, Peel and Halton, Ont. Patients were included if they had been admitted to hospital or stayed overnight in the emergency department, had serological evidence of WNV infection and had clinical evidence of WNV fever, aseptic meningitis, encephalomyelitis or motor neuronopathy. RESULTS: In all, 64 patients met the inclusion criteria; 57 had encephalitis or neuromuscular weakness or both, 5 had aseptic meningitis, and 2 had WNV fever. The mean age was 61 years (range 26-87). The patients were predominantly active, middle-aged or elderly people living independently in the community. Seven patients were immunocompromised A febrile prodromal illness preceded the neurological symptoms in almost all cases. The most common neurological abnormality was decreased level of consciousness; this frequently evolved to severe lower motor neuron neuromuscular weakness. Ataxia and swallowing disorders were frequent and important problems. Sixteen patients (25%) required intubation and mechanical ventilation because of a decreased level of consciousness, inability to clear secretions or respiratory muscle weakness; 9 others had disabling muscle weakness of one or more limbs. Ten patients died. The study patients were in hospital a total of 1856 patient-days, including 532 patient-days in an intensive care unit. Only 28% (13/47) of the patients who survived encephalitis or neuromuscular weakness, or both, were discharged home without additional support. Slow turnaround time for serological test results resulted in delayed diagnosis. INTERPRETATION: The 2002 WNV infection outbreak in Ontario caused serious morbidity and mortality in the subset of patients who had encephalitis or neuromuscular weakness severe enough to require hospital admission.

[The course of the tick-born encephalitis (TBE) in patients hospitalized at the Department of Infectious Diseases in Bialystok in the year 2001]. / Przebieg kleszczowego zapalenia mózgu (kzm) u chorych hospitalizowanych w klinice chorób zakaznych i neuroinfekcji AMB w roku 2001.

AIM: To characterize epidemiological and clinical features of TBE in the Northeastern Poland. METHODS: Analysis of clinical and epidemiological data of patients hospitalized with the diagnosis of TBE in the Department of the Infectious Diseases and Neuroinfections of the Medical University in Bialystok in 2001. MAIN OBSERVATIONS: TBE was diagnosed in 48 patients. From that number 18 (37.5%) presented symptoms of meningitis, 24 (50.0%) meningoencephalitis, 5 (10.4%) meningoencephalomyelitis and 1 (2.1%) meningoencephaloradiculitis. RESULTS: Headache (100%) and fever (87.5%) were the most common complaints. Signs of meningitis were observed in 35 patients (72.9%). Common neurological abnormalities were Oppenheim and Babinski signs (18 patients, 37.5%), pareses (8; 16.7%), ataxia (7; 14.58%) and impaired consciousness (6; 12.5%). Cytosis in cerebrospinal fluid (csf) was observed in all patients, frequently accompanied by high csf protein concentration, raised erythrocyte sedimentation rate (61.5%), leucocytosis (31.25%) and aminotrasferase activity (12.5%). There were no professional forest workers among the patients.