Outcome predictors of post-COVID conditions in the European Academy of Neurology COVID-19 registry.

Several neurological manifestations are part of the post-COVID condition. We aimed to: (1) evaluate the 6-month outcome in the cohort of patients with neurological manifestations during the COVID-19 acute phase and surviving the infection, and find outcome predictors; (2) define the prevalence and type of neurological symptoms persistent at six months after the infection. Data source was an international registry of patients with COVID-19 infection and neurological symptoms, signs or diagnoses established by the European Academy of Neurology. Functional status at six-month follow-up was measured with the modified Rankin scale (mRS), and defined as: "stable/improved" if the mRS at six months was equal as or lower than the baseline score; "worse" if it was higher than the baseline score. By October 30, 2022, 1,003 lab-confirmed COVID-19 patients were followed up for a median of 6.5 months. Compared to their pre-morbid status, 522 patients (52%) were stable/improved, whereas 465 (46%) were worse (functional status missing for 16). Age, hospitalization, several pre-COVID-19 comorbidities, and COVID-19 general complications were predictors of a worse status. Amongst neurological manifestations, stroke carried the highest risk for worse outcome (OR 5.96), followed by hyperactive delirium (2.8), and peripheral neuropathies (2.37). On the other hand, hyposmia/hypogeusia (0.38), headache (0.40), myalgia (0.45), and COVID-19 vaccination (0.52) were predictors of a favourable prognosis. Persisting neurological symptoms or signs were reported by 316/1003 patients (31.5%), the commonest being fatigue (n = 133), and impaired memory or concentration (n = 103). Our study identified significant long-term prognostic predictors in patients with COVID-19 and neurological manifestations.

Epilepsy hospitalizations and mental disorders: A Portuguese population-based observational retrospective study (2008-2015).

BACKGROUND: Psychiatric comorbidities are highly frequent in people with epilepsy and were found to be markers of poorer prognosis. These comorbidities increase the use of healthcare resources, including emergency department visits and inpatient care. Despite this, there is little information on healthcare utilization associated with a wide range of comorbid mental disorders in people with epilepsy (PWE). OBJECTIVE: To characterize registered mental disorders among all hospitalizations with a primary diagnosis of epilepsy and to analyze their association with crucial hospitalization outcomes. METHODS: An observational retrospective study was performed using administrative data from hospitalization episodes with epilepsy as the primary diagnosis discharged between 2008 and 2015. Mental disorder categories 650 to 670 from Clinical Classification Software were selected as secondary diagnoses. Mann-Whitney U, Kruskall-Wallis, and Chi-squared tests were used to establish comparisons. For each episode, data regarding hospitalization outcomes was retrieved, including length of stay (LoS), in-hospital mortality (IHM), 8-year period readmissions, and total estimated charges. RESULTS: Overall, 27,785 hospitalizations were analyzed and 33.9% had registered mental disorders, with alcohol-related disorders being the most prevalent (11.7%). For episodes with a concomitant register of a mental disorder, LoS was significantly longer (5.0 vs. 4.0 days, P <0.001), and IHM was higher (2.8% vs. 2.2%, P <0.001), as were readmissions (25.5% vs. 23.7%, P <0.001), and median episodes' charges (1,578.7 vs. 1,324.4 euros, P <0.001). CONCLUSION: Epilepsy-related hospitalizations with registered mental disorders heightened the utilization of healthcare resources, stressing the importance of diagnosing and treating mental disorders in PWE.

Comparative features and outcomes of major neurological complications of COVID-19.

BACKGROUND AND PURPOSE: The aim of this study was to assess the neurological complications of SARS-CoV-2 infection and compare phenotypes and outcomes in infected patients with and without selected neurological manifestations. METHODS: The data source was a registry established by the European Academy of Neurology during the first wave of the COVID-19 pandemic. Neurologists collected data on patients with COVID-19 seen as in- and outpatients and in emergency rooms in 23 European and seven non-European countries. Prospective and retrospective data included patient demographics, lifestyle habits, comorbidities, main COVID-19 complications, hospital and intensive care unit admissions, diagnostic tests, and outcome. Acute/subacute selected neurological manifestations in patients with COVID-19 were analysed, comparing individuals with and without each condition for several risk factors. RESULTS: By July 31, 2021, 1523 patients (758 men, 756 women, and nine intersex/unknown, aged 16-101 years) were registered. Neurological manifestations were diagnosed in 1213 infected patients (79.6%). At study entry, 978 patients (64.2%) had one or more chronic general or neurological comorbidities. Predominant acute/subacute neurological manifestations were cognitive dysfunction (N = 449, 29.5%), stroke (N = 392, 25.7%), sleep-wake disturbances (N = 250, 16.4%), dysautonomia (N = 224, 14.7%), peripheral neuropathy (N = 145, 9.5%), movement disorders (N = 142, 9.3%), ataxia (N = 134, 8.8%), and seizures (N = 126, 8.3%). These manifestations tended to differ with regard to age, general and neurological comorbidities, infection severity and non-neurological manifestations, extent of association with other acute/subacute neurological manifestations, and outcome. CONCLUSIONS: Patients with COVID-19 and neurological manifestations present with distinct phenotypes. Differences in age, general and neurological comorbidities, and infection severity characterize the various neurological manifestations of COVID-19.

Cognitive impairment and markers of optical neurodegeneration in early multiple sclerosis.

INTRODUCTION: Cognitive impairment and retinal atrophy have been proposed as two potential markers of neurodegeneration in multiple sclerosis (MS). We aimed at assessing the relation between peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell layer (mGCL) atrophy and cognitive performance in early MS. METHODS: This is a multicenter cross-sectional study on patients with early MS (clinically isolated syndrome and relapsing-remitting MS), with an EDSS score ≤ 3.0. Patients with previous optic neuritis, other ocular diseases, psychiatric illness, or recent relapse were excluded. All patients underwent standardized optical coherence tomography (OCT) and neuropsychological evaluation with validated tests for MS patients. Cognitive impairment was defined as having two cognitive tasks below age- and education-adjusted norms. RESULTS: We recruited 52 patients with early MS, with an average age of 37 years (SD = 10.5), an average disease duration of 3.69 years (SD = 2.3), and a median EDSS of 1.0 (IQR = 0.5). In this sample, 15/52 patients presented cognitive impairment. Regarding OCT measurements, 7/52 patients had an average pRNFL below the 5th percentile and 2/52 had an average mGCL below the 5th percentile. The average pRNFL thickness was comparable in cognitively impaired and cognitively preserved patients (100.3 µm vs 103.1 µm, p = 0.52); the average mGCL thickness had also similar values between groups (50.5 µm vs 53 µm, p = 0.38). CONCLUSIONS: Cognitive impairment was frequent in our sample of early MS. However, no association with reduced pRNFL or mGCL thickness was found. When compared to OCT, cognitive assessment could provide an earlier marker of neurodegeneration in MS.

Natural history of relapsing remitting multiple sclerosis in a long-lasting cohort from a tertiary MS centre in Portugal.

BACKGROUND: Several disease-modifying therapies (DMTs) have emerged in the last two decades for the treatment of multiple sclerosis (MS). The increasing use of these therapies has enhanced the need to study its impact on long-term disease progression and on the natural history of MS. This study aimed to characterize a Portuguese MS patient cohort in what concerns the natural history of disease by exploring differences throughout 3 decades. METHODS: Longitudinal, retrospective, non-interventional study. Patients aged ≥ 18 years old, with confirmed diagnosis of relapsing-remitting MS (RRMS), were included. Biodemographic and clinical characteristics (MS diagnosis, patient follow-up, relapses, treatment, and exams) were assessed and compared according to the first appointment date throughout 10-year spans (1987-1996; 1997-2006; 2007-2016). RESULTS: 548 patients were included in this analysis. Significant differences were observed between decades for evoked potential (EP) and cerebrospinal fluid (CSF) exams conducted at diagnosis, the first with less expression on the last decade; the median number of relapses per year (higher in the subgroup 07-16); EDSS at baseline and at last appointment (both higher in the subgroup 87-96); and the percentage of patients achieving EDSS 3.0 and EDSS 6.0 (increased in the subgroup 87-96). Additionally, time from diagnosis to first treatment was significantly lower in patients from the most recent decade, and a greater percentage of such patients, compared to the other two subgroups, was, at last appointment, under a second line DMT. CONCLUSION: In general, our study reflects findings from longitudinal studies on MS progression already published in the literature. In recent years, the growing number of more effective DMTs, along with earlier disease detection, and improvements in access to healthcare appear to have had a positive impact on patients' access to treatment and, consequently, disease progression. Additional studies, with increased follow up time, are needed to further investigate the effect of treatment improvement in the natural history of MS.

Neuro-COVID frequency and short-term outcome in the Northern Portuguese population.

BACKGROUND AND PURPOSE: COVID-19-related acute neurological phenotypes are being increasingly recognised, with neurological complications reported in more than 30% of hospitalised patients. However, multicentric studies providing a population-based perspective are lacking. METHODS: We conducted a retrospective multicentric study at five hospitals in Northern Portugal, representing 45.1% of all hospitalised patients in this region, between 1 March and 30 June 2020. RESULTS: Among 1261 hospitalised COVID-19 patients, 457 (36.2%) presented neurological manifestations, corresponding to a rate of 357 per 1000 in the North Region. Patients with neurologic manifestations were younger (68.0 vs. 71.2 years, p = 0.002), and the most frequent neurological symptoms were headache (13.4%), delirium (10.1%), and impairment of consciousness (9.7%). Acute well-defined central nervous system (CNS) involvement was found in 19.1% of patients, corresponding to a rate of 217 per 1000 hospitalised patients in the whole region. Assuming that all patients with severe neurological events were hospitalised, we extrapolated our results to all COVID-19 patients in the region, estimating that 116 will have a severe neurological event, corresponding to a rate of nine per 1000 (95% CI = 7-11). Overall case fatality in patients presenting neurological manifestations was 19.8%, increasing to 32.6% among those with acute well-defined CNS involvement. CONCLUSIONS: We characterised the population of hospitalised COVID-19 patients in Northern Portugal and found that neurological symptoms are common and associated with a high degree of disability at discharge. CNS involvement with criteria for in-hospital admission was observed in a significant proportion of patients. This knowledge provides the tools for adequate health planning and for improving COVID-19 multidisciplinary patient care.

Systemic inflammation status at admission affects the outcome of intracerebral hemorrhage by increasing perihematomal edema but not the hematoma growth.

Acute stress and inflammation responses are associated with worse outcomes in intracerebral hemorrhage (ICH) but the precise mechanisms involved are unclear. We evaluated the effect of neutrophil-to-lymphocyte ratio (NLR) in ICH outcome, with focus on hematoma expansion and early cerebral edema. In a retrospective study, we included all patients with primary ICH admitted to our center within 24-h from symptom onset from January 2014 to February 2015. We retrieved demographic and medical history data, Glasgow Coma Scale scores, blood cell counts, glucose, and C-reactive protein, and calculated NLR. We obtained hematoma volumes by computerized planimetry. Outcomes included independence at 90 days (modified Rankin scale 0-2), mortality at 30 days, significant hematoma expansion (> 33% or > 6 mL) and early cerebral edema causing significant midline shift (> 2.5 mm) at 24 h. We included 135 patients. NLR independently associated with independence at 90 days (adjusted odds ratio (aOR) 0.79, 95% CI 0.67-0.93, p = 0.006) significant cerebral edema (aOR 1.08, 95%CI 1.01-1.15, p = 0.016) but not hematoma expansion (aOR 0.99, 95%CI 0.94-1.04, p = 0.736). The severity of midline shift was positively correlated with NLR (adjusted beta = 0.08, 95% CI 0.05-0.11, p < 0.001). In ICH, an immediate and intense systemic inflammatory response reduces the likelihood of a better functional outcome at 90 days, which is more likely to be explained by perihematomal edema growth than due to a significant hematoma expansion. These findings could have implications in new treatment strategies and trial designs, which endpoints tend to target exclusively hematoma enlargement.

Optic neuropathy: A 15-year retrospective observational study.

BACKGROUND: Optic neuropathies (ON) have several aetiologies and sometimes the diagnosis established ab initio is redefined after further investigations and/or new neurological events. We aim with this study to report clinical, paraclinical findings, treatment choices and disease course in patients admitted with a suspicion of acute or subacute optic neuropathy and to explore the diagnosis redefinition during follow-up and evaluate possible predictive factors that may influence that change. METHODS: We retrospectively reviewed the medical records of 156 patients with ON admitted to the ward of our Neurology Department, between January 2004 and August 2019. Clinical, laboratory and imaging data, as well as treatment protocols and follow-up were analysed. RESULTS: At the time of discharge from the ward, our cohort comprised 83 idiopathic ON (53.2%), 38 multiple sclerosis-related ON (24.4%), 23 ischemic ON (14.7%), 5 neuromyelitis optica spectrum disorder-related ON (3.2%), 1 Chronic relapsing inflammatory optic neuropathy (0.6%), 1 Leber hereditary optic neuropathy (0.6%), 1 vitamin B12 deficiency ON (0.6%), 2 Behçet ON (1.3%), 1 systemic lupus erythematosus - associated ON (0.6%), 1 syphilitic ON (0.6%). During follow-up, 129 patients retained the ward's discharge diagnosis (82.7%) while in 27 it was redefined (17.3%). The median time between admission and change in diagnosis was 12.3 (5.4 - 42.9) months. 67.1% of valid patients manifested atypical characteristics of optic neuritis (presence of one of the following clinical findings: bilateral eye involvement, visual acuity ≤ 0.1 at admission, worsening or non-substantial recovery of visual acuity during hospitalization), while only 32.9% presented with ON typical for optic neuritis. Idiopathic ON was the "etiology" at discharge that changed the most during follow-up both in ON typical and atypical for optic neuritis. More than a half of the individuals with MS-RON in our study presented visual acuity at admission ≤ 0.1. Multivariate Cox regression analysis demonstrated that the patients with ON atypical for optic neuritis had lower risk of having the initial diagnosis changed (HR = 0.320, 95% CI = 0.138-0.743, p = 0.008). CONCLUSION: Our study illustrates that some patients admitted with ON may have their diagnosis redefined during follow-up and it demonstrates that patients with ON atypical for optic neuritis are those in which the diagnosis is more likely to remain during follow-up. Furthermore, our population has clinical and paraclinical characteristics that reinforce conclusions from previous international studies.

Brody disease: when myotonia is not myotonia.

A 56-year-old man presented with painless impairment of muscle relaxation on vigorous contraction (eg, eyelid closure, hand grip, running). There were no episodes of paralysis, symptom progression, weakness or extramuscular symptoms. Five of his fifteen siblings had similar complaints. His serum creatine kinase was normal. Electromyography showed electrical silence on muscle relaxation, without myotonic discharges. DMPK, ClCN1 and SCN4A genetic testing was normal, but he had a homozygous pathogenic variant of ATP2A1 (c.1315G>A; pGlu439Lys). Brody disease is a rare autosomal recessive myopathy due to ATP2A1 mutations that reduce sarcoplasmic reticulum calcium-ATPase1 activity, hence delaying muscle relaxation.

Vanishing Pseudotumoral White Matter Lesions Presenting as Aphasia and Altered Mental Status in a 71-Year-Old Male.

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disorder that usually affects the central nervous system (CNS) after an infection and/or vaccination. It is more common in infancy. Here we present a case of late onset ADEM. A 71-year-old male was admitted to the emergency department due to speech difficulty and somnolence. Upon neurological examination he had a mixed aphasia. He performed a brain computed tomography which showed multiple white matter hypodense lesions. After admission to the neurology ward, he performed a lumbar puncture which showed a mildly inflammatory cerebrospinal fluid, negative serological testing and negative oligoclonal bands. Brain magnetic resonance imaging (MRI) confirmed the presence of multiple T2 hyperintense lesions, extensive bilateral frontoparietal lesions with abundant perilesional edema, four with gadolinium enhancement in an open-ring pattern and no mass effect. Anti-aquaporin 4 antibody, virologic and bacteriologic blood testing, screening of autoimmune disorders and occult neoplasm were all unremarkable. He was treated with intravenous methylprednisolone (1 gr) during five days and started to recover, maintaining a slight verbal fluency deficiency. Post-treatment brain MRI showed reduction of previous lesions, corroborating the probable inflammatory/demyelinating etiology. After discharge he maintained follow-up at the neurology outpatient clinic and he is currently asymptomatic with no new lesions and further reduction of the previous ones on follow-up MR scan. Both clinical follow-up of the patient, revealing a monophasic course with complete recovery, and temporal evolution of his brain lesions were essential to establish a diagnosis of ADEM in a septuagenarian patient, in whom other diagnoses have to be considered.