Sex differences in Wake-Up Stroke patients characteristics and outcomes.

OBJECTIVES: Wake-up Stroke (WUS) accounts for about 25% of all ischemic strokes. Differences according to sex in the WUS subgroup has been poorly investigated so far, so we aimed to assess these differences by differentiating the enrolled population based on treatment administered. MATERIALS & METHODS: We retrospectively analysed clinical and imaging data of WUS patients admitted to our hospital between November 2013 and December 2018 dividing them in two groups: rTPA-treated and non-rTPA treated group. To point out outcome differences we evaluated: NIHSS at 7 days or at discharge, mRS at discharge and ΔNIHSS. RESULTS: We enrolled 149 WUS patients, 74 rTPA treated and 75 non-rTPA treated. Among rTPA treated patients, time from last known well (LKW) to Emergency Department (ED) admission was longer in females than males (610 vs 454 min), while females had a higher ΔNIHSS than males (5 vs 3). Finally, among non-rTPA treated patients, females were older than males (85 vs 79 years), had a higher pre-admission mRS (although very low in both cases), had a longer length of stay (17 vs 13 days) and shown a higher NIHSS at discharge (4 vs 2) compared to males. CONCLUSIONS: Females not receiving thrombolytic treatment had worse functional outcome than males, showing a higher NIHSS at discharge but, in contrast, when treated with rTPA they showed better neurological recovery as measured by a greater ΔNIHSS. We emphasize the importance of a prompt recognition of WUS in females since they seem to benefit more from rTPA treatment.

Co-ultraPEALut in Subjective Cognitive Impairment Following SARS-CoV-2 Infection: An Exploratory Retrospective Study.

Neurological involvement following coronavirus disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an anti-inflammatory molecule) and luteolin (an anti-oxidant) have shown promising results as neuroinflammation antagonists. The aim of this study was to describe cognitive impairment in patients with post-COVID-19 treated with co-ultraPEALut. The Montreal Cognitive Assessment (MoCA), the Prospective-Retrospective Memory Questionnaire (PRMQ), the Fatigue Severity Scale (FSS), and a subjective assessment were administered at baseline and after 10 months. Patients treated with co-ultraPEALut were retrospectively compared with controls. Twenty-six patients treated with co-ultraPEALut showed a significant improvement in PRMQ (T0: 51.94 ± 10.55, T1: 39.67 ± 13.02, p < 0.00001) and MoCA raw score (T0: 25.76 ± 2.3, T1: 27.2 ± 2, p 0.0260); the MoCA-adjusted score and the FSS questionnaires also showed an improvement, even though it was not statistically significant; and 80.77% of patients reported a subjective improvement. In the control subjects (n = 15), the improvement was not as pronounced (PRMQ T0: 45.77 ± 13.47, T1: 42.33 ± 16.86, p 0.2051; FSS T0: 4.95 ± 1.57, T1: 4.06 ± 1.47, p 0.1352). Patients treated with co-ultraPEALut and corticosteroids were not statistically different from those treated with co-ultraPEALut alone. Neuro-post-COVID-19 patients treated with co-ultraPEALut scored better than controls in MoCA and PRMQ questionnaires after 10 months: this may support the importance of neuroinflammation modulation for neuro-long-COVID-19.

Differences in musculoskeletal dysfunctions and in postural alterations between chronic migraine and chronic tension type headache: A cross-sectional study.

OBJECTIVE: The aim of present study is to assess postural alterations and musculoskeletal dysfunctions over all spine in patients with chronic migraine and chronic tension type headache, moreover to highlight the differences between these two forms of primary headache. METHODS: A Cross sectional study was adopted to evaluate the musculoskeletal profile in patients with chronic migraine and with chronic tension type headache. The Bio photogrammetric evaluation was performed using the postural assessment software PAS/SAPO, while unilateral passive accessory intervertebral motion (PAIMs) were applied for manual examinations of spine segments from C0 to L5 vertebra. The One-way Analysis of Variance (ANOVA) test was used to compare the three groups with the software GraphPad InStat 3.06. RESULTS: A total of 60 patients were recruited, 20 for chronic tension type group, 20 for chronic migraine group and 20 healthy controls. The most interesting findings was that patients with chronic primary headaches presented postural alterations in all parameters (cranio-vertebral angle and lumbar-pelvic angle) and musculoskeletal dysfunctions in all spine with respect to healthy controls. Finally, the most clinically relevant finding was that no differences were found between chronic migraine and chronic tension type headache concerning the postural alterations nor the musculoskeletal dysfunctions. CONCLUSION: The sensitization acts as a substrate or consequence of these musculoskeletal dysfunctions in chronic primary headache. Therefore, non-pharmacological treatments targeted in the musculoskeletal system may be a good option in the management of chronic primary headache, especially when these therapies integrate various techniques that involve all spine.

Epidemiology and management of transient ischemic attack in Trieste district, how day hospital assessment improves outcomes: a five-year retrospective study.

BACKGROUND: Transient ischemic attack (TIA) is defined as a transient episode of neurologic dysfunction, without acute infarction or tissue injury lasting less than 24 h. Previous data suggest TIA precedes 15% of ischemic strokes, with a higher risk in the first week. Current practice guidelines advise evaluation through rapid neurological visit or admission to hospital. We provide data on TIA incidence in Trieste, and we compare three different types of assessment: day hospital (DH), stroke unit (SU), and emergency department/outpatients (ED). METHODS: This is a 5-year retrospective study of transient cerebrovascular events admitted in the University Hospital of Trieste (230.623 inhabitants), between 2016 and 2020. We calculated TIA prevalence in Trieste district's general population. Our primary endpoint is ischemic recurrences within 90 days, and we evaluate the possible association between different types of management. RESULTS: TIA incidence rate was 0.54/1000 inhabitants. In the multivariate analysis remained significantly associated with primary endpoint: ABCD2 (OR 1.625, CI 95% 1.114-2.369, p = 0.012) and DH evaluation (OR 0.260, CI 95% 0.082-0.819, p = 0.021). CONCLUSIONS: Incidence of TIA in Trieste district is in line with previous data. We demonstrate the crucial role of DH evaluation over the outpatient/ED in reducing overall mortality and recurrence rate. Prompt recognition of patients at high risk for cerebrovascular events and specialist follow-up may reduce the incidence of major vascular events and death.

Status Epilepticus after mechanical thrombectomy: The role of early EEG assessment in Stroke Unit, clinical and radiological prognostication.

BACKGROUND: Convulsive (CSE) and non-convulsive (NCSE) Status Epilepticus are a complication in 0.2-0.3% ischemic strokes. Large stroke and cortical involvement are the main risk factors for developing SE. This study evaluates the prevalence of SE in patients treated with endovascular thrombectomy (EVT) through EEG recording within 72- h from admission. Moreover, we compared clinical, radiological, and outcome measures in SE and no-SE patients. MATERIALS AND METHODS: We collected retrospectively demographical and clinical characteristics of acute ischemic stroke patients who underwent EVT, admitted in the Stroke Unit (SU) of the University Hospital of Trieste between January 2018 and March 2020 who underwent EEG recording within 72- h from the symptoms' onset. RESULTS: Out of 247 EVT patients, 138 met the inclusion criteria, of whom 9 (6.5%) showed SE with median onset time of 1 day (IQR 1-2). No difference was found between the two groups as for age, sex, risk factors, grade of recanalization, etiology of stroke, and closed vessel. The no-SE group presented higher NIHSS improvement rate (p=0.025) compared to the SE group. The sum of the lobes involved in the ischemic lesion was significantly higher in SE group (p=0.048). CONCLUSION: SE after EVT in large strokes is a non-rare complication, with most being NCSE. Performing a rapid EEG assessment in a Stroke Unit setting may allow for a prompt recognition and treatment of SE in the acute/hyper-acute phase. SE may be correlated with worse clinical outcomes in patients with large vessel occlusion.

Insights into attention and memory difficulties in post-COVID syndrome using standardized neuropsychological tests and experimental cognitive tasks.

The COVID-19 pandemic has given rise to post-acute cognitive symptoms, often described as 'brain fog'. To comprehensively grasp the extent of these issues, we conducted a study integrating traditional neuropsychological assessments with experimental cognitive tasks targeting attention control, working memory, and long-term memory, three cognitive domains most commonly associated with 'brain fog'. We enrolled 33 post-COVID patients, all self-reporting cognitive difficulties, and a matched control group (N = 27) for cognitive and psychological assessments. Our findings revealed significant attention deficits in post-COVID patients across both neuropsychological measurements and experimental cognitive tasks, evidencing reduced performance in tasks involving interference resolution and selective and sustained attention. Mild executive function and naming impairments also emerged from the neuropsychological assessment. Notably, 61% of patients reported significant prospective memory failures in daily life, aligning with our recruitment focus. Furthermore, our patient group showed significant alterations in the psycho-affective domain, indicating a complex interplay between cognitive and psychological factors, which could point to a non-cognitive determinant of subjectively experienced cognitive changes following COVID-19. In summary, our study offers valuable insights into attention challenges faced by individuals recovering from COVID-19, stressing the importance of comprehensive cognitive and psycho-affective evaluations for supporting post-COVID individuals.

Instrumental assessment of pressure pain threshold over trigeminal and extra-trigeminal area in people with episodic and chronic migraine: a cross-sectional observational study.

BACKGROUND: Central and peripheral sensitization are characterized by widespread hyperalgesia that is manifested by larger pain extent area and reduction in pressure pain threshold (PPT). PPT decreases in patients with migraine not only over the trigeminal cervical complex but also throughout the body. METHODS: A cross-sectional study was adopted to assess the local and widespread hyperalgesia in chronic and episodic migraine patients respect to healthy controls. The guidelines of Andersen's were used to evaluate the PPT bilaterally over 3 muscles in the trigemino-cervical complex (temporalis, sub-occipitalis, trapezius) and over 1 muscle far from this area (tensor fasciae latae). RESULTS: Thirty subjects with episodic migraine (35.8 ± 2.82 years), 30 with chronic migraine (53.03 ± 19.79 years), and 30 healthy controls (29.06 ± 14.03 years) were enrolled. The interaction effect was present for the trapezius muscle with a significant difference between the right and the left side in episodic group (p = 0.003). A group effect was highlighted in all four muscles analyzed such as suboccipital (p < 0.001), temporalis (p > 0.001), trapezius (p < 0.001), and TFL (p < 0.001). PPT was usually higher in the control group than in the episodic group which in turn was characterized by higher PPT values than the chronic group. CONCLUSIONS: People with chronic and episodic migraine presented lower PPT than healthy controls both in the trigeminal and in the extra-trigeminal area. People with chronic migraine presented lower PPT than episodic migraine only in the trigeminal area. Temporalis and sub-occipitalis are the most sensitive muscles in people with chronic and episodic migraine.

Narcissistic Personality Disorder as Prodromal Feature of Early-Onset, GRN-Positive bvFTD: A Case Report.

Background: Behavioral variant frontotemporal dementia (bvFTD) typically involves subtle changes in personality that can delay a timely diagnosis. Objective: Here, we report the case of a patient diagnosed of GRN-positive bvFTD at the age of 52 presenting with a 7-year history of narcissistic personality disorder, accordingly to DSM-5 criteria. Methods: The patient was referred to neurological and neuropsychological examination. She underwent 3 Tesla magnetic resonance imaging (MRI) and genetic studies. Results: The neuropsychological examination revealed profound deficits in all cognitive domains and 3T brain MRI showed marked fronto-temporal atrophy. A mutation in the GRN gene further confirmed the diagnosis. Conclusions: The present case documents an unusual onset of bvFTD and highlights the problematic nature of the differential diagnosis between prodromal psychiatric features of the disease and primary psychiatric disorders. Early recognition and diagnosis of bvFTD can lead to appropriate management and support for patients and their families. This case highlights the importance of considering neurodegenerative diseases, such as bvFTD, in the differential diagnosis of psychiatric disorders, especially when exacerbations of behavioral traits manifest in adults.

Thrombolysis in Stroke-Heart Syndrome: a useful tool for neurocardiac wellness?

INTRODUCTION: Stroke-heart syndrome is a physiopathological condition of cardiac suffering due to cerebral injury secondary to major vessel occlusion in anterior circulation. It can be detected by increase in cardiac blood biomarkers. Our aim was to investigate a possible ancillary effect of thrombolysis in mitigating Stroke-Heart Syndrome after acute ischaemic stroke. PATIENTS AND METHODS: We retrospectively collected ischaemic stroke patients admitted to our Stroke Unit between August 1, 2017 and December 31, 2020 and acutely treated for an intracranial anterior circulation occlusion, without anamnestic ischaemic cardiopathy. We divided patients into Group B ("Bridge") including patients treated with both thrombolysis and thrombectomy and Group D ("Direct") including primary thrombectomies. RESULTS: 120 patients were included in the study. Group B consisted of 92 patients, Group D of 28 patients, without significant differences in age, baseline and discharge NIHSS, cardiovascular risk factors or TOAST aetiology. Whilst admission, troponin levels were similar in both groups, significant differences in troponin peak (median 16 ng/L in Group B vs 45 ng/L in Group D, p = 0.022) and BNP values (median 455 pg/mL in Group B vs 784 pg/mL in Group D, p = 0.031) were found in the first 72 h since admission. Functional independence at discharge was significantly higher in Group B than Group D (mRS 0-2 36% vs 10%, p = 0.011). DISCUSSION AND CONCLUSION: Significant differences in troponin peak and BNP values suggest a reduced stroke-related heart impairment in patients treated with bridge therapeutic approach: thrombolysis prior to thrombectomy could have a complementary effect on reducing Stroke-Heart Syndrome, improving overall neurological outcome.

Improving acute stroke assessment in non-enhanced computed tomography: automated tool for early ischemic lesion volume detection.

BACKGROUND AND OBJECTIVES: ASPECTs is a widely used marker to identify early stroke signs on non-enhanced computed tomography (NECT), yet it presents interindividual variability and it may be hard to use for non-experts. We introduce an algorithm capable of automatically estimating the NECT volumetric extension of early acute ischemic changes in the 3D space. We compared the power of this marker with ASPECTs evaluated by experienced practitioner in predicting the clinical outcome. METHODS: We analyzed and processed neuroimaging data of 153 patients admitted with acute ischemic stroke. All patients underwent a NECT at admission and on follow-up. The developed algorithm identifies the early ischemic hypodense region based on an automatic comparison of the gray level in the images of the two hemispheres, assumed to be an approximate mirror image of each other in healthy patients. RESULTS: In the two standard axial slices used to estimate the ASPECTs, the regions identified by the algorithm overlap significantly with those identified by experienced practitioners. However, in many patients, the regions identified automatically extend significantly to other slices. In these cases, the volume marker provides supplementary and independent information. Indeed, the clinical outcome of patients with volume marker = 0 can be distinguished with higher statistical confidence than the outcome of patients with ASPECTs = 10. CONCLUSION: The volumetric extension and the location of acute ischemic region in the 3D-space, automatically identified by our algorithm, provide data that are mostly in agreement with the ASPECTs value estimated by expert practitioners, and in some cases complementary and independent.

Efficacy of dual-task augmented reality rehabilitation in non-hospitalized adults with self-reported long COVID fatigue and cognitive impairment: a pilot study.

BACKGROUND: Cognitive impairment and chronic fatigue represent common characteristics of the long COVID syndrome. Different non-pharmacological treatments have been proposed, and physiotherapy has been proposed to improve the symptoms. This study aimed to evaluate the effects of a dual-task augmented reality rehabilitation protocol in people with long COVID fatigue and cognitive impairment. METHODS AND MATERIALS: Ten non-hospitalized adults with reported fatigue and "brain fog" symptoms after COVID (7/10 females, 50 years, range 41-58) who participated in 20 sessions of a 1-h "dual-task" training, were compared to 10 long COVID individuals with similar demographics and symptoms (9/10 females, 56 years, range 43-65), who did not participate to any rehabilitation protocol. Cognitive performance was assessed with the Trail Making Test (TMT-A and -B) and Frontal Assessment Battery (FAB), and cardiovascular and muscular fatigue were assessed with the fatigue severity scale (FSS), six-minute walking test and handgrip endurance. Finally, transcranial magnetic stimulation (TMS) investigated cortical excitability. RESULTS: The mixed-factors analysis of variance found a significant interaction effect only in cognitive performance evaluation, suggesting TMT-B execution time decreased (- 15.9 s, 95% CI 7.6-24.1, P = 0.001) and FAB score improved (1.88, 95% CI 2.93-0.82, P = 0.002) only in the physiotherapy group. For the remaining outcomes, no interaction effect was found, and most parameters similarly improved in the two groups. CONCLUSION: The preliminary results from this study suggest that dual-task rehabilitation could be a feasible protocol to support cognitive symptoms recovery after COVID-19 and could be helpful in those individuals suffering from persisting and invalidating symptoms.

Elderly Onset of Functional Motor Disorders: Clinical Correlates from the Italian Registry.

BACKGROUND: Functional motor disorders (FMD) are a frequent neurological condition affecting patients with movement disorders. Commonly described in younger adults, their manifestation can be also associated to an elderly onset. OBJECTIVE: To assess the prevalence and describe the clinical manifestations of FMD with elderly and younger onset and their relationship with demographical and clinical variables. METHODS: We recruited patients with a "clinically definite" diagnosis of FMD from the Italian Registry of FMD. Patients underwent extensive clinical assessments. For elderly onset, we set a chronological cut-off at 65 years or older according to WHO definition. Multivariate regression models were implemented to estimate adjusted odds ratio of elderly FMD onset related to clinical characteristics. RESULTS: Among the 410 patients, 34 (8.2%) experienced elderly-onset FMD, with a mean age at onset of 70.9 years. The most common phenotype was tremor (47.1%), followed by gait disorders, weakness, and dystonia (29.4%, 23.5%, 14.7%, respectively). Eleven elderly patients had a combined phenomenology: 9 exhibited two phenotypes, 2 had three phenotypes. Weakness was isolated in 3/8 patients and combined with another phenotype in 5/8, manifesting as paraplegia (n = 4); upper limb diplegia (n = 2), hemiparesis/hemiplegia (n = 1), and tetraparesis/tetraplegia (n= 1). Non-motor and other functional neurological disorders occurred more frequently in the younger group (89.1%) than the elderly (73.5%). Neurological and non-neurological comorbidities were more prevalent in the elderly group (82.4%) as opposed to the younger (32.7%). In a multivariate regression analysis, elderly-onset FMD was significantly associated with neurological comorbidities, including parkinsonism (OR 6.73) and cerebrovascular diseases (OR 5.48). CONCLUSIONS: These results highlight the importance of achieving an accurate diagnosis of FMD in the elderly, as it is crucial for effectively managing FMD symptoms and addressing neurological comorbidities.

Neurophysiological and Clinical Outcomes in Episodic Migraine Without Aura: A Cross-Sectional Study.

OBJECTIVE: The aim of this study was to assess differences between people with episodic migraine and healthy controls in some neurophysiological and clinical outcomes, which, in turn, may highlight the differences in sensory processing, especially in cortical excitability, pain processing, and executive function. METHODS: A cross-sectional study was performed, including the following outcomes: pressure pain thresholds with algometry; resting motor threshold, short-interval intracortical inhibition, and intracortical facilitation with transcranial magnetic stimulation; and executive functions with the trail making test and the frontal assessment battery. RESULTS: Thirty adults with migraine (36 ± 10 years) and 30 healthy controls (29 ± 14 years) were included in this study. Compared with the healthy controls, participants with migraine presented lower pressure pain thresholds values in all the assessed muscles ( P < 0.001), lower resting motor threshold (-10.5% of the stimulator output, 95% CI: -16.8 to -4.2, P = 0.001, Cohen d = 0.869) and higher short-interval intracortical inhibition motor-evoked potential's amplitude at 3 ms (0.25, 95% CI: 0.05 to 0.46, P = 0.015, Cohen d = 0.662), and worse performances both in trail making test (7.1, 95% CI: 0.9 to 13.4, P = 0.027, Cohen d = 0.594) and frontal assessment battery (-1.1, 95% CI: -1.7 to -0.5, P = 0.001, Cohen d = 0.915). CONCLUSIONS: Participants with migraine presented significant differences in cortical excitability, executive functions, and pressure pain thresholds, compared with healthy controls.

Using illusions to understand hallucinations: differences in perceptual performances on illusory figures may underscore specific visuoperceptual impairments in Parkinson's disease.

Visual hallucinations are prevalent, potentially disabling symptoms of Parkinson's Disease. Multiple impairments in bottom-up sensory processing and top-down perceptual modulation are implicated in the pathophysiology of these phenomena. In healthy individuals, visual illusions are elicited by illusory figures through parametric manipulations of geometrical configurations, contrast, color, or spatial relationships between stimuli. These illusory percepts provide insight on the physiologic processes subserving conscious and unconscious perception. In this exploratory, cross-sectional, controlled study, perceptual performance on illusory figures was assessed on 11 PD patients with hallucinations, 10 non-hallucinating PD patients, and 10 age-matched healthy individuals. In order to characterize potential neural substrates of perceptual performances, patients' brain metabolic patterns on FDG PET were also analyzed. Illusions relying on attentional modulation and global perception were attenuated in PD patients without hallucinations. This pattern was no longer recognizable in hallucinating patients. Conversely, illusory effects normally counteracted by figure to background segregation and overlapping figures recognition were enhanced in PD patients with hallucinations. FDG PET findings further suggest that perceptual differences between PD patients might be linked to abnormal top-down perceptual modulation.

Neuromuscular assessment of force development, postural, and gait performance under cognitive-motor dual-tasking in healthy older adults and people with early Parkinson's disease: Study protocol for a cross-sectional Mobile Brain/Body Imaging (MoBI) study.

Background: Neuromuscular dysfunction is common in older adults and more pronounced in neurodegenerative diseases. In Parkinson's disease (PD), a complex set of factors often prevents the effective performance of activities of daily living that require intact and simultaneous performance of the motor and cognitive tasks. Methods: The cross-sectional study includes a multifactorial mixed-measure design. Between-subject factor grouping the sample will be Parkinson's Disease (early PD vs. healthy). The within-subject factors will be the task complexity (single- vs. dual-task) in each motor activity, i.e., overground walking, semi-tandem stance, and isometric knee extension, and a walking condition (wide vs. narrow lane) will be implemented for the overground walking activity only. To study dual-task (DT) effects, in each motor activity participants will be given a secondary cognitive task, i.e., a visual discrimination task for the overground walking, an attention task for the semi-tandem, and mental arithmetic for the isometric extension. Analyses of DT effects and underlying neuronal correlates will focus on both gait and cognitive performance where applicable. Based on an a priori sample size calculation, a total N = 42 older adults (55-75 years) will be recruited. Disease-specific changes such as laterality in motor unit behavior and cortical control of movement will be studied with high-density surface electromyography and electroencephalography during static and dynamic motor activities, together with whole-body kinematics. Discussion: This study will be one of the first to holistically address early PD neurophysiological and neuromuscular patterns in an ecologically valid environment under cognitive-motor DT conditions of different complexities. The outcomes of the study aim to identify the biomarker for early PD either at the electrophysiological, muscular or kinematic level or in the communication between these systems. Clinical Trial Registration: ClinicalTrials.Gov, NCT05477654. This study was approved by the Medical Ethical Committee (106/2021).

A likely association between low mannan-binding lectin level and brain fog onset in long COVID patients.

Brain fog can be described as a constellation of new-onset neuropsychiatric sequelae in the post-acute phase of COVID-19 (long COVID). The symptoms include inattention, short-term memory loss, and reduced mental acuity, which may undermine cognition, concentration, and sleep. This cognitive impairment, persisting for weeks or months after the acute phase of SARS-CoV-2 infection, can significantly impact on daily activities and the quality of life. An important role for the complement system (C) in the pathogenesis of COVID-19 has emerged since the beginning of pandemic outbreak. A number of pathophysiological characteristics including microangiopathy and myocarditis have been attributed to dysregulated C activation due to SARS-CoV-2 infection. Mannan-binding lectin (MBL), the first recognition subcomponent of the C lectin pathway, has been shown to bind to glycosylated SARS-CoV-2 spike protein, genetic variants of MBL2 are suggested to have an association with severe COVID-19 manifestations requiring hospitalization. In the present study, we evaluated MBL activity (lectin pathway activation) and levels in the sera of a cohort of COVID-19 patients, presenting brain fog or only hyposmia/hypogeusia as persistent symptoms, and compared them with healthy volunteers. We found significantly lower levels of MBL and lectin pathway activity in the sera of patients experiencing brain fog as compared to recovered COVID-19 patients without brain fog. Our data indicate that long COVID-associated brain fog can be listed among the variegate manifestations of increased susceptibility to infections and diseases contributed by MBL deficiency.

Incidence and Long-term Functional Outcome of Neurologic Disorders in Hospitalized Patients With COVID-19 Infected With Pre-Omicron Variants.

BACKGROUND AND OBJECTIVES: A variety of neurologic disorders have been reported as presentations or complications of coronavirus disease 2019 (COVID-19) infection. The objective of this study was to determine their incidence dynamics and long-term functional outcome. METHODS: The Neuro-COVID Italy study was a multicenter, observational, cohort study with ambispective recruitment and prospective follow-up. Consecutive hospitalized patients presenting new neurologic disorders associated with COVID-19 infection (neuro-COVID), independently from respiratory severity, were systematically screened and actively recruited by neurology specialists in 38 centers in Italy and the Republic of San Marino. The primary outcomes were incidence of neuro-COVID cases during the first 70 weeks of the pandemic (March 2020-June 2021) and long-term functional outcome at 6 months, categorized as full recovery, mild symptoms, disabling symptoms, or death. RESULTS: Among 52,759 hospitalized patients with COVID-19, 1,865 patients presenting 2,881 new neurologic disorders associated with COVID-19 infection (neuro-COVID) were recruited. The incidence of neuro-COVID cases significantly declined over time, comparing the first 3 pandemic waves (8.4%, 95% CI 7.9-8.9; 5.0%, 95% CI 4.7-5.3; 3.3%, 95% CI 3.0-3.6, respectively; p = 0.027). The most frequent neurologic disorders were acute encephalopathy (25.2%), hyposmia-hypogeusia (20.2%), acute ischemic stroke (18.4%), and cognitive impairment (13.7%). The onset of neurologic disorders was more common in the prodromic phase (44.3%) or during the acute respiratory illness (40.9%), except for cognitive impairment whose onset prevailed during recovery (48.4%). A good functional outcome was achieved by most patients with neuro-COVID (64.6%) during follow-up (median 6.7 months), and the proportion of good outcome increased throughout the study period (r = 0.29, 95% CI 0.05-0.50; p = 0.019). Mild residual symptoms were frequently reported (28.1%) while disabling symptoms were common only in stroke survivors (47.6%). DISCUSSION: Incidence of COVID-associated neurologic disorders decreased during the prevaccination phase of the pandemic. Long-term functional outcome was favorable in most neuro-COVID disorders, although mild symptoms commonly lasted more than 6 months after infection.