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.

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.

Cognitive deficit in post-acute COVID-19: an opportunity for EEG evaluation?

BACKGROUND AND PURPOSE: Among the most common post-COVID symptoms, many patients experienced subjective cognitive deficit, commonly named "brain fog," that might be present also in those individuals without severe acute COVID-19 respiratory involvement. Some studies have investigated some of the mechanisms that might be associated with the brain fog with objective techniques including transcranial magnetic stimulation and neuroimaging. METHODS: The aim of this study was to investigate the presence of electroencephalographic (EEG) alterations in people with post-COVID self-reported cognitive deficit. RESULTS: Out of the 90 patients attending the post-COVID neurology ambulatory service, twenty patients presenting brain fog at least 4 weeks after acute non-severe COVID-19 infection, and without previous history of epilepsy, were investigated with 19-channel EEG, Montreal Cognitive Assessment (MoCA), and magnetic resonance imaging (MRI). EEG was found altered in 65% of the sample, among which 69% presented a slowing activity and 31% were characterized by epileptic discharges principally in the frontal areas. None of the patients showed DWI MRI lesions. CONCLUSIONS: These findings highlight the usefulness of EEG analysis to objectively describe possible neurophysiological abnormalities in post-COVID patients presenting subjective cognitive deficit.

Stuttering-Like Dysfluencies as a Consequence of Long COVID-19.

PURPOSE: We present two patients who developed neurogenic stuttering after long COVID-19 related to SARS-CoV-2 infection. METHODS AND RESULTS: Both patients experienced both physical (e.g., fatigue) and cognitive difficulties, which led to impaired function of attention, lexical retrieval, and memory consolidation. Both patients had new-onset stuttering-like speech dysfluencies: Blocks and repetitions were especially evident at the initial part of words and sentences, sometimes accompanied by effortful and associated movements (e.g., facial grimaces and oro-facial movements). Neuropsychological evaluations confirmed the presence of difficulties in cognitive tasks, while neurophysiological evaluations (i.e., electroencephalography) suggested the presence of "slowed" patterns of brain activity. Neurogenic stuttering and cognitive difficulties were evident for 4-5 months after negativization of SARS-CoV-2 nasopharyngeal swab, with gradual improvement and near-to-complete recovery. CONCLUSIONS: It is now evident that SARS-CoV-2 infection may significantly involve the central nervous system, also resulting in severe and long-term consequences, even if the precise mechanisms are still unknown. In the present report, long COVID-19 resulted in neurogenic stuttering, as the likely consequence of a "slowed" metabolism of (pre)frontal and sensorimotor brain regions (as suggested by the present and previous clinical evidence). As a consequence, the pathophysiological mechanisms related to the appearance of neurogenic stuttering have been hypothesized, which help to better understand the broader and possible neurological consequences of COVID-19.

Optimal MoCA cutoffs for detecting biologically-defined patients with MCI and early dementia.

OBJECTIVE: In this phase II psychometric study on the Montreal cognitive assessment (MoCA), we tested the clinicometric properties of Italian norms for patients with mild cognitive impairment (PwMCI) and early dementia (PwD) and provided optimal cutoffs for diagnostic purposes. METHODS: Retrospective data collection was performed for consecutive patients with clinically and biologically defined MCI and early dementia. Forty-five patients (24 PwMCI and 21 PwD) and 25 healthy controls were included. Raw MoCA scores were adjusted according to the conventional 1-point correction (Nasreddine) and Italian norms (Conti, Santangelo, Aiello). The diagnostic properties of the original cutoff (< 26) and normative cutoffs, namely, the upper limits (uLs) of equivalent scores (ES) 1, 2, and 3, were evaluated. ROC curve analysis was performed to obtain optimal cutoffs. RESULTS: The original cutoff demonstrated high sensitivity (0.93 [95% CI 0.84-0.98]) but low specificity (0.44 [0.32-0.56]) in discriminating between patients and controls. Nominal normative cutoffs (ES0 uLs) showed excellent specificity (SP range = 0.96-1.00 [0.88-1.00]) but poor sensitivity (SE range = 0.09-0.24 [0.04-0.36]). The optimal cutoff for Nasreddine's method was 23.50 (SE = 0.82 [0.71-0.90]; SP = 0.72 [0.60-0.82]). Optimal cutoffs were 20.97, 22.85, and 22.29 (SE range = 0.69-0.73 [0.57-0.83], SP range = 0.88-0.92 [0.77-0.97]) for Conti's, Santangelo's, and Aiello's methods, respectively. CONCLUSION: Using the 1-point correction, combined with a cutoff of 23.50, might be useful in ambulatory settings with a large turnout. Our optimal cutoffs can offset the poor sensitivity of Italian cutoffs.

Using the ATN system as a guide for the neuropsychological assessment of Alzheimer's disease.

INTRODUCTION: Many studies have attempted to determine whether Alzheimer's disease (AD) in-vivo biomarkers can predict neuropsychological performance since pathophysiological changes precede cognitive changes by several years. Nonetheless, neuropsychological measures can also detect cognitive deterioration in cognitively normal individuals with AD-positive biomarkers. Recent studies have investigated whether cognitive measures can be used as a proxy for biomarkers. This is a crucial issue since biomarker analysis is expensive, invasive, and not yet widespread in clinical practice. However, these studies have so far considered only one or two classes of AD biomarkers. Here, we aim at preliminarily evaluating whether and which neuropsychological measures can discriminate individuals that have been classified according to the full scheme of biomarkers known as ATN system. This scheme groups biomarkers as a function of the three main AD-related pathologic processes they measure (i.e., ß-amyloidosis, tauopathy, and neurodegeneration) to provide an unbiased and descriptive definition of the Alzheimer's continuum. METHOD: Biomarkers and neuropsychological data from 78 patients (70.01 ± 9.15 years; 38 females) with suspected cognitive decline were extracted from a medical database. Participants' biomarker profiles were classified into the following ATN categories: normal AD biomarkers; Alzheimer's continuum; non-AD pathologic change. Data were analyzed using a Bayesian approach, to guarantee reliable result interpretation of data stemming from small samples. RESULTS: The discrimination ability of each neuropsychological measure varied depending on the pairs of ATN categories compared. The best-discriminating predictor in the Alzheimer's continuum vs. normal biomarkers comparison was the figure naming ability. In contrast, in the Alzheimer's continuum vs. non-AD pathologic change comparison the best predictor was the wordlist forgetting rate. CONCLUSIONS: Although the study was exploratory in nature, the proposed methodological approach may have the potential to identify the best neuropsychological measures for estimating AD neuropathological changes, leading to a more biologically informed use of neuropsychological assessment.

Smart technology for physical activity and health assessment during COVID-19 lockdown.

BACKGROUND: The worldwide lockdown in response to COVID-19 pandemics has often led to physical inactivity and social distancing. When combined, these factors may affect quality and life and increase the risk of different diseases. Therefore, assessment of physical activity levels should be encouraged to monitor and identify those at a higher risk of inactivity. Smart technology is a promising tool to assess physical activity and health and may be particularly useful during a period of general lockdown. METHODS: An online survey was developed and shared among the Italian general population to collect data about physical activity and daily routine changes between January 2020 and the lockdown period from March 23 to March 29. Participants were asked to provide data such as daily step count (Steps) or heart rate (HR) measured and collected by their smart technology devices. RESULTS: Four hundred participants were included in the final analysis. During the lockdown, the number of steps dropped from 8284±4390 to 3294±3994 steps (P<0.001), while mean peak HR decreased from 61.3±18.2% to 55.9±17.3% (P<0.001). CONCLUSIONS: These findings provide objective data about the effects of the COVID-19 lockdown on physical activity, thus encouraging the use of smart devices to monitor and promote healthy lifestyles while faced with a confinement condition.

Thrombolysis' benefits on early post-stroke language recovery in aphasia patients.

INTRODUCTION: Thrombolysis may affect ischemic stroke-related size, pattern and nature of infarcts, and has the potential to change aphasia presentation and recovery. Data on evolution of post-stroke aphasia following thrombolysis are still scarce. The aim of this study was to determine the course of language recovery through a well-validated language assessment battery after acute ischemic stroke and investigate whether traditional categorical classifications of aphasia can describe the clinical picture in post-thrombolysis phase. MATERIALS AND METHODS: Demographic, clinical, and language assessment data of 116 patients presenting sub-acute ischemic stroke aphasia (41 treated with r-tPA; 75 non-treated) were retrospectively analyzed. The participants were assessed by a clinical neuropsychologist with a variety of subtests taken from a well-validated Italian language battery (Neuro-Psychological Aphasia Evaluation). RESULTS: The percentage of resolved aphasia was significantly higher in treated patients compared to non-treated patients (p = 0.005) and global aphasia was more common in the non-treated group (non-treated 30.7% vs treated 17.1%). Aphasia subtypes and stroke etiologies showed no significant association, except for small vessel etiology and resolved aphasia (p = 0.041). Reperfusion treatment, baseline NIHSS, and lacunar stroke were the predictors of aphasia recovery. CONCLUSION: The percentage of resolved aphasia was significantly higher in the treated patients compared to the non-treated, with the latter showing a higher percentage of global aphasia. Identifying classic aphasia subtypes after thrombolysis is still possible since reperfused areas do not necessary change the classification or lead to completely different aphasic syndromes. Reperfusion treatment, baseline NIHSS, and lacunar stroke were the main predictors of aphasia recovery.

Connected Speech Deficit as an Early Hallmark of CSF-defined Alzheimer's Disease and Correlation with Cerebral Hypoperfusion Pattern.

BACKGROUND: Diagnosis of prodromal Alzheimer's disease (AD) still represents a hot topic and there is a growing interest for the detection of early and non-invasive biomarkers. Although progressive episodic memory impairment is the typical predominant feature of AD, communicative difficulties can be already present at the early stages of the disease. OBJECTIVE: This study investigated the narrative discourse production deficit as a hallmark of CSFdefined prodromal AD and its correlation with cerebral hypoperfusion pattern. METHODS: Narrative assessment with a multilevel procedure for discourse analysis was conducted on 28 subjects with Mild Cognitive Impairment (15 MCI due to AD; 13 MCI non-AD) and 28 healthy controls. The diagnostic workup included CSF AD biomarkers. Cerebral hypoperfusion pattern was identified by SPECT image processing. RESULTS: The results showed that the discourse analysis of global coherence and lexical informativeness indexes allowed to identify MCI due to AD from MCI non-AD and healthy subjects. These findings allow to hypothesize that the loss of narrative efficacy could be a possible early clinical hallmark of Alzheimer's disease. Furthermore, a significant correlation of global coherence and lexical informativeness reduction with the SPECT hypoperfusion was found in the dorsal aspect of the anterior part of the left inferior frontal gyrus, supporting the hypothesis that this area has a significant role in communicative efficacy, and in particular, in semantic selection executive control. CONCLUSION: This study contributes to the understanding of the neural networks for language processing and their involvement in prodromal Alzheimer's disease. It also suggests an easy and sensitive tool for clinical practice that can help identifying individuals with prodromal Alzheimer's disease.

Stuttering-like hesitation in speech during acute/post-acute phase of immune-mediated encephalitis.

PURPOSE: Neurogenic stuttering may be evident after a lesion/dysfunction of wider neural networks. Here we present a case of acquired stuttering as the consequence of immune-mediated encephalitis. METHODS: The case of a 71-year old male who complained about the progressive onset of stuttering and disequilibrium as the consequence of immune-mediated encephalitis, is here reported. Administration of corticosteroid methylprednisolone was useful to recover from impairments. An in depth analysis of the electroencephalography (relative power of brain rhythms and source localization) during different phases of the disease/treatment was also realized. RESULTS: The patient showed a stuttering-like slowed speech with blocks and repetitions, especially at the beginning of words/sentences, with associated movements of the oro-facial muscles. Speech and general motor skills resulted slowed in their preparation/execution phases. Electroencephalography showed a "slowed" pattern, with delta/theta waves mainly in the prefrontal cortex and in sensorimotor networks. CONCLUSION: This case reports a probable immune-mediated encephalitis that resulted in acquired stuttering. The effect of "slowed" oscillatory brain activity on motor skills requesting sequencing and fine coordination (e.g. speech) could result in less "synchronized" systems, easily prone to disruptions.

A new MAPT deletion in a case of speech apraxia leading to corticobasal syndrome.

Speech apraxia is a disorder of speech motor planning/programming leading to slow rate, articulatory distortion, and distorted sound substitutions. We describe the clinical profile evolution of a patient presenting with slowly progressive isolated speech apraxia that eventually led to the diagnosis of corticobasal syndrome (CBS), supporting the evidence that this rare speech disorder can be the first presentation of CBS. Moreover, we found a novel variant in MAPT gene, which is hypothesized to be disease-causing mutation. These results underscore the importance of genetic analysis - particularly in selected atypical cases - for in vivo understanding of possible pathophysiological disease process.

Early Recovery of Aphasia through Thrombolysis: The Significance of Spontaneous Speech.

BACKGROUND: Aphasia is one of the most devastating stroke-related consequences for social interaction and daily activities. Aphasia recovery in acute stroke depends on the degree of reperfusion after thrombolysis or thrombectomy. As aphasia assessment tests are often time-consuming for patients with acute stroke, physicians have been developing rapid and simple tests. The aim of our study is to evaluate the improvement of language functions in the earliest stage in patients treated with thrombolysis and in nontreated patients using our rapid screening test. MATERIALS AND METHODS: Our study is a single-center prospective observational study conducted at the Stroke Unit of the University Medical Hospital of Trieste (January-December 2016). Patients treated with thrombolysis and nontreated patients underwent 3 aphasia assessments through our rapid screening test (at baseline, 24 hours, and 72 hours). The screening test assesses spontaneous speech, oral comprehension of words, reading aloud and comprehension of written words, oral comprehension of sentences, naming, repetition of words and a sentence, and writing words. RESULTS: The study included 40 patients: 18 patients treated with thrombolysis and 22 nontreated patients. Both groups improved over time. Among all language parameters, spontaneous speech was statistically significant between 24 and 72 hours (P value = .012), and between baseline and 72 hours (P value = .017). CONCLUSIONS: Our study demonstrates that patients treated with thrombolysis experience greater improvement in language than the nontreated patients. The difference between the 2 groups is increasingly evident over time. Moreover, spontaneous speech is the parameter marked by the greatest improvement.

Allographic agraphia for single letters.

The case is reported of a patient (PS) who, following acute encephalitis with residual occipito-temporal damage, showed a selective deficit in writing cursive letters in isolation, but no difficulty to write cursive-case words and non-words. Notably, he was able to recognize the same allographs he could not write and to produce both single letters and words in print. In addition to this selective single letter writing difficulty, the patient demonstrated an inability to correctly perform a series of imagery tasks for cursive letters. PS's performance may indicate that single letter production requires explicit imagery. Explicit imagery may not be required, instead, when letters have to be produced in the context of a word: letter production in this case may rely on implicit retrieval of well learned scripts in a procedural way.

Decompressive craniectomy and early cranioplasty for the management of severe head injury: a prospective multicenter study on 147 patients.

OBJECTIVE: In emergency care of patients with severe blunt head injury, uncontrollable high intracranial pressure is one of major causes of morbidity and mortality. The purpose of this study was to evaluate the efficacy of aggressive surgical treatment in managing uncontrollable elevated intracranial pressure coupled with early skull reconstruction. METHODS: This was a prospective study on a series of 147 consecutive patients, managed according to the same protocol by five different neurosurgical units, for severe head injuries (Glasgow coma scale score ≤8/15 and high intracranial pressure >25 mm Hg) during a five-year period. All patients received a wide decompressive craniectomy and duroplasty in the acute phase, and a cranioplasty was also performed within 12 weeks (median 6 weeks, range 4-12 weeks). RESULTS: The emergency decompressive surgery was performed within 28 hours (median 16 hours, range 6-28 hours) after sustaining the head injury. The median preoperative Glasgow coma scale score was 6/15 (range 3-8/15). At a mean follow-up of 26 months (range 14-74 months) 14 patients were lost to long-term follow-up, leaving only 133 patients available for the study. The outcome was favorable in 89 (67%, Glasgow outcome score 4 or 5), it was not favorable in 25 (19%, Glasgow outcome score 2 and 3), and 19 patients (14%) died. A younger age (<50 years) and earlier operation (within 9 hours from trauma) had a significant effect on positive outcomes (P < 0.0001 and P < 0.03, respectively). CONCLUSIONS: A prompt aggressive surgery, including a wide decompressive craniectomy coupled with early cranioplasty, could be an effective treatment method to improve the outcome after a severe closed head injury reducing, perhaps, many of the complications related to decompressive craniectomy.

Good division, but bad addition, subtraction and multiplication. A "leftmost-first" bug?

The present investigation reports the case of patient AS, ambidextrous, who showed a selective problem with arithmetical procedures in addition, subtraction and multiplication, contrasting with complete sparing of division. AS displayed a specific and never described "bug" error, involving the selection of digits that have to be added, subtracted or multiplied. This bug consisted in inverting the order of the numbers that have to be selected to correctly solve the operation. In particular, AS selected the numbers beginning from the leftmost position. This bug spared division, since it is the only operation that requires starting from the leftmost digit(s). The present case would suggest that some aspects of arithmetical procedures are operation independent. Moreover, an account of the nature of the syntactic rule getting lost in AS's performance has been proposed.

Allographic agraphia: a case study.

We report the case of patient MN, diagnosed with frontotemporal dementia, who exhibited a severe impairment in writing letters and words in upper-case print in the face of accurate production of the same stimuli in lower-case cursive. In contrast to her written production difficulties, MN was unimpaired in recognizing visually presented letters and words in upper-case print. We find a modest benefit of visual form cueing in the written production of upper-case letters, despite an inability to describe or report visual features of letters in any case or font. This case increases our understanding of the allographic level of letter-shape representation in written language production. It provides strong support for previous reports indicating the neural independence of different types of case and font-specific letter-shape information; it provides evidence that letter-shape production does not require explicit access to information about the visual attributes of letter shapes and, finally, it reveals the possibility of interaction between processes involved in letter-shape production and perception.