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.

Guillain-Barré syndrome and COVID-19: A 1-year observational multicenter study.

BACKGROUND AND PURPOSE: Many single cases and small series of Guillain-Barré syndrome (GBS) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were reported during the coronavirus disease 19 (COVID-19) outbreak worldwide. However, the debate regarding the possible role of infection in causing GBS is still ongoing. This multicenter study aimed to evaluate epidemiological and clinical findings of GBS diagnosed during the COVID-19 pandemic in northeastern Italy in order to further investigate the possible association between GBS and COVID-19. METHODS: Guillain-Barré syndrome cases diagnosed in 14 referral hospitals from northern Italy between March 2020 and March 2021 were collected and divided into COVID-19-positive and COVID-19-negative. As a control population, GBS patients diagnosed in the same hospitals from January 2019 to February 2020 were considered. RESULTS: The estimated incidence of GBS in 2020 was 1.41 cases per 100,000 persons/year (95% confidence interval 1.18-1.68) versus 0.89 cases per 100,000 persons/year (95% confidence interval 0.71-1.11) in 2019. The cumulative incidence of GBS increased by 59% in the period March 2020-March 2021 and, most importantly, COVID-19-positive GBS patients represented about 50% of the total GBS cases with most of them occurring during the two first pandemic waves in spring and autumn 2020. COVID-19-negative GBS cases from March 2020 to March 2021 declined by 22% compared to February 2019-February 2020. CONCLUSIONS: Other than showing an increase of GBS in northern Italy in the "COVID-19 era" compared to the previous year, this study emphasizes how GBS cases related to COVID-19 represent a significant part of the total, thus suggesting a relation between COVID-19 and GBS.

Clinical neurophysiology and cerebrospinal liquor analysis to detect Guillain-Barré syndrome and polyneuritis cranialis in COVID-19 patients: A case series.

We report a case series of five patients affected by SARS-CoV-2 who developed neurological symptoms, mainly expressing as polyradiculoneuritis and cranial polyneuritis in the 2 months of COVID-19 pandemic in a city in the northeast of Italy. A diagnosis of Guillain-Barré syndrome was made on the basis of clinical presentation, cerebrospinal fluid analysis, and electroneurography. In four of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 g/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases a significant decrease in amplitude of compound motor action potential compound muscle action potential (cMAP). Four patients presented a mild facial nerve involvement limited to the muscles of the lower face, with sparing of the forehead muscles associated to ageusia. In one patient, taste assessment showed right-sided ageusia of the tongue, ipsilateral to the mild facial palsy. In three patients we observed albuminocytological dissociation in the cerebrospinal fluid, and notably, we found an increase of inflammatory mediators such as the interleukin-8. Peripheral nervous system involvement after infection with COVID-19 is possible and may include several signs that may be successfully treated with immunoglobulin therapy.

Cerebrospinal fluid and serum interleukins 6 and 8 during the acute and recovery phase in COVID-19 neuropathy patients.

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.

Multimodal CT pc-ASPECTS in infratentorial stroke: diagnostic and prognostic value.

BACKGROUND AND PURPOSE: Diagnosis of posterior circulation stroke may be challenged. National Institutes of Health Stroke Scale (NIHSS) and brain imaging (non-contrast brain computed tomography-CT) are used for diagnosis; evaluation on posterior circulation stroke remains a limit of NIHSS, and the value of non-contrast CT (NCCT) is limited due to artifacts caused by the bones of the base of the skull. We tested the validity and prognostic value of posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) in patients with posterior circulation stroke. METHODS: Pc-ASPECTS allots the posterior circulation 10 points. We studied 50 patients with posterior circulation stroke. We applied pc-ASPECTS to NCCT, CT angiography, and CT Perfusion. We evaluated the correlation of pc-ASPECT with outcome parameters for stroke. RESULTS: Out of 50 patients, CTP showed abnormalities in 34 cases. The pc-ASPECT score calculated on brain CT and on the brain CT + angio CT had a sensibility of 24%, calculated on brain CT, angio CT and CTPerfusion gain a sensibility of 72%. Pc-ASPECT MTT resulted to be the more reliable parameter: outcome given by NIHSS score at discharge, mRS at discharge, and at 3 months was more severe in patients with Pc-ASPECT MTT alteration. Outcome given by NIHSS score at discharge and mRS at discharge and 1 at 3 months was more severe in patients with higher NIHSS score at admission. CONCLUSION: We evaluated the usefulness of pc-ASPECTS on CTP in predicting functional outcome in acute posterior circulation stroke that appears to be a powerful marker for predicting functional outcome.

Miller Fisher syndrome diagnosis and treatment in a patient with SARS-CoV-2.

This case report describes the clinical characteristics of a 50-year-old woman that developed SARS-CoV-2 pneumonia and was admitted at the COVID-19 dedicated unit where she developed neurological symptoms 10 days after admission. After neurological examination, including a panel of blood cerebrospinal fluid biomarkers, a diagnosis of Miller Fisher syndrome (MFS) was hypothesized and intravenous immunoglobulin therapy (IVIG) was initiated. Fourteen days after the start of IVIG treatment, the patient has been discharged at home with the resolution of respiratory symptoms and only minor hyporeflexia at the lower limbs, without any side effect.

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.

Lost diagnoses in not otherwise specified headache in Emergency Department.

 The diagnosis of Not Otherwise Specified (NOS) headaches in the Emergency Department (ED) is frequent despite many specialist visits performed. The aim of the study was to examine specialist visits carried out in the patients discharged from ED with diagnosis of NOS headache to evaluate discrepancies between specialist and ED diagnosis at discharge. We retrospectively (1.6.2018-31.12.2018) analyzed all the patients admitted with non-traumatic headache to the ED of the tertiary-care University Hospital of Trieste. We evaluated the patients discharged from ED with a final diagnosis of NOS headache and who underwent at least one specialist examination. Demographic data, specialist and ED diagnosis were analyzed.  One hundred twenty-four patients (93 F, 31 M, mean age 44 ± 15 years) were included. 71.8% of patients were examined only by a neurologist, 12.9% by non-neurologists, 15.3% by both neurologist and non-neurologist. Only 37% of the patients received a precise diagnosis. Neurologist made a diagnosis slightly more frequently than the other consultants (40.5% vs 37.5%). Neurologists diagnosed primary headaches, headaches secondary to neurological diseases, and facial neuralgia, instead non-neurologists diagnosed only headaches secondary to non-neurological diseases. Primary headaches were diagnosed in 25.7% of cases, migraine being the most frequent. Physicians did not report any specialist diagnoses in the ED discharge sheet. Specialist consultants made specific diagnoses in about one-third of patients that were not reported as final in the discharge records by the ED physician. This leads to a loss of diagnoses and to an overestimation of NOS headache.

Sex-dependent characteristics of Neuro-Long-COVID: Data from a dedicated neurology ambulatory service.

"Long-COVID" is a clinical entity that consists of persisting post-infectious symptoms that last for more than three months after the onset of the first acute COVID-19 symptoms. Among these, a cluster of neurological persisting symptoms defines Neuro-Long-COVID. While the debate about the pathogenesis of Long-COVID is still ongoing, sex differences have been individuated for both the acute and the chronic stage of the infection. We conducted a retrospective study describing sex differences in a large sample of patients with Neuro-Long-COVID. Demographic and clinical data were collected in a specifically designed Neuro-Long-Covid outpatient service. Our sample included 213 patients: 151 were females and 62 were males; the mean age was similar between females (53 y, standard deviation 14) and males (55 y, standard deviation 15); no significant differences was present between the demographic features across the two groups. Despite the prevalence of the specific chronic symptoms between male and females showed no significant differences, the total number of females accessing our service was higher than that of males, confirming the higher prevalence of Neuro-Long-COVID in female individuals. Conversely, a worse acute phase response in males rather than females was confirmed by a significant difference in the rates of acute respiratory symptoms (p = 0.008), dyspnea (p = 0.018), respiratory failure (p = 0.010) and the consequent need for ventilation (p = 0.015), together with other acute symptoms such as palpitations (p = 0.049), headache (p = 0.001) and joint pain (p = 0.049). Taken together, these findings offer a subgroup analysis based on sex-dependent characteristics, which can support a tailored-medicine approach.

Olfactory swab sampling optimization for α-synuclein aggregate detection in patients with Parkinson's disease.

BACKGROUND: In patients with Parkinson's disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not as accurate as in other α-synucleinopathies. It is unknown whether these variable results might be related to a different distribution of pathological α-syn in OM. Thus, we investigated whether nasal swab (NS) performed in areas with a different coverage by olfactory neuroepithelium, such as agger nasi (AN) and middle turbinate (MT), might affect the detection of pathological α-syn. METHODS: NS was performed in 66 patients with PD and 29 non-PD between September 2018 and April 2021. In 43 patients, cerebrospinal fluid (CSF) was also obtained and all samples were analyzed by RT-QuIC for α-syn. RESULTS: In the first round, 72 OM samples were collected by NS, from AN (NSAN) or from MT (NSMT), and 35 resulted positive for α-syn RT-QuIC, including 27/32 (84%) from AN, 5/11 (45%) from MT, and 3/29 (10%) belonging to the non-PD patients. Furthermore, 23 additional PD patients underwent NS at both AN and MT, and RT-QuIC revealed α-syn positive in 18/23 (78%) NSAN samples and in 10/23 (44%) NSMT samples. Immunocytochemistry of NS preparations showed a higher representation of olfactory neural cells in NSAN compared to NSMT. We also observed α-syn and phospho-α-syn deposits in NS from PD patients but not in controls. Finally, RT-QuIC was positive in 22/24 CSF samples from PD patients (92%) and in 1/19 non-PD. CONCLUSION: In PD patients, RT-QuIC sensitivity is significantly increased (from 45% to 84%) when NS is performed at AN, indicating that α-syn aggregates are preferentially detected in olfactory areas with higher concentration of olfactory neurons. Although RT-QuIC analysis of CSF showed a higher diagnostic accuracy compared to NS, due to the non-invasiveness, NS might be considered as an ancillary procedure for PD diagnosis.

Hiccups, severe vomiting and longitudinally extensive transverse myelitis in a patient with prostatic adenocarcinoma and Aquaporin-4 antibodies.

Neuromyelitis optica spectrum disorder (NMOSD) is not defined as a classical paraneoplastic neurological syndrome, however there are growing evidences that NMOSD may be rarely associated with cancer. Older (>45 years old) male patients with longitudinally extensive transverse myelitis (LETM) or patients with "area postrema" syndrome (intractable vomiting and hiccups) at onset are at higher risk for neoplasm-associated NMOSD. We report the case of 79-years old man who developed, a month after radiotherapy for prostatic adenocarcinoma, an area postrema syndrome rapidly followed by a LETM involving the whole spinal cord (from C2 to the conus). Aquaporin-4-IgG antibodies were positive in serum.

Does the Degree of Trunk Bending Predict Patient Disability, Motor Impairment, Falls, and Back Pain in Parkinson's Disease?

Background: Postural abnormalities in Parkinson's disease (PD) form a spectrum of functional trunk misalignment, ranging from a "typical" parkinsonian stooped posture to progressively greater degrees of spine deviation. Objective: To analyze the association between degree of postural abnormalities and disability and to determine cut-off values of trunk bending associated with limitations in activities of daily living (ADLs), motor impairment, falls, and back pain. Methods: The study population was 283 PD patients with ≥5° of forward trunk bending (FTB), lateral trunk bending (LTB) or forward neck bending (FNB). The degrees were calculated using a wall goniometer (WG) and software-based measurements (SBM). Logistic regression models were used to identify the degree of bending associated with moderate/severe limitation in ADLs (Movement Disorders Society Unified PD Rating Scale [MDS-UPDRS] part II ≥17), moderate/severe motor impairment (MDS-UPDRS part III ≥33), history of falls (≥1), and moderate/severe back pain intensity (numeric rating scale ≥4). The optimal cut-off was identified using receiver operating characteristic (ROC) curves. Results: We found significant associations between modified Hoehn & Yahr stage, disease duration, sex, and limitation in ADLs, motor impairment, back pain intensity, and history of falls. Degree of trunk bending was associated only with motor impairment in LTB (odds ratio [OR] 1.12; 95% confidence interval [CI], 1.03-1.22). ROC curves showed that patients with LTB of 10.5° (SBM, AUC 0.626) may have moderate/severe motor impairment. Conclusions: The severity of trunk misalignment does not fully explain limitation in ADLs, motor impairment, falls, and back pain. Multiple factors possibly related to an aggressive PD phenotype may account for disability in PD patients with FTB, LTB, and FNB.