Acute TNFα levels predict cognitive impairment 6-9 months after COVID-19 infection.

BACKGROUND: A neurocognitive phenotype of post-COVID-19 infection has recently been described that is characterized by a lack of awareness of memory impairment (i.e., anosognosia), altered functional connectivity in the brain's default mode and limbic networks, and an elevated monocyte count. However, the relationship between these cognitive and brain functional connectivity alterations in the chronic phase with the level of cytokines during the acute phase has yet to be identified. AIM: Determine whether acute cytokine type and levels is associated with anosognosia and functional patterns of brain connectivity 6-9 months after infection. METHODS: We analyzed the predictive value of the concentration of acute cytokines (IL-1RA, IL-1ß, IL-6, IL-8, IFNγ, G-CSF, GM-CSF) (cytokine panel by multiplex immunoassay) in the plasma of 39 patients (mean age 59 yrs, 38-78) in relation to their anosognosia scores for memory deficits via stepwise linear regression. Then, associations between the different cytokines and brain functional connectivity patterns were analyzed by MRI and multivariate partial least squares correlations for the whole group. RESULTS: Stepwise regression modeling allowed us to show that acute TNFα levels predicted (R2 = 0.145; ß = -0.38; p = .017) and were associated (r = -0.587; p < .001) with scores of anosognosia for memory deficits observed 6-9 months post-infection. Finally, high TNFα levels were associated with hippocampal, temporal pole, accumbens nucleus, amygdala, and cerebellum connectivity. CONCLUSION: Increased plasma TNFα levels in the acute phase of COVID-19 predict the presence of long-term anosognosia scores and changes in limbic system functional connectivity.

Frequency of Abnormally Low Neuropsychological Scores in Post-COVID-19 Syndrome: the Geneva COVID-COG Cohort.

OBJECTIVE: Several studies have reported poor long-term neuropsychological performances in patients following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but none has yet considered the effect of administering multiple intercorrelated neuropsychological tests and assessed the frequency of cognitive deficits in a normative population. Our aim was therefore to assess the presence of cumulative neuropsychological deficits in an actual post-coronavirus disease of 2019 (COVID-19) comparison group versus one simulated using Monte-Carlo methods. METHOD: Validated neuropsychological Monte-Carlo simulation methods were applied to scores from a battery of neuropsychological tests (memory, executive, attentional, perceptual, logical reasoning, language, and ideomotor praxis) administered to 121 patients who had had mild, moderate, or severe COVID-19 (mean age: 56.70 years; 32% women), 222 ± 43 days post-infection. The cumulative percentages of the three severity subgroups were compared with the results of a false discovery rate-corrected probability analysis based on normative data. RESULTS: The cumulative percentages of deficits in memory and executive functions among the severe and moderate patients were significantly higher than those estimated for the normative population. Moderate patients also had significantly more deficits in perception and logical reasoning. In contrast, the mild group did not have significantly more cumulative deficits. CONCLUSIONS: Moderate and severe forms of COVID-19 cause greater long-term neuropsychological deficits than those that would be found in a normative population, reinforcing the hypothesis of long-term effects of SARS-CoV-2 on cognitive function, independent of the severity of the initial infection.

Monocytosis in the acute phase of SARS-CoV-2 infection predicts the presence of anosognosia for cognitive deficits in the chronic phase.

Reduced awareness of neuropsychological disorders (i.e., anosognosia) is a striking symptom of post-COVID-19 condition. Some leukocyte markers in the acute phase may predict the presence of anosognosia in the chronic phase, but they have not yet been identified. This study aimed to determine whether patients with anosognosia for their memory deficits in the chronic phase presented specific leukocyte distribution in the acute phase, and if so, whether these leukocyte levels might be predictive of anosognosia. First, we compared the acute immunological data (i.e., white blood cell differentiation count) of 20 patients who displayed anosognosia 6-9 months after being infected with SARS-CoV-2 (230.25 ± 46.65 days) versus 41 patients infected with SARS-Cov-2 who did not develop anosognosia. Second, we performed an ROC analysis to evaluate the predictive value of the leukocyte markers that emerged from this comparison. Blood circulating monocytes (%) in the acute phase of SARS-CoV-2 infection were associated with long-term post-COVID-19 anosognosia. A monocyte percentage of 7.35% of the total number of leukocytes at admission seemed to predict the presence of chronic anosognosia 6-9 months after infection.

SARS-CoV-2 and Guillain-Barré syndrome: AIDP variant with a favourable outcome.

BACKGROUND AND PURPOSE: The spectrum of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2), includes different neurologic manifestations of the central and peripheral nervous system. METHODS: From March through April 2020, in two university hospitals located in western Switzerland, we examined three patients with Guillain-Barré syndrome (GBS) following SARS-CoV-2. RESULTS: These cases were characterized by a primary demyelinating electrophysiological pattern (Acute inflammatory demyelinating polyneuropathy or AIDP) and a less severe disease course compared to recently published case series. Clinical improvement was observed in all patients at week five. One patient was discharged from hospital after full recovery with persistence of minor neurological signs (areflexia). Two of the three patients remained hospitalized: one was able to walk and the other could stand up with assistance. CONCLUSIONS: We report three cases of typical GBS (AIDP) occurring after SARS-CoV-2 infection and presenting with a favourable clinical course. Given the interval between COVID-19-related symptoms and neurological manifestations (mean of 15 days) we postulate a secondary immune-mediated mechanism rather than direct viral damage.

Fulminant multifocal relapse in a fingolimod-treated multiple sclerosis patient.

BACKGROUND: Fingolimod is the first approved oral disease-modifying treatment for relapsing-remitting multiple sclerosis. Fingolimod targets lymphocytes, exerting a modulator effect on cell-surface sphingosine-1-phosphate receptors and thus blocking lymphocytes egression from secondary lymphoid organs. Recent reports describe fingolimod cessation being followed by severe or pseudo-tumoral relapse, but it usually does not happen on continuous long-term treatment. CASE PRESENTATION: Here we present the case of a patient on continuous long-term fingolimod treatment who presented with fulminant atypical multifocal relapse involving over 30 new and active lesions. CONCLUSION: This case is unique since this fulminant multifocal relapse occurred in a patient with grade 3 lymphopenia and irreproachable adherence. This observation should be known as a possible side effect of fingolimod treatment.

Diagnostic tools for immune causes of encephalitis.

BACKGROUND: Autoimmune encephalitis (AE) refers to a central nervous system (CNS) antibody-mediated entity characterized by a rapid onset behavioural and cognitive decline that can be associated with movement disorders, epileptic and dysautonomic features. Interestingly, it is thought to be as common as its infectious disease counterpart and can share some clinical, radiological, and laboratory findings. OBJECTIVES: The aim is to describe the main clinical features of AE caused by antibodies targeting cell-surface neuronal agents and the diagnostic means to identify them. Paraneoplastic syndromes, associated with intracellular antibodies, will not be tackled in this review. SOURCES: PubMed/MEDLINE were the sources. CONTENT: According to a recent population-based study, autoimmunity is one of the most frequent cause of encephalitis after infectious agents. Its diagnosis lies upon 'classic' clinical features, which are dominated by neuropsychiatric symptoms and epileptic seizures. Cerebral spinal fluid (CSF) and serum autoantibody testing can confirm AE. Complementary examination with magnetic resonance imaging (MRI) and electroencephalogram (EEG) may be helpful for excluding other causes and managing seizures. In addition, exclusion of infectious and other origins must be considered. IMPLICATIONS: AE misdiagnosis can lead to a delay in treatment onset and, thus, clinical worsening. In this sense, identifying the causative agent is of utmost importance. However, the absence of CSF or serum antibody detection does not exclude the diagnosis of AE. Despite extensive testing, many encephalitis cases remain of unknown origin. It is obvious that some autoantibodies have not yet been identified in AE. Since radiological and biological examinations are not always contributive, early symptom recognition might help to hasten the diagnostic process.

Real-life long-term effectiveness of fingolimod in Swiss patients with relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: In 2011, fingolimod was approved in Switzerland for the treatment of relapsing-remitting multiple sclerosis (RRMS). The aim of the present study was to assess the effectiveness and retention of fingolimod in a real-life Swiss setting, in which patients can receive fingolimod as both first- and second-line treatment for RRMS. METHODS: This cross-sectional, observational study with retrospective data collection was performed at 19 sites that comprised both hospitals and office-based physicians across Switzerland. Sites were asked to document eligible patients in consecutive chronological order to avoid selection bias. Demographic and clinical data from 274 consenting adult patients with RRMS who had received treatment with fingolimod were analyzed. RESULTS: Mean treatment duration with fingolimod was 32 months. Under fingolimod, 77.7% of patients remained free from relapses and 90.3% did not experience disability progression. The proportion of patients who were free from any clinical disease activity, i.e. without relapses and disability progression, was 72.1%. A total of 28.5% of patients had been RRMS treatment-naïve prior to fingolimod therapy. High long-term treatment retention rates ranging between 95.7% at 24 months and 87.8% at 36 months were observed. CONCLUSION: In this Swiss cohort of naïve and pre-treated subjects with RRMS, the majority of patients under fingolimod treatment showed freedom from relapses and disability progression. In addition, treatment retention rate over 2 and 3 years was high, irrespective of previous treatment.

Postural control is associated with cognition and fear of falling in patients with multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease affecting various neurological domains, such as postural control, cognition, fear of falling, depression-anxiety, and fatigue. This study examined the associations of cognitive functions, fear of falling, depression-anxiety, and fatigue with postural control in patients with MS. Postural control (sway velocity) of 63 patients with MS (age 39.0 ± 8.9 years; %female 57%; Expanded Disability Status Scale score median (interquartile range) 2.0 (1.5)) was recorded on two platforms at stable and unstable conditions. Cognition, fear of falling, depression-anxiety, and fatigue were evaluated by a comprehensive neuropsychological assessment. The associations between these domains and postural control have been measured by multivariable linear regression (adjusted for age, gender, disability, and education). In stable condition, only working memory was associated with postural control (p < 0.05). In unstable condition, working memory, executive functions, attention/processing speed, and fear of falling were associated with postural control (p < 0.05). Specific cognitive domains and fear of falling were associated with postural control in MS patients, particularly in unstable condition. These findings highlight the association of cognitive functions and fear of falling with postural control in MS.

Successful long-term ambulatory norepinephrine infusions in a patient with pure autonomic failure.

We present a case study of a patient with pure autonomic failure who was successfully treated with ambulatory norepinephrine (NE) infusions over a 9-year-period of time before death occurred unexpectedly. Given this patient's response to the NE infusion treatment, we discuss the option of ambulatory NE infusions as a treatment for severe orthostatic hypotension that is refractory to common treatments.

Walking while talking in patients with multiple sclerosis: the impact of specific cognitive loads.

OBJECTIVES: Gait and cognitive disorders are frequently reported in patients with multiple sclerosis, leading to decreased quality of live. The objective of this prospective study was to examine the impact of four specific cognitive tasks on gait in patients with relapsing-remitting multiple sclerosis (RRMS) with low disability. METHODS: The mean±standard deviation (SD) of walking speed, stride time and stride length were measured in 25 patients with RRMS (age: 39.46±8.32years; Expanded Disability Status Scale [EDSS] score: 1.90±1.01; disease duration: 5.62±5.12years) and in 25 age-matched controls. Gait was assessed during single task and while doing four different cognitive tasks (forward counting, backward counting, semantic verbal fluency, phonemic verbal fluency). Spatiotemporal gait parameters were recorded by a 12-camera optoelectronic system. RESULTS: Patients walked slower and with a decrease stride length during the single task and the four dual tasks than controls, except for the condition of backward counting. RRMS patients and controls presented the same cognitive performances for the four conditions during walking. EDSS score was correlated with gait speed and stride length in single task, and in the dual tasks of the backward counting and phonemic fluency. CONCLUSION: Quantitative gait assessment reveals subtle gait disorders in patients with low disability of relapsing-remitting multiple sclerosis. The impact of different cognitive domains on gait induces specific gait disturbances that highlight the strong interaction between gait and cognition.

[Neuroborreliosis, tick-borne encephalitis and neurosyphilis]. / Neuroborréliose, méningo-encéphalite verno-estivale et neurosyphilis.

Infections affecting frequently the nervous system include Lyme disease, tick-borne encephalitis and syphilis. These three most dreaded neuro-infectious diseases observed in Switzerland are discussed, based on diagnostic criteria, screening testing, and treatments modalities. Neuroborreliosis and neurosyphilis are bacterial infectious diseases treatable by antibiotics, whereas the treatment of tick-borne encephalitis, a viral disease, is only based on preventive vaccination.

[Neuropathies associated with paraproteinemia (monoclonal gammopathy)]. / Neuropathies associées aux paraprotéinémies (gammapathies monoclonales).

Coexistence of neuropathy and paraproteinemia (monoclonal gammopathy) is a common and complex problem seen in clinical practice and requires the distinction of specific syndromes. The clinical courses of these neuropathies are typically chronic and progressive. A precise distinction of the type of haematologic disorder associated (benign or malignant), investigation of other organs manifestations, and assessment of specific markers are mandatory. These steps are important to initiate an appropriate therapy that may include chemotherapy and/or immunosuppressive treatment targeting the neuropathy and the haematological dysfunction.

[Dysimmune neuromuscular disorders: diagnostic challenges and new ways of management]. / Maladies auto-immunes neuromusculaires: diagnostic et prise en charge.

This review describes some dysimmune neuromuscular disorders and their recent management: syndrome of peripheral nerve hyperexcitability (treatment of cramps, immunosuppressors); Guillain-Barré syndrome (new mechanisms and consensus treatment); chronic inflammatory demyelinating polyradiculoneuropathy (new indication for the use of pulse dexamethasone, new scores of activity); importance of subcutaneous immunoglobulin in multifocal motor neuropathy and of infusions of rituximab in myasthenia gravis; new entities in myositis and their treatment.

[New treatment options in multiple sclerosis and their complications]. / Traitement de tla sclérose en plaques: nouveautés et complications.

A new therapeutic era opened for multiple sclerosis (MS) with the appearance of molecules given p.o. and/or molecules with greater efficiency. Early diagnosis is critical, as the time and the choice of therapeutic intervention. The initiation of treatments must be personalized, including the risks associated with MS and those potentially related to the treatment chosen, answering the question >. Monitoring tools that allow to objectively evaluate: I) MS activity and aggressiveness for each patient and 2) the safety of treatments and their risks of complications, must be further investigated.

Adapted timed up and go: a rapid clinical test to assess gait and cognition in multiple sclerosis.

BACKGROUND/AIMS: To measure the Timed Up and Go (TUG), imagined TUG (iTUG), and the difference of time between these two tests (delta time) in 20 patients with relapsing-remitting multiple sclerosis (RRMS) and 20 healthy age-matched controls and to examine whether an association with cognitive functions, motor impairment, and behavioral changes can be determined. METHODS: The mean ± SD of TUG, iTUG and delta time were used as outcomes. Spatiotemporal gait parameters were recorded by a 12-camera optoelectronic system during straight walking at usual self-selected speed. Cognitive functions were assessed by a standardized neuropsychological examination. RESULTS: Patients performed the TUG slower than the controls (10.00 ± 1.70 s vs. 8.71 ± 1.04 s, p = 0.01, respectively). The TUG was correlated with gait parameters, cognitive functions, and behavior, whereas delta time was correlated only with cognitive functions. CONCLUSION: TUG represents an interesting test to reveal subtle deficits in RRMS patients with low disability and is related to motor, cognitive, and behavioral functioning. Combining with the TUG, delta time could easily give additional information on specific cognitive functions in the assessment of patients with RRMS.