Circulatory shock associated with left insular stroke and chronic steroid treatment.

BACKGROUND: Damage to the insula has been associated with various types of cardiovascular dysfunction, including arrhythmias and blood pressure imbalances. Acute neuroendocrine disturbances following insular damage have also been described. CASE PRESENTATION: A 50-year-old right-handed man with a left insular ischemic lesion exhibited aphasia and right central VII nerve palsy. Five days after the stroke, the patient exhibited severe bradycardia and hypotension. He had been treated for ocular trauma with prednisone for the preceding 3 weeks. Cortisol and adrenocorticotropic hormone levels indicated secondary adrenal insufficiency. Despite adequate fluid intake, the patient's blood pressure dropped, requiring norepinephrine administration. Midodrine was also initiated, leading to clinical improvement. The therapy was gradually discontinued as vital signs normalized. By Day 24, electrocardiogram monitoring was unremarkable, hormonal levels normalized, and the neurological examination revealed only mild residual speech fluency impairment. Computed tomography scans confirmed a recovering ischemic lesion of the left insula. CONCLUSIONS: This case reveals the inhibitory effect exerted by a left-sided insular stroke on the autonomic system. It also highlights the still largely unexplored neuroendocrine complications of damage to this brain region.

Perspectives on the diagnosis and management of functional cognitive disorder: An international Delphi study.

BACKGROUND: Current proposed criteria for functional cognitive disorder (FCD) have not been externally validated. We sought to analyse the current perspectives of cognitive specialists in the diagnosis and management of FCD in comparison with neurodegenerative conditions. METHODS: International experts in cognitive disorders were invited to assess seven illustrative clinical vignettes containing history and bedside characteristics alone. Participants assigned a probable diagnosis and selected the appropriate investigation and treatment. Qualitative, quantitative and inter-rater agreement analyses were undertaken. RESULTS: Eighteen diagnostic terminologies were assigned by 45 cognitive experts from 12 countries with a median of 13 years of experience, across the seven scenarios. Accurate discrimination between FCD and neurodegeneration was observed, independently of background and years of experience: 100% of the neurodegenerative vignettes were correctly classified and 75%-88% of the FCD diagnoses were attributed to non-neurodegenerative causes. There was <50% agreement in the terminology used for FCD, in comparison with 87%-92% agreement for neurodegenerative syndromes. Blood tests and neuropsychological evaluation were the leading diagnostic modalities for FCD. Diagnostic communication, psychotherapy and psychiatry referral were the main suggested management strategies in FCD. CONCLUSIONS: Our study demonstrates the feasibility of distinguishing between FCD and neurodegeneration based on relevant patient characteristics and history details. These characteristics need further validation and operationalisation. Heterogeneous labelling and framing pose clinical and research challenges reflecting a lack of agreement in the field. Careful consideration of FCD diagnosis is advised, particularly in the presence of comorbidities. This study informs future research on diagnostic tools and evidence-based interventions.

Heart rate variability modification as a predictive factor of sudden unexpected death in epilepsy: How far are we? A systematic review and meta-analysis.

BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is a sudden, unexpected death in people with epilepsy, with or without evidence of an epileptic seizure. The pathophysiological mechanism underlying SUDEP appears to be partly associated with an autonomic nervous system (ANS) dysfunction. Heart rate variability (HRV) analysis is a reliable, non-invasive method for detecting fluctuations in the ANS. In this systematic review we analyzed the data available in the literature on changes in HRV parameters in patients with SUDEP. METHODS: We carried out a systematic search of the literature to identify the quantitative variations of HRV in epileptic patients with SUDEP. The following databases were used: Pubmed, Google Scholar, EMBASE, and CrossRef. A pooled analysis was carried out, and the results obtained were compared using mean difference (MD). The review was registered on the PROSPERO platform (CRD42021291586). RESULTS: Seven articles were included, with a total of 72 SUDEP cases associated with altered HRV parameters. Generally, a reduction of SDNN (standard deviation of the RR intervals) and RMSSD (root mean square differences of successive RR intervals) was reported in most SUDEP patients. According to MD, the SUDEP patients showed no differences in time and frequency domain parameters compared to controls. However, a trend toward increased low frequency and high frequency ratio (LF/HF) was observed in the SUDEP patients. CONCLUSIONS: HRV analysis is a valuable method for assessing cardiovascular risk and cardioautonomic impairment. Although a possible association between HRV variation and SUDEP has been reported, further studies are needed to assess the potential role of HRV modifications as a SUDEP biomarker.

Altered Medial Prefrontal Connectivity in Parkinson's Disease Patients with Somatic Symptoms.

BACKGROUND: The high co-occurrence of somatic symptom disorder (SSD) in Parkinson's disease (PD) patients suggests overlapping pathophysiology. However, little is known about the neural correlates of SSD and their possible interactions with PD. Existing studies have shown that SSD is associated with reduced task-evoked activity in the medial prefrontal cortex (mPFC), a central node of the default-mode network (DMN). SSD is also associated with abnormal γ-aminobutyric acid (GABA) content, a marker of local inhibitory tone and regional hypoactivity, in the same area when SSD co-occurs with PD. OBJECTIVES: To disentangle the individual and shared effects of SSD and PD on mPFC neurotransmission and connectivity patterns and help disclose the neural mechanisms of comorbidity in the PD population. METHODS: The study cohort included 18 PD patients with SSD (PD + SSD), 18 PD patients, 13 SSD patients who did not exhibit neurologic disorders, and 17 healthy subjects (HC). Proton magnetic resonance (MR) spectroscopy evaluated GABA levels within a volume of interest centered on the mPFC. Resting-state functional MR imaging investigated the region's functional connectivity patterns. RESULTS: Compared to HC or PD groups, the mPFC of SSD subjects exhibited higher GABA levels and connectivity. Higher mPFC connectivity involved DMN regions in SSD patients without PD and regions of the executive and attentional networks (EAN) in patients with PD comorbidity. CONCLUSIONS: Aberrant reconfigurations of connectivity patterns between the mPFC and the EAN are distinct features of the PD + SSD comorbidity. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Non convulsive refractory status epilepticus induced by thiocolchicoside (TCC) intrathecal injection: A case report.

TCC is a semisynthetic molecule widely used in clinical settings as a pain killer and myorelaxant. Several neurological side effects have been reported in association with TCC treatment including somnolence, confusion and seizure, the latter in a lower percentage of patients. Some previous reports described seizure onset after TCC intake in adulthood. However, major epileptological complication, namely status epilepticus, has never been previously reported in association with TCC treatment. In our report, we describe a case of acute refractory non-convulsive status epilepticus (NCSE) in the context of a TCC-induced acute toxic encephalopathy (ATE) in a woman without any previous neurological or physical comorbidities.

Hyperconnectivity in Dementia Is Early and Focal and Wanes with Progression.

We investigated in a longitudinal multicenter cohort study functional cortical connectivity changes along the course of frontotemporal dementia (FTD) and Alzheimer's disease (AD) from the prodromal stage of the diseases. Electroencephalography (EEG) was recorded in 18 FTD and 18 AD patients at the prodromal stage of dementia, at dementia onset, and 3 years after dementia onset. Twenty healthy controls (HC) underwent EEG recordings at the same time interval as the patients. Mutual information (MI) analysis measured the strength of functional network connectivity. FTD and AD patients showed greater MI at the prodromal stage of dementia (FTD vs. HC P = 2 × 10-8; AD vs. HC P = 4 × 10-3). Local connectivity was higher in left and right frontal areas of FTD (P = 7 × 10-5 and 0.03) and in left and right posterior areas in AD (P = 3 × 10-5 and 5 × 10-5) versus HC. We showed cortical hyperconnectivity at the prodromal stage of dementia in areas involved in the specific pathological process of FTD (frontal regions) and AD (posterior regions). Hyperconnectivity disappeared during follow-up, thus suggesting that it is an early electrophysiological feature of dementia, potentially useful to identify prodromal FTD and AD.

Accuracy of the clinical diagnosis of dementia with Lewy bodies (DLB) among the Italian Dementia Centers: a study by the Italian DLB study group (DLB-SINdem).

INTRODUCTION: Dementia with Lewy bodies (DLB) may represent a diagnostic challenge, since its clinical picture overlaps with other dementia. Two toolkits have been developed to aid the clinician to diagnose DLB: the Lewy Body Composite Risk Score (LBCRS) and the Assessment Toolkit for DLB (AT-DLB). We aim to evaluate the reliability of these two questionnaires, and their ability to enhance the interpretation of the international consensus diagnostic criteria. METHODS: LBCRS and AT-DLB were distributed to 135 Italian Neurological Centers for Cognitive Decline and Dementia (CDCDs), with the indication to administer them to all patients with dementia referred within the subsequent 3 months. We asked to subsequently apply consensus criteria for DLB diagnosis, to validate the diagnostic accuracy of the two toolkits. RESULTS: A total of 23 Centers joined the study; 1854 patients were enrolled. We found a prevalence of possible or probable DLB of 13% each (26% total), according to the consensus criteria. LBCRS toolkit showed good reliability, with a Cronbach alpha of 0.77, stable even after removing variables from the construct. AT-DLB toolkit Cronbach alpha was 0.52 and, after the subtraction of the "cognitive fluctuation" criterion, was only 0.31. Accuracy, sensitivity, and specificity were higher for LBCRS vs. AT-DLB. However, when simultaneously considered in the logistic models, AT-DLB showed a better performance (p < 0.001). Overall, the concordance between LBCRS positive and AT-DLB possible/probable was of 78.02% CONCLUSIONS: In a clinical setting, the LBCRS and AT-DLB questionnaires have good accuracy for DLB diagnosis.

Migraine Pharmacological Treatment and Cognitive Impairment: Risks and Benefits.

Migraine is a common neurological disorder impairing the quality of life of patients. The condition requires, as an acute or prophylactic line of intervention, the frequent use of drugs acting on the central nervous system (CNS). The long-term impact of these medications on cognition and neurodegeneration has never been consistently assessed. The paper reviews pharmacological migraine treatments and discusses their biological and clinical effects on the CNS. The different anti-migraine drugs show distinct profiles concerning neurodegeneration and the risk of cognitive deficits. These features should be carefully evaluated when prescribing a pharmacological treatment as many migraineurs are of scholar or working age and their performances may be affected by drug misuse. Thus, a reconsideration of therapy guidelines is warranted. Furthermore, since conflicting results have emerged in the relationship between migraine and dementia, future studies must consider present and past pharmacological regimens as potential confounding factors.

Preexisting Bipolar Disorder Influences the Subsequent Phenotype of Parkinson's Disease.

BACKGROUND: Patients with bipolar spectrum disorders (BSDs) exhibit an increased risk of Parkinson's disease (PD). OBJECTIVE: The aim is to investigate whether a previous diagnosis of BSDs influences the phenotype of PD. METHODS: Of 2660 PD patients followed for at least 6 years (6-27), 250 (BSD-PD) had BSDs, 6-20 years before PD diagnosis; 48%-43% had a PD or BSD family history, and 34 carried glucocerebrosidase (GBA) and Parkin (PRKN) mutations. The cohort was split into a subset of 213 BSD-PD patients, compared with 426 matched PD patients without BSDs, and a subset of 34 BSD-PD and 79 PD patients carrying GBA or PRKN mutations. Carriers of mutations absent in BSD-PD patients and of synuclein triplication were excluded. Structured clinical interviews and mood disorder questionnaires assessed BSDs. Linear mixed models evaluated the assessment scales over time. Thirteen BSD-PD patients underwent subthalamic nucleus deep brain stimulation (STN-DBS) and were compared with 27 matched STN-DBS-treated PD patients. RESULTS: Compared to PD patients, BSD-PD showed (1) higher frequency of family history of PD (odds ratio [OR] 3.31; 2.32-4.71) and BSDs (OR 6.20; 4.11-9.35) 5); (2) higher incidence of impulse control disorders (hazard ratio [HR] 5.95, 3.89-9.09); (3) higher frequency of functional disorders occurring before PD therapy (HR, 5.67, 3.95-8.15); (4) earlier occurrence of delusions or mild dementia (HR, 7.70, 5.55-10.69; HR, 1.43, 1.16-1.75); and (5) earlier mortality (1.48; 1.11-1.97). Genetic BSD-PD subjects exhibited clinical features indistinguishable from nongenetic BSD-PD subjects. STN-DBS-treated BSD-PD patients showed no improvements in quality of life compared to the control group. CONCLUSIONS: BSDs as a prodrome to PD unfavorably shape their course and are associated with detrimental neuropsychiatric features and treatment outcomes. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Status epilepticus and COVID-19: A systematic review.

PURPOSE: In March 2020, the World Health Organization declared the SARS-CoV-2 infection-related coronavirus Disease (COVID-19) a pandemic. During the first and second waves of the pandemic spread, there have been several reports of COVID-19-associated neurological manifestations, including acute seizures and status epilepticus (SE). In this systematic review, we summarized the available data on clinical features, diagnosis, and therapy of COVID-19-related SE. METHODS: We performed a systematic search of the literature to identify data on demographics, clinical, neurophysiological, and neuroradiological data of patients with COVID-19-related SE. We used regression models (linear or logistic) with a stepwise forward method to identify features associated with mortality or severity of SE. RESULTS: Thirty-nine articles were included with a total of 47 cases of SE associated with COVID-19. Age, time between the acute respiratory phase of SARS-CoV-2 infection and SE onset, and hospitalization correlated with a higher SE severity as assessed by quantitative validated scales. CONCLUSIONS: SE can be a neurological manifestation of SARS-CoV-2 infection. Although a possible association between SE and COVID-19 has been reported, the exact mechanisms are still not fully understood. Systemic inflammatory syndrome due to cytokine release could play a role in COVID-19-related SE.

New-onset refractory status epilepticus (NORSE) in post SARS-CoV-2 autoimmune encephalitis: a case report.

The 2019 new coronavirus (SARS-CoV-2) is a novel respiratory virus which has increasingly spread all over the world. Although the predominant clinical presentation is represented by respiratory symptoms, neurological manifestation of SARS-CoV-2 is being increasingly recognized. In the present report, we present a case of post SARS-CoV-2 autoimmune encephalitis associated with a new-onset refractory status epilepticus (NORSE).

The factitious/malingering continuum and its burden on public health costs: a review and experience in an Italian neurology setting.

Factitious disorder is classified as one of the five aspects of somatic symptom disorders. The fundamental element of factitious disorder is deception, i.e., pretending to have a medical or psychiatric disorder, but the enactment of deception is considered unconscious. Indeed, volition, i.e., the perception of deliberate deception, is blurred in patients presenting with factitious disorder. In the USA and the UK, factitious disorder has received constant media attention because of its forensic implications and outrageous costs for the National Health Systems. Unfortunately, a comparable level of attention is not present in Italian National Health System or the Italian mass media. The review analyzes the classifications, disorder mechanisms, costs, and medico-legal implications in the hope of raising awareness on this disturbing issue. Moreover, the review depicts 13 exemplification cases, anonymized and fictionalized by expert writers. Finally, our paper also evaluates the National Health System's expenditures for each patient, outlandish costs in the range between 50,000 and 1 million euros.

Cognitive dysfunction in amyotrophic lateral sclerosis: can we predict it?

BACKGROUND AND AIM: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motoneurons in the brain and spinal cord leading to motor and extra-motor symptoms. Although traditionally considered a pure motor disease, recent evidences suggest that ALS is a multisystem disorder. Neuropsychological alterations, in fact, are observed in more than 50% of patients: while executive dysfunctions have been firstly identified, alterations in verbal fluency, behavior, and pragmatic and social cognition have also been described. Detecting and monitoring ALS cognitive and behavioral impairment even at early disease stages is likely to have staging and prognostic implications, and it may impact the enrollment in future clinical trials. During the last 10 years, humoral, radiological, neurophysiological, and genetic biomarkers have been reported in ALS, and some of them seem to potentially correlate to cognitive and behavioral impairment of patients. In this review, we sought to give an up-to-date state of the art of neuropsychological alterations in ALS: we will describe tests used to detect cognitive and behavioral impairment, and we will focus on promising non-invasive biomarkers to detect pre-clinical cognitive decline. CONCLUSIONS: To date, the research on humoral, radiological, neurophysiological, and genetic correlates of neuropsychological alterations is at the early stage, and no conclusive longitudinal data have been published. Further and longitudinal studies on easily accessible and quantifiable biomarkers are needed to clarify the time course and the evolution of cognitive and behavioral impairments of ALS patients.

Clinical presentation of strokes confined to the insula: a systematic review of literature.

BACKGROUND AND PURPOSE: The insular cortex serves a wide variety of functions in humans, ranging from sensory and affective processing to high-level cognition. Hence, insular dysfunction may result in several different presentations. Ischemic strokes limited to the insular territory are rare and deserve a better characterization, to be quickly recognized and to receive the appropriate treatment (e.g. thrombolysis). METHODS: We reviewed studies on patients with a first-ever acute stroke restricted to the insula. We searched in the Medline database the keywords "insular stroke" and "insular infarction", to identify previously published cases. Afterwards, the results were divided depending on the specific insular region affected by the stroke: anterior insular cortex (AIC), posterior insular cortex (PIC) or total insula cortex (TIC). Finally, a review of the clinical correlates associated with each region was performed. RESULTS: We identified 25 reports including a total of 49 patients (59.7 ± 15.5 years, 48% male) from systematic review of the literature. The most common clinical phenotypes were motor and somatosensory deficits, dysarthria, aphasia and a vestibular-like syndrome. Atypical presentations were also common and included dysphagia, awareness deficits, gustatory disturbances, dysautonomia, neuropsychiatric or auditory disturbances and headache. CONCLUSIONS: The clinical presentation of insular strokes is heterogeneous; however, an insular stroke should be suspected when vestibular-like, somatosensory, speech or language disturbances are combined in the same patient. Further studies are needed to improve our understanding of more atypical presentations.

Low molecular weight heparin in COVID-19 patients prevents delirium and shortens hospitalization.

BACKGROUND: COVID-19 patients present with delirium during their hospitalization. AIMS: To assess the incidence of delirium in hospitalized COVID-19 patients and analyze the possible association with demographic, clinical, laboratory, and pharmacological factors. METHODS: COVID-19 patients were assessed for clinical signs of delirium and administered the assessment test for delirium and cognitive impairment (4AT) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) scales. RESULTS: Out of the 56 patients of our cohort, 14 (25.0%) experienced delirium. The use of low molecular weight heparin (LMWH) (enoxaparin 1 mg/kg/daily) was less frequent in patients with delirium (p = 0.004) and was accompanied by lower C reactive protein (CRP) levels (p = 0.006). DISCUSSION: The use of LMWH was associated with absence of delirium, independently of comorbidities and age. CONCLUSIONS: The use of LMWH may help preventing the occurrence of delirium in COVID-19 patients, with possible reduction of length of stay in the hospital and sequelae.

New daily persistent headache after SARS-CoV-2 infection: a report of two cases.

BACKGROUND: The 2019 Coronavirus (SARS-CoV-2) is a novel respiratory virus which causes Coronavirus Disease19 (COVID-19). Although the predominant clinical picture of COVID-19 is represented by respiratory symptoms, neurological manifestations are being increasingly recognized. Headache, in particular migraine-like and tension types, has been largely reported in patients suffering from COVID-19 both in the acute and the healing phase of the infection. New daily persistent headache (NDPH) is a primary headache characterized by persistent and daily painful symptoms, with pain becoming continuous and non-remitting within 24 h, and lasting more than 3 months. Even though an increasing number of reports describe patients who develop a persistent headache, diagnosis of NPDH has been rarely explored in the context of COVID-19. METHODS: Two patients with persistent headache and Sars-CoV-2 infection were identified. Both underwent a full clinical and neuroradiological evaluation. Blood sample with inflammatory biomarkers search was also performed. RESULTS: According to International Classifications of Headache Disorders diagnosis of probable new daily persistent headache was made. The treatment with high doses of steroids was associated with relief of symptoms. CONCLUSIONS: Our report described two cases of probable NDPH due to SARS-CoV-2 infection. Clinical evaluation of COVID-19 patients presenting with persistent headache should take into consideration NDPH. Given the supposed major role for neuroinflammation in the genesis of Sars-CoV-2-driven NDPH, immunomodulatory therapy should be promptly started. In line with this hypothesis, we obtained a good therapeutic response to short-term high dose of corticosteroids.

Delirium in COVID-19 patients: a multicentric observational study in Italy.

INTRODUCTION: Although recent data show that SARS-CoV-2 infection seems to affect the central nervous system (CNS), little is known about the neuropsychiatric effects resulting from this condition. In addition to the well-known neurotrophism of coronaviruses, recent evidence shows also that the "cytokine storm" induced by the infection is at the basis of the neuroinflammation of the CNS. Furthermore, prolonged hospitalization, polypharmacotherapy, and isolation could be at the basis of the onset of delirium in hospitalized COVID patients. This multicentric observational study explores the incidence of the onset of delirium in an Italian cohort of SARS-CoV-2 positive inpatients. METHODS: Data were collected in the COVIDhospitals of Brescia, Bergamo, Chieti, and Genova. Different socio-demographic, medical, neurological, and pharmacological parameters were collected. As a rapid screening for delirium, the 4AT scale was used. Eighty COVID-19 inpatients (mean age 74.7 ± 14.5 years) met the inclusion criteria (confirmed positivity to the SARS-CoV-2 virus; the presence of delirium and/or psychomotor agitation and/or new onset of other neuropsychiatric symptoms during hospitalization). RESULTS: The majority of these patients (68.8%) had "hyperactive delirium" subtype. Polypharmacotherapy, current treatment with corticosteroids, and higher age were associated with delirium severity. CONCLUSION: These data provide an insight into the onset of delirium among COVID-19 patients underlining the need for monitoring, especially in elderly patients, the neuropsychiatric symptoms, and the therapy in order to have shorter hospitalization times and better outcomes.

Diaphragmatic myoclonus due to SARS-CoV-2 infection.

A wide range of neurological signs and symptoms have been associated with SARS-CoV-2 infection. In the present report, we described two Italian patients diagnosed with diaphragmatic myoclonus after COVID-19. In both cases, mild lymphocytosis at cerebrospinal fluid analysis and no structural brain changes were reported. The pathophysiological origin of the myoclonus in the two cases was different. In case 1, electroencephalogram did not reveal any cortical correlates and brain imaging of the spine was unremarkable, while in case 2, cortical origin of myoclonus was demonstrated. With the present two cases, we confirm and extend the neurological manifestations of SARS-CoV-2 infection.

The Italian version of cognitive function instrument (CFI): reliability and validity in a cohort of healthy elderly.

The Alzheimer's disease Cooperative Study (ADCS)-Cognitive Function Instrument (CFI) is a 14-item questionnaire administered to the subject and the referent, aimed at detecting early changes in cognitive and functional abilities in individuals without clinical impairment. It is used for monitoring annual variations in cognitive functioning in prevention trials. The aim of the present study was to validate the Italian version of the CFI. A consecutive series of 257 functionally independent subjects was recruited among relatives of patients or as volunteers. They were administered CFI and global cognition measurements: Mini-Mental Status Examination (MMSE) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The reliability and criterion validity were comparable to the original in both self- and partner-report. Similarly to what reported in the original version, we found a corrected item-total correlation ranging between 0.38 and 0.54 in self-report and between 0.33 and 0.64 in partner-report. Cronbach's α was 0.77 (95% CI 0.72-0.83) in self-report and 0.78 (95% CI 0.73-0.84) in partner-report. Total partner- and self-report scores were significantly correlated (rS = 0.31, p < 0.001). CFI self-report and CFI total-score (partner + self-report) were negatively correlated with MMSE (rS = - 0.15, p = 0.022; rS = - 0.17, p = 0.008) and RBANS (rS = - 0.22, p < 0.001; rS = - 0.25, p < 0.001). Analogous trends were found in the partner score, with a correlation with RBANS (rS = - 0.17, p = 0.014) and MMSE (rS = - 0.11, p = 0.071). Our results support the reliability and validity of the Italian version of CFI. In order to definitely propose the use of CFI for tracking longitudinal changes of cognitive and functional abilities in subjects without clinical impairment, data from the follow-up of this cohort are needed.