Embolic Stroke Following Ingestion of Liquid Nicotine Refill Solution.

The use of e-cigarettes is gaining popularity despite knowing about cardiovascular health risks. Cases of intentional or accidental intoxication following ingestion of the refill solution are also a growing concern. Most of these cases were fatal and related to cardiac arrest and hypoxic brain injury. We report the case of a 54-year-old woman who developed bilateral acute ischemic stroke in the anterior and posterior cerebral circulation following intentional oral intake of e-liquid nicotine refill solution. The diagnostic work-up concluded an etiology of embolic stroke of undetermined source, most likely of cardiac origin. We assume that sympathetic overactivation lead to temporary cardiac arrhythmia and subsequent thrombi formation. Moreover, we discuss several additional pathogenic aspects of oral intake of e-liquid refill solution for the development of central nervous system pathology. This case expands the clinical spectrum of health hazards associated with the introduction of e-cigarettes and raises awareness of the need for preventive measures.

Optimization of cognitive assessment in Parkinsonisms by applying artificial intelligence to a comprehensive screening test.

The assessment of cognitive deficits is pivotal for diagnosis and management in patients with parkinsonisms. Low levels of correspondence are observed between evaluations assessed with screening cognitive tests in comparison with those assessed with in-depth neuropsychological batteries. A new tool, we named CoMDA (Cognition in Movement Disorders Assessment), was composed by merging Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Frontal Assessment Battery (FAB). In total, 500 patients (400 with Parkinson's disease, 41 with vascular parkinsonism, 31 with progressive supranuclear palsy, and 28 with multiple system atrophy) underwent CoMDA (level 1-L1) and in-depth neuropsychological battery (level 2-L2). Machine learning was developed to classify the CoMDA score and obtain an accurate prediction of the cognitive profile along three different classes: normal cognition (NC), mild cognitive impairment (MCI), and impaired cognition (IC). The classification accuracy of CoMDA, assessed by ROC analysis, was compared with MMSE, MoCA, and FAB. The area under the curve (AUC) of CoMDA was significantly higher than that of MMSE, MoCA and FAB (p < 0.0001, p = 0.028 and p = 0.0007, respectively). Among 15 different algorithmic methods, the Quadratic Discriminant Analysis algorithm (CoMDA-ML) showed higher overall-metrics performance levels in predictive performance. Considering L2 as a 3-level continuous feature, CoMDA-ML produces accurate and generalizable classifications: micro-average ROC curve, AUC = 0.81; and AUC = 0.85 for NC, 0.67 for MCI, and 0.83 for IC. CoMDA and COMDA-ML are reliable and time-sparing tools, accurate in classifying cognitive profile in parkinsonisms.This study has been registered on ClinicalTrials.gov (NCT04858893).

Spontaneous spinal cord infarction in Austria: a two-center comparative study.

Background: Spinal cord infarction (SCI) is a neurological emergency associated with high rates of persistent neurological deficits. Knowledge about this rare but potentially treatable condition needs to be expanded. Objective: To describe the characteristics of spontaneous SCI in a large retrospective series of patients treated at two tertiary care centers in Austria. Methods: We performed a descriptive and comparative analysis of spontaneous SCI treated at the University Hospitals of Salzburg and Graz between the years 2000 and 2020. The analysis included pre- and in-hospital procedures, clinical presentation, etiology, diagnostic certainty, reperfusion therapy, and functional outcome at discharge. Results: We identified 88 cases, 61% were ascertained in the second half of the study period. The median age was 65.5 years [interquartile range (IQR) = 56-74], 51.1% were women. Anterior spinal artery infarction was the predominant syndrome (82.9%). Demographics, vascular comorbidities, and clinical presentation did not differ between the centers. The most frequent etiology and level of diagnostic certainty were distinct, with atherosclerosis (50%) and definite SCI (42%), and unknown (52.5%) and probable SCI (60%) as front runners in Salzburg and Graz, respectively. Patients arrived after a median of 258.5 min (IQR = 110-528) at the emergency room. The first magnetic resonance imaging (MRI) of the spinal cord was performed after a median of 148 min (IQR = 90-312) from admission and was diagnostic for SCI in 45%. Two patients received intravenous thrombolysis (2.2%). The outcome was poor in 37/77 (48%). Conclusion: Demographics, clinical syndromes, and quality benchmarks for spontaneous SCI were consistent at two Austrian tertiary care centers. Our findings provide the foundation for establishing standards for pre- and in-hospital care to improve outcomes.

TMS for the functional evaluation of cannabis effects and for treatment of cannabis addiction: A review.

The knowledge about the effects of cannabis on human cortical brain processes is increasing. In this regard, transcranial magnetic stimulation (TMS) enables the evaluation of central nervous system function, including drug effects. Moreover, repetitive TMS (rTMS) has been used therapeutically in several substance use disorders. In this scoping review, we summarize and discuss studies that have employed TMS and rTMS techniques in users of cannabis for recreational purposes. In subjects with a history of persistent cannabis use, TMS studies showed reduced short-interval cortical inhibition (SICI). This observation points more at neurobiological changes of chronic cannabis use than to a direct effect of cannabis on gamma-aminobutyric acid (GABA) A receptors. Moreover, individuals vulnerable to becoming long-term users of cannabis may also have underlying pre-existing abnormalities in SICI. Of note, the use of cannabis is associated with an increased risk of schizophrenia, and the down-regulation of GABAergic function may play a role. Less frequent cannabis use and spontaneous craving were observed following rTMS applied to the dorsolateral prefrontal cortex (DLPFC). There is emerging evidence that the posterior cingulate cortex and the precuneus are potential targets for rTMS intervention in cannabis use disorder. However, larger and randomized trials should corroborate these encouraging findings.

Visuomotor integration in early Alzheimer's disease: A TMS study.

BACKGROUND AND PURPOSE: Cortical visuomotor integration is altered in Alzheimer's disease (AD), even at an early stage of the disease. The aim of this study was to assess the connections between the primary visual (V1) and motor (M1) areas in patients with early AD using a paired-pulse, twin-coil transcranial magnetic stimulation (TMS) technique. METHODS: Visuomotor connections (VMCs) were assessed in 13 subjects with probable AD and 16 healthy control subjects. A conditioning stimulus over the V1 phosphene hotspot was followed at interstimulus intervals (ISIs) of 18 and 40 ms by a test stimulus over M1, to elicit motor evoked potentials (MEPs) in the contralateral first dorsal interosseous muscle. RESULTS: Significant effects due to VMCs, consisting of enhanced MEP suppression at ISI of 18 and 40 ms, were observed in the AD patients. Patients with AD showed an excessive inhibitory response of the right M1 to inputs travelling from V1 at given ISIs. CONCLUSIONS: This study provides neurophysiological evidence of altered functional connectivity between visual and motor areas in AD.

The Manchester Triage System's performance in clinical risk prioritisation of patients presenting with headache in emergency department: A retrospective observational study.

OBJECTIVE: Non-traumatic headache is a frequent reason for visits to the emergency department (ED). We evaluated the performance of the Manchester Triage System (MTS) in prioritising patients presenting to the ED with non-traumatic headache. METHODS: In this single-centre observational retrospective study, we compared the association of MTS priority classification codes with a final diagnosis of a severe neurological condition requiring timely management (ischaemic or haemorrhagic stroke, subarachnoid haemorrhage, cerebral sinus venous thrombosis, central nervous system infection or brain tumour). The study was conducted and reported according to the STROBE statement. The overall prioritisation accuracy of MTS was estimated by the area under the receiver operating characteristic (ROC) curve. The correctness of triage prediction was estimated based on the "very urgent" MTS grouping. An undertriage was defined as a patient with an urgent and severe neurological who received a low priority/urgency MTS code (green/yellow). RESULTS: Over 30 months, 3002 triage evaluations of non-traumatic headache occurred (1.7% of ED visits). Of these, 2.3% (68/3002) were eventually diagnosed with an urgent and severe neurological condition. The MTS had an acceptable prioritisation accuracy, with an area under the ROC curve of 0.734 (95% CI 0.668-0.799). The sensitivity of the MTS for urgent codes (yellow, orange and red) was 79.4% (95% CI 74.5-84.3), with a specificity of 54.1% (95% CI 52.9-55.3). The triage prediction was incorrect in only 6.3% (190/3002) of patients with headache. CONCLUSION: The MTS is a safe and accurate tool for prioritising patients with non-traumatic headache in the ED. However, MTS may need further specific tools for evaluating the more complicated symptoms and for correctly identifying patients with urgent and severe underlying pathologies. RELEVANCE TO CLINICAL PRACTICE: The triage nurse using MTS may need additional tools to improve the assessment of patients with headache, although MTS provides a good safety profile.

Acute symptomatic seizures: an educational, evidence-based review.

Acute symptomatic seizures occurring in close temporal relationship with an acute CNS insult are distinct from epilepsy and occur frequently in clinical practice. The aim of this educational review is to provide information on the most important aspects related to acute symptomatic seizures that will allow clinicians to accurately distinguish acute symptomatic seizures from epilepsy in their patients. We explain the definition of acute symptomatic seizures and we illustrate how acute symptomatic seizures differ from epilepsy. We describe acute symptomatic seizures in the context of their various underlying aetiologies and we discuss the approach to the management of patients with acute symptomatic seizures.

Involvement of central sensory pathways in subjects with restless legs syndrome: A neurophysiological study.

In patients with restless legs syndrome (RLS) a motor cortical disinhibition has been reported in transcranial magnetic stimulation (TMS) studies, but the neuronal excitability in other cortical areas has been poorly explored. The aim of this study was the functional evaluation of thalamo-cortical circuits and inhibitory cortical responses in the sensory cortex in RLS. We assessed the high-frequency somatosensory evoked potentials (HF-SEP) in sixteen subjects suffering from RLS of different degrees of severity. In patients with severe or very severe RLS we found a significant desynchronization with amplitude reduction of both pre- and post-synaptic HF-SEP bursts, which suggest an impairment in the thalamo-cortical projections and in the cortical inhibitory interneurons activity, respectively. The assessment of the central sensory pathways by means of HF-SEP may shed light on the pathophysiological mechanisms of RLS.

Brain functional reorganization in children with hemiplegic cerebral palsy: Assessment with TMS and therapeutic perspectives.

Transcranial magnetic stimulation (TMS) can be a useful tool for the assessment of the brain functional reorganization in subjects with hemiplegic cerebral palsy (HCP). In this review, we performed a systematic search of all studies using TMS in order to explore the neuroplastic changes that occur in HCP patients. We aimed at investigating the usefulness of TMS to explore cortical excitability, plasticity and connectivity changes in HCP. Children with HCP due to unilateral lesions of the corticospinal system had ipsilateral motor evoked potentials (MEPs) similar to those recorded contralaterally. TMS studies demonstrated that occupational and constraint-induced movement therapy were associated with significant improvements in contralateral and ipsilateral corticomotor projection patterns. In addition, after intensive bimanual therapy, children with HCP showed increased activation and size of the motor areas controlling the affected hand. A TMS mapping study revealed a mediolateral location of the upper and lower extremity map motor cortical representations. Deficits in intracortical and interhemispheric inhibitory mechanisms were observed in HCP. Early hand function impairment correlated with the extension of brain damage, number of involved areas, and radiological signs of corticospinal tract (CST) degeneration. Clinical mirror movements (MMs) correlated with disability and CST organization in subjects with HCP and a positive relationship was found between MMs and MEPs strength. Therefore, TMS studies have shed light on important pathophysiological aspects of motor cortex and CST reorganization in HCP patients. Furthermore, repetitive TMS (rTMS) might have therapeutic effects on CST activities, functional connectivity and clinical status in children with HCP.

Neural mechanisms underlying the Rubber Hand Illusion: A systematic review of related neurophysiological studies.

INTRODUCTION: Many researchers took advantage of the well-established rubber hand illusion (RHI) paradigm to explore the link between the sense of body ownership and the different brain structures and networks. Here, we aimed to review the studies that have investigated this phenomenon by means of neurophysiological techniques. METHODS: The MEDLINE, accessed by Pubmed and EMBASE electronic databases, was searched using the medical subject headings: "Rubber hand illusion" AND "Transcranial magnetic stimulation (TMS)" OR "Evoked potentials (EP)" OR "Event related potentials (ERP)" OR "Electroencephalography (EEG)". RESULTS: Transcranial magnetic stimulation studies revealed a significant excitability drop in primary motor cortex hand circuits accompanying the disembodiment of the real hand during the RHI experience and that the perceived ownership over the rubber hand is associated with normal parietal-motor communication. Moreover, TMS provided causal evidence that the extrastriate body area is involved in the RHI and subsequently in body representation, while neuromodulation of ventral premotor area and the inferior parietal lobe did not result in an enhancement of embodiment. EP and ERP studies suggest that pre-existing body representations may affect larger stages of tactile processing and support predictive coding models of the functional architecture of multisensory integration in bodily perceptual experience. High-frequency oscillations on EEG play a role in the integrative processing of stimuli across modalities, and EEG activity in γ band activity in the parietal area reflects the visuotactile integration process. EEG studies also revealed that RHI is associated with the neural circuits underlying motor control and that premotor areas play a crucial role in mediating illusory body ownership. CONCLUSION: Neurophysiological studies shed new light on our understanding of the different aspects that contribute to the formation of a coherent self-awareness in humans.

Quantitative EEG biomarkers for epilepsy and their relation to chemical biomarkers.

The electroencephalogram (EEG) is the most important method to diagnose epilepsy. In clinical settings, it is evaluated by experts who identify patterns visually. Quantitative EEG is the application of digital signal processing to clinical recordings in order to automatize diagnostic procedures, and to make patterns visible that are hidden to the human eye. The EEG is related to chemical biomarkers, as electrical activity is based on chemical signals. The most well-known chemical biomarkers are blood laboratory tests to identify seizures after they have happened. However, research on chemical biomarkers is much less extensive than research on quantitative EEG, and combined studies are rarely published, but highly warranted. Quantitative EEG is as old as the EEG itself, but still, the methods are not yet standard in clinical practice. The most evident application is an automation of manual work, but also a quantitative description and localization of interictal epileptiform events as well as seizures can reveal important hints for diagnosis and contribute to presurgical evaluation. In addition, the assessment of network characteristics and entropy measures were found to reveal important insights into epileptic brain activity. Application scenarios of quantitative EEG in epilepsy include seizure prediction, pharmaco-EEG, treatment monitoring, evaluation of cognition, and neurofeedback. The main challenges to quantitative EEG are poor reliability and poor generalizability of measures, as well as the need for individualization of procedures. A main hindrance for quantitative EEG to enter clinical routine is also that training is not yet part of standard curricula for clinical neurophysiologists.

Effects of Intermittent Theta Burst Stimulation on the Clock Drawing Test Performances in Patients with Alzheimer's Disease.

The clock drawing test (CDT) is widely used in clinical neuropsychological practice. However, its neuroanatomical correlates have not been well established. This study investigated the effects of theta burst stimulation (TBS) applied over different brain regions on CDT scores in patients with Alzheimer's disease (AD). The 10-20 positions F3, F4, T3, T4, TP3, TP4, P3, P4, as determined by a 10-20 positioning cap, were targeted. Excitatory intermittent TBS (iTBS) was given over the above-mentioned eight regions to ten AD patients and ten control subjects on separate days. CDT was administered at baseline (T0), during the 5 min following the TBS (T1) and 60 min after TBS (T2), with an inter-session interval of at least 4 days. iTBS over TP4 and P4 transiently increased Rouleau CDT score in AD patients. When targeting TP4 and P4, mainly the area of the supramarginal/angular gyrus and the inferior parietal lobe, corresponding respectively to the Brodmann areas 40/39 and 7/40, are reached. iTBS thus seems able to modulate activity of the right posterior parietal cortex in AD patients performing the CDT. Our results provide physiological evidence that those parietal regions are functionally important for the execution of the Rouleau CDT. This finding suggests that CDT has reliable neuroanatomical correlates, and support the notion that this test can be used as a good marker of right parietal brain dysfunction. The present study also highlights the therapeutic potential of the induction of neuromodulatory effects using non-invasive brain stimulation techniques.

TMS-EEG Co-Registration in Patients with Mild Cognitive Impairment, Alzheimer's Disease and Other Dementias: A Systematic Review.

An established method to assess effective brain connectivity is the combined use of transcranial magnetic stimulation with simultaneous electroencephalography (TMS-EEG) because TMS-induced cortical responses propagate to distant anatomically connected brain areas. Alzheimer's disease (AD) and other dementias are associated with changes in brain networks and connectivity, but the underlying pathophysiology of these processes is poorly defined. We performed here a systematic review of the studies employing TMS-EEG co-registration in patients with dementias. TMS-EEG studies targeting the motor cortex have revealed a significantly reduced TMS-evoked P30 in AD patients in the temporo-parietal cortex ipsilateral to stimulation side as well as in the contralateral fronto-central area, and we have demonstrated a deep rearrangement of the sensorimotor system even in mild AD patients. TMS-EEG studies targeting other cortical areas showed alterations of effective dorsolateral prefrontal cortex connectivity as well as an inverse correlation between prefrontal-to-parietal connectivity and cognitive impairment. Moreover, TMS-EEG analysis showed a selective increase in precuneus neural activity. TMS-EEG co-registrations can also been used to investigate whether different drugs may affect cognitive functions in patients with dementias.

Stroke management during the coronavirus disease 2019 (COVID-19) pandemic: experience from three regions of the north east of Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige).

BACKGROUND: Efficiency of care chain response and hospital reactivity were and are challenged for stroke acute care management during the pandemic period of coronavirus disease 2019 (COVID-19) in North-Eastern Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige), counting 7,193,880 inhabitants (ISTAT), with consequences in acute treatment for patients with ischemic stroke. METHODS: We conducted a retrospective data collection of patients admitted to stroke units eventually treated with thrombolysis and thrombectomy, ranging from January to May 2020 from the beginning to the end of the main first pandemic period of COVID-19 in Italy. The primary endpoint was the number of patients arriving to these stroke units, and secondary endpoints were the number of thrombolysis and/or thrombectomy. Chi-square analysis was used on all patients; furthermore, patients were divided into two cohorts (pre-lockdown and lockdown periods) and the Kruskal-Wallis test was used to test differences on admission and reperfusive therapies. RESULTS: In total, 2536 patients were included in 22 centers. There was a significant decrease of admissions in April compared to January. Furthermore, we observed a significant decrease of thrombectomy during the lockdown period, while thrombolysis rate was unaffected in the same interval across all centers. CONCLUSIONS: Our study confirmed a decrease in admission rate of stroke patients in a large area of northern Italy during the lockdown period, especially during the first dramatic phase. Overall, there was no decrease in thrombolysis rate, confirming an effect of emergency care system for stroke patients. Instead, the significant decrease in thrombectomy rate during lockdown addresses some considerations of local and regional stroke networks during COVID-19 pandemic evolution.

Connectivity Analysis during Rubber Hand Illusion-A Pilot TMS-EEG Study in a Patient with SCI.

Background: Bodily self-perception is an important concept for several neurological disorders, including spinal cord injury (SCI). Changing one's bodily self-perception, e.g., via rubber hand illusion (RHI), induces alterations of bottom-up and top-down pathways and with this the connectivity between involved brain areas. We aim to examine whether (1) this process can be manipulated by changing cortical excitability, (2) connectivity between relevant brain areas differ when the RHI cannot be evoked, and (3) how this projection differs in a patient with SCI. Method: We applied RHI and facilitatory theta burst stimulation (TBS) on the right primary somatosensory cortex (S1) of 18 healthy participants and one patient with incomplete, cervical SCI. During RHI, we recorded high-density electroencephalography (HD-EEG) and extracted directed and nondirected connectivity measures. Results: There is no difference in connectivity between sham and real TBS or in the effectivity of RHI. We observed a higher laterality in the patient, i.e., higher connectivity of the right and lower of the left hemisphere. Besides this, connectivity patterns do not differ between healthy participants and the patient. Conclusion: This connectivity pattern might represent a neuroplastic response in the attempt to overcome the functional impairment of the patient resulting in a similar overall connectivity pattern to the healthy participants, yet with a higher sensitivity towards RHI and a higher laterality. The cortico-cortical communication was not altered depending on whether the illusion was provoked or not; hence, the perceptory illusion could not be observed in the EEG analysis.

The Babinski sign in the first Italian reports.

The Babinski sign, named after Joseph François Félix Babinski (1857-1932), is one of the most important in clinical neurology. It refers to the upward movement of the great toe following stimulation of the foot sole and is associated with a dysfunction of the pyramidal tract. The BS was recognized and adopted by neurologists all over the world immediately after its first description. In 1899, this sign was first introduced to the Italian scientific community at two different medical meetings. Some opinions on its clinical value and underlying pathophysiology were discordant, possibly reflecting suboptimal diagnostic accuracy of the first observations. Giovanni Mingazzini (1859-1929) first suggested that the BS reflects a complex mechanism emerging in patients with pyramidal tract dysfunction, whereas Giovanni Boeri (1867-1946) emphasized that the BS can be elicited if the neuromuscular structures underlying it are intact. Although some of their opinions eventually proved wrong, early Italian neurologists further contributed to the advancement in the understanding of this phenomenon.

Classification accuracy of TMS for the diagnosis of mild cognitive impairment.

OBJECTIVE: To evaluate the performance of a Random Forest (RF) classifier on Transcranial Magnetic Stimulation (TMS) measures in patients with Mild Cognitive Impairment (MCI). METHODS: We applied a RF classifier on TMS measures obtained from a multicenter cohort of patients with MCI, including MCI-Alzheimer's Disease (MCI-AD), MCI-frontotemporal dementia (MCI-FTD), MCI-dementia with Lewy bodies (MCI-DLB), and healthy controls (HC). All patients underwent TMS assessment at recruitment (index test), with application of reference clinical criteria, to predict different neurodegenerative disorders. The primary outcome measures were the classification accuracy, precision, recall and F1-score of TMS in differentiating each disorder. RESULTS: 160 participants were included, namely 64 patients diagnosed as MCI-AD, 28 as MCI-FTD, 14 as MCI-DLB, and 47 as healthy controls (HC). A series of 3 binary classifiers was employed, and the prediction model exhibited high classification accuracy (ranging from 0.72 to 0.86), high precision (0.72-0.90), high recall (0.75-0.98), and high F1-scores (0.78-0.92), in differentiating each neurodegenerative disorder. By computing a new classifier, trained and validated on the current cohort of MCI patients, classification indices showed even higher accuracy (ranging from 0.83 to 0.93), precision (0.87-0.89), recall (0.83-1.00), and F1-scores (0.85-0.94). CONCLUSIONS: TMS may be considered a useful additional screening tool to be used in clinical practice in the prodromal stages of neurodegenerative dementias.