Charcot's international visitors and pupils from Europe, the United States, and Russia.

The foundation by Jean-Martin Charcot (1825-1893) of the Salpêtrière School in Paris had an influential role in the development of neurology during the late-nineteenth century. The international aura of Charcot attracted neurologists from all parts of the world. We here present the most representative European, American, and Russian young physicians who learned from Charcot during their tutoring or visit in Paris or Charcot's travels outside France. These include neurologists from Great Britain and Ireland, the United States, Germany and Austria, Switzerland, Russia, Italy, Spain, Belgium and the Netherlands, Scandinavia and Finland, Poland, Bohemia, Hungary, and Romania. Particularly emblematic among the renowned foreign scientists who met and/or learned from Charcot were Charles-Edouard Brown-Séquard, who had interactions with Paris University and contributed to the early development of British and American neurological schools; John Hughlings Jackson, who was admired by Charcot and influenced French neurology similarly as Charcot did on British neurology; Silas Weir Mitchell, the pioneer in American neurology; Sigmund Freud, who was trained by Charcot to study patients with hysteria and then, back in Vienna, founded a new discipline called psychoanalysis; Aleksej Yakovlevich Kozhevnikov and almost all the founders of the Russian institutes of neurology who were instructed in Paris; and Georges Marinesco, who established the Romanian school of neurology and did major contributions thanks to his valuable relation with Charcot and French neurology.

ChatGPT vs. neurologists: a cross-sectional study investigating preference, satisfaction ratings and perceived empathy in responses among people living with multiple sclerosis.

BACKGROUND: ChatGPT is an open-source natural language processing software that replies to users' queries. We conducted a cross-sectional study to assess people living with Multiple Sclerosis' (PwMS) preferences, satisfaction, and empathy toward two alternate responses to four frequently-asked questions, one authored by a group of neurologists, the other by ChatGPT. METHODS: An online form was sent through digital communication platforms. PwMS were blind to the author of each response and were asked to express their preference for each alternate response to the four questions. The overall satisfaction was assessed using a Likert scale (1-5); the Consultation and Relational Empathy scale was employed to assess perceived empathy. RESULTS: We included 1133 PwMS (age, 45.26 ± 11.50 years; females, 68.49%). ChatGPT's responses showed significantly higher empathy scores (Coeff = 1.38; 95% CI = 0.65, 2.11; p > z < 0.01), when compared with neurologists' responses. No association was found between ChatGPT' responses and mean satisfaction (Coeff = 0.03; 95% CI = - 0.01, 0.07; p = 0.157). College graduate, when compared with high school education responder, had significantly lower likelihood to prefer ChatGPT response (IRR = 0.87; 95% CI = 0.79, 0.95; p < 0.01). CONCLUSIONS: ChatGPT-authored responses provided higher empathy than neurologists. Although AI holds potential, physicians should prepare to interact with increasingly digitized patients and guide them on responsible AI use. Future development should consider tailoring AIs' responses to individual characteristics. Within the progressive digitalization of the population, ChatGPT could emerge as a helpful support in healthcare management rather than an alternative.

Sex differences in ischemic stroke during COVID-19 first outbreak in northern Italy.

INTRODUCTION: COVID-19 pandemic had a great impact on outcome in SARS-CoV-2 positive patients with ischemic stroke during the first wave in Italy. Few data are available on outcome stratified by sex. METHODS: The Italian Society of Hospital Neuroscience conducted a multi-center, retrospective, observational study on neurological complications in COVID-19 patients with ischemic stroke. All the patients admitted from March 1st to April 30th, 2020 in 20 Neurology Units in Northern Italy were recruited. Demographical and clinical features, treatment and outcome data were compared focusing on sex differences. RESULTS: 812 patients with ischemic stroke were enrolled, of whom 129 with COVID-19; males were 53.8%. In-hospital mortality in COVID-19 patients was 35.3% in males and 27.9% in females while 8.5% in male and 5.8% in female patients without COVID-19. SARS-CoV-2 positive patients had a higher frequency of stroke of undetermined etiology, than negative ones (32.8% vs 22.5%; p = 0.02), especially in females compared to males (36.1% vs 27.9%), albeit without statistical significance. Male patients with SARS-CoV-2 were more likely to require cPAP (30.9% vs 14.8%; p = 0.03), endotracheal tube (14.9% vs 3.3%; p = 0.02) and reperfusion strategies (29.4% vs 11.5%; p = 0.01) than females, as well as to have a higher CRP and D-dimer. These elements together with older age, a total anterior circulation stroke and lymphopenia were predictors of a worse outcome. DISCUSSION: Our study detected some differences due to sex in ischemic stroke with and without COVID-19, supporting the possibility to perform sex analyses for SARS-CoV-2 positive patients for a better clinical management.

State of the Art and Challenges in Epilepsy-A Narrative Review.

Epilepsy is a common condition worldwide, with approximately 50 million people suffering from it. A single seizure does not mean epilepsy; almost 10% of the population can have a seizure during their lifetime. In particular, there are many other central nervous system disorders other than epilepsy in which seizures occur, either transiently or as a comorbid condition. The impact of seizures and epilepsy is, therefore, widespread and easily underestimated. It is estimated that about 70% of patients with epilepsy could be seizure-free if correctly diagnosed and treated. However, for patients with epilepsy, quality of life is influenced not only by seizure control but also by antiepileptic drug-adverse reactions, access to education, mood, employment, and transportation.

Methodology for clinical research.

A clinical research requires a systematic approach with diligent planning, execution and sampling in order to obtain reliable and validated results, as well as an understanding of each research methodology is essential for researchers. Indeed, selecting an inappropriate study type, an error that cannot be corrected after the beginning of a study, results in flawed methodology. The results of clinical research studies enhance the repertoire of knowledge regarding a disease pathogenicity, an existing or newly discovered medication, surgical or diagnostic procedure or medical device. Medical research can be divided into primary and secondary research, where primary research involves conducting studies and collecting raw data, which is then analysed and evaluated in secondary research. The successful deployment of clinical research methodology depends upon several factors. These include the type of study, the objectives, the population, study design, methodology/techniques and the sampling and statistical procedures used. Among the different types of clinical studies, we can recognize descriptive or analytical studies, which can be further categorized in observational and experimental. Finally, also pre-clinical studies are of outmost importance, representing the steppingstone of clinical trials. It is therefore important to understand the types of method for clinical research. Thus, this review focused on various aspects of the methodology and describes the crucial steps of the conceptual and executive stages.

Dietary supplements for the management of COVID-19 symptoms.

SARS-CoV-2, the etiological agent of COVID-19, caused a pandemic in 2020, which is only recently slowing down. The symptoms of COVID-19 range from cough to fever and pneumonia and may persist beyond the active state of the infection, in a condition called post-COVID syndrome. The aim of this paper is to review the relationship between COVID-19 and nutrition and to discuss to most up-to-date dietary supplements proposed for COVID-19 treatment and prevention. Nutrition and nutritional dysregulations, such as obesity and malnutrition, are prominent risk factors for severe COVID-19. These factors exert anti-inflammatory and proinflammatory effects on the immune system, thus exacerbating or reducing the immunological response against the virus. As for the nutritional habits, the Western diet induces a chronic inflammatory state, whereas the Mediterranean diet exerts anti-inflammatory effects and has been proposed for ameliorating COVID-19 evolution and symptoms. Several vaccines have been researched and commercialized for COVID-19 prevention, whereas several drugs, although clinically tested, have not shown promising effects. To compensate for the lack of treatment, several supplements have been recommended for preventing or ameliorating COVID-19 symptoms. Thus, it is critical to review the dietary supplements proposed for COVID-19 treatment. Supplements containing α-cyclodextrin and hydroxytyrosol exhibited promising effects in several clinical trials and reduced the severity of the outcomes and the duration of the infection. Moreover, a supplement containing hydroxytyrosol, acetyl L-carnitine, and vitamins B, C, and D improved the symptoms of patients with post-COVID syndrome.

Ethical considerations regarding animal experimentation.

Animal experimentation is widely used around the world for the identification of the root causes of various diseases in humans and animals and for exploring treatment options. Among the several animal species, rats, mice and purpose-bred birds comprise almost 90% of the animals that are used for research purpose. However, growing awareness of the sentience of animals and their experience of pain and suffering has led to strong opposition to animal research among many scientists and the general public. In addition, the usefulness of extrapolating animal data to humans has been questioned. This has led to Ethical Committees' adoption of the 'four Rs' principles (Reduction, Refinement, Replacement and Responsibility) as a guide when making decisions regarding animal experimentation. Some of the essential considerations for humane animal experimentation are presented in this review along with the requirement for investigator training. Due to the ethical issues surrounding the use of animals in experimentation, their use is declining in those research areas where alternative in vitro or in silico methods are available. However, so far it has not been possible to dispense with experimental animals completely and further research is needed to provide a road map to robust alternatives before their use can be fully discontinued.

Cognitive and behavioral involvement in ALS has been known for more than a century.

BACKGROUND: Among clinicians and researchers, it is common knowledge that, in ALS, cognitive and behavioral involvement within the spectrum of frontotemporal degenerations (FTDs) begun to be regarded as a fact in the late 1990s of the twentieth century. By contrast, a considerable body of evidence on cognitive/behavioral changes in ALS can be traced in the literature dating from the late nineteenth century. METHODS: Worldwide reports on cognitive/behavioral involvement in ALS dating from 1886 to 1981 were retrieved thanks to Biblioteca di Area Medica "Adolfo Ferrate," Sistema Bibliotecario di Ateneo, University of Pavia, Pavia, Italy and qualitatively synthetized. RESULTS: One-hundred and seventy-four cases of ALS with co-occurring FTD-like cognitive/behavioral changes, described in Europe, America, and Asia, were detected. Neuropsychological phenotypes were consistent with the revised Strong et al.'s consensus criteria. Clinical observations were not infrequently supported by histopathological, post-mortem verifications of extra-motor, cortical/sub-cortical alterations, as well as by in vivo instrumental exams-i.e., assessments of brain morphology/physiology and psychometric testing. In this regard, as earlier as 1907, the notion of motor and cognitive/behavioral features in ALS yielding from the same underlying pathology was acknowledged. Hereditary occurrences of ALS with cognitive/behavioral dysfunctions were reported, as well as familial associations with ALS-unrelated brain disorders. Neuropsychological symptoms often occurred before motor ones. Bulbar involvement was at times acknowledged as a risk factor for cognitive/behavioral changes in ALS. DISCUSSION: Historical observations herewith delivered can be regarded as the antecedents of current knowledge on cognitive/behavioral impairment in the ALS-FTD spectrum.

Special Issue "Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment".

Chronic fatigue syndrome, or myalgic encephalomyelitis (CFS/ME), is a debilitating disease with unknown causes that is more common in women and tends to develop between patients' mid-20s and mid-40s [...].

Vincenzo Neri (1880-1960) and his sign to detect leg weakness due to corticospinal tract injury.

The Italian neurologist Vincenzo Neri (1880-1960), a pupil of Joseph Babinski (1857-1932), greatly contributed to refining the semiotics of neurological examination and was a pioneer in medical cinematography. In 1909, Neri proposed a sign to diagnose leg paresis due to a pyramidal tract lesion. According to Neri, if a patient standing with the legs apart and the arms crossed on the chest bends the trunk of the pelvis, when the trunk has almost reached the horizontal line, the leg on the paralyzed side flexes, whereas the unaffected leg remains extended. This sign reflects a spinal hyperfunctioning emerging after a pyramidal lesion, and should be interpreted as a part of a triple flexion reflex. Beyond the acute stage, it could reflect an unusual pattern of flexor spasticity involving the lower limb due to corticospinal tract injury. The sign described by Neri retains its validity in identifying this organic leg weakness due to pyramidal lesions, particularly when it is mild or in its early stages.

Paraneoplastic Neurological Syndromes: Transitioning Between the Old and the New.

PURPOSE OF REVIEW: Paraneoplastic neurological syndromes (PNS) are caused by nervous system-targeting aberrant anti-tumoral immune responses. We review the updated criteria for PNS diagnosis, incorporating novel information on clinical phenotypes, neuronal autoantibodies (Nabs), and tumors. The impact of the oncologic use of immune checkpoint inhibitors (ICI) on PNS occurrence is also addressed. RECENT FINDINGS: Clinical phenotypes and Nabs are redefined as "high/intermediate/low" risk, following the frequency of cancer association. Nabs, the diagnostic hallmark of PNS, can target intracellular or surface neuronal proteins, with important prognostic and pathogenic implications. Many novel assays have been incorporated into laboratory diagnostics, that is becoming increasingly complex. ICI fight tumors, but favor autoimmunity, thus increasing the incidence of PNS-like disorders. Overcoming the old PNS criteria, the new ones are centered around the presence of tumor. Clinical presentation, Nabs, and tumor findings are translated in diagnostic scores, providing a useful tool for PNS diagnosis and management.

Systematic review and meta-analysis of cognitive impairment in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is commonly associated with cognitive complaints. To bring out the neuropsychological symptomatology inherent to ME/CFS, we conducted a systematic review according to PRISMA and MOOSE guidelines of the literature through the analysis of 764 studies published between 1988 and 2019 by using PubMed Central website and Clarivate analytics platform. We performed a meta-analysis to delineate an idea of the neuropsychological profile inherent in ME/CFS. The clinical picture typically affects visuo-spatial immediate memory (g = - 0.55, p = 0.007), reading speed (g = - 0.82, p = 0.0001) and graphics gesture (g = - 0.59, p = 0.0001). Analysis also revealed difficulties in several processes inherent in episodic verbal memory (storage, retrieval, recognition) and visual memory (recovery) and a low efficiency in attentional abilities. Executive functions seemed to be little or not affected and instrumental functions appeared constantly preserved. With regard to the complexity and heterogeneity of the cognitive phenotype, it turns out that determining a sound clinical picture of ME/CFS cognitive profile must go through a neuropsychological examination allowing a complete evaluation integrating the notion of agreement between the choice and the number of tests and the complexity intrinsic to the pathology.

Camillo Negro (1861-1927) and the "bulbo-palpebral hyperkinetic phenomenon" in peripheral facial palsy.

Camillo Negro (1861-1927) was a leading Italian neurologist and neuropathologist between the nineteenth and twentieth centuries. He is best known for describing the cogwheel sign in Parkinson disease. In an article published in 1906, Camillo Negro described the "bulbo-palpebral hyperkinetic phenomenon": in peripheral facial paralysis, if the patient is asked to look up, the eyeball deviates outwards and elevates farther on the affected side. Negro thoroughly investigated the neuroanatomic and neurophysiological basis of this phenomenon that gained a certain popularity and was reported in several articles and textbooks. This sign retains some utility in peripheral facial palsy to identify a doubtful or very slight impairment of the upper face muscles, which may otherwise go unnoticed. The interest towards the semiology of peripheral facial palsy was shared by Negro's assistant Giuseppe Roasenda (1879-1959), who in 1933 described the incomplete convergence of the eyeballs in this condition.

Jean-Martin Charcot (1825-1893) and the "Alice in Wonderland syndrome".

The "Alice in Wonderland syndrome" (AIWS) is a neurological disorder characterized by altered body schema perception, visual, or somesthetic symptoms, which is frequently associated with migraine. In this article, we present the earliest known description of symptoms attributable to AIWS in the medical literature. During a lecture held on November 22, 1887, at the Salpêtrière, Jean-Martin Charcot (1825-1893) examined a patient with somesthetic symptoms (partial macrosomatognosia) in the context of migraine with aura. Although this condition was not known at the time, Charcot tried to provide an accurate semiological and nosographic framework of this case, attributing the complex of symptoms to migraine with aura and epilepsy with sensory symptoms. With intellectual honesty and clinical prudence, Charcot correctly pointed to a disturbance in the excitability of cortical areas responsible for processing and perceiving sensory stimuli.

Adolph Seeligmüller (1837-1912) and the first graphic illustration of the "toe phenomenon" (later called "Babinski sign") in the medical literature.

The "toe phenomenon" refers to the extension (dorsiflexion) of the great toe, which occurs instead of the normal flexion following stimulation of the foot sole. Its clinical significance was not fully appreciated until Joseph Jules François Félix Babinski (1857-1932) described it in 1896. In 1881, Ernst Strümpell (1853-1925) had described a continuous (tonic) extension of the big toe, a finding that years later the French neurologist Jean-Athanase Sicard (1872-1929) recognized as an equivalent of the "toe phenomenon", also indicating pyramidal tract dysfunction. Previously, this phenomenon had been mentioned in patients only passingly and without providing a picture of it. In 1887, the German neurologist Adolph Seeligmüller (1837-1912) mentioned the tonic extension of the big toe among the characteristic clinical features of spastic infantile hemiplegia-a condition first described by the Austrian physician Moritz Benedikt (1835-1920) in 1868. Seeligmüller incorrectly attributed the tonic extension of the big toe to spastic contracture of the extensor hallucis longus muscle. However, he put great emphasis on this sign and considered it worth being illustrated. Adolph Seeligmüller therefore provided the very first graphic illustration of the (tonic) "toe phenomenon" in the medical literature. Of note, the first photographic illustration of this sign made by Babinski appeared only in 1900, when it had already been adopted by neurologists all over the world.

Camillo Negro (1861-1927) and his method for eliciting the extensor toe sign.

The "toe phenomenon", or extensor toe sign, is characterized by the extension (dorsiflexion) of the great toe elicited by plantar stimulation, and indicates pyramidal tract dysfunction. This phenomenon was first extensively described and studied by Joseph Jules François Félix Babinski (1857-1932), who introduced it in clinical practice. In 1912, the famous Italian neurologist Camillo Negro (1861-1927) proposed a new method of eliciting the extensor toe sign by inviting the patient, lying in bed in dorsal decubitus position, to raise the paretic limb with the leg extended on the thigh. This sign appeared during voluntary effort and could not be elicited by raising the unaffected lower limb. Negro was also the first to investigate the influence of cold upon the appearance of the "toe phenomenon" and to propose the use of (faradic) electrical stimulation to evoke it.

A multimodal imaging approach to foreign accent syndrome. A case report.

This article describes a case of Foreign accent syndrome (FAS) in an Italian woman who developed a Canadian-like foreign accent without brain damage (functional FAS). The patient underwent an in-depth neuroimaging and (neuro)psychological evaluation. Language networks in the frontotemporal-parietal areas were typically activated bilaterally through fMRI and MEG assessments based on task-based data. Resting-state fMRI showed preserved connectivity between language areas. An obsessive-compulsive personality profile and mild anxiety were found, suggesting psychological and psychiatric factors may be relevant. Accordingly with our findings, multimodal imaging is beneficial to understand FAS neurological and functional etiologies.