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.

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.

Achille Sclavo (1861-1930) and His Innovative Contributions to Italian Preventive Medicine and Healthcare Policy.

Achille Sclavo was a scientist with a multifaceted personality; throughout his life, he steadfastly maintained his commitment to research and teaching, while also gaining precious experience as an educator, politician and entrepreneur. He carried forward these various activities with the aim of bringing relief to a country smitten by epidemic diseases, of spreading the gospel of hygiene, and of creating and training medical and healthcare personnel that would be able to tackle the difficult problem of public health in Italy at the beginning of the twentieth century. In this regard, Achille Sclavo can undoubtedly be considered a precursor of modern public health and preventive medicine.

Soft Skills Are Hard Skills-A Historical Perspective.

The increasingly swift changes in the field of medicine require a reassessment of the skills necessary for the training of technically qualified doctors. Today's physicians also need to be capable of managing the complex issue of personal relationships with patients. Recent pedagogical debates have focused on so-called "soft skills", whose acquisition is presented in literature as a quite recent addition to medical studies. Moreover, the historical investigation of deontological texts dating from the mid-nineteenth century back to the Hippocratic Oath shows that medicine has always discussed the need to integrate technical expertise in medicine with specific personal and relationship-based skills. Debates have often circled around whether these "soft skills" could actually be taught or how they could be successfully transmitted to training physicians. The belief that defining medicine is more complex than defining other similar sciences and that the instruments to be used in the relationship with patients cannot be limited to those provided by technical aspects shows a new awareness. Today, this view is often stated as an innovative realization on the part of doctors with regard to the complexity of training and action in a delicate area in which they are entrusted with the management of the balance of the system that is the human body.

The Greek hero Achilles and his mysterious death: transdisciplinary analysis of the gouty hypothesis.

Achilles is a character of Greek mythology whose deeds are mainly told in the Iliad by Homer. Achilles distinguishes himself on the battlefield of Troy with his dexterity and strength, appearing invincible, yet he dies wounded by an arrow in his heel. How could an arrow shot to the heel kill anybody, no matter whether vulnerable or invulnerable? Many researchers have tried to give a medical explanation to this mythological conundrum starting from a literary interpretation of the Homeric text: poisoning, infection, allergy, haemophilia or thyroid storm. In a way, the oldest medical interpretation was suggested by Lucian of Samosata (ca. 120 to after 180 AD). In his parodic tragedy "Gout", he claimed that the warrior actually died of gout. In this article we consider the gouty hypothesis and analyse the clinical aspects that support it.

"You Are Older, although You Do Not Know That": Time, Consciousness, and Memory in "A Kind of Alaska" by Harold Pinter (1930-2008).

"A Kind of Alaska" is a one-act play by the British playwright and Nobel Prize winner Harold Pinter (1930-2008), based on the book Awakenings by the neurologist Oliver Sacks (1933-2015). This play, first performed in 1982, is centered around the character of Deborah, a middle-aged woman, struck by encephalitis lethargica ("sleeping sickness") at the age of 16, who wakes up after 29 years of apparent sleep following the injection of an unnamed drug. This article analyzes how Pinter's drama investigated the mysterious and fascinating relationship between time, memory, and consciousness. The term "awakenings," chosen by Sacks himself, clearly refers to the restoration of voluntary motor function in patients with postencephalitic parkinsonism who responded to levodopa. However, it also suggests that these patients had an impairment of awareness. Actually, beyond the acute phase, subjects with postencephalitic parkinsonism were not sleeping but severely akinetic and therefore probably aware of the passage of time. Oliver Sacks probably did not entirely recognize the intrinsic contradiction between prolonged sleep (with consequent impairment of awareness and subjective "time gap") of the acute lethargic phase and the severe akinesia with preserved awareness of the time-passing characteristic of postencephalitic parkinsonism. This confusion was further compounded by Harold Pinter in his play.

Googling for Neurological Disorders: From Seeking Health-Related Information to Patient Empowerment, Advocacy, and Open, Public Self-Disclosure in the Neurology 2.0 Era.

Since its introduction, the internet has played a major role in reshaping patient-physician communication and interactions, having fostered a shift from a paternalistic to a patient-centered model. Because of its dynamic nature, the internet has been used as a platform to not only disseminate knowledge-favored by improved access to an increasing wealth of available resources-but also to spread advocacy and awareness, contribute to fund-raising, and facilitate open, public self-disclosure of one's own disease, thus eliminating any taboo and reducing the stigma associated with it. The era of Medicine 2.0 is characterized by openness, collaboration, participation, and social networking. The current situation is completely different from the time when Lorenzo Odone's parents, after his diagnosis of adrenoleukodystrophy, decided to attend medical school in order to collect information about a devastating, unknown disease and had to contend with medical authorities at that establishment to convince them of the alleged effectiveness and safety of their discovered therapeutics. Orphan and rare neurological diseases have currently received recognition on web-based resources. However, while the intention is not to ridicule Odone's family legacy and the "complicated lessons" they have reported, some issues should be carefully addressed by health authorities, such as the reputability, reliability, and accuracy of material available on the internet and prevention of the dissemination of material that could instill illusions and unjustified hopes in individuals seeking medical treatment. Neurologists should be aware of such digital resources, participate in web-based activities, and recommend select high-quality websites to their patients.

The 'Health Transformation Plan' in Iran: A policy to achieve universal health coverage in slums and informal settlement areas.

Universal health coverage (UHC) is one of the strategies that health decision- and policy-makers worldwide are implementing to guarantee a good health status to everyone. Living in slums is characterized by several issues, including homelessness and malnutrition, environmental challenges, lack of sanitation and access to safe, healthy drinking water, waste disposal problems, widespread social disruptions, job insecurity, feelings of dissatisfaction and inadequacy. In Iran, the 'Health Transformation Plan' (HTP), despite its weaknesses, has had good effects on the health level of people living in slums, ensuring insurance coverage and reducing many economic, social and cultural problems, with a dramatic decline in out-of-pocket expenditures. Good governmental financial support and an adequate revision of the initial packages of health services and provisions have resulted in a higher access rate to healthcare. The HTP has been, indeed, a major step towards reaching UHC in Iran. If policy- and decision-makers can further improve the present situation and provide more and better-quality services to these people, it can be expected that health indicators in suburbs will be significantly improved. Researchers should monitor the impact of HTP and examine its effects on health indicators, specifically among particularly vulnerable groups such as children, women and the elderly.

"Spreading the word of the master": the contribution of Italian physicians in the early dissemination of Jean-Martin Charcot's theories.

Jean-Martin Charcot (1825-1893) laid the foundations of modern neurology. The lectures he gave at La Salpêtrière Hospital in Paris attracted a large number of visitors from all over the world. Some of them transcribed these clinical lessons, translating and publishing them when returning home. This article discusses the contribution of some Italian physicians (Gaetano Rummo, 1853-1917; Domenico Miliotti; Giulio Melotti, 1857-19?; and Augusto Tebaldi, 1833-1895), who were pioneers in disseminating the ideas and discoveries of Charcot. The early Italian translations were based on personal handwritten notes and memories, not relying on official French versions personally revised or edited by Charcot himself. As such, their veracity cannot always be verified, particularly in the lack of other independent works reporting details on the same lectures. However, the Italian transcriptions providing information which cannot be found elsewhere in Charcot's corpus of works represent an invaluable and a unique source for fully understanding some theories by the French neurologist. Furthermore, they are the first documents providing original materials related to Charcot's teaching translated in a foreign language. The first Italian publications that included photographs of patients were deeply influenced by and clearly modeled on the famous volumes of the Iconographie photographique de la Salpêtrière and further contributed to the early dissemination of Charcot's theories.

Fedor Krause (1857-1937): the father of neurosurgery.

Fedor Krause's inspiring biography shows the value of translational thinking: one of the fathers of modern neurosurgery, this gifted child was recognized for his musical talent; he was able to study medicine thanks to financial support in recognition for his study performances. He wrote his doctor thesis on pneumology, and contributed to general surgery, neuroanaesthesiology, and neurosurgery application of novel technologies in neurosurgery and ethics. More in detail, in the neurosurgical field, he performed the first lumbar discectomy, set up intraoperative nerve monitoring, and pioneered trigeminal and acusticus nerve surgery, epilepsy surgery, and cortical mapping. His passion and engagement for surgery allowed him to make small centers turn into great centers recognized as renowned academic environments.

A brief history of typical absence seizures - Petit mal revisited.

In this article, we have traced back the history of typical absence seizures, from their initial clinical description to the more recent nosological position. The first description of absence seizures was made by Poupart in 1705 and Tissot in 1770. In 1824, Calmeil introduced the term "absences", and in 1838, Esquirol for the first time used the term petit mal. Reynolds instead used the term "epilepsia mitior" (milder epilepsy) and provided a comprehensive description of absence seizures (1861). In 1854, Delasiauve ranked absences as the seizure type with lower severity and introduced the concept of idiopathic epilepsy. Otto Binswanger (1899) discussed the role of cortex in the pathophysiology of "abortive seizures", whereas William Gowers (1901) emphasized the importance of a detailed clinical history to identify nonmotor seizures or very mild motor phenomena which otherwise may go unnoticed or considered not epileptic. At the beginning of the 20th Century, the term pyknolepsy was introduced, but initially was not universally considered as a type of epilepsy; it was definitely recognized as an epileptic entity only in 1945, based on electroencephalogram (EEG) recordings. Hans Berger, the inventor of the EEG, made also the first EEG recording of an atypical absence (his results were published only in 1933), whereas the characteristic EEG pattern was reported by neurophysiologists of the Harvard Medical School in 1935. The discovery of EEG made it also possible to differentiate absence seizures from so called "psychomotor" seizures occurring in temporal lobe epilepsy. Penfield and Jasper (1938) considered absences as expression of "centrencephalic epilepsy". Typical absences seizures are now classified by the International League Against Epilepsy among generalized nonmotor (absence) seizures.

Epilepsy in Hildegard of Bingen's writings: A comprehensive overview.

Hildegard of Bingen (1098-1179AD) is one of the most relevant figures of the Middle Ages. She wrote two medical books, Physica (Natural history) and Causae et curae (Causes and remedies). Our aim was to provide a comprehensive account of Hildegard of Bingen's conception of epilepsy, of the remedies proposed to treat it, and of the medical and physiological theories behind their use. We searched Hildegard of Bingen's entire body of writings to identify any possible reference to epilepsy or epileptic seizures. We reported the identified passages referring to epilepsy and discussed their content in light of medieval medical and physiological theories. Most references to epilepsy were found in Physica and Causae et curae. The suggested remedies against epilepsy range from herbal preparations to animal remedies and jewel therapy. Hildegard's conception of epilepsy gives the impression of an original revisitation of the traditional theory of humors, and carries strong moral connotations. Hildegard of Bingen's conception of epilepsy appears strongly rooted in medieval thinking and less in physiological theories. However, it differs in many respects to the traditional medieval beliefs and is a further proof of her unique personality. As living testimony of the past, Hildegard's writings enable us to shed a fascinating light on the beliefs concerning epilepsy in the middle ages.

Health-related quality of life among healthy elderly Iranians: a systematic review and meta-analysis of the literature.

BACKGROUND: Health-related quality of life (HRQoL) measurement in elderly people can provide appropriate information for an optimal management of physical/mental conditions. The main objective of the present study was to quantitatively assess the HRQoL among healthy elder Iranian individuals as measured by the Short-Form 36 (SF-36) questionnaire, both overall and at the level of each its single component/domain. METHODS: This study was designed as a systematic review and meta-analysis, following the "Preferred Reporting Results of Systematic Reviews and Meta-Analyses" (PRISMA) guidelines. Embase, PubMed/MEDLINE, ISI/Web of Science (WOS), Scopus, and Iranian databases such as MagIran, SID and Irandoc were mined from inception up to 1st September 2017. Also the grey literature (via Google Scholar) was mined. Two reviewers independently screened titles/abstracts, assessed full-text articles, extracted data, and appraised their quality using the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) checklist. RESULTS: Twenty five studies were included. Mean overall HRQoL was 54.92 [95%CI 51.50-58.33], lower than the value found by studies done in other countries, especially in those economically developed. The sensitivity analysis indicated stability and reliability of results. Pooled scores of each HRQoL domain/sub-scale of the SF-36 questionnaire ranged from 49.77 (physical role functioning) to 63.02 (social role functioning). CONCLUSIONS: HRQoL among healthy elder Iranian individuals is generally low. Health policy-makers should put HRQoL among the elderly as a priority of their agenda, implementing ad hoc programs and providing social, economic and psychological support, as well as increasing the participation of old people in the community life and use their experiences.

'Infantile convulsions' in the early nineteenth century. Abnormal brain blood flow and leeches, teething and gums' scarification and food and purgatives: the historical contribution of John Clarke (1760-1815).

In this article, we discuss on the role of the British physician and midwifery practitioner John Clarke (1760-1815) in the characterisation of the various types of seizures and epilepsy and related phenomena ('convulsions') occurring in children. In his unfinished work Commentaries on Some of the Most Important Diseases of Children (1815), Clarke discussed the pathophysiology of convulsions and was the first to describe, 12 years before the French neurologist Louis Francois Bravais (1801-1843) and more than 30 years before the Irish-born physician Robert Bentley Todd (1809-1860), the postictal paresis. He believed that convulsions originated from changes in pressure within the ventricles as a consequence of abnormal blood flow to the cerebral vessels. In keeping with the theories of his time (e.g. Baumes 1789, 1805; Brachet 1824), Clarke believed that teething was a major cause of 'infantile convulsions'. His proposed remedies ranged from scarification of the gums to ammonia, application of leeches, cold water, and purgatives. The use of antispasmodics, quite popular at the time, was instead questioned. In his Practical Observations on the Convulsions of Infants (1826), the London practitioner and midwifery John North (1790-1873) deeply criticised Clarke's view that convulsions arise inevitably as a consequence of organic brain lesions. North inferred that the results of autopsies of children who had died of convulsions revealed no brain damages, and claimed that cerebral irritation could also occur as the effect of distant lesions. Other Clarke's contemporaries (e.g. Jean Baptiste Timothée Baumes-1756-1828) inferred that all convulsions reflected a hereditary diathesis, which rendered children (especially those with softer and limper nervous and muscular tissues!) extremely sensitive to all sorts of provocation that could trigger convulsions, including bad digestion (more pronounced at the time of teething), loud noise, and bright light. Although almost every aspect of Clarke's view on convulsions was subsequently proved wrong, his (and his contemporaries') work provides fascinating insights into the theories and therapies of seizures, which were popular at the dawn of modern neurology.

The Fight Against Tuberculosis in the Mid-nineteenth Century: The Pivotal Contribution of Edoardo Maragliano (1849-1940).

The second half of the nineteenth century saw the development of new medical "specialties", which, like the idea of constitutional disease, had a profound influence on medical practice. Against this lively "backdrop", Edoardo Maragliano played a central role in medicine's "renaissance" in Italy. Having graduated in medicine in 1870 at the University of Naples, he worked as an assistant in the University Medical Clinic. After beginning his academic career as professor of pathology at the Faculty of Medicine in Genoa in 1877, he became full professor of internal medicine in 1881. While he studied all fields of internal medicine, his research focused mainly on tuberculosis.His experiments in the medical clinic enabled Maragliano to announce the possibility of immunization against Mycobacterium tuberculosis. Although criticized for using an inactivated vaccine, Maragliano continued to advocate vaccination with any type of vaccine.In the Senate of the Kingdom of Italy, Maragliano actively debated social, economic and sanitary questions, without neglecting his duties as a physician and professor. As an officer during the First World War, he organized military health services and taught medicine at the Military University of Padua.In 1924, Maragliano created the first Italian specialty school in the study of tuberculosis, which provided physicians with specific training in the diagnosis, therapy and prevention of the disease. His scientific zeal and his vision of modern medicine prompted the introduction of new specializations, such as radiology and, especially, pneumology, which led to the creation of one of Europe's most renowned medical schools.

Iran's Health System Transformation Plan: A SWOT analysis.

Background: Societies are characterized by evolving health needs, which become more challenging throughout time, to which health system should respond. As such, a constant monitoring and a periodic review and reformation of healthcare systems are of fundamental importance to increase the efficiency and effectiveness of healthcare services delivery, equity, and sustainable funding. The establishment of President Rouhani's government in Iran, on May 5, 2014, the settlement of the new Ministry of Health and Medical Education administration (MoHME) and the need for change in the provision of healthcare services has led to the "Health System Transformation Plan" (HSTP). The aim of the current investigation was to critically evaluate the health transformation plan in Iran. Methods: Strengths, Weaknesses, Opportunities and Threats (SWOT) analysis enables to identify and assess the strengths and weaknesses within an organization or program, as well as the threats and opportunities outside the given organization or program. To identify SWOT of the HSTP in Iran, all articles concerning this program published in scholarly databases as well as in the gray literature were systematically searched. Subsequently, all factors identified at the first round were thematically classified into four categories and for reaching consensus on this classification, the list of points and factors was sent to 40 experts - policy- and decisionmakers, professors and academicians, health department workers, health activists, journalists. Results: Thirty-four subjects expressed comments on classification. Incorporating their suggestions, the SWOT analysis of Iran's HSTP was revised, finalized and then performed. Conclusion: HSTP in Iran, like many of the initiatives that have been recently introduced and not fully implemented, have various challenges, difficulties and pitfalls that health policymakers need to pay attention to. Interacting with criticisms, taking into account public opinion and strengthening the plan can make the project more effective, and it can be anticipated that in the future, better conditions in the health sector will be achieved.

Low birth weight in Iran: Implications from a systematic review of the literature and meta-analysis in the period 1999-2017.

Background: Low birth weight (LBW), a crucial determinant of neonatal complications, represents a major public health concern worldwide. Epidemiological research is of crucial importance for designing and implementing ad hoc interventions for this issue, helping and guiding decision- and policy-makers in each country to prevent the increased prevalence of LBW in infants through estimating the prevalence rate, identifying and controlling major risk factors. The present investigation aimed to systematically assess LBW prevalence rate in Iran and its determinants. Methods: PubMed/Medline via Ovid, Embase, Web of Science and Scopus as well as Magiran, SID and Irandoc were searched from inception until November 2016. Also, the grey literature (via Google Scholar) was mined. The DerSimonian-Laird model was exploited. The I2 and Q-test tests were used to investigate heterogeneity between the studies. Sensitivity and subgroup analyses were performed to ensure the robustness and validity of our findings. Different cumulative meta-analyses were conducted stratifying according to the year of publication and sample size. Any potential bias in publication was assessed carrying out the Egger's test. Results: LBW prevalence rate was estimated to be 8% (95%CI: 7-9) in Iran. Sensitivity analysis confirmed the stability of finding. Studies were cumulated by the year of publication, and the results did not change pre- and post-cumulative meta-analysis. No publication bias could be observed. Conclusion: LBW prevalence rate in Iran is well comparable with the prevalence figures of both developed and developing countries. This could be due to the health reforms implemented in Iran throughout the years.

The Public Health Impact of the So-Called "Fluad Effect" on the 2014/2015 Influenza Vaccination Campaign in Italy: Ethical Implications for Health-Care Workers and Health Communication Practitioners.

Seasonal influenza, causing complications, hospitalizations and deaths, generates a serious socio-economic burden, especially among elderly and high-risk subjects, as well as among adult individuals. Despite the availability and active free-of charge offer of influenza vaccines, vaccine coverage rates remain low and far from the target established by the Ministry of Health. Notwithstanding their effectiveness, vaccines are victims of prejudices and false myths, that contribute to the increasing phenomenon of vaccine hesitancy and loss of confidence. Media and, in particular, new media and information and communication technologies (ICTs) play a major role in disseminating health-related information. They are extremely promising devices for delivering health education and promoting disease prevention, including immunization. However, they can also have a negative impact on population's health attitudes and behaviors when channeling wrong, misleading information. During the 2014/2015 influenza vaccination campaign, the report of four deaths allegedly caused by administration of an adjuvanted influenza vaccine, Fluad - the so-called "Fluad case" - received an important media coverage, which contributed to the failure of the vaccination campaign, dramatically reducing the influenza vaccine uptake. In the extant literature, there is a dearth of information concerning the effect of the "Fluad case". The current study aims at quantifying the impact of the "Fluad effect" at the level of the Local Health Unit 3 (LHU3) ASL3 Genovese, Genoa, Italy. Ethical implications for health-care workers and health communication practitioners are also envisaged.