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Currarino syndrome is a rare congenital disorder characterized by the triad of anorectal anomalies, sacrococcygeal dysgenesis and presacral mass. Because of the anorectal anomalies, the extrinsic compression due to the presacral mass and neurologic deficits, patients usually present with gastrointestinal symptoms, most commonly chronic constipation. Most cases of Currarino syndromes are diagnosed in childhood, at birth or in the pre-birth period and, even if adult presentation has been reported in few sporadic case reports, the diagnosis in the late stages of life remains extremely rare. In this paper, we describe the imaging findings of an elderly man with a past medical history of megacolon surgically treated in his childhood, who was diagnosed with Currarino syndrome at the age of 72.

Since the end of 2019, the whole world has been seized by the COVID-19 pandemic caused by the SARS-CoV2 virus. To date, the infection has led to more than 4 million deaths worldwide, and to more than 140 thousand deaths in Russia. COVID-19 (abbreviation for COronaVIrus Disease 2019) is a potentially severe acute respiratory infection caused by the SARS-CoV-2 coronavirus (2019-nCoV). Vaccination against COVID-19 plays a key role in stopping the pandemic. According to existing experience in infections prevention, mass vaccination will reduce the virus’s expansion and the risk of vaccine-resistant strains’ development. In the context of the COVID-19 the question of the feasibility and safety of vaccination of patients with Primary Immunodeficiency and Hereditary Angioedema arises. The Russian Association of Allergists and Clinical Immunologists and the National Association of Experts in Primary Immunodeficiencies have developed and approved a position paper on vaccination of patients with Primary Immunodeficiency and Hereditary Angioedema against COVID-19. This position paper provides answers to key questions regarding the vaccination of patients with these diseases.

Fibrous Solitary Tumors are infrequent neoplasms originating from mesenchymal tissues, most commonly arising from the visceral pleura and frequently exhibiting a benign behavior. Extra-pleural localization is unusual and the site of origin of these tumors from the parenchyma of the parotid gland is considered extremely rare. We report the case of a 66-years old woman with non-painful slow-growing left latero-cervical mass, who underwent a gadolinium-enhanced Magnetic Resonance Imaging showing a mass originating from the deep lobe of the parotid gland extending into the retro-pharyngeal space. After a total parotidectomy with tumor excision, a diagnosis of histologically proven fibrous solitary tumor of the parotid gland was made. Two years later, CT scan showed post-operative recurrence and further satellite localization in the neck, distant from the initial mass. We performed a literature review of the published similar cases, in order to clinicopathological and imaging features of this rare entity.

Spinocerebellar ataxias (SCAs) represent a large group of hereditary degenerative diseases of the nervous system, in particular the cerebellum, and other systems that manifest with a variety of progressive motor, cognitive, and behavioral deficits with the leading symptom of cerebellar ataxia. SCAs often lead to severe impairments of the patient's functioning, quality of life, and life expectancy. For SCAs, there are no proven effective pharmacotherapies that improve the symptoms or substantially delay disease progress, i.e., disease-modifying therapies. To study SCA pathogenesis and potential therapies, animal models have been widely used and are an essential part of pre-clinical research. They mainly include mice, but also other vertebrates and invertebrates. Each animal model has its strengths and weaknesses arising from model animal species, type of genetic manipulation, and similarity to human diseases. The types of murine and non-murine models of SCAs, their contribution to the investigation of SCA pathogenesis, pathological phenotype, and therapeutic approaches including their advantages and disadvantages are reviewed in this paper. There is a consensus among the panel of experts that (1) animal models represent valuable tools to improve our understanding of SCAs and discover and assess novel therapies for this group of neurological disorders characterized by diverse mechanisms and differential degenerative progressions, (2) thorough phenotypic assessment of individual animal models is required for studies addressing therapeutic approaches, (3) comparative studies are needed to bring pre-clinical research closer to clinical trials, and (4) mouse models complement cellular and invertebrate models which remain limited in terms of clinical translation for complex neurological disorders such as SCAs.

Hereditary angioedema is a rare, potentially life-threatening genetic disease that manifests with skin and mucous/submucosal swelling that occurs under the influence of bradykinin. The clinical guidelines for hereditary angioedema (code for the International Statistical Classification of Diseases and Related Health Problems D84.1) were developed in December 2020 by the Russian Association of Allergology and Clinical Immunology, Association of Medical Geneticists, National Association of Experts in the Field of Primary Immunodeficiencies, Union of Pediatricians of Russia. In December 2020, the project was approved at a meeting of the Scientific and Practical Council of the Ministry of Health of the Russian Federation (December 10, 2020 No. 743/12). The clinical guidelines are devoted to optimizing the clinical care of patients with hereditary angioedema. The topic is relevant owing to the under-diagnosis of hereditary angioedema and insufficient awareness of doctors of various specialties about this problem, as well as the difficulties in managing this category of patients. The clinical guidelines contain information about the epidemiology, etiology, classification, pathogenesis, and common clinical manifestations of hereditary angioedema. Thus, the paper described actual diagnostic approaches and differential diagnosis of hereditary angioedema and established its diagnostic criteria. Medical care algorithms to patients with hereditary angioedema at the prehospital and hospital stages are also described. The principles of pharmacotherapy, including long-term prophylaxis, short-term prophylaxis, and acute therapy, for hereditary angioedema are also presented. Treatment regimens are stratified according to patients age and gender. Non-drug measures for the prevention hereditary angioedema attacks are considered. Sections were also added in the edition of the new clinical guidelines of hereditary angioedema. Clinical guidelines for hereditary angioedema are intended for practicing doctors of all specialties, students and teachers of medical universities, residents, graduate students of medical universities.

BACKGROUND: In 2018, a new form of hereditary angioedema without C1-inhibitor deficiency hereditary angioedema with a mutation in the plasminogen gene was identified. The world scientific literature describes a small number of patients with this form of the disease and, therefore, new research is relevant. AIMS: To identify the sociodemographic and clinical features of patients with hereditary angioedema with plasminogen gene mutation; to evaluate the treatment efficacy; to conduct a comparative analysis in a group of patients with hereditary angioedema type I/II. MATERIAL AND METHODS: 14 patients (1 male and 13 females, mean age 51.6413.55 years) with hereditary angioedema with c.988AG mutation in the plasminogen gene (p.Lys330Glu; K330E) were enrolled in a retrospective study. The comparison group included 194 patients with hereditary angioedema type I/II (56 males and 138 females, mean age 37.0316.23 years). RESULTS: The average age at disease onset in patients with hereditary angioedema with a mutation in the plasminogen gene is 25.0710.46 years, which is significantly higher than in patients with hereditary angioedema type I/II 11.588.92 years (p 0.001). Peripheral angioedema was reported in 21.4% of patients with hereditary angioedema with a mutation in the plasminogen gene, abdominal attacks in 28.6%, which is less common than in patients with hereditary angioedema type I/II (peripheral edema 97.4%, p 0.001; abdominal attacks 86.6%, p 0.001). Face and neck angioedema was observed in all patients with hereditary angioedema with a mutation in the plasminogen gene (100%) and in 72.2% of patients in the group of hereditary angioedema type I/II (p=0.023). 85.7% of patients with hereditary angioedema with a mutation in the plasminogen gene had edema of the tongue. A decrease in the severity and duration of 28 out of 29 attacks by an average of 71.4% was reported by 4/5 of patients who used icatibant (Firazyr); 3/4 of patients reported a decrease in the frequency of attacks during treatment with tranexamic acid. CONCLUSIONS: The diseases manifestation in adulthood, the predominance of face and tongue angioedema are common features of hereditary angioedema with a mutation in the plasminogen gene. The efficacy of tranexamic acid and icatibant was demonstrated in the observed cohort of patients.

Angioedema is caused by a local increase in vascular permeability induced by bradykinin or mast cell mediators. The main challenge of the differential diagnosis of angioedema lies in the fact that different pathophysiological processes may lead to a very similar clinical picture. Moreover, verification of the type of angioedema is crucial for selection of appropriate therapy. In 2020, a school for doctors Chronic urticaria: scientific and medical accomplishments and practical aspects of patient management was held on the basis of the National Research Center Institute of Immunology of the FMBA of Russia as part of the work of the reference center that provides expert assistance to patients with urticaria (GALEN UCARE). A clinical case series of related patients with hereditary angioedema due to a mutation in the PLG gene was presented to demonstrate the challenges of the differential diagnosis between types of angioedema. This article focused on the description of this series.

Traumatic peripheral nerve injury (TPNI) represents a major medical problem that results in loss of motor and sensory function, and in severe cases, limb paralysis and amputation. To date, there are no effective treatments beyond surgery in selective cases. In repurposing studies, we found that daily systemic administration of the FDA-approved drug 4-aminopyridine (4-AP) enhanced functional recovery after acute peripheral nerve injury. This study was aimed at constructing a novel local delivery system of 4-AP using thermogelling polymers. We optimized a thermosensitive (4-AP)–poly(lactide-co-glycolide)–b-poly(ethylene glycol)–b-poly(lactide-co-glycolide) (PLGA–PEG–PLGA) block copolymer formulation. (4-AP)–PLGA–PEG exhibited controlled release of 4-AP both in vitro and in vivo for approximately 3 weeks, with clinically relevant safe serum levels in animals. Rheological investigation showed that (4-AP)–PLGA–PEG underwent a solution to gel transition at 32 °C, a physiologically relevant temperature, allowing us to administer it to an injured limb while subsequently forming an in situ gel. A single local administration of (4-AP)–PLGA–PEG remarkably enhanced motor and sensory functional recovery on post-sciatic nerve crush injury days 1, 3, 7, 14, and 21. Moreover, immunohistochemical studies of injured nerves treated with (4-AP)-PLGA-PEG demonstrated an increased expression of neurofilament heavy chain (NF-H) and myelin protein zero (MPZ) proteins, two major markers of nerve regeneration. These findings demonstrate that (4-AP)–PLGA–PEG may be a promising long-acting local therapeutic agent in TPNI, for which no pharmacologic treatment exists.

Stroke of the cerebellum represents about 10% of strokes of the brain. Both infarction and hemorrhage manifest with symptoms related to the location and extent of the lesion(s). Bilateral cerebellar infarcts constitute up to one third of all cerebellar infarctions. The leading cause of cerebellar infarcts is emboli of cardiac origin or from intra-arterial sources. Potential complications include brainstem compression and hydrocephalus. Malignant cerebellar edema is a life-threatening complication of ischemic posterior circulation stroke requiring urgent management. The advent of MRI has revolutionized the early diagnosis in vivo, showing small and large territorial infarcts, hemorrhages, and venous infarcts. Endovascular procedures are growingly applied and are impacting on the prognosis of stroke, although cerebellar stroke from occlusion of small cerebellar arteries is currently not accessible to thrombectomy. Surgical procedures of space-occupying stroke include external ventricular drainage, suboccipital craniotomy, or combined procedures. In 1849, Robert Dunn (1799-1877), an English surgeon, reported the details of a case of apoplexy of the cerebellum in a 52-year-old man, pointing to the importance of post-mortem studies of patients followed meticulously during lifetime. Dunn discussed inflammation surrounding hemorrhage as a source of cerebral degeneration, linking for the first time cerebellar stroke, neuroinflammation, and atherosclerosis.

Background Functional recovery following primary nerve repair of a transected nerve is often poor even with advanced microsurgical techniques. Recently, we developed a novel sciatic nerve transection method where end-to-end apposition of the nerve endings with minimal gap was performed with fibrin glue. We demonstrated that transected nerve repair with gluing results in optimal functional recovery with improved axonal neurofilament distribution profile compared to the end-to-end micro-suture repair. However, the impact of axonal misdirection and misalignment of nerve fascicles remains largely unknown in nerve-injury recovery. We addressed this issue using a novel nerve repair model with gluing. Methods In our complete “Flip and Transection with Glue” model, the nerve was “first” transected to 40% of its width from each side and distal stump was transversely flipped, then 20 µL of fibrin glue was applied around the transection site and the central 20% nerve was completely transected before fibrin glue clotting. Mice were followed for 28 days with weekly assessment of sciatic function. Immunohistochemistry analysis of both sciatic nerves was performed for neurofilament distribution and angiogenesis. Tibialis anterior muscles were analyzed for atrophy and histomorphometry. Results Functional recovery following misaligned repair remained persistently low throughout the postsurgical period. Immunohistochemistry of nerve sections revealed significantly increased aberrant axonal neurofilaments in injured and distal nerve segments compared to proximal segments. Increased aberrant neurofilament profiles in the injured and distal nerve segments were associated with significantly increased nerve blood-vessel density and branching index than in the proximal segment. Injured limbs had significant muscle atrophy, and muscle fiber distribution showed significantly increased numbers of smaller muscle fibers and decreased numbers of larger muscle fibers. Conclusions These findings in a novel nerve transection mouse model with misaligned repair suggest that aberrant neurofilament distributions and axonal misdirections play an important role in functional recovery and muscle atrophy.

Non-invasive cerebellar stimulation (NICS) aims to modulate cerebello-cerebral loops and cerebro-spinal loops, both for research and clinical applications. It is of paramount importance to establish and validate morphological and functional tools to quantify cerebellar reserve, defined as the capacity for restoration and compensation to pathology of the cerebellum. Using NICS without efforts to estimate cerebellar reserve will end up in conflicting results due to the very high heterogeneity of cerebellar disorders encountered in daily practice.

The virtual practice has made major advances in the way that we care for patients in the modern era. The culture of virtual practice, consulting, and telemedicine, which had started several years ago, took an accelerated leap as humankind was challenged by the novel coronavirus pandemic (COVID19). The social distancing measures and lockdowns imposed in many countries left medical care providers with limited options in evaluating ambulatory patients, pushing the rapid transition to assessments via virtual platforms. In this novel arena of medical practice, which may form new norms beyond the current pandemic crisis, we found it critical to define guidelines on the recommended practice in neurotology, including remote methods in examining the vestibular and eye movement function. The proposed remote examination methods aim to reliably diagnose acute and subacute diseases of the inner-ear, brainstem, and the cerebellum. A key aim was to triage patients into those requiring urgent emergency room assessment versus non-urgent but expedited outpatient management. Physicians who had expertise in managing patients with vestibular disorders were invited to participate in the taskforce. The focus was on two topics: (1) an adequate eye movement and vestibular examination strategy using virtual platforms and (2) a decision pathway providing guidance about which patient should seek urgent medical care and which patient should have non-urgent but expedited outpatient management. Electronic supplementary material The online version of this article (10.1007/s12311-020-01178-8) contains supplementary material, which is available to authorized users.

Immunoglobulin replacement therapy is the most important treatment for the majority of Primary immunodeficiency (PID) forms. It is very important not only to prescribe replacement therapy, but also to choose the appropriate one according to individual patients needs at the very moment. Furthermore, in reallife clinical practice some comorbid conditions, which can occur in patient, necessitate the choice of a specific drug from a wide range of IVIG preparations presented on the Russian pharmaceutical market.

Purpose of review Providing an update on the pathophysiology, cause, diagnosis and treatment of cerebellar ataxias. This is a group of sporadic or inherited disorders with heterogeneous clinical presentation and notorious impact on activities of daily life in many cases. Patients may exhibit a pure cerebellar phenotype or various combinations of cerebellar deficits and extracerebellar deficits affecting the central/peripheral nervous system. Relevant animal models have paved the way for rationale therapies of numerous disorders affecting the cerebellum. Recent findings Clinically, the cerebellar syndrome is now divided into a cerebellar motor syndrome, vestibulocerebellar syndrome and cerebellar cognitive affective syndrome with a novel clinical scale. This subdivision on three cornerstones is supported by anatomical findings and neuroimaging. It is now established that the basal ganglia and cerebellum, two major subcortical nodes, are linked by disynaptic pathways ensuring bidirectional communication. Inherited ataxias include autosomal recessive cerebellar ataxias (ARCAs), autosomal dominant spinocerebellar ataxias and episodic ataxias and X-linked ataxias. In addition to the Movement Disorders Society genetic classification of ARCAs, the classification of ARCAs by the Society for Research on the Cerebellum and Ataxias represents major progress for this complex subgroup of cerebellar ataxias. The advent of next-generation sequencing has broadened the spectrum of cerebellar ataxias. Summary Cerebellar ataxias require a multidisciplinary approach for diagnosis and management. The demonstration of anatomical relationships between the cerebellum and basal ganglia impacts on the understanding of the cerebello-basal ganglia-thalamo-cortical system. Novel therapies targeting deleterious pathways, such as therapies acting on RNA, are under development.

Purpose of review Major therapeutic advances have been made in patients with episodic and progressive cerebellar ataxias, downbeat nystagmus and some vestibular disorders. We provide an update review on this subject highlighting important research findings from the last two years. Recent findings Recently, the use of omaveloxolone for 2 years significantly improved upright stability in Friedreich's ataxia patients. In an open-label study, N-acetyl-L-leucine administered for 6-weeks significantly improved clinical impression of change, ataxia, and quality of life in patients with Niemann-Pick disease type C1. A 12-week treatment with dalfampridine was associated with improved standing balance in a subgroup of patients with multiple sclerosis. A gluten-free diet alone improved ataxia in half of patients with antiglutamic acid decarboxylase (GAD) ataxia, suggesting that gluten sensitivity might be part of the underlying pathogenesis in anti-GAD ataxia. In a head-to-head trial, both prolonged-release 4-aminopyridine (4-AP) and acetazolamide effectively reduced the attacks up to 60% in patients with episodic ataxia type 2 (EA2), albeit 4-AP had fewer adverse effects. Small observational studies have shown that patients with episodic vestibular syndrome who cannot be diagnosed as definite or probable vestibular migraine, might still improve vestibular symptoms following preventive treatment for migraine. The use of vitamin D supplementation in benign paroxysmal positional vertigo, steroids in acute unilateral vestibulopathy, and betahistine in Meniere's disease patients remains controversial. Summary Although the use of several therapies is being established in the treatment of cerebellar and vestibular disorders, there is an urgent need for prospective controlled therapeutic trials.

The cerebellum is involved in multiple closed-loops circuitry which connect the cerebellar modules with the motor cortex, prefrontal, temporal, and parietal cortical areas, and contribute to motor control, cognitive processes, emotional processing, and behavior. Among them, the cerebello-thalamo-cortical pathway represents the anatomical substratum of cerebellum-motor cortex inhibition (CBI). However, the cerebellum is also connected with basal ganglia by disynaptic pathways, and cerebellar involvement in disorders commonly associated with basal ganglia dysfunction (e.g., Parkinson’s disease and dystonia) has been suggested. Lately, cerebellar activity has been targeted by non-invasive brain stimulation (NIBS) techniques including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) to indirectly affect and tune dysfunctional circuitry in the brain. Although the results are promising, several questions remain still unsolved. Here, a panel of experts from different specialties (neurophysiology, neurology, neurosurgery, neuropsychology) reviews the current results on cerebellar NIBS with the aim to derive the future steps and directions needed. We discuss the effects of TMS in the field of cerebellar neurophysiology, the potentials of cerebellar tDCS, the role of animal models in cerebellar NIBS applications, and the possible application of cerebellar NIBS in motor learning, stroke recovery, speech and language functions, neuropsychiatric and movement disorders.

Ethanol consumption remains a major concern at a world scale in terms of transient or irreversible neurological consequences, with motor, cognitive, or social consequences. Cerebellum is particularly vulnerable to ethanol, both during development and at the adult stage. In adults, chronic alcoholism elicits, in particular, cerebellar vermis atrophy, the anterior lobe of the cerebellum being highly vulnerable. Alcohol-dependent patients develop gait ataxia and lower limb postural tremor. Prenatal exposure to ethanol causes fetal alcohol spectrum disorder (FASD), characterized by permanent congenital disabilities in both motor and cognitive domains, including deficits in general intelligence, attention, executive function, language, memory, visual perception, and communication/social skills. Children with FASD show volume deficits in the anterior lobules related to sensorimotor functions (Lobules I, II, IV, V, and VI), and lobules related to cognitive functions (Crus II and Lobule VIIB). Various mechanisms underlie ethanol-induced cell death, with oxidative stress and endoplasmic reticulum (ER) stress being the main pro-apoptotic mechanisms in alcohol abuse and FASD. Oxidative and ER stresses are induced by thiamine deficiency, especially in alcohol abuse, and are exacerbated by neuroinflammation, particularly in fetal ethanol exposure. Furthermore, exposure to ethanol during the prenatal period interferes with neurotransmission, neurotrophic factors and retinoic acid-mediated signaling, and reduces the number of microglia, which diminishes expected cerebellar development. We highlight the spectrum of cerebellar damage induced by ethanol, emphasizing physiological-based clinical profiles and biological mechanisms leading to cell death and disorganized development.

Cerebellar reserve refers to the capacity of the cerebellum to compensate for tissue damage or loss of function resulting from many different etiologies. When the inciting event produces acute focal damage (e.g., stroke, trauma), impaired cerebellar function may be compensated for by other cerebellar areas or by extracerebellar structures (i.e., structural cerebellar reserve). In contrast, when pathological changes compromise cerebellar neuronal integrity gradually leading to cell death (e.g., metabolic and immune-mediated cerebellar ataxias, neurodegenerative ataxias), it is possible that the affected area itself can compensate for the slowly evolving cerebellar lesion (i.e., functional cerebellar reserve). Here, we examine cerebellar reserve from the perspective of the three cornerstones of clinical ataxiology: control of ocular movements, coordination of voluntary axial and appendicular movements, and cognitive functions. Current evidence indicates that cerebellar reserve is potentiated by environmental enrichment through the mechanisms of autophagy and synaptogenesis, suggesting that cerebellar reserve is not rigid or fixed, but exhibits plasticity potentiated by experience. These conclusions have therapeutic implications. During the period when cerebellar reserve is preserved, treatments should be directed at stopping disease progression and/or limiting the pathological process. Simultaneously, cerebellar reserve may be potentiated using multiple approaches. Potentiation of cerebellar reserve may lead to compensation and restoration of function in the setting of cerebellar diseases, and also in disorders primarily of the cerebral hemispheres by enhancing cerebellar mechanisms of action. It therefore appears that cerebellar reserve, and the underlying plasticity of cerebellar microcircuitry that enables it, may be of critical neurobiological importance to a wide range of neurological/neuropsychiatric conditions.

Relevance. Replacement therapy with human immunoglobulins is the leading pathogenetic method of treatment of primary immunodeficiency with impaired antibody synthesis. Currently, several preparations of human immunoglobulins for intravenous administration are available in Russia. Purposes. Evaluation of the efficacy and safety of Privigen immunoglobulin intravenous 10% liquid in real clinical practice within 12 clinical months. Methods. Twenty adults diagnosed with common variable immunodeficiency or X-linked agammaglobulinemia received intravenous Privigen® infusions (0.2-0.4 mg/kg) at 24±3 intervals over a 12-month period. The primary endpoint was the annual rate of infections and adverse events. Results. Sufficient level of IgG was achieved in most patients during the study. Severe adverse reactions during the treatment were not registered. Conclusions. High efficacy and safety of monthly replacement therapy in patients with primary immunodeficiency with impaired antibody synthesis has been demonstrated.

There is currently no accepted classification of autosomal recessive cerebellar ataxias, a group of disorders characterized by important genetic heterogeneity and complex phenotypes. The objective of this task force was to build a consensus on the classification of autosomal recessive ataxias in order to develop a general approach to a patient presenting with ataxia, organize disorders according to clinical presentation, and define this field of research by identifying common pathogenic molecular mechanisms in these disorders. The work of this task force was based on a previously published systematic scoping review of the literature that identified autosomal recessive disorders characterized primarily by cerebellar motor dysfunction and cerebellar degeneration. The task force regrouped 12 international ataxia experts who decided on general orientation and specific issues. We identified 59 disorders that are classified as primary autosomal recessive cerebellar ataxias. For each of these disorders, we present geographical and ethnical specificities along with distinctive clinical and imagery features. These primary recessive ataxias were organized in a clinical and a pathophysiological classification, and we present a general clinical approach to the patient presenting with ataxia. We also identified a list of 48 complex multisystem disorders that are associated with ataxia and should be included in the differential diagnosis of autosomal recessive ataxias. This classification is the result of a consensus among a panel of international experts, and it promotes a unified understanding of autosomal recessive cerebellar disorders for clinicians and researchers.

Hypertension is a heart disease and blood vessels that are marked by an increase in blood pressure. One non-pharmacological therapy for hypertension is boarding. Elderly gymnastics is a series of regular and directed and planned tone movements performed individually or groups. The general objective in this study was to study the differences in the effectiveness of elderly gymnastics and healthy heart gymnastics to decrease blood pressure in hypertensive patients at the Nusa Indah Health Center Bengkulu City in 2018. Was the amount of this study using a quasi experimental design of pre and post test. The population in this study were all hypertensive patients in gymnastics members at the Nusa Indah Health Center in Bengkulu City in 2018.Sampling was taken from the entire population. Has research using the Shapiro-Wilk test showed that the value p = 0.247 (a=0.05) meaning that there was no difference in exercise effectiveness. Elderly and healthy cardiac gymnastics against a reduction in systolic blood pressure in patients hypertension at Nusa Indah Health Center Bengkulu City in 2018. The value p = 0.450 (a=0.05) means that there is not difference in the effectiveness of elderly gymnastics and healthy heart gymnastics against a decrease in diastolic blood pressure in hypertensive patients at Nusa Indah Health Center in Bengkulu City in 2018. Expected to hypertensive patients to more regularly take part in gymnastics activities to maintain blood pressure stability. Keywords : Elderly Gymnastics, Healthy Heart Gymnastics, Hypertension

Hereditary angioedema (HAE) due to of C1-inhibitor deficiency is a rare disease, which causes a strong physical and psychological impact on patients’ lives. HAE affects daily life, career opportunities, and social activity. In addition, fear of the edema development, as well as the associated with it pain and risk of death leads to depressive disorders specific for chronic (especially life-threatening) diseases. The emergence of modern pathogenetic drugs can minimize the effect of HAE and improve the patients’ quality of life. There are three different therapeutic strategies that are used for HAE treatment: long-term prophylaxis, short-term and on-demand therapy for acute attacks. This article focuses on long-term prophylaxis.

Introduction Invasive candidiasis (IC) can be a life-threatening infection in immunocompromised patients, particularly those with cancer, hematologic diseases and/or hematopoietic stem cell transplantation (HSCT) recipients. The objective of this study was to evaluate the effectiveness of micafungin in patients with hematologic malignancies or HSCT recipients, relevant to clinical presentation of IC, in real-life practice in Greece. Methods ASPIRE was a phase IV, multicenter, non-interventional, prospective cohort study, conducted at ten tertiary hospitals in Greece, in adults with hematologic disease. Micafungin treatment for IC or prophylaxis for Candida infection was administered per standard clinical practice until a clinical outcome (success or failure) was reached. Treatment success was defined by the EORTC/MSG criteria for invasive fungal infections (IFI) and was assessed by the investigator. Treatment discontinuation and safety were also evaluated. Results One hundred forty-three patients were enrolled. Median age was 62; 85 (59.4%) patients were male, and 133 (93.0%) had Greek ethnicity. One hundred twenty-six (88.1%) patients had hematologic malignancies, and 21 (14.7%) had received HSCT. Prophylaxis was administered to 74 (51.7%) patients [median (range) dose: 50 (50–150) mg/day] with no signs of IFI. Overall, 52 (36.4%) patients with possible IFI at baseline received micafungin treatment [100 (50–125) mg/day] versus 12 (17.2%) with probable [100 (75–150) mg/day] and 5 (3.5%) with confirmed [125 (100–150) mg/day] IFI. Treatment success was 91.6% (95% CI 85.80–95.59; n = 131) overall and 90.5% (n = 67) in patients receiving prophylaxis. Median time on treatment was 13 days. Treatment discontinuation (n = 26; 18.2%) was not related to adverse events. No treatment-related serious adverse events were reported. Conclusion Micafungin treatment for IC or prophylaxis for Candida infection was effective and well tolerated in patients with hematologic disorders in clinical practice in Greece. These results demonstrate that micafungin could be used more widely for prophylaxis. Further work is required to determine the efficacy and safety of micafungin for the management of IFIs in hematologic settings. Funding Astellas Pharma Inc.

Labyrinthine fistula is one of the most frequent complications of cholesteatoma (CHO), occurring in about 8% of cases in the literature. In about 90% of cases, it is located at the level of the lateral semicircular canal, and its clinical manifestation includes vertigo, nystagmus and positive Hennebert and Tullio signs. The management of lateral semicircular canal fistula (LSCF) secondary to CHO classically requires a retroauricular access by performing a canal wall-up (CWU) or canal wall-down (CWD) mastoidectomy. However, in case of a CHO confined to the tympanic cavity causing a LSCF on the ampullar arm, a transcanal exclusive endoscopic approach could be considered. The aim of this study is to describe the feasibility of a transcanal exclusive endoscopic approach in the management of a CHO confined to the tympanic cavity causing a LSCF on the ampullar arm. From January 2019 to December 2020, three patients with LSCF secondary to mesotympanic CHO underwent transcanal exclusive endoscopic ear surgery repair at the Department of Otolaryngology-Head and Neck Surgery, University Hospital of Modena, Italy. This technique was successfully employed to treat LSCF in all three cases and was planned as a two-stage surgery, performing ossiculoplasty after 12–18 months. Functional outcomes were also satisfactory: complete eradication of CHO, hearing preservation and complete resolution of symptoms. In case of a CHO confined to the tympanic cavity causing an LSCF on the ampullar arm, a transcanal exclusive endoscopic approach could be considered as a feasible and safe technique.

Lesions in the Guillain–Mollaret (G–M) triangle frequently cause various types of tremors or tremor-like movements. Nevertheless, we know relatively little about their generation mechanisms. The deep cerebellar nuclei (DCN), which is a primary node of the triangle, has two main output paths: the primary excitatory path to the thalamus, the red nucleus (RN), and other brain stem nuclei, and the secondary inhibitory path to the inferior olive (IO). The inhibitory path contributes to the dentato-olivo-cerebellar loop (the short loop), while the excitatory path contributes to the cerebrocerebellar loop (the long loop). We propose a novel hypothesis: each loop contributes to physiologically distinct type of tremors or tremor-like movements. One type of irregular tremor-like movement is caused by a lesion in the cerebrocerebellar loop, which includes the primary path. A lesion in this loop affects the cerebellar forward model and deteriorates its accuracy of prediction and compensation of the feedback delay, resulting in irregular instability of voluntary motor control, i.e., cerebellar ataxia (CA). Therefore, this type of tremor, such as kinetic tremor, is usually associated with other symptoms of CA such as dysmetria. We call this type of tremor forward model-related tremor. The second type of regular tremor appears to be correlated with synchronized oscillation of IO neurons due, at least in animal models, to reduced degrees of freedom in IO activities. The regular burst activity of IO neurons is precisely transmitted along the cerebellocerebral path to the motor cortex before inducing rhythmical reciprocal activities of agonists and antagonists, i.e., tremor. We call this type of tremor IO-oscillation-related tremor. Although this type of regular tremor does not necessarily accompany ataxia, the aberrant IO activities (i.e., aberrant CS activities) may induce secondary maladaptation of cerebellar forward models through aberrant patterns of long-term depression (LTD) and/or long-term potentiation (LTP) of the cerebellar circuitry. Although our hypothesis does not cover all tremors or tremor-like movement disorders, our approach integrates the latest theories of cerebellar physiology and provides explanations how various lesions in or around the G–M triangle results in tremors or tremor-like movements. We propose that tremor results from errors in predictions carried out by the cerebellar circuitry.

Since the first description of immune-mediated cerebellar ataxias (IMCAs) by Charcot in 1868, several milestones have been reached in our understanding of this group of neurological disorders. IMCAs have diverse etiologies, such as gluten ataxia, postinfectious cerebellitis, paraneoplastic cerebellar degeneration, opsoclonus myoclonus syndrome, anti-GAD ataxia, and primary autoimmune cerebellar ataxia. The cerebellum, a vulnerable autoimmune target of the nervous system, has remarkable capacities (collectively known as the cerebellar reserve, closely linked to plasticity) to compensate and restore function following various pathological insults. Therefore, good prognosis is expected when immune-mediated therapeutic interventions are delivered during early stages when the cerebellar reserve can be preserved. However, some types of IMCAs show poor responses to immunotherapies, even if such therapies are introduced at an early stage. Thus, further research is needed to enhance our understanding of the autoimmune mechanisms underlying IMCAs, as such research could potentially lead to the development of more effective immunotherapies. We underscore the need to pursue the identification of robust biomarkers.

Cerebellum contains the highest number of neurons in the brain and is a site for several pathologies. Cerebellar reserve is defined as the capacity for compensation and restoration following cerebellar pathological changes. When the etiology immediately elicits structural damage in a limited area (e.g., in cases of stroke and traumatic injury), the lost cerebellar functions can be compensated for by other areas not affected by the structural loss (structural cerebellar reserve). On the other hand, when the etiology weakens cerebellar neurons in a diffuse area, gradually leading to cell death (e.g., in cases of metabolic, immune-mediated, and degenerative cerebellar ataxias), the affected lesion itself can replenish vanishing cerebellar functions (functional cerebellar reserve). Cause-cure treatment should be introduced in the very initial phases to minimize damage to the cerebellum, at the stage when cerebellar impairment is still within the frame of sufficient cerebellar reserve. In case of acute and restricted pathologies, extension should be avoided as soon as possible, whereas in case of progressive and diffuse pathologies, the progression should be halted in the early stages to prevent further neuronal loss. When cerebellar reserve is still preserved, subsequent neuromodulation therapies can improve cerebellar ataxias.

Background: Human immunodeficiency viruses (HIV) infection is associated with a broad range of neurological manifestations, including opsoclonus-myoclonus ataxia syndrome (OMAS) occurring in primary infection, immune reconstitution syndrome or in case of opportunistic co-infection.Case: We report the exceptional case of a 43-year-old female under HIV treatment for 10 years who presented initially with suspected epileptic seizure. Although the clinical picture slightly improved under anti-epileptic treatment, it was rapidly attributed to OMAS. The patient exhibited marked opsoclonus, mild dysarthria, upper limbs intermittent myoclonus, ataxia in 4 limbs, truncal ataxia, and a severe gait ataxia (SARA score: 34). The diagnostic work-up showed radiological and biological signs of central nervous system (CNS) inflammation and cerebral venous sinus thromboses. The HIV viral load was higher in cerebrospinal fluid (CSF) than in the blood (4,560 copies/ml vs. 76 copies/ml). She was treated for 5 days with pulsed corticotherapy. Dolutegravir and anticoagulation administration were initiated. Follow-ups at 2 and 4 months showed a dramatic improvement of clinical neurologic status (SARA score at 4 months: 1), reduction of CNS inflammation and revealed undetectable CSF and serum viral loads.Conclusion: This case underlines the importance of the evaluation of the CSF viral load in HIV patients developing OMAS and suggests CSF HIV RNA escape as a novel cause for OMAS.

The terminology of cerebellar dysmetria embraces a ubiquitous symptom in motor deficits, oculomotor symptoms, and cognitive/emotional symptoms occurring in cerebellar ataxias. Patients with episodic ataxia exhibit recurrent episodes of ataxia, including motor dysmetria. Despite the consensus that cerebellar dysmetria is a cardinal symptom, there is still no agreement on its pathophysiological mechanisms to date since its first clinical description by Babinski. We argue that impairment in the predictive computation for voluntary movements explains a range of characteristics accompanied by dysmetria. Within this framework, the cerebellum acquires and maintains an internal forward model, which predicts current and future states of the body by integrating an estimate of the previous state and a given efference copy of motor commands. Two of our recent studies experimentally support the internal-forward-model hypothesis of the cerebellar circuitry. First, the cerebellar outputs (firing rates of dentate nucleus cells) contain predictive information for the future cerebellar inputs (firing rates of mossy fibers). Second, a component of movement kinematics is predictive for target motions in control subjects. In cerebellar patients, the predictive component lags behind a target motion and is compensated with a feedback component. Furthermore, a clinical analysis has examined kinematic and electromyography (EMG) features using a task of elbow flexion goal-directed movements, which mimics the finger-to-nose test. Consistent with the hypothesis of the internal forward model, the predictive activations in the triceps muscles are impaired, and the impaired predictive activations result in hypermetria (overshoot). Dysmetria stems from deficits in the predictive computation of the internal forward model in the cerebellum. Errors in this fundamental mechanism result in undershoot (hypometria) and overshoot during voluntary motor actions. The predictive computation of the forward model affords error-based motor learning, coordination of multiple degrees of freedom, and adequate timing of muscle activities. Both the timing and synergy theory fit with the internal forward model, microzones being the elemental computational unit, and the anatomical organization of converging inputs to the Purkinje neurons providing them the unique property of a perceptron in the brain. We propose that motor dysmetria observed in attacks of ataxia occurs as a result of impaired predictive computation of the internal forward model in the cerebellum.

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia whose most common features include late closure of fontanelles, absent or hypoplastic clavicles, and dental abnormalities. This disorder is primarily due to mutations in RUNX2 (CBFA1) gene. Here we present a Filipino child with clinical and radiologic features of CCD who was also diagnosed with B-cell acute lymphoblastic leukemia (ALL). On history, the patient’s father and paternal grandfather also presented with short stature and similar facial features. Association of leukemia and CCD has been noted in the literature. Hence, this report adds to the potential role of RUNX2 gene in leukemogenesis. With the potential predisposition to developing leukemia, this provides implications in genetic counselling and possible recommendations for surveillance later on.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the cause of the current pandemic coronavirus disease 2019 (COVID-19), primarily targets the respiratory system. Some patients also experience neurological signs and symptoms ranging from anosmia, ageusia, headache, nausea, and vomiting to confusion, encephalitis, and stroke. Approximately 36% of those with severe COVID-19 experience neurological complications. The virus may enter the central nervous system through the olfactory nerve in the nasal cavity and damage neurons in the brainstem nuclei involved in the regulation of respiration. Patients with cerebellar ataxia (CA) are particularly vulnerable to severe outcome if they contract COVID-19 because of the complexity of their disease, the presence of comorbidities, and their use of immunosuppressive therapies. Most CA patients burdened by progressive neurologic deficits have substantially impaired mobility and other essential functions, for which they rely heavily on ambulatory services, including rehabilitation and psychosocial care. Cessation of these interventions because of isolation restrictions places the CA patient population at risk of further deterioration. This international panel of ataxia experts provides recommendations for neurologists caring for patients with CA, emphasizing a pro-active approach designed to maintain their autonomy and well-being: continue long-term medications, promote rehabilitation efforts, utilize the technology of virtual visits for regular contact with healthcare providers, and pay attention to emotional and psychosocial health. Neurologists should play an active role in decision-making in those CA cases requiring escalation to intensive care and resuscitation. Multi-disciplinary collaboration between care teams is always important, and never more so than in the context of the current pandemic.

Introduction COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory arrest, and death. At present, anti-IL-6, antiviral therapy, convalescent plasma, hydroxychloroquine, and azithromycin among others are being investigated as potential treatments for COVID-19. As the disease etiology and precise therapeutic interventions are still not definitively defined, we wanted to review the roles that complement and the contact system may have in either the treatment or pathogenesis of the disease. Methods We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. The manuscript complies with ethics guidelines and was deemed exempt from institutional review board approval according to Human Subjects Protection Office guidelines. Results Mouse models are available for the study of coronavirus and complement. Although complement is effective in protecting against many viruses, it does not seem to be protective against coronavirus. C3 knockout mice infected with SARS-CoV had less lung disease than wild-type mice, suggesting that complement may play a role in coronavirus pathogenesis. Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists. Summary Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions.

The emergence of highly effective therapy has led to an increase in the life expectancy of patients with primary immunodeficiency (PID). Currently, we have the opportunity to observe the first generation of adults suffering from PID. Objective. To study the structure of the PID forms in Russian adults of the register of Institute of immunology of FMBA Russia. Materials and methods. The analysis of PID structure, demographic data and need for therapy was carried out on the basis of472 patient’s case histories who were treated in the Institute of immunology from 1983 to 2017. Results. The main part of patients older than 18 years (472 people) of Russian PID population are presented with predominant antibody deficiency - 61,22% and hereditary angioedema (HAE) - 30,72%, other PID forms are presented by isolated clinical cases. In 21,82% of cases, the disease debuted at the age of 18 years, with the diagnosis of PID was established after 18 years in 62,4% of cases (294 patients out of472). The average age of adult registry of PID patients is 39,6±6 years, median age - 35,6 years, maximum age - 86 years. Persistent disability is observed in 12,5% of cases. A study of the availability and adequacy of therapy showed that replacement therapy with immunoglobulins (IVIG) in need by 53,7%, but only 27,4% have it on the regularly and conditionally adequate dose, for 5,7% IVIG therapy is unavailable, while the majority of patients - 66,8% receive IVIG irregular and/or in inadequate dose. The presence of splenomegaly, hepatomegaly and enteropathy significantly lengthen the diagnosis period (p

Immune-mediated cerebellar ataxias (IMCAs), a clinical entity reported for the first time in the 1980s, include gluten ataxia (GA), paraneoplastic cerebellar degenerations (PCDs), antiglutamate decarboxylase 65 (GAD) antibody-associated cerebellar ataxia, post-infectious cerebellitis, and opsoclonus myoclonus syndrome (OMS). These IMCAs share common features with regard to therapeutic approaches. When certain factors trigger immune processes, elimination of the antigen( s) becomes a priority: e.g., gluten-free diet in GA and surgical excision of the primary tumor in PCDs. Furthermore, various immunotherapeutic modalities (e.g., steroids, immunoglobulins, plasmapheresis, immunosuppressants, rituximab) should be considered alone or in combination to prevent the progression of the IMCAs. There is no evidence of significant differences in terms of response and prognosis among the various types of immunotherapies. Treatment introduced at an early stage, when CAs or cerebellar atrophy is mild, is associated with better prognosis. Preservation of the “cerebellar reserve” is necessary for the improvement of CAs and resilience of the cerebellar networks. In this regard, we emphasize the therapeutic principle of “Time is Cerebellum” in IMCAs.

Many studies have shown that toxicities of anticancer drugs and their adverse effects are related to their chemical structure and high molecular weight that may result in a number of metabolites interacting with drug off-target networks. These factors require further attention for advancing cancer treatment and decreasing toxicities caused by the molecular complexity of antineoplastic agents. Providing more target-selective and tolerable cancer therapy with fewer side effects would not only improve patients’ compliance, but also would decrease cancer-remission rates. This review presents several antineoplastic agents and their metabolites with molecular weights greater than 500 g/mol, which reportedly cause more than fifteen types of adverse reactions during breast cancer therapy.

Chondrosarcoma is a rare malignant tumour arising from the cartilage with a high variability in the clinicalcourse and overall prognosis. This entity has, generally, a predilection for long bones of the limbs and pelvis and the location in the cranial bones is quite rare. We report a case of a 38 year male with a large and poorly symptomatic parafalcine chondrosarcoma of the cranial vault which was removed en bloc. The described location is extremely rare. Magnetic Resonance Imaging permitted to better delineate the lesion and plan the most appropriate therapeutic approach. Final diagnosis was based on histological examination, which confirmed the hypothesis of low-grade parafalcine chondrosarcoma. Even though surgery remains the mainstay of treatment for cerebral chondrosarcomas, adjuvant radiotherapy such as stereotactic, proton beam or carbon ion-beam therapy might be necessary in aggressive or incomplete removed cases.

Background & Objective: Neurotransplantation has been recently the focus of interest as a promising therapy to substitute lost cerebellar neurons and improve cerebellar ataxias. However, since cell differentiation and synaptic formation are required to obtain a functional circuitry, highly integrated reproduction of cerebellar anatomy is not a simple process. Rather than a genuine replacement, recent studies have shown that grafted cells rescue surviving cells from neurodegeneration by exerting trophic effects, supporting mitochondrial function, modulating neuroinflammation, stimulating endogenous regenerative processes, and facilitating cerebellar compensatory properties thanks to neural plasticity. On the other hand, accumulating clinical evidence suggests that the self-recovery capacity is still preserved even if the cerebellum is affected by a diffuse and progressive pathology. We put forward the period with intact recovery capacity as “restorable stage” and the notion of reversal capacity as “cerebellar reserve”. Conclusion: The concept of cerebellar reserve is particularly relevant, both theoretically and practically, to target recovery of cerebellar deficits by neurotransplantation. Reinforcing the cerebellar reserve and prolonging the restorable stage can be envisioned as future endpoints of neurotransplantation.

Background and aim: The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII). Methods and results: Questionnaires investigating the organisation of diabetes care centres, individuals’ clinical and metabolic features and pump technology and its management were sent to adult and paediatric diabetes centres that use CSII for treatment in Italy. Information on standard clinical variables, demographic data and acute and chronic diabetic complications was derived from local clinical management systems. The sample consisted of 6623 people with diabetes, which was obtained from 93 centres. Of them, 98.8% had type 1 diabetes mellitus, 57.2% were female, 64% used a conventional insulin pump and 36% used a sensor-augmented insulin pump. The median glycated haemoglobin (HbA1c) level was 60 mmol/mol (7.6%). The HbA1c target (i.e. 18 years) was achieved in 43.4% of paediatric and 23% of adult participants. Factors such as advanced pump functions, higher rate of sensor use, pregnancy in the year before the study and longer duration of diabetes were associated with lower HbA1c levels. The most common chronic complications occurring in diabetes were retinopathy, microalbuminuria and hypertension. In the year before the study, 5% of participants reported ≥1 episode of severe hypoglycaemic (SH) episodes (SH) and 2.6% reported ≥1 episode of ketoacidosis. Conclusions: Advanced personal skills and use of sensor-based pump are associated with better metabolic control outcomes in Italian people with diabetes who were treated with CSII. The reduction in SH episodes confirms the positive effect of CSII on hypoglycaemia. Clinical trial registration number: NCT 02620917 (ClinicalTrials.gov).

Novel coronavirus, SARS-CoV2, has caused pandemic of highly contagious disease called coronavirus disease 2019 (COVID-19), with epicenters in China, Italy, Spain, and the USA. Primarily affecting the human respiratory system, SARS-CoV2 has some impact on the human brain, but apparently minimal on the cerebellum, at least so far. Neurological involvement in the acute phase appears to manifest with confusion, dizziness, impaired consciousness, propensity to develop acute strokes, anosmia, hypogeusia, ataxia, epilepsy, and neuralgia. Cerebellar scholars are facing a time of uncertainty. Telemedicine has suddenly emerged as an alternative to follow patients. There is an urgent need to develop novel platforms to assess and follow ataxic patients remotely, especially because cerebellar patients often require ambulatory care to maintain their autonomy.

Posterior reversible encephalopathy syndrome (PRES) is a potentially severe disorder of the autoregulation of cerebral perfusion. The major clinical manifestations are headache, seizures, altered mental status, and visual loss. The typical radiological finding is vasogenic edema predominating in the white matter of occipital and parietal lobes. PRES is increasingly recognized as a clinico-radiological entity owing to improvements and fast availability of brain imaging, especially magnetic resonance imaging (MRI). We present the exceptional case of a 67-year-old female patient with a gastric adenocarcinoma at stage IIB (T3N0M0) treated by FLOT chemotherapy (5-fluorouracil, oxaliplatin, docetaxel, and folinic acid). Two months after the unique administration of FLOT regimen, she developed sudden posterior headache and visual loss. Blood pressure values were normal. Cerebral tomography showed ischemic-like occipital bilateral lesions, and angiographic sequences revealed breakdown of the blood–brain barrier (BBB). MRI revealed bilateral parieto-occipital T1 hypointensity and T2 hyperintensity, which demonstrated vasogenic edema. The rest of the parts of the lesions were T1 hyperintensity, T2 hyperintensity, and diffusion-weighted imaging (DWI) hyperintensity, which indicate cortical laminar necrosis. After injection of gadolinium, a linear enhancement of the cortex was observed. She was treated with oral nimodipine. Follow-up was characterized by permanent visual sequelae and tetraparesis. PRES represents an urgent neurological condition. Our observation highlights that PRES should be considered in patients under chemotherapy, even when their blood pressure remains within normal range. This is the first report of PRES triggered by FLOT chemotherapy and with a silent window of 2 months between chemotherapy and PRES, widening further the spectrum of chemotherapy-induced PRES. Our case highlights the potential role of FLOT regimen in the pathogenesis of PRES and the need for a novel approach in terms of prevention of this potentially fatal complication when patients receive chemotherapy.

Various etiopathologies affect the cerebellum, resulting in the development of cerebellar ataxias (CAs), a heterogeneous group of disorders characterized clinically by movement incoordination, affective dysregulation, and cognitive dysmetria. Recent progress in clinical and basic research has opened the door of the ‘‘era of therapy” of CAs. The therapeutic rationale of cerebellar diseases takes into account the capacity of the cerebellum to compensate for pathology and restoration, which is collectively termed cerebellar reserve. In general, treatments of CAs are classified into two categories: cause-cure treatments, aimed at arresting disease progression, and neuromodulation therapies, aimed at potentiating cerebellar reserve. Both forms of therapies should be introduced as soon as possible, at a time where cerebellar reserve is still preserved. Clinical studies have established evidence-based cause-cure treatments for metabolic and immune-mediated CAs. Elaborate protocols of rehabilitation and non-invasive cerebellar stimulation facilitate cerebellar reserve, leading to recovery in the case of controllable pathologies (metabolic and immune-mediated CAs) and delay of disease progression in the case of uncontrollable pathologies (degenerative CAs). Furthermore, recent advances in molecular biology have encouraged the development of new forms of therapies: the molecular targeting therapy, which manipulates impaired RNA or proteins, and the neurotransplantation therapy, which delays cell degeneration and facilitates compensatory functions. The present review focuses on the therapeutic rationales of these recently developed therapeutic modalities, highlighting the underlying pathogenesis.

Sporadically advocated over the last two centuries, a cerebellar role in cognition and affect has been rigorously established in the past few decades. In the clinical domain, such progress is epitomized by the “cerebellar cognitive affective syndrome” (“CCAS”) or “Schmahmann syndrome.” Introduced in the late 1990s, CCAS reflects a constellation of cerebellar-induced sequelae, comprising deficits in executive function, visuospatial cognition, emotion–affect, and language, over and above speech. The CCAS thus offers excellent grounds to investigate the functional topography of the cerebellum, and, ultimately, illustrate the precise mechanisms by which the cerebellum modulates cognition and affect. The primary objective of this task force paper is thus to stimulate further research in this area. After providing an up-to-date overview of the fundamental findings on cerebellar neurocognition, the paper substantiates the concept of CCAS with recent evidence from different scientific angles, promotes awareness of the CCAS as a clinical entity, and examines our current insight into the therapeutic options available. The paper finally identifies topics of divergence and outstanding questions for further research.

Essential tremor is a neurological disorder with a tremor of the arms and hands. It is well known thatessential tremor is characterized by the postural tremor and the action tremor. There has been no report on the quan-titative difference in the characteristics of two tremor types. The purpose of this study was to investigate the possibledifference in tremor characteristics of postural and action tremors. Seventeen patients with essential tremor (68.9± 7.9years, 7 men, 10 women) participated in this study. Patients performed the tasks of postural maintenance (armsoutstretched) and daily actions (spiral drawing). Three-axes (pitch, roll and yaw) gyro sensors were attached on indexfinger, back of hand and forearm, from which the segment and the joint angular velocities were calculated. Outcomemeasure was the tremor amplitude defined as the root-mean-square mean of the vector-sum angular velocity at seg-ments and joints. Two-way ANOVA showed that task and joint had main factor on the tremor amplitude (p 0.05). However, tremor amplitude at the wrist joint differed among the tasks (p < 0.05), and it was greater inthe action tasks than in postural task. Tremor was greater at finger segments than at hand and forearm and itincreased in action tasks. The results of this study would be helpful for the understanding and task-specific treat-ments of the essential tremor.Key words: essential tremor, task specific, angular velocity, action tremor, postural tremor

Background While there is currently no cure for multiple sclerosis (MS), treatment with biologic diseasemodifying drugs (bDMDs) can reduce the impact of the condition on the lives of patients. In Greece, the regulatory change in the distribution system of bDMDs, limited their administration through the designated pharmacies of the National Organization for Healthcare Services Provision (EOPYY) or the National Health System (ESY) hospitals, thus potentially impacting access to MS treatment. In this context, the aim of this paper was to assess the barriers to bDMDs, by recording MS patients’ experiences. Methods A survey research was conducted between January and February 2014 in Athens and 5 other major Greek cities with the methods of personal and telephone interview. A structured questionnaire was used to elicit socio-economic and medical information, information related to obstacles in accessing bDMDs and medical treatment, from MS patients that visited EOPYY pharmacies during the study period. Results During the last year 69% of 179 participants reported that the distribution system of bDMDs has improved. Thirteen percent of participants encountered problems in accessing their medication, and 16.9% of participants in accessing their physician, with the obstacles being more pronounced for non-Athens residents. Frequent obstacles to bDMDs were the distance from EOPYY pharmacies and difficulties in obtaining a diagnosis from an EOPYY/ESY physician, while obstacles to medical care were delays in appointment booking and travel difficulties. Conclusion Even though the major weaknesses of the distribution system of bDMDs have improved, further amelioration of the system could be achieved through the home delivery of medicines to patients living in remote areas, and through the development of a national MS registry.

In Diabetes Mellitus the loss of capacity to regulate immunity, the reduction of pulmonary functions and the pro-thrombotic state determine the severity of COVID-19.

The capacity to understand another person's emotions, intentions, beliefs and personality traits, based on observed or communicated behaviors, is termed social cognition. During the last decade, social neuroscience has made great progress in understanding the neural correlates of social cognition. However, because the cerebellum is traditionally viewed as only involved in motor processing, the contribution of this major part of the brain in social processing has been largely ignored and its specific role in social cognition remains unclear. Nevertheless, recent meta-analyses have made its crucial contribution to social cognition evident. This raises the question: What is the exact function of the cerebellum in social cognition? We hypothesize that the cerebellum builds internal action models of our social inter-actions to predict how other people's actions will be executed, what our most likely responses are to these actions, so that we can automatize our interactions and instantly detect disruptions in these action sequences. This mechanism likely allows to better anticipate action sequences during social interactions in an automatic and intuitive way and to fine-tune these anticipations, making it easier to understand behaviors and to detect violations. This hypothesis has major implications in neurological disorders affecting the cerebellum such as autism, with detrimental effects on social functionality, especially on more complex and abstract social cognitive processes. Because the fundamental anatomical organization of the cerebellum is identical in many species (cerebellar microcomplexes), this hypothesis could have major impacts to elucidate social interactions in social animals.