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Alemtuzumab (Lemtrada) is a humanized monoclonal antibody indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis with active disease defined by clinical or imaging features. Alemtuzumab demonstrated superior efficacy over active comparator in both treatment naive patients and those with inadequate response to prior therapy. Alemtuzumab is associated with a consistent and manageable safety and tolerability profile. Treatment with alemtuzumab for multiple sclerosis increases the risk for autoimmune adverse events including immune thrombocytopenia (ITP). Complete blood counts with differential should be obtained prior to initiation of treatment and at monthly intervals thereafter for 48 months after the last infusion. After this period of time, testing should be performed based on clinical findings suggestive of ITP. If ITP onset is confirmed, appropriate medical intervention should be promptly initiated, including immediate referral to a specialist. This paper presents the consensus of Belgian multiple sclerosis specialists and hematologists to guide the treating physician with practical recommendations. ispartof: Acta Neurologica Belgica vol:118 issue:1 pages:7-11 ispartof: location:Italy status: published

This paper deals with thyroid disease that can occur after treatment with alemtuzumab (humanized monoclonal anti-CD52) for relapsing–remitting multiple sclerosis (MS). The 5-year incidence of thyroid adverse events in phase 3 clinical trials is up to 40.7%. In most cases, the thyroid dysfunction is mild and easily manageable and only few serious thyroid adverse events have been reported. The need for patient education on the risk of thyroid dysfunction, as well as regular clinical and biochemical thyroid function screening is well described. However, practical clinical guidance in case of abnormal thyroid-related findings prior to or after alemtuzumab treatment is currently lacking. Therefore, a Belgian taskforce consisting of MS and thyroid experts was created in 2016, with the objective of issuing a clinical thyroid management algorithm based on available scientific evidence and personal experience with regard to alemtuzumab treatment-related thyroid adverse events., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Primary Sjogren's syndrome (pSS) is a chronic autoimmune disorder characterized by lymphocytic infiltrates of the exocrine glands, particularly the salivary and lacrimal glands, resulting in oral and ocular dryness. pSS has been linked to various neurological manifestations, including cerebellar dysfunction. We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS-related cerebellar ataxia. Methods A systematic literature search in the PubMed database was performed and 19 papers were eligible to be included in this paper. Results The pooled prevalence of cerebellar ataxia in pSS is estimated to be 1.5% (95% CI 0.3-6.8%). pSS patients with cerebellar involvement have a female-to-male ratio of 6:1. Although most of the patients are adults in their fifth decade of life when diagnosed, cases of children with pSS and cerebellar involvement have been reported. Typical cerebellar ataxia related to pSS manifests with vermian dysfunction, namely gait ataxia and/or cerebellar speech. Cerebellar ataxia due to pSS may also mimic degenerative cerebellar ataxia, especially when the onset is progressive. Conclusions The diagnostic approach to a patient with cerebellar ataxia of unknown etiology should include evaluation for an underlying pSS. A thorough history and clinical examination, antibody testing, brain MRI imaging and/or MRS of the cerebellum will assist in establishing the diagnosis. Setting up a joint neuro-rheumatology clinic can be valuable given that rheumatic and neurological diseases share comorbidities.

To make assessment of neurocognitive decline in patients with brain metastases more reliable and feasible, Brainlab AG developed an application 'Cognition' for the iPad by gamifying validated paper and pencil tests. This study aims at validating the computerized tests. We assessed reliability and comparability of 'Cognition' with similar well-established paper and pencil tests in two consecutive sessions per participant. The electronic tests used the same assignments with different stimuli than the paper and pencil tests. Domains involved are learning and memory, attention and processing speed, verbal fluency and executive functions. In total 5 employees and 25 cancer patients without disease in the CNS participated, of whom 24 completed both sessions. Reliability was found satisfying for the domains learning and memory (p = 0.08; p = 0.612; p = 0.4445) and verbal fluency (p = 0.064). A learning effect showed for attention and processing speed (p = 0.001) while executive functioning showed a significant decline, possibly due to radiotherapy-related fatigue (p = 0.013). Concerning comparability between electronic and paper results, a significant correlation was found for attention and processing speed (p = 0.000), for verbal fluency (p = 0.03), for executive functions (p = 0.000), but not for learning and memory (p = 0.41; p = 0.25). Overall 'Cognition' showed moderate comparability, probably caused by the consecution of tests during sessions and the unfamiliarity with electronic test in older patients. After improving its functionality, the application needs to be validated in patients with brain metastases before it can detect cognitive decline and possible early radiation toxicity or relapses.

Multiple Sclerosis (MS) is a disease determined by inflammatory demyelination and neurodegeneration in the Central Nervous System (CNS). Despite the extensive utilization of Complementary and Alternative Medicine (CAM) in MS, there is a need to have comprehensive evidence regarding their application in the management of MS symptoms. This manuscript is a Systematic Literature Review and classification (SLR) of CAM therapies for the management of MS symptoms based on the International Classification of Functioning Disability and Health (ICF) model.Studies published between 1990 and 2020 IN PubMed, Science Direct, Scopus, Pro-Quest, and Google Scholar using CAM therapies for the management of MS symptoms were analyzed.Thirty-one papers on the subject were analyzed and classified. The findings of this review clearly show that mindfulness, yoga, and reflexology were frequently used for managing MS symptoms. Moreover, most of the papers used mindfulness and yoga as a CAM therapy for the management of MS symptoms, which mostly devoted to mental functions such as fatigue, depression, cognition, neuromuscular functions such as gait, muscle strength, and spasticity, and sensory function such as balance, in addition to, reflexology is vastly used to management of mental functions of MS patients.Evidence suggested that CAM therapies in patients with MS have the potential to target and enhancement numerous elements outlined in the ICF model. Although the use of CAM therapies in MS symptom management is promising, there is a need for strict clinical trials. Future research direction should concentrate on methodologically powerful studies to find out the potential efficacy of CAM intervention.

To make assessment of neurocognitive decline in patients with brain metastases more reliable and feasible, Brainlab AG developed an application 'Cognition' for the iPad by gamifying validated paper and pencil tests. This study aims at validating the computerized tests. We assessed reliability and comparability of 'Cognition' with similar well-established paper and pencil tests in two consecutive sessions per participant. The electronic tests used the same assignments with different stimuli than the paper and pencil tests. Domains involved are learning and memory, attention and processing speed, verbal fluency and executive functions. In total 5 employees and 25 cancer patients without disease in the CNS participated, of whom 24 completed both sessions. Reliability was found satisfying for the domains learning and memory (p = 0.08; p = 0.612; p = 0.4445) and verbal fluency (p = 0.064). A learning effect showed for attention and processing speed (p = 0.001) while executive functioning showed a significant decline, possibly due to radiotherapy-related fatigue (p = 0.013). Concerning comparability between electronic and paper results, a significant correlation was found for attention and processing speed (p = 0.000), for verbal fluency (p = 0.03), for executive functions (p = 0.000), but not for learning and memory (p = 0.41; p = 0.25). Overall 'Cognition' showed moderate comparability, probably caused by the consecution of tests during sessions and the unfamiliarity with electronic test in older patients. After improving its functionality, the application needs to be validated in patients with brain metastases before it can detect cognitive decline and possible early radiation toxicity or relapses.

Objective: Due to the growing number of older people with dementia (PWD) worldwide, there is an urgent need to improve undergraduate medical education on dementia and skills of future health professionals to provide the best quality care for PWD. The study aimed to determine attitudes and knowledge regarding dementia among medical students. Methods: This cross-sectional, survey- based study included 231 final-year medical students who completed the paper-and-pencil questionnaire with seven categories of questions including two dementia knowledge tests. Results: Students have relatively neutral attitudes towards working with PWD and a rather poor theoretical knowledge in the dementia knowledge exam. Students showed the best theoretical knowledge about the symptoms of Alzheimer's disease, while their knowledge was poor in the field of differential diagnoses, epidemiology, and pathogenesis of Alzheimer's disease. One in 11 sixth-year medical students has never had contact with a person with dementia. The opinion of most students was that they should have spent more time with PWD during their medical education and that there are too few classes in the field of dementia at the School of Medicine. The dementia knowledge test with 23 Multiple- Choice Questions showed a higher internal consistency compared to the Alzheimer's Disease Knowledge Scale. Conclusion: There is an urgent need to increase the interest and improve attitudes and knowledge towards dementia for all future health care professionals from the earliest student days to provide the best care for PWD.

Digital Subtraction Angiography (DSA) is the gold-standard imaging modality in acute cerebrovascular diagnosis. The role of DSA has become increasingly prominent since the incorporation of endovascular therapy in standards of care for acute ischemic stroke. It is used in the assessment of cerebral vessel patency; however, the therapeutic role of DSA from a prognostic standpoint merits further investigation. The current paper provides an update on current practice on diagnostic, therapeutic and prognostic use of DSA in acute cerebrovascular diseases and various indications and perspectives that may apply, or limit its use, in ongoing surveillance or prognosis. Pre-clinical and clinical studies on the aspects, including but not limited to the morphology of cerebrovasculature in acute ischaemic stroke, are required to delineate and inform its prognostic role.

The aim of this paper is to analyse the pathological background of very early Guillain-Barré (VEGBS) (≤ 4 days after onset) comparing it with initial stages of experimental autoimmune neuritis (EAN). The pathological hallmark of VEGBS is inflammatory oedema predominating in proximal nerve trunks. In EAN inflammatory oedema precedes the development of demyelination or axonal degeneration; such oedema may increase endoneurial fluid pressure (EFP) stretching the perineurium and constricting the transperineurial microcirculation. Centrofascicular or wedge-shaped areas of nerve ischemia have been reported in GBS and EAN. Additional support for proximal VEGBS pathology comes from electrophysiology showing alterations in late responses as the most frequent features, and ultrasonography illustrating that main changes rely on ventral rami of spinal nerves. Selective inefficiency of the blood-nerve barrier would explain the topography of changes in VEGBS. Increased serum neurofilament light chain concentration has recently been reported in VEGBS, with no difference between demyelinating and axonal subtypes. This is a marker of axonal damage, which could be correlated with endoneurial ischemia caused by increased EFP. Inflammatory oedema of proximal nerve trunks may be pathogenic in VEGBS, and consequently there is a pressing need for therapeutic strategies to stop its rapid impact on the axons.

Restless Legs Syndrome (RLS) is a chronic neurological disorder and the incidence of RLS is a more common disease than known is accepted. This study was performed to identify and analyze the characteristics of RLS-related articles published from 2001 to 2020 using bibliometric analyses.RLS-related articles published from 2001 to 2020 were retrieved from the Web of Science Core Collection database with predefined search terms. VOSviewer software was used to visualize various bibliographic coupling networks on data. The top 10 lists (about organizations, papers, journals, most commonly cited articles, authors, countries, and keywords) extracted from 2001 to 2020 were also analyzed.A total of 2311 articles were included and the total number of publications from 2001 to 2020 was increased by 5.02-fold. The highest number of RLS publications (n = 171) since 2001 was observed in 2020. The United States is contributed the highest number of RLS-related publications (34.53%). The top productive journal was Sleep Medicine and the most prominent organization was Johns Hopkins University. In the list of top 10 authors, Allen RP was the first author.This study is the first bibliometric analysis that provides a general perspective on the RLS from 2001 to 2020 and may be useful as a guide for further research in this field.

This statement paper deals with the key role an neurologist plays in the management of victims of chemical warfare/terrorist attacks. Because terrorist factions have expanded the war zone creating a worldwide risk of terrorist attacks, not only limited to some conflict zones in the Middle East, neurologists in all countries/regions have to be prepared for disaster response. The scope of this paper is to provide guidelines for the neurological management of victims of chemical and biological terrorist attacks.

Spinal epidural angiolipomas are rare lesions composed of mature lipomatous and angiomatous elements. In this paper, the authors review a surgical series of ten patients with epidural angiolipomas. All patients had performed preoperative and postoperative magnetic resonance imaging. The diagnosis of angiolipoma was based on pathology. All the follow-up data were obtained during office visits. There were 5 males and 5 females with a mean age of 53.6 years. One tumor was located in the cervicothoracic, six in the thoracic, and three in the lumbar spine. The most common symptom was progressive motor deficit. Gross total resection of the tumor was achieved in nine cases, and subtotal resection was obtained in one case. No recurrence or regrowth of the residual tumor was observed during a follow-up period of 50.8 months. At the last follow-up, 90% of patients experienced improvement in the neurological function. Epidural angiolipomas are benign but clinically progressive lesions. Early surgery should be performed to prevent irreversible neurological deficits. Postoperative radiotherapy is not recommended. The risk of long-term recurrence/regrowth of the lesions is low, and a good clinical outcome after total or subtotal removal can be expected.

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder characterized by lymphocytic infiltrates of the exocrine glands, particularly the salivary and lacrimal glands, resulting in oral and ocular dryness. pSS has been linked to various neurological manifestations, including cerebellar dysfunction. We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS-related cerebellar ataxia.A systematic literature search in the PubMed database was performed and 19 papers were eligible to be included in this paper.The pooled prevalence of cerebellar ataxia in pSS is estimated to be 1.5% (95% CI 0.3-6.8%). pSS patients with cerebellar involvement have a female-to-male ratio of 6:1. Although most of the patients are adults in their fifth decade of life when diagnosed, cases of children with pSS and cerebellar involvement have been reported. Typical cerebellar ataxia related to pSS manifests with vermian dysfunction, namely gait ataxia and/or cerebellar speech. Cerebellar ataxia due to pSS may also mimic degenerative cerebellar ataxia, especially when the onset is progressive.The diagnostic approach to a patient with cerebellar ataxia of unknown etiology should include evaluation for an underlying pSS. A thorough history and clinical examination, antibody testing, brain MRI imaging and/or MRS of the cerebellum will assist in establishing the diagnosis. Setting up a joint neuro-rheumatology clinic can be valuable given that rheumatic and neurological diseases share comorbidities.

Coronavirus disease 2019 (COVID-19), caused by the late 2019 outbreak of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a respiratory disease which could put myasthenia gravis patients at a greater risk of developing severe disease course. This paper presents a single-institution case series of hospitalized myasthenia gravis patients with COVID 19. We identified eight patients previously diagnosed with myasthenia gravis, four of whom presented with clear signs of myasthenia gravis symptom worsening on admission. No form of respiratory support was needed during the complete duration of stay for three patients, oxygen therapy was administered to two patients, while the remaining three patients required mechanical ventilation. Treatment was successful for seven patients, six of whom were discharged without any myasthenia gravis symptoms. One patient died after eleven days of intensive care unit treatment. Although treatment of patients with myasthenia gravis and COVID-19 patients is challenging, case series of myasthenia gravis patients with COVID-19 treated in our institution demonstrates relatively favorable treatment outcome. Our data seem to support the notion that immunosuppressive medication does not seem to result in worse outcomes. Our data also support the notion that intravenous immunoglobulin treatment is safe and should be administered to patients with myasthenia gravis and COVID-19 in case of myasthenia gravis worsening since benefits seem to greatly outweigh the risks.

Patients with refractory epilepsy can suffer from psychological and physical problems. Epilepsy can also be associated with menstruation abnormalities in women. In this paper, we aim to survey women with focal refractory epilepsy who also suffer from menstrual abnormalities. This cross-sectional study was performed in 2018 in Tertiary Epilepsy Center in Kashani Hospital, Isfahan, Iran and Milad hospital, Isfahan, Iran. A total number of 381 patients diagnosed with refractory epilepsy joined the study based on an inclusion and exclusion criteria. Clinical characteristics of epilepsy, menstrual issues and brain MRI findings were assessed. Among 381 women with refractory epilepsy, 250 had refractory focal epilepsy (65.61%), and the others (34.39%) had generalized refractory epilepsy. 132 patients out of 381 had menstrual abnormalities (34.65%). Among 132 women with coexisting refractory epilepsy and menstrual abnormalities, 86 (65.15%) were diagnosed with refractory focal epilepsy, and 46 (34.86%) had generalized refractory epilepsy (p value = 0.041). Oligomenorrhea–hypomenorrhea was the most common type of menstrual abnormality in women with refractory epilepsy seen in 83 (62.87%) (p value = 0.039). The most common brain MRI pathology in women with refractory focal epilepsy was mesial temporal sclerosis (MTS) (39.20%, p = 0.00). We report that almost one-third of women with refractory epilepsy suffer from menstrual disorders, and the most common disorder was Oligomenorrhea–hypomenorrhea, and the most common brain pathology was MTS. It has also been a hypothesis that reproductive dysfunctions are connected to temporal lobe malfunctions, and more specific studies are required in this issue.

Inter-individual heterogeneity of tumors leads to non-effectiveness of unique therapy plans. This issue has caused a growing interest in the field of personalized medicine and its application in tumor growth evaluation. Accordingly, in this paper, a framework of personalized medicine is presented for growth prediction of brain glioma tumors. A convection-diffusion-reaction model is used as the patient-specific tumor growth model which is associated with multimodal magnetic resonance images (MRIs). Two parameters of intracellular area fraction (ICAF) and metabolic rate have been used to incorporate the physiological data obtained from medical images into the model. The framework is tested on the data of two cases of glioma tumors to document the approach; parameter estimation is made using particle swarm optimization (PSO) and genetic algorithm (GA) and the model is evaluated by comparing the predicted tumors with the observed tumors in terms of root mean square error of the ICAF maps (IRMSE), relative area difference (RAD) and Dice's coefficient (DC). Results show the differences of IRMSE, RAD and DC in 4.1 ∓ 1.15%, 0.099 ∓ 0.041 and 85.5 ∓ 7.5%, respectively. Survival times are estimated by assuming the tumor radius of 35 mm as the fatal burden. Results confirm that less-diffusive tumors lead to higher survival times. The represented framework makes it possible to personally predict the growth behavior of glioma tumors only based on patients' routine MRIs and provides a basis for modeling the personalized therapy and walking in the path of personalized medicine.

We read with great interest the paper by Davide Boeris et al. [2] titled ‘‘Pontine compression caused by ‘‘surgiceloma’’ after trigeminal decompression: case report and literature review’’. The authors describe a rare complication after microvascular decompression (MVD) of the trigeminal nerve using Surgicel and fibrin glue. The procedure was complicated by postoperative hemiparesis due to brainstem compression, caused by swelling of the Surgicel–glue complex. After reexploration and subsequent removal of the mass, the patient recovered well without neurological symptoms. Compression due to so-called surgiceloma (usually Surgicel soaked with blood forming a firm mass) is a well-known complication after application of Surgicel [4, 7, 8]. Surgiceloma can occur anywhere but is especially harmful when in close contact with neural structures, as shown in the aforementioned publication [2]. We were confused about the fact that the authors use Surgicel (oxidized cellulose) as a sponge to decompress the trigeminal nerve. Surgicel, which is a form of processed cellulose, was first described by Yackel and Kenyon of the Eastman Kodak Laboratories in 1942 [11]. The hemostatic use of oxidized cellulose was first introduced by Frantz in 1943 [5], while oxidized regenerated cellulose was launched in 1960. The use of oxidized cellulose has gained widespread acceptance since the 50s and 60s in neurosurgery, mainly to stop oozing in the cerebral resection cavity. It is a common practice for neurosurgeons to cover the brain bed cavity with sheets of cellulose, even if it does not actively bleed. This preventive hemostasis technique has never been proven scientifically and it seems to be more of a habit and a psychological reassurance to the neurosurgeon. The incidence of complications is relatively low considering the frequent usage of the product. However, swelling leading to neurological deficit has been reported in the neurosurgical, thoracic, and orthopedic literature [4, 7, 8]. The literature search through Pubmed and common neurosurgical textbooks did not show any previous report of the use of Surgicel for microvascular decompression, except one paper from Italy [3]. In our opinion, Surgicel is not a material for MVD. First of all, Surgicel has a low pH that might not be that good for an already irritated nerve root. Second, it is known that Surgicel swells after application and that is why it is recommended by the manufacturer not to place Surgicel in bony canals or in anatomical cavities, where it can lead to pressure on neural structures. Third, a significant amount of Surgicel has to be applied to serve as a cushion between the nerve and the offending artery. As any other foreign body material, Surgicel causes a foreign body reaction with an inflammatory reaction around the implanted material. Finally, once it is absorbed by the body, one can imagine what happens at the artery–nerve interface. Recurrence of neurovascular conflict seems not unlikely. As a consequence of the abovementioned arguments, we would be very cautious to use Surgicel for MVD. We have made some negative experience with Surgicel before. After removal of Surgicel after a laminectomy surgery—it appeared like a trichobezoar (mass of hairs), very firm, and it T. Menovsky (&) Department of Neurosurgery, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium e-mail: tomas.menovsky@uza.be

Recent discovery of nusinersen, an antisense oligonucleotide drug, has provided encouragement for improving treatment of spinal muscular atrophy. No therapeutic options currently exist for this autosomal recessive motor neuron disorder. Nusinersen is developed for intrathecal use and binds to a specific sequence within the survival motor neuron 2 pre-messenger RNA, modifying the splicing process to promote expression of full-length survival motor neuron protein. We performed a MEDLINE and CENTRAL search to investigate the current evidence for treatment with nusinersen in patients with spinal muscular atrophy. Four papers were withheld, including two phase-3 randomized controlled trials, one phase-2 open-label clinical trial and one phase-1 open-label clinical trial. Outcome measures concerned improvement in motor function and milestones, as well as event-free survival and survival. Results of these trials are hopeful with significant and clinically meaningful improvement due to treatment with intrathecal nusinersen in patients with early- and later-onset spinal muscular atrophy, although this does not restore age-appropriate function. Intrathecal nusinersen has acceptable safety and tolerability. Further trials regarding long-term effects and safety aspects as well as trials including broader spinal muscular atrophy and age categories are required and ongoing.

Friedrich Nietzsche (1844-1900), one of the most profound and influential modern philosophers, suffered since his very childhood from severe migraine. At 44 he had a mental breakdown ending in a dementia with total physical dependence due to stroke. From the very beginning, Nietzsche's dementia was attributed to a neurosyphilitic infection. Recently, this tentative diagnosis has become controversial.To use historical accounts and original materials including correspondence, biographical data and medical papers to document the clinical characteristics of Nietzsche's illness and, by using this pathography, to discuss formerly proposed diagnoses and to provide and support a new diagnostic hypothesis.Original letters from Friedrich Nietzsche, descriptions by relatives and friends, and medical descriptions. Original German sources were investigated. Biographical papers published in medical journals were also consulted.Nietzsche suffered from migraine without aura which started in his childhood. In the second half of his life he suffered from a psychiatric illness with depression. During his last years, a progressive cognitive decline evolved and ended in a profound dementia with stroke. He died from pneumonia in 1900. The family history includes a possible vascular-related mental illness in his father who died from stroke at 36.Friedrich Nietzsche's disease consisted of migraine, psychiatric disturbances, cognitive decline with dementia, and stroke. Despite the prevalent opinion that neurosyphilis caused Nietzsche's illness, there is lack of evidence to support this diagnosis. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) accounts for all the signs and symptoms of Nietzsche's illness. This study adds new elements to the debate and controversy about Nietzsche's illness. We discuss former diagnoses, comment on the history of a diagnostic mistake, and integrate for the first time Nietzsche's medical problems.

Hypoxia as one of the most common clinical disturbances in pregnancy period can cause destructive changes in motor sensory cortex and can lead to imperfect organization in motor reactions. Crocin, a water-soluble carotenoid, is the most active ingredients of saffron and a lot of studies declare its positive effectiveness on improving motor activity. Since the hypoxia intensity affects its malicious amount on movement, in this paper, we have studied the effect of crocin in three maternal hypoxia protocols with different oxygen intensities on motor activity and balance in rat offspring. In this experiment, female rats (Wistar) were used on the 20th day of pregnancy. The rats were randomly divided into eight experimental groups: sham, crocin, hypoxia with three different intensities: 10% oxygen and 90% nitrogen for 1 h (hypoxia-ɪ), 7% oxygen and 93% nitrogen for 1 h (hypoxia-ɪɪ), 7% oxygen and 93% nitrogen for 3 h (hypoxia-ɪɪɪ) and treated-crocin hypoxia groups. To produce hypoxia, pregnant rats were placed in a hypoxia box. In crocin group, rat offspring received 30 mg/kg crocin via IP injection at P14–28. Control group also received saline injection at the same time. Finally, balance and motor activity in offspring were measured respectively by rotarod and open-field devices. Results showed that motor activity significantly decreased in hypoxia-ɪɪɪ group as compared with sham group (p

While the influence of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on the comprehension of pragmatic language in Parkinson's disease (PD) has been the focus of studies, its impact on production, however, has yet to be elucidated. (1) Investigating the inf luence of DBS STN on pragmatic language production in spontaneous speech by comparing different stimulation conditions and (2) evaluating the effect of asymmetric dopaminergic denervation. This paper included 18 patients with advanced idiopathic PD with STN DBS. [Ten PD patients with predominantly left hemispheric dopamine denervation (PD-left) and eight PD patients with predominantly right-hemispheric dopamine denervation (PD-right).] The pragmatic components 'communicative functions' and 'conversational skills' were evaluated by analysing the spontaneous language production in four stimulation conditions. STN stimulation did not appear to influence the pragmatic production skills. Only when asymmetric dopamine depletion was taken into account the parameter 'giving an explanation' interaction was detectable. STN DBS appears to have some influence on the production of pragmatic language depending on asymmetric dopaminergic denervation. Suggestions are made for further research of pragmatic production in Parkinson's disease.

Hashimoto's encephalopathy (HE) is a rare neurological disorder associated with autoimmune thyroiditis, with heterogenous group of neurological symptoms in patients with high titers of antithyroid antibodies. Clinical manifestations of HE may include acute or subacute encephalopaty with seizures, behavioral and psychiatric manifestations, movement disorders, and coma. Early diagnosis and adequate therapy is very important due to the fact that this autoimmune disorder is potentially lethal. Hashimoto's encephalopathy is usually steroid-responsive. In this paper we describe three patients with Hashimoto's encephalopathy, presented with different clinical pictures, disease course and response to the treatment with corticosteroids.

The first step in the treatment of epilepsy is the confirmation of the diagnosis. A correct diagnosis not only includes the epileptic origin of the event, but also the diagnosis of the seizure type and the epileptic syndrome. The second step is to try to find the aetiology of the seizures. Some papers have shown that the prognosis of epilepsy is better if the seizures are treated earlier, but other papers did not find any difference in the long-term prognosis between patients treated after the first seizure or after several seizures. Therefore, one of the most difficult points, after confirmation of the diagnosis, with a first or few seizures will be to identify the risks of relapse in some patients and to immediately treat them and to avoid treating the others who will have only one or rare seizures during their lives without any damage. In most cases, the first treatment will be the prescription of an antiepileptic drug (AED) in monotherapy. If the cause is treatable, it will be treated concomitantly. In generalised epilepsies, especially in idiopathic syndromes, valproate will be the first choice, most of the classic AEDs may worsen some seizure types in these syndromes. In partial epilepsies, there are no statistically significant differences in efficacy between the 4 classic major AEDs (carbamazepine, phenytoin, phenobarbitone and valproate) in pooled data. The choice of the drug should be more influenced by considerations of safety profile, dosing frequency, and costs for equivalent advantages. Accordingly, valproate is a good first choice in patients in whom the epilepsy syndrome is not clearly defined. Efficacy of newer AEDs is similar to old AEDs but most are better tolerated. However, some studies including seizure control, side effects, medical consultation, inpatient, accidental injuries, and laboratory investigations showed that newer AEDs are more expensive in newly diagnosed patients, compared to classic major AEDs and this notion should be taken into account for the prescription.

Familial amyloid polyneuropathy (FAP) is a most often length-dependent axonal neuropathy, often part of a multisystem disorder also affecting other organs, such as cardiac, gastrointestinal, genitourinary, renal, meningeal and eye tissue. It is most frequently the result of a mutation in the TTR gene, most commonly a p.Val50Met mutation. TTR-FAP is a rare autosomal dominant heritable disabling, heterogeneous disease in which early diagnosis is of pivotal importance when attempting treatment. This paper discusses the course of four Belgian FAP patients with different TTR mutations (p.Val48Met; p.Val52Ala; p.Ala59Val; p.Val50Met). We also review the diagnosis and differential diagnosis of TTR-FAP, diagnostic studies, follow-up, its current treatment and those in development, prognosis and the importance of genetic counseling. At first, TTR-FAP is often misdiagnosed as a chronic inflammatory demyelinating polyneuropathy or chronic idiopathic axonal polyneuropathy. Genetic testing is obligatory to confirm the diagnosis of TTR-FAP, except in familial cases. Biopsy samples are an asset in diagnosing TTR-FAP but can be falsely negative. At the moment, tafamidis meglumine is considered as first-line treatment in stage I neurological disease. Patients eligible for liver transplantation should be carefully selected when first-line therapy fails.

Myotonia congenita is an inherited muscle disease present from childhood that is characterized by impaired muscle relaxation after contraction resulting in muscle stiffness; moreover, skeletal striated muscle groups may be involved. Myotonia congenita occurs due to chloride (Cl) channel mutations that reduce the stabilizing Cl conductance, and it is caused by mutations in the CLCN1 gene. This paper describes four patients from two different healthy consanguineous Turkish families with muscle stiffness and easy fatigability. A genetic investigation was performed. Mutation analyses showed a homozygous p.Tyr150* (c.450C > A) mutation in patients 1, 2 and 3 and a homozygous p.Leu159Cysfs*11 (c.475delC) mutation in patient 4 in the CLCN1 gene. These mutations have never been reported before and in silico analyses showed that the mutations were disease causing. They may be predicted to cause nonsense-mediated mRNA decay. Our data expand the spectrum of CLCN1 mutations and provide insights for genotype–phenotype correlations of myotonia congenita.

The aim of this study was to analyse the frequency of genotypes and alleles of single-nucleotide polymorphism (SNP)-G2677T/A (rs2032582) of MDR1 gene and to investigate the significance this genetic variation exerts on drug-resistant epilepsy (DRE) in the Polish adult population. The study comprised 340 patients treated for DRE and 240 patients treated for drug-responsive epilepsy. Three hundred and sixty disease-free individuals were used as controls. Genomic DNA was isolated, and the SNP G2677T/A of MDR1 was determined by High-Resolution Melter technique. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each genotype and allele. In this paper, we have demonstrated that A allele of SNP G2677T/A of MDR1 may reduce the risk of DRE (OR 0.44; 95% CI 0.33-0.58, p 0.0001), whereas allele G itself may be a risk factor for this disease. No differences were found in the distribution of the genotypes and alleles in the studied groups, depending on sex as well as on concomitant diseases (p 0.05). G2677T/A polymorphism of MDR1 may play a significant role in the development of DRE in the Polish patients.

Joob and Wiwanitkit [1] raised two points regarding our paper on neurocysticercosis in Western Europe [2]. First, they considered that there should be comparative data to support our suggestions that the prevalence of neurocysticercosis in Western Europe may be on the rise. This was based on the comparison of reported cases over the past four decades. As clearly stated on our paper, the number of publications and patients with neurocysticercosis steadily increased from 1970 to 2011. Of the 779 patients captured in our review, only 28 were published from 1970 to 1985, and the remaining 751 were reported from 1996 to date. Such an increase goes far beyond an enhanced interest of physicians for publishing neurocysticercosis cases, and clearly reflects an increase in its prevalence. Regarding the second topic raised by Joob and Wiwanitkit, the authors must have been confused. Taeniasis is a food-borne disease acquired by eating undercooked pork meat infested by cysticerci. In contrast, cysticercosis is mostly transmitted from person-to-person [3, 4]. It would be wise to review the life cycle of Taenia solium—clearly described more than one century ago—before commenting on this point, as it may create confusion among readers who are not familiar with the disease complex taeniasis/ cysticercosis. Humans become infected by cysticerci after ingesting Taenia eggs from a Taenia carrier.

The electromagnetic fields (EMF) have various behavioral and biological effects on human body. There are growing concerns about the consequences of exposure to EMF. However, some studies have shown beneficial effects of these waves on human. In this paper, we study the effect of acute, sub acute and long-term exposure to 50 Hz, 0.1 mT magnetic fields (MF) on the seizure induction threshold in mice. 64 mice are used and divided into four groups. Eight mice in any group were selected to be exposed to MF for specific duration and the others were used as a control group. The duration of the applied exposures was as follows: (1) 1 day (acute), (2) 3 days (sub acute), (3) 2 weeks (sub acute), (4) 1 month (long term). The mice were exposed 2 h for a day. After exposure, the pentylentetrazol (PTZ) is injected to the mice to induce seizure and the needed dose for the seizure induction threshold is measured. In the acute exposure, the threshold to induce seizure in the exposed and sham-exposed groups was 44.25 and 46.5 mg, respectively, while the difference was not significant (p value = 0.5). In the sub acute exposure (3 days), the mean amount of drug to induce seizure was 47.38 mg in the exposed and 43.88 mg in the sham-exposed groups, however, the difference was not significant (p value = 0.3). The results were 52.38 and 46.75 mg after 2 weeks of exposure which were not significantly different either (p value = 0.2). After 1 month of exposure to MF, the threshold for the induction of seizure was significantly increased (p value

The aim of this study is to present a diagnostic and therapeutic approach in patients with LETM. In a period between June 2008 and June 2010, all patients who fulfilled criteria for LETM were included in the study. All patients underwent a standardized protocol of investigations presented in this paper. Ten patients were included (5 male, 5 female, with the age distribution from 24 to 70 years). Four patients were diagnosed with NMO/spatially limited NMO spectrum disorder, three patients were diagnosed with spinal cord ADEM, two multiple sclerosis (MS) and one patient with copper deficiency myelopathy. Laboratory support for the diagnosis of NMO was positive NMO-IgG antibody ; for the diagnosis of ADEM signs of peripheral nervous system involvement on electromyoneurography ; and for the diagnosis of MS brain MRI lesions typical for MS, as well as positive oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). All cases with inflammatory myelopathy were treated either with steroids or plasma exchange and copper replacement was started in the case of copper deficiency. The mean time from the first symptom until the final diagnosis was 16.3 months (range 1 month to 7 years). As each of idiopathic inflammatory demyelinating diseases that can present with LETM have specific therapy, the postponement in making the correct diagnosis can lead to a poor recovery. In patients with LETM, a standardized diagnostic approach can result in a correct diagnosis and appropriate treatment.

For the most part, the central nervous system is unable to regenerate. The majority of injuries of vascular, inflammatory, degenerative and traumatic aetiology lead to an irreversible loss of central nervous system function. The paper presents the role of Nogo-A, MAG and OMgp proteins in the inhibition of central nervous system regeneration, and their potential clinical significance.

In patients with drug resistant epilepsy it is accepted to try different lines of dual therapy before adding a third antiepileptic drug (AED). The usefulness of triple therapy is questionable since it is not likely to improve symptoms but it can increase adverse effects and drug interactions [1]. Despite this, in regular clinical practice it is still used in selected patients. Our paper approaches this controversy from a different angle: in our case series we analyze the outcome after withdrawal of one AED in patients with triple therapy. Our objective is to analyze the change in seizure frequency after reduction of antiepileptic polytherapy from three to two drugs (AEDs). We have analyzed in the database of our Outpatient Epilepsy Clinic the data

A decade ago, stroke was the first leading cause of morbidity and mortality in Croatia. Nowadays, we record reduction in stroke incidence, as well as stroke consequences—invalidity and mortality. These are due to long-term planned actions in the field of public health as well as actions performed by professional organizations. Today, we can be satisfied with improvement in that field, but there are still things we can improve, at the first place improvement of the emergency medicine network due to Croatian-specific topographical characteristics to reduce onset-to- door time. In this paper, we evaluated results from 11 Croatian hospitals in the period 11/2005– 11/2012. To find out about the past and present state in applying thrombolytic therapy in Croatia and to plan further actions in light of new studies and efforts in Europe and in the world, all with the aim of improvement in stroke prevention and acute treatment resulting in reduction of stroke morbidity, mortality and symptomatic intracerebral hemorrhage as well as better functional outcome. Our results have shown that we improved stroke treatment in the last decade, but further actions should be performed to raise public stroke awareness and to improve emergency medicine network as well as in hospital protocols.

The prevalence of restless legs syndrome (RLS) is increased in gluten sensitive enteropathy (GSE); but prevalence of GSE is not known in RLS. 96 RLS patients and 97 healthy controls, both with or without iron deficiency were enrolled. All secondary RLS patients except iron deficiency were excluded. Subjects underwent a thorough biochemistry and routine blood analyses, and tissue transglutaminase antibodies (TTGA), endomysium antibodies (EMA) and gliadin antibodies (AGA) were also tested. In RLS patients positivity rates of all GSE antibodies were similar to those in controls. The rate of iron deficiency anaemia in RLS patients with at least one positive GSE antibody was significantly higher than that of RLS patients whose GSE antibodies were all negative. The prevalence of GSE antibodies in RLS patients is not increased. GSE might have a role in the aetiology of RLS in association with iron deficiency anaemia. Since the prevalence of GSE antibodies is not increased in RLS, it seems unlikely that GSE is involved in the aetiology of RLS through different mechanisms (e.g. immunological mechanisms) other than iron deficiency as proposed in some published papers.

Focal cortical dysplasia is a malformation caused by abnormalities of cortical development. It is characterized by no dysmorphic or ballon cells (type I), dysmorphic neurons witout or with ballon cells (type II). It is the main cause of pharmacoresistant epilepsy. The combination of clinical and neurophysiological findings provided by VEEG and MRI had lead to an improvement in the diagnosis and outcome of FCD. This paper describes our experience in the form of a retrospective study conducted on the patients affected by FCD who were treated in the Clinical Neurophysiology Service at University Hospital of Lille in France.

This paper proposes therapeutic guidelines for the management of some epileptic syndromes in infants, children, and adolescents, based on available medical literature and clinical practice in the French Community of Belgium. The guidelines address both epileptic encephalopathies (West syndrome, Lennox-Gastaut syndrome, and Dravet syndrome) and idiopathic epilepsies (typical absence seizures, epilepsy with centro-temporal spikes and juvenile myoclonic epilepsy).

In patients with Parkinson's disease with higher prevalence than in current population there appear pathological behaviours characterized by compulsion, repetitiveness and impulsivity, which are connected with material profit or pleasurable experience. They are, in particular, pathological gambling, hypersexuality, compulsive shopping and compulsive eating (in the literature they are collectively referred to as impulse control disorders). Pathological preoccupation with repeated mechanical activities (so-called punding) and excessive compulsive intake of dopaminergic medication (so-called dopamine dysregulation syndrome or also syndrome of hedonistic homeostatic dysregulation) are of similar nature. The paper treats briefly the risk factors and prevalence of these pathological behaviours. In current clinical practice, these psychiatric complications frequently escape doctors' attention, they are underdiagnosed. Although no generally valid recommendations for their therapy are currently available, they can be influenced medically. Of advantage can be modified dopaminergic medication (usually dose reduction ofdopaminergic agonists); multidisciplinary approach to the problem is appropriate. The pathological behaviours given above can frequently lead to considerable material losses and markedly aggravate patients' handicap in the social sphere; it can be expected that in the future they can become a problem also from the ethical and legal points of view.

While the most common neurological disorder associated with Human T lymphotropic virus type-1 (HTLV-1) infection in the endemic areas is HTLV-1 associated myelopathy also know as tropical spastic paraparesis (HAM/TSP), other disorders such as optic neuropathy, peripheral neuropathy and cerebellar diseases have also been reported in patient with this infection. In this paper, we studied the prevalence of peripheral nerve involvement in patients with HAM/TSP.Seventy three patients diagnosed with HAM/TSP in accordance to criteria set by the World Health Organization (WHO) were evaluated in this cross-sectional study. Clinical and electrodiagnostic criteria were used for the diagnosis of peripheral neuropathy.Electrodiagnostic studies showed that 30.1% of patients with HAM/TSP had peripheral nerve involvement. All patients had predominantly axonal neuropathy with sensory-motor polyneuropathy being the most common neuropathy observed in our patients.Peripheral neuropathy may be more common than previously thought and should be checked systematically in all patients with HAM/TSP.

Several abnormal synkinetic eye movements during jaw movements may often be seen after trauma or congenitally in the Marcus Gunn jaw winking phenomenon. The most frequent type consists of unilateral ptosis and retraction of the ptotic lid upon moving the jaw. The authors describe a case with isolated simultaneous adduction of the left eye upon jaw movement. This paper presents a rare case of Marcus Gunn jaw winking with trigemino-oculomotor synkinesis.

Epilepsy is one of the most frequent neurological disorders. Despite the advances and improvements in treatment of seizure disorders, immunologic alterations related to anticonvulsant drugs have been described. The aim of this paper is to assess the effect of some antiepileptic drugs on serum immunoglobulin levels in epileptic patients. Seventy-one patients with epilepsy were included in the study. Participants were divided into three groups based on their treatment with carbamazepine (n=33), sodium valproate (n=22) or phenobarbital (n=16) as monotherapy. Three samples were taken from each patient and serum immunoglobulin levels were measured before treatment, 3 months and 6 months after therapy. Overall, eleven patients out of 71 (15.5%) had a decrease in at least one serum immunoglobulin level (more than 2SD below age-matched control). In the patients receiving carbamazepine, 8 patients (24.2%) showed significant decline in at least one immunoglobulin (3 cases in IgA and 5 cases in IgG). In the group of treated with sodium valproate, 2 patients showed significant decrease in serum IgA level. Results of the last group indicated a significant reduction in serum IgG concentration only in one patient. No patient at all showed significant decrease in serum IgM level. This study suggests that anti-epileptic drugs could reduce serum immunoglobulins, especially IgA and IgG; among them carbamazepine effect is of more concern.

The large choice of antiepileptic drugs (AEDs) in Belgium complicates the selection of the appropriate product for the individual patient. International guidelines on the treatment of epilepsy have been published, but are not tailored to the Belgian situation. This publication presents recommendations from a group of Belgian epilepsy experts for the practical management of epilepsy in general practice in Belgium. It includes recommendations for initial monotherapy and add-on treatment in adult patients (or = 16 years) and initial monotherapy in paediatric patients (16 years). For these three situations a first choice AED is recommended. One or more alternative first choice AEDs are defined for patients in which certain patient- or AED-related factors preclude the use of the first choice product. Selection of compounds was based on the registration and reimbursement status in Belgium, the level of evidence of efficacy, common daily practice and the personal views and experiences of the authors. The paper reflects the situation in 2008. In addition to the treatment recommendations, other relevant points to consider in the treatment of epilepsy with AEDs are addressed, including comorbidity and age of the patient, the interaction potential, pharmacokinetic properties and safety profile of the AEDs, and generic substitution.

The large choice of antiepileptic drugs (AEDs) in Belgium complicates the selection of the appropriate product for the individual patient. International guidelines on the treatment of epilepsy have been published, but are not tailored to the Belgian situation. This publication presents recommendations from a group of Belgian epilepsy experts for the practical management of epilepsy in general practice in Belgium. It includes recommendations for initial monotherapy and add-on treatment in adult patients (> 16 years) and initial monotherapy in paediatric patients (< 16 years). For these three situations a first choice AED is recom mended. One or more alternative first choice AEDs are defined for patients in which certain patient- or AED-related factors preclude the use of the first choice product. Selection of compounds was based on the registration and reimbursement status in Belgium, the level of evidence of efficacy, common daily practice and the personal views and experiences of the authors. The paper reflects the situation in 2008. In addition to the treatment recommendations, other relevant points to consider in the treatment of epilepsy with AEDs are addressed, including comorbidity and age of the patient, the interaction potential, pharmacokinetic properties and safety profile of the AEDs, and generic substitution.

We read with interest the comments of Prof. Garraux on our recent case report describing a 71-year-old woman presenting with right-sided hemidystonia following an ischemic stroke. The initial title of our paper was: ‘‘Hemidystonia caused by a frontoparietal cortical infarction’’. However, we now receive the comment that according to the published computed tomography axial images of the brain, the causal lesion is located in the postcentral gyrus of the left parietal lobe. Indeed, we must agree that the lesion shown in image 1A of the manuscript is located in the left postcentral gyrus of the parietal lobe. Compliance with ethical standards

Seizures starting in patients over 60 years old are frequent. Diagnosis is sometimes difficult and frequently under- or overrated. Cerebrovascular disorders are the main cause of a first seizure. Because of more frequent comorbidities, physiologic changes, and a higher sensitivity to drugs, treatment has some specificity in elderly people. The aim of this paper is to present the result of a consensus meeting held in October 2004 by a Belgian French-speaking group of epileptologists and to propose guidelines for the management and the treatment of epilepsy in elderly people.

Epilepsy and psychiatric diseases are frequent comorbidities. Psychoses in patients with epilepsy have special physiopathology and several clinical presentations and prognoses. Their treatments are also specific, according to the specific diagnosis. This paper represents the summary of a consensus meeting held in November 2003 by a Belgian French-speaking group of neurologists, neuropediatricians and psychiatrists and proposes guidelines for the recognition and treatment of those entities.

The spinal cord, brain, optic nerves and peripheral nerves may be affected by vitamin B12 (cobalamin) deficiency. Deficiency of vitamin B12 also causes megaloblastic anaemia, meaning that the red blood cells are usually larger than normal. In this paper we report a 16-year old girl who was referred to us for the evaluation of mild paraparesis and paresthesias marked by tingling "pins and needles" feelings and general weakness. The patient, her parents and sisters were on a strict vegan diet, which made us believe that vitamin B12 deficiency may be the possible cause of the neurologic clinical manifestations. The serum level of vitamin B12 was low, but there was no macrocytosis in the routine blood examination. The electrophoresis of haemoglobin was pathologic, there was 3.7% of HbA2 and 11.6% of HbF (heterozygous form of beta-thalassaemia). When megaloblastic anaemia occurs in combination with a condition that gives rise to microcytic anaemia, many megaloblastic features may be masked. Instead of being macrocytic, the anaemia could be normocytic or even microcytic. Vitamin B12 deficiency is a diagnosis that must not be overlooked. This case report turns the light on the fact that increased MCV is a hallmark in vitamin B12 deficiency, but it is not an obligatory sign.

Dear Readers, On behalf of the editorial team of the Acta Neurologica Belgica I wish you and your family all the best for 2013. 2013 will be our 2nd ‘‘Springer’’ year and should further increase the success and visibility of the journal. To give you a brief overview of some ANB’s life, I shall pinpoint some of the figures presented by our editorial manager Paola Teti during the editorial board meeting of December 11, 2012. Submissions increased to 431 in 2012, an absolute record for the ANB. Only 30 % were accepted for publication: 101 articles were printed in volume 112, but 63 articles were in addition already published online at the end of 2012. ANB benefits from the world’s leading internet scientific information portal, ‘‘SpringerLink’’, and from the numerous consortia agreements for online deals by Springer. As by December 2012, 3,275 full text downloads were performed for ANB articles and 4,701 tables of contents (ToC) alerts were sent. The increase in visibility has generated an important supplementary workload for the editors and I take this opportunity to sincerely thank my co-editors. However, one other crucial step in the success chain of the journal is the peer review process. This is why we are especially grateful to our reviewers who are listed below with the number of papers they handled. We hope that we can continue to count on you for the rest of volume 113,.. and beyond. Thank you!