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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.

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.

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.

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.

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

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.

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.

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

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.

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.

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.

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