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Recovery from ischaemic stroke is determined in the acute phase by the lesion impact of ischaemia and subsequently, by functional and structural network changes in the spared brain tissue. Neurorehabilitation supports the restitution of function using repetitive, learning-based and, more recently, technology-based training strategies.

Background The biomechanical properties of the brain have increasingly been shown to relate to brain pathology in neurological diseases, including multiple sclerosis (MS). Inflammation and demyelination in MS induce significant changes in brain stiffness which can be linked to the relative abundance of glial cells in lesions. We hypothesize that the biomechanical, in addition to biochemical, properties of white (WM) and gray matter (GM)-derived microglia may contribute to the differential microglial phenotypes as seen in MS WM and GM lesions. Methods Primary glial cultures from WM or GM of rat adult brains were treated with either lipopolysaccharide (LPS), myelin, or myelin+LPS for 24 h or left untreated as a control. After treatment, microglial cells were indented using dynamic indentation to determine the storage and loss moduli reflecting cell elasticity and cell viscosity, respectively, and subsequently fixed for immunocytochemical analysis. In parallel, gene expression of inflammatory-related genes were measured using semi-quantitative RT-PCR. Finally, phagocytosis of myelin was determined as well as F-actin visualized to study the cytoskeletal changes. Results WM-derived microglia were significantly more elastic and more viscous than microglia derived from GM. This heterogeneity in microglia biomechanical properties was also apparent when treated with LPS when WM-derived microglia decreased cell elasticity and viscosity, and GM-derived microglia increased elasticity and viscosity. The increase in elasticity and viscosity observed in GM-derived microglia was accompanied by an increase in Tnfα mRNA and reorganization of F-actin which was absent in WM-derived microglia. In contrast, when treated with myelin, both WM- and GM-derived microglia phagocytose myelin decrease their elasticity and viscosity. Conclusions In demyelinating conditions, when myelin debris is phagocytized, as in MS lesions, it is likely that the observed differences in WM- versus GM-derived microglia biomechanics are mainly due to a difference in response to inflammation, rather than to the event of demyelination itself. Thus, the differential biomechanical properties of WM and GM microglia may add to their differential biochemical properties which depend on inflammation present in WM and GM lesions of MS patients.

Application of continuous repetition of motor imagery can improve the performance of exercise tasks. However, there is a lack of more detailed neurophysiological evidence to support the formulation of clear standards for interventions using motor imagery. Moreover, identification of motor imagery intervention time is necessary because it exhibits possible central fatigue. Therefore, the purpose of this study was to elucidate the development of fatigue during continuous repetition of motor imagery through objective and subjective evaluation. The study involved two experiments. In experiment 1, 14 healthy young volunteers were required to imagine grasping and lifting a 1.5-L plastic bottle using the whole hand. Each participant performed the motor imagery task 100 times under each condition with 48 hours interval between two conditions: 500 mL or 1500 mL of water in the bottle during the demonstration phase. Mental fatigue and a decrease in pinch power appeared under the 1500-mL condition. There were changes in concentration ability or corticospinal excitability, as assessed by motor evoked potentials, between each set with continuous repetition of motor imagery also under the 1500-mL condition. Therefore, in experiment 2, 12 healthy volunteers were required to perform the motor imagery task 200 times under the 1500-mL condition. Both concentration ability and corticospinal excitability decreased. This is the first study to show that continuous repetition of motor imagery can decrease corticospinal excitability in addition to producing mental fatigue. This study was approved by the Institutional Ethics Committee at the Nagasaki University Graduate School of Biomedical and Health Sciences (approval No. 18121302) on January 30, 2019., Neural Regeneration Research, 16(6), pp.1031-1036; 2020

Contains fulltext : 231758.pdf (Publisher’s version ) (Open Access) It was hypothesized that mesenchymal stem cells (MSCs) could provide necessary trophic factors when seeded onto the surfaces of commonly used nerve graft substitutes. We aimed to determine the gene expression of MSCs when influenced by Avance® Nerve Grafts or NeuraGen® Nerve Guides. Human adipose-derived MSCs were cultured and dynamically seeded onto 30 Avance® Nerve Grafts and 30 NeuraGen® Nerve Guides for 12 hours. At six time points after seeding, quantitative polymerase chain reaction analyses were performed for five samples per group. Neurotrophic [nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), pleiotrophin (PTN), growth associated protein 43 (GAP43) and brain-derived neurotrophic factor (BDNF)], myelination [peripheral myelin protein 22 (PMP22) and myelin protein zero (MPZ)], angiogenic [platelet endothelial cell adhesion molecule 1 (PECAM1/CD31) and vascular endothelial cell growth factor alpha (VEGFA)], extracellular matrix (ECM) [collagen type alpha I (COL1A1), collagen type alpha III (COL3A1), Fibulin 1 (FBLN1) and laminin subunit beta 2 (LAMB2)] and cell surface marker cluster of differentiation 96 (CD96) gene expression was quantified. Unseeded Avance® Nerve Grafts and NeuraGen® Nerve Guides were used to evaluate the baseline gene expression, and unseeded MSCs provided the baseline gene expression of MSCs. The interaction of MSCs with the Avance® Nerve Grafts led to a short-term upregulation of neurotrophic (NGF, GDNF and BDNF), myelination (PMP22 and MPZ) and angiogenic genes (CD31 and VEGFA) and a long-term upregulation of BDNF, VEGFA and COL1A1. The interaction between MSCs and the NeuraGen® Nerve Guide led to short term upregulation of neurotrophic (NGF, GDNF and BDNF) myelination (PMP22 and MPZ), angiogenic (CD31 and VEGFA), ECM (COL1A1) and cell surface (CD96) genes and long-term upregulation of neurotrophic (GDNF and BDNF), angiogenic (CD31 and VEGFA), ECM genes (COL1A1, COL3A1, and FBLN1) and cell surface (CD96) genes. Analysis demonstrated MSCs seeded onto NeuraGen® Nerve Guides expressed significantly higher levels of neurotrophic (PTN), angiogenic (VEGFA) and ECM (COL3A1, FBLN1) genes in the long term period compared to MSCs seeded onto Avance® Nerve Grafts. Overall, the interaction between human MSCs and both nerve graft substitutes resulted in a significant upregulation of the expression of numerous genes important for nerve regeneration over time. The in vitro interaction of MSCs with the NeuraGen® Nerve Guide was more pronounced, particularly in the long term period (> 14 days after seeding). These results suggest that MSC-seeding has potential to be applied in a clinical setting, which needs to be confirmed in future in vitro and in vivo research.

TheKleine-Levin syndrome (KLS)is classied among rare diseases[1, 2]. It belongs to the central hypersomnias said to be recurrent and dened according to the International Classication of Sleepiness Disorders, 3rd version (ICSD-3), revised in 2014. For the ICSD-3, the Kleine-Levin syndrome is a disorder characterized by recurrent episodes of hypersomnia andhyperphagia (rapidconsumptionof a large amountoffood),usually with onset in early adolescence inmales but occasionally in laterlife and in women.Amonosymptomatic form of the disorder with hypersomnia only can occur with- out binge eating or hypersexuality [1]. Usually affecting adolescent males, episodes normally last up to a few weeks and terminate with total and spontaneous recovery. Possibly rst reported by Brierre de Bosmont in 1862, the condition however received its name from Willi Kleinewho,in1925,reporteda seriesof casesofperiodichypersomnia and also Max Levin who described a case of periodic hypersomnia and excessive appetite in1930[2].The exactprevalence remainsunknown.But it seems very rare: around one to two cases per million. All cases are not published. A review of the inter- national literature of language between 1962and2004,byArnulf et al.[2], estimatedthenumberofpublishedcases at186.Accordingtotheseauthors,theannualincidencewas2.7in1970,3.5 in 1980, and 5.8 in the 1990s. For these authors, this growth would rather correspond to the extension ofthe globalscientic communication than an actual increase in the prevalence of the syndrome. Patients were described aroundtheworld,includingAsiaandAfrica,withcuriouslyone-sixthofthe world's cases described in Israel [1, 2]. Its etiology remains unknown. The genetic trail was discussed in the presence of familial cases [1, 2]. The diseasemainlyaffectsyoungmales[1,2].Itsdiagnosisisclinical[1,3,4].

ObjectivesIncident ischaemic stroke (IS) risk may increase not only with lipids concentration but also with longer duration of exposure. This study aimed to investigate the impact of cumulative burden of lipid profiles on risk of incident IS.MethodsA total of 43 836 participants were enrolled who participated in four surveys during 2006–2013. Individual cumulative lipid burden was calculated as number of years (2006–2013) multiplied by the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C and triglyceride (TG), respectively. The primary outcome was defined as the incident IS during 2012–2017.ResultsDuring 4.67 years (±0.70 years) follow-up on average, we identified 1023 (2.33%) incident IS. Compared with respective reference groups, the HRs (95% CIs) of the upper tertile in cumulative TG burden, cumulative LDL-C burden, cumulative TC burden and cumulative non-HDL-C burden were 1.26 mmol/L (1.02–1.55 mmol/L), 1.47 mmol/L (1.25–1.73 mmol/L), 1.33 mmol/L (1.12–1.57 mmol/L) and 1.51 mmol/L (1.28–1.80 mmol/L) for incidence of IS, respectively. However, this association was not significant in cumulative HDL-C burden and IS (HR: 1.09; 95% CI: 0.79 to 1.52), after adjustment for confounding variables. Among 16 600 participants with low cumulative LDL-C burden, HRs (95% CI) for TC, TG, non-HDL-C and HDL-C with IS were 1.63 mmol/L (1.03–2.57 mmol/L), 1.65 mmol/L (1.19–2.31 mmol/L), 1.57 mmol/L (1.06–2.32 mmol/L) and 0.98 mmol/L (0.56–1.72 mmol/L), respectively.ConclusionsWe observed the correlation between cumulative burden of lipid profiles, except for cumulative burden of HDL-C, with the risk of incident IS. Cumulative burden of TC, TG and non-HDL-C may still predict IS in patients with low cumulative LDL-C burden.Trial registration numberChiCTR-TNRC-11001489.

Introduction: Cannabis and its synthetic analogues are currently the most widely consumed illicit substances worldwide. Multiple alterations have been linked to its use, including cerebrovascular disease (CVD) or stroke, whose association with the substance has been based mainly on the hypothesis of transient vasoconstriction, which explains a large proportion of the cases reported. However, epidemiological studies have not performed an individual analysis of patients without other cardiovascular risk factors, which may limit the estimation of the risk of stroke associated with cannabis use alone. Development: A systematic literature review was conducted through Medline, EBSCOhost, EMBASE, Lilacs, and Scielo to gather case reports published before 13 May 2016 presenting patients with a diagnosis of CVD or transient ischaemic attack, a history of cannabinoid use, and no other cardiovascular risk factors. Key words such as stroke, cerebrovascular disease, cannabis, and marijuana, among others, were used. A total of 18 case reports were selected from the 566 references found. Conclusions: There is a wide variety of reports of stroke associated with cannabis use in patients with no other risk factors. Noteworthy findings were presentation at young age and a strong temporal association, which place cannabis use as a potential risk factor for this population in line with the epidemiological and pathophysiological studies in this area. Resumen: Introducción: El cannabis y sus análogos sintéticos corresponden actualmente a las sustancias ilícitas de mayor consumo a nivel mundial. Resultan múltiples las alteraciones con las cuales se ha relacionado su consumo, y dentro de estas se encuentra la enfermedad cerebrovascular (ECV) o ictus, cuya asociación con esta sustancia se ha fundamentado principalmente a través de la hipótesis de vasoconstricción transitoria, la cual explica una amplia proporción de los casos descritos. Sin embargo, los estudios epidemiológicos realizados no han desarrollado un análisis individual en los pacientes sin otros factores de riesgo cardiovascular, lo que puede limitar la estimación del riesgo que confiere por sí mismo el consumo de esta droga. Desarrollo: Se realizó una revisión sistemática de la literatura a través de Medline, EBSCOhost, EMBASE, Lilacs y Scielo hasta el 13 de mayo de 2016 considerando estudios de tipo «Caso clínico» que presentaran pacientes con diagnóstico de ECV o ataque isquémico transitorio e historia de consumo de cannabinoides sin otros factores de riesgo cardiovascular. Se utilizaron palabras clave como ictus; enfermedad cerebrovascular; cannabis; marihuana, entre otras. Finalmente, de las 566 referencias encontradas fueron seleccionados 18 casos clínicos. Conclusiones: Existe una amplia variedad de publicaciones de ictus asociado a consumo concomitante de cannabis en pacientes sin otros factores de riesgo, destacando una presentación a edad joven y una alta temporalidad, lo que, en concordancia con los estudios epidemiológicos y fisiopatológicos en esta área, ubica a esta sustancia como un potencial factor de riesgo para esta población.

Background Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare and rapidly progressive leukoencephalopathy characterized by cognitive, motor, and neuropsychiatric symptoms, which is often misdiagnosed. Magnetic resonance imaging (MRI) signs and follow-up MRI of CSF1R-related leukoencephalopathy could help in establishing a diagnosis, but these features are not widely known by general neurologists. Case presentation A 34-year-old man was admitted for progressive weakness of the right limbs over 8 months. His father and sister had a similar clinical evolution. The primary neurological signs were hemiplegia, cognitive decline, dysarthria, pyramidal signs, ataxia and parkinsonism, and rapid disease progression. Cerebrospinal fluid analysis results were normal. Despite receiving treatment for improving cerebral metabolism and relieving the muscle spasm, his symptoms did not improve significantly. Brain MRI showed lesions concentrated in the corpus callosum and the deep white matter of the bilateral parieto-occipital lobes, periventricular areas, and corticospinal tracts. There was an enhanced lesion after a gadolinium-enhanced MRI scan. Over the 8-month progression, the lesions always exhibited restricted diffusion. The diffuse lesions gradually increased as the disease progressed. Genetic sequencing results showed a novel heterozygous missense mutation (c.2267 T > C p.L756P) in the CSF1R gene. The patient was treated with citicoline and idebenone for 4 days to improve cerebral metabolism, but his symptoms did not improve significantly. Conclusion The multiple lesions involving the pyramidal tract and white matter showed continuously restricted diffusion on brain imaging and gradually increased with disease progression.

Achmed Pircher,1,2 Albert Neutzner,3 Margherita Montali,4 Andreas Huber,5 Hendrik PN Scholl,2,6 Jatta Berberat,7 Luca Remonda,7 Hanspeter E Killer3 1Department of Neuroscience/Ophthalmology, Uppsala University, Uppsala, Sweden; 2Department of Ophthalmology, University Hospital Basel & University Basel, Basel, Switzerland; 3Department of Biomedicine, University Hospital Basel & University Basel, Basel, Switzerland; 4Department of Ophthalmology, San Bassiano Hospital, Bassano del Grappa, Italy; 5Department of Medicine, Private University of the Principality of Lie Triesen, Triesen, Liechtenstein; 6Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland; 7Department of Neuroradiology, Cantonal Hospital Aarau, Aarau, SwitzerlandCorrespondence: Achmed PircherDepartment of Neuroscience/Ophthalmology, Uppsala University, Uppsala, SwedenTel +46 76 496 37 51Email achmed.pircher@gmail.comObjective: To report on the lipocalin-type prostaglandin D synthase (L-PGDS) concentrations in the cerebrospinal fluid (CSF) of the perioptic and lumbar subarachnoid space (SAS) in patients with radiologically proven optic nerve (ON) sheath compartmentation presenting as normal-tension glaucoma (NTG).Methods: Retrospective biochemical analysis of CSF in thirteen patients with ON sheath compartmentation presenting as NTG (four females, mean age 70± 8 years). CSF was sampled from the SAS of the ON during ON sheath fenestration for ON sheath compartmentation and from the lumbar SAS at the time of lumbar puncture. Nephelometry was used for the quantification of L-PGDS and albumin concentration. Albumin was measured in order to assess the amount of contamination with serum in the CSF samples taken from the ON SAS. Main outcome measures were L-PGDS concentrations in the CSF of the perioptic and lumbar SAS.Results: Mean L-PGDS concentration was 24± 8 mg/L in the lumbar SAS compared to 33± 27 mg/L without correction of serum contamination and 45± 39 mg/L after correction of serum contamination in the perioptic SAS. The difference between the lumbar and the perioptic SAS was statistically significant (P=0.0047 without correction of serum contamination, P=0.0002 with correction of serum contamination; Mann–Witney U-test).Conclusion: This study demonstrates a concentration gradient of L-PGDS levels within the CSF with a statistically significant higher concentration in the compartmentalized perioptic SAS compared to that in the lumbar SAS. Biochemical changes in the perioptic SAS might be involved in the pathophysiology in NTG patients with ON sheath compartmentation.Keywords: lipocalin-type prostaglandin D synthase, cerebrospinal fluid, optic nerve sheath compartment syndrome, normal-tension glaucoma, optic nerve

Background We examined in cognitively intact older adults the relative weight of cognitive, genetic, structural and amyloid brain imaging variables for predicting cognitive change over a 4-year time course. Methods One hundred-eighty community-recruited cognitively intact older adults (mean age 68 years, range 52–80 years, 81 women) belonging to the Flemish Prevent Alzheimer’s Disease Cohort KU Leuven (F-PACK) longitudinal observational cohort underwent a baseline evaluation consisting of detailed cognitive assessment, structural MRI and 18F-flutemetamol PET. At inclusion, subjects were stratified based on Apolipoprotein E (APOE) ε4 and Brain-Derived Neurotrophic Factor (BDNF) val66met polymorphism according to a factorial design. At inclusion, 15% were amyloid-PET positive (Centiloid >23.4). All subjects underwent 2-yearly follow-up of cognitive performance for a 4-year time period. Baseline cognitive scores were analysed using factor analysis. The slope of cognitive change over time was modelled using latent growth curve analysis. Using correlation analysis, hierarchical regression and mediation analysis, we examined the effect of demographic (age, sex, education) and genetic variables, baseline cognition, MRI volumetric (both voxelwise and region-based) as well as amyloid imaging measures on the longitudinal slope of cognitive change. Results A base model of age and sex explained 18.5% of variance in episodic memory decline. This increased to 41.6% by adding baseline episodic memory scores. Adding amyloid load or volumetric measures explained only a negligible additional amount of variance (increase to 42.2%). A mediation analysis indicated that the effect of age on episodic memory scores was partly direct and partly mediated via hippocampal volume. Amyloid load did not play a significant role as mediator between age, hippocampal volume and episodic memory decline. Conclusion In cognitively intact older adults, the strongest baseline predictor of subsequent episodic memory decline was the baseline episodic memory score. When this score was included, only very limited explanatory power was added by brain volume or amyloid load measures. The data warn against classifications that are purely biomarker-based and highlight the value of baseline cognitive performance levels in predictive models.

Short survival of glioblastoma (GBM) patients is due to systematic tumor recurrence. Our laboratory identified a GBM cell subpopulation able to leave the tumor mass (TM) and invade the subventricular zone (SVZ-GBM cells). SVZ-GBM cells escape treatment and appear to contribute to GBM recurrence. This study aims to identify proteins specifically expressed by SVZ-GBM cells and to define their role(s) in GBM aggressiveness and recurrence. The proteome was compared between GBM cells located in the initial TM and SVZ-GBM cells using mass spectrometry. Among differentially expressed proteins, we confirmed B7-H3 by western blot (WB) and quantitative RT-PCR. B7-H3 expression was compared by immunohistochemistry and WB (including expression of its isoforms) between human GBM (N = 14) and non-cancerous brain tissue (N = 8), as well as newly diagnosed GBM and patient-matched recurrences (N = 11). Finally, the expression of B7-H3 was modulated with short hairpin RNA and/or over-expression vectors to determine its functional role in GBM using in vitro assays and a xenograft mouse model of GBM. B7-H3 was a marker for SVZ-GBM cells. It was also increased in human GBM pericytes, myeloid cells and neoplastic cells. B7-H3 inhibition in GBM cells reduced their tumorigenicity. Out of the two B7-H3 isoforms, only 2IgB7-H3 was detected in non-cancerous brain tissue, whereas 4IgB7-H3 was specific for GBM. 2IgB7-H3 expression was higher in GBM recurrences and increased resistance to temozolomide-mediated apoptosis. To conclude, 4IgB7-H3 is an interesting candidate for GBM targeted therapies, while 2IgB7-H3 could be involved in recurrence through resistance to chemotherapy. Supplementary Information The online version contains supplementary material available at 10.1186/s40478-021-01167-w.

Parkinson's disease (PD) is characterised by motor alterations, which are commonly treated with l-DOPA. However, long-term l-DOPA use may cause dyskinesia. Although the pathogenic mechanism of l-DOPA-induced dyskinesia is unclear, the condition has been associated with alterations in dopamine receptors, among which D2 receptors (D2R) have received little attention. This study aims to: (i) develop and standardise an experimental model of l-DOPA-induced dyskinesia in rats with hemiparkinsonism; and (ii) evaluate the correlation between D2R expression and presence of abnormal involuntary movements (AIM). We allocated 21 male Wistar rats into 3 groups: intact controls, lesioned rats (with neurotoxin 6-hydroxydopamine (6-OHDA)), and dyskinetic rats (injected with l-DOPA for 19 days). Sensorimotor impairment was assessed with behavioural tests. Dyskinetic rats gradually developed AIMs during the treatment period; front leg AIMs were more severe and locomotor AIMs less severe (P

Resumen: La enfermedad de Parkinson (EP) se caracteriza por una serie de deficiencias motoras que son tratadas comúnmente con L-DOPA; sin embargo, tras un uso crónico se desarrollan disquinesias inducidas por L-DOPA (DIL). Por otra parte, el origen de las DIL no está del todo claro, pero se asocia con alteración en receptores dopaminérgicos, donde los receptores D2 (RD2) han sido poco estudiados. El presente trabajo buscó: 1) desarrollar y estandarizar un modelo experimental de disquinesia con L-DOPA en ratas hemiparkinsonizadas, y 2) evaluar la correlación entre la expresión del RD2 y la manifestación de movimientos involuntarios anormales (MIA). Se utilizaron 21 ratas Wistar macho asignadas a 3 grupos: control intacto, lesionados (con la neurotoxina 6-OHDA) y lesionados disquinéticos (inyectados con L-DOPA durante 19 días). Los reactivos biológicos se sometieron a pruebas comportamentales para evaluar el deterioro sensoriomotor. Los animales del grupo disquinético desarrollaron de forma gradual MIA durante el tratamiento, siendo mayores los MIA de miembro anterior y menores los de tipo locomotor (p

Objective: This study aimed to investigate the role and prognosis of Alzheimer disease biomarkers in patients with mild cognitive impairment (MCI) at a memory clinic in Latin America. Methods: We studied 89 patients with MCI, 43 with Alzheimer-type dementia, and 18 healthy controls (matched for age, sex, and educational level) at our memory clinic (Instituto FLENI) in Buenos Aires, Argentina. Patients and controls underwent an extensive demographic, neurological, and neuropsychological assessment. All subjects underwent a brain MRI scan; FDG-PET scan; amyloid PET scan; apolipoprotein E genotyping; and cerebrospinal fluid concentrations of Aβ1-42, tau, and phosphorylated tau. Patients were categorised as positive or negative for the presence of amyloid pathology and neurodegeneration. Results: Amyloid pathology was observed in cerebrospinal fluid results in 18% of controls, 64% of patients with MCI, and 92% of patients with Alzheimer-type dementia. Suspected non-Alzheimer disease pathophysiology was found in 11% of controls, 6% of patients with MCI, and 8% of patients with Alzheimer-type dementia. At 30 months of follow-up, 45% of amyloid-positive patients with MCI and 20% of amyloid-negative patients with MCI showed progression to dementia. Conclusions: This study demonstrates biomarker-based MCI prognosis and supports its role in clinical decision-making in daily practice. Resumen: Objetivo: El objetivo de este estudio fue investigar el rol y pronóstico de los biomarcadores de enfermedad de Alzheimer en pacientes con diagnóstico clínico de deterioro cognitivo leve (DCL) en una clínica de memoria de Latinoamérica. Método: Ochenta y nueve pacientes con DCL, 43 con demencia tipo Alzheimer y 18 controles normales apareados por edad, sexo y escolaridad fueron estudiados con un extenso protocolo demográfico, neurológico y neuropsicológico en la clínica de memoria del Instituto FLENI de Buenos Aires. Todos completaron una RM cerebral, una PET con FDG, una PET con estudios amiloideo (PIB), genotipificación de APOE y estudio de Aβ1-42, tau and f-tau de líquido cefalorraquídeo. Basado en la presencia/ausencia de patología amiloidea y neurodegeneración los pacientes fueron categorizados como A+/A− y N+/N− respectivamente. Resultados: En el estudio de líquido cefalorraquídeo el 18% de los controles, el 64% de los DCL y el 92% de las demencia tipo Alzheimer tenían patología amiloidea; y un 11% de los controles, el 6% de los DCL y el 8% de las DTA eran sospechosos de fisiopatología no Alzheimer. En el seguimiento a los 30 meses el 45% de los DCL con amiloide positivo y el 20% de los que presentaron amiloide negativo progresaron a demencia. Conclusiones: Este estudio muestra el pronóstico de los DCL basado en los biomarcadores, y respalda su importancia en la toma de decisiones en la práctica diaria.

Purpose Since pharmacologic agents are the mainstay of epilepsy treatment, drug compliance is one of the most important factors in seizure control. Once-daily levetiracetam (LEV) has been proven to have the same efficacy as that of an immediate-release (IR) formulation. A reduced number of doses may improve drug compliance and patient satisfaction. The aim of this study was to assess drug compliance and patient satisfaction when changing from IR to an extended-release (ER) formulation. Methods Adolescent patients diagnosed with epilepsy who were taking LEV from 2018 to 2020 were included in this study. Compliance charts were reviewed retrospectively. We compared the frequency of seizure occurrence with the frequency of skipping doses and adverse effects before and after changing formulations. Changes in subjective compliance and satisfaction were also investigated. Results Among 585 patients taking LEV, 44 were included in this study. The average age of the included patients was 16.4±2.0 years. There was no significant change in the average seizure frequency (P=0.491) after switching formulations. Objective compliance based on chart records significantly improved after switching formulations (P=0.021). Additionally, 26 of 44 patients mentioned how they felt about switching formulations, of whom 25 (96.2%) were satisfied with the ER formulation. Thirteen of 24 patients (54.2%) reported better compliance. Conclusion Our study shows that the efficacy of LEV ER was similar to that of the IR formulation. The reduced number of medication doses improved patient satisfaction and medication compliance. LEV ER may be preferable in adolescent epilepsy patients.

Resumen: Introducción: Las hemorragias subaracnoideas corticales (HSAc) tienen numerosas etiologías. No hay estudios prospectivos que indiquen su evolución a largo plazo. El objetivo de este trabajo es describir las características clínicas y etiológicas de los pacientes con HSAc y conocer su pronóstico. Métodos: Estudio observacional, prospectivo y multicéntrico. Se recogieron variables clínicas y radiológicas, y se siguió la evolución al año, observando la mortalidad, dependencia, tasa de resangrado y aparición de demencia. Resultados: Se incluyeron 34 pacientes (edad media 68,3 años, rango 27-89). Los síntomas más frecuentes fueron el déficit neurológico focal, con frecuencia transitorio y de repetición, y la cefalea. El TAC fue patológico en 28 pacientes (85%). Se realizó RM cerebral en 30 pacientes (88%), con isquemia aguda en 10 (29%), sangrados antiguos en 7 (21%) y siderosis superficial en otros 2 (6%). Se encontró etiología en 26 pacientes (76,5%): angiopatía amiloide (n = 8), ictus isquémico (n = 5), vasculitis (n = 4), encefalopatía posterior reversible (n = 2), trombosis venosa (n = 2), síndrome de vasoconstricción cerebral reversible (n = 2), oclusión carotidea (n = 1), síndrome de Marfan (n = 1) y carcinomatosis meníngea (n = 1). Durante el seguimiento fallecieron 3 pacientes (en 2 de ellos relacionado con la causa de la HSAc). Tres pacientes desarrollaron una demencia, 3 presentaron un hematoma lobar y otro una nueva HSAc. Conclusiones: En nuestra serie las causas más frecuentes de HSAc fueron la angiopatía amiloide, el ictus isquémico y la vasculitis. La HSAc tiene peor pronóstico que otras HSA no aneurismáticas. Puede tener numerosas causas y su pronóstico depende de la etiología subyacente. En el anciano existe una frecuente asociación con hemorragia intracraneal y deterioro cognitivo. Abstract: Introduction: Cortical subarachnoid haemorrhage (cSAH) has multiple aetiologies. No prospective study has reported the long-term progression of the condition. The objective of this study is to describe the clinical and aetiological characteristics of patients with cSAH and to gain insight into prognosis. Methods: We performed a prospective, observational, multi-centre study. Data on clinical and radiological variables were collected; during a one-year follow-up period, we recorded data on mortality, dependence, rebleeding, and the appearance of dementia. Results: The study included 34 patients (mean age, 68.3 years; range, 27-89). The most frequent symptoms were headache and focal neurological deficits, which were frequently transient and recurrent. CT scans returned pathological findings in 28 patients (85%). Brain MRI scans were performed in 30 patients (88%), revealing acute ischaemia in 10 (29%), old haemorrhage in 7 (21%), and superficial siderosis in 2 (6%). Aetiology was identified in 26 patients (76.5%): causes were cerebral amyloid angiopathy in 8, ischaemic stroke in 5, vasculitis in 4, reversible posterior encephalopathy in 2, venous thrombosis in 2, reversible cerebral vasoconstriction syndrome in 2, carotid occlusion in 1, Marfan syndrome in 1, and meningeal carcinomatosis in 1. Three patients died during follow-up (2 due to causes related to the cause of cSAH). Three patients developed dementia, 3 had lobar haemorrhages, and one had a second cSAH. Conclusions: The most frequent causes of cSAH in our series were cerebral amyloid angiopathy, ischaemic stroke, and vasculitis. This type of haemorrhage has a worse prognosis than other non-aneurysmal cSAH. There are numerous possible causes, and prognosis depends on the aetiology. In elderly patients, intracranial haemorrhage is frequently associated with cognitive impairment.

Background Immune-mediated neuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP) are treatable neuropathies. Among individuals with diabetic neuropathy, it remains a challenge to identify those individuals who develop CIDP. Corneal confocal microscopy (CCM) has been shown to detect corneal nerve fiber loss and cellular infiltrates in the sub-basal layer of the cornea. The objective of the study was to determine whether CCM can distinguish diabetic neuropathy from CIDP and whether CCM can detect CIDP in persons with coexisting diabetes. Methods In this multicenter, case-control study, participants with CIDP (n = 55) with (n = 10) and without (n = 45) diabetes; participants with diabetes (n = 58) with (n = 28) and without (n = 30) diabetic neuropathy, and healthy controls (n = 58) underwent CCM. Corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD), and dendritic and non-dendritic cell density, with or without nerve fiber contact were quantified. Results Dendritic cell density in proximity to corneal nerve fibers was significantly higher in participants with CIDP with and without diabetes compared to participants with diabetic neuropathy and controls. CNFD, CNFL, and CNBD were equally reduced in participants with CIDP, diabetic neuropathy, and CIDP with diabetes. Conclusions An increase in dendritic cell density identifies persons with CIDP. CCM may, therefore, be useful to differentiate inflammatory from non-inflammatory diabetic neuropathy.

Pablo Galarza,1,* Elhanan Parnasa,2,* Noah Guttmann,3 Joshua M Kruger1 1Neuro-Ophthalmology Service, Department of Ophthalmology, Hadassah Medical Center, Jerusalem, Israel; 2Hebrew University-Hadassah School of Medicine, Jerusalem, Israel; 3Independent Researcher, Toronto, Ontario, Canada*These authors contributed equally to this workCorrespondence: Joshua M KrugerNeuro-Ophthalmology Service, Department of Ophthalmology, Hadassah Medical Center, Jerusalem, IsraelTel +972508946493Email kruger@hadassah.org.ilPurpose: To assess the reliability of automated visual field studies with neurological abnormalities and normal reliability indices that were inconsistent with the remainder of the neuro-ophthalmic assessment.Methods: Retrospective observational study from the clinical practice of a neuro-ophthalmologist at a tertiary referral center.Results: From 2230 patient charts, ten cases were identified that met the inclusion criteria. In eight of the cases repeat visual field testing had no reproducible abnormality. Four of these cases were concerning for a bitemporal or homonymous hemianopia. None of the patients, including the two cases with a reproducible defect, developed any convincing manifestations of an organic disease related to the visual field defect.Conclusion: Our findings suggest that even marked neurological abnormalities on reliable automated visual field tests can be false. When the remainder of the neuro-ophthalmic evaluation is inconsistent with the test result, we recommend that clinicians attempt to immediately repeat the visual field study.Keywords: automated perimetry, visual field, Humphrey, reliability

Resumen: Introducción La pérdida neuronal/axonal progresiva se considera la causa más importante de discapacidad neurológica en la esclerosis múltiple (EM). El sistema visual está frecuentemente afectado en esta enfermedad y su accesibilidad a test funcionales y estructurales ha permitido que se convierta en un modelo para estudiar in vivo la patogenia de la EM. La ecografía orbitaria permite evaluar, de forma no invasiva y en tiempo real, las diversas estructuras de la órbita, incluido el nervio óptico. Material y métodos: Se ha llevado a cabo un estudio observacional ambispectivo en pacientes con EM recogiéndose datos evolutivos de la enfermedad. La ecografía orbitaria se realizó en todos los pacientes según el principio de mínima potencia necesaria (ALARA). También se recogieron los datos de tomografía de coherencia óptica (OCT) en aquellos que tenían realizadas ambas pruebas. El estudio estadístico se efectuó con el programa SPSS 22.0. Resultados: Se encontraron correlaciones estadísticamente significativas entre las medidas ecográficas y la progresión de la enfermedad (p = 0,041 para el ojo derecho y p = 0,037 para el ojo izquierdo), y la Expanded Disability Status Scale (EDSS) final en el seguimiento (p = 0,07 para el ojo derecho y p = 0,043 para el ojo izquierdo). No fue así para los datos referentes a brotes y a otras variables clínicas. Discusión: La medición del diámetro del nervio óptico por ecografía podría utilizarse como medida predictiva en la evolución de la EM, ya que la disminución del mismo se asocia con progresión clínica y mayor discapacidad, medidas con la EDSS. Abstract: Introduction: Progressive neuronal and axonal loss are considered the main causes of disability in patients with multiple sclerosis (MS). The disease frequently involves the visual system; the accessibility of the system for several functional and structural tests has made it a model for the in vivo study of MS pathogenesis. Orbital ultrasound is a non-invasive technique that enables various structures of the orbit, including the optic nerve, to be evaluated in real time. Material and methods: We conducted an observational, ambispective study of MS patients. Disease progression data were collected. Orbital ultrasound was performed on all patients, with power set according to the ‘as low as reasonably achievable’ (ALARA) principle. Optical coherence tomography (OCT) data were also collected for those patients who underwent the procedure. Statistical analysis was conducted using SPSS version 22.0. Results: Disease progression was significantly correlated with ultrasound findings (P = .041 for the right eye and P = .037 for the left eye) and with Expanded Disability Status Scale (EDSS) score at the end of the follow-up period (P = .07 for the right eye and P = .043 for the left eye). No statistically significant differences were found with relation to relapses or other clinical variables. Discussion: Ultrasound measurement of optic nerve diameter constitutes a useful, predictive factor for the evaluation of patients with MS. Smaller diameters are associated with poor clinical progression and greater disability (measured by EDSS).

Background and purposeCurrent randomised controlled trials (RCTs) showed an uncertain benefit of haemostatic therapy on preventing haematoma expansion and improving the outcome in patients with intracerebral haemorrhage (ICH). This meta-analysis aims to systematically evaluate the effect of haemostatic agents on the prevention of haemorrhage growth in patients with high-risk spontaneous ICH predicted by CT signs in RCTs.MethodsA comprehensive search of PubMed, EMBASE and Cochrane library from 1 January 2005 to 30 June 2021 was conducted. RCTs that compared haemostatic agents with placebo for the treatment of spontaneous patients with ICH with high-risk haemorrhage growth were included. The primary endpoint was haematoma expansion at 24 hours. Other major endpoints of interest included 90-day functional outcome and mortality.ResultsThe meta-analysis included four RCTs that randomised 2666 patients with ICH with high-risk haemorrhage growth. Haemostatic therapy reduced the rate of haematoma expansion at a marginally statistically significant level when compared with placebo (OR 0.84; 95% CI 0.70 to 1.00; p=0.051). Subgroup analysis for patients with black hole sign on CT revealed a significant reduction of haematoma expansion with haemostatic therapy (OR 0.61; 95% CI 0.39 to 0.94; p=0.03). However, both the primary analysis and subgroup analyses showed that haemostatic therapy could not reduce the rate of poor functional outcome (modified Rankin Scale >3) or death.ConclusionsHaemostatic therapy showed a marginally significant benefit in reducing early haematoma expansion in patients with high-risk spontaneous ICH predicted by markers on CT scan. However, no significant improvement in functional outcome or reduction of mortality was observed.

Background The cerebrospinal fluid tap test (CSF TT) is used for selecting shunt surgery candidates among patients with idiopathic normal pressure hydrocephalus (iNPH). We aimed to evaluate the predictive value of the CSF TT, by using the Hellström iNPH scale for shunted iNPH patients with a standardized method. Methods One hundred and sixteen shunt-operated iNPH patients were retrospectively included in this study. The gait and balance domains in the iNPH scale were used as outcome measures for the CSF TT and the total iNPH scale score as the postoperative outcome. A positive response to CSF TT was defined as a change of ≥ 5 points in the gait domain and ≥ 16 points in the balance domain. Differences between CSF TT responders and non-responders, sensitivity, specificity, positive and negative predictive values, accuracy, and correlations between changes from baseline to post CSF TT and from baseline to the postoperative follow-up, were calculated. Results In the CSF TT there were 63.8% responders in the gait domain and correspondingly 44.3% in the balance domain. CSF TT responders had a significantly better postoperative outcome in the total scale score (gait P ≤ 0.001, balance P ≤ 0.012) and gait CSF TT responders improved more in gait (P ≤ 0.001) and balance CSF TT responders in balance (P ≤ 0.001). No differences between CSF TT gait or balance responders could be found in neuropsychological or urinary continence assessments postoperatively. The sensitivity and specificity of the CSF TT and the outcome of the total iNPH scale score postoperatively were 68.1% and 52.0% for gait and 47.8% and 68.0% for balance, respectively. Conclusions The CSF TT, with the Hellström iNPH scale as the outcome measure, has clear limitations in predicting postoperative results. The gait domain may be used to predict outcomes for gait, but the balance domain is too insensitive.

Resumen: Introducción: El cannabis y sus análogos sintéticos corresponden actualmente a las sustancias ilícitas de mayor consumo a nivel mundial. Resultan múltiples las alteraciones con las cuales se ha relacionado su consumo, y dentro de estas se encuentra la enfermedad cerebrovascular (ECV) o ictus, cuya asociación con esta sustancia se ha fundamentado principalmente a través de la hipótesis de vasoconstricción transitoria, la cual explica una amplia proporción de los casos descritos. Sin embargo, los estudios epidemiológicos realizados no han desarrollado un análisis individual en los pacientes sin otros factores de riesgo cardiovascular, lo que puede limitar la estimación del riesgo que confiere por sí mismo el consumo de esta droga. Desarrollo: Se realizó una revisión sistemática de la literatura a través de Medline, EBSCOhost, EMBASE, Lilacs y Scielo hasta el 13 de mayo de 2016 considerando estudios de tipo «Caso clínico» que presentaran pacientes con diagnóstico de ECV o ataque isquémico transitorio e historia de consumo de cannabinoides sin otros factores de riesgo cardiovascular. Se utilizaron palabras clave como ictus; enfermedad cerebrovascular; cannabis; marihuana, entre otras. Finalmente, de las 566 referencias encontradas fueron seleccionados 18 casos clínicos. Conclusiones: Existe una amplia variedad de publicaciones de ictus asociado a consumo concomitante de cannabis en pacientes sin otros factores de riesgo, destacando una presentación a edad joven y una alta temporalidad, lo que, en concordancia con los estudios epidemiológicos y fisiopatológicos en esta área, ubica a esta sustancia como un potencial factor de riesgo para esta población. Abstract: Introduction: Cannabis and its synthetic analogues are currently the most widely consumed illicit substances worldwide. Multiple alterations have been linked to its use, including cerebrovascular disease (CVD) or stroke, whose association with the substance has been based mainly on the hypothesis of transient vasoconstriction, which explains a large proportion of the cases reported. However, epidemiological studies have not performed an individual analysis of patients without other cardiovascular risk factors, which may limit the estimation of the risk of stroke associated with cannabis use alone. Development: A systematic literature review was conducted through Medline, EBSCOhost, EMBASE, Lilacs, and Scielo to gather case reports published before 13 May 2016 presenting patients with a diagnosis of CVD or transient ischaemic attack, a history of cannabinoid use, and no other cardiovascular risk factors. Key words such as stroke, cerebrovascular disease, cannabis, and marijuana, among others, were used. A total of 18 case reports were selected from the 566 references found. Conclusions: There is a wide variety of reports of stroke associated with cannabis use in patients with no other risk factors. Noteworthy findings were presentation at young age and a strong temporal association, which place cannabis use as a potential risk factor for this population in line with the epidemiological and pathophysiological studies in this area.

Background Progressive multifocal leukoencephalopathy (PML) can rarely occur in Multiple Sclerosis (MS) patients undergoing dimethyl fumarate (DMF) treatment. Our case stresses the limits of current diagnostic and stratification risk criteria, highlighting the potential role of Magnetic Resonance Imaging (MRI) in advising clinical choices. Case presentation A 54 years old MS male patient treated with DMF, after 3 years of clinical stability developed a subacute clinical worsening. He had no severe lymphopenia but MRI signs suggestive of a coexistence of PML and MS activity. Although his viral title was negative, DMF was discontinued, with clinical and radiological improvement. Conclusions This case highlights the challenges behind PML diagnosis, especially in patients not fulfilling the risk stratification criteria and that might present with concurrent disease activity, stressing the potential role of MRI in informing therapeutic decisions.

Prion diseases are fatal, infectious, and incurable neurodegenerative disorders caused by misfolding of the cellular prion protein (PrPC) into the infectious isoform (PrPSc). In humans, there are sporadic, genetic and infectious etiologies, with sporadic Creutzfeldt-Jakob disease (sCJD) being the most common form. Currently, no treatment is available for prion diseases. Cellular cholesterol is known to impact prion conversion, which in turn results in an accumulation of cholesterol in prion-infected neurons. The major elimination of brain cholesterol is achieved by the brain specific enzyme, cholesterol 24-hydroxylase (CYP46A1). Cyp46A1 converts cholesterol into 24(S)-hydroxycholesterol, a membrane-permeable molecule that exits the brain. We have demonstrated for the first time that Cyp46A1 levels are reduced in the brains of prion-infected mice at advanced disease stage, in prion-infected neuronal cells and in post-mortem brains of sCJD patients. We have employed the Cyp46A1 activator efavirenz (EFV) for treatment of prion-infected neuronal cells and mice. EFV is an FDA approved anti-HIV medication effectively crossing the blood brain barrier and has been used for decades to chronically treat HIV patients. EFV significantly mitigated PrPSc propagation in prion-infected cells while preserving physiological PrPC and lipid raft integrity. Notably, oral administration of EFV treatment chronically at very low dosage starting weeks to months after intracerebral prion inoculation of mice significantly prolonged the lifespan of animals. In summary, our results suggest that Cyp46A1 as a novel therapeutic target and that its activation through repurposing the anti-retroviral medication EFV might be valuable treatment approach for prion diseases.

Background Stroke incidence is reportedly increasing in younger populations, although the reasons for this are not clear. We explored possible reasons by quantifying trends in neurologically focused emergency department (ED) visits, classification of stroke vs. TIA, and imaging use. Methods We performed a retrospective, serial, cross-sectional study using the National Hospital Ambulatory Medical Care Survey to examine time trends in age-stratified primary reasons for visit, stroke/TIA diagnoses, and MRI utilization from 1995 to 2000 and 2005–2015. Results Five million eight hundred thousand ED visits with a primary diagnosis of stroke (CI 5.3 M–6.4 M) were represented in the data. The incidence of neurologically focused reason for visits (Neuro RFVs) increased over time in both the young and in older adults (young: + 111 Neuro RFVs/100,000 population/year, CI + 94 − + 130; older adults: + 70 Neuro RFVs/100,000 population/year, CI + 34 − + 108). The proportion of combined stroke and TIA diagnoses decreased over time amongst older adults with a Neuro RFV (OR 0.95 per year, p p = 0.88, CI 0.95–1.04). Within the stroke/TIA population, no changes in the proportion of stroke or TIA were identified. MRI utilization rates amongst patients with a Neuro RFV increased for both age groups. Conclusions We found, but did not anticipate, increased incidence of neurologically focused ED visits in both age groups. Given the lower pre-test probability of a stroke in younger adults, this suggests that false positive stroke diagnoses may be increasing and may be increasing more rapidly in the young than in older adults.

Introduction: Progressive neuronal and axonal loss are considered the main causes of disability in patients with multiple sclerosis (MS). The disease frequently involves the visual system; the accessibility of the system for several functional and structural tests has made it a model for the in vivo study of MS pathogenesis. Orbital ultrasound is a non-invasive technique that enables various structures of the orbit, including the optic nerve, to be evaluated in real time. Methods: We conducted an observational, ambispective study of MS patients. Disease progression data were collected. Orbital ultrasound was performed on all patients, with power set according to the ALARA (“as low as reasonably achievable”) principle. Optical coherence tomography (OCT) data were also collected for those patients who underwent the procedure. Statistical analysis was conducted using SPSS version 22.0. Results: Disease progression was significantly correlated with ultrasound findings (P = .041 for the right eye and P = .037 for the left eye) and with Expanded Disability Status Scale (EDSS) score at the end of the follow-up period (P = .07 for the right eye and P = .043 for the left eye). No statistically significant differences were found with relation to relapses or other clinical variables. Discussion: Ultrasound measurement of optic nerve diameter constitutes a useful, predictive factor for the evaluation of patients with MS. Smaller diameters are associated with poor clinical progression and greater disability (measured by EDSS). Resumen: Introducción: La pérdida neuronal/axonal progresiva se considera la causa más importante de discapacidad neurológica en la esclerosis múltiple (EM).El sistema visual está frecuentemente afectado en esta enfermedad y su accesibilidad a test funcionales y estructurales ha permitido que se convierta en un modelo para estudiar in vivo la patogenia. La ecografía orbitaria permite evaluar, de forma no invasiva y en tiempo real, las diversas estructuras de la órbita, incluido el nervio óptico (NO). Material y métodos: Se ha realizado un estudio observacional ambispectivo en pacientes con EM recogiéndose datos evolutivos de la enfermedad. La ecografía orbitaria se realizó en todos los pacientes según el principio de mínima potencia necesaria. También se recogieron los datos de tomografía de coherencia óptica (OCT) en aquellos que tenían realiza ambas pruebas. El estudio estadístico se realizó con el programa SPSS 22.0. Resultados: Se encontraron correlaciones estadísticamente significativas entre las medidas ecográficas y la progresión de la enfermedad (p 0.041 para ojo derecho (OD) y p 0.037 para ojo izquierdo (OI), y la EDSS final en el seguimiento (p 0,07 para OD y p 0,043 para OI). No fue así para los datos referentes a brotes y a otras variables clínicas.. Discusión: La medición del diámetro del NO por ecografía podría utilizarse como medida predictiva en la evolución de la enfermedad, ya que la disminución del mismo se asocia con progresión clínica y mayor discapacidad, medidas por EDSS.

Background Aducanumab is an anti-amyloid-β (Aβ) antibody that achieved reduced amyloid pathology in Alzheimer’s disease (AD) trials; however, it is controversial whether it also improved cognition, which has been suggested would require a sufficiently high cumulative dose of the antibody in the brain. Therapeutic ultrasound, in contrast, has only begun to be investigated in human AD clinical trials. We have previously shown that scanning ultrasound in combination with intravenously injected microbubbles (SUS), which temporarily and safely opens the blood-brain barrier (BBB), removes amyloid and restores cognition in APP23 mice. However, there has been no direct testing of how the effects of SUS compare to immunotherapy or whether a combination therapy is more effective. Methods In a study comprising four treatment arms, we tested the efficacy of an Aducanumab analog, Adu, both in comparison to SUS, and as a combination therapy, in APP23 mice (aged 13–22 months), using sham as a control. The active place avoidance (APA) test was used to test spatial memory, and histology and ELISA were used to measure amyloid. Brain antibody levels were also determined. Results We found that both Adu and SUS reduced the total plaque area in the hippocampus with no additive effect observed with the combination treatment (SUS + Adu). Whereas in the cortex where there was a trend towards reducing the total plaque area from either Adu or SUS, only the combination treatment yielded a statistically significant decrease in total plaque area compared to sham. Only the SUS and SUS + Adu groups included animals that had their plaque load reduced to below 1% from above 10%. There was a robust improvement in spatial memory for the SUS + Adu group only, and in this group the level of Adu, when measured 3 days post-treatment, was 5-fold higher compared to those mice that received Adu on its own. Together, these findings suggest that SUS should be considered as a treatment option for AD. Alternatively, a combination trial using Aducanumab together with ultrasound to increase brain levels of the antibody may be warranted.

Purpose Syntaxin-binding protein 1 (STXBP1) mutations are known to result in various phenotypes including Ohtahara syndrome, West syndrome, and autism, collectively referred as STXBP1 encephalopathy. This study aimed to expand our understanding of the genotype–phenotype spectrum of STXBP1 encephalopathy in the Korean pediatric population. Methods Ten patients with STXBP1 mutations were enrolled for a retrospective chart review. The patients were investigated for developmental delay of unknown cause and epileptic encephalopathy at a single center. Results Ten different STXBP1 mutations were identified. Three mutations had not previously been reported (c.1212A>C, c.1497C>G, c1030-2A>G). Eight patients showed early-onset epileptic encephalopathy as the main feature, while the main feature was developmental delay and non-epileptic movements in two patients. The most commonly seen electroencephalographic change was focal/multifocal epileptiform discharges, which were observed in nine patients (90%). The classical burst-suppression pattern was observed in four patients, two of which evolved to show hypsarrthymia. All patients with seizures had drug-resistant epilepsy. The patients suffered from severe developmental delay regardless of seizure frequency. Six patients showed an associated movement disorder or behavioral disorder. Conclusion This study describes the STXBP1 encephalopathy patients in Korean pediatric population, further expanding knowledge of its phenotype spectrum.

Background The risk factors for seizures in patients with intracerebral hemorrhage (ICH) stroke and the effect of seizure prevention by anticonvulsant are not well understood. Limited studies have investigated the risk of seizure after discontinuing antiepileptic drugs in patients with ICH. This study aimed to investigate the role of valproic acid (VA) for seizure prevention and to access the risk of seizure after anticonvulsant withdrawal in patients with spontaneous ICH. Methods Between 2013 and 2015, 177 patients with ICH were enrolled in this 3-year retrospective study. Seizures were classified as early seizure (first seizure within 1 week of ICH), delayed seizure (first seizure after 1 week), and late seizure (any seizure after 1 week). Binary logistic regression was used to evaluate the relationship between baseline clinical factors and late seizures between study periods. VA was prescribed or discontinued based on the decision of the physician in charge. Results Seizures occurred in 24 patients, including early seizure in 6.78% (12/177) of the patients, delayed seizure in 7.27% (12/165) of the patients without early seizure, and late seizure in 9.60% (17/177) of the patients. Most seizures occurred within the first year. Binary logistic regression analysis showed ICH with cortex involvement as the independent risk factor for seizures. VA did not decrease the risk of seizures. Patients with ICH with cortical involvement using anticonvulsants for longer than 3 months did not have a decreased risk of seizures (odds ratio 1.86, 95% CI: 0.43–8.05). Conclusions Spontaneous ICH with cortex involvement is the risk factor for seizure. Most seizures occurred within 1 year after stroke onset over a 3-year follow up. Discontinuation of antiepileptic drug within 3 months in patients does not increase the risk of seizure.

Purpose Through a study of rotavirus gastroenteritis (RVGE) cases experienced over 20 years at our center, we aimed to investigate changes in the ratio of rotavirus-associated benign convulsions with mild gastroenteritis (RaCwG) to RVGE and in patients’ demographics after rotavirus vaccination. Methods We analyzed the data of patients aged ≤6 years who visited Inha University Hospital between January 1999 and December 2019 and were confirmed to have RVGE. Patients were divided according to whether they had convulsions with mild gastroenteritis, and their demographics were compared. The yearly and monthly ratios of RaCwG to RVGE were evaluated. To investigate the effects of rotavirus vaccination, data regarding demographics and prevalence were divided into periods I (pre-vaccination, 1999–2009) and II (post-vaccination, 2010–2019) and compared. Results Altogether, 2,100 children had RVGE, and 50 (2.4%) had RaCwG. RaCwG occurred frequently every 4 to 6 years. Although the total number of RVGE and RaCwG cases significantly decreased in period II versus period I, the ratio of RaCwG to RVGE did not differ between the two groups (P=0.921). The age distribution shifted upwards in period II versus period I (P=0.001), but the sex ratio and seasonal distribution showed no significant difference. Conclusion Considering that the ratio of RaCwG to RVGE is dynamic, an increase in the ratio of RaCwG may be possible in the future. Although there was no change in the ratio of RaCwG to RVGE, the number of RVGE and RaCwG patients decreased simultaneously, suggesting that rotavirus vaccination was effective in preventing RaCwG.

Background As molecular advances have deepened the knowledge on low-grade glioma (LGG), we investigated the effect of higher radiation dose on the survival of IDH-wildtype (IDHwt) LGG. Methods In the current study, 52 IDHwt LGG patients who received radiotherapy were enrolled from the Chinese Glioma Genome Atlas dataset. Radiation doses > 54 Gy were defined as high-dose, whereas doses ≤ 54 Gy were defined as low-dose. We performed univariate and multivariate survival analyses to examine the prognostic role of high-dose radiotherapy. Results In total, the radiation dose ranged from 48.6 Gy to 61.2 Gy, with a median of 55.8 Gy, and 31 patients were grouped into high-dose radiation. Univariate survival analysis indicated that high-dose radiotherapy (p = 0.015), tumors located in the frontal lobe (p = 0.009), and pathology of astrocytoma (p = 0.037) were significantly prognostic factors for overall survival. In multivariate survival analysis, high-dose radiotherapy (p = 0.028) and tumors located in the frontal lobe (p = 0.016) were independently associated with better overall survival. Conclusions In conclusion, high-dose radiotherapy independently improved the survival of IDHwt LGG. This can guide treatments for glioma with known molecular characteristics.

Introduction: Medication overuse headache is a secondary headache in which the regular or frequent use of analgesics can increase the frequency of the episodes, causing the transition from episodic to chronic headache. The prevalence of medication overuse headache is approximately 1%-2%, with higher rates among women aged 30-50 years and with comorbid psychiatric disorders such as depression or anxiety, or other chronic pain disorders. It is important to be familiar with the management of this disease. To this end, the Spanish Society of Neurology’s Headache Study Group has prepared a consensus document addressing this disorder. Development: These guidelines were prepared by a group of neurologists specialising in headache after a systematic literature review and provides consensus recommendations on the proper management and treatment of medication overuse headache. The treatment of medication overuse headache is often complex, and is based on 4 fundamental pillars: education and information about the condition, preventive treatment, discontinuation of the drug being overused, and treatment for withdrawal symptoms. Follow-up of patients at risk of recurrence is important. Conclusions: We hope that this document will be useful in daily clinical practice and that it will update and improve understanding of medication overuse headache management. Resumen: Introducción: La cefalea con uso excesivo de medicación es una cefalea secundaria en la que el uso regular o frecuente de medicación analgésica produce un aumento de la frecuencia de una cefalea de base, pasando de episódica a crónica. La prevalencia de esta entidad está en torno al 1-2%, siendo más frecuente en mujeres entre 30 y 50 años con comorbilidades psiquiátricas como depresión o ansiedad y otros procesos de dolor crónico. Es importante conocer el manejo de esta entidad. Por este motivo, el Grupo de Estudios de Cefaleas de la Sociedad Española de Neurología ha pretendido realizar este documento de consenso sobre esta patología. Desarrollo: Esta guía ha sido redactada por un grupo de expertos a partir de la revisión de la evidencia científica publicada y estableciendo recomendaciones prácticas para su adecuado manejo y tratamiento. El tratamiento de la cefalea con uso excesivo de medicación tiene varios pilares fundamentales y suele ser complejo: información y educación sobre el desarrollo de la cefalea con uso excesivo de medicación, tratamiento preventivo, suspensión del fármaco de uso frecuente y tratamiento de deshabituación. Es importante el seguimiento de pacientes con riesgo de recurrencias. Conclusiones: Esperamos que este documento resulte de utilidad y permita su aplicación práctica en la consulta diaria y que sirva para actualizar y mejorar el conocimiento del manejo de esta patología.

Introduction Transient ischemic attack (TIA) is considered to be an important risk factor for the development of ischemic stroke and requires complete etiopathogenic evaluation and prompt initiation of secondary prevention treatment. In addition, an accurate differential diagnosis should be performed in order to exclude other disorders mimicking TIA. Methods In this case report, we describe the clinical and neuroimaging evaluation and the differential diagnosis of a patient with suspected crescendo TIAs. Results A 79-year-old man presented with recurrent episodes of right-sided numbness over the past 7 months, despite different single and dual antiplatelet therapies that were sequentially prescribed for suspected TIAs. Brain MRI revealed cortical superficial siderosis, symmetrical periventricular leukoencephalopathy and enlarged perivascular spaces. Cerebral amyloid angiopathy was considered in the differential diagnosis of the patient. Antiplatelet withdrawal was recommended and led to complete remission of the patient’s transient focal neurological episodes (TFNE) that were initially misdiagnosed as TIAs. Discussion Cortical superficial siderosis has been implicated as a key neuroimaging feature of cerebral amyloid angiopathy, a diagnosis which can be supported by the additional radiological findings of symmetrical white matter hyperintensities and enlarged perivascular spaces. Antiplatelet treatment in patients with cortical superficial siderosis may increase the frequency and severity of TFNE, while it increases exponentially the risk of intracerebral hemorrhage. The present case highlights that recognition of cortical superficial siderosis is crucial in the management of patients presenting with transient focal neurological symptoms that can be misdiagnosed as recurrent TIAs.

Objective: This study aimed to investigate the role and prognosis of Alzheimer disease biomarkers in patients with mild cognitive impairment (MCI) at a memory clinic in Latin America. Methods: We studied 89 patients with MCI, 43 with Alzheimer-type dementia, and 18 healthy controls (matched for age, sex, and educational level) at our memory clinic (Instituto FLENI) in Buenos Aires, Argentina. Patients and controls underwent an extensive demographic, neurological, and neuropsychological assessment. All subjects underwent a brain MRI scan; FDG-PET scan; amyloid PET scan; apolipoprotein E genotyping; and cerebrospinal fluid concentrations of Aβ1-42, tau, and phosphorylated tau. Patients were categorised as positive or negative for the presence of amyloid pathology and neurodegeneration. Results: Amyloid pathology was observed in cerebrospinal fluid results in 18% of controls, 64% of patients with MCI, and 92% of patients with Alzheimer-type dementia. Suspected non–Alzheimer disease pathophysiology was found in 11% of controls, 6% of patients with MCI, and 8% of patients with Alzheimer-type dementia. At 30 months of follow-up, 45% of amyloid-positive patients with MCI and 20% of amyloid-negative patients with MCI showed progression to dementia. Conclusions: This study demonstrates biomarker-based MCI prognosis and supports its role in clinical decision-making in daily practice. Objetivo: este estudio tuvo como objetivo investigar el papel y el pronóstico de los biomarcadores de la enfermedad de Alzheimer en pacientes con deterioro cognitivo leve (MCI) en una clínica de memoria en América Latina. Métodos: Estudiamos 89 pacientes con LM, 43 con demencia de tipo Alzheimer y 18 controles sanos (emparejados por edad, sexo y nivel educativo) en nuestra clínica de memoria (Instituto FLENI) en Buenos Aires, Argentina. Los pacientes y los controles se sometieron a una extensa evaluación demográfica, neurológica y neuropsicológica. Todos los sujetos se sometieron a una resonancia magnética cerebral; FDG-PET scan; tomografía PET amiloide; apolipoproteína E genotipado; y concentraciones de líquido cefalorraquídeo de Aβ1-42, tau y tau fosforilada. Los pacientes fueron categorizados como positivos o negativos por la presencia de patología amiloide y neurodegeneración. Resultados: se observó patología de amiloide en los resultados del líquido cefalorraquídeo en el 18% de los controles, el 64% de los pacientes con LM y el 92% de los pacientes con demencia de tipo Alzheimer. La sospecha de fisiopatología no relacionada con la enfermedad de Alzheimer se encontró en el 11% de los controles, el 6% de los pacientes con MCI y el 8% de los pacientes con demencia de tipo Alzheimer. A los 30 meses de seguimiento, el 45% de los pacientes con amiloide positivo con MCI y el 20% de los pacientes con amiloide negativo con MCI mostraron progresión a demencia. Conclusiones: este estudio demuestra el pronóstico de MCI basado en biomarcadores y apoya su papel en la toma de decisiones clínicas en la práctica diaria.

Introduction Brachial plexus lipomas are extremely rare benign tumors that may cause slow progression of neurological deficits leading to thoracic outlet syndrome. Up to now, surgery remains challenging. The aim of this study is to present our surgical treatment regime and long-term neurological outcome in three cases of giant brachial plexus lipomas and to show results of systematic review.Patients and Methods Retrospective analysis of our database “peripheral nerve lesion” to identify patients suffering from brachial plexus lipomas between January 1, 2012, and December 31, 2019. Systematic review was performed for literature published until March 31, 2020, analyzing PubMed, Google Scholar, Scopus, and the Cochrane Collaboration Library independently by two authors.Results Over the past years, three patients suffering from giant brachial plexus lipomas attended to our neurosurgical department. All patients underwent preoperative magnetic resonance imaging (MRI), ultrasound examinations, and electrophysiological testing. Tumors were removed microsurgically via anterior/posterior, supraclavicular/infraclavicular, and combined approaches. The patients were accessed postoperatively by MRI and clinical follow-up. Systematic review of the literature revealed 22 cases, which were analyzed in regard to demographics, surgical treatment, and neurological outcome.Conclusion Brachial plexus lipomas are an extremely rare cause for brachial plexus compression. Total microsurgical removal with intraoperative electrophysiological monitoring is the treatment of choice with excellent long-term MRI and clinical outcome.

The central role of the resident innate immune cells of the brain (microglia) in neurodegeneration has become clear over the past few years largely through genome-wide association studies (GWAS), and has rapidly become an active area of research. However, a mechanistic understanding (gene to function) has lagged behind. That is now beginning to change, as exemplified by a number of recent exciting and important reports that provide insight into the function of two key gene products – TREM2 (Triggering Receptor Expressed On Myeloid Cells 2) and PLCγ2 (Phospholipase C gamma2) – in microglia, and their role in neurodegenerative disorders. In this review we explore and discuss these recent advances and the opportunities that they may provide for the development of new therapies.

Objective There is a scarcity of research evaluating gender differences in depressive symptoms among patients undergoing cervical surgery. This study investigated gender differences with regard to depressive symptom severity, measured by Patient Health Questionnaire-9 (PHQ-9), in patients following anterior cervical discectomy and fusion (ACDF) or artificial disc replacement (ADR). Methods A prospectively maintained surgical registry was retrospectively reviewed for eligible spine surgeries. Depressive symptom severity was evaluated by PHQ-9 at both preand postoperative timepoints (e.g. , 6 weeks, 12 weeks, 6 months, 1 year, and 2 years). A chi-square test and Student t-test evaluated differences between the gender for demographic and operative variables where appropriate. Differences between the gender subgroup mean PHQ-9 scores were assessed using a t-test pre- and postoperatively (e.g. , 6 weeks, 12 weeks, 6 months, and 1 year) and a paired t-test was used to assess differences from preoperative scores at each postoperative time point. Results A total of 170 subjects underwent 125 ACDFs and 45 ADRs. Both pre- and postoperative timepoints demonstrated no significant differences between mean PHQ-9 scores by gender. Female patients demonstrated statistically significant improvement in PHQ-9 scores at 6 weeks, and 12 weeks, but not through 2 years. Male patients demonstrated statistically significant improvement in PHQ-9 scores at 6 weeks, 12 weeks, 6 months, 1 year, and 2 years. Conclusion Although there were no significant differences between mean PHQ-9 score between the genders, there was a difference in magnitude of improvement. Females had a significant improvement in depressive symptom severity over baseline at the 6- and 12-week timepoints only, whereas males had significant improvement through 2 years postoperatively.

Objective Diffuse idiopathic skeletal hyperostosis (DISH) causes spinal ankylosis, which can result in patients suffering specific spinal fractures that lead to a reduction in the activities of daily life in older patients. Currently, DISH is associated with diabetes mellitus and cardiovascular disease; however, the association between DISH and metabolic syndrome has not been established. The purpose of this study was to investigate a potential association between DISH and metabolic syndrome. Methods We retrospectively reviewed clinical data from consecutive subjects undergoing the musculoskeletal health medical checkups, and enrolled 327 subjects (174 men and 153 women; mean, 63.4 ± 13.7-years). Subjects who had spinal ankylosis at least 4 contiguous vertebral bodies were classified as the DISH group (n = 39) while the others were part of the non-DISH group (n = 288). The definition of the metabolic syndrome comes from diagnostic criteria used by the Japanese Society for Internal Medicine. Age, sex, body max index (BMI), hematological evaluation, blood pressure, presence of metabolic syndrome, the visceral fat area on abdominal computed tomography, and spinal epidural lipomatosis (SEL) on magnetic resonance imaging were evaluated. Results Compared to the non-DISH group, in the DISH group, mean age (DISH group, 74.3 years; non-DISH group, 1.9 years; p < 0.001), male prevalence were higher (DISH group, 82.1%; non-DISH group, 49.3%; p < 0.001), and BMI was greater (DISH group, 24.8; non-DISH group, 23.0; p = 0.006). the metabolic syndrome was more frequently observed in DISH group (28.9%) than in the non-DISH group (16.0%) (p = 0.045). The visceral fat area was significantly larger in the DISH group than in the non-DISH group (DISH group, 130.7 ± 58.2 cm2; Non-DISH group, 89.0 ± 48.1 cm2; p < 0.001). The prevalence of SEL was similar between the 2 groups (10.3% in the DISH group vs. 8.7% in the nonDISH group; p = 0.464). Poisson regression analysis revealed that the metabolic syndrome was significantly associated with DISH with odds ratio of 2.0 (95% confidence interval, 1.0–3.7; p = 0.004). Conclusion Metabolic syndrome was significantly associated with DISH. Our data showed metabolic syndrome is potentially related to DISH.

Objective Obesity has become a public health crisis and continues to be on the rise. An elevated BMI has been linked to higher rates of spinal degenerative disease requiring surgical intervention. Limited studies exist that evaluate the effects of obesity on peri-operative complications in patients undergoing anterior cervical discectomy and fusion (ACDF). Our study aims to determine the incidence of obesity in the ACDF population and the effects it may have on postoperative in-patient complications. Methods The National Inpatient Sample was evaluated from 2004 to 2014 and discharges with International Classification of Diseases procedure codes indicating ACDF were identified. This cohort was stratified into patients with diagnosis codes indicating obesity. Separate univariable followed by multivariable logistic regression analysis were performed for the likelihood of peri-operative inpatient outcomes among the patients with obesity. Results From 2004 to 2014 an estimated 1,212,475 ACDFs were identified in which 9.2% of the patients were obese. The incidence of obesity amongst ACDF patients has risen dramatically during those years from 5.8% to 13.4%. Obese ACDF patients had higher inpatient likelihood of dysphagia, neurological, respiratory, and hematologic complications as well as pulmonary emboli, and intraoperative durotomy. Conclusion Obesity is a well-established modifiable comorbidity that leads to increased perioperative complications in various surgical specialties. We present one of the largest retrospective analyses evaluating the effects of obesity on inpatient complications following ACDF. Our data suggests that the number of obese patients undergoing ACDF is steadily increasing and had a higher inpatient likelihood of developing peri-operative complications.

Objective Joint manipulation for craniovertebral junction instability is often hindered by the C2-ganglion (C2G). Our study aims to compare the surgical outcome among patients with or without C2G preservation and discuss the technical nuances. Methods We did a prospective, bicentric study and included all the operated patients with craniovertebral junction anomaly. The outcome was assessed by the Pain Numeric Rating Scale, Patient Satisfactions Score, and Stony Brook Scar Evaluation Scale. The fusion was assessed using Lenke fusion grade. Results One hundred seventy-one patients (88 in group A and 83 in group B) were included. The most common symptom was spastic quadriparesis (n = 165, 96.5%) with median Nurick grade 3.3. Thirteen patients had suboccipital numbness and 12 patients had paraesthesia. Mean blood loss in group A was 490 ± 96.2 mL and group B was 525 ± 45.7 mL; median operative time was 217.9 and 162.2 minutes in the groups A and B, respectively (p < 0.05). At the follow-up (median, 46.8 months), Lenke fusion grade A was achieved in 92.4% and grade B in 7.6%. A trend suggesting better functional outcomes (numbness, parestheisa, scar outcome, and postoperative ulcer formation) in group A was seen with all 6 patients, who underwent O-C2 fixation, developed pressure sore. Conclusion Our results support ganglion preservation, especially in the subset of patients where occipital plating is required. Although the study fails to show any statistical significance, we suggest that one should always start with an ‘intent’ of preservation as the functional outcome is better.

Objective The conventional criteria for defining the basilar invagination (BI) focus on the relationship of odontoid tip to basion and opisthion, landmarks that are intrinsically variable especially in presence of occipitalised atlas. A universal single reference line is proposed that helps in unequivocally establishing the diagnosis of BI, may be relevant in establishing both Goel types A and B BI, as well as in differentiating a ‘very high’ from ‘regular’ BI. Methods Study design – case-control study. In 268 patients (group I with BI [n = 89] including Goel type A BI [n = 66], Goel type B BI [n = 23], and group II controls [n = 179]), the perpendicular distance between odontoid tip and line subtended between posterior tip of hard palate-internal occipital protuberance (P-IOP line) was measured. Logistic regression analysis determined factors influencing the proposed parameter (p < 0.05). Results In patients with a ‘very high’ BI (n = 5), the odontoid tip intersected/or was above the P-IOP line. In patients with a ‘regular’ BI (n = 84), the odontoid tip was 6.56 ± 3.9mm below the P-IOP line; while in controls, this distance was 12.53 ± 4.28 mm (p < 0.01). In Goel type A BI, the distance was 7.01 ± 3.78 mm and in type B BI, it was 5.07 ± 4.19 mm (p = 0.004). Receiver-operating characteristic curve analysis identified 9.0 mm (8.92–9.15 mm) as the cut-point for diagnosing BI using the odontoid tip-P-IOP line distance as reference. Conclusion The odontoid tip either intersecting the P-IOP line (very high BI) or being < 9 mm below the P-IOP line (Goel types A and B BI) is recommended as highly applicable criteria to establish the diagnosis of BI. This parameter may be useful in establishing the diagnosis in all varieties of BI.

Objective This retrospective study aimed to compare vertebral endplate cyst formation (VECF), an early predictor for pseudoarthrosis, in different types of interbody cages. Methods We reviewed 84 cases treated with single-level posterior/transforaminal lumbar interbody fusion. We utilized a polyetheretherketone cage in 20 cases (group P), a titanium cage in 16 cases (group Ti), a titanium-coating polyetheretherketone cage in 13 cases (group TiP) and a porous tantalum cage in 35 cases (group Tn). VECF was evaluated comparing the computed tomography scans taken at day 0 and 6-month postoperation. We defined VECF (+) as enlargement of a pre-existing cyst or de novo formation of a cyst with the diameter over 2 mm. We calculated the adjusted odds ratio (OR) and 95% confidence intervals (CIs) as an indicator of association between different types of cages and VECF using a logistic regression model. Results VECF was observed in 13 (65%), 7 (44%), 9 (69%), and 8 (23%) cases in groups P, Ti, TiP and Tn, respectively. VECF correlated with the type of cage (p = 0.04). In comparison with group P, the proportion of VECF (+) cases was lower in group Tn (OR, 0.16; 95% CI, 0.04-0.60) but not different in group Ti (OR, 0.47; 95% CI, 0.10-2.20) and group TiP (OR, 1.06; 95% CI, 0.21-5.28). No patient underwent additional surgery for the fused spinal level during the follow-up periods (average, 37.9 months; range, 6-76 months). Conclusion VECF was the least in the porous Tn cage, suggesting its potential superiority for initial stability.

Objective Vertebral aspergillosis is quite rare conditions, often misdiagnosed, that requires long-term antibiotic therapy, and sometimes, surgical treatments. The present investigations were aimed to investigate the epidemiology, clinical-radiological aspects, treatment protocols, and outcomes of Aspergillus-mediated vertebral osteomyelitis. Methods A systematic review of the pertinent English literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed. The research was conducted on Cochrane library, MEDLINE, PubMed, and Scopus using as search-terms “Aspergillus,” “vertebral osteomyelitis,” “spondylodiscitis,” “spine infection.” A case of vertebral aspergillosis conservatively managed was also reported. Results Eighty-nine articles were included in our systematic review. Including the reported case, our analysis covered 112 cases of vertebral aspergillosis. Aspergillus fumigatus was isolated in 68 cases (61.2%), Aspergillus flavus in 14 (12.6%), Aspergillus terreus in 4 (3.6%), Aspergillus nidulans in 2 (1.8%). Seventy-three patients (65.7%) completely recovered at the last follow-up evaluation; in 7 patients (6.3%) radiological signs of chronic infection were reported, whereas 32 patients (28.8%) died during the follow-up. Conclusion This systematic review summarized the state of the art on vertebral aspergillosis, retrieving data on clinical features, diagnostic criteria and current limitations, treatment alternatives, and their outcomes.

We report a long-lived patient with Lafora disease (LD). A 34-year-old woman experienced onset of seizures at the age of 11 years. She was bedridden in her early twenties due to frequent generalized tonic-clonic seizures, myoclonus, and progressive mental deterioration. Her seizures occurred all the time despite administration of multiple anticonvulsants at high doses. At the age of 31, she started perampanel, which resulted in reduction of anticonvulsants after her visible myoclonus and convulsions disappeared. Brain magnetic resonance imaging showed marked cerebral and cerebellar atrophy, and single-photon emission computed tomography using N-isopropyl-p-[123I] iodoamphetamine (IMP-SPECT) revealed significant hypoperfusion of the frontal lobe and cerebellum. We identified a W219R homozygous mutation in exon 1 of the NHLRC1 gene. Because perampanel may not only control seizures but also prevent mental deterioration in LD, we propose that perampanel should be administered from the early stage of LD.

Medial medullary infarction (MMI) is a vascular occlusion in the medulla oblongata leading to certain constellations of neurological symptoms and seriously affecting the patient. Effective evidence-based treatment of severe dysphagia as sole symptom of MMI has not yet been reported. This case study aims to report successful effects of evidence-based therapy based on findings of dysphagia symptoms and pathophysiology of swallowing by flexible endoscopic evaluation of swallowing (FEES) in severe isolated dysphagia after MMI. FEES was performed to evaluate swallowing pathophysiology and dysphagia symptoms in a 57-year-old male with severe dysphagia after MMI. On the basis of FEES findings, simple and high-frequent evidence-based exercises for improvement of swallowing were implemented: thermal stimulation of faucial arches, Jaw Opening Exercise, and Jaw Opening Against Resistance. After 7 weeks of high-frequent evidence-based therapy and regular FEES evaluation the patient was set on full oral diet with no evidence of aspiration risk. In a first case report of isolated dysphagia in MMI our case illustrates that high-frequent evidence-based dysphagia therapy in combination with FEES as the method to evaluate and monitor swallowing pathophysiology can lead to successful and quick rehabilitation of severely affected dysphagic patients.

BackgroundHaemorrhages of brainstem cavernous malformations (CMs) can lead to neurological deficits, the natural history of which is uncertain. The study aimed to evaluate the neurological outcomes of untreated brainstem CMs and to identify the adverse factors associated with worsened outcomes.MethodsFrom 2009 to 2015, 698 patients (321 women) with brainstem CMs were entered into the prospective cohort after excluding patients lost to follow-up (n=43). All patients were registered, clinical data were collected and scheduled follow-up was performed.ResultsAfter a median follow-up of 60.9 months, prospective haemorrhages occurred in 167 patients (23.9%). The mean modified Rankin Scale scores at enrolment and at censoring time were 1.6 and 1.2. Neurological status was improved, unchanged and worsened in 334 (47.9%), 293 (42.0%) and 71 (10.2%) patients, respectively; 233 (33.4%) recovered to normal levels. Lesions crossing the axial midpoint (relative risk (RR) 2.325, p=0.003) and developmental venous anomaly (DVA) (RR 1.776, p=0.036) were independently significantly related to worsened outcomes. The percentage of worsened outcomes was 5.3% (18 of 337) in low-risk patients (neither DVA nor crossing the axial point) and increased to 26.0% (13 of 50) in high-risk patients (with both DVA and crossing the axial point). The percentage of worsened outcomes significantly increased as the number of prospective haemorrhages increased (from 1.5% (8 of 531, if 0 prospective ictus) to 37.5% (48 of 128, if 1 ictus) and 38.5% (15 of 39, if >1 ictus)).ConclusionsThe neurological outcomes of untreated brainstem CMs were improved/unchanged in majority of patients (89.8%) with a fatality rate of 1.7% in our cohort, which seemed to be favourable. Radiological features significantly predicted worsened outcomes. Our results provide evidence for clinical consultation and individualised treatment. The referral bias of our cohort was underlined.

The most malignant type of intrinsic brain tumor is glioblastoma (WHO grade IV). Primary leptomeningeal spread is rare and leads to a variety of differential considerations, as there is no typical clinical or imaging pattern. Here we present a rare and uncommon case of a primary leptomeningeal glioblastoma in combination with a low-grade glioma in a 21-year-old male, initially presenting with only headache and lower back pain. The presented case illustrates the challenging differential considerations and the severe course of leptomeningeal glioblastomas.

The treatment of intracranial aneurysms (IA) has been transformed by the development of flow-diversion (FD) devices. Initially, these revolutionary devices were conceived for giant and fusiform aneurysms located on the internal carotid artery (ICA). Technological improvements have expanded their indications. Distal middle cerebral, anterior cerebral artery aneurysms, or even posterior fossa aneurysms can now benefit from this technology. One other category of aneurysms that can be treated is multiple IA’s. Multiple IA’s are encountered in approximately one-quarter of patients presenting with subarachnoid haemorrhage. Endovascular management of such cases is complex, requiring different devices and treatment strategies to secure all lesions. FD’s can be successfully employed to reconstruct vessels, which harbour more than one aneurysm, especially multiple ICA lesions. Multiple aneurysms located on both ICA’s are generically known as tandem aneurysms. We present the case of a patient with tandem aneurysms located on both intracranial internal carotid arteries that we treated simultaneously with the Pipeline Flex with Shield Technology in one single session. To the best of our knowledge, this is the first case reported in the literature so far.

We analyzed the outcomes of surgical treatment for pituitary metastasis (PM) based on 35 observations. We registered the best estimates of resection radicalism in patients with minor PM, its inconsiderable spread ascending and descending from the diaphragm of the sella turcica, slightly bleeding metastasis, and no invading to the cavernous sinus. Positive changes in the PM patients’ quality of life are chiefly associated with regressed visual impairment, local pain syndrome, and, to a lesser degree, oculomotor disorders. No post-operative regress or intensifying of hormonal impairments, such as diabetes insipidus and hypopituitarism, were seen. The age of patients, the time interval between the cancer diagnosis and the PM occurrence, control of the underlying disease, size of the tumour are the factors determining the life expectancy in PM patients.