Post-reperfusion acute MR diffusion in stroke is a potential predictor for clinical outcome in rats.

Middle cerebral artery occlusion (MCAO) models show substantial variability in outcome, introducing uncertainties in the evaluation of treatment effects. Early outcome predictors would be essential for prognostic purposes and variability control. We aimed to compare apparent diffusion coefficient (ADC) MRI data obtained during MCAO and shortly after reperfusion for their potentials in acute-phase outcome prediction. Fifty-nine male rats underwent a 45-min MCAO. Outcome was defined in three ways: 21-day survival; 24 h midline-shift and neurological scores. Animals were divided into two groups: rats surviving 21 days after MCAO (survival group, n = 46) and rats dying prematurely (non-survival/NS group, n = 13). At reperfusion, NS group showed considerably larger lesion volume and lower mean ADC of the initial lesion site (p < 0.0001), while during occlusion there were no significant group differences. At reperfusion, each survival animal showed decreased lesion volume and increased mean ADC of the initial lesion site compared to those during occlusion (p < 10-6), while NS group showed a mixed pattern. At reperfusion, lesion volume and mean ADC of the initial lesion site were significantly associated with 24 h midline-shift and neurological scores. Diffusion MRI performed soon after reperfusion has a great impact in early-phase outcome prediction, and it works better than the measurement during occlusion.

Investigation of oxidative stress in patients with multifocal motor neuropathy.

Background and purpose: Multifocal motor neuropathy (MMN) is a rare, immune-mediated illness attacking ex-clusively motor nerves. It is known that oxidative stress is present in peripheral neuropathies, but it has not been investigated MMN. Methods: We measured in our prospective study the L-arginine, symmetric and asymmetric dimethylarginine (SDMA, ADMA) serum concentrations of 10 patients and 10 controls before and after intravenous immunoglobulin treatment (IVIG), as markers of the L-arginine/NO pathway involved in chronic inflammation and oxidative stress. The functions of motor nerves were tested in all patients and the serum antiganglioside antibody levels were de-tec-ted, as well. Results: MMN patients showed significantly higher ADMA (p = 0.0048; 0.98 and 0.63, respectively) and SDMA le-vels (p = 0.001; 0.88 and 0.51, respectively) than healthy controls, while L-arginine was not different. Controlling for the covariant age, ADMA (B = -0.474; p = 0.041) or SDMA (B = -0.896; p < 0.0005) serum levels proved to be the significant predictors of the presence of MMN. IVIG therapy decreased significantly ADMA concentrations (p = 0.025; 0.98 and 0.84, respectively) and showed a trend to reduce SDMA levels (p = 0.1; 0.88 and 0.74, respectively). The dimethylamine levels did not correlate with the number of affected nerves, disease duration, or the presence of ganglioside antibodies. The conduction block-related peripheral motor dysfunction improved right after the IVIG treatment. Conclusion: Dimethylamine levels are elevated in the serum and are responsive to IVIG therapy in MMN. These findings support the presence of oxidative stress in MMN.

Prevalence of and Theoretical Explanation for Type 2 Benign Paroxysmal Positional Vertigo.

BACKGROUND AND PURPOSE: A variant of benign paroxysmal positional vertigo (BPPV) involves the subjective report of vertigo without the coinciding nystagmus. This presentation includes truncal retropulsion when sitting up from the ipsilesional provocative test (ie, Dix-Hallpike), which we term type 2 BPPV. The primary objective of this study is to prospectively determine the prevalence and describe the clinical course of type 2 BPPV. We offer a theoretical explanation for the absence of nystagmus. METHODS: Prospective, observational study carried out in 2 tertiary hospitals. One hundred eighty patients (134 women, 46 men) met the inclusion criteria and were included between January 10, 2018, and October 30, 2019. Efficacy of physical therapy maneuvers was determined at 1-week follow-up. Three-dimensional reconstructions of the planes of the semicircular canal cupula from histological preparations are offered as evidence for the theoretical explanation. RESULTS: One-third of the patients met the criteria for type 2 BPPV; the remainder had typical posterior or horizontal semicircular canal involvement. Symptoms from type 2 BPPV were longer in duration yet responded favorably to physical therapy maneuvers. Upon repeat testing, 19 patients treated for posterior canalithiasis developed a slight, persistent positional downbeat nystagmus in the Dix-Hallpike position that we propose as evidence the otoconia entered the short arm of the posterior semicircular canal. DISCUSSION AND CONCLUSIONS: Our data and 3-dimensional rendering suggest the report of vertigo, yet absent nystagmus in type 2 BPPV is from otoconia aligning with the gravitoinertial vector during provocative testing that precludes cupular stimulation. Type 2 BPPV appears to be a common and treatable form of vertigo.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A372).

Population-based head-to-head comparison of the clinical characteristics and epidemiology of AQP4 antibody-positive NMOSD between two European countries.

BACKGROUND: Population-based clinical studies in neuromyelitis optica spectrum disorder (NMOSD) and epidemiological and clinical comparisons of White ethnicities are missing. In a large population-based international cohort, we extensively characterized aquaporin-4 antibody seropositive (AQP4-Ab+) NMOSD, and also compared the clinical, radiological and epidemiological features between two European populations residing in different areas. METHODS: Between self-reported Danish and Hungarian ethnicities, we compared the population-based clinical features, disability outcomes, and death of 134 AQP4-Ab+ NMOSD cases fulfilling the 2015 International Panel for NMO Diagnosis (IPND) criteria. For precise comparison of epidemiology, we conducted a population-based head-to-head comparative study of the age-standardized prevalence (January 1, 2014) and incidence (2007-2013) of AQP4-Ab+ NMO/NMOSD among adults (≥16 years) in Denmark (4.6 million) and Hungary (6.4 million) by applying 2015 IPND (NMOSD) criteria and 2006 Wingerchuk (NMO). RESULTS: Danes were more likely to present with transverse myelitis and were more affected by spinal cord damage on long-term disability. Hungarians presented most often with optic neuritis, although visual outcome was similar in the groups. No differences were observed in sex, disease course, relapse rate, autoimmune comorbidity, mortality, brain MRI, and treatment strategies. The age-standardized prevalence estimates of AQP4-Ab+ NMOSD (2015 IPND criteria) in Denmark vs. Hungary were 0.66 vs. 1.43 (/100,000) while incidence rates were 0.04 vs. 0.11 (/100,000 person-years); similar differences were found based on the 2006 NMO criteria. CONCLUSIONS: This head-to-head comparative study indicates different disease characteristics and epidemiology among White populations in Europe, and substantiates the need for population-based genetic and environmental studies in NMOSD.

Fast 3 T nigral hyperintensity magnetic resonance imaging in Parkinson's disease.

The absence of nigral hyperintensity is a promising MR marker for Parkinson's disease (PD), but its small size imposes limitations on its routine use. Our aim was to compare Multi Echo Data Image Combination (MEDIC), segmented echo-planar imaging (EPISEG) and fluid-attenuated inversion recovery (FLAIR) sequences, as well as both magnitude (MAG) and susceptibility-weighted imaging (SWI) reconstructions of single-echo gradient echo for nigral hyperintensity imaging. Twenty-five healthy and twenty PD subjects were included. Sensitivity to motion artefacts, confidence of the radiologist in interpretation, rate of nondiagnostic scans and diagnostic accuracy were assessed. EPISEG was less motion-sensitive than MEDIC, MAG, and SWI, while FLAIR was less motion-sensitive than MAG and SWI. The reviewers were more confident when using EPISEG compared to any other techniques and MEDIC was superior to FLAIR. The proportions of nondiagnostic scans were lower for EPISEG than for other sequences. The best diagnostic performance was achieved for EPISEG (sensitivity = 65%, specificity = 96%). Using EPISEG, the absence of nigral hyperintensity in PD was associated with higher Hoehn-Yahr stage and MDS-UPDRS II + III. Nigral hyperintensity may be intact at the very early stages of PD. The promising properties of EPISEG may help the transfer of nigral hyperintensity imaging into daily clinical practice.

Application of video-assisted thoracoscopy in the surgical treatment of myasthenia gravis in adults without thymoma / Jobb oldali videoasszisztált thoracoscopos thymectomia a thymoma nélküli, felnottkori myasthenia gravis sebészi kezelésében

Introduction: Surgical technique of thymectomy performed for treatment of myasthenia gravis has considerably changed in the last almost 30 years. In addition to standard interventions ­ transsternal and transcervical thymectomy ­, video-assisted thoracoscopic interventions (VATS), later on robotic surgery came into general use. In our two institutions, we apply VATS thymectomy since 2011. Methods: There are several different surgical techniques for this purpose; we approached the mediastinum through the right thoracic cavity. We prepared initially 3, later on 2 perimammal ports for the access of the thymus; the patients were in supine position during surgery. We used an ultrasonic cutting device in all cases. In order to perform extended thymectomy, we removed the fatty tissue around the thymus and opened widely the left thoracic cavity, too. During patient enrollment, we preferred patients with normal or lower body weight. Results: During 8 years and 4 months, we operated on 92 patients using this method for myasthenia gravis without thymoma; there were 20 male and 72 female patients at the age of 33 years on average (19­75 years). Duration of surgery was 35­160 minutes, 82.3 minutes on average. The bulky fatty tissue around the thymus made the orientation and the complete removal more difficult in a few patients. We experienced vascular injury in 4 cases and injury of the contralateral lung in 3 cases. Conversion was necessary in 2 cases (1 sternotomy and 1 thoracotomy), there were no nerve injuries. Assisted ventilation was necessary in case of ten patients in the postoperative period for a few hours; all other patients were extubated on the operating table. There was no need for repeated intubation and tracheostomy; there was no respiratory insufficiency and perioperative mortality. Duration of ICU care was 1.1 days on the average (0­11 days), that of the total hospital care 4.8 days on average (3­15 days). Duration of thoracic drainage was 1.16 days on average (1­4 days). Two patients (2.41%) died within one and five years after surgery. During 12­108 months (48 months on average) follow-up of 81 patients, 21 patients (25.3%) suffering from myasthenia total recovery was observed, pharmacologic remission was achieved in 4 patients (5.3%), minimal manifestation remained in 23 patients (24.1%), while in 28 patients (33.73%) other improvement was observed. The status of 4 patients (4.82%) remained unchanged and that of 4 patients (5.3%) worsened. Conclusion: VATS thymectomy represents a completely new surgical method for surgeons having experience in transsternal surgical technique. Bulky mediastinal fatty tissue makes surgery very difficult. The perioperative period is advantageous for the patients and also the long term follow-up results are acceptable. It is questionable that the thymus can be completely removed with this method in all cases.

Single Residue Variation in Skeletal Muscle Myosin Enables Direct and Selective Drug Targeting for Spasticity and Muscle Stiffness.

Muscle spasticity after nervous system injuries and painful low back spasm affect more than 10% of global population. Current medications are of limited efficacy and cause neurological and cardiovascular side effects because they target upstream regulators of muscle contraction. Direct myosin inhibition could provide optimal muscle relaxation; however, targeting skeletal myosin is particularly challenging because of its similarity to the cardiac isoform. We identified a key residue difference between these myosin isoforms, located in the communication center of the functional regions, which allowed us to design a selective inhibitor, MPH-220. Mutagenic analysis and the atomic structure of MPH-220-bound skeletal muscle myosin confirmed the mechanism of specificity. Targeting skeletal muscle myosin by MPH-220 enabled muscle relaxation, in human and model systems, without cardiovascular side effects and improved spastic gait disorders after brain injury in a disease model. MPH-220 provides a potential nervous-system-independent option to treat spasticity and muscle stiffness.

Status epilepticus 2020. / Status epilepticus 2020

Status epilepticus is the second most common neurological emergency with 15‒25% mortality rate. The principle of "time is brain" is also true for the treatment of status epilepticus: the earlier we start an adequate treatment, the more likely we are to stop progression. With treatment protocols based on high-level evidence, the progression of status epilepticus can be prevented in 75­90% of cases: we can avoid the induced coma or death. At the beginning of status epilepticus, parenteral benzodiazepine should be given immediately: intramuscular midazolam (0.2 mg/kg, max. 10 mg). In the case of easy veinous access, benzodiazepines can also be given intravenously. If the first benzodiazepine bolus does not stop the status epilepticus, we speak about established (benzodiazepine refractory) status epilepticus. In this case, a fast-acting non-benzodiazepine antiepileptic drug should be given: intravenous valproate (40 mg/kg, max. 3000 mg, within 10 minutes) or levetiracetam (60 mg/kg, max. 4500 mg, within 10 minutes). Refractory status epilepticus that persists for more than 1 hour and does not respond to either benzodiazepines or antiepileptics should be treated with general anesthesia (full narcosis). Induced coma can be achieved with fast-acting anesthetics, a combination of propofol with midazolam is the most frequently used one. Orv Hetil. 2020; 161(42): 1779­1786.

Maternal mosaicism underlies the inheritance of a rare germline AKT3 variant which is responsible for megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome in two Roma half-siblings.

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a developmental brain disorder characterized by an enlarged brain size with bilateral perisylvian polymicrogyria and a variable degree of ventriculomegaly. MPPH syndrome is associated with oromotor dysfunction, epilepsy, intellectual disability and postaxial hexadactyly. The molecular diagnosis of this disorder is established by the identification of a pathogenic variant in either AKT3, CCND2 or PIK3R2. Previously reported AKT3 variants are associated with various brain abnormalities and may lead to megalencephaly. MPPH syndrome is usually due to germline pathogenic AKT3 variants. Somatic mosaic pathogenic variants associated with hemimegalencephaly, which is similar to MPPH, have also been observed. A Hungarian Roma family with two half-siblings, which present with intellectual disability, dysmorphic features, epilepsy, brain malformations, and megalencephaly was studied. Whole exome sequencing (WES) analysis was performed. WES analysis revealed a heterozygous c.1393C > T p.(Arg465Trp) pathogenic missense AKT3 variant in both affected half-siblings. The variant was verified via Sanger sequencing and was not present in the DNA sample from the healthy mother, which was derived from peripheral blood, suggesting maternal germline mosaicism. In conclusion, this is the first report in which maternal germline mosaicism of a rare pathogenic AKT3 variant leads to autosomal dominantly inherited MPPH syndrome.

Small Fiber Neuropathy: Clinicopathological Correlations.

Small fiber neuropathy develops due to the selective damage of the thin fibers of peripheral nerves. Many common diseases can cause this condition, including diabetes, infections, autoimmune and endocrine disorders, but it can occur due to genetic alterations, as well. Eighty-five skin biopsy-proven small-fiber neuropathy cases were analyzed. Forty-one (48%) cases were idiopathic; among secondary types, hypothyreosis (9.4%), diabetes mellitus (7%), cryoglobulinemia (7%), monoclonal gammopathy with unproved significance (4.7%), Sjögren's disease (3%), and paraneoplastic neuropathy (3%) were the most common causes. Two-thirds (68%) of the patients were female, and the secondary type started 8 years later than the idiopathic one. In a vast majority of the cases (85%), the distribution followed a length-dependent pattern. Intraepidermal fiber density was comparable in idiopathic and secondary forms. Of note, we found significantly more severe pathology in men and in diabetes. Weak correlation was found between patient-reported measures and pathology, as well as with neuropathic pain-related scores. Our study confirmed the significance of small fiber damage-caused neuropathic symptoms in many clinical conditions, the gender differences in clinical settings, and pathological alterations, as well as the presence of severe small fiber pathology in diabetes mellitus, one of the most common causes of peripheral neuropathy.

[Treatment of complex regional pain syndrome with amitriptyline]. / Komplex regionális fájdalom szindróma amitriptylinkezelése.

Introduction - Complex regional pain syndrome is a di-stressing neuropathic pain condition without known etiology and evidence based treatment. Case presentation - Here a posttraumatic severe case of complex regional pain syndrome is presented, successfully treated by amitriptyline monotherapy. Amitriptyline is one of the most effective evidence based treatments of peri-pheral diabetic neuropathic pain and other neuropathic pain syndromes. Discussion - Amitriptyline seems to be effective to decrease pain, autonomic and motor symptoms in chronic regional pain syndrome. Conclusion - Controlled trials may be warranted to test the effectiveness of amitriptyline in complex regional pain syndrome.

[Myasthenia gravis: perioperative complications of 1002 transsternal thymectomies - historical overwiev of 34 years long practice at one institution]. / Myasthenia gravis: 1002 transsternalis thymectomia perioperatív szövodményei ­ egy intézmény 34 éves gyakorlata történeti áttekintésben.

Introduction: Thymectomy became an important part of the treatment of myasthenia gravis, since Alfred Blalock reported about his first surgery 80 years ago. Despite of several different surgical techniques already accepted abroad, sternal approach was the almost exclusive exposure for thymectomy in Hungary till 2006. In this publication, we analyze the direct surgical consequences and complications of this method. Methods: At the Surgical Department of Budai MÁV Hospital, 1002 transsternal thymectomies were performed during 34 years on patients suffering from myasthenia gravis. Surgeries were performed for neurological indications, following careful medical investigations, involving specialists in neurology and internal medicine. In cases associated with thymoma, surgery was indicated for two reasons: removal of the thymus and the tumor at the same time. Neurological indications, patient preparation, perioperative treatment and surgical technique have considerably changed during these 34 years. We interpret the results according to the two eras based on the most frequently applied surgical techniques (simple and extended thymectomy); we publish the data separately of the patients with thymoma and those who underwent repeated surgery, focusing basically on breath-related complications. Results: The patients' age was 32 years on the average (8-73 years). Women/men ratio: 3.5:1. Myasthenia gravis was associated with thymoma in 12.7% of the patients. Repeated thymectomy was necessary in case of 11 patients; further two patients required repeated sternotomy after cardiac surgery. Respiratory failure occurred in 21,3% out of 525 myasthenic patients operated in the first 19-year-old era, emergency re-intubation and tracheostomy happened in 12,8% and in 11,2% as well. In the second 15-year-old period postoperative respiratory failure occurred in 12,7% with emergency re-intubation in 7,1% and tracheostomy only in 1,2% out of 338 myasthenic patients. Respiratory failure occurred in 19.1% out of 126 patients operated for thymoma; re-intubation was necessary in 12.8% of the cases and tracheostomy was performed in 20.6% of the patients. Respiratory failure occurred in 13 patients, who underwent repeated surgery (46.1%); the ratio of re-intubation was 15.4% and that of tracheostomies 46.1%. Serious surgical complications were infrequent also in the entire group of patients: 2 patients required repeated surgery due to sternal bleeding; one more patient underwent repeated surgery due to rupture of the drainage tube, 4 cases of mediastinitis in the first group, two cases of heart injury and one case of sternal disruption occurred in the second period. The overall mortality was 1.4%: 1.3% in the first period, 0.3% in the second period, 4% in the thymoma group and 7.7% after repeated surgeries. Conclusions: In a historical overview, the ratio of serious respiratory and airway complications and the mortality after transsternal thymectomies has considerably decreased, but the postoperative respiratory failure and the surgical risk of transsecting the sternum still pose a real risk.

[Chronic orofacial pain]. / Krónikus orofacialis fájdalmak.

Orofacial pain is the common name of a variety of disorders from inflammatory diseases to neuropathic pain syndromes. This condition is quite common, it may involve 7% of the whole population. Patients (and doctors) are not aware of the origin of their complaints, therefore initial management falls among the variety of healthcare professionals. The aim of our review was to summarize the current evidence of chronic orofacial pain including diagnosis, management and pitfalls. Orv Hetil. 2019; 160(27): 1047-1056.

Relationship of Iron Metabolism and Short-Term Cuprizone Treatment of C57BL/6 Mice.

One of the models to investigate the distinct mechanisms contributing to neurodegeneration in multiple sclerosis is based on cuprizone (CZ) intoxication. CZ is toxic to mature oligodendrocytes and produces demyelination within the central nervous system but does not cause direct neuronal damage. The CZ model is suitable for better understanding the molecular mechanism of de- and remyelination processes of oligodendrocytes. CZ is a copper chelating agent and it also affects the iron metabolism in brain and liver tissues. To determine the early effect of CZ treatment on iron homeostasis regulation, cytosolic and mitochondrial iron storage, as well as some lipid metabolism genes, we investigated the expression of respective iron homeostasis and lipid metabolism genes of the corpus callosum (CC) and the liver after short-term CZ administration. In the present study C57BL/6 male mice aged four weeks were fed with standard rodent food premixed with 0.2 w/w% CZ for two or eight days. The major findings of our experiments are that short-term CZ treatment causes significant changes in iron metabolism regulation as well as in the expression of myelin and lipid synthesis-related genes, even before apparent demyelination occurs. Both in the CC and the liver the iron uptake, utilization and storage are modified, though not always the same way or to the same extent in the two organs. Understanding the role of iron in short-term and long-term CZ intoxication could provide a partial explanation of the discrepant signs of acute and chronic MS. These could contribute to understanding the development of multiple sclerosis and might provide a possible drug target.

Wnt pathway markers in molecular subgroups of glioblastoma.

Glioblastoma (GBM) is a highly heterogeneous and aggressive brain tumor. Comprehensive genomic and transcriptomic analyses revealed that GBM segregates into three subgroups with characteristic signaling pathways. The Wnt pathway recently received increasing attention with the recognition of its importance in tumor development and recurrence through the promotion of glioma stem cells. As an extension of our previous translational studies, here we tested the possible interactions between key subgroup markers (IDH-1 R132H, EGFRvIII and both cytoplasmic and nuclear loss [c-/n-] of NF-1 expression) and the canonical (Wnt3a and beta-catenin) and non-canonical (Wnt5a and Fzd2) Wnt pathway markers by immunohistochemistry. These analyses revealed increased expression levels of both Wnt pathway markers with significant quantitative differences within, but not among subgroups. Wnt5a and Fzd2 levels were higher than the canonical marker levels in all subgroups. The strongest evidence for correlation between expression levels of the EGFRvIII subgroup marker and the Fzd2 Wnt marker was found, but weaker correlations also could be noted for IDH-1 R132H and NF-1 and some Wnt markers. The correlations detected between markers of the canonical and non-canonical pathways raised the possibility of cross-talk between the two pathways. Analyses of tumors with various NF-1 expression patterns (c+/n-; c-/n+ combined with c+/n+, and c-/n-) revealed that aberrant nuclear accumulation of NF-1 is accompanied by nuclear accumulation of beta-catenin, suggesting that they may act synergistically to define the tumor's biology. Altogether, our study presents expression characteristics of Wnt ligands and receptors, and suggests complex molecular interactions in subgroups of GBM.

[Postoperative outcome of surgical interventions for epilepsy between 2005 and 2016 at the Epilepsy Center of Pécs]. / Epilepsziasebészeti beavatkozások eredményei a Pécsi Epilepszia Centrumban 2005 és 2016 között.

INTRODUCTION: Epilepsy as a chronic, severe neurologic disease significantly influences the quality of life of the epileptic patients. In candidates well selected for surgery, the seizure freedom is realistically achievable, and the quality of life can be further improved with complex individual rehabilitation. AIM: We aimed to evaluate the postoperative outcome of patients who underwent epilepsy surgery between 2005 and 2016 at the Epilepsy Center at Pécs. METHOD: We evaluated seizure status at regular follow-up visits after surgery and the quality of life using questionnaires focusing on employment and social status. RESULTS: 76% of the 72 patients who underwent surgical resection for epilepsy were free from disabling seizures , and 10% had rare disabling seizures (almost seizure-free), 7% experienced worthwhile improvement and 7% had no worthwhile improvement. Comparing the employment status of patients free from disabling seizures to patients not free from disabling seizures, we found that the employment status is significantly influenced by seizure freedom (p<0.01, Fisher's exact test). While 67% of seizure-free patients were employed, only 19% of patients not free from disabling seizures were hired. CONCLUSION: Our results resemble the international tendencies and success rate, proving epilepsy surgery as an available, valid and effective treatment in well selected patients. Orv Hetil. 2019; 160(7): 270-278.

Investigation of Cuprizone-Induced Demyelination in mGFAP-Driven Conditional Transient Receptor Potential Ankyrin 1 (TRPA1) Receptor Knockout Mice.

Transient receptor potential ankyrin 1 (TRPA1) receptors are non-selective cation channels responsive to a variety of exogenous irritants and endogenous stimuli including products of oxidative stress. It is mainly expressed by primary sensory neurons; however, expression of TRPA1 by astrocytes and oligodendrocytes has recently been detected in the mouse brain. Genetic deletion of TRPA1 was shown to attenuate cuprizone-induced oligodendrocyte apoptosis and myelin loss in mice. In the present study we aimed at investigating mGFAP-Cre conditional TRPA1 knockout mice in the cuprizone model. These animals were generated by crossbreeding GFAP-Cre+/- and floxed TRPA1 (TRPA1Fl/Fl) mice. Cuprizone was administered for 6 weeks and demyelination was followed by magnetic resonance imaging (MRI). At the end of the treatment, demyelination and glial activation was also investigated by histological methods. The results of the MRI showed that demyelination was milder at weeks 3 and 4 in both homozygous (GFAP-Cre+/- TRPA1Fl/Fl) and heterozygous (GFAP-Cre+/- TRPA1Fl/-) conditional knockout animals compared to Cre-/- control mice. However, by week 6 of the treatment the difference was not detectable by either MRI or histological methods. In conclusion, TRPA1 receptors on astrocytes may transiently contribute to the demyelination induced by cuprizone, however, expression and function of TRPA1 receptors by other cells in the brain (oligodendrocytes, microglia, neurons) warrant further investigation.

Ictal piloerection is associated with high-grade glioma and autoimmune encephalitis-Results from a systematic review.

PURPOSE: To comprehensively analyze ictal piloerection (IP) in a large number of subjects. METHODS: We performed a systematic review on case report studies of patients diagnosed with IP (1929-2017) with additional cases included from the Department of Neurology of University of Pécs, the National Institute of Clinical Neurosciences, and Odense University Hospital. Each included case was characterized regarding patient history, IP seizure characteristics, diagnostic work-up, and therapy. Comparative analyses were also carried out based on sex and pathology. RESULTS: Altogether, 109 cases were included. We observed a strong male predominance (p < 0.001). The mean age at onset of epilepsy was 39.5 ± 20.7 years (median: 38, IQR:24-57). The seizure onset zone was temporal (p < 0.001), and was lateralized to the ipsilateral hemisphere in unilateral localization (p = 0.001). The seizure was accompanied by cold shiver in 53%, and by other autonomic symptoms in 47% of cases. In 53% of patients, IP never progressed into complex partial or generalized tonic-clonic seizure; 16% of the patients reported occasional, and 31% regular generalization. Seizure frequency was higher among females (median:25/day, IQR:3-60) than among males (median:3/day, IQR:1-11) (p = 0.017). The two most common underlying pathologies were limbic encephalitis (23%) and astrocytoma (23%, among them 64% WHO III-IV astrocytoma). CONCLUSION: IP was particularly associated with autoimmune encephalitis and high-grade glioma, suggesting IP's particular clinical importance in directing diagnostic work-up.

Comparing Sensitivity and Specificity of Addenbrooke's Cognitive Examination-I, III and Mini-Addenbrooke's Cognitive Examination in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by numerous motor and nonmotor symptoms. Neurocognitive disorders (NCD) are one of the most troublesome problems and their diagnosis is often challenging. METHODS: We compared the sensitivity and specificity of several versions of Addenbrooke Cognitive Examination (ACE, ACE-III, and Mini-ACE) on 552 subjects with PD. Normal cognition, mild and major NCD were judged in accordance with the respective criteria of the Diagnostic and Statistical Manual of Mental Disorders 5th edition. Subsequently, we applied the receiver operation characteristic (ROC) analysis in comparison of different education levels. RESULTS: For subjects with education level 0-8 and 9-12 years, the ACE-III had the best discriminating capabilities for mild NCD (cut-off scores: 83.5 and 85.5 points, respectively), while Mini-ACE was the best for subjects having education > 12 years (cut-off score: 25.5 points). For detecting major NCD, ACE-III had the best diagnostic accuracy in all levels of education (cut-off scores: 70.5, 77.5, and 78.5 points for subjects having education level 0-8, 9-12, and >12 years, respectively). CONCLUSION: ACE-III and its nested version, the Mini-ACE, had the best screening abilities for detecting mild and major NCD in PD.

Behavioural alterations and morphological changes are attenuated by the lack of TRPA1 receptors in the cuprizone-induced demyelination model in mice.

We have recently reported that the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor deficiency significantly attenuated cuprizone-induced demyelination by reducing the apoptosis of mature oligodendrocytes. The aim of the present study was to gather additional data on the role of TRPA1 by investigating the time course of behavioural alterations and morphological changes in cuprizone-treated TRPA1 receptor gene-deficient mice. Demyelination was induced by feeding male wild-type (WT) and TRPA1 gene-deleted (TRPA1 KO) mice with 0.2% cuprizone for 6 weeks. Behavioural tests were performed once per week to follow cuprizone-induced functional changes. Mechanonociceptive thresholds were investigated by a dynamic plantar aesthesiometer and von Frey filaments. Motor performance was assessed by accelerating RotaRod and horizontal grid tests. For the study of spontaneous activity, the open field test was used. The time course of corpus callosum demyelination was also followed weekly by magnetic resonance imaging (MRI). Histological analysis of myelin loss was performed with Luxol Fast Blue (LFB) staining at week 3 and electron microscopy (EM) at week 6. Astrocyte and microglia accumulation at week 3 was assessed by immunohistochemistry (IHC). Cuprizone treatment induced no changes in mechanonociception or motor performance. In the open arena, cuprizone-treated mice spent more time with locomotion, their mean velocity was significantly higher and the distance they travelled was longer than untreated mice. No statistical difference was detected between WT and TRPA1 KO mice in these parameters. On the other hand, significantly increased rearing behaviour was induced in WT mice compared to TRPA1 KO animals. Morphological changes detected with MRI, LFB, IHC and EM analysis revealed reduced damage of the myelin and attenuated accumulation of astrocytes and microglia in cuprizone-treated TRPA1 KO animals, at each examined time point. Our recent data further suggest that inhibition of TRPA1 receptors could be a promising therapeutic approach to limit central nervous system damage in demyelinating diseases.