Leg spasticity in degenerative compression myelopathy causes impairment of fast and rapid repetitive movements, which tends to appear despite the disproportionate paucity of clinical weakness. As clinically useful measures used to quantify the slowness of voluntary leg movements in this pathological condition, we compared the foot tapping test (FTT) with the simple walking test, which is now considered the gold standard in this field.

This article reviews the current and most neurologic uses of botulinum neurotoxin type A (BoNT-A), beginning with relevant historical data, neurochemical mechanism at the neuromuscular junction. Current commercial preparations of BoNT-A are reviewed, as are immunologic issues relating to secondary failure of BoNT-A therapy. Clinical uses are summarized with an emphasis on controlled clinical trials (as appropriate), including facial movement disorders, focal neck and limb dystonias, spasticity, hypersecretory syndromes, and pain.

The human cholinergic basal forebrain (CBF) is comprised of magnocellular hyperchromic neurons within the septal/diagonal band complex and nucleus basalis (NB) of Meynert. CBF neurons provide the major cholinergic innervation to the hippocampus, amygdala and neocortex. They play a role in cognition and attentional behaviors, and are dysfunctional in Alzheimer's disease (AD). The human CBF displays a continuum of large cells that contain various cholinergic markers, nerve growth factor (NGF) and its cognate receptors, calbindin, glutamate receptors, and the estrogen receptors, ERalpha and ERbeta. Admixed with these cholinergic neuronal phenotypes are smaller interneurons containing the m2 muscarinic acetylcholine receptor (mAChRs), NADPH-diaphorase, GABA, calcium binding proteins and several inhibitory neuropeptides including galanin (GAL), which is over expressed in AD. Studies using human autopsy material indicate an age-related dissociation of calbindin and the glutamate receptor GluR2 within CBF neurons, suggesting that these molecules act synergistically to induce excitotoxic cell death during aging, and possibly during AD. Choline acetyltrasnferease (ChAT) activity and CBF neuron number is preserved in the cholinergic basocortical system and up regulated in the septohippocampal system during prodromal as compared with end stage AD. In contrast, the number of CBF neurons containing NGF receptors is reduced early in the disease process suggesting a phenotypic silence and not a frank loss of neurons. In end stage AD, there is a selective reduction in trkA mRNA but not p75(NTR) in single CBF cells suggesting a neurotrophic defect throughout the progression of AD. These observations indicate the complexity of the chemoanatomy of the human CBF and suggest that multiple factors play different roles in its dysfunction in aging and AD.

Introduction: Patients with glioblastoma (GBM), one of the most aggressive forms of primary brain tumors, exhibit a wide range of neurologic signs, ranging from headaches to neurologic deficits and cognitive impairment, at first clinical presentation. While such variability is attributed to inter-individual differences in increased intracranial pressure, tumor infiltration, and vascular compromise, a direct association with disease stage, tumor size and location, edema, and necrotic cell death has yet to be established. The lack of specificity of neurologic symptoms often confounds the diagnosis of GBM. It also limits clinicians' ability to elect treatment regimens that not only prolong survival but also promote symptom management and high quality of life. Methods: To decipher the heterogeneous presentation of neurologic symptoms in GBM, we investigated differences in the molecular makeup of tumors from patients with and without preoperative neurologic deficits. We used the Ivy GAP (Ivy Glioblastoma Atlas Project) database to integrate RNA sequencing data from histologically defined GBM tumor compartments and neurologic examination records for 41 patients. We investigated the association of neurologic deficits with various tumor and patient attributes. We then performed differential gene expression and co-expression network analysis to identify a transcriptional signature specific to neurologic deficits in GBM. Using functional enrichment analysis, we finally provided a comprehensive and detailed characterization of involved pathways and gene interactions. Results: An exploratory investigation of the association of tumor and patient variables with the early development of neurologic deficits in GBM revealed a lack of robust and consistent clinicopathologic prognostic factors. We detected significant differences in the expression of 728 genes (FDR-adjusted p-value ≤ 0.05 and relative fold-change ≥ 1.5), unique to the cellular tumor (CT) anatomical compartment, between neurologic deficit groups. Upregulated differentially expressed genes in CT were enriched for mesenchymal subtype-predictive genes. Applying a systems approach, we then identified co-expressed gene sets that correlated with neurological deficit manifestation (FDR-adjusted p-value < 0.1). Collectively, these findings uncovered significantly enriched immune activation, oxidative stress response, and cytokine-mediated proinflammatory processes. Conclusion: Our study posits that inflammatory processes, as well as a mesenchymal tumor subtype, are implicated in the pathophysiology of preoperative neurologic deficits in GBM.

Background: The correlation between the severity of hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) and involvement of the complement system has been examined in a small number of studies, with conflicting results. In the present study, we investigated whether serum C3 levels on admission are associated with neurologic involvement. Methods: To this purpose, 68 consecutive STEC-HUS patients were recruited and main clinical and laboratory variables ad hospital admission were compared between those with or without neurologic involvement. Results: STEC-HUS patients who developed neurologic involvement (NI) showed significant higher leukocyte count, C-reactive protein and hemoglobin, and lower sodium levels as compared with those without. Interestingly, baseline serum levels of C3 were significantly lower in patients with NI as compared with those without (p < 0.001). Moreover, when stratified according to need of Eculizumab rescue therapy due to severe NI, patients treated with this drug showed baseline C3 serum levels significantly lower than those who were not (p < 0.001). Low C3 was independent risk factor for NI in our patients' population when entered as covariate in a multivariate logistic regression analysis including other major variables previously proposed as possible predictors of poor prognosis in STEC-HUS (for instance, leukocyte count, c-reactive protein, sodium levels) (HR 6.401, 95%CI 1.617-25.334, p = 0.008 for C3). To underline the role of complement in the worsening of STEC-HUS patients' clinical conditions and outcomes, all patients were divided into two groups according to the baseline lower vs. normal serum levels of C3 and the main data on care needs were assessed. Interestingly more patients with lower C3 serum levels required renal replacement therapy (p = 0.024), anti-hypertensive therapy (p = 0.011), Intensive Care Unit admission (p = 0.009), and longer hospitalization (p = 0.003), thus displaying significantly more severe disease features as compared with those with normal C3 serum levels. Conclusions: Our data suggests that children with STEC-HUS with decreased C3 concentrations at admission are more likely to develop neurologic involvement and are at increased risk of having severe clinical complications.

Achondroplasia is the most common dwarfing disorder. It can result in a variety of sequelae, including neurologic complications, among which high cervical myelopathy is one of particular concern. However, some individuals with achondroplasia appear to have persistent signs by physical examination that, while they might suggest the presence of high cervical myelopathy, remain isolated, non-progressive and apparently benign. To document and quantify these apparently benign craniocervical signs (ABCS) a cohort of 477 individuals with achondroplasia was retrospectively analyzed and information regarding persistent neurologic features suggestive of high cervical myelopathy was recorded in a REDCap database.

Headache is a common symptom during pregnancy and in puerperium that requires careful consideration, as it may be caused by a life-threatening condition. Headaches in pregnant women and women in puerperium are classified as primary or secondary; acute, severe and newly diagnosed headaches should prompt further investigation. We aimed to further characterise the demographic features, symptoms, examination findings, and neuroimaging results of cases of headache during pregnancy and in puerperium. All pregnant women or women in postpartum conditions who attended neurological consultations at the emergency department of the clinic for Gynaecology, Obstetrics and Reproductive Medicine of Saarland University/Germany between 2001/2015 and 2012/2019 were enrolled in this retrospective chart review. Data collected from the charts included demographic/pregnancy characteristics, clinical features and imaging findings. Descriptive statistics as well as binary logistic regression were performed. More than 50% of 97 patients had abnormal findings in their neurological examination. Magnetic resonance imaging findings were pathological for almost 20% of patients-indicating conditions such as cerebral venous thrombosis, reversible posterior leukoencephalopathy, brain tumour and intracranial bleeding. The odds of abnormal neuroimaging results were 2.2-times greater among women with abnormal neurological examination findings than among those with normal examination results. In cases of headache during pregnancy and in puerperium, neuroimaging should be indicated early on. Further research is needed to determine which conditions indicate a need for immediate neuroimaging.

We describe a case series of 35 Ebola virus disease (EVD) survivors during the epidemic in West Africa who had neurologic and accompanying psychiatric sequelae. Survivors meeting neurologic criteria were invited from a cohort of 361 EVD survivors to attend a preliminary clinic. Those whose severe neurologic features were documented in the preliminary clinic were referred for specialist neurologic evaluation, ophthalmologic examination, and psychiatric assessment. Of 35 survivors with neurologic sequelae, 13 had migraine headache, 2 stroke, 2 peripheral sensory neuropathy, and 2 peripheral nerve lesions. Of brain computed tomography scans of 17 patients, 3 showed cerebral and/or cerebellar atrophy and 2 confirmed strokes. Sixteen patients required mental health followup; psychiatric disorders were diagnosed in 5. The 10 patients who experienced greatest disability had co-existing physical and mental health conditions. EVD survivors may have ongoing central and peripheral nervous system disorders, including previously unrecognized migraine headaches and stroke.

Evidences from either small series or spontaneous reporting are accumulating that SARS-CoV-2 involves the Nervous Systems. The aim of this study is to provide an extensive overview on the major neurological complications in a large cohort of COVID-19 patients.

Ancillary tests are frequently used in death determination by neurologic criteria (DNC), particularly when the clinical neurologic examination is unreliable. Nevertheless, their diagnostic accuracy has not been extensively studied. Our objective was to synthesize the sensitivity and specificity of commonly used ancillary tests for DNC.

Background This study provides a detailed imaging assessment in a large series of patients infected with coronavirus disease 2019 (COVID-19) and presenting with neurologic manifestations. Purpose To review the MRI findings associated with acute neurologic manifestations in patients with COVID-19. Materials and Methods This was a cross-sectional study conducted between March 23 and May 7, 2020, at the Pitié-Salpêtrière Hospital, a reference center for COVID-19 in the Paris area. Adult patients were included if they had a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with acute neurologic manifestations and referral for brain MRI. Patients with a prior history of neurologic disease were excluded. The characteristics and frequency of different MRI features were investigated. The findings were analyzed separately in patients in intensive care units (ICUs) and other departments (non-ICU). Results During the inclusion period, 1176 patients suspected of having COVID-19 were hospitalized. Of 308 patients with acute neurologic symptoms, 73 met the inclusion criteria and were included (23.7%): thirty-five patients were in the ICU (47.9%) and 38 were not (52.1%). The mean age was 58.5 years ± 15.6 [standard deviation], with a male predominance (65.8% vs 34.2%). Forty-three patients had abnormal MRI findings 2-4 weeks after symptom onset (58.9%), including 17 with acute ischemic infarct (23.3%), one with a deep venous thrombosis (1.4%), eight with multiple microhemorrhages (11.3%), 22 with perfusion abnormalities (47.7%), and three with restricted diffusion foci within the corpus callosum consistent with cytotoxic lesions of the corpus callosum (4.1%). Multifocal white matter-enhancing lesions were seen in four patients in the ICU (5%). Basal ganglia abnormalities were seen in four other patients (5%). Cerebrospinal fluid analyses were negative for SARS-CoV-2 in all patients tested (n = 39). Conclusion In addition to cerebrovascular lesions, perfusion abnormalities, cytotoxic lesions of the corpus callosum, and intensive care unit-related complications, we identified two patterns including white matter-enhancing lesions and basal ganglia abnormalities that could be related to severe acute respiratory syndrome coronavirus 2 infection. © RSNA, 2020 Online supplemental material is available for this article.

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19-74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2-3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4-5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years.

The use of telemedicine has dramatically increased due to the coronavirus disease 2019 pandemic. Many neurosurgeons are now using telemedicine technologies for preoperative evaluations and routine outpatient visits. Our goal was to standardize the telemedicine motor neurologic examination, summarize the evidence surrounding clinical use of telehealth technologies, and discuss financial and legal considerations.

There is evidence that the transplantation of mesenchymal stem cells into rat models of cerebral ischemia reduces ischemic damage; however, the mechanism remains to be elucidated. The present study aimed to assess the effect of transplantation of human bone marrow stromal cells (hBMSCs) on neurologic function and the expression of vascular endothelial growth factor (VEGF) in a rat model of focal cerebral ischemia. The left middle cerebral artery of adult Wistar rats was occluded for 90 min using a nylon thread, followed by reperfusion for 1 h. hBMSCs labeled with 5-bromo-2-deoxyuridine (BrdU) were stereotaxically injected into the ischemic boundary zone. Behavioral analysis using the Neurological Severity Score (NSS) was conducted on days 1, 3, 7 and 28, and a histologic evaluation was performed simultaneously. VEGF was detected by immunofluorescence staining and western blot analysis. Fifty rats were divided equally into five groups: Normal control, sham‑operated, operated (no transplantation), Dulbecco's medium Eagle's medium (DMEM)-injected (received only serum-free DMEM), and hBMSC-transplanted. The hBMSC-transplanted group showed significantly improved behavioral recovery compared with the operated and DMEM-transplanted groups on days 3, 7 and 28. Histological examination showed that transplanted cells migrated from the injection site into nearby areas including the cortex. Expression of VEGF was significantly greater in the hBMSC group compared with the other four groups on each assessment day. The expression of VEGF was found to be beneficial for functional recovery following cerebral ischemic injury and hBMSC transplantation stimulated the expression of VEGF. Transplantation of BMSCs may be a promising therapeutic strategy for treating cerebral infarction.

Circadian rhythms are biological processes that cycle across 24 h and regulate many facets of neurophysiology, including learning and memory. Circadian variation in spatial memory task performance is well documented; however, the effect of sex across circadian time (CT) remains unclear. Additionally, little is known regarding the impact of time-of-day on hippocampal neuronal physiology. Here, we investigated the influence of both sex and time-of-day on hippocampal neurophysiology and memory in mice. Performance on the object location memory (OLM) task depended on both circadian time and sex, with memory enhanced at night in males but during the day in females. Long-term synaptic potentiation (LTP) magnitude at CA3-CA1 synapses was greater at night compared with day in both sexes. Next, we measured spontaneous synaptic excitation and inhibition onto CA1 pyramidal neurons. Frequency and amplitude of inhibition was greater during the day compared with night, regardless of sex. Frequency and amplitude of excitation was larger in females, compared with males, independent of time-of-day, although both time-of-day and sex influenced presynaptic release probability. At night, CA1 pyramidal neurons showed enhanced excitability (action potential firing and/or baseline potential) that was dependent on synaptic excitation and inhibition, regardless of sex. This study emphasizes the importance of sex and time-of-day in hippocampal physiology, especially given that many neurologic disorders impacting the hippocampus are linked to circadian disruption and present differently in men and women. Knowledge about how sex and circadian rhythms affect hippocampal physiology can improve the translational relevancy of therapeutics and inform the appropriate timing of existing treatments.

This study aimed to investigate whether the demographic variable-adjustment and supplementation of Frontal Assessment Battery (FAB) score can improve the screening ability of Mini-Mental State Examination (MMSE) for dementia and its subtypes. Five hundred forty-one non-demented comparison (NC) and 474 dementia (320 Alzheimer's disease [AD]; 139 non-Alzheimer's disease dementia [NAD]; and 15 mixed AD-NAD dementia) individuals living in the community were included. Education-adjusted MMSE (MMSE-edu) score showed significantly better screening accuracy for overall dementia, AD, and NAD than MMSE raw score. FAB-supplemented MMSE (MMSE-FAB) score had significantly better screening ability for NAD, but not for overall dementia and AD, than MMSE raw score alone. Additional supplementation of FAB to MMSE-edu further increased the ability for overall dementia or NAD screening, but not for AD screening. Further education adjustment of MMSE-FAB also improved its ability for overall dementia, AD, and NAD screening. These results strongly support the usefulness of education-adjustment and supplementation of frontal function assessment to improve screening performance of MMSE for dementia and its subtypes, NAD in particular.

Medical three dimensional (3D) printing is performed for neurosurgical and otolaryngologic conditions, but without evidence-based guidance on clinical appropriateness. A writing group composed of the Radiological Society of North America (RSNA) Special Interest Group on 3D Printing (SIG) provides appropriateness recommendations for neurologic 3D printing conditions.

To assess clinical and/or imaging features useful to distinguish between Susac syndrome (SuS) and primary angiitis of central nervous system (PACNS).

We investigated the effect of crenezumab, a humanized anti-amyloid-beta (Aβ) immunoglobulin (Ig)G4 monoclonal antibody, on biomarkers of amyloid pathology, neurodegeneration, and disease progression in patients with mild-to-moderate Alzheimer's disease (AD).

Rapid eye movement sleep behavior disorder (RBD) is a common prodromic non-motor symptom of Parkinson's disease (PD). Only few studies have evaluated the personality of RBD patients with conflicting results. Aim of the study was to evaluate the frequency of Personality Disorders (PeDs)in RBD. RBD patients, PD patients and healthy controls (HC) were enrolled. All the enrolled subjects underwent a full neurological examination. Motor symptoms were evaluated with the UPDRS-Motor Examination. PeDs were assessed with the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II). Twenty-nine RBD patients [14 men (48.3%); mean age 55.6 ± 11.1], 30 PD patients [17 men (56.7%); mean age 65.7 ± 10.7] and 30 HC [12 men (40%); mean age 65.7 ± 5.4] were enrolled in the study. PD patients had a disease duration of 4.5 ± 4.6 and presented a mean UPDRS-ME score of 26.7 ± 9.4. The most frequent PeDs was the Obsessive-Compulsive one (OCPeD); OCPeD was significantly more frequent in RBD (55.2%) patients than HC (13.3%; p-value < 0.001). No significant differences were found comparing the frequency of OCPeD in RBD patients to that in PD. In the present study, the prevalence of OCPeD in RBD patients was close to that reported in PD patients. Our data could suggest the existence of a common disease-specific RBD-PD personality profile.