Hindfoot varus and neurologic disorders

Muscle imbalance from numerous underlying neurologic disorders can cause dynamic and static hindfoot varus deformity. Most etiologies are congenital, and therefore affect bone morphology and the shape of the foot during growth. Weak and strong muscle groups, bone deformity, and soft-tissue contractures have to be carefully assessed and considered for successful management. Because of the variety of the etiologies and the differences in presentation, treatment decisions in varus hindfoot caused by neurologic disorders must be individualized. Deformity correction includes release of soft tissue contractures, osteotomies and arthrodeses, and tenotomies or tendon transfers to balance muscle strength and prevent recurrence. To decrease elevated anteromedial ankle joint contact stress and provide lateral hindfoot stability during the entire gait cycle, the goal of static and dynamic hindfoot varus realignment is to fully correct all components of the deformity, but particularly the varus tilt of the talus.

Zika Virus as a Cause of Neurologic Disorders.

Zika virus infections have been known in Africa and Asia since the 1940s, but the virus's geographic range has expanded dramatically since 2007. Between January 1, 2007, and March 1, 2016, local transmission was reported in an additional 52 countries and territories, mainly in the Americas and the western Pacific, but also in Africa and southeast Asia. Zika virus infections acquired by travelers visiting those countries have been discovered at sites worldwide. Aedes aegypti mosquitoes are the principal vectors, though other mosquito species may contribute to transmission. The virus was found to be neurotropic in animals in experiments conducted in . . .

Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions

OBJECTIVE The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown.METHODS: HIV-infected, antiretroviral therapy-naive individuals in the HIV-CAUSAL Collaboration who started an antiretroviral regimen were classified according to the CNS Penetration Effectiveness (CPE) score of their initial regimen into low (<8), medium (8-9), or high (>9) CPE score. We estimated "intention-to-treat" hazard ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE scores compared with regimens with a low score. We used inverse probability weighting to adjust for potential bias due to infrequent follow-up.RESULTS: A total of 61,938 individuals were followed for a median (interquartile range) of 37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169 cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence interval) for initiating a combined antiretroviral therapy regimen with a high vs low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71, 2.47) for progressive multifocal leukoencephalopathy. The respective hazard ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73, 1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58).CONCLUSIONS: We estimated that initiation of a combined antiretroviral therapy regimen with a high CPE score increases the risk of HIV dementia, but not of other neuroAIDS conditions.

Feature-invariant image registration method for quantification of surgical outcomes in patients with craniosynostosis: a preliminary study

Craniosynostosis consists of a premature fusion of the sutures in an infant skull that restricts skull and brain growth. During the last decades, there has been a rapid increase of fundamentally diverse surgical treatment methods. At present, the surgical outcome has been assessed using global variables such as cephalic index, head circumference, and intracranial volume. However, these variables have failed in describing the local deformations and morphological changes that may have a role in the neurologic disorders observed in the patients. This report describes a rigid image registration-based method to evaluate outcomes of craniosynostosis surgical treatments, local quantification of head growth, and indirect intracranial volume change measurements. The developed semiautomatic analysis method was applied to computed tomography data sets of a 5-month-old boy with sagittal craniosynostosis who underwent expansion of the posterior skull with cranioplasty. Quantification of the local changes between pre- and postoperative images was quantified by mapping the minimum distance of individual points from the preoperative to the postoperative surface meshes, and indirect intracranial volume changes were estimated. The proposed methodology can provide the surgeon a tool for the quantitative evaluation of surgical procedures and detection of abnormalities of the infant skull and its development.

Systems medicine and integrated care to combat chronic noncommunicable diseases

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Forensic application of postmortem diffusion-weighted and diffusion tensor MR imaging of the human brain in situ

DWI and DTI of the brain have proved to be useful in many neurologic disorders and in traumatic brain injury. This prospective study aimed at the evaluation of the influence of the PMI and the cause of death on the ADC and FA for the application of DWI and DTI in forensic radiology.

β1-integrin/matrix interactions support blood-brain barrier integrity

Brain microvascular endothelium forms an active permeability barrier, the blood-brain barrier (BBB). In neurologic disorders, barrier properties of the BBB are often lost indicating their dependance on molecular cues of the brain microenvironment. In this issue, Osada et al demonstrate that the endothelial extracellular matrix (ECM) provides one of these cues. Their study shows that β1-integrin-mediated adhesion of brain endothelial cells to the surrounding ECM is critical for stabilizing claudin-5 in BBB tight junctions (TJs) and BBB integrity. These observations point to a novel intracellular signaling pathway from β1-integrin/ECM endothelial adhesions to BBB TJs contributing to BBB integrity.

Transient loss of consciousness and syncope

Syncope describes a sudden and brief transient loss of consciousness (TLOC) with postural failure due to cerebral global hypoperfusion. The term TLOC is used when the cause is either unrelated to cerebral hypoperfusion or is unknown. The most common causes of syncopal TLOC include: (1) cardiogenic syncope (cardiac arrhythmias, structural cardiac diseases, others); (2) orthostatic hypotension (due to drugs, hypovolemia, primary or secondary autonomic failure, others); (3) neurally mediated syncope (cardioinhibitory, vasodepressor, and mixed forms). Rarely neurologic disorders (such as epilepsy, transient ischemic attacks, and the subclavian steal syndrome) can lead to cerebal hypoperfusion and syncope. Nonsyncopal TLOC may be due to neurologic (epilepsy, sleep attacks, and other states with fluctuating vigilance), medical (hypoglycemia, drugs), psychiatric, or post-traumatic disorders. Basic diagnostic workup of TLOC includes a thorough history and physical examination, and a 12-lead electrocardiogram (ECG). Blood testing, electroencephalogram (EEG), magnetic resonance imaging (MRI) of the brain, echocardiography, head-up tilt test, carotid sinus massage, Holter monitoring, and loop recorders should be obtained only in specific contexts. Management strategies involve pharmacologic and nonpharmacologic interventions, and cardiac pacing.

Validation of network communicability metrics for the analysis of brain structural networks.

Computational network analysis provides new methods to analyze the brain's structural organization based on diffusion imaging tractography data. Networks are characterized by global and local metrics that have recently given promising insights into diagnosis and the further understanding of psychiatric and neurologic disorders. Most of these metrics are based on the idea that information in a network flows along the shortest paths. In contrast to this notion, communicability is a broader measure of connectivity which assumes that information could flow along all possible paths between two nodes. In our work, the features of network metrics related to communicability were explored for the first time in the healthy structural brain network. In addition, the sensitivity of such metrics was analysed using simulated lesions to specific nodes and network connections. Results showed advantages of communicability over conventional metrics in detecting densely connected nodes as well as subsets of nodes vulnerable to lesions. In addition, communicability centrality was shown to be widely affected by the lesions and the changes were negatively correlated with the distance from lesion site. In summary, our analysis suggests that communicability metrics that may provide an insight into the integrative properties of the structural brain network and that these metrics may be useful for the analysis of brain networks in the presence of lesions. Nevertheless, the interpretation of communicability is not straightforward; hence these metrics should be used as a supplement to the more standard connectivity network metrics.

Disease Caused by Mutations in NaV-β Subunit Genes

NaV-b subunits associate with the NaV-a or pore-forming subunit of the voltage-dependent sodium channel and play critical roles in channel expression, voltage dependence of the channel gating, cell adhesion, signal transduction, and channel pharmacology. Five NaV-b subunits have been identified in humans, all of them implicated in many primary arrhythmia syndromes that cause sudden death or neurologic disorders, including long QT syndrome, Brugada syndrome, cardiac conduction disorders, idiopathic ventricular fibrillation, epilepsy, neurodegenerative diseases, and neuropsychiatric disorders.

Comparison of Routine Brain Imaging at 3 T and 7 T.

OBJECTIVE The aim of this study was to compare quantitative and semiquantitative parameters (signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], image quality, diagnostic confidence) from a standard brain magnetic resonance imaging examination encompassing common neurological disorders such as demyelinating disease, gliomas, cerebrovascular disease, and epilepsy, with comparable sequence protocols and acquisition times at 3 T and at 7 T. MATERIALS AND METHODS Ten healthy volunteers and 4 subgroups of 40 patients in total underwent comparable magnetic resonance protocols with standard diffusion-weighted imaging, 2D and 3D turbo spin echo, 2D and 3D gradient echo and susceptibility-weighted imaging of the brain (10 sequences) at 3 T and 7 T. The subgroups comprised patients with either lesional (n = 5) or nonlesional (n = 4) epilepsy, intracerebral tumors (n = 11), demyelinating disease (n = 11) (relapsing-remitting multiple sclerosis [MS, n = 9], secondary progressive MS [n = 1], demyelinating disease not further specified [n = 1]), or chronic cerebrovascular disorders [n = 9]). For quantitative analysis, SNR and CNR were determined. For a semiquantitative assessment of the diagnostic confidence, a 10-point scale diagnostic confidence score (DCS) was applied. Two experienced radiologists with additional qualification in neuroradiology independently assessed, blinded to the field strength, 3 pathology-specific imaging criteria in each of the 4 disease groups and rated their diagnostic confidence. The overall image quality was semiquantitatively assessed using a 4-point scale taking into account whether diagnostic decision making was hampered by artifacts or not. RESULTS Without correction for spatial resolution, SNR was higher at 3 T except in the T2 SPACE 3D, DWI single shot, and DIR SPACE 3D sequences. The SNR corrected by the ratio of 3 T/7 T voxel sizes was higher at 7 T than at 3 T in 10 of 11 sequences (all except for T1 MP2RAGE 3D).In CNR, there was a wide variation between sequences and patient cohorts, but average CNR values were broadly similar at 3 T and 7 T.DCS values for all 4 pathologic entities were higher at 7 T than at 3 T. The DCS was significantly higher at 7 T for diagnosis and exclusion of cortical lesions in vascular disease. A tendency to higher DCS at 7 T for cortical lesions in MS was observed, and for the depiction of a central vein and iron deposits within MS lesions. Despite motion artifacts, DCS values were higher at 7 T for the diagnosis and exclusion of hippocampal sclerosis in mesial temporal lobe epilepsy (improved detection of the hippocampal subunits). Interrater agreement was 69.7% at 3 T and 93.3% at 7 T. There was no significant difference in the overall image quality score between 3 T and 7 T taking into account whether diagnostic decision making was hampered by artifacts or not. CONCLUSIONS Ultra-high-field magnetic resonance imaging at 7 T compared with 3 T yielded an improved diagnostic confidence in the most frequently encountered neurologic disorders. Higher spatial resolution and contrast were identified as the main contributory factors.

Magnetic Resonance Imaging Finding in Small Ruminants with Brain

Brain disease is an important cause of neurologic deficits in small ruminants, however few MRI features have been described. The aim of this retrospective, case series study was to describe MRI characteristics in a group of small ruminants with confirmed brain disease. A total of nine small ruminants (six sheep and three goats) met inclusion criteria. All had neurologic disorders localized to the brain and histopathologic confirmation. In animals with toxic-metabolic diseases, there were bilaterally symmetric MRI lesions affecting either the gray matter (one animal with polioencephalomalacia) or the white matter (two animals with enterotoxemia). In animals with suppurative inflammation, asymmetric focal brainstem lesions were present (two animals with listeric encephalitis), or lesions typical of an intra-axial (one animal) or dural abscess (one animal), respectively. No MRI lesions were detected in one animal with suspected viral cerebellitis and one animal with parasitic migration tracts. No neoplastic or vascular lesions were identified in this case series. Findings from the current study supported the use of MRI for diagnosing brain diseases in small ruminants.

Familial occurrence and heritable connective tissue disorders in cervical artery dissection

OBJECTIVE In a large series of patients with cervical artery dissection (CeAD), a major cause of ischemic stroke in young and middle-aged adults, we aimed to examine frequencies and correlates of family history of CeAD and of inherited connective tissue disorders. METHODS We combined data from 2 large international multicenter cohorts of consecutive patients with CeAD in 23 neurologic departments participating in the CADISP-plus consortium, following a standardized protocol. Frequency of reported family history of CeAD and of inherited connective tissue disorders was assessed. Putative risk factors, baseline features, and 3-month outcome were compared between groups. RESULTS Among 1,934 consecutive patients with CeAD, 20 patients (1.0%, 95% confidence interval: 0.6%-1.5%) from 17 families (0.9%, 0.5%-1.3%) had a family history of CeAD. Family history of CeAD was significantly more frequent in patients with carotid location of the dissection and elevated cholesterol levels. Two patients without a family history of CeAD had vascular Ehlers-Danlos syndrome with a mutation in COL3A1. This diagnosis was suspected in 2 additional patients, but COL3A1 sequencing was negative. Two patients were diagnosed with classic and hypermobile Ehlers-Danlos syndrome, one patient with Marfan syndrome, and one with osteogenesis imperfecta, based on clinical criteria only. CONCLUSIONS In this largest series of patients with CeAD to date, family history of symptomatic CeAD was rare and inherited connective tissue disorders seemed exceptional. This finding supports the notion that CeAD is a multifactorial disease in the vast majority of cases.

Early co-occurrence of a neurologic-psychiatric disease pattern in Niemann-Pick type C disease: a retrospective Swiss cohort study

BackgroundNiemann-Pick disease type C (NP-C) is a rare autosomal recessive disorder of lysosomal cholesterol transport. The objective of this retrospective cohort study was to critically analyze the onset and time course of symptoms, and the clinical diagnostic work-up in the Swiss NP-C cohort.MethodsClinical, biochemical and genetic data were assessed for 14 patients derived from 9 families diagnosed with NP-C between 1994 and 2013. We retrospectively evaluated diagnostic delays and period prevalence rates for neurological, psychiatric and visceral symptoms associated with NP-C disease. The NP-C suspicion index was calculated for the time of neurological disease onset and the time of diagnosis.ResultsThe shortest median diagnostic delay was noted for vertical supranuclear gaze palsy (2y). Ataxia, dysarthria, dysphagia, spasticity, cataplexy, seizures and cognitive decline displayed similar median diagnostic delays (4¿5y). The longest median diagnostic delay was associated with hepatosplenomegaly (15y). Highest period prevalence rates were noted for ataxia, dysarthria, vertical supranuclear gaze palsy and cognitive decline. The NP-C suspicion index revealed a median score of 81 points in nine patients at the time of neurological disease onset which is highly suspicious for NP-C disease. At the time of diagnosis, the score increased to 206 points.ConclusionA neurologic-psychiatric disease pattern represents the most characteristic clinical manifestation of NP-C and occurs early in the disease course. Visceral manifestation such as isolated hepatosplenomegaly often fails recognition and thus highlights the importance of a work-up for lysosomal storage disorders. The NP-C suspicion index emphasizes the importance of a multisystem evaluation, but seems to be weak in monosymptomatic and infantile NP-C patients.

Sleep-wake disorders persist 18 months after traumatic brain injury but remain underrecognized

OBJECTIVE This study is a prospective, controlled clinical and electrophysiologic trial examining the chronic course of posttraumatic sleep-wake disturbances (SWD). METHODS We screened 140 patients with acute, first-ever traumatic brain injury of any severity and included 60 patients for prospective follow-up examinations. Patients with prior brain trauma, other neurologic or systemic disease, drug abuse, or psychiatric comorbidities were excluded. Eighteen months after trauma, we performed detailed sleep assessment in 31 participants. As a control group, we enrolled healthy individuals without prior brain trauma matched for age, sex, and sleep satiation. RESULTS In the chronic state after traumatic brain injury, sleep need per 24 hours was persistently increased in trauma patients (8.1 ± 0.5 hours) as compared to healthy controls (7.1 ± 0.7 hours). The prevalence of chronic objective excessive daytime sleepiness was 67% in patients with brain trauma compared to 19% in controls. Patients significantly underestimated excessive daytime sleepiness and sleep need, emphasizing the unreliability of self-assessments on SWD in trauma patients. CONCLUSIONS This study provides prospective, controlled, and objective evidence for chronic persistence of posttraumatic SWD, which remain underestimated by patients. These results have clinical and medicolegal implications given that SWD can exacerbate other outcomes of traumatic brain injury, impair quality of life, and are associated with public safety hazards.