TMS: a navigator for NIRS of the primary motor cortex?

Near-infrared spectroscopy (NIRS) is a non-invasive optical imaging technique, which is increasingly used to measure hemodynamic responses in the motor cortex. The location at which the NIRS optodes are placed on the skull is a major factor in measuring the hemodynamic responses optimally. In this study, the validity of using transcranial magnetic stimulation (TMS) in combination with a 3D motion analysis system to relocate the TMS derived position was tested. In addition, the main goal was to quantify the advantage of using TMS to locate the optimal position in relation to the most commonly used EEG C3 position. Markers were placed on the TMS coil and on the head of the subject. In eleven subjects, a TMS measurement was performed to determine the individual motor-evoked potential center-of-gravity (MEP-CoG). This procedure was repeated in nine subjects to test the validity. Subsequently, hemodynamic responses were measured at the MEP-CoG position and at the C3 position during a thumb abduction and adduction task. On average, the MEP-CoG location was located 19.2 mm away from the C3 position. The reproducibility study on the MEP-CoG relocation procedure revealed no systematic relocations. No differences in early and delayed hemodynamic responses were found between the C3 and MEP-CoG position. These results indicate that using TMS for NIRS optodes positioning on the motor cortex does not result in higher hemodynamic response amplitudes. This could be explained if NIRS and TMS assess slightly different functions.     

A case series of LMWH use in pregnancy: Should trough anti-Xa levels guide dosing?

Introduction

Pregnancy is a thrombogenic state, increasing the risk for venous thromboembolism (VTE), and the risk of valve thrombosis amongst women with mechanical heart valves (MHV). While low molecular weight heparins (LMWH) are generally dosed based on weight (i.e., enoxaparin 1 mg/kg every 12 hours), data in pregnant women have shown that weight-based dosing does not consistently achieve target anti-Xa levels. In women with MHV, our practice includes titrating LMWH doses to target both trough and peak anti-Xa levels, while for those with VTE peak anti-Xa levels guide dosing.

Materials/Methods

This retrospective case series included pregnant women requiring LMWH treatment doses with at least 3 peak (+/− trough) anti-Xa levels. Our primary objective was to describe the actual LMWH dose required to achieve targeted anti-Xa levels relative to weight-based dosing in patients with MHV. Secondarily, we compared the same for VTE patients; compared actual dosing between those with MHV and VTE; and examined maternal and fetal outcomes.

Results/Conclusion

Women with MHV (N = 4) required greater than weight-based dosing of enoxaparin (1.35 mg/kg Q12H) to achieve targeted anti-Xa levels. Importantly, achieving target peak anti-Xa levels did not always ensure maintenance of minimum trough levels. VTE patients (N = 12) did not require more enoxaparin (0.96 mg/kg Q12H) than weight based dosing. MHV patients received more enoxaparin compared to VTE patients (P < 0.001). No bleeding or clotting complications were associated with LMWH administration. In pregnant women with MHV at high risk of thromboembolism, LMWH dosing guided by trough and peak anti-Xa levels should be considered.     

Finger extension weakness and downbeat nystagmus motor neuron disease syndrome: A novel motor neuron disorder?

Introduction: Disturbances of eye movements are infrequently encountered in motor neuron diseases (MNDs) or motor neuropathies, and there is no known syndrome that combines progressive muscle weakness with downbeat nystagmus. Methods: To describe the core clinical features of a syndrome of MND associated with downbeat nystagmus, clinical features were collected from 6 patients. Results: All patients had slowly progressive muscle weakness and wasting in combination with downbeat nystagmus, which was clinically most obvious in downward and lateral gaze. Onset was in the second to fourth decade with finger extension weakness, progressing to other distal and sometimes more proximal muscles. Visual complaints were not always present. Electrodiagnostic testing showed signs of regional motor axonal loss in all patients. Discussion: The etiology of this syndrome remains elusive. Because finger extension weakness and downbeat nystagmus are the discriminating clinical features of this MND, we propose the name FEWDON‐MND syndrome. Muscle Nerve 56 : 1164–1168, 2017     

Does early intervention in infants at high risk for a developmental motor disorder improve motor and cognitive development?

Infants at high risk for developmental motor disorders are in general referred to early intervention (EI) services. It is a matter of debate to which extent EI may facilitate outcome in various developmental domains. We reviewed the effects of EI programmes aiming at promoting motor and cognitive development. With respect to motor development the data indicated that EI prior to term age probably is most effective when it aims at mimicking the intrauterine environment; after term age general developmental programmes probably are most effective. Some evidence was provided that EI prior to term age has a beneficial effect on cognitive development regardless the type of intervention which is applied. After term age only general developmental programmes seemed to have an effect on cognitive development. The review concludes with preliminary data on the effect a new intervention programme, COPCA, applied between 3 and 6 months corrected age on developmental outcome till 18 months. The results indicated that COPCA was more beneficial for the development of sitting behaviour and cognition than traditional paediatric physiotherapy.     

Deficits of entropy modulation of the EEG: A biomarker for altered function in schizophrenia and bipolar disorder?

BackgroundThe synchronized activity of distributed neural assemblies — reflected in the electroencephalogram (EEG) — underpins mental function. In schizophrenia, modulation deficits of EEG spectral content during a P300 task have been replicated. The effects of treatment, chronicity and specificity in these deficits and their possible relationship with anatomic connectivity remain to be explored.MethodsWe assessed spectral entropy modulation of the EEG during a P300 task in 79 patients with schizophrenia (of those, 31 were in their first episode), 29 patients with bipolar disorder and 48 healthy controls. Spectral entropy values summarize EEG characteristics by quantifying the irregularity of spectral content. In a subsample, we calculated the network architecture of structural connectivity using diffusion tensor imaging and graph-theory parameters.ResultsWe found significant spectral entropy modulation deficits with task performance in patients with chronic or first-episode schizophrenia and in patients with bipolar disorder, without significant pre-stimulus spectral entropy differences. The deficits were unrelated to treatment doses, and spectral entropy modulation did not differ between patients taking or not taking antipsychotics, lithium, benzodiazepines or antidepressants. Structural connectivity values were unrelated to spectral entropy modulation. In patients with schizophrenia, spectral entropy modulation was inversely related to negative symptoms and directly related to verbal memory.LimitationsAll patients were taking medication. Patients with bipolar disorder were euthymic and chronic. The cross-sectional nature of this study prevented a more thorough analysis of state versus trait criteria for spectral entropy changes.ConclusionSpectral entropy modulation with task performance is decreased in patients with schizophrenia and bipolar disorder. This deficit was not an effect of psychopharmacological treatment or structural connectivity and might reflect a deficit in the synchronization of the neural assemblies that underlie cognitive activity.     

Reduced mu suppression and altered motor resonance in euthymic bipolar disorder: Evidence for a dysfunctional mirror system?

Social cognitive difficulties are common in the acute phase of bipolar disorder and, to a lesser extent, during the euthymic stage, and imaging studies of social cognition in euthymic bipolar disorder have implicated mirror system brain regions. This study aimed to use a novel multimodal approach (i.e., including both transcranial magnetic stimulation (TMS) and electroencephalogram (EEG)) to investigate mirror systems in bipolar disorder. Fifteen individuals with euthymic bipolar disorder and 16 healthy controls participated in this study. Single-pulse TMS was applied to the optimal site in the primary motor cortex (M1), which stimulates the muscle of interest during the observation of hand movements (goal-directed or interacting) designed to elicit mirror system activity. Single EEG electrodes (C3, CZ, C4) recorded mu rhythm modulation concurrently. Results revealed that the patient group showed significantly less mu suppression compared to healthy controls. Surprisingly, motor resonance was not significantly different overall between groups; however, bipolar disorder participants showed a pattern of reduced reactivity on some conditions. Although preliminary, this study indicates a potential mirror system deficit in euthymic bipolar disorder, which may contribute to the pathophysiology of the disorder.     

Dystonia and the cerebellum: A new field of interest in movement disorders?

Although dystonia has traditionally been regarded as a basal ganglia dysfunction, recent provocative evidence has emerged of cerebellar involvement in the pathophysiology of this enigmatic disease. This review synthesizes the data suggesting that the cerebellum plays an important role in dystonia etiology, from neuroanatomical research of complex networks showing that the cerebellum is connected to a wide range of other central nervous system structures involved in movement control to animal models indicating that signs of dystonia are due to cerebellum dysfunction and completely disappear after cerebellectomy, and finally to clinical observations in secondary dystonia patients with various types of cerebellar lesions. We propose that dystonia is a large-scale dysfunction, involving not only cortico-basal ganglia-thalamo-cortical pathways, but the cortico-ponto-cerebello-thalamo-cortical loop as well. Even in the absence of traditional “cerebellar signs” in most dystonia patients, there are more subtle indications of cerebellar dysfunction. It is clear that as long as the cerebellum’s role in dystonia genesis remains unexamined, it will be difficult to significantly improve the current standards of dystonia treatment or to provide curative treatment.     

Cerebellar abnormalities in Huntington's disease: A role in motor and psychiatric impairment?

The cerebellum has received limited attention in Huntington's disease (HD), despite signs of possible cerebellar dysfunction, including motor incoordination and impaired gait, which are currently attributed to basal ganglia atrophy and disrupted fronto‐striatal circuits. This study is the first to investigate a potential contribution of macro‐ and microstructural cerebellar damage to clinical manifestations of HD. T1‐ and diffusion‐weighted 3T magnetic resonance imaging (MRI) scans were obtained from 12 controls and 22 early‐stage HD participants. Manual delineation and voxel‐based morphometry were used to assess between‐group differences in cerebellar volume, and diffusion metrics were compared between groups within the cerebellar gray and white matter. Associations between these imaging measures and clinical scores were examined within the HD group. Reduced paravermal volume was detected in HD compared with controls using voxel‐based morphometry (P < 0.05), but no significant volumetric differences were found using manual delineation. Diffusion abnormalities were detected in both cerebellar gray matter and white matter. Smaller cerebellar volumes, although not significantly reduced, were significantly associated with impaired gait and psychiatric morbidity and of borderline significance with pronate/supinate‐hand task performance. Abnormal cerebellar diffusion was associated with increased total motor score, impaired saccade initiation, tandem walking, and timed finger tapping. In conclusion, atrophy of the paravermis, possibly encompassing the cerebellar nuclei, and microstructural abnormalities within the cerebellum may contribute to HD neuropathology. Aberrant cerebellar diffusion and reduced cerebellar volume together associate with impaired motor function and increased psychiatric symptoms in stage I HD, potentially implicating the cerebellum more centrally in HD presentation than previously recognized. © 2014 International Parkinson and Movement Disorder Society     

A debate on current eating disorder diagnoses in light of neurobiological findings: is it time for a spectrum model?

ABSTRACT: BACKGROUND: Sixty percent of eating disorders do not meet criteria for anorexia- or bulimia nervosa, as defined by the Diagnostic and Statistical Manual version 4 (DSM-IV). Instead they are diagnosed as 'eating disorders not otherwise specified' (EDNOS). Discrepancies between criteria and clinical reality currently hampering eating disorder diagnoses in the DSM-IV will be addressed by the forthcoming DSM-V. However, future diagnoses for eating disorders will rely on current advances in the fields of neuroimaging and genetics for classification of symptoms that will ultimately improve treatment. DISCUSSION: Here we debate the classification issues, and discuss how brain imaging and genetic discoveries might be interwoven into a model of eating disorders to provide better classification and treatment. The debate concerns: a) current issues in the classification of eating disorders in the DSM-IV, b) changes proposed for DSM-V, c) neuroimaging eating disorder research and d) genetic eating disorder research. SUMMARY: We outline a novel evidence-based 'impulse control' spectrum model of eating disorders. A model of eating disorders is proposed that will aid future diagnosis of symptoms, coinciding with contemporary suggestions by clinicians and the proposed changes due to be published in the DSM-V.     

Is severity of motor coordination difficulties related to co-morbidity in children at risk for developmental coordination disorder?

Aim of the study was to investigate whether 7–9 year old children with severe motor difficulties are more at risk of additional difficulties in activities in daily living, academic skills, attention and social skills than children with moderate motor difficulties. Children (N = 6959) from a population based cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), were divided into three groups based on their scores on the ALSPAC Coordination Test at age 7: control children (scores above 15th centile; N = 5719 [82.1%]); children with moderate (between 5th and 15th centile; N = 951 [13.7%]); and children with severe motor difficulties (below 5th centile N = 289 [4.2%]). Children with neurological disorders or an IQ < 70 were excluded. Logistic regression was used to compare children with moderate and severe motor coordination difficulties with each other and with control children regarding their risk of co-morbidity defined as significant (<10th centile) difficulties with activities of daily living (ADL); academic skills (reading, spelling and handwriting); attention; social skills (social cognition and nonverbal skills). Children with severe motor difficulties demonstrated a higher risk of difficulties in ADL, handwriting, attention, reading, and social cognition than children with moderate motor difficulties, who in turn had a higher risk of difficulties than control children in five out of seven domains. Screening and intervention of co-morbid problems is recommended for children with both moderate and severe motor difficulties.     

Mapping cortical hand motor representation using TMS: A method to assess brain plasticity and a surrogate marker for recovery of function after stroke?

ObjectiveStroke is associated with reorganization within motor areas of both hemispheres. Mapping the cortical hand motor representation using transcranial magnetic stimulation may help to understand the relationship between motor cortex reorganization and motor recovery of the affected hand after stroke.MethodsA standardized review of the pertinent literature was performed.ResultsWe identified 20 trials, which analyzed the relationship between the extent and/or location of cortical hand motor representation using transcranial magnetic stimulation and motor function and recovery of the affected hand. Several correlations were found between cortical reorganization and measures of hand motor impairment and recovery.ConclusionA better understanding of the relationships between the extent and location of cortical hand motor representation and the motor impairment and motor recovery of the affected hand after stroke may contribute to a targeted use of non-invasive brain stimulation protocols. In the future motor mapping may help to guide brain stimulation techniques to the most effective motor area in an affected individual.     

Long-term use of temozolomide: Could you use temozolomide safely for life in gliomas?

Temozolomide (TMZ) is an alkylating agent used in the management of gliomas. Although TMZ is generally safe and acute toxicity is well documented, there are limited data on long-term toxicities. We present three patients with glioma; all patients started on TMZ after having progressed following primary treatment. These patients have continued TMZ for 5 years, 7 years and 8 years respectively. So far they have had no serious side effects. We discuss these patients while raising the question of prolonged TMZ use.