Neuronal injury in the motor cortex after chronic stroke and lower limb motor impairment: a voxelbased lesion symptom mapping study

Many studies have examined motor impairments using voxel-based lesion symptom mapping, but few are reported regarding the corresponding relationship between cerebral cortex injury and lower limb motor impairment analyzed using this technique. This study correlated neuro- nal injury in the cerebral cortex of 16 patients with chronic stroke based on a voxel-based lesion symptom mapping analysis. Neuronal injury in the corona radiata, caudate nucleus and putamen of patients with chronic stroke could predict walking speed. The behavioral measure scores were consistent with motor deficits expected after damage to the cortical motor system due to stroke. These findings suggest that voxel-based lesion symptom mapping may provide a more accurate prognosis of motor recovery from chronic stroke according to neuronal injury in cerebral motor cortex.     

How many raters are needed for a reliable diagnosis?

If each of a sample of patients is evaluated by enough raters and is independently diagnosed as either positive or negative, we can evaluate the reliability (kappa coefficient and corresponding confidence interval) of each consensus of 2, 3, 4 … M raters. We can select the optimal consensus, and demonstrate an increase in reliability with multiple diagnoses. Results indicate that the majority rule (for example, two out of three, three out of five raters) does not always yield the highest reliability, nor does any other single rule, which leaves determination of the optimal consensus to empirical evaluation. The kappa coefficient and the confidence intervals are calculated using a jackknife technique for these cases and the optimal consensus is determined. Copyright © 2001 Whurr Publishers Ltd.     

Do alternate methods of analysing motor evoked potentials give comparable results?

This study assessed the reliability of alternate methods of analysis of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). We recorded two sets of MEPs (Time 1 and Time 2) at the optimal scalp sites for both the right first dorsal interosseous (FDI) and flexor carpi ulnaris (FCU) at two different stimulation intensities in 10 healthy subjects. MEP magnitude was determined in each of the following three ways: the mean peak-to-peak amplitude and area of the 20 individual responses; the amplitude and area of the ensemble averaged waveform; and the amplitude and area of the maximal response. There was no significant difference in amplitude or area for either muscle using any of the three methods between Time 1 and 2. However, the ensemble average (area and amplitude) was significantly smaller that the mean MEP, and the maximal MEP amplitude was significantly larger. Intraclass correlation analysis demonstrated that reliability of MEP measures over time was poor regardless of method. Reliability was similar between methods for FDI, but FCU had lower reliability values for the mean and ensemble average methods than the maximal method.     

Abnormalities of somatosensory evoked potentials in konzo – an upper motor neuron disorder

Objective: To determine whether the somatosensory pathways are involved or not in konzo.Methods: In 1998, 21 konzo subjects (15 females and 6 males; mean age 21 years) underwent a SEP study with a two-channel-equipment (Medtronic Keypoint, Denmark) whereas in 2000, 15 subjects (7 females and 8 males; mean age 21 years) participated in a study with a 4-channel-equipment.Results: Most subjects (19/21 in 1998 and 12/15 in 2000) showed normal median SEPs. The remainders had no median cortical responses. All 21 subjects in 1998 and 9 out of 15 in 2000 showed abnormalities of tibial SEPs mainly consisting of absence of cortical responses, prolonged cortical latencies, and central sensory delay to the lumbar spine. Most subjects showed normal absolute latencies both at peripheral and spinal levels. The SEP findings did not correlate with the severity, neither the duration of konzo, nor the experience or not of sensory symptoms at the onset of the disease.Conclusion: Our findings are not specific of konzo. However, they suggest involvement of intracranial somatosensory pathways and point to similarities with other motor neuron diseases.     

How many treatment sessions and patients are needed to create a stable score of adherence and competence in the treatment of cocaine dependence?

The study utilized a generalizability theory analysis of adherence and competence ratings to evaluate the number of sessions and patients needed to yield dependable scores at the patient and therapist levels. Independent judges' ratings of supportive expressive therapy (n = 94), cognitive therapy (n = 103), and individual drug counseling (n = 98) were obtained on tapes of sessions from the NIDA Collaborative Cocaine Treatment Study. Generalizability coefficients revealed that, for all three treatments, ratings made on approximately five to 10 sessions per patient are needed to achieve sufficient dependability at the patient level. At the therapist level, four to 14 patients need to be evaluated (depending on the modality), to yield dependable scores. Many studies today use fewer numbers.     

Motor evoked potentials induced by electrical stimulation of the spine in dogs: which structures are involved?

A minimally invasive method for the stimulation of the spinal cord in dogs was developed. Electrical stimuli were delivered to the spine at the T8 vertebral level through partially insulated needles and under ketamine anesthesia. This allowed the recording of reproducible responses in hind limb muscles of intact dogs. Chronic unilateral deafferentation suppressed the muscle responses on the operated side. A cordotomy sparing the dorsal columns at the L1 level did not completely suppress the muscle responses. It was concluded that motoneuron activation through antidromic conduction in first-order sensory neurons was possible with thoracic spine stimulation and that the recording of muscle responses did not necessarily assess central motor pathways.     

Event related aspects of somatosensory and auditory evoked potentials: noise or signals?

The so-called Vertex Potential (VP) of human scalp-conducted and event related brain potential (ERBP), which occur as a slow and often large, biphasic sinusoid within the 100-400 msec time segment after transient stimulation in the three main sensory modalities, are the longest researched of all human evoked potential (EP) phenomena. Its variable amplitude has been directly correlated, in experiments expressly tailored for the purpose, with input/output variables such as the rate of acceleration of given stimulus parameters from a state of relative rest (RM function), interstimulus interval (ISI), stimulus intensity, skin potential and resistance changes (SPR and SRR), the peripheral electroneurogram (ENG), and experimentally isolated C-fiber afference; and with neuropsychological variables such as attention or vigilance, visual acuity, response time, subjective stimulus probability or expectancy, acute pain of both fast and slow kinds, intelligence quotient (IQ), and psychometric personality scores (e.g., extraversion versus introversion and neuroticism versus normality). Unfortunately, the cerebral, neural origins of the VP, if any, are unknown; it is reported as usually absent from cortex-surface EP in those primates and mammals hitherto studied, and also from human extracranial event related magnetic fields of the brain (ERMFb) insofar as these reveal only superficial tangential sources; but a possible analog has been recorded from deep subcortical electrodes during human neurosurgery. In view of the increasing published range and quantity of direct correlates of VP amplitude, and of the scarcity of data about its neuroanatomy and neurophysiology, it seemed a good idea to do some rudimentary signal analysis. Preliminary results from five subjects confirm earlier data: The VP of somatosensory (SEP) and auditory (AEP) evoked potentials, as obtained by scalp-conductance and either averaged or single-epoch, can be resolved into inconsistently stimulus synchronized frequency components which are also present as relatively unsynchronized waves in the theta and alpha bands (approx. 2-13 Hz) of the unstimulated or near-threshold-stimulated electroencephalogram (EEG). In averages of numerous single trials (20 less than N less than 102), initiated at interstimulus intervals longer than 2.5 sec and deliberately sequenced so that the initiator could learn to estimate the timing of stimulus onsets, the phase coherence of the power-dominant alpha and theta waves within the 100-400 msec time segment of ERBP is obvious when the stimulus is an intense transient and psychologically not "habituated".(ABSTRACT TRUNCATED AT 400 WORDS)     

Standard neurophysiological studies and motor evoked potentials in evaluation of traumatic brachial plexus injuries – A brief review of the literature

Purpose

Traumatic damage to the brachial plexus is associated with temporary or permanent motor and sensory dysfunction of the upper extremity. It may lead to the severe disability of the patient, often excluded from the daily life activity. The pathomechanism of brachial plexus injury usually results from damage detected in structures taking origin in the rupture, stretching or cervical roots avulsion from the spinal cord. Often the complexity of traumatic brachial plexus injury requires a multidisciplinary diagnostic process including clinical evaluation supplemented with clinical neurophysiology methods assessing the functional state of its structures. Their presentation is the primary goal of this paper.

How representative of everyday clinical populations are schizophrenia patients enrolled in clinical trials?

INTRODUCTION: There has been considerable discussion whether clinical trials accurately depict everyday practice. Restrictive inclusion/exclusion criteria, ethical considerations, differences in the severity of psychopathology between clinical and trial patients, or safety issues may bias results, which in turn may rather represent outcome for the "ideal" than for the "average"patient. Therefore, translation into psychiatric practice may be difficult. METHODS: A retrospective case-control study was performed. Schizophrenia inpatients at the LMU Department of Psychiatry, Munich, Germany, who had participated in clinical trials were compared to regular patients serving as controls. Probands and controls were matched by DSM-IV diagnosis, gender and age. The AMDP module, CGI and GAF were used to compare psychopathology. In addition, charts were reviewed for medication dosages, concurrent medical and neurological illness, and clinical history such as age of onset or family history. RESULTS: A total of 200 probands (100/100) were enrolled in the study. With respect to psychopathology, formally thought disordered or suicidal patients were significantly less likely to be study participants (n = 3) than controls (n = 22; p < or = 0.05). Similarly, negative schizophrenia symptoms were significantly less often present in study participants (n = 17) than in controls (n = 38; p < or = 0.05). Study participants were also medically and neurologically healthier than controls. (p = 0.05 respectively). No differences in overall illness severity as depicted by CGI and GAF were observed. CONCLUSION: We found the patients included in our clinical trials representative of the patient encountered in routine clinical practice. Adherence to inclusion and exclusion criteria prevents inclusion of severely ill (e. g. suicidal) patients requiring a more intensive treatment setting. Illness severity was found to be similar in trial participants and controls, and indicates an overall comparably severe psychopathology. The more chronic, rather treatment refractory patients were also not reflected in the trial participant pool; this population may arguably not represent the average clinical patient either. A more careful administration of antipsychotic medication was found in trial participants and may effectively be considered "good clinical practice".     

How many genes are involved in schizophrenia? A simple simulation

We attempted to estimate how many genes are involved in schizophrenia using a simulation based on the polygenic threshold model. The basic assumptions were as follows: (1) All genes involved are transmitted independently; (2) every locus is composed of two alleles - one pathogenic and the other non-pathogenic; (3) all pathogenic alleles are dominant; (4) the two alleles at any locus are in Hardy-Weinberg Equilibrium (HWE) in the general population (GP) but not within the patient (PP) or non-patient (NP) subpopulations; (5) the number of affected loci determines the disease genetically; and (6) only a fraction of genetically determined individuals actually becomes ill. A range of the total number of disease-related genes (N) and threshold genetic load (T) was set for the simulation. Assuming that the number of affected loci follows a binomial distribution, the mean gene frequencies satisfying a disease prevalence of 1.12% in the GP were sought for various N and T combinations. Based on these gene frequencies, the odds ratio and the incidence rate in relatives under random mating were calculated. These results were then compared with real genetic epidemiologic data to obtain best-fit estimates for N and T. The results indicated that a polygenic threshold model with an N greater than 100 and a T in the range of 0.3-0.8 fits the empirical data. It was estimated that at least several hundreds of study subjects are required to yield a statistically significant frequency difference for a single gene between the patient and the control groups.     

How many and which are the psychopathological dimensions in schizophrenia? Issues influencing their ascertainment

During the last two decades, much effort has been made to precisely characterize the symptom dimensions of schizophrenia. A number of dimensional models have been proposed, the most popular of which has been a three-dimensional model consisting of psychotic, negative and disorganizational symptoms. This model, however, has been criticized as too simplistic, and more complex models have been proposed, although to date there has been no consensus as to the number and nature of dimensions necessary to account for the whole range of schizophrenic symptoms. In the present paper, the authors review the main methodological issues which have led to the current confusion about the number of dimensions underlying schizophrenic psychopathology. Among the main issues influencing the delimitation of dimensions are: statistical procedures for determining the number of factors, phase of the illness, level of analysis of symptoms (i.e., symptoms or groups of symptoms), and measurement instrument used. Studies analyzing either a broad range of symptoms or particular symptoms at a finer level have produced a rather complex picture of schizophrenic dimensions. There is evidence supporting the existence of eight major dimensions of psychopathology: psychosis, disorganization, negative, mania, depression, excitement, catatonia and lack of insight. The dimensional structure of symptoms becomes even more complex if one considers that these big dimensions can be further divided into more elementary components. A hierarchical approach for organizing the complex dimensional structure of schizophrenic symptoms is proposed.     

Mesenchymal stromal cells in stroke: improvement of motor recovery or functional compensation?

Experimental stroke treatment by mesenchymal stem cell (MSC) populations is an attractive paradigm in stroke research. There are many studies describing improved functional outcomes after MSC delivery in stroke, but the mechanisms through which the transferred cells exert these effects are less well understood. Moreover, commonly applied functional tests may not be suitable for discriminating real functional recovery from compensation, which is a frequently encountered phenomenon in rodents. This commentary highlights some of the potential risks for the translational process associated with these tests and proposes some alternative test arrays which may achieve more specific functional phenotyping.     

How are observed actions mapped to the observer's motor system? Influence of posture and perspective

Previous studies using transcranial magnetic stimulation (TMS) have shown that during the observation of actions performed by others, the observer's primary motor cortex (M1) becomes facilitated in a highly muscle specific fashion. Here, we used TMS to explore the effect of posture, perspective and body side on muscle specific facilitation of left M1. Subjects viewed video's showing left and right hand extension (palm-down) movements from a first person or third person perspective with their hand posture either congruent (palm-down) or incongruent (palm-up) to the posture of the observed model. Data indicated that facilitation of left M1 was substantially different for observing actions executed with the right (contralateral) or left (ipsilateral) hand. For right hand actions, facilitation of left M1 was shown to be highly specific to the muscle used in the observed action ('intrinsic mapping'). During the observation of left hand stimuli, only half of the subjects displayed this muscle specific facilitation, whereas in the other half, M1 was facilitated according to the observed movement direction ('extrinsic mapping'). Absolute effect magnitude was particularly high when right hand actions were observed from a first person perspective, whereas, for left hand actions, the third person perspective was more efficient. The degree of postural congruency between body parts of the observer and observed model only mildly influenced M1 facilitation. Since action observation is increasingly considered in rehabilitation therapies, the present findings may help identifying the most effective conditions for stimulating the motor system during action observation.