J.W. Pasman

Definition dependent properties of the cortical silent period in upper-extremity muscles, a methodological study

BackgroundTo explore if stimulus–response (S-R) characteristics of the silent period (SP) after transcranial magnetic stimulation (TMS) are affected by changing the SP definition and by changing data presentation in healthy individuals. This information would be clinically relevant to predict motor recovery in patients with stroke using stimulus–response curves.MethodsDifferent landmarks to define the SP onset and offset were used to construct S-R curves from the biceps brachii (BB) and abductor digiti minimi (ADM) muscles in 15 healthy participants using rectified versus non-rectified surface electromyography (EMG). A non-linear mixed model fit to a sigmoid Boltzmann function described the S-R characteristics. Differences between S-R characteristics were compared using paired sample t-tests. The Bonferroni correction was used to adjust for multiple testing.ResultsFor the BB, no differences in S-R characteristics were observed between different SP onset and offset markers, while there was no influence of data presentation either. For the ADM, no differences were observed between different SP onset markers, whereas both the SP offset marker “the first return of any EMG-activity” and presenting non-rectified data showed lower active motor thresholds and less steep slopes.ConclusionsThe use of different landmarks to define the SP offset as well as data presentation affect SP S-R characteristics of the ADM in healthy individuals.

StartReact Restores Reaction Time in HSP: Evidence for Subcortical Release of a Motor Program

Startling acoustic stimuli (SAS) can accelerate reaction times (“StartReact” effect), but the underlying mechanism remains unclear. Both direct release of a subcortically stored motor program and a subcortically mediated trigger for a cortically stored motor program have been hypothesized. To distinguish between these hypotheses, we examined the StartReact effect in humans with pure hereditary spastic paraplegia (HSP). Delayed reaction times in HSP patients in trials both with and without a SAS would argue in favor of a cortically stored response. We instructed 12 HSP patients and 12 matched controls to respond as rapidly as possible to a visual imperative stimulus, in two different conditions: dorsiflexion of the dominant ankle; or flexion of the dominant wrist. In 25% of trials, a SAS was delivered simultaneously with the imperative stimulus. Before these tests, subjects received five SAS while standing to verify normal function of the reticulospinal tract in HSP. Latencies of startle responses in sternocleidomastoid and tibialis anterior muscles were comparable between patients and controls. During the ankle dorsiflexion task, HSP patients had an average 19 ms delay in reaction times compared with controls. Administration of a SAS accelerated ankle dorsiflexion in both groups, but more so in the patients, which completely normalized their latencies. The wrist flexion task yielded no differences in onset latencies between HSP patients and controls. The reticulospinal tract seems unaffected in HSP patients, because startle reflex onsets were normal. The corticospinal tract was affected, as reflected by delayed ankle dorsiflexion reaction times. These delayed onsets in HSP were normalized when the imperative stimulus was combined with a SAS, presumably through release of a subcortically stored motor program conveyed by the preserved reticulospinal tract.

Task-Free Functional MRI in Cervical Dystonia Reveals Multi-Network Changes That Partially Normalize with Botulinum Toxin

Cervical dystonia is characterized by involuntary, abnormal movements and postures of the head and neck. Current views on its pathophysiology, such as faulty sensorimotor integration and impaired motor planning, are largely based on studies of focal hand dystonia. Using resting state fMRI, we explored whether cervical dystonia patients have altered functional brain connectivity compared to healthy controls, by investigating 10 resting state networks. Scans were repeated immediately before and some weeks after botulinum toxin injections to see whether connectivity abnormalities were restored. We here show that cervical dystonia patients have reduced connectivity in selected regions of the prefrontal cortex, premotor cortex and superior parietal lobule within a distributed network that comprises the premotor cortex, supplementary motor area, primary sensorimotor cortex, and secondary somatosensory cortex (sensorimotor network). With regard to a network originating from the occipital cortex (primary visual network), selected regions in the prefrontal and premotor cortex, superior parietal lobule, and middle temporal gyrus areas have reduced connectivity. In selected regions of the prefrontal, premotor, primary motor and early visual cortex increased connectivity was found within a network that comprises the prefrontal cortex including the anterior cingulate cortex and parietal cortex (executive control network). Botulinum toxin treatment resulted in a partial restoration of connectivity abnormalities in the sensorimotor and primary visual network. These findings demonstrate the involvement of multiple neural networks in cervical dystonia. The reduced connectivity within the sensorimotor and primary visual networks may provide the neural substrate to expect defective motor planning and disturbed spatial cognition. Increased connectivity within the executive control network suggests excessive attentional control and while this may be a primary trait, perhaps contributing to abnormal motor control, this may alternatively serve a compensatory function in order to reduce the consequences of the motor planning defect inflicted by the other network abnormalities.

Detectability of auditory evoked response components in preterm infants

In determining the detectability of brainstem, middle latency and cortical auditory evoked responses in preterm newborns, one has to deal with the ongoing maturation of the auditory system. In the preterm period the detectability of evoked responses is closely related to the appearance of the individual evoked response components. The detectability of the individual evoked response components in preterm infants is important, because low detectability rates make the absence of a particular evoked response component irrelevant with respect to the clinical-neurophysiological correlation. In a longitudinal study we determined the detectability and cumulative detectability, i.e. the presence of individual evoked response components in one or more recordings of evoked response components in 37 low risk preterm infants between 30 and 41 weeks conceptional age (CA). On the basis of their detectability it is concluded that evoked response components, determined between 30 and 34 weeks CA, are generally of limited use for clinical application, except for auditory brainstem response (ABR) components I, IIn, V and Vc and middle latency response (MLR) component Na. Our study made clear that improvement can be achieved by performing more than one examination within a period of approximately 4 weeks between the recording sessions. The cumulative detectability rates after two recordings showed improvement for all components involved in this study. The cumulative detectability rates of ABR components I, II, IIN, III, V, IIc, IIINc, Vc, MLR components Na and P0, and auditory cortical response (ACR) components PbP1 and N2p are sufficient to use as measures in the neurophysiological judgement of functional integrity of the central auditory pathway in preterm infants.

The effects of early and late preterm birth on brainstem and middle-latency auditory evoked responses in children with normal neurodevelopment

In preterm and term infants, brainstem and middle latency auditory evoked responses (ABR and MLR) were obtained at 40 and 52 weeks conceptional age (CA) and at 5 years of age. A neurological and neuropsychological evaluation was performed at 5 years of age. To study the effect of preterm birth on the maturation of the ABR and MLR, the preterm infants were divided into early and late preterm groups. Only children with a normal neurodevelopmental outcome at 5 years of age were entered into the study. For ABR, the late preterm group showed significantly longer mean latencies IIc, III, V, and Vc when compared with the term group at 52 weeks CA. There was a trend to longer ABR latencies I in the early preterm group compared with the term group. At 52 weeks CA, the late preterm group showed longer mean interpeak latencies III-I and V-I when compared with the term as well as the early preterm group. At 5 years, the late preterm group showed significantly longer mean ABR latencies IIc and III when compared to the early preterm group. For MLR, the early preterm group showed significantly longer mean latencies of MLR component PO when compared with the term group at 40 weeks CA. At 52 weeks, the late preterm group also had longer mean MLR latencies P0 than the term group. At 5 years of age, the term group showed higher mean peak-to-peak amplitudes Na-P0 than the early as well as the late preterm group. To a large extent, the ABR results support the hypothesis that middle ear effusions in combination with retarded myelination of the central auditory pathway are responsible for the ABR differences found between term and preterm infants with a normal neurodevelopmental outcome at 5 years of age. The longer latencies and interpeak latencies found in late preterm infants when compared with early preterm infants might be explained by an augmented vulnerability of the auditory pathway between 30 and 34 weeks CA. The MLR differences found between term and preterm infants might be explained by a difference in the maturation of primary and nonprimary MLR components.

Are clinical characteristics associated with upper-extremity hypertonia in severe ischaemic supratentorial stroke?

OBJECTIVEnThe primary goal of this study was to identify clinical risk factors, in addition to muscle weakness, for upper-extremity hypertonia in patients with severe ischaemic supratentorial stroke. The secondary goal was to investigate the time course of upper-extremity hypertonia in these patients during the first 26 weeks post-stroke.nnnDESIGNnInception cohort.nnnPATIENTSnForty-three consecutive patients with an acute ischaemic supratentorial stroke and an initial upper-extremity paralysis admitted to an academic hospital.nnnMAIN OUTCOME MEASURESnnnnPRIMARY OUTCOMEnhypertonia assessed by the Ashworth scale at week 26 post-stroke. Potential risks factors: motor functions assessed by the upper-extremity subscore of the Fugl-Meyer motor assessment, Barthel Index at week 1, consciousness, sensory disturbances, apraxia, neglect, and hyper-reflexia. Secondary outcome: time course of upper-extremity hypertonia by assessing its prevalence at 6 consecutive moments post-stroke during a follow-up period of 26 weeks.nnnRESULTSnTwenty-five patients (63%) developed hypertonia during the follow-up period of 26 weeks. During this period, the prevalence of hypertonia followed a rather dynamic course, with cases of early, transient and late hypertonia. Univariate analyses yielded none of the selected clinical characteristics as significantly associated with hypertonia.nnnCONCLUSIONnDespite the high incidence of hypertonia (63%) observed, none of the selected clinical characteristics could be identified as a risk factor for hypertonia.

Neonatal risk factors and risk scores including auditory evoked responses

Abstract In a prospective study, 81 preterm infants and 25 healthy term infants were neurologically and neurophysiologically evaluated in the neonatal period. At 5–7 years of age the neurodevelopmental outcome was assessed. The validity and predictive value of the Neonatal Neurological Inventory (NNI) and the Neurobiological Risk Score (NBRS), including an additional gestational age factor (GAF) and an auditory evoked response factor (AERF) were assessed. Three of the 53 surviving preterm infants showed major neurological abnormalities at 5–7 years. Five infants showed neuropsychological abnormalities and 12 infants showed both neurological and neuropsychological abnormalities. An important subgroup of preterm infants could be identified as high-risk using the NNI and NBRS. The low sensitivity and negative predictive value resulted in a number of false-negative results. Logistic regression showed that intraventricular haemorrhage (IVH) and bilirubin levels contributed highly to the prediction of neurological outcome. For neuropsychological outcome these factors were IVH and assisted ventilation. Addition of the GAF and AERF as separate items to the NBRS did not affect the predictive power. Combined addition of the GAF and AERF showed improvement of both validity and predictive value.nConclusion This study shows that IVH, bilirubin and assisted ventilation contribute most to the validity and predictive value of the NBRS. Furthermore, regarding neurological outcome addition of a GAF in combination with an AERF resulted in a substantial improvement of the validity and predictive value. The shortcomings of the current neonatal risk scores require a careful interpretation of clinical perinatal data regarding the prediction of neurodevelopmental outcome in preterm infants.

Diagnostic and Predictive Value of Auditory Evoked Responses in Preterm Infants: II. Auditory Evoked Responses

In this study, the diagnostic and predictive value of brainstem, middle latency, and cortical auditory evoked responses (BMC-AERs) obtained in the neonatal period in 81 preterm infants was assessed in relation to neurodevelopmental outcome. The preterm infants were neonatally classified according to risk category and gestational age. The BMC-AERs were analyzed with respect to detectability, latencies, and amplitudes as well as derived latency and amplitude measures. At 5 y of age the neurodevelopmental outcome was assessed from neurologic and neuropsychologic evaluations. The results showed that BMC-AER differences mainly correlated with risk category (low risk/high risk) and to some extent with degree of prematurity. In view of these findings the degree of prematurity and the effect of risk category have to be taken into account, when BMC-AERs are applied in the preterm period to predict neurodevelopmental outcome. In this study the BMC-AERs for infants with abnormal neurodevelopmental outcome were scarcely distinguishable from the BMC-AERs for infants with normal neurodevelopmental outcome. Thus far, this and previous reports have indicated that BMC-AERs in preterm infants are useful in maturational studies and with infants showing symptoms related to lesions or dysfunction of the peripheral and/or central auditory system. For predicting neurodevelopmental outcome in preterm infants, BMC-AERs are of limited clinical value.

A Gait Paradigm Reveals Different Patterns of Abnormal Cerebellar Motor Learning in Primary Focal Dystonias

Accumulating evidence points to a role of the cerebellum in the pathophysiology of primary dystonia. The aim of this study was to investigate whether the abnormalities of cerebellar motor learning in primary dystonia are solely detectable in more pure forms of cerebellum-dependent associative motor learning paradigms, or whether these are also present in other motor learning paradigms that rely heavily on the cerebellum but in addition require a more widespread sensorimotor network. Twenty-six patients with various forms of focal dystonia and 10 age-matched healthy controls participated in a motor learning paradigm on a split-belt treadmill. By using reflective markers, three-dimensional kinematics were recorded using a 6-camera motion analysis system. Adaptation walking parameters were analyzed offline, comparing the different dystonia groups and healthy controls. Patients with blepharospasm and writer’s cramp were significantly impaired on various adaptation walking parameters. Whereas results of cervical dystonia patients did not differ from healthy controls in terms of adaptation walking parameters, differences in parameters of normal gait were found. We have here demonstrated abnormal sensorimotor adaptation with the split-belt paradigm in patients with blepharospasm and writer’s cramp. This reinforces the current concept of cerebellar dysfunction in primary dystonia, and that this extends beyond more pure forms of cerebellum-dependent associative motor learning paradigms. However, the finding of normal adaptation in cervical dystonia patients indicates that the pattern of cerebellar dysfunction may be slightly different for the various forms of primary focal dystonia, suggesting that actual cerebellar pathology may not be a primary driving force in dystonia.

Supratentorial ischemic stroke: more than an upper motor neuron disorder.

Summary: The primary goal of this study was to identify secondary functional changes in the peripheral motor units of the paretic upper extremity (UE) in patients with severe ischemic stroke and to determine how these changes develop during the first weeks after stroke. An inception cohort of 27 consecutive patients with an acute ischemic supratentorial stroke and an initial UE paralysis was compared with 10 healthy control subjects. The ulnar nerve was electrically stimulated proximal to the wrist and electromyographic recordings were obtained from the abductor digiti minimi muscle. Hemiparetic side mean values of the compound muscle action potential (CMAP) 1 and 3 weeks after stroke were compared with the nonparetic side and with CMAP values obtained from healthy control subjects. The mean CMAP amplitude in patients was significantly lower on the paretic side compared with the nonparetic side and with control subjects. Decrease in CMAP amplitude was observed in more than half of the stroke patients, sometimes as early as 4 days after stroke, and persisted in most cases. Whenever present, it was accompanied by absence of motor recovery at that specific time after stroke. Decreased CMAP amplitude in the abductor digiti minimi muscle can be seen already in the very acute phases after stroke unrelated to peripheral neuropathy, radiculopathy, or plexopathy, and it is accompanied by absence of UMN recovery. This knowledge is important for interpreting electrophysiological data in stroke patients.