The effects of pyronin on sprouting and regeneration of mouse motor nerves

Administration to mice of a 0.1% solution of pyronin G in their drinking water caused an acceleration both of axonal sprouting from nodes of Ranvier in partly denervated gluteus maximus muscles, and of motor nerve regeneration following a crush to the soleus nerve. Sprouting from soleus motor nerve terminals in response to botulinum toxin-induced paralysis was, however, unaffected. Removal of degenerating axons following nerve section was also accelerated by pyronin treatment. Pyronin is therefore likely to act upon the process of Wallerian degeneration, rather than upon intact motor nerves directly.     

Retrograde analysis of the cerebellar projections to the posteroventral part of the ventral lateral thalamic nucleus in the macaque monkey

The organization of cerebellothalamic projections was investigated in macaque monkeys using injections of retrograde tracers (cholera toxin B and fluorescent dextrans) in the posteroventral part of the ventrolateral thalamic nucleus (VLpv), the main source of thalamic inputs to the primary motor cortex. Injections that filled all of VLpv labeled abundant neurons that were inhomogeneously distributed among many unlabeled cells in the deep cerebellar nuclei (DCbN). Single large pressure injections made in face-, forelimb-, or hindlimb-related portions of VLpv using physiological guidance labeled numerous neurons that were broadly dispersed within a coarse somatotopographic anteroposterior (foot to face) gradient in the dentate and interposed nuclei. Small iontophoretic injections labeled fewer neurons with the same somatotopographic gradient, but strikingly, the labeled neurons in these cases were as broadly dispersed as in cases with large injections. Simultaneous injections of multiple tracers in VLpv (one tracer per somatic region with no overlap between injections) confirmed the general somatotopography but also demonstrated clearly the overlapping distributions and the close intermingling of neurons labeled with different tracers. Significantly, very few neurons (<2%) were double-labeled. This organizational pattern contrasts with the concept of a segregated "point-to-point" somatotopy and instead resembles the complex patterns that have been observed throughout the motor pathway. These data support the idea that muscle synergies are represented anatomically in the DCbN by a general somatotopography in which intermingled neurons and dispersed but selective connections provide the basis for plastic, adaptable movement coordination of different parts of the body. Indexing terms:     

Osteopontin is an alpha motor neuron marker in the mouse spinal cord

Motor neurons (MNs) are designated as alpha/gamma and fast/slow based on their target sites and the types of muscle fibers innervated; however, few molecular markers that distinguish between these subtypes are available. Here we report that osteopontin (OPN) is a selective marker of alpha MNs in the mouse spinal cord. OPN was detected in approximately 70% of postnatal choline acetyltransferase (ChAT)-positive MNs with relatively large somas, but not in those with smaller somas. OPN+/ChAT+ MNs were also positive for NeuN, an alpha MN marker, but were negative for Err3, a gamma MN marker. The size distribution of OPN+/ChAT+ cells was nearly identical to that of NeuN+/ChAT+ alpha MNs. Group Ia proprioceptive terminals immunoreactive for vesicular glutamate transporter-1 were selectively detected on the OPN+/ChAT+ cells. OPN staining was also detected at motor axon terminals at neuromuscular junctions, where the OPN+ terminals were positive or negative for SV2A, a marker distinguishing fast/slow motor endplates. Finally, retrograde labeling following intramuscular injection of fast blue indicated that OPN is expressed in both fast and slow MNs. Collectively, our findings show that OPN is an alpha MN marker present in both the soma and the endplates of alpha MNs in the postnatal mouse spinal cord.     

A new approach to motor unit estimation with surface EMG triggered averaging technique

A new method for estimating the number of motor units using a surface EMG triggered averaging technique is described. This method provides an estimation of mean motor unit potential (MUP) amplitude at different leveles of contraction, which can be utilized to estimate the number of motor units in a given muscle. Motor unit count estimated in abductor pollicis brevis (APB) muscle of 11 normal healthy subjects ranged from 131 to 371 with a mean of 246 ± 68. In our preliminary study of patients with lower motor neuron lesions, there was a significant reduction in the number of motor units. We believe our new noninvasive method of motor unit counting is a relatively simple and reproducible physiological technique.© 1995 John Wiley &Sons, Inc.     

Invited review: motor unit estimation: methods, results, and present status

The renewed interest in motor unit estimation (counting) has coincided with the introduction of computer-based methodology and with the application of the technique to proximal as well as distal muscles. The advantages and disadvantages of the different methods are considered, together with the assumptions inherent in this type of examination. In normal subjects, the extensor digitorum brevis (EDB) muscle has approximately 200 motor units while each of the intrinsic muscles of the hand has about 100 units; larger muscles in the limbs contain greater numbers of units. Beyond the age of 60 years, there is a decline in the number of functioning motor units in both proximal and distal muscles. In denervating disorders, motor unit estimation is useful for diagnosis and assessment; abnormal values may often be observed in muscles judged clinically to be unaffected. Serial studies have enabled the rate of motor unit loss to be determined in ALS and in spinal muscular atrophy. Depletion of motor units has also been found following upper motoneuron lesions caused by injury to the spinal cord or by cerebral hemorrhage; trans-synaptic dysfunction has been presumed responsible. Rather surprisingly, reduced numbers of motor units have been observed in a variety of myopathic disorders; of these, the most consistent abnormalities have been reported in myotonic muscular dystrophy.     

Feed-forward control of preshaping in the rat is mediated by the corticospinal tract

Rats are used to model human corticospinal tract (CST) injury and repair. We asked whether rats possess the ability to orient their paw to the reaching target and whether the CST mediates this skill, as it does in primates. To test this ability, called preshaping, we trained rats to reach for pieces of pasta oriented either vertically or horizontally. We measured paw angle relative to the target and asked whether rats used target information attained before contact to preshape the paw, indicating feed-forward control. We also determined whether preshaping improved with practice. We then selectively lesioned the CST in the medullary pyramid contralateral to the reaching forepaw to test whether preshaping relies on the CST. Rats significantly oriented their paw to the pasta orientation before contact, demonstrating feed-forward control. Both preshaping and reaching efficiency improved with practice, while selective CST lesion abrogated both. The loss of preshaping was greatest for pasta oriented vertically, suggesting loss of supination, as seen with human CST injury. The degree of preshaping loss strongly correlated with the amount of skill acquired at baseline, suggesting that the CST mediates the learned component of preshaping. Finally, the amount of preshaping lost after injury strongly correlated with reduced retrieval success, showing an important functional consequence for preshaping. We have thus demonstrated, for the first time, preshaping in the rat and dependence of this skill on the CST. Understanding the basis for this skill and measuring its recovery after injury will be important for studying higher-level motor control in rats.     

Motor chronic inflammatory demyelinating polyneuropathy (CIDP) in 17 patients: Clinical characteristics,electrophysiological study,and response to treatment

Motor chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare and poorly described subtype of CIDP. We aimed to study their clinical and electrophysiological characteristics and response to treatment. From a prospective database of CIDP patients, we included patients with definite or probable CIDP with motor signs and without sensory signs/symptoms at diagnosis. Patients were considered to have pure motor CIDP (PM‐CIDP) if sensory conductions were normal or to have motor predominant CIDP (MPred‐CIDP) if ≥2 sensory nerve action potential amplitudes were abnormal. Among the 700 patients with CIDP, 17 (2%) were included (PM‐CIDP n = 7, MPred‐CIDP n = 10); 71% were male, median age at onset was 48 years (range: 13‐76 years), 47% had an associated inflammatory or infectious disease or neoplasia. At the more severe disease stage, 94% of patients had upper and lower limb weakness, with distal and proximal weakness in 4 limbs for 56% of them. Three‐quarters (75%) responded to intravenous immunoglobulins (IVIg) and four of five patients to corticosteroids including three of three patients with MPred‐CIDP. The most frequent conduction abnormalities were conduction blocks (CB, 82%) and F‐wave abnormalities (88%). During follow up, 4 of 10 MPred‐CIDP patients developed mild sensory symptoms; none with PM‐CIDP did so. Patients with PM‐CIDP had poorer outcome (median ONLS: 4; range: 22‐5) compared to MPred‐CIDP (2, range: 0‐4; P = .03) at last follow up. This study found a progressive clinical course in the majority of patients with motor CIDP as well as frequent associated diseases, CB, and F‐wave abnormalities. Corticosteroids might be considered as a therapeutic option in resistant IVIg patients with MPred‐CIDP.     

Negative motor seizure arising from the negative motor area: Is it ictal apraxia?

Purpose:   Seizure manifesting motor arrest, that is, negative motor seizure (NMS), is a rare epileptic condition in which only inability to conduct voluntary movements or praxis is produced, although consciousness is preserved. The negative motor area (NMA) seems to be responsible, but its generator mechanism has not yet been clarified.
Patients and Methods:   Three patients manifesting NMS were investigated. Two patients (ages 33 and 17) with intractable frontal lobe epilepsy had subdural grid implantation for epilepsy surgery, and one (age 77) had scalp electroencephalography (EEG) monitoring.
Results:   Ictal semiologies commonly observed, at least in the two patients, were found as follows; (1) indescribable or ill-localized aura, (2) repetitive involuntary vocalization, (3) inability to speak, (4) inability to move the extremities, and (5) subsequent evolution to positive motor seizures. Awareness and comprehension were preserved throughout the episode before generalized seizures. In two patients with epicortical EEG recording, ictal activity arose from the lateral NMA in one, and from the rostral supplementary motor area in the other. Cortical stimulation at NMA in one patient elicited symptoms identical to NMS. Another patient had scalp EEG and magnetic resonance imaging (MRI) abnormality, both suggesting the epileptogenic focus in the mesial frontal area.
Conclusion:   We showed that (1) NMS was a rare condition in patients with seizure focus in the frontal lobe, and (2) that the NMA was responsible for the symptoms. The documented state in the present study may reflect ictal apraxia, but it requires further investigation.     

An 11-year follow-up of motor speech abilities in elderly adults

An 11-year follow-up study of a group of elderly adults suggested a speed-accuracy trade-off for labial and lingual movements associated with syllable repetition tasks. Pre-post repetition data from one subject, apparently healthy in 1980 but diagnosed with Parkinson's disease in 1984–85, were analysed separately from the rest of the group. Rate/timing variability relationships for this subject differed significantly from ‘normally ageing’ peers. As perturbation measures have been shown to be relevant indicators of laryngeal behaviour, rate/timing control measures may also prove to be useful, age-sensitive indices of supralaryngeal speech motor control.     

Single motor unit variability with threshold stimulation in patients with amyotrophic lateral sclerosis and normal subjects

Repetitive nerve stimulation often shows responses with an abnormal decrement in patients with amyotrophic lateral sclerosis (ALS), suggesting instability of the neuromuscular junction; however, the pathophysiology and response characteristics of this instability are not clear. We evaluated response variability of 47 single motor units from 16 patients with ALS and 51 units from 10 normal subjects, acquired by delivering threshold stimuli sporadically at 0.5 HZ or less. In addition, in 46 other different single motor units obtained from 21 patients with ALS, variability was studied at both 1- and 3-HZ stimulation rates. Motor units from patients with ALS were significantly more variable than those from normal subjects, even when their larger amplitude was accounted for. This increased variability was not rate dependent. Response variability is a critical measure in the statistical method of motor unit number estimation and is attributed to variability in the number of units activated; the fact that variability of single motor units varies with disease state may be a potentially confounding factor in the application of the technique.     

A study of motor unit structure by means of scanning EMG.

We used the scanning EMG technique to investigate the structure of human quadriceps muscle motor units. A group of healthy volunteers and 2 groups of patients with proven neurogenic or myogenic neuromuscular pathology have been studied. In total, 86 scans were obtained. An estimate of the motor unit territory (S) separates the 2 patient groups: the majority of territories of myogenic patients are smaller than 4 mm, whereas almost all motor unit territories of neurogenic patients are larger. However, the sizes of the pathologic units only occasionally exceed the upper and lower limits of normal units (2 to 8 mm). The myogenic scans show, on average, a much larger temporal dispersion (T) between the MUAPs within a motor unit than the normal scans. These findings are in accordance with observations with the same technique by others. For the neuropathic scans, there is a significant positive correlation between S and T, which is completely absent in myopathic scans. These observations are confronted with current morphometrical knowledge on motor unit physiology and anatomy.     

The spectrum of lower motor neuron syndromes

Abstract. This review discusses the most important lower motor neuron syndromes. This relatively rare group of syndromes has not been well described clinically. Two subgroups can be distinguished: patients in whom motor neurons (lower motor neuron disease (LMND)) are primarily affected or motor axons and their surrounding myelin (multifocal motor neuropathy (MMN)), both leading to muscle atrophy and weakness.Both hereditary and sporadic forms of LMND have been described. The discussion of recent advances in the genetic knowledge of several hereditary forms of LMND may lead to a better understanding of the pathophysiology and the development of therapeutic strategies. By contrast, the pathogenesis of sporadic LMND is largely unknown. It is, therefore, difficult to consider the various sporadic forms of LMND, discussed in this review, as separate diseases. Because the diagnostic and therapeutic options may differ, it would seem rational to consider sporadic LMND as a spectrum of syndromes which can be distinguished from each other on the basis of clinical presentation.MMN is a lower motor neuron syndrome with presumed immunemediated pathogenesis. Evidence of motor conduction block on nerve conduction studies and a positive response to treatment with intravenous immunoglobulins (IVIg) are considered the most relevant criteria for the diagnosis of MMN. As it is treatable, it is important to distinguish MMN from LMND. Careful electrophysiological analysis in the search for conduction block is, therefore, required in all adult patients with pure lower motor neuron syndromes. For the individual patient, dist inction between the various lower motor neuron syndromes is important as it enables the physician to provide adequate information over the disease course in LMND and to facilitate early treatment in MMN.Supported by a grant from the Prinses Beatrix Fonds.     

Subcortical electrostimulation to identify network subserving motor control

Objectives: Recent anatomical–functional studies have transformed our understanding of cerebral motor control away from a hierarchical structure and toward parallel and interconnected specialized circuits. Subcortical electrical stimulation during awake surgery provides a unique opportunity to identify white matter tracts involved in motor control. For the first time, this study reports the findings on motor modulatory responses evoked by subcortical stimulation and investigates the cortico‐subcortical connectivity of cerebral motor control. Experimental design: Twenty‐one selected patients were operated while awake for frontal, insular, and parietal diffuse low‐grade gliomas. Subcortical electrostimulation mapping was used to search for interference with voluntary movements. The corresponding stimulation sites were localized on brain schemas using the anterior and posterior commissures method. Principal observations: Subcortical negative motor responses were evoked in 20/21 patients, whereas acceleration of voluntary movements and positive motor responses were observed in three and five patients, respectively. The majority of the stimulation sites were detected rostral of the corticospinal tract near the vertical anterior‐commissural line, and additional sites were seen in the frontal and parietal white matter. Conclusions: The diverse interferences with motor function resulting in inhibition and acceleration imply a modulatory influence of the detected fiber network. The subcortical stimulation sites were distributed veil‐like, anterior to the primary motor fibers, suggesting descending pathways originating from premotor areas known for negative motor response characteristics. Further stimulation sites in the parietal white matter as well as in the anterior arm of the internal capsule indicate a large‐scale fronto‐parietal motor control network. Hum Brain Mapp 34:3023–3030, 2013. © 2012 Wiley Periodicals, Inc.     

Diagnosis of motor neuropathy

Motor neuropathy is a clinical entity which leads to consideration of a wide spectrum of peripheral nerve disorders. Firstly, it may be distinguished from other causes of peripheral motor involvement such as muscle diseases and disorders of the neuromuscular junction. Secondly, it may be discussed in two different forms: acute and chronic. Acute chronic neuropathies are mainly observed in Guillain-Barré syndrome, in which electrophysiological studies allow us to recognize the classical demyelinating form and the axonal form. The other causes of acute motor neuropathy are mainly poliomyelitis and porphyrias. Chronic motor neuropathies are mainly observed in motor neuron diseases, mainly amyotrophic lateral sclerosis, but also Kennedy's disease and other lower motor neuron diseases which may be inherited or acquired. The other causes are multifocal motor neuropathy and the predominantly motor forms of chronic inflammatory demyelinating polyneuropathy. The characterization of these different types of chronic neuropathy is of major importance because of the therapeutic consequences which may lead to the proposal of specific treatments.     

Fine and gross motor skills differ between healthy-weight and obese children

Within the obesity literature, focus is put on the link between weight status and gross motor skills. However, research on fine motor skills in the obese (OB) childhood population is limited. Therefore, the present study focused on possible weight related differences in gross as well as fine motor skill tasks. Thirty-four OB children (12 ♀ and 22 ♂, aged 7–13 years) were recruited prior to participating in a multidisciplinary treatment program at the Zeepreventorium (De Haan, Belgium). Additionally, a control group of 34 age and gender-matched healthy-weight (HW) children was included in the study. Anthropometric measures were recorded and gross and fine motor skills were assessed using the Bruininks–Oseretsky Test of Motor Proficiency, second edition (BOT-2). Results were analyzed by independent samples t-tests, multivariate analysis of variance, and a chi-squared test. Being OB was detrimental for all subtests evaluating gross motor skill performance (i.e., upper-limb coordination, bilateral coordination, balance, running speed and agility, and strength). Furthermore, OB children performed worse in fine motor precision and a manual dexterity task, when compared to their HW peers. No group differences existed for the fine motor integration task. Our study provides evidence that lower motor competence in OB children is not limited to gross motor skills alone; OB children are also affected by fine motor skill problems. Further investigation is warranted to provide possible explanations for these differences. It is tentatively suggested that OB children experience difficulties with the integration and processing of sensory information. Future research is needed to explore whether this assumption is correct and what the underlying mechanism(s) could be.     

Evidence of motor-control difficulties in children with attention deficit hyperactivity disorder,explored through a hierarchical motor-systems perspective

Introduction: Attention deficit hyperactivity disorder (ADHD) may reflect a disorder of neural systems that regulate motor control. The current study investigates motor dysfunction in children with ADHD using a hierarchical motor-systems perspective where frontal–striatal/“medial” brain systems are viewed as regulating parietal/“lateral” brain systems in a top down manner, to inhibit automatic environmentally driven responses in favor of goal-directed behavior. It was hypothesized that due to frontal–striatal hypoactivation, children with ADHD would have difficulty with higher order motor control tasks felt to be dependent on these systems, yet have preserved general motor function. Method: A total of 63 children—ADHD and matched controls—completed experimental motor tasks that required maintenance of internal motor representations and the ability to inhibit visually driven responses. Children also completed a measure of motor inhibition, and a portion of the sample completed general motor function tasks. Results: On motor tasks that required them to maintain internal motor representations and to inhibit automatic motor responses, children with ADHD had significantly greater difficulty than controls, yet on measures of general motor dexterity, their performance was comparable. Children with ADHD displayed significantly greater intraindividual (subject) variability than controls. Intraindividual variability (IIV) contributed to variations in performance across the motor tasks, but did not account for all of the variance on all tasks. Conclusions: These findings suggest that children with ADHD may be more controlled by external stimuli than by internally represented information, possibly due to dysfunction of the medial motor system. However, it is likely that children with ADHD also display general motor-execution problems (as evidenced by IIV findings), suggesting that atypicalities may extend to both medial and lateral motor systems. Findings are interpreted within the context of contemporary theories regarding motor dysfunction in ADHD, and implications for understanding externalizing behaviors in ADHD are discussed.     

Unusual form of proprioceptive facilitation during recovery from hemiplegia.

Proprioceptive facilitation (PF) is a phenomenon occasionally seen during motor restoration following acute hemiplegia. At an early stage of recovery, a number of brief passive muscle stretches can facilitate voluntary contraction in the stretched muscles. Here we present a patient who during early recovery from a left hemispheric stroke causing right hemiplegia was able to develop maximum isometric arm force if, during this effort, large-amplitude passive stretches of the elbow were applied as conditioning stimuli. Based on clinical and positron emission tomography findings, possible physiological mechanisms of PF and the role of proprioception in stroke recovery are discussed.     

Clinical evolution of pure upper motor neuron disease/dysfunction (PUMMD)

Introduction: PLS is defined as pure upper motor neuron disease/dysfunction (PUMND) beyond 48 months after symptom onset. We know little about its early stages, but such knowledge would help to identify the mechanisms underlying PLS and ALS and determine why PLS patients seem to be protected against lower MND (LMND). Methods: We reviewed 622 MND cases during a 4‐year period and identified 34 patients with PUMND (5.4%). Results: Among 23 cases with follow‐up data/electromyograms (EMGs; 2 had only 1 EMG), 13 (57%) remained classified as PUMND, and 8 (35%) developed LMND (mean, 51.4 months after onset). Of these 8, LMND developed in 3 after 48 months from symptom onset. Patients with PUMND and LMND were more functionally impaired (P = 0.02). Separately, we identified 5 patients with PUMND who developed LMND long after 48 months (range, 50–127 months). Conclusions: PLS belongs to the ALS spectrum, and perhaps all cases eventually develop LMND. Muscle Nerve, 2013