A special kind of anterior horn cell involvement in juvenile myoclonic epilepsy demonstrated by macro electromyography

Juvenile myoclonic epilepsy (JME) is not an uncommon seizure disorder, occurring in 5–10% of epileptic patients. A subclinical anterior horn cell involvement has been suggested in some JME patients by concentric needle electromyography (EMG) and turn/amplitude analysis. In this study, 22 JME patients and 17 normal control subjects have been studied with macro EMG, which is a sensitive method to assess the size of motor units. Most JME patients (19 of 22) had a pathologically increased number of individual large macro motor unit action potentials (MUAPs) compared to control subjects. For both biceps brachii and tibialis anterior muscles, means of median macro MUAP amplitudes were significantly greater than those of normal controls, whereas the fiber density values were only slightly increased. This suggested another kind of anterior horn cell involvement in JME than seen in motor neuron diseases. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 148–152, 1997.     

Possible neurogenic factor in muscular dystrophy: its similarity to denervation atrophy

Muscle biopsy specimens from 179 cases of muscular dystrophies and from 140 cases of anterior horn cell disorders (from a total of 1,348 biopsied patients) were examined histologically. There were 72 cases of Duchenne type muscular dystrophy (DMD), five of Becker type MD, four girls with myopathy resembling DMD, 40 with limb-girdle, 10 with facioscapulohumeral, seven with late onset, 13 with congenital, and 28 with unclassifiable muscular dystrophies. Groups of small atrophied muscle fibres were encountered in 42 (23%) of the cases in this group, most frequently in patients with limb-girdle, facioscapulohumeral, and least frequently with DM dystrophy. In the second group there were 25 cases of infantile, 38 of juvenile, and 39 of adult spinal muscular atrophy (SMA); there were 21 patients with motor neurone disease (MND), six with poliomyelitis, and 11 with an unclassifiable type of anterior horn cell disorder. Pseudomyopathic changes were encountered in 43 (30%) of all cases in this group. They were most frequently present among patients with juvenile and adult SMA and in those with MND. The presence of group atrophy in muscular dystrophy is considered significant myopathological evidence of a denervation process. On the other hand, pseudomyopathic changes, variation in fibre size, rounding, central nuclei, and increase in connective tissue occurring in various anterior horn cell disorders are seen not to be specific `myopathic'' changes. Thus there was an overlap of pathological reactions in muscles from the dystrophies and the neurogenic atrophies. Comparably atrophied fibres (much less than 2 SDs below the normal mean diameter) and hypertrophied fibres (much more than 2 SDs above the normal mean diameter) were encountered in both dystrophy and neurogenic atrophy, considering the large muscles of the limb. Likewise, the mean fibre diameters were comparable in DMD and in juvenile SMA. The fourth evidence of a neurogenic factor in muscular dystrophy was derived from an examination of SDH preparations of muscle. There was a preponderance of type I muscle fibres in dystrophic muscles compared with specimens from controls, suggesting depletion of type II fibres. It appears that the concept of muscular dystrophy as a primary muscle disease needs to be re-examined.     

Difference in neuropathogenetic mechanisms in human furious and paralytic rabies

Whereas paralysis is the hallmark for paralytic rabies, the precise pathological basis of paralysis is not known. It is unclear whether weakness results from involvement of anterior horn cells or of motor nerve fibers. There is also no conclusive data on the cause of the neuropathic pain which occurs at the bitten region, although it has been presumed to be related to sensory ganglionopathy. In this study, six laboratory-proven rabies patients (three paralytic and three furious) were assessed clinically and electrophysiologically. Our data suggests that peripheral nerve dysfunction, most likely demyelination, contributes to the weakness in paralytic rabies. In furious rabies, progressive focal denervation, starting at the bitten segment, was evident even in the absence of demonstrable weakness and the electrophysiologic study suggested anterior horn cell dysfunction. In two paralytic and one furious rabies patients who had severe paresthesias as a prodrome, electrophysiologic studies suggested dorsal root ganglionopathy. Postmortem studies in two paralytic and one furious rabies patients, who had local neuropathic pain, showed severe dorsal root ganglionitis. Intense inflammation of the spinal nerve roots was observed more in paralytic rabies patients. Inflammation was mainly noted in the spinal cord segment corresponding to the bite in all cases; however, central chromatolysis of the anterior horn cells could be demonstrated only in furious rabies patient. We conclude that differential sites of neural involvement and possibly different neuropathogenetic mechanisms may explain the clinical diversity in human rabies.     

多发性硬化伴肌萎缩

本文报道２例多发性硬化（ｍｕｔｉｐｌｅｓｃｌｅｒｏｓｉｓ，ＭＳ）伴肌肉萎缩患者，发现这种萎缩以出现早、较局限、以手肌最早受累为特点。结合国外有关研究及本组电生理检查，推测ＭＳ伴肌萎缩的原因有两种：（１）中枢性萎缩；（２）前角及前根髓内病变。临床上应注意与肌萎缩侧索硬化相鉴别。     

Chronic spinal muscular atrophy simulating facioscapulohumeral type and limb-girdle type of muscular dystrophy. Report of two cases

Two cases of chronic spinal muscular atrophy simulating the clinical picture of the facioscapulohumeral type and limb-girdle type of muscular dystrophy are reported. Both patients had a waddling gait, Gowers' maneuver in arising, terminal atrophies and pseudohypertrophies of some muscles, marked fasciculations, and fascicular tremor. The electromyogram revealed signs of anterior horn cell disease. Calf muscle biopsy (case 2) revealed 'myopathic' changes.     

Myokymic discharges in amyotrophic lateral sclerosis (ALS): A rare electrophysiologic finding?

Myokymic discharges (MDs) are uncommonly recognized in amyotrophic lateral sclerosis (ALS). The electrophysiologic findings in 96 ALS patients were retrospectively reviewed. MDs were found in 5.2% of patients, in 0.81% of total muscles examined (8.2% cranial muscles vs. 0.15% limb muscles). The higher frequency of MDs in cranial muscles suggests a difference in the metabolic environment or other mechanism of instability of the anterior horn cells in the brainstem compared to the spinal cord. Muscle Nerve 41: 107–109, 2010     

Neuronal nitric oxide synthase immunoreactivity in the spinal cord in amyotrophic lateral sclerosis

We investigated the spinal cords of 15 patients with sporadic amyotrophic lateral sclerosis (ALS) immunohistochemically using an anti-human neuronal nitric oxide synthase (nNOS) antibody to examine whether there is increased nNOS immunoreactivity in anterior horn neurons. Specimens from 16 patients without any neurological disease served as controls. In the controls, nNOS immunoreactivity of large anterior horn neurons was detected in 10 out of 16 cases. However, there were few nNOS-positive neurons, and most of large anterior horn neurons were spared. In the ALS patients, the mean number of nNOS-positive anterior horn neurons per transverse section of L4 and L5 was significantly larger (16.2 +/- 10.9) than that in the controls (7.0 +/- 9.2) (P < 0.0001). Moreover, 41.4% of large anterior horn neurons in ALS showed nNOS immunoreactivity in remarkable contrast to 7.6% in the controls. All ALS patients, whether showing mild, moderate or severe depletion of anterior horn neurons, displayed a higher percentage of nNOS-positive anterior horn neurons than the control patients showing nNOS immunoreactivity (P < 0.01). Most of the remaining anterior horn neurons in ALS showed more intense nNOS immunoreactivity on the surface of the neurons and their neuronal processes compared with the controls. Degenerated anterior horn neurons frequently demonstrated more intense nNOS immunoreactivity on the surface of the neurons than normal-appearing neurons. Some anterior horn cells displayed nNOS immunoreactivity in the somata. Dot-like nNOS deposits on anterior horn neurons were also positively immunoreactive with anti-synaptophysin antibody. Thus, increased nNOS expression is located mainly at the synaptic sites on the anterior horn neurons in sporadic ALS, which may be related to the degeneration of anterior horn neurons in this disease. Further studies are needed to determine whether the increased nNOS immunoreactivity plays a neuroprotective or neurotoxic role in the anterior horn neurons, and to show nitric oxide production in ALS.     

Scoliosis associated with syringomyelia presenting in children

The clinical presentations and radiological features of scoliosis accompanying syringomyelia were analyzed in 14 cases of syringomyelia associated with a Chiari malformation in children. Scoliosis was the initial symptom in 11 out of 16 patients (64%) with syringomyelia and present in 14 (88%) at the initial examination. The scoliosis associated with syringomyelia was characterized by a higher incidence of a single curve (6 cases, 43%) and convexity to the left (7 cases, 50%) than seen in idiopathic scoliosis. The syrinx was shifted to the convex side of scoliosis on the axial section at the middle or lower thoracie level in patients with a single curve, and at the cervical or upper thoracic level in patients with a double curve. The authors think that the scoliosis develops in children as a result of damage done to the anterior horn, which innervates the muscles of the trunk, by an asymmetrically expanded syrinx.     

Anterior horn cell disease seen in South India.

Thirty-two patients with clinical evidence of anterior horn cell dysfunction are descirbed. This group of patients could be divided into those with bulbar dysfunction, and those without. Eighth cranial nerve involvement was seen in 10%. The commonest perpheral distribution seen was symmetrical involvement of all four extremities. During the period of follow-up (1 to 5 years) none of the patients without bulbar dysfunction initially developed such symptoms. In all these patients electromyographic evidence of anterior horn cell disease was confirmed. The motor nerve conduction velocities in all of these patients were normal. None of them showed signs of pyramidal tract involvement. Muscle biopsy showed evidence of group fibre atrophy in 10 cases, was normal in 3, and showed a myopathic pattern in 1. Sural nerve biopsy obtained in a single patient was considered histologically normal. Plasma citrate and plasma pyruvate levels obtained in 5 patients of this group, showed elevated values for plasma citrate with normal plasma pyruvate levels. Conspicuous absence of pyramidal signs, elevated plasma citrate, normal plasma pyruvate values and the extremely slow progression suggest that this group of patients are different from other varieties of anterior horn cell dysfunction previously described.     

Electromyographic and computed tomographic findings in five patients with monomelic spinal muscular atrophy

Five patients with monomelic spinal muscular atrophy are described. Clinical features included insidious onset of wasting and weakness of one limb, lack of involvement of the cranial nerves, brain stem, pyramidal tracts and sensory system, and a stable condition over a period of 4-20 years. Clinical findings, electromyography and/or muscle biopsy were consistent with anterior horn cell lesion. Central cavities were excluded by magnetic resonance imaging studies of the spinal cord. Computed tomography of skeletal musculature and electromyography indicated more diffuse lower motor neuron involvement by revealing abnormalities in clinically unaffected muscles in 4 of the 5 patients. Myokymic discharges were found in the affected limb of 1 patient.     

Post-radiotherapy anterior horn cell syndrome

Three patients developed a progressive flaccid paraparesis without sensory or sphincter disturbances, following radiotherapy for lymphoma in two cases and carcinoma of testis in one case. The course was progressive with stabilization between two and four years. Electrophysiological study suggested anterior horn cell damage the mechanism of which remains unclear.     

Denervation in wasted hand muscles in a case of primary cerebellar ectopia without syringomyelia.

Wasting of hand muscles and electromyographic changes of denervation in a case of primary cerebellar ectopia without evidence of syringomyelia is described. It is suggested that the wasting is due to anterior horn cell damage secondary to grey matter venous obstruction at high cervical cord levels.     

Nerve conduction studies, skeletal muscle EMG, and sphincter EMG in multiple system atrophy.

Although autonomic failure, parkinsonism, and cerebellar and pyramidal signs are well documented in multiple system atrophy, much less is known about the frequency and severity of involvement of the peripheral nervous system. The frequency and nature of peripheral nerve involvement has therefore been determined in 74 patients with multiple system atrophy using nerve conduction studies and skeletal muscle EMG. These findings were compared with those on sphincter EMG. Ninety per cent of the patients had an abnormal sphincter EMG, indicating denervation and reinnervation consistent with anterior horn cell loss in Onuf's nucleus, but only 40% had either abnormal nerve conduction studies (mixed sensorimotor axonal neuropathy in 17.5%) or abnormal skeletal muscle EMG (suggesting partial denervation in 22.5%). These data indicate a remarkable selective vulnerability of the anterior horn cells of Onuf's nucleus innervating external sphincter muscles relative to those supplying skeletal muscle in patients with multiple system atrophy. If this selective pattern of involvement can be explained it may be a clue to pathogenetic mechanisms in multiple system atrophy.     

Cutaneous nerve stimulation and motoneuronal excitability: I, soleus and tibialis anterior excitability after ipsilateral and contralateral sural nerve stimulation.

Modification of soleus and anterior tibial anterior horn cell excitability following ipsilateral and contralateral stimulations of the sural nerve was studied by either the H reflex (for the soleus and anterior tibial muscles) or the F response (for the anterior tibial muscles). Several intensities of stimulation were employed. In every instance the recovery curves showed two distinct peaks of facilitation, which appeared with the same delay in muscles with antagonist functions. Also, reciprocal facilitation and inhibition phenomena which occurred after a 25 ms delay and which lasted more than 1000 ms were observed. The intervention of suprasegmentary neuronal mechanisms is proposed to explain the facilitation peaks, while the longer lasting phenomena are probably dependent on spinal processes.     

An investigation of possible transynaptic neuronal degeneration in human spinal cord injury

Neurophysiological studies suggested that transynaptic neuronal degeneration of the anterior horn cells (AHC) may occur after an upper motoneuron lesion as the result of "deafferentation". To test this observation anatomically, patients with spinal cord injury (SCI) who had come to post mortem were investigated. Four patients with longstanding clinically and pathologically "complete" SCI were selected for comparison with 4 age-matched normal controls and with 2 patients who died of motoneuron disease (MND). The total number of AHCs in the L3 spinal cord segment was counted in each of the cases. The lesions in the traumatic group were all above the L3 segment. No significant differences in the number of AHC between the test cases and the normal controls was found. There was, as expected, a highly significant difference between the test cases and those with MND. The conclusion drawn from the study is that transynaptic neuronal degeneration of AHCs does not occur following complete transection of the human spinal cord. Thus the neurophysiological hypothesis is not supported anatomically.     

Experimental intrauterine infection of akabane virus. Pathological studies of skeletal muscles and central nervous system of newborn hamsters with relevances to the Fukuyama type congenital muscular dystrophy

A vertical infection system in hamsters produced by inoculating with Akabane virus was established as an experimental model of congenital muscular dystrophy (Fukuyama type) (FCMD) and arthrogryposis multiplex congenita (AMC) in humans. Swollen fetuses, mummified fetuses, arthrogryposis and cranial deformities were produced in 13 of 415 newborn hamsters inoculated transplacentally (3.1%). The incidence was significantly higher than that in the control group (p less than 0.05). Eight cases presenting apparent abnormalities were examined histologically and virologically. Pictures of skeletal muscles showing such immature features as chains of internal nuclei and myotubular muscle fibers were demonstrated in all cases. In addition, perivascular infiltration of small round cells and thickening of vascular walls were seen in 5 cases, while myogenic changes such as broken myofibrils, small muscle fibers and changes in fiber size were observed in 6 cases. In the anterior horn of the spinal cord, swelling and loss of nuclei and cell matrices were noticed in 4 cases. In the cerebral cortex, disarrangement of cell layers, edematous changes and loss of nerve cells were revealed in 5 cases. In 4 cases virus particles were found on electron microscopy in the cerebral cortex. The authors considered that this experimental system of intrauterine viral infection would be useful for the etiological study of FCMD and AMC in humans in which not only skeletal muscles but also the central nervous system is affected congenitally.     

Neuromuscular abnormalities in ataxia telangiectasia: a clinical, electrophysiological and muscle ultrasound study

Thirteen classical ataxia telangiectasia (A-T) patients, varying in age from 1 to 25 years, were studied clinically, electrophysiologically as well as by muscle ultrasound to chart the development and spectrum of neuromuscular abnormalities in A-T. The most prominent finding was a progressive axonal sensorimotor polyneuropathy, apparent by electromyography and muscle ultrasound from the age of 8 years and becoming clinically discernible around 12 years of age. Before the age of 8 years decreased tendon reflexes and slightly slowed sensory nerve conduction velocities could already be observed. With routine electrophysiological techniques the severe polyneuropathy precludes conclusions about the presence of anterior horn cell loss in older patients.     

The pathology of the lower leg muscles in pure forefoot pes cavus

Enlargement of the peroneus longus muscle is a common occurrence in patients with forefoot pes cavus, and may contribute to the cavus deformity. The present study compares the morphology of up to five lower leg muscles from 17 patients with forefoot pes cavus with those of normal muscles. Eight cases had an identifiable neurogenic cause for the cavus. In four cases of hereditary motor-sensory neuropathy, the tibialis anterior showed more severe damage than the peroneus longus. In two cases of cerebral palsy, fibre atrophy and increased oxidative enzyme activity were observed. In nine clinically idiopathic cases, the histological appearances ranged from normal to generalised fibre atrophy or hypertrophy in individual muscles. There was a trend for the mean fibre area to be greater in peroneus longus than in tibialis anterior in six of the idiopathic group of patients. The muscle cross-sectional area on magnetic resonance imaging was correlated closely with the mean fibre area measured on tissue sections. In idiopathic forefoot pes cavus, fibre hypertrophy in peroneus longus (relative to tibialis anterior) may contribute to the cavus deformity. Muscle fibre hyperplasia may contribute to the peroneal muscle enlargement in Friedreich's ataxia. In none of the cases was peroneus longus enlargement due to fat or fibrous tissue replacement.     

Detection of anterior horn lesions by MRI in central European tick-borne encephalomyelitis

We report a case of central European tick-borne encephalitis with cervical myelitis presenting clinically as a lower motor neuron syndrome of the upper limbs with proximal asymmetrical pareses and atrophies. There were no sensory deficits nor signs of lesions of the spinal pathways or signs of encephalitis or meningitis. The affected motor fibers of the upper limbs were electrically inexcitable, but sensory findings were normal. Electromyography of the paralyzed muscles revealed pathological denervation activity without voluntary activation. The initial magnetic resonance imaging (MRI) showed a large hyperdense lesion in the anterior part of the cervical cord from C3 to T1. Despite the fact that MRI changes disappeared completely within 6 weeks the patient showed only little improvement in the paralyzed muscles after 6 months. To our knowledge, these MRI changes in patients with tick-borne encephalitis, consistent with an isolated anterior horn lesion, have never been reported previously. The course may have been aggravated by an initial antibiotic treatment with cephalosporins. Received: 4 May 1999 Received in revised form: 22 July 1999 Accepted: 26 July 1999