Neurogenic Defects Research Articles

Inherited muscular disorder in mutant Japanese quail ( Coturnix coturnix japonica): an immunohistochemical study

Cryostat sections of myofibres from the Musculus pectoralis thoracicus of a newly established mutant strain (LWC) of Japanese quail with a myotonic dystrophy-like myopathy were labelled with antibody against myosin heavy chain (MHC) isoforms and neural cell adhesion molecule (N-CAM). The characteristic lesions found in sections of muscle of LWC quail stained with haematoxylin and eosin were type 2B fibre atrophy, sarcoplasmic masses, and ring fibres. Immunohistochemical examination failed to distinguish type 2A and 2B fibres in the LWC quail. Antibody to adult fast MHC, which reacted only with type 2A fibres in normal quail, reacted in LWC quail with type 2B fibres, and to a limited degree with type 2A fibres. Sarcoplasmic masses reacted with both fast and slow MHC antibodies. Some masses also reacted with NCAM antibody, but apparently independently of similar reactions in fibres. These findings suggest that the changes observed in the myofibres of the LWC quail were not neurogenic but represented defects in both the plasma membrane and intermediate filaments.

Abnormal rectosigmoid myoelectric response to eating in patients with severe idiopathic constipation (slow-transit type).

Pathophysiologic mechanisms responsible for severe chronic constipation are poorly understood. In particular, most of the published studies have lumped together patients having different subtypes of constipation, with different and often conflicting results. We studied six patients complaining of severe idiopathic constipation and displaying homogeneous clinical and pathophysiologic features (i.e., patients with slow-transit type constipation) to evaluate their myoelectric spiking responses to food ingestion. Ten healthy subjects acted as controls. The constipated patients failed to show the increase in myoelectric spiking activity that was seen in controls immediately following the meals, suggesting the possibility of a neurogenic defect in this condition.

The anal sphincter in patients with myotonic muscular dystrophy

The objective of this prospective study was to determine anal sphincter function and thickness of the anal musculature in patients with myotonic muscular dystrophy. Manometric studies were performed in 16 patients with myotonic dystrophy and in 16 healthy controls. Patients had significantly lower basal and squeeze pressures than control subjects (P < 0.01). The results of ultrasonographic studies of the anal canal in 7 patients and 7 control subjects suggest that this decrease in muscle strength is partly explained by muscular atrophy. In addition, patients with myotonic dystrophy showed exaggerated rebound contractions following anal sphincter relaxation that was induced by rectal distention. The pattern of this response and the results of electromyographic studies in 6 patients with myotonic dystrophy suggest that such abnormalities are explained by a neurogenic defect rather than a myotonic response of the anal musculature. It is concluded that patients with myotonic dystrophy show a multitude of defects in the anal sphincter that are an expression of myopathy, muscular atrophy, and neural abnormalities.

Neurological defects of the voiding reflex arcs in chronic urinary retention and their relation to spina bifida occulta.

A group of 37 patients (24 female and 13 male) with chronic urinary retention and without demonstrable mechanical obstruction had neurophysiological measurements of their lower urinary tracts to detect any neurological abnormality which might relate to the disorder. These consisted of measurements of the electrosensitivity of the dorsal nerve of the penis/clitoris and of the urethra, measurement of the sacral reflex latencies (SRL) from dorsal nerve to urethra and to anus and between urethra and anus and EMG studies of the urethral and anal sphincters. The results suggest that female patients in particular have significant neurogenic defects in the voiding reflex arcs which find their clinical expression in detrusor underactivity with urinary retention. Plain X-rays of the renal tracts (KUB films) were also studied for the presence of spina bifida occulta. The prevalence of this defect was significantly higher than in normal controls, suggesting that in some of these patients the nerve defect might be related to a tethered cord in association with spina bifida occulta.

Neurophysiological measurements in patients with genuine stress incontinence of urine and the relation of neurogenic defects to the presence of spina bifida occulta.

Neurophysiological measurements comprising surface electromyography (EMG) of the urethral and anal sphincters, measurement of the sensory thresholds of the dorsal nerve (DN) of the clitoris and the urethra and sacral reflex latencies from the dorsal nerve to urethra and anus and from the urethra to anus were performed in 44 females with genuine stress incontinence, in order to detect any relationship between the clinical disorder and a neurogenic defect in the innervation of the muscles involved in maintaining continence. Plain X-rays of the renal tracts (KUB films) were also studied to establish whether the prevalence of spina bifida occulta was increased in this group of patients and was a likely explanation for the nerve defects. Forty-three patients were found to have abnormal neurophysiological responses and the prevalence of spina bifida occulta was 50%, which compares with a prevalence of 17% in normal female controls. Genuine stress incontinence appears to be at least partly associated with defective innervation of the lower urinary tract and it is likely that in some cases the defect may be related to the presence of spina bifida occulta.

Mental retardation in a North Swedish isolate.

Twenty-six mentally retarded patients from a North Swedish geographically isolated population were studied. The mentally retarded patients were short with pycnic body type. Neurological and psychiatric stigmata of variating functions and degrees were recorded. Neurogenic hearing defects, impaired vision, pathological EEG, widened subarachnoidal space found in CT, were among these stigmata. In three patients a urinary substance, probably urocanyl-glycine, was found. The erythrocyte uroporphyrinogen-I-synthetase activity was high in four patients. Chromosome analysis showed some abnormalities which, however, were not systematically present. In the near family 23 persons with schizophrenia were found. The relationship between the mental retardation and the schizophrenic psychosis in the present families has not been explained. Further studies are called for to elucidate the genetic and environmental factors responsible for the two conditions.

The wide bladder neck and posterior urethra in childhood

Involvement of anomalies of the bladder and urethra in recurrent urinary tract infections and micturition disorders in children are examined in the light of published evidence and of the authors' own observations. The data of 300 children followed up for a wide bladder neck and posterior urethra at the Nephrology Clinic of Heim Pál Children's Hospital, Budapest, are reviewed. The dilatation in question is regarded as functional, attributable to a congenital neurogenic or myogenic defect. For the management and prevention of the recurrent ascending infections long-term urinary disinfection and meticulous toilet of the external meatus are recommended. The symptoms are expected to subside spontaneously at the age of menarche. The importance of a close nephrologic follow-up is emphasized.

Children's accidents

<h3>Abstract</h3> Fragile X Syndrome (FXS) is the leading known monogenic form of autism and the most common form of inherited intellectual disability. FXS results from silencing the <i>FMR1</i> gene during embryonic development, leading to loss of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein that regulates mRNA transport, stability, and translation. FXS is commonly thought of as a disease of synaptic dysfunction; however, FMRP expression is lost early in embryonic development, well before most synaptogenesis occurs. Recent studies suggest that loss of FMRP results in aberrant neurogenesis, but neurogenic defects have been variable. We investigated whether FMRP affects neurogenesis in <i>Xenopus laevis</i> tadpoles that express a homolog of <i>FMR1</i>. We used <i>in vivo</i> time-lapse imaging of neural progenitor cells and their neuronal progeny to evaluate the effect of acute loss or overexpression of FMRP on neurogenesis in the developing optic tectum. We complimented the time-lapse studies with SYTOX labeling to quantify apoptosis and CldU labeling to measure cell proliferation. Animals with increased or decreased levels of FMRP have significantly decreased neuronal proliferation and survival. They also have increased neuronal differentiation, but deficient dendritic arbor elaboration. The presence and severity of these defects was highly sensitive to FMRP levels. These data demonstrate that FMRP plays an important role in neurogenesis and suggest that endogenous FMRP levels are carefully regulated. These studies show promise in using <i>Xenopus</i> as an experimental system to study fundamental deficits in brain development with loss of FMRP and give new insight into the pathophysiology of FXS.

Rate and extent of functional reinnervation in fast-twitch and slow-twitch muscles of the dystrophic mouse ( [formula omitted

The extent of functional reinnervation of fast-twitch extensor digitorum longus muscle in dystrophic and normal mice was determined at various times after nerve transection. Functional reinnervation was assessed by measuring the twitch tension evoked by stimulation of the nerve central to the site of transection. In control mice aged 4 to 6 weeks at the time of denervation, complete reinnervation was observed after 6 weeks. In dystrophic mice of the same age reinnervation was clearly impaired. The ratio of functional innervation of the operated leg to that of the contralateral unoperated leg was only 0.62 after 6 weeks. In older dystrophic mice (4 to 6 months at the time of nerve transection) the reinnervation ratio was even lower, 0.43 after 12 weeks. Reinnervation of slow-twitch soleus muscle was assessed 8 weeks after denervation and was also found to be reduced in the older dystrophic animals. The extent of reinnervation was reflected in the measured values of muscle weight, twitch tension per unit wet weight, and twitch time course. The impairment of reinnervation of dystrophic muscle is consistent with, but not proof of, a neurogenic defect in murine muscular dystrophy.

Familial neurogenic acroosteolysis, amputation or skin grafting

A patient with familial neurogenic acroosteolytic defect of the foot was treated with a full thickness skin graft in order to prevent amputation of the lower leg. This graft proved to be of good weight bearing capacity. The clinical and morphological features and implications of the disease are discussed.

Are Muscle Fibers Denervated in Myotonic Dystrophy?

An underlying neurogenic abnormality has recently been postulated in the muscular dystrophies. To test this hypothesis, we applied a widely accepted criterion of denervation-ie, and increase in extrajunctional acetyicholine (ACh) receptor sites--to muscles biopsy specimens from nine patients with myotonic dystrophy and three with amyotrophic lateral scierosis (ALS). The ACh receptor sites were determined by means of iodine 125-labeled alpha-bungarotoxin binding, measured by scintillation counting and autoradiography. None of the myotonic dystrophy muscles showed increased extrajunctiona ACh receptor sites, even in the smallest fibers. By contrast, muscle biopsy specimens from patients with ALS showed notably increased extrajunctional ACh receptor sites, especially in the small fibers. Our findings do not support the hypothesis of a neurogenic defect in myotonic dystrophy.

Neuromuscular function in fast and slow muscles of genetically dystrophic mice

We have determined the frequency of miniature end plate potentials (mepps) in the extensor digitorum longus (EDL) and the soleus (SOL) muscles of normal and dystrophic mice at various ages. In the normal animal the frequencies in the two muscles are very similar soon after birth. The frequency continues to increase in the EDL to reach a level of 19.12 sec −1 while the frequency in the SOL seems to reach its adult level of 12.36 sec −1 much earlier (20–30 days). Dystrophy does not affect the frequency in the SOL but in the adult dystrophic EDL the value is significantly lower than its normal counterpart. Since this effect occurs at a later time than the onset of the symptoms of the disease we consider it to be a secondary phenomenon. This does not, however, rule out the possibility of a neurogenic defect in the etiology of murine muscular dystrophy.

The neurogenic factor in vesical dysfunction following radical hysterectomy for carcinoma of the cervix.

Twenty-seven women who underwent radical hysterectomy with bilateral pelvic lymphadenectomy by Meigs' technique were examined 6 months or more after the operation for possible neurogenic defect in the bladder function, using a test based on the supersensitivity of denervated detrusor muscle cells to cholinergic stimulation, and the results were correlated to the clinical picture. the presence of voiding difficulties is found to be a very reliable sign of damage to the innervation due to the operation, while absence of this symptom does not exclude the presence of even severe paresis. Similarly, the loss of normal desire to void seems to be a very reliable symptom of detrusor paresis, while no conclusions can be based on preserved sensation of bladder filling. Absence of residual urine is by no means rare even in cases of severe paresis, but in many of these patients the degree of bladder emptying varied from one voiding to the next depending, among other factors, on the toilet conditions, the time and the...