Lumbar motor neuron size and number is affected by age in male F344 rats

Motor neurons in the spinal cord of old rats appear similar in size but less numerous compared with those in mature rats; they also contain a large amount of lipofuscin, the lipid peroxidation by-product whose function is largely unknown. The object of this study was to morphometrically characterize motor neurons found in the L4/L5 lumbar spinal cord of mature (6-month) and old (22-month) rats. Paraformaldehyde-fixed, lumbar spinal cords from six rats at each age were embedded in paraffin, sectioned at 6 microm and stained with 0.1% toluidine blue. The nucleolar diameter and area from a minimum of 34 motor neurons per spinal cord were measured. Motor neuron number was calculated using Abercrombie's (Abercrombie, 1946) formula after correcting for tissue shrinkage. Motor neuron number was decreased with age while the neuronal area increased with age. Nucleolar diameter also increased in old rats. Frequency distributions of motor neuron area revealed unimodal distributions of motor neurons rats of both ages. We suggest that larger nucleolar diameter reflects more metabolically active neurons in old rats while larger neuron area is a reflection of the presence of lipofuscin in old motor neurons.     

A test of the 1992 International Standards for Neurological and Functional Classification of Spinal Cord Injury

This study was designed to test the 1992 International Standards for Neurological and Functional Classification of Spinal Cord Injury. One hundred and six professionals in the field of spinal cord injury attending an instructional course at the 1994 ASIA Meeting participated in the test. Participants completed a pretest and posttest in which they classified two patients who had a spinal cord injury (one with complete tetraplegia and one with incomplete paraplegia) by sensory and motor levels, zone of partial preservation (ZPP), ASIA Impairment Scale and completeness of injury. Between tests, three members of the ASIA Standards Executive Committee gave presentations on the neurological assessment, scoring, scaling and classification of spinal cord injury and a video of the actual examinations of the two cases was viewed. Percent 'correct' (as defined by the ASIA Standards Committee) was calculated for sensory and motor levels, ZPP, ASIA Impairment and completeness. Overall, the analyses showed that participants had very little difficulty in correctly classifying the patient with complete tetraplegia. Pretests scores ranged from 72% (left motor level) to 96% (complete injury), posttest scores from 73% (left motor level) to 100% correct (complete injury). For the patient with incomplete paraplegia (Case 2), scores were considerably lower. Pretest scores ranged from 16% (right motor level) to 95% correct (incomplete injury); posttest scores from 21% (right motor level) to 97% correct (incomplete injury). The results showed that further revisions of the 1992 Standards and more training is needed to ensure accurate classification of spinal cord injury.     

Combined surgical and physical treatment in traumatic painful syndromes of the cervical spine

Clinical observations suggest the need for changing therapeutic management to a more active one in cases of cervical spine injury with damage to the spinal cord and nerve roots or brachial plexus. In 248 patients with these injuries treated initially conservatively the incidence of cervicobrachial pain was analysed. Neuralgic pains were present in 31.5% of cases, causalgic pains in 2.4% and sympathalgic pains in 2%. Conservative treatment conducted in these patients (89 cases) during many months after trauma had no effect on return of mobility. Long-term application of physioterapy prevented only temporarily the development of trophic changes and only partially relieved pains. Only surgical decompression of the spinal cord or spinal nerves with stabilization of damaged vertebrae caused disappearance of painful syndromes and improvement in the motor activity of the extremities. These observations show that early surgical intervention for decompression of the spinal cord, roots or brachial plexus should be advocated in these cases.     

A study of patients who leave without notice in an A & E department

Neuronal degradation accompanied with axonal degeneration has been known to occur in spinal motor neurons after an upper level of spinal cord lesion. In the present study, the functional integrity of neuromuscular transmission was assessed by utilizing a sensitive electrodiagnostic method comprising of stimulated single-fiber electromyography (SFEMG), along with axonal microstimulation, in paralytic muscles of patients with spinal cord injury (SCI). Neuromuscular jitter was measured in anterior tibial muscles for 30 patients with SCI and also for 12 normal controls. Mean jitter of 37.4 +/- 14.7 (mean +/- SD) micros, as obtained in SCI patients, was found to be significantly greater than the results of 20.1 +/- 8.4 micros in normal controls (P < 0.01). Jitter measurement was not significantly different in varied functional scales of SCI. A positive correlation was noted between the increased jitter and the disease duration from the onset of cord lesion till the time of stimulated SFEMG test (r = 0.68; P < 0.01). The present abnormal finding of neuromuscular jitter provides an electrophysiologic evidence for axonal degeneration and suggests that transsynaptic degeneration of motor neuron may occur below the level of cord lesion in SCI patients. Furthermore, the neuronal degradation in SCI was positively correlated with the course duration of the disease.     

Androgen concentration in motor neurons of cranial nerves and spinal cord

After injection of [3H]dihydrotestosterone, a major testosterone metabolite, radioactivity is concentrated in nuclei of certain cells in the midbrain, pons, medulla oblongata, cerebellum, and spinal cord. While there is some overlap between androgen and estrogen target neuron distribution, certain motor neurons appear to be selectively labeled by androgen; in contrast, estrogen localization prevails in sensory neurons. These results may help to explain why male sexual behavior in some rodents is not fully activated with dihydrotestosterone alone but in addition requires estradiol, a testosterone metabolite.     

A comparison of two functional tests in quadriplegia: the quadriplegia index of function and the functional independence measure

Individuals with spinal cord injury are evaluated according to a set of guidelines based on motor, sensory, and functional tests. The resulting scores are used to quantify the extent of neurological injury and functional loss. The purpose of the present study was to compare certain scoring systems using the same group of patients. Twenty-nine subjects with cervical spine cord injury were evaluated by the same examiner using three scales: (1) The American Spinal Cord Injury Association (ASIA) (2) The Quadriplegia Index of Function (QIF) (3) The Functional Independence Measure (FIM) Assessments were made both at admission to, and discharge from, the rehabilitation center. Positive change in motor score is widely used as an indicator of recovery after spinal cord injury. We assessed the relationship of the two functional tests, the FIM and the QIF, to ASIA scores and found strong correlations in both cases. The feeding and dressing categories of QIF showed an even stronger correlation to ASIA motor scores, though the statistical significance was the same for corresponding categories of FIM and QIF. The percent of recovery on ASIA motor scores was significantly correlated only to gain in QIF scores, not FIM. FIM lacks the category of bed activities. Some additions to the FIM may be useful, especially in the feeding and dressing categories, and a category of bed activities could be included as well, in order to improve sensitivity.     

Tibial intramedullary nailing without open drilling

There are presently two competitive theories that attempt to explain the etiology of multiple sclerosis (MS). Briefly summarized, they are: 1. An infection, probably of viral type, may attack the oligodendroglia of the central nervous system; or, 2. An autoimmune process may begin with an infection of the peripheral lymphatic immune system, producing antibodies that cross the blood-brain barrier, leading to myelinoclasia. Since 1935, research has been directed toward myelin of the central nervous system and the myelin sheaths of peripheral nerve; however, dorsal root and cranial sensory ganglia (DRG) have apparently not been studied. The present hypothesis states that an infectious agent (probably viral) finds privileged sanctuary in the dorsal root and cranial sensory ganglia (DRG): thereafter periodically invading the spinal cord, brain, or peripheral nerve. Previously reported erratic spinal fluid viral titers and cultures can be explained by differences in the anatomy of the DRG in which there is a variable and limited contact of spinal fluid with sensory ganglia. Clues to this hypothesis were noted by the author during routine neurological examinations of patients with MS, in which sensory signs and symptoms were frequently encountered. This clinical observation has also been reported by others who found such symptoms in 75% of MS patients, ranking second only to incoordination.     

Pretherapy dental decisions in patients with head and neck cancer. A proposed model for dental decision support

OBJECTIVE: Sensory and motor abnormalities are common among patients with complex regional pain syndrome (CRPS). The purpose of the present study was to define and characterize these abnormalities and to develop a hypothesis regarding the area of the central nervous system from which they derive. DESIGN: Data were acquired from study subjects using clinical examination and quantitative assessment of neurological function. Subjects were divided into four groups. CRPS patients were differentiated into two groups based on the presence or absence of sensory deficit on the face to clinical examination. The other two groups were composed of patients with other chronic pain syndromes and normal individuals without chronic pain or disability. Clinical and quantitative data were compared between groups. PATIENTS: One hundred forty-five CRPS patients, 69 patients with other pain conditions, and 26 normal individuals were studied. RESULTS: A high incidence of trigeminal hypoesthesia was observed in CRPS patients. CRPS patients with trigeminal hypoesthesia manifested bilateral deficits of sensory function, with a predominant hemilateral pattern. These patients also manifested bilateral motor weakness with a more prominent hemiparetic pattern. Both sensory and motor deficits were greatest ipsilateral to the painful side of the body. These features differed significantly from those of CRPS patients lacking clinical trigeminal deficit, other pain patients, and normals. A lower cranial nerve abnormality (sternocleidomastoid weakness) and a myelopathic feature (Hoffman's reflex) were more common in CRPS patients with trigeminal hypoesthesia. CONCLUSIONS: Nearly half of CRPS patients had abnormalities of spinothalamic, trigeminothalamic, and corticospinal function that may represent dysfunction of the medulla. One-third of the remaining CRPS patients had neuroimaging evidence of spinal cord or brain pathology. The majority of CRPS patients in this study have measurable abnormalities of the sensory and motor systems or neuroimaging evidence of spinal cord or brain dysfunction.     

Inductions of 3-L-nitrotyrosine in motor neurons after transient spinal cord ischemia in rabbits

The induction and distribution of 3-L-nitrotyrosine (NO2-Tyr) were examined with HPLC and immunohistochemistry in rabbit spinal cords after 15 minutes of transient ischemia until 7 days of the reperfusion. After the 15-minute ischemia, there was a significant decrease of neurologic scores in the ischemic group compared with the sham-operated control group at 7 days of reperfusion (P = 0.0017), and the majority of motor neurons was selectively lost at 7 days of reperfusion (P = 0.0039). NO2-Tyr was transiently induced at 8 hours of reperfusion in the ventral part of the spinal cord (0.47%+/-0.86%, NO2-Tyr/total tyrosine; P = 0.0021), but was not induced at any time point of reperfusion in the dorsal part of the spinal cord. Strong immunoreactivity for NO2-Tyr was selectively induced in large pyramidal motor neurons at 8 hours of reperfusion and was still weakly present until 7 days of reperfusion. (There may be a difference in sensitivity between the two techniques.) These results suggested that protein tyrosine nitration by nitric oxide plays a role in the selective motor neuron cell damage after transient spinal cord ischemia.     

Expression patterns of transmembrane and released forms of neuregulin during spinal cord and neuromuscular synapse development

We mapped the distribution of neuregulin and its transmembrane precursor in developing, embryonic chick and mouse spinal cord. Neuregulin mRNA and protein were expressed in motor and sensory neurons shortly after their birth and levels steadily increased during development. Expression of the neuregulin precursor was highest in motor and sensory neuron cell bodies and axons, while soluble, released neuregulin accumulated along early motor and sensory axons, radial glia, spinal axonal tracts and neuroepithelial cells through associations with heparan sulfate proteoglycans. Neuregulin accumulation in the synaptic basal lamina of neuromuscular junctions occurred significantly later, coincident with a reorganization of muscle extracellular matrix resulting in a relative concentration of heparan sulfate proteoglycans at endplates. These results demonstrate an early axonal presence of neuregulin and its transmembrane precursor at developing synapses and a role for heparan sulfate proteoglycans in regulating the temporal and spatial sites of soluble neuregulin accumulation during development.     

The distribution of SMN protein complex in human fetal tissues and its alteration in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder characterized by degeneration of motor neurons of the spinal cord and muscular atrophy. SMA is caused by alterations to the survival of motor neuron (SMN) gene, the function of which has hitherto been unclear. Here, we present immunoblot analyses showing that normal SMN protein expression undergoes a marked decay in the postnatal period compared with fetal development. Morphological and immunohistochemical analyses of the SMN protein in human fetal tissues showed a general distribution in the cytoplasm, except in muscle cells, where SMN protein was immunolocalized to large cytoplasmic dot-like structures and was tightly associated with membrane-free heavy sedimenting complexes. These cytoplasmic structures were similar in size to gem. The SMN protein was markedly deficient in tissues derived from type I SMA fetuses, including skeletal muscles and, as previously shown, spinal cord. While our data do not help decide whether SMA results from impaired SMN expression in spinal cord, skeletal muscle or both, they suggest a requirement for SMN protein during embryo-fetal development.     

The ice-water test in the diagnosis and treatment of the neurogenic bladder

OBJECTIVE: To determine the usefulness of the ice-water test (IWT) in the diagnosis and treatment of neurological bladder disease. PATIENTS AND METHODS: The IWT was carried out in 148 patients with neuropathic bladder dysfunction resulting from a traumatic lesion, to assist in their diagnosis and treatment, and in 130 patients with neuropathic bladder dysfunction and multiple pathogenic disorders; the results of the IWT were used to classify those patients with hyperactive bladders. RESULTS: The IWT was positive in 95% of patients affected by complete and in 86% of patients with incomplete medullary lesions. The IWT in patients with lower motor neuron medullary lesions was always negative. The test was used diagnostically in all patients with lower and in 43% of those with upper motor neuron lesions. In the latter, it was used in 48% of patients as a rehabilitation method during the medullary-shock phase to accelerate the appearance of the micturition reflex. In 9% of patients it was used to induce micturition during cystography. CONCLUSION: Because it is simple to perform, the IWT is a useful complement to urodynamic examinations in patients with neurological bladder disease and in patients with micturitional disorders that are otherwise difficult to interpret.     

Motor neuron syndromes in cancer patients

Previous reports indicate that motor neuron disease (MND) may rarely be associated with systemic cancer. We have encountered 14 patients with MND and cancer who formed three distinct groups. Group 1: Three patients developed a rapidly progressive MND, less prominent symptoms of involvement of other areas of the nervous system, and anti-Hu antibodies. Group 2: Five women developed signs of upper motor neuron (UMN) disease, initially resembling primary lateral sclerosis (PLS), and breast cancer. In 4, symptoms of UMN occurred within 3 months of cancer diagnosis or tumor recurrence. They had no metastases or spinal cord compression. Serum anti-neuronal antibodies were negative. Three patients are alive (follow-up of 156, 15, and 12 months), and 2 remain without lower motor neuron signs. Group 3: Six patients developed MND resembling amyotrophic lateral sclerosis between 47 months before and 48 months after their cancer diagnosis. In group 1, the MND associated with the anti-Hu antibody is unequivocally paraneoplastic. In group 2, the proximate onset of MND with the diagnosis of cancer or its recurrence, its pure or long-lasting UMN signs, and its association with breast cancer, suggest that the disorder may be paraneoplastic. Although for most cancer patients who develop MND the occurrence of both disorders is probably coincidental, in some patients with MND a careful search for an underlying cancer is warranted (ie, patients in groups 1 and 2).     

Oxidative stress, mutant SOD1, and neurofilament pathology in transgenic mouse models of human motor neuron disease

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily affects motor neurons in the spinal cord and brain stem. About 10% of all ALS cases are familial (FALS), inherited in an autosomal dominant manner. One fifth of FALS patients carry mutations in the Cu/Zn superoxide dismutase (SOD1) gene, and several lines of transgenic mice have been engineered to express mutant forms of the SOD1 gene that are linked to FALS. Significantly, many of these transgenic lines of mice develop a motor neuron disease (MND) that resembles human FALS. Oxidative stress induced by human SOD1 mutations is believed to play an important role in the pathogenesis of FALS and the FALS-like MND seen in the mutant SOD1 transgenic mice. For example, two lines of these mice showed prominent degeneration of mitochondria and endoplasmic reticulum in spinal cord neurons. Furthermore, recent studies have shown that neurofilament (NF)-rich spheroids. Lewy body-like NF inclusions, altered ubiquitin immunoreactivity, and Golgi fragmentation occur in the spinal cord motoneurons of these mutant SOD1 transgenic mice. Because these lesions recapitulate hallmark abnormalities of human ALS, mutant SOD1 transgenic mice provide a useful model for studies designed to elucidate the pathogenesis of ALS. Furthermore, transgenic mice that overexpress NF proteins also develop a clinical and pathologic phenotype similar to human MND, and polymorphisms in an NF gene have been linked to patients with ALS. Collectively, these observations implicate NF protein abnormalities in the pathogenesis of this disorder. Accordingly, this review summarizes recent insights into mechanisms of motor neuron degeneration in ALS that have emerged from studies of these new animal models of this neurodegenerative disease.     

Hyperhidrosis as the presenting symptom in post-traumatic syringomyelia

Post-traumatic syringomyelia is now a well known entity and occurs months or years after a spinal cord injury. The presenting symptoms are usually pain, progressive motor weakness, sensory changes, and increased spasticity. Profuse sweating or hyperhidrosis can be a symptom of the post-traumatic syrinx or can occur in autonomic dysreflexia provoked by peripheral stimuli. We present two patients with cervical spine fractures whose presenting symptom of post-traumatic syringomyelia was hyperhidrosis affected by posture. The pathophysiology involved and the management of these patients is discussed.     

Congenital tethered spinal cord syndrome in adults

OBJECT: The management of tethered spinal cord syndrome with onset of symptomatology occurring in adulthood remains controversial, although the necessity of early surgery in the pediatric tethered cord syndrome population is well established. To ascertain the results of surgery in adult patients with this anomaly, the authors undertook a retrospective review of 34 cases. METHODS: The authors studied the hospital records of 34 consecutive patients who presented in adulthood with tethered cord syndrome and conducted follow-up phone interviews with 28 of them. The population consisted of 12 men and 22 women, ranging in age from 18 to 70 years (mean 34 years). The most common presenting feature was pain, followed by weakness and incontinence. All patients underwent surgery. The most common operative findings were tight filum terminale, split cord malformation, and lipomyelomeningocele, paralleling those observed in pediatric studies. Long-term surgical results and patient outcome ratings were encouraging. After a mean clinical follow-up period of 4 years, significant improvement occurred in 22 of 27 patients presenting with pain, 13 of 27 patients with motor or sensory dysfunction, and 11 of 18 patients with bowel and bladder disturbance. In addition, telephone interviews were obtained after a period of 8.6 years. Twenty-two (79%) of 28 patients called the operation a long-term success; 21 (75%) of 28 patients believed that they had significant postoperative improvement (and not just stabilization) in pain and/or neurological function. Surgical complications were generally minor. Nineteen (86%) of 22 employed patients returned to work after surgery. Two (33%) of six patients who were not employed before surgery worked full time postoperatively. Only two of the 28 patients interviewed had received Workers' Compensation benefits; both of these had good outcomes and returned to work. CONCLUSIONS: Tethered spinal cord syndrome in adults is an uncommon entity that can become symptomatic. Although surgery in adults involves greater risk of neurological injury than in children, it is a low-risk procedure with encouraging results. Because neurological deficits are generally irreversible, early surgery is recommended.     

Delayed and selective motor neuron death after transient spinal cord ischemia: a role of apoptosis?

OBJECTIVE: The mechanism of spinal cord injury has been thought to be related to tissue ischemia, and spinal motor neuron cells are suggested to be vulnerable to ischemia. We hypothesized that delayed and selective motor neuron death is apoptosis. METHODS: Thirty-seven Japanese domesticated white rabbits weighing 2 to 3 kg were used in this study and were divided into two subgroups: a 15-minute ischemia group and a sham control group. Animals were allowed to recover at ambient temperature and were killed at 8 hours, and 1, 2, 4, and 7 days after reperfusion (n = 3 at each time point). By means of this model, cell damage was histologically analyzed. Detection of ladders of oligonucleosomal DNA fragment was investigated with gel electrophoresis up to 7 days of the reperfusion. Immunocytochemistry, in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining was also performed. RESULTS: After 15 minutes of ischemia, most of the motor neurons showed selective cell death at 7 days of reperfusion. Typical ladders of oligonucleosomal DNA fragments were detected at 2 days of reperfusion. Immunocytochemistry showed in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end staining was detected at 2 days of reperfusion selectively in the nuclei of motor neurons. CONCLUSION: These results suggest that delayed and selective death of the motor neuron cells after transient ischemia may not be necrotic but rather predominantly apoptotic.     

Intradural parenchymal involvement in the spinal subarachnoid space associated with primary lung cancer

BACKGROUND: Intradural parenchymal involvement (IPI) in the spinal subarachnoid space associated with primary lung cancer is rare. A retrospective study was undertaken to investigate the clinical and pathologic features of IPI. METHOD: A total of 1215 cases of primary lung cancer were studied at autopsy; the results were reviewed retrospectively. RESULTS: Twenty (1.65%) of the cases revealed IPI in the spinal subarachnoid space. The histologic diagnoses were small cell carcinoma in ten cases, adenocarcinoma in eight cases, and squamous cell carcinoma in two cases. In 14 (70%) cases, the IPI was located between the lumbar and cauda equina of the spinal cord. However, no metastases were observed in the cervical spinal cord. Brain metastasis, vertebral metastasis, and meningeal carcinomatosis were seen in 70%, 60%, and 40% of the 20 cases, respectively, suggesting that these metastases may be related to the metastatic pathway to the spinal cord. Most patients had neurologic symptoms or signs referable to IPI; IPI could be diagnosed before death in only one patient by magnetic resonance imaging. The median interval between diagnosis of lung cancer and development of IPI and median survival after the onset of neurologic symptoms referable to IPI were 415 days and 110 days, respectively. CONCLUSION: The authors retrospectively received 1215 autopsies of patients with primary lung cancer and found 20 (1.65%) with IPI.