Peter V. Hall

Glycine and experimental spinal spasticity

Spasticity may result in part from segmental spinal disinhibition. We determined the content and specific activity of glycine (the putative neurotransmitter thought to mediate spinal postsynaptic inhibition) and serine (the probable precursor of glycine) in feline spastic spinal cord following the intra-aortic administration of two labelled precursors of glycine—14C-D-glucose and 14C-L-serine. The specific activities of both glycine and serine were significantly reduced in the ventromedial, central, and dorsal spinal gray matter in spastic animals. Glycine content remained at control values but serine content increased in spastic spinal cord. This study suggests that glycine turnover decreases in spasticity, owing to its diminished release, and supports neurophysiologic evidence of a decrement in postsynaptic inhibition.

Myelodysplasia and Developmental Scoliosis: A Manifestation of Syringomyelia

Fourteen of 15 myelodysplastic patients evaluated for developmental scoliosis were found to have communicating hydrosyringomyelia, a manifestation of spontaneously arrested hydrocephalus. Eight of these patients had progressive extremity paralysis in addition to the scoliosis. Treatment by ventricular decompression was associated with short term stabilization in 6 early cases of scoliosis. However, more advanced scoliosis in 2 patients continued to progress. Neurologic deficits were improved even in advanced cases by ventricular shunting. The authors propose that hydromyelia and syringomyelia are the cause of developmental scoliosis in myelodysplasia and suggest methods of investigating and treating patients with these conditions.

A Study of Experimental Syringomyelia by Scanning Electron Microscopy

Experimental hydromyelia and syringomyelia, induced by kaolin in dogs, has been investigated by scanning electron microscopy. This study demonstrated that communication between the 4th ventricle and the spinal central canal is normally occluded by a plug of acellular material lying within the central canal. This plug is broken down following the onset of hydrocephalus and communication is rapidly established between the ventricles and the central canal. The canal distends and ruptures dorsally into the spinal gray matter with the development of extensive intramedullary cavities, lined by glial and neuronal elements. The morphological changes demonstrated are consistent with a physical destructive process of the cord resulting from CSF dissection.

Neurochemical correlates of spasticity

Abstract Dogs were made paraplegic by complete mid-thoracic spinal cord transection. The content of glycine, glutamate, aspartate, and γ-aminobutyric acid were determined in ventral and central grey matter from the lumbar enlargement of the spinal cord at 1, 3 and 8 weeks after transection. A rapid decrease in the content of aspartate and glycine accompanied the onset of spasticity. By the eight week post-transection, aspartate and glycine had decreased to less than 50% of control levels.

Meningomyelocele and Syringohydromyelia

Twenty meningomyelocele patients with nonfunctional ventricular shunts or no shunts were studied radiologically. This group was compared to a second group of 4 patients with functional shunts. The various techniques are compared and discussed. Pantopaque ventriculography is a potentially dangerous procedure. Radioisotope ventriculography appears to be a safe and useful method of diagnosing syringohydromyelia. Ventricular decomposition by means of a shunt appears to be an effective treatment.

Alterations of amino acid transmitter systems in spinal cords of chronic paraplegic dogs

Abstract: The high‐affinity uptake of [3H]serotonin, [3H]glutamate, and [3H]‐γ‐aminobutyric acid (3H]GABA) and the Na+‐independent binding of [3H]glutamate and [3H]GABA were studied using spinal cord preparations obtained from normal mongrel dogs and from dogs made paraplegic by midthoracic spinal cord crush. Lumbosa‐cral regions of the spinal cord were removed either before (1 week) or after (3 to 8 weeks) onset of spasticity. A myelin‐free synaptosomal fraction was obtained by cen‐trifugation and used for studying high‐affinity uptake and for preparing synaptic plasma membranes for Na+‐inde‐pendent binding experiments. For the paraplegic groups, the uptake of 30 nM [3H]serotonin was 66 and 18% of control values after 1 and 3 weeks, respectively. Eadie‐Hofstee analysis of [3H]serotonin uptake showed a 90% reduction in Vmax for the paraplegic group relative to control values, thereby indicating the expected loss of descending serotonergic pathways. The high‐affinity uptakes of 1 μM [3H]glutamate and [3H]GABA were the same in both the control and nonspastic paraplegic groups after 1 week. However, after 3 weeks, the uptakes of [3H]glutamate and [3H]GABA were 60‐70% higher for the spastic group than for the control animals. For both amino acids, Eadie‐Hofstee plots revealed no difference in Km and higher Vmax for the spastic group relative to control values. After 1 and 3 weeks, the Na+ ‐independent binding of 5 nM [3H]glutamate was 40‐85% higher and the binding of 10 nM [3H]GABA was 40‐60% lower for the paraplegic groups relative to the values for the control animals. Scatchard analysis revealed significant changes in Bmax values for both amino acids. Overall, the data indicate an increase in segmental amino acid excitatory influence which occurred when signs of spasticity were evident.

Effects of glycine administration on canine experimental spinal spasticity and the levels of glycine, glutamate, and aspartate in the lumbar spinal cord.

Twelve female mongrel dogs were made paraplegic by midthoracic spinal cord transection. Beginning at 9 weeks posttransection, either glycine (50 mg/kg) or saline was injected intramuscularly each day and the signs of spinal spasticity were assessed clinically. After treating the dogs for 3 weeks, we removed the lumbar enlargement of each dog and microdissected it into gray and white areas which we assayed for glycine, glutamate, and aspartate content. Some of the clinical signs of spasticity improved in the animals injected with glycine compared to the saline-injected controls. The content of glycine was significantly elevated in the central gray matter and ventral medial white matter of the glycine-treated dogs. The levels of glutamate were also significantly elevated in the central, lateral ventral, and medial ventral gray matter and in the dorsal lateral and ventral medial white matter of the glycine-treated dogs. The possible role of these segmental putative neurotransmitters in spinal spasticity is discussed.

Levels of ɤ-aminobutyric acid in the dorsal grey lumbar spinal cord during the development of experimental spinal spasticity

Abstract Dogs were made paraplegic by complete mid-thoracic spinal cord transection. At one, three, eight, and twelve weeks post-transection the lumbar cord was removed and the dorsal grey matter microdissected from L 2–3 and the content of ɤ-aminobutyric acid (GABA) determined. An initial decrease in GABA levels was followed by a gradual increase in content which correlated with the progressive development of spinal spasticity. By twelve weeks post-transection, GABA was elevated 68% above controls.

Alterations in Cerebrospinal Fluid Dynamics in Syringomyelia, Hydromyelia, and Myelomeningocele

Syringomyelia is a relatively uncommon disease of cystic cavitation of the spinal cord, generally found at the cervical and thoracic levels. Characteristically, the syringomyelic cyst lies separate from the spinal central canal, as distinct from hydromyelia, in which the central canal is distended with cerebrospinal fluid (CSF). However, the two conditions may coexist and may be difficult to distinguish histologically.24 Furthermore, some investigators, noting that syringomyelia and hydromyelia may share a common etiology, have substituted the term syringohydromyelia.3

Effects of dorsal bilateral rhizotomy treatment on transmitter systems in the spinal cord of normal and spastic dogs.

The high‐affinity uptakes of [3H]serotonin, [3H]‐glutamate, and γ‐[3H]aminobutyric acid were studied using a myelin‐free crude synaptosomal fraction prepared from the spinal cords of normal dogs and spastic dogs following sham treatment or dorsal bilateral rhizotomy surgery. Compared to sham‐operated controls, rhizotomy surgery of normal dogs produced, after 1 week, a 30% reduction in the Vmax value of [3H]glutamate, but did not alter the uptake of γ‐[3H]aminobutyric acid. This treatment also produced a 60% decrease in the Vmax value of [3H]serotonin. Comparison of the effect of rhizotomy surgery on normal and spastic dogs revealed that the spastic group had 60% higher Vmax values for uptakes of [3H]glutamate and γ‐[3H]aminobutyric acid. Comparison of sham‐operated spastic dogs and rhizotomy‐treated spastic animals showed that there was a 25% decrease in the uptake of both amino acids in the rhizotomy‐treated spastic group. Overall, the data (a) support the hypothesis that glutamate is the neurotransmitter from some of the primary afferents, and (b) suggest that sprouting of interneuronal amino acid transmitter systems may occur in the spinal cords of spastic dogs.