Shokei Yamada, M.D., Ph.D.
Adam Conley, M.D.
Bermans Iskandar, M.D.
Graham Fieggen, M.D.
Ann Ritter, M.D.
Editor in Chief
Rick Abbott, M.D.
Since 1910, several articles suggested that spinal cord traction by caudal anomalies might be the cause of reversible neurological dysfunction (13). However, these clinical and pathological reports lacked pathophysiological explanation for reversible neurological dysfunction. Hence, skepticism toward the concept of “spinal cord tethering” continued before the publication of two articles. In 1976, Hoffman et al. described patients with motor and sensory deficits in lower limbs and incontinence associated with an elongated cord and thickened filum terminale (3). On observing neurological improvement after sectioning the filum, they attributed the neurological deficit to the caudal traction effect of the thickened filum on the spinal cord, and coined the term “tethered spinal cord” for this condition. In 1981, Yamada et al. demonstrated impaired oxidative metabolism in the lumbosacral cord of patients who presented with the same symptomatic and anatomical abnormalities (5). Furthermore, parallel metabolic and neurological improvement occurred after sectioning of the thickened filum. These authors adopted the term “tethered cord syndrome” (TCS) to include the patients with a thickened filum as well as those with caudal lipomas, lipomyelomeningoceles, and myelomeningoceles. These two articles clarified the pathophysiology of the stretch-induced spinal cord disorder, and the rationale for sectioning or resectioning of any of the inelastic structures anchoring the spinal cord (2, 3). Below are the research studies to correlate the pathophysiology with the symptomatology of tethered cord syndrome.
Pathophysiological studies included three experimental methods, anatomical, biochemical, and physiological:
- Anatomic study of cat filum: Anatomically, the cat filum was tractioned caudad, and the elongation rate of each cord segment was measured. The filum elongated much greater than any cord segment, indicating that the viscoelastic filum prevents overstretching the spinal cord exerted by any traction force. In contrast, the inelastic rigid filum provides no protection for the spinal cord, as seen in patients with TCS.
- Biochemical analysis of neuronal metabolism: The biochemical study was based on the link between neurological function and metabolic activity, since the CNS relies absolutely on oxidative metabolism to produce ATP. The study was carried out non-invasively by dual wavelength reflectance spectrophotometry. This technology allowed for moment-to-moment measurement of reduction/oxidation ratio (redox) of cytochrome a,a3. Mitochondria are the source of energy in neurons, and ATP is the energy-donating molecule necessary for neuronal function and cell survival. Cytochrome a,a3, studded to mitochondrial cristae, is the key enzyme for oxidation. Oxidized cytochrome accelerates electron transport, which is tightly coupled with ADP phosphorylation, thus producing ATP. Instead, when the cytochrome is reduced, neuronal dysfunction due to decreased ATP production occurs as a manifestation of energy deficiency. The same pattern of impaired oxidative metabolism observed in experimental animals confirms the pathophysiology of human tethered spinal cord.
- Physiological study of impaired metabolism: Electrophysiological studies showed deterioration in interneuron potentials that occurred simultaneously with impaired oxidative metabolism in tethered spinal cord. In conclusion, the changes demonstrated by anatomical, biochemical, and physiological studies correlated to neurological dysfunction of tethered cord syndrome patients.
Additional Research on Tethered Spinal Cord
To further elucidate the correlation between the pathophysiology and clinical manifestations, other studies have been carried out in the experimental model, including spinal cord blood flow, glucose metabolism, light microscopic histology, chronically tractioned cord, ultrastructural changes in suddenly tractioned cord, and horseradish peroxidase transport in the long tract.
- Decoupling of blood flow from metabolism with severe traction: Blood flow decrease corresponds to metabolic and electrophysiological changes in mild degrees of cord traction. Under heavy traction, however, there is dissociation between blood flow and metabolic and electrophysiological function, that is, no further decrease in blood flow despite further deterioration of the latter. Na+ and K+ channel disturbances associated with overstretching of neuronal cell membranes probably explain the discrepancy.
- Gray matter mainly affected: 2D-dioxyglucose metabolism indicates that the gray matter of the spinal cord is mainly impaired, corresponding to the results obtained by redox of cytochrome a,a3 and potential studies. To support this view, axonal transport in long sensory tracts were studied with horseradish peroxidase and found to be intact.
- No histological injury: In the experimentally tractioned cord, no histological damage is found under acute (isotonic) or chronic (isometric) traction.
- Change in filum characteristics: The inelastic filum in patients with TCS is filled with fibrous (collagenous) tissue that has replaced glial-ependymal tissue, found in normal individuals.
- Conus medullaris sensitive to injury: From pathophysiological studies, there is high vulnerability of the conus medullaris, which supports the observation that incontinence becomes irreversible earlier than motor and sensory dysfunction in patients with TCS.
In conclusion, tethered spinal cord (Hoffman et al.) and TCS (Yamada et al.) represent a potentially reversible stretched-induced functional disorder of the spinal cord, with the cord’s caudal end anchored by inelastic structures (3,5) This definition of TCS, however, has been interpreted differently by some authors as a synonym of the term “tethered cord.” Since this term originated from visual and anatomical observations (6), Yamada felt that categorization into three groups was needed: Category 1, true TCS, which meets all the requirements of the syndrome as described; Category 2, partial TCS, with the combination of stretch-induced signs and symptoms found cephalic to the location of an anomaly (e.g., lipoma) and those at the anomaly level that are caused by compression or ischemic effect, and partly by dysgenesis of the neural component (often glial tissue mixed with fat or fibrosis); Category 3, with total paraplegia and incontinence due to agenesis, e.g., failure of embryonic neurulation, or severe fibrous scar formation covering the entire lumbosacral cord.