Serum oxidative stress influences neurological recovery after surgery to treat acutely worsening symptoms of compression myelopathy: a cross-sectional human study.

BACKGROUND: Recent reports indicate that oxidative stress induced by reactive oxygen species is associated with the pathobiology of neurodegenerative disorders that involve neuronal cell apoptosis. Here we conducted a cross-sectional study to evaluate serum levels of oxidative stress in cervical compression myelopathy. METHODS: Thirty-six serum samples were collected preoperatively from patients treated for acutely worsening compression myelopathy (AM) and chronic compression myelopathy (CM). Serum levels of oxidative stress markers were evaluated by measuring derivatives of reactive oxygen metabolites (ROM), which reflect concentrations of hydroperoxides. ROM in healthy individuals range from 250 to 300 (U. CARR), whereas ROM >340-400 and > 400 define moderate and severe levels of oxidative stress, respectively. Difference of ROM by the cause of disorders whether cervical spondylotic myelopathy (CSM) or cervical ossification of longitudinal ligament (OPLL), correlations between ROM and patient age, body mass index (BMI), history of smoking, existence of diabetes were examined. Neurological evaluations according to Japanese Orthopaedic Association (JOA) scores were performed and correlated with ROM. RESULTS: ROM increased to 349.5 ± 54.8, representing a moderate oxidative stress, in CM samples. ROM increased to 409.2 ± 77.9 in AM samples, reflecting severe oxidative stress which were significantly higher than for CM samples (p < 0.05). There was no significant difference by the cause of disorders (CSM or OPLL). ROM were significantly increased in AM serum samples from female patients versus AM male and CM patients (p < 0.05). There were no correlations between ROM and age, BMI, history of smoking, and existence of diabetes. A negative correlation between ROM and recovery rate of JOA score (R2 = 0.454, p = 0.047) was observed in the AM group. CONCLUSIONS: Although moderate oxidative stress was present in patients with CM, levels of oxidative stress increased in severity in patients with AM. These results suggest that postsurgical neurological recovery is influenced by severe oxidative stress in AM.

Minimal Access vs. Open Spine Surgery in Patients With Metastatic Spinal Cord Compression - A One-Center Randomized Controlled Trial.

BACKGROUND/AIM: We conducted a randomized controlled trial to investigate whether minimally access spine surgery (MASS) is less morbid than open surgery (OS) in patients with metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: A total of 49 MSCC patients were included in the trial. The outcome measures were bleeding (L), operation time (min), re-operations and prolonged wound healing. RESULTS: The median age was 67 years (range=42-85 years) and 40% were men. The peri-operative blood loss in the MASS-group was significantly lower than that in the OS-group; 0.175L vs. 0.500L, (p=0.002). The median operation time for MASS was 142 min (range=72-203 min) vs. 103 (range=59-435 min) for OS (p=0.001). There was no significant difference between the two groups concerning revision surgery or delayed wound healing. CONCLUSION: The MASS technique in MSCC patients is associated with less blood loss, but a longer operation time when compared to the OS technique.

Significance of serial S100b and NSE serum measurements in surgically treated patients with spondylotic cervical myelopathy.

BACKGROUND: Predicting functional outcome following surgery performed for spinal cord compression is still a considerable problem. Recent observations, though, strongly suggest that with serial measurements of serum S100b, this might be possible in patients with subacute spinal cord compression. The aim of this study was to examine whether this potential significance of S100b applies as well to patients with spondylotic cervical myelopathy. A further purpose was to assess the value of NSE in this regard, another biochemical marker widely used to monitor cerebral lesions. METHODS: Fifty-one patients were included in this prospective study. Outcome was considered as favourable in case of neurological improvement with preservation or retrieval of walking ability, whereas non-improvement without restoration of gait function was regarded as unfavourable. The preoperative levels of S100b and NSE were correlated with the degree of paresis, duration of symptoms, and presence of intramedullary high signal intensities on MRI. The postoperative values of both markers were correlated with outcome. FINDINGS: The preoperative levels of S100b were neither correlated with degree or duration of paresis nor with outcome. In case of an uncomplicated course the postoperative levels of S100b were also not correlated with outcome. In complicated courses with acute postoperative deterioration normal values on the 3rd day after the event were associated with a favourable outcome, whereas one patient with unfavourable outcome showed a persistent pathological increase. The serum levels of NSE were not correlated with clinical parameters or with outcome in any of the cases. CONCLUSIONS: Serial S100b serum measurements do not permit prediction of functional outcome in patients with spondylotic cervical myelopathy in case of an uncomplicated postoperative course. In complicated courses with postoperative deterioration, such measurements reflect postoperative events with possibly prognostic relevance. NSE does not have any significance in these patients with chronic lesions of the spinal cord.

Spinal IgG4-Related Hypertrophic Pachymeningitis with Spinal Cord Compression: Case Report and Literature Review.

BACKGROUND: Back pain is a leading reason for patients to seek medical attention. Although musculoskeletal causes are common, patients can also present with rarer etiologies. CASE DESCRIPTION: A 50-year-old man presented with 2 months of isolated upper back pain initially suspected to be secondary to overuse muscular strain. During the next 3 months, his pain worsened, and he developed lower extremity dysesthesia and subjective weakness, despite normal neurological examination findings. Nonrevealing laboratory workup included normal muscle enzymes, C-reactive protein, urinalysis, and human leukocyte antigen B27. Magnetic resonance imaging revealed a normal brain but a hypointense C7-T5 epidural mass, prompting a neurosurgical recommendation for laminectomy with evacuation of the suspected hematoma. His symptoms fully and promptly resolved after a 5-day course of prednisone 40 mg. When his symptoms recurred within 2 months, he underwent T4-T5 laminectomy with biopsy of a mass confluent with the dura mater. Initial pathological examination revealed fibrotic tissue of unclear etiology with polyclonal lymphoid infiltrate but no malignant cells, vasculitis, or granulomas. After months of recurrent, steroid-responsive symptoms, he presented to the rheumatology clinic. Repeat spinal magnetic resonance imaging demonstrated progression of epidural thickening with suspected spinal cord compression. Previous biopsy samples were then immunostained for IgG4, revealing focally dense IgG4-positive plasma cells, up to 29 cells per high power field, consistent with spinal IgG4-related hypertrophic pachymeningitis. He began rituximab therapy with a prednisone taper and demonstrated symptomatic and neurologic improvement with successful withdrawal from corticosteroids. CONCLUSIONS: To the best of our knowledge, the present case represents the 12th reported case of spinal IgG4-related hypertrophic pachymeningitis. An early diagnosis and treatment could prevent progression to permanent neurological impairment and functional disability.

Excellent and durable response to radiotherapy in a rare case of spinal cord compression due to extra-medullary hematopoiesis in ß-thalassemia intermedia: case report and clinicoradiological correlation.

Spinal cord compression (SCC) is an unusual sequale of extra-medullary hematopoiesis (EMH). We report a patient diagnosed with ß-thalassemia intermedia at the age of 7 years presenting as a 24-year-old with symptoms suggestive of paraparesis. MR imaging revealed long masses of EMH opposite T5-T11 and L5-S2 vertebrae with cord compression at T6 vertebrae. Patient was treated with external beam radiotherapy (EBRT) to a low dose of 20 Gy in 10 fractions over 2 weeks. The patient had symptomatic relief of paraparesis by the 5th fraction and nearly regained full power in bilateral lower limbs by EBRT conclusion. Patient was begun on hydroxyurea post EBRT and was symptom free at 2-month follow up. With a follow-up of 18 months so far, he remains asymptomatic and free of recurrence. MRI correlation of pre-EBRT, post-EBRT and at first follow-up showed a significant reduction in the size of EMH, increase in diameter of spinal canal post EBRT but a persistent edema which had no clinical manifestation. Though there was a 58% drop in leukocyte count by the end of EBRT, there was no leukocytopenia. We suggest that EBRT should be treatment of choice for SCC due to EMH as it produces as rapid and durable response with minimal acute hematological side-effects.

Inflammation Level after Decompression Surgery for a Rat Model of Chronic Severe Spinal Cord Compression and Effects on Ischemia-Reperfusion Injury.

Delayed neurological deterioration in the absence of direct spinal cord insult following surgical decompression is a severe postoperative complication in patients with chronic severe spinal cord compression (SCC). The spinal cord ischemia-reperfusion injury (IRI) has been verified as a potential etiology of the complication. However, the exact pathophysiologic mechanisms of the decompression-related IRI remain to be defined. In this study, we developed a practical rat model of chronic severe SCC. To explore the underlying role of inflammation in decompression-related IRI, immunoreactivity of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and interleukin-1ß (IL-1ß) before and after decompression were measured. In addition, expression level of TNF-α and IL-1ß was examined with Western blot. Immunohistochemical staining showed negative result in gray matters in the sham group and sham-decompression group. In the severe compression group, strong positive staining of TNF-α and IL-1ß were found, suggesting a dramatic infiltration of inflammatory cells in gray matters. Furthermore, the severe compression group showed a significant increase in expression level of TNF-α and IL-1ß as compared with the sham group (p < 0.05). In the severe compression-decompression group, both immunostaining and Western blot showed significant increase of TNF-α and IL-1ß levels in the spinal cord compared with the severe compression group (p < 0.05). The results demonstrated that surgical decompression plays a stimulative role in inflammation through increasing the expression of inflammatory cytokines in the rat model of chronic severe SCC injury. Inflammation may be one of the important pathological mechanisms of decompression-related IRI of chronic ischemia.

Phosphorylated neurofilament subunit levels in the serum of cervical compressive myelopathy patients.

We investigated the serum levels of the phosphorylated form of the high molecular weight neurofilament subunit (pNF-H) in patients with cervical compressive myelopathy. pNF-H is becoming increasingly recognized as a biomarker for axonal injury, however, it remains unclear whether serum pNF-H is elevated in chronic spinal cord compression. We examined 26 patients who underwent surgery for cervical compressive myelopathy. Peripheral blood samples were obtained both preoperatively and 1 week after surgery to evaluate the serum pNF-H levels using an enzyme-linked immunosorbent assay. A history of recent aggravation of myelopathy was also investigated. Of the 26 myelopathy patients, the preoperative serum pNF-H level was negative in 20 patients and moderately elevated in six. Patients who were positive for pNF-H were more likely to have had a recent aggravation of myelopathy compared with the pNF-H negative patients (83 versus 25%; p=0.02). All patients who were positive for pNF-H before surgery remained positive after surgery. Two patients who became positive after surgery demonstrated a neurologic deterioration associated with the surgery. In conclusion, the serum pNF-H level was negative in the majority of patients with cervical compressive myelopathy. Our results suggest that an elevated serum level of pNF-H is associated with an acute worsening of myelopathy and that a positive conversion of pNF-H after surgery is a marker of perioperative neural damage.

Effect of hypertonic saline on leukocyte activity after spinal cord injury.

STUDY DESIGN: The effect of intravenous administration of hypertonic saline on leukocyte adhesion after compression injury of the spinal cord was evaluated. OBJECTIVES: To investigate changes in leukocyte adhesion after spinal cord injury and to evaluate the effect of hypertonic saline on this process. SUMMARY OF BACKGROUND DATA: Leukocytes have been thought to exacerbate tissue injury after ischemia-reperfusion. Downregulating and reducing the number of circulating leukocytes has attenuated tissue damage in various models of cerebral ischemia. Recently, investigators have reported that leukocytes exacerbate injury in the spinal cord after trauma. Other recent findings have indicated that hypertonic saline may play a role in decreasing leukocyte adhesion and activation. METHODS: Sprague-Dawley rats were anesthetized, and a C3-C5 laminectomy was performed. Injury was caused by 35 g of compression applied to the cord for 10 minutes. Animals were divided into three groups: sham treated, untreated, and treated. The treated animals received 7.5% hypertonic saline (5 mL/kg, intravenously) 5 minutes after the injury. Sticking leukocytes and shear rate were measured using fluorescence microscopy. RESULTS: Administration of 7.5% hypertonic saline after injury significantly decreased the number of sticking leukocytes in the venules and arterioles. Shear rate was unchanged between the groups. CONCLUSIONS: The results show that an increase in leukocyte adhesion after a compressive injury is attenuated by the administration of 7.5% hypertonic saline. The decrease in adhesion cannot be attributed to changes in the shearing forces, because no significant change was observed in the shear rate. Hypertonic saline may interfere with leukocytes directly by interfering with their ability to swell and thus may prevent activation.

[Clinical and biochemical mechanisms of the formation of chronic low back pain].

A comprehensive survey of 78 patients with chronic vertebral low back pain was conducted. Among them were 23 (29,5%) patients with radiculopathy and 55 (70,5%) patients with reflex syndromes without exacerbations. It was shown that patients with compressive syndromes of lumbar dorsopathy were characterized by the high intensity of pain, pronounced neuropathic pain component, lower quality of life as well as the significantly low serum serotonin content that was correlated with the degree of neuropathic pain severity and depression level.

Spinal-cord compression related to pseudohypoparathyroidism.

We report a 24-year-old male with pseudohypoparathyroidism and a 6-month history of sensory disturbance in both legs which was associated with difficulty in walking. His physical signs included a short stature, a thick neck, short fourth metacarpals and metatarsals, a spastic paraparesis and sphincteric disturbance. His serum electrolytes included low serum calcium and high serum phosphorus levels. CT reconstruction showed compression of the spinal cord in association with ossified ligamentum flavum at the C2-7 and T9-10 levels. These findings were confirmed by MRI scans.

Experimental subacute spinal cord compression: correlation of serial S100B and NSE serum measurements, histopathological changes, and outcome.

OBJECTIVE: To correlate serial measurements of serum S100B and neuron-specific enolase (NSE) with histopathological changes of the spinal cord and to assess their prognostic significance in a set-up of experimental spinal cord compression. METHODS: The thoracic cords of 22 rabbits were increasingly compressed and decompressed once paresis had developed. After decompression, outcome was rated as favorable or unfavorable. Following sacrifice of the animals, the cord was analyzed microscopically and morphometrically. Serum S100B and NSE were measured daily, and levels were correlated with initial degree of paresis, outcome after decompression, and histopathological changes of the cord. RESULTS: Regardless of the initial degree of paresis, animals with favorable outcome had significantly higher cell counts than animals with unfavorable outcome. The time course of S100B values following decompression was correlated with outcome. Animals with favorable outcome had either always normal levels or levels that were initially increased but normalized within 2 days. The values of animals with unfavorable outcome were elevated throughout (P<0.0001). No correlation was found between NSE levels and outcome. CONCLUSIONS: The initial degree of paresis is not a prognostic factor to predict outcome. Despite timely decompression, pronounced structural lesions of the cord may develop, resulting in an unfavorable outcome. In cases with favorable outcome, sufficient tissue is preserved to maintain function regardless of the initial extent of paresis. This different reaction of the cord may be followed indirectly with serial measurements of S100B serum levels. Thus, S100B is a reliable biochemical marker allowing for prediction of outcome. NSE does not have this prognostic significance.

Conservative management of an acute spontaneous holocord epidural hemorrhage in a hemophiliac infant.

Central nervous system hemorrhages are an uncommon but severe complication of hemophilia, occurring in only 2-8% of children with hemophilia. Less than 10% of these CNS hemorrhages are intraspinal. The authors report on their care of an infant with hemophilia A who presented with irritability, meningismus, and decreased spontaneous movement. These symptoms prompted imaging studies, which revealed a spinal epidural hematoma (SEH) extending from C-1 through the cauda equina. The boy was treated with factor replacement and close monitoring. Repeat radiographic imaging 14 days later demonstrated complete resolution, and the patient had returned to his normal baseline status. A literature review in the modern treatment era revealed 24 cases of SEH in children with hemophilia. Of these 24 cases, 11 underwent laminectomy and 13 received conservative treatment. All conservatively treated patients, 5 of whom had presented with weakness, experienced a full recovery. Of the 11 laminectomy patients, 10 presented with weakness and all but 3 experienced full neurological improvement. These 3 patients were notable for having previously undiagnosed hemophilia. An increased index of suspicion facilitates the essential management features of prompt diagnosis and correction of coagulopathies in children who present with SEHs. The authors apply a multidisciplinary approach involving a pediatric hematologist, neurosurgeon, and pediatric intensive care unit to ensure timely correction of the coagulation disorder, maintenance of adequate factor levels, and close hemodynamic and neurological monitoring. Observation with aggressive correction of coagulopathy is a reasonable treatment choice for hemophilic patients presenting with SEH and a stable neurological examination.

Waldenstrom's macroglobulinemia presenting with spinal cord compression: a case report.

Waldenstrom's macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma characterized by a wide range of clinical presentations related to direct tumor infiltration and the production of IgM. Most commonly it presents with cytopenia, hepatosplenomegaly, lymphadenopathy, constitutional symptoms, and hyperviscosity syndrome. We report a case of WM in an 81-year-old man who initially presented with severe back pain. The patient had no peripheral lymphadenopathy or hepatosplenomegaly and his peripheral blood smear was normal. MRI of the spine revealed an epidural mass causing spinal cord compression at T9. Surgical decompression was performed and pathological analysis of the mass revealed a lymphoproliferative B-cell process. The diagnosis of WM was established after cytomorphologic and immunohistochemical analysis of the patient's bone marrow revealed the presence of a lymphoid/lymphoplasmacytoid-like bone marrow infiltrate along with an elevated serum IgM level. The patient responded both clinically and serologically to local radiotherapy. This case is unusual because the patient lacked all common clinical features of WM. This is the first reported case of epidural spinal cord compression as the initial manifestation of WM, adding to the spectrum of clinical presentations seen in this disease.

Experimental study of reflectance spectrophotometric analysis of the dog's dural sac--in the open decompressed state and after the application of external dural pressure.

Haemoperfusion and oxygen saturation were studied by tissue reflection spectra on the dural sac of dogs, Experimentally, decompression laminectomy and external pressure on the dural sac were carried out. Haemoperfusion and oxygen saturation were investigated in the open state, and after an external pressure was applied. After the application of external pressure, paraplegia occurred. The tissue Spectrum Analyser 'TS-200' (Sumitomo Electric Industries Co. Ltd, Japan) was used for the measurement of haemoperfusion and oxygen saturation. With this apparatus, an optical fibre probe is applied to irradiate tissue with white light, and the absorption spectrum of the reflected light from tissue is analysed. It has been confirmed that oxygen saturation was not changed in either state, however, haemoperfusion was decreased when external pressure was applied.

Spinal cord compression in multiple myeloma: who gets it?

Of 97 Chinese patients with multiple myeloma seen over a 12-year period, 23.7% were found to have cauda equina or spinal cord compression (SCC). Predictive features for SCC include paraprotein type, hemoglobin level, and the extent of bone lesion at initial hematological diagnosis. A discriminant function derived from this analysis can be used to predict the likelihood of SCC with 79% accuracy. It is postulated that when the cortex is more involved than the medulla in a vertebra, it will predispose to SCC while hemopoiesis is relatively preserved. Our patients presented late with advanced neurological deficit so that treatment was unsatisfactory. It is emphasised that early recognition of back pain and neurological symptoms is essential, as any delay would jeopardize the chance of neurological recovery.

Protein S-100b for individual prediction of functional outcome in spinal epidural empyema.

STUDY DESIGN: A study correlating protein S-100b serum levels with postoperative functional outcome in patients with spinal cord compression resulting from epidural empyema. OBJECTIVES: To evaluate the potential value of protein S-100b for prediction of individual functional outcome in medullary lesions resulting from spinal epidural empyema. SUMMARY OF BACKGROUND DATA: Despite modern medical advances, a reliable individual prediction of functional outcome in case of spinal epidural empyema is still not possible. METHODS: Forming two outcome groups, clinical outcome following surgery was considered to be favorable in case of neurologic improvement with preservation or retrieval of walking ability, whereas nonimprovement without restoration of gait function was regarded to be unfavorable. Venous blood samples for protein S-100b were taken from all patients immediately after admission and regularly after operative decompression. Initial levels of S-100b were correlated with preoperative degree and duration of paresis, and the individual time course of S-100b measurements was correlated with clinical outcome. RESULTS: The initial level of protein S-100b is not correlated with preoperative degree and duration of paresis or with functional outcome. The individual time course of S-100b measurements, however, is different in both outcome groups. Levels of protein S-100b that were either always normal or that were initially increased but normalized rapidly within 3 days were invariably associated with retrieval of gait function, whereas none of those patients recovered in whom increased levels of S-100b persisted beyond the third postoperative day (P < 0.003). CONCLUSIONS: Protein S-100b might be a promising serum marker with prognostic significance in the event of spinal cord compression resulting from epidural empyema.

Protein S-100b as serum marker for prediction of functional outcome in metastatic spinal cord compression.

BACKGROUND: To evaluate the significance of protein S-100b as a serum marker for the prediction of functional outcome in the event of symptomatic spinal cord compression due to epidural metastases. METHOD: 34 patients with paresis due to metastatic spinal cord compression were included in this prospective study. Venous blood samples for protein S-100b were taken after admission and regularly after operative decompression. The individual time course of protein S-100b levels was correlated with the clinical outcome by means of motor function. Outcome was considered to be favourable in case of neurological improvement and preservation or retrieval of walking ability whereas non-improvement or further neurological deterioration without restoration of function of ambulation was regarded to be unfavourable. FINDINGS: Patients with favourable outcome had serum levels of S-100b which were either normal all the time or which were initially increased but normalised within 2 to 3 days. Patients with unfavourable outcome, however, had increased levels throughout which showed either a further increase or only a slow decrease within approximately two weeks (p=0.0001). INTERPRETATION: These preliminary results suggest that, analogous to cerebral disorders, protein S-100b might be a promising serum marker to predict functional outcome in symptomatic spinal cord compression.