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Biomedical subjects

C Nordborg

Publications and source records attributed to C Nordborg.

At least 37 records · Page 2Linked to original sources

Surgical treatment of epilepsy--clinical, radiological and histopathological findings in 139 children and adults.

The present study relates clinical and radiological data to histopathological diagnoses in the first 139 patients (children and adults) in the Göteborg Epilepsy Surgery series. Temporal lobe resections were most common (54.0%) followed by frontal lobe (18.0%) and multilobar resections (11.5%). All histopathological specimens were re-evaluated in connection with this study. Parenchymal malformations and atrophic-gliotic lesions were the most common histopathological findings. Microdysgenesis was more common than major malformations (24.5% versus 11.5%). When the MRI scans were blindly re-evaluated the MRI findings correlated with histopathological diagnosis in all of the vascular malformations, in 77.8% of the tumours, in 76.5% of the cases with hippocampal sclerosis but only in 28.6% of the major cortical development malformations. Hemispherectomies carried the best seizure outcome prognosis followed by temporal lobe resections (75.0% versus 57.3% seizure free 2 years after surgery). Vascular malformations carried the best, and microdysgenesis the worst prognosis (76.9% versus 39.4% seizure free).

Adolescent↗

Microdysgenesis in surgical specimens from patients with epilepsy: occurrence and clinical correlations.

Malformations of cortical development are commonly associated with epilepsy. In the first 139 consecutive patients in the Göteborg epilepsy surgery series, parenchymal malformations were found in 56. 1% of the children and in 23.1% of the adults. Microdysgenesis (MDG), which was the most common parenchymal malformation, was found in 35. 1% of the children and in 16.7% of the adults. The aim of this study was to identify clinical characteristics of patients with MDG. Mental retardation was found to be significantly more common in patients with major parenchymal malformations and in patients with MDG compared with patients without parenchymal malformations. Patients with major parenchymal malformations as well as patients with MDG also had a significantly earlier onset of seizures than patients without parenchymal malformations, also when adjusting for mental retardation. Patients with MDG were in these clinical aspects shown to closely resemble patients with major malformations. These findings suggest that MDG is a pathoanatomical entity of clinical relevance, with implications both in mental retardation and in epileptogenesis.

Adolescent↗

Effects of lidocaine on nucleus pulposus-induced nerve root injury. A neurophysiologic and histologic study of the pig cauda equina.

STUDY DESIGN: Application of autologous nucleus pulposus on nerve roots and treatment with local application of lidocaine in the pig. OBJECTIVES: Studies of the effects of lidocaine on nucleus pulposus-exposed nerve roots. SUMMARY OF BACKGROUND DATA: Nerve root infiltration may improve radicular symptoms beyond the pharmacologic duration of local anesthetics, but the mechanisms for this effect are not known. METHODS: Nucleus pulposus was harvested from a lumbar disc and placed onto the sacrococcygeal cauda equina in pigs. In Series 1, early lidocaine treatment of nucleus pulposus-induced nerve root injury, pigs received 2% lidocaine (n = 5) or saline (n = 5) before and after surgery. Nerve conduction velocity and histologic appearance were studied after 3 days. In Series 2, delayed lidocaine treatment of nucleus pulposus-induced nerve root injury, after 7 days 2% lidocaine was administered epidurally to nucleus pulposus-exposed (n = 4) and -nonexposed (n = 4) nerve roots. Nerve conduction velocity, muscle action potentials, and histologic appearance were assessed. RESULTS: In Series 1, early treatment with lidocaine limited the reduction in nerve conduction velocity. The epidural inflammation was less in lidocaine treated animals. In Series 2, nerve conduction velocity was lower in nucleus pulposus-exposed animals than in nonexposed animals. The initial reduction of nerve conduction velocity and muscle action potential was similar between the groups, but the recovery of muscle action potential was slower and less complete in nucleus pulposus-exposed nerve roots. There was minimal histologic nerve injury in both series and in both protocols. CONCLUSIONS: Early treatment with lidocaine may reduce nucleus pulposus-induced nerve root injury. Lidocaine induced a delayed recovery in nerve roots exposed to nucleus pulposus. Further studies are needed to clarify the therapeutic effects of nerve root infiltration and the pathophysiology of nucleus pulposus-induced nerve root injury.

Anesthetics, Local↗

Early effects of nucleus pulposus application on spinal nerve root morphology and function.

It is known that 24 h or more after epidural application of autologous nucleus pulposus, functional and structural changes are established in adjacent nerve roots. It is, however, not known how soon after the application these changes appear. The aim of this study was to reduce the exposure duration to 3 h and to evaluate nerve function and histological changes in the nerve tissue during this time period. A total of 12 pigs was used. In ten pigs, autologous nucleus pulposus (NP) was applied epidurally on the cauda equina. Nerve function was then monitored for 3 h by measurements of muscle action potentials (MAP) in the tail muscles, following nerve root stimulation cranial to the exposed zone. In five of the ten pigs with NP application, nerve root compression to 50 mm Hg was added by means of an inflatable balloon. In two control animals, neither NP nor compression was applied. At the end point, nerve root specimens were harvested for histological assessment. No reduction of MAP amplitude was detected in any of the series. However, there was an epidural accumulation of leucocytes and mast cells, as well as minor axonal and Schwann cell changes in both the NP and NP+ compression series, as compared to the control series. Morphological changes in terms of an epidural inflammatory reaction and minor axonal and Schwann cell damage may thus be demonstrated within 3 h of NP application, with or without compression. However, there is no functional deterioration of the nerve roots detectable within this time period.

Animals↗

Neurogenesis in the adult human hippocampus.

The genesis of new cells, including neurons, in the adult human brain has not yet been demonstrated. This study was undertaken to investigate whether neurogenesis occurs in the adult human brain, in regions previously identified as neurogenic in adult rodents and monkeys. Human brain tissue was obtained postmortem from patients who had been treated with the thymidine analog, bromodeoxyuridine (BrdU), that labels DNA during the S phase. Using immunofluorescent labeling for BrdU and for one of the neuronal markers, NeuN, calbindin or neuron specific enolase (NSE), we demonstrate that new neurons, as defined by these markers, are generated from dividing progenitor cells in the dentate gyrus of adult humans. Our results further indicate that the human hippocampus retains its ability to generate neurons throughout life.

Adult↗

A model for chronic nerve root compression studies. Presentation of a porcine model for controlled, slow-onset compression with analyses of anatomic aspects, compression onset rate, and morphologic and neurophysiologic effects.

STUDY DESIGN: Compression onset rate, anatomic aspects, and morphologic and neurophysiologic effects in spinal nerve roots were studied in a nerve root compression model in pigs. OBJECTIVES: To analyze the compression onset rate by measuring the gradual reduction of the inner diameter of the constrictor, the motor nerve conduction velocity by electromyography, the morphologic changes by light microscopy, and the gross and vascular anatomy by dissection and ink injections, respectively, in a model for experimental chronic nerve root compression. SUMMARY OF BACKGROUND DATA: Chronic nerve root compression is recognized to be related to back pain syndromes, including sciatica. Various aspects of morphologic and physiologic changes have been studied previously in models for acute compression and chronic nerve root irritation, but a controlled, graded chronic nerve root compression model has not been described. METHODS: An ameroid constrictor was applied around a spinal nerve root just cranial to the dorsal root ganglion. The inner diameter of this constrictor gradually becomes reduced. After 1 week or 4 weeks, electromyographic measurements were performed, and tissue samples were harvested for histologic analyses. The gross and vascular anatomy of the pigs' spinal nerve roots were studied by dissection and ink injections. RESULTS: There was a statistically significant decrease in the nerve conduction velocity in compressed compared with noncompressed spinal nerve roots after 1 week and after 4 weeks. The ameroid constrictors induced nerve fiber damage, endoneural hyperemia, bleeding, and inflammation at the compression zone. There was often a severe reduction in the number of myelinated fibers after 4 weeks. CONCLUSION: A model for controlled, chronic, partial nerve root injury using a gradual compression-onset constrictor is presented. This model allows for induction of a controlled graded chronic nerve root injury and can be used for research on basic pathophysiologic mechanisms and on the effects of various interventions on nerve root injury development.

Animals↗

The effects of normal, frozen, and hyaluronidase-digested nucleus pulposus on nerve root structure and function.

STUDY DESIGN: Autologous nucleus pulposus was modified and applied to the cauda equina in pigs. Histology and neurophysiology were assessed after 7 days. OBJECTIVES: To assess if alterations of the nucleus pulposus would change the degree and distribution of the nerve injury induced by autologous nucleus pulposus. SUMMARY OF BACKGROUND DATA: It was reported recently that nucleus pulposus may induce structural and functional changes in nerve roots after epidural application. The basic mechanisms causing these changes are not fully understood. METHODS: Nucleus pulposus was harvested from lumbar discs and submitted to either of three treatments; 37 C for 24 hours (n = 5), -20 C for 24 hours (n = 5), or digestion by hyaluronidase for 24 hours (n = 6). In two additional pigs, nucleus pulposus was applied just after harvest as a control to verify previous observations. After 7 days, nerve conduction velocity was recorded, and specimens were processed for blinded light microscopic assessment. RESULTS: When nucleus pulposus was applied just after harvest, or when it had been kept at 37 C or digested by hyaluronidase for 24 hours, there was a significant reduction in nerve conduction velocity similar to previous observations. When nucleus pulposus had been kept at -20 C for 24 hours, however, there was no reduction in conduction velocity. There were no apparent differences between the groups at the histologic assessment. Staining of the nucleus pulposus showed that the cells in the nucleus pulposus exposed to -20 C were lysed, whereas the cells in the nucleus pulposus treated by the two other methods were mainly unaffected. CONCLUSIONS: Because freezing of the nucleus pulposus probably kills the cells but does not affect other components, one may assume that the biologic effects induced by the nucleus pulposus may be related to its cell population.

Animals↗

Early-infantile galactosialidosis with multiple brain infarctions: morphological, neuropathological and neurochemical findings.

Post-mortem morphological, neuropathological and neurochemical findings are described in a girl, aged 14 months, with the early-infantile form of galactosialidosis. An elevation in non-lipid sialic acid was noted in both the grey and white matter of the brain, whereas the white matter displayed a clear reduction in all the major lipids. Multiple cortical-subcortical infarctions were found in the brain, most probably caused by compromised circulation due to endothelial luminal encroachment. Electron microscopy of cerebral blood vessels revealed major swelling of the endothelium due to prominent cytoplasmic vacuolisation. Multiple cytoplasmic vacuoles containing sparse granular or membranous matter were also seen in neurons and glial cells of the brain and spinal cord. Zebra bodies were found in the Purkinje cells, as well as in the spinal anterior horn cells. Prominent endothelial vacuolisation was noted in the liver and kidneys. The renal vascular encroachment was probably the cause of the arterial hypertension with elevated plasma renin activity in the present case. There were innumerable fine vacuoles in the renal epithelium and in the Kupffer cell of the liver, whereas coarser vacuoles were observed in the hepatocytes. The neuronal ultrastructural findings in the present case bear some resemblance to the few reported cases of late-infantile and adult cases of galactosialidosis. The prominent endothelial vacuolisation and focal cerebrovascular lesions, that have not previously been described in galactosialidosis, may be features specific to the rapidly progressive early-infantile form.

Brain↗

Spinal epidural metastasis: implications for spinal analgesia to treat "refractory" cancer pain.

Two hundred one consecutive patients with cancer pain who received intrathecal pain treatment between 1985 and 1993 were included in this retrospective study undertaken to test the hypothesis that epidural metastasis is a common cause of "refractory" cancer pain and that its presence may affect the efficacy and the complication rates of intraspinal pain treatment. Fifty-seven (approximately 28%) patients were investigated by metrizamide myelography, computerized tomography (CT), magnetic resonance imaging (MRI), laminectomy, or neurohistopathology. Epidural metastases were found in 40 (70%) and spinal stenosis in 33 (approximately 58%); 7 patients with total and 26 with partial occlusion of the spinal canal. Presence of epidural metastasis affected catheter insertion complications, daily dosages, and complications of the intrathecal pain treatment only when it was associated with spinal canal stenosis (partial or total). During the period of the intrathecal treatment, the patients with confirmed epidural metastasis and total spinal canal stenosis needed significantly (P < 0.05) higher daily doses of opioid (means = 77 +/- 103 versus 22 +/- 29 mg) and intrathecal bupivacaine (means = 65 +/- 44 versus 33 +/- 20 mg) and had significantly (P < 0.05) higher rates (14% versus 0%) of radicular pain at injection and poor distribution of analgesia than those without epidural metastasis and spinal canal stenosis. In contrast, the rate of occurrence of post-dural puncture headache was significantly (P < 0.05) lower in patients with partial (4%) and total (14%) spinal stenosis than in those without (29%). Unexpected paraplegia occurred in four patients and was due to accidental injury during attempted dural puncture (N = 1) and collapse (due to cerebrospinal fluid leakage leading to "medullary coning" of an unknown epidural metastasis (N = 3).

Adolescent↗

Intracranial tumors after radium treatment for skin hemangioma during infancy--a cohort and case-control study.

The risk of developing intracranial tumors was studied in a Swedish cohort of 11,805 infants treated with 226Ra for hemangioma of the skin between 1930 and 1965. The cohort was followed up in the Swedish Cancer Register during the years 1958 through 1992, giving 402,958 person-years at risk. Forty-seven intracranial tumors developed in 46 individuals. The standardized incidence ratio (SIR) was 1.80 (95% CI 1.32-2.39). An excess number of cases was found for many histopathological subgroups, although the excess was statistically significant only for gliomas (n = 23, SIR 1.89, 95% CI 1.20-2.83) and meningiomas (n = 8, SIR 2.42, 95% CI 1.06-4.77). Absorbed doses to the brain have been calculated. The mean dose to the brain was only 7.2 cGy. The dose response was evaluated by Poisson regression methods. There was an excess of intracranial tumors in all dose categories, but no clear dose-response relationship could be seen for the data. This indicates that explanations other than irradiation may also be involved. The selection of the reference population has been studied and confirmed to be representative. For individuals treated before 7 months of age, however, the data could be fitted to both the linear and the linear-quadratic model. These results may indicate that the youngest infants may be more sensitive to ionizing radiation and that even very low doses to the brain may increase the risk for intracranial tumors.

Brain Neoplasms↗

Chondroitinase ABC (pharmaceutical grade) for chemonucleolysis. Functional and structural evaluation after local application on intraspinal nerve structures and blood vessels.

STUDY DESIGN: The effects on nerve tissue and blood vessels of locally applied chondroitinase ABC were studied in two experimental models using chymopapain and the vehicle of chondroitinase ABC for controls. OBJECTIVES: To assess the effects of chondroitinase ABC on blood vessels and nerve tissue after local application. SUMMARY OF BACKGROUND DATA: Chondroitinase ABC has been suggested for chemonucleolysis because it has a high specificity for nucleus pulposus matrix, which could mean a high efficiency in dissolving disc tissue combined with a low risk of side effects on other tissues. METHODS: Chondroitinase ABC or controls were injected intrathecally in the pig, and nerve conduction velocity and histologic changes were assessed after 7 days. The same substances were injected into the hamster cheek pouch and studied for 60 minutes for microvascular effects. The vehicle for the enzyme was used as a negative control and chymopapain in a therapeutic concentration served as a positive control. RESULTS: In all series there was a slight intrathecal fibrotic reaction that was most pronounced after chymopapain injection. The effects on nerve conduction velocity and nerve morphology were similar between chondroitinase ABC and its vehicle. Chymopapain induced a significant reduction in nerve conduction velocity and pronounced histologic changes. In the cheek pouch, chymopapain induced a stand-still of blood flow at the injection site, and microhemorrhage and macromolecular leakage from the vessels at the border of the injection site. Only a slightly reduced blood flow was occasionally found after injection of chondroitinase ABC and controls. CONCLUSIONS: In agreement with the current literature, these observations indicate that chondroitinase ABC is safe regarding adverse effects on nerve tissue and blood vessels. The slight reduction in conduction velocity after intrathecal injection of chondroitinase ABC or its vehicle is most likely the result of surgical injury while releasing the nerve roots from the intrathecal fibrous adhesions. Such adhesions may be related to the laminectomy per se, and probably have no pathophysiologic significance.

Animals↗

Ultrastructural changes in spinal nerve roots induced by autologous nucleus pulposus.

STUDY DESIGN: Ultrastructural changes were analyzed by transmission electron microscopy in nerve roots exposed to autologous nucleus pulposus experimentally. OBJECTIVES: To assess if ultrastructural changes were present in areas with no light microscopic changes in nerve roots exposed to autologous nucleus pulposus in a pig model. SUMMARY OF BACKGROUND DATA: Previous analyses have shown that there is focal nerve fiber damage in nerve roots exposed to autologous nucleus pulposus in the pig. These changes could not fully explain the reduction in nerve conduction velocity seen in the same nerve roots. In the present study, the parts of the nerve roots that did not display breakdown of axons or myelin sheaths at the light microscopic level were analyzed regarding ultrastructural changes. METHODS: In a previous study, nucleus pulposus was harvested from a lumbar disc and placed epidurally onto the cauda equina at the sacrococcygeal level in pigs. Retroperitoneal fat was used as control. After 1, 3, and 7 days, the nerve roots were excised and processed for light microscopy. Parts of the nerve roots that appeared normal at the light microscopic level were further processed for the present electron microscopic examination. RESULTS: Significant ultrastructural changes, such as expansion of the Schwann cell cytoplasm and intracellular edema with vesicular swelling of the Schmidt-Lanterman incisures, were observed in nerve fibers with normal axons. Although present after nucleus pulposus and control application, the changes were more pronounced after the application of nucleus pulposus. CONCLUSIONS: Epidural application of autologous nucleus pulposus without any pressure may induce not only nerve function impairment but also axonal injury and significant primary Schwann cell damage with vesicular swelling of Schmidt-Lanterman incisures. However, because axonal and Schwann cell changes affected only part of the nerve fibers, further causes of the impaired nerve conduction need to be determined.

Animals↗

Mechanical and biochemical injury of spinal nerve roots: a morphological and neurophysiological study.

Compression may induce morphological and neurophysiological changes in nerve roots. However, it has also been demonstrated experimentally that nucleus pulposus, without any compression, may induce similar changes when applied epidurally. The present study was undertaken to examine the morphological and functional effects of autologous nucleus pulposus and the combination of nucleus pulposus and compression in a pig model. Nucleus pulposus from a lumbar disc in the same animal was applied epidurally around the first sacral nerve root in the pig, with or without a specially designed constrictor. After 1 week, nerve root conduction velocity was determined in the exposed and in the contralateral control nerve root by local electrical stimulation and EMG recordings in the back muscles. Nerve root specimens were processed for blinded light-microscopic evaluation. There was a significant reduction in nerve conduction velocity for all exposed nerve roots as well as contralateral control nerve roots when nucleus pulposus had been applied. There were no statistically significant differences between the nerve conduction velocities recorded following the combined application of nucleus pulposus and compression and those recorded after application of nucleus pulposus alone. The reductions were similar to the reduction induced by the constrictor per se, as seen in a previous study. In all series there was also a decrease in conduction velocity in the control nerve roots, in contrast to previous studies. Light microscopy demonstrated axonal changes only in nerve roots exposed to the constrictor. In conclusion, both epidural nucleus pulposus and compression may induce a significant reduction in nerve conduction velocity. The combination, however, of these two agents does not increase the magnitude of such dysfunction. The potency of nucleus pulposus to induce changes in nerve roots after epidural application was further indicated by the fact that reduction in nerve conduction velocity also occurred in the contralateral control nerve roots in this series. The histological data suggest that axonal injury can not alone explain the reduction in nerve conduction velocity, and that the morphological basis for the functional changes must be sought at the subcellular level.

Animals↗

Secondary thalamic lesions after ligation of the middle cerebral artery: an ultrastructural study.

Earlier light microscopic, immunocytochemical and morphometric investigations indicate that noxious substances transported with the vasogenic edema from hemispheric infarcts influence the character, timing and extent of the secondary thalamic lesions. The object of the present study was to analyze the ultrastructure of the secondary damage and the cytolytic nerve cell change which ensues in the thalamus within a week after the infarction. Adult spontaneously hypertensive rats (SHR) were studied either 7 days after permanent ligation of the right middle cerebral artery (MCA) (n = 4) or 7 days after a 2-h temporary occlusion of the MCA (n = 4). Light microscopy revealed damage in the ipsilateral thalamic nuclei and the electron microscopic analysis showed that the cytolytic nerve cell degeneration was somatodendritic. Central chromatolysis was not observed. Somatodendritic nerve cell degeneration, as found in the secondary thalamic lesions in the present study, has been described in excitotoxic brain damage as well as in chronic, edematous lesions in stroke-prone spontaneously hypertensive rats. The possibility that the cytolytic thalamic nerve cell lesion is influenced by excitatory, noxious substances spreading with the edema fluid from the infarct has, thus, to be considered.

Animals↗

Neonatal pre-ganglionic sympathectomy affects morphometrically defined architecture in rat cerebral arteries.

In order to clarify further the nature of the long-term influence on the cerebral vasculature by the sympathetic nerves, a bilateral cervical pre-ganglionic denervation was performed in 1-week-old rats. Four weeks later, morphometric determinations of the vascular dimensions revealed diminished media cross-sectional areas and luminal radii in the middle cerebral and posterior cerebral arteries, whereas these parameters were unaffected in the basilar artery. In the latter artery, however, a 40% increase in the cross-sectional area of the internal elastic membrane was found. No re-innervation of the denervated ganglia occurred during the course of the experiment. The results suggest that the long-term effect exerted by the sympathetic nerves is associated with the nerve activity, rather than being a true trophic influence.

Animals↗

Atrophy of the aortic media in giant cell arteritis.

Aortic tissue from seven patients with giant cell arteritis (GCA) was investigated using light microscopy and immunocytochemistry. Four surgical cases and three autopsy cases were included. All the specimens displayed a severe reduction in the size and number of media smooth muscle cells immunopositive for alpha-smooth muscle actin (alpha-SMA). A subtotal loss of alpha-SMA-positive cells was seen in non-inflamed media tissue, continuing gradually towards multiple calcified acellular lesions totally devoid of alpha-SMA immunoreactivity. There was a slight to moderate granulomatous inflammatory reaction in the tissue surrounding part of the acellular lesions. Foreign body giant cell reaction and elastin degradation were found at the ends of the acellular calcified areas. The present findings indicate that the atrophy and the loss of alpha-SMA-positive cells in the aortic media in GCA is primary, and that the granulomatous reaction is secondary and directed against atrophic calcified media tissue.

Actins↗

The influence of sectional interval on the reliability of temporal arterial biopsies in polymyalgia rheumatica.

Temporal arterial biopsies from 27 patients with a clinical diagnosis of pure polymyalgia rheumatica (PMR) were examined using light microscopy on paraffin and plastic sections. The primary routine examination of the paraffin-embedded parts of the biopsies (biopsy length: 12.7 +/- 4.5 mm, sub-segments: 4.9 +/- 1.2 mm) revealed 4 positive cases, whereas the primary examination of the smaller plastic-embedded parts showed inflammation in 6 cases (biopsy length: 2.7 +/- 1.2 mm, sub-segments: 0.7 +/- 0.3 mm). Serial sectioning with a 50 microns interval of arteries which were negative primarily revealed three new positive cases in the paraffin-embedded material (total length: 174.0 mm), whereas sectioning the plastic-embedded material (total length: 52.8 mm) produced one more positive artery. All the new cases displayed a focal inflammatory process in atrophic, calcified arterial segments. The high yield of positive biopsies in the present material (11 of 27; 40.7%) demonstrates the diagnostic value of temporal arterial biopsy in PMR and the importance of a careful histologic examination. The results also indicate the influence of biopsy length on the yield of positive biopsies. The division of fixed temporal arterial biopsies into approximately 1-mm-long sub-segments before the embedding and the further serial sectioning of those negative biopsies which are atrophic and/or calcified is recommended in cases of pure PMR.

Aged↗