Marc Tadié

Spinal cord intradural arteriovenous fistulae: Anatomic, clinical, and therapeutic considerations in a series of 32 consecutive patients seen between 1981 and 2000 with emphasis on endovascular therapy

OBJECTIVE:To review our series of intradural spinal cord arteriovenous fistulas (SCAVFs), analyzing symptoms and related angioarchitecture, and to study the morphological and clinical results of embolization. METHODS:Thirty-two SCAVFs (in 22 adults and 10 children) were treated between 1981 and 2000. These lesions were classified as microarteriovenous fistulas (mAVFs) or macroarteriovenous fistulas (MAVFs) according to shunt morphology. Location, architecture, presenting symptoms, and age group were detailed. The selection of patients for endovascular versus surgical treatments was analyzed, as were the anatomic and clinical results obtained by embolization with n-butylcyanoacrylate. Clinical status was evaluated according to the Karnofsky Performance Scale score. RESULTS:Ten SCAVFs were found in the pediatric population (four mAVFs and six MAVFs). All four mAVFs presented with acute symptoms. Three mAVFs (two cervical and one thoracic) presented hematomyelia; in one patient with a thoracic AVF, subarachnoid hemorrhage was suspected. All six MAVFs were located in the thoracolumbar cord (five associated with hereditary hemorrhagic telangiectasias). Four of the six MAVFs presented with hemorrhage. In the adult population, there were 21 mAVFS (95%) and one MAVF (5%). Only two mAVFs were found in the cervical cord, all other shunts affecting the thoracolumbar region. Hemorrhage was present in 6 of the 22 cases seen in adults (27%). The symptoms of SCAVFs did not differ from those found in spinal cord arteriovenous shunts of nidus type. Pial venous reflux and congestion were the most frequently encountered features in both the adult and pediatric groups. Arterial aneurysms (different from false aneurysms) were not found in association with hemorrhagic presentation of SCAVFs. Mean follow-up in our series was 3.3 years. Of the MAVFs, 86% were embolized, with 67% cured. The others had more than 75% occlusion. All patients followed up improved significantly. Of the mAVFs, 48% were treated endovascularly. Successful embolization was performed in 75% of patients. One patient was not embolized because of vasospasm, whereas 67% percent of mAVFs were completely occluded, 22% were more than 90% occluded, and 11% were 75% occluded. Complementary surgery was deemed unnecessary. All patients with mAVFs improved significantly at follow-up. Transient complications occurred in 22% of all patients, with no permanent morbidity or mortality. No patient bled or rebled after embolization. Thirty-six percent of mAVFs were operated on because of anticipated technical difficulties for endovascular approach or distal localization of the shunt. CONCLUSION:Endovascular treatment of SCAVFs stabilizes, normalizes, or improves neurological symptoms in all patients at long-term follow-up, with no bleeds or rebleeds. Embolization of SCAVFs with glue is a safe treatment that compares favorably with other approaches and significantly improves the poor natural history of the disease.

Axonal regrowth through a collagen guidance channel bridging spinal cord to the avulsed C6 roots: Functional recovery in primates with brachial plexus injury

Intraspinal implantation of a collagen guidance channel (CGC) to promote axon regeneration was investigated in marmosets with brachial plexus injury. After avulsion of the right C5, C6 and C7 spinal roots, a CGC containing (group B) or not (group A) a nerve segment, or a nerve graft (group C), was ventro‐laterally implanted into the cord to bridge the ventral horn and the avulsed C6 roots. No spinal cord dysfunction was observed following surgery. Two months later, the postoperative flaccid paralysis of the lesioned arm improved. In five months, a normal electromyogram of the affected biceps muscle was recorded in all repaired animals. Motor evoked potentials were obtained with a mean amplitude of 13.37 ± 13.66 μV in group A, 13.21 ± 5.16 μV in group B and 37.14 ± 35.16 μV in group C. The force of biceps muscle contraction was 27.33 ± 20.03 g (group A), 24.33 ± 17.03 g (group B) and 37.38 ± 21.70 g (group C). Retrograde tracing by horseradish peroxidase showed labelled motoneurons ipsilaterally located in the C5 and C6 ventral horn, nearby the implantation site. The mean labelled neurons was 32.33 ± 21.13, 219.33 ± 176.29 and 64.33 ± 23.54 in group A, B and C respectively. Histological analysis presented numerous myelinated and unmyelinated regenerating axons in the implant of these animals. Statistical analysis did not show significant difference among the three repaired groups. Our results indicate that spinal neurons can regenerate through a CGC to avulsed nerve roots and induce motor recovery in primates. J. Neurosci. Res. 51:723–734, 1998.

Intramedullary spinal ependymomas: analysis of a consecutive series of 82 adult cases with particular attention to patients with no preoperative neurological deficit.

OBJECTIVE Surgery should be considered for patients with intramedullary spinal ependymomas (ISE), particularly those presenting with a neurological deficit preoperatively. In contrast, it is still a debatable matter whether to recommend the same approach for patients with no neurological impairment. To investigate this matter, we analyzed the data of 82 consecutive patients with ISEs treated at our institution. METHODS We reviewed the medical charts of all ISE patients undergoing operation at our institution between 1985 and 2000. Particular attention was given to patients without neurological deficit before surgery. RESULTS Eighty-two consecutive ISE patients were included in this study. Preoperatively, a neurological deficit of variable severity was present in 72 patients (Group A, 88%) and absent in 10 patients (Group B, 12%). In the latter group, seven patients had progressive and nonspecific pain as the only presenting symptom; two had arm dysesthesias; and in one patient, ISE was diagnosed incidentally. The mean duration of their symptoms was 21 months. We achieved a total tumor excision in nine patients and subtotal removal in one. At the last follow-up assessment (mean, 45 mo), all Group B patients remained at Grade I of the McCormick classification, except one, who deteriorated to Grade Ib. Furthermore, nonspecific pain diminished in three patients, stabilized in four, and worsened in one. Arm dysesthesias diminished in one patient and stabilized in the other. No surgery-related complication or recurrence was recorded in these patients. CONCLUSION Surgery should be carefully considered for ISE patients with no objective neurological deficit preoperatively because, in our experience, it resolves their preoperative complaints in 30% of cases, stabilizes them in 60%, and worsens them in 10%.

Long-term follow-up of Chiari-related syringomyelia in adults: analysis of 157 surgically treated cases.

OBJECTIVETo determine the long-term outcome of surgically treated Chiari-related syringomyelia. METHODSThe medical charts of 157 consecutive surgically treated patients with Chiari-related syringomyelia were retrospectively analyzed. Factors predicting outcome, either clinical or radiological, are discussed, and our results are compared with those of other large series in the literature. RESULTSThe study included 74 men and 83 women (age range, 16–75 years; mean age at surgery, 38.3 years). Pain and sensory disturbance were the most frequent initial symptoms. The average duration of preoperative symptoms was 8.2 years. The follow-up period ranged from 82 to 204 months (median, 88 months). At the end of the study, 99 patients (63.06%) had improved, 48 (30.58%) had stabilized, 9 (5.73%) had worsened, and 1 (0.63%) had died during the postoperative period. Factors predicting improvement or stabilization were young age at the time of surgery and clinical signs of paroxysmal intracranial hypertension. Factors associated with a poor outcome were older age at the time of surgery, arachnoiditis, and a clinical feature of long-tract impairment syndrome. The presence of arachnoiditis or of basilar invagination was associated with poor clinical presentation (P = 0.05 and 0.0001, respectively). The extent of the cyst on postoperative magnetic resonance imaging was a predictor of poor clinical outcome (P = 0.002). CONCLUSIONOur results confirmed that surgery is an effective and safe treatment of Chiari-related syringomyelia, with a 90% chance of long-term stabilization or improvement on average. Surgery should be proposed as soon as possible in patients with clearly progressing clinical features.

AXONAL REGROWTH THROUGH COLLAGEN TUBES BRIDGING THE SPINAL CORD TO NERVE ROOTS

The capacity of central nervous system (CNS) axons to elongate from the spinal cord to the periphery throughout a tubular implant joining the ventral horn of the spinal cord to an avulsed root was investigated in a model of brachial plexus injury. The C5‐C7 roots were avulsed by controlled traction and the C6 root was bridged to the spinal cord over a 3 mm gap by the use of a collagen cylinder containing or not containing an autologous nerve segment, or an autologous nerve graft. Nine months later, the functionnality and the quality of the axonal regrowth was evaluated by electrophysiology, retrograde labelling of neurons, and histological examination of the gap area. A normal electromyogram of the biceps was observed in all animals where the C6 root was bridged to the spinal cord. The mean average amplitude of the motor evoked potentials was comprised between 17.51 ± 12.03 μV in animals repaired with a collagen cylinder, and 27.83 ± 22.62 μV when a nerve segment was introduced in the tube. In nonrepaired animals spontaneous potentials reflecting a muscle denervation were observed at electromyography. Retrograde labelling indicated that a mean number of 58.88 ± 37.89 spinal cord neurons have reinnervated the biceps in animals repaired with a tube versus 78.38 ± 62.11 when a nerve segment was introduced in the channel, and 97.25 ± 56.23 in nerve grafting experiments. Analyses of the repair site showed the presence of numerous myelinated regenerating axons. In conclusion, our results indicate that spinal cord neurons can regenerate through tubular implants over a 3 mm gap, and that this axonal regrowth appeared as effective as in nerve grafting experiments. The combination of an implant and a nerve segment did not significantly increase the regeneration rate. J. Neurosci. Res. 49:425–432, 1997.

Curable Cause of Paraplegia. Spinal Dural Arteriovenous Fistulae

Background and Purpose— The rarity of spinal dural arteriovenous fistulae makes physicians often overlook this potential diagnosis in patients with progressive gait disturbance and paraparesis. Consequently, patients with spinal dural arteriovenous fistulae can gradually become completely paraplegic if the final diagnosis is delayed considerably. The objective of the current study is to demonstrate that, particularly in patients with paraplegia, surgical treatment of fistula is necessary and often has a favorable outcome. Methods— Of 42 patients with spinal dural arteriovenous fistulae treated in our institution (surgery or endovascular treatment), 6 were paraplegic preoperatively (Grade IV on the McCormick scale and Grade V on the Aminoff scale, Grade 5 of modified Rankin Scale with motor ASIA between 0 and 10 for both lower limbs). Their clinical history revealed that paraplegia appeared progressively within a period of <3 months. All patients were clinically evaluated at 6 weeks, 6 months, and then annually during an average follow-up of 3 years. Patients received at least one spinal angiography and MRI test during the follow-up period. Results— Total exclusion of the fistula was performed surgically in all cases and was confirmed by spinal angiography. No surgical complications were recorded. All patients improved postoperatively. Three patients showed almost normal walking (Grade I on the McCormick scale, I on the Aminoff scale, Grade 1 of modified Rankin Scale) and 3 were able to walk with a cane (Grade II on McCormick, Grade III on Aminoff scale, Grade 2 of modified Rankin Scale). MRI tests were normal in all patients. Conclusions— Our results indicate that treatment of fistula is a necessary intervention, even in patients with complete paraplegia.

Reduction of postoperative perineural adhesions by Hyaloglide gel: an experimental study in the rat sciatic nerve.

OBJECTIVE: To assess the effects of Hyaloglide gel (or auto-cross-linked polysaccharide [ACP] gel; Fidia Advanced Biopolymers, Abano Terme, Italy), a hyaluronan-derivative polymer, on peripheral nerve scarring and nerve regeneration. METHODS: We performed two surgical procedures in adult rats: 1) neurolysis of the sciatic nerve and separation of its tibial and peroneal branches, and 2) transection and immediate suture of the sciatic nerve. After nerve manipulation, ACP gel was applied onto the site of operation. We tested two solutions of ACP gel having different viscosities. Additional animals received Adcon-T/N (Gliatech, Inc., Cleveland, OH), an antiadhesive agent currently available for clinical use. No gel was applied on the contralateral side, which served as a control side. Four weeks later, the animals underwent reoperation. We assessed the quality of wound healing, the presence of perineural adherences, and the separability of nerves from surrounding tissues. RESULTS: Significantly fewer perineural adhesions were found in animals treated with ACP gel (high viscosity) and Adcon-T/N compared with controls. Quantitative histological analysis revealed a statistically significant reduction in the amount of scar tissue surrounding the nerves treated with ACP gel. No evidence of toxicity was found, and the gel did not interfere with nerve regeneration (counts of regenerating myelinated axons). CONCLUSION: ACP gel with high viscosity seems to be safe and effective in reducing perineural adhesions and scar formation after peripheral nerve surgery.

Regrowth of the rostral spinal axons into the caudal ventral roots through a collagen tube implanted into hemisected adult rat spinal cord.

OBJECTIVEA collagen tube was used to guide axonal regrowth from the spinal cord to the periphery to contribute to improvement of paralysis after lower thoracic spinal cord injury. METHODSThe spinal cords of adult male Sprague-Dawley rats were lesioned by removing the left hemicord from T12 to 5 mm below this level and additionally sectioning all left lumbar ventral roots. In experimental animals (n = 9), a collagen tube was inserted into this gap, spanning the rostral hemisected cord to the caudal sectioned lumbar ventral roots (gap, 7 mm). In control animals (n = 6), no treatment was performed. RESULTSSix months after surgery, the return of some tension and resistance of the paralyzed hindlimb muscles was observed in all experimental rats except the untreated controls. Nine months postoperatively, muscle action potentials were recorded from the target muscles of the experimental animals while electrostimulating the tissue continuity within the collagen tube. Horseradish peroxidase retrograde labeling showed that the neurons in the rostral cord near the implantation site regrew into the reconnected lumbar ventral roots. Histological examination indicated numerous myelinated axons in the reconnected root pathways and newly formed endplates in the target muscles. No axonal regeneration was found in the control rats. CONCLUSIONThese results indicate that the rostral spinal axons can regrow into the caudal sectioned and reconnected ventral roots through a collagen tube, thus innervating the denervated peripheral targets in adult rats after spinal cord injury. This surgical repair model also provides a means for testing the use of trophic factors that may further promote axonal regeneration.

Comparison of dopamine and norepinephrine after traumatic brain injury and hypoxic-hypotensive insult

After severe brain trauma, blood-brain barrier disruption and alteration of cerebral arteriolar vasoreactive properties may modify the cerebral response to catecholamines. Therefore, the goal of the present study was to compare the effects of dopamine and norepinephrine in a model of brain injury that consisted of a weight-drop model of injury complicated by a 15-min hypoxic-hypotensive insult (HH). Sprague-Dawley rats (n = 7 in each group) received, after brain injury, an infusion of either norepinephrine (TNE group) or dopamine (TDA group) in order to increase cerebral perfusion pressure (CPP) above 70 mm Hg. In addition, a control group (C group, no trauma) and a trauma group (T group, brain injury, no catecholamine infusion) were studied. Mean arterial pressure (MAP), intracranial pressure (ICP, intraparenchymal fiberoptic device), and local cerebral blood flow (LCBF, extradural laser-Doppler fiber) were measured throughout the protocol. In T group, brain injury and HH induced a decrease in CPP (by an increase of ICP and a decrease of MAP), and a decrease of LCBF. Both norepinephrine and dopamine failed to increase CPP, and ICP was significantly higher in TNE and TDA groups than in T group. Interestingly, norepinephrine was not able to alleviate the decrease in MAP. Neither norepinephrine or dopamine could induce an increase of MAP. LCBF decreased similarly in T, TNE and TDA groups. In conclusion, norepinephrine and dopamine are not able to restore values of CPP above 70 mm Hg in a model of severe brain trauma. Furthermore, their systemic vasopressor properties are altered.

Reinnervation of denervated lumbar ventral roots and their target muscle by thoracic spinal motoneurons via an implanted nerve autograft in adult rats after spinal cord injury

Intraspinally implanting a nerve autograft (NAG) to promote axonal regeneration toward periphery was investigated as a surgical treatment for spinal cord injury in adult rats. Fifteen animals underwent a left hemisection of the spinal cord at T12 level and an intradural section of all ipsilateral lumbar ventral roots. In repaired animals (n = 9), the electrophysiologically selected left L3 and L4 lumbar ventral roots supplying the quadriceps muscle were anastomosed to a NAG. The NAG was taken from the right peroneal nerve and then ventrolaterally implanted into the cord at a level 7 mm rostral to the hemisection. In the control group (n = 6), sectioned lumbar ventral roots were left unrepaired. Nine months later, the animals were assessed with clinical, electrophysiological, and histological examinations. Muscle action potential and motor evoked potential were obtained from the denervated/reinnervated quadriceps in all repaired animals, with a mean amplitude of 918.3 ± 328.9 μV and 215.8 ± 39.7 μV, respectively. Horseradish peroxidase retrograde labeling from the denervated/repaired lumbar ventral roots, performed in five repaired animals, showed that the mean of labeled neurons, ipsilaterally located in the thoracic ventral horn near the implantation site, was 145.8 ± 111.7. Histological analysis showed numerous myelinated axons in the NAG and denervated/repaired lumbar ventral roots of all repaired animals. The study of neuromuscular junctions furthermore confirmed numerous newly formed endplates appearing in the denervated/reinnervated quadriceps. These changes were absent in the control animals. These data indicate that the rostral thoracic spinal motoneurons can innervate the caudal denervated/repaired lumbar ventral roots and the target quadriceps via an implanted NAG, thereby inducing some functional recovery in adult rats after lower thoracic spinal cord injury. J. Neurosci. Res. 56:506–517, 1999.