[Early surgery or a wait-and-see policy in lumbosacral radicular syndrome: a randomized study]. / Vroeg opereren of langer afwachten voor het lumbosacraal radiculair syndroom: een gerandomiseerd onderzoek.

OBJECTIVE: To compare early surgery with expectative policy and later surgery if necessary in patients with sciatica that did not resolve within 6 weeks. DESIGN: Randomized multicentre clinical trial (ISRCTN 26872154). METHODS: Patients who had had severe sciatica for 6 to 12 weeks were randomized to early surgery or to prolonged conservative treatment with later surgery if necessary. The primary outcomes were the Roland Disability Questionnaire score, the visual-analogue scale for leg pain score, and the patient's report of their perceived recovery over the first year after randomization. Repeated measures analysis according to the intention-to-treat principle was used to analyse the outcome curves for both groups. RESULTS: A total of 283 patients were included and randomized. Of 141 patients assigned to undergo early surgery, 125 (89%) underwent microdiscectomy after a mean of 2.2 weeks. Of 142 patients assigned to conservative treatment, 55 (39%) still had to undergo surgical treatment after a mean of 18.7 weeks. There was no significant overall difference in disability scores during the first year (p = 0.13). Leg pain lessened more quickly in patients assigned to early surgery (p < 0.001). Patients assigned to early surgery also reported a faster rate of perceived recovery (hazard ratio (HR): 1.97; 95% CI: 1.72-2.22; p < 0.001). In both groups, however, the probability of perceived recovery after 1 year of follow-up was 95%. CONCLUSIONS: The 1-year outcomes were similar for patients assigned to early surgery and those assigned to extended conservative treatment with later surgery if necessary but the rates of reduction of leg pain and of perceived recovery were faster in those assigned to early surgery.

Adhesion and proliferation of human Schwann cells on adhesive coatings.

Attachment to and proliferation on the substrate are deemed important considerations when Schwann cells (SCs) are to be seeded in synthetic nerve grafts. Attachment is a prerequisite for the SCs to survive and fast proliferation will yield large numbers of SCs in a short time, which appears promising for stimulation of peripheral nerve regeneration. The aim of the present study was to compare the adhesion and proliferation of human Schwann cells (HSCs) on different substrates. The following were selected for their suitability as an internal coating of synthetic nerve grafts; the extracellular matrix proteins fibronectin, laminin and collagen type I and the poly-electrolytes poly(d-lysine) (PDL) and poly(ethylene-imine) (PEI). On all coatings, attachment of HSCs was satisfactory and comparable, indicating that this factor is not a major consideration in choosing a suitable coating. Proliferation was best on fibronectin, laminin and PDL, and worst on collagen type I and PEI. Since nerve regeneration is enhanced by laminin and/or fibronectin, these are preferred as coatings for synthetic nerve grafts seeded with SCs.

The axonal response after ventral root avulsions at the cervical 7 level in the cat spinal cord.

The ventral cervical 7th root was avulsed from the adult cat spinal cord and the reaction of the torn axons in the underlying white matter was studied by light microscopy using histochemical staining for acetylcholinesterase and immunocytochemical staining for neurofilament and by electron microscopy, after different survival times. One day postoperatively some of the torn axonal ends were enlarged in the intraspinal trajectory of the root fibers in the white matter between the ventral horn and the pial surface as observed by acetylcholinesterase staining. The formation of terminal clubs had accordingly started at this postlesional survival time. From day 2, terminal clubs positive to neurofilament antibody were found. The number of terminal clubs increased during the first 4 days after the avulsion, remained present at 30 days and then disappeared gradually during the next months. One such unmyelinated axonal terminal club was studied at the ultrastructural level. From its distal end an unmyelinated protrusion emanated which appeared myelinated on the most distal part. This protrusion may be the ultrastructural parallel of the ramifications from terminal axonal clubs described by Ramon Y Cajal after avulsion.

Ventral root avulsion versus transection at the cervical 7 level of the cat spinal cord.

The results of unilateral ventral root avulsions at the cervical 7 (C7) level were compared using light microscopy with unilateral transactions of the ventral root C7 at the surface of the cat spinal cord after survival times ranging from one to 90 days. Sections were stained for Nissl, acetylcholinesterase, neurofilaments, glial fibrillary acidic protein, and B-50/GA P43. A distinct difference in neuronal reaction was found between the effects of avulsion and transection of ventral root C7. After avulsion, changes in the Nissl-and acetylcholinesterase-stained sections and the sections stained with antibodies against neurofilaments remained present up to 90 days, although the number of neurons in the ventral horn on the avulsed side had significantly decreased at 60 and 90 days. This was in contrast to the transection where the changes in the stainings tended to return to the normal situation between 30 and 60 days and showed the normal pattern 90 days after transection. No decrease in the number of neurons was found. Both lesions were situated in the transitional region of the nerve roots. After avulsion axons break in the white matter of the CNS, while the axons were transected in the PNS compartment of the CNS-PNS transitional region. After avulsion, not only were the axons disconnected, as in transection, but the connections of recurrent motor axon collaterals probably were damaged. This may explain the different reaction after avulsion and transection.

Open fetal spinal cord surgery in rats with low mortality achieved by prevention of oligohydramnios.

Myelotomies were performed with an open microsurgical technique in rat fetuses aged between E16 and E18. In 87 consecutively treated fetuses the net surgical mortality was as low as 7%. The cause of death due to fetal surgery is shown to be amniotic fluid loss. The high survival rate is attributed to the prevention of oligohydramnios. The technique is described in detail and the results are discussed.

Nerve grafting from spinal cord to spinal nerve: a microsurgical technique in cats.

A ventral surgical approach is described for the grafting of autologous saphenous nerves between the spinal cord and the avulsed C7 ventral root in the cat. To overcome serious blood loss from the epidural venous plexus, the cats were hyperventilated (end tidal PCO2 to about 23 mmHg) and controlled hypotension was induced (mean arterial pressure to about 60 mmHg). After selective avulsion of the ventral rootlets C7 the saphenous grafts were implanted into the spinal cord and coaptated to the avulsed spinal nerve. The combination of advanced anesthetic methods and microsurgical techniques appeared to be mandatory to achieve a low surgical mortality. Regenerated axons were retrogradely traced using retrograde horseradish peroxidase (HRP), and their functional recovery was evaluated by means of electrophysiological methods.

Spinal cord transections in fetal rats. Open intrauterine surgery with low mortality.

Open myelotomies were performed in rat fetuses in stages E15-E19 with a microsurgical technique. To prevent oligohydramnios, considered to be one of the main causes of death associated with fetal surgery, amniotic fluid loss was reduced as much as possible. With this technique a reduction of the mortality rate to 38% was reached in 75 consecutive fetuses.

Optic glioma with intraocular tumor and seeding in a child with neurofibromatosis.

We treated a 3-year-old boy with neurofibromatosis who had an optic glioma, intraocular extension with seeding, and iris tumors. On the basis of results of ultrasonography, computed tomography, magnetic resonance imaging, and fine needle aspiration, other intraocular and orbital tumors were excluded. Because of the malignant intraocular aspect, the optic nerve glioma was extirpated. Histologic examination confirmed the diagnosis of an optic nerve glioma with intraocular extension, seeding, and iris nodules. In this juvenile pilocytic astrocytoma with secondary perineural fibrous hyperplasia, several mitoses were found in the orbital and intraocular parts. In the optic canal, three small islands were found that were compatible with the diagnosis of malignant astrocytoma, grade 3. The iris nevi appeared as iris pits and not like the Lisch nodules typical of neurofibromatosis. Café au lait spots were present on the skin. The family history was positive for neurofibromatosis. The results of this study demonstrate that optic gliomas are true astrocytomas and not hamartomas, and have a continuous scale from benign to malignant differentiation.

Predictive value of temporary external lumbar drainage in normal pressure hydrocephalus.

In a prospective study on the effect of shunting, 22 patients diagnosed as suffering from normal pressure hydrocephalus (NPH) were investigated by means of temporary external lumbar drainage (ELD). Five patients had to be excluded from the study because of complications of ELD or definitive shunting. ELD correctly predicted the outcome of shunting in all of the remaining 17 patients. The value of external lumbar drainage in NPH is discussed on the basis of personal experience and data from the literature. It seems to be a safe and valuable tool for predicting the outcome of definitive shunting procedures.

Cortical excitability of the biceps muscle after intercostal-to-musculocutaneous nerve transfer.

OBJECTIVE: Restoration of volitional control over elbow flexion has been demonstrated in patients who have undergone intercostal-to-musculocutaneous nerve transfer. We investigated the cortical area involved in the control over elbow flexion after intercostal-to-musculocutaneous nerve transfer. METHODS: Maps of magnetically excitable cortical areas of the affected arms of five patients were compared with maps of their healthy arms and maps of both arms of four healthy control subjects. The intercostal cortical area was also studied, requiring needle electromyography mapping (n = 1). RESULTS: The cortical areas of affected arms were smaller and less excitable than those of healthy arms. The locations of these areas could not be distinguished from that of the normal cortical biceps area but seemed to differ from that of the intercostal cortical area. CONCLUSION: The existence of a biceps-like cortical area related to the reinnervated muscle can be explained in two ways. Interneurons from the original biceps area might excite the cortical neurons controlling the intercostal muscles. Alternatively, corticospinal neurons of the original biceps area may project directly onto spinal intercostal motor neurons. Cerebral plasticity does occur in intercostal-to-musculocutaneous nerve transfers and may be crucial for their clinical success.

Evaluation of intercostal to musculocutaneous nerve transfer in reconstructive brachial plexus surgery.

OBJECT: Direct coaptation of intercostal nerves (ICNs) to the musculocutaneous (MC) nerve was performed to restore elbow flexion in 25 patients with brachial plexus root avulsions. METHODS: Seventy-five ICNs were transected as close as possible to the sternum to obtain sufficient length and then tunneled to the axilla and coapted to the MC nerve. Direct coaptation was achieved in 95% of ICNs, and functional elbow flexion was regained in 64% of the patients. The results were compared with several reported transfer techniques in which either an ICN or other donor nerves were used. CONCLUSIONS: Direct coaptation was equally effective and more straightforward than transfers involving interposition of grafts. The use of alternative donors such as the accessory nerve carries inherent disadvantages compared with the use of ICNs, and the results are not substantially better. Direct ICN-MC nerve transfer is a valuable reconstructive procedure.

Changing central nervous system control following intercostal nerve transfer.

OBJECT: The goal of this study was to find which central nervous system (CNS) pathways are involved in volitional control over reinnervated biceps or pectoral muscles. METHODS: Intercostal nerves (ICNs) were coapted to the musculocutaneous nerve (MCN) or the medial pectoral nerve (MPN) in 23 patients with root avulsions of the brachial plexus to restore biceps or pectoral muscle function. The facilitatory effects of respiration and voluntary contraction on cortical motor-evoked potentials of biceps or pectoral muscles were used to study CNS control over the reinnervated muscles. The time course of the facilitatory effect of respiration and voluntary contraction differed significantly. In the end stage of nerve regeneration, the facilitatory effect of voluntary contraction was significantly larger than that of respiration, indicating that the CNS control network over the muscle comes to resemble that of the recipient nerve (MCN or MPN) rather than that of the donor nerve (ICN). CONCLUSIONS: The strengthening of previously subthreshold synaptic connections in a CNS network connecting ICN to MCN or MPN neurons may underlie changing excitability.

Initial report on the limited value of hypoglossal nerve transfer to treat brachial plexus root avulsions.

OBJECT: Hypoglossal nerve (12th cranial nerve) transfer was performed to treat the sequelae of brachial plexus root avulsion in 12 adults and two infants, and the patients were followed to assess the effectiveness of the surgery. METHODS: The 12th cranial nerve was transected at the base of the tongue, and a sural nerve graft was used to bridge the gap between the donor (12th) and recipient nerves: C-5 spinal, axillary, suprascapular, or musculocutaneous nerve. The mean graft length in adult patients was 15.75 +/- 5.5 cm (+/- standard deviation, median 14.5 cm) and in the two infants the graft lengths were 7 and 8 cm, respectively. After a mean postoperative interval of 1138 +/- 254 days, electromyographic examination of the target muscles showed tongue movement-related activity in all patients. Muscle force strength measured according to the Medical Research Council's guidelines, was Grade 3 or higher in 21% of patients. Contraction, however, could only be attained by tongue movements, and volitional control was not achieved. CONCLUSIONS: Although recovery of muscle strength was obtained by 12th cranial nerve transfer, the functional gain remained virtually nonexistent because central control was missing.

Neurofibrosarcoma of the cauda equina. Case report.

A case of a malignant neurofibroma of the cauda equina is described. Its location seems to be rare. An extensive surgical resection including the adjacent neural tissue and the enveloping dural sac was carried out, followed by radiotherapy.

Reinnervation of avulsed and reimplanted ventral rootlets in the cervical spinal cord of the cat.

Spinal nerve root avulsions frequently occur in brachial plexus injuries caused by traction. Such lesions are considered to afflict the central nervous system (CNS) and are, therefore, believed to be beyond surgical repair. The present experimental study was initiated to challenge this hypothesis. The ventral rootlets of C-7 were avulsed from the spinal cord in 28 cats via an anterior approach and subsequently reimplanted into the cord at the site of origin. In nonoperated control cats and cats undergoing reimplantation, electrophysiological experiments were performed and horseradish peroxidase was administered to the spinal nerve on the reimplanted side after survival times ranging from 6 to 293 days. Spinal cord sections in all cats were stained for neurofilament, acetylcholinesterase (AChE), Nissl, and glial fibrillary acidic protein. Horseradish peroxidase-labeled ventral horn motoneurons were found as early as 14 days after reimplantation and their number increased with time. On Days 209 and 293, the number of labeled neurons equaled the number of labeled ventral horn neurons in the two control cats that did not undergo surgery. Starting on Day 6 after reimplantation, the appearance of the ventral horn and the white matter in the neurofilament, AChE, and Nissl-stained sections changed as a result of the CNS response to the injury. A return to their normal appearance could be observed in these stainings from Day 209 onward. Glial fibrillary acidic protein-positive astrocytic tissue was consistently found in the ventral horn and in the white matter reimplantation area. From Day 69 onward, electrophysiological stimulation of the spinal nerve C-7 on the reimplanted side elicited an electromyogram response in the spinodeltoid muscle. The latency and threshold intensity of the C-7 responses were initially increased but equalized to match the nonoperated controls between 98 and 122 days after reimplantation. The results of this study show that functional regeneration of ventral horn neurons after root avulsion and subsequent reimplantation in the cat is possible.

Correlation between histopathological findings in C-5 and C-6 nerve stumps and motor recovery following nerve grafting for repair of brachial plexus injury.

OBJECT: Proximal spinal nerve stumps were used as donor sites for grafts to repair brachial plexus traction lesions. The quality of the stumps was assessed histologically, and its correlation with the strength attained in the target muscle was studied. METHODS: Four histopathological parameters in frozen tissue sections of 31 C-5 or C-6 nerve stumps were examined by a neuropathologist. The total quantity of myelin was compared with normal values. Also, thick myelinated fibers, fibrosis, and misdirected axons were assessed. Stumps embedded in plastic were used in a morphometric study of myelinated fiber profiles. The fiber density, mean size, and size distribution in five donor stumps were determined; three normal C-5 spinal nerves obtained at autopsy served as controls. Finally, the relative area occupied by fiber profiles and interspace was computed. Linear regression was used as a multivariate analysis, adjusting the outcome of surgical repair for effects of age, interval between trauma and surgery, and graft length. Histopathological examination showed that the total quantity of myelin in donor stumps used for biceps muscle reinnervation was considerably reduced. On morphometric examination the fiber density did not differ significantly between stumps obtained in patients and control stumps obtained at autopsy. However, a significant reduction of the area occupied by myelinated fibers was measured: from 46% in controls to 13% in patients (p < 0.0001). Likewise, a significant reduction was found in the mean fiber size: from 7.4 microm in controls to 3.7 microm in patients (p < 0.0001). The relationship between the myelin quantity in the proximal stump and the grade of biceps muscle recovery was statistically significant (p = 0.02). From the 95% confidence interval it was concluded that the estimated effect of a mean increase of myelinated fibers by 25% almost equals an increase in recovery of one point on the Medical Research Council scale (grade range 0-5). CONCLUSIONS: Both histopathological and morphometric examination showed a reduction of the quantity of myelin in C-5 or C-6 stumps used as donor sites for grafts. The amount of myelin is significantly correlated with biceps muscle function after nerve grafting. Because it is possible to assess the quantity of myelin by intraoperative examination of frozen sections, this correlation is potentially useful in the decision-making process of whether to use stumps for grafting or to use nerve transfer procedures to restore biceps muscle function.

Cervical myelopathy in rheumatoid arthritis.

Results obtained in 43 Rheumatoid arthritis (RA) patients with cervical myelopathy are described; all patients showed several alarm signs together with neurological disturbances. Thirty-four cases were operable; nine patients were not operated upon for various reasons (refusal, and general condition). In the surgically treated patients, the changes were localized in the C1-C2 area (n = 20), in the area below C2 (n = 5), or in both (n = 9). The patients were put on skull traction pre- and post-operatively and nursed on a circo-electric bed. Pre-operatively, the duration of traction varied from a few days to weeks (mean 3 weeks). Post-operatively, the patients were given continuous skull traction for 2 1/2-3 months. This procedure yielded neurological improvement and a stable graft in all but two patients. On follow-up, recurrence of neurological complaints was seen in nine patients, in four due to a new slip at a lower level. Three of these cases were reoperated with good results. Twenty-three patients have died: four 'early' (one pre-operatively and three within 6 weeks post-operatively) and 19 'late'. The mean duration of follow-up was 4.5 years. In those who died 'late', the cause of death was due to the effects of an unstable graft in two cases and in the others the causes were not related to changes in the cervical spine. In the 10 patients who are still alive the mean duration of follow-up is 5 years. The nine patients who were not operated upon all died within a year, 4 of them due to consequences of cord compression. If cervical spondylodesis is feasible in an RA patient with myelopathy, the procedure is advocated.

Innervation of "painful" lumbar discs.

STUDY DESIGN: The authors investigated the innervation of discographically confirmed degenerated and "painful" human intervertebral discs. OBJECTIVE: To determine the type and distribution patterns of nerve fibers present in degenerated human intervertebral discs. SUMMARY OF BACKGROUND DATA: The innervation of intervertebral discs has previously been extensively described in fetal and adult animals as well as humans. However, little is yet known about the innervation of severely degenerated human lumbar discs. The question may be posed whether a disc that has been removed for low back pain possesses an increased innervation compared with normal discs. METHODS: The presence of nerve fibers was investigated using acetylcholinesterase enzyme histochemistry, as well as neurofilament and substance P immunocytochemistry. From 10 degenerated and 2 control discs, the anterior segments were excised and their nerve distribution studied by examining sequential sections. RESULTS: In all specimens, nerve fibers of different diameters were found in the anterior longitudinal ligament and in the outer region of the disc. In 8 of 10 degenerated discs, fibers were also found in the inner parts of the disc. Substance P-immunoreactive nerve fibers were sporadically observed in the anterior longitudinal ligament and the outer zone of the anulus fibrosus. CONCLUSIONS: Findings indicate a more extensive disc innervation in the severely degenerated human lumbar disc compared with normal discs. The nociceptive properties of at least some of these nerves are highly suggested by their substance P immunoreactivity, which provides further evidence for the existence of a morphologic substrate of discogenic pain.

Recovery of brachial plexus injuries.

Despite technical advances, the ability to restore function following severe brachial plexus traction lesions is limited. Major problems hampering good results are the inability to recognize corresponding fascicles in case of a large nerve gap and the lack of a proximal nerve stump in root avulsions. This article discusses the diagnosis and treatment of such injuries in combination with research in this field.

Surgical repair of brachial plexus injury.

This preliminary report surveys the authors' experience in the treatment of 66 patients with brachial plexus traction injuries. The results of nerve reconstructive surgery obtained in 44 patients with a follow-up of at least 2 years were disappointing; on average, 10% of upper limb function was added. The role of several factors involved in this type of injury and the major draw-backs of treatment are discussed in combination with future possibilities. Current techniques of neurotizations are presented in one case.