[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 value of temporary external lumbar CSF drainage in predicting the outcome of shunting on normal pressure hydrocephalus.

OBJECTIVE: It has been reported that temporary external lumbar CSF drainage (ELD) is a very accurate test for predicting the outcome after ventricular shunting in patients with normal pressure hydrocephalus (NPH). However, only a limited number of patients have been studied for assessing the predictive accuracy of ELD. Therefore, the value of ELD in predicting the outcome after a ventriculoperitoneal shunt in patients with presumed NPH was assessed. METHODS: All patients with presumed NPH were invited to participate in this study. Clinical assessment, MRI, and neuropsychological evaluation were followed by a lumbar CSF tap test consisting of removing 40 ml CSF. When this test resulted in marked clinical improvement of gait impairment, mental disturbances, or both, the patient was shunted without further tests. In patients with either questionable or no improvement after the CSF tap test, ELD was carried out. The value of ELD for predicting the outcome after shunting was calculated by correlating the results of ELD with that of ventriculoperitoneal shunting. RESULTS: Between January 1994 and December 2000, 49 presumed NPH patients from three institutes were included. Forty three had idiopathic, and the remaining six had secondary NPH. Forty eight patients were shunted; 39 had an ELD of whom 38 completed the test. After 2 months 35 of the 48 (73%) shunted patients had improved. The predictive value of a positive ELD was 87% (95% confidence interval (95% CI) 62-98) and that of a negative ELD 36% (95% CI 17-59). In two patients serious test related complications (meningitis) occurred without residual deficit. CONCLUSION: The study suggests that although the predictive value of a positive ELD is high, that of a negative ELD is deceptively low because of the high rate of false negative results. The costs and invasiveness of the test and the possibility of serious test related complications further limits its usefulness in managing patients with presumed NPH.

Ultrastructural and quantitative motoneuronal changes after ventral root avulsion favor early surgical repair.

This study assesses qualitative and quantitative morphological changes that occur in motoneurons after ventral root avulsion. The motoneuronal perikaryal changes in the ventral horn of the cat's C7 cord segment were studied after survival times of 2, 8, 14, 30, 60 and 90 days. Generally, large motoneurons showed a light type of reaction, and the small ones either light or dark. In addition, neurons with a normal ultrastructural appearance were found. These latter are considered to be in a 'steady state', which may be associated with regenerative potency. All these types of neuron reactions were present at all survival times, but the number of cells marked by a specific reaction depends on the time of survival. Qualitative and quantitative evidence is given for cell death in 36% of the motoneuronal population between 2 and 14 days after avulsion. This reduction primarily concerns large, presumably alpha motoneurons with the light type reaction. Small, presumably gamma motoneurons become seriously affected after 14 days. These findings suggest that early surgical repair may have the better chances for clinical recovery.

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.

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.

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.

Acromesomelic dysplasia Maroteaux type maps to human chromosome 9.

Acromesomelic dysplasias are skeletal disorders that disproportionately affect the middle and distal segments of the appendicular skeleton. We report genetic mapping studies in four families with acromesomelic dysplasia Maroteaux type (AMDM), an autosomal recessive osteochondrodysplasia. A peak LOD score of 5.1 at recombination fraction 0 was obtained with fully informative markers on human chromosome 9. In three of the four families, the affected offspring are products of consanguineous marriages; if it is assumed that these affected offspring are homozygous by descent for the region containing the AMDM locus, a 6.9-cM AMDM candidate interval can be defined by markers D9S1853 and D9S1874. The mapping of the AMDM locus to human chromosome 9 indicates that AMDM is genetically distinct from the two other mapped acromesomelic dysplasias, Hunter-Thompson type and Grebe type, which are caused by mutations in CDMP1 on human chromosome 20.

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.

The process of decompaction and myelin removal after C7 ventral root avulsion in the cat.

An electron microscopical study was carried out on the ventral horn in order to investigate the microvascular changes after C7 ventral root avulsion in cats. Endothelial cells: At 2 days after avulsion the endothelial cells contained vacuoles filled with fibrous-like substances. After 14 days the endothelial phagosomes also contained myelin sheath-like and "soap-bubble" structures. Tight junctions between the endothelial cells remained present without exception. From 14 up to 90 days, intraluminal debris was observed. Edema and glia: From 2 up to 30 days after avulsion perivascular edema was noted around blood vessels and polymorphonuclear granulocytes were found mainly in the peri-endothelial space. Eight days after avulsion, the number of astrocytic processes around the blood vessels and the phagocytic activity of perivascular cells increased. Myelin sheath-like structures were encountered in phagosomes of the pericytes. After 14 days the distribution of astrocytic processes around the blood vessels had stabilized and remained so until day 90 after avulsion. In the same period the phagocytic activity decreased, and the myelin sheath-like material in the perivascular cell phagosomes gradually disappeared. The amount of microglial cells around the blood vessels showed an increase after 30 days survival and then stabilized. These results indicate transport of debris from the neuropil across the endothelial cells into the blood vessel lumen after ventral root avulsion.

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.

Control of complications in the midfrontobasal approach.

Many surgical techniques are employed for access to midline lesions of the anterior and middle fossa. A convenient one is the midfrontobasal approach. For various indications this surgical procedure was performed in 105 patients. Its benefits are outlined and a method for dealing with the two main drawbacks, postoperative loss of the sense of smell and the presumed risk of infection related to the inevitable opening of the frontal sinus, are described. In 83% of the cases the authors were able to anatomically retain the olfactory nerves, with preservation of the sense of smell in at least 65% of them. The frontal sinus was opened in 76% of the cases. The incidence of infection in the simple and quick integral reconstruction appeared 1%, equal to the rate of infection in the classical reduction of the frontal sinus by a periosteal flap.

Use of the Gigli saw in performing a mid-frontobasal or pterional craniotomy.

The use of the Gigli saw to deal with the inner bony ridges encountered in a mid-frontobasal or pterional craniotomy is presented. Despite the fact that power-driven craniotomes have certain advantages, the authors favour the Gigli saw in this situation.

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.

Immunocytochemical localization of neurofilaments in the fibre systems of the developing rat spinal cord white matter.

The appearance and localization of the protein subunits of neurofilaments in the ascending and descending fibre systems of the developing rat spinal cord white matter were studied. The monoclonal antibody NF-90 (specific for the phosphorylated NF-L, NF-M and NF-H subunits) was used as neurofilament marker in fresh cryostat and Bouin fixed paraffin sections. The results were compared with Nissl and Bodian stained sections. Within the white matter, phosphorylated neurofilament proteins were expressed with regional variations. At embryonal day 12 (E12), the first positive fibres were found in the lateral funiculus. During further development, the peripheral region of the lateral funiculus showed an intense neurofilament staining, due to the presence of a higher number of fibres. From postnatal day 12 (P12) on, an increased amount of neurofilaments was found in the region close to the periphery, probably due to the presence of large calibre fibres. The dorsolateral part of the lateral funiculus filled in with fibres after birth, which indicated the extended development of the rubrospinal tract. At E13, positive fibres were present in the ventral commissure and the ventral funiculus. At E14, an increased amount of neurofilaments was detected in the periphery of the ventral funiculus. At maturity, an intense staining in the subsurface region could be found, due to the presence of large calibre fibres of the fasciculus longitudinalis medialis. At E13, the first neurofilament positive fibres were present in the dorsal funiculus. At this day, a concentration of fibres was found in the dorsal part of the dorsal root bifurcation zone and three days later, more fibres were detected in the medial part of the dorsal funiculus. At E18, a higher number of fibres was present in the dorsal region of the fasciculus gracilis. The mature fasciculus cuneatus showed an intense neurofilament staining, which was mainly present in large calibre fibres. The ventral part of the dorsal funiculus filled in with neurofilament positive fibres after birth. This indicated the relative late arrival of the corticospinal tract.

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.

Aneurysmal bleeding. A plea for early surgery in good-risk patients.

From 1985 onwards we have aimed at operating on good-risk patients, i.e., those graded I-III on the WFNS SAH Scale, within 3 days after the aneurysmal bleed. We report on a series of 100 consecutive operations for saccular aneurysm, covering a period of 5 1/2 years. Early operations (in the above sense) were done in 57 good-risk but otherwise unselected patients. After a one year follow-up, 47 of them (82%) were found to have made a good recovery (Glasgow Outcome Score I). The outcome of (mostly early) surgery in 15 selected poor-risk patients (WFNS SAH Scale IV and V) was much less favourable. Late surgery (4 or more days after SAH) was performed in 28 good-risk patients, most of whom had been admitted several days or weeks after the bleeding. Almost all of these patients had a good outcome. It is argued that the known management results of delayed surgery, which during the deliberately chosen interval exposes the patient to the risk of rebleeding and vasospasm, have by now been surpassed by those of early surgery. However excellent the surgical results of delayed operations may be, early operation should become the treatment of choice in good-risk patients.