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Pharmacological treatment of acute spinal cord injury: how do we build on past success?

Most acute spinal cord injuries (SCI) do not involve complete transection of the spinal cord; typically, a rim of white matter survives. The potential for neurological recovery depends on optimal preservation of the ascending and descending white matter axons and their normal myelination. Pharmacologic strategies focus on the control of secondary injury processes, primarily lipid peroxidation (LP), and the salvage of as much white matter as possible. The first effective neuroprotective agent was methylprednisolone (MP), a glucocorticosteroid that in high doses improves neurological recovery in animals and humans following acute SCI. Tirilazad is a more targeted non-glucocorticoid LP inhibitor that has been shown to be neuroprotective and has fewer side effects than MP. Future SCI therapy is likely to encompass various neuroprotective agents, including inhibitors of LP, inhibitors of the nitric oxide-derived reactive oxygen species peroxynitrite, inhibitors of calpain (which is responsible for degrading the spinal cord cytoskeleton), and inhibitors of post-traumatic apoptosis of neurons and myelin-forming oligodendroglia. In addition, neuroprotective strategies will eventually be followed by neurorestorative agents that stimulate the plasticity of surviving neural pathways, and will be used in conjunction with other neurorestorative therapies like cell transplantation and gene therapy techniques.

Acute Disease↗

Interleukin-10 improves outcome and alters proinflammatory cytokine expression after experimental traumatic brain injury.

Traumatic injury to the central nervous system initiates inflammatory processes that are implicated in secondary tissue damage. These processes include the synthesis of proinflammatory cytokines, leukocyte extravasation, vasogenic edema, and blood-brain barrier breakdown. Interleukin-10 (IL-10), a cytokine with antiinflammatory properties, negatively modulates proinflammatory cascades at multiple levels. We examined the hypothesis that IL-10 treatment can improve outcome in a clinically relevant model of traumatic brain injury (TBI). IL-10 was administered via different routes and dosing schedules in a lateral fluid-percussion model of TBI in rats. Intravenous administration of IL-10 (100 micrograms) at 30 min before and 1 h after TBI improved neurological recovery and significantly reduced TNF expression in the traumatized cortex at 4 h after injury. Such treatment was associated with lower IL-1 expression in the injured hippocampus, and to a lesser extent, in the injured cortex. Subcutaneous IL-10 administration (100 micrograms) at 10 min, 1, 3, 6, 9, and 12 h after TBI also enhanced neurological recovery. In contrast, intracerebroventricular administration of IL-10 (1 or 6 micrograms) at 15 min, 2, 4, 6, and 8 h after TBI was not beneficial. These results indicate that IL-10 treatment improves outcome after TBI and suggest that this improvement may relate, in part, to reductions in proinflammatory cytokine synthesis.

Animals↗

Bladder function after incomplete spinal cord injury in mice: quantifiable outcomes associated with bladder function and efficiency of dehydroepiandrosterone as a therapeutic adjunct.

OBJECT: The authors conducted a study to establish outcomes associated with bladder function in a mouse model of spinal cord injury (SCI) and to assess the sensitivity of these outcomes in determining the efficacy of pharmacological treatments. METHODS: A mouse model of moderate contusive SCI was used. Outcome parameters included physiological, behavioral, and morphological measurements. To test the sensitivity of these outcomes, the authors used a dehydroepiandrosterone (DHEA) treatment that they had previously shown to promote neurological recovery effectively after SCI. A behavioral scale was used to identify the day at which autonomic function of the bladder was recovered. The reduction in the daily volume of urine during the period of functional recovery paralleled this scale. They then determined the day postinjury at which the functional differences between the vehicle- and DHEA-treated mice exhibited the maximal amplitude. Changes were measured in the composition of the extracellular matrix relative to collagen expression in the layer muscularis of the detrusor at this time point. They found that SCI increases the ratio of collagen type III to collagen type I in the detrusor. Moreover, in the DHEA-treated group, this ratio was similar to that demonstrated in sham-operated mice, establishing the sensitivity of this outcome to assess therapeutic benefits to the bladder function. They next examined the relationship between measurements of neurological recovery and controlled voiding by using cluster analysis. CONCLUSIONS: The authors found that early recovery of controlled voiding is predictive of motor recovery.

Animals↗

An evidence-based review of decompressive surgery in acute spinal cord injury: rationale, indications, and timing based on experimental and clinical studies.

OBJECT: The authors conducted an evidence-based review of the literature to evaluate critically the rationale and indications for and the timing of decompressive surgery for the treatment of acute, nonpenetrating spinal cord injury (SCI). METHODS: The experimental and clinical literature concerning the role of, and the biological rationale for, surgical decompression for acute SCI was reviewed. Clinical studies of nonoperative management of SCI were also examined for comparative purposes. Evidence from clinical trials was categorized as Class I (well-conducted randomized prospective trials), Class II (well-designed comparative clinical studies), or Class II (retrospective studies). Examination of studies in which animal models of SCI were used consistently demonstrated a beneficial effect of early decompressive surgery, although it is difficult to apply these data directly to the clinical setting. The clinical studies provided suggestive (Class III and limited Class II) evidence that decompressive procedures improve neurological recovery after SCI. However, no clear consensus can be inferred from the literature as to the optimum timing for decompressive surgery. Many authors have advocated delayed treatment to avoid medical complications, although good evidence from recent Class II trials indicates that early decompressive surgery can be performed safely without causing added morbidity or mortality. CONCLUSIONS: There is biological evidence from experimental studies in animals that early decompressive surgery may improve neurological recovery after SCI, although the relevant interventional timing in humans remains unclear. To date, the role of surgical decompression in patients with SCI is only supported by Class III and limited Class II evidence. Accordingly, decompressive surgery for SCI can only be considered a practice option. Furthermore, analysis of the literature does not allow definite conclusions to be drawn regarding appropriate timing of intervention. Hence, there is a need to conduct well-designed experimental and clinical studies of the timing and neurological results of decompressive surgery for the treatment of acute SCI.

Acute Disease↗

General diseases of the spine in rheumatoid arthritis.

The past year has contributed to a better understanding of the management of cervical spine instability in patients with rheumatoid arthritis. Neurologic recovery after surgery is better and the percentage of recurrence is lower in cases of isolated atlantoaxial subluxation (AAS) compared with cases of AAS associated with basilar invagination or with subaxial subluxation. This suggests that the sooner surgery is undertaken in limited AAS, the better the outcome. The atlantoaxial posterior interval seems to be the best predictor of neurologic recovery following posterior fusion for AAS. Osteoporosis is a major problem in patients with rheumatoid arthritis. Recent studies show that corticosteroids, even in a low dosage, contribute to spinal bone loss. This bone loss may be partially reversible after ceasing corticoid therapy. A new corticosteroid, deflazacort, which does not inhibit intestinal absorption of calcium, seems to limit bone loss.

Adrenal Cortex Hormones↗

Cervical laminoplasty to enlarge the spinal canal in multilevel ossification of the posterior longitudinal ligament with myelopathy.

We studied 23 patients with severe myeloradiculopathy involving multiple (more than three) levels of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine, who were treated with laminoplasty to enlarge the spinal canal. The resected spinous processes were used as bone grafts to support the opened laminae. These patients were analyzed pre- and postoperatively with a neurological evaluation according to the Japanese Orthopedic Association (JOA) score system for cervical myelopathy. Follow-up was from 2.0 to 5.3 years with an average of 31.5 months. The results were compared with those in 31 patients with the same degree (multilevel) of OPLL who had been operated upon previously by laminectomy (14 cases) or anterior resection (17 cases). Postoperative neurological recovery by improvement ratio of the JOA score was observed in 81.2% of those who had undergone expansive laminoplasty, in 72.4% of those with laminectomy, and in 63.6% of those with anterior decompression. We concluded that expansive laminoplasty is a safer procedure with fewer complications. Stability is achieved by fixing the expanded laminae permanently with a bone graft. The neurological recovery following our technique of laminoplasty and fusion appears to be superior to that with laminectomy or anterior decompression.

Adult↗

Pott's paraplegia in patients with severely deformed dorsal or dorsolumbar spines: treatment and prognosis.

STUDY DESIGN: Pott's paraplegic patients with severe spinal deformity were reviewed retrospectively after being treated with chemotherapy and/or decompressive surgery. OBJECTIVES: To determine the most appropriate treatment protocol and to predict the prognosis for Pott's paraplegics with severe spinal deformity. SETTING: Catholic University of Korea Medical Center and Moon-Kim's Institute of Orthopedic Research, Seoul, Korea from 1971 to 1996. METHOD: In this study, there were 33 patients (eight children and 25 adults), ranging from 13 to 56 years of age. They developed spinal tuberculosis at the age of 9 years (range, 2-29 years), and remained neurologically symptom free from an average of 16 years (range, 4-27 years). Four adults who responded well to treatment initially suffered relapses of paraplegia. Only six patients had previously received a full course of triple chemotherapy. Seven (two children, five adults) had healed disease, and 26 (six children, 20 adults) had active disease. Eleven cases had frequent drainage from the sinuses. Kyphoscoliosis was found in 11 patients: four children and seven adults. The remaining patients had kyphosis only. Among the 26 patients with active tuberculosis, 10 had triple chemotherapy itself and the rest had additional decompression surgery (10 anterior and six posterior). All seven patients with healed tuberculosis were subjected only to surgery (two anterior and five posterior). RESULTS: In seven patients with healed tuberculosis, surgery did not improve neurologically except in one child patient. In four patients, the severity of paralysis remained unchanged and two patients, deteriorated neurologically after surgery. In six children with active tuberculosis, there were remarkable neurological recoveries by either conservative treatment or surgical decompression. Seven adults with active tuberculosis recovered slowly, improving by one or two Frankel grades (three Frankel C, three D, one E). In 11 out of 13 surgically treated adults with active disease, paralysis that had persisted for less than 3 months gradually improved by one or two Frankel grades. One Frankel A and one Frankel B paraplegic patients who had paralysis that had lasted through 6 months did not recover after surgery. CONCLUSION: The neurological recovery of Pott's paraplegics with severe spinal deformity resulted in three different outcomes: (1) severe deformity is different from moderate and mild deformities; (2) patients with healed tuberculosis had poorer prognosis than patients with active tuberculosis; (3) children had better prognosis than adults. Furthermore, patients with paralysis persisting over 6 months did not recover neurologically after surgery.

Adolescent↗

Primary epidural non-Hodgkin lymphoma: spinal cord compression syndrome as the initial form of presentation in childhood non-Hodgkin lymphoma.

BACKGROUND: Primary epidural non-Hodgkin lymphoma (NHL) is a rare but devastating event in pediatric oncology. Spinal cord compression due to an epidural mass from NHL, although it presents as a localized problem, in fact, is a systemic disease. Over the last 3 decades, aggressive systemic treatments with central nervous system prophylaxis have been designed with improving results. PROCEDURE: We reviewed the 20-year experience of the treatment of NHL with the LSA2-L2 protocol in our institution. Among 256 patients treated, five presented with primary epidural mass. Clinical features, treatment, and outcome of those five patients are presented. RESULTS: Three patients out of five responded favorably, and after a median follow-up of 10 years, they are cured. After presenting with paraplegia, functional and neurological recoveries were excellent. Of the patients who failed treatment, relapse occurred early, either during the treatment or right after completion of therapy. The relapses were within the central nervous system as well as systemic. CONCLUSIONS: Patients with primary epidural NHL presented with long histories of persistent back pain. Plain films of the spine were useless. All patients were diagnosed when neurologic damage had already been established. However, when the epidural NHL is treated aggressively with systemic chemotherapy and vigorous rehabilitation, the prognosis for complete neurological recovery and cure of the lymphoma is encouraging.

Adolescent↗

[Hypothermia helps in the drowned child. Report of a case].

Near-drowning is a leading cause of childhood mortality. Early induction of deep hypothermia has a protective effect on the brain, however. Favorable factors, most marked in early childhood, are both anatomic and physiologic. No parameter capable of predicting good neurologic recovery was identified by a review of the literature. Management rests on internal warming techniques and should be initiated immediately whenever apparent death occurs after exposure to cold. The case of a 29-month-old child who had complete cardiorespiratory arrest and a fall in body temperature to 22 degrees C after near-drowning and who made a full neurologic recovery is reported.

Body Temperature↗

A moderate dose of propofol and rapidly induced mild hypothermia with extracorporeal lung and heart assist (ECLHA) improve the neurological outcome after prolonged cardiac arrest in dogs.

BACKGROUND AND PURPOSE: Propofol has been shown to protect against neuronal damage induced by brain ischaemia in small animal models. We reported previously that mild hypothermia (33 degrees C) in combination with extracorporeal lung and heart assist (ECLHA) improved the neurological outcome in dogs with cardiac arrest (CA) of 15 min induced during normothermia. In the present study, we investigated the neuroprotective effect of propofol infusion under mild hypothermia with ECLHA in this model. METHODS: Twenty-one female dogs (15 mongrel dogs and 6 beagles) were divided into three groups: Midazolam 0.1 mg/(kg h) infusion group (M, n=7), Propofol 2 mg/(kg h) infusion group (P2, n=7), Propofol 4 mg/(kg h) infusion group (P4, n=7). Normothermic ventricular fibrillation (VF) was induced in all dogs for 15 min, followed by brief ECLHA and 168 h of intensive care. The drug infusion was initiated at a constant rate after the restoration of spontaneous circulation (ROSC) to 24 h. Mild hypothermia (33 degrees C) was maintained for 20 h. Neurological deficit scores (NDS: 0%=normal, 100%=brain death) were evaluated for neurological function from 33 to 168 h. RESULTS: One dog in the M group died, and the remaining dogs survived for 168 h. The P4 group showed better neurological recovery compared with the M group (48 h, 21+/-16% versus 32+/-15%; 72 h, 7+/-6% versus 25+/-11%; 96 h, 6+/-6% versus 21+/-6%; 120 h, 5+/-5% versus 20+/-6%; 144 h, 4+/-4% versus 20+/-6%; 168 h, 4+/-4% versus 20+/-6%, p<0.05). One dog in the P2 and three dogs in the P4 group achieved full neurological recovery (NDS: 0%). The number of intact pyramidal cells in the hippocampal CA1 was greater in the propofol groups than midazolam group (p<0.05). CONCLUSION: The combination of propofol infusion at a rate of 4 mg/(kg h), 24h and rapidly induced mild hypothermia (33 degrees C) with ECLHA might provide a successful means of cerebral resuscitation from CA.

Anesthetics, Intravenous↗

Motor nerve palsy following primary total hip arthroplasty.

BACKGROUND: Nerve palsy is a potentially devastating complication following total hip arthroplasty. The purpose of this study was to retrospectively identify risk factors for, and the prognosis associated with, a motor nerve palsy following primary total hip arthroplasty. METHODS: Between 1970 and 2000, 27,004 primary total hip arthroplasties were performed at our institution. Forty-seven patients (0.17%) with postoperative motor nerve dysfunction were identified by a review of the complications log of a total joint database. The medical record of each patient provided the data for this study. The average age of the patients was fifty-seven years at the time of surgery. The patients had serial clinical examinations for a minimum of two years, or until neurologic recovery or death. The nerve palsies were classified as complete or incomplete, and only patients with objective motor weakness were included in the study. The limb lengths were measured on preoperative and postoperative radiographs, and those data were then compared with the limb lengths in a matched cohort of patients who had not sustained a nerve injury after a primary total hip arthroplasty. The extent of neurologic recovery, the need for braces or walking aids, and the use of medications for neurogenic pain were evaluated. RESULTS: There were twenty-nine complete motor nerve palsies (sixteen peroneal, eleven sciatic, and two femoral) and eighteen incomplete motor nerve palsies (fourteen peroneal, three sciatic, and one femoral). A preoperative diagnosis of developmental dysplasia of the hip (p = 0.0004) or posttraumatic arthritis (p = 0.01), the use of a posterior approach (p = 0.032), lengthening of the extremity (p < 0.01), and cementless femoral fixation (p = 0.03) were associated with a significantly increased odds ratio for the development of a postoperative motor nerve palsy. Of the twenty-eight patients with a complete palsy who were available for follow-up, only ten (36%) had complete recovery of motor strength, which took an average of 21.1 months. Seven of the eighteen patients with an incomplete palsy fully recovered their preoperative strength. Twenty-one patients required walking aids, and fifteen required permanent use of an ankle-foot orthosis. Five patients required daily medication for chronic neurogenic pain. CONCLUSIONS: Motor nerve palsy is uncommon following primary total hip arthroplasty. A preoperative diagnosis of developmental dysplasia of the hip or posttraumatic arthritis, the use of a posterior approach, lengthening of the extremity, and use of an uncemented femoral implant increased the odds ratio of sustaining a motor nerve palsy. The majority of the motor nerve deficits in our series, whether complete or incomplete, did not fully resolve.

Aged↗

Device for zone-II flexor tendon repair. A multicenter, randomized, blinded, clinical trial.

BACKGROUND: The stainless-steel Teno Fix tendon-repair device has improved biomechanical characteristics compared with those of suture repair, and it was well tolerated in a canine model. The purpose of this study was to compare the Teno Fix with suture repair in a clinical setting. METHODS: Sixty-seven patients with isolated zone-II flexor tendon injury were randomized to be treated with a Teno Fix or a four-stranded cruciate suture repair. There were eighty-five injured digits: thirty-four were treated with the Teno Fix, and fifty-one served as controls. A modified Kleinert rehabilitation technique was employed, with active flexion starting at four weeks postoperatively. Patients were followed for six months by blinded observers who determined the range of motion, Disabilities of the Arm, Shoulder and Hand (DASH) score, pinch and grip strength, and pain score on a verbal scale and assessed swelling and neurologic recovery. Adverse outcomes, including device migration and rupture, were monitored at frequent intervals. RESULTS: Nine of the fifty-one suture repairs ruptured, whereas none of the Teno Fix repairs ruptured (p < 0.01). Five of the nine ruptures were caused by resistive motion against medical advice. There were no differences between the two groups in terms of range of motion, DASH score, pinch and grip strength, pain, swelling, or neurologic recovery. The Teno Fix group had slightly slower resolution of pain and swelling compared with the control group. Of the patients who were available for follow-up at six months, sixteen of the twenty-four treated with a Teno Fix repair and nineteen of the twenty-seven treated with a control repair had a good or excellent result. One Teno Fix device migrated and extruded secondary to a wound infection. Of all eighty-five digits that were operated on, four were thought to have tendons of inadequate size to accommodate the device and nine were deemed to have inadequate exposure to allow placement of the anchors. CONCLUSIONS: The Teno Fix is safe and effective for flexor tendon repair if the tendon size and exposure are sufficient. Tendon repairs with the Teno Fix have lower rupture rates and similar functional outcomes when compared with conventional repair, particularly in patients who are noncompliant with the rehabilitation protocol.

Adult↗

A device for zone-II flexor tendon repair. Surgical technique.

BACKGROUND: The stainless-steel Teno Fix tendon-repair device has improved biomechanical characteristics compared with those of suture repair, and it was well tolerated in a canine model. The purpose of this study was to compare the Teno Fix with suture repair in a clinical setting. METHODS: Sixty-seven patients with isolated zone-II flexor tendon injury were randomized to be treated with a Teno Fix or a four-stranded cruciate suture repair. There were eighty-five injured digits: thirty-four were treated with the Teno Fix, and fifty-one served as controls. A modified leinert rehabilitation technique was employed, with active flexion starting at four weeks postoperatively. Patients were followed for six months by blinded observers who determined the range of motion, Disabilities of the Arm, Shoulder and Hand (DASH) score, pinch and grip strength, and pain score on a verbal scale and assessed swelling and neurologic recovery. Adverse outcomes, including device migration and rupture, were monitored at frequent intervals. RESULTS: Nine of the fifty-one suture repairs ruptured, whereas none of the Teno Fix repairs ruptured (p < 0.01). Five of the nine ruptures were caused by resistive motion against medical advice. There were no differences between the two groups in terms of range of motion, DASH score, pinch and grip strength, pain, swelling, or neurologic recovery. The Teno Fix group had slightly slower resolution of pain and swelling compared with the control group. Of the patients who were available for follow-up at six months, sixteen of the twenty-four treated with a Teno Fix repair and nineteen of the twenty-seven treated with a control repair had a good or excellent result. One Teno Fix device migrated and extruded secondary to a wound infection. Of all eighty-five digits that were operated on, four were thought to have tendons of inadequate size to accommodate the device and nine were deemed to have inadequate exposure to allow placement of the anchors. CONCLUSIONS: The Teno Fix is safe and effective for flexor tendon repair if the tendon size and exposure are sufficient. Tendon repairs with the Teno Fix have lower rupture rates and similar functional outcomes when compared with conventional repair, particularly in patients who are non-compliant with the rehabilitation protocol.

Equipment Design↗

Dumbbell hydatid cyst of the spine: case report and review of the literature.

STUDY DESIGN: A case report of a hydatid cyst in the retropleural space at T7-T8 with an extension into the spinal canal through an intervertebral foramen complicated by paraparesis due to thoracic cord compression. OBJECTIVE: To confirm that hydatid cyst should be considered in the differential diagnosis for any mass discovered in the human body. SUMMARY OF BACKGROUND DATA: Appearance of a dumbbell-shaped mass in the thoracic spine is highly suggestive of neurofibroma. Hydatid cyst, although very rare, may have the same appearance. The spine is involved in 50% of hydatid disease of the bone. A hydatid cyst of the bone and muscle is always primary. Neurologic recovery is possible because it is a slow-growing lesion. METHOD: Clinical symptoms, differential diagnosis, and treatment are reviewed. The patient was treated successfully by total surgical excision of the lesion through a posterior retropleural approach. No medical treatment was prescribed. RESULTS: Surgical excision is effective in the treatment of hydatid disease of the spine, particularly if there is no extensive bony destruction and it is possible to achieve neurologic recovery after decompression of the thoracic spine. CONCLUSION: Extra spinal hydatidosis may lead to spinal cord compression by extension through the intervertebral foramen. The possibility of cure is high when there is no bony involvement.

Adult↗

Long-term survival, prognosis, and life-care planning for 29 patients with chronic locked-in syndrome.

We present a life-table analysis of a cohort of 29 locked-in syndrome (LIS) patients followed for a minimum of five years, and we report on the status of the chronic LIS patient. Twenty-nine LIS patients who remained locked-in for more than one year were identified. Inpatient charts were reviewed for demographic, medical, and functional data. Telephone followup was obtained to examine medical complications after discharge, survival, neurologic recovery, care issues, and permanent disposition. A life-table analysis was performed on survival data. Cerebrovascular disease was the most common cause of LIS. Survival ranged from 2.02 to 18.15 years. Twenty of the 26 patients available for five-year followup survived; hence, five-year survival was 81%. An alternative method of communication and emotional stress for the patient's caregiver was the key issue in patient care. Most patients were cared for in their own homes. Although minimal late neurologic recovery occurs in chronic LIS, survival may, nonetheless, be prolonged with adequate supportive care. Modern computerized technology offers LIS patients the ability to interact with their environment. This information may assist physicians in making ethical and long-term care decisions with the patient rather than for the patient with LIS.

Adult↗

Congenital anteroposterior spinal dissociation in Larsen's Syndrome: report on two operated cases with long-term follow-up.

STUDY DESIGN: The outcome of two patients with Larsen's syndrome after spinal surgery was evaluated after follow-up for 9 and 16 years. OBJECTIVE: To report on a new phenomenon of anteroposterior dissociation of the vertebrae in Larsen's syndrome. To demonstrate that it can be visualized before surgery with imaging and also seen intraoperatively. To show that the neurologic recovery after surgery is sustained and to review the technical reasons for the difficulties in achieving a surgical fusion. The critical role of CT scanning will be illustrated. SUMMARY OF BACKGROUND DATA: The results of preoperative and postoperative radiologic investigations and intraoperative findings are presented to support this new phenomenon. METHODS: Two patients underwent multiple spinal surgeries because of a deteriorating myelopathic clinical status. Intraoperatively, anteroposterior dissociation was documented in both patients. There was great difficulty in obtaining a surgical fusion, and an unusually long circumferential fusion was eventually necessary to obtain stability. Prolonged halo-vest immobilization was essential. RESULTS: Neurologic recovery was sustained over time, and the spinal deformity did not deteriorate. CONCLUSION: Awareness of this phenomenon is essential to the management of spinal deformities in Larsen's syndrome when presenting with myelopathy. Special features in the radiologic workup should be sought after so as to plan staged surgical procedures. Conventional principles of planning of fusion levels are inadequate. Early treatment is advocated, as the neurologic compromise is reversible.

Bone and Bones↗

Fractured odontoid: the management of delayed neurological symptoms.

Undiagnosed and untreated odontoid fractures are relatively common in developing countries where treatment for minor injuries is not considered. As a result, patients frequently present with neurological deterioration secondary to delayed odontoid dislocation. Fifty-one consecutive patients with this problem were entered into a management protocol and reviewed for this report. After diagnosis, reducibility was analyzed by extension films, and all patients who could not be reduced were initially managed in cranial long traction. Thirty-seven were reduced spontaneously or by traction alone, and 12 required transoral decompression. All underwent posterior C1-C2 fusion. Postoperatively, all were treated in external orthoses. The neurological recovery was excellent in 34 patients. Seven patients could function but had some disability, three patients had disabling spasticity, and three remained bedridden. Four deaths occurred as a result of respirator-dependent patients being taken home for social and financial reasons. As a result of this case-controlled study, we recommend that the treatment protocol first analyze reducibility by extension x-rays and then try traction for as long as 14 days to attempt reduction in patients who did not reduce in extension. Failure of reduction is indication for transoral decompression, and all patients require C1-C2 fusion. The neurological recovery is related to initial impairement but can be satisfactory in > 75% of patients.

Adolescent↗

Diabetic neuropathy after pancreas transplantation: determinants of recovery.

Although simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia and correction of uremia in type I diabetic patients with renal failure, little data are available on long-term outcome and clinical determinants of recovery of peripheral neuropathy. In this prospective study, 219 electrophysiological studies using a standardized protocol were performed before and up to 8 years after SPK in 44 patients. Nine control diabetic recipients with functioning kidney but nonfunctioning pancreas transplants were studied on 35 occasions. Patients were 38.5+/-7.9 years old (mean+/-SD) with pretransplant diabetes present for 25.2+/-7.6 years. Significant polyneuropathy (total nerve conduction scores [NCS] <-1.0) was present in 89% before transplantation, which correlated with body weight (r=0.628, P<0.001). Two distinct patterns of neurological recovery were observed after SPK. Conduction velocity (CV) improved in a biphasic pattern, with a rapid initial recovery followed by subsequent stabilization. In contrast, the recovery of nerve amplitude was monophasic, and continued to improve for up to 8 years. Initial improvement in NCS was primarily due to an increase in CV (P=0.002 vs. baseline), and was best in shorter and younger patients. Recovery of total NCS at 6 months after SPK, assessed by multivariate analysis, was least in obese recipients and when performed in patients who had started dialysis before SPK, and was associated with lower transplant kidney isotopic glomerular filtration rate and HLA mismatch (P<0.05 to 0.001). Subsequent improvement was associated with less severe initial neuropathy, smaller body weight, and longer duration of diabetes (P<0.01 to 0.001). Fasting hyperinsulinemia was associated with impairment of initial recovery and subsequent NCS after SPK, but was worse in the control group. Recovery of nerve action potential amplitudes was predicted by better initial amplitudes and HLA mismatch, lower body weight, and the use of nifedipine (P<0.05 to 0.001). Nifedipine was used for hypertension in 33% of SPK and was associated with better CV and amplitudes, particularly in the upper limbs, where there was less neuropathy. The use of angiotensin-converting enzyme inhibitors also appeared beneficial, but this was confined to the lower limbs. SPK resulted in a gradual, sustained, and late improvement in nerve action potential amplitudes, consistent with axonal regeneration and partial reversal of diabetic neuropathy. These data suggest that early transplantation of uremic diabetic patients before onset of severe neuropathy, minimizing obesity and optimizing renal transplant function, maximizes neurological recovery after SPK. Furthermore, the preliminary data support randomized clinical trials for evaluation of nifedipine and angiotensin-converting enzyme inhibitors in diabetic neuropathy.

Adult↗