Fabrice Parker

Intravenous lidocaine in central pain A double-blind, placebo-controlled, psychophysical study

Objective: To investigate the effects of systemic administration of lidocaine on different components of neuropathic central pains by quantitative sensory testing. Methods: The efficacy of systemic lidocaine (5 mg/kg IV over 30 minutes) was evaluated in a double-blind, placebo-controlled, and cross-over fashion, on both spontaneous ongoing pain and evoked pains (allodynia and hyperalgesia) in 16 patients with chronic poststroke (n = 6) or spinal cord injury (n = 10) related pain. Results: Lidocaine was significantly superior to the placebo (saline) in reducing the intensity of spontaneous ongoing pain for up to 45 minutes after the injection: 10 of 16 patients (62.5%) receiving lidocaine showed a significant reduction in spontaneous pain, whereas only six patients showed this after the placebo. Lidocaine also significantly reduced the intensity of brush-induced allodynia and mechanical hyperalgesia, but was no better than the placebo against thermal allodynia and hyperalgesia. In general, the side effects were moderate and consisted mainly of lightheadedness (44%). Conclusions: Systemic lidocaine can induce a significant and selective reduction of several components of pain caused by CNS injuries. The observed preferential antihyperalgesic and antiallodynic effects of this drug suggest a selective central action on the mechanisms underlying these evoked pains.

Factors predicting relapse of nonfunctioning pituitary macroadenomas after neurosurgery: a study of 142 patients

CONTEXT Adequate postoperative management of nonfunctioning pituitary macroadenomas (NFMAs) remains a challenge for the clinician. OBJECTIVE To identify predictive factors of NFMA relapse after initial surgery. PATIENTS AND METHODS This retrospective study included 142 patients operated for an NFMA in two academic centers (CHU Bicêtre in France and UCL St Luc in Belgium). The rate of tumor relapse, defined as recurrence after total surgical resection or regrowth of a surgical remnant, as well as predictive factors was analyzed. RESULTS During a mean follow-up of 6.9 years, 10 out of 42 patients (24%) who had complete macroscopic resection of their tumor had recurrence, and 47 out of 100 patients (47%) with a surgical remnant experienced regrowth. The overall relapse rates were 25, 43, and 61% at 5, 10, and 15 years respectively. Invasion of the cavernous sinus, absence of immediate radiotherapy after the first neurosurgery, and immunohistochemical features of the tumor (mainly positive immunostaining for several hormones or for hormones other than gonadotropins) were independent risk factors for tumor relapse. Incomplete excision was only associated with relapse when invasion was withdrawn from the analysis, suggesting that these two factors are closely linked. CONCLUSION NFMAs frequently recur/regrow after initial surgery, particularly when tumor is invasive, precluding complete removal. Immunohistochemical features such as positive immunostaining for several hormones or for hormones other than gonadotropins could help to predict undesirable outcomes.

Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of malignant glioma: a randomized phase II trial.

OBJECTIVE:This study was a randomized, multicenter Phase II trial comparing the effect of perioperative implantation of 5-fluorouracil-releasing microspheres followed by early radiotherapy (Arm A) and early radiotherapy alone (Arm B) in patients with gross total resection of high-grade glioma. METHODS:Patients were randomized on clinical and radiological assumption of supratentorial high-grade glioma. All patients underwent surgery, and after resection and histological confirmation, patients randomized to Arm A received multiple injections of microsphere suspension (130 mg of 5-fluorouracil). Conventional fractionated radiotherapy (59.4 Gy) was initiated between the second and the seventh day after surgery for both arms. RESULTS:A total of 95 patients were randomized. Seventy-seven patients were treated and analyzed in intention to treat for efficacy and safety. Overall survival was 15.2 months in Arm A and 13.5 months in Arm B. In the subpopulation of patients with complete resection, overall survival was 15.2 months in Arm A versus 12.3 months in Arm B. However, these differences were not significant. Safety was acceptable with prophylactic high doses of corticosteroids. CONCLUSION:It may be hypothesized that the implantation of 5-fluorouracil-loaded microspheres in the wall of the cavity resection did increase the overall survival, but the present study was not designed and sufficiently powered to demonstrate this.

Charcot's disease of the spine: diagnosis and treatment.

Study Design. Retrospective study. Objective. To report nine cases of Charcot’s joint of the spine, to clarify the difficulty in diagnosis and treatment, and to analyze the literature. Summary of Background. Charcot’s joint of the spine, also known as spinal neuropathic or neurogenic arthropathy, is a destructive condition that affects the intervertebral disc and the adjacent vertebral bodies. It is the result of a loss of joint protection mechanisms, generally secondary to a spinal cord lesion. We report a series of nine patients treated surgically. Methods. Eight men and one woman suffering from paraplegia or tetraplegia were reviewed. The time interval between the neurologic disorder and the diagnosis of neuropathic spinal arthropathy was 10 to 36 years. The most frequent presenting symptom was an evolutive thoracolumbar kyphosis, sometimes associated with back pain or increased spasticity in the lower limbs. The neuropathic arthropathy involved the thoracic spine in four patients and the lumbar spine in four other patients. The remaining patient presented two arthropathies, one thoracic and one lumbosacral. A percutaneous vertebral biopsy was performed in five patients suspected to have an infection or a tumor. Treatment was always surgical. In eight cases, a circumferential fusion was performed in the area of the dislocated vertebral levels. The postoperative follow-up was from 3 years to 10 years. Results. A solid and stable circumferential fusion of the spine was obtained in all patients. The functional status improved in all patients. Pain and sagittal imbalance were successfully treated. The increased spasticity observed at the initial examination improved in all patients who returned to the neurological deficit initially present before the onset of Charcot’s arthropathy. Conclusions. The diagnosis of Charcot’s arthropathy of the spine must be considered in paraplegic and tetraplegic patients with spinal deformity with bone destruction and vertebral dislocation in the absence of an infection or neoplastic disease. The treatment of a Charcot’s spine is circumferential fusion and osteosynthesis. Monitoring by clinical and imaging examination must be continued, because multifocal vertebral lesions can occur in cases of extensive proprioceptive deficit.

Outcome in 53 patients with spinal cord cavernomas

BACKGROUND Prevalence of cerebral cavernomas in the general population is close to 0.5%. In contrast, SCCs are rare. The aim of this study was to determine the outcome of SCC in a large sample of patients. METHODS Clinical and neuroradiologic findings were retrospectively collected in a multicentric study. Diagnosis was based on pathologic criteria or MR findings. RESULTS Fifty-three patients were included (26 males, 27 females). Mean age at onset of symptoms was 40.2 years (11-80 years). Initial symptoms were progressive (32) or acute myelopathy (20). One case was asymptomatic. Triggering factors were found in 14 of the patients (26%). Clinical symptoms were related to spinal cord compression (27) and hemorrhage (22). Spinal cord cavernoma was thoracic in 41 cases and cervical in 12. Mean size of the lesions was 16.3 mm (3-54 mm). In the 40 surgical patients, long-term follow-up was available in 37 cases for a mean time of 7.3 years (0.4-50 years). During the follow-up period, 20 patients improved, 6 remained on their preoperative baseline, and 11 got worse. Surgical improvement was more often found in posterior rather than anterior location. Using McCormick classification, 22 patients were autonomous (grades 1-2), 12 handicapped (grade 3), and 3 bedridden (grade 4) at the end of the follow-up. CONCLUSIONS This study has defined clinical and MR patterns of spinal cavernomas. Surgery lastingly improved more than half of the patients.

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%.

Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is associated with 9p loss, genomic instability, and angiogenic gene expression

BACKGROUND The aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs). METHODS The MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays. RESULTS Most of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2. CONCLUSION In AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume.

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.

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.

Effects of surgery on the sensory deficits of syringomyelia and predictors of outcome: a long term prospective study

Objective: To quantify the effects of surgery on the thermal deficits of syringomyelia and assess the predictors for such effects. Methods: The subjects were 16 consecutive patients (12 men, 4 women; mean (SD) duration of sensory symptoms, 5.1 (4.5) years) presenting with the typical symptoms of syringomyelia related to Chiari I malformation or trauma, and requiring surgical treatment. They were evaluated before surgery, then at six months and two years. Sensory evaluation included determination of the extent of thermal deficits and quantitative assessment of thermal, mechanical, vibration detection, and pain thresholds. Neuropathic pain intensity was evaluated on visual analogue scales. Magnetic resonance imaging was done before and after surgery to measure syrinx dimensions. Results: The magnitude and extent of thermal deficits improved in a subgroup of patients and this was best predicted by the duration of sensory symptoms: patients operated on less than two years after the onset of their symptoms tended to improve, while those operated on later were stabilised or deteriorated slightly. The effect of surgery on thermal deficits was correlated with the duration of sensory symptoms. Surgery also affected vibration deficits in patients with the Chiari malformation, neuropathic pain on effort, and syrinx dimensions. Conclusions: The duration of sensory deficits is the best predictive factor of the efficacy of surgery for the thermal symptoms of syringomyelia. Early surgery is required if these deficits are to be minimised.