Pulsed electromagnetic field stimulation may improve fusion rates in cervical arthrodesis in high-risk populations.

OBJECTIVES: Pulsed electromagnetic field (PEMF) stimulation was evaluated after anterior cervical discectomy and fusion (ACDF) procedures in a randomized, controlled clinical study performed for United States Food and Drug Administration (FDA) approval. PEMF significantly increased fusion rates at six months, but 12-month fusion outcomes for subjects at elevated risk for pseudoarthrosis were not thoroughly reported. The objective of the current study was to evaluate the effect of PEMF treatment on subjects at increased risk for pseudoarthrosis after ACDF procedures. METHODS: Two evaluations were performed that compared fusion rates between PEMF stimulation and a historical control (160 subjects) from the FDA investigational device exemption (IDE) study: a post hoc (PH) analysis of high-risk subjects from the FDA study (PH PEMF); and a multicentre, open-label (OL) study consisting of 274 subjects treated with PEMF (OL PEMF). Fisher's exact test and multivariate logistic regression was used to compare fusion rates between PEMF-treated subjects and historical controls. RESULTS: In separate comparisons of PH PEMF and OL PEMF groups to the historical control group, PEMF treatment significantly (p < 0.05, Fisher's exact test) increased the fusion rate at six and 12 months for certain high-risk subjects who had at least one clinical risk factor of being elderly, a nicotine user, osteoporotic, or diabetic; and for those with at least one clinical risk factor and who received at least a two- or three-level arthrodesis. CONCLUSION: Adjunctive PEMF treatment can be recommended for patients who are at high risk for pseudoarthrosis.Cite this article: D. Coric, D. E. Bullard, V. V. Patel, J. T. Ryaby, B. L. Atkinson, D. He, R. D. Guyer. Pulsed electromagnetic field stimulation may improve fusion rates in cervical arthrodesis in high-risk populations. Bone Joint Res 2018;7:124-130. DOI: 10.1302/2046-3758.72.BJR-2017-0221.R1.

A review of facial nerve outcome in 100 consecutive cases of acoustic tumor surgery.

OBJECTIVE: To determine the facial nerve outcomes at a tertiary neurotological referral center specializing in acoustic neuroma and skull base surgery. STUDY DESIGN: Retrospective review of 100 consecutive patients in whom acoustic neuromas were removed using all of the standard surgical approaches. METHODS: Functional facial nerve outcomes were independently assessed using the House-Brackmann facial nerve grading system. RESULTS: The tumors were categorized as small, medium, large, and giant. If one excludes the three patients with preoperative facial palsies, 100% of the small tumors, 98.6% of the medium tumors, 100% of the large tumors, and 71% of the giant tumors had facial nerve function grade I-II/VI after surgery. CONCLUSION: Facial nerve results from alternative nonsurgical treatments must be compared with facial nerve outcomes from experienced surgical centers. Based on the facial nerve outcomes from our 100 consecutive patients, microsurgical resection remains the preferred treatment modality for acoustic tumors.

The caudalis DREZ for facial pain.

During a 3-year period, 25 caudalis dorsal root entry zone (DREZ) operations were done for severe, facial pain. Intraoperative brainstem recordings were done before and after DREZ in all patients. Primary diagnosis included refractory trigeminal neuralgia, atypical headaches or facial pain, posttraumatic closed head injuries, postsurgical anesthesia dolorosa, multiple sclerosis, brainstem infarction, postherpetic neuralgia and cancer-related pain. At the time of discharge, good to excellent pain relief was present in 24/25 patients and fair relief in 1. At 1 month, 19/25 (76%) patients had good to excellent results and at 3 months following surgery, 17/25 (68%) continued to have good to excellent pain relief. One year following surgery, 18 patients could be evaluated, 12/18 (67%) still considered their relief as good to excellent, 2 fair and 4 poor. Transient postoperative ataxia was present in 15/25 patients (60%), but was largely resolved at 1 months. In 3/18 (17%) patients, a degree of ataxia was still present at 1 year although in none was it disabling. Two patients had transient diplopia, and 3 had increased corneal anesthesia with 1 later developing a keratitis. No surgical or postsurgical mortality was noted. This procedure has proven to be a satisfactory treatment for many patients with debilitating facial pain syndromes with acceptable morbidity.

Evolution of principles of stereotactic neurosurgery.

Stereotactic neurosurgery is the arena in which the past meets the present on many levels. Preserved skulls from South America, Africa, and Europe testify to man's early attempts at cranial surgery. Stereotactic approaches and systems, as well as the new innovative interactive image-guided devices, are efforts to explore and treat the afflictions of the human brain in both its literal and figurative aspects.

Duration of amnesia associated with midazolam/fentanyl intravenous sedation.

The purpose of this study was to determine the duration of amnesia associated with the intravenous usage of midazolam and fentanyl. The midazolam was administered in three different dosages based on the patient's weight in kilograms. Patients were shown a series of pen-and-ink drawings at various times throughout the procedure and tested the next day for memory of the drawings using both free recall and match-to-sample paradigms. The results indicate that the low-dosage group (0.07 mg/kg) had insufficient amnesia, whereas the medium (0.10 mg/kg) and high (0.13 mg/kg) groups displayed adequate amnesia in the intraoperative period.

Gasserian ganglion schwannoma with orbital extension.

A patient with painless proptosis and no associated neurologic symptoms was found to have a cystic retrobulbar orbital mass. The initial computed tomography (CT) scan did not demonstrate any intracranial involvement. On orbital biopsy a schwannoma was encountered and repeat CT scan with contrast revealed a large middle cranial fossa mass with extension into the orbit through the optic canal and superior orbital fissure. On lateral transfrontal craniotomy the lesion was noted to arise from the gasserian ganglion and to involve the right cavernous sinus. Subtotal resection was performed, and the patient has remained asymptomatic and free of recurrence for 18 months.

Intraoperative impedance monitoring during CT-guided stereotactic biopsies.

In this study, the relationships among computed tomography (CT) characteristics, intraoperative impedance monitoring, and histologic features were evaluated in 46 patients. Preoperatively, the CT characteristics of the proposed trajectory of the biopsy needle were determined and correlated intraoperatively with the impedance profile as obtained with a monopolar electrode. An excellent correlation between high-resolution CT density characteristics and impedance patterns was seen (r = 0.897). A correlation was also seen between CT patterns/impedance profiles and histologic features. Impedance values were also useful in predicting variation between predicted and actual needle trajectory, determining the proximity of normal structures to the probe tip and detecting loculations within cystic structures.

Paraneoplastic limbic encephalopathy with testicular carcinoma. A reversible neurologic syndrome.

Limbic encephalitis (encephalopathy) is a rare paraneoplastic syndrome which rarely responds to antineoplastic therapy. The authors report the first case of limbic encephalopathy associated with testicular carcinoma and the first histologically confirmed encephalopathy which responded to antineoplastic therapy of the associated neoplasm. The clinical and pathologic characteristics of paraneoplastic encephalopathies are discussed along with the potential for reversal of the neurologic process with effective antitumor therapy.

A hyperthermic syndrome in two subjects with acute hydrocephalus.

Although intracranial hypertension may cause autonomic disturbances, as well as alterations in the regulation of body temperature, an acute hyperthermic syndrome with autonomic disturbance as a consequence of hydrocephalus has not been described previously. Two subjects presented with such a syndrome, with each of several episodes of acute shunt failure and hydrocephalus. With correction of the hydrocephalus, the autonomic disturbances and fever immediately cleared. Observations from human and experimental studies suggest some potential mechanisms for the development of the syndrome. One of the subjects of this report was being treated with neuroleptics at the time of hospitalization; in him, and potentially in other similar patients, the syndrome could easily be confused with the neuroleptic malignant syndrome. The need for prompt appreciation of the correct diagnosis was emphasized by the rapid clearing of all neurological signs after correction of the shunt malfunction in both of these patients.

Treatment of intracranial human glioma xenografts with 131I-labeled anti-tenascin monoclonal antibody 81C6.

Lack of tumor specificity renders current modalities for treating malignant glioma ineffective. The administration of 131I-labeled monoclonal antibody (Mab) 81C6, which reacts with the glioma-associated extracellular matrix antigen, tenascin, to nude mice carrying s.c. human glioma xenografts has resulted in significant tumor growth delay and tumor regression. In this study, we evaluated the therapeutic efficacy of 131I-labeled 81C6 in athymic rats bearing intracranial human glioma xenografts, a more appropriate model for human gliomas. Mab 81C6, an IgG2b immunoglobulin, and an isotype-matched control Mab, 45.6, were labeled at 12.5-23.6 mCi/mg with chloramine-T. The Mabs were given i.v. at 1.25 and 2.5 mCi/animal for 131I-labeled 81C6, and 1.25 mCi for 131I-labeled 45.6 control. Therapeutic response was evaluated by survival prolongation using Wilcoxon rank sum analysis. Three experiments were done. No significant survival prolongation was found in the trial in which the average tumor size at the time of Mab administration was 60 +/- 14 mm3, two-thirds the size which causes animal death. In experiment 2, Mab was given at 16 +/- 14 mm3 average intracranial tumor volume. Statistically significant (P less than or equal to 0.005) survival prolongation was found for animals treated with 2.5 mCi 131I-labeled 81C6. In that experiment, male animals with intracranial xenografts had significantly shorter survival than females (P less than or equal to 0.005). When only female animals were used in the analysis, the 1.25-mCi 81C6 group also was found to have longer survival benefit (P less than or equal to 0.01). In the third experiment, only female animals were used and the tumor size at the initiation of treatment was 20 +/- 9 mm3. Highly significant survival prolongation again was found in both 1.25 (P = 0.001) and 2.5 mCi (P less than 0.001) 131I-labeled 81C6 groups. The estimated dose to intracranial tumors from 1.25 mCi of 131I-labeled Mab was 1585 rads for 81C6 and 168 rads for 45.6. Dose to other organs from 81C6 and 45.6 was similar, ranging between 31 rads to the brain and 734 rads to the bone marrow. However, normocellularity was observed in most marrow tissue examined microscopically. Three animals receiving the low dose (1.25 mCi 81C6) survived for more than 71 days with apparent cures. In conclusion, intracranial human glioma xenografts were treated successfully with 131I-labeled 81C6 but not control Mab.

Ependymomas: a clinicopathologic study.

Since 1924, when ependymomas were first classified as a distinctive glial neoplasm by Bailey, much has been published concerning these tumors, but there are important points of interest that are still not clear. In order to study more fully the clinical and pathologic characteristics of the ependymoma, we identified 62 patients with histologically proven neoplasms. Twenty-two were supratentorial, 21 were infratentorial, and 19 were intramedullary spinal cord tumors. These groups had mean ages of 17, 7, and 41 years, respectively, at the time of first symptoms. The presenting and accompanying symptoms were related to location and included headaches, nausea, visual changes, hemiparesis, and neck, back, and radicular pain. Neurological signs included papilledema, nystagmus, gait disturbance, cranial nerve palsies, altered mental status, paraparesis, and sensory dysfunction. Radiologic modalities of particular importance included computed tomography and myelography. Surgery and radiation therapy were the primary treatment modalities with median survival times from first symptoms being 92, 36, and 117 months for the above groups, respectively. Based on computer-generated survival curves, several characteristics significantly affected survival. These included tumor site, age, and neuraxis metastases. In patients with supratentorial tumors, cranial nerve palsies, microcystic changes, and mitotic figures were important, while in patients with infratentorial tumors, widened sutures, increased head circumference, age, epithelial features, and subependymal features significantly affected survival. Patients who had complete gross resection of a spinal cord tumor had no recurrences or mortality.

Therapeutic efficacy of antiglioma mesenchymal extracellular matrix 131I-radiolabeled murine monoclonal antibody in a human glioma xenograft model.

The development of Mabs, particularly those reactive with primary brain tumors but not with normal brain, provides a potential means of delivering therapeutic agents selectively to human malignant gliomas. Mab 81C6, an IgG2b immunoglobulin, which defines an epitope of the glioma-associated extracellular matrix protein tenascin, has been shown to bind to human glioma cell lines, glioma xenografts in nude mice, and primary human gliomas, but not to normal adult or fetal brain. To test the therapeutic potential of this Mab for targeted delivery of isotopes, nude mice bearing progressively growing s.c. xenografts of D-54 MG, a human glioma cell line, were given injections via the tail vein of either buffer, unlabeled 81C6, 131I-labeled 81C6, or 131I-labeled 45.6, a nonspecific control Mab of the same isotype. Specific activities of the Mab range from 6.0 to 15.5 mCi/mg with protein doses from 7.6 to 167 micrograms. The doses given by injection per animal for labeled 81C6 were 50, 250, 500, and 1000 mu Ci and 500 and 1000 mu Ci for 45.6. Tumor response was measured by growth delay in reaching 1000 or 5000 mm3 tumor volumes using the Wilcoxon rank sum test, and by comparing the proportion of tumors that had regression in volume after treatment using the Fisher exact test. Statistically significant growth delays at 1000 mm3 were noted in 1 of 3 experiments with 500 mu Ci 81C6 (P less than 0.001) and 2 of 3 for 1000 mu Ci 81C6 (P = 0.001 and less than 0.001). At 5000 mm3, statistically significant growth delays were seen with radiolabeled 81C6 in 2 of 2 experiments at 250 mu Ci (P = 0.01 and 0.02), 4 of 4 at 500 mu Ci (P = 0.03-less than 0.001), and 2 of 2 at 1000 mu Ci (P = less than or equal to 0.001) and with radiolabeled 45.6 in 1 of 1 at 1000 mu Ci (P = 0.01). The percentage of animals with tumor regression progressively increased with increasing doses of isotope. For radiolabeled 45.6, there were 0 of 10 regressors at 500 and 1 of 10 at 1000 mu Ci. For radiolabeled 81C6, there were 0 of 6 regressors at 50 mu Ci, 1 of 16 (6%) at 250 mu Ci, 7 of 38 (18%) at 500, and 15 of 28 (54%) at 1000 mu Ci. Statistically significant tumor regression was seen only at doses of 500 and 1000 mu Ci of 131I-81C6.(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluation of memory and language function pre- and postthalamotomy with an attempt to define those patients at risk for postoperative dysfunction.

Memory and language dysfunction has been sporadically reported following stereotaxic thalamotomies. In order to determine which patients are at greatest risk and to better define the nature of this dysfunction, we have prospectively evaluated 18 patients undergoing stereotaxic thalamotomies for movement disorders (MDs). Patients were evaluated clinically, with computed tomography (CT) and with memory and language protocols (MLPs) pre- and postoperatively. Patients exhibiting postoperative deficits were again evaluated with the MLP on follow-up visits to the clinic. Significant changes in memory and language function occurred in 7 out of 18 patients. These 7 patients had diverse etiologies for their MDs. Five of the 18 patients had undergone previous thalamotomies on the contralateral side. Three of these 5 patients with bilateral thalamotomies experienced postoperative functional impairments in memory and language while only 4 of 13 patients with a unilateral thalamotomy experienced these problems. The postoperative functional impairments noted were primarily those requiring orientation and speech. All patients with postoperative memory and language impairments were again evaluated with MLPs months after the operation. In 3 of 7 patients, no improvement was noted, while the remaining 4 did recover to baseline. More severe deficits tended to occur in those patients with ventriculomegaly or evidence of other major cerebral tissue loss by preoperative CT scan and in those patients with lower MLP scores preoperatively. Postoperative memory and language dysfunction was not correlated with the number or size of the lesions made, the postoperative general neurologic examination or CT scans, or the clinical response of the MDs. From our data, it appears that patients with more profound neurologic compromise and/or bilateral involvement as evidenced by poor performance on the MLP, tissue loss on CT scanning, or previous thalamic lesion, are most at risk for memory and language dysfunction postoperatively. However, this dysfunction is not necessarily permanent. Preoperative evaluation with MLPs and CT scanning appear to be of value in predicting those patients at greatest risk for postoperative and language dysfunction.

The localisation of radiolabelled murine monoclonal antibody 81C6 and its Fab fragment in human glioma xenografts in athymic mice.

The localisation of the radioiodinated Fab fragment of monoclonal antibody (Mab) 81C6, reactive with a glioma-associated extracellular matrix antigen, was studied in athymic mice bearing subcutaneous and intracranial xenografts of D-54 MG glioma cells. In vitro 81C6 Fab showed a marked loss of immunoreactivity and affinity for antigen compared to intact Mab 81C6. In vivo, the plasma half-life of 81C6 Fab was 7.0 hours compared to 2.1 days for 81C6. 81C6 Fab levels in tumours peaked at 2.6-3.8% injected dose/g in 2-6 h; Mab 81C6 reached 33.9% dose/g at 48 h. Localisation indices and tumour:tissue ratios were superior for Mab 81C6. Estimated radiation doses to tumour and normal tissues were lower for 131I-81C6 Fab than 131I-81C6. To realise the theoretical benefits of fragments as localising agents, Fab fragments of higher immunoreactivity and affinity, or bivalent F(ab')2 fragments are required.

The role of monopolar stimulation during computed-tomography-guided stereotactic biopsies.

44 patients underwent intraoperative stimulation with a monopolar electrode prior to computed tomography (CT)-guided stereotactic biopsy. Stimulation at 2-100 Hz resulted in functional responses in 6/21 patients with subcortical or callosal lesions, 4/6 with basal ganglion lesions, 8/10 with thalamic and 4/4 with brainstem lesions. In all but 2 patients with mesencephalic lesions, where limited biopsy sites were available, an alternative biopsy site was used if a functional response was obtained. No morbidity was seen among these patients, although postbiopsy CT scans demonstrated small 3- to 7-mm hematomas in 5/11 patients. Retrospective review of 79 patients who underwent biopsies without stimulation demonstrated hematomas in 6/10 patients and a 3.3% transient surgical morbidity. These data indicate that postbiopsy hematomas are a relatively common occurrence, that intraoperative electrical stimulation within abnormal lesions can identify functional potential, and that avoidance of biopsies within these functional areas may be associated with reduced morbidity.

Impedance measurements of the spinal cord of man and animals.

The measurement of electrical impedance of normal and pathologic tissue has not been fully utilized in neurosurgery. This is a report of electrical impedance measurement in the central nervous system of both man and animals. We show the results of the laboratory study done in animals, in the brain and in the spinal cord as well. Also we show the clinical experience of the impedance recordings in the DREZ procedure for some chronic pain conditions, correlating the measurements at the time of the operation with normal conditions, with comments about the findings.

The use of computed tomography-guided stereotactic techniques in the treatment of brain stem abscesses.

A case of a brain stem abscess that was successfully treated using CT guided stereotaxy together with antibiotic therapy is presented. The literature is reviewed and the role of stereotaxy in the treatment of brain stem abscess is discussed.

The autonomic dysfunction syndrome: aetiology and treatment.

Nine patients with autonomic dysfunction syndrome (ADS) characterised by sympathetic discharge and extensor posturing are presented. Morphine was given to three patients and in all cases consistently stopped the episodes. Dantrolene was given to one patient and reduced the severity of the extensor posturing without affecting the other components of the ADS. Bromocriptine was given to three patients and appeared to have both short- and long-term effects. Acutely, the drug partially corrected the hyperthermia and diaphoresis associated with these episodes. Two patients were given bromocriptine long-term. In one patient, the ADS was completely controlled and in the other, the frequency of the episodes decreased. The autonomic dysfunction syndrome appears to be related to both severe closed head injury and acute hydrocephalus. The clinical similarity of the two diverse etiologic groups and the absence of precipitating increased ICP in the former suggests the common theme is a release of the brain stem from higher control. The responses to morphine and bromocriptine suggest that the opiate and dopaminergic pathways play roles in the entity.