Lack of efficacy of levetiracetam in oromandibular and cranial dystonia.

OBJECTIVE: To determine the efficacy of levetiracetam in oromandibular or cranial dystonia. METHODS: We recruited seven subjects with oromandibular or cranial dystonia. Five completed the study, median age was 71 years (range 42-79 years), median disease duration was 12 years (range 2-30 years). Participants were randomized to receive levetiracetam or placebo and were then crossed over. They titrated up to a total daily dose of 4000 mg or the maximum tolerated dose over 3 weeks and maintained that dose for another 3 weeks. The primary endpoint was the percent change of the eyes, mouth, speech, and swallowing Burke-Fahn-Marsden (BFM) subscores from baseline to weeks 6 and 14. Additional endpoints included the BFM subscore at weeks 3 and 11, and the global dystonia severity (GDS) subscore at weeks 3, 6, 11, and 14, as well as all adverse side effects. RESULTS: The mean percent increase in the BFM subscore (placebo: 31.25%, levetiracetam: 12.16%) was not significantly different between the two arms according to the Friedman analysis. The Wilcoxon signed-rank test showed that these percent changes were not significant, indicating that there was no statistical clinical worsening in either arm. The mean percent change of the BFM subscore at weeks 3 and 11 and the mean percent change of the GDS subscore at weeks 3, 6, 11, and 14 were not significantly different between the two arms, and the Wilcoxon signed-rank test did not show statistical significance. CONCLUSION: Levetiracetam does not appear to be efficacious in patients with oromandibular or cranial dystonia.

Disk-caused nerve compression in patients with acute low-back pain: diagnosis with MR, CT myelography, and plain CT.

Ninety-five patients with acute low-back and radicular pain underwent magnetic resonance (MR) imaging and either plain computed tomography (CT) (n = 32) or CT myelography (n = 63) for diagnosis of herniated nucleus pulposus-caused nerve compression (HNPNC). Patients were followed up for at least 6-12 months. Fifty-six patients underwent surgery, and 39 received conservative treatment. Receiver operating characteristic (ROC) analysis was performed on correlation of results of blinded image reading with "true" diagnoses determined by an expert panel [corrected]. Results in subgroup analysis for ROC curve areas were MR, 0.84, versus plain CT, 0.86; MR, 0.81, versus CT myelography, 0.83; and MR, 0.82, versus findings with both CT techniques, 0.85. Results indicate no statistically significant difference in diagnostic accuracy of HNPNC among the three modalities. Thus, factors of cost, radiation dose, and invasiveness influence selection of modality. On the basis of accuracy findings, the authors suggest that MR should replace CT myelography because of the invasiveness of myelography but that MR should not replace plain CT because plain CT is equally accurate and much less costly.

Two forms of DNA polymerase delta from mouse cells. Purification and properties.

A procedure is described for the purification from cultured mouse cells of two DNA polymerase "delta-like" enzymes, as defined by intrinsic 3'-exonuclease activity, inhibition by aphidicolin, and relative insensitivity to N2-(p-n-butylphenyl)-dGTP. One of the two enzymes has been purified to near homogeneity and, similar to the DNA polymerase delta from calf thymus described by Lee et al. (Lee, M. Y. W. T., Tan, C. K., Downey, K. M., and So, A. G. (1984) Biochemistry 23, 1906-1913), it has a total molecular mass of 178 kDa (from sedimentation velocity of 8.0 S and Stokes radius of 54 A) and is composed of one each of 125- and 50-kDa polypeptides. It also resembles the DNA polymerase delta of Lee et al. in being stimulated by proliferating cell nuclear antigen (PCNA). It is the first clear structural and functional counterpart of the calf thymus enzyme. The major difference between the mouse DNA polymerase delta and the calf thymus enzyme of Lee et al. is that, under specific conditions, the mouse enzyme is active with poly(dA).oligo(dT) in the absence of PCNA, whereas the activity of the calf thymus enzyme with this template is reported to be completely dependent on PCNA. The reason for this difference is not known at this time. The second mouse cell enzyme has a molecular mass of 112 kDa (from sedimentation velocity of 6.3 S and Stokes radius of 43.0 A) and consists of a single polypeptide of 123-125 kDa in denaturing gels (p125). On the basis of its apparent formation by dissociation of DNA polymerase delta, and multiple similarities with DNA polymerase delta in enzymatic properties, the p125 is provisionally identified as the 125-kDa polypeptide of DNA polymerase delta. The p125 does not respond to PCNA, suggesting that the 50-kDa polypeptide is required for the stimulation of DNA polymerase delta by PCNA. The presence of the p125 in cell extracts would explain reports that DNA polymerase delta consists of a single polypeptide of approximately 125 kDa and/or thast it has a smaller molecular mass than DNA polymerase delta of Lee et al. and is not affected by PCNA (this does not apply to PCNA-independent DNA polymerase delta-like enzymes with higher molecular mass than the polymerase delta of Lee et al., which have recently been named DNA polymerases epsilon).

Clinical and roentgenographic evaluation of bipolar prostheses with noncemented anatomic medullary locking femoral stems.

Fifty-six DePuy anatomic medullary locking femoral bipolar prostheses were reviewed clinically and roentgenographically in 50 patients at an average follow-up period of 30 months (range, 24-71 months). Forty-four of the implantations were in 40 male and 12 were in ten female patients. Forty-five devices were placed in primary operations, while 11 were used in revisions. The overall average age was 53.5 years. The average Harris hip scores for the primary bipolars were 29.8 preoperative and 77.3 postoperative, while the revision bipolars had Harris hip scores of 35.9 preoperative and 75.1 postoperative. Nearly one-half (47%) of all primary and 54% of the revision patients experienced pain to some degree on ambulation. Roentgenographically, all femoral components appeared to be well fixed biologically. Roentgenographic changes occurred with time in both primary and revision prostheses. On roentgenographic zonal analysis of primary prostheses, radiolucencies greater than 1 mm were present most frequently in the most proximal lateral zone and at the distal tip of the prosthesis. Although the use of noncemented bipolar prostheses generally shows acceptable clinical results, noncemented fixed acetabular components with noncemented femoral components produce a more satisfactory clinical result.

Open reduction and internal fixation of delayed union and nonunion of the distal humerus.

Nonunion of a condylar fracture of the distal humerus rarely occurs, but when present it is difficult to manage. We recommend internal fixation of the nonunion in combination with decortication and autogenous iliac crest bone grafting along with careful selection and placement of the implant. Postoperatively, the goal is preservation of elbow motion until the nonunion heals. We reviewed the cases of five patients who had surgery for nonunion of this fracture, all of which healed within 2-3 months after surgery. At final follow-up their average arc of motion was 88 degrees.

Experimental and human brain neoplasms: detection with in vivo sodium MR imaging.

Elevations of intracellular sodium concentration have been observed in rapidly proliferating cells and malignant neoplasms. Sodium magnetic resonance (MR) imaging (with repetition times of 133 msec and echo times of 13, 26, 39, and 42 msec) was performed in ten patients and three dogs with central nervous system neoplasms. In all instances the neoplasms were associated with an increased sodium signal compared with that of normal brain. Unfortunately, the available echo times did not enable discrimination of intracellular sodium from extracellular sodium, which was present in high concentrations in adjacent vasogenic edema fluid. Further study is necessary to establish the utility of sodium MR imaging for the investigation of malignant neoplasms.

Cerebellopontine angle-petromastoid mass lesions: comparative study of diagnosis with MR imaging and CT.

Capabilities of computed tomography (CT) and magnetic resonance (MR) imaging in the diagnosis of cerebellopontine angle-petromastoid (CPA-PM) lesions were compared in 75 patients. CT and MR demonstrated 95.8% and 98.7% of the lesions, respectively. MR was often more helpful for characterization of neuromas, epidermoid cysts, exophytic gliomas, and vascular lesions, while CT was usually more informative for meningiomas, metastases, and tympanomastoid cholesteatomas. A specific diagnosis could be made with MR for most types of lesions through use of relaxation parameters and characteristic morphologic changes. Size, shape, location, and contour of the lesions, however, were generally more helpful for differential diagnosis than relaxation times. With the exception of metastatic lesions, cholesteatomas, and some meningiomas, MR was usually more helpful than CT in defining the full extent of the lesions and their relationships to contiguous structures. MR, because of its high accuracy in lesion detection, characterization, and localization, is a suitable primary diagnostic modality for evaluating patients with suspected CPA-PM lesions.

Clinical and experimental vasogenic edema: in vivo sodium MR imaging. Work in progress.

To investigate the sodium magnetic resonance (MR) imaging characteristics of acute vasogenic edema, an experimental canine model was developed. Vasogenic edema was produced in the hemisphere of the dogs by the intraarterial infusion of hypertonic mannitol (25%). This solution opens the blood-brain barrier, allowing the influx of water, electrolytes, and proteins into the brain. The main advantage of this model over the established "cold injury" model is the lack of associated brain necrosis. Two patients with chronic vasogenic edema secondary to well-circumscribed meningiomas also underwent MR imaging. The sodium signal was markedly elevated in both clinical and experimental studies of vasogenic edema fluid compared with signal in healthy brain tissue. Extracellular sodium associated with vasogenic edema displayed MR imaging characteristics similar to that of sodium in serum. There was a trend toward a shortened T2 in edema fluid secondary to the presence of serum macromolecules.

Iotrol versus metrizamide in lumbar myelography: a double-blind study.

In a prospective, randomized, double-blind study, 49 patients underwent lumbar myelography using iotrol (24 patients) or metrizamide (25 patients). The diagnostic imaging adequacy of iotrol was comparable with that of metrizamide. After iotrol myelography, adverse reactions were fewer, less severe, and of shorter duration than were those following metrizamide myelography. Thirteen of 24 patients (54%) receiving iotrol reported some adverse reactions compared with 24 of 25 patients (96%) receiving metrizamide. Five moderate and one severe adverse reaction occurred in the group receiving iotrol. Fourteen moderate and eight severe adverse reactions occurred in the group receiving metrizamide. Thirty-eight patients underwent electroencephalography both before and after myelography (19 iotrol and 19 metrizamide). None of the EEGs obtained after iotrol myelography changed from baseline, while seven of the EEGs obtained after metrizamide myelography showed changes from baseline. Iotrol was judged superior to metrizamide as a contrast medium in this patient population.

Clivus epidural hematoma: a case report.

An acute traumatic epidural hematoma extending from the odontoid process to the dorsum sella is described. The mechanism for the formation of an extradural hematoma in this unusual location seems to be related to age and a severe hyperflexion injury.

The spectrum of multiple sclerosis lesions using a multiple spin echo pulse sequence and a high field strength.

Seventy-one patients having clinical laboratory findings consistent with multiple sclerosis (MS) were imaged with a 1.5 tesla MR instrument using multiple spin echo sequences (TR = 2,000 ms and TE = 30, 60, 90, 120 ms). Multiple spin echo is a sensitive method for detecting MS lesions. Sixty-seven patients (94%) demonstrated lesions consistent with MS. With the exception of those located in the cortex, optic nerve and chiasm the lesions detected correlated with pathologic data. Lesions of the cerebral hemispheres, corpus callosum and cerebellum were generally multiple while lesions of the brain stem and optic tracts were generally singular. The majority of the lesions were associated with the white matter tracts of the cerebral hemispheres and brain stem.

Iohexol for cervical myelography via C1-C2 puncture: study of efficacy and adverse reactions.

Cervical myelography with iohexol via C1-C2 puncture was performed in 30 patients in two medical centers using a concentration of 240 mg l/ml. The study demonstrated iohexol to be a safe contrast medium without significant changes in neurologic and physical examination, vital signs, electrocardiogram, or hematologic or blood chemistry parameters. Fifteen patients had electroencephalograms (EEGs); two were abnormal. In one patient the baseline EEG demonstrated nonspecific slow waves in the temporal regions bilaterally that remained unchanged after myelography. In the second patient, transient changes in the left hemisphere during either hyperventilation or photic stimulation on postmyelographic EEG had not been present on the baseline recording. The relation of these changes to the drug remains unclear. Iohexol was found to be an efficacious myelographic contrast agent, with good to excellent myelograms in 93% of cases. Headache occurred in 13% and nausea in 3%.

Chymopapain chemonucleolysis: correlation of diagnostic radiographic factors and clinical outcome.

The therapeutic response to treatment of lumbar disk herniation with chymopapain chemonucleolysis is significantly influenced by the criteria used for patient selection. Although careful clinical selection of patients reduces the frequency of treatment failure, some patients do not achieve satisfactory relief of pain with chemonucleolysis. In an attempt to identify objective pretreatment radiographic findings that might refine selection criteria and further reduce the failure rate of chemonucleolysis, a retrospective correlation of pretreatment radiographs and clinical responses was made of 200 consecutive chemonucleolysis patients. Marked improvement in sciatica occurred in 79.9% and 79.3% of patients at early and late follow-up, respectively. There was a significantly higher response rate, however, in patients who had definite radiographic evidence of focal disk herniation and in those patients with definite radiographic evidence of nerve-root compression (marked nerve-root deviation, nerve-root flattening or edema, root-sleeve amputation) by disk material. Those patients with a preinjection disk height greater than the mean had a slightly better response rate (91.1%) than those whose disk height was smaller than the mean (80.0%). Most cases of treatment failure could be attributed to an incorrect radiographic diagnosis, treatment of patients with equivocal diagnostic studies, the presence of "free" disk fragments, and causes of nerve-root compression unresponsive to chymopapain.

Chymopapain chemonucleolysis: CT changes after treatment.

Chymopapain chemonucleolysis is now used extensively in this country to treat lumbar disk herniation. Despite increasing experience in patient selection, there continue to be patients who do not respond to treatment and require diagnostic reevaluation. Interpretation of postchemonucleolysis computed tomographic (CT) scans in these patients requires a knowledge of the CT changes that normally occur after treatment with chemonucleolysis. To define these temporal changes, a prospective CT evaluation was performed of 29 treated interspaces in 26 patients who returned for routine postchemonucleolysis follow-up. Despite a successful clinical response in 17 of 21 patients, changes in the size, location, shape, homogeneity, and density of the disk herniation were uncommon at the 6 week follow-up. In 24 treated interspaces, the most common changes at 6 week CT follow-up were the development of vacuum phenomenon in three (12.5%) and a slight decrease in the size of two (8.3%) disk herniations. A successful response was noted in 17 of 21 patients scanned at 6 month follow-up, with five (22.7%) of 22 injected interspaces exhibiting vacuum phenomenon and 13 (59.1%) interspaces showing an observable decrease in the size of the disk herniation. Early improvement of sciatica after chemonucleolysis often occurs without a change in the size of the disk herniation and may be mediated by chymopapain-induced disk-space narrowing. Continued improvement may be accompanied by both a decrease in the disk height and a reduction in the size of the disk protrusion.