Neurological and spinal manifestations of the Ehlers-Danlos syndromes.

The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin extensibility, and tissue fragility. This communication briefly reports upon the neurological manifestations that arise including the weakness of the ligaments of the craniocervical junction and spine, early disc degeneration, and the weakness of the epineurium and perineurium surrounding peripheral nerves. Entrapment, deformation, and biophysical deformative stresses exerted upon the nervous system may alter gene expression, neuronal function and phenotypic expression. This report also discusses increased prevalence of migraine, idiopathic intracranial hypertension, Tarlov cysts, tethered cord syndrome, and dystonia, where associations with EDS have been anecdotally reported, but where epidemiological evidence is not yet available. Chiari Malformation Type I (CMI) has been reported to be a comorbid condition to EDS, and may be complicated by craniocervical instability or basilar invagination. Motor delay, headache, and quadriparesis have been attributed to ligamentous laxity and instability at the atlanto-occipital and atlantoaxial joints, which may complicate all forms of EDS. Discopathy and early degenerative spondylotic disease manifest by spinal segmental instability and kyphosis, rendering EDS patients prone to mechanical pain, and myelopathy. Musculoskeletal pain starts early, is chronic and debilitating, and the neuromuscular disease of EDS manifests symptomatically with weakness, myalgia, easy fatigability, limited walking, reduction of vibration sense, and mild impairment of mobility and daily activities. Consensus criteria and clinical practice guidelines, based upon stronger epidemiological and pathophysiological evidence, are needed to refine diagnosis and treatment of the various neurological and spinal manifestations of EDS. © 2017 Wiley Periodicals, Inc.

Microsurgical treatment of sacral perineural (Tarlov) cysts: case series and review of the literature.

OBJECTIVE Tarlov cysts (TCs) occur most commonly on extradural components of the sacral and coccygeal nerve roots. These lesions are often found incidentally, with an estimated prevalence of 4%-9%. Given the low estimated rates of symptomatic TC and the fact that symptoms can overlap with other common causes of low-back pain, optimal management of this entity is a matter of ongoing debate. Here, the authors investigate the effects of surgical intervention on symptomatic TCs and aim to solidify the surgical criteria for this disease process. METHODS The authors performed a retrospective review of data from consecutive patients who were surgically treated for symptomatic TCs from September 2011 to March 2013. Clinical evaluations and results from surveying pain and overall health were used. Univariate statistical analyses were performed. RESULTS Twenty-three adults (4 males, 19 females) who had been symptomatic for a mean of 47.4 months were treated with laminectomy, microsurgical exposure and/or imbrication, and paraspinous muscle flap closure. Eighteen patients (78.3%) had undergone prior interventions without sustained improvement. Thirteen patients (56.5%) underwent lumbar drainage for an average of 8.7 days following surgery. The mean follow-up was 14.4 months. Univariate analyses demonstrated that an advanced age (p = 0.045), the number of noted perineural cysts on preoperative imaging (p = 0.02), and the duration of preoperative symptoms (p = 0.03) were associated with a poor postoperative outcome. Although 47.8% of the patients were able to return to normal activities, 93.8% of those surveyed reported that they would undergo the operation again if given the choice. CONCLUSIONS This is one of the largest published studies on patients with TCs treated microsurgically. The data suggest that patients with symptomatic TCs may benefit from open microsurgical treatment. Although outcomes seem related to patient age, duration of symptoms, and extent of disease demonstrated on imaging, further study is warranted and underway.

Prevention of percutaneous spinal cord stimulation electrode migration: a 15-year experience.

OBJECTIVES: Percutaneous spinal cord stimulation electrodes have a propensity to migrate longitudinally, which is a costly complication that often compromises therapeutic effect. After implementing simple changes to our percutaneous electrode anchoring technique, we no longer encounter this migration. The current retrospective study updates previously reported results. MATERIALS AND METHODS: We retrospectively examined data in a consecutive series of patients in whom we had secured a new percutaneous electrode by injecting < 0.1 cm(3) of adhesive into the silicone elastomer lead anchor. From 1998 through 2006, we used whichever anchor was supplied with each lead until we observed one case of migration through a short anchor; thereafter, we used a long, tapered anchor exclusively. From 2007 through 2013, we further modified our technique by adding a fascial incision to accommodate the tip of the anchor and by increasing the strength of our suture material. RESULTS: In the first series of 291 patients, followed through July 2007 (mean 4.75 years, range 1.1-9.0 years), 4 (1.37%) experienced electrode migration requiring surgical revision. Only one lead had moved with respect to its anchor; the other three anchors remained securely bonded to their leads. No migration (0.00%) occurred in the second series of 142 patients, followed through 2013 (mean follow-up 2.86 years, range 0.10-5.45 years). CONCLUSION: Improvements to our simple, inexpensive technique apparently have eliminated the most common complication of spinal cord stimulation.

Off-label use of drugs and devices: role of medical professionals in the establishment of parameters for their use.

UNLABELLED: Physicians may use approved drugs and devices in ways not approved by the US Food and Drug Administration, a process termed off-label use. Often, because there is not suitable data defining safety and efficacy, the results of such use may become problematic, as occurred with the off-label use by spine surgeons of bone morphogenetic proteins in anterior cervical fusions. Using this undesirable history of bone morphogenetic proteins, and the historical record of the introduction of another drug, chymopapain, a method is developed and presented whereby such drugs or devices in the future may be studied by the professional medical specialties themselves outside the New Drug Application process, but with appropriate input from government and industry. ABBREVIATIONS: : AANS, American Association of Neurological SurgeonsACDF, anterior cervical discectomy and fusionACF, anterior cervical fusionBMP, bone morphogenetic proteinCNS, Congress of Neurological SurgeonsDJDD, degenerative joint and disc diseaseFDA, US Food and Drug Administration.

Tarlov cysts: an overlooked clinical problem.

Symptomatic Tarlov cysts typically cause chronic pelvic and lower extremity pain and sacral nerve root radiculopathy. Historically, open surgical treatment involved significant patient morbidity, particularly postoperative cerebrospinal fluid (CSF) leaks and infection. These CSF leaks often required multiple surgical procedures to seal. Over the past 20 years, there have been two or three isolated case reports of computed tomography (CT)-guided needle aspirations that offered limited evidence of treatment efficacy and safety. Some have reported high rates of postprocedure aseptic meningitis that were not well explained. These poor results dissuaded physicians from caring for these patients. As a group these patients are usually treated dismissively and told their cysts are asymptomatic and their pain must be coming from somewhere else. Many of them have had an unnecessary discectomy or a spinal fusion, and when these procedures did not relieve their pain they were told they are a "failed back patient." We have treated more than a hundred patients with symptomatic Tarlov cysts by CT fluoroscopic-guided needle aspiration and fibrin injection and have had excellent results with no meaningful complications and never a case of aseptic meningitis. We believe this is a safe, highly effective first-line treatment for symptomatic Tarlov cysts.

Perioperative and long-term outcomes from the management of parasagittal meningiomas invading the superior sagittal sinus.

BACKGROUND: Parasagittal meningiomas invading the superior sagittal sinus (SSS) pose formidable obstacles to surgical management. Invasion is often considered a contraindication to surgery because of associated morbidity, such as cerebral venous thrombosis. OBJECTIVE: We report our most recent experience with the resection of parasagittal meningiomas invading the SSS. METHODS: Between 1992 and 2004, 110 patients with parasagittal meningiomas underwent surgery at the Johns Hopkins Medical Institutions. Clinical charts, radiological studies, pathological features, and operative notes were retrospectively analyzed; only those patients with minimum 24 months follow-up (n = 61) were further studied. RESULTS: Tumor distribution by location along the SSS was: 21% anterior, 62% middle, and 17% posterior. All patients were managed with initial surgical resection with radiosurgery for residual/recurrent disease if indicated (19.6%). Pathological examination revealed 80% grade I meningiomas, 13% grade II meningiomas, and 7% grade III meningiomas. Simpson grade I/II resection was achieved in 81% of patients. Major complications included venous thrombosis/infarction (7%), intraoperative air embolism (1.5%), and death (1.5%); long-term outcomes assessed included recurrence (11%) and improvement in Karnofsky Performance Score (85%). CONCLUSION: On the basis of our study, the incidence of postoperative venous sinus thrombosis is 7% in the setting of a recurrence rate of 11% with a mean follow-up of 41 months. In comparison with the published literature, the data corroborate the rationale for our treatment paradigm; lesions invading the sinus can initially be resected to the greatest extent possible without excessive manipulation of vascular structures, whereas residual/recurrent disease can be observed and managed with radiosurgery.

Competency-based medical education: theory to practice.

Although competency-based medical education (CBME) has attracted renewed interest in recent years among educators and policy-makers in the health care professions, there is little agreement on many aspects of this paradigm. We convened a unique partnership - the International CBME Collaborators - to examine conceptual issues and current debates in CBME. We engaged in a multi-stage group process and held a consensus conference with the aim of reviewing the scholarly literature of competency-based medical education, identifying controversies in need of clarification, proposing definitions and concepts that could be useful to educators across many jurisdictions, and exploring future directions for this approach to preparing health professionals. In this paper, we describe the evolution of CBME from the outcomes movement in the 20th century to a renewed approach that, focused on accountability and curricular outcomes and organized around competencies, promotes greater learner-centredness and de-emphasizes time-based curricular design. In this paradigm, competence and related terms are redefined to emphasize their multi-dimensional, dynamic, developmental, and contextual nature. CBME therefore has significant implications for the planning of medical curricula and will have an important impact in reshaping the enterprise of medical education. We elaborate on this emerging CBME approach and its related concepts, and invite medical educators everywhere to enter into further dialogue about the promise and the potential perils of competency-based medical curricula for the 21st century.

The role of assessment in competency-based medical education.

Competency-based medical education (CBME), by definition, necessitates a robust and multifaceted assessment system. Assessment and the judgments or evaluations that arise from it are important at the level of the trainee, the program, and the public. When designing an assessment system for CBME, medical education leaders must attend to the context of the multiple settings where clinical training occurs. CBME further requires assessment processes that are more continuous and frequent, criterion-based, developmental, work-based where possible, use assessment methods and tools that meet minimum requirements for quality, use both quantitative and qualitative measures and methods, and involve the wisdom of group process in making judgments about trainee progress. Like all changes in medical education, CBME is a work in progress. Given the importance of assessment and evaluation for CBME, the medical education community will need more collaborative research to address several major challenges in assessment, including "best practices" in the context of systems and institutional culture and how to best to train faculty to be better evaluators. Finally, we must remember that expertise, not competence, is the ultimate goal. CBME does not end with graduation from a training program, but should represent a career that includes ongoing assessment.

Long-term back pain after a single-level discectomy for radiculopathy: incidence and health care cost analysis.

OBJECT: The most common spinal procedure performed in the US is lumbar discectomy for disc herniation. Longterm disc degeneration and height loss occur in many patients after lumbar discectomy. The incidence of mechanical back pain following discectomy varies widely in the literature, and its associated health care costs are unknown. The authors set out to determine the incidence of and the health care costs associated with mechanical back pain attributed to segmental degeneration or instability at the level of a prior discectomy performed at their institution. METHODS: The authors retrospectively reviewed the data for 111 patients who underwent primary, single-level lumbar hemilaminotomy and discectomy for radiculopathy. All diagnostic modalities, conservative therapies, and operative treatments used for the management of postdisectomy back pain were recorded. Institutional billing and accounting records were reviewed to determine the billed costs of all diagnostic and therapeutic measures. RESULTS: At a mean follow-up of 37.3 months after primary discectomy, 75 patients (68%) experienced minimal to no back pain, 26 (23%) had moderate back pain requiring conservative treatment only, and 10 (9%) suffered severe back pain that required a subsequent fusion surgery at the site of the primary discectomy. The mean cost per patient for conservative treatment alone was $4696. The mean cost per patient for operative treatment was $42,554. The estimated cost of treatment for mechanical back pain associated with postoperative same-level degeneration or instability was $493,383 per 100 cases of first-time, single-level lumbar discectomy ($4934 per primary discectomy). CONCLUSIONS: Postoperative mechanical back pain associated with same-level degeneration is not uncommon in patients undergoing single-level lumbar discectomy and is associated with substantial health care costs.

Recurrent lumbar disc herniation after single-level lumbar discectomy: incidence and health care cost analysis.

OBJECTIVE: Same-level recurrent lumbar disc herniation complicates outcomes after primary discectomy in a subset of patients. The health care costs associated with the management of this complication are currently unknown. We set out to identify the incidence and health care cost of same-level recurrent disc herniation after single-level lumbar discectomy at our institution. METHODS: We retrospectively reviewed 156 consecutive patients undergoing primary single-level lumbar discectomy at one institution. The incidence of symptomatic same-level recurrent disc herniation either responding to conservative therapy or requiring revision discectomy was assessed. Institutional billing and accounting records were reviewed to determine the billing costs of all diagnostic and therapeutic measures used for patients experiencing recurrent disc herniation. RESULTS: Twelve months after surgery, 141 patients were available for follow-up. Of these patients, 124 (88%) were symptom free or had minimal symptoms not affecting their daily activity. Radiographically proven symptomatic same-level recurrent disc herniation developed in 17 patients (12%) a median of 8 months after primary discectomy. Eleven patients (7%) required revision surgery, whereas 6 (3.9%) responded to conservative therapy alone. Diagnosis and management of recurrent disc herniation were associated with a mean cost of $26,593 per patient, and the mean cost was markedly less for patients responding to conservative treatment ($2315) compared with those requiring revision surgery ($39,836) (P < 0.001). Of 141 primary lumbar discectomies performed at our institution with the patients followed for 1 year, the total cost associated with the management of subsequent recurrent disc herniation was $452,083 ($289,797 per 100 primary discectomies). CONCLUSION: In our experience, recurrent lumbar disc herniation occurred in more than 10% of patients and was associated with substantial health care costs. Development of novel techniques to prevent recurrent lumbar disc herniation is warranted to decrease the health care costs and morbidity associated with this complication. Prolonged conservative management should be attempted when possible to reduce the health care costs of this complication.

Genesis of the use of corticosteroids in the treatment and prevention of brain edema.

BACKGROUND: Since the groundbreaking article from the University of Minnesota in 1961 by Drs. Galicich, French, and Melby describing the use of dexamethasone for peritumoral cerebral edema, the use of corticosteroids in patients with brain tumors has become routine. Unfortunately, little has been reported regarding the environment that fostered arguably the greatest translational research contribution in the history of neurosurgery. METHODS: During a pilot study to assess corticosteroid uptake in brain tumors, Dr. Galicich observed that patients given a large dose of corticosteroids just before craniotomy had a relatively benign postoperative course. This led, in October 1959, to the administration of high-dose corticosteroids to a patient with a large recurrent glioblastoma who was semicomatose and severely hemiparetic. The results were dramatic, with almost complete resolution of neurological deficit during a period of several days and marked reduction of midline shift on repeat angiograms. This finding prompted the studies that confirmed the efficacy of high-dose corticosteroids in reducing peritumoral brain edema in humans reported in the 1961 article. RESULTS: After publication, a revolution in brain tumor management occurred because corticosteroid therapy markedly reduced the morbidity and mortality associated with brain tumors both in the United States and worldwide. CONCLUSION: The combination of astute clinical observation and follow up by rigorous clinical research at the University of Minnesota resulted in one of the greatest contributions in the history of neurosurgery, rivaled only by the operative microscope in its effect on morbidity, and unsurpassed in reduction of mortality.

Laminar screw fixation of the axis.

OBJECT: Laminar fixation of the axis with crossing bilateral screws has been shown to provide rigid fixation with a theoretically decreased risk of vertebral artery damage compared with C1-2 transarticular screw fixation and C-2 pedicle screw fixation. Some studies, however, have shown restricted rigidity of such screws compared with C-2 pedicle screws, and others note that anatomical variability exists within the posterior elements of the axis that may have an impact on successful placement. To elucidate the clinical impact of such screws, the authors report their experience in placing C-2 laminar screws in adult patients over a 2-year period, with emphasis on clinical outcome and technical placement. METHODS: Sixteen adult patients with cervical instability underwent posterior cervical and cervicothoracic fusion procedures at our institution with constructs involving C-2 laminar screws. Eleven patients were men and 5 were women, and they ranged in age from 28 to 84 years (mean 57 years). The reasons for fusion were degenerative disease (9 patients) and treatment of trauma (7 patients). In 14 patients (87.5%) standard translaminar screws were placed, and in 2 (12.5%) an ipsilateral trajectory was used. All patients underwent preoperative radiological evaluation of the cervical spine, including computed tomography scanning with multiplanar reconstruction to assess the posterior anatomy of C-2. Anatomical restrictions for placement of standard translaminar screws included a deeply furrowed spinous process and/or an underdeveloped midline posterior ring of the axis. In these cases, screws were placed into the corresponding lamina from the ipsilateral side, allowing bilateral screws to be oriented in a more parallel, as opposed to perpendicular, plane. All patients were followed for >2 years to record rates of fusion, instrumentation failure, and other complications. RESULTS: Thirty-two screws were placed without neurological or vascular complications. The mean follow-up duration was 27.3 months. Complications included 2 revisions, one for pseudarthrosis and the other for screw pullout, and 3 postoperative infections. CONCLUSIONS: Placement of laminar screws into the axis from the standard crossing approach or via an ipsilateral trajectory may allow a safe, effective, and durable means of including the axis in posterior cervical and cervicothoracic fusion procedures.

Laparoscopic treatment of anterior sacral meningocele.

BACKGROUND: Anterior sacral meningocele is a rare congenital malformation, whose open surgical treatment is well accepted. We present a laparoscopic approach as an adjunctive approach. METHODS: Five women who underwent laparoscopic transperitoneal surgery were clinically, radiologically, and surgically evaluated. RESULT: All 5 patients underwent laparoscopic transperitoneal surgery and showed satisfactory results. They had no major complications. Three patients had headaches as minor complications, but it was gone in at most 3 days. Decrease in operative time, blood loss, and length of hospitalization were the advantages of the procedure. CONCLUSIONS: The laparoscopic approach to treating anterior sacral meningocele was feasible and safe, with only minor complications.

Reduction of cerebrospinal fluid rhinorrhea after vestibular schwannoma surgery by reconstruction of the drilled porus acusticus with hydroxyapatite bone cement.

OBJECT: Cerebrospinal fluid (CSF) rhinorrhea remains a significant cause of morbidity after resection of vestibular schwannomas (VSs), with rates of rhinorrhea after this procedure reported to range between 0 and 27%. The authors investigated whether reconstruction of the drilled posterior wall of the porus acusticus with hydroxyapatite cement (HAC) would decrease the incidence of postoperative CSF rhinorrhea. METHODS: A prospective observational study of 130 consecutive patients who underwent surgery for reconstruction of the posterior wall of the drilled porus acusticus with HAC was conducted between October 2002 and September 2005. All patients underwent a retrosigmoid transmeatal approach for VS resection and were followed up to document cases of CSF rhinorrhea, incisional CSF leak, meningitis, or rhinorrhea-associated meningitis. A cohort of 150 patients with VSs who were treated with the same surgical approach but without HAC reconstruction served as a control group. RESULTS: The authors found that HAC reconstruction of the porus acusticus wall significantly reduced the rate of postoperative CSF rhinorrhea in their patients. In the patients treated with HAC, rhinorrhea developed in only three patients (2.3%) compared with 18 patients (12%) in the control group. This was a statistically significant finding (p = 0.002, odds ratio = 5.8). CONCLUSIONS: The use of HAC in the reconstruction of the drilled posterior wall of the porus acusticus, occluding exposed air cells, greatly reduces the risk of CSF rhinorrhea.

Prospective evaluation of pain and analgesic use following major elective intracranial surgery.

OBJECT: Opioid administration after major intracranial surgery is often limited by a presumed lack of need and a concern that opioids will adversely affect the postoperative neurological examination. The authors conducted a prospective study to evaluate the incidence, severity, and treatment of postoperative pain in patients who underwent major intracranial surgery. METHODS: One hundred eighty-seven patients (77 men and 110 women, mean age 52 +/- 15 years, mean weight 78.1 +/- 19.9 kg) underwent either supratentorial (129 patients) or infratentorial (58 patients) procedures. Sixty-nine percent of the patients reported experiencing moderate to severe pain (> or =4 on a 0-10 scale) during the 1st postoperative day. Pain scores greater than or equal to 4 persisted in 48% on the 2nd postoperative day. Approximately 80% of patients were treated with acetaminophen on the 1st postoperative day, whereas opioids (primarily intravenous fentanyl) were administered to 58%. Compared with patients who underwent supratentorial procedures, those who underwent infratentorial procedures reported more severe pain at rest (mean score 4.9 +/- 2.2 compared with 3.8 +/- 2.6; p = 0.015) and with movement (mean score 6.3 +/- 2.6 compared with 4.5 +/- 2.7; p < 0.001) on the 1st postoperative day. On both the 1st and 2nd postoperative days, patients who underwent infratentorial procedures received greater quantities of opioid (p < or = 0.019) and nonopioid (p < or = 0.013) analgesics than those who underwent supratentorial procedures. Patients' dissatisfaction with analgesic therapy was significantly associated with elevated pain levels on the first 2 postoperative days (p < 0.001). CONCLUSIONS: In contrast to prevailing assumptions, the study findings reveal that most patients undergoing elective major intracranial surgery will experience moderate to severe pain for the first 2 days after surgery and that this pain is often inadequately treated.

The Lumbar Spine Outcomes Questionnaire: its development and psychometric properties.

BACKGROUND CONTENT: There are currently a number of generic and disease-specific instruments for assessing complaints of low back pain (LBP). None provide the comprehensive coverage of the wide range of factors that are considered essential in evaluating treatment outcomes. PURPOSE: To develop and evaluate the psychometric properties of a comprehensive, disease-specific questionnaire for characterizing complaints of LBP and evaluating the outcomes of treatments for these complaints. STUDY DESIGN: A clinical-cohort study of a large, convenience sample of LBP patients. METHODS: We have developed a comprehensive, disease-specific questionnaire for characterizing complaints of LBP and evaluating the outcomes of treatments for these complaints. A large group of patients who sought treatment for LBP (n=2539) completed the Lumbar Spine Outcomes Questionnaire (LSOQ) before treatment, and at 12 and 24 months after treatment. For each subject and for each evaluation period, scores on six composite measures were derived from the subjects' responses to the questionnaire: a LBP severity score, a leg pain severity score, a functional disability score, a psychological distress score, a physical symptoms score, and a health-care utilization score. These scores were used to evaluate the reliability, validity, and responsiveness of the questionnaire. RESULTS: Test-retest reliability of the LSOQ was evaluated by correlating the subject's 12-month scores on each composite measure with the corresponding 24-month scores. Intraclass coefficients of correlation were used. The obtained coefficients of correlation [(a) LBP severity, 0.87; (b) leg pain severity, 0.85; (c) functional disability, 0.87; (d) psychological distress, 0.88; (e) physical symptoms other than pain, 0.82; and (f) health-care utilization, 0.76] indicate good test-retest reliability for the LSOQ. Construct validity was evaluated by correlating scores on the composite measures derived from the LSOQ with scores on measures of the same constructs derived from the Oswestry Low Back Pain Disability Questionnaire and the Short Form 36-Item Health Survey. The coefficients of correlation were relatively high (mostly between .7 and .9), indicating good construct validity. Construct validity was also evaluated by comparing the scores of groups of subjects who were known to differ or not to differ on the composite measures, using multivariate analyses of variance. Significant multivariate and univariate differences were obtained between groups who were expected to differ (ie, surgically and nonsurgically treated patients). No significant differences were found for groups who were not expected to differ (ie, patients with similar diagnosis, but different surgical treatments). Responsiveness was assessed by evaluating differences in the 24-month change scores between improved and unimproved subjects. Large and significant differences were obtained between improved and unimproved subjects for all composite measures derived from the LSOQ. The observed effect sizes ranged from .68 to 1.17 indicating that the LSOQ is highly responsive. CONCLUSION: The LSOQ appears to be acceptable to patients, easy to administer, highly reliable, valid, and responsive. It provides information on demographics, pain severity, functional disability, psychological distress, physical symptoms, health-care utilization, and satisfaction. It should be considered for use in both clinical and research applications as well as regulatory review involving patients with LBP complaints.

Microsatellite analysis of recurrent vestibular schwannoma (acoustic neuroma) following stereotactic radiosurgery.

HYPOTHESIS: Genetic and immunohistochemical studies may provide insight into the mechanisms of vestibular schwannoma (VS) recurrence following radiation therapy. BACKGROUND: Stereotactic radiation therapy is an increasingly common alternative to microsurgical resection for the primary management of sporadic VS. The molecular mechanisms associated with recurrent vestibular schwannoma (VS) following radiation therapy are not known. METHODS: Primary or irradiated VS tumors were fresh-frozen at the time of surgical resection and microdissected to undergo DNA extraction. Lymphocytic control DNA was isolated from blood obtained by venipuncture. Paired normal and tumor DNA specimens were analyzed for allelic loss by PCR amplification of polymorphic dinucleotide repeat sequences. Immunohistochemical studies were performed on paraffin-embedded, irradiated surgical specimens. RESULTS: Using 16 polymorphic microsatellite markers, 20 of 26 non-irradiated VS demonstrated loss of heterozygosity (LOH) in at least one locus of chromosome 22q. In contrast, none of the four irradiated recurrent VS demonstrated LOH on chromosome 22q (p = 0.008). No allelic loss was seen in either the primary or irradiated VS utilizing markers mapping to chromosome 10. Deletions on chromosome 10 are seen in both benign and higher-grade meningiomas and intracranial malignancies associated with radiotherapy. Immunohistochemical studies were performed to detect the protein product of the NF2 gene, merlin, in the four irradiated VS. NF2 staining was not observed. CONCLUSION: This study represents the first microsatellite and immunohistochemical analysis of recurrent VS following radiation therapy. Our preliminary observations suggest an alternative mechanism of NF2 inactivation that may correlate with radioresistance in VS.