Phosphaturic Mesenchymal Tumor.

Phosphaturic mesenchymal tumors (PMTs) are neoplasms associated with tumor-induced osteomalacia. Patients typically present with pathologic fractures in the setting of chronic hypophosphatemic hyperphosphaturic osteomalacia, as well as gradual muscle weakness, bone pain, and difficulty walking. Because of their rarity and nonspecific symptomatology, phosphaturic mesenchymal tumors often go undiagnosed for years. Even when discovered on imaging, the tumors can be diagnostically challenging for radiologists. Phosphaturic mesenchymal tumors often tend to be small and can be located nearly anywhere in the body, and, therefore, can mimic many other tumors. This case highlights the imaging and pathologic markers of a phosphaturic mesenchymal tumor, often found in a patient with tumor-induced osteomalacia.

Quantitative Modeling of External Ventricular Drain Output to Predict Shunt Dependency in Aneurysmal Subarachnoid Hemorrhage: Cohort Study.

BACKGROUND: Acute hydrocephalus is a common complication of aneurysmal subarachnoid hemorrhage (aSAH); however, attempts to predict shunt-dependent chronic hydrocephalus using clinical parameters have been equivocal. METHODS: Cohort study of aSAH is treated with external ventricular drainage (EVD) placement at our institution, 2001-2016, via logistic regression. EVD-related parameters included mean/total EVD output (days 0-2), EVD days, EVD days ≤ 5 mmHg, and wean/clamp fails. aSAH outcomes assessed included ventriculoperitoneal shunt (VPS) placement, delayed cerebral ischemia (DCI), radiographic infarction (RI), symptomatic vasospasm (SV), age, and aSAH grades. RESULTS: Two hundred and ten aSAH patients underwent EVD treatment for a median 12 days (range 1-54); 85 required VPS (40%). On univariate analysis, EVD output, total EVD days, EVD days ≤ 5 mmHg, and wean/clamp trial failures were significantly associated with VPS placement (p < 0.01 for all parameters). No EVD output parameter demonstrated a significant association with DCI, RI, or SV. On multivariate analysis, EVD output was a significant predictor of VPS placement, after adjusting for age and clinical and radiological grades; the optimal threshold for predicting VPS placement was mean daily output > 204 ml on days 0-2 (OR 2.59, 95% CI 1.31-5.07). Multiple wean failures were associated with unfavorable functional outcome, after adjusting for age, grade, and VPS placement (OR 1.65, 95% CI 1.10-2.47). We developed a score incorporating age, grade and EVD parameters (MAGE) for predicting VPS placement after aSAH. CONCLUSIONS: EVD output parameters and wean/clamp trial failures predicted shunt dependence in an age- and grade-adjusted multivariable model. Early VPS placement may be warranted in patients with MAGE score ≥ 4, particularly following 2 failed wean trials.

Prospective hemorrhage risk of intracerebral cavernous malformations.

OBJECTIVE: Our goal was to describe the prospective risk and timing of symptomatic hemorrhage in a large cohort of followed patients with intracerebral cavernous malformations (ICMs). METHODS: All patients between 1989 and 1999 with the radiographic diagnosis of intracerebral cavernous malformation were identified retrospectively. The records and radiographic data were reviewed, and follow-up after diagnosis was obtained. An incidence rate was used to calculate annual risk of symptomatic hemorrhage. Predictive factors for outcomes used univariate and multivariable analysis with p < 0.05. RESULTS: A total of 292 patients were identified (47.3%male) with 2,035 patient years of follow-up. Seventy-four patients presented with hemorrhage, 108 with symptoms not related to hemorrhage (seizure or focal deficit), and 110 as asymptomatic. The overall annual rate of hemorrhage in those presenting initially with hemorrhage, with symptoms not related to hemorrhage, or as an incidental finding was 6.19%, 2.18%, and 0.33%, respectively. Patients who presented initially with symptomatic hemorrhage (hazard ratio 5.14; 95% confidence interval [CI] 2.54-10.4; p < 0.001) were at higher risk for future hemorrhage, and hemorrhage risk decreased with time. Male gender (hazard ratio 2.36; 95% CI 1.14-4.89; p = 0.02), and multiplicity of ICMs (hazard ratio 2.65; 95% CI 1.30-5.43; p = 0.01) also increased the risk of hemorrhage. The median time from first to second hemorrhage was 8 months. CONCLUSIONS: This study provides an estimate of prospective annual symptomatic hemorrhage risk in patients with ICMs stratified by initial presenting symptom. Prior hemorrhage, male gender, and multiplicity of ICMs may predict future hemorrhage. Hemorrhage risk decreases with time in those initially presenting with hemorrhage.

Pilot study of bright-light therapy reflected toward the eyes for the pruritus of chronic liver disease.

OBJECTIVE: It is proposed that the pruritus of cholestasis is, in part, centrally mediated by endogenous opioid peptides. The expression of these peptides and their receptors on neurons displays a circadian rhythm, as does the scratching activity in patients with cholestasis and pruritus. Because light has regulatory effects on circadian rhythms via retinothalamic pathways, we hypothesized that bright-light therapy (BLT) reflected toward the eyes might alter the pruritus of cholestasis. To test this hypothesis, we studied the effect of BLT on this form of pruritus. METHODS: Eight patients with chronic liver disease of different etiologies and pruritus were studied in an open-label, pilot study of 8-wk duration. BLT (10,000 lux) was administered for up to 60 min twice a day. Pruritus was assessed subjectively by a visual analog scale from which a visual analog score (VAS) was derived, and objectively, by a scratching activity monitoring system that recorded hourly scratching activity (HSA). RESULTS: In seven of the eight patients studied, the mean HSA was lower during BLT. BLT was associated with a mean decrease in HSA of 32.2% (p = 0.123). The mean VAS for pruritus was lower in six patients during BLT; the mean VAS score derived from the eight patients studied decreased by 42% (p = 0.05) during treatment. CONCLUSIONS: The results of this short-term study suggest that the pruritus of cholestasis is responsive to bright light reflected toward the eyes and that in some patients, BLT may ameliorate this form of pruritus.

Meningioma radiosurgery: tumor control, outcomes, and complications among 190 consecutive patients.

OBJECTIVE: To determine local control (LC) and complication rates for patients with intracranial meningiomas who underwent radiosurgery. METHODS: One hundred ninety consecutive patients with 206 meningiomas underwent radiosurgery between 1990 and 1998. One hundred forty-seven tumors (77%) involved the cranial base. The median age at the time of radiosurgery was 58 years (range, 20-90 yr). There were 126 female patients (66%). One hundred twelve patients (59%) had undergone one or more previous operations (median, 1; range, 1-5). Twenty-two patients (12%) had either atypical (n = 13) or malignant (n = 9) tumors. The median prescription isodose volume was 8.2 cm(3) (range, 0.5-50.5 cm(3)), and the median tumor margin dose was 16 Gy (range, 12-36 Gy). The median imaging and clinical follow-up periods were 40 and 47 months, respectively. RESULTS: Overall survival rates for the entire cohort at 5 and 7 years were 82 and 82%, respectively; cause-specific survival rates at 5 and 7 years were 94 and 92%, respectively. The cause-specific survival rates at 5 years for patients with benign, atypical, and malignant tumors were 100, 76, and 0%, respectively (P < 0.0001). The 5-year LC rate was 89%, with 114 tumors (56%) decreasing in size. LC rates were correlated with tumor histological features (P < 0.0001); patients with benign tumors exhibited a 5-year LC rate of 93%, compared with 68 and 0% for patients with atypical or malignant meningiomas, respectively. No correlation was observed between radiation dose and LC rate. Twenty-four patients (13%) experienced treatment-related complications, including cranial nerve deficits (8%), symptomatic parenchymal changes (3%), internal carotid artery stenosis (1%), and symptomatic cyst formation (1%). Only six patients (3%) exhibited decreases in functional status that were directly related to radiosurgery. Tumor volume, tumor margin dose, or previous radiotherapy was not associated with the development of radiation-related complications. CONCLUSION: Radiosurgery is an effective management strategy for many patients with meningiomas. Patients with atypical or malignant tumors exhibit high recurrence rates despite the use of radiosurgery, and these patients continue to exhibit worse cause-specific survival rates despite aggressive treatment, including surgery, external-beam radiotherapy, and radiosurgery. Further study is needed to determine the tumor control and complication rates 10 years or more after meningioma radiosurgery.

Stereotactic radiosurgery for cavernous malformations.

OBJECT: The use of stereotactic radiosurgery to treat cerebral cavernous malformations (CMs) is controversial. To evaluate the efficacy and safety of CM radiosurgery, the authors reviewed the experience at the Mayo Clinic during the past 10 years. METHODS: Seventeen patients underwent radiosurgery for high-surgical-risk CMs in the following sites: thalamus/basal ganglia (four patients), brainstem (12 patients), and corpus callosum (one patient). All patients had experienced at least two documented hemorrhages before undergoing radiosurgery. Stereotactic magnetic resonance (MR) imaging was used for target localization in all cases. The median margin radiation dose was 18 Gy and the median maximum dose was 32 Gy. The median length of follow-up review following radiosurgery was 51 months. The annual hemorrhage rate during the 51 months preceding radiosurgery was 40.1%, compared with 8.8% in the first 2 years following radiosurgery and 2.9% thereafter. In 10 patients (59%) new neurological deficits developed that were associated with regions of increased signal on long-repetition time MR imaging performed a median of 8 months (range 5-16 months) after radiosurgery. Three patients recovered, giving the group a permanent radiation-related morbidity rate of 41%. Compared with 31 patients harboring arteriovenous malformations (AVMs) of sizes and in locations similar to those of the aforementioned CMs, who underwent radiosurgery during the same time period, the patients with CMs were more likely to experience radiation-related complications (any complication, 59% compared with 10%; p < 0.001; permanent complication, 41% compared with 10%; p = 0.02). CONCLUSIONS: It is impossible to conclude that radiosurgery protects patients with CMs against future hemorrhage risk based on the available data, although it appears that some reduction in the bleeding rate occurs after a latency interval of several years. The risk of radiation-related complications after radiosurgery to treat CMs is greater than that found after radiosurgery in AVMs, even when adjusting for lesion size and location and for radiation dose.

Gamma knife radiosurgery for skull base meningiomas.

Radiosurgery has been proven to be a safe and effective management strategy for skull base meningiomas either primarily or for tumor recurrence or progression after prior microsurgical resection. With its steep radiation falloff, radiosurgery provides long-term tumor growth control without the complications associated with conventional fractionated radiation therapy. Stereotactic MR imaging has allowed better definition of the tumor margin for precise multiisocenter conformal dose planning, and our current radiation dose prescription has decreased the incidence of new cranial nerve deficits after radiosurgery to less than 10%. Tumor growth control after radiosurgery remains greater than 90%; patients with subsequent growth typically have tumor outside the irradiated volume or a histologic diagnosis of atypical or malignant meningioma. Still, longer follow-up is needed to ensure that tumor growth control remains permanent after radiosurgery. For patients with large tumors of the skull base, radiosurgery can be part of a staged approach with microsurgery. Initially, the tumor is debulked without an attempt at resection involving the cranial nerves or basal vessels. Radiosurgery can then be performed for the small remaining tumor volume with little risk of cranial nerve deficits. Such multimodality treatment should result in reduced patient morbidity, with long-term tumor control.

Results of repeated gamma knife radiosurgery for medically unresponsive trigeminal neuralgia.

OBJECT: Gamma knife radiosurgery (GKS) is being increasing performed in the management of patients with medically unresponsive trigeminal neuralgia. The authors report the results of repeated GKS in patients with recurrent facial pain after their initial procedure. METHODS: Between April 1997 and December 1999, 100 patients with idiopathic trigeminal neuralgia underwent GKS at the authors' center. To date, 26 patients have required additional surgery because GKS provided no significant pain relief (15 patients) or because they had recurrent facial pain (11 patients). Ten of these patients underwent repeated GKS at a median of 13 months (range 4-27 months). All patients undergoing repeated GKS had a significant reduction in their facial pain after the first procedure (eight were pain free); no patient developed facial numbness or paresthesias. Initially, nine of 10 patients became pain free 1 to 4 weeks following repeated GKS. At a median follow up of 15 months (range 3-32 months), eight patients remained pain free and required no medication. All eight patients with persistent pain relief developed minor neurological dysfunction after repeated GKS (six patients had facial numbness and two had paresthesias). CONCLUSIONS: Repeated GKS can be associated with a high rate of pain relief for patients with trigeminal neuralgia who experienced a significant reduction in their facial pain after the first operation. However, every patient with sustained pain relief after the second operation also developed some degree of trigeminal dysfunction. These findings of improved pain relief for patients who develop facial numbness after GKS for trigeminal neuralgia support the experimental data currently available.

A comparison between endovascular and surgical management of basilar artery apex aneurysms.

OBJECT: The goal of this retrospective study was to evaluate endovascular treatment by means of Guglielmi detachable coils (GDCs) compared with surgical management for basilar artery (BA) apex aneurysms. METHODS: Forty-one patients presented with saccular BA apex aneurysms with angiographically definable necks that were judged suitable for either treatment. Of 20 patients who underwent surgery and 21 who underwent GDC embolization, 15 (75%) and 11 (52%), respectively, were treated in the acute phase after subarachnoid hemorrhage (SAH). Twenty-four (92%) of the 26 patients presenting with an SAH had a Hunt and Hess Grade III or better. Fifteen patients with unruptured or ruptured aneurysms more than 14 days post-SAH were treated electively. Patients in the endovascular and surgical treatment groups had aneurysms with comparable dimensions and configurations. Overall, 15 (75%) of the surgical patients and 20 (95%) of the patients in whom GDC embolization was performed had a good outcome (Glasgow Outcome Scale score of 4 or 5). Among those patients treated in the acute stage post-SAH, 11 (73%) of the surgical group and 10 (91%) of the endovascular group did well. Fourteen patients treated electively (93%) had good outcomes. There were two deaths (10%) in the surgical group and none in the endovascular group. Patients treated surgically were hospitalized twice as long and incurred twice the expenses of patients who underwent endovascular treatment (p<0.001). CONCLUSIONS: Endovascular GDC embolization of select BA apex aneurysms may be a competitive alternative to direct surgical clipping. Long-term follow up is needed to better define the natural history of the endovascularly treated aneurysm and to further evaluate the accuracy of these preliminary results.

Cervicomedullary compression: an unrecognized cause of vocal cord paralysis in rheumatoid arthritis.

Cervicomedullary compression (CMC) from traumatic, infectious, or congenital processes of the atlanto-axial joint is a known cause of vocal cord immobility. Cervicomedullary compression can also occur from destructive arthritic changes and inflammatory pannus formation at the occipito-atlanto-axial joint in patients with rheumatoid arthritis (RA). We present findings suggesting that CMC in patients with RA is an unrecognized cause of vocal cord immobility. Previously, vocal cord immobility in patients with RA has been assumed to be cricoarytenoid arthritis with joint fixation. We report 3 patients with RA and radiographically demonstrated CMC with vocal cord immobility. One patient had bilateral vocal cord immobility and airway obstruction; 2 patients had unilateral cord paralysis and contralateral paresis without airway compromise. All patients had myelopathy and neck pain in addition to brain stem symptoms. All patients underwent transoral-transpharyngeal decompression of the anterior craniocervical junction with subsequent posterior fusion. These patients demonstrated full return of vocal cord function within 3 months of decompression. We propose that CMC is a cause of vocal cord paralysis in patients with RA that may go unrecognized without appropriate imaging studies of the skull base and physician awareness of symptoms of occipito-atlanto-axial subluxation and/or basilar invagination with brain stem compression. Our results demonstrate that CMC in RA is a potentially reversible cause of vocal cord paralysis.

The role of radiosurgery and particulate embolization in the treatment of dural arteriovenous fistulas.

Over the past 5 years 29 patients with dural arteriovenous fistulas (AVFs) were treated by the authors using the Leksell radiosurgical gamma knife unit. Within 2 days after radiosurgery, 17 patients with AVFs that exhibited retrograde pial or cortical venous drainage (12 patients) and/or produced intractable bruit (eight patients) underwent particulate embolization of external carotid feeding vessels. The rationale for this treatment strategy was that radiosurgery was expected to cause obliteration of most fistulas after 12 to 36 months. In patients with bruit, ocular symptoms, or in those at risk for hemorrhage, treatment with embolization after radiosurgery kept the fistulas angiographically visible for radiosurgical targeting yet offered palliation of symptoms and temporary, partial protection from hemorrhage during the latency period. In 12 patients, preobliteration embolization immediately reduced (10 patients) or eliminated (two patients) retrograde pial venous drainage. To date, no lesion has hemorrhaged after treatment. Angiography 1 to 3 years posttreatment in 18 patients showed total obliteration of 13 fistulas (72%) and partial obliteration of five (28%). Radiosurgery, followed by embolization when retrograde pial venous drainage, intractable bruit, and/or major external carotid artery supply is present, appears to be a promising treatment for selected patients with symptomatic dural AVFs.

Pneumatic nerve root compression: epidural gas in association with lateral disc herniation. Report of two cases.

Extreme lateral disc herniations are increasingly recognized as a cause of lumbar nerve root compression syndromes. This disorder often presents major diagnostic and therapeutic challenges, especially in the presence of multiple degenerative changes and chronic back pain in elderly patients. The authors describe two patients with presentations and findings that have not been previously described in the literature. Both patients had histories of upper lumbar back and leg pain. Degenerative spine disease, gaseous degeneration of the intervertebral discs, and epidural gas in the lateral recesses were noted on imaging studies. However, because both patients had undergone prior epidural diagnostic and therapeutic procedures, the epidural gas in the lateral recesses could be attributed either to gaseous disc degeneration or to the previous intraspinal procedures. One patient was found to have a large, far lateral extruded disc fragment that contained air. The nerve root in the second patient was impaled by an unusual combination of a small extruded disc fragment as well as an air-filled sac that was surrounded by the walled-off fragment's capsule and which freely communicated with the gaseous degenerated disc space. The suspected mechanism of root compression is illustrated and discussed. The possibility of disc herniation should be seriously considered in cases of nerve root compression in which epidural gas is present, especially those associated with gaseous degenerated discs.

Prewhitening for intelligibility gain in hearing aid arrays.

In this article, prewhitening multimicrophone data prior to use in an optimum spatial-filter preprocessor for a monaural hearing aid is considered. Considering preprocessor capabilities, interference signal spectral content and intelligibility, it is argued that prewhitening is advantageous. This advantage is illustrated via simulation of a head worn array. Also, an effective procedure for the design of (prewhitening) digital filters is presented. The effectiveness of this filter design technique is shown by presenting several prewhitening filter design examples.

Spontaneous midbrain hemorrhage: report of seven new cases.

Spontaneous midbrain hemorrhage is a unique brain-stem vascular lesion. Sixty-six cases have been reported in the literature, to which we add seven. Of the total of 73 patients reviewed, most presented acutely (66%), but subacute (22%) and chronic onsets (12%) also occurred. Neuro-ophthalmologic abnormalities were found in 88% of patients. Some alteration of consciousness and headache occurred in most patients. Hemiparesis, hemisensory loss, and ataxia were less frequent manifestations. Vascular malformations were suspected or proved in 37% of patients, hypertension was present in 21%, and a bleeding diathesis was noted in 5%. No underlying cause was apparent in 37%. Most patients improved with supportive care only. At follow-up, 23% of patients had no neurologic deficits. In 51% of patients, minor neurologic deficits persisted, related chiefly to cranial nerves III and IV. Moderate deficits persisted in 16% of patients, and 5% of patients died.

Effects of magnesium sulfate on pentylenetetrazol-induced status epilepticus.

The use of magnesium sulfate (MgSO4) as an anticonvulsant is controversial. Status epilepticus was induced in 0.5% halothane-anesthetized Wistar rats with a threshold (90 mg/kg) or suprathreshold (200 mg/kg) dose of intravenous (i.v.) pentylenetetrazol (PTZ) under stereotactic hippocampal depth electrode monitoring. Fifteen minutes after seizure induction, the maximum hemodynamically tolerated dose of MgSO4 (10 mg/kg/min in 22 min) was administered i.v. MgSO4 was ineffective in altering seizure discharge. A subgroup of nine animals received hypertonic mannitol before MgSO4 to open the blood-brain barrier (BBB) to facilitate Mg2+ CNS penetration. Again MgSO4 was ineffective in attenuating epileptic activity. These results support the contention that MgSO4 is not an effective treatment for status epilepticus. We hypothesize that because Mg2+ blocks Ca2+ influx into the neuron through the N-methyl-D-aspartate (NMDA) receptor-operated calcium channel in a voltage-dependent manner it would be ineffective in neurons that are continuously depolarizing as in status epilepticus.

Tumor localization in nude mice bearing human breast carcinoma xenografts using 111In-DTPA conjugates of monoclonal antibodies.

Biodistribution of monoclonal antibody T43 and its F(ab')2 111In-DTPA conjugates were determined in nu/nu mice bearing human breast tumor and rat pituitary tumor xenografts. T43 localized in the target tumor with tumor/blood ratios of 3.9 (P less than 0.01) and 4.5 (P less than 0.05) at 48 and 72 h, respectively. T43 F(ab')2 fragments localized with tumor/blood ratio of 14.2 (P less than 0.1) at 72 h. Tumors as small as 4 mm were detected without computer subtraction technique. These studies suggest that T43 and T43 F(ab')2 might be useful reagents in radioimaging.

Efficacy of brief, intense light exposure for treatment of winter depression.

A high-intensity fluorescent lighting system, tilted downward toward the head, and emitting negligible levels of ultraviolet radiation, was tested under two random crossover protocols in winter-depressed patients: 30-minute sessions at (a) 3,000 lux vs. 10,000 lux in early morning, and (b) morning vs. evening sessions at 10,000 lux. Judgment of clinical remission was based jointly on relative and absolute score improvements on a Structured Interview Guide for the Hamilton Depression Scale--Seasonal Affective Disorder Version (SIGH-SAD) and a set of supplementary atypical-vegetative items. Data are presented for 24 subjects who showed relapse upon withdrawal. An overall remission rate of 75 percent was found for morning light at 10,000 lux. The rates for evening light (25%) and 3,000 lux morning light (19%) were significantly lower. The remission rate for morning light treatment of 10,000 lux for 30 minutes approximately equalled 2,500 lux treatment for 2 hours (data from our earlier studies), suggesting a reciprocity between dosing dimensions of intensity and duration. No pathological changes were revealed by ophthalmological examinations given after 2 to 6 weeks of daily treatment.