Image-guided, direct convective delivery of glucocerebrosidase for neuronopathic Gaucher disease.

OBJECTIVE: To determine if convection-enhanced delivery (CED) of glucocerebrosidase could be used to treat targeted sites of disease progression in the brain and brainstem of a patient with neuronopathic Gaucher disease while monitoring enzyme distribution using MRI. METHODS: A CED paradigm in rodents (n = 8) and primates (n = 5) that employs co-infusion of a surrogate MRI tracer (gadolinium diethylenetriamine penta-acetic acid [Gd-DTPA]) with glucocerebrosidase to permit real-time monitoring of distribution was developed. The safety and feasibility of this delivery and monitoring paradigm were evaluated in a patient with type 2 Gaucher disease. RESULTS: Animal studies revealed that real-time, T1-weighted, MRI of Gd-DTPA accurately tracked enzyme distribution during CED. Targeted perfusion of clinically affected anatomic sites in a patient with neuronopathic Gaucher disease (frontal lobe and brainstem) with glucocerebrosidase was successfully performed. Real-time MRI revealed progressive and complete filling of the targeted region with enzyme and Gd-DTPA infusate. The patient tolerated the infusions without evidence of toxicity. CONCLUSIONS: Convection-enhanced delivery can be used to safely perfuse large regions of the brain and brainstem with therapeutic levels of glucocerebrosidase. Co-infused imaging surrogate tracers can be used to monitor and control the distribution of therapeutic agents in vivo. Patients with neuronopathic Gaucher disease and other intrinsic CNS disorders may benefit from a similar treatment paradigm.

Evolution of VHL tumourigenesis in nerve root tissue.

Haemangioblastomas are the key central nervous system manifestation of von Hippel-Lindau (VHL) disease, which is caused by germline mutation of the VHL gene. We have recently shown that 'tumour-free' spinal cord from patients with VHL disease contains microscopic, poorly differentiated cellular aggregates in nerve root tissue, which we descriptively designated 'mesenchymal tumourlets'. Here we have investigated spinal cord tissue affected by multiple tumours. We show that a small subset of mesenchymal tumourlets extends beyond the nerve root to form proliferative VHL-deficient mesenchyme and frank haemangioblastoma. We thus demonstrate that tumourlets present potential, but true precursor material for haemangioblastoma. We further show that intraradicular tumourlets consist of scattered VHL-deficient cells with activation of HIF-2alpha and HIF-dependent target proteins including CAIX and VEGF, and are associated with an extensive angiogenic response. In contrast, activation of HIF-1alpha was only observed in the later stages of tumour progression. In addition, ultrastructural examination reveals gradual transition from poorly differentiated VHL-deficient cells into vacuolated cells with a 'stromal' cell phenotype. The evolution of frank haemangioblastoma seems to involve multiple steps from a large pool of precursor lesions.

Differential cortical thickness across the central sulcus: a method for identifying the central sulcus in the presence of mass effect and vasogenic edema.

BACKGROUND AND PURPOSE: Identification of the motor strip on MR imaging studies is difficult in the presence of mass effect and vasogenic edema because sulcal landmarks are obscured. We hypothesize that a difference in cortical thickness between the motor and sensory strips is readily apparent on T2-weighted images in the presence of vasogenic edema and reliably identifies the central sulcus. METHODS: Thirteen patients with brain tumors resulting in vasogenic edema near the central sulcus were identified. The cortical thickness of the anterior and posterior banks of the central sulcus as well as the neighboring sulci in the frontal and parietal lobes were measured from T2-weighted images. Similar measures were obtained from neighboring sulci in the frontal and parietal lobes. Location of the central sulcus was confirmed with standard anatomic landmarks in all patients and by intraoperative cortical mapping in 2 patients. RESULTS: A twofold difference in cortical thickness between the anterior and posterior banks of the central sulcus uniquely identified the central sulcus on T2-weighted images in the presence of vasogenic edema, despite the marked distortion of sulcal anatomy as a result of mass effect. This relationship was not present in neighboring sulci. CONCLUSION: Cytoarchitectonic differences in the motor and sensory cortices result in a markedly thicker posterior than anterior bank of the central sulcus that is readily visible on routine T2-weighted images in the presence of vasogenic edema. Therefore, the cortical thickness can serve as a complementary method in identification of the motor strip in patients with mass effect.

Epididymal cystadenomas and epithelial tumourlets: effects of VHL deficiency on the human epididymis.

Although epididymal cystadenomas (ECAs) are among the most frequent VHL disease-associated tumours, fundamental questions about their pathogenesis have remained unanswered. Classification of ECAs is controversial, and the cell of origin is unknown. It is also unknown whether ECAs-like other VHL disease-associated tumours-arise as a result of VHL gene inactivation, and whether ECAs exhibit subsequent activation of hypoxia-inducible factor HIF. Moreover, the morphological spectrum of earliest ECA formation is unknown. In a detailed molecular pathological analysis of a series of epididymides collected from VHL patients at autopsy, we found that ECAs are true neoplasms that arise secondary to inactivation of the wild-type copy of the VHL gene, followed by early and simultaneous activation of HIF1 and HIF2 associated with up-regulation of downstream targets, including CAIX and GLUT-1. The observations also indicate that ECA formation evolves from a variety of microscopic epithelial tumourlets, and that these tumourlets are confined to the efferent ductular system. Although genetic and immunohistochemical analysis of precursor structures consistently revealed VHL gene inactivation and activation of HIF in the precursor lesions, only a small subset appears to progress into frank cystadenoma. Thus, ECA tumorigenesis in VHL disease shares fundamental principles with tumorigenesis in other affected organ systems.

Vertebral osteomyelitis secondary to Pseudallescheria boydii.

Because Pseudallescheria boydii vertebral osteomyelitis is rare and frequently resistant to available antifungal agents, the proper treatment of this lesion has not been defined. To better determine the best treatment of this lesion, the authors evaluated a case P. boydii vertebral osteomyelitis and reviewed the literature. A 48-year-old man had isolated thoracic vertebral osteomyelitis resulting from P. boydii and associated severe thoracic back pain and proximal lower extremity pain and weakness. Magnetic resonance imaging studies revealed continued collapse of the T6--T7 vertebrae despite previous posterior debridement and appropriate antifungal chemotherapy. On admission to the authors' institution, the patient underwent a right thoracotomy, anterior debridement with transthoracic T6--T7 corpectomies and strut grafting, followed by posterior fusion and stabilization with pedicle screws. After operation, the patient's pain, hyperalgesia, and lower extremity symptoms resolved. He was treated with a 12-month course of itraconazole. Imaging and laboratory studies show no evidence of recurrence. P. boydii vertebral osteomyelitis can have devastating neurologic sequelae if not treated properly. The frequent lack of response of this unusual fungal infection to systemic therapy requires frequent serial follow-up examinations. Patients with evidence of progression on imaging studies or neurologic findings should undergo early and aggressive surgical debridement.

Direct anterior screw fixation for recent and remote odontoid fractures.

OBJECT: The management of odontoid fractures remains controversial. Only direct anterior screw fixation provides immediate stabilization of the spine and may preserve normal C1-2 motion. To determine the indications, optimum timing, and results for direct anterior screw fixation of odontoid fractures, the authors reviewed the surgery-related outcome of patients who underwent this procedure at two institutions. METHODS: One hundred forty-seven consecutive patients (98 males and 49 females) who underwent direct anterior screw fixation for recent (< or = 6 months postinjury [129 patients]) or remote (> or = 18 months postinjury [18 patients]) Type II (138 cases) or III (nine cases) odontoid fractures at the University of Utah (94 patients) and National Institute of Traumatology in Budapest, Hungary (53 patients) between 1986 and 1998 are included in this study (mean follow up 18.2 months). Data obtained from clinical examination, review of hospital charts, operative findings, and imaging studies were used to analyze the surgery-related results in these patients. In patients with recent fractures there was an overall bone fusion rate of 88%. The rate of anatomical bone fusion of recent fractures was significantly (p < or = 0.05) higher in fractures oriented in the horizontal and posterior oblique direction (compared with anterior oblique), but this finding was independent (p > or = 0.05) of age, sex, number of screws placed (one or two), and the degree or the direction of odontoid displacement. In patients with remote fractures there was a significantly lower rate of bone fusion (25%). Overall, complications related to hardware failure occurred in 14 patients (10%) and those unrelated to hardware in three patients (2%). There was one death (1%) related to surgery. CONCLUSIONS: Direct anterior screw fixation is an effective and safe method for treating recent odontoid fractures (<6 months postinjury). It confers immediate stability, preserves C1-2 rotatory motion, and achieves a fusion rate that compares favorably with alternative treatment methods. In contradistinction, in patients with remote fractures (> or = 18 months postinjury) a significantly lower rate of fusion is found when using this technique, and these patients are believed to be poor candidates for this procedure.

Adult tethered cord syndrome.

Although often overlooked, the diagnosis of adult "tethered cord syndrome" (TCS) is important because the manifestations of this syndrome are readily reversible by untethering. Too often, adult patients with TCS are misdiagnosed as having "failed back syndrome" or other unrelated spinal problems. As a result, many patients are treated with modalities which fail to improve neurological function. The aims of this review are to acquaint readers with the pathophysiology, symptomatology, diagnosis, and treatment of adult TCS based on author's experience in 70 cases. Adult TCS manifested by severe back and leg pain, a subtle onset of motor/sensory changes and musculoskeletal deformities is correlated to TCS pathophysiology and imaging studies. Timely diagnosis of TCS can lead to pain relief and restoration of neurologic function and patient gratification.

Focal delivery during direct infusion to brain: role of flow rate, catheter diameter, and tissue mechanics.

Direct interstitial infusion is a technique capable of delivering agents over both small and large dimensions of brain tissue. However, at a sufficiently high volumetric inflow rate, backflow along the catheter shaft may occur and compromise delivery. A scaling relationship for the finite backflow distance along this catheter in pure gray matter (x(m)) has been determined from a mathematical model based on Stokes flow, Darcy flow in porous media, and elastic deformation of the brain tissue: x(m) = constant Q(o)(3)R(4)r(c)(4)G(-3)mu(-1) 1/5 [corrected] = volumetric inflow rate, R = tissue hydraulic resistance, r(c) = catheter radius, G = shear modulus, and mu = viscosity). This implies that backflow is minimized by the use of small diameter catheters and that a fixed (minimal) backflow distance may be maintained by offsetting an increase in flow rate with a similar decrease in catheter radius. Generally, backflow is avoided in rat gray matter with a 32-gauge catheter operating below 0.5 microliter/min. An extension of the scaling relationship to include brain size in the resistance term leads to the finding that absolute backflow distance obtained with a given catheter and inflow rate is weakly affected by the depth of catheter tip placement and, thus, brain size. Finally, an extension of the model to describe catheter passage through a white matter layer before terminating in the gray has been shown to account for observed percentages of albumin in the corpus callosum after a 4-microliter infusion of the compound to rat striatum over a range of volumetric inflow rates.

Scanning electron microscopy of arteriovenous malformations.

Although arteriovenous malformations (AVMs) have been known to have direct communications between arteries and veins without interposing capillaries, the exact location of arterial and venous junctions have not been defined. Utilizing microscopic and endoscopic observations, Yamada and associates identified shunting arterioles (50 mu-250 mu) directly connected to the AVM core vessels. While dissecting the AVMs in functional areas of the brain, shunting arterioles were sectioned to interrupt the arterial blood supply. This technique allowed cleavage formation between the core vessels and surrounding brain, thus avoiding brain tissue removal and preserving microcirculation to functionally critical brain. We demonstrate histologically for the first time by scanning electron microscopy shunting arterioles and communicating venules (20 mu-200 mu).

Convection-enhanced selective excitotoxic ablation of the neurons of the globus pallidus internus for treatment of parkinsonism in nonhuman primates.

OBJECT: Selective treatment of central nervous system (CNS) structures holds therapeutic promise for many neurological disorders, including Parkinson's disease (PD). The ability to inhibit or augment specific neuronal populations within the CNS reliably by using present therapeutic techniques is limited. To overcome this problem, the authors modeled and developed a method in which convection was used to deliver compounds to deep brain nuclei in a reproducible, homogeneous, and targeted manner. To determine the feasibility and clinical efficacy of convective drug delivery for treatment of a neurological disorder, the investigators selectively ablated globus pallidus internus (GPi) neurons with quinolinic acid (QA), an excitotoxin, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model of primate parkinsonism. METHODS: After the parameters of convective distribution to the GPi were confirmed by infusion of biotinylated albumin into the GPi of a primate (Macaca mulatta), seven adult monkeys of this species were rendered either fully parkinsonian by intravenous injections of MPTP (five animals) or hemiparkinsonian by a right-sided intracarotid injection of this agent (two monkeys). Using convection-enhanced delivery to the GPi, animals were infused with either QA (three fully parkinsonian, two hemiparkinsonian) or saline (two fully parkinsonian). The three fully parkinsonian animals that underwent GPi lesioning with QA had substantial improvement of PD symptoms, manifested by a marked increase in activity (34 +/- 2.5%; mean +/- standard deviation) and dramatic improvement of parkinsonian clinical scores. In contrast, the control animals did not improve (activity monitor change = -1.5 +/- 0.5%). The two hemiparkinsonian animals that underwent QA lesioning of the GPi had dramatic recovery of extremity use. Histological examination revealed selective neural ablation of GPi neurons (mean loss 87%) with sparing of surrounding gray and white matter structures. No animal developed worsening signs of PD or neurological deficits after infusion. CONCLUSIONS: Convection-enhanced delivery of QA permits selective, region-specific (GPi), and safe lesioning of neuronal subpopulations, resulting in dramatic improvement in parkinsonian symptomatology. The properties of convection-enhanced delivery indicate that this method could be used for chemical neurosurgery for medically refractory PD and that it may be ideal for cell-specific therapeutic ablation or trophic treatment of other targeted structures associated with CNS disorders.

Convective delivery of macromolecules into the naive and traumatized spinal cords of rats.

OBJECT: Many macromolecules have the potential to enhance recovery after injury and other lesions of the spinal cord, but because of the limited penetration of these compounds across the blood-spinal cord barrier, they cannot be used effectively. To determine if convective delivery could be used in a common animal model to investigate potential therapeutic macromolecules and to examine the effects of trauma on convective delivery in that model, the authors examined the distribution of a macromolecule in naive and traumatized rat spinal cords. METHODS: Using convection, various infusion volumes ([Vi]; 1, 2, and 4 microl) of 14C-albumin were infused into the dorsal columns of 13 naive and five traumatized rat spinal cords. Volume of distribution (Vd), homogeneity, percentage of recovery, and anatomical location were determined using quantitative autoradiography, scintillation analysis, calculation of kurtosis (K) value, and histological analysis. In the nontraumatized group, Vd was linearly proportional (R2 = 0.98) to Vi (Vd/Vi, 4.3+/-0.6; mean +/- standard deviation), with increases in Vd resulting from linear expansion (R2 = 0.94) primarily in the craniocaudal dimension. In the traumatized spinal cords, the Vd/Vi ratio (3.7+/-0.5) was smaller (p<0.02) and distributions were less confined to the craniocaudal dimension, with significantly larger cross-sectional distributions in the region of injury (p<0.02) compared to the noninjured spinal cords. Histological analysis revealed that after infusion into the dorsal columns, albumin distribution in naive cords was limited to the dorsal white matter, but in the traumatized cords there was penetration into the central gray matter. The distribution of the infusate was homogeneous in the nontraumatized (K = -1.1) and traumatized (K = -1.1) spinal cords. Recovery of radioactivity was not significantly different (p>0.05) between the nontraumatized (84.8+/-6.8%) and traumatized (79.7+/-12.1%) groups. CONCLUSIONS: Direct convective delivery of infusate can be used to distribute macromolecules in a predictable, homogeneous manner over significant volumes of naive and traumatized rat spinal cord. These characteristics make it a valuable tool to investigate the therapeutic potential of various compounds for the treatment of injury and spinal cord disease.

Telomerase activity in microdissected human gliomas.

Future improvements in the diagnosis and treatment of human gliomas might rely on obtaining more specific information concerning the biologic characteristics of individual tumor cells. Telomerase, a ribonucleoprotein that synthesizes telomeres, has been reported to be expressed in a majority of human tumors, including several subtypes of brain tumor. We hypothesized that a quantitative assay for telomerase activity, combined with selective microdissection of tumor or normal brain cells, might reveal telomerase gain-of-function to be important in the pathogenesis of gliomas and that telomerase levels might have prognostic significance. We used tissue microdissection for selective analysis of tumor cells obtained from eight patients with glioma, one with a meningioma, and one with a primary B-cell lymphoma of the central nervous system. Normal brain tissue microdissected from another patient was used as a control. Telomerase activity was screened by an electrophoretic method and then assayed by a quantitative ELISA method. All of the eight gliomas had positive telomerase activity, as did the lymphoma. The meningioma and normal brain were negative. Quantitative analysis of telomerase activity did not correlate with tumor grade nor predict outcome. Selective tissue microdissection, combined with qualitative and quantitative telomerase assays, permits rapid and reliable detection of telomerase activity in diverse brain tumor tissues. These preliminary findings suggest that telomerase reactivation is a frequent event in glioma tumorigenesis that can be sensitively and specifically detected in gliomas of all histologic grades. Furthermore, specific detection of telomerase reactivation represents another mechanism by which tumor formation and progression might become the target of novel therapeutics.

Variables affecting convection-enhanced delivery to the striatum: a systematic examination of rate of infusion, cannula size, infusate concentration, and tissue-cannula sealing time.

OBJECT: Although recent studies have shown that convection can be used to distribute macromolecules within the central nervous system (CNS) in a homogeneous, targeted fashion over clinically significant volumes and that the volume of infusion and target location (gray as opposed to white matter) influence distribution, little is known about other factors that may influence optimum use of convection-enhanced distribution. To understand the variables that affect convective delivery more fully, we examined the rate of infusion, delivery cannula size, concentration of infusate, and preinfusion sealing time. METHODS: The authors used convection to deliver 4 microl of 14C-albumin to the striatum of 40 rats. The effect of the rate of infusion (0.1, 0.5, 1, and 5 microl/minute), cannula size (32, 28, and 22 gauge), concentration of infusate (100%, 50%, and 25%), and preinfusion sealing time (0 and 70 minutes) on convective delivery was examined using quantitative autoradiography, National Institutes of Health image analysis software, scintillation analysis, and histological analysis. Higher rates of infusion (1 and 5 microl/minute) caused significantly (p < 0.05) more leakback of infusate (22.7+/-11.7% and 30.3+/-7.8% [mean+/-standard deviation], respectively) compared with lower rates (0.1 microl/minute [4+/-3.6%] and 0.5 microl/minute [5.2+/-3.6%]). Recovery of infusate was significantly (p < 0.05) higher at the infusion rate of 0.1 microl/minute (95.1+/-2.8%) compared with higher rates (85.2+/-4%). The use of large cannulae (28 and 22 gauge) produced significantly (p < 0.05) more leakback (35.7+/-8.1% and 21.1+/-7.5%, respectively) than the smaller cannula (32 gauge [5.2+/-3.6%]). Varying the concentration of the infusate and the preinfusion sealing time did not alter the volume of distribution, regional distribution, or infusate recovery. CONCLUSIONS: Rate of infusion and cannula size can significantly affect convective distribution of molecules, whereas preinfusion sealing time and variations in infusate concentration have no effect in this small animal model. Understanding the parameters that influence convective delivery within the CNS can be used to enhance delivery of potentially therapeutic agents in an experimental setting and to indicate the variables that will need to be considered for optimum use of this approach for drug delivery in the clinical setting.

Direct convective delivery of macromolecules to peripheral nerves.

OBJECT: Although many macromolecules have treatment potential for peripheral nerve disease, clinical use of these agents has been restricted because of limitations of delivery including systemic toxicity, heterogeneous dispersion, and inadequate distribution. In an effort to overcome these obstacles, the authors examined the use of convection to deliver and distribute macromolecules into peripheral nerves. METHODS: For convective delivery, the authors used a gas-tight, noncompliant system that provided continuous flow through a small silica cannula (inner diameter 100 microm, outer diameter 170 microm) inserted into a peripheral nerve. Increases in the volume of infusion (Vi) (10, 20, 30, 40, and 80 microl) of 14C-labeled (nine nerves) or gadolinium-labeled (two nerves) albumin were infused unilaterally or bilaterally into the tibial nerves of six primates (Macaca mulatta) at 0.5 microl/minute. The volume of distribution (Vd), percentage recovery, and delivery homogeneity were determined using quantitative autoradiography, an imaging program developed by the National Institutes of Health, magnetic resonance (MR) imaging, scintillation counting, and kurtosis (K) analysis. One animal that was infused bilaterally with gadolinium-bound albumin (40 microl to each nerve) underwent MR imaging and was observed for 16 weeks after infusion. The Vd increased with the Vi in a logarithmic fashion. The mean Vd/Vi ratio over all Vi was 3.7+/-0.8 (mean+/-standard deviation). The concentration across the perfused region was homogeneous (K=-1.07). The infusate, which was limited circumferentially by the epineurium, followed the parallel arrangement of axonal fibers and filled long segments of nerve (up to 6.8 cm). Recovery of radioactivity was 75.8+/-9%. No neurological deficits arose from infusion. CONCLUSIONS: Convective delivery of macromolecules to peripheral nerves is safe and reliable. It overcomes obstacles associated with current delivery methods and allows selective regional delivery of putative therapeutic agents to long sections of nerve. This technique should permit the development of new treatments for numerous types of peripheral nerve lesions.

Direct convective delivery of macromolecules to the spinal cord.

OBJECT: Because of the limited penetration of macromolecules across the blood-spinal cord barrier, numerous therapeutic compounds with potential for treating spinal cord disorders cannot be used effectively. The authors have developed a technique to deliver and distribute macromolecules regionally in the spinal cord by using convection in the interstitial space. METHODS: The authors designed a delivery system connected to a "floating" silica cannula (inner diameter 100 microm, outer diameter 170 microm) that provides for constant volumetric inflow to the spinal cord. A solution containing albumin that was either unlabeled or labeled with carbon-14 or gadolinium was infused at various volumes (3, 6, 10, 20, 40, or 50 microl) at a rate of 0.1 microl/minute into the spinal cord dorsal columns of nine swine and into the lateral columns of three primates (Macaca mulatta). Volume of distribution (Vd), concentration homogeneity, and percentage of recovery were determined using scintillation analysis, kurtosis calculation (K), and quantitative autoradiography (six swine), magnetic resonance imaging (one swine and three primates), and histological analysis (all animals). Neurological function was observed for up to 3 days in four of the swine and up to 16 weeks in the three primates. The Vd of 14C-albumin was linearly proportional (R2=0.97) to the volume of infusion (Vi) (Vd/Vi=4.4+/-0.5; [mean+/-standard deviation). The increases in Vd resulting from increases in Vi were primarily in the longitudinal dimension (R2=0.83 in swine; R2=0.98 in primates), allowing large segments of spinal cord (up to 4.3 cm; Vi 50 microl) to be perfused with the macromolecule. The concentration across the area of distribution was homogeneous (K=-1.1). The mean recovery of infused albumin from the spinal cord was 85.5+/-5.6%. Magnetic resonance imaging and histological analysis combined with quantitative autoradiography revealed the albumin infusate to be preferentially distributed along the white matter tracts. No animal exhibited a neurological deficit as a result of the infusion. CONCLUSIONS: Regional convective delivery provides reproducible, safe, region-specific, and homogeneous distribution of macromolecules over large longitudinal segments of the spinal cord. This delivery method overcomes many of the obstacles associated with current delivery techniques and provides for research into new treatments of various conditions of the spinal cord.

Tumor devascularization by intratumoral ethanol injection during surgery. Technical note.

Preoperative reduction in tumor vascularity has been accomplished previously by selective catheterization of tumor vessels and delivery of occlusive materials. The results of percutaneous infusion of vertebral hemangiomas and other vascular lesions led the authors to speculate that rapid devascularization of tumors by direct injection of ethanol (ETOH) could be used to reduce bleeding and facilitate resection during surgery. Thus, the use of intratumoral injection of ETOH and its effects on tumor hemostasis and resectability were examined. Four patients received direct injection of ETOH into either a spinal epidural (two renal cell carcinomas and one rhabdomyosarcoma) or a large cerebellar neoplasm (hemangioblastoma). Intraoperative perfusion of the tumors with ETOH produced immediate blanching and devascularization and enhanced visualization and resection. Incremental tumor devascularization is achieved by careful injection of small amounts of ETOH directly into the lesion, producing immediate and complete regional tumor devascularization. Use of this technique reduces intratumoral bleeding and enhances the ease and effectiveness of resection.

Bypass coaptation procedures for cervical nerve root avulsion.

In the past, patients with cervical spinal nerve root avulsions were resigned to accept a natural crippling from upper extremity neurological deficits. Recently, bypass coaptation procedures have resulted in functional return of denervated muscles after such avulsions, much to the appreciation of patients. Presented are 12 patients with avulsion of cervical spinal nerve roots that form either the brachial plexus upper trunk (n = 7), lower trunk (n = 1), or all three trunks (n = 4). The patients underwent the new bypass coaptation procedures with complete or partial return of motor and sensory function, which otherwise would be totally nonfunctional. The most dramatic results were noted in those patients who underwent operations within 6 weeks of injury. The results of these procedures offer patients a valid therapeutic modality for an enhanced quality of life after cervical nerve root avulsion.

Simultaneous bilateral pallidoansotomy for idiopathic dystonia musculorum deformans.

A 17-year-old Russian male with a 9-year diagnosed history of dystonia musculorum deformans manifested as severe tortipelvis, lordosis, and axial and appendicular spastic dystonia, refractory to medical therapy, is reported. This patient underwent a simultaneous bilateral pallidoansotomy with dramatic results. Postoperative evaluation revealed sustained alleviation of all dystonic symptoms and abnormal movements. Rapid recovery of useful strength in all limbs as well as dramatic improvement in coordination occurred. Bilateral posteroventral pallidotomy and pallidoansotomy in the past have proven effective in alleviation of all parkinsonian symptoms, including dyskinesia and dystonia, without the concurrent risk of intransigent side effects associated with bilateral thalamotomy or other stereotactic surgical procedures. Pallidoansotomy may prove to be the treatment of choice for idiopathic torsion dystonia and merits further investigation.