Can the Charlson Comorbidity Index be used to predict the ASA grade in patients undergoing spine surgery?

BACKGROUND: The American Society of Anaesthesiologists' Physical Status Score (ASA) is a key variable in predictor models of surgical outcome and "appropriate use criteria". However, at the time when such tools are being used in decision-making, the ASA rating is typically unknown. We evaluated whether the ASA class could be predicted statistically from Charlson Comorbidy Index (CCI) scores and simple demographic variables. METHODS: Using established algorithms, the CCI was calculated from the ICD-10 comorbidity codes of 11'523 spine surgery patients (62.3 ± 14.6y) who also had anaesthetist-assigned ASA scores. These were randomly split into training (N = 8078) and test (N = 3445) samples. A logistic regression model was built based on the training sample and used to predict ASA scores for the test sample and for temporal (N = 341) and external validation (N = 171) samples. RESULTS: In a simple model with just CCI predicting ASA, receiver operating characteristics (ROC) analysis revealed a cut-off of CCI ≥ 1 discriminated best between being ASA ≥ 3 versus < 3 (area under the curve (AUC), 0.70 ± 0.01, 95%CI,0.82-0.84). Multiple logistic regression analyses including age, sex, smoking, and BMI in addition to CCI gave better predictions of ASA (Nagelkerke's pseudo-R2 for predicting ASA class 1 to 4, 46.6%; for predicting ASA ≥ 3 vs. < 3, 37.5%). AUCs for discriminating ASA ≥ 3 versus < 3 from multiple logistic regression were 0.83 ± 0.01 (95%CI, 0.82-0.84) for the training sample and 0.82 ± 0.01 (95%CI, 0.81-0.84), 0.85 ± 0.02 (95%CI, 0.80-0.89), and 0.77 ± 0.04 (95%CI,0.69-0.84) for the test, temporal and external validation samples, respectively. Calibration was adequate in all validation samples. CONCLUSIONS: It was possible to predict ASA from CCI. In a simple model, CCI ≥ 1 best distinguished between ASA ≥ 3 and < 3. For a more precise prediction, regression algorithms were created based on CCI and simple demographic variables obtainable from patient interview. The availability of such algorithms may widen the utility of decision aids that rely on the ASA, where the latter is not readily available.

Heat storage in Asian elephants during submaximal exercise: behavioral regulation of thermoregulatory constraints on activity in endothermic gigantotherms.

Gigantic size presents both opportunities and challenges in thermoregulation. Allometric scaling relationships suggest that gigantic animals have difficulty dissipating metabolic heat. Large body size permits the maintenance of fairly constant core body temperatures in ectothermic animals by means of gigantothermy. Conversely, gigantothermy combined with endothermic metabolic rate and activity likely results in heat production rates that exceed heat loss rates. In tropical environments, it has been suggested that a substantial rate of heat storage might result in a potentially lethal rise in core body temperature in both elephants and endothermic dinosaurs. However, the behavioral choice of nocturnal activity might reduce heat storage. We sought to test the hypothesis that there is a functionally significant relationship between heat storage and locomotion in Asian elephants (Elephas maximus), and model the thermoregulatory constraints on activity in elephants and a similarly sized migratory dinosaur, Edmontosaurus. Pre- and post-exercise (N=37 trials) measurements of core body temperature and skin temperature, using thermography were made in two adult female Asian elephants at the Audubon Zoo in New Orleans, LA, USA. Over ambient air temperatures ranging from 8 to 34.5°C, when elephants exercised in full sun, ~56 to 100% of active metabolic heat production was stored in core body tissues. We estimate that during nocturnal activity, in the absence of solar radiation, between 5 and 64% of metabolic heat production would be stored in core tissues. Potentially lethal rates of heat storage in active elephants and Edmontosaurus could be behaviorally regulated by nocturnal activity.

Acute respiratory distress syndrome and acute lung injury in patients with vertebral column fracture(s) and spinal cord injury: a nationwide inpatient sample study.

STUDY DESIGN: Retrospective Nationwide Inpatient Sample (NIS) study. OBJECTIVES: To determine national trends in prevalence, risk factors and mortality for vertebral column fracture (VCF) and spinal cord injury (SCI) patients with and without acute respiratory distress syndrome/acute lung injury (ARDS/ALI). SETTING: United States of America, 1988 to 2008. METHODS: The NIS was utilized to select 284 612 admissions for VCF with and without acute SCI from 1988 to 2008 based on ICD-9-CM. The data were stratified for in-hospital complications of ARDS/ALI. RESULTS: Patients with SCI were more likely to develop ARDS/ALI compared with those without (odds ratio (OR): 4.9, 95% confidence interval (CI) 4.7-5.2, P<0.001). Compared with patients with lumbar fractures, those with cervical, thoracic and sacral fractures were more likely to develop ARDS/ALI (P<0.001). ARDS/ALI was statistically more prevalent (P<0.01) in VCF/SCI patients with epilepsy, sepsis, cardiac arrest, congestive heart failure (CHF), hypertension, chronic obstructive pulmonary disease and metabolic disorders. Patients with female gender, surgery at rural practice setting, and coronary artery disease and diabetes were less likely to develop ARDS/ALI (P<0.001). VCF/SCI patients who developed ARDS/ALI were more likely to die in-hospital than those without ARDS/ALI (OR 6.5, 95% CI 6.0-7.1, P<0.001). Predictors of in-hospital mortality after VCF/SCI include: older age, male sex, epilepsy, sepsis, hypertension, CHF, chronic obstructive pulmonary disease and liver disease. Patients who developed ARDS/ALI stayed a mean of 25 hospital days (30-440 days) while patients without ARDS/ALI stayed a mean of 6 days (7-868 days, P<0.001). CONCLUSION: Our analysis demonstrates that SCI patients are more at risk for ARDS/ALI, which carries a significantly higher risk of mortality.

Spinal injuries after falls from hunting tree stands.

BACKGROUND CONTEXT: Spinal injuries are common sequelae of falls from hunting tree stands. Significant neurological injury is not uncommon and can result in significant morbidity as well as enormous expenditure of health care dollars. Recent literature on the subject is limited. PURPOSE: The purpose of this study was to identify precipitating causes, characterize the spectrum of spinal injury, and determine potential interventional safety and prevention recommendations. STUDY DESIGN: A retrospective study. METHODS: Medical record review of 22 patients admitted either directly or via referral to a level I spinal cord injury referral center over a 10-year period (1995-2005) after a fall from a hunting tree stand. RESULTS: All patients were men with a mean age of 46 years (range, 27-80 years). Initial acute care hospitalization averaged 10 days (range, 2-28 days). The average height of fall was 18 feet (range, 10-30 feet). Four of 19 falls (21%) occurred during the morning hours, 2 of 19 falls occurred during the afternoon, and 13 of 19 falls (68%) occurred during the evening hours. Time lapse from injury to presentation to an emergency department ranged from 30 minutes to 14 hours. Alcohol use was a factor in 2 of 20 falls (10%). Hypothermia complicated 3 of 21 cases (14%). Associated injuries were present in 12 of 21 patients (57%) and included fractures to the axial and appendicular skeleton, pneumothoraces, a retroperitoneal bleed, and a brachial plexopathy. Eight of 22 patients (37%) sustained injury to the cervical spine. Five of these 8 patients (63%) had neurological deficits (3 complete and 2 incomplete spinal cord injuries). Thirteen of 22 (59%) patients sustained injury to the thoracic or lumbar spine. Ten of these 13 (77%) had neurologic deficits (3 complete and 7 incomplete). Nine of 22 (41%) patients were treated nonoperatively; the remaining 13 (59%) underwent operative intervention. CONCLUSIONS: Falls from hunting tree stands remain a significant cause of spinal injury and subsequent disability. The best intervention for these injuries is prevention. There is a continued need for hunter safety education to reduce the incidence of these injuries with emphasis on safety harness usage, proper installation and annual inspection of tree stands, hunting in groups with periodic contact, the use of communication devices, and abstinence from alcohol consumption while hunting.

An alloantibody to a high-prevalence MNS antigen in a person with a GP.JL/Mk phenotype.

The low-prevalence MNS blood group antigenTSEN is located at the junction of glycophorin A (GPA) to glycophorin B (GPB) in several hybrid glycophorin molecules. Extremely rare people have RBCs with a double dose of the TSEN antigen and have made an antibody to a high-prevalence MNS antigen. We report the first patient who is heterozygous for GYP.JL and Mk. During prenatal tests,an alloantibody to a high-prevalence antigen was detected in the serum of a 21-year-old Hispanic woman. The antibody detected an antigen resistant to treatment by papain, trypsin, alpha-chymotrypsin, or DTT. The antibody was strongly reactive by the IAT with all RBCs tested except those having the MkMk, GP.Hil/GP.Hil, or GP.JL/GP.JL phenotypes. The patient's RBCs typed M+N-S+/-s-U+, En(a+/-), Hut-, Mi(a-), Mur-, Vw-, Wr(a-b-), and were TSEN+, MINY+. Reactivity with Glycine soja suggested that her RBCs had a decreased level of sialic acid. Immunoblotting showed the presence of monomer and dimer forms of a GP(A-B) hybrid and an absence of GPA and GPB. Sequencing of DNA and PCR-RFLP using the restriction enzyme RsaI confirmed the presence of a hybrid GYP(AB). The patient's antibody was determined to be anti-EnaFR. She is the first person reported with the GP.JL phenotype associated with a deletion of GYPA and GYPB in trans to GYP.JL.

Thermal decomposition of generation-4 polyamidoamine dendrimer films: decomposition catalyzed by dendrimer-encapsulated Pt particles.

The thermal decomposition of hydroxyl-terminated generation-4 polyamidoamine dendrimer (G4OH) films deposited on Au surfaces has been compared with decomposition of the same dendrimer encapsulating an approximately 40-atom Pt particle (Pt-G4OH). Infrared absorption reflection spectroscopy studies showed that, when the films were heated in air to various temperatures up to 275 degrees C, the disappearance of the amide vibrational modes occurred at lower temperature for the Pt-G4OH film. Dendrimer decomposition was also investigated by thermogravimetric analysis (TGA) in both air and argon atmospheres. For the G4OH dendrimer, complete decomposition was achieved in air at 500 degrees C, while decomposition of the Pt-G4OH dendrimer was completed at 400 degrees C, leaving only platinum metal behind. In a nonoxidizing argon atmosphere, a greater fraction of the G4OH decomposed below 300 degrees C, but all of the dendrimer fragments were not removed until heating above 550 degrees C. In contrast, Pt-G4OH decomposition in argon was similar to that in air, except that decomposition occurred at temperatures approximately 15 degrees C higher. Thermal decomposition of the dendrimer films on Au surfaces was also studied by temperature programmed desorption (TPD) and X-ray photoelectron spectroscopy (XPS) under ultrahigh vacuum conditions. Heating the G4OH films to 250 degrees C during the TPD experiment induced the desorption of large dendrimer fragments at 55, 72, 84, 97, 127, 146, and 261 amu. For the Pt-G4OH films, mass fragments above 98 amu were not observed at any temperature, but much greater intensities for H(2) desorption were detected compared to that of the G4OH film. XPS studies of the G4OH films demonstrated that significant bond breaking in the dendrimer did not occur until temperatures above 250 degrees C and heating to 450 degrees C caused dissociation of C=O, C-O, and C-N bonds. For the Pt-G4OH dendrimer films, carbon-oxygen and carbon-nitrogen bond scission was observed at room temperature, and further decomposition to atomic species occurred after heating to 450 degrees C. All of these results are consistent with the fact that the Pt particles inside the G4OH dendrimer catalyze thermal decomposition, allowing dendrimer decomposition to occur at lower temperatures. However, the Pt particles also catalyze bond scission within the dendrimer fragments so that decomposition of the dendrimer to gaseous hydrogen is the dominant reaction pathway compared to desorption of the larger dendrimer fragments observed in the absence of Pt particles.

Gunshot wounds to the neck.

Gunshot wounds to the neck are diagnostically and therapeutically challenging cases. We report such a case with vascular and neurologic injuries and describe the therapeutic options. Initial treatment is aimed at hemodynamic stabilization. Zone II neck injuries are managed selectively, and physical examination alone may dictate emergency surgical exploration. Spinal cord injury must be suspected and assessed clinically, as well as by computed tomography and angiography. Deteriorating or stable neurologic status and cord compression by bullet or bone fragments require surgical decompression. Improving neurologic status may be managed conservatively. In gunshot wounds to the neck, treatment should be individualized and multidisciplinary.

Outcome study of surgical treatment for axial neck pain.

BACKGROUND: We reviewed our surgical treatment of chronic axial cervical pain over a 4-year period to determine whether surgery in selected cases was associated with favorable outcomes. METHODS: We retrospectively studied 27 consecutive cases (20 patients with follow-up) of longstanding axial cervical spine pain treated surgically by a single surgeon from June 1994 through August 1998. Diagnostic workup included the following when appropriate: Minnesota Multiphasic Personality Inventory (MMPI) with interview, provocative diskography (with a nonpainful control level), single photon emission computed tomography (SPECT), and diagnostic facet injection. Twenty patients (74%) responded to a postoperative telephone survey. RESULTS: For general outcome measures, 85% of patients reported satisfaction with pain relief and surgical result. Ninety-five percent stated they would repeat the procedure; 85% manifested improvement in Prolo score. CONCLUSIONS: Surgical treatment of chronic axial neck pain, when preceded by thorough evaluation, can yield excellent clinical results.

Root and spinal cord compression from methylmethacrylate vertebroplasty.

STUDY DESIGN: Case report and literature review. OBJECTIVES: Clinicians use methylmethacrylate vertebroplasty to treat vertebral hemangiomas, metastases, and osteoporotic fractures. Cement may leak out of the vertebral body and compress the adjacent spinal cord and nerve roots. We review a case of nerve-root and cord compression from methylmethacrylate extrusion during vertebroplasty. SUMMARY OF BACKGROUND DATA: A 50-year-old female presented with disabling thoracic back pain. A metastasis to T1 was discovered, with collapse of the vertebral body but without cord compression. Methylmethacrylate vertebroplasty was performed. After injection, portable computed tomography (CT) showed a leakage of methylmethacrylate into the C8 and T1 foramina and spinal canal. Radiculopathy and myelopathy developed. Surgical decompression using the anterior approach was necessary. METHODS: Case report. RESULTS: Early surgical intervention decompressed the neural elements and relieved the neurological deficits. CONCLUSIONS: Neurologic complications of methylmethacrylate vertebroplasty necessitate active involvement of spine surgeons in patient evaluation and management.

Convection-enhanced delivery in intact and lesioned peripheral nerve.

OBJECT: Although the use of multiple agents is efficacious in animal models of peripheral nerve injury, translation to clinical applications remains wanting. Previous agents used in trials in humans either engendered severe side effects or were ineffective. Because the blood-central nervous system barrier exists in nerves as it does in the brain, limited drug delivery poses a problem for translation of basic science advances into clinical applications. Convection-enhanced delivery (CED) is a promising adjunct to current therapies for peripheral nerve injury. In the present study the authors assessed the capacity of convection to ferry macromolecules across sites of nerve injury in rat and primate models, examined the functional effects of convection on the intact nerve, and investigated the possibility of delivering a macromolecule to the spinal cord via retrograde convection from a peripherally introduced catheter. METHODS: The authors developed a rodent model of convective delivery to lesioned sciatic nerves (injury due to crush or laceration in 76 nerves) and compared the results to a smaller series of five primates with similar injuries. In the intact nerve, convective delivery of vehicle generated only a transient neurapraxic deficit. Early after injury (postinjury Days 1, 3, 7, and 10), infusion failed to cross the site of injury in crushed or lacerated nerves. Fourteen days after crush injury, CED of radioactively-labeled albumin resulted in perfusion through the site of injury to distal growing neurites. In primates, successful convection through the site of crush injury occurred by postinjury Day 28. In contrast, in laceration models there was complete occlusion of the extracellular space to convective distribution at the site of laceration and repair, and convective distribution in the extracellular space crossed the site of injury only after there was histological evidence of completion of nerve regeneration. Finally, in two primates, retrograde infusion into the spinal cord through a peripheral nerve was achieved. CONCLUSIONS: Convection provides a safe and effective means to deliver macromolecules to regenerating neurites in crush-injured peripheral nerves. Convection block in lacerated and suture-repaired nerves indicates a significant intraneural obstruction of the extracellular space. a disruption that suggests an anatomical obstruction to extracellular and, possibly, intraaxonal flow, which may impair nerve regeneration. Through peripheral retrograde infusion, convection can be used for delivery to spinal cord gray matter. Convection-enhanced delivery provides a promising approach to distribute therapeutic agents to targeted sites for treatment of disorders of the nerve and spinal cord.

Multiple pituitary adenomas in Cushing's disease.

OBJECT: Clinically evident multiple pituitary adenomas rarely occur. The authors assess the incidence and clinical relevance of multiple adenomas in Cushing's disease. METHODS: A prospective clinical database of 660 pituitary surgeries was analyzed to assess the incidence of multiple pituitary adenomas in Cushing's disease. Relevant radiographic scans, medical records, and histopathological reports were reviewed. Thirteen patients with at least two separate histopathologically confirmed pituitary adenomas were identified. Prolactinomas (nine patients) were the most common incidental tumors. Other incidental tumors included secretors of growth hormone ([GH], one patient) and GH and prolactin (two patients), and a null-cell tumor (one patient). In two patients, early repeated surgery was performed because the initial operation failed to correct hypercortisolism, in one instance because the tumor excised at the initial surgery was a prolactinoma, not an adrenocorticotropic hormone-secreting tumor. One patient had three distinct tumors. CONCLUSIONS: Multiple pituitary adenomas are rare, but may complicate management of patients with pituitary disease.

Osteochondroma of the C5 lamina with cord compression: case report and review of the literature.

STUDY DESIGN: Case report of a solitary osteochondroma of the cervical spine causing myelopathy in a 66-year-old woman. OBJECTIVES: To review the relevant literature and describe a highly unusual clinical manifestation of solitary osteochondroma. SUMMARY OF BACKGROUND DATA: Osteochondromas are common benign bony lesions that seldom occur in the axial skeleton. These lesions are more commonly reported with neural compression in cases of hereditary multiple exostoses (Bessel-Hagel syndrome, diaphyseal aclasis). METHODS: Chart review, review of relevant radiographic examinations and histopathologic specimens, clinical follow-up with examination, and literature review. RESULTS: Manifestation with new neurologic deficit in a 66-year-old patient was singular. CONCLUSIONS: Osteochondromas are unusual in the axial skeleton, and are rarely signaled by neural compression. Occurrence is generally in young adults in the second and third decades. Initial manifestation with a new neurologic deficit in a 66-year-old patient was highly unusual.

Increased MRI signal intensity in association with myelopathy and cervical instability: case report and review of the literature.

BACKGROUND: Increased T2-weighted signal intensity in patients with cervical myelopathy has been extensively reviewed in the literature. A variety of etiologies with similar MRI appearances have been described; attempt at correlation of MRI findings with clinical presentation and outcomes after treatment has led to a limited consensus. METHODS: We present a case of cervical myelopathy with associated hyperintense T2-weighted signal characteristics, secondary to cervical spondylosis and instability. RESULTS: Rapid resolution of radiographic abnormalities after surgical decompression and fusion was noted. Clinical improvement did not parallel radiographic resolution. CONCLUSION: These findings are important in considering the pathophysiology of MRI changes in cervical myelopathy.

Arteriovenous fistula with associated aneurysms coexisting with dural arteriovenous malformation of the anterior inferior falx. Case report and review of the literature.

This 24-year-old man presented with an unusual case of a high-flow arteriovenous fistula (AVF). This lesion was similar to giant AVFs in children that have been previously described in the literature. In patients in whom abnormalities of the vein of Galen have been excluded and in whom presentation occurs after 20 years of age, a diagnosis of congenital AVF is quite unusual. The fistula in this case originated in an enlarged callosomarginal artery and drained into the superior sagittal sinus via a saccular vascular abnormality. Two giant aneurysmal dilations of the fistula were present. In an associated finding, a small falcine dural arteriovenous malformation (AVM) was also present. Arterial supply to the AVM arose from both external carotid arteries and the left vertebral artery, with drainage through an aberrant vein in the region of the inferior sagittal sinus into the vein of Galen. Craniotomy with exposure and trapping of the AVF was performed, with subsequent radiosurgical (linear accelerator) treatment of the dural AVM. Through this combination of microsurgical trapping of the AVF and radiotherapy of the dural AVM, an excellent clinical outcome was achieved.

Intramedullary tuberculoma of the spinal cord. Case report and review of the literature.

Intramedullary spinal tuberculosis infection remains an extremely rare disease entity. In the most recent reviews only 148 cases have been reported in the world literature, although numerous recent reports from developing countries and on human immunodeficiency virus (HIV)-positive patients have increased this number. The authors present an unusual case of intramedullary tuberculoma in an HIV-negative patient from the southern United States who demonstrated no other signs or symptoms of tuberculosis infection. The authors believe that this is the first case of its kind to be presented in recent literature. The presentation of miliary disease via an isolated intramedullary spinal mass in a patient with no evident risk factors for tuberculosis infection emphasizes the importance of including tuberculosis in the differential diagnosis of spinal cord masses.

Long-term survival of fetal porcine lateral ganglionic eminence cells in the hippocampus of rats.

Embryonic porcine brain tissue from the lateral ganglionic eminence was transplanted into the adult rat hippocampus to determine whether fetal striatal cells could survive, differentiate, and integrate in a heterotopic site. The hippocampus, a common site of epileptic seizure activity, was chosen to determine if fetal striatal cells could supply inhibitory GABAergic neurons that may serve to block seizures. Cells were either implanted with a single deposit using a standard metal cannula or by five smaller disseminated deposits with a glass micropipette. At 20-24 weeks, animals immunosuppressed with cyclosporin showed long-term survival of porcine cells in the adult hippocampus. Analysis by immunohistochemistry and in situ hybridization showed that the grafts contained glial and neuronal cell types, including GABAergic neurons within graft core and networks of porcine neuronal fibers extending from the graft into the host parenchyma. In addition, a marker of porcine presynaptic terminals, synaptobrevin, was abundant within the grafts and was found associated with hippocampal structures and cell layers suggesting functional integration of grafted cells within the host. The survival of xenografts in the hippocampus and potential integration of inhibitory components provides evidence that these grafts may serve as an internal negative feedback mechanism to quench epileptiform activity.

Tethered cord syndrome in adults.

Adult onset of tethered cord syndrome is a rare pathologic entity. Its treatable nature makes early diagnosis and timely surgical intervention important goals. Because of present referral patterns, adult patients with tethered cord syndrome may present initially to their primary care physician. We present a recent representative case of adult-onset tethered cord syndrome, with emphasis on initial complaints and the symptom constellation relevant to the primary care physician. Thorough clinical history and physical examination should direct investigators to include tethered cord syndrome in the differential diagnosis of select patients.

Regulated expression of the homeobox gene, rPtx2, in the developing rat.

Using degenerate primers designed to amplify genes containing homeodomains, we have used reverse transcription and polymerase chain reaction to amplify and clone a rat homeobox gene. Based on the nucleotide and predicted amino acid sequences, the rat cDNA clone contains a high degree of sequence similarity to murine genes which are members of the paired-like class of homeobox genes (Ptx2, Otlx2, solurshin and Ptx1). Considering the high degree of sequence similarity and similar restricted expression patterns, we have named the cloned rat gene rPtx2 (rat Ptx2 homolog). Northern analysis revealed two rPtx2 transcripts expressed in the developing rat brain. Yet, only a single gene was detected by Southern blot hybridization, suggesting that multiple messages are the result of alternative transcriptional initiation, splicing or processing of a common message. The expression pattern of rPtx2 was further delineated by in situ hybridization to rat embryos. Within the brain, tissue specific expression was observed in the differentiating neural cells of the posterior hypothalamus, tegmentum, and rhombomere r1. Expression was also observed in the developing pituitary, maxilla, mandible, tongue and umbilical cord. To further study the control of Ptx2 gene expression, we used an in vitro model for neural differentiation by treating mouse embryonic stem cells with retinoic acid. Within 24 h and prior to detection of a neural phenotype in the culture, murine Ptx transcripts were induced and remained elevated for at least 6 days. This suggests that retinoic acid may be an important inductive signal which regulates the developmental and tissue-specific expression of Ptx2.

Blastula-stage stem cells can differentiate into dopaminergic and serotonergic neurons after transplantation.

In order to assess the potential of embryonic stem cells to undergo neuronal differentiation in vivo, totipotent stem cells from mouse blastocysts (D3 and E14TG2a; previously expanded in the presence of leukemia inhibitory factor) were transplanted, with or without retinoic acid pretreatment, into adult mouse brain, adult lesioned rat brain, and into the mouse kidney capsule. Intracerebral grafts survived in 61% of cyclosporine immunosuppressed rats and 100% of mouse hosts, exhibited variable size and morphology, and both intracerebral and kidney capsule grafts developed large numbers of cells exhibiting neuronal morphology and immunoreactivity for neurofilament, neuron-specific enolase, tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT), and cells immunoreactive for glial fibrillary acidic protein. Though graft size and histology were variable, typical grafts of 5-10 mm3 contained 10-20,000 TH+ neurons, whereas dopamine-beta-hydroxylase+ cells were rare. Most grafts also included nonneuronal regions. In intracerebral grafts, large numbers of astrocytes immunoreactive for glial fibrillary acidic protein were present. Both TH+ and 5-HT+ axons from intracerebral grafts grew into regions of the dopamine-lesioned host striatum. TH+ axons grew preferentially into striatal gray matter, while 5-HT+ axons showed no white/gray matter preference. These findings demonstrate that transplantation to the brain or kidney capsule can induce a significant fraction of totipotent embryonic stem cells to become putative dopaminergic or serotonergic neurons and that when transplanted to the brain these neurons are capable of innervating the adult host striatum.