Irreversible Deficits Research Articles

Cognition, behavior, and respiratory function in amyotrophic lateral sclerosis.

Objective. To examine the relationship between respiratory functioning and neuropsychological performance, mood, and frontal-lobe-mediated behaviors in ALS patients. Methods. Forty-four patients with probable or definite ALS (El Escorial criteria) completed comprehensive pulmonary and neuropsychological assessments as part of their baseline neurological evaluation. Based on their full vital respiratory capacity, 24 and 20 patients were classified as having impaired or intact respiration, respectively. Results. Comparable demographic characteristics, neuropsychological performance, and self-reported mood symptoms were found between ALS patients with intact versus impaired respiration. However, more respiratory-impaired patients were reported by their caregivers as having clinically significant impairments in frontal-lobe-mediated behaviors. Nevertheless, declines in behavior were evidenced from pre- to post-ALS symptom onset for both respiratory groups, and exploratory analyses revealed greater executive functioning deficits in patients with bulbar versus limb onset as well as respiratory-impaired patients not receiving pulmonary interventions versus those utilizing such interventions at the time of testing. Conclusions. Results suggest that the respiratory insufficiency of ALS patients may potentially produce irreversible deficits in executive functioning; yet once treated, impairments in more basic cognitive abilities may be less evident.

Atoh1 expression and function during auditory hair cell regeneration in post-hatch chickens

Loss of hair cells in humans leads to irreversible hearing deficits, since auditory hair cells are not replaced. In contrast, hair cells are regenerated in the auditory epithelium of mature birds after damage by non-sensory supporting cells that transdifferentiate into hair cells by mitotic and/or non-mitotic mechanisms. Factors controlling these processes are poorly understood. The basic helix-loop-helix transcription factor ATOH1 is both necessary and sufficient for developmental hair cell differentiation, but it is unclear if it plays the same role in the mitotic and non-mitotic pathways in hair cell regeneration. We examined Atoh1 expression and function during hair cell regeneration in chickens. Atoh1 transcripts were increased in many supporting cells in the damaged auditory epithelium shortly after ototoxin administration and later became restricted to differentiating hair cells. Fate-mapping in vitro using an Atoh1 enhancer reporter demonstrated that only 56% of the supporting cells that spontaneously upregulate Atoh1 enhancer activity after damage acquired the hair cell fate. Inhibition of notch signaling using a gamma secretase antagonist stimulated an increase in Atoh1 reporter activity and induced a higher proportion of supporting cells with Atoh1 activity (73%) to differentiate as hair cells. Forced overexpression of Atoh1 in supporting cells triggered 66% of them to acquire the hair cell fate and nearly tripled their likelihood of cell cycle entry. These findings demonstrate that Atoh1 is broadly upregulated in supporting cells after damage, but a substantial proportion of supporting cells with Atoh1 activation fails to acquire hair cell features, in part due to gamma secretase-dependent activities.

Short- and Long-Term Cognitive Effects of Chronic Cannabinoids Administration in Late-Adolescence Rats

The use of cannabis can impair cognitive function, especially short-term memory. A controversial question is whether long-term cannabis use during the late-adolescence period can cause irreversible deficits in higher brain function that persist after drug use stops. In order to examine the short- and long-term effects of chronic exposure to cannabinoids, rats were administered chronic i.p. treatment with the CB1/CB2 receptor agonist WIN55,212-2 (WIN; 1.2 mg/kg) for two weeks during the late adolescence period (post-natal days 45–60) and tested for behavioral and electrophysiological measures of cognitive performance 24 hrs, 10 and 30 days after the last drug injection. The impairing effects of chronic WIN on short-term memory in the water maze and the object recognition tasks as well as long-term potentiation (LTP) in the ventral subiculum (vSub)-nucleus accumbens (NAc) pathway were temporary as they lasted only 24 h or 10 d after withdrawal. However, chronic WIN significantly impaired hippocampal dependent short-term memory measured in the object location task 24 hrs, 10, 30, and 75 days after the last drug injection. Our findings suggest that some forms of hippocampal-dependent short-term memory are sensitive to chronic cannabinoid administration but other cognitive impairments are temporary and probably result from a residue of cannabinoids in the brain or acute withdrawal effects from cannabinoids. Understanding the effects of cannabinoids on cognitive function may provide us with tools to overcome these impairments and for cannabinoids to be more favorably considered for clinical use.

Effect of Dietary <i>Kaempferia parviflora</i> on Ischemic Brain Injury in the rat

Problem statement: Stroke often causes irreversible neuronal damage and related behavioral deficits. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional plant medicines. We investigated the ability of consuming Kaempferia parviflora extract, a Thai medicinal plant reputed for neuroprotective effects against brain damage, reduced infarct volume and improve neurological outcome in rats with permanent right Middle Cerebral Artery Occlusion (MCAO). Approach: Male adult Wistar rats were administrated an alcoholic extract of KP orally once daily at a period of 14 days before and 7 days after MCAO. Neurological function assessment was performed at 7 days after MCAO using the 6-points postural reflex test. The brain infarct volume and the densities of survival neurons in hippocampus were also determined at the end of experiment. Results: Oral administration with KP at a dose of 200 mg kg-1 BW significantly improved the neurological behavior performances and reduced the infarct volume when compared to the vehicle treated group. The reductions of survival neurons densities were also mitigated. Conclusion: The consumption of KP extract may have the possibility of protective effect against neurological disorders such as brain ischemia, while further investigations about precise underlying the defense mechanism against cerebral ischemia are still required.

Early Exposure to Environmental Toxin Contributes to Neuronal Vulnerability and Axonal Pathology in a Model of Familial ALS

Adult onset amyotrophic lateral sclerosis (ALS) arises due to progressive and irreversible functional deficits to the central nervous system, specifically the loss of motor neurons. Sporadic ALS causality is not well understood, but is almost certainly of multifactorial origin involving a combination of genetic and environmental factors. The discovery of endemic ALS in the native Chamorro population of Guam during the 1950s and the co-occurrence of Parkinsonism and dementia in some patients led to searches for environmental toxins that could be responsible. In the present paper, we report that an environmental neurotoxin enhances mutant superoxide dismutase (SOD)-induced spinal motor neuron death and pathology and induces motor axon abnormalities. These results cumulatively confirm earlier findings that exposure to an environmental toxin is sufficient to produce the disease phenotype and indicate a role for gene-environment interaction in some forms of the disease.

Delay in diagnosis of primary intradural spinal cord tumors

Background:It has been our impression in recent years that there is a significant delay in diagnosis (DID) of patients in Israel harboring intradural spinal cord tumors (IDSCTs). DID can lead to irreversible deficits and unnecessary suffering. Our goal was to identify the incidence and the specific reasons for DID of IDSCTs in patients operated upon at our institution.Methods:A retrospective record review, with additional telephone survey, of 101 patients operated upon at our institute between the years 1996 and 2009 was conducted. The patients who were not diagnosed locally and those who were diagnosed during routine spinal imaging studies as part of their basic disease check-up were excluded. Accordingly, neurofibromatosis and medical tourist patients were excluded.Results:The clinical presentation of IDSCTs in our study was similar to the descriptions given in previous reports. The average age was 41.9 ± 23.3 years. Most tumors were ependymomas, astrocytomas, and schwannomas. The most common symptoms were motor or sensory disturbance, back pain, walking disturbance, and sphincter control deficit. The median time to diagnosis was 12.0 ± 37.0 months (range 3 days to 20 years). We found DID in 82.2% of the cases. 62.4% of the cases were defined as “unreasonable delay.” The most common reasons for DID were “classical symptoms with a wrong diagnosis” and “delayed imaging.”Conclusions:Based on the results of this study, the incidence of unreasonable delays in diagnosis of primary IDSCTs in Israel is very high. In order to shorten the time to diagnosis, primary and secondary care physicians need to increase their awareness of symptoms that may be associated with these lesions. We hereby offer feedback for care providers, relevant to the diagnostic workup of these patients. Such a feedback must be delivered by neurosurgeons to the community they are serving.

Early exposure to environmental toxin contributes to neuronal vulnerability and axonal pathology in a model of familial ALS

AbstractAdult onset amyotrophic lateral sclerosis (ALS) arises due to progressive and irreversible functional deficits to the central nervous system, specifically the loss of motor neurons. Sporadic ALS causality is not well understood, but is almost certainly of multifactorial origin involving a combination of genetic and environmental factors. The discovery of endemic ALS in the native Chamorro population of Guam during the 1950s and the co-occurrence of parkinsonism and dementia in some patients led to searches for an environmental toxins that could be responsible. In the present paper, we report that an environmental neurotoxin enhances mutant superoxide dismutase (SOD)-induced spinal motor neuron death and pathology and induces motor axon abnormalities. These results cumulatively confirm earlier findings that exposure to an environmental toxin is sufficient to produce the disease phenotype and indicate a role for gene-environment interaction in some forms of the disease.

Editorial: Brain sag

Alaraj and colleagues1 report on 5 patients who, following the surgical repair of ruptured anterior communicating artery (ACoA) aneurysms aided by spinal drainage with or without fenestration of the lamina terminalis, demonstrated clinical “brain sag” with classic CT features: elongation of the midbrain and effacement of the basal cisterns. In all cases the angiogram obtained during the “sag episode” showed inferior displacement of the basilar artery when compared with the “pre-sag” angiogram, and in 3 cases, this displacement was so severe that the basilar artery kinked. Vertebral artery kinking was seen in some cases as well. In 4 of the 5 cases, brain sag was recognized in a timely fashion, and patients responded favorably to conventional maneuvers, most notably placement in the Trendelenburg position. In 3 of the 4 patients who improved with positional changes together with a blood patch or clamping of the spinal drain, a “post-sag” angiogram showed marked improvement in the displacement of the basilar artery. The fourth patient whose condition improved did not undergo post-sag angiography, as it was not deemed clinically necessary. The authors are careful to note that this angiographic picture was not seen in a similar population of patients lacking clinical brain sag who were being studied for vasospasm. While the authors’ series is small, it is carefully documented and provides dramatic evidence that the clinical symptoms of brain sag may not be solely due to mechanical displacement of the brainstem. Instead, regional posterior circulation cerebral ischemia may be a contributing factor. The fact that a surprisingly high percentage of their patients also exhibited early signs of vasospasm leads one to wonder whether brain sag is more common but becomes symptomatic only when there is concomitant vascular compromise. My initial impression, based on routine examination of early postsurgical CT scans, is that it is decidedly rare to see dramatic CT evidence of sag in an otherwise stable patient, although a more systematic review is needed. Such a review should clearly focus on ACoA aneurysms treated with spinal drainage. At my institution, our initial impression was that the combination of lamina terminalis fenestration and spinal drainage predisposes to brain sag,2 but maybe it is more a function of the subarachnoid dissection in this region given that ACoA aneurysm rupture often may have already rendered the ventricles in communication with the suprasellar cistern. In any case, since we recognized this phenomenon some years ago, we have kept all patients with spinal drainage and lamina terminalis fenestration flat in the immediate postoperative period, and we are quick to place a patient in the Trendelenburg position in the rare instance that it is needed. Using this approach we rarely need to resort to blood patch, and no patient has exhibited obvious irreversible deficits from the sag episode.3 That said, we have not looked to see whether patients with brain sag were more likely to develop delayed cerebral infarction from vasospasm or neurocognitive symptoms with delayed follow-up. While assuming the Trendelenburg position, many patients may have experienced increased systemic blood pressure, as vasospasm may have been in the differential diagnosis. Whether induced hypertension led to a more rapid reversal of symptoms was not examined. In conclusion, the proceeding paper is important because it documents for the first time the angiographic features of brain sag and leads us to reexamine what we think we know about its underlying pathophysiology, as well as how best to prevent it, treat it, and determine its true sequelae.

Comparison of performance of the Assessment of Spondyloarthritis International Society, the European Spondyloarthropathy Study Group and the modified New York criteria in a cohort of Chinese patients with spondyloarthritis

Early diagnosis of spondyloarthritis (SpA) is essential as anti-tumor necrosis factor therapy can achieve significant symptomatic relief and control of disease activity. This study aims to compare the clinical characteristics, disease activity, and functional status of a Chinese cohort of SpA patients who were re-classified into ankylosing spondylitis (AS) patients fulfilling the modified New York (MNY) criteria, those with undifferentiated SpA (USpA) fulfilling the European Spondyloarthropathy Study Group (ESSG) classification criteria only (USpA/ESSG) and those who fulfill Assessment of SpondyloArthritis International Society (ASAS) only (USpA/ASAS). Disease activity was evaluated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), severity of morning stiffness, patient global assessment, and C-reactive protein. Functional status was evaluated by Bath Ankylosing Spondylitis Functional Index (BASFI), modified Schober index, and dimension of chest expansion. One hundred and twenty-eight patients with disease duration of 16.3 ± 10.4 years were recruited. Patients in USpA/ESSG and USpA/ASAS were significantly younger (p = 0.01), had shorter disease duration (p < 0.01), and lower BASFI (p = 0.03) than established AS patients. All three groups have active disease with comparable BASDAI >3. BASFI correlated inversely with dimension of chest expansion and negatively modified Schober index in AS patients (p < 0.01) and modestly with BASDAI (r = 0.25, p < 0.01). BASFI correlated moderately with BASDAI in USpA/ESSG (r = 0.61, p < 0.01) but not with chest expansion or modified Schober index. Compared with established AS patients recognized by MNY criteria, patients fulfilling USpA defined by ESSG or ASAS criteria had earlier disease, as active disease and less irreversible functional deficit.

Detection of acute brain injury by Raman spectral signature

Brain injury can lead to irreversible tissue loss and functional deficit along with significant health care costs. Raman spectroscopy can be used as a non-invasive technique to provide detailed information on the molecular composition of diseased and damaged tissues. This technique was used to examine acute mouse brain injury, focusing on the motor cortex, a region directly involved in controlling execution of movement. The spectral profile obtained from the injured brain tissue revealed a markedly different signature, particularly in the amide I and amide III vibrational region when compared to that of healthy brain tissue. Most noticeably, there was a significant reduction of the amide I vibration at the acute injury site and the appearance of two distinct features at 1586 and 1618 cm(-1). Complementary immunohistochemical analysis of the injured brain tissue showed an abundant expression of Caspase 3 (a cysteine protease marker used for apoptosis), suggesting that the injury-induced specific Raman shifts may be correlated with cell death. Taken together, this study demonstrates that Raman spectroscopy can play an important role in detecting the changes that occur in the injured brain and provide a possible technology for monitoring the recovery process.

Epidemiology of the Origins of Airflow Limitation in Asthma

There is now conclusive evidence that, as a group, subjects with asthma have lower levels of lung function as compared with their peers and that a significant proportion of subjects with persistent asthma are at risk of developing non-fully reversible airflow limitation, the clinical hallmark of chronic obstructive pulmonary disease. Although at the population level the most conspicuous form of airflow limitation in asthma seems to be that of subjects who wheeze during the first years of life and whose symptoms persist into adult life, asthma-related lung deficits can be related to both acquired deficits in growth of lung function in childhood and steeper decline of lung function in adult life. These trajectories of lung function are likely to differ across subgroups of individuals with asthma, suggesting that different windows of opportunity may exist to modify the natural course of the disease before irreversible deficits are established. These observations indicate the importance of identifying biomarkers that can be used to target children and adults with asthma at increased risk for airflow limitation and determining whether pharmacological interventions can protect these patients from the development of chronic obstructive pulmonary disease.

Sciatic Neurilemoma a Benign Lesion with Potential Devastating Sequelae-A Case Report

Background: A neurilemoma, also known as a schwannoma, is a benign nerve sheath tumor. Although the neurilemoma is benign, it poses potential severe surgical complications such as an iatrogenic injury causing an irreversible deficit to the involved nerve, especially when the tumor is large and deep-seated. Aim and Objectives: By presenting a rare case of sciatic neurilemoma thoughtfully, surgeons may increase the familiarity of this benign lesion to avoid the unexpected devastating sequelae. Materials and Methods: A 47-year-old woman complained of a right posterior thigh mass that she had discovered two months earlier. Serial examinations showed a large neurogenic tumor about 4.8 cm in maximal diameter originating from the right sciatic nerve. Intraoperatively, we found the tumor encapsulated by the stretching nerve fibers. It was feasible to peel off these fibers from the tumor; therefore, we removed the tumor without severing the sciatic nerve. The pathology confirmed the diagnosis of neurilemoma. Results: This patient recovered uneventfully without any neurological sequelae. Conclusion: We believe that complete familiarity with the specific lesion, respect for the involved soft tissue, and meticulous surgical techniques are required to manage a deep-seated sciatic neurilemoma. The main principle is ”Do No Harm”, which means that the innocent nerve should be protected.

Neuropsychologie bei Epilepsie

In order to understand cognitive impairment associated with epilepsy, it is essential to appreciate that independent static and dynamic factors affect brain function in this disease. Whereas morphological lesions or structural changes are associated with more or less irreversible deficits, epileptic activity, seizures, and the treatment of epilepsy can cause dynamic and principally reversible impairment. The relative contribution of these factors differs depending on the type of epilepsy, the age at lesion/epilepsy onset, the localization and lateralization of epilepsy and individual demographic patient characteristics. Altered brain structure and function can result in epilepsy, but epilepsy can also alter the functional cerebral organization of the brain. Thus epilepsy-related cognitive impairment must be integrated within a developmental neuropsychological framework. The aetiology of epilepsy is strongly related to the age of onset. From a neuropsychological point of view, it makes a big difference for cognitive outcome as to whether epilepsy hits the maturing versus mature or aging brain. Dependent on this, epilepsy can result in retardation, loss of acquired functions, or accelerated mental decline. It will be demonstrated that cognitive impairments in epilepsy mostly exist from the beginning of epilepsy, that early onset lesions/epilepsy interfere with mental development, and that a progressive aetiology, severe seizures, and lesions secondary to epilepsy may accelerate mental decline. It will furthermore be discussed that uncontrolled epilepsy and epileptic activity may reversibly and irreversibly contribute to cognitive impairment. The same is demonstrated with regard to the pharmacological treatment of epilepsy. Finally, the cognitive risks and benefits of epilepsy surgery and the advantages of selective surgery will be addressed. The consequences for the neuropsychological assessment are discussed in part two of this review.

Pseudoaneurysm of axillary artery secondary to proximal humeral fracture: clinical features

We present here a case wherein the patient developed an unsuspected pseudoaneurysm (also called a false aneurysm) secondary to a low-energy proximal humeral fracture. Massive hemorrhaging from the pseudoaneurysm occurred around 4 months from the initial injury. Neurovascular deficit and necrosis were present upon examination and the limb was unsalvageable. The delay in treatment resulted in a severe and irreversible neurovascular deficit. A shoulder disarticulation was performed and postoperative progress was favorable. Early diagnosis and surgical intervention is critical to recovery in such cases. Common features and challenges associated with this sort of injury are here described based on a review of past case reports and on our own case. Although early diagnosis is difficult, the following are some clinical features of a pseudoaneurysm secondary to a proximal humeral fracture (1) delayed presentation; (2) severe anteromedial displacement of the fracture; (3) somewhat atypical symptoms such as a recurrence or persistence of shoulder swelling and pain.

The importance of hepatic encephalopathy: Pre-transplant and post-transplant

The importance of hepatic encephalopathy: Pre-transplant and post-transplant

Ethical dimensions of non-aggressive fetal management

This article discusses the clinical ethics concept of the fetus as a patient, and identifies the implications of this for non-aggressive fetal management. The clinical ethical concept of the fetus as a patient is explained by reference to the ethical principles of beneficence and respect for autonomy. We argue that non-aggressive fetal management is ethically justified when there is a very high probability -- but sometimes less than complete certainty -- about the diagnosis, and either (1) a very high probability of death as an outcome of the anomaly diagnosed, or (2) survival with a very high probability of a severe and irreversible deficit of cognitive developmental capacity as a result of the anomaly diagnosed.

Occurrence and detection of iron-deficiency anemia in infants and toddlers.

Infants and toddlers are particularly vulnerable to developing iron deficiency, which can cause irreversible deficits in neurodevelopment. Children at highest risk include premature and low birth weight infants, those who are fed cow's milk rather than breast milk or formula prior to age one, and those who drink large amounts of cow's milk as toddlers. It is important to detect iron deficiency before it becomes frank anemia through the use of appropriate laboratory tests. Hemoglobin or hematocrit testing, at around age one, has been the usual screening test. These tests, however, do not become abnormally low until frank anemia has developed. Over the past decade, research has shown the assay for reticulocyte hemoglobin content to be a much earlier indicator of iron deficiency. This article provides an overview of the epidemiology, occurrence, and detection of iron deficiency and iron deficiency anemia in young children as well as a comparison of the utility of various laboratory tests.

Irreversible Lung Function Deficits in Young Adults With a History of Childhood Asthma

Limb SL, Brown KC, Wood RA, et al. J Allergy Clin Immunol. 2005;116:1213–1219 PURPOSE OF THE STUDY. Asthma is traditionally characterized as reversible airway obstruction. Yet, it is readily apparent that some individuals develop varying degrees of fixed obstruction associated with structural changes in the airway and that such a course is often marked early in life. These investigators sought to study the frequency, severity, and reversibility of pulmonary deficits in adults with a history of previously well-characterized moderate-to-severe childhood allergic asthma. STUDY POPULATION. Subjects (N = 121) previously enrolled onto a randomized trial of immunotherapy for childhood asthma were recalled. This original group, aged 5 to 12 years at randomization between 1984 and 1994, had physician-diagnosed asthma and required daily medications for at least 1 year before enrollment. The original study evaluations included daily symptom diaries, home visits, allergy skin testing, and methacholine challenges with associated spirometry. The primary outcome variable was daily medication-usage score as a measure of disease severity. No differences between the placebo and active-immunotherapy groups were appreciated over the course of the study; both groups saw decreases in medication use and methacholine sensitivity. METHODS. With the current study, an attempt was made to contact all 121 original study subjects, now aged 18 to 31 years. Subjects underwent spirometry and allergy skin testing, and interim medical histories were taken. Individuals with postbronchodilator forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), or FEV1/FVC of ≤5th percentile or at least 2 of these parameters at &amp;lt;10th percentile were categorized as abnormal. These subjects were prescribed 1 mg/kg per day prednisone for 1 week before follow-up pulmonary-function testing, physical examination, and a chest radiograph to assess steroid responsiveness of lung deficits. RESULTS. Of the 84 subjects reevaluated, 40 (48%) had ≥1 abnormal spirometric index (P &amp;lt; .0001). Of these 40 subjects, 28 were reassessed after prednisone, and 21 (75%) did not improve. Adult and childhood spirometric results were positively correlated. Abnormal adult spirometric results were associated with a longer duration of asthma at enrollment in the original trial, increased childhood methacholine sensitivity, and birth prematurity. Childhood immunotherapy status was unrelated to adult lung function. CONCLUSIONS. Many adults with a history of moderate-to-severe allergic asthma in childhood have irreversible lung-function deficits. Childhood parameters that might identify such individuals at a young age include spirometry, duration of asthma, methacholine sensitivity, and birth prematurity. REVIEWER COMMENTS. The authors pointed out that their findings mesh with others’ observations of early disease magnitude, including measurable airway obstruction, which serves as a major predictor of continuation of significant disease into adulthood. Should not every child on maintenance asthma-drug therapy have spirometry results documented, if not monitored? Because all subjects in the current study were allergic, allergy itself did not stand out here as a risk factor, although it most definitely was. To date, no drug-therapy intervention convincingly alters this disease entrenchment.

Spectrum and Risk Factors of Complications After Gastric Bypass

To study the spectrum of and risk factors for complications after gastric bypass (GBP). Prospective cohort study. Academic tertiary referral center. All morbidly obese patients who underwent open or laparoscopic GBP between January 2003 and December 2006. Complications were stratified by grade: grade I, only bedside procedure; grade II, therapeutic intervention but without lasting disability; grade III, irreversible deficits; and grade IV, death. Data were analyzed using logistic regression to identify independent risk factors of complications after GBP. Predictors investigated were age, race, sex, marital and insurance status, body mass index, obesity-associated comorbidities, American Society of Anesthesiologists Physical Status Class, operating room time, open or laparoscopic approach, and surgeon experience. Of the 404 morbidly obese patients who underwent consecutive open (n = 72) or laparoscopic (n = 332) GBP, 74 (18.3%) experienced 107 complications. Grade I and II complications were more frequent after open GBP (grade I, 19.4% after open vs 3.9% after laparoscopic operations, P < .001; grade II, 20.8% after open vs 8.4% after laparoscopic operations, P < .001), and 55% were wound related. Grades III and IV complications occurred in only 4 patients (1%), and frequency was similar for open and laparoscopic cases. Three factors were independently predictive of complications: diabetes mellitus (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.3; P = .02), early surgeon experience (OR, 2.5; 95% CI, 1.4-4.2; P = .001), and open approach (OR, 3.9; 95% CI, 2.1-7.3; P < .001). Complications occurred in 18.3% of patients, but 95% were treated without leading to lasting disability. Presence of diabetes, early surgeon experience, and an open approach are risk factors of complications.

Reestablishment of damaged adult motor pathways by grafted embryonic cortical neurons

Damage to the adult motor cortex leads to severe and frequently irreversible deficits in motor function. Transplantation of embryonic cortical neurons into the damaged adult motor cortex was previously shown to induce partial recovery, but reports on graft efferents have varied from no efferent projections to sparse innervation. Here, we grafted embryonic cortical tissue from transgenic mice overexpressing a green fluorescent protein into the damaged motor cortex of adult mice. Grafted neurons developed efferent projections to appropriate cortical and subcortical host targets, including the thalamus and spinal cord. These projections were not a result of cell fusion between the transplant and the host neurons. Host and transplanted neurons formed synaptic contacts and numerous graft efferents were myelinated. These findings demonstrate that there is substantial anatomical reestablishment of cortical circuitry following embryonic cortex grafting into the adult brain. They suggest that there is an unsuspected potential for neural cell transplantation to promote reconstruction after brain injury.