Clinical Neurological Outcome Research Articles

Diagnosis and treatment of posterior reversible encephalopathy syndrome in children

Objective Three patients with posterior reversible encephalopathy syndrome (PRES) in childhood were reviewed retrospectively in this study.There were 1 case(case 1) with hypertension due to hyperreninism, and 2 patients (case 2 and case 3)with induction chemotherapy for childhood acute lymphoblastic leukemia (ALL). Clinical radiological features, electroencephalogram (EEG) data and neurological outcomes of the cases were analyzed with related literature reviews to highlight the clinical features of PRES in childhood. Methods Retrospective analysis was made in terms of etiology, clinical manifestations, magnetic resonance imaging (MRI) scanning of the brain, EEG and neurological outcomes of 3 cases of PRES. Results Present symptoms included seizures, altered mental function, hea-dache and visual disturbance, with hypertension or the blood pressure 25% higher than the baseline.Typical PRES findings were seen in 2 patients, consisting of bilateral symmetrical in parietal and occipital lobes, and 1 case with extensive involvement in bilateral frontotemporal lobe in adition.Case 2 and case 3 had epileptiform discharges on their EEG, while continuous EEG monitoring found non-convulsive status epilepticus(NCSE) in case 3 who had experienced status epilepticus(SE). Case 1 showed complete recovery after antihypertensive treatment during the acute stage; Associated offending chemotherapeutic agents were withdrawn in both case 2 and case 3, while dexamethasone plus variety of anti-epileptic agents were provided in case 3, and case 2 remained neurologically normal during the following 3 years.Case 3 subsequently developed refractory epilepsy and was found with hippocampal sclerosis in MRI after 1.5 years. Conclusions Hypertension and ALL induction chemotherapy regimens comprised the main predisposing factors for PRES in these cases.There is a high rate of convulsions incidence in children.PRES is not fully reversible, SE and NCSE during acute stage will cause sequelae and refractory epilepsy.High-dose steroids may trigger PRES, which should be used with caution in treatment of PRES. Key words: Posterior reversible encephalopathy syndrome; Magnetic resonance imaging; Electroencephalogram; Treatment; Clinical manifestation; Child

G100(P) Hyperinsulinaemic Hypoglycaemia of Short Duration – Can It Be Associated with Severe Hypoglycaemic Brain Injury?

BackgroundNeurological damage is a known risk associated with hyperinsulinaemic hypoglycaemia (HH). Insulin suppresses ketone body formation and hence no alternative fuels are available for the brain to use; however it...

Aprikalim a potassium adenosine triphosphate channel opener reduces neurologic injury in a rabbit model of spinal cord ischemia

BackgroundPotassium adenosine triphosphate (KATP) channel openers have been involved in the enhancement of ischemic tolerance in various tissues. The purpose of the present study is to evaluate the effects of aprikalim, a specific KATP channel opener, on spinal cord ischemic injury. MethodsFifty-four rabbits were randomly assigned to three groups: group 1 (n = 18, sham operation), group 2 (n = 18, 30 min of normothermic aortic cross-clamping) and group 3 (n = 18, aprikalim 100 μg/kg was administered 15 min before 30 min of normothermic aortic cross-clamping). Neurologic evaluation was performed according to the modified Tarlov scale. Six animals from each group were sacrificed at 24, 48 and 168 h postoperatively. The lumbar spinal cords were harvested and examined histologically. The motor neurons were counted and the histologic lesions were scored (0–3, 3: normal). ResultsGroup 3 (aprikalim group) had better Tarlov scores compared to group 2 at all-time points (P < 0.025). The histologic changes were proportional to the Tarlov scores and group 3 had better functional outcome as compared to group 2 at 168 h (number of neurons: 21.2 ± 4.9 vs. 8.0 ± 2.7, P < 0.001 and histologic score: 1.67 ± 1.03 vs. 0.50 ± 0.55, P = 0.03). Although aprikalim exhibited improved effect on clinical and histologic neurologic outcome when compared to normothermic spinal cord ischemia, animals in group 3 had worse Tarlov score, reduced number of motor neurons and worse histologic score when compared to group 1 (sham operation) at 168 h (P = 0.003, P = 0.001 and P = 0.019 respectively). ConclusionAprikalim reduces the severity of spinal cord ischemic injury in a rabbit model of spinal cord ischemia.

Compound heterozygosity of two functional null mutations in the ALPL gene associated with deleterious neurological outcome in an infant with hypophosphatasia

Hypophosphatasia (HPP) is a heterogeneous rare, inherited disorder of bone and mineral metabolism caused by different mutations in the ALPL gene encoding the isoenzyme, tissue-nonspecific alkaline phosphatase (TNAP). Prognosis is very poor in severe perinatal forms with most patients dying from pulmonary complications of their skeletal disease. TNAP deficiency, however, may also result in neurological symptoms such as neonatal seizures. The exact biological role of TNAP in the human brain is still not known and the pathophysiology of neurological symptoms due to TNAP deficiency in HPP is not understood in detail. In this report, we describe the clinical features and functional studies of a patient with severe perinatal HPP which presented with rapidly progressive encephalopathy caused by new compound heterozygous mutations in the ALPL gene which result in a functional ALPL “knock out”, demonstrated in vitro. In contrast, an in vitro simulation of the genetic status of his currently asymptomatic parents who are both heterozygous for one mutation, showed a residual in vitro AP activity of above 50%. Interestingly, in our patient, the fatal outcome was due to progressive encephalopathy which was refractory to antiepileptic therapy including pyridoxine, rather than hypomineralization and respiratory insufficiency often seen in HPP patients. The patient's cranial MRI showed progressive cystic degradation of the cortex and peripheral white matter with nearly complete destruction of the cerebrum. To our knowledge, this is the first MRI-based report of a deleterious neurological clinical outcome due to a progressive encephalopathy in an infant harboring a functional human ALPL “knock out”.This clinical course of disease suggests that TNAP is involved in development and may be responsible for multiple functions of the human brain. According to our data, a certain amount of residual TNAP activity might be mandatory for normal CNS function in newborns and early childhood.

Hypovolemia in Extracorporeal Life Support Can Lead to Arterial Gaseous Microemboli

Next to severely decreased pump flow, hypovolemia in extracorporeal life support (ELS) can result in subatmospheric venous line pressure. Such pressure may lead to degassing and resultant gaseous microemboli (GME), with potential changes in neurological clinical outcome. CME activity resulting from degassing was investigated in relation to subatmospheric venous line pressure, partial oxygen pressure (pO2 ), and hematocrit in a model of a centrifugal pump-based circuit for long-term ELS. Additionally, a device that provides instantaneous volume buffer capacity during hypovolemia was evaluated in relation to GME appearance. An exponential relationship was found between decreasing venous line pressure and GME downstream of the centrifugal pump (P = 0.001). Arterial bubble activity appeared at subatmospheric venous line pressures of -200 mm Hg and less. A rising (pO2 ) increased formation of GME (P = 0.05). A rise in hematocrit, in contrast, did not affect embolic activity (P = 0.22). With simulated hypovolemia, volume buffer capacity added to the venous line dampened fluctuations of venous line pressure by approximately 40%, but a significant reduction in GME formation could not be found (P = 0.22). Moreover, the device enabled a 14% higher support flow. With ELS flow being related to patient volume status, hypovolemia can diminish support. A coherent decrease of venous line pressure triggers degassing of blood-dissolved gases and causes arterial GME, which can become massive during persistent conditions of limited venous return. Incorporation of a volume buffer capacity device into the extracorporeal support circuit enables a higher and more stable support flow in critically low patient filling.

Abstract WP88: Predictors of Outcome for Procedural Perforation During Coiling of Intracranial Aneurysms: A Single Center Experience

Background: Despite significant advances in coil embolization of intracranial aneurysms (IA), intra-procedural perforation (IPP) remains a dreaded complication associated with significant morbidity (up to 50%) and mortality (up to38%). Objective: In this study, we sought to analyze all IPP during IA coiling at our center over a 10 year period to determine what characteristics may predict outcome. Methods: This is a retrospective chart review of 1029 consecutive patients who underwent IA coiling from January 2002-May 2012. Variables evaluated included clinical presentation, aneurysm location, morphological aspects and neurological outcomes at discharge. Good outcomes were defined as modified Rankin scale (mRS) 1-3. Results: IPP occurred in 24 patients (2.3% of the cohort). Of all IPP, 83% occurred in previously ruptured IA, 17% in unruptured IA. This corresponded to an overall IPP rate of 4% and 0.8% respectively. Overall morbidity at discharge (mRS 4,5) was 31.8% and mortality 8.3%. Overall, good outcome was noted in 44.4% immediately post-procedure and 68.2% at discharge. Among patients with unruptured IA and those with good Hunt-Hess (HH) grade (1-3), 92% had good outcome at discharge vs. 54.6% with poor HH, p=0.03. Patients with proximal IA (proximal to internal carotid artery bifurcation or close to basilar artery stem) had better discharge outcomes (41.7%) than distal IA (33.3%), p= 0.04; this was statistically significant after controlling for HH in logistic regression analysis. Between 2002-2007, balloon-assisted coiling (BAC) was utilized in only 20% of IPP cases and 2 mortalities were recorded. After 2007, BAC was used in 60% of IPP cases with no subsequent mortalities. Conclusion: It appears that the incidence of IPP is very low, with good outcomes occurring in a significant portion of the patients. Patients with good neurological exam at presentation are likely to have good discharge outcomes despite IPP. Proximal IA are associated with better discharge outcomes: IPP in this location may be easier to control endovascularly. Techniques like BAC allow for prompt hemostasis once IPP occurs, and might reduce mortality rates.

Motor evoked potentials and compound muscle action potentials as prognostic tools for neonates with spina bifida

MEPs and CMAPs as prognostic tools for spina bifida. AimThe aim of this prospective study was to determine the prognostic value of neurophysiological investigations compared to clinical neurological examination in infants with spina bifida. MethodsThirty-six neonates born with spina bifida between 2002 and 2007 were evaluated and followed for 2 years. Lumbar motor evoked potentials (MEPs) and compound muscle action potentials (CMAPs) were obtained at the median age of 2 days old before surgical closure of the spinal anomaly. MEPs were recorded from the quadriceps femoris, tibialis anterior, and gastrocnemius muscles and CMAPs from the latter two muscles. Areas under the curve and latencies of the MEPs and CMAPs were measured. Clinical neurological outcome at the age of 2 years was described using Muscle Function Classes (MFCs) and ambulation status. ResultsThe areas under the curve of MEPs and CMAPs in the legs were associated with lower neonatal levels of motor and sensory impairment. Better muscle function class of the lower limbs at 2 years of age was associated with larger MEP and CMAP areas of the gastrocnemius and tibialis anterior muscles at neonatal age. DiscussionMEPs and CMAPs of the gastrocnemius and tibialis anterior muscles are of prognostic value for clinical neurological outcome in neonates born with spina bifida.

Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity

Chemotherapy-induced neurotoxicity is a serious consequence of cancer treatment, which occurs with some of the most commonly used chemotherapies1,2. Chemotherapy-induced peripheral neuropathy produces symptoms of numbness and paraesthesia in the limbs and may progress to difficulties with fine motor skills and walking, leading to functional impairment. In addition to producing troubling symptoms, chemotherapy-induced neuropathy may limit treatment success leading to dose reduction or early cessation of treatment. Neuropathic symptoms may persist long-term, leaving permanent nerve damage in patients with an otherwise good prognosis3. As chemotherapy is utilised more often as a preventative measure, and survival rates increase, the importance of long-lasting and significant neurotoxicity will increase. There are no established neuroprotective or treatment options and a lack of sensitive assessment methods. Appropriate assessment of neurotoxicity will be critical as a prognostic factor and as suitable endpoints for future trials of neuroprotective agents. Current methods to assess the severity of chemotherapy-induced neuropathy utilise clinician-based grading scales which have been demonstrated to lack sensitivity to change and inter-observer objectivity4. Conventional nerve conduction studies provide information about compound action potential amplitude and conduction velocity, which are relatively non-specific measures and do not provide insight into ion channel function or resting membrane potential. Accordingly, prior studies have demonstrated that conventional nerve conduction studies are not sensitive to early change in chemotherapy-induced neurotoxicity4-6. In comparison, nerve excitability studies utilize threshold tracking techniques which have been developed to enable assessment of ion channels, pumps and exchangers in vivo in large myelinated human axons7-9. Nerve excitability techniques have been established as a tool to examine the development and severity of chemotherapy-induced neurotoxicity10-13. Comprising a number of excitability parameters, nerve excitability studies can be used to assess acute neurotoxicity arising immediately following infusion and the development of chronic, cumulative neurotoxicity. Nerve excitability techniques are feasible in the clinical setting, with each test requiring only 5 -10 minutes to complete. Nerve excitability equipment is readily commercially available, and a portable system has been devised so that patients can be tested in situ in the infusion centre setting. In addition, these techniques can be adapted for use in multiple chemotherapies. In patients treated with the chemotherapy oxaliplatin, primarily utilised for colorectal cancer, nerve excitability techniques provide a method to identify patients at-risk for neurotoxicity prior to the onset of chronic neuropathy. Nerve excitability studies have revealed the development of an acute Na+ channelopathy in motor and sensory axons10-13. Importantly, patients who demonstrated changes in excitability in early treatment were subsequently more likely to develop moderate to severe neurotoxicity11. However, across treatment, striking longitudinal changes were identified only in sensory axons which were able to predict clinical neurological outcome in 80% of patients10. These changes demonstrated a different pattern to those seen acutely following oxaliplatin infusion, and most likely reflect the development of significant axonal damage and membrane potential change in sensory nerves which develops longitudinally during oxaliplatin treatment10. Significant abnormalities developed during early treatment, prior to any reduction in conventional measures of nerve function, suggesting that excitability parameters may provide a sensitive biomarker.

Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity

Chemotherapy-induced neurotoxicity is a serious consequence of cancer treatment, which occurs with some of the most commonly used chemotherapies1,2. Chemotherapy-induced peripheral neuropathy produces symptoms of numbness and paraesthesia in the limbs and may progress to difficulties with fine motor skills and walking, leading to functional impairment. In addition to producing troubling symptoms, chemotherapy-induced neuropathy may limit treatment success leading to dose reduction or early cessation of treatment. Neuropathic symptoms may persist long-term, leaving permanent nerve damage in patients with an otherwise good prognosis3. As chemotherapy is utilised more often as a preventative measure, and survival rates increase, the importance of long-lasting and significant neurotoxicity will increase.There are no established neuroprotective or treatment options and a lack of sensitive assessment methods. Appropriate assessment of neurotoxicity will be critical as a prognostic factor and as suitable endpoints for future trials of neuroprotective agents. Current methods to assess the severity of chemotherapy-induced neuropathy utilise clinician-based grading scales which have been demonstrated to lack sensitivity to change and inter-observer objectivity4. Conventional nerve conduction studies provide information about compound action potential amplitude and conduction velocity, which are relatively non-specific measures and do not provide insight into ion channel function or resting membrane potential. Accordingly, prior studies have demonstrated that conventional nerve conduction studies are not sensitive to early change in chemotherapy-induced neurotoxicity4-6. In comparison, nerve excitability studies utilize threshold tracking techniques which have been developed to enable assessment of ion channels, pumps and exchangers in vivo in large myelinated human axons7-9.Nerve excitability techniques have been established as a tool to examine the development and severity of chemotherapy-induced neurotoxicity10-13. Comprising a number of excitability parameters, nerve excitability studies can be used to assess acute neurotoxicity arising immediately following infusion and the development of chronic, cumulative neurotoxicity. Nerve excitability techniques are feasible in the clinical setting, with each test requiring only 5 -10 minutes to complete. Nerve excitability equipment is readily commercially available, and a portable system has been devised so that patients can be tested in situ in the infusion centre setting. In addition, these techniques can be adapted for use in multiple chemotherapies.In patients treated with the chemotherapy oxaliplatin, primarily utilised for colorectal cancer, nerve excitability techniques provide a method to identify patients at-risk for neurotoxicity prior to the onset of chronic neuropathy. Nerve excitability studies have revealed the development of an acute Na+ channelopathy in motor and sensory axons10-13. Importantly, patients who demonstrated changes in excitability in early treatment were subsequently more likely to develop moderate to severe neurotoxicity11. However, across treatment, striking longitudinal changes were identified only in sensory axons which were able to predict clinical neurological outcome in 80% of patients10. These changes demonstrated a different pattern to those seen acutely following oxaliplatin infusion, and most likely reflect the development of significant axonal damage and membrane potential change in sensory nerves which develops longitudinally during oxaliplatin treatment10. Significant abnormalities developed during early treatment, prior to any reduction in conventional measures of nerve function, suggesting that excitability parameters may provide a sensitive biomarker.

Acute Ischemic Stroke in the Corpus Callosum: Characteristics, Risk Factors, and Outcomes (P03.019)

Objective: To demonstrate the clinical characteristics, risk factors, and neurological outcomes in patients with acute ischemic strokes in the corpus callosum. Background Ischemic strokes in the corpus callosum are rare. There is scant information in the literature about stroke mechanisms and functional outcomes in patients with acute ischemic strokes in the corpus callosum. Design/Methods: Retrospective chart review. The study was approved by our Institutional Review Board. Results: We identified 6 patients (1%) with acute ischemic strokes in the corpus callosum amongst consecutive strokes admitted to our stroke center between October 2010 and September 2011. Of them, 5 patients were female and 5 patients were African American. Mean age was 65 years (range 50 to 92 years). Hypertension was the most common stroke risk factor. On admission mean NIHSS score was 3 (range 1 to 6). Four patients had infarcts in the splenium, two in the genu, and one in the body of the corpus callosum confirmed with brain MRI. We found that all patients had large-artery atherosclerotic strokes using the TOAST classification after complete stroke work up including MR angiogram, echocardiogram and non-invasive cardiac monitoring during hospital stay. Mean modified Rankin Scale (mRS) score was 1 (range 0 to 2) at hospital discharge. Conclusions: Our study suggests that patients with ischemic strokes in the corpus callosum have favorable functional outcomes (mRS scores ≤ 2) in spite of the fact that all patients had large-artery atherosclerotic strokes. Further research is warranted. Disclosure: Dr. Bhole has nothing to disclose. Dr. Rochestie has nothing to disclose. Dr. Brown has nothing to disclose. Dr. Arora has nothing to disclose. Dr. Giraldo has received personal compensation for activities with Boehringer Ingelheim Pharmaceuticals, Inc. as a speaker.

Abstract 3117: Role of Methamphetamine use on Severity of Initial Presentation and Clinical Outcomes in Aneurysmal Subarachnoid Hemorrhage

Introduction: Methamphetamine is believed to have an effect on cerebral vasculature through its vasoactive properties. It has been linked to multiple medical complications, including subarachnoid hemorrhage in patients of a younger population. We hypothesized that methamphetamine use in patients with aneurysmal subarachnoid hemorrhage (aSAH) would be associated with more severe clinical presentations, adverse neurologic outcomes, and an increased incidence of vasospasm. Methods: We performed a retrospective review of patients who were admitted to the OHSU Neurosurgery service with aSAH between January 2005 and January 2011. The cases included patients who used methamphetamine, as documented by personal or family report and toxicology screening. We performed a multivariate analysis to examine the role of age, Hunt and Hess and Fisher grade on presentation, length of stay and Glascow outcome score. Results: An analysis of 374 patient charts included by criteria of having aSAH. Of these, 28 (7%) had a history of or were currently using methamphetamine as documented by a positive toxicology screen. On average the methamphetamine users were ten years younger (45.2 vs 55.9, p &lt; 0.001). Despite the young age they had significantly higher Hunt and Hess grades (3 vs 2.5 and 2, p &lt;0.001) than non-methamphetamine users and age-matched controls, respectively. Methamphetamine users had significantly higher rates of vasospasm (92.9% vs 71.1%, p= 0.015) than non-users, but there was no difference when compared to age-matched controls (92.9% vs 89.3%, p= 0.639). Methamphetamine users also had significantly lower Glascow outcome scores than age-matched non-user counterparts (3 vs 5, p&lt;0.001) but not compared to the entire non-meth user group (3 vs 4, p=0.170). There was no difference in the length of stay (18 vs 16, p=0.431 and 18 vs 14, p= 0.250) for the methamphetamine user group verses both all non-users and age-matched controls. Conclusion: Methamphetamine use is associated with more severe clinical presentation and worse neurologic outcome compared to age-matched controls. Young patients have similar rates of vasospasm regardless of methamphetamine use.

Urea cycle disorders: brain MRI and neurological outcome

Urea cycle disorders encompass several enzyme deficiencies that can result in cerebral damage, with a wide clinical spectrum from asymptomatic to severe. The goal of this study was to correlate brain MRI abnormalities in urea cycle disorders with clinical neurological sequelae to evaluate whether MRI abnormalities can assist in guiding difficult treatment decisions. We performed a retrospective chart review of patients with urea cycle disorders and symptomatic hyperammonemia. Brain MRI images were reviewed for abnormalities that correlated with severity of clinical neurological sequelae. Our case series comprises six urea cycle disorder patients, five with ornithine transcarbamylase deficiency and one with citrullinemia type 1. The observed trend in distribution of brain MRI abnormalities as the severity of neurological sequelae increased was the peri-insular region first, extending into the frontal, parietal, temporal and, finally, the occipital lobes. There was thalamic restricted diffusion in three children with prolonged hyperammonemia. Prior to death, this site is typically reported to be spared in urea cycle disorders. The pattern and extent of brain MRI abnormalities correlate with clinical neurological outcome in our case series. This suggests that brain MRI abnormalities may assist in determining prognosis and helping clinicians with subsequent treatment decisions.

Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI99-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01)

BackgroundWe recently published the results of the PCI99 randomised trial comparing the effect of a prophylactic cranial irradiation (PCI) at 25 or 36 Gy on the incidence of brain metastases (BM) in 720 patients with limited small-cell lung cancer (SCLC). As concerns about neurotoxicity were a major issue surrounding PCI, we report here midterm and long-term repeated evaluation of neurocognitive functions and quality of life (QoL). Patients and methodsAt predetermined intervals, the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and brain module were used for self-reported patient data, whereas the EORTC–Radiation Therapy Oncology Group Late Effects Normal Tissue–Subjective, Objective, Management, Analytic scale was used for clinicians’ assessment. For each scale, the unfavourable status was analysed with a logistic model including age, grade at baseline, time and PCI dose. ResultsOver the 3 years studied, there was no significant difference between the two groups in any of the 17 selected items assessing QoL and neurological and cognitive functions. We observed in both groups a mild deterioration across time of communication deficit, weakness of legs, intellectual deficit and memory (all P < 0.005). ConclusionPatients should be informed of these potential adverse effects, as well as the benefit of PCI on survival and BM. PCI with a total dose of 25 Gy remains the standard of care in limited-stage SCLC.

Long-Term Clinical Outcome of Neonatal EEG Findings

The aim of the study is to determine how specific EEG findings during neonatal period correlate with clinical outcome on follow-up. This is a retrospective study of 118 term newborns who had EEG in the first month of life and subsequent clinical assessment between 4 and 16 years. Clinical neurologic outcome was classified into "favorable" when patients had no or only mild limitation in assessment, "unfavorable" when patients had moderate to severe abnormalities in assessment, and "epilepsy" when patients had seizures. Of the 118 neonates, 36 (30.5%) had favorable and 82 (69.5%) had unfavorable outcome; 89 (75.4%) had epilepsy and 28 (23.7%) had not. Sixty-seven (57%) had abnormal EEG background of which 56 had both unfavorable outcome and epilepsy; 102 (86%) had sharp transient discharges of which 75 had unfavorable outcome; 20 (17%) had ictal epileptiform discharges of which 18 had unfavorable outcome; 98 (83%) had abnormal overall EEG impression of which 77 had unfavorable outcome and 80 had epilepsy. Abnormal EEG background (particularly suppression) during neonatal period may be predictive of Unfavorable outcome. Overall impression of EEG may be predictive of clinical outcome, even when individual parameters were not predictive. Other findings did not appear to be predictive.

Stroke Patterns in Neonatal Group B Streptococcal Meningitis

Neonatal group B streptococcus meningitis causes neurologic morbidity and mortality. Cerebrovascular involvement is a common, poorly studied, and potentially modifiable pathologic process. We hypothesized that imaging patterns of focal brain infarction are recognizable in neonatal group B streptococcal meningitis. A consecutive case series included term neonates with the following: (1) bacterial meningitis, (2) acute group B streptococcal infection (positive cerebrospinal fluid/blood culture), (3) brain magnetic resonance imaging within 14 days, and (4) acute intraparenchymal focal infarctions (restricted diffusion). Lesions within known arterial territories were classified as arterial ischemic stroke. Clinical presentations, investigations, and neurologic outcomes were recorded. Eight newborns (50% female) with focal infarction were identified. Five presented early (<1 week), and all manifested clinical shock and elevated acute-phase reactants. Less than 50% had prenatal group B streptococcal screening, while 2 of 3 screened were negative. Two distinct patterns of focal infarction were identified: (1) deep perforator arterial stroke to basal ganglia, thalamus, and periventricular white matter (7/8, 88%), and (2) superficial injury with patchy, focal infarctions of the cortical surface (6/8, 75%). Outcomes (mean 23.8 months) were poor, with severe disability or death in 6/8 (75%). Recognizable stroke patterns contribute to severe neurologic outcomes and represent a potentially modifiable pathophysiologic process in neonatal group B streptococcal meningitis.

A importância da monitorização intraoperatória multimodal nas cirurgias espinais

ResumoA monitorização intraoperatória multimodal (MIOM) tornou-se um método amplamente utilizado para monitorização da função neural durante as cirurgias espinais. Um estudo prospectivo de 52 pacientes que foram monitorados durante os procedimentos cirúrgicos, entre outubro de 2009 e dezembro de 2010, no Hospital do Servidor Público Estadual de São Paulo, a fim de determinar a sensibilidade e especificidade das técnicas utilizadas para monitorar a medula espinhal e raízes nervosas durante as cirurgias espinais. Portanto, o objetivo deste estudo prospectivo foi avaliar a eficácia da MIOM, que inclui os potenciais evocados somatossensitivos (PESS), os potenciais evocados motores com estimulação transcraniana (MEPS), a eletromiografia contínua (EMG) captada nos músculos eletricamente estimulados a partir do córtex motor, na própria medula espinal, na cauda equina e nas raízes nervosas, comparando os dados eletrofisiológicos com os achados clínicos neurológicos no pós-operatório imediato. A MIOM visa monitorar tanto as vias ascendentes quanto as descendentes, fornecendo informações com feedback imediato sobre qualquer déficit neurológico durante o procedimento que permita uma identificação rápida de possíveis danos das estruturas neurais e prevenção por meio de ações corretivas. Técnicas que visam apenas avaliar as vias ascendentes ou as vias descendentes isoladamente não podem fornecer resultados com sensitividade ou especificidade adequados. Cinquenta e dois pacientes foram submetidos à MIOM. Desses, 49 casos foram verdadeiramente negativos, dois casos foram verdadeiramente positivos e 1 caso foi falso-positivo, resultando em sensibilidade de 100% e especificidade de 98% (p &gt; 0,05). Não foram obtidos falsos-negativos. Com base nos resultados deste estudo, a MIOM é um método eficaz de monitorar a integridade funcional da medula espinal e, consequentemente, melhorar os resultados pós-operatórios.

Neurogenic pathway mediated remote preconditioning protects the brain from transient focal ischemic injury

Attenuation of ischemic injury can be achieved by priming the brain with a sub-lethal ischemic insult, a phenomenon known as ischemic preconditioning (IP). We sought to determine if subjecting a distant organ, such as the lower limb, to a similar priming ischemic insult would result in protection of the brain from a subsequent severe ischemic injury, as induced by middle cerebral artery occlusion (MCAo) and if this protection is mediated via a neurogenic pathway. Adult Wistar male rats were subjected to either remote preconditioning (RPC) or sham surgery and then subsequently underwent 2 h MCAo 24, 48 or 72 h after the RPC/sham RPC stimulus. Of the animals undergoing RPC, only those that sustained MCAo 24 h later showed significantly smaller cerebral infarct volumes (150.34 ± 30.91 mm 3) and better clinical neurological outcomes (1.15 ± 0.69) as compared to the sham RPC group (infarct volume 250.25 ± 26.98mm 3; neurological score 1.80 ± 0.87) ( P < 0.05). RPC animals sustaining MCAo at 48 and 72 h later did not show significant differences in cerebral infarct volumes or clinical neurological outcomes as compared to the sham RPC group. Furthermore, attenuation of the neuroprotective effect by the ganglion blocker hexamethonium suggested a neurogenically mediated pathway responsible for this phenomenon. Remote sub-lethal ischemic injury to both lower limbs results in cerebral protection from subsequent ischemia within 24 h of initiation of the RPC stimulus and this protection in part may be mediated via a neurogenic pathway.

Diagnostic and prognostic role of MRI in spinal trauma, its comparison and correlation with clinical profile and neurological outcome, according to ASIA impairment scale

Aims and objectives:To evaluate the role of magnetic resonance imaging (MRI) as a non-invasive diagnostic tool in patients with acute and chronic spinal trauma and to compare and correlate the MRI findings with those of patients’ clinical profile and neurological outcome according to ASIA impairment scale to assess prognostic and clinical value of MRI.Materials and Methods:Sixty two patients of spinal trauma formed the study group in a prospective fashion. The patients undergoing MR imaging and magnetic resonance images were analyzed and correlated with findings on neurological examination according to American Spinal Injury Association (ASIA) impairment scale (AIS) at the time of MRI examination and subsequently at sub-acute interval to assess neurological outcome.Statistical Analysis:Sample profile was described in terms of 95% confidence limit and proportion. To describe strength of association between extent of spinal cord injury and outcome, odd's ratio, bivariate and multi variant analysis, was used. Pearson's chi square (χ) 2 statistics was applied to test the association between two categorical variables. Data were analyzed using statistical software package, STATA 9.2 and the difference was considered to be significant if ‘P’ value was <0.05.Observation and Results:The cord edema without hemorrhage was the most common MR finding (41.5%). The others were sizable focus of hemorrhage within the cord (33%), epidural hematoma (5.0%), and normal cord (26%). Majority of MR findings correlated well with clinical profile of the patient according to ASIA impairment scale. This study demonstrated that patients with presence of sizable focus of haemorrhage had larger cord edema and more severe grade of initial ASIA impairment scale( AIS) with poor recovery at follow up (P=0.032).Improvement in upper extremity was more than lower extremity. Severe cord compression was also associated with poor neurological outcome; however it was not statistically significant (P=0.149).Conclusions:With this study the authors concluded that various MRI findings in acute spinal cord injury correlated well with the initial clinical findings and on follow-up according to ASIA impairment scale. MRI is useful for initial diagnosis of acute spinal cord injury and its prognostication for predicting neurological recovery.

Outcomes Following Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Cerebral Variant Adrenoleukodystrophy: A Modern, Single-Institution Experience

AbstractAbstract 3543X-linked adrenoleukodystrophy (ALD) is a peroxisomal disorder affecting 1 in 21,000 males. Approximately 40% of patients manifest the devastating childhood-onset cerebral variant (ccALD), characterized by rapid progression to death from cerebral demyelination and ensuing neurologic dysfunction. To date, only allogeneic hematopoietic stem cell transplantation (HSCT) has been shown to alter the natural course of ccALD; additionally, the use of peri-HSCT N-acetylcysteine (NAC) has been shown to enhance survival in boys with extensive pre-HSCT cerebral disease. We reviewed characteristics of as well as survival and neurologic functional outcomes for 60 consecutive boys undergoing allo-HSCT for ccALD at the University of Minnesota between 2000 and 2009; to our knowledge, this analysis represents the largest, single-institution experience in HSCT for ccALD.Seventeen (28%) boys were diagnosed due to a family history; 37 (62%) were diagnosed secondary to signs of disease; 6 (10%) had an unknown instigation for diagnosis. All (100%) had magnetic resonance imaging (MRI) evidence of cerebral involvement at the time of HSCT. The median age at HSCT was 8.7 years (range 4.0 to 23.3 yrs). MRI severity scoring was according to the system published by Loes (0 = no disease on MRI, 34 = maximal involvement); the median pre-HSCT Loes score was 9 (range 2 to 19). Clinical neurologic involvement was graded per a neurologic function scale (NFS, 0 = no neurologic findings, 25 = maximal neurologic findings) spanning the domains of hearing/communication, vision, gait/movement, swallowing, incontinence, and the presence of seizures; the median pre-HSCT NFS was 1 (range 0 to 14).Eighteen (30%) had a related donor, while 42 (70%) received an alternative graft. Twenty-eight (47%) were marrow recipients; 32 (53%) received umbilical cord blood. The preparative regimen was busulfan/cyclophosphamide-based in 28 (46%) boys; cyclophosphamide/total body irradiation-based in 16 (27%); and reduced-intensity conditioning in 16 (27%). Since 2005, all patients (34 boys, 57%) received peri-HSCT NAC.Forty-seven (78%) are alive at the time of analysis; median follow-up among survivors is 3.7 years (range 0.7 to 9.6 yrs). Death was from disease progression in 5 boys, graft failure in 3, infection in 2, and 1 patient each died from acute graft-versus-host disease (aGvHD), hemorrhage, and hemolytic anemia. Eleven (18%) boys experienced grade II-IV aGvHD; 4 (7%) developed grade III-IV aGvHD.In univariate survival analysis of pre-HSCT factors, Loes score was statistically significant [pre-HSCT Loes < 10, 89% 5 year survival (95% CI: 70% - 96%); Loes ≥ 10, 60% (34% - 78%); p = 0.03]. A trend toward better survival was seen for patients with no pre-HSCT neurologic signs of disease [NFS = 0 pre-HSCT, 91% (69% - 98%); NFS ≥ 1, 66% (46% - 81%); p = 0.08] and for those who received NAC [NAC exposed, 80% 1 year survival (72% - 95%); no NAC exposure, 73% (52% - 86%); p = 0.08]. Graft source, age at HSCT, conditioning regimen, presence of adrenal insufficiency, nor reason for diagnosis impacted survival. Of note, of 8 boys with pre-HSCT Loes < 10 who received a related allograft, all (100%) are alive at the time of analysis.In univariate analysis of pre-HSCT factors on post-HSCT clinical neurologic outcomes, both pre-HSCT Loes score and NFS demonstrated significant impact. For those with a pre-HSCT Loes < 10, the most recent NFS assessment (median 2.9 yrs, post-HSCT, range 0.2 to 8.3 yrs) showed a median change of 0 points (range -1 to 20) when compared to the pre-HSCT score; while for those with a pre-HSCT Loes ≥ 10, most recent NFS (median 2.1 yrs, range 0.8 to 6.6 yrs) showed a median change of 7.5 points (range 0 to 23 points); p < 0.01. For those with pre-HSCT NFS of 0, the most recent NFS (median 2.2 yrs, range 0.2 to 8.3 yrs) a median change of 0 points (range 0 to 8) was observed; while for those with a pre-HSCT NFS ≥ 1, most recent NFS (median 2.3 yrs, range 0.8 to 7.2 yrs) showed a median change of 7 points (range -1 to 23); p < 0.01.In summary, we report a large, recent, single-institution experience of allo-HSCT for ccALD. While HSCT in early disease yields encouraging functional outcomes and survival in comparison to untreated ccALD, additional modifications will be necessary to achieve optimal results for patients transplanted with advanced disease. Finally, this data continues to support the need for early diagnosis of those affected by this devastating disease. Disclosures:No relevant conflicts of interest to declare.

Tamoxifen as an effective neuroprotectant in an endovascular canine model of stroke

Tamoxifen has been shown to be a potent neuroprotectant against stroke in rodents. Because other neuroprotectant medications have failed in human trials, a study of tamoxifen in a large-animal model was necessary to further assess the drug's effectiveness. For this study, the authors developed an endovascular model of anterior circulation infarction in canines to mimic the human clinical condition. They assessed the following hypotheses: 1) that they will be able to consistently produce an internal carotid artery (ICA) terminus infarction and 2) that tamoxifen is an effective neuroprotectant against stroke in canines. In 24 male beagles (weight 9-11 kg), bilateral femoral artery cutdowns were performed, and the vertebral artery and left ICA were each selectively catheterized. Under fluoroscopic guidance, a microcatheter was introduced via the vertebral artery, guiding the catheter into the basilar artery, posterior communicating artery, and ICA terminus. A 1-ml clot was injected in the terminus, occluding the middle cerebral artery (MCA) and anterior cerebral artery (ACA) origin. In the first 12 canines, the occlusions were confirmed by angiography. A Canine Stroke Score (CSS) was assigned (score range 0-18 [0 = intact on examination, 18 = comatose]). The animals were then killed and their brains stained with 2,3,5-triphenyltetrazolium chloride (TTC). The subsequent 12 canines underwent a blinded randomized study in which the authors compared the results of tamoxifen (5 mg/kg) infused intravenously 1 hour after clot injection with an equal volume of vehicle (dimethylsulfoxide). After 3 hours, the animals underwent MR imaging, were extubated, and clinical examinations were performed. The canines were killed at 8 hours after clot injection, and TTC staining was used. In the first group, infarct volume and CSSs were consistent with the extent of the occlusion of the angiographic vessels. An occlusion of the ACA, MCA, and posterior cerebral artery resulted in larger infarcts and higher stroke scores than occlusion of the ACA and MCA. In the second group, tamoxifen significantly reduced infarct size and improved clinical outcomes. In tamoxifen-treated animals, the mean infarct volume reduction was 40% (p < 0.05) and the mean CSS was significantly less than vehicle-treated animals (p < 0.001). There were significant correlations among MR imaging-determined volume, TTC-determined volume, and neurological clinical outcome (p < 0.05). Using this endovascular model of stroke, the authors were able to consistently produce an infarction in the canines that was similar in scope to a carotid terminus occlusion in humans. Also, angiography could predict subsequent clinical course and infarct size. Tamoxifen was effective at significantly improving the canine neurological deficits and reducing the size of the stroke. This study took the first step in demonstrating the effectiveness of a promising human neuroprotectant in a large animal.