Abnormal Neurological Examination Research Articles

Community-acquired meningitis in older adults: clinical features, etiology, and prognostic factors.

To investigate the epidemiology and outcomes of community-acquired meningitis in older adults. Retrospective study. Participants adults in Houston, Texas, with community-acquired meningitis hospitalized between January 1, 2005, and January 1, 2010 (N = 619; n = 54, 8.7%, aged ≥65; n = 565 aged <65). An adverse clinical outcome was defined as a Glasgow Outcome Scale score of 4 or less. Older adults had higher rates of comorbidities, abnormal neurological and laboratory (serum white blood cell count >12,000/μL, and cerebrospinal fluid protein >100 mg/dL) findings (P < .001), abnormalities on computed tomography and magnetic resonance imaging of the head (P = .002), and adverse clinical outcomes (ACOs) (P < .001). The majority of participants (65.8%) had meningitis of unknown etiology. Bacterial meningitis was an infrequent cause of community-acquired meningitis (7.4%). Of the known causes, bacterial meningitis and West Nile virus were more common in older than younger adults; younger participants more frequently had cryptococcal and viral meningitis. On logistic regression, female sex was predictive of a poor outcome in the older participants (P = .002), whereas abnormal neurological examination (P < .001), fever (P = .01), and a cerebrospinal fluid glucose level less than 45 mg/dL (P = .002) were significant poor prognostic factors in younger participants. Most cases of community-acquired meningitis are of unknown origin. Older adults are more likely than younger adults to have bacterial meningitis and West Nile virus infection when a cause can be identified. They also have more neurological abnormalities, laboratory and imaging abnormalities, and adverse clinical outcomes.

An exploratory study using a statistical approach as a platform for clinical reasoning in canine epilepsy

Links between deficits identified on neurological examination, age of seizure onset and the presence of structural forebrain disease have often been postulated in dogs presenting with a history of seizures. The purpose of this study was to assess the influence of such factors on the likelihood of structural or functional brain disease, via a thorough history taking process and interictal neurological examination. Four hundred and four dogs with seizures due to intracranial causes were included. Data including age, sex, neuter status, time until diagnosis, age of seizure onset in years, type of seizure, seizure symmetry, seizure severity, interictal neurological deficits, MRI changes and side effects associated with antiepileptic drugs were extracted from medical files.Two hundred and fifty-eight dogs were diagnosed with epilepsy of unknown origin (EUO), 11 with symmetrical structural lesions and 135 with asymmetrical structural lesions. Multinomial analysis demonstrated that dogs that were older at seizure onset were significantly more likely to have an asymmetrical structural lesion than EUO (OR 95% CI: 1.4–1.8). Dogs that had single seizures rather than cluster seizures were less likely to have asymmetrical structural lesions than dogs with EUO (OR 95% CI: 0.2–0.7). Dogs with abnormal neurological examinations were 16.5 times more likely to have asymmetrical structural lesions (OR 95% CI: 8.5–32.1) and 12.5 times more likely to have symmetrical structural lesions (OR 95% CI: 3.0–52.3) than EUO. These findings support the importance of considering interictal neurological deficits and seizure history in clinical reasoning.

Case Scenario: Postoperative Brachial Plexopathy Associated with Infraclavicular Brachial Plexus Blockade

Case Scenario: Postoperative Brachial Plexopathy Associated with Infraclavicular Brachial Plexus Blockade

PWE-149 Minimal Hepatic Encephalopathy Is A Significant Complication In Cirrhotic Patients Admitted To Hospital

IntroductionMinimal hepatic encephalopathy (MHE) is a subtle cognitive impairment in patients with cirrhosis or porto-systemic shunts in the absence of abnormalities in standard neurological examination. The diagnosis of MHE has...

Seizure occurrence during pediatric short-term EEG.

To identify the patients who are more likely to experience a seizure during short-term EEG recording. We retrospectively reviewed the EEG recordings and medical records of 294 patients, who were admitted to the Pediatric Departments in Assaf Harofeh Medical Center, and referred for a short-term EEG during a 5-years period following a seizure. Fifteen (5.1%) patients had seizures during short-term EEG. The likelihood of seizure occurrence was increased by history of seizures (odds ratio 11.86, 95% confidence interval 2.54-55.37), abnormal neurological examination (odds ratio 3.33, 95% confidence interval 1.05-10.55), and the presence of interictal epileptiform discharges (odds ratio 10.07, 95% confidence interval 1.26-80.42). Treatment with antiepileptic drugs and mental retardation were significantly more common among patients with seizures. Children with a higher likelihood of a seizure during short-term EEG can be identified using data mainly obtained by history and neurological examination.

Early (< 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants.

Chronic lung disease remains a major problem in neonatal intensive care units. Persistent inflammation in the lungs is the most likely underlying pathogenesis. Corticosteroids have been used to either prevent or treat chronic lung disease because of their potent anti-inflammatory effects. To examine the relative benefits and adverse effects of postnatal corticosteroids commenced within the first seven days of life to preterm infants at risk of developing chronic lung disease. We sought randomised controlled trials (RCTs) of postnatal corticosteroid therapy from the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 8), MEDLINE (1966 to August 2013), handsearching paediatric and perinatal journals, and by examining previous review articles and information received from practising neonatologists. We contacted authors of all studies, where possible, to confirm details of reported follow-up studies, or to obtain any information about long-term follow-up where none had been reported. We selected RCTs of postnatal corticosteroid treatment within the first seven days of life (early) in high-risk preterm infants for this review. Most studies evaluated the use of dexamethasone but we also included studies that assessed hydrocortisone, even if it was used primarily to manage hypotension. We extracted and analysed data regarding clinical outcomes that included mortality, chronic lung disease, death or chronic lung disease, failure to extubate, complications during the primary hospitalisation, and long-term health outcomes. Twenty-nine RCTs enrolling a total of 3750 participants were eligible for inclusion in this review. The overall risk for bias was probably low as all were randomised controlled trials, and most trials have used rigorous methods. There were significant benefits for the following outcomes: lower rates of failure to extubate and decreased risks of chronic lung disease at both 28 days and 36 weeks' postmenstrual age, death or chronic lung disease at 28 days and 36 weeks' postmenstrual age, patent ductus arteriosus and ROP, including severe ROP. There were no significant differences in the rates of neonatal or subsequent mortality, infection, severe intraventricular haemorrhage, periventricular leukomalacia, necrotising enterocolitis or pulmonary haemorrhage. Gastrointestinal bleeding and intestinal perforation were important adverse effects. The risks of hyperglycaemia, hypertension, hypertrophic cardiomyopathy and growth failure were also increased. In the 12 trials that reported late outcomes, several adverse neurological effects were found at follow-up examinations, including developmental delay (not defined), cerebral palsy and abnormal neurological examination. However, major neurosensory disability was not significantly increased, either overall in the seven studies where this outcome could be determined, or in the two individual studies where the rates of cerebral palsy or abnormal neurological examination were significantly increased. Moreover, the rates of the combined outcomes of death or cerebral palsy, or of death or major neurosensory disability, were not significantly increased. Dexamethasone was used in most studies (n = 20); only nine studies used hydrocortisone. In subgroup analyses by type of corticosteroid, most of the beneficial and harmful effects were attributable to dexamethasone; hydrocortisone had little effect on any outcomes except for an increase in intestinal perforation and a borderline reduction in patent ductus arteriosus. The benefits of early postnatal corticosteroid treatment (≤ 7 days), particularly dexamethasone, may not outweigh the adverse effects of this treatment. Although early corticosteroid treatment facilitates extubation and reduces the risk of chronic lung disease and patent ductus arteriosus, it causes short-term adverse effects including gastrointestinal bleeding, intestinal perforation, hyperglycaemia, hypertension, hypertrophic cardiomyopathy and growth failure. Long-term follow-up studies report an increased risk of abnormal neurological examination and cerebral palsy. However, the methodological quality of the studies determining long-term outcomes is limited in some cases; the surviving children have been assessed predominantly before school age, and no study has been sufficiently powered to detect important adverse long-term neurosensory outcomes. There is a compelling need for the long-term follow-up and reporting of late outcomes, especially neurological and developmental outcomes, among surviving infants who participated in all randomised trials of early postnatal corticosteroid treatment. Hydrocortisone in the doses and regimens used in the reported RCTs has few beneficial or harmful effects and cannot be recommended for the prevention of chronic lung disease.

Late (> 7 days) postnatal corticosteroids for chronic lung disease in preterm infants.

Many preterm infants who survive go on to develop chronic lung disease. This is probably due to persistent inflammation in the lungs. Corticosteroids have powerful anti-inflammatory effects and have been used to treat established chronic lung disease. However, it is unclear whether any beneficial effects outweigh the adverse effects of these drugs. To determine the relative benefits and adverse effects associated with late (> 7 days) postnatal systemic corticosteroid treatment compared with control (placebo or nothing) in the preterm infant with evolving or established chronic lung disease. We sought randomised controlled trials (RCTs) of postnatal corticosteroid therapy from the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 8), MEDLINE (1966 through August 2013), handsearching paediatric and perinatal journals, and by examining previous review articles and information received from practising neonatologists. When possible, we contacted authors of all studies to confirm details of reported follow-up studies or to obtain any information about long-term follow-up where none had been reported. We selected RCTs of postnatal corticosteroid treatment initiated after seven days after birth in preterm infants with evolving or established chronic lung disease for this review. We extracted and analysed data regarding clinical outcomes including mortality, chronic lung disease, death or chronic lung disease, failure to extubate, complications in the primary hospitalisation, and long-term health outcomes Twenty-one RCTs enrolling a total of 1424 participants were eligible for this review. All were randomised controlled trials, but the methods for random allocation were not always clear. Allocation concealment, blinding of the intervention and blinding of the outcome assessments were mostly satisfactory. Late steroid treatment was associated with a reduction in neonatal mortality (at 28 days), but not mortality at discharge or latest reported age. Benefits of delayed steroid treatment included reductions in failure to extubate by three, seven or 28 days, chronic lung disease at both 28 days and 36 weeks' postmenstrual age, need for late rescue treatment with dexamethasone, discharge on home oxygen, and death or chronic lung disease at both 28 days and 36 weeks' postmenstrual age. There was a trend towards an increase in risk of infection and gastrointestinal bleeding, but not necrotising enterocolitis. Short-term adverse affects included hyperglycaemia, glycosuria and hypertension. There was an increase in severe retinopathy of prematurity, but no significant increase in blindness. There was a trend towards a reduction in severe intraventricular haemorrhage, but only 247 infants were enrolled in five studies reporting this outcome. The trends to an increase in cerebral palsy or abnormal neurological examination were partly offset by a trend in the opposite direction in death before late follow-up. The combined rate of death or cerebral palsy was not significantly different between steroid and control groups. Major neurosensory disability, and the combined rate of death or major neurosensory disability, were not significantly different between steroid and control groups. There were no substantial differences between groups for other outcomes in later childhood, including respiratory health or function, blood pressure or growth, although there were fewer with a clinically important reduction in the forced expired volume in one second (FEV1) on respiratory function testing. The benefits of late corticosteroid therapy may not outweigh actual or potential adverse effects. Although there continues to be concern about an increased incidence of adverse neurological outcomes in infants treated with postnatal steroids, this review of postnatal corticosteroid treatment for chronic lung disease initiated after seven days of age suggests that late therapy may reduce neonatal mortality without significantly increasing the risk of adverse long-term neurodevelopmental outcomes. However, the methodological quality of the studies determining the long-term outcome is limited in some cases; in some studies the surviving children have only been assessed before school age, when some important neurological outcomes cannot be determined with certainty, and no study was sufficiently powered to detect increased rates of important adverse long-term neurosensory outcomes. Given the evidence of both benefits and harms of treatment, and the limitations of the evidence at present, it appears prudent to reserve the use of late corticosteroids for infants who cannot be weaned from mechanical ventilation and to minimise the dose and duration of any course of treatment.

Developmental trajectories of children with birth asphyxia through 36 months of age in low/low–middle income countries

BackgroundResuscitation following birth asphyxia reduces mortality, but may be argued to increase risk for neurodevelopmental disability in survivors. AimsTo test the hypothesis that development of infants who received resuscitation following birth asphyxia is not significantly different through 36months of age from infants who had healthy births. Study designProspective observational cohort design comparing infants exposed to birth asphyxia with resuscitation or healthy birth. SubjectsA random sample of infants with birth asphyxia who received bag-and-mask resuscitation was selected from birth records in selected communities in 3 countries. Exclusion criteria: birth weight<1500g, severely abnormal neurological examination at 7days, mother<15years, unable to participate, or not expected to remain in the target area. A random sample of healthy-birth infants (no resuscitation, normal neurological exam) was also selected. Eligible=438, consented=407, and ≥1 valid developmental assessment during the first 36months=376. Outcome measure(s)Bayley Scales of Infant Development-II Mental (MDI) and Psychomotor (PDI) Development Index. ResultsTrajectories of MDI (p=.069) and PDI (p=.143) over 3 yearly assessments did not differ between children with birth asphyxia and healthy-birth children. Rather there was a trend for birth asphyxia children to improve more than healthy-birth children. ConclusionsThe large majority of infants who are treated with resuscitation and survived birth asphyxia can be expected to evidence normal development at least until age 3. The risk for neurodevelopmental disability should not justify the restriction of effective therapies for birth asphyxia.

Brain Magnetic Resonance Imaging of Infants with Bacterial Meningitis

To describe the results of brain magnetic resonance imaging (MRI) of infants with bacterial meningitis and how the findings affected clinical management. This retrospective study included all infants <12 months of age who were hospitalized at Children's Medical Center, Dallas and had culture-confirmed bacterial meningitis and a brain MRI from January 1, 2001 to December 1, 2011. Infants were identified by review of all positive bacterial cultures of cerebrospinal fluid (CSF) from the Children's Medical Center Microbiology Laboratory. Demographic, clinical, laboratory, and neuroimaging data were reviewed. Infants with ventriculoperitoneal shunt or whose CSF culture yielded skin commensals were excluded. A neuroradiologist blinded to clinical information reviewed all MRI studies. Of the 440 infants who had a positive CSF culture result, 111 (25%) had a pathogen isolated from CSF and were enrolled in the study. Of these, 68% (75/111) had a brain MRI performed during the hospitalization; abnormalities included leptomeningeal enhancement (57%), cerebral infarct (43%), subdural empyema (52%), cerebritis (26%), hydrocephalus (20%), and abscess (11%). By multiple logistic regression analysis, infants with late seizures and an abnormal neurologic examination were more likely to have an abnormal MRI (P < .05). MRI results led to neurosurgical intervention in 23% of infants; a positive bacterial culture of CSF obtained >48 hours after initiation of antibiotic therapy was associated with neurosurgical intervention (P = .01). Fourteen (19%) infants with bacterial meningitis had a normal brain MRI. Brain MRIs were performed frequently and often were abnormal in infants with bacterial meningitis, leading to changes in clinical management.

Neurological abnormalities predict disability: the LADIS (Leukoaraiosis And DISability) study.

To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed at evaluating age-related white matter changes (ARWMC) as an independent predictor of the transition to disability (according to Instrumental Activities of Daily Living scale) or death in independent elderly subjects that were followed up for 3 years. At baseline, a standardized neurological examination was performed. MRI assessment included age-related white matter changes (ARWMC) grading (mild, moderate, severe according to the Fazekas' scale), count of lacunar and non-lacunar infarcts, and global atrophy rating. Of the 633 (out of the 639 enrolled) patients with follow-up information (mean age 74.1 ± 5.0 years, 45 % males), 327 (51.7 %) presented at the initial visit with ≥1 neurological abnormality and 242 (38 %) reached the main study outcome. Cox regression analyses, adjusting for MRI features and other determinants of functional decline, showed that the baseline presence of any neurological abnormality independently predicted transition to disability or death [HR (95 % CI) 1.53 (1.01-2.34)]. The hazard increased with increasing number of abnormalities. Among MRI lesions, only ARWMC of severe grade independently predicted disability or death [HR (95 % CI) 2.18 (1.37-3.48)]. In our cohort, presence and number of neurological examination abnormalities predicted global functional decline independent of MRI lesions typical of the aging brain and other determinants of disability in the elderly. Systematically checking for neurological examination abnormalities in older patients may be cost-effective in identifying those at risk of functional decline.

Telemedicine for genetic and neurologic evaluation in the neonatal intensive care unit

ObjectivesEvaluate whether telemedicine can be used to perform dysmorphology and neurologic examinations in the neonatal intensive care unit (NICU) by determining the examination accuracy, limitations, and optimized procedures.Study designProspective evaluation of NICU patients referred for subspecialty consultation for dysmorphic features (n=10) or encephalopathy (n=10). A physician at bedside (bedside clinician) performed an in-person examination which was viewed in real-time by a remote physician (remote consultant). Standardized examinations were recorded and compared. Subsequently, a qualitative approach established technique adjustments and optimization procedures necessary to improve visualization.ResultsTelemedicine examinations identified 81 of 87 (93%) dysmorphology examination abnormalities and 37 of 39 (92%) neurologic examination abnormalities. Optimization of remote consultant visualization required an active bedside clinician assisting in camera and patient adjustments.ConclusionsTelemedicine can be used to accurately perform many components of the dysmorphology or neurologic examinations in NICU patients, but physicians must be mindful of specific limitations.

A Rare Cause of Constipation and Acute Malnutrition: Primary Intestinal Lymphoma

Constipation is the group of disease that is most frequently consulted with experts in pediatric gastroenterology. Abnormal neurological examination, non-intestinal symptoms or cases unresponsive to treatment should be stimulative and suggestive of another underlying cause to the doctor. Mature B-cell malignant disease (Burkitt lymphoma) forms 35-40 % of all non-Hodgkin lymphoma patients. Burkitt lymphoma can be a mass in gastrointestinal system. In this paper, a four-year-old boy who was hospitalized for 17 days in other centers with a diagnosis of malnutrition and constipation and diagnosed as primary intestinal lymphoma in our clinic is presented. Primary intestinal lymphomas discussed under the light of literature.

Repeat Head Computed Tomography in Anticoagulated Traumatic Brain Injury Patients: Still Warranted

Anticoagulation agents are proven risk factors for intracranial hemorrhage (ICH) in traumatic brain injury (TBI). The aim of our study is to describe the epidemiology of prehospital coumadin, aspirin, and Plavix (CAP) patients with ICH and evaluate the use of repeat head computed tomography (CT) in this group. We performed a retrospective study from our trauma registry. All patients with intracranial hemorrhage on initial CT with prehospital CAP therapy were included. Demographics, CT scan findings, number of repeat CT scans, progressive findings, and neurosurgical intervention were abstracted. A comparison between prehospital CAP and no-CAP patients was done using χ(2) and Mann-Whitney U test. A total of 1606 patients with blunt TBI charts were reviewed of whom 508 patients had intracranial bleeding on initial CT scan and 72 were on prehospital CAP therapy. CAP patients were older (P < 0.001), had higher Injury Severity Score and head Abbreviated Injury Scores on admission (P < 0.001), were more likely to present with an abnormal neurologic examination (P = 0.004), and had higher hospital and intensive care unit lengths of stay (P < 0.005). Eighty-four per cent of patients were on antiplatelet therapy and 27 per cent were on warfarin. The CAP patients have a threefold increase in the rate of worsening repeat head CT (26 vs 9%, P < 0.05). Prehospital CAP therapy is high risk for progression of bleeding on repeat head CT. Routine repeat head CT remains an important component in this patient population and can provide useful information.

Risk factors for developing epilepsy after neonatal seizures

Neonatal seizures are the most frequent neurological disorder in the neonatal period. The incidence is reported to be higher than at any other period in life. Because of the unique nature of neonatal brain anatomy, connections and the paradoxical nature of neurotransmitters, seizures in this age group vary in semiology from those in older children. They may cause irreversible changes to the synapses in the immature brain and progress to epilepsy. The aim of the study was to analyse laboratory, clinical, neurophysiological and neuroimaging risk factors for epilepsy in a group of children who experienced seizures in the neonatal period. A retrospective study of 176 newborns admitted to the Department of Neonatology, University Children’s Hospital Ljubljana, due to seizures, was performed. Metabolic disorders and hypoxic-ischaemic encephalopathy were the most frequent aetiological factors associated with seizures. Epilepsy rate in the group was 18%. Pathological cardiotocography, reanimation after delivery, myoclonic type of seizures, more than one type of seizures, severely abnormal electroencephalography, abnormal neurological examination and neuroimaging, treatment with more than one antiepileptic drug and duration of treatment more than one month constituted statistically significant independent predictive factors for epilepsy (p< 0.05). The results of our study further elucidate risk factors for epilepsy after neonatal seizures.

Lower extremity nerve entrapments in athletes.

Nerve entrapments are a potential cause of lower extremity pain in athletes. Signs and symptoms suggestive of nerve entrapment include anesthesia, dysesthesias, paresthesias, or weakness in the distribution of a peripheral nerve. The physical examination may reveal an abnormal neurologic examination finding in the distribution of a peripheral nerve, positive nerve provocative testing, and positive Tinel sign over the area of entrapment. Electrodiagnostic studies, radiographs, magnetic resonance imaging studies, and sonographic evaluation may assist with the diagnosis of these disorders. Initial treatment usually involves conservative measures, but surgical intervention may be required if conservative treatment fails. This article discusses the diagnosis and treatment of common lower extremity nerve entrapments in athletes. A high index of suspicion for nerve entrapments enables the clinician to identify these conditions in a timely manner and institute an appropriate management program, thus improving patient outcomes.

Adherence to Hypothermia Guidelines: A French Multicenter Study of Fullterm Neonates

AimThe objective of this study was to describe the French practice of hypothermia treatment (HT) in full-term newborns with hypoxic-ischemic encephalopathy (HIE) and to analyze the deviations from the guidelines of the French Society of Neonatology.Materials and MethodsFrom May 2010 to March 2012 we recorded all cases of HIE treated by HT in a French national database. The population was divided into three groups, "optimal HT" (OHT), “late HT” (LHT) and “non-indicated” HT (NIHT), according to the guidelines.ResultsOf the 311 newborns registered in the database and having HT, 65% were classified in the OHT group, 22% and 13% in the LHT and NIHT groups respectively. The severity of asphyxia and HIE were comparable between newborns with OHT and LHT, apart from EEG. HT was initiated at a mean time of 12 hours of life in the LHT group. An acute obstetrical event was more likely to be identified among newborns with LHT (46%), compared to OHT (34%) and NIHT (22%). There was a gradation in the rate of complications from the NIHT group (29%) to the LHT (38%) group and the OHT group (52%). Despite an insignificant difference in the rates of death or abnormal neurological examination at discharge, nearly 60% of newborns in the OHT group had an MRI showing abnormalities, compared to 44% and 49% in the LHT and NIHT groups respectively.ConclusionThe conduct of the HT for HIE newborns is not consistent with French guidelines for 35% of newborns, 22% being explained by an excessive delay in the start of HT, 13% by the lack of adherence to the clinical indications. This first report illustrates the difficulties in implementing guidelines for HT and should argue for an optimization of perinatal care for HIE.

The Use Of Transcranial Doppler Ultrasonography In Adult Patients With Sickle Cell Disease: A Retrospective Analysis

Background Unlike in children, Transcranial Doppler Ultrasound (TCD) can not currently be used to predict stroke risk in adults with Sickle Cell Disease, and this is confounded by an age related decline in TCD and lack of an established normal TCD velocity range for adults. In addition abnormalities in the extracranial circulation have been associated with increased incidence of stroke in children with SCD, but this has not been shown in adults. Aims To retrospectively review TCD and carotid duplex ultrasound results from adults with SCD and to correlate with neurological outcome. Methods TCD and carotid duplex data were collected from 112 patients from January 2003 to December 2012 and analysed retrospectively. Imaging and non-imaging TCD and carotid duplex were performed as a routine out-patient investigation as part of an annual review in the comprehensive adult sickle cell clinic in our unit. STOP velocity criteria were used for stroke risk stratification. Carotid disease was defined as non-significant (&lt;50%), moderate stenosis (50-69%) and severe disease (≥70%). Results The mean age of patients was 35.4 (range 17-79) years; 65% were female and 78% had HbSS. There were 5 patient exclusions based on the TCD findings; two were non-diagnostic and three had abnormal scans as part of childhood screening. The remaining 107 patients were divided into two groups; Group I patients had a normal neurological examination (n = 95) and Group II had an abnormal neurological examination with a clinical diagnosis of stroke that preceded TCD/carotid duplex examination (n = 12). In Group I there were 4 abnormal TCD scans according to STOP criteria; two showed significant asymmetry (&gt;25%) and two showed abnormally low velocities (&lt;50cm/s), one of whom subsequently developed a silent stroke. Although the remaining 91 patients had normal TCD findings; a limited TCD examination was noted in 6 patients and asymmetrical velocities that fell below the 25% threshold were observed in 7 patients, one of whom subsequently developed a symptomatic lacunar infarct. A further eight patients showed extracranial (ICA) disease and one of these also had evidence of a silent stroke on MRI. In Group II, 5 patients showed abnormal TCD findings; four had low velocities (&lt;50cm/sec) and one had low velocities and significant asymmetry. Six patients had severe extracranial ICA stenosis or occlusion on carotid duplex. There was a significant increase in the incidence of abnormal TCD (C2=19.4, p&lt;0.001) and duplex findings (C2=16.2, p&lt;0.001) in patients in Group II compared to Group I. Conclusions Routine screening of adults with SCD using TCD did not show any asymptomatic patients with elevated TCD flow-velocities (&gt;170cm/s), confirming previous studies. However, other abnormal ultrasound findings were observed including; abnormally low or asymmetric TCD velocities and extracranial ICA disease. These abnormalities were associated with stroke in three cases; TCD asymmetry preceded a lacunar infarct by five years, abnormally low velocities preceded a silent infarct by two years and severe extracranial ICA stenosis was associated with a silent infarct. There was a significantly increased incidence of abnormal ultrasound findings in patients who had neurological symptoms (91.6% versus 12.6%). Further investigation of the incidence and implications of abnormal TCD and extracranial carotid duplex findings in adults with sickle cell disease is required. Longitudinal follow-up of patients with low or asymmetric velocities and ICA disease will clarify if these abnormalities are associated with increased neurological morbidity; if so, intervention may be justified. The traditional STOP criteria of raised TCD velocities are inadequate in the adult sickle population, new velocity criteria are required to stratify the risk of stroke in this population. Disclosures: Howard: Sangart: Membership on an entity’s Board of Directors or advisory committees.

Clinical and Magnetic Resonance Imaging (MRI) Distinctions Between Tumefactive Demyelination and Brain Tumors in Children

Tumefactive demyelinating lesions can be difficult to distinguish from tumors. Clinical and magnetic resonance imaging features of children with tumefactive demyelination and supratentorial brain tumors were compared. Patients were identified through a 23-site national demyelinating disease study, and from a single-site neuroradiology database. For inclusion, lesions met at least 1 of 3 criteria: maximal cross-sectional diameter >20mm, local or global cerebral mass effect, or presence of perilesional edema. Thirty-one children with tumefactive demyelination (5 with solitary lesions) were identified: 27 of 189 (14.3%) from the demyelinating disease study and 4 from the database. Thirty-three children with tumors were identified. Children with tumefactive demyelination were more likely to have an abnormal neurologic examination and polyfocal neurologic deficits compared to children with tumors. Tumefactive demyelination was distinguished from tumor by the presence of multiple lesions, absence of cortical involvement, and decrease in lesion size or detection of new lesions on serial imaging.

Long-term neurological outcome of a cohort of 80 patients with classical organic acidurias

BackgroundClassical organic acidurias including methylmalonic aciduria (MMA), propionic aciduria (PA) and isovaleric aciduria (IVA) are severe inborn errors of the catabolism of branched-chain amino acids and odd-numbered chain fatty acids, presenting with severe complications.MethodsThis study investigated the long-term outcome of 80 patients with classical organic aciduria (38 with MMA, 24 with PA and 18 with IVA) by integrating clinical, radiological, biochemical and genetic data.ResultsPatients were followed-up for a mean of 14 years [age 3.3-46.3 years]. PA included a greater number of patients with abnormal neurological examination (37% in PA, 24% in MMA and 0% in IVA), lower psychometric scores (abnormal evaluation at age 3 years in 61% of patients with PA versus 26% in MMA and 18% in IVA) and more frequent basal ganglia lesions (56% of patients versus 36% in MMA and 17% in IVA). All patients with IVA presented a normal neurological examination and only 1/3 presented cognitive troubles. Prognosis for MMA was intermediate. Biochemical metabolite analysis excluding acute decompensations revealed significant progressive increases of glycine, alanine and glutamine particularly in PA and possibly in MMA but no correlation with neurological outcome. A significant increase of plasma methylmalonic acid was found in MMA patients with intellectual deficiency (mean level of 199 μmol/L versus 70 μmol/L, p < 0.05), with an estimated significant probability of severe outcome for average levels between birth and age 6 years above 167 μmol/L. Urinary 3-hydroxypropionate (3-HP) levels were significantly higher in PA patients with intellectual deficiency (mean level of 68.9 μmol/mmol of creatinine versus 34.6 μmol/mmol of creatinine, p < 0.01), with an estimated significant probability of severe outcome for average levels between birth and age 6 years above 55 μmol/mmol. As for molecular analysis, prognosis of MMA patients with mutations involving the MMAA gene was better compared to patients with mutations involving the MUT gene.ConclusionPropionic aciduria had the most severe neurological prognosis. Our radiological and biochemical data are consistent with a mitochondrial toxicity mechanism. Follow-up plasma MMA and urinary 3-HP levels may have prognostic significance calling for greater efforts to optimize long-term management in these patients.

Injuries in Adolescents with Childhood-Onset Epilepsy Compared with Sibling Controls

To compare the occurrence of injuries in adolescents with childhood-onset epilepsy and matched sibling controls. Retrospective case-control lifetime injury assessments were obtained from a community-based cohort of adolescents with childhood-onset epilepsy diagnosed 9 years earlier and their siblings. The children with epilepsy (n = 501; mean age, 15.3 years) included those with complicated (abnormal neurologic examination or IQ <80; n = 133) and uncomplicated (normal neurologic examination and IQ ≥80; n = 368) epilepsy. Children with uncomplicated epilepsy were matched to sibling controls (n = 210 pairs). The children reported whether or not they had ever (before and after epilepsy diagnosis) experienced injuries "serious enough to require medical attention" and if so, the type of treatment required. Almost one-half (49.1%) of the children with epilepsy experienced injury, of whom 8.9% required surgery/hospitalization and 17.1% had injury related to a seizure. Fewer children with uncomplicated epilepsy had seizure-related injuries versus those with complicated epilepsy (13.6% vs 27.4%; P ≤ .01). The proportion of children with epilepsy with any injury by type (not mutually exclusive) were: 25.2% with fractures (n = 126); 24.4% with head injuries (n = 122); 10.2% with other injuries (n = 51); 8.4% with dental injuries (n = 42); and 8% with burns/scalds (n = 40). A similar proportion of children with uncomplicated epilepsy experienced any injury (overall and by type) compared to matched sibling controls, with the exception that more children with uncomplicated epilepsy had head injuries (30.0% vs 19.5%; P < .02). With the exception of head injuries, we found no evidence of an increased risk of injury in a representative cohort of children with epilepsy compared with matched sibling controls. This finding may reflect the fact that the sample was not biased to more severe cases, or that safety precautions to prevent injury were widely used.