Normal Neurological Exam Research Articles

Burden and Risk of Neurological and Cognitive Impairment in Pediatric Sickle Cell Anemia in Uganda (BRAIN SAFE): Interim Overall Results

Sickle Cell Anemia (SCA) is highly prevalent in sub-Saharan Africa (SSA). In Uganda, approximately 20,000 children are born with SCA annually (Ndeezi G, 2016). Sickle brain vasculopathy causes both overt strokes and clinically “silent infarcts,” affecting neurological and cognitive function (DeBaun MR, 2012). Incidence of strokes has markedly decreased through standardized preventative measures. Study objectives are to determine the age-related spectrum and burden of brain injury associated with SCA in Ugandan children, determine predisposing risk factors and build capacity to support interventions for stroke prevention. Here we present preliminary results.Methods: BRAIN SAFE is a cross-sectional study of a random sample of 250 children with SCA, ages 1-12 years, who receive care at the Mulago Hospital SCD clinic in Kampala.Potential participants were randomly selected from the clinic roster. Study exclusion criteria: hemoglobinopathy other than HbSS or HbS B0 thalassemia, age >12, acute illness, Hb <6.0gm/dl, recent transfusion, participation in another clinical study.Stroke history and examination: were performed using the pediatric NIH Stroke Scale. Psychometric testing: Age-appropriate KABC-II, TOVA, BRIEF and Mullen testing were performed by skilled testers using validated versions in English or the predominant local language.Transcranial doppler ultrasounds (TCDs) were performed (with good inter-operator reliability) by two study staff, both health professionals. They had been trained by a U.S.-based “STOP” trial TCD research nurse and a co-investigator who had TCD training in the U.S. The latter also performed standardized readings (Adams RJ, 1998). Quality assurance for TCD readings was provided by an independent stroke neurologist.Brain Magnetic imaging (MRI/MRA): Using a single 1.5T scanner, a subset of subjects enriched for a history of stroke, abnormal neurological exam and/or cognitive testing. Two radiologists performed clinical reads. An independent neuroradiologist assessed sickle vasculopathy, per “SWiTCH” protocol (Helton KJ, 2014), blinded to clinical and radiological data.Primary and secondary stroke prevention : Subjects with persistently non-normal TCDs on repeat testing or vasculopathy on MRI/MRAswill be offered hydroxyurea .Results: Of the 248 participants screened in the 1st funding year, 233 were enrolled (mean age 5.62 years (range 1-12). Study exclusions due to age >12, acute illness, severe anemia, recent transfusion or participation in another study.History and neurological exam : Overall, 7 of 233 had history consistent with a stroke, and an abnormal neurological exam, 5 had a history consistent with stroke but a normal neurological exam, 6 had abnormal neurological findings but no history of stroke (total abnormal 18/233, 7.7%).Psychometrics : To date, cognitive test data results have been performed on 80 children; 30 (37.5%) were impaired with varying severity. (Full reports to follow.)TCDs : A total of 224 non-imaging TCDs have been performed. Using standard criteria, 190 were normal, 4 abnormal (1.8%), and 30 conditional (13.4%). Repeat TCDs have been performed on 13 of those with non-normal reads and so far, 2 were abnormal, 6 conditional, 4 normal,1 had difficult windows.MRI/MRAs: A subset of 29 subjects were selected with more clinical and/or historical stroke pathology (N= 25, 86%) and have undergone MR imaging to date (see Table). Mean age was 7.1 years (range 3-12); male: 55%. Of 26 with clinical radiological reads, 16 / 26 (61.5%) were abnormal. To date, scans from 12 subjects have had SCD vascular reads: 2 had no vasculopathy; 10 were abnormal: 6 with infarcts and arterial stenoses, 3 with infarcts only, 1 with bilateral stenoses only.Conclusions: BRAIN SAFE, a Kampala-based cross-sectional study, has already enrolled and completed a large proportion of study procedures. Considerable brain pathology has been identified in all aspects tested, with high prevalence of abnormal history or physical findings, abnormal psychometrics, abnormal cerebral blood flow and/or brain MR imaging. Completion of enrollment and testing for the target sample will provide baseline data for longitudinal assessment and intervention. Building research capacity for faculty and trainees is ongoing.Acknowledgments: 1R21HD089791 (PIs: Idro, Green) and Latanya Bowman, RN, Augusta University Sickle Cell Center. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Ruling out intra-abdominal injuries in blunt trauma patients using clinical criteria and abdominal ultrasound.

to identify victims of blunt abdominal trauma in which intra-abdominal injuries can be excluded by clinical criteria and by complete abdominal ultrasonography. retrospective analysis of victims of blunt trauma in which the following clinical variables were analyzed: hemodynamic stability, normal neurologic exam at admission, normal physical exam of the chest at admission, normal abdomen and pelvis physical exam at admission and absence of distracting lesions (Abbreviated Injury Scale >2 at skull, thorax and/or extremities). The ultrasound results were then studied in the group of patients with all clinical variables evaluated. we studied 5536 victims of blunt trauma. Intra-abdominal lesions with AIS>1 were identified in 144 (2.6%); in patients with hemodynamic stability they were present in 86 (2%); in those with hemodynamic stability and normal neurological exam at admission in 50 (1.8%); in patients with hemodynamic stability and normal neurological and chest physical exam at admission, in 39 (1.5%); in those with hemodynamic stability, normal neurological, chest, abdominal and pelvic physical exam at admission, in 12 (0.5%); in patients with hemodynamic stability, normal neurological, chest, abdominal and pelvic physical exam at admission, and absence of distracting lesions, only two (0.1%) had intra-abdominal lesions. Among those with all clinical variables, 693 had normal total abdominal ultrasound, and, within this group, there were no identified intra-abdominal lesions. when all clinical criteria and total abdominal ultrasound are associated, it is possible to identify a group of victims of blunt trauma with low chance of significant intra-abdominal lesions.

A developmental deficit in seeing the orientation of typical 2D objects

We report the results from a single-case study of an adolescent, Davida, with no remarkable medical history, normal neurological exam, brain MRI and electroencephalogram, who has a highly specific deficit in perceiving the orientation of static, moving, flashed and flickering 2D shapes such as black, grey or colored letters, arrows, abstract shapes and line drawing of objects and faces. Davida reports seeing multiple orientations of these stimuli concurrently (the correct orientation and the equivalent of its rotation by 90, 180 and 270 degrees). Davida's results in non-speeded tasks probing her perception of orientation through verbal judgments, visual illusions, direct copy, and directed movements corroborated this difficulty. For instance, when asked to point to the tip of an arrow shown on a computer screen, she typically pointed where the tip of the arrow would be if the arrow was rotated by 90, 180 or 270 degrees. In contrast, (a) the processing of orientation from auditory, tactile and kinesthetic information is intact; (b) visual judgments about the identity, shape, distance, color, size, movement and location of the same kind of stimuli are intact; and (c) the perception of the orientation of the same shapes (letters, arrows, abstract shapes) shown in 3D, under very low luminance contrast and very low spatial frequencies is intact. The dissociation between processes engaged in the perception of the orientation of 2D shapes under medium to high luminance contrast and spatial frequency from those involved in the perception of the identity, shape, distance, color, size, movement and location of the same kind of stimuli, and those involved in the perception of the orientation of low contrast and low spatial frequency 2D and 3D shapes raises intriguing questions about the interaction of dorsal and ventral visual processes across the two hemispheres. Meeting abstract presented at VSS 2017

Heat Illness- Running

HISTORY: A 14 year-old highly competitive runner presented to our sports medicine clinics one week after collapsing during his first 10 km race in a hot and humid climate. His goal was to achieve a time similar to adult elite runners. He felt dizzy but did not want to slow down. At 8 km he was seen disoriented and stumbling and soon after collapsed. He was taken unconscious to a local ER, where IV hydration was given. After ~25 min he regained consciousness but was disoriented and irrational. He did not remember having collapsed or transport to the ER. After ~two hours he was alert and felt better, and was discharged. Upon arrival to his home he showered with cold water. He reported a mild sore throat the day before and leg pain after the race. PHYSICAL EXAMINATION: Normal vital signs (BP: 116/68; HR: 68 bpm), alert, does not remember details of race. Normal cardiovascular, pulmonary, musculoskeletal and neurological exam. DIFFERENTIAL DIAGNOSIS: 1. Syncope associated to dehydration 2. Syncope associated to hypoglycemia 3. Rhabdomyolysis 4. Syncope associated to exertional heat stroke TEST AND RESULTS: In ER: According to the athlete’s parents: his blood pressure was low, body temperature was not measured nor any blood analysis performed. He was discharged with a diagnosis of “dehydration”. Two days after discharge from ER his primary care physician ordered urinalysis and CBC: Blood and protein trace in urine; Blood glucose=84 mg/dL; Creatinine=0.94 mg/dL; Na+= 142 and K+= 4.7 mmol/L; AST: 1,923 and ALT: 1,996 U/L. CK was not ordered. At 9 days: AST: 100 and ALT: 424 U/L; CK ordered but not done. At 16 days: AST: 55 and ALT: 170 U/L; CK=151 U/L Five weeks after discharge from ER: Heat Tolerance Test (running outdoors @ 12.8 to 13.8 km/hr in 32°C, 75% RH). Test stopped at 40 min when Tc= 39.3°C. HR=145-173 bpm. Sweat rate=1.8 L/h; Fluid replaced=16% Dehydration=1.9%; Rating of hot/overheated= 8 and thirst= 8 (0-10 scale). FINAL /WORKING DIAGNOSIS: Exertional heat stroke related to inadequate heat acclimatization. TREATMENT AND OUTCOMES: 1. Allowed to swim and run in cool environment after 2 weeks at reduced pace but no running in the heat for 5 weeks. 2. Recommendations about proper hydration and gradual heat exposure to acclimatize to heat. 3. Referred to sports psychologist. 4. Repeat heat tolerance test for clearance to compete in the heat.

Broad autism spectrum and obsessive–compulsive symptoms in adults with the fragile X premutation

Objective: Clinical observations and a limited number of research studies provide evidence that the fragile X premutation may confer risk for autism, executive dysfunction, and psychopathology. The link to autism spectrum symptoms and social cognition deficits with the premutation remains uncertain, and thus was the focus of the present investigation.Method: Our sample included 131 individuals, 42 men/22 women with the FMR1 premutation (mean age = 31.83 ± 8.59 years) with a normal neurological exam, and 48 men/19 women healthy age-matched controls (mean age = 29.48 ± 7.29 years). Individuals completed a comprehensive neuropsychological battery with additional assessments for social cognition, broad autism spectrum, and obsessive–compulsive (OC) symptoms.Results: Premutation carriers self-reported higher rates of autism-related symptoms (Autism Quotient; p = .001). Among males only, premutation carriers showed more atypical social interaction (p < .001) and stereotyped behavior (p = .014) during standardized clinical examination on the Autism Diagnostic Observation Schedule (ADOS) relative to controls. Female premutation carriers reported significantly higher rates of OC symptoms compared to control females (p = .012). Molecular measures defining the expanded premutation (FMR1 CGG repeat length and/or mRNA) were significantly associated with a measure of theory of mind (Reading the Mind in the Eyes Task).Conclusions: The results of this study indicate a higher rate of broad autism spectrum symptoms in some males with the premutation and provide evidence for an obsessive–compulsive subtype in female premutation carriers.

Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders

ObjectivesMagnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease.MethodsMultivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into ‘definite’ (n = 17, ≥1 major criteria), ‘probable’ (n = 10, ≥2 minor criteria), ‘possible’ (n = 17, 1 minor criterion) and ‘unlikely’ mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten ‘unlikely’ children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained.ResultsMRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate.ConclusionMRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children.Key points• MRS-detected brain tissue lactate levels can be quantified.• MRS lactate and lactate/Cr are increased in children with mitochondrial disease.• CSF lactate is less suitable as marker of mitochondrial disease.

Exacerbation of Anxiety and Depression Symptoms following Concussion in a High School Softball Athlete.

HISTORY: A 16-year-old female softball athlete with a history of pre-pubertal migraines sustained a concussion while doing hill sprints. The injury coincided with a loss of consciousness and anterograde amnesia of 20-30 minutes. She presented to clinic six weeks post-injury with symptoms including headache, academic difficulty, and mood lability. Sleep habits were stable, though quality was reported as poor. Headaches occurred daily with variable intensity, were predominately frontal, and were exacerbated by cognitive effort and bright lights. A previously high-achieving student, she experienced difficulty in her classes, particularly foreign language studies. Patient reported pre-injury mood was poor, but had become more irritable than usual with frequent mood swings. Friends and family commented on her increased irritability. Social history significant for death of mother two years previously. PHYSICAL EXAMINATION: Accommodation insufficiency and difficulty with smooth pursuit on visual examination. Cervical spine tenderness and reproduction of headache with palpation. Otherwise normal neurologic and musculoskeletal exams. DIFFERENTIAL DIAGNOSIS: 1.Post-concussion syndrome with visual dysfunction 2.Depression or anxiety disorder exacerbated by trauma TESTS AND RESULTS: Sensory Organization Test: -Composite score of 68 - abnormal Visual domain. Computerized neurocognitive testing: -Composite score of 48 (baseline 105). -Multiple domains affected. Patient Health Questionnaire-9: -12 of 27 (baseline 7). -21% age-adjusted positive predictive value for depressive disorder. Generalized Anxiety Disorder-7: -12 of 21 (baseline 9). -Increased risk of generalized anxiety disorder. Buffalo College Treadmill Testing: -Maximum heart rate of 160. -No symptom exacerbation. FINAL WORKING DIAGNOSIS: Post-concussion syndrome with predominately neuropsychiatric and visual dysfunction likely contributing to headache and cognitive difficulties. TREATMENT AND OUTCOMES: 1. Referral for full neuropsychological evaluation to assess cognitive function and mood disorder and provide specific recommendations for treatment. 2. Physical Therapy for possible cervicogenic component of headaches. 3. Visual assessment and rehabilitation with neuro-optometrist.

Cervical spine immobilization may be of value following firearm injury to the head and neck

BackgroundPenetrating injuries to the head and neck may not be able to cause unstable fractures without concomitant spinal cord injury, rendering prehospital spinal immobilization (PHSI) ineffectual, and possibly harmful. However, this premise is based on reports including predominantly chest and abdominal injuries, which are unlikely to cause cervical spine (CS) injuries. MethodsWe performed a retrospective review of all patients presenting with a penetrating wound to the head or neck over a 4-year period at an urban, level 1 trauma center to determine if there was a benefit of PHSI. ResultsOne hundred seventy-two patients were identified, of which 16 (9.3%) died prior to CS evaluation. Of 156 surviving patients, mechanism was gunshot wound (GSW) in 36 (28%) and stab wound (SW) in 120 (72%). Fifty-eight patients had PHSI placed (37%), and GSW patients' odds of having PHSI were greater than SW patients (OR 2.3; CI 1.08-4.9). Eight of 156 surviving patients eventually died (5.1%), and the odds of mortality were greater among those that had PHSI than those without (OR 5.54; CI 1.08–28.4). Six (3.8%; 5 GSW, 1 SW) patients had a CS fracture. Two GSW patients (5.6%) had unstable CS fractures with a normal neurological exam at initial evaluation. ConclusionsOf patients with a GSW to the head or neck that survived to be evaluated, 5.6% had unstable fractures without an initial neurologic deficit. PHSI may be appropriate in this population. Further studies are warranted prior to a determination that PHSI is unnecessary in penetrating head and neck injuries.

A Unique Case of Bilateral Frontal Lobe Abscesses in a Young Male

A brain abscess is a serious complication that may arise from a source of infection from within the cranium or from an extracranial source. We discuss a unique case of a 36 year-old male with a history of heroin abuse who presented with pan-sinusitis and bilateral frontal lobe abscesses. The patient presented with the symptoms of prolonged drowsiness and a left eyelid infection for which he was already receiving treatment. He had a normal neurological exam upon admission. CT scan of the head was performed which showed left orbital cellulitis, pan-sinusitis, and bilateral frontal lobe abscesses. A follow-up MRI was performed as well which showed cerebral edema. The patient was started on broad spectrum antibiotics, and neurosurgical aspiration and drainage of the abscesses was performed. Microbiological culture results enabled us to narrow the spectrum of the antibiotics. The patient completed his course of antibiotics. At a follow up exam 6 weeks later, the patient had no neurological deficits, and the abscesses seemed to be improving as seen in the imaging.

Caracterización de los pacientes con epilepsia refractaria de un hospital de tercer nivel en Costa Rica

Thirty percent of patients with epilepsy have recurrent seizures, representing fifteen million people in the world. This population has been scarcely described. To characterize sociodemographic and clinically the patients diagnosed with refractory epilepsy in a tertiary referral hospital of the Costa Rican social security. This study presents an analysis of all cases of refractory epilepsy evaluated at the epilepsy unit of San Juan de Dios Hospital from August, 2012 to October, 2014. Clinical records of 91 patients were studied; patients with psychogenic seizures were analyzed separately. The mean age of onset was 13.1 ± 11.1 years, secondary generalized seizures were the predominant type (81.3%), the most frequent etiology was mesial temporal sclerosis (48.3%) and the majority had normal neurological exams and normal or low neuropsychological assessments. Around half (48.8%) of the patients had been medicated with a range of 4-6 antiepileptic drugs, being lamotrigine, carbamazepine, valproic acid and phenytoin the most prescribed. Treatment optimization, neurosurgery, and further analysis were standard recommendations. Sociodemographic characteristics, patient management, and antiepileptic drugs used are similar to the described in other latitudes. Differences between the age of onset and gender; seizure frequency and gender; age of onset and failed treatments and time of evolution of the disease and employment were observed. The percentage and characteristics of recurrent seizures of psychogenic nature found are comparable to other refractory epilepsy studies. Sociodemographic characteristics, management of patients, antiepileptic drugs used and the differences observed are similar to those previously described.

Small Bowel Polyposis Without Diagnosis

A 19 year old male presents with nausea and vomiting. He is treated for gastroenteritis but returns with intussusception and small bowel obstruction that is managed conservatively. Two months later the intussusception recurs with 30 pound weight loss and hematochezia. An exploratory laparotomy is performed and a segment of jejunum with carpeting polyps is resected. He denies a history of cognitive delay and mucocutaneous freckling. On physical exam he is well-developed with a head circumference of 62cm. He has normal abdominal, skin, genital and neurologic exams. Upper endoscopy shows H. pylori gastritis and a stricture at the surgical anastomosis which is dilated. A colonoscopy and capsule endoscopy reveal only lymphoid follicles in the terminal ileum. Pathology from the jejunal resection is significant for hamartomatous polyps containing gastric type tissue. The patient's clinical condition is most consistent with Cowden Syndrome/PTEN Hamartoma Syndrome. He undergoes genetic testing that reveals a variant of uncertain significance (VUS) in the phosphatase and tensin homolog (PTEN) gene. Cowden syndrome is a rare genetic condition that carries an increased risk for multiple cancers. Our patient had two major clinical criteria, macrocephaly (>97th percentile) and hamartomatous intestinal polyps. Approximately 85% of individuals with an operational diagnosis of Cowden syndrome have autosomal dominant mutations identified in the PTEN gene on chromosome 10, which acts as a negative regulator of cell cycle pathways including mTOR and PI3K-AKT. Mutations can be deleterious or a VUS. Our case is unique in that the polyps architecturally resembled Peutz-Jeghers Syndrome (PJS) with an arborizing lamina propria and a lack of significant inflammation or dysplasia. However, the polyps were almost entirely composed of gastric foveolar and pyloric type mucosa, which is highly atypical in small bowel PJS. Furthermore, there have been few reports of small bowel hamartomas associated with Cowden syndrome, and none involving the jejunum to our knowledge. The patient also did not have any classic mucocutaneous findings or family members with a similar phenotype. Up to 44% of CS/PTHS cases arise from de novo PTEN mutations. It is not yet known if his VUS impacts protein function and/or predisposes to increased cancer risk. It is also unclear if the H. pylori infection contributed to his polyposis, however polyp regression after antibiotic therapy is reported.Figure 1Figure 2Figure 3

Appropriate use of neuroimaging in headache.

Headache may be caused by primary disorders, such as migraines, or secondary disorders, such as intracranial neoplasm or hemorrhage. Imaging plays an important role in differentiating between primary and secondary headache disorders. This article reviews the effectiveness of computed tomography (CT) and magnetic resonance imaging (MRI) in the evaluation of a patient with a headache. It also discusses the utility and cost-effectiveness of performing imaging studies in patients with a headache and a normal neurological exam. Emerging imaging techniques such as functional MRI, positron emission tomography (PET) scans, and voxel-based morphometry (VBM) are also discussed.

Neuroimaging in Outpatients with Tension Type Headache

Background: Research into the role of neuroimaging in primary headaches such as tension type headache (TTH) is ongoing. In the present study, we aim to evaluate the ability of neuroimaging to detect potential abnormalities in patients with new onset TTH and normal neurological exam. Materials and Methods: In a prospective study, 294 cases of new onset TTH with normal neurological exam, that had neuroimaging, were selected. Imaging was evaluated for significant abnormalities. The percentage of abnormal findings in imaging was calculated. Results: 64(21.8%) patients had MRI. Of them, 21.8% of MRIs revealed abnormal findings. Meanwhile, from 238 CTs, only 0.4% showed abnormalities. Conclusion: Neuroimaging with current quality does not play an important role in management of patients with new onset TTH and normal neurological exam. [GMJ.2015;4(2):62-66]

Re-evaluating the need for hospital admission and observation of pediatric traumatic brain injury after a normal head CT

There is no consensus on the optimal management of pediatric patients with suspected trauma brain injury and a normal head CT. This study characterizes the clinical outcomes of patients with a normal initial CT scan of the head. A retrospective chart review of pediatric blunt trauma patients who underwent head CT for closed head injury at two trauma centers was performed. Charts were reviewed for demographics, neurologic function, CT findings, and complications. 631 blunt pediatric trauma patients underwent a head CT. 63% had a negative CT, 7% had a non-displaced skull fracture, and 31% had an intracranial hemorrhage and/or displaced skull fracture. For patients without intracranial injury, the mean age was 8years, mean ISS was 5, and 92% had a GCS of 13–15 on arrival. All patients with an initial GCS of 13–15 and no intracranial injury were eventually discharged to home with a normal neurologic exam and no patient required craniotomy. Not admitting those children with an initial GCS of 13–15, normal CT scan, and no other injuries would have saved 1.8±1.5 hospital days per patient. Pediatric patients who have sustained head trauma, have a negative CT scan, and present with a GCS 13–15 can safely be discharged home without admission.

Neurological outcome in newborns with congenital heart disease and seizures

Background: Newborns with congenital heart disease have a high risk of seizures, associated to developmental delay, cerebral palsy, and epilepsy.In this study we analyzed the etiology of seizures, electroencephalographic findings and outcome of newborns with congenital heart disease and seizures.Methods: We retrospectively identified 29 newborns with congenital heart disease, who presented with at least one seizure during their admission to the Neonatal Intensive Care Unit of the Hospital Italiano.Results: All newborns had structural/metabolic seizures. Median gestational age was 38 weeks (30-40 weeks, four pre-term) and median birth weight was 3100 g. (range: 1200-4375). Neurological exam was normal in seven neonates (24%), fourteen had only one seizure and four developed status epilepticus. The EEGs were abnormal in 21 newborns (72%). Ten showed focal paroxysms, ten showed minimal alterations with low amplitude and one had a burst-suppression pattern.Nine newborns (31%) died, due to hemodynamic decompensation. They all had an abnormal EEG (p=0.027), an abnormal neurological exam (p: 0.05) and four presented status epilepticus. (p=0.0053).At six months, two more newborns died and two had refractory epilepsy. Of the 18 patients, six had a normal neurological exam. These 6 patients, had had a normal neonatal neurological exam before hospital discharge and four had had only one seizure. Of the six newborns, five had a normal EEG (p= 0.03).Conclusions: In this population we observed a high mortality and an adverse neurological outcome. Abnormal EEG, abnormal neurological exam and status epilepticus were significantly related to mortality.

Abstract T MP86: A Prospective Study of the Effect of Dehydration on Stroke Severity and Short Term Outcome

Background: Many ischemic stroke patients present to the hospital in a state of dehydration. We hypothesized that patients who were dehydrated at the time of acute stroke would have more severe stroke and worse short term outcomes. Methods: We enrolled consecutive ischemic stroke patients within 12 hours from their last normal neurological exam at a single academic health system. Patients with renal failure or who were unable to undergo MRI were excluded. Surrogate markers for dehydration were defined as BUN/Creatinine ratio &gt;15 and urine specific gravity &gt;1.010. Stroke severity was determined based on clinical examination (NIHSS score) and lesion volume measured on diffusion weighted MRI. The primary outcome of interest was change in NIHSS from admission to discharge. Results: We surveyed 383 ischemic stroke admissions to our comprehensive stroke center. Of these, 168 met inclusion criteria with 126/168 (75%) having complete laboratory and MRI data. 44% of our patients were dehydrated at the time of admission, with no difference in demographics between the dehydrated and hydrated groups. Baseline NIHSS (6.7 vs 7.3; p=0.63) and lesion volumes (12 vs 16; p=0.48) were similar in the two groups. 42% of dehydrated patients were in the worst short term quartile of NIHSS change, as compared with 17% of the hydrated group (p=0.02). Dehydration remained a significant predictor of having the worst NIHSS change, after adjustment for age, initial NIHSS, lesion volume, and admission glucose (OR=4.34, 95% CI 1.75-10.76). Conclusions: Nearly half of acute stroke patients admitted to the hospital are dehydrated by surrogate laboratory markers. Acute stroke patients with markers of dehydration demonstrate greater worsening in NIHSS scores as compared with hydrated patients, independent of infarct size. Results suggest an opportunity for an inexpensive and globally available treatment to optimize functional outcomes of the stroke patient.

Pedigree analysis in patients with Fabry disease: Evaluating changes in referral and diagnosis over successive generations

CO RR EC TE D P RO OF 1.5%; all events were non-serious, mild, and did not result in dose reduction or discontinuation. Three were considered possibly related to eliglustat by the treating physician. Combined incidence of PN (n = 8) and polyneuropathy (n = 1) was 2.3%. No event was serious; most (7/9) were assessed as unrelated to eliglustat. All events of tremor and PN occurred only once in each patient; none resulted in eliglustat discontinuation or dose decrease. Six PN events occurred within 18 months of eliglustat initiation. Excluding the underlying Gaucher disease (itself a known cause of PN), review of the medical history showed that the vast majority of patients had additional risk factors for developing neurological symptoms or medical conditions associated with neuropathy including: hypothyroidism, Hashimoto's thyroiditis, diabetes mellitus, vitamin B12 deficiency, and monoclonal gammopathy. Most patients with PN had normal neurologic exams, non-progression of symptoms despite continuation of drug, anatomic locations inconsistent with druginduced neuropathy, and lack of supportive NCV findings. In the four patients reporting adverse events of PN in the ENCORE trial, three had NCV results available at baseline and 12 months; none had changes from baseline or findings of clinical significance on neurologic exams supporting a causal role of eliglustat. Notably, the patient who experienced both PN and paraesthesia had decompensated diabetes, hypothyroidism, and a history of paraesthesia. Evidence from the eliglustat safety database supports the claim that eliglustat does not promote tremor (1 event/100 person-years) or PN. The rate of PN adverse events noted after eliglustat treatment (2 events/100 person-years) is well within the rate of neuropathy that might be expected to develop spontaneously in the GD1 population (2.9 events/100 person-years); both rates are higher than that of the general population (between 0.0046 and 0.015/100 person-years) recently reported by Biegstraaten et al. (Brain 2010:133;2909).

Congenital Bilateral Vocal Fold Paralysis in a Two-Year-Old Girl

Congenital Bilateral Vocal Fold Paralysis in a Two-Year-Old Girl

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.

Early-onset of multiple sclerosis in a 5-year-old girl

Childhood multiple sclerosis is a rare demyelinating autoimmune disease with particular features. Onset of multiple sclerosis is extremely uncommon in early childhood, particularly before 6 years of age. We report the case of a 5-year-old girl admitted to the hospital for altered consciousness and rapid onset of right hemiparaplegia. Magnetic resonance imaging (MRI) of the brain showed multifocal white matter disease with T2 hyperintense oval lesions in subcortical, periventricular, and cerebellar hemispheres. Treatment with high dose intravenous methylprednisolone (30 mg/kg/day for 3 days) improved symptoms. Intravenous corticosteroid therapy was followed by 1mg/kg/day of oral prednisone. A second MRI, 40 days later, revealed new disseminated T2 hyperintense lesions in the frontal periventricular white matter, corpus callosum, left middle cerebellar peduncle, and dorsal spinal cord, leading to the diagnosis of multiple sclerosis. Azathioprine (2.5 mg/kg/day) was started and the steroid dose was tapered before being stopped after 3 months. After 2 years of follow-up, the patient has remained asymptomatic with a normal neurological exam and with no relapse or side effects of azathioprine. This work shows the particularities in clinical and radiological features of multiple sclerosis in a child aged less than 6 years.