Bio

Clinical Focus


  • Neurology - Prenatal Neurologic Consultation
  • Neurology, Pediatric
  • Neurology - Child Neurology

Academic Appointments


Administrative Appointments


  • Medical Director of Clinical Informatics, Lucile Packard Children's Hospital (2012 - Present)
  • Chief Medical Information Officer, Lucile Packard Children's Hospital (2004 - 2008)
  • Division Chief, Pediatric Neurology, Stanford Dept. of Neurology (1996 - 2008)
  • Executive Committee, Stanford Center for Clinical Informatics (SCCI) (2004 - 2008)
  • Co-director, NSADA (Neurologic Sciences Academic Development Award) Stanford (2004 - 2008)
  • Director of Child Neurology Residency Training Program, Dept. of Neurology & Neurological Sciences (1991 - 2008)
  • Service Chief, Neurology, Lucile Packard Children's Hospital (1991 - 2005)
  • Counselor from West, Professors of Child Neurology (2004 - 2006)
  • Chairman of CNS Electronic Communications Committee, Child Neurology Society (1999 - 2005)

Professional Education


  • Board Certification, American Board of Psychiatry and Neurology, Clinical Neurophysiology (1992)
  • Board Certification, American Board of Preventive Medicine, Clinical Informatics (2013)
  • Residency:Children's Hospital Boston (1987) MA
  • Residency:Children's Hospital Boston (1984) MA
  • Fellowship:Stanford University School of Medicine (1989) CA
  • Medical Education:Harvard Medical School (1982) MA
  • Internship:Children's Hospital Boston (1983) MA
  • Board Certification: Neurology - Child Neurology, American Board of Psychiatry and Neurology (1989)
  • Board Certification: Pediatrics, American Board of Pediatrics (1987)
  • MD, Harvard Medical School, Medicine (1982)
  • Fellowship, Stanford Biomedical Informatics, Clinical Informatics (1999)

Community and International Work


  • India Medical Mission, Southern India

    Topic

    Healthcare to underserved in India

    Partnering Organization(s)

    Operation Mobilisation India & PBC

    Populations Served

    Pediatrics

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • Amor Ministry, Baja California, Mexico

    Topic

    Building Homes in Mexico

    Partnering Organization(s)

    Peninsula Bible Church

    Populations Served

    Indigent Mexicans

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

Research & Scholarship

Current Research and Scholarly Interests


Clinical research: Brain Malformations, Neonatal seizures

Clinical Informatics: Developing EMR and Clinical Decision Support System for Lucile Packard Children's Hospital

Teaching

2013-14 Courses


Publications

Journal Articles


  • Agenesis of Corpus Callosum and Associated Malformations: From Aicardi to Zellweger Syndromes NeoReviews Hahn JS, MacLean J, Yeom K 2012; 13 (4): e224
  • Rapid Implementation of Inpatient Electronic Physician Documentation at an Academic Hospital Applied Clinical Informatics Hahn JS, Bernstein JA, McKenzie RB, King BJ, Longhurst CA 2012; 3 (2): 175-185
  • Septopreoptic Holoprosencephaly: A Mild Subtype Associated with Midline Craniofacial Anomalies AMERICAN JOURNAL OF NEURORADIOLOGY Hahn, J. S., Barnes, P. D., Clegg, N. J., Stashinko, E. E. 2010; 31 (9): 1596-1601

    Abstract

    HPE is a congenital brain malformation characterized by failure of the prosencephalon to divide into 2 hemispheres. We have identified 7 patients who have a mild subtype of HPE in which the midline fusion was restricted to the septal region or preoptic region of the telencephalon. This subtype, which we call septopreoptic HPE, falls in the spectrum of lobar HPE, but lacks significant frontal neocortical fusion seen in lobar HPE. Other imaging characteristics include thickened or dysplastic fornix, absent or hypoplastic anterior CC, and single unpaired ACA. The SP was fully formed in 4, partially formed in 2, and absent in 1. Mild midline craniofacial malformation, such as SMMCI and CNPAS were found in 86% and 71%, respectively. Patients outside of infancy often manifested language delay, learning disabilities, or behavioral disturbances, while motor function was relatively spared.

    View details for DOI 10.3174/ajnr.A2123

    View details for Web of Science ID 000283011300009

    View details for PubMedID 20488907

  • Decrease in Hospital-wide Mortality Rate After Implementation of a Commercially Sold Computerized Physician Order Entry System PEDIATRICS Longhurst, C. A., Parast, L., Sandborg, C. I., Widen, E., Sullivan, J., Hahn, J. S., Dawes, C. G., Sharek, P. J. 2010; 126 (1): 14-21

    Abstract

    Implementations of computerized physician order entry (CPOE) systems have previously been associated with either an increase or no change in hospital-wide mortality rates of inpatients. Despite widespread enthusiasm for CPOE as a tool to help transform quality and patient safety, no published studies to date have associated CPOE implementation with significant reductions in hospital-wide mortality rates.The objective of this study was to determine the effect on the hospital-wide mortality rate after implementation of CPOE at an academic children's hospital.We performed a cohort study with historical controls at a 303-bed, freestanding, quaternary care academic children's hospital. All nonobstetric inpatients admitted between January 1, 2001, and April 30, 2009, were included. A total of 80,063 patient discharges were evaluated before the intervention (before November 1, 2007), and 17,432 patient discharges were evaluated after the intervention (on or after November 1, 2007). On November 4, 2007, the hospital implemented locally modified functionality within a commercially sold electronic medical record to support CPOE and electronic nursing documentation.After CPOE implementation, the mean monthly adjusted mortality rate decreased by 20% (1.008-0.716 deaths per 100 discharges per month unadjusted [95% confidence interval: 0.8%-40%]; P = .03). With observed versus expected mortality-rate estimates, these data suggest that our CPOE implementation could have resulted in 36 fewer deaths over the 18-month postimplementation time frame.Implementation of a locally modified, commercially sold CPOE system was associated with a statistically significant reduction in the hospital-wide mortality rate at a quaternary care academic children's hospital.

    View details for DOI 10.1542/peds.2009-3271

    View details for Web of Science ID 000279431000003

    View details for PubMedID 20439590

  • Neuroimaging Advances in Holoprosencephaly: Refining the Spectrum of the Midline Malformation AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS Hahn, J. S., Barnes, P. D. 2010; 154C (1): 120-132

    Abstract

    Holoprosencephaly (HPE) is a complex congenital brain malformation characterized by failure of the forebrain to bifurcate into two hemispheres, a process normally completed by the fifth week of gestation. Modern high-resolution brain magnetic resonance imaging (MRI) has allowed detailed analysis of the cortical, white matter, and deep gray structural anomalies in HPE in living humans. This has led to better classification of types of HPE, identification of newer subtypes, and understanding of the pathogenesis. Currently, there are four generally accepted subtypes of HPE: alobar, semilobar, lobar, and middle interhemispheric variant. These subtypes are defined primarily by the degree and region of neocortical nonseparation. Rather than there being four discrete subtypes of HPE, we believe that there is a continuum of midline neocortical nonseparation resulting in a spectrum disorder. Many patients with HPE fall within the border zone between the neighboring subtypes. In addition, there are patients with very mild HPE, where the nonseparation is restricted to the preoptic (suprachiasmic) area. In addition to the neocortex, other midline structures such as the thalami, hypothalamic nuclei, and basal ganglia are often nonseparated in HPE. The cortical and subcortical involvements in HPE are thought to occur due to a disruption in the ventral patterning process during development. The severity of the abnormalities in these structures determines the severity of the neurodevelopmental outcome and associated sequelae.

    View details for DOI 10.1002/ajmg.c.30238

    View details for Web of Science ID 000274471700015

    View details for PubMedID 20104607

  • Differential diagnosis and evaluation in pediatric multiple sclerosis NEUROLOGY Hahn, J. S., Pohl, D., Rensel, M., Rao, S. 2007; 68: S13-S22

    Abstract

    The differential diagnosis for multiple sclerosis (MS) in childhood and adolescence includes infectious, inflammatory, and neoplastic disorders as well as metabolic neurogenetic leukodystrophies, toxic leukodystrophies, and vascular conditions. The evaluation is determined by the clinical and neuroradiologic presentation. A minimal diagnostic battery is proposed. More expanded evaluations are indicated for specific or atypical clinical presentations.

    View details for Web of Science ID 000245782100004

    View details for PubMedID 17438234

  • Acute disseminated encephalomyelitis NEUROLOGY Tenembaum, S., Chitnis, T., Ness, J., Hahn, J. S. 2007; 68: S23-S36

    Abstract

    Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory disorder of the CNS characterized by a widespread demyelination that predominantly involves the white matter of the brain and spinal cord. The condition is usually precipitated by a viral infection or vaccination. The presenting features include an acute encephalopathy with multifocal neurologic signs and deficits. Children are preferentially affected. In the absence of specific biologic markers, the diagnosis of ADEM is still based on the clinical and radiologic features. Although ADEM usually has a monophasic course, recurrent or multiphasic forms have been reported, raising diagnostic difficulties in distinguishing these cases from multiple sclerosis (MS). The International Pediatric MS Study Group proposes uniform definitions for ADEM and its variants. We discuss some of the difficulties in the interpretation of available literature due to the different terms and definitions used. In addition, this review summarizes current knowledge of the main aspects of ADEM, including its clinical and radiologic diagnostic features, epidemiology, pathogenesis, and outcome. An overview of ADEM treatment in children is provided. Finally, the controversies surrounding pediatric MS and ADEM are addressed.

    View details for Web of Science ID 000245782100005

    View details for PubMedID 17438235

  • Links between abnormal brain structure and cognition in holoprosencephaly PEDIATRIC NEUROLOGY Roesler, C. P., Paterson, S. J., Flax, J., Hahn, J. S., Kovar, C., Stashinko, E. E., Jing, H., Benasich, A. A. 2006; 35 (6): 387-394

    Abstract

    Converging information on medical issues, motor ability, and cognitive outcomes is essential when addressing long-term clinical management in children with holoprosencephaly. This study considered whether adding more informative structural indices to classic holoprosencephaly categories would increase prediction of cognitive outcomes. Forty-two children with holoprosencephaly were examined to determine the association of deep gray nuclei abnormalities with cognitive abilities and the effect of motor skill deficits on cognitive performance. Additionally, a cognitive profile was described using the Carter Neurocognitive Assessment, an experimental diagnostic instrument designed specifically for young children with severe neurodevelopmental dysfunction. Findings indicated that nonseparation of the deep gray nuclei was significantly associated with the cognitive construct of vocal communication, but not with the cognitive constructs of social awareness, visual attention, or auditory comprehension. Importantly, motor skill deficits did not significantly affect performance on the Carter Neurocognitive Assessment. This study is the first investigation to provide a descriptive overview of specific cognitive skills in this group of children. The results also strongly suggest that this feature of the brain's structure does not predict all aspects of neurodevelopmental function. These findings contribute a critical component to the growing body of knowledge regarding the medical and clinical outcomes of children with holoprosencephaly.

    View details for Web of Science ID 000242780400003

    View details for PubMedID 17138007

  • Factor analysis of neuroanatomical and clinical characteristics of holoprosencephaly BRAIN & DEVELOPMENT Hahn, J. S., Barkovich, A. J., Stashinko, E. E., Kinsman, S. L., Delgado, M. R., Clegg, N. J. 2006; 28 (7): 413-419

    Abstract

    The objective of this study is to better understand the relationship between neuroradiologic and clinical characteristics in holoprosencephaly (HPE) using the multivariate analysis called factor analysis. HPE is a brain malformation characterized by incomplete cleavage of the cerebral hemispheres and deep gray structures. We performed evaluations on 89 children with HPE that included their history, developmental assessment, and physical examination. Ten clinical variables included in factor analysis were the grade of spasticity, dystonia, choreoathetosis, hypotonia, mobility, upper extremity/hand function, expressive language, feeding/swallowing difficulty, endocrinopathies, and temperature dysregulation. Five neuroimaging variables graded by pediatric neuroradiologists were the grade of HPE (from least to most severe: lobar, semilobar, and alobar) and the degree of non-separation of caudate, lentiform, thalamic, and hypothalamic nuclei. Factor analysis using principle component extraction and varimax rotation was utilized. Four significant factors were identified: (1) neuroimaging/developmental factor, (2) motor factor, (3) hypothalamic/oromotor factor, and (4) hypotonia factor. These four factors accounted for 65.2% of the variance. In this factor analysis of HPE patients, we were able to reduce the large number of clinical and radiological variables into four factors. These factors and the constructs underlying them provide structure to the data and provide key parameters for future studies involving neurodevelopmental outcomes in HPE.

    View details for DOI 10.1016/j.braindev.2005.09.008

    View details for Web of Science ID 000239401200001

    View details for PubMedID 16503393

  • Endocrine disorders associated with holoprosencephaly JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM Hahn, J. S., Hahn, S. M., Kammann, H., Barkovich, A. J., Clegg, N. J., Delgado, M. R., Levey, E. 2005; 18 (10): 935-941

    Abstract

    To investigate the incidence of endocrinopathies in holoprosencephaly (HPE) and correlate the severity of the endocrinopathies with the neuroanatomic abnormalities.We reviewed the histories and medical records of 117 children with HPE for endocrinopathies and related treatments. Neuroimaging studies were graded for severity of HPE, hypothalamus non-separation, and pituitary abnormalities.Diabetes insipidus (DI) occurred in 70% of patients with classic HPE. The severity of the DI correlated with the grade of HPE and hypothalamic non-separation (p < 0.0001). Anterior pituitary dysfunctions were much less common. Hypothyroidism was identified in 11% of patients, hypocorticism in 7%, and growth hormone deficiency in 5%. Only one patient with middle interhemispheric variant of holoprosencephaly (MIH) had any of these disorders.Patients with HPE have a high incidence of DI that may be related to the failure of cleavage of hypothalamic nuclei. Anterior pituitary dysfunctions are much less common than DI.

    View details for Web of Science ID 000233922000002

    View details for PubMedID 16355806

  • Evaluation and management of children with holoprosencephaly PEDIATRIC NEUROLOGY Hahn, J. S., Plawner, L. L. 2004; 31 (2): 79-88

    Abstract

    Recent advances in genetics and neuroimaging have greatly contributed to our understanding of the spectrum of midline brain and craniofacial malformations known as holoprosencephaly. Neuroradiologic studies have provided detailed characteristics of four major types of holoprosencephaly: alobar, semilobar, lobar, and middle interhemispheric variant. Clinical studies in children with these types of holoprosencephaly have revealed a wide range of survival and neurologic outcomes. Motor and developmental dysfunctions correlate with the severity of the brain malformation in holoprosencephaly. These findings have implications in the management of medical problems associated with holoprosencephaly and overall prognostication.

    View details for DOI 10.1016/j.pediatrneurol.2004.03.006

    View details for Web of Science ID 000223407000001

    View details for PubMedID 15301825

  • A retrospective survey of perinatal risk factors of 104 living children with holoprosencephaly AMERICAN JOURNAL OF MEDICAL GENETICS PART A Stashinko, E. E., Clegg, N. J., Kammann, H. A., Sweet, V. T., Delgado, M. R., Hahn, J. S., Levey, E. B. 2004; 128A (2): 114-119

    Abstract

    Holoprosencephaly (HPE) is a brain malformation resulting from a primary defect in development of the basal forebrain during early gestation. Prenatal genetic and environmental factors and birth outcomes were described in a population of 104 children with holoprosencephaly referred to three clinical centers from 1998 through 2002. The mean child age was 4 years. Of cases karyotyped, 9% presented with a chromosomal abnormality. This study of living children with holoprosencephaly, the majority of whom are cytogenetically normal, provides new information on the subsample of children with a less severe phenotype. Most children were born at term; about 51% were microcephalic at birth. Consistent with previous research, the association between HPE and maternal history of diabetes merits further investigation. Several findings have important implications for future research. Only 22% of the children in this study sample were diagnosed with holoprosencephaly prenatally. The vast majority of children (72%) were diagnosed with HPE between birth and 1 year of age. Also, 19% of the cases referred to the Carter Centers with HPE were not confirmed on scan review. When possible, future population-based epidemiological studies should emphasize mechanisms that identify children with HPE outside of the newborn period and confirm the diagnosis by review of MRI or high quality CT brain scan.

    View details for DOI 10.1002/ajmg.a.30070

    View details for Web of Science ID 000222567900003

    View details for PubMedID 15213999

  • Electroencephalography in holoprosencephaly: findings in children without epilepsy CLINICAL NEUROPHYSIOLOGY Hahn, J. S., Delgado, M. R., Clegg, N. J., Sparagana, S. P., Gerace, K. L., Barkovich, A. J., Olson, D. M. 2003; 114 (10): 1908-1917

    Abstract

    To evaluate the electroencephalographic characteristics of patients with holoprosencephaly (HPE) without epilepsy.We evaluated the electroencephalograms (EEGs) of 18 children with HPE who lacked a history of seizures. Neuroimaging studies were assessed for severity of HPE and thalamic non-separation and the presence of dorsal cysts and cortical malformations.Hypersynchronous theta activity occurred in 50 and 60% of EEGs during wakefulness or drowsiness/sleep, respectively, and correlated with the grade of thalamic non-separation (p<0.05). Hypersynchronous beta activity during sleep occurred in 41% of EEGs. Posterior amplitude attenuation occurred in 33% of EEGs and correlated with the presence of a dorsal cyst (p

    View details for DOI 10.1016/S1388-2457(03)00169-X

    View details for Web of Science ID 000185982300016

    View details for PubMedID 14499753

  • Hydranencephaly owing to twin-twin transfusion: Serial fetal ultrasonography and magnetic resonance imaging findings JOURNAL OF CHILD NEUROLOGY Hahn, J. S., Lewis, A. J., Barries, P. 2003; 18 (5): 367-370

    Abstract

    We report a newborn girl with hydranencephaly. In the setting of a monochorionic twin pregnancy, one twin's demise was detected by ultrasonography at 18 weeks of gestation, apparently the result of a twin-twin transfusion. In the surviving twin, the evolution of ventriculomegaly, first noted at 18 weeks, to hydranencephaly at 27 weeks is documented by serial sonograms. These findings were confirmed with fetal and postnatal magnetic resonance imaging.

    View details for Web of Science ID 000183405600013

    View details for PubMedID 12822826

  • Unilateral schizencephaly and contralateral polymicrogyria associated with umbilical cord mass JOURNAL OF CHILD NEUROLOGY Hahn, J. S., Lewis, A. J. 2003; 18 (3): 232-234

    Abstract

    We report a 6-month-old boy with diffuse hypertonia and developmental delay who had unilateral separated-lip schizencephaly and contralateral polymicrogyria. The contralateral polymicrogyria was associated with an incomplete clefting in that hemisphere. An umbilical cord hamartoma is presumed to have caused hypoperfusion to the early developing brain, resulting in bilateral lesions.

    View details for Web of Science ID 000182349200014

    View details for PubMedID 12731650

  • MRI shows abnormal white matter maturation in classical holoprosencephaly NEUROLOGY Barkovich, A. J., Simon, E. M., Glenn, O. A., Clegg, N. J., Kinsman, S. L., Delgado, M., Hahn, J. S. 2002; 59 (12): 1968-1971

    Abstract

    In an attempt to assess white matter maturation in holoprosencephaly (HPE), MRI scans of 47 patients with HPE were retrospectively reviewed. White matter maturation was delayed in 25/47 patients, including 24/29 patients with classic HPE who were

    View details for Web of Science ID 000179931100026

    View details for PubMedID 12499493

  • Middle interhemispheric variant of holoprosencephaly - A distinct cliniconeuroradiologic subtype NEUROLOGY Lewis, A. J., Simon, E. M., Barkovich, A. J., Clegg, N. J., Delgado, M. R., Levey, E., Hahn, J. S. 2002; 59 (12): 1860-1865

    Abstract

    The middle interhemispheric variant (MIH) is a subtype of holoprosencephaly (HPE) in which the posterior frontal and parietal areas lack midline separation, whereas more polar areas of the cerebrum are fully cleaved. While the neuroradiologic features of this subtype have been recently detailed, the clinical features are largely unknown.To present the clinical manifestations of MIH and to compare them with classic subtypes (alobar, semilobar, and lobar) of HPE.The authors evaluated 15 patients with MIH in a multicenter study. Neuroimaging and clinical data were collected and correlated. They compared the data with those of 68 patients who had classic HPE.The frequency of endocrinopathy in MIH (0%) was lower compared with the classic subtypes (72%) (p < 0.0001). This correlated with the lack of hypothalamic abnormalities. The percentage of patients with seizures (40%) did not significantly differ from classic HPE. Spasticity was the most common motor abnormality, seen in 86% of MIH patients, similar to other subtypes. The frequency of choreoathetosis in MIH (0%) was lower than that for semilobar HPE (41%) (p < 0.0039). This correlated with the lack of caudate and lentiform nuclei abnormalities. Developmental functions, including mobility, upper-extremity function, and language, of the MIH group were similar to the least severe classic type, lobar HPE.MIH is a recognizable variant of HPE with differing clinical prognosis. Similar to the lobar subtype by functional measures, MIH differs from classic HPE by the absence of endocrine dysfunction and choreoathetosis.

    View details for Web of Science ID 000179931100007

    View details for PubMedID 12499474

  • Holoprosencephaly: genetic, neuroradiological, and clinical advances. Seminars in pediatric neurology Hahn, J. S., Pinter, J. D. 2002; 9 (4): 309-319

    Abstract

    Recent advances in genetics and neuroimaging have greatly contributed to our understanding of the spectrum of midline brain and craniofacial malformations known as holoprosencephaly. This review summarizes our current understanding of the epidemiology and molecular-genetic bases of these malformations, as well as recent neuroradiological and clinical studies, which have revealed that the manifestations of holoprosencephaly are far more variable than previously appreciated. We also discuss the implications for and importance of accurate diagnosis, prognosis, management of common medical problems, and counseling for affected families.

    View details for PubMedID 12523555

  • Neuroanatomy of holoprosencephaly as predictor of function - Beyond the face predicting the brain NEUROLOGY Plawner, L. L., Delgado, M. R., Miller, V. S., Levey, E. B., Kinsman, S. L., Barkovich, A. J., Simon, E. M., Clegg, N. J., Sweet, V. T., Stashinko, E. E., Hahn, J. S. 2002; 59 (7): 1058-1066

    Abstract

    Despite advances in neuroimaging and molecular genetics of holoprosencephaly (HPE), the clinical spectrum of HPE has remained inadequately described.To better characterize the clinical features of HPE and identify specific neuroanatomic abnormalities that may be useful predictors of neurodevelopmental function.The authors evaluated 68 children with HPE in a multicenter, prospective study. Neuroimaging studies were assessed for the grade of HPE (lobar, semilobar, and alobar), the degree of nonseparation of the deep gray nuclei, and presence of dorsal cyst or cortical malformation.In general, the severity of clinical problems and neurologic dysfunctions correlated with the degree of hemispheric nonseparation (grade of HPE). Nearly three-quarters of the patients had endocrinopathies, with all having at least diabetes insipidus. The severity of endocrine abnormalities correlated with the degree of hypothalamic nonseparation (p = 0.029). Seizures occurred in approximately half of the children with HPE. The presence of cortical malformations was associated with difficult-to-control seizures. The presence and degree of dystonia correlated with the degree of nonseparation of the caudate and lentiform nuclei and the grade of HPE (p < 0.05). Hypotonia correlated with the grade of HPE (p < 0.05). Mobility, upper extremity function, and language correlated with the degree of nonseparation of the caudate, lentiform and thalamic nuclei, and grade of HPE (p < 0.01).Patients with HPE manifest a wide spectrum of clinical problems and neurologic dysfunction. The nature and severity of many of these problems can be predicted by specific neuroanatomic abnormalities found in HPE.

    View details for Web of Science ID 000178440600017

    View details for PubMedID 12370462

  • Analysis of the cerebral cortex in holoprosencephaly with attention to the sylvian fissures AMERICAN JOURNAL OF NEURORADIOLOGY Barkovich, A. J., Simon, E. M., Clegg, N. J., Kinsman, S. L., Hahn, J. S. 2002; 23 (1): 143-150

    Abstract

    Analysis of specific features in the brain of patients with holoprosencephaly (HPE) may clarify normal and abnormal brain development and help predict outcomes for specific children. We assessed sulcal and gyral patterns of cerebral cortex in patients with HPE and developed a method of grading brain development.Neuroimaging studies (75 MR imaging, 21 CT) of 96 patients with HPE were retrospectively reviewed, with specific attention paid to the cerebral cortex. Thickness of cortex, width of gyri, and depth of sulci were assessed subjectively and by measurement. The angle between lines drawn tangential to the sylvian fissures ("sylvian angle") was measured in each patient with HPE and in 20 control patients.Thickness of cortex was normal in all 96 patients. Gyral shape and width and sulcal depth were normal in 80 patients. Twelve patients, all with very severe HPE and microcephaly, had reduced sulcal depth, diffusely in eight and limited to the anteromedial cortex in four with lobar HPE. Four patients had subcortical heterotopia, located anterior to the interhemispheric fissure, associated with shallow sulci in the overlying cortex. Sylvian fissures were displaced further anteriorly and medially as HPE became more severe, until, in the most severe cases, no sylvian fissures could be identified. Sylvian angle measurements corresponded closely with severity of HPE, being largest in the most severe and smallest in the least severe cases. All patients with HPE had sylvian angles significantly larger than the mean of 15 degrees measured in the control patients.The only true malformations of cortical development were subcortical heterotopia. However, diffuse and focal abnormal sulci were observed. We propose our sylvian angle measurement of extent of frontal lobe development as an objective means of quantifying the severity of HPE.

    View details for Web of Science ID 000174478400023

    View details for PubMedID 11827887

  • Holoprosencephaly: recent advances and new insights. Current opinion in neurology Kinsman, S. L., Plawner, L. L., Hahn, J. S. 2000; 13 (2): 127-132

    Abstract

    Holoprosencephaly is a relatively common brain malformation occurring in 5-12/100,000 live births. The astonishing growth in molecular genetic medicine has provided the field of developmental nervous system malformations with new perspectives and tools for unraveling its mysteries and offering better information for clinicians and families. This is particularly evident in the group of complex midline malformations known as holoprosencephaly. Although new molecular findings have shed light on some of the causes and manifestations of this malformation, there remains a need to build on the existing clinical knowledge so that we may develop more effective treatments and improve the quality of life of these patients.

    View details for PubMedID 10987568

  • The impact of an Online Social Network With Wireless Monitoring Devices on Physical Activity and Weight Loss Journal of Primary Care & Community Health Greene Jessica, Sacks R, Piniewski B, Kil D, Hahn JS 2012; epublished
  • The Impact of an Online Social Network With Wireless Monitoring Devices on Physical Activity and Weight Loss Journal of Primary Care & Community Health Jessica Greene, Sacks R, Piniewski B, Kil D, Hahn JS 2012; epublished
  • The Impact of an Online Social Network With Wireless Monitoring Devices on Physical Activity and Weight Loss Journal of Primary Care & Community Health Jessica Greene, Sacks R, Piniewski B, Kil D, Hahn JS 2012; epublished
  • The Impact of an Online Social Network With Wireless Monitoring Devices on Physical Activity and Weight Loss Journal of Primary Care & Community Health Jessica Greene, Sacks R, Piniewski B, Kil D, Hahn JS 2012; epublished
  • Mutations in ZIC2 in human holoprosencephaly: description of a Novel ZIC2 specific phenotype and comprehensive analysis of 157 individuals JOURNAL OF MEDICAL GENETICS Solomon, B. D., Lacbawan, F., Mercier, S., Clegg, N. J., Delgado, M. R., Rosenbaum, K., Dubourg, C., David, V., Olney, A. H., Wehner, L., Hehr, U., Bale, S., Paulussen, A., Smeets, H. J., Hardisty, E., Tylki-Szymanska, A., Pronicka, E., Clemens, M., McPherson, E., Hennekam, R. C., Hahn, J., Stashinko, E., Levey, E., Wieczorek, D., Roeder, E., Schell-Apacik, C. C., Booth, C. W., Thomas, R. L., Kenwrick, S., Cummings, D. A., Bous, S. M., Keaton, A., Balog, J. Z., Hadley, D., Zhou, N., Long, R., Velez, J. I., Pineda-Alvarez, D. E., Odent, S., Roessler, E., Muenke, M. 2010; 47 (8): 513-524

    Abstract

    Holoprosencephaly (HPE), the most common malformation of the human forebrain, may be due to mutations in genes associated with non-syndromic HPE. Mutations in ZIC2, located on chromosome 13q32, are a common cause of non-syndromic, non-chromosomal HPE.To characterise genetic and clinical findings in patients with ZIC2 mutations.Through the National Institutes of Health and collaborating centres, DNA from approximately 1200 individuals with HPE spectrum disorders was analysed for sequence variations in ZIC2. Clinical details were examined and all other known cases of mutations in ZIC2 were included through a literature search.By direct sequencing of DNA samples of an unselected group of unrelated patients with HPE in our NIH laboratory, ZIC2 mutations were found in 8.4% (49/582) of probands. A total of 157 individuals from 119 unrelated kindreds are described, including 141 patients with intragenic sequence determined mutations in ZIC2. Only 39/157 patients have previously been clinically described. Unlike HPE due to mutations in other genes, most mutations occur de novo and the distribution of HPE types differs significantly from that of non-ZIC2 related HPE. Evidence is presented for the presence of a novel facial phenotype which includes bitemporal narrowing, upslanting palpebral fissures, a short nose with anteverted nares, a broad and well demarcated philtrum, and large ears.HPE due to ZIC2 mutations is distinct from that due to mutations in other genes. This may shed light on the mechanisms involved in formation of the forebrain and face and will help direct genetic counselling and diagnostic strategies.

    View details for DOI 10.1136/jmg.2009.073049

    View details for Web of Science ID 000280274200002

    View details for PubMedID 19955556

  • Compound Heterozygosity for Mutations in PAX6 in a Patient With Complex Brain Anomaly, Neonatal Diabetes Mellitus, and Microophthalmia AMERICAN JOURNAL OF MEDICAL GENETICS PART A Solomon, B. D., Pineda-Alvarez, D. E., Balog, J. Z., Hadley, D., Gropman, A. L., Nandagopal, R., Han, J. C., Hahn, J. S., Blain, D., Brooks, B., Muenke, M. 2009; 149A (11): 2543-2546

    Abstract

    We report on a patient with trisomy 21, microophthalmia, neonatal diabetes mellitus, hypopituitarism, and a complex structural brain anomaly who was a member of a large bilineal family with eye anomalies. The patient inherited a different mutation in PAX6 from each parent and is the only known living and second reported patient with compound heterozygosity for mutations in PAX6. PAX6 is a transcription factor involved in eye and brain development and has roles in pancreatic and pituitary development. Clinical evaluation of the propositus and his parents demonstrated the effects of mutations of differing severity in multiple individuals.

    View details for DOI 10.1002/ajmg.a.33081

    View details for Web of Science ID 000271587600031

    View details for PubMedID 19876904

  • Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function JOURNAL OF MEDICAL GENETICS Lacbawan, F., Solomon, B. D., ROESSLER, E., El-Jaick, K., Domene, S., Velez, J. I., Zhou, N., Hadley, D., Balog, J. Z., Long, R., Fryer, A., Smith, W., Omar, S., McLean, S. D., Clarkson, K., LICHTY, A., Clegg, N. J., Delgado, M. R., Levey, E., Stashinko, E., Potocki, L., VANALLEN, M. I., Clayton-Smith, J., Donnai, D., Bianchi, D. W., Juliusson, P. B., Njolstad, P. R., Brunner, H. G., Carey, J. C., Hehr, U., Muesebeck, J., Wieacker, P. F., Postra, A., Hennekam, R. C., van den Boogaard, M. H., van Haeringen, A., Paulussen, A., Herbergs, J., Schrander-Stumpel, C. T., Janecke, A. R., Chitayat, D., Hahn, J., McDonald-McGinn, D. M., Zackai, E. H., Dobyns, W. B., Muenke, M. 2009; 46 (6): 389-398

    Abstract

    Holoprosencephaly (HPE) is the most common structural malformation of the human forebrain. There are several important HPE mutational target genes, including the transcription factor SIX3, which encodes an early regulator of Shh, Wnt, Bmp and Nodal signalling expressed in the developing forebrain and eyes of all vertebrates.To characterise genetic and clinical findings in patients with SIX3 mutations.Patients with HPE and their family members were tested for mutations in HPE-associated genes and the genetic and clinical findings, including those for additional cases found in the literature, were analysed. The results were correlated with a mutation-specific functional assay in zebrafish.In a cohort of patients (n = 800) with HPE, SIX3 mutations were found in 4.7% of probands and additional cases were found through testing of relatives. In total, 138 cases of HPE were identified, 59 of whom had not previously been clinically presented. Mutations in SIX3 result in more severe HPE than in other cases of non-chromosomal, non-syndromic HPE. An over-representation of severe HPE was found in patients whose mutations confer greater loss of function, as measured by the functional zebrafish assay. The gender ratio in this combined set of patients was 1.5:1 (F:M) and maternal inheritance was almost twice as common as paternal. About 14% of SIX3 mutations in probands occur de novo. There is a wide intrafamilial clinical range of features and classical penetrance is estimated to be at least 62%.Our data suggest that SIX3 mutations result in relatively severe HPE and that there is a genotype-phenotype correlation, as shown by functional studies using animal models.

    View details for DOI 10.1136/jmg.2008.063818

    View details for Web of Science ID 000266536300005

    View details for PubMedID 19346217

  • Holoprosencephaly. Handbook of clinical neurology Hahn, J. S. 2008; 87: 13-37

    View details for DOI 10.1016/S0072-9752(07)87002-3

    View details for PubMedID 18809016

  • Functional analysis of mutations in TGIF associated with holoprosencephaly MOLECULAR GENETICS AND METABOLISM El-Jaick, K. B., Powers, S. E., Bartholin, L., Myers, K. R., Hahn, J., Orioli, I. M., Ouspenskaia, M., Lacbawan, F., Roessler, E., Wotton, D., Muenke, M. 2007; 90 (1): 97-111

    Abstract

    Holoprosencephaly (HPE) is the most common structural malformation of the forebrain and face in humans. Our current understanding of the pathogenesis of HPE attempts to integrate genetic susceptibility, evidenced by mutations in the known HPE genes, with the epigenetic influence of environmental factors. Mutations or deletions of the human TGIF gene have been associated with HPE in multiple population cohorts. Here we examine the functional effects of all previously reported mutations, and describe four additional variants. Of the eleven sequence variations in TGIF, all but four can be demonstrated to be functionally abnormal. In contrast, no potentially pathogenic sequence alterations were detected in the related gene TGIF2. These results provide further evidence of a role for TGIF in HPE and demonstrate the importance of functional analysis of putative disease-associated alleles.

    View details for DOI 10.1016/j.ymgme.2006.07.011

    View details for Web of Science ID 000243476600016

    View details for PubMedID 16962354

  • Mild developmental delay in terminal chromosome 6p deletion AMERICAN JOURNAL OF MEDICAL GENETICS PART A Chen, K. M., Cherry, A. M., Hahn, J. S., Enns, G. M. 2004; 129A (2): 201-205

    Abstract

    Deletions involving the short arm of chromosome 6 are relatively rare. Although features of this condition are variable, common findings include developmental delay, ocular abnormalities, hearing loss, and cardiac defects. In an effort to define further the clinical variability of this condition, we report a 6-year-old female with a de novo terminal deletion of chromosome 6 at band 6p24, with mild gross motor delays and normal cognition.

    View details for DOI 10.1002/ajmg.a.30127

    View details for Web of Science ID 000223478900020

    View details for PubMedID 15316977

  • Microangiopathy of brain, retina, and inner ear (Susac's syndrome) in an adolescent female presenting as acute disseminated encephalomyelitis PEDIATRICS Hahn, J. S., Lannin, W. C., Sarwal, M. M. 2004; 114 (1): 276-281

    Abstract

    Susac's syndrome is a rare disorder that consists of microangiopathy of the brain, retina, and inner ear and usually affects young women in young adulthood. The triad of clinical manifestations consists of acute encephalopathy with neurologic signs, branch retinal artery occlusion (BRAO), and sensorineural hearing loss. We present a case of an adolescent female who presented at age 16 years with clinical and neuroimaging features of acute disseminated encephalomyelitis (ADEM). The full triad did not develop until 2.5 years after the initial neurologic presentation.

    View details for Web of Science ID 000222439200067

    View details for PubMedID 15231946

  • Frontal lobe seizures and uveitis associated with acute human parvovirus B19 infection JOURNAL OF CHILD NEUROLOGY Hsu, D., Sandborg, C., Hahn, J. S. 2004; 19 (4): 304-306

    Abstract

    We report a 5-year-old girl who developed repeated episodes of behavioral alterations shortly after human parvovirus B19 infection and uveitis. Video-electroencephalographic study demonstrated that these brief episodes were frontal lobe seizures. Seizures responded promptly to antiepilepsy medications. Further diagnostic testing did not reveal any rheumatologic disorders. Human parvovirus B19 infections in children are more commonly associated with febrile seizures and meningoencephalitis. Our case demonstrates that, rarely, it may be associated with the development of partial epilepsy.

    View details for Web of Science ID 000221419000013

    View details for PubMedID 15163099

  • Stimulus-induced drop episodes in Coffin-Lowry syndrome PEDIATRICS Nelson, G. B., Hahn, J. S. 2003; 111 (3)

    Abstract

    Coffin-Lowry syndrome (CLS) is a rare disorder characterized by moderate to severe mental retardation, facial dysmorphism, tapering digits, and skeletal deformity. Paroxysmal drop attacks occur in patients with CLS, characterized by sudden loss of muscle tone induced by unexpected tactile or auditory stimuli. Our objective is to characterize these attacks better using neurophysiologic studies.We report 2 teenage boys with CLS and stimulus-induced drop episodes (SIDEs). Simultaneous surface electromyogram (EMG) and video electroencephalogram were performed during SIDEs on our 2 patients.Both patients had SIDEs stimulated by a loud noise, unexpected light touch stimulation, or visual threat that were characterized by abrupt episodes of complete or partial loss of lower extremity tone. These events were not associated with impairment of consciousness, and immediate recovery was noted. Simultaneous surface EMG and video electroencephalogram revealed no epileptiform discharges in either patient. In the first patient, after unexpected tactile or auditory stimulation, tonic EMG activity in paraspinal muscles was lost briefly, similar to that seen in cataplexy. In the second patient, at 6 years of age, sudden nonepileptic drop episodes were induced by an unexpected tactile, auditory, or visual stimulation. At 11 years of age, his episodes had changed to brief myoclonic jerk and tonic spasm that were triggered by unexpected tactile and auditory stimuli. An increase in tonic EMG activity occurred during the attacks, consistent with hyperekplexia.Our data suggest that SIDEs in CLS are a heterogeneous group of nonepileptic events that may manifest features of both cataplexy and hyperekplexia, even in the same patient.

    View details for Web of Science ID 000181294000001

    View details for PubMedID 12612271

  • Short duration of benign partial epilepsy in infancy JOURNAL OF CHILD NEUROLOGY Nelson, G. B., Olson, D. M., Hahn, J. S. 2002; 17 (6): 440-445

    Abstract

    It has previously been reported that benign partial epilepsy in infancy constitutes up to 29% of the epilepsies presenting in the first 2 years of life. To determine the proportion of benign partial epilepsy in our epilepsy population, we retrospectively reviewed 331 patients with greater than two afebrile seizures in the first 2 years of life between 1993 and 2000. Inclusion criteria were (1) partial seizures with or without secondary generalization, (2) normal development, (3) no other neurologic abnormalities, (4) normal interictal electroencephalograms (EEGs), and (5) good response to treatment. Exclusion criteria included seizures that (1) were caused by acute central nervous system insult, (2) occurred only within the first month of life, and (3) lasted longer than 30 minutes. Of 331 patients, 22 (6.6%) fulfilled the criteria with a minimum of 2 years and a mean of 4 years of follow-up off antiepilepsy drug treatment. Six (27%) had complex partial seizures, and 16 (73%) had complex partial seizures with secondary generalization. Neuroimaging studies were normal in all patients. Of the 6 patients with ictal EEGs, 3 had a temporal lobe focus, 1 had an occipital lobe focus, and the remaining 2 had dual foci. Median onset was 4.0 months (range 0.8-9.3). Seizures remitted within 4 months in 20 (91%). Mean duration of seizure persistence was 2.1 months (range 0-8.3) and was longer in treated patients. Median age at last seizure was 6.4 months (range 2-18). Nineteen were treated with antiepilepsy drugs. At last follow-up (mean duration of 52.2 months), all patients were seizure free and off antiepilepsy drugs. Benign partial epilepsy in infancy is an epilepsy syndrome of short duration and is easily recognized using accepted classification criteria. Benign partial epilepsy in infancy appears to be an idiopathic localization-related epilepsy with a favorable prognosis. The incidence in our population is not as common as previously reported. Based on our findings, we suggest weaning of antiepilepsy drugs 6 months after seizure onset.

    View details for Web of Science ID 000177202900008

    View details for PubMedID 12174965

  • Holoprosencephaly: A review AMERICAN JOURNAL OF ELECTRONEURODIAGNOSTIC TECHNOLOGY Clegg, N. J., Gerace, K. L., Sparagana, S. P., Hahn, J. S., Delgado, M. R. 2002; 42 (2): 59-72
  • Congenital hypomyelination neuropathy in a newborn infant: Unusual cause of diaphragmatic and vocal cord paralyses PEDIATRICS Hahn, J. S., Henry, M., Hudgins, L., Madan, A. 2001; 108 (5)

    Abstract

    We report a case of congenital hypomyelination neuropathy presenting at birth. The infant had generalized hypotonia and weakness. There was decreased respiratory effort along with a right phrenic nerve and left vocal cord paralyses. Tongue fasciculations were present. Deep tendon reflexes were absent in the upper extremities and hypoactive (1+) in the lower extremities. Magnetic resonance imaging of the head revealed no intracranial abnormalities, including normal cerebral myelination. Nerve conduction study showed absence of motor and sensory action potentials in the hands when the nerves in the upper limbs were stimulated. A motor response could be elicited only in the proximal leg muscles. Needle electromyography study was normal in the proximal limb muscles, but showed active denervation in the distal muscles of the arm and leg. These findings were thought to be consistent with a length-dependent sensorimotor peripheral polyneuropathy of axonal type with greater denervation of the distal muscles. A biopsy of the quadriceps muscle showed mild variability in fiber diameter, but no group typing or group atrophy. The muscle fibers showed no intrinsic abnormalities. Biopsy of the sural nerve showed scattered axons with very thin myelin sheaths. There was also a nearly complete loss of large diameter myelinated fibers. No onion bulb formations were noted. These findings were thought to be consistent with congenital hypomyelination neuropathy with a component of axonopathy. DNA analysis for identification of previously characterized mutations in the genes MPZ, PMP22, and EGR2 was negative. Several attempts at extubation failed and the infant became increasingly ventilator-dependent with increasing episodes of desaturation and hypercapnea. He also developed increasing weakness and decreased movement of all extremities. He underwent surgery at 2 months of age for placement of a gastrostomy tube and a tracheostomy. He was discharged from the hospital on a ventilator at 6 months of age. The infant was 13 months old at the time of submission of this report. Although he appears cognitively normal, he remains profoundly hypotonic and is on a home ventilator. There was no evidence of progressive weakness. Congenital hypomyelination neuropathy is a rare form of neonatal neuropathy that should be considered in the differential diagnosis of a newborn with profound hypotonia and weakness. It appears to be a heterogeneous disorder with some of the cases being caused by specific genetic mutations.

    View details for Web of Science ID 000171925200018

    View details for PubMedID 11694679

  • Sedation of children for electroencephalograms PEDIATRICS Olson, D. M., Sheehan, M. G., Thompson, W., Hall, P. T., Hahn, J. 2001; 108 (1): 163-165

    Abstract

    Sedation sometimes is necessary to perform an electroencephalogram (EEG) on a child. A dramatic decline in the need to use conscious sedation in our EEG laboratory prompted this review of our sedation experience. The purpose of this review was to determine the incidence of adverse sedation effects and to determine why the need for sedation had declined.All 513 attempts to administer sedation to children who were undergoing EEG studies during a 4-year period were reviewed retrospectively. Parameters studied included type and amount of the sedative agents, need for repeated dosing, successful completion of the EEG, and complications attributed to the sedative.Sedation was attempted in 513 (18%) of 2855 EEGs performed during the 4-year period. Ninety-one percent of the EEGs performed with sedation were completed successfully. Chloral hydrate was the most frequently administered sedative. Complications (transient oxygen desaturation) occurred in 3 children, all of whom had recognized risk factors for airway compromise. The proportion of children who required sedation decreased from 32% to just 2% during that time period.Sedation of children who are undergoing EEG examinations is effective and safe. Complications are infrequent. The need for sedation can be decreased greatly by adequate preparation and by creating a less-threatening, child-friendly environment in which to perform the study.

    View details for Web of Science ID 000169571400044

    View details for PubMedID 11433070

  • Moyamoya syndrome in children with Alagille syndrome: Additional evidence of a vasculopathy PEDIATRICS Woolfenden, A. R., Albers, G. W., Steinberg, G. K., Hahn, J. S., Johnston, D. C., Farrell, K. 1999; 103 (2): 505-508

    View details for Web of Science ID 000078437800023

    View details for PubMedID 9925853

  • Progressive multifocal leukoencephalopathy in a 15-year-old boy with scleroderma and secondary amyloidosis PEDIATRICS Hahn, J. S., Harris, B. T., Gutierrez, K., Sandborg, C. 1998; 102 (6): 1475-1479

    View details for Web of Science ID 000077311500033

    View details for PubMedID 9832587

  • Celiac disease presenting as gait disturbance and ataxia in infancy JOURNAL OF CHILD NEUROLOGY Hahn, J. S., Sum, J. M., Bass, D., Crowley, R. S., Horoupian, D. S. 1998; 13 (7): 351-353

    View details for Web of Science ID 000075150900010

    View details for PubMedID 9701487

  • Wernicke encephalopathy and Beriberi during total parenteral nutrition attributable to multivitamin infusion shortage PEDIATRICS Hahn, J. S., Berquist, W., Alcorn, D. M., Chamberlain, L., Bass, D. 1998; 101 (1)

    Abstract

    Wernicke encephalopathy (WE) is an acute neurologic disorder characterized by a triad of ophthalmoplegia, ataxia, and mental confusion. WE is attributable to thiamine (vitamin B1) deficiency. Beriberi is the systemic counterpart of thiamine deficiency and often manifests in cardiovascular collapse. WE is usually associated with alcoholism and malnutrition. It has also been seen in people with gastrointestinal diseases with malabsorption. Patients who have received total parenteral nutrition (TPN) without proper replacement of thiamine have also developed WE. Since November 1996, there has been a shortage of multivitamin infusion (MVI). Many patients who were on chronic TPN with MVI ceased to receive the MVI and were converted to an oral form of the multivitamin. As a result, there have been several reports of children and adults on TPN who have developed WE as a result of thiamine deficiency. With this case report, we bring to attention the association of the MVI shortage and WE. Early diagnosis of WE is important, because if it is treated with thiamine in the acute stages, the neurologic and cardiovascular abnormalities can be reversed.We report a 20-year-old female patient with Crohn's disease who developed WE as a result of thiamine deficiency. She had Crohn's disease since age 9 years and was on chronic TPN. Two months before admission, MVI was discontinued in the TPN because of the shortage of its supply. An oral multivitamin tablet was substituted instead. She was admitted to the hospital for persistent vomiting. In the hospital, she continued to receive TPN without MVI, but continued taking an oral multivitamin preparation. Two weeks after admission, she developed signs of WE including diplopia, ophthalmoplegia, nystagmus, and memory disturbance. She also developed hypotension that was thought to be caused by beriberi. She was treated with 50 mg of intravenous thiamine. Within hours of the intravenous thiamine, her hypotension resolved. The day after the infusion, she no longer complained of diplopia, and her ophthalmoplegia had improved dramatically. Magnetic resonance imaging showed several areas of abnormally high signal on T2-weighted images in the brainstem, thalamus, and mamillary bodies. The topographic distribution of these changes was typical of WE. After 2 months, her mental status and neurologic status had recovered completely.WE and thiamine deficiency should be considered in all patients with malabsorption, malnutrition, and malignancies. WE from thiamine deficiency can occur as a result of cessation of MVI in the TPN infusion. Even if an oral multivitamin preparation is given instead of MVI, patients with malabsorption may not absorb thiamine adequately. Prompt diagnosis of WE is important because it is potentially fatal and readily treatable with thiamine supplementation. Early recognition of WE may be more difficult in children, because the classic triad of symptoms may not develop fully. Magnetic resonance imaging may be useful in these cases to confirm the diagnosis of WE. Because the shortage of MVI is expected to be a long-term, there are likely to be more cases of WE in the pediatric population of TPN-dependent children. Because there is no shortage of intravenous thiamine, it should be administered with TPN even if MVI is not available.

    View details for Web of Science ID 000071331400026

    View details for PubMedID 9417174

  • Bilateral tonic-clonic epileptic seizures in non-benign familial neonatal convulsions PEDIATRIC NEUROLOGY Alfonso, I., Hahn, J. S., Papazian, O., Martinez, Y. L., Reyes, M. A., Aicardi, J. 1997; 16 (3): 249-251

    Abstract

    We report an electroclinical pattern considered characteristic of benign familial neonatal convulsions (BFNC) in two neonates without BFNC. Both neonates were products of uncomplicated pregnancies, labor, and deliveries. The cause of the seizures was not established. There was no family history of seizures or epilepsy. Seizures started on the second and third days after birth. Ten seizures were captured by continuous video-EEG telemetry. The electroclinical events began with generalized tonic posturing coinciding with the appearance of diffuse attenuation of the EEG activity. After several seconds, bilateral clonic movements accompanied by bilateral repetitive sharp waves or spikes occurred in the EEG. One patient had normal development; the other became autistic. We conclude that the electroclinical pattern occurring in BFNC can occur in other types of neonatal seizures.

    View details for Web of Science ID A1997XB93800012

    View details for PubMedID 9165519

  • Phenytoin-related chorea in children with deep hemispheric vascular malformations JOURNAL OF CHILD NEUROLOGY Koukkari, M. W., Vanefsky, M. A., Steinberg, G. K., Hahn, J. S. 1996; 11 (6): 490-491

    View details for Web of Science ID A1996VW88600015

    View details for PubMedID 9120230

  • Intravenous gammaglobulin therapy in recurrent acute disseminated encephalomyelitis NEUROLOGY Hahn, J. S., Siegler, D. J., ENZMANN, D. 1996; 46 (4): 1173-1174

    View details for Web of Science ID A1996UG63500061

    View details for PubMedID 8780119

  • Predictive value of EEG for outcome and epilepsy following neonatal seizures ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY ORTIBUS, E. L., Sum, J. M., Hahn, J. S. 1996; 98 (3): 175-185

    Abstract

    The value of the electroencephalogram in predicting outcome and epilepsy was examined in neonates who had experienced EEG-confirmed neonatal seizures. Electroencephalogram, neuroimaging studies, and other clinical variables were systematically analyzed in 81 consecutive neonates with EEG-confirmed seizures. The surviving subjects were followed for a mean of 17 months to determine if they developed post-neonatal seizures (PNS) and abnormal neurodevelopmental outcome. Several EEG variables were correlated with neurodevelopmental outcome and PNS when analyzed with univariate and multivariate statistical analyses. The EEG background activity and the presence of status epilepticus were strong predictors of outcome, but were not associated with PNS. The presence of rhythmic theta-alpha bursts was highly favorable for both outcome and PNS. In the interictal EEG, the number of negative sharp waves in the temporal region correlated with outcome and PNS. Clinical variables associated with unfavorable outcomes included an abnormal neonatal neurologic exam and certain seizure etiologies (e.g. cerebral dysgenesis and infections). Global abnormalities on neuroimaging studies were invariably associated with an unfavorable outcome and with the development of PNS in 66% of cases. Using multivariate analysis, prediction of outcome (favorable versus unfavorable) was accurately achieved in 85% of cases when combining EEG variables with neuroimaging and clinical findings. In conclusion, in neonates with EEG-confirmed seizures, the EEG is a useful predictor of outcome, but is a less useful predictor of PNS.

    View details for Web of Science ID A1996UF90800001

    View details for PubMedID 8631277

  • BRAIN-STEM MULTIPLE-SCLEROSIS IN AN 11-YEAR-OLD CHILD PRESENTING AS ACUTE DISSEMINATED ENCEPHALOMYELITIS JOURNAL OF CHILD NEUROLOGY Mostafapour, S. P., ENZMANN, D., North, W., Hahn, J. S. 1995; 10 (6): 476-480

    Abstract

    Multiple sclerosis and acute disseminated encephalomyelitis are demyelinating disorders of the central nervous system that can present initially as an acute focal demyelinating syndrome. We report an 11-year-old girl who initially presented with intractable vomiting and hypertension and later developed a subacute onset of focal neurologic (brainstem) signs. Magnetic resonance imaging (MRI) demonstrated a large solitary demyelinating lesion of the brain stem consistent with acute disseminated encephalomyelitis. Because of the morbidity associated with biopsy and its questionable value in the course of management of this patient, she was treated empirically with aggressive supportive measures and high-dose corticosteriod therapy. She had near full recovery, with only minimal neurologic sequelae. Six months later, she presented with similar focal neurologic signs, and a new lesion was found on MRI. Because of the separation of her two episodes in time and central nervous system location, a diagnosis of multiple sclerosis was made. Herein, we used this patient to illustrate the difficulty in distinguishing acute disseminated encephalomyelitis from multiple sclerosis in patients who present initially with an acute focal demyelinating syndrome.

    View details for Web of Science ID A1995TD66300011

    View details for PubMedID 8576560

  • KERNICTERUS IN A FULL-TERM INFANT PEDIATRICS Penn, A. A., Enzmann, D. R., Hahn, J. S., Stevenson, D. K. 1994; 93 (6): 1003-1006

    View details for Web of Science ID A1994NP67800024

    View details for PubMedID 7794295

  • UNUSUAL MRI FINDINGS AFTER STATUS EPILEPTICUS DUE TO CAT-SCRATCH DISEASE PEDIATRIC NEUROLOGY Hahn, J. S., Sum, J. M., Lee, K. P. 1994; 10 (3): 255-258

    Abstract

    A 4-year-old girl with status epilepticus and severe encephalopathy associated with cat-scratch disease is described. She had prolonged seizures lasting more than 2 weeks and required treatment with pentobarbital coma. She developed unusual abnormalities on magnetic resonance imaging scans that involved the thalami and the cortex of the temporal, parietal, and occipital lobes. She has developed a persistent encephalopathy manifesting as visual disturbance and frequent partial seizures.

    View details for Web of Science ID A1994NM78000015

    View details for PubMedID 8060432

  • DISSEMINATED MULTIFOCAL HERPES-ZOSTER LEUKOENCEPHALITIS AND SUBCORTICAL HEMORRHAGE IN AN IMMUNOSUPPRESSED CHILD JOURNAL OF CHILD NEUROLOGY Herrold, J. M., Hahn, J. S. 1994; 9 (1): 56-58

    Abstract

    We describe a rare case of multifocal varicella-zoster leukoencephalitis in an immunosuppressed adolescent boy who developed a herpetiform rash on his groin and subsequently presented with a subacute encephalopathy, aphasia, and hemiparesis. Magnetic resonance imaging scan of the brain revealed multifocal bi-hemispheric target-like lesions predominantly in the white matter. A magnetic resonance imaging scan 2 weeks later showed a subcortical hemorrhage in the left insular region. He received long-term high-dose intravenous acyclovir and had significant improvement in his neurologic status.

    View details for Web of Science ID A1994MP94700014

    View details for PubMedID 8151085

  • CONTROVERSIES IN TREATMENT OF NEONATAL SEIZURES PEDIATRIC NEUROLOGY Hahn, J. S. 1993; 9 (4): 330-331

    View details for Web of Science ID A1993LU53500017

    View details for PubMedID 8216551

  • ELECTROENCEPHALOGRAPHIC AND NEUROIMAGING FINDINGS IN NEONATES UNDERGOING EXTRACORPOREAL MEMBRANE-OXYGENATION NEUROPEDIATRICS Hahn, J. S., Vaucher, Y., Bejar, R., Coen, R. W. 1993; 24 (1): 19-24

    Abstract

    Electroencephalograms (EEGs) were recorded on 36 infants who were treated with arteriovenous extracorporeal membrane oxygenation (ECMO) between 1986 and 1989. Twelve of 36 infants had EEGs prior to and during ECMO. Twenty-one infants who met ECMO criteria but were treated with mechanical ventilation only served as a comparison (COMP) group. Electrographic seizures occurred in 7 of the 36 (19%) ECMO patients and in 3 of the 21 (14%) COMP patients. Five of 7 ECMO infants had electrographic status epilepticus. Three infants developed electrographic seizures during ECMO in association with an acute cerebral injury. These patients did not have significant hemispheric predominance in the origin of electrographic seizures (2 right, 3 left and 2 bilateral). Repetitive or periodic discharges (RPD) with frequencies between 0.5 and 5 Hz were seen after starting therapy in 23 of the 36 (64%) ECMO patients and 15 of the 21 (71%) of the COMP group. Only in the ECMO patients did RPD arise significantly more frequently from the right hemisphere (13 right, 4 left and 6 bilateral; p = 0.015). Neuroimaging studies showed evidence of ischemic lesion in 8 of the 36 (22%) ECMO patients with significantly right-sided predominance (5 right, 1 left and 2 bilateral; p = .05). Cerebellar hemorrhages occurred in 3 ECMO patients. Ischemic lesions occurred in 3 of the 21 (14%) COMP patients, all occurring on the left side. In the ECMO group, severe outcome or death was significantly associated with the presence of electrographic seizures, status epilepticus, and suppression-burst pattern (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1993KR42000004

    View details for PubMedID 8474607

  • PROGNOSTIC VALUE OF EEG IN NEONATAL MENINGITIS - RETROSPECTIVE STUDY OF 29 INFANTS PEDIATRIC NEUROLOGY CHEQUER, R. S., Tharp, B. R., Dreimane, D., Hahn, J. S., Clancy, R. R., Coen, R. W. 1992; 8 (6): 417-422

    Abstract

    Neonatal meningitis is associated with significant neurologic sequelae. Previous studies from our laboratory and others demonstrated electroencephalography (EEG) to be a useful tool in predicting long-term neurologic outcome in at-risk neonates. We, therefore, retrospectively studied 29 infants with culture-proved neonatal meningitis who died in the neonatal period or survived to follow-up at a mean of 34.4 months. Seventy-five EEGs were obtained during the acute phase of infection; the degree of EEG background abnormality proved to be an accurate predictor of outcome. Infants who had normal or mildly abnormal backgrounds had normal outcomes, whereas those with markedly abnormal EEGs died or manifested severe neurologic sequelae at follow-up. When the EEG was considered with the presence or absence of seizures and the level of consciousness, an accurate prediction of neurologic outcome was obtained in 27 infants (93%). Although the EEG patterns were generally nonspecific, some abnormalities, such as positive rolandic sharp waves, persistent hemispheric or focal voltage attenuation, suggested more specific pathology (i.e., deep white matter necrosis, large-vessel infarction and abscess, respectively). EEG was also valuable for the recognition of subtle and subclinical seizures. Therefore, we conclude that EEG is a valuable tool for predicting the long-term prognoses of infants with neonatal meningitis.

    View details for Web of Science ID A1992KE22800001

    View details for PubMedID 1476568

  • DETECTION OF NEONATAL SEIZURES THROUGH COMPUTERIZED EEG ANALYSIS ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY Liu, A., Hahn, J. S., Heldt, G. P., Coen, R. W. 1992; 82 (1): 30-37

    Abstract

    Neonatal seizures are a symptom of central nervous system disturbances. Neonatal seizures may be identified by direct clinical observation by the majority of electrographic seizures are clinically silent or subtle. Electrographic seizures in the newborn consist of periodic or rhythmic discharges that are distinctively different from normal background cerebral activity. Utilizing these differences, we have developed a technique to identify electrographic seizure activity. In this study, autocorrelation analysis was used to distinguish seizures from background electrocerebral activity. Autocorrelation data were scored to quantify the periodicity using a newly developed scoring system. This method, Scored Autocorrelation Moment (SAM) analysis, successfully distinguished epochs of EEGs with seizures from those without (N = 117 epochs, 58 with seizure and 59 without). SAM analysis showed a sensitivity of 84% and a specificity of 98%. SAM analysis of EEG may provide a method for monitoring electrographic seizures in high-risk newborns.

    View details for Web of Science ID A1992GY30200005

    View details for PubMedID 1370141

  • NEONATAL SUBEPENDYMAL GIANT-CELL ASTROCYTOMA ASSOCIATED WITH TUBEROUS SCLEROSIS - MRI, CT, AND ULTRASOUND CORRELATION NEUROLOGY Hahn, J. S., Bejar, R., Gladson, C. L. 1991; 41 (1): 124-128

    Abstract

    We describe a term newborn with tuberous sclerosis who presented with a neonatal brain tumor, diagnosed as a subependymal giant cell astrocytoma. We compare the various imaging modalities used in the diagnosis of this tumor.

    View details for Web of Science ID A1991ER63300025

    View details for PubMedID 1985277

  • Winner of the Brazier Award. The dysmature EEG pattern in infants with bronchopulmonary dysplasia and its prognostic implications. Electroencephalography and clinical neurophysiology Hahn, J. S., Tharp, B. R. 1990; 76 (2): 106-113

    Abstract

    Bronchopulmonary dysplasia (BPD) is a chronic lung disease which occurs in premature infants who require prolonged mechanical ventilation and supplemental oxygen support. Infants with severe BPD often have neurological sequelae or early mortality. We have observed a pattern of delay in the maturation of cerebral electrical activity of some infants who have more severe forms of BPD. This delayed electroencephalographic (EEG) maturation or 'dysmaturity' is best recognized when the conceptional age (CA) of the premature infant approaches term and is characterized by the presence of EEG activity which normally disappears in premature infants by 36-37 weeks CA. We studied 36 infants with BPD who had serial EEGs and at least 1 EEG between 37 and 42 weeks CA. Dysmature EEGs were found in 23 infants. Unfavorable outcomes were found in 83% (19/23) of these infants, including 22% (5/23) mortality, and 61% (14/23) abnormal or suspect neurological outcome. Thirteen infants had EEGs which lacked dysmature features. Of these infants, 62% (8/13) had normal neurological outcome, and 38% (5/13) had unfavorable outcome (1 death, 2 abnormal, and 2 suspect). In 2 of the 5 infants with unfavorable outcomes without dysmature EEGs, a suppression-burst pattern (known to be associated with neurological sequelae) was found. The presence of dysmature patterns in the near-term or term EEG was associated with significantly less favorable outcome (P = 0.01). Several other clinical factors which were associated with dysmature EEGs are also discussed.

    View details for PubMedID 1697238

  • INTERBURST INTERVAL MEASUREMENTS IN THE EEGS OF PREMATURE-INFANTS WITH NORMAL NEUROLOGICAL OUTCOME ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY Hahn, J. S., Monyer, H., Tharp, B. R. 1989; 73 (5): 410-418

    Abstract

    Interburst intervals (IBIs) are quiescent periods of cerebral activity, which normally occur in the electroencephalograms (EEGs) of premature infants. Although it is generally felt that the duration of these intervals shorten with increasing conceptional age (CA), no systemic studies of IBIs have been done in a large group of normal premature infants with long-term follow-up and using multichannel routine EEGs. In this study, we measured the IBIs, using defined criteria, in 36 premature infants who were normal at 3 years. The IBIs were measured in 104 EEGs, obtained from these infants, using standard recording techniques. Mean and the maximum IBIs were calculated. IBI duration decreased with increasing CA, although this trend was not very prominent when very restrictive criteria for measurement of IBI length were used. Less restrictive criteria for defining an IBI led to trends which are similar to those of previous studies. Various clinical factors, such as mild encephalopathies, small intraventricular/subependymal hemorrhages, mild bronchopulmonary dysplasia, or patent ductus arteriosus did not significantly alter IBI durations. Comparison with other techniques of IBI measurement and recording are discussed. The longest period of continuous activity during a routine recording was also measured and was found to increase with increasing CA.

    View details for Web of Science ID A1989CA70100007

    View details for PubMedID 2479519

  • NEUROLOGICAL COMPLICATIONS OF HEMOLYTIC-UREMIC SYNDROME JOURNAL OF CHILD NEUROLOGY Hahn, J. S., Havens, P. L., Higgins, J. J., OROURKE, P. P., Estroff, J. A., Strand, R. 1989; 4 (2): 108-113

    Abstract

    Of 78 children identified with hemolytic-uremic syndrome at the Children's Hospital, Boston, from 1976 to 1986, 16 patients (20.5%) had neurological manifestations during their hospitalization. The most common manifestations were significant alterations in consciousness (coma, stupor) in 12 patients, and either generalized or partial seizures in ten patients. Others included hemiplegia (4 patients), decerebrate posturing (3), cortical blindness (2), hallucinations (1), and dystonic posturing (1). Cranial computed tomographic scans were abnormal in eight of 11 patients scanned. The abnormalities included diffuse cerebral edema (4 patients), large vessel infarctions (3), diffuse multiple small infarcts (4), and multiple hemorrhages (1). Five patients died as a result of their central nervous system complications, and six had neurological sequelae at discharge. Five patients recovered and at discharge had no evidence of neurological dysfunction.

    View details for Web of Science ID A1989U278100006

    View details for PubMedID 2715605

  • LABORATORY AND CLINICAL-VARIABLES TO PREDICT OUTCOME IN HEMOLYTIC-UREMIC SYNDROME AMERICAN JOURNAL OF DISEASES OF CHILDREN Havens, P. L., OROURKE, P. P., Hahn, J., Higgins, J., Walker, A. M. 1988; 142 (9): 961-964

    Abstract

    To develop a guide to the prognosis of children with hemolytic-uremic syndrome, we reviewed the medical records of 78 patients with this diagnosis seen at The Children's Hospital, Boston, from 1976 through 1986. Two outcome groups were defined as follows: a "good outcome" group, which contained 6 patients with no serious sequelae at hospital discharge, and a "bad outcome" group, which contained 12 patients who died, had chronic renal failure, or had central nervous system sequelae at hospital discharge. Differences between the two groups in routine laboratory tests available within 48 hours of admission were identified by bivariate analysis. Using serum calcium (less than or equal to 2 mmol/L) plus urine output (less than 0.4 mL/kg/h) over a 24-hour period as a test to predict outcome, we identified patients who died, had chronic renal failure, or had serious central nervous system sequelae, with 75% sensitivity, 98% specificity, and 90% positive predictive value.

    View details for Web of Science ID A1988P928200022

    View details for PubMedID 3414627

  • CENTRAL MAMMALIAN NEURONS NORMALLY RESISTANT TO GLUTAMATE TOXICITY ARE MADE SENSITIVE BY ELEVATED EXTRACELLULAR CA-2+ - TOXICITY IS BLOCKED BY THE N-METHYL-D-ASPARTATE ANTAGONIST MK-801 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Hahn, J. S., Aizenman, E., Lipton, S. A. 1988; 85 (17): 6556-6560

    Abstract

    It is widely held that a glutamate-like toxin that resembles N-methyl-D-aspartate may be responsible for the death of nerve cells seen after severe neurological insults including stroke, seizures, and degenerative disorders, such as Huntington disease, Alzheimer disease, and the amyotrophic lateral sclerosis-parkinsonism-dementia complex found on Guam. One puzzling fact about these maladies is the differential vulnerability of specific groups of neurons peculiar to each condition. We report here that an identified population of central neurons, rat retinal ganglion cells, are resistant to the neurotoxic effects of millimolar concentrations of glutamate under otherwise normal culture conditions. Patch-clamp experiments show that this resistance is associated with a very small ionic current response to N-methyl-D-aspartate. Varying the ionic milieu by increasing the extracellular Ca2+ concentration, however, results in a striking increase in glutamate-induced cell death in this population. Under these conditions, Mg2+ or the amino acid antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo-(alpha,gamma)-cyclohepten-5 ,10-imine maleate], blockers of N-methyl-D-aspartate receptor-coupled ion channels, completely abrogate the lethal effects of glutamate. These findings strongly suggest that Ca2+ entry through N-methyl-D-aspartate-activated channels is responsible for this type of neuronal death and suggest strategies that may be clinically useful in the treatment of various neurological disorders.

    View details for Web of Science ID A1988Q047600071

    View details for PubMedID 2901101

  • SERUM SICKNESS TRIGGERED BY ANAPHYLAXIS - A COMPLICATION OF IMMUNOTHERAPY JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Umetsu, D. T., Hahn, J. S., PEREZATAYDE, A. R., Geha, R. S. 1985; 76 (5): 713-718

    Abstract

    An 8-year-old boy developed anaphylaxis after receiving his maintenance dose of immunotherapy and proceeded to display the signs and symptoms of serum sickness. These consisted of fever, arthralgia, arthritis, urticaria followed by a hemorrhagic palpable rash, edema, lymphadenopathy, splenomegaly, abdominal pain, proteinuria, and neurologic manifestations consistent with vascular compromise of the posterior cerebral circulation. A skin biopsy specimen revealed perivascular infiltrates of lymphocytes and few polymorphonuclear neutrophils. The timing of events in this patient suggests that immunotherapy initiated a chain of events beginning with anaphylaxis and leading to serum sickness. It is hypothesized that the enhanced vascular permeability that accompanied the anaphylaxis allowed immune complexes that may have preexisted in the circulation to deposit in the blood vessels of the patient. These complexes may or may not have been related to the immunotherapy itself. Because antihistamines are known to prevent the induction of serum sickness, early and aggressive treatment of anaphylaxis during immunotherapy may prevent the occurrence of immune complex disease.

    View details for Web of Science ID A1985AUU3400010

    View details for PubMedID 4056255

Conference Proceedings


  • Structured data management - the design and implementation of a web-based video archive prototype Zou, H., Lu, Q. C., Durack, J. C., Chao, C., Strasberg, H. R., Zhang, Y., Tsai, M., Melmon, K., Hahn, J. S. BMJ PUBLISHING GROUP. 2001: 786-790

    Abstract

    In response to the lack of readily available multimedia rich medical knowledge sources to support medical education and patient care, we designed and implemented a web-based video publishing platform. In order to promote the development of high-quality, up-to-date educational content, we have devised a scalable structure that allows online submissions and continuous updating of video and accompanying textual descriptions. Our goal is to enable experts in varied medical domains to collaborate in the construction of a video library using an intuitive web-based interface. Neurologists at Stanford built a well-annotated neurology video collection that initially emphasized childhood and adult movement disorders. The collection may be accessed either as a stand-alone resource or as part of the Stanford Skolar MD, an integrated online medical knowledge provider. This manuscript discusses the design framework and implementation details of structured media content development. We present examples illustrating media data collection, content indexing using UMLS concepts, media storage, and web presentation.

    View details for Web of Science ID 000172263400160

    View details for PubMedID 11825293

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