Clinical Focus

  • Leukodystrophies
  • Autoimmune Diseases of the Nervous System
  • Neurology - Child Neurology

Academic Appointments

Honors & Awards

  • PERF-CNF Scientific Award, Child Neurology Foundation (2011)
  • Moore Award, Honorable Mention, American Association of Neuropathology (2003)
  • Chief Resident, Stanford Dept Neurology (2009-2010)
  • Medical Student Teaching Award, Stanford Dept Neurology (2009-2010)
  • Commencement Speaker, University of Rochester School of Medicine (2005)
  • Inductee, Arnold Gold Humanism Honor Society (2004)

Boards, Advisory Committees, Professional Organizations

  • Founding Member, ALD Connect (2014 - Present)
  • Founding Member, The Global Leukodystrophy Initiative (GLIA) (2014 - Present)

Professional Education

  • Post-doc, Stanford University Steinman & Robinson Labs, Neuroimmunology (2013)
  • Residency:Stanford University - Dept of Neurology (2010) CA
  • Residency:Massachusetts General Hospital (2007) MA
  • Internship:Massachusetts General Hospital (2006) MA
  • Board Certification: Neurology - Child Neurology, American Board of Psychiatry and Neurology (2010)
  • Medical Education:University of Rochester School of Medicine (2005) NY

Research & Scholarship

Current Research and Scholarly Interests

Our research group is dedicated to improving care for children with degenerative neurological disorders. We are particularly focused on genetic and autoimmune disorders that cause damage to the myelin (the fatty insulation around the nerves) of the brain and spinal cord. X-linked adrenoleukodystrophy (genetic) and multiple sclerosis (autoimmune) are the prototypical examples of degenerative disorders of myelin; these are the two disorders we study most intensively.

Our group has two primary areas of interest:

1. In the laboratory, we are hard at work developing diagnostic and therapeutic biomarkers for multiple sclerosis (MS) and X-linked adrenoleukodystrophy (ALD)

2. In the clinic, we are leading efforts to develop innovative care strategies for patients with demyelinating disorders.

One of the great obstacles to understanding and treating MS is its pathological heterogeneity. MS is currently defined solely by clinical and radiological criteria. Although these criteria have improved over time, abundant evidence suggests that pathophysiologic "subtypes" of MS still exist and, moreover, are indistinguishable from one another using current diagnostic criteria. Because potential differences in MS pathogenesis may result in divergent responses to the same treatment, this pathogenic variability poses serious hurdles to developing and implementing treatment strategies for affected patients.

The inflammatory cerebral demyelination of ALD represents a potential genetic model for MS. ALD is a monogenetic, X-linked disorder involving a gene (ABCD1) that encodes a peroxisomal protein. The incidence is ~1:17,000. The biochemical hallmark of the disease is an accumulation of very-long chain fatty acids in several tissues, including myelin and blood. Cerebral demyelination occurs in only a subset of patients, but is not related to genotype, suggesting a role for environmental modifiers, much like MS.

Our group is on the verge of exciting breakthroughs with the potential to shed important insight on the pathogenic and therapeutic pathways common to both MS and ALD. We hope to move these insights into clinical trials in the very near future.

We are proud to partner with disease consortiums and patient advocacy groups from around the world in the fight against these diseases.


Journal Articles

  • Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing-remitting multiple sclerosis MULTIPLE SCLEROSIS JOURNAL Van Haren, K., Tomooka, B. H., Kidd, B. A., Banwell, B., Bar-Or, A., Chitnis, T., Tenembaum, S. N., Pohl, D., Rostasy, K., Dale, R. C., O'Connor, K. C., Hafler, D. A., Steinman, L., Robinson, W. H. 2013; 19 (13): 1726-1733


    BACKGROUND AND OBJECTIVE: Acute disseminated encephalomyelitis (ADEM) and relapsing-remitting multiple sclerosis (RRMS) share overlapping clinical, radiologic and laboratory features at onset. Because autoantibodies may contribute to the pathogenesis of both diseases, we sought to identify autoantibody biomarkers that are capable of distinguishing them. METHODS: We used custom antigen arrays to profile anti-myelin-peptide autoantibodies in sera derived from individuals with pediatric ADEM (n = 15), pediatric multiple sclerosis (Ped MS; n = 11) and adult MS (n = 15). Using isotype-specific secondary antibodies, we profiled both IgG and IgM reactivities. We used Statistical Analysis of Microarrays software to confirm the differences in autoantibody reactivity profiles between ADEM and MS samples. We used Prediction Analysis of Microarrays software to generate and validate prediction algorithms, based on the autoantibody reactivity profiles. RESULTS: ADEM was characterized by IgG autoantibodies targeting epitopes derived from myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein, and alpha-B-crystallin. In contrast, MS was characterized by IgM autoantibodies targeting myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein and oligodendrocyte-specific protein. We generated and validated prediction algorithms that distinguish ADEM serum (sensitivity 62-86%; specificity 56-79%) from MS serum (sensitivity 40-87%; specificity 62-86%) on the basis of combined IgG and IgM anti-myelin autoantibody reactivity to a small number of myelin peptides. CONCLUSIONS: Combined profiles of serum IgG and IgM autoantibodies identified myelin antigens that may be useful for distinguishing MS from ADEM. Further studies are required to establish clinical utility. Further biological assays are required to delineate the pathogenic potential of these antibodies.

    View details for DOI 10.1177/1352458513485653

    View details for Web of Science ID 000326893900010

    View details for PubMedID 23612879

  • Case Report of Subdural Hematoma in a Patient With Sturge-Weber Syndrome and Literature Review: Questions and Implications for Therapy JOURNAL OF CHILD NEUROLOGY Lopez, J., Yeom, K. W., Comi, A., Van Haren, K. 2013; 28 (5): 672-675


    Sturge-Weber syndrome is a neurocutaneous disorder associated with vascular abnormalities in the skin, eye, and brain leading to both acute and chronic cerebral hypoperfusion and, in some affected children, brain injury. Aspirin can reduce stroke-like events and seizure episodes and prevent further brain injuries in these patients. Although a few cases of intracranial hemorrhage in patients with Sturge-Weber syndrome have been reported, prior reports have not discussed this complication with regard to particular therapies. The authors present a toddler with Sturge-Weber syndrome who developed a subdural hematoma in the setting of a mechanical fall with minor head trauma. They discuss the possible role of aspirin in contributing to, or perhaps protecting against, intracranial hemorrhage in patients with Sturge-Weber syndrome. Further data are needed to establish the utility of aspirin in Sturge-Weber syndrome.

    View details for DOI 10.1177/0883073812449514

    View details for Web of Science ID 000317683900018

    View details for PubMedID 22805242

  • Therapeutic Advances in Pediatric Multiple Sclerosis. The Journal of pediatrics Van Haren, K., Waubant, E. 2013

    View details for PubMedID 23726542

  • Identification of Naturally Occurring Fatty Acids of the Myelin Sheath That Resolve Neuroinflammation SCIENCE TRANSLATIONAL MEDICINE Ho, P. P., Kanter, J. L., Johnson, A. M., Srinagesh, H. K., Chang, E., Purdy, T. M., Van Haren, K., Wikoff, W. R., Kind, T., Khademi, M., Matloff, L. Y., Narayana, S., Hur, E. M., Lindstrom, T. M., He, Z., Fiehn, O., Olsson, T., Han, X., Han, M. H., Steinman, L., Robinson, W. H. 2012; 4 (137)


    Lipids constitute 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain, and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives. Administration of these lipids ameliorated experimental autoimmune encephalomyelitis by suppressing activation and inducing apoptosis of autoreactive T cells, effects mediated by the lipids' saturated fatty acid side chains. Thus, phospholipids represent a natural anti-inflammatory class of compounds that have potential as therapeutics for MS.

    View details for DOI 10.1126/scitranslmed.3003831

    View details for Web of Science ID 000305075700005

    View details for PubMedID 22674551

  • Immune response in Leukodystrophies PEDIATRIC NEUROLOGY Eichler, F., Van Haren, K. 2007; 37 (4): 235-244


    Although the genetics and biochemistry of leukodystrophies have been extensively explored, the immune response in these disorders has received relatively little attention. Both the disease course and its response to treatment may be highly dependent on the immune system. In this review, we compare three common leukodystrophies, each with a different immune response: (1) X-linked adrenoleukodystrophy, which demonstrates a severe, lymphocytic inflammatory response; (2) metachromatic leukodystrophy, which yields a histiocytic response; and (3) vanishing white-matter disease, in which no inflammation is typically seen. We highlight the biochemical, pathologic, and clinical differences, while focusing on the immune response in each disease. We also review the response of leukodystrophies to immunomodulatory therapies and interventions such as hematopoietic stem-cell transplantation. Future studies may delineate specific inflammatory markers as possible candidates for therapeutic intervention.

    View details for DOI 10.1016/j.pediatrneurol.2007.06.011

    View details for Web of Science ID 000250295000001

    View details for PubMedID 17903666

  • The unfolded protein response in vanishing white matter disease JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY van der Voorn, J. P., van Kollenburg, B., Bertrand, G., Van Haren, K., Scheper, G. C., Powers, J. M., van der Knaap, M. S. 2005; 64 (9): 770-775


    Leukoencephalopathy with vanishing white matter (VWM) is an autosomal-recessive disorder in which febrile infections may provoke major neurologic deterioration. Characteristic pathologic findings include cystic white matter degeneration, foamy oligodendrocytes, dysmorphic astrocytes and oligodendrocytes, oligodendrocytosis, and apoptotic losses of oligodendrocytes. VWM is caused by mutations in eukaryotic initiation factor (eIF) 2B (eIF2B). eIF2B plays an important role in the regulation of protein synthesis. Mutant eIF2B may impair the ability of cells to regulate protein synthesis in response to stress and perhaps even under normal conditions. An overload of misfolded proteins in the endoplasmic reticulum activates the unfolded protein response (UPR), a compensatory mechanism that inhibits synthesis of new proteins and induces both prosurvival and proapoptotic signals. We have studied the activation of the UPR in VWM through the immunohistochemical expression of its upstream components PERK and phosphorylated eIF2alpha (eIF2alphaP) and combined immunohistochemical and Western blot analysis of the downstream effector proteins activating transcription factor-4 (ATF4) and C/EBP homologous protein (CHOP) in 4 VWM brains and 3 age-matched controls. We demonstrate activation of the UPR in glia of patients with VWM. Our findings may point to a possible explanation for the dysmorphic glia, the increased numbers of oligodendrocytes, and the apoptotic loss of oligodendrocytes in VWM.

    View details for Web of Science ID 000231781300004

    View details for PubMedID 16141786

  • The life and death of Oligodendrocytes in vanishing white matter disease JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY Van Haren, K., van der Voorn, J. P., PETERSON, D. R., van der Knaap, M. S., Powers, J. M. 2004; 63 (6): 618-630


    Vanishing white matter disease (VWM) is a progressive cavitating disease of central white matter due to a deficiency of the translation initiation factor eIF2B. Oligodendrocytes appear to be numerically increased in some white matter areas, while decreased in others. We compared oligodendrocytes of cerebral, cerebellar, and pontine white matter from 5 VWM patients with those of age-matched controls by light microscopy and immunohistochemistry using antibodies to activated caspase-3, bak, bax, bcl-2, survivin, and Ki-67, as well as by the TUNEL technique. Oligodendrocytes were identified morphologically and quantified using an ocular grid. We observed statistically significant increases in their densities at all sites; Ki-67-labeled oligodendrocytes were identified in 2 of 5 patients. Apoptotic oligodendrocytes were documented in 3 of 5 patients, while bcl-2 and survivin labeling was observed in 2 of 5 and 2 of 2 patients, respectively. There was a trend toward an increase in apoptotic labeling of oligodendrocytes that was strongest in the cerebrum, the major locus of VWM, in the youngest and most severely affected patients. These data conclusively demonstrate increased oligodendrocytic densities in VWM; the increase is not an artifact of white matter contraction. Our data also document that oligodendrocytes undergo apoptosis, perhaps in conjunction with major neurologic crises, and that a subset of oligodendrocytes are able to persist and proliferate. Conflicting proliferative, cell-death, and survival signals impact the oligodendrocytes of VWM.

    View details for Web of Science ID 000221897100006

    View details for PubMedID 15217090

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