Daniel H. Lowenstein (physician)

Last updated
Daniel H. Lowenstein
NationalityAmerican
Alma mater University of Colorado
Pennsylvania State University
Harvard Medical School
AwardsNumerous teaching awards; American Epilepsy Society Basic Research Award (2001)
Scientific career
Fields Neurology
Institutions University of California, San Francisco

Daniel H. Lowenstein is an American neurologist who is the Robert B. and Ellinor Aird Professor of Neurology and Executive Vice Chancellor and Provost at the University of California, San Francisco (UCSF). He is known for his work in the field of epilepsy including laboratory-based and clinical research, the clinical care of patients with epilepsy, and advocacy for the needs of patients and family members living with epilepsy. He was the originator of the “Academy of Medical Educators” concept, and is the recipient of teaching awards both at UCSF and nationally. He has served as the Dean for Medical Education at Harvard Medical School, and as President of the American Epilepsy Society. In 2017, he was elected to the National Academy of Medicine in recognition of his contributions to American medicine. [1]

Contents

Education and academic career

Lowenstein graduated with a B.A. in Mathematics from the University of Colorado (1973), obtained an M.S. degree in Man-Environment Relations from Pennsylvania State University (1978), and received his M.D. from Harvard Medical School in 1983.[ citation needed ] At the University of California, San Francisco (UCSF), he completed an internship in pediatrics (1983–84), a residency in neurology (1984–87), a two-year fellowship in Stanley Prusiner's Laboratory, and then became a faculty member at UCSF in the Department of Neurology where, in 1998, he was named the Robert B. and Ellinor Aird Professor of Neurology. While at UCSF, he established the UCSF Epilepsy Research Laboratory, and has served as Co-Chair for the Chancellor's Steering Committee on Diversity, and Chair of the “Blue Sky” Curriculum Design Task Force that helped design the new medical school curriculum. [1]

From 2000 to 2003, Lowenstein was Dean for Medical Education at Harvard Medical School (HMS). While there, he oversaw a re-organization of curricular governance, the creation of a new educational technology program, and the establishment of the HMS Academy.[ citation needed ] In 2003, he returned to UCSF as Division Chief of the UCSF Epilepsy Center, and director of the university's physician-scientist training programs. In February 2015, Chancellor Sam Hawgood tapped the physician-scientist to be second-in-command as the Executive Vice Chancellor and Provost for the university. In this role, Lowenstein leads UCSF's research enterprise and academic program, consisting of four professional schools and a Graduate Division. [1] [2]

Lowenstein has been a Member of the Advisory Council of the National Institute of Neurological Disorders and Stroke (NINDS), which helps to define scientific policy at the national level; President of the American Epilepsy Society (2003-2004); Chair of the NINDS Epilepsy Benchmarks Oversight Committee (2000-2014); and Chair of the International League Against Epilepsy Commission on Genetics (2013-2017). [1]

Awards

His national teaching awards include:

Lowenstein has also advocated for cultural diversity issues at UCSF, for which he received the 1998 Black Student Health Association's Faculty Award, the 1998 UCSF Dr. Martin Luther King, Jr. Award, and the 2006 Holly Smith Award for Exceptional Service to the UCSF School of Medicine. In 2009, he received the Chancellor's Award for Public Service in recognition of his creation and leadership of the Iraq Action Group which sponsored numerous programs to educate the Bay Area community about the health consequences of the Iraq War.[ citation needed ]

In 2015 Lowenstein received the Chancellor”s Diversity Award for Disability Service as result of his efforts to remove the stigma associated with mental illness among health professions students.[ citation needed ]

In 2017, Lowenstein was elected to the National Academy of Medicine in recognition of his contributions to epilepsy research, medical education and leadership in academic medicine.[ citation needed ]

Research

Lowenstein's clinical and research interests include the genetic factors thought to underlie many forms of epilepsies (idiopathic epilepsies) and the management and treatment of patients with status epilepticus (unusually prolonged seizures). [1]

His laboratory studies (carried out from 1989 to 2002) have addressed the fundamental mechanisms of neuronal network remodeling that occur during epileptogenesis, the process in which a normal network transforms into a hyperexcitable network capable of producing or relaying seizure activity. The main efforts of his research group focused on the various forms of cellular reorganization that are observed in humans with temporal lobe epilepsy, and the parallels between reorganization in the adult nervous system and normal developmental processes. Important findings by his team included the observation of selective neuronal loss in the setting of traumatic brain injury, the discovery that seizure activity in an adult model of temporal lobe epilepsy causes a marked increase in the birth of hippocampal neurons (with post-doc Jack Parent), and the recognition that numerous molecules responsible for normal development are also expressed in this same brain region in the adult.[ citation needed ]

In 2002, Lowenstein turned his attention toward questions related to the genetic basis of common forms of human epilepsy. Working with colleagues from throughout the world, he helped create the Epilepsy Phenome/Genome Project (EPGP), an international, multi-institutional, collaborative study that aimed to collect detailed phenotype data on 5,250 subjects with specific forms of epilepsy, with the goal of finding the genetic determinants of their disease through whole exome and whole genome sequencing. EPGP enrolled over 4,000 participants and, at the time, compiled the most extensive and detailed phenotype dataset in the history of epilepsy research. In 2011, Lowenstein and colleagues were successful in receiving funding for a new NINDS Epilepsy Center Without Walls, the “Epi4K: Gene Discovery in 4,000 Epilepsy Genomes” which had as one of its goals the analysis of the EPGP cohorts.[ citation needed ]

The first major findings of the collaborative effort between EPGP and Epi4K, which demonstrated the role of de novo mutations as the cause of many patients with epileptic encephalopathy, appeared in a 2013 issue of Nature. Numerous findings have since been published based on the combined work of EPGP and Epi4K, including a paper in Lancet Neurology describing the role of ultra-rare variants in the common epilepsies. In addition, Lowenstein has helped oversee the phenotyping efforts of the International League Against Epilepsy (ILAE) Consortium on Complex Epilepsies, which completed a meta-analysis of available genotype data on approximately 15,000 epilepsy patients. He is one of the leaders of Epi25, an international effort that has the ultimate goal of completing whole exome and whole genome sequencing on 25,000 patients with epilepsy in collaboration with the Broad Institute and other partner institutions.[ citation needed ]

Lowenstein's clinical research related to status epilepticus began with retrospective studies of patients admitted to San Francisco General Hospital, as well as a highly cited article suggesting a revision of the definition of status epilepticus. In the 1990s, he was the Principal Investigator of a prospective, multi-centered, NINDS-sponsored clinical trial looking at the potential benefits of active treatment of patients in status epilepticus in the pre-hospital setting. This five-year study, completed in 1999, helped define the optimal therapy for these patients nationally. From 2005 to 2015, Lowenstein served as Co-Principal Investigator and member of the Neurological Emergency Treatment Trials (NETT) Clinical Coordinating Center, which oversaw a network of academic centers and affiliated hospitals in the U.S. carrying out numerous clinical trials related to acute neurological disease. As part of this effort, he was Co-Principal Investigator with Dr. Robert Silbergleit for the Rapid Anticonvulsant Medications Prior to Arrival Trial (RAMPART) study, where he was involved in the design, oversight and implementation of a trial that unambiguously demonstrated the benefits of the administration of intramuscular midazolam in this setting.

RAMPART was selected as the “2013 Clinical Trial of the Year” by the Society for Clinical Trials. Most recently, working with colleagues in the field, Lowenstein helped in the design and implementation of the Established Status Epilepticus Treatment Trial (ESETT), a NINDS-funded, randomized, prospective study of fos-phenytoin, valproate or levetiracetam in the treatment of status epilepticus.[ citation needed ]

Other accomplishments

While chairing the UCSF “Blue Sky” Curriculum Design Task Force in the late 1990s, Lowenstein is credited for coming up with the idea of “The Academy”, a new approach for supporting the teaching mission of medical schools. The academy movement now involves over 35 institutions across the U.S. [1]

During the first White House-initiated Curing Epilepsy conference held in 2000, Lowenstein suggested that members of the epilepsy research community should attempt to capture the field's current 'state of the art' and define a series of goals for the field that could serve as a research agenda. This led to the adoption by the National Institutes of Neurological Disorders and Stroke (NINDS) of the “Epilepsy Research Benchmarks”, a program that has been led by Lowenstein and used by the NINDS and other funding agencies to help prioritize grant opportunities and demonstrate progress to the legislature and the public at-large. [1]

In April 2013, Lowenstein was selected by the students at UCSF to give “The Last Lecture”, where he was asked to respond to the prompt: “If you had but one lecture to give, what would you say?” Lowenstein's hour-long talk to over 700 members of the campus community was organized into four threads: adventure, passion, justice, and joy & sorrow. It was described by observers as “alternately inspiring, hilarious, and profoundly moving”. [1]

Publications

Lowenstein has published over 175 scholarly professional journal articles [4] that include:

Related Research Articles

<span class="mw-page-title-main">Epilepsy</span> Group of neurological disorders causing seizures

Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. An epileptic seizure is the clinical manifestation of an abnormal, excessive, and synchronized electrical discharge in the neurons. The occurrence of two or more unprovoked seizures defines epilepsy. The occurrence of just one seizure may warrant the definition in a more clinical usage where recurrence may be able to be prejudged. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical activity in the brain. These episodes can result in physical injuries, either directly, such as broken bones, or through causing accidents. In epilepsy, seizures tend to recur and may have no detectable underlying cause. Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy. People with epilepsy may be treated differently in various areas of the world and experience varying degrees of social stigma due to the alarming nature of their symptoms.

<span class="mw-page-title-main">Seizure</span> Period of symptoms due to excessive or synchronous neuronal brain activity

A seizure is a sudden change in behavior, movement, and/or consciousness due to abnormal electrical activity in the brain. Seizures can look different in different people. It can be uncontrolled shaking of the whole body or a person spacing out for a few seconds. Most seizures last less than two minutes. They are then followed by confusion/drowsiness before the person returns to normal. If a seizure lasts longer than 5 minutes, it is a medical emergency and needs immediate treatment.

Anticonvulsants are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain.

<span class="mw-page-title-main">Levetiracetam</span> Medication

Levetiracetam, sold under the brand name Keppra among others, is a medication used to treat epilepsy. It is used for partial-onset, myoclonic, or tonic–clonic seizures and is taken either by mouth as an immediate or extended release formulation or by injection into a vein.

<span class="mw-page-title-main">Clonazepam</span> Benzodiazepine medication

Clonazepam, sold under the brand name Klonopin among others, is a benzodiazepine medication used to prevent and treat anxiety disorders, seizures, bipolar mania, agitation associated with psychosis, obsessive–compulsive disorder (OCD), and akathisia. It is a long-acting tranquilizer of the benzodiazepine class. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. It is typically taken orally but is also used intravenously. Effects begin within one hour and last between eight and twelve hours in adults.

<span class="mw-page-title-main">Ruben Kuzniecky</span>

Ruben Kuzniecky is a neurologist scientist who is Vice-chair academic affairs and professor of neurology at Northwell Health specializing in the field of epilepsy, epilepsy surgery and neuro-imaging.

<span class="mw-page-title-main">Status epilepticus</span> Medical condition

Status epilepticus (SE), or status seizure, is a medical condition consisting of a single seizure lasting more than 5 minutes, or 2 or more seizures within a 5-minute period without the person returning to normal between them. Previous definitions used a 30-minute time limit. The seizures can be of the tonic–clonic type, with a regular pattern of contraction and extension of the arms and legs, or of types that do not involve contractions, such as absence seizures or complex partial seizures. Status epilepticus is a life-threatening medical emergency, particularly if treatment is delayed.

<span class="mw-page-title-main">Lennox–Gastaut syndrome</span> Rare form of childhood-onset epilepsy

Lennox–Gastaut syndrome (LGS) is a complex, rare, and severe childhood-onset epilepsy syndrome. It is characterized by multiple and concurrent seizure types including tonic seizure, cognitive dysfunction, and slow spike waves on electroencephalogram (EEG), which are very abnormal. Typically, it presents in children aged 3–5 years and most of the time persists into adulthood with slight changes in the electroclinical phenotype. It has been associated with perinatal injuries, congenital infections, brain malformations, brain tumors, genetic disorders such as tuberous sclerosis and numerous gene mutations. Sometimes LGS is observed after infantile epileptic spasm syndrome. The prognosis for LGS is marked by a 5% mortality in childhood and persistent seizures into adulthood.

<span class="mw-page-title-main">Spinocerebellar ataxia</span> Medical condition

Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of spinocerebellar ataxia at any given time. SCA is hereditary, progressive, degenerative, and often fatal. There is no known effective treatment or cure. SCA can affect anyone of any age. The disease is caused by either a recessive or dominant gene. In many cases people are not aware that they carry a relevant gene until they have children who begin to show signs of having the disorder. Currently, research is being conducted at Universities, such as the University of Minnesota, to elucidate many of the unknown characteristics of the disease.

Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy (SMEI), is an autosomal dominant genetic disorder which causes a catastrophic form of epilepsy, with prolonged seizures that are often triggered by hot temperatures or fever. It is very difficult to treat with anticonvulsant medications. It often begins before one year of age, with six months being the age that seizures, char­ac­ter­ized by prolonged convulsions and triggered by fever, usually begin.

Complex partial status epilepticus (CPSE) is one of the non-convulsive forms of status epilepticus, a rare form of epilepsy defined by its recurrent nature. CPSE is characterized by seizures involving long-lasting stupor, staring and unresponsiveness. Sometimes this is accompanied by motor automatisms, such as eye twitching.

Post-traumatic epilepsy (PTE) is a form of acquired epilepsy that results from brain damage caused by physical trauma to the brain. A person with PTE experiences repeated post-traumatic seizures more than a week after the initial injury. PTE is estimated to constitute 5% of all cases of epilepsy and over 20% of cases of acquired epilepsy.

Post-traumatic seizures (PTS) are seizures that result from traumatic brain injury (TBI), brain damage caused by physical trauma. PTS may be a risk factor for post-traumatic epilepsy (PTE), but a person having a seizure or seizures due to traumatic brain injury does not necessarily have PTE, which is a form of epilepsy, a chronic condition in which seizures occur repeatedly. However, "PTS" and "PTE" may be used interchangeably in medical literature.

The Epilepsy Phenome/Genome Project (EPGP) is a government-funded study to identify genes that influence the development of epilepsy and genes that affect the response to treatment. The study involves 25 major epilepsy centers and more than 150 scientists and clinical staff around the United States, Australia and Argentina. The goal is to create a repository of clinical and genetic information on a select group of patients with epilepsy. The hope is that this information will reveal new insights and improve diagnosis and treatment.

The Center for Cerebrovascular Research at the University of California, San Francisco is a collective of faculty and staff investigating matters related to cerebral circulation, particularly cerebrovascular disease resulting from narrowing of major blood vessels in the brain and vascular malformation of the brain. While research offices are located on Parnassus campus, San Francisco General Hospital hosts the center's laboratories and facilities. The center coordinates with additional faculty in various fields of neuroscience and vascular biology. Sponsors include the National Institute of Neurological Disorders and Stroke and the UCSF departments of Anesthesia, Neurological Surgery and Neurology.

Epilepsy-intellectual disability in females also known as PCDH19 gene-related epilepsy or epileptic encephalopathy, early infantile, 9 (EIEE9), is a rare type of epilepsy that affects predominately females and is characterized by clusters of brief seizures, which start in infancy or early childhood, and is occasionally accompanied by varying degrees of cognitive impairment. The striking pattern of onset seizures at a young age, genetic testing and laboratory results, potential developmental delays or developmental regression and associated disorders, eases diagnosis.

Michael G Hanna is Director of the UCL Institute of Neurology, University College London and professor in clinical neurology and consultant neurologist at the National Hospital for Neurology and Neurosurgery, Queen Square, London, and also Director of the Medical Research Council (MRC) Centre for Neuromuscular Disease.

Ashalatha Radhakrishnan is an Indian neurologist and a professor of neurology at the Sree Chitra Tirunal Institute for Medical Sciences and Technology. Her research on various neurological disorders have been documented by a number of articles. She has also contributed to several books, including Status Epilepticus: Practical Guidelines in Management, a handbook on Status epilepticus. She was the convener of workshop on epilepsy at the Monsoon Summit 2017 organized by the Kerala Association of Neurologists. The Department of Biotechnology of the Government of India awarded her the National Bioscience Award for Career Development, one of the highest Indian science awards, for her contributions to biosciences, in 2010.

<span class="mw-page-title-main">Michael Jeffrey Aminoff</span> American clinical neurologist and neurophysiologist

Michael Jeffrey Aminoff is a clinical neurologist and neurophysiologist whose later clinical work focused on treating Parkinson's disease and related movement disorders. He retired in 2022 and lives in San Francisco, California.

David Rowitch, FMedSci, FRS is an American physician-scientist known for his contributions to developmental glial biology and treatment of white matter diseases. He heads the Department of Paediatrics at the University of Cambridge and is an adjunct professor of pediatrics at the University of California San Francisco (UCSF).

References

  1. 1 2 3 4 5 6 7 8 9 Lowenstein, Daniel. "Executive Vice Chancellor & Provost". UC San Francisco. UCSF.
  2. "Driven by Science, Humanism and Service, Dan Lowenstein Joins UCSF Leadership Team". 29 January 2015.
  3. Alpha Omega Alpha Robert J. Glaser Distinguished Teacher Awards: Previous Award Recipients Archived 2010-06-13 at the Wayback Machine (Accessed 29 May 2010).
  4. 88 items were found in a search on the ISI Web of Science database, refined by: Subject Areas=( NEUROSCIENCES & NEUROLOGY OR BIOCHEMISTRY & MOLECULAR BIOLOGY OR PHARMACOLOGY & PHARMACY OR GENETICS & HEREDITY OR CELL BIOLOGY ) AND Authors=( LOWENSTEIN, DH ) (search conducted 29 May 2010)