Int J Neurosci. 2009;119(11):2118-23.
Tracing the origin of L-2-hydroxyglutaric aciduria in a family.
Sass JO, Romrell JS, Vinson SY, Fernandez HH, Fischer J, Rodriguez RL, Okun MS.

Labor für Klinische Biochemie und Stoffwechsel, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Freiburg, Mathildenstr. 1, 79106, Freiburg, Germany.

J Neurol. 2009 Oct 8. [Epub ahead of print]

The number and nature of emergency department encounters in patients with deep brain stimulators.

Resnick AS, Foote KD, Rodriguez RL, Malaty IA, Moll JL, Carden DL, Krock NE, Medley MM, Burdick A, Haq IU, Okun MS.
Department of Neurology, University of Florida, Gainesville, USA

Deep brain stimulation (DBS) has become an increasingly common modality for control of several neurological disorders such as Parkinson’s disease, dystonia, essential tremor (ET), and others. Our experience has demonstrated the need for emergency physicians to familiarize themselves with the potential complications of the DBS device as well as the device itself. Therefore, our aim in this paper was to elucidate the number and nature of DBS and non-DBS presentations to the emergency department (ED) and to educate and familiarize ED physicians about DBS devices and their potential complications. We also aimed to devise a simple protocol for DBS management so that all ED physicians would have access to the knowledge or referral capabilities when managing a DBS patient. The objective of the present study was to review the number and nature of ED encounters in patients with deep brain stimulation (DBS) devices implanted for movement and neuropsychiatric disorders. Methods: The series of encounters reviewed included 215 unique patients with DBS implantation who were identified using an IRB approved database and a paper chart review. Patients in the study included those implanted at University of Florida (UF), as well as those implanted at outside institutions, so long as they were followed at UF. The cohort included n = 215 DBS patients. 25.6% of all 215 patients presented to the ED at least once, with the most common presentation occurring as a result of a decline in mental status when taking into account all visits (6%). Reasons for presentation to the ED included neurological (54.6%), infections/hardware issues (27.9%), orthopedic/focal problems (10.5%), and medical issues (7%). In total, 29 patients arrived at the ED for DBS related issues (23.2%). Of those who presented to the ED (n = 55), the average age was 53.1 (range 10-80 years). Headache was the most common complaint within the neurological category (22.1%), followed by change in mental status (15.1%), and syncope (9.3%). When examining the data by ED diagnosis, change in mental status occurred most commonly in Parkinson’s disease (19.6%). Falls were most common in essential tremor (27.2%), and headache occurred most commonly in the dystonia group (52.1%). Across all diseases, mental status change was the most common indication for an ED encounter (6%). Parkinson disease patients most commonly presented with altered mental status (8%), essential tremor patients revealed a high preponderance of falls (6.5%), and dystonia patients tended to present with headache (7.1%). It was concluded that a large number of patients with DBS will present to the ED for many reasons, the majority of which will not be direct complications of their DBS device. Neurological issues were the most common chief complaint, with individual differences depending on the underlying disease. It is important for ED physicians to consider non-DBS related complaints in the presentation of these unique patients since these issues comprise the majority of the ED visits. However, when properly evaluating these patients, management of their DBS device, or referrals to neurosurgery and neurology, if necessary, are imperative. In addition to device management, regular ED standards of care should apply to this special cohort of patients.

The foundation demands that scientists share results and tools, and it closely monitors their work. But it also encourages them to take risks, devoting roughly $2-million a year to a rapid-response fund that gets money quickly into the hands of scientists who come up with new ideas.

In less than six weeks, a scientist can have the seed money to test out a hypothesis and see if it is worth pursuing. Most of the time, it doesn’t pan out, which is why government funding agencies prefer to support research that will lead to steady but incremental advances.

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Together, the findings suggest that gene therapy to enable the brain to retain its ability to produce dopamine, a neurotransmitter that falls in critically short supply in Parkinson’s patients, could be safely attempted during earlier stages of the disease with an added likelihood of success.

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“We have worked every day for 10 years to design a construct to the gene delivery vector that enhances the safety profile of gene transfer for Parkinson’s disease,” said Ronald Mandel, a professor of neuroscience at UF’s McKnight Brain Institute and the Powell Gene Therapy Center. “With that added measure of safety, we believe we can intervene with gene transfer in patients at earlier stages of the disease. We strongly believe that trials to save dopamine-producing connections in patients with Parkinson’s disease have failed because the therapy went into patients who were in the late stages of the disease and who had too few remaining dopamine-producing connections.”

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“With this technique, you could adjust the therapy in the patient,” said Fredric P. Manfredsson, a postdoctoral associate in UF’s department of neuroscience. “That would be extremely helpful because no one is really certain yet what dosage is required for a protective effect in humans. The process is also much more sensitive than we had imagined it would be. GDNF production can be shut down completely with a dose of doxycycline that is much smaller than what is commonly prescribed.”

Coronal images of subcortical structures in the A) T1-w 3D MP-RAGE, B) T2-w 3D FLAIR, C) T1-w FGATIR, and a Sagittal image D) T1-w FGATIR with deformable atlas contours overlaid. The contour colors for the deformable atlas are (from most anterior to most posterior): striatum (blue), GPe (green), anterior commissure (black), GPi (red), optic tract (yellow), thalamus (green), various VL thalamic nuclei (green), STN (red), and SNr (black).

Learn more about Deep Brain Stimulation surgery.

A growth factor used in clinical experiments to rescue dying brain cells in Parkinson patients may cause unwanted weight loss if delivered to specific areas of the brain, according to University of Florida researchers in the March online edition of Molecular Therapy.

The discovery is a cautionary warning for experimental treatments to treat Parkinson’s disease that use GDNF, short for glial line-derived neurotrophic growth factor.

In addition, the finding broadens understanding of the brain’s role in the regulation of metabolism and body weight, suggesting that gene therapy techniques in the brain potentially could control obesity.

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Doctors may be able to tailor a specialized form of brain surgery to more closely match the needs of Parkinson patients, according to results from the first large-scale effort to compare the two current target areas of deep brain stimulation surgery, or DBS.

Called the COMPARE Trial, the National Institutes of Health-funded study conducted at the University of Florida evaluated 45 patients for mood and cognitive changes related to DBS. UF investigators found that DBS in either brain target effectively treated motor symptoms such as tremors, stiffness and slowness. However, DBS also produced unique effects depending on the target location, especially in patients’ moods and mental sharpness.

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