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Biomedical subjects

Steven J Frucht

Publications and source records attributed to Steven J Frucht.

At least 19 recordsLinked to original sources
PubMed2006

Tetrabenazine therapy of pediatric hyperkinetic movement disorders.

Tetrabenazine (TBZ), a presynaptic dopamine depletor and postsynaptic dopamine receptor blocker, is widely used for the treatment of hyperkinetic movement disorders in adults. However, reports of its use in children are limited. We review the efficacy and tolerability of TBZ therapy in 31 children with hyperkinetic movement disorders refractory to other medications. TBZ was effective in reducing the severity of movement disorders resistant to treatment with other medicines. When compared to adult patients, pediatric patients required higher doses. Side effects were similar to the adult population; however, children had a lower incidence of drug-induced Parkinsonism.

Adolescent↗
PubMed2006

Ventriculoperitoneal shunting of idiopathic normal pressure hydrocephalus increases midbrain size: a potential mechanism for gait improvement.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (INPH) is characterized by a classic clinical triad of symptoms, including dementia, urinary incontinence, and gait disturbance. Recent work has demonstrated that the maximal midbrain anteroposterior (AP) diameter is significantly smaller in patients with INPH than in healthy, age-matched controls. The current study was undertaken to determine the effect of ventriculoperitoneal shunt placement on midbrain dimensions in INPH patients. METHODS: Twelve consecutive INPH patients undergoing ventriculoperitoneal shunt placement with pre- and postoperative computed tomographic scans at the Columbia University Medical Center were enrolled. Each patient's pre- and postoperative maximum AP and left-to-right diameters of the midbrain at the pontomesencephalic junction were independently measured in a blinded fashion by two of the authors. The average value of each dimension was computed by calculating the mean values of the measurements of the two observers. RESULTS: Both the mean AP diameter (preoperative mean, 2.06 +/- 0.04 cm; postoperative mean, 2.27 +/- 0.05; P = 0.0007) and left-to-right diameter (preoperative mean, 2.80 +/- 0.07; postoperative mean, 3.03 +/- 0.08; P = 0.0029) increased from pre- to postoperative imaging. The approximate cross-sectional area determined as the product of AP and left-to-right diameters also increased from pre- to postoperative images (preoperative mean, 5.79 +/- 0.22 cm; postoperative mean, 6.90 +/- 0.25 cm; P = 0.00049). CONCLUSION: This study provides supportive evidence that midbrain cytoarchitecture may play a role in the pathophysiology and post-ventriculoperitoneal shunt gait improvement of INPH patients.

Aged↗
PubMed2005

Subthalamic stimulation for Parkinson disease: determination of electrode location necessary for clinical efficacy.

OBJECT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) performed using intraoperative microelectrode recording (MER) to adjust electrode placement has become a widely used treatment for patients with advanced Parkinson disease (PD). Few studies have been conducted to examine the location of implanted electrodes relative to the intended target, and even fewer have been undertaken to investigate the degree to which variations in the location of these electrodes impacts their clinical efficacy. This study was performed to examine these issues. METHODS: The authors located 52 bilaterally implanted DBS electrode tips on postoperative magnetic resonance (MR) images obtained in 26 consecutive patients. Postoperative and preoperative planning MR images were merged to determine the DBS electrode tip coordinates relative to the midcommissural point. Surgical records listed the intended target coordinates for each DBS electrode tip. Clinical outcome assessment included the Unified PD Rating Scale (UPDRS) motor score at 1 year, standardized questionnaires, and routine follow-up visits. The mean difference between electrode tip location and intended target for all 52 electrodes was less than 2 mm in all axes. Only one electrode was farther than 3 mm from the intended target, and this was the only electrode that had to be replaced due to lack of clinical efficacy (lack of tremor suppression); its reimplantation 4 mm more medially provided excellent tremor control. High correlation coefficients indicate that the MR imaging analysis accurately determined the anatomical location of the electrode tips. Blinded videotape reviews of UPDRS motor scores comparing effects of stimulation in patients who were "on" and "off" medication identified subgroups in whom there was minimal and maximal stimulation response. Patients in these subgroups had no differences between the MR imaging-determined actual electrode tip location and its intended location. Similarly, improvements of dyskinesias and severity of symptoms encountered during the wearing-off period for the drug did not correlate with variations of electrode tip location. CONCLUSIONS: The findings in this study lead the authors to suggest that a DBS electrode placed anywhere within a 6-mm-diameter cylinder centered at the presumed middle of the STN (based on stereotactic atlas coordinates) provides similar clinical efficacy. Future studies may be warranted to evaluate prospectively the degree to which MER modification of the anatomically and/or image-determined target improves clinical efficacy of DBS electrodes.

Adult↗
PubMed2005

Marked amelioration of alcohol-responsive posthypoxic myoclonus by gamma-hydroxybutyric acid (Xyrem).

We conducted an open-label, dose-finding, blinded-rating trial of gamma-hydroxybutyric acid (Xyrem) in a single patient with severe alcohol-responsive posthypoxic myoclonus refractory to treatment with standard antimyoclonic agents. Xyrem was given in divided doses during the day and was well tolerated. Intensity of myoclonus was measured using the Unified Myoclonus Rating Scale, and blinded videotape review demonstrated complete resolution of myoclonus at rest and stimulus-sensitive myoclonus. Action myoclonus and functional performance also improved in ways that were practically meaningful, allowing her to feed herself, to accomplish daily hygiene tasks, and to walk with assistance. The possible mechanisms of action and potential uses of this agent in other alcohol-responsive movement disorders are discussed.

Adult↗
PubMed2005

Classification conundrums in paroxysmal dyskinesias: a new subtype or variations on classic themes?

Paroxysmal movement disorders are a group of heterogeneous entities that have been categorized based on their most salient features. The four classic categories of paroxysmal dyskinesias are kinesigenic, nonkinesigenic, hypnogenic, and exercise-induced. The phenotypic variability of these disorders, coupled with new insights into their possible etiologies, has made the task of classification increasingly problematic. We describe 4 cases that do not fit easily into the current classification scheme, compare them with four others recently described in the literature, and raise the question as to whether they constitute a new subtype.

Anticonvulsants↗
PubMed2005

A pilot tolerability and efficacy trial of sodium oxybate in ethanol-responsive movement disorders.

Sodium oxybate is currently approved in the United States exclusively for the treatment of cataplexy in narcoleptic patients. In a prior article published in this journal, we reported a patient with severe posthypoxic myoclonus whose myoclonus improved with ethanol and also with treatment with sodium oxybate. We extend this preliminary observation to five other patients with ethanol-responsive movement disorders in an open-label, dose-titration, add-on, 8-week trial. All five patients (one with severe alcohol-responsive posthypoxic myoclonus, two with epsilon-sarcoglycan-linked myoclonus-dystonia, and two with essential tremor) experienced improvement from baseline of 50% or greater as measured by blinded videotape review. Tolerability was satisfactory, with dose-dependent sedation as the most common side effect. Further studies of this drug in hyperkinetic movement disorders are warranted.

Adjuvants, Anesthesia↗
PubMed2005

Movement disorder emergencies.

For the past 4 years, Dr. Stanley Fahn and I have given a course at the American Academy of Neurology annual meeting on the topic of movement disorder emergencies. The purpose of this review article is to summarize the topic and to present it to readers of this journal. The text of this article has appeared in nearly the same form as the Academy syllabus accompanying our course. It is being presented here so that readers of the journal may review the material.

Acute Disease↗
PubMed2005

Myoclonus.

Myoclonus is defined as sudden, brief, shock-like involuntary movements affecting one or more muscles. The term encompasses a wide range of different physiologic and pathologic processes. When evaluating a patient with myoclonus, the first step is to identify the underlying etiology. Initial treatment should be directed against any underlying toxic or metabolic conditions. Next, targeted pharmacotherapy should be chosen, principally on the basis of the probable anatomical localization. Although treatment is initiated with a single agent, polytherapy usually is necessary to achieve adequate symptomatic control. The prognosis of myoclonus is highly variable, and largely depends on the underlying cause.

Journal Article↗
PubMed2005

Treatment of Parkinson's disease : what's on the horizon?

Few neurological diseases have received as much attention and investment in research as Parkinson's disease. Although great strides have been made in the development of agents to treat this neurodegenerative disease, none yet address the underlying problem associated with it, the progressive loss of dopaminergic neurons. Current therapeutic strategies for Parkinson's disease focus primarily on reducing the severity of its symptoms using dopaminergic medications. Although providing substantial benefit, these agents are burdened by adverse effects and long-term complications. This review highlights new and emerging therapies for Parkinson's disease, categorised as symptomatic, neuroprotective and neurorestorative, although at times, this distinction is not easily made. Novel symptomatic treatments target nondopaminergic areas in the hope of avoiding the motor complications seen with dopaminergic therapies. Two emerging treatment approaches under investigation are adenosine A(2A) receptor antagonists (such as istradefylline [KW-6002]) and glutamate AMPA receptor antagonists (such as talampanel [LY-300164]). In 2003, the results from two studies using istradefylline in patients with Parkinson's disease were published, with both showing a positive benefit of the study drug when used as adjunctive therapy to levodopa. In non-human primate models of Parkinson's disease, talampanel has been found to have antiparkinsonian effects when administered as high-dose monotherapy and antidyskinetic effects on levodopa-induced dyskinesias. NS-2330, another drug currently undergoing clinical trials, is a triple monoamine reuptake inhibitor that has therapeutic potential in both Parkinson's and Alzheimer's disease. A phase II proof-of-concept study is currently underway in early Parkinson's disease. However, a recently published study in advanced Parkinson's disease showed no therapeutic benefit of NS-2330 in this patient population. Even more exciting are agents that have a neuroprotective or neurorestorative role. These therapies aim to prevent disease progression by targeting the mechanisms involved in the pathogenesis of Parkinson's disease. Several lines of investigation for neuroprotective therapies have been taken, including the antioxidant coenzyme Q10 (ubidecarenone) and anti-apoptotic agents such as CEP-1347. Studies in patients with Parkinson's disease with coenzyme Q10 have suggested that it slows down functional decline. The PRECEPT study is currently in progress to assess the neuroprotective role of CEP-1347 in the early phase of the disease. Gene therapy is another exciting arena and includes both potentially neuroprotective and neurorestorative agents. Novel methods include subthalamic glutamic acid decarboxylase gene therapy and the use of glial cell line-derived neurotrophic factor (GDNF). Eleven of 12 patients have been enrolled in the first FDA-approved phase I subthalamic glutamic acid decarboxylase gene therapy trial for Parkinson's disease, with currently no evidence of adverse events. GDNF delivered intracerebroventricularly was studied in a small population of patients with Parkinson's disease, but unfortunately did not reveal positive results. Other methods of administering GDNF include direct delivery via infusions into the basal ganglia and the use of viral vectors; thus far, these approaches have shown promising results. This is an exciting and rewarding time for research into Parkinson's disease. With so many therapies currently under investigation, the time is ripe for the beginning of a new phase of treatment strategies.

Animals↗
PubMed2004

The metabolic topography of posthypoxic myoclonus.

Posthypoxic myoclonus (PHM) is a syndrome of action and intention myoclonus that occurs in some patients who survive a cardiac arrest. Using PET and statistical parametric mapping, the authors observed a significant bilateral increase in glucose metabolism in the ventrolateral thalamus and pontine tegmentum in patients relative to controls. Interventions such as deep brain stimulation that interrupt networks that involve these structures may be useful in patients with severe PHM.

Adult↗
PubMed2004

Diagnosis and management of pergolide-induced fibrosis.

We report on 2 patients treated with pergolide, 1 of whom developed pleural fibrosis and the other retroperitoneal fibrosis. In both cases, an extensive diagnostic evaluation and surgical intervention were required to reach a diagnosis. Based on our experience with these patients and a review of cases of pergolide-induced fibrosis in the English-language literature, we propose guidelines for the diagnosis and management of this rare complication.

Aged↗
PubMed2004

Movement disorder emergencies in the perioperative period.

Movement disorder emergencies are uncommon in the perioperative period; however, when they occur, then carry significant morbidity. By paying attention to the phenomenology of the movement disorder, the effects of medications administered in the operating room, and unusual sequelae of surgery, neurologists can have a positive impact on the outcome of these patients.

Humans↗
PubMed2004

Parkinson disease: an update.

BACKGROUND: Over the past decade, the treatment of Parkinson disease (PD) has undergone tremendous changes. New drugs have been introduced to manage the cardinal motor symptoms of PD, and other agents have been borrowed to treat the nonmotor manifestations of the illness. For neurologists faced with the task of treating PD patients, the available array of medications may be confusing and intimidating. REVIEW SUMMARY: In this review, I summarize the newest approved medications for the treatment of PD, including the new dopamine agonists and catechol-O-methyl-transferase inhibitors. I also describe agents that are used to treat common problems in PD patients, including hallucinations, orthostasis, nausea, erectile dysfunction, depression, and memory loss. Guidelines for handling common scenarios in PD patients will be illustrated by 10 case histories. Finally, the most promising PD drugs that are currently in development will be reviewed. CONCLUSIONS: Neurologists have a vast armamentarium to treat both motor and nonmotor manifestations of PD. Understanding this array allows the astute clinician to improve the lives of their patients with PD.

Adult↗
PubMed2003

Chemotherapy-induced parkinsonism responsive to levodopa: an underrecognized entity.

Parkinsonism is a rare neurological complication of cancer treatment. Although individual case reports of this syndrome have been reported, the clinical features and prevalence of this syndrome are unknown. We present 3 patients, encountered over 6 months at one institution, who developed parkinsonism after treatment with various chemotherapeutic agents. Parkinsonism was severe in 2 patients, affecting postural reflexes, speech, and swallowing. All 3 patients responded dramatically to treatment with levodopa, and parkinsonism spontaneously improved or remitted over months. This unusual complication of cancer therapy is treatable and may be underappreciated.

Aged↗
PubMed2003

Tetrabenazine in the treatment of severe pediatric chorea.

Tetrabenazine (TBZ) is widely used to treat adults with hyperkinetic movement disorders; however, published experience with the drug in pediatric patients is limited. We report on 5 children with severe chorea who were treated with TBZ. TBZ effectively controlled chorea in 4 patients, and despite the need for relatively high doses, it was well tolerated.

Anti-Dyskinesia Agents↗
PubMed2003

Myoclonus.

PURPOSE OF REVIEW: Myoclonus, one of the most common involuntary movement disorders, poses particular challenges for the treating physician. The evaluation of a patient with myoclonus depends completely on the clinical history and examination, supported when necessary by electrophysiology, neuroimaging and selected genetic and laboratory testing. The sudden, shock-like jerks which define myoclonus may be highly disabling, and when they persist, often require treatment. RECENT FINDINGS: In a paper published in this journal, we reviewed the published trials of antimyoclonic agents, and formulated a treatment algorithm based on the available evidence. In the current paper, we present our approach for evaluating patients with myoclonus, and suggest practical guidelines for treating patients based on the pre-2000 literature and on studies published in the last 2 years. The newer medications which are being used in management of myoclonus are levetiracetam and gamma-hydroxybutyric acid. Levetiracetam is especially useful for posthypoxic myoclonus and gamma-hydroxybutyric acid for alcohol-sensitive myoclonus. A combination of medications is often needed to obtain adequate control of symptoms. Botulinum toxin is also being introduced for focal myoclonus with encouraging results. SUMMARY: There are no approved medications for myoclonus, and most therapies are borrowed from the antiepileptic and psychiatric armamentarium. Nonetheless, there is a logic to the choice and dosing of antimyoclonic drugs, and we hope that by applying a few simple principles, neurologists will approach the care of these patients with confidence.

Anticonvulsants↗