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Comprehensive NeuroScience

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Gorman J.M.,Comprehensive NeuroScience
Journal of Neuropsychiatry and Clinical Neurosciences | Year: 2010

An elegant theory that links hippocampal neurogenesis to mood and anxiety disorders and to the mechanism of action of antidepressant drugs has gained widespread attention. However, depression and anxiety disorders involve multiple areas of the brain, such as the amygdala and prefrontal cortex, where neurogenesis does not appear to occur in the adult mammalian brain. A complementary theory is proposed here in which neurogenesis is seen as an epiphenomenon of a more widespread alteration in dendritic length and spine number. According to this theory, exposure to chronic stress and stressful life events increases excitotoxic glutamatergic neurotransmission in multiple brain areas. To protect neurons from consequent apoptosis, dendrites retract and spine number decreases, thus limiting the number of exposed glutamate receptors. Drugs that reduce glutamatergic neurotransmission under these circumstances, many of which have already been shown helpful in treating mood and anxiety disorders, may prevent this dendritic retraction and thus protect synaptic connections throughout the brain. Copyright © 2010 American Psychiatric Publishing, Inc.

BACKGROUND AND PURPOSE—: Less than half of acute ischemic stroke patients treated with mechanical thrombectomy obtain permanent clinical benefits. Consequently, there is an urgent need to identify mechanisms implicated in the limited efficacy of early reperfusion. We evaluated the predictors and prognostic significance of vessel wall permeability impairment and its association with blood–cerebrospinal fluid barrier (BCSFB) disruption after acute stroke treated with thrombectomy. METHODS—: A prospective cohort of acute stroke patients treated with stent retrievers was analyzed. Vessel wall permeability impairment was identified as gadolinium vessel wall enhancement (GVE) in a 24- to 48-hour follow-up contrast-enhanced magnetic resonance imaging, and severe BCSFB disruption was defined as subarachnoid hemorrhage or gadolinium sulcal enhancement (present across >10 slices). Infarct volume was evaluated in follow-up magnetic resonance imaging, and clinical outcome was evaluated with the modified Rankin Scale at day 90. RESULTS—: A total of 60 patients (median National Institutes of Health Stroke Scale score, 18) were analyzed, of whom 28 (47%) received intravenous alteplase before mechanical thrombectomy. Overall, 34 (57%) patients had GVE and 27 (45%) had severe BCSFB disruption. GVE was significantly associated with alteplase use before thrombectomy and with more stent retriever passes, along with the presence of severe BCSFB disruption. GVE was associated with poor clinical outcome, and both GVE and severe BCSFB disruption were associated with increased final infarct volume. CONCLUSIONS—: These findings may support the clinical relevance of direct vessel damage and BCSFB disruption after acute stroke and reinforce the need for further improvements in reperfusion strategies. Further validation in larger cohorts of patients is warranted. © 2017 American Heart Association, Inc.

Chahine L.M.,Comprehensive NeuroScience
International review of neurobiology | Year: 2011

It has long been recognized that monoamine oxidase (MAO) inhibitors have a role in the management of Parkinson's disease (PD). The MAO-B inhibitor rasagiline has neuroprotective effects in animal models, mediated partly by its antiapoptotic activity. Rasagiline has been shown to be effective as monotherapy for early PD and as an adjunct to dopaminergic therapy. Clinical trials have also shown putative disease-modifying effects, though rasagiline's potential to alter the long-term course of PD remains controversial. Given the demonstrated benefits of rasagiline, along with its safety and tolerability profile, it has an important role to play in PD therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Galanopoulou A.S.,Yeshiva University | Moshe S.L.,Comprehensive NeuroScience
Advances in Experimental Medicine and Biology | Year: 2014

Seizures have variable effects on brain. Numerous studies have examined the consequences of seizures, in light of the way that these may alter the susceptibility of the brain to seizures, promote epileptogenesis, or functionally alter brain leading to seizure-related comorbidities. In many -but not all- situations, seizures shift brain function towards a more immature state, promoting the birth of newborn neurons, altering the dendritic structure and neuronal connectivity, or changing neurotransmitter signaling towards more immature patterns. These effects depend upon many factors, including the seizure type, age of seizure occurrence, sex, and brain region studied. Here we discuss some of these findings proposing that these seizure-induced immature features do not simply represent rejuvenation of the brain but rather a de-synchronization of the homeostatic mechanisms that were in place to maintain normal physiology, which may contribute to epileptogenesis or the cognitive comorbidities. © 2014 Springer Science+Business Media Dordrecht.

Harden C.L.,Hofstra University | Harden C.L.,Comprehensive NeuroScience | Pennell P.B.,Harvard University
The Lancet Neurology | Year: 2013

Complex, multidirectional interactions between hormones, seizures, and the medications used to control them can present a challenge for clinicians treating patients with epilepsy. Many hormones act as neurosteroids, modulating brain excitability via direct binding sites. Thus, changes in endogenous or exogenous hormone levels can affect the occurrence of seizures directly as well as indirectly through pharmacokinetic effects that alter the concentrations of antiepileptic drugs. The underlying structural and physiological brain abnormalities of epilepsy and the metabolic activity of antiepileptic drugs can adversely affect hypothalamic and gonadal functioning. Knowledge of these complex interactions has increased and can now be incorporated in meaningful treatment approaches for men and women with epilepsy. © 2013 Elsevier Ltd.

Stern M.B.,Comprehensive NeuroScience | Siderowf A.,Comprehensive NeuroScience
Movement Disorders | Year: 2010

The treatment of Parkinson's disease (PD) has revolved around pharmacologic interventions that primarily treat the cardinal (dopaminergic) manifestations of tremor, rigidity, and bradykinesia; yet, we now know that the pathology of PD is widespread, accounting for more disabling symptoms such as cognitive impairment, autonomic problems, and postural instability. Further, attempts at modifying PD may be hampered as much by the imperfection of therapeutic interventions as by the extent of neuronal damage that exists even in early PD, when most putative neuroprotective agents are tried. Our approach to PD must therefore evolve and include strategies for detecting PD earlier in its course and, eventually, intervening when the disease process is in its nascent stages. Parkinson's associated risk syndrome (PARS) is the term we have coined to describe patients at risk for developing PD. These patients may have genetic risk factors or may have subtle, early non-motor symptoms including abnormalities in olfaction, gastrointestinal function, cardiac imaging, vision, behavior, and cognition. Changes in neuroimaging modalities can predict the emergence of neurologic signs and symptoms within several years. The PARS study is now underway to determine the feasibility of screening a large cohort of subjects to identify those at highest risk for developing PD. If successful, we will have the tools to identify cohorts for clinical trials of PD prevention or, at the very least, delay of disease onset, and long-term disability. Further, our concept of PD risk will change the nosology of PD as those now considered "at-risk" may ultimately be considered to already have the disease. © 2010 Movement Disorder Society.

Scott Perry M.,Comprehensive NeuroScience | Duchowny M.,Miami Childrens Hospital | Duchowny M.,University of Miami
Epilepsia | Year: 2013

Nearly one third of patients with epilepsy become medically intractable, and the likelihood of achieving seizure freedom decreases with each additional medication trial. For appropriately chosen patients, epilepsy surgery affords the opportunity to achieve seizure freedom and potentially wean off medications. Epilepsy surgery, as with medical management, is not without adverse effects; to counsel patients wisely, practitioners need to understand the advantages and disadvantages of both. Randomized controlled trials in temporal lobe epilepsy reveal that epilepsy surgery achieves superior outcome compared to continued medical management. Although seizure freedom is the ultimate goal of any therapy, it represents a single outcome measure among a variety of other domains that affect patient welfare. It is imperative that providers understand the patient variables that affect these outcome measures and how these measures impact each other. Because the data comparing surgical therapy versus medical management for refractory epilepsy are limited, we review the available evidence comparing outcomes beyond seizure freedom including quality of life, cognition, psychosocial function, mortality, and financial costs.© 2013 International League Against Epilepsy.

Chahine L.M.,Comprehensive NeuroScience | Stern M.B.,Comprehensive NeuroScience
Current Opinion in Neurology | Year: 2011

Purpose of Review: This review enumerates recent developments in the early diagnosis of Parkinson's disease, with an emphasis on detection of preclinical Parkinson's disease. Recent Findings: Several clinical, laboratory, and imaging tests are now being investigated as potential early markers of Parkinson's disease. These include various nonmotor features that predate the motor manifestations of Parkinson's disease, including sleep abnormalities, neurobehavioral symptoms, and olfactory dysfunction. Tests of the autonomic nervous system, such as cardiac functional imaging, allow for a measure of cardiac sympathetic denervation. Cerebrospinal fluid and serum tests, including α-synuclein and DJ-1, are being developed and refined. Various imaging modalities have contributed to the diagnostic armamentarium in Parkinson's disease, including transcranial Doppler ultrasonography, radiolabeled tracer imaging, and magnetic resonance imaging. Early Parkinson's disease detection will pave the way for major advances in disease modifying therapies. Summary: Various diagnostic modalities hold promise for the early and preclinical diagnosis of Parkinson's disease. It is likely that the future diagnosis of Parkinson's disease will rely on a combination of clinical, laboratory, imaging, and genetic data. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Dessy A.,Middlebury College | Gorman J.M.,Comprehensive NeuroScience
Clinical Pharmacology and Therapeutics | Year: 2011

Several challenges have been encountered in the attempt to apply RNA interference (RNAi) to the treatment of disease, including lack of effective delivery, off-target responses, and instability of reagents. The treatment of neuropsychiatric disorders poses additional obstacles, given that drugs have only limited access to the central nervous system (CNS) and that the neurons are in a postmitotic state. Despite these inherent limitations, much progress has been made toward attaining a better understanding of diseases of the CNS, and the development of effective treatments appears to be a distinct possibility in the near future.

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