Therapeutic efficacy of unilateral subthalamotomy in Parkinson's disease: results in 89 patients followed for up to 36 months

Álvarez, L.; Macıás, R.; Pavón, Nancy; López, G.; Rodríguez-Oroz, M.C.; Rodríguez, Rafael; Álvarez, Mario; Pedroso, I.; Teijeiro, Juan José Fernández; Fernández, Raúl de la Fuente; Casabona, Enrique; Salazar, Sonia; Maragoto, Carlos; Carballo, Manuel; García, I.; Guridi, Jorge; Juncos, Jorge L.; DeLong, Mahlon R.; Obeso, José A.

doi:10.1136/jnnp.2008.154948

Cited by 144 publications

(113 citation statements)

References 35 publications

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“…Similar conditions do not exist in developing countries, amounting to a continued need to optimize and develop less-costly alternatives, including ablative procedures. An important advancement in this field has been the demonstration that STN lesions are effective in the treatment of PD (Alvarez et al, 2001(Alvarez et al, , 2005(Alvarez et al, , 2009Parkin et al, 2001;Su et al, 2002;Patel et al, 2003). A significant complication is, however, the development of persistent hemi-chorea in a small percentage of patients, requiring subsequent pallidotomy.…”

Section: Dbs Vs Ablative Surgeries For Pdmentioning

confidence: 99%

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Smith

Wichmann

Factor

et al. 2011

Neuropsychopharmacol

194

137

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The demonstration that dopamine loss is the key pathological feature of Parkinson's disease (PD), and the subsequent introduction of levodopa have revolutionalized the field of PD therapeutics. This review will discuss the significant progress that has been made in the development of new pharmacological and surgical tools to treat PD motor symptoms since this major breakthrough in the 1960s. However, we will also highlight some of the challenges the field of PD therapeutics has been struggling with during the past decades. The lack of neuroprotective therapies and the limited treatment strategies for the nonmotor symptoms of the disease (ie, cognitive impairments, autonomic dysfunctions, psychiatric disorders, etc.) are among the most pressing issues to be addressed in the years to come. It appears that the combination of early PD nonmotor symptoms with imaging of the nigrostriatal dopaminergic system offers a promising path toward the identification of PD biomarkers, which, once characterized, will set the stage for efficient use of neuroprotective agents that could slow down and alter the course of the disease.

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Section: Dbs Vs Ablative Surgeries For Pdmentioning

confidence: 99%

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Smith

Wichmann

Factor

et al. 2011

Neuropsychopharmacol

194

137

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show abstract

“…It is noteworthy that decreased burst discharge of STN or even silenced STN (by TTX or local lesions) may be beneficial for the PD patient in terms of all major categories of symptoms, including rigidity, bradykinesia, and tremor (52,56). This observation seems to imply that the major symptoms of PD actually are ascribable to a gain rather than a loss of function in the motor circuits.…”

Section: Possible Origin Of the Differential Effects Between High-andmentioning

confidence: 99%

Modulation of subthalamic T-type Ca2+ channels remedies locomotor deficits in a rat model of Parkinson disease

Tai¹,

Yang²,

Pan³

et al. 2011

J. Clin. Invest.

108

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An increase in neuronal burst activities in the subthalamic nucleus (STN) is a well-documented electrophysiological feature of Parkinson disease (PD). However, the causal relationship between subthalamic bursts and PD symptoms and the ionic mechanisms underlying the bursts remain to be established. Here, we have shown that T-type Ca 2+ channels are necessary for subthalamic burst firing and that pharmacological blockade of T-type Ca 2+ channels reduces motor deficits in a rat model of PD. Ni 2+ , mibefradil, NNC 55-0396, and efonidipine, which inhibited T-type Ca 2+ currents in acutely dissociated STN neurons, but not Cd 2+ and nifedipine, which preferentially inhibited L-type or the other non-T-type Ca 2+ currents, effectively diminished burst activity in STN slices. Topical administration of inhibitors of T-type Ca 2+ channels decreased in vivo STN burst activity and dramatically reduced the locomotor deficits in a rat model of PD. Cd 2+ and nifedipine showed no such electrophysiological and behavioral effects. While low-frequency deep brain stimulation (DBS) has been considered ineffective in PD, we found that lengthening the duration of the low-frequency depolarizing pulse effectively improved behavioral measures of locomotion in the rat model of PD, presumably by decreasing the availability of T-type Ca 2+ channels. We therefore conclude that modulation of subthalamic T-type Ca 2+ currents and consequent burst discharges may provide new strategies for the treatment of PD.

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“…This would be akin to the improvement in movement observed in patients with Parkinson's disease after surgical lesioning of the subthalamic nucleus (to remove control from the D 2 R-modulated indirect pathway, which inhibits locomotor activity), even when they have very low DA levels (Alvarez et al, 2009). So, while we showed a significant decrease in signaling through the striatal D 1 R direct pathway with chronic cocaine exposure, the longer-lasting inhibition of the striatal D 2 R indirect pathway during cocaine intoxication could analogously be expected to allow the direct pathway to drive the behavior of cocaine reward and consumption.…”

Section: Discussionmentioning

confidence: 99%

Chronic Cocaine Dampens Dopamine Signaling during Cocaine Intoxication and Unbalances D₁over D₂Receptor Signaling

et al. 2013

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Therapeutic efficacy of unilateral subthalamotomy in Parkinson's disease: results in 89 patients followed for up to 36 months

Cited by 144 publications

References 35 publications

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Modulation of subthalamic T-type Ca2+ channels remedies locomotor deficits in a rat model of Parkinson disease

Chronic Cocaine Dampens Dopamine Signaling during Cocaine Intoxication and Unbalances D₁over D₂Receptor Signaling

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Therapeutic efficacy of unilateral subthalamotomy in Parkinson's disease: results in 89 patients followed for up to 36 months

Cited by 144 publications

References 35 publications

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Modulation of subthalamic T-type Ca2+ channels remedies locomotor deficits in a rat model of Parkinson disease

Chronic Cocaine Dampens Dopamine Signaling during Cocaine Intoxication and Unbalances D1over D2Receptor Signaling

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Resources

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Chronic Cocaine Dampens Dopamine Signaling during Cocaine Intoxication and Unbalances D₁over D₂Receptor Signaling