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   Evidence for Ear...
  The Earlystim Study
   Is Deep Brain St...
   How Significant ...
  Conclusion
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Table of Contents    
EDITORIAL
Year : 2016  |  Volume : 64  |  Issue : 1  |  Page : 8-9

When to do deep brain stimulation surgery in Parkinson disease? Early or late?


Department of Neurology, Govind Ballabh Pant Hospital, Delhi, India

Date of Web Publication11-Jan-2016

Correspondence Address:
Sanjay Pandey
Department of Neurology, Govind Ballabh Pant Hospital, Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.173621

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How to cite this article:
Pandey S. When to do deep brain stimulation surgery in Parkinson disease? Early or late?. Neurol India 2016;64:8-9

How to cite this URL:
Pandey S. When to do deep brain stimulation surgery in Parkinson disease? Early or late?. Neurol India [serial online] 2016 [cited 2019 Oct 17];64:8-9. Available from: http://www.neurologyindia.com/text.asp?2016/64/1/8/173621


Deep brain stimulation (DBS) has proven to be a successful treatment in patients suffering from Parkinson disease (PD) but its application until recently was mainly in the advanced stage of the disease with the mean disease duration being 14 years.[1]

Several large, randomized, multicenter studies have proven that the beneficial effects of DBS lasts for 15–20 years.[2] In this issue, Krishnan et al., have published a study where patients with PD undergoing subthalamic nucleus (STN) DBS were followed for 7 (25 patients) and 10 (12 patients) years.[3] The authors concluded that although the motor signs and motor fluctuations remained in a reduced state even at 7 and 10 years, the improvement in quality of life (QOL) was sustained for 5 years only. This limitation in the improvement of QOL was mainly due to the worsening of nonmotor symptoms, which are an integral part of the symptomatology of PD.

The natural history of PD is characterized by an excellent response to levodopa in the beginning, known as 'the honeymoon period,' followed by a period of motor fluctuation and dyskinesia. Later part of the disease is mainly dominated by the nonmotor symptoms due to the worsening of neuropsychiatric and cognitive symptoms. Given the excellent effects of DBS on QOL in PD patients, clinicians and researchers have debated whether or not DBS might be done in the early stages of the disease.[4]


  Evidence for Early Deep Brain Stimulation In parkinson Disease Top


Schupbach et al., published a randomized study in 2007 where 20 PD patients (10 in each group) either underwent bilateral STN stimulation or received medical treatment only.[5] Improvement in QOL was significantly better in the surgical (24%) than the nonsurgical (0%) group. The authors concluded that STN DBS should be a therapeutic option in the early stages of PD.


  The Earlystim Study Top


In February 2013, results from a controlled trial of DBS in patients in early stages of PD (EARLYSTIM) were published.[6] In this study, the disease duration of the included patients was shorter (≥4 years) and their disease severity was below 3 (Hoehn and Yahr scale) on stable medication. The patients had fluctuations or dyskinesias present for 3 years or less, and they had significant improvement in motor signs (50% or more) with dopaminergic medications. There were 124 patients in the neurostimulation group and 127 patients in the best medical therapy group. The mean duration of PD was similar in the neurostimulation (7.3 ± 3.1 years) and medical therapy (7.7 ± 2.7 years) groups. In the neurostimulation group, summary index of PD questionnaire (PDQ 39) score was significantly lower than that from the best medical treatment group, indicating better QOL in the neurostimulation group. Changes in the subscores for different domains of PDQ (mobility, activities of daily living, stigma, body discomfort, emotional support, social well–being, and cognition) were also better in the neurostimulation group, indicating improvement. The investigators concluded that even at a relatively early stage of PD before the appearance of severe motor complications, neurostimulation was superior to medical therapy alone. They also opined that neurostimulation may be considered as a therapeutic option for patients at an earlier stage of PD.


  Is Deep Brain Stimulation Neuroprotective If Applied Early? Top


There has been some evidence that STN DBS may have a disease-modifying role in animal models of PD, as a higher frequency of STN stimulation has led to a significant reduction in the dopaminergic cell death.[7] However, clinical data have not supported this hypothesis, and the rate of loss of dopaminergic terminals was similar in the medically treated and the neurostimulation groups. Similarly, none of the studies have proven that neurostimulation led to an improvement in the nonmotor symptoms such as cognition and repeated falls.[7]


  How Significant Is the Surgical Risk? Top


Surgical risks associated with DBS have been a major concern in advocating an early DBS procedure. Complications may be related to the surgery or neurostimulation performed. The surgery-related complications include intracranial hemorrhage, infection, cerebrospinal fluid leak, pneumonia, and pulmonary embolism. Some surgical complications may be hardware related and include lead fracture, erosion, migration, and malfunction of the device.[1] The neurostimulation-related complications can be early or delayed. Tingling sensation on the face and limb, diplopia, and concentration difficulty are the common early complications. Depression, gait abnormalities, and language/speech dysfunctions are usually the late complications.

In EARLYSTIM study, adverse events were more common in the neurostimulation group than the medical group mainly owing to more incidence of adverse events related to surgery.[5] However, nonsurgical adverse events were more common in the medical group owing to motor fluctuations, psychosis, decreased mobility, anxiety, and impulse control disorders. In the neurostimulation group, 26 surgery-related complications occurred in 22 patients, but all improved over a 2 year follow-up period, except in one patient who was left with a mild scarring. In the neurostimulation group, depression was more common than in the medical group, but the incidence of suicide attempts were similar in the two groups. One reason for fewer complications in this study was the excellent multidisciplinary care and the shorter duration of PD symptoms. The advances in the surgical techniques, device design, and neuroimaging will further reduce the surgical risks in future.[8]


  Conclusion Top


Even if the evidence for neuroprotection is weak and surgical risks exist, we may soon be entering an era where DBS may be a treatment option in the early course of the disease, as it leads to a significant improvement in the QOL in patients with PD due to improvement in the motor fluctuation and dyskinesia, reduction in the dopaminergic medications, and delay in the secondary physical and psychosocial consequences.

 
  References Top

1.
Pandey S, Sarma N. Deep brain stimulation: Current status. Neurol India 2015;63:9-18.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
2.
Merola A, Zibetti M, Angrisano S, Rizzi L, Ricchi V, Artusi CA, et al. Parkinson's disease progression at 30 years: A study of subthalamic deep brain-stimulated patients. Brain 2011;134:2074-84.  Back to cited text no. 2
    
3.
Krishnan S, Prasad S, Pisharady KK, Sarma G, Sarma SP, Kishore A. The decade after subthalamic stimulation in advanced Parkinson's disease: A balancing act. Neurol India 2016;64:81-9.  Back to cited text no. 3
  Medknow Journal  
4.
Woopen C, Pauls KA, Koy A, Moro E, Timmermann L. Early application of deep brain stimulation: Clinical and ethical aspects. Prog Neurobiol 2013;110:74-88.  Back to cited text no. 4
    
5.
Schüpbach WM, Maltête D, Houeto JL, du Montcel ST, Mallet L, Welter ML, et al. Neurosurgery at an earlier stage of Parkinson disease: A randomized, controlled trial. Neurology 2007;68:267-71.  Back to cited text no. 5
    
6.
Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L, et al. EARLYSTIM Study Group. Neurostimulation for Parkinson's disease with early motor complications. N Engl J Med 2013;368:610-22.  Back to cited text no. 6
    
7.
Deuschl G, Agid Y. Subthalamic neurostimulation for Parkinson's disease with early fluctuations: Balancing the risks and benefits. Lancet Neurol 2013;12:1025-34.  Back to cited text no. 7
    
8.
Schüpbach WM, Rau J, Houeto JL, Krack P, Schnitzler A, Schade-Brittinger C, et al. Myths and facts about the EARLYSTIM study. Mov Disord 2014;29:1742-50.  Back to cited text no. 8
    



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