Subthalamic DBS replaces levodopa in Parkinson’s disease: Two-year follow-up
JLHoueto, Centre d'Investigation Clinique Paris France[email protected]
V Mesnage, ML Welter, BP Bejjani, L Mallet, and Y Agid
Submitted September 11, 2002
We read with interest the report of Vingerhoets et al. [1] showing,
as others, [2] that long-term subthalamic (STN) stimulation monotherapy
can be achieved in up to 50% of patients with Parkinson's disease (PD),
thereby allowing similar motor improvement as that provided by levodopa
treatment before the operation. Authors suggest that STN stimulation can
replace levodopa treatment, which should therefore be routinely withdrawn
in patients treated neurosurgically. We believe that this statement
warrants a prerequisite and deserves a comment.
In their study, parkinsonian motor disability was ameliorated by only
45%. [1] This response to levodopa is lower than that described in other
report, [3] and is very likely explained by the characteristics of
patients included. The residual motor score, which was unresponsive to
levodopa, was not improved by STN stimulation since, as stated by the
authors themselves, STN-stimulation "replaces levodopa", but no more. An
almost complete disappearance of parkinsonian symptoms postoperatively
implies to select PD patients who dramatically respond to levodopa
treatment preoperatively, in particular in the absence of axial motor
symptoms such as freezing, hypophonia and postural instability. [3]
Despite satisfactory postoperative motor results, social adjustment
disorders and behavioral complications such as anxiety, apathy and
depression can emerge, which may limit the quality of life of several
patients. [4, 5] probably as a result of the dramatic reduction in
levodopa treatment. [4] In support of the latter hypothesis, we observed
among 82 PD patients operated between 1997 and 2001 that 17%
(postoperative follow-up= 18 ± 10 months; improvement in parkinsonian
score "on" stimulation "off" drug = 77± 16%) no longer needed dopaminergic
therapy postoperatively. However, dopamine agonists or levodopa were
reintroduced in all
14 patients 16 ± 14 weeks after surgery (levodopa-equivalent dosage = 250
± 134 mg/day) to improve affective blunting, in the absence of significant
additional parkinsonian motor improvement. Since the administration of
levodopa is known to reestablish a normal dopaminergic transmission within
both the nigrostriatal and the meso-cortico-limbic pathways (implicated in
the modulation of psychic and cognitive functions), it may be postulated
that STN stimulation improved motor symptoms, thereby compensating for the
decreased dopaminergic nigrostriatal transmission, without compensating
for the decreased extrastriatal dopaminergic systems. We postulate that
the still present dopaminergic denervation in cortical associative and
limbic territories needed to be compensated for using small doses of
dopamine agonists to avoid persistence or reactivation of behavioral
symptoms such as apathy and anxiety. [4, 5] A direct deleterious effect of
neurosurgery cannot be ruled out. [4] However in contrast to the report by
Vingerhoets et al., [1] we suggest that systematic withdrawal of
dopaminergic therapy postoperatively may negatively impact the quality of
life in some patients and should not be advocated systematically.
References:
1. Vingerhoets FJG, Villemure J-G, Temperli P, et al. Subthalamic DBS
replaces levodopa in Parkinson's disease, two years follow-up. Neurology
2002;58:396-401.
2. Valledeoriola F, Pilleri M, Tolosa E, et al. Bilateral subthalamic
stimulation monotherapy in advanced Parkinson's disease: long-term follow-
up. Movement Disorders 2002;17(1):121-132.
3. Welter ML, Houeto JL, Tezenas du Montcel S, et al. Subthalamic
stimulation in Parkinson's disease: clinical predictive factors. Brain
2002;25:575-583.
4. Volkmann J, Allert N, Voges J, et al. Safety and efficacy of
pallidal or subthalamic stimulation in advanced PD. Neurology 2001;56:548-
551.
We read with interest the report of Vingerhoets et al. [1] showing, as others, [2] that long-term subthalamic (STN) stimulation monotherapy can be achieved in up to 50% of patients with Parkinson's disease (PD), thereby allowing similar motor improvement as that provided by levodopa treatment before the operation. Authors suggest that STN stimulation can replace levodopa treatment, which should therefore be routinely withdrawn in patients treated neurosurgically. We believe that this statement warrants a prerequisite and deserves a comment.
In their study, parkinsonian motor disability was ameliorated by only 45%. [1] This response to levodopa is lower than that described in other report, [3] and is very likely explained by the characteristics of patients included. The residual motor score, which was unresponsive to levodopa, was not improved by STN stimulation since, as stated by the authors themselves, STN-stimulation "replaces levodopa", but no more. An almost complete disappearance of parkinsonian symptoms postoperatively implies to select PD patients who dramatically respond to levodopa treatment preoperatively, in particular in the absence of axial motor symptoms such as freezing, hypophonia and postural instability. [3]
Despite satisfactory postoperative motor results, social adjustment disorders and behavioral complications such as anxiety, apathy and depression can emerge, which may limit the quality of life of several patients. [4, 5] probably as a result of the dramatic reduction in levodopa treatment. [4] In support of the latter hypothesis, we observed among 82 PD patients operated between 1997 and 2001 that 17% (postoperative follow-up= 18 ± 10 months; improvement in parkinsonian score "on" stimulation "off" drug = 77± 16%) no longer needed dopaminergic therapy postoperatively. However, dopamine agonists or levodopa were reintroduced in all 14 patients 16 ± 14 weeks after surgery (levodopa-equivalent dosage = 250 ± 134 mg/day) to improve affective blunting, in the absence of significant additional parkinsonian motor improvement. Since the administration of levodopa is known to reestablish a normal dopaminergic transmission within both the nigrostriatal and the meso-cortico-limbic pathways (implicated in the modulation of psychic and cognitive functions), it may be postulated that STN stimulation improved motor symptoms, thereby compensating for the decreased dopaminergic nigrostriatal transmission, without compensating for the decreased extrastriatal dopaminergic systems. We postulate that the still present dopaminergic denervation in cortical associative and limbic territories needed to be compensated for using small doses of dopamine agonists to avoid persistence or reactivation of behavioral symptoms such as apathy and anxiety. [4, 5] A direct deleterious effect of neurosurgery cannot be ruled out. [4] However in contrast to the report by Vingerhoets et al., [1] we suggest that systematic withdrawal of dopaminergic therapy postoperatively may negatively impact the quality of life in some patients and should not be advocated systematically.
References:
1. Vingerhoets FJG, Villemure J-G, Temperli P, et al. Subthalamic DBS replaces levodopa in Parkinson's disease, two years follow-up. Neurology 2002;58:396-401.
2. Valledeoriola F, Pilleri M, Tolosa E, et al. Bilateral subthalamic stimulation monotherapy in advanced Parkinson's disease: long-term follow- up. Movement Disorders 2002;17(1):121-132.
3. Welter ML, Houeto JL, Tezenas du Montcel S, et al. Subthalamic stimulation in Parkinson's disease: clinical predictive factors. Brain 2002;25:575-583.
4. Volkmann J, Allert N, Voges J, et al. Safety and efficacy of pallidal or subthalamic stimulation in advanced PD. Neurology 2001;56:548- 551.
5. Houeto JL, Mesnage V, Mallet L, et al. Behavioural disorders, Parkinson's disease and subthalamic stimulation. J Neurol Neurosurg Psychiatry 2002;72:701-707.