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Brain Communications 2023Subthalamic nucleus deep brain stimulation is commonly indicated for symptomatic relief of idiopathic Parkinson's disease. Despite the known improvement in motor scores,...
Subthalamic nucleus deep brain stimulation is commonly indicated for symptomatic relief of idiopathic Parkinson's disease. Despite the known improvement in motor scores, affective, cognitive, voice and speech functions might deteriorate following this procedure. Recent studies have correlated motor outcomes with intraoperative microelectrode recordings. However, there are no microelectrode recording-based tools with predictive values relating to long-term outcomes of integrative motor and non-motor symptoms. We conducted a retrospective analysis of the outcomes of patients with idiopathic Parkinson's disease who had subthalamic nucleus deep brain stimulation at Tel Aviv Sourasky Medical Centre (Tel Aviv, Israel) during 2015-2016. Forty-eight patients (19 women, 29 men; mean age, 58 ± 8 years) who were implanted with a subthalamic nucleus deep brain stimulation device underwent pre- and postsurgical assessments of motor, neuropsychological, voice and speech symptoms. Significant improvements in all motor symptoms (except axial signs) and levodopa equivalent daily dose were noted in all patients. Mild improvements were observed in more posterior-related neuropsychological functions (verbal memory, visual memory and organization) while mild deterioration was observed in frontal functions (personality changes, executive functioning and verbal fluency). The concomitant decline in speech intelligibility was mild and only partial, probably in accordance with the neuropsychological verbal fluency results. Acoustic characteristics were the least affected and remained within normal values. Dimensionality reduction of motor, neuropsychological and voice scores rendered six principal components that reflect the main clinical aspects: the tremor-dominant versus the rigidity-bradykinesia-dominant motor symptoms, frontal versus posterior neuropsychological deficits and acoustic characteristics versus speech intelligibility abnormalities. Microelectrode recordings of subthalamic nucleus spiking activity were analysed off-line and correlated with the original scores and with the principal component results. Based on 198 microelectrode recording trajectories, we suggest an intraoperative subthalamic nucleus deep brain stimulation score, which is a simple sum of three microelectrode recording properties: normalized neuronal activity, the subthalamic nucleus width and the relative proportion of the subthalamic nucleus dorsolateral oscillatory region. A threshold subthalamic nucleus deep brain stimulation score >2.5 (preferentially composed of normalized root mean square >1.5, subthalamic nucleus width >3 mm and a dorsolateral oscillatory region/subthalamic nucleus width ratio >1/3) predicts better motor and non-motor long-term outcomes. The algorithm presented here optimizes intraoperative decision-making of deep brain stimulation contact localization based on microelectrode recording with the aim of improving long-term (>1 year) motor, neuropsychological and voice symptoms.
PubMed: 38025270
DOI: 10.1093/braincomms/fcad268 -
Neurosurgery Jun 2005To evaluate the benefits and adverse effects of bilateral subthalamic nucleus stimulation in the treatment of Parkinson's disease (PD) by systematically reviewing the... (Review)
Review
OBJECTIVE
To evaluate the benefits and adverse effects of bilateral subthalamic nucleus stimulation in the treatment of Parkinson's disease (PD) by systematically reviewing the published literature.
METHODS
A search of the PubMed database using the key words subthalamic, nucleus, and stimulation yielded 624 articles published between 1966 and December 2003. Only articles that included original, nonduplicated descriptions of patients with PD treated with bilateral subthalamic nucleus stimulation were selected for further analysis.
RESULTS
A total of 38 studies from 34 neurosurgical centers in 13 countries were identified for critical review. The outcomes for 471 patients with PD treated with bilateral subthalamic nucleus stimulation were assessed according to the Unified Parkinson's Disease Rating Scale in both on-medication and off-medication conditions. With stimulation, Unified Parkinson's Disease Rating Scale motor scores in the off-medication condition improved by 50% after 6 months, 56% after 12 months, 51% after 2 years, and 49% after 5 years compared with preoperative off-medication scores. At 12 months of subthalamic nucleus stimulation, the mean improvement in tremor was 81%, in rigidity was 63%, in bradykinesia was 52%, in gait was 64%, and in postural instability was 69% when compared with preoperative off-medication subscores. On-medication dyskinesias were reduced by 94%, as assessed 12 months after stimulation using the Unified Parkinson's Disease Rating Scale IV complications of therapy score. There was an overall 52% reduction in the l-dopa-equivalent dose intake after 12 months of stimulation. Most adverse effects were mild to moderate. There was a 1 to 2% incidence of severe adverse effects (death or permanent neurological deficits related to intracerebral hemorrhages). Nineteen percent of the patients had adverse effects related to stimulation that could be reversed by changing stimulation parameters. There was a 9% incidence of adverse effects related to the hardware (infections, lead and pulse generator problems).
CONCLUSION
Bilateral subthalamic nucleus stimulation is effective in the treatment of PD. Further refinements in patient selection and surgical technique may lessen the incidence of complications associated with this procedure.
Topics: Electric Stimulation Therapy; Humans; Parkinson Disease; PubMed; Subthalamic Nucleus; Treatment Outcome
PubMed: 15918948
DOI: 10.1227/01.neu.0000159714.28232.c4 -
Movement Disorders : Official Journal... Apr 2020Apathy is one of the most disabling neuropsychiatric symptoms in Parkinson's disease (PD) patients and has a higher prevalence in patients under subthalamic nucleus deep...
BACKGROUND
Apathy is one of the most disabling neuropsychiatric symptoms in Parkinson's disease (PD) patients and has a higher prevalence in patients under subthalamic nucleus deep brain stimulation. Indeed, despite its effectiveness for alleviating PD motor symptoms, its neuropsychiatric repercussions have not yet been fully uncovered. Because it can be alleviated by dopaminergic therapies, especially D and D dopaminergic receptor agonists, the commonest explanation proposed for apathy after subthalamic nucleus deep brain stimulation is a too-strong reduction in dopaminergic treatments. The objective of this study was to determine whether subthalamic nucleus deep brain stimulation can induce apathetic behaviors, which remains an important matter of concern. We aimed to unambiguously address this question of the motivational effects of chronic subthalamic nucleus deep brain stimulation.
METHODS
We longitudinally assessed the motivational effects of chronic subthalamic nucleus deep brain stimulation by using innovative wireless microstimulators, allowing continuous stimulation of the subthalamic nucleus in freely moving rats and a pharmacological therapeutic approach.
RESULTS
We showed for the first time that subthalamic nucleus deep brain stimulation induces a motivational deficit in naive rats and intensifies those existing in a rodent model of PD neuropsychiatric symptoms. As reported from clinical studies, this loss of motivation was fully reversed by chronic treatment with pramipexole, a D and D dopaminergic receptor agonist.
CONCLUSIONS
Taken together, these data provide experimental evidence that chronic subthalamic nucleus deep brain stimulation by itself can induce loss of motivation, reminiscent of apathy, independently of the dopaminergic neurodegenerative process or reduction in dopamine replacement therapy, presumably reflecting a dopaminergic-driven deficit. Therefore, our data help to clarify and reconcile conflicting clinical observations by highlighting some of the mechanisms of the neuropsychiatric side effects induced by chronic subthalamic nucleus deep brain stimulation. © 2020 International Parkinson and Movement Disorder Society.
Topics: Animals; Apathy; Deep Brain Stimulation; Dopamine Agonists; Humans; Parkinson Disease; Rats; Subthalamic Nucleus
PubMed: 31930749
DOI: 10.1002/mds.27953 -
Neurology May 2008
Review
Topics: Deep Brain Stimulation; Humans; Neural Pathways; Parkinson Disease; Subthalamic Nucleus
PubMed: 18490619
DOI: 10.1212/01.wnl.0000313022.39329.65 -
Brain : a Journal of Neurology Jan 2004The subthalamic nucleus (STN) has been regarded as an important modulator of basal ganglia output. It receives its major afferents from the cerebral cortex, thalamus,... (Review)
Review
The subthalamic nucleus (STN) has been regarded as an important modulator of basal ganglia output. It receives its major afferents from the cerebral cortex, thalamus, globus pallidus externus and brainstem, and projects mainly to both segments of the globus pallidus, substantia nigra, striatum and brainstem. The STN is essentially composed of projection glutamatergic neurons. Lesions of the STN induce choreiform abnormal movements and ballism on the contralateral side of the body. In animal models of Parkinson's disease this nucleus may be dysfunctional and neurons may fire in oscillatory patterns that can be closely related to tremor. Both STN lesions and high frequency stimulation ameliorate the major motor symptoms of parkinsonism in humans and animal models of Parkinson's disease and reverse certain electrophysiological and metabolic consequences of dopamine depletion. These new findings have led to a renewed interest in the STN. The aim of the present article is to review briefly the major anatomical, pharmacological and physiological aspects of the STN, as well as its involvement in the pathophysiology and treatment of Parkinson's disease.
Topics: Animals; Humans; Neurons, Efferent; Neurotransmitter Agents; Parkinson Disease; Subthalamic Nucleus
PubMed: 14607789
DOI: 10.1093/brain/awh029 -
Annals of Neurology Apr 2000Severe dyskinesias or ballism can occur following hemorrhagic events in the subthalamic nucleus (STN), and it has recently been established that the STN plays a major... (Review)
Review
Severe dyskinesias or ballism can occur following hemorrhagic events in the subthalamic nucleus (STN), and it has recently been established that the STN plays a major role in the pathophysiology of the motor dysfunction of Parkinson's disease (PD) and that STN inhibition improves parkinsonian dysfunction. Deep brain stimulation of the STN in PD patients is therefore currently being evaluated as a therapy. High-frequency stimulation of the STN in PD patients can induce intense dyskinesias that are similar to those induced by levodopa. These may occur with a variable latency and resemble all types of levodopa-induced dyskinesias (LIDs). They can be decreased by reducing the levodopa dosage, which is permitted by the antiparkinsonian effect of stimulating the STN. STN stimulation has been shown to improve all types of LIDs, with the most dramatic effect being that on off-period dystonia. The improvement in LIDs may relate to the decrease in drug dosage, while the off-period dystonia is likely improved by the simultaneous administration of levodopa and STN stimulation. It is thought that the STN is an important node in a network, which can produce dyskinesias when disturbed by a lesion, and is particularly sensitive for the induction of these abnormal movements.
Topics: Animals; Dopamine Agents; Dyskinesia, Drug-Induced; Humans; Levodopa; Parkinson Disease; Subthalamic Nucleus
PubMed: 10762147
DOI: No ID Found -
Progress in Neurobiology Sep 2000The basal ganglia circuitry processes the signals that flow from the cortex, allowing the correct execution of voluntary movements. In Parkinson's disease, the... (Review)
Review
The basal ganglia circuitry processes the signals that flow from the cortex, allowing the correct execution of voluntary movements. In Parkinson's disease, the degeneration of dopaminergic neurons of the substantia nigra pars compacta triggers a cascade of functional changes affecting the whole basal ganglia network. The most relevant alterations affect the output nuclei of the circuit, the medial globus pallidus and substantia nigra pars reticulata, which become hyperactive. Such hyperactivity is sustained by the enhanced glutamatergic inputs that the output nuclei receive from the subthalamic nucleus. The mechanisms leading to the subthalamic disinhibition are still poorly understood. According to the current model of basal ganglia organization, the phenomenon is due to a decrease in the inhibitory control exerted over the subthalamic nucleus by the lateral globus pallidus. Recent data, however, suggest that additional if not alternative mechanisms may underlie subthalamic hyperactivity. In particular, given the reciprocal innervation of the substantia nigra pars compacta and the subthalamic nucleus, the dopaminergic deficit might influence the subthalamic activity, directly. In addition, the increased excitatory drive to the dopaminergic nigral neurons originating from the hyperactive subthalamic nucleus might sustain the progression of the degenerative process. The identification of the role of the subthalamic nucleus and, more in general, of the glutamatergic mechanisms in the pathophysiology of Parkinson's disease might lead to a new approach in the pharmacological treatment of the disease. Current therapeutic strategies rely on the use of L-DOPA and/or dopamine agonists to correct the dopaminergic deficit. Drugs capable of antagonizing the effects of glutamate might represent, in the next future, a valuable tool for the development of new symptomatic and neuroprotective strategies for therapy of Parkinson's disease.
Topics: Animals; Basal Ganglia; Brain; Cerebral Cortex; Humans; Nerve Degeneration; Parkinson Disease
PubMed: 10821982
DOI: 10.1016/s0301-0082(99)00067-2 -
Journal of Neural Transmission (Vienna,... Apr 2013The non-motor consequences of subthalamic stimulation are largely questioned. Cognition, motivation, anxiety, depression and even occurrence of suicides have been... (Review)
Review
The non-motor consequences of subthalamic stimulation are largely questioned. Cognition, motivation, anxiety, depression and even occurrence of suicides have been considered as a potential consequence of the surgical intervention. Non-motor fluctuations are present in all the patients with motor fluctuations and may sometimes be even more invalidating. Interestingly, subthalamic deep brain stimulation alleviates non-motor fluctuations allowing strikingly successful effects on sensory, dysautonomic and cognitive fluctuations while psychic fluctuations respond less consistently to this treatment. Nevertheless, severe mood fluctuations, oscillating from Off dysphoria to ON hypomania, are frequently associated with addictive behaviors and improve dramatically after subthalamic stimulation. This may be a further argument to support the indication of surgery for these patients.
Topics: Autonomic Nervous System Diseases; Deep Brain Stimulation; Depression; Humans; Pain Management; Parkinson Disease; Subthalamic Nucleus
PubMed: 23263599
DOI: 10.1007/s00702-012-0958-9 -
Journal of Neurology, Neurosurgery, and... Oct 2019Subthalamic deep brain stimulation (DBS) is beneficial when delivered at a high frequency. However, the effects of current amplitude and pulse width on subthalamic...
INTRODUCTION
Subthalamic deep brain stimulation (DBS) is beneficial when delivered at a high frequency. However, the effects of current amplitude and pulse width on subthalamic neuronal activity during high-frequency stimulation have not been investigated.
METHODS
In 20 patients with Parkinson's disease each undergoing subthalamic DBS, we recorded single-unit subthalamic activity using one microelectrode, while a separate microelectrode was used to deliver 5-10 s trains of stimulation at 100 Hz using varying current amplitudes and pulse widths (44 neurons investigated).
RESULTS
Analysis of variance tests confirmed significant (p<0.001) main effects of both current amplitude and pulse width on subthalamic neuronal firing during stimulation and on poststimulus inhibitory silent periods. Prolonged silent periods were often followed by postinhibitory rebound burst excitations. Additionally, a significant (p<0.0001) correlation was found between neuronal firing and total electrical energy delivered (TEED). With TEED values≤31.2 µJ/s (associated with DBS parameters of ≤2.0 mA, 130 Hz stimulation frequency and 60 µs pulse width, assuming 1 kΩ impedance), neuronal firing was sustained at a rate of 32.4%±3.3% (mean±SE), while with values>31.2 µJ/s, neurons fired at only 4.3%±1.2%.
CONCLUSIONS
Neuronal suppression is likely an important mechanism of action of therapeutically beneficial subthalamic DBS, which may underlie clinically relevant behavioural changes.
Topics: Deep Brain Stimulation; Humans; Neural Inhibition; Parkinson Disease; Subthalamic Nucleus
PubMed: 31422369
DOI: 10.1136/jnnp-2019-321140 -
Journal of Neurosurgery Dec 2000
Topics: Brain Mapping; Dominance, Cerebral; Electric Stimulation Therapy; Humans; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Parkinson Disease; Subthalamic Nucleus
PubMed: 11117859
DOI: 10.3171/jns.2000.93.6.1091