movement disorders are neurological conditions that affect the speed , fluency , quality , and ease of movement
. there may be either an excess of movement or a paucity of voluntary and automatic movements , unrelated to weakness or spasticity .
movement is produced and coordinated by several interacting brain structures , such as the motor cortex , the cerebellum , and the basal ganglia ( bg ) .
the motor system is part of the central nervous system that is involved with voluntary and involuntary movements .
the extrapyramidal system is part of the motor system that causes involuntary reflexes and movement , and modulation of movement ( i.e. , coordination ) .
the bg comprises a group of interconnected deep brain nuclei , namely , the caudate and putamen , the globus pallidus internus ( gp ) , the substantia nigra ( sn ) , and the subthalamic nucleus ( stn ) .
these nuclei ( via their connections with the thalamus and the cortex ) influence the involuntary components of movement and muscle tone .
disruption of such complex circuitry within the bg causes movement disorders , such as parkinson 's disease ( pd ) , essential tremor ( et ) , and dystonia .
intimate structural and functional connections between cerebellum and basal ganglia appear to be involved in patients with dystonia . in certain types of dystonia , cerebellar dysfunction ( such as compensatory activity )
clinical , biochemical , pathological , and imaging studies suggest an abnormal functioning of the cerebellum in et .  
movement disorders can be classified as hyperkinesias ( excess of movements ) , dyskinesias ( unnatural movements ) , and abnormal involuntary movements .
there is also decreased amplitude of movement ( or hypokinesia ) , but the terms bradykinesia ( slowness of movement ) and akinesia ( loss of movement ) are used as well .
for example , acute morbidities encountered in movement disorders include those related to parkinson 's disease , acute drug reactions ( acute dystonia , neuroleptic malignant syndrome , serotonergic syndrome , and malignant hyperthermia ) , acute exacerbation of chronic movement disorders ( status dystonicus ) , hemiballism , and stiff - person syndrome .   the year 2012 marks the 25th anniversary of the birth of modern dbs .
it was initially created to treat tremor of the ventral intermediate nucleus ( vim ) of the thalamus . since then
, dbs has become a highly effective and safe surgical treatment for severe et , advanced parkinson 's disease , and dystonia .
dbs is widely administered with voltage - controlled devices , in which current is variable [ 9 , 10 ] .
high frequency dbs leads to a kind of functional deafferentation of the stimulated structure and to the modulation of cortical activity .
up to date , tens of thousands patients have undergone implantation of dbs electrodes , mainly for the treatment of parkinson 's disease , severe et , and for primary ( idiopathic ) dystonia .
new uses of dbs include epilepsy and psychiatric disorders such as depression , obsessive compulsive disorder , and tourette 's syndrome .
motor cortex stimulation is used for intractable neuropathic pain ( including central poststroke pain ) .
the role of dbs for parkinson 's disease , et , and dystonia is a well - established treatment option that is currently approved for use in north america , europe , and in countries such as australia and new zealand .
the aims of this narrative paper are to explore the use of dbs in the treatment of movement disorders to review indications for its use and its mechanisms of action . the implantation technique for dbs and its possible adverse effects
future technological advances clarifying pathophysiology of movement disorders and the need for improved research designs are discussed as well .
the paper is based on an extensive search of the literature ( pubmed , embase ) in relation to the topics covered without strict inclusion or exclusion criteria in the search strategy .
indications for the use of dbs include the need to improve function , reduce medication dependency , and avoid ablative neurosurgery .
dbs has arisen to the forefront as a highly effective , safe , and reversible treatment of parkinson 's disease , et , and dystonia .
the possible target sites for dbs include the ventral intermediate ( vim ) nucleus of the thalamus , the gpi , and the stn .
parkinson 's disease is a chronic progressive neurodegenerative movement disorder affecting the extrapyramidal motor system .
the loss of sn pars compacta dopaminergic neurones projecting to the caudate and putamen is considered its neuropathological hallmark .
class one evidence exists for the usefulness of dbs for parkinson 's disease [ 11 , 13 , 14 ] .
it is estimated that more than 10% of parkinson 's disease patients could benefit from dbs treatment .  
dbs should be reserved for patients with levodopa - responsive parkinson 's disease who have levodopa - related complications that can not be adequately controlled with medications .
the three currently accepted primary targets used for dbs in the treatment of idiopathic advanced parkinson 's disease refractory to medical therapy are the vim thalamus , the gpi , and the stn .
the overall clinical outcome of stn and gpi dbs for control of dyskinesia and motor fluctuations is similar .  
reduction of dopaminergic therapy after stn dbs may help in reducing visual hallucinations and impulse control abnormalities .
the use of constant - current bilateral dbs of the stn for parkinson 's disease results in significant improvements in motor function and daily fluctuations of response to levodopa .
the evidence to date shows that dbs is generally safe from the cognitive standpoint in well - selected pd patients .
however , there is a clear risk of postsurgical cognitive decline that seems greater whenever the stn dbs is used .  
significant improvements occur in patients with advanced parkinson 's disease ( particularly those with severe motor fluctuations ) when treated with gpi dbs .
these include improvements in gait and posture , reduction of dyskinesias , and the reduction of both the amount and severity of on / off fluctuations .
however , both primary and various types of secondary dystonia can be treated very effectively with gpi dbs .  
such tremors include parkinsonian tremors , ets , cerebellar tremors , tremors of multiple sclerosis , and orthostatic tremors .  
dbs of the vim thalamus remains an effective target for treatment of certain patients with tremor dominant parkinson 's disease refractory to medical therapy .
the frequency of stimulation is a key factor in determining clinical efficacy [ 21 , 22 ] .
stimulation starts to reduce tremor at a frequency of approximately 50  hz and reaches a plateau at 200  hz . for more than five years after implantation
, thalamic dbs has been shown to benefit tremor control [ 20 , 23 ] . in severe parkinsonian tremor
, promising results have recently been obtained from the use of dbs in the posterior subthalamic area ( including the caudal zona incerta ) .  
et is the most common movement disorder affecting up to 5.5% of individuals aged 65 years or older .
the main exclusion criteria of dbs treatment for et include altered cognition and the presence of an untreated or disabling psychiatric illness .
the usefulness of thalamic stimulation in the treatment of essential head and voice tremor remains unproven .  
dbs has been an emerging therapy for disabling cerebellar tremors of different aetiologies ( multiple sclerosis , stroke , trauma , cavernous haemangiomas , tumours , and degenerative disease ) .
better control in posttraumatic tremor occurred when dual deep brain stimulator leads were placed over a larger region of the ventral thalamus [ 8 , 28 ] .
bilateral thalamic stimulation has demonstrated beneficial effects in case reports in treatment - resistant orthostatic tremor [ 29 , 30 ] .  
. it might be primary ( idiopathic ) or secondary to a known structural lesion of the brain ( e.g. , cerebral palsy from perinatal hypoxia , infections , stroke , trauma , drugs , and wilson 's disease ) or associated with a complex regional pain syndrome .
the interaction between the bg and cerebellar circuits plays a major role in its pathophysiology .
it presents with sustained , uncontrolled , and often painful muscle contractions causing repetitive movements and abnormal postures .
dystonia is divided into focal ( affecting a single body region ) , segmental ( two or more adjacent areas ) , or generalized ( involving the legs , or one leg and the trunk , plus at least one other area of the body ) .
focal dystonias include cervical dystonia ( spasmodic torticollis ) , blepharospasm , oculogyric crisis , oromandibular dystonia , spasmodic dysphonia or laryngeal dystonia , and focal hand dystonia .  
the gpi shows abnormal firing activity in dystonia and is therefore the usual target of dbs ( e.g. , for primary dystonia and for cervical dystonia orspasmodic torticollis ) . the optimal frequency and amplitude stimulation settings needed for dbs in dystonia are higher than for gpi dbs and stn dbs in parkinson 's disease patients .
positive effects of dbs on dystonia scales , quality of life , and pain reduction have been confirmed in many studies [ 2 , 32 , 33 ] . in primary generalised dystonia
long - term sustainability of these benefits has been demonstrated . in tardive dystonia ( from neuroleptics , metoclopramide , and prochlorperazine ) , there is significant improvement in dystonic symptoms from dbs .   whereas the maximum beneficial effect on tremor and rigidity is reached within minutes , the delay for maximal improvement in akinesia
is minutes to hours , and the improvement in dystonia gradually develops over several weeks [ 22 , 3740 ] .
the third is that high - frequency stimulation induces long - term synaptic changes ( plasticity ) .
recent evidence suggests that dbs has more complex mechanisms of action than the pure functional inactivation of the target region .
the ultimate effect of modulating the network activity within the bg can be viewed as the takeover on hyperactive elements or structures of the cortico - bg - thalamocortical complex circuit [ 8 , 4143 ] .
for example , reducing the abnormally enhanced synchronisation of basal ganglia output is an essential mechanism in the therapeutic effect of dbs in parkinson 's disease .  
other possible mechanisms of action for high - frequency dbs include local neuronal inhibition with concomitant activation of surrounding fibres , thus resulting in increased synaptic output   and activation of afferent axon terminals ( e.g. , the cortical inputs in the case of high - frequency stimulation of the stn or nucleus accumbens ) [ 22 , 44 , 45 ] .
this could be of benefit for the treatment of obsessive - compulsive disorders and depression [ 22 , 46 ] .  
dbs may modulate specific neurones that release specific neurotransmitters , thereby affecting these systems in the brain .
the use of volume of tissue - activated studies , other functional imaging , microelectrode multisite recordings , local field potentials , eegs , and magnetoencephalographic studies will promote understanding of the stimulation effects on local and long - range neuronal networks .
for example , patient selection criteria for dbs in parkinson 's disease are as follows : ( 1 ) a diagnosis of medically refractory intractable parkinson 's disease , primary generalised dystonia , or et , with symptoms that substantially interfere with the patient 's quality of life and functionality , ( 2 ) intact cognition , ( 3 ) the absence of an untreated or disabling psychiatric illness , ( 4 ) realistic expectations , ( 5 ) the ability and willingness to participate in regular followup visits , and ( 6 ) the absence of comorbidities that are contraindications to dbs [ 18 , 47 ] .  
the dbs technique uses continuous high - frequency stimulation of specific brain regions ( figure 1 ) .
it involves the implantation of a microelectrode into a deep target within the brain that is connected to a stimulator ; the stimulator is programmed to emit electrical impulses at varying strengths and frequencies .
impulses travel to the implanted electrodes from a pulse generator ( similar to a cardiac pacemaker ) that is telemetrically programmable .
medtronic dbs device ( minneapolis inc . ) is currently the most widely utilised system in functional surgery across the world .
the device used has three separate components including the electrode , the extension wires connecting the intracranial electrodes with impulse programming generator ( ipg ) , and the ipg ( figure 2 ) .
although details regarding surgical techniques may vary , all combine a stereotactic technique with detailed image guidance .
stereotaxis is a minimally invasive surgical procedure that makes use of a three - dimensional coordinate system to accurately locate a target in a deep - seated area of the brain .
electrodes are implanted into the target brain area by means of this stereotactic surgical procedure with electrophysiological recordings at the cellular or pathway level .  
a stereotactic head frame is placed on the patient under local anaesthesia in the operating room .
a computed tomography ( ct ) scan or , more commonly , a magnetic resonance imaging ( mri ) scan is obtained ; this identifies the anterior commissure , posterior commissure , and the midcommissural point .
based on the location of these structures , well - established x , y , and z target coordinates are used to plan electrode placement . planning software determines the target coordinates ; an entry point is found that will allow passage of the electrode through the brain without traversing the ventricle or damaging vascular structures .  
surgery is usually performed while the patient is awake , off drug therapy , and under local anaesthesia , as this enables reliable microelectrode recording ( mer ) to be obtained ; it allows evaluation of the intraoperative stimulation and possible adverse effects caused by the current diffusion to adjacent structures .
general anaesthesia is generally contraindicated during mer , as it depresses neural activity , suppresses clinical symptoms ( tremors and rigidity ) , and interferes with the evaluation of clinical benefits . in patients unable to tolerate an 
awake  procedure , ketamine is a safe and effective alternative to other drugs used to induce general anaesthesia , as the feasibility of microelectrode recording is preserved .  
a scalp incision and burr hole are placed in the skull at the predetermined entry point .
electrodes of 1.3  mm in diameter integrating four contacts of 1.5  mm length each , connected to a pulse generator , are used .
verbal feedback is received from the  awake  patient regarding unwanted adverse effects ( such as paraesthesias or visual phenomena ) .
proper placement is confirmed by intraoperative fluoroscopy and postoperative mri or ct scanning .   once trial stimulation has been deemed successful , a permanent pulse generator ( similar to a pacemaker ) is placed in the subclavicular space .
stimulation parameters ( frequency , amplitude , and pulse widths ) may vary . programming these parameters
several time - consuming visits may be required before the best therapeutic effect is reached .
bilateral lead implantations can be performed either during a single surgery or in a staged procedure separated by 24 weeks .
pulse generators can be placed in a subclavicular position either on the same day or as part of a staged procedure after lead implantation .
successful outcomes are correlated with patient selection , accurate placement of the electrodes in their surgical target , and optimal programming of patients .   at what stage
however , an eight - year followup study in parkinson 's disease showed that stn dbs can be considered safe from a cognitive standpoint but did not seem to modify the cognitive evolution along the course of the disease .
on the basis of these observations , it may be appropriate to perform surgery earlier than currently indicated .
adverse effects noted include those related to the surgery , the hardware , and the stimulation per se .
surgical complications include primarily intracerebral haemorrhage ( less than 2% in most centres ) and infection ( in about 4% of the cases ) [ 2 , 51 ] . intraoperative or postoperative haemorrhage is the most dreaded complication of dbs .
haemorrhages may occur due to laceration of intracerebral vessels during microelectrode recording or lead implantation .
surgery on the gpi carries a greater haemorrhagic risk than does that on the stn .
hardware complications ( device - related problems occur in 4.5% of the patients )   include the following : erosion over the connector ; electrode ruptures or malfunction ; electrode migration ; lead fractures ; infections ; skin erosion ; battery failure ; device malfunction ; mri safety concerns .
erosion of the subcutaneous portions of the hardware occurs in patients with a very low body mass index .
electrode impedance should be checked and recorded at each clinical visit [ 15 , 55 ] .  
stimulation signals with amplitudes greater than those required to achieve symptom control can affect neighbouring structures causing adverse effects ; these are reversible with amplitude adjustments . to avoid this
dyskinesia , worsening of axial symptoms ( freezing , balance , and gait disturbance ) , speech disturbance , involuntary muscle contractions , paraesthesia , and diplopia are among the common stimulation - related and transient side effects .  
stn dbs can worsen speech and gait in some patients , requiring stimulation parameters to be adjusted .
other adverse effects observed after stn dbs include neuropsychiatric problems , cognitive deterioration , eyelid opening apraxia , weight gain , stimulation - induced dyskinesias , and worsening akinesia [ 56 , 57 ] .
the neuropsychiatric symptoms following stn dbs in parkinson 's disease patients are generally transient and mild if managed appropriately .   with gpi dbs , adverse effects include paresthesias , muscle contractions , visual flashes , worsening akinesia , dysarthria , weight gain , eyelid opening apraxia , confusion , and cognitive decline .
a recent study reported that depression worsened with stn dbs but improved with gpi dbs .  
years later , patients can develop disabling levodopa - resistant symptoms , such as gait disturbances and cognitive impairment .
stimulation - induced dyskinesia is frequently managed with a reduction in the dosage of dopaminergic medications . to control symptoms with fewer medication adverse effects , programming of dbs
can be performed concurrently with changes in levodopa doses .   in dbs for et ,
the most frequent stimulation - induced adverse effects are paresthesias , followed by dysarthria and pain ; these are reversible once the stimulation is turned off . gait or balance may worsen following dbs for medication refractory et .
adverse effects of dbs may include modulation of affect , cognition , and behaviour , or possible changes of personality .
some data suggest that the implantation  per se  and not the stimulation is the main cause of the decline in executive function .
dbs is generally safe from the cognitive standpoint in well - selected pd patients when looking at measures of global cognition .
nevertheless , there is a clear risk of postsurgical cognitive decline that seems greater whenever the stn dbs is used , although data with other targets is limited .
only one large randomized , double - blind trial has focused mainly on motor efficacy issues of stn dbs versus gpi dbs .
postsurgical decline in verbal fluency has been the most consistently reported cognitive adverse effect in patients undergoing subthalamic dbs [ 18 , 59 ] .
the demonstration of long - term cognitive effects from the surgical procedure or stimulation is difficult .
it remains challenging to differentiate these from the natural progression of the disease and other confounding variables ( such as drug therapy , brain vascular lesions , pd progression , and concurrent degenerative pathology ) .
short - term clear cut changes are most probably due to the surgical procedure itself and the electrical stimulation .
the factors ( such as age , pd duration , disease phenotype , and levodopa responsiveness ) that predict postsurgical cognitive decline remain unsatisfactory .
a wireless instantaneous neurotransmitter concentration system ( wincs ) has been developed to promote understanding of the neurocircuitry involved [ 61 , 62 ] .
the wincs system provides real - time neurotransmitter monitoring to reveal underlying neuromodulatory mechanisms of dbs action .
this device is capable of monitoring the release of a variety of neurochemicals ( dopamine , serotonin , histamine , and adenosine ) during dbs using the electroanalytical techniques of fast - scan cyclic voltammetry at a carbon fibre microelectrode , and fixed potential amperometry   at enzyme - linked biosensors .  
dbs systems ; these would provide feedback from brain electrical activity to direct the stimulation and neuroimaging modalities . computational analysis or electrophysiological modelling
dbs would then depend on the use of multiple electrodes with these  closed - loop
it might even allow the performance of effective and safe programming through remote access , such as via the telephone or the internet . by disentangling the neuronal network codes , closed - loop devices   could provide stimulation  on demand  .  
on - going clinical trials with dbs are investigating its use in tremor in multiple sclerosis , in mood disorders , in pain and cluster headache , in hypertension , in obesity , in memory impairment , in aggressiveness , in drug addiction , and in other central nervous system disorders ; this will enhance indications for its use in future . advances in functional imaging are providing  new
offer preoperative modelling for dbs surgery , including nerve fibre tracts ( diffusion tensor imaging ) , and imaging of volume of tissue activated by a specific electrode .
computational analysis techniques for dbs include mathematical models of the abnormally synchronized electrical activity that underlies epilepsy , movement disorders , and many mood disorders as well .
new programming options such as interleaving   and constant current devices   are now on the market .
constant - current stimulation provides more accurate control of the spread of the electrical field than do voltage - controlled devices , as adjustments can be for heterogeneity in tissue impedance [ 10 , 68 ] .
the development of new electrodes with improved variability of stimulation direction should aid progress as well .
finding the right anatomical areas to stimulate to gain the best outcomes remains a challenge .
a more recent experimental target is the pedunculopontine nucleus ( ppn ) that may be appropriate for patients with gait freezing or postural instability gait difficulty [ 6971 ] .
the centremedian / parafascicular thalamic complex has been proposed as a successful target for control of tremor as well .  
fibre tracts rather than nuclei might be the correct target of choice ( not only in parkinson 's disease , but also in thalamic stimulation for et ) .
optogenetic studies suggest that stn stimulation and stimulation of afferents from cortical areas might form the main mechanism of action of dbs [ 11 , 41 ] .
movement disorders encompass acute and chronic diseases characterised by involuntary movements or loss of control or efficiency in voluntary movements . in movement disorders , dbs is a highly effective , safe , and reversible surgical treatment for advanced parkinson 's disease , tremor , and dystonia . its use has promoted interdisciplinary clinical team work and provided an improved understanding of the complex neurocircuitry associated with these disorders . for improvement of outcomes after dbs , a refinement of patient selection criteria is needed .
dbs is a useful therapeutic option in carefully selected patients that significantly improves motor symptoms , functional status , and quality of life .
dbs remains an expensive resource , and its future clinical use will continue to raise many regulatory and ethical issues .
further evidence , particularly in the form of prospective studies and randomised controlled trials , is required to better establish the pathophysiology of movement disorders and its role therein .
 movement disorders are neurological conditions affecting speed , fluency , quality , and ease of movement . 
 deep brain stimulation ( dbs ) is used to treat advanced parkinson 's disease , essential tremor , and dystonia . 
 possible target sites for dbs include the ventral intermediate nucleus of the thalamus , the globus pallidus internus , and the subthalamic nucleus . 
 high - frequency dbs leads to a kind of functional deafferentation of the stimulated structure and to the modulation of cortical activity . 
 this has a profound effect on the efficiency of movement . 
 indications for the use of dbs include the need to improve function , reduce medication dependency , and avoid ablative neurosurgery . 
 appropriate patient selection is critical for success . 
 the implantation technique is briefly described . 
 programming stimulation parameters are performed via telemetry . 
 the adverse effects of dbs are discussed . 
 the future should see the development of  closed - loop  systems . 
 its use has promoted interdisciplinary team work and provided an improved understanding of the complex neurocircuitry associated with these disorders . 
 dbs is a highly effective , safe , and reversible surgical treatment for advanced parkinson 's disease , tremor , and dystonia . 
 it is a useful therapeutic option in carefully selected patients that significantly improves motor symptoms , functional status , and quality of life . 