***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: BACKGROUND Gait-related symptoms are often refractory to current available treatment options with a significant reduction in quality of life in Parkinson 's disease . OBJECTIVES The objective of this study was to determine the long-term efficacy and safety of unilateral pedunculopontine area stimulation for refractory gait and balance impairment in Parkinson 's disease . METHODS This study used periodic r and omized double-blinded assessment s until 4 years postoperatively . The primary outcomes were gait-related items of the UPDRS part II and the MDS-UPDRS part III . RESULTS At baseline , the median age and disease duration was 63 years ( interquartile range : 62 , 65 ) and 15 years ( interquartile range : 11 , 20 ) . At 2 years , patient-reported freezing ( UPDRS part II , off-time ) was significantly better when compared with baseline ( P = .028 ) , with 62.5 % of responders . At 4 years , there was no significant change in the used outcomes , but 66.7 % ( n = 4 of 6 ) were responders for off-time patient-reported freezing and falling .  CONCLUSIONS Pedunculopontine area stimulation has an initial but not sustained benefit for gait-related symptoms . © 2016 International Parkinson and Movement Disorder Society Gait freezing and postural instability are disabling features of Parkinsonian disorders , treatable with pedunculopontine nucleus stimulation . Both features are considered deficits of proximal and axial musculature , innervated predominantly by reticulospinal pathways and tend to manifest when gait and posture require adjustment . Adjustments to gait and posture are amenable to pre-preparation and rapid triggered release . Experimentally , such accelerated release can be elicited by loud auditory stimuli — a phenomenon known as ‘ StartReact ’ . We observed StartReact in healthy and Parkinsonian controls . However , StartReact was absent in Parkinsonian patients with severe gait freezing and postural instability  . Pedunculopontine nucleus stimulation restored StartReact proximally and proximal reaction times to loud stimuli correlated with gait and postural disturbance . These findings suggest a relative block to triggered , pre-prepared movement in gait freezing and postural instability , relieved by pedunculopontine nucleus stimulation Objectives Attentional augmentation and enhanced motor function are potential mechanisms by which stimulation of the region of the pedunculopontine nucleus ( PPN ) may improve gait in parkinsonism . Here , the authors assess the impact of stimulation of this region on attentional and motor aspects of reaction task performance in patients with parkinsonism . Methods Eleven patients implanted with PPN stimulators  underwent computerised assessment of simple , choice and digit vigilance reaction tasks . Patients were assessed ‘ off medication ’ during stimulation at different frequencies ( 0 Hz , 5 Hz , 10 Hz and ‘ therapeutic ’ 20–35 Hz ) . There were two primary endpoints : ‘ Speed of Reaction ’ ( sum of the mean task reaction times ) and ‘ Accuracy of Reaction ’ ( reflecting omissions and percentage of correct responses ) . Baseline performance was compared with age- and sex-matched healthy controls . Clinical effects of stimulation were assessed using the Unified Parkinson 's Disease Rating Scale and a falls frequency scale . Results Compared with healthy controls , subjects had significant deficits in ‘ Speed of Reaction ’ and in all mean task reaction times . ‘ Accuracy of Reaction ’ was not different from healthy controls and did not improve with stimulation . ‘ Speed of Reaction ’ significantly improved with stimulation at therapeutic frequencies ( 20–35 Hz ) . Of the individual tasks , only simple reaction time improved significantly . Simple reaction time distribution analysis revealed a general speeding of responses rather than a selective reduction in outliers . Acute PPN stimulation improved gait and balance but not akinesia scores . Chronic PPN stimulation significantly improved falls frequency . Falls score improvement significantly correlated with changes to simple reaction time with therapeutic stimulation . Conclusion The pattern of reaction time improvement with stimulation of the PPN area suggests a benefit on motor performance , rather than augmentation of attention Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps . Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing , even where refractory to medication . However , the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established . The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral . Here , in a double-blinded study using objective spatiotemporal gait analysis , we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson ’s disease . Under experimental conditions , while OFF medication , Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions ; off stimulation , unilateral stimulation and bilateral stimulation . Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls . Pedunculopontine nucleus stimulation improved objective measures of gait freezing , with bilateral stimulation more effective than unilateral . During unconstrained walking , Parkinsonian patients who experience gait freezing  had reduced step length and increased step length variability compared to patients without gait freezing ; however , these deficits were unchanged by pedunculopontine nucleus stimulation . Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Question naire scores , reflecting a reduction of the freezing encountered in patients ’ usual environments and medication states . This study provides objective , double-blinded evidence that in a specific subgroup of Parkinsonian patients , stimulation of a caudal pedunculopontine nucleus region selectively improves gait freezing but not background deficits in step length .  Bilateral stimulation was more effective than unilateral BACKGROUND Pedunculopontine nucleus ( PPN ) stimulation is a novel therapy for Parkinson disease . However , controversies remain regarding the clinical application of this new therapy , including patient selection , electrode positioning , and how best to assess outcomes . OBJECTIVE To clarify the clinical application of PPN stimulation in Parkinson disease . METHODS Five consecutive patients with Parkinson disease complicated by severe gait freezing , postural instability , and frequent falls ( all persisting even while the patient was on medication ) received bilateral stimulation of the mid-lower PPN without costimulation of other brain targets . Outcomes were assessed prospect ively over 2 years with gait-specific question naires and the Unified Parkinson Disease Rating Scale ( part III ) . RESULTS The primary outcome , the Gait and Falls Question naire score , improved significantly with stimulation . Benefits were maintained over 2 years . Unified Parkinson Disease Rating Scale ( part III ) items assessing gait and posture were relatively insensitive to these treatment effects . Beneficial effects often appeared to outlast stimulation for hours or longer . Thus , single-session on- vs off-stimulation assessment s may be susceptible to “ delayed washout effects . ” Stimulation of the PPN did not change akinesia scores or dopaminergic medication requirements . CONCLUSION Bilateral stimulation of the mid-lower PPN ( more caudal than previous reports ) without costimulation of other brain targets may be beneficial for the subgroup of patients with Parkinson disease who experience severe gait freezing and postural instability with frequent falls , which persist even while on medication . Choosing appropriate outcome measures and accounting for the possibility of prolonged stimulation washout effects appear to be important for detecting the clinical benefits Gait and balance disorders are the major source of motor disabilities in advanced forms of Parkinson ’s disease ( PD ) .  Low-frequency stimulation of the pedunculopontine nucleus area ( PPNa-DBS ) has been recently proposed to treat these symptoms with variable clinical results . To further underst and the effects of PPNa-DBS on resistant gait and balance disorders , we performed a r and omised double-blind cross-over study in six PD patients . Evaluation included clinical assessment of parkinsonian disability , quality of life and neurophysiological recordings of gait . Evaluations were done 1 month before , 4 and 6 months after surgery with four double-blinded conditions assessed : with and without PPNa-DBS , with and without levodopa treatment .  Four patients completed the study and two patients were excluded from the final analysis because of peri-operative adverse events ( haematoma , infection ) . Clinical ly , the combination of PPNa-DBS and levodopa treatment produced a significant decrease of the freezing episodes . The frequency of falls also decreased in three out of four patients . From a neurophysiological point of view , PPNa-DBS significantly improved the anticipatory postural adjustments and double-stance duration , but not the length and speed of the first step . Interestingly , step length and speed improved after surgery without PPNa-DBS , suggesting that the lesioning effect of PPNa-DBS surgery alleviates parkinsonian akinesia . Quality of life was also significantly improved with PPNa-DBS . These results suggest that PPNa-DBS could improve gait and balance disorders in well-selected PD patients . However , this treatment may be riskier than others DBS surgeries in these patients with an advanced form of PD In Parkinson ’s disease ( PD ) , the effects of deep brain stimulation of the pedunculopontine nucleus ( PPTg-DBS ) on gait has been object of international debate . Some evidence demonstrated that , in the late swing-early stance phase of gait cycle , a reduced surface electromyographic activation ( sEMG ) of tibialis anterior ( TA ) is linked to the striatal dopamine deficiency in PD patients . In the present study we report preliminary results on the effect of PPTg-DBS on electromyographic patterns during gait in individual PD patients . To evaluate the sEMG amplitude of TA , the root mean square ( RMS ) of the TA burst in late swing-early stance phase ( RMS-A ) was normalized as a percent of the RMS of the TA burst in late stance-early swing ( RMS-B ) . We studied three male patients in the following conditions : on PPTg-DBS/on l-dopa , on PPTg-DBS/off l-dopa , off PPTg-DBS/on l-dopa , off PPTg-DBS/off l-dopa .  For each assessment the UPDRS III was filled in . We observed no difference between on PPTg-DBS/off l-dopa and off PPTg-DBS/off l-dopa in UPDRS III scores . In off PPTg-DBS/off l-dopa , patient A ( right implant ) showed absence of the right and left RMSA , respectively , in 80 % and 83 % of gait cycles . Patient B ( right implant ) showed absence of the right RMS-A in 86 % of cycles . RMS-A of the patient C ( left implant ) was bilaterally normal . In on PPTg- DBS/off l-dopa , no patient showed reduced RMS-A. Although the very low number of subjects we evaluated , our observations suggest that PPTg plays a role in modulating TA activation pattern during the steady state of gait Objective To compare the influence of low-frequency ( 10–25 Hz ) versus higher ( 60–80 Hz ) frequency stimulation of the pedunculopontine nucleus area ( PPNa ) on akinaesia , freezing of gait and daytime sleepiness . Method We included nine patients with Parkinson 's disease ( PD ) and severe gait disorders . In this double-blind r and omised cross-over study , patients were assessed after 24 h of PPNa stimulation . Assessment s included the motor part of the Unified Parkinson 's Disease Rating Scale , the Epworth Sleepiness Scale and a behavioural gait assessment . Results Compared with 60–80 Hz , 10–25 Hz PPNa stimulation led to decreased akinaesia , gait difficulties and daytime sleepiness in 7/9 patients . In one patient , these symptoms were aggravated under 10–25 Hz stimulation compared with 60–80 Hz . Conclusion These results are in keeping with the benefits of chronic PPNa stimulation for gait and postural difficulties in patients with PD , and with regard to the influence of patients ' clinical characteristics , differential neuronal loss in the PPNa and electrode location . We conclude that in patients with PPNa stimulation , low frequency provides a better outcome than high-frequency stimulation 
    Output:
    
PPN – DBS is a potential therapeutic target that could improve gait and fall disorders in patients with PD .
Our findings will help improve the clinical application of DBS in PD patients with gait disorder