Joseph Candelario-Mckeown - Academia.edu (original) (raw)

Papers by Joseph Candelario-Mckeown

Movement Disorders, Feb 14, 2014

BackgroundSpeech changes following bilateral subthalamic nucleus deep brain stimulation (STN-DBS)... more BackgroundSpeech changes following bilateral subthalamic nucleus deep brain stimulation (STN-DBS) can be variable, with the majority of patients experiencing speech deterioration over time. The aim of this study was to describe the perceptual characteristics of speech following chronic STN-DBS and to analyse clinical and surgical factors that could predict speech change.MethodFifty-four consecutive patients (34 male, mean age 58.8±6.3years, mean disease duration 12.5±4.7years, mean levodopa equivalent 1556±671mg/day, UPDRS-III off-medication 48.1±17.9 range 20–89, UPDRS-III on medication 12.4±7.8 range 2–31) participated in this study. They were assessed before and at one year following surgery using the Assessment of Intelligibility for the Dysarthric Speech, the perceptual scale from Darley et al and the UPDRS-III.ResultsSpeech intelligibility deteriorated on average by 14.4% (p=0.0006) after one year of STN-DBS when off-medication and by 12.3% (p=0.001) when on-medication. The effect on speech was not linked to age at surgery, unlike the effect on motor outcome. The most significant predictive factors for deterioration of speech intelligibility when patients were off-medication/on-stimulation were a lower pre-operative speech intelligibility on-medication, a longer disease duration and medially placed left hemisphere active electrode contact.ConclusionSpeech change following STN-DBS is variable and multifactorial. Consistent pre-operative speech evaluation would help inform patients on the possible effects of surgery. Appropriate consideration of speech deficits might assist surgical targeting, particularly of the left electrode.

Journal of Parkinson's disease, Feb 5, 2019

Background: Subthalamic Deep Brain Stimulation (STN-DBS) is an established treatment for late sta... more Background: Subthalamic Deep Brain Stimulation (STN-DBS) is an established treatment for late stage Parkinson's disease (PD). Speech intelligibility (SI) and verbal fluency (VF) have been shown to deteriorate following chronic STN-DBS. It has been suggested that speech might respond favourably to low frequency stimulation (LFS). Objective: We examined how speech intelligibility, perceptual speech characteristics, phonemic and semantic VF and processes underlying it (clustering and switching) respond to LFS of 60 and 80Hz in comparison to high frequency stimulation (HFS) (110, 130 and 200 Hz). Methods: In this double-blind study, 15 STN-DBS PD patients (mean age 65, SD=5.8, 14 right handed, three females), were assessed at five stimulation frequencies: 60Hz, 80Hz, 110Hz, 130Hz and 200Hz. In addition to the clinical neurological assessment of speech, VF and SI were assessed. Results: Speech intelligibility and in particular articulation, respiration, phonation and prosody improved with LFS (all p<0.05). Phonemic VF switching improved with LFS (p=0.005) but this did not translate to an improved phonemic VF score. A trend for improved semantic VF was found. A negative correlation was found between perceptual characteristics of speech and duration of chronic stimulation (all p<0.05). Conclusions: These findings highlight the need for meticulous programming of frequency to maximise speech intelligibility in chronic STN-DBS. The findings further implicate stimulation frequency in changes to specific processes underlying VF, namely phonemic switching and demonstrate the potential to address such deficits through advanced adjustment of stimulation parameters.

Movement Disorders, Jun 7, 2017

Background: Subthalamic deep brain stimulation (STN-DBS) is an effective treatment for Parkinson'... more Background: Subthalamic deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's disease (PD), but can have side effects caused by stimulus spread to structures outside the target volume such as the pyramidal tract. Objectives: To assess the relevance of pyramidal tract activation with STN-DBS in PD. Methods: In a multimodal, blinded study in 20 STN-DBS patients, we measured stimulation thresholds for evoking electromyographic activity in orbicularis oris and first dorsal interosseous muscles at each of 150 electrode sites. We also modeled the electric field spread and calculated its overlap with the estimated anatomical location of corticospinal and corticobulbar tracts from primary motor cortex using 3 Tesla MRI probabilistic tractography. Results: Mean resting motor thresholds were significantly lower for the contralateral orbicularis oris (3.5 6 1.0 mA) compared with ipsilaterally (4.1 6 1.1 mA) and with the contralateral first dorsal interosseous (4.0 6 1.2 mA). The modeled volumes of corticobulbar and corticospinal tract activated correlated inversely with the resting motor threshold of the contralateral orbicularis oris and first dorsal interosseous, respectively. Active motor thresholds were significantly lower compared with resting motor thresholds by around 30% to 35% and correlated with the clinically used stimulation amplitude. Backward multiple regression in 12 individuals with a "lateral-type" speech showed that stimulation amplitude, levodopa equivalent dose reduction postsurgery, preoperative speech intelligibility, and first dorsal interosseous resting motor thresholds explained 79.9% of the variance in postoperative speech intelligibility. Conclusions: Direct pyramidal tract activation can occur at stimulation thresholds that are within the range used in clinical routine. This spread of current compromises increase in stimulation strengths and is related to the development of side effects such as speech disturbances with chronic stimulation. V

Lancet Neurology, Jun 1, 2015

Background Deep brain stimulation (DBS) has been proposed as a treatment option for severe Touret... more Background Deep brain stimulation (DBS) has been proposed as a treatment option for severe Tourette syndrome (TS), based on open-label series and blinded data from a small number of individuals. This study aimed to further evaluate the safety and efficacy of bilateral globus pallidus internus (GPi) DBS in this patient group. Methods In this randomized, double-blind, crossover trial, eligible patients (severe medically refractory TS, aged ≥20 years old) were recruited from 2 tertiary movement disorders clinics in the UK, received GPi DBS surgery, then were randomly assigned (1:1) to either "stimulation-ON first" or "stimulation-OFF first" for a three-month period followed by a switch to the opposite condition for a further three-month period. Neither patients nor rating clinicians were aware of their computer-generated treatment allocation. An unmasked clinician was responsible for programing the stimulation. The primary endpoint was the difference in Yale Global Tic Severity Scale (YGTSS) total score between the two blinded conditions using repeated measures ANOVA. After completing the double-blind crossover period, patients continued to have open-label stimulation adjustments and objective assessments of tic severity until database lock one month after the final patient's final trial related visit. The trial was registered with ClinicalTrials.gov, number NCT01647269. Findings Data were collected between August 2011 and December 2014. Of the 15 patients enrolled, 13 patients completed the double-blinded period. The mean YGTSS total score was 87•9 (SD 9•2) at baseline, 80•7 (SD 12•0) with DBS OFF and 68•3 (SD 18•6) with DBS ON. Repeated measures ANOVA revealed a significant interaction between timepoint and YGTSS total scores (Wilks Lamba =0•45, F(2,11)= 6•6, p=0•013). Pairwise comparisons in YGTSS total scores after Bonferroni correction were significantly lower at the end of the ON compared to the OFF blinded stimulation condition with a mean improvement of 12•4 points (95% CI 0•10-24•7, p=0•048) equivalent to 15•3%. Between trial commencement and database lock, 3 serious adverse events were observed; 2 DBS hardware infections, (2 & 7 weeks post-operatively) & 1 episode of DBS induced hypomania, during the blinded ON stimulation phase, all of which resolved with treatment. Interpretation Globus pallidus stimulation led to a significant improvement in tics during the ON compared to the OFF blinded condition, with an overall acceptable safety profile. Future research should concentrate on identifying the most effective deep brain stimulation target to control both tics and associated comorbidities, and further clarify those factors predicting individual patient responses to this treatment option.

Movement Disorders Clinical Practice, Jan 21, 2016

Ataxia-telangiectasia (A-T) is an autosomal-recessive disorder characterized by cerebellar ataxia... more Ataxia-telangiectasia (A-T) is an autosomal-recessive disorder characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, radiosensitivity, increased prevalence of malignancies, and increased level of alpha-fetoprotein (AFP). 1 The responsible gene AT mutated (ATM), localized to chromosome 11q22-2, is a serine/threonine protein kinase that is involved in the cellular response to DNA damage. Whereas the classic form, genetically marked by truncating mutations of the ATM, is a severe, fast progressive disease with no residual ATM kinase activity, patients with variant AT show a milder form of the disease, often presenting with a plethora of different extrapyramidal manifestations-choreoathetosis, resting tremor, and myoclonus-dystonia (M-D) and still have some residual ATM-kinase activity; they are usually carriers of at least one missense or leaky splice site mutation. 1,2 We present a case of a variant AT with mainly M-D presenting features and a favorable outcome after bilateral DBS of the globus pallidus pars interna (GPi-DBS).

Movement Disorders, Sep 27, 2011

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment for patie... more Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment for patients with Parkinson's disease (PD). Speech impairment is a frequent side effect of the surgery. This study examined the efficacy of an intensive speech treatment (the Lee Silverman Voice Treatment, LSVT) on dysarthria after STN-DBS. The LSVT was administered in ten patients with STN-DBS (surgical group) and ten patients without (medical group). Patients were assessed before, immediately after and six months following the speech treatment using sustained phonation, a speech intelligibility scale and monologue. Vocal loudness, speech intelligibility and perceptual ratings were the primary outcome measures. Vocal loudness and perceptual scores improved significantly across tasks for the medical group only. Speech intelligibility did not significantly change for either group. Results in the surgical group were variable with some patients deteriorating. Treatment of dysarthria following STN-DBS needs further investigation due to the variable response to LSVT.

Journal of Neurosurgery, Apr 1, 2017

D eep brain stimulation (DBS) was popularized by the Grenoble group 2 and surpassed stereotactic ... more D eep brain stimulation (DBS) was popularized by the Grenoble group 2 and surpassed stereotactic ablation as the predominant treatment in functional neurosurgery at the end of the last millennium. DBS is now an established treatment for a number of movement disorders including Parkinson's disease, dystonia, and tremor. This has raised interest in the possible use of DBS for severe and unremitting psychiatric disorders including obsessive-compulsive disorder and depression. 31 Despite the surge in popularity of DBS only a small number of publications have specifically analyzed the complications of DBS surgery, 3,4,6,15,32,40,41 and even fewer have assessed interventions that can reduce the rate of adverse events. 3,14,24,26,28,37,46 Reported infection rates vary between centers from 0% to 22%. 7,42 Our group recently published data demonstrating that infection rates after implantable pulse generator (IPG) replacement are significantly higher when compared with other types of DBS-related surgery. 32 Other authors have reported similar trends. 3 However, the overall picture is far from clear, as other groups reported infection rates similar to de novo surgery. 4,36 Miller and colleagues previously reported a significant improvement in hardware-related infection in all stereotactic and functional neurosurgical procedures with ABBREVIATIONS DBS = deep brain stimulation; IPG = implantable pulse generator; MRSA = methicillin-resistant Staphylococcus aureus.

Journal of Neurology, Neurosurgery, and Psychiatry, Apr 29, 2014

Background Subthalamic nucleus (STN) deep brain stimulation (DBS) represents a well-established t... more Background Subthalamic nucleus (STN) deep brain stimulation (DBS) represents a well-established treatment for patients with advanced Parkinson's disease (PD) insufficiently controlled with medical therapies. This study presents the long-term outcomes of patients with PD treated with STN-DBS using an MRI-guided/MRI-verified approach without microelectrode recording. Methods A cohort of 41 patients who underwent STN-DBS were followed for a minimum period of 5 years, with a subgroup of 12 patients being followed for 8-11 years. Motor status was evaluated using part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III), in on-and off-medication/on-stimulation conditions. Preoperative and postoperative assessments further included activities of daily living (UPDRS-II), motor complications (UPDRS-IV), neuropsychological and speech assessments, as well as evaluation of quality of life. Active contacts localisation was calculated and compared with clinical outcomes. Results STN-DBS significantly improved the offmedication UPDRS-III scores, compared with baseline. However, UPDRS scores increased over time after DBS. Dyskinesias, motor fluctuations and demands in dopaminergic medication remained significantly reduced in the long term. Conversely, UPDRS-III on-medication scores deteriorated at 5 and 8 years, mostly driven by axial and bradykinesia subscores. Quality of life, as well as depression and anxiety scores, did not significantly change at long-term follow-up compared with baseline. In our series, severe cognitive decline was observed in 17.1% and 16.7% of the patients at 5 and 8 years respectively. Conclusions Our data confirm that STN-DBS, using an MRI-guided/MRI-verified technique, remains an effective treatment for motor 'off' symptoms of PD in the long term with low morbidity.

Journal of Parkinson's disease, Jun 13, 2018

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for ... more BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for selected Parkinson's disease (PD) patients, but therapy is often limited by side effects. Previous studies indicate an inverse relationship of the therapeutic window (TW) to pulse width (PW) settings down to 60µs, but there is limited data available on the effect of shorter PWs. OBJECTIVES: To define the TW of STN-DBS in PD at PW of 30µs (PW30) relative to standard PW settings at 60µs (PW60), and to compare speed of gait and intelligibility of speech on the two PW conditions. METHODS: Monopolar review data of 15 consecutive PD patients who had screening of contacts performed at PW60 and PW30 was used to calculate the TWs on each setting. We compared the TWs of the most efficacious contact per STN, and a secondary analysis was performed comparing all contacts. Speed of gait with timed 10 metre walk test and intelligibility of speech were also compared at the efficacy thresholds for PW60 and PW30. RESULTS: The TW was significantly greater at PW30 [3.8±1.6mA] than at PW60 [1.7±1.1mA]. In the secondary analysis, 110 TWs could be calculated and these remained significantly higher at PW30. The timed 10 metre walk at PW30 was faster than at PW60, and the mean speech intelligibility assessment scores were significantly improved at PW30. CONCLUSIONS STN-DBS in PD patients using a PW of 30µs significantly increases the TW compared to standard PW settings, and this effect is consistent across all contacts of an electrode. Speed of gait and speech intelligibility are also improved at 30µs settings.

Journal of Parkinson's disease, Sep 19, 2022

Background: Parkinson's disease severity is typically measured using the Movement Disorder Societ... more Background: Parkinson's disease severity is typically measured using the Movement Disorder Society Unified Parkinson's disease rating scale (MDS-UPDRS). While training for this scale exists, users may vary in how they score a patient with the consequence of intra-rater and inter-rater variability. Objectives: In this study we explored the consistency of an artificial intelligence platform compared with traditional clinical scoring in the assessment of motor severity in PD. Methods: Twenty two PD patients underwent simultaneous MDS-UPDRS scoring by 2 experienced MDS-UPDRS raters and the 2 sets of accompanying video footage were also scored by an artificial intelligence video analysis platform known as KELVIN. Results: KELVIN was able to produce a summary score for 7 MDS-UPDRS part 3 items with good inter-rater reliability (Intraclass Correlation Coefficient (ICC) 0.80 in the OFF medication state, ICC 0.73 in the ON medication state). Clinician scores had exceptionally high levels of inter-rater reliability in both the OFF (0.99) and ON (0.94) medication conditions (possibly reflecting the highly experienced team). There was an ICC of 0.84 in the OFF medication state and 0.31 in the ON medication state between the mean Clinician and mean Kelvin scores for the equivalent 7 motor items, possibly due to dyskinesia impacting on the KELVIN scores. Conclusions; We conclude that KELVIN can usefully capture and score multiple items of MDS-UPDRS part 3 with levels of consistency not far short of that achieved by experienced MDS-UPDRS clinical raters.

British Journal of Neuroscience Nursing

Deep brain stimulation (DBS) is an effective surgical treatment in ameliorating symptoms of Parki... more Deep brain stimulation (DBS) is an effective surgical treatment in ameliorating symptoms of Parkinson's disease (PD), dystonia and tremor. DBS involves the surgical insertion of electrode(s) to stimulate either the subthalamic nucleus, globus pallidum interna or ventral intermediate nucleus of the thalamus, depending on the condition being treated. These structures play a critical role in the relay of electrical signals within the basal ganglia to facilitate movement. The mechanism by which DBS improves symptoms is not clearly understood. However, one notion is that the local effects of stimulation cause neuromodulation resulting in subsequent distant effects within connecting neural networks. Important factors to be considered when selecting patients for DBS include establishing a diagnosis, assessment of the patient's levodopa responsiveness if diagnosed with PD, neuropsychological and psychiatric evaluations, and a pre-DBS magnetic resonance imaging scan. Rare complicatio...

Parkinsonism & Related Disorders, 2019

Introduction: In a double-blind randomized crossover trial, we previously established that bilate... more Introduction: In a double-blind randomized crossover trial, we previously established that bilateral deep brain stimulation of the anteromedial globus pallidus internus (GPiam-DBS) is effective in significantly reducing tic severity in patients with refractory Tourette syndrome (TS). Here, we report the effects of bilateral GPiam-DBS on cognitive function in 11 of the 13 patients who had participated in our double-blind cross-over trial of GPi-DBS. Methods: Patients were assessed at baseline (4 weeks prior to surgery) and at the end of each of the three-month blinded periods, with stimulation either ON or OFF. The patients were evaluated on tests of memory (California Verbal Learning Test-II (CVLT-II); Corsi blocks; Short Recognition Memory for Faces), executive function (D-KEFS Stroop color-word interference, verbal fluency, Trail-making test, Hayling Sentence Completion test), and attention (Paced Auditory Serial Addition Test, Numbers and Letters Test). Results: GPiam-DBS did not produce any significant change in global cognition. Relative to preoperative baseline assessment verbal episodic memory on the CVLT-II and set-shifting on the Trail-making Test were improved with DBS OFF. Performance on the cognitive tests were not different with DBS ON versus DBS OFF. GPiam-DBS did not alter aspects of cognition that are impaired in TS such as inhibition on the Stroop interference task or the Hayling Sentence Completion test. Conclusions: This study extends previous findings providing data showing that GPiam-DBS does not adversely affect cognitive domains such as memory, executive function, verbal fluency, attention, psychomotor speed, and information processing. These results indicate that GPiam-DBS does not produce any cognitive deficits in TS.

Journal of Parkinson's Disease, 2018

Movement disorders : official journal of the Movement Disorder Society, Jan 7, 2017

Subthalamic deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's diseas... more Subthalamic deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's disease (PD), but can have side effects caused by stimulus spread to structures outside the target volume such as the pyramidal tract. To assess the relevance of pyramidal tract activation with STN-DBS in PD. In a multimodal, blinded study in 20 STN-DBS patients, we measured stimulation thresholds for evoking electromyographic activity in orbicularis oris and first dorsal interosseous muscles at each of 150 electrode sites. We also modeled the electric field spread and calculated its overlap with the estimated anatomical location of corticospinal and corticobulbar tracts from primary motor cortex using 3 Tesla MRI probabilistic tractography. Mean resting motor thresholds were significantly lower for the contralateral orbicularis oris (3.5 ± 1.0 mA) compared with ipsilaterally (4.1 ± 1.1 mA) and with the contralateral first dorsal interosseous (4.0 ± 1.2 mA). The modeled volumes of corticobulba...

Journal of Neurosurgery, 2017

OBJECTIVE Infection of deep brain stimulation (DBS) hardware has a significant impact on patient ... more OBJECTIVE Infection of deep brain stimulation (DBS) hardware has a significant impact on patient morbidity. Previous experience suggests that infection rates appear to be higher after implantable pulse generator (IPG) replacement surgery than after the de novo DBS procedure. In this study the authors examine the effect of a change in practice during DBS IPG replacements at their institution. METHODS Starting in January 2012, patient screening for methicillin-resistant Staphylococcus aureus (MRSA) and, and where necessary, eradication was performed prior to elective DBS IPG change. Moreover, topical vancomycin was placed in the IPG pocket during surgery. The authors then prospectively examined the infection rate in patients undergoing DBS IPG replacement at their center over a 3-year period with at least 9 months of follow-up. RESULTS The total incidence of infection in this prospective consecutive series of 101 IPG replacement procedures was 0%, with a mean follow-up duration of 24 ...