Clinician-Focused Overview and Developments in Polysomnography.

PURPOSE OF REVIEW: Polysomnography (PSG) represents a fundamental diagnostic tool used in the evaluation of sleep disorders. It represents a simultaneous recording of sleep staging, eye movements, electromyographic tone, respiratory parameters, and electrocardiogram. It is particularly helpful in the assessment of sleep-disordered breathing and its management, propensity for excessive sleepiness, complex behaviors during sleep, including motor disturbances of sleep, sleep-related epilepsy, and parasomnias. This review is intended to summarize the indications for PSG, the limitations and challenges of this diagnostic tool, indications for home sleep apnea testing options, and new developments and trends in polysomnography. RECENT FINDINGS: The polysomnogram is fundamentally important in the evaluation of sleep-disordered breathing in the setting of cardiovascular comorbidities and neurologic conditions such as neuromuscular disease, stroke, and epilepsy and in the evaluation of dream enactment behavior in the setting of REM sleep behavior disorder (RBD). Because RBD is predictive of neurodegenerative disorders, recent data highlights the importance of PSG in corroborating the diagnosis of RBD and identifying people who may be at risk. However, due to cost as well as limitations in access to care, further testing has been developed and implemented including the home sleep apnea test (HSAT). The evolution of consumer wearable devices has also been a growing trend in sleep medicine; however, few have received appropriate validation. SUMMARY: PSG has been used in both the clinical and research settings and remains the gold standard clinical diagnostic test for suspected obstructive sleep apnea (OSA) or central sleep apnea (CSA). Clinicians must be familiar with the basic indications for a PSG but also recognize when it is absolutely required. At this time, the PSG is essential in the evaluation of nocturnal hypoventilation disorders of sleep, periodic limb movements of sleep, and central nervous system hypersomnia (in the absence of CSF hypocretin) when combined with the multiple sleep latency test (MSLT) and is probably the only way to help differentiate among complex behaviors during sleep, especially in the setting of RBD. The capacity to establish an early diagnostic risk of potential dementia would be of critical importance once neuroprotective agents become available.

Phenomenology and Management of Subthalamic Stimulation-Induced Dyskinesia in Patients With Isolated Dystonia.

BACKGROUND: The pallidum has been the preferred DBS target for dystonia, but recent studies have shown equal or greater improvement in patients implanted in the STN.1 Transient stimulation-induced dyskinesia (SID) is frequently observed when stimulating this novel target, and there are no previously published video case reports of this phenomenon. CASES: We describe in detail the SID phenomenology experienced by 4 patients who had been implanted with STN DBS for isolated dystonia. CONCLUSIONS: SID can occur in focal, segmental, axial, or generalized distribution, can resemble levodopa-induced dyskinesia choreiform or dystonic movements observed in Parkinson's disease, and is generally transient and resolves with customized DBS programming. Providers should be aware that SID can occur after STN DBS when treating isolated dystonia and not assume movements are the result of worsening or spread of the underlying dystonia.

Subthalamic nucleus deep brain stimulation in isolated dystonia: A 3-year follow-up study.

OBJECTIVE: To report long-term safety and efficacy outcomes of a large cohort of patients with medically refractory isolated dystonia treated with subthalamic nucleus (STN) deep brain stimulation (DBS). METHODS: Twenty patients (12 male, 8 female; mean age 49 ± 16.3 years) with medically refractory isolated dystonia were studied (14 were followed for 36 months). The primary endpoints were change in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score and Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score at 36 months compared to preoperative baseline. Multiple secondary outcomes were also assessed (ClinicalTrials.gov NCT00773604). RESULTS: Eighteen of 20 patients showed improvement 12 months after STN DBS with sustained benefit persisting for 3 years (n = 14). At 36 months, BFMDRS motor scores improved 70.4% from a mean 17.9 ± 8.5 to 5.3 ± 5.6 (p = 0.0002) and total TWSTRS scores improved 66.6% from a mean 41.0 ± 18.9 to 13.7 ± 17.9 (p = 0.0002). Improvement at 36 months was equivalent to that seen at 6 months. Disability and quality of life measures were also improved. Three hardware-related and 24 stimulation-related nonserious adverse events occurred between years 1 and 3 (including 4 patients with dyskinesia). CONCLUSIONS: This study offers support for long-term tolerability and sustained effectiveness of STN DBS in the treatment of severe forms of isolated dystonia. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that STN DBS decreases long-term dystonia severity in patients with medically refractory isolated dystonia.

Clinical outcomes using ClearPoint interventional MRI for deep brain stimulation lead placement in Parkinson's disease.

OBJECTIVE: The ClearPoint real-time interventional MRI-guided methodology for deep brain stimulation (DBS) lead placement may offer advantages to frame-based approaches and allow accurate implantation under general anesthesia. In this study, the authors assessed the safety and efficacy of DBS in Parkinson's disease (PD) using this surgical method. METHODS: This was a prospective single-center study of bilateral DBS therapy in patients with advanced PD and motor fluctuations. Symptom severity was evaluated at baseline and 12 months postimplantation using the change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III "off" medication score as the primary outcome variable. RESULTS: Twenty-six PD patients (15 men and 11 women) were enrolled from 2010 to 2013. Twenty patients were followed for 12 months (16 with a subthalamic nucleus target and 4 with an internal globus pallidus target). The mean UPDRS Part III "off" medication score improved from 40.75 ± 10.9 to 24.35 ± 8.8 (p = 0.001). "On" medication time without troublesome dyskinesia increased 5.2 ± 2.6 hours per day (p = 0.0002). UPDRS Parts II and IV, total UPDRS score, and dyskinesia rating scale "on" medication scores also significantly improved (p < 0.01). The mean levodopa equivalent daily dose decreased from 1072.5 ± 392 mg to 828.25 ± 492 mg (p = 0.046). No significant cognitive or mood declines were observed. A single brain penetration was used for placement of all leads, and the mean targeting error was 0.6 ± 0.3 mm. There were 3 serious adverse events (1 DBS hardware-related infection, 1 lead fracture, and 1 unrelated death). CONCLUSIONS: DBS leads placed using the ClearPoint interventional real-time MRI-guided method resulted in highly accurate lead placement and outcomes comparable to those seen with frame-based approaches.

Effect of subthalamic nucleus deep brain stimulation on dual-task cognitive and motor performance in isolated dystonia.

OBJECTIVE: Subthalamic nucleus (STN) deep brain stimulation (DBS) can improve motor complications of Parkinson's disease (PD) but may worsen specific cognitive functions. The effect of STN DBS on cognitive function in dystonia patients is less clear. Previous reports indicate that bilateral STN stimulation in patients with PD amplifies the decrement in cognitive-motor dual-task performance seen when moving from a single-task to dual-task paradigm. We aimed to determine if the effect of bilateral STN DBS on dual-task performance in isolated patients with dystonia, who have less cognitive impairment and no dementia, is similar to that seen in PD. METHODS: Eight isolated predominantly cervical patients with dystonia treated with bilateral STN DBS, with average dystonia duration of 10.5 years and Montreal Cognitive Assessment score of 26.5, completed working memory (n-back) and motor (forced-maintenance) tests under single-task and dual-task conditions while on and off DBS. RESULTS: A multivariate, repeated-measures analysis of variance showed no effect of stimulation status (On vs Off) on working memory (F=0.75, p=0.39) or motor function (F=0.22, p=0.69) when performed under single-task conditions, though as working memory task difficulty increased, stimulation disrupted the accuracy of force-tracking. There was a very small worsening in working memory performance (F=9.14, p=0.019) when moving from single-task to dual-tasks when using the 'dual-task loss' analysis. CONCLUSIONS: This study suggests the effect of STN DBS on working memory and attention may be much less consequential in patients with dystonia than has been reported in PD.

Interventional MRI-guided deep brain stimulation in pediatric dystonia: first experience with the ClearPoint system.

OBJECT: The placement of deep brain stimulation (DBS) leads in adults is traditionally performed using physiological confirmation of lead location in the awake patient. Most children are unable to tolerate awake surgery, which poses a challenge for intraoperative confirmation of lead location. The authors have developed an interventional MRI (iMRI)-guided procedure to allow for real-time anatomical imaging, with the goal of achieving very accurate lead placement in patients who are under general anesthesia. METHODS: Six pediatric patients with primary dystonia were prospectively enrolled. Patients were candidates for surgery if they had marked disability and medical therapy had been ineffective. Five patients had the DYT1 mutation, and mean age at surgery was 11.0 ± 2.8 years. Patients underwent bilateral globus pallidus internus (GPi, n = 5) or sub-thalamic nucleus (STN, n = 1) DBS. The leads were implanted using a novel skull-mounted aiming device in conjunction with dedicated software (ClearPoint system), used within a 1.5-T diagnostic MRI unit in a radiology suite, without physiological testing. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used at baseline, 6 months, and 12 months postoperatively. Further measures included lead placement accuracy, quality of life, adverse events, and stimulation settings. RESULTS: A single brain penetration was used for placement of all 12 leads. The mean difference (± SD) between the intended target location and the actual lead location, in the axial plane passing through the intended target, was 0.6 ± 0.5 mm, and the mean surgical time (leads only) was 190 ± 26 minutes. The mean percent improvement in the BFMDRS movement scores was 86.1% ± 12.5% at 6 months (n = 6, p = 0.028) and 87.6% ± 19.2% at 12 months (p = 0.028). The mean stimulation settings at 12 months were 3.0 V, 83 µsec, 135 Hz for GPi DBS, and 2.1 V, 60 µsec, 145 Hz for STN DBS). There were no serious adverse events. CONCLUSIONS: Interventional MRI-guided DBS using the ClearPoint system was extremely accurate, provided real-time confirmation of DBS placement, and could be used in any diagnostic MRI suite. Clinical outcomes for pediatric dystonia are comparable with the best reported results using traditional frame-based stereotaxy. Clinical trial registration no.: NCT00792532 ( ClinicalTrials.gov ).

Effect of frequency on subthalamic nucleus deep brain stimulation in primary dystonia.

BACKGROUND: Subthalamic nucleus deep brain stimulation (DBS) is an alternative target choice for treating primary dystonia, but little is known about the most effective programming parameters. OBJECTIVE: Here we prospectively evaluate the effect of low versus high frequency subthalamic nucleus DBS in patients with predominantly cervical or upper extremity primary dystonia. METHODS: Seven patients were stimulated at low frequency stimulation (60 Hz) for the first three months and then switched to high frequency stimulation (130 Hz) until month six. Severity of dystonia was determined by a blinded rater (unaware of the patient's pre or post-operative status) who scored the Burke Fahn Marsden dystonia rating scale movement score (BFMDRS-M) and the Toronto Western Spasmodic Torticollis Rating Scale severity score (TWSTRS-S) preoperatively, three, six, and twelve months post-surgery. RESULTS: Patients had a lower mean improvement of 16.6% in BFMDRS-M and 9.5% in TWSTRS-S at three months using low frequency stimulation compared to a 52.3% (p = 0.018) and 45.2% (p = 0.028), respectively, noted at six months using high frequency stimulation. At 12 months (using 130 Hz), the BFMDRS-M and TWSTRS-S improved by 51.8% (p = 0.022) and 56% (p = 0.034). Patients developed transient dyskinesia (during low and high frequency stimulation) which improved with programming adjustments. CONCLUSION: This study offers further support of the effectiveness of subthalamic nucleus DBS in the treatment of primary dystonia and finds that high frequency stimulation was more effective than low frequency stimulation.

Predictive factors of outcome in primary cervical dystonia following pallidal deep brain stimulation.

BACKGROUND: Improvement after bilateral globus pallidus internus deep brain stimulation (DBS) in primary generalized dystonia has been negatively associated with disease duration and age, but no predictive factors have been identified in primary cervical dystonia (CD). METHODS: Patients treated with bilateral globus pallidus internus DBS for primary CD from 2 DBS centers with preoperative and postoperative Toronto Western Spasmodic Torticollis Rating Scales (TWSTRS) were studied retrospectively to explore possible predictors of response. RESULTS: Patients showed significantly improved TWSTRS total and severity scores (n = 28, mean 55.6% and 50.8%, respectively, both P < .001). Patients with lateral shift at baseline had less improvement in TWSTRS severity subscores (P = .02). No correlations between outcomes and disease duration, age at dystonia onset or surgery, baseline scores, or other included variables were found. CONCLUSIONS: Although this is the largest study supporting efficacy of bilateral pallidal DBS in primary CD, no major clinical predictive outcomes of surgical benefit were identified.

Clinical outcomes of PD patients having bilateral STN DBS using high-field interventional MR-imaging for lead placement.

OBJECTIVE: Recently, an iMRI-guided technique for implanting DBS electrodes without MER was developed at our center. Here we report the clinical outcomes of PD patients undergoing STN DBS surgery using this surgical approach. METHODS: Consecutive PD patients undergoing bilateral STN DBS using this method were prospectively studied. Severity of PD was determined using the UPDRS scores, Hoehn and Yahr staging score, stand-sit-walk testing, and the dyskinesia rating scale. The primary outcome measure was the change in UPDRS III off medication score at 6 months. DBS stimulation parameters, adverse events, levodopa equivalent daily dose (LEDD), and DBS lead locations were also recorded. Seventeen advanced PD patients (9M/8F) were enrolled from 2007 to 2009. RESULTS: The mean UPDRS III off medication score improved from 44.5 to 22.5 (49.4%) at 6 months (p=0.001). Other secondary outcome measures (UPDRS II, III on medication, and IV) significantly improved as well (p<0.01). LEDD decreased by an average of 24.7% (p=0.003). Average stimulation parameters were: 2.9V, 66.4µs, 154Hz. CONCLUSION: This pilot study demonstrates that STN DBS leads placed using the iMRI-guided method results in significantly improved outcomes in PD symptoms, and these outcomes are similar to what has been reported using traditional frame-based, MER-guided stereotactic methods.

Shorter disease duration correlates with improved long-term deep brain stimulation outcomes in young-onset DYT1 dystonia.

BACKGROUND: Treatment with deep brain stimulation (DBS) of the globus pallidus internus in children with DYT1 primary torsion dystonia is highly effective; however, individual response to stimulation is variable, and a greater understanding of predictors of long-term outcome is needed. OBJECTIVE: To report the long-term outcomes of subjects with young-onset DYT1 primary torsion dystonia treated with bilateral globus pallidus DBS. METHODS: Fourteen subjects (7 male, 7 female) treated consecutively from 2000 to 2010 at our center were included in this retrospective study. The Burke-Fahn-Marsden Dystonia Rating Scale was performed at baseline and at 1, 2, and up to 6 years postoperatively. RESULTS: Pallidal DBS was well tolerated and highly effective, with mean Burke-Fahn-Marsden Dystonia Rating Scale movement scores improving from baseline by 61.5% (P < .001) at 1 year, 64.4% (P < .001) at 2 years, and 70.3% (P < .001) at the final follow-up visit (mean, 32 months; range, 7-77 months). Disability scores also improved significantly. Multiple linear regression analysis revealed a significant influence of duration of disease as a predictor of percent improvement in Burke-Fahn-Marsden Dystonia Rating Scale movement score at long-term follow-up (duration of disease, P < .05). Subjects with fixed orthopedic deformities (4) had less improvement in these regions. Location of the active DBS electrode used at final follow-up visit was not predictive of clinical outcome. CONCLUSION: Our findings highlight the sustained benefit from DBS and the importance of early referral for DBS in children with medically refractory DYT1 primary torsion dystonia, which can lead to improved long-term benefits.

Outcomes of natural cycles versus programmed cycles for 1677 frozen-thawed embryo transfers.

The study compares outcomes for patients with frozen embryos who had frozen-thawed embryo transfer (FET) timed to their natural ovulation cycle versus cycles in which endometrial timing was programmed with oestrogen and progesterone. A total of 1205 patients undergoing 1677 FET cycles between 1 January 2000 and 31 December 2006 were analysed. Comparisons were made for patients undergoing modified natural versus programmed FET cycles, as well as between patients using their own eggs for frozen embryos versus those using donor-egg-derived embryos. Clinical pregnancy (gestational sac on 7 week ultrasound) rates (CPR), as well as miscarriage rates, were significantly higher in programmed FET cycles in patients using their own eggs (106/262, 40.5% per embryo transfer, P = 0.015) However, there was not a difference in delivered pregnancies between cycle types in own egg patients (natural cycle delivery rate 245/862, 28.4%; programmed cycle delivery rate 77/262, 29.4%). Furthermore, CPR were not different in natural (38/129, 29.5%) versus programmed cycles (144/424, 34.0%) for ovum donor recipients, nor were delivered pregnancy rates different in natural (33/129, 25.6%) versus programmed cycles (114/424, 26.9%) for ovum donor recipients. In conclusion, there is no significant difference in delivery rates for FET in natural (278/991, 28.1%) versus programmed (191/686, 27.8%) cycles using both own embryos and donor-egg-derived embryos.