Ludy C. Shih

Perfusion-Weighted Magnetic Resonance Imaging Thresholds Identifying Core, Irreversibly Infarcted Tissue

Background and Purpose— Identifying core, irreversibly infarcted tissue and salvageable penumbral tissue is crucial to informed, physiologically guided decision making regarding thrombolytic and other interventional therapies in acute ischemic stroke. Pretreatment perfusion MRI offers promise as a means to differentiate core from penumbral tissues. Methods— Diffusion-perfusion MRIs were performed before treatment and on day 7 in patients undergoing successful vessel recanalization with intra-arterial thrombolytic therapy. Perfusion maps of the time to peak of the residue function (Tmax) were generated after deconvolution of an arterial input function. Initial perfusion abnormalities and final infarct regions were outlined by hand. Posttreatment images were coregistered to the pretreatment study. Voxel-by-voxel and volume analyses were performed to identify thresholds of perfusion abnormalities that best predict core, irreversibly infarcted tissue. Results— Fourteen patients (4 men, 10 women) with vessel recanalization were studied. Mean age was 73 years, and median entry National Institutes of Health Stroke Scale score was 12. Mean time from symptom onset to start of intra-arterial infusion was 245 minutes and to recanalization was 338 minutes. With a voxel-by-voxel analysis, Tmax ≥6 and ≥8 seconds (sensitivity, 71% and 53%; specificity, 63% and 80%) correlated most highly with day 7 final infarct. With a volume analysis, Tmax ≥6 and ≥8 seconds (r2=0.704 and r2=0.705) correlated most highly with day 7 final infarct. Conclusions— Perfusion-weighted imaging measures of ischemia severity accurately differentiate irreversibly injured core from penumbral, salvageable tissue. The best threshold for identifying core infarcted tissue is adjusted Tmax of ≥6 to 8 seconds.

A Web-Based System for Home Monitoring of Patients With Parkinson's Disease Using Wearable Sensors

This letter introduces MercuryLive, a platform to enable home monitoring of patients with Parkinsons disease (PD) using wearable sensors. MercuryLive contains three tiers: a resource-aware data collection engine that relies upon wearable sensors, web services for live streaming and storage of sensor data, and a web-based graphical user interface client with video conferencing capability. Besides, the platform has the capability of analyzing sensor (i.e., accelerometer) data to reliably estimate clinical scores capturing the severity of tremor, bradykinesia, and dyskinesia. Testing results showed an average data latency of less than 400 ms and video latency of about 200 ms with video frame rate of about 13 frames/s when 800 kb/s of bandwidth were available and we used a 40% video compression, and data feature upload requiring 1 min of extra time following a 10 min interactive session. These results indicate that the proposed platform is suitable to monitor patients with PD to facilitate the titration of medications in the late stages of the disease.

Deep brain stimulation for the treatment of atypical parkinsonism.

Deep brain stimulation (DBS) has gained widespread acceptance for improving motor function and disability in Parkinsons disease (PD). Patients with features suggestive of atypical parkinsonism (AP) usually have a poorer and less sustained response to levodopa and a poorer prognosis overall when compared with patients with PD. However, experience in the use of DBS with this group of patients is limited and evidence is lacking with regards to its efficacy and adverse effects. We review in detail the experience of DBS surgery in patients with several forms of AP including multiple system atrophy. On the basis of the limited available data reviewed here, DBS for patients with AP is not recommended.

Home monitoring of patients with Parkinson's disease via wearable technology and a web-based application

Objective long-term health monitoring can improve the clinical management of several medical conditions ranging from cardiopulmonary diseases to motor disorders. In this paper, we present our work toward the development of a home-monitoring system. The system is currently used to monitor patients with Parkinsons disease who experience severe motor fluctuations. Monitoring is achieved using wireless wearable sensors whose data are relayed to a remote clinical site via a web-based application. The work herein presented shows that wearable sensors combined with a web-based application provide reliable quantitative information that can be used for clinical decision making.

Loss of benefit in VIM thalamic deep brain stimulation (DBS) for essential tremor (ET): how prevalent is it?

Ventralis intermedius (Vim) thalamic deep brain stimulation for medication-refractory essential tremor (ET) has been shown to significantly improve severity of limb tremor in several large case series with significant reduction in objective motor scores. A variable proportion of patients experience decline in benefit over time, however, most studies have not been designed to describe the phenomenon of waning benefit in terms that are helpful for patient counseling. In this retrospective single center study, we define waning benefit as a phenomenon that occurs after patients begin to require reprogramming visits to optimize DBS benefit on tremor. We employed a survival analysis with time to escape (TTE) as a quantitative measure of time elapsed between implantation and the need for subsequent reprogramming. In our cohort of ET patients operated on with Vim DBS from 1994 to 2009, among 45 subjects who met inclusion criteria, 73% reported waning benefit at some point during a mean follow-up period of 56 months (range 12-152 months). The mean TTE from implantation date was 18 months (range 3-75 months). We conclude that loss of benefit over time from Vim DBS for ET is more prevalent than previously published estimates have indicated and should be discussed during patient counseling regarding durability of expected benefit. In addition, this data suggests that a disease-based explanation rather than technical factors are more likely to explain the decline in benefit.

The diagnostic discrimination of cutaneous α-synuclein deposition in Parkinson disease

Objective: To determine the diagnostic discrimination of cutaneous α-synuclein deposition in individuals with Parkinson disease (PD) with and without autonomic dysfunction on autonomic testing, in early and late stages of the disease, and of short and long duration. Methods: Twenty-eight participants with PD and 23 control participants were studied by skin biopsies at multiple sites, autonomic function testing, and disease-specific scales. Results: Skin biopsies provide >90% sensitivity and >90% specificity to distinguish PD from control participants across all biopsies sites with quantification of either pilomotor or sudomotor α-synuclein deposition. All individuals with PD have significantly higher cutaneous α-synuclein deposition than control participants, even those individuals with PD and no evidence of autonomic dysfunction. Deposition of α-synuclein is most prominent in sympathetic adrenergic nerve fibers innervating the arrector pili muscles, but is also present in sudomotor (sympathetic cholinergic) nerve fibers. α-Synuclein is present even in the early stages of disease and disease of short duration. α-Synuclein ratios were higher in individuals with autonomic failure, with more advanced stages of disease and disease of longer duration. Conclusions: The α-synuclein ratio provides a sensitive and specific diagnostic biomarker of PD even in patients without autonomic failure. Classification of evidence: This study provides Class III evidence that cutaneous α-synuclein deposition accurately identifies patients with PD.

Proceedings of the Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies

The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tanks contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies.

Singing in groups for Parkinson's disease (SING-PD): A pilot study of group singing therapy for PD-related voice/speech disorders

Parkinsons disease related speech and voice impairment have significant impact on quality of life measures. LSVT(®)LOUD voice and speech therapy (Lee Silverman Voice Therapy) has demonstrated scientific efficacy and clinical effectiveness, but musically based voice and speech therapy has been underexplored as a potentially useful method of rehabilitation. We undertook a pilot, open-label study of a group-based singing intervention, consisting of twelve 90-min weekly sessions led by a voice and speech therapist/singing instructor. The primary outcome measure of vocal loudness as measured by sound pressure level (SPL) at 50 cm during connected speech was not significantly different one week after the intervention or at 13 weeks after the intervention. A number of secondary measures reflecting pitch range, phonation time and maximum loudness also were unchanged. Voice related quality of life (VRQOL) and voice handicap index (VHI) also were unchanged. This study suggests that a group singing therapy intervention at this intensity and frequency does not result in significant improvement in objective and subject-rated measures of voice and speech impairment.

Improvement of pisa syndrome with contralateral pedunculopontine stimulation.

Pedunculopontine nucleus (PPN) deep brain stimulation (DBS) has been proposed to improve gait freezing and other axial motor features in advanced Parkinson’s disease (PD) patients [1–4]. However, its effects on abnormal posture such as Pisa syndrome [5] have not been specifically described. A 62-year-old right handed woman presented with a six-year history of PD, initially manifesting as right hand resting tremor and difficulty writing. Tremor, rigidity and bradykinesia responded well to dopaminergic medications. After 5-year disease duration, she developed right sided axial lean and postural instability with falls occurring 2–3 times daily. Plain films demonstrated complex sigmoid scoliosis with mild dextroscoliosis within the thoracic spine, without osteoporosis. Trials of rotigotine, donepezil, and amantadine did not reduce fall frequency. Therefore, she was referred for PPN DBS surgery. Medications at the time of pre-surgical evaluation included carbidopa/levodopa 25/100 1.5 tabs five times daily and pramipexole 3 mg daily. Pre-operative off-medication motor UPDRS score was 18.5/108, with right upper extremity resting tremor, right greater than left rigidity, mild focal bradykinesia in the hands, slow gait with significant right tilt, and mild but recoverable retropulsion on pull test. The motor score improved to 12.5/108, 30 minutes after 350 mg levodopa challenge. She was offered left lead implantation given right greater than left PD severity. Left PPN DBS surgery was performed at the Toronto Western Hospital under local anesthesia. The surgical procedure has been previously described [2]. An implantable pulse generator (Soletra, Medtronic, Inc.) was implanted the same day under general anesthesia. She tolerated surgery well, aside from mild post-operative encephalopathy and word finding difficulty which recovered within two weeks. Programming of the left PPN stimulation started 1 month after surgery. The patient was programmed weekly using monopolar stimulation at each contact at 1.0V, at 20Hz, 50Hz, 70Hz and 130Hz over 16 weeks. The patient kept a diary of falls, which significantly decreased from 2–3 falls/daily to less than 1 fall per week. The best setting was found as contacts 3+ 2−/1.5V/90μsec/130Hz. Videos taken throughout 14 months of follow-up demonstrate progressive improvement of her asymmetric bradykinetic gait and right axial lean (Video). Lateral flexion of the trunk has been described in PD, either as scoliosis related to parkinsonism with leaning usually opposite the most affected side or as Pisa syndrome, originally described as an axial dystonia in patients treated with neuroleptics but also seen in patients with PD [5]. Prior studies of PPN DBS in PD patients have not described significant alterations in axial lean, which can contribute significantly to falls and postural instability whereas several small case series and reports describe mixed results of STN DBS on various postural abnormalities including Pisa syndrome [6]. Stimulation of the PPN and surrounding pontomesencephalic tegmental field may not only affect gait but also extensor muscle tone, thus leading to changes in posture. Chronic electrical stimulation of ventral parts of this region in freely moving cats is accompanied by an increase in tone and facilitation of walking [7]. Based on this patient’s improvement in Pisa syndrome following PPN DBS, we suggest that further studies investigating the impact of PPN DBS closely examine postural abnormalities prior to and following stimulation. The video demonstrates pre- and post-operative gait and posture examinations all taken 3 hours post-levodopa intake. The improvement in the axial lean was temporally related to the reduction of falls.

Longitudinal monitoring of patients with Parkinson's disease via wearable sensor technology in the home setting

Objective longitudinal monitoring of symptoms related motor fluctuations can provide valuable information for the clinical management of patients with Parkinsons disease. Current methods for long-term monitoring of motor fluctuations, such as patient diaries, are ineffective due to their time consuming and subjective nature. Researchers have shown that wearable sensors such as accelerometers can be used to gather objective information about a patients motor symptoms. In this paper, we present preliminary results from our analysis on wearable sensor data gathered during longitudinal monitoring of 5 patients with PD. Our results indicate that it is possible to track longitudinal changes in motor symptoms by training a regression model based on Random Forests.