Browsing by Author "Aziz, Tipu"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Balance control systems in Parkinson’s disease and the impact of pedunculopontine area stimulation
    (Brain, 2018-08) Perera, Thushara; Tan, Joy; Cole, Michael; Yohanandan, Shivanthan; Silberstein, Paul; Cook, Raymond; Peppard, Richard; Aziz, Tipu; Coyne, Terry; Brown, Peter; Silburn, Peter; Thevathasan, Wesley
    Impaired balance is a major contributor to falls and diminished quality of life in Parkinson's disease, yet the pathophysiology is poorly understood. Here, we assessed if patients with Parkinson's disease and severe clinical balance impairment have deficits in the intermittent and continuous control systems proposed to maintain upright stance, and furthermore, whether such deficits are potentially reversible, with the experimental therapy of pedunculopontine nucleus deep brain stimulation. Two subject groups were assessed: (i) 13 patients with Parkinson's disease and severe clinical balance impairment, implanted with pedunculopontine nucleus deep brain stimulators; and (ii) 13 healthy control subjects. Patients were assessed in the OFF medication state and blinded to two conditions; off and on pedunculopontine nucleus stimulation. Postural sway data (deviations in centre of pressure) were collected during quiet stance using posturography. Intermittent control of sway was assessed by calculating the frequency of intermittent switching behaviour (discontinuities), derived using a wavelet-based transformation of the sway time series. Continuous control of sway was assessed with a proportional-integral-derivative (PID) controller model using ballistic reaction time as a measure of feedback delay. Clinical balance impairment was assessed using the 'pull test' to rate postural reflexes and by rating attempts to arise from sitting to standing. Patients with Parkinson's disease demonstrated reduced intermittent switching of postural sway compared with healthy controls. Patients also had abnormal feedback gains in postural sway according to the PID model. Pedunculopontine nucleus stimulation improved intermittent switching of postural sway, feedback gains in the PID model and clinical balance impairment. Clinical balance impairment correlated with intermittent switching of postural sway (rho = - 0.705, P < 0.001) and feedback gains in the PID model (rho = 0.619, P = 0.011). These results suggest that dysfunctional intermittent and continuous control systems may contribute to the pathophysiology of clinical balance impairment in Parkinson's disease. Clinical balance impairment and their related control system deficits are potentially reversible, as demonstrated by their improvement with pedunculopontine nucleus deep brain stimulation.
  • Thumbnail Image
    Item
    Pedunculopontine Nucleus Region Deep Brain Stimulation in Parkinson Disease: Surgical Anatomy and Terminology
    (Karger AG, Basel, 2016-10) Hamani, Clement; Aziz, Tipu; Bloem, Bastiaan; Brown, Peter; Chabardes, Stephen; Coyne, Terry; Foote, Kelly; Garcia-Rill, Edgar; Hirsch, Etienne; Lozano, Andres; Mazzone, Paolo; Okun, Michael; Hutchison, William; Silburn, Peter; Zrinzo, Ludvic; Alam, Mesbah; Goetz, Laurent; Pereira, Erlick; Rughani, Anand; Thevathasan, Wesley; Moro, Elena; Krauss, Joachim
    Several lines of evidence over the last few years have been important in ascertaining that the pedunculopontine nucleus (PPN) region could be considered as a potential target for deep brain stimulation (DBS) to treat freezing and other problems as part of a spectrum of gait disorders in Parkinson disease and other akinetic movement disorders. Since the introduction of PPN DBS, a variety of clinical studies have been published. Most indicate improvements in freezing and falls in patients who are severely affected by these problems. The results across patients, however, have been variable, perhaps reflecting patient selection, heterogeneity in target selection and differences in surgical methodology and stimulation settings. Here we outline both the accumulated knowledge and the domains of uncertainty in surgical anatomy and terminology. Specific topics were assigned to groups of experts, and this work was accumulated and reviewed by the executive committee of the working group. Areas of disagreement were discussed and modified accordingly until a consensus could be reached. We demonstrate that both the anatomy and the functional role of the PPN region need further study. The borders of the PPN and of adjacent nuclei differ when different brainstem atlases and atlas slices are compared. It is difficult to delineate precisely the PPN pars dissipata from the nucleus cuneiformis, as these structures partially overlap. This lack of clarity contributes to the difficulty in targeting and determining the exact localization of the electrodes implanted in patients with akinetic gait disorders. Future clinical studies need to consider these issues.
  • Thumbnail Image
    Item
    Tremor Reduction by Deep Brain Stimulation Is Associated With Gamma Power Suppression in Parkinson's Disease
    (John Wiley and Sons, 2015-07) Beudel, Martjin; Little, Simon; Pogosyan, Alek; Ashkan, Keyoumars; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Bogdanovic, Marko; Cheeran, Binith; Green, Alexander; Aziz, Tipu; Thevathasan, Wesley; Brown, Peter
    Objectives Rest tremor is a cardinal symptom of Parkinson's disease (PD), and is readily suppressed by deep brain stimulation (DBS) of the subthalamic nucleus (STN). The therapeutic effect of the latter on bradykinesia and rigidity has been associated with the suppression of exaggerated beta (13–30 Hz) band synchronization in the vicinity of the stimulating electrode, but there is no correlation between beta suppression and tremor amplitude. In the present study, we investigate whether tremor suppression is related to suppression of activities at other frequencies. Materials and Methods We recorded hand tremor and contralateral local field potential (LFP) activity from DBS electrodes during stimulation of the STN in 15 hemispheres in 11 patients with PD. DBS was applied with increasing voltages starting at 0.5 V until tremor suppression was achieved or until 4.5 V was reached. Results Tremor was reduced to 48.9% ± 10.9% of that without DBS once stimulation reached 2.5–3 V (t14 = −4.667, p < 0.001). There was a parallel suppression of low gamma (31–45 Hz) power to 92.5% ± 3% (t14 = −2.348, p = 0.034). This was not seen over a band containing tremor frequencies and their harmonic (4–12 Hz), or over the beta band. Moreover, low gamma power correlated with tremor severity (mean r = 0.43 ± 0.14, p = 0.008) within subjects. This was not the case for LFP power in the other two bands. Conclusions Our findings support a relationship between low gamma oscillations and PD tremor, and reinforce the principle that the subthalamic LFP is a rich signal that may contain information about the severity of multiple different Parkinsonian features.