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Purpose Dysautonomia can be a debilitating feature of Parkinson disease (PD). Pedunculopontine nucleus (PPN) stimulation may improve gait disorders in PD, and may also result in changes in autonomic performance. Methods To determine whether pedunculopontine nucleus stimulation improves cardiovascular responses to autonomic challenges of postural tilt and Valsalva manoeuver, eight patients with pedunculopontine nucleus deep brain stimulation were recruited to the study; two were excluded for technical reasons during testing. Participants underwent head up tilt and Valsalva manoeuver with stimulation turned ON and OFF. Continuous blood pressure and ECG waveforms were recorded during these tests. In a single patient, local field potential activity was recorded from the implanted electrode during tilt. Results The fall in systolic blood pressure after tilt was significantly smaller with stimulation ON (mean − 8.3% versus − 17.2%, p = 0.044). Valsalva ratio increased with stimulation from median 1.15 OFF to 1.20 ON (p = 0.028). Baroreflex sensitivity increased during Valsalva compared to rest with stimulation ON versus OFF (p = 0.028). The increase in baroreflex sensitivity correlated significantly with the mean depth of PPN stimulating electrode contacts. This accounted for 89% of its variance (r = 0.943, p = 0.005). Conclusion PPN stimulation can modulate the cardiovascular system in patients with PD. In this study, it reduced the postural fall in systolic blood pressure during head-up tilt and improved the cardiovascular response during Valsalva, presumably by altering the neural control of baroreflex activation.

Objective Respiratory abnormalities such as upper airway obstruction are common in Parkinson's disease (PD) and are an important cause of mortality and morbidity. We tested the effect of pedunculopontine region (PPNr) stimulation on respiratory maneuvers in human participants with PD, and separately recorded PPNr neural activity reflected in the local field potential (LFP) during these maneuvers. Methods Nine patients with deep brain stimulation electrodes in PPNr, and seven in globus pallidus interna (GPi) were studied during trials of maximal inspiration followed by forced expiration with stimulation OFF and ON. Local field potentials (LFPs) were recorded in the unstimulated condition. Results PEFR increased from 6.41 ± 0.63 L/sec in the OFF stimulation state to 7.5 L ± 0.65 L/sec in the ON stimulation state (z = −2.666, df = 8, P = 0.024). Percentage improvement in PEFR was strongly correlated with proximity of the stimulated electrode contact to the mesencephalic locomotor region in the rostral PPN (r = 0.814, n = 9, P = 0.008). Mean PPNr LFP power increased within the alpha band (7–11 Hz) during forced respiratory maneuvers (1.63 ± 0.16 μV2/Hz) compared to resting breathing (0.77 ± 0.16 μV2/Hz; z = −2.197, df = 6, P = 0.028). No changes in alpha activity or spirometric indices were seen with GPi recording or stimulation. Percentage improvement in PEFR was strongly positively correlated with increase in alpha power (r = 0.653, n = 14 (7 PPNr patients recorded bilaterally), P = 0.0096). Interpretation PPNr stimulation in PD improves indices of upper airway function. Increased alpha‐band activity is seen within the PPNr during forced respiratory maneuvers. Our findings suggest a link between the PPNr and respiratory performance in PD.

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 80 Hz 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: 60 Hz, 80 Hz, 110 Hz, 130 Hz and 200 Hz. 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.

Background: Bowstringing may occur when excessive fibrosis develops around extension cables in the neck after deep brain stimulation (DBS) surgery. Though the occurrence of this phenomenon is rare, we have noted that it tends to cause maximal discomfort when the cables cross superficially over the convexity of the clavicle. We hypothesise that bowstringing may be avoided by directing the extension cables towards the suprasternal notch. Methods: When connecting DBS leads to an infraclavicular pectoral implantable pulse generator (IPG), tunnelling is directed towards the suprasternal notch, before being directed laterally towards the IPG pocket. In previously operated patients with established fibrosis, the fibrous tunnel is opened and excised as far cranially as possible, allowing medial rerouting of cables. Using this approach, we reviewed our series of patients who underwent DBS surgery over 10 years. Results: In 429 patients, 7 patients (2%) with cables tunnelled over the convexity of the clavicle complaining of bowstringing underwent cable exploration and rerouting. This eliminated bowstringing and provided better cosmetic results. When the cable trajectory was initially directed towards the suprasternal notch, no bowstringing was observed. Conclusion: The tunnelling trajectory appears to influence postoperative incidence of fibrosis associated with DBS cables. Modifying the surgical technique may reduce the incidence of this troublesome adverse event.

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 Questionnaire 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. © 2012 The Author.

Tremor in multiple sclerosis is considered to be a persistent and progressive sign. We describe five patients with multiple sclerosis in whom upper limb tremor severity gradually decreased over a period of several years after deep brain stimulation. In every case this attenuation of tremor was accompanied by increasing pyramidal weakness in the relevant upper limb. In two patients this attenuation of tremor remained after stimulation was permanently switched off. In one other patient, where upper limb strength remained normal, tremor severity gradually worsened in spite of continuing stimulation. There was a highly significant difference (p = 0.0007) between the changes in intention tremor severities when the arms with increasing pyramidal weakness (n = 9) were compared to those in which normal strength was retained throughout follow-up period (n = 3); intention tremor decreased in the former and increased in the latter by means of -3.66 and +4.0 points of a 0-10 tremor scale respectively. There was also a significant correlation (0.699; p = 0.0359) between decreasing upper limb strength and decreasing intention tremor severity for the upper limbs of patients that had undergone contralateral DBS.

Infection in the context of implant surgery is a dreaded complication, usually necessitating the removal of all affected hardware. Severe dystonia is a debilitating condition that can present as an emergency and can occasionally be life threatening. The authors present 2 cases of severe dystonia in which deep brain stimulation was maintained despite the presence of infection, using ongoing stimulation by externalization of electrode wires and an extracorporeal pulse generator. This allowed the infection to clear and wounds to heal while maintaining stimulation. This strategy is similar to that used in the management of infected cardiac pacemakers. The authors suggest that this prolonged extracorporeal stimulation should be considered by neurosurgeons in the face of this difficult clinical situation.

We present the case of an unexpected response by the cerebral vasculature to bypass surgery. A 66-year-old man sustained a subarachnoid haemorrhage and cerebral angiography showed a large fusiform anterior communicating artery (ACoA) aneurysm and an anomalous anterior circulation. The right A1 segment was hypoplastic and blood supply to the entire right A2 was from the left anterior circulation via the ACoA. The aneurysm was therefore not amenable to endovascular coiling or surgical clipping alone. An extracranial-intracranial bypass was performed to revascularize the territory of the right A2 independently of the ACoA to allow the latter vessel to be clipped. Although the bypass graft was patent on post-operative cerebral angiography, it was in fact only perfusing a limited, peripheral anterior cerebral artery territory. The bulk of the right anterior circulation was derived retrogradely by latent collaterals from the internal carotid and ophthalmic arteries via small dural vessels which were not apparent prior to surgery.

We report a 79-year-old man whose third burr hole craniotomy evacuation for recurrent chronic subdural haematoma (CSDH) was complicated by cerebellar haemorrhage. The patient died 9 days later. Two previously documented cases in which this complication arose after evacuation of extra-axial collections also resulted in death. Remote cerebellar haemorrhage is a rare complication of neurosurgery but is associated with high mortality. This complication should be considered among the differential diagnoses after neurological deterioration following CSDH evacuation.

Electric deep brain stimulation (DBS) in midbrain nuclei in humans alters cardiovascularparameters, presumably by modulating autonomic and baroreflex function. Baroreflex modulation of sympathetic outflow is crucial for cardiovascular regulation and is hypothesized to occur at two distinct brain locations. This study aimed to evaluate sympathetic outflow in humans with DBS electrodes during ON and OFF stimulation of specific midbrain nuclei known to regulate cardiovascular function. Muscle sympathetic nerve activity (MSNA) was recorded during DBS ON and OFF in patients with chronic neuropathic pain (n=7) and Parkinson’s disease (n=10). Arterial blood pressure (ABP), heart rate and respiration were monitored during the recording session and spontaneous vasomotor and cardiac baroreflex sensitivity (BRS) were assessed. Head-up tilt testing was performed separately in the Parkinson’s patients post-operatively. Stimulation of the dorsal most part of the subthalamic nucleus (STN) and ventrolateral periaqueducta...

We present the first case of spontaneous otogenic pneumocephalus presenting with a rapid deterioration in conscious level. This occurred in a 69-year-old woman who was subsequently treated with a subtemporal, extradural exploration and packing of the multiple defects in the mastoid air cells. The patient made a full neurological recovery within 10 weeks. Spontaneous otogenic pneumocephalus is a rare condition and was previously understood to present with subtle symptoms of headache, aphasia and cognitive deficits. This case, however, establishes how it can cause a rapid decline towards coma.

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 prospectively over 2 years with gait-specific questionnaires and the Unified Parkinson Disease Rating Scale (part III). RESULTS: The primary outcome, the Gait and Falls Questionnaire 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 assessments 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.

BACKGROUND: The midbrain periaqueductal grey (PAG) area is important for both pain modulation and cardiovascular control via the autonomic nervous system (ANS). While changes in blood pressure dependent upon dorsal or ventral electrode positioning have been described with PAG deep brain stimulation (DBS), little is known mechanistically about the relationships between pain and cardiovascular regulation in humans. Heart rate variability (HRV) is an established measure of cardiovascular regulation, and an index of autonomic function. METHODS AND RESULTS: 16 patients undergoing DBS of the rostral PAG for chronic neuropathic pain were investigated post-operatively to determine whether PAG stimulation would alter HRV, and the subjects' perception of pain. Mean heart rate together with HRV, time and frequency domain measures, low frequency (LF) and high frequency (HF) power components of heart rate and the ratio of LF to HF were calculated before and during DBS. Ventral but not dorsal PAG DBS significantly decreased the ratio of LF to HF power (p

We report the case of a 56 year-old woman who presented with worsening speech and poor seizure control eleven years after undergoing wrapping of a middle cerebral artery aneurysm. Radiological and histological findings were consistent with a muslin granuloma with a large cystic component. The cyst was drained endoscopically and an Omaya reservoir placed. The patient's speech improved and so did their seizure control.This is the first case in which this rare complication of aneurysm surgery has caused speech deterioration. This is also the first case in which neuroendoscopy has been successfully employed to obtain tissue for diagnosis and to treat such a lesion.

Electric deep brain stimulation (DBS) in midbrain nuclei in humans alters cardiovascularparameters, presumably by modulating autonomic and baroreflex function. Baroreflex modulation of sympathetic outflow is crucial for cardiovascular regulation and is hypothesized to occur at two distinct brain locations. This study aimed to evaluate sympathetic outflow in humans with DBS electrodes during ON and OFF stimulation of specific midbrain nuclei known to regulate cardiovascular function. Muscle sympathetic nerve activity (MSNA) was recorded during DBS ON and OFF in patients with chronic neuropathic pain (n=7) and Parkinson’s disease (n=10). Arterial blood pressure (ABP), heart rate and respiration were monitored during the recording session and spontaneous vasomotor and cardiac baroreflex sensitivity (BRS) were assessed. Head-up tilt testing was performed separately in the Parkinson’s patients post-operatively. Stimulation of the dorsal most part of the subthalamic nucleus (STN) and ventrolateral periaqueducta...

Major head injury is a common reason for admission to the ICU. Knowledge of factors that predict mortality provides clues to the pathophysiology of head injury, how clinicians' interventions can be most effective, allows audit between different units or time points and provides objective data with which to communicate with patients' relatives. Several established risk prediction models exist in the ICU; however, they have been shown to have suboptimal discrimination and calibration in this patient group [1]. Our aim was therefore to develop a novel model to predict mortality specifically for head injury.

Traumatic brain injury is a potentially fatal condition and a common cause of admission to ICUs in the United Kingdom. We describe the case mix and outcomes of head injury patients requiring intensive care and evaluate the ability of five risk prediction models to predict mortality in these patients.

This report describes the case mix and outcome (mortality, intensive care unit (ICU) and hospital length of stay) for admissions to ICU for head injury and evaluates the predictive ability of five risk adjustment models. A secondary analysis was conducted of data from the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme, a high quality clinical database, of 374,594 admissions to 171 adult critical care units across England, Wales and Northern Ireland from 1995 to 2005. The discrimination and calibration of five risk prediction models, SAPS II, MPM II, APACHE II and III and the ICNARC model plus raw Glasgow Coma Score (GCS) were compared. There were 11,021 admissions following traumatic brain injury identified (3% of all database admissions). Mortality in ICU was 23.5% and in-hospital was 33.5%. Median ICU and hospital lengths of stay were 3.2 and 24 days, respectively, for survivors and 1.6 and 3 days, respectively, for non-survivors. The ICNARC model, SAPS II and MPM II discriminated best between survivors and non-survivors and were better calibrated than raw GCS, APACHE II and III in 5,393 patients eligible for all models. Traumatic brain injury requiring intensive care has a high mortality rate. Non-survivors have a short length of ICU and hospital stay. APACHE II and III have poorer calibration and discrimination than SAPS II, MPM II and the ICNARC model in traumatic brain injury; however, no model had perfect calibration.

Background Fever suppression may be beneficial for patients with traumatic brain injury (TBI) and stroke, but for patients with meningitis or encephalitis [central nervous system (CNS) infection], the febrile response may be advantageous. Objective To evaluate the relationship between peak temperature in the first 24 h of intensive care unit (ICU) admission and all-cause hospital mortality for acute neurological diseases. Design, setting and participants Retrospective cohort design from 2005 to 2013, including 934,159 admissions to 148 ICUs in Australia and New Zealand (ANZ) and 908,775 admissions to 236 ICUs in the UK. Results There were 53,942 (5.8 %) patients in ANZ and 56,696 (6.2 %) patients in the UK with a diagnosis of TBI, stroke or CNS infection. For both the ANZ (P = 0.02) and UK (P

BACKGROUND: Deep brain stimulation (DBS) of subcortical brain areas such as the periaqueductal grey and subthalamic nucleus has been shown to alter cardiovascular autonomic performance. The supramedullary circuitry controlling respiratory airways is not well defined and has not been tested in humans. OBJECTIVE: To use direct electric stimulation via DBS macroelectrodes to test whether airway resistance could be manipulated by these areas in awake humans. METHODS: Thirty-seven patients with in-dwelling deep brain electrodes for movement disorders or chronic pain underwent spirometry according to the European Respiratory Society guidelines. Testing was performed randomly 3 times on stimulation and 3 times off stimulation; patients were blinded to the test. Thoracic diameter changes were measured by a circumferential pressure-sensitive thoracic band. Ten periaqueductal grey and 10 subthalamic nucleus patients were tested. To control for confounding pain and movement disorder relief, the sensory thalamus in 7 patients and globus pallidus interna in 10 patients, respectively, were also tested. RESULTS: Peak expiratory flow rate (PEFR) increased significantly with periaqueductal grey and subthalamic nucleus stimulation by up to 14% (P = .02 and .005, respectively, paired-samples Student t tests). Stimulation of control nuclei produced no significant PEFR change. Similarly, changes in thoracic diameter reflecting skeletal activity rather than airway caliber did not correlate with the improvement in PEFR. Forced expiratory volume in 1 second was unchanged by stimulation. CONCLUSION: DBS can improve PEFR in chronic pain and movement disorder patients. This finding provides insights into the neural modulation of respiratory performance and may explain some of the subjective benefits of DBS.