Sixty-hertz stimulation improves bradykinesia and amplifies subthalamic low-frequency oscillations.

BACKGROUND: The objective of this study was to investigate the hypothesis that attenuation of subthalamic nucleus (STN) alpha-/beta-band oscillations is causal to improvement in bradykinesia. METHODS: STN local field potentials from a sensing neurostimulator (Activa® PC+S; Medtronic, Inc.) and kinematics from wearable sensors were recorded simultaneously during 60- and 140-Hz deep brain stimulation (DBS) in 9 freely moving PD subjects (15 STNs) performing repetitive wrist flexion-extension. Kinematics were recorded during 20-Hz DBS in a subgroup. RESULTS: Both 60- and 140-Hz DBS improved the angular velocity and frequency of movement (P = 0.002 and P = 0.029, respectively, for 60 Hz; P < 0.001 and P < 0.001, respectively, for 140 Hz), but 60-Hz DBS did not attenuate beta-band power (13-30 Hz). In fact, 60-Hz DBS amplified alpha/low-beta (11-15 Hz, P = 0.007) and attenuated high-beta power (19-27 Hz, P < 0.001), whereas 140-Hz DBS broadly attenuated beta power (15-30 Hz, P < 0.001). Only 60-Hz DBS improved the regularity of angular range (P = 0.046) and 20-Hz DBS did not worsen bradykinesia. There was no correlation between beta-power modulation and bradykinesia. CONCLUSIONS: These novel results obtained from freely moving PD subjects demonstrated that both 140- and 60-Hz DBS improved bradykinesia and attenuated high beta oscillations; however, 60-Hz DBS amplified a subband of alpha/low-beta oscillations, and DBS at a beta-band frequency did not worsen bradykinesia. Based on recent literature, we suggest that both 140- and 60-Hz DBS decouple the cortico-STN hyperdirect pathway, whereas 60-Hz DBS increases coupling within striato-STN circuitry. These results inform future algorithms for closed-loop DBS in PD. © 2016 International Parkinson and Movement Disorder Society.

Lower urinary tract dysfunction in patients with dysautonomia.

OBJECTIVE: With the goal of better defining the types of bladder dysfunction observed in this population, we present the chief urologic complaints, results of urodynamic studies, and treatments of patients with dysautonomia-related urinary symptoms. METHODS: All patients with dysautonomia referred to our neurourology clinic between 2005 and 2015 for management of lower urinary tract dysfunction were retrospectively reviewed. Each patient's chief urologic complaint was recorded and used to initially characterize the bladder storage or voiding symptoms. Patient evaluation included history and physical examination, urinalysis, post void bladder ultrasound, and urodynamic studies. Successful treatment modalities that subjectively or objectively improved symptoms were recorded. RESULTS: Of 815 patients with the diagnosis of dysautonomia, 82 (10 %) were referred for evaluation of lower urinary tract dysfunction. Mean age was 47 years (range 12-83) and 84 % were female. The chief complaint was urinary urgency ± incontinence in 61 % and hesitancy in 23 % of patients. Urodynamic findings demonstrated detrusor overactivity ± incontinence in 50 % of patients, although chief complaint did not reliably predict objective findings. Successful objective and subjective treatments were multimodal and typically non-operative. INTERPRETATION: Lower urinary tract dysfunction may develop in at least 10 % of patients with dysautonomia, predominantly females. Bladder storage or voiding complaints do not reliably predict urodynamic findings. Urodynamically, most patients exhibited detrusor overactivity. The majority of patients were successfully managed with medical or physical therapy.

Autonomic dysfunction, vasomotor rhinitis, and extraesophageal manifestations of gastroesophageal reflux.

OBJECTIVE: Several recent reports suggest there may be a relationship between chronic rhinitis and extraesophageal manifestations of gastroesophageal reflux (EER). It is hypothesized that this relationship is a result of autonomic nervous system (ANS) dysfunction. STUDY DESIGN: Patients with isolated vasomotor rhinitis (VR), both VR and EER, and a control group were studied by a battery of tests designed to objectively evaluate ANS function. In addition all 3 groups underwent barium esophagogram and 4-site (proximal pharynx, distal pharynx, proximal esophagus, and distal esophagus) ambulatory pH monitoring. Adult patients fulfilling diagnostic criteria for VR, and with both VR and EER underwent objective ANS testing in a recently developed ANS testing laboratory. The control group consisted of age- and sex-matched adults without diagnostic criteria for VR or EER. RESULTS: In patients with VR only (n = 9), 2 patients had a positive esophagogram, whereas a positive pharyngeal reflux probe was found in 1 and an abnormal composite autonomic scoring scale (CASS) was found in 8 (mean VR CASS = 1.750 vs control CASS 0.556, P =.02). The group with VR and EER (n = 12) had a positive esophagogram in 10 patients, positive pharyngeal reflux by probe in 9, and all 12 had an abnormal CASS (mean CASS VR/EER = 2.909 vs CASS control = 0.556, P =.001 and vs VR CASS = 1.750, P =.05). The control patients (n = 9) had normal transesophageal gastroduodenoscopy in 8, 1 had a positive pharyngeal probe study, and all 9 had a normal CASS. In addition ANS testing in patients with diagnostic criteria for both VR/EER revealed statistically significant evidence of an adrenergic deficit as compared with control patients on the basis of mean phase II blood pressure response to Valsalva maneuver (mean phase II VR/EER = -16.730 vs control = -7.780, P =.05). In the VR only group, the phase II blood pressure decrease was greater than in control patients, but did not reach statistical significance (mean phase II VR = -9.370 vs control = -7.780, P = 0.672). CONCLUSION: Patients with VR and VR/EER have objective evidence of ANS dysfunction when compared with a group of age- and sex-matched control patients. Patients with both VR/EER demonstrate a significantly greater degree of ANS dysfunction than patients with isolated VR. The mechanism by which VR and EER interact is not entirely clear, but ANS dysfunction is objectively associated with both disorders. In addition, patients with VR/EER seem to demonstrate hypofunction of the adrenergic component of the ANS, in contrast to the generally held hypothesis that VR results from increased cholinergic activity. Further characterization of the type of ANS abnormality may allow the development of novel pharmacologic therapies for these disorders.

Evaluation of the autonomic nervous system.

This article has reviewed the laboratory evaluation of autonomic disorders. Autonomic testing can be divided into the assessment of three functional domains: sudomotor (assessed best by the thermoregulatory sweat test or QSART), cardiovagal (assessed by the Valsalva ratio and heart rate response to deep breathing or standing up), and adrenergic (assessed by the blood pressure response to the Valsalva maneuver or head-upright tilt). Tables 2 and 3 summarize the test findings in a variety of clinical disorders affecting autonomic nervous system function.

Surface-evoked laryngeal sensory action potential evaluation in neurogenic chronic cough.

OBJECTIVES: Neurogenic chronic cough is currently a diagnosis of exclusion. We hypothesized that surface-evoked laryngeal sensory action potential (SELSAP) testing could be used to help establish a diagnosis of laryngeal sensory neuropathy as a cause of chronic cough, based on altered SELSAP waveform morphology. STUDY DESIGN: Retrospective cohort study. METHODS: Laryngeal electromyographic (EMG) data including SELSAP waveform testing from patients with chronic cough were directly compared with a control population without significant laryngeal symptoms, and statistical analysis of unilateral and bilateral neuropathy injury subgroups was performed. RESULTS: Thirty patients with a chief complaint of chronic cough underwent laryngeal EMG testing since January 2000 with needle EMG and surface nerve conduction studies. SELSAP waveform analysis of unilateral and bilateral laryngeal neuropathy demonstrated significantly lowered median SELSAP peak amplitude compared with controls (P < 0.01). CONCLUSIONS: Patients with suspected neurogenic chronic cough demonstrate statistically significant alterations in SELSAP waveform that can support a diagnosis of laryngeal sensory neuropathy.

A new noninvasive method for determination of laryngeal sensory function.

OBJECTIVES/HYPOTHESIS: We report a new surface technique for studying sensory conduction in the superior laryngeal nerve (SLN). STUDY DESIGN: Prospective controlled cohort study at an academic tertiary care hospital. METHODS: Surface stimulation of the vagus nerve 7-10 cm proximal to a surface electrode placed over the cricothyroid muscle was performed in controls and in subjects with needle electromyographic-confirmed laryngeal neuropathy. Cathodal stimulation was applied below the mastoid process behind the sternocleidomastoid muscle. Nerve conduction parameters were determined. RESULTS: Noninvasive SLN evoked potential studies were performed on healthy volunteers (n = 28) as well as neuropathic subjects (n = 27). Compared to controls, the neuropathic subjects had statistically significant differences in baseline-to-peak amplitude, conduction velocity, and intrasubject side-to-side amplitude ratio (P <.01) of their surface evoked laryngeal sensory action potential (SELSAP). CONCLUSIONS: Laryngeal sensory nerve conduction can be determined noninvasively by evaluating SELSAP waveform. This study provides a reproducible method for electrophysiologic evaluation of a sensory branch of the SLN.

Simultaneous ERP and fMRI of the auditory cortex in a passive oddball paradigm.

Infrequent occurrences of a deviant sound within a sequence of repetitive standard sounds elicit the automatic mismatch negativity (MMN) event-related potential (ERP). The main MMN generators are located in the superior temporal cortex, but their number, precise location, and temporal sequence of activation remain unclear. In this study, ERP and functional magnetic resonance imaging (fMRI) data were obtained simultaneously during a passive frequency oddball paradigm. There were three conditions, a STANDARD, a SMALL deviant, and a LARGE deviant. A clustered image acquisition technique was applied to prevent contamination of the fMRI data by the acoustic noise of the scanner and to limit contamination of the electroencephalogram (EEG) by the gradient-switching artifact. The ERP data were used to identify areas in which the blood oxygenation (BOLD) signal varied with the magnitude of the negativity in each condition. A significant ERP MMN was obtained, with larger peaks to LARGE deviants and with frontocentral scalp distribution, consistent with the MMN reported outside the magnetic field. This result validates the experimental procedures for simultaneous ERP/fMRI of the auditory cortex. Main foci of increased BOLD signal were observed in the right superior temporal gyrus [STG; Brodmann area (BA) 22] and right superior temporal plane (STP; BA 41 and 42). The imaging results provide new information supporting the idea that generators in the right lateral aspect of the STG are implicated in processes of frequency deviant detection, in addition to generators in the right and left STP.