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IN THIS RANDOMIZED, OPEN-LABEL TRIAL, THE INVESTIGATORS recruited 366 patients with Parkinson's disease (PD) who did not have an adequate benefit from medications. Patients were randomly assigned to a group treated with medication and surgery, or medical therapy alone. Of the total, 178 patients had surgery (174 had subthalamic nucleus DBS, and four had globus pallidus interna DBS), and 171 patients had only medical therapy (12 patients switched over to DBS after the assignment). Dyskinesia and severe "off" periods were the most common reasons for considering surgery. Patients' self-evaluating, 39-item, PD questionnaire summary index improved by 5 points in the surgical group and by 0.3 point in the medical group. There was no evidence that the degree of improvement in favor of surgery varied with age, disease duration, Hoehn & Yahr stage, reason for surgery, or whether apomorphine treatment was planned. Total Unified Parkinson's Disease Rating Scale (UPDRS) score in the "on-medication" state improved by 6.6 points in the surgical group, but worsened by 1.6 points in the medical group. Total UPDRS score in the "off-med" state improved by 27.4 points in the surgical group and by 0.9 points in the medical group. Of note, patients in the surgical group were evaluated while DBS was on in either the "on-med" or "off-med" state. At one year, 75 patients in the surgical group had no dyskinesia and 45 reported no "off" time. On the contrary, 21 patients in the medical group had no dyskinesia, and five reported no "off" time. Dementia Rating Scale Score decreased by 0.4 points in both groups. Only a subset of patients had detailed neuropsychological evaluation. Utilizing the Delis-Kaplan executive function system, phonemic mean score and verbal fluency decreased by 6.5 and 4.5 points in the surgical group, and by 0.6 and 0.2 point in the medical group. Wechsler abbreviated scale of intelligence vocabulary reduced by 1.5 point in the surgical group, but improved by 0.6 point in the medical group. Patients in the surgical group required 34% less medication compared to the patients in medical group. At baseline, 45 patients in each group were on apomorphine. By one year, this had decreased to 13 (six with continuous infusion) in the surgical group, but had increased to 63 (48 with continuous infusion) in the medical group. Thirty-six patients in the surgical group had 43 surgery-related serious adverse events, of which infections were the most common. There were 25 PD-related or drug-related serious adverse events in 20 patients in the surgical group and 14 events in 13 patients in the medical group. One patient who had previously attempted suicide before the study had an unsuccessful suicide attempt after the surgery. Two patients in the surgical group died (intraoperative hemorrhage and preoperative pneumonia). One patient in the medical group died from stroke. [ABSTRACT FROM AUTHOR]

ALTHOUGH THERE ARE MANY STUDIES ON THE EFFECTS OF subthalamic nucleus deep brain stimulation (STN DBS) on motor functions in Parkinson's disease (PD), there are a few studies investigating the effects of STN DBS on the sensory system. This study tested the effects of STN DBS on somatosensory temporal discrimination (STD) in PD. Thirteen patients with advanced PD and 13 age-matched healthy controls were recruited. The indications for DBS were severe motor fluctuations, dyskinesias, and motor deficits. Inclusion criteria were treatment with STN DBS for at least 12 months, mini-mental state examination (MMSE) > 24, absence of clinical sensory deficits with DBS switched on, and no changes in stimulation or medications within the past 3 months. The patients were evaluated in four conditions (off-med/off-stim, off-med/ on-stim, on-med/off-stim, and on-med/on-stim). The experimental conditions were randomly assigned and counterbalanced across the patients. MMSE, attentive matrices, Raven's Progressive Matrices, Corsi's test, Rey's test, and verbal fluency test did not significantly change across conditions. STD threshold was tested in the index finger (hand), periorbital region (eye), and neck. The thresholds were higher in the patients compared to healthy subjects, with the highest STD thresholds in the hand. There was no significant correlation between the individual UPDRS scores for the hand, neck, and face with their respective STD thresholds in all experimental conditions. The thresholds were lower in the on-med state compared to the off-med state. In the on-med state, the thresholds were higher in the on-stim than in the off-stim condition. However, in the off-med state, the thresholds were not different in the off- or onstim condition. These findings suggest that dopaminergic therapy improves STD processing whereas STN DBS degrades the process. Given that cognition and attention were not different among four conditions, worsening in STD processing in the on-stim state cannot be explained by the DBS potential effects on cognition and attention. The study also showed that the amplitudes of the upper limb somatosensory evoked potential (SEP) parietal component were larger in the off-stim than in the on-stim condition. There was no significant correlation between the changes in SEP component amplitudes and changes in STD thresholds in on-med/on-stim and on-med/off stim states. The authors explained that DBS might decrease SEP amplitudes by interfering with subcortical somatosensory pathways. However, given the finding that STD thresholds changed to a similar extent on both body sides in patients with unilateral as well as those with bilateral DBS, it was unlikely that DBS interfered with the nearby somatosensory pathways. The authors proposed that DBS-induced chronic STN inactivation actively elicits changes in central somatosensory processing, possibly by altering the interplay between cortical (pre-supplementary motor area and somatosensory primary areas) and subcortical neural circuits (thalamus, striatum, subthalamic nucleus, and cerebellum). Concerning the effects of dopaminergic therapy, the authors explained that dopamine might directly modulate the neural circuits for STD process. [ABSTRACT FROM AUTHOR]

GAIT DISTURBANCE AND POSTURAL INSTABILITY ARE MAJOR causes of disability in Parkinson's disease. Medications and deep brain stimulation (DBS) in the subthalamic nucleus or internal globus pallidus sometimes do not alleviate freezing of gait and usually do not provide a direct benefit on postural stability. Pedunculopontine nucleus (PPN) is a reticular structure belonging to the mesencephalic reticular formation. Studies in non-human primates suggested a role of PPN and related brainstem areas in gait and posture control. Recent open-label studies also suggested that PPN DBS may provide benefit on gait disorders. Ferraye and Moro and their respective groups conducted double-blind studies on the effects of PPN DBS. Ferraye evaluated the effects of bilateral PPN DBS in six patients with Parkinson's disease with severe gait freezing, unresponsive to levodopa and STN DBS. At one-year follow-up, during the open-label assessment, although freezing of gait improved in the off-medication / on PPN stimulation state, there was no significant change in the on-medication state compared to pre-surgery condition whether or not PPN DBS was on or off. Moreover, during the double-blind evaluation, there was no significant difference in gait freezing and motor scores between off and on stimulation states. The best stimulation contacts located slightly posterior to the PPN, in the cuneiform and subcuneiform nuclei. Bipolar stimulation was used in most patients with stimulation frequency ranging from 15 to 25 Hz, voltage between 1.2 and 3.8 V, and pulse width of 60 and 90 µs. Because they observed a trend for the benefit to wear off, cyclic stimulation with continuous stimulation during the day and off stimulation at night was preferred after the study. Adverse events included ipsilateral oscillopsia and limb myoclonus induced by low frequency-stimulation (5-35 Hz), and contralateral paresthesia induced by stimulation over 60 Hz. Three patients reported improvement in sleep with an increase in daytime vigilance. Moro evaluated the effects of unilateral PPN DBS in six patients with Parkinson's disease with freezing of gait and postural instability. However, unlike Ferraye's study, the patients in Moro's study did not have STN DBS. The contacts used were located in the anterolateral tegmentum of the pontomesencephalic junction. PPN DBS did not provide an acute benefit, but it induced reversible and intensity-and frequency-dependent adverse effects, including contralateral paresthesia, unilateral oscillopsia, and contralateral warm sensation. Settings with frequency of 50 Hz and 70 Hz, pulse width of 60 µs, and voltage of 1.9 usually produced better motor scores. Bipolar stimulation provided better motor outcomes than monopolar stimulation. There was no significant difference in UPDRS II and III total scores and subscores for falling, freezing, or gait and balance between on and off stimulation in either on and off medication conditions during the double-blind assessment after three months and 12 months of continuous stimulation. But, during the open-label assessment, there was improvement in total UPDRS II scores (particularly subscores for freezing and fall) in the off-medication/onstimulation state at three months and 12 months. Total motor scores and subscores for gait and postural stability (open-label assessment) also improved, but the improvement did not reach the statistical significance. [ABSTRACT FROM AUTHOR]

MYOCLONUS IS A MOVEMENT DISORDER DESCRIBED AS brief, shock-like movements caused by muscle contraction or inhibition of ongoing muscle activity. It may originate from the central or peripheral nervous system. Spinal myoclonus originates from the spinal cord and can be subdivided into spinal segmental myoclonus and propriospinal myoclonus. In spinal segmental myoclonus, myoclonus is limited to muscles innervated by one or two contiguous spinal segments. Propriospinal myoclonus is characterized by axial muscle contractions as a result of a spinal myoclonic generator recruiting axial muscles up and down the spinal cord via propriospinal pathways. Although spinal cord lesions can be seen in patients with spinal myoclonus, structural lesions may not be present in some patients. Distinguishing myoclonus of organic origin from psychogenic myoclonus can also be difficult. Detection of a Bereitschaftspotential (BP) by EEG-EMG back averaging analysis can be helpful in differentiating between these two etiologies. BP consisted of early BP and late BP. The early BP starts two seconds and late BP starts about 400 milliseconds before the onset of a voluntary jerk. In this study, the authors looked clinically and electrophysiologically at a series of 20 patients with idiopathic spinal myoclonus. EMG showed a pattern consistent with spinal segmental myoclonus in four patients and with propriospinal myoclonus in 16 patients. Seven patients showed a consistent pattern of muscle propagation, but 13 patients did not show a consistent pattern. A definite BP was detected in six patients and possible BP was detected in nine patients. BP was absent in five patients. Clinically, organic myoclonus was considered in five patients and psychogenic myoclonus was considered in 10 patients. In the remaining five patients, two clinicians had different opinions on the diagnosis. In the clinically diagnosed organic myoclonus group (n = 5), definite BP was detected in four cases and possible BP was detected in one case. In the clinically diagnosed psychogenic myoclonus group (n = 10), there was one case with definite BP, six cases with possible BP, and three cases with absent BP. In five patients with unclear clinical diagnosis, one case had definite BP, two cases had possible BP, and two cases had no BP. The authors concluded that although BP detection is a useful tool, it has limitations because it may not be possible to reach a definite conclusion as to whether a BP is present or not. Moreover, if the jerking movements are too frequent (> 1 every 5 seconds), a BP may not be able to be recorded even if the movements are performed voluntarily. It is also difficult to assess for BP if the movements are very infrequent. In addition, head movements can create movement artifacts in the EEG recording. [ABSTRACT FROM AUTHOR]

DROOLING IS COMMON IN PARKINSON'S DISEASE (PD), and it can affect the patient's quality of life. Current treatment options, including anticholinergics, parotid gland irradiation, and salivary gland ligation or excision, are limited because of their potential side effects and invasiveness. Because botulinum toxin (BTX) can inhibit acetylcholine release at the autonomic nerve terminals, it may be able to reduce saliva secretion. Given a higher incidence of autonomic effects of BTX-B compared to BTX-A, BTX-B can provide some advantages in the treatment of drooling. A previous randomized, controlled trial already showed benefit of BTX-B injections into parotid and submandibular glands in 16 PD patients. This study was designed to ascertain the effectiveness of BTX-B on PD-related drooling and to determine duration of its effect. PD patients with moderate to severe drooling were recruited and were randomly assigned to receive either BTX-B 4000 U (0.8 ml) or placebo (0.8 ml of 0.9% saline) into each pre-auricular portion of the parotid gland, guided by anatomic landmark. Clinical assessment was performed at baseline and one month after the injections using both subjective measures (Drooling Severity and Frequency Scale. patient embarrassment within the familial and social context, drooling and dysphagia subscores of UPDRS, and Global Impression Score) and objective measures (weight of five dental rolls retained in the mouth for five minutes and evaluation of masseter strength and resistance). Duration of action was determined by patients" subjective report and objective measures of saliva production. Thirty-six subjects (26 men and 10 women: age 71.9 ± 5.9 years) with disease duration of 12.0 + 6.8 years and Hoehn and Yahr (H&Y) stage II to IV were randomly assigned to receive BTX-B or placebo (18 subjects each group). One month after the injections, subjects in BTX-B group had less drooling, whereas most controls did not have significant change in drooling severity. All subjects given BTX-B were satisfied with the result, but only seven controls were satisfied. The odds ratio of achieving a moderate to dramatic improvement after BTX-B treatment compared to placebo was 59.5 (95% confidence limits: 5.9-595). Three BTX-B patients had mild, transient dysphagia which started 10 days after the injections and recovered within two weeks. One BTX-B patient had a transient mild jaw weakness. No patient had hematoma, facial palsy or any other adverse events. The duration of effect on drooling from the injections was 19.2 ± 6.3 weeks in BTX-B group and 6.7 ± 1.4 weeks in seven controls who reported an improvement. [ABSTRACT FROM AUTHOR]

BOTULINUM TOXIN TYPE A (BTX-A) HAS BEEN USED for dystonia, spasticity, and glandular hyperactivity. Ranoux and colleagues investigated the analgesic effects of one-time intradermal injections of BTX-A in patients with focal neuropathic pain associated with allodynia, using a randomized, double-blind, placebo-controlled, parallel group design. In the BTX-A group (n=12), the mean number of injection sites was 20 ± 8.3, with doses ranging from 20 to 190 units. In the placebo group (n=10), the number of injection sites was 19.8 ± 5.2, with total volumes of injection similar to the BTX-A group (3.9 ± 1.1 for placebo and 4.4 ± 1.6 for BTX-A). BTX-A improved average pain intensity 2 weeks after the injections. The effect increased for up to 4 weeks and was sustained for up to 14 weeks. The area and intensity of allodynia to brush and cold pain thresholds were reduced, without an effect on thresholds to non-painful thermal and mechanical stimuli, or on heat and mechanical pain thresholds. Although burning, paroxysmal pain, and allodynia were improved by BTX-A, deep pain, paresthesia, and dysesthesia were unaffected. BTX-A also improved general activity and anxiety. However, depression was unchanged. The analgesic effects of BTX-A did not correlate with sex, age, pain duration or intensity, or neuropathic symptoms. But, it was inversely related with the magnitude of thermal deficits, burning pain, and brush-evoked pain. Besides pain due to injections, there was no other local or systemic side effect. The pain was greater when the injections were to the hand or elbow. Preclinical data showed that BTX-A blocks protein kinase C potentiation of transient receptor potential vanilloid 1, a capsaicin and heat-sensitive ion channel expressed in nociceptors. So, it is possible that BTX-A acts on sensitized nociceptive fibers to produce analgesic effects. However, there are discrepancies in the results of studies concerning BTX effects on pain due to different preparations of BTX, different experimental stimuli, and different binding capacity of BTX to the receptors in acute and chronic conditions (probably greater in chronic conditions). A possible central effect of BTX-A cannot be ruled out. The authors concluded that BTX-A may induce direct analgesic effects on nociceptive fibers in patients with chronic focal neuropathic pain independent of its effects on muscle tone. In an accompanying editorial, Murinson commented that this study is an important landmark in the treatment of neuropathic pain. However, the application to a broader patient population is limited because neuropathic pain in the patients in this study was only due to postherpetic neuralgia or focal nerve injury. Although it is known that BTX-A blocks cholinergic transmission at the neuromuscular junction, many studies show that BTX-A effects are not limited to cholinergic neurons and that its effects on pain control are likely independent of neuromuscular blocking property. For instance, BTX-A can block calcitonin gene-related peptide (CGRP) release from rat trigeminal neurons. In addition, cultured dorsal root ganglion neurons are highly sensitive to BTX-A effects on potassium-evoked substance P release. For basic signaling of painful sensations, it is clear that exocytic signaling in the periphery is not required. However, there is evidence supporting a role for exocytosis in painful inflammatory conditions. Moreover, there has been some controversy about whether primary pain afferents contain the machinery necessary to support the exocytic signaling in the periphery and whether primary pain afferents synthesize and package compounds, that if released, would produce pain or augment pain signaling. Murinson suggested that each of the pain models needs to be considered separately and weighed for relevance to human forms of neuropathic pain.… [ABSTRACT FROM AUTHOR]

ALTHOUGH DEEP BRAIN STIMULATION OF THE INTERNAL globus pallidus (GPi-DBS) is an effective treatment for patients with primary dystonia, there is no well defined outcome predictor of this treatment. To determine the predictors of the response to GPi-DBS, Isaias and colleagues retrospectively reviewed the DBS outcomes in 35 patients with early-onset dystonia (26 years old). Twenty-five patients had DYT1 gene mutation. Seven patients had fixed skeletal deformity. The severity of dystonia was evaluated before the surgery and 3 and 12 months after the surgery using Burke- Fahn-Marsden Dystonia Rating Scale (BFMDRS). Dystonia patients with fixed skeletal deformity had a significantly poorer outcome at 12 months due to the poor resolution of limb and axial symptoms. For this reason, the authors excluded this subgroup of patients from further outcome analysis. Patients older than age 21 years at surgery (n=17) improved 38% less than patients younger than 21 years (n=15) at 3 months after surgery, and 15% less at 1 year. Patients with disease duration longer than 15 years (n=12) improved 49% less than those with shorter disease duration (n=20) at 3 months, and 13% less at 1 year. Because disease duration and age at the surgery were related, the authors used multiple regression analysis to identify which factor had a stronger predictive value and found that disease duration was the only independent variable correlated with DBS outcome. Patients with DYT1 gene mutation (n=22) were younger at symptom onset and younger at surgery than those without DYT1 gene mutation. They exhibited a greater BFMDRS percentage improvement at 3 months and 1 year. However, when patients were stratified by disease duration, this difference was lost. Disease severity and phasic/tonic predominance of dystonia symptoms did not predict response to DBS. Of 26 patients who were taking medications before surgery, 9 patients had completely discontinued medications at one year. Concerning DBS parameters, at 3 months, mean voltage was 2.8 V, mean pulse width was 217.2 µsec, and mean frequency was 82.7 Hz. At 12 months, mean voltage was 3.0 V, mean pulse width was 226.6 µsec, and mean frequency was 76.9 Hz. Monopolar stimulation was predominantly used. [ABSTRACT FROM AUTHOR]

ALTHOUGH MOTOR SYMPTOMS CONSTITUTE THE CARDINAL features of Parkinson's disease (PD), non-motor symptoms, including neuropsychiatric conditions (depression, anxiety, psychosis, and cognitive impairment), autonomic disorders (orthostatic hypotension, urinary dysfunction, and gastrointestinal disturbance), sleep disorders, and sensory symptoms (pain and dysesthesias) also contribute greatly to disability and quality of life. Many studies have provided compelling evidence of long-term benefit of subthalamic nucleus deep brain stimulation (STN DBS) on motor symptoms. However, the influence of STN DBS on non-motor symptoms is less well established. In this study, the authors investigated the impact of STN DBS on motor and non-motor symptoms in 36 PD patients (14 women and 22 men) at 12 and 24 months after DBS surgery. Mean age at surgery was 61.2 ± 6.2 years. Mean disease duration was 16.7 ± 4.4 years. Unified Parkinson's Disease Rating Scale (UPDRS) was used as an assessment tool. Data concerning constipation and urological dysfunction were collected from clinical charts in the form of nominal data (presence or absence). Daily PD medication requirement data were collected in the form of levodopa equivalent dosage. Comparing between preoperative off-medication and postoperative off-medication/on-stimulation condition, UPDRS III (objective motor scores) improved 52% and 55% at 12 and 24 months after surgery, respectively. Total UPDRS II score (motor and non-motor items of activity of daily living) improved 60% and 59% at 12 and 24 months, respectively. Off-duration was reduced by 92% and 98% at 12 and 24 months. Levodopa equivalent daily dosage was reduced by 60% and 59% at 12 and 24 months, comparing to the preoperative dosage. Postoperative total UPDRS I score and subscores (intellectual impairment, thought disorder, depression, and motivation) were not different compared to preoperative scores. However, when analyzing each patient individually, 3 patients developed moderate memory loss at 24 months, 3 patients developed benign hallucinations, 6 patients developed depression, and 6 patients developed motivation impairment. Preoperatively, UPDRS II non-motor subscores for salivation, swallowing, and sensory complaints were improved by medications. Postoperatively, these scores also were improved by the combination of medication and stimulation comparable to preoperative medication effect, while PD medication dosage was markedly reduced. In addition, sleep-related problems and constipation improved after surgery. However, falling unrelated to freezing, nausea, symptomatic orthostatic hypotension, and urological dysfunction were unchanged. The authors concluded that STN DBS improved motor symptoms and some non-motor symptoms such as salivation, swallowing, sensory complaints, sleep problems, and constipation. The improvement in those non-motor symptoms was explained by the improvement in bradykinesia, relatively constant motor control, and dopaminergic medication reduction. The authors also pointed out that this study had some weak points, including a small number of patients, low prevalence of some non-motor symptoms, and limitation of UPDRS in capturing the extent of non-motor features. [ABSTRACT FROM AUTHOR]

DEEP BRAIN STIMULATION (DBS) OF THE GLOBUS PALlidus interna (GPi) is an effective therapy for primary dystonia. In most case series, high frequencies (130-185 Hz) and wide pulse width (120-450 mcsec) were used based on the experience in Parkinson's disease and essential tremor. This can result in excessive battery consumption and may cause muscle contractions because of current spreading to the adjacent internal capsule. Alterman and colleagues reported their experience in using 60 Hz stimulation in 15 consecutive patients with primary dystonia (12 men and 3 women). Twelve had DYT1 gene mutation (9 men and 3 women). Median age at the time of surgery was 20 years, with a median symptom duration of six years. The electrodes were placed in posteroventral GPi (bilateral in 13 patients and unilateral in 2 patients). The stimulation was set at 60 Hz in all patients. The stimulating contacts were selected from four available contacts (0-3) on each side based on the clinical response and tolerability. The initial voltage and pulse width were set at 2.5 volts and 120 mcsec based on their experience. Voltage or pulse width was then adjusted monthly or bimonthly to maximize the benefit or to reduce adverse effects. Frequency was kept constant at 60 Hz. The motor subscales of Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-M) and disability subscales (BFMDRS-D) were employed for clinical assessment in an open-label fashion at baseline (within 1 week of surgery), and at 1, 3, 6, and 12 months after the initial programming. At the baseline, the median BFMDRS-M and BFMDRS-D scores were 35 and 8, respectively. Median improvement in BFMDRS-M was 38%, 76%, 82%, and 89% at 1, 3, 6, and 12 months, respectively. Median improvement in BFMDRS-D was 25%, 64%, 70%, and 75% at 1, 3, 6, and 12 months, respectively. The outcome correlated with age at the time of surgery (better in patients younger than 21) and the duration of symptoms, but did not correlate with DYT1 status, age at disease onset, disease severity, or gender. There were no differences in the outcome at one year between patients with phasic and tonic dystonia. However, patients with phasic dystonia had a trend toward better improvement at one month. Of 13 patients who were taking medications for dystonia preoperatively, 7 were able to stop medications at their last follow-up (12-30 months). Six patients were able to reduce medications by at least 50%. The intrathecal baclofen pump required by one patient could be removed. Of 28 electrodes, 27 were unipolar stimulation (11 with single monopolar, 14 with double contiguous monopolar, and 2 with triple monopolar) with a mean amplitude of 3.0 ± 0.3 volts. The most common contact used was contact 1 (37%), followed by contacts 2, 0, and 3. Pulse widths at the last follow-up ranged from 120 to 270 mcsec. The average battery consumption was 55 microAmp, which was approximately half of what was observed in stimulation with higher frequency according to the authors' unpublished observations. [ABSTRACT FROM AUTHOR]

Synopsis: The sequence of disease progression in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) is different, with earlier limbic cortical involvement in DLB. Limbic cortical involvement may explain the more severe autonomic dysfunction that occurs in DLB and PD with dementia. AUTONOMIC DYSFUNCTION IS COMMON IN PARKINSON'S disease without dementia (PD), Parkinson's disease with dementia (PDD), and in dementia with Lewy bodies (DLB). However, autonomic dysfunction appears to be more severe in DLB and PDD than in PD. This study shows the difference in autonomic nervous system involvement among these three entities. Sudomotor, skin vasomotor, and cardiovascular reflexes were studied in 12 patients with DLB, 12 with PDD, 12 with PD, and 12 age-matched healthy controls. The tests included sympathetic sweat response (SSwR) on the palm side of the thumb, and skin vasomotor reflex (SkVR) at the index fingertip during sympathetic activation procedures (deep inspiration, mental arithmetic task, exercise, and tactile stimulation), and head-up tilt test. The basal sweat output, basal skin blood flow, as well as baseline systolic blood pressure and heart rate in the supine position did not differ among four groups. Seven DLB patients, six PDD, and three PD showed absence of SSwR, but there was no significant difference in mean amplitudes of SSwR among these three groups. One DLB patient and three PDD had no SkVR. The SkVR amplitudes in PD and controls were comparable, but SkVR amplitudes in DLB and PDD were lower than those in controls. Orthostatic hypotension was observed in six DLB, eight PDD, and three PD. However, unlike PD, mean decreases in systolic and diastolic blood pressure during tilt test in DLB and PDD were lower than that in controls. Although mean change in heart rate during tilt test did not differ among four groups, abnormally low coefficient of variation of R-R intervals (CVR-R) was observed in six DLB, three PDD, and three PD, with the lowest mean CVR-R in DLB. The authors explained that the impairment in sudomotor and skin vasomotor reflexes may be related to pathology in raphe nuclei. Furthermore, because a decrease in SSwR on the palm indicated a dysfunction in a so-called emotional sweating, they suggested that limbic involvement may explain autonomic dysfunction in PDD and DLB since limbic system plays an important role in emotional sweating as well as cardiovascular regulation. Moreover, given similarities in autonomic dysfunction in PDD and DLB, there is a possible uniformity of autonomic nervous system impairment in these two diseases. COMMENTARY: Findings from this study suggest that, although autonomic dysfunction can occur in PD, PDD, and DLB, it is more severe in PDD and DLB. Many parts of the nervous system, including hypothalamus, brainstem, spinal cord, and limbic system, are involved in autonomic nervous system regulation. Given the predominant limbic and neocortical pathology in DLB, the more severe autonomic dysfunction in PDD and DLB may be partly explained by limbic involvement. However, this study has two weak points, including a small number of patients and no pathological diagnosic confirmation of the clinical syndromes. [ABSTRACT FROM AUTHOR]

ALTHOUGH BILATERAL SUBTHALAMIC NUCLEUS STIMUlation (STN DBS) significantly improves motor performance in patients with advanced Parkinson's disease (PD), it may be associated with cognitive decline. However, the incidence of neuropsychological effects appears to be less in unilateral STN DBS compared to bilateral STN DBS. For a better understanding of the effects of STN DBS on a performance requiring both cognitive and motor function resembling a real-life situation, Alberts et al conducted this study using cognitive-motor dual task. Eight PD patients between the ages of 48 and 70 years (mean = 56.5) participated in this study. All of them underwent bilateral STN DBS surgery at least 12 months prior to the study and their stimulation parameters were stable for at least six months, with the active contacts in the dorsal border of the STN. They were evaluated in the off-medication state with three stimulation modes -- bilateral stimulation, unilateral stimulation (in most affected side of the brain), and off-stimulation. In each state, they performed a cognitive (n-back task) and motor (force tracking) task under single- and dual-task conditions. UPDRS-III scores (motor scores for PD) were improved by 33% with unilateral stimulation and by 46% with bilateral stimulation. Under simple dual-task conditions, there was no difference in cognitive or motor performance between unilateral and bilateral stimulation. However, as dual tasks became more complex, cognitive and motor performances were significantly worse, with bilateral stimulation compared to unilateral stimulation, and reached the level of the off-stimulation state with the most complex task. This finding supports the hypothesis that bilateral STN DBS interferes with patients' ability to handle higher demands placed on cognitive processes, particularly in a dual task. Given the very small size of STN, even when the lead is located in the sensorimotor region, the stimulation current can spread to limbic and associative areas as well as adjacent structures that may also be involved in cognition. Since unilateral stimulation did not result in the same level of working memory decline, it indicates that the non-stimulated basal ganglia may be able to compensate for the disruption induced by stimulation, or that unilateral stimulation is not enough to disrupt the working memory function. Interestingly, one study showed that 44% of patients who were working prior to the DBS surgery did not return to work because of cognitive dysfunction. Given that more young patients are undergoing STN DBS surgery, detection and prevention of subtle cognitive decline may allow them to remain in the workforce longer. [ABSTRACT FROM AUTHOR]

Aim: We sought to identify markers of motor and nonmotor function in Parkinson's disease (PD) using advanced neuroimaging techniques in subjects with PD., Methods: We enrolled 26 nondemented PD subjects and 12 control subjects. All subjects underwent [(18)F]fluorodeoxyglucose positron emission computed tomography (FDG-PET) and magnetic resonance imaging, and a complete neuropsychological battery., Results: FDG-PET of subjects with PD revealed significant metabolic elevations in the bilateral posterior lentiform nucleus, posterior cingulate, and parahippocampus, and metabolic reductions in the bilateral temporoparietal association cortex and occipital lobe versus controls. PD subjects had significant reductions in executive/attention function, memory/verbal learning, and speed of thinking, and significantly increased depression, anxiety and apathy scores compared with controls. Motor dysfunction correlated with increased metabolism in the posterior lentiform nucleus, pons, and cerebellum, and decreased metabolism in the temporoparietal lobe. Cognitive dysfunction correlated with increased posterior cingulate metabolism and decreased temporoparietal lobe metabolism. Depressive symptoms correlated with increased amygdala metabolism; anxiety scores correlated with decreased caudate metabolism, and apathy scores correlated with increased metabolism in the anterior cingulate and orbitofrontal lobe and decreased metabolism in the temporoparietal association cortex., Conclusions: Our findings showed that motor, cognitive, and emotional dysfunction in PD are associated with distinct patterns of cerebral metabolic changes.