Characterizing the Mechanisms of Central and Peripheral Forms of Neurostimulation in Chronic Dysphagic Stroke Patients

BackgroundSwallowing problems following stroke may result in increased risk of aspiration pneumonia, malnutrition, and dehydration.Objective/hypothesisOur hypothesis was that three neurostimulation techniques would produce beneficial effects on chronic dysphagia following stroke through a common brain mechanism that would predict behavioral response.MethodsIn 18 dysphagic stroke patients (mean age: 66 ± 3 years, 3 female, time-post-stroke: 63 ± 15 weeks [±SD]), pharyngeal electromyographic responses were recorded after single-pulse transcranial magnetic stimulation (TMS) over the pharyngeal motor cortex, to measure corticobulbar excitability before, immediately, and 30 min, after real and sham applications of neurostimulation. Patients were randomized to a single session of either: pharyngeal electrical stimulation (PES), paired associative stimulation (PAS) or repetitive TMS (rTMS). Penetration-aspiration scores and bolus transfer timings were assessed before and after both real and sham interventions using videofluoroscopy.ResultsCorticobulbar excitability of pharyngeal motor cortex was beneficially modulated by PES, PAS and to a lesser extent by rTMS, with functionally relevant changes in the unaffected hemisphere. Following combining the results of real neurostimulation, an overall increase in corticobulbar excitability in the unaffected hemisphere (P = .005, F_1,17 = 10.6, ANOVA) with an associated 15% reduction in aspiration (P = .005, z = −2.79) was observed compared to sham.ConclusionsIn this mechanistic study, an increase in corticobulbar excitability the unaffected projection was correlated with the improvement in swallowing safety (P = .001, rho = −.732), but modality-specific differences were observed. Paradigms providing peripheral input favored change in neurophysiological and behavioral outcome measures in chronic dysphagia patients. Further larger cohort studies of neurostimulation in chronic dysphagic stroke are imperative.     

Impaired short-term plasticity in restless legs syndrome: a pilot rTMS study

BackgroundPrevious studies showed an impairment of the LTP-like plasticity to TMS in restless legs syndrome (RLS). Clinically, repetitive TMS (rTMS) was effective in alleviating the sensory-motor complaints of patients, although the effects induced by low-frequency (inhibitory) rTMS have not yet been investigated. An impaired LTD-like mechanism of cortical plasticity has been hypothesized, which we have directly assessed in this pilot study.MethodsMotor evoked potentials (MEPs) from the right first dorsal interosseus muscle were recorded at the stimulus intensity of 110% of the resting motor threshold (rMT) from 13 right-handed patients and ten age-matched right-handed healthy controls. Median peak-to-peak amplitudes were calculated in all participants at baseline (T₀), after the first train of a single evening session of low-frequency (1 Hz) rTMS over the left primary motor cortex (T₁), and after the whole rTMS procedure (T₂), which consists of 20 trains with 50 stimuli per train and intertrain interval of 30 s (1000 stimuli in total).ResultsNo differences were found for rMT and MEPs size between the two groups at T₀. Smaller MEPs amplitudes at both T₁ and T₂ were observed in all subjects, although this was significantly more pronounced in controls than in patients.ConclusionsCompared to normal individuals, patients exhibited an impairment of the LTD-like mechanisms induced by inhibitory rTMS, thus adding support to the involvement of GABA in RLS pathophysiology. Although future studies with a larger population are needed, TMS is confirmed to be effective in noninvasive probing of the neurophysiology and neurochemistry of RLS.     

Effect of Transcranial Static Magnetic Field Stimulation Over the Sensorimotor Cortex on Somatosensory Evoked Potentials in Humans

BackgroundThe motor cortex in the human brain can be modulated by the application of transcranial static magnetic field stimulation (tSMS) through the scalp. However, the effect of tSMS on the excitability of the primary somatosensory cortex (S1) in humans has never been examined.ObjectiveThis study was performed to investigate the possibility of non-invasive modulation of S1 excitability by the application of tSMS in healthy humans.MethodstSMS and sham stimulation over the sensorimotor cortex were applied to 10 subjects for periods of 10 and 15 min. Somatosensory evoked potentials (SEPs) following right median nerve stimulation were recorded before and immediately after, 5 min after, and 10 min after tSMS from sites C3′ and F3 of the international 10-20 system of electrode placement. In another session, SEPs were recorded from 6 of the 10 subjects every 3 min during 15 min of tSMS.ResultsAmplitudes of the N20 component of SEPs at C3′ significantly decreased immediately after 10 and 15 min of tSMS by up to 20%, returning to baseline by 10 min after intervention. tSMS applied while recording SEPs every 3 min and sham stimulation had no effect on SEP.ConclusionstSMS is able to modulate cortical somatosensory processing in humans, and thus might be a useful tool for inducing plasticity in cortical somatosensory processing. Lack of change in the amplitude of SEPs with tSMS implies that use of peripheral nerve stimulation to cause SEPs antagonizes alteration of the function of membrane ion channels during exposure to static magnetic fields.     

Focused Ultrasound-mediated Non-invasive Brain Stimulation: Examination of Sonication Parameters

BackgroundTranscranial focused ultrasound (FUS) has emerged as a new brain stimulation modality. The range of sonication parameters for successful brain stimulation warrants further investigation.ObjectiveThe objective of this study was to examine the range of FUS sonication parameters that minimize the acoustic intensity/energy deposition while successfully stimulating the motor brain area in Sprague–Dawley rats.MethodsWe transcranially administered FUS to the somatomotor area of the rat brain and measured the acoustic intensity that caused excitatory effects with respect to different pulsing parameters (tone-burst duration, pulse-repetition frequency, duty cycle, and sonication duration) at 350 and 650 kHz of fundamental frequency.ResultsWe observed that motor responses were elicited at minimum threshold acoustic intensities (4.9–5.6 W/cm² in spatial-peak pulse-average intensity; 2.5–2.8 W/cm² in spatial-peak temporal-average intensity) in a limited range of sonication parameters, i.e. 1–5 ms of tone-burst duration, 50% of duty cycle, and 300 ms of sonication duration, at 350 kHz fundamental frequency. We also found that the pulsed sonication elicited motor responses at lower acoustic intensities than its equivalent continuous sonication.ConclusionOur results suggest that the pulsed application of FUS selectively stimulates specific brain areas-of-interest at an acoustic intensity that is compatible with regulatory safety limits on biological tissue, thus allowing for potential applications in neurotherapeutics.     

Subclinical neurological involvement does not develop if Wilson's disease is treated early

Background & aimsWilson's disease (WD) is a genetic disorder of copper metabolism causing dysfunctions of various organs, mostly the liver and brain. If untreated, WD is fatal, but early treatment results in a good prognosis, although the long-term neurological outcome has not yet been clarified. To address this issue, we evaluated the neurological status of early-treated WD patients without overt nervous system impairment using neurophysiological, neuropsychological and neuroimaging procedures at least 10 years after treatment onset.MethodsThirty-eight WD patients (18 females, aged 24.47 ± 7.50 years), who received an early diagnosis (in presymptomatic or mild/moderate liver disease stages without neurological involvement) and prompt treatment, were clinically evaluated with the Global Assessment Scale. Presentation was hepatic in 36 subjects (95%), while 2 patients (5%) were presymptomatic. A neurophysiological study was performed to explore the central motor conduction time of the upper and lower limbs, and motor cortex excitability using single pulses and paired-pulse transcranial magnetic stimulation. Neuroimages were obtained with brain magnetic resonance scans. Cognitive abilities, and psychiatric and behavioral disturbances were evaluated with neuropsychological tests.ResultsPatients were undergoing treatment with penicillamine (7 patients) or zinc salts (31 patients) with good adherence. They did not present any neurological signs at clinical evaluation or at specific scale of impairment, the mean Global Assessment Scale score was 0.3 ± 0.7. Magnetic resonance imaging, transcranial magnetic stimulation studies and neuropsychological/neuropsychiatric assessment ruled out subclinical involvement.ConclusionsThis study suggests that early diagnosis and treatment of WD may prevent the onset of neurologic damage, even at subclinical level.     

Evidence for Pretreatment LICI Deficits Among Depressed Children and Adolescents With Nonresponse to Fluoxetine

BackgroundResearch suggests that alterations in gamma-aminobutyric acid receptor functioning have a role in depression. Paired-pulse transcranial magnetic stimulation (TMS) paradigms are noninvasive measures of cortical inhibitory and excitatory circuits.Objective/hypothesisThe present study examined pretreatment short-interval intracortical inhibition (SICI), long-interval cortical inhibition (LICI), and intracortical facilitation (ICF) in children and adolescents with major depressive disorder who were initiating fluoxetine treatment. The primary objective was to examine the relationship of these measures with subsequent treatment response. It was hypothesized that alterations in pretreatment GABA and glutamate mediated neurotransmission, would be associated with fluoxetine nonresponse.MethodsSixteen children and adolescents with major depressive disorder underwent paired-pulse TMS testing before beginning fluoxetine treatment. Response was prospectively characterized by scores of 1 or 2 on the Clinical Global Impression Scale and less than 40 on the Children's Depression Rating Scale-Revised after 6 weeks of fluoxetine treatment (20–40 mg/day).ResultsEight patients responded to treatment. Least-squares mean LICI values were consistently higher bilaterally for treatment nonresponders. Higher LICI values indicate less inhibition and impaired GABA_B functioning. There was no significant effect of treatment response on the measures of SICI and ICF.ConclusionsOur findings suggest that deficits in pretreatment GABA_B may be related to fluoxetine nonresponse in depressed youth. This is congruent with prior work demonstrating that GABA_B interneurons have serotonergic input and antidepressants modulate GABA_B receptors. These findings also show that TMS paradigms have utility in studying the neurophysiology and treatment of childhood mood disorders.RegistrationsCortical Excitability and Inhibition in Children and Adolescents With Major Depressive Disorder, http://www.clinicaltrials.gov/ct2/show/NCT00896090?term=cortical+excitability+and+inhibition&rank=2, NCT00896090; Sequential Treatment of Pediatric MDD to Increase Remission and Prevent Relapse, http://www.clinicaltrials.gov/ct2/show/NCT00612313?term=Sequential+Treatment+and+MDD&rank=1, NCT00612313.     

Smartphone-based tactile cueing improves motor performance in Parkinson's disease

IntroductionVisual and auditory cueing improve functional performance in Parkinson's disease (PD) patients. However, audiovisual processing shares many cognitive resources used for attention-dependent tasks such as communication, spatial orientation, and balance. Conversely, tactile cues (TC) may be processed faster, with minimal attentional demand, and may be more efficient means for modulating motor-cognitive performance. In this study we aimed to investigate the efficacy and limitations of TC for modulating simple (heel tapping) and more complex (walking) motor tasks (1) over a range of cueing intervals, (2) with/without a secondary motor task (holding tray with cups of water).MethodsTen PD patients (71 ± 9 years) and 10 healthy controls (69 ± 7 years) participated in the study. TCs was delivered through a smart phone attached to subjects' dominant arm and were controlled by a custom-developed Android application.ResultsPD patients and healthy controls were able to use TC to modulate heel tapping (F(3.8,1866.1) = 1008.1, p < 0.001), and partially modulate walking (F(3.5,1448.7) = 187.5, p < 0.001) tasks. In the walking task, PD patients modulated performance over a narrower range of cueing intervals (R² = 0.56) than healthy controls (R² = 0.84; group difference F(3.5,1448.7) = 8.6, p < 0.001). TC diminished synchronization error associated with performance of secondary motor task during walking in PD patients and healthy controls (main effect of Task (F(1,494) = 0.4; p = 0.527), Task X Group interaction (F(1,494) = 0.5; p = 0.493)).ConclusionThis study expands modalities of TC usage for movement modulation and motor-cognitive integration in PD patients. The smartphone TC application was validated as a user-friendly movement modulation aid.     

Progression of small vessel disease correlates with cortical thinning in Parkinson’s disease

ObjectiveCerebral small-vessel disease (SVD) is a risk factor for dementia in Parkinson’s disease (PD), however the pathophysiological role of SVD in PD-dementia is unclear. We investigated the impact of baseline and progression of SVD on cortical thickness and the correlation to cognition.MethodsSeventy-three mild PD patients with baseline and follow-up structural MRI scans, serial clinical and neuropsychological assessments were studied. SVD included the load of white matter hyperintensities (WMH), lacunes and perivascular spaces (PVS). WMH progression was assessed using the modified Rotterdam Progression scale, while for lacunes and PVS, development of new lesions was considered as lesion progression. Patients were classified as having SVD-progression and SVD-no-progression based on the longitudinal changes in their SVD measures. Freesurfer was used to measure baseline and follow-up regional cortical thickness and subcortical volumes and correlated to cognitive performance.ResultsFourteen patients were classified as SVD-progression and 59 as SVD-no-progression. Over 18 months, PD SVD-progression demonstrated significant cortical thinning in the left frontal and bilateral parietal regions with associated decline in memory, executive function, and motor functions. PD SVD-progression also had reduced volumes in the nucleus accumbens and amygdala at baseline and greater atrophy in the caudate nucleus over 18 months.DiscussionThe extent and progression of SVD is associated with focal cerebral atrophy and domain-specific cognitive dysfunction. Measures to retard SVD may be potentially useful in preventing dementia in PD.     

Hypertrophic olivary degeneration: A clinico-radiologic study

IntroductionThe frequency and causes of hypertrophic olivary degeneration (HOD) are unknown. We compared the clinical and radiological characteristics of unilateral HOD and bilateral HOD.MethodsWe performed a search of a radiologic report database for patients who were radiologically diagnosed as having HOD. This database includes the patients examined at the Mayo Clinic in Florida and Arizona. We used the search terms “hypertrophic olivary degeneration”, “HOD”, and “olivary” in the reports recorded from 1995 to 2015. Pertinent medical records and magnetic resonance imaging (MRI) scans of the brain for those with HOD were reviewed retrospectively.ResultsWe identified 142 MRI studies on 95 cases who had radiologically proven HOD, 39 cases had unilateral HOD and 56 with bilateral HOD. In symptomatic cases, the most common symptom was ataxia. Palatal tremor was observed in almost half of all HOD cases. While cerebrovascular diseases were the most frequent etiology in both types of HOD (n = 24, 62% in unilateral; n = 17, 30% in bilateral), more than half of bilateral HOD cases had an unknown etiology (52%, n = 29), whereas only 13% (n = 5) of the unilateral cases had an unknown etiology (χ² test, P < 0.001). The lesions of unilateral HOD had a tendency to improve radiologically over time, whereas those associated with bilateral HOD were likely to worsen (χ² test, P < 0.05).ConclusionsOur study showed that bilateral HOD is more common than unilateral HOD. Half of bilateral HOD cases had no obvious cause and some worsened over time. This may implicate a possible primary neurodegenerative process.     

Non-invasive Vagus Nerve Stimulation in Healthy Humans Reduces Sympathetic Nerve Activity

BackgroundVagus nerve stimulation (VNS) is currently used to treat refractory epilepsy and is being investigated as a potential therapy for a range of conditions, including heart failure, tinnitus, obesity and Alzheimer's disease. However, the invasive nature and expense limits the use of VNS in patient populations and hinders the exploration of the mechanisms involved.ObjectiveWe investigated a non-invasive method of VNS through electrical stimulation of the auricular branch of the vagus nerve distributed to the skin of the ear – transcutaneous VNS (tVNS) and measured the autonomic effects.MethodsThe effects of tVNS parameters on autonomic function in 48 healthy participants were investigated using heart rate variability (HRV) and microneurography. tVNS was performed using a transcutaneous electrical nerve stimulation (TENS) machine and modified surface electrodes. Participants visited the laboratory once and received either active (200 μs, 30 Hz; n = 34) or sham (n = 14) stimulation.ResultsActive tVNS significantly increased HRV in healthy participants (P = 0.026) indicating a shift in cardiac autonomic function toward parasympathetic predominance. Microneurographic recordings revealed a significant decrease in frequency (P = 0.0001) and incidence (P = 0.0002) of muscle sympathetic nerve activity during tVNS.ConclusiontVNS can increase HRV and reduce sympathetic nerve outflow, which is desirable in conditions characterized by enhanced sympathetic nerve activity, such as heart failure. tVNS can therefore influence human physiology and provide a simple and inexpensive alternative to invasive VNS.     

Distal muscle activity alterations during the stance phase of gait in restless leg syndrome (RLS) patients

ObjectiveTo assess if there is a circadian variation in electromyographical (EMG) muscle activity during gait in restless legs syndrome (RLS) patients and healthy control participants.MethodsGait assessment was done in 14 RLS patients and 13 healthy control participants in the evening (PM) and the morning (AM). Muscle activity was recorded bilaterally from the tibialis anterior (TA), lateral gastrocnemius (GL), rectus femoris (RF) and biceps femoris (BF) muscles.ResultsA circadian variation during the stance phase in only TA (PM > AM, p < 0.005) and BF (PM < AM, p = 0.008) activity was observed in control participants. Conversely no circadian variation was seen in any muscles in the RLS patients. RLS patients had an increased TA and GL activity (RLS > Controls, p < 0.05) during early stance and decreased GL activity (RLS < Controls, p < 0.01) during terminal stance in comparison to control participants in the evening. No other significant differences were noted between RLS patients and control participants. Activation of GL during the swing phase was noted in 79% of RLS patients and in 23% of control participants in the morning compared to 71% and 38% in the evening, respectively.ConclusionEMG muscle activity shows no circadian variation in RLS patients. Evening differences in gait muscle activation patterns between RLS patients and control participants are evident. These results extend our knowledge about alterations in spinal processing during gait in RLS. A possible explanation for these findings is central pattern generator sensitization caused by increased sensitivity in cutaneous afferents in RLS patients.     

A systematic review of mirror neuron system function in developmental coordination disorder: Imitation,motor imagery,and neuroimaging evidence

PURPOSEThe aim of this systematic review was to investigate the evidence of abnormal functioning of the mirror neuron system (MNS) in children and adults with developmental coordination disorder (DCD), through examination of imitation, motor imagery, and neuroimaging literature.METHODSThe following databases were comprehensively searched for relevant articles: CINAHL Plus, Embase, MEDLINE, PsycINFO, Pubmed, and Web of Science. Full-text articles of all potentially relevant citations were obtained and assessed for eligibility by two authors. Outcome measures of interest at a motor behaviour level were any measures of imitation or motor imagery proficiency and, at a neurological level, were any measures of neural activity in MNS brain regions. Due to differences in outcome measures between studies and the variables reported, a narrative review was undertaken to synthesise findings from the studies.RESULTSOverall, 31 articles met the inclusion criteria. Children and adults with DCD display deficits imitating meaningful and novel gestures and demonstrate different response patterns to controls when undertaking complex motor imagery tasks. Children with DCD present reduced activation and connectivity of frontal, parietal, and temporal MNS regions.CONCLUSIONSPreliminary evidence indicates some deficit in the functioning of the MNS at a motor behaviour and neurological level. As no published neuroimaging studies have been designed specifically to explore MNS function, these results must be interpreted with caution. Further research to explore the MNS hypothesis in greater detail, particularly from a neuroimaging perspective, has the potential to provide information on the underlying mechanisms of DCD, inform future research into the aetiology of this disorder, and inform intervention approaches.     

Determinants of denervation-independent depletion of putamen dopamine in Parkinson's disease and multiple system atrophy

BackgroundSevere putamen dopamine depletion characterizes Parkinson's disease (PD) and multiple system atrophy (MSA). The extent of the depletion is greater than can be accounted for by loss of nigrostriatal dopaminergic terminals alone. We used putamen tissue levels and ratios of cysteinyl and parent catechols to explore possible denervation-independent abnormalities of dopamine synthesis and fate in PD and MSA. 5-S-Cysteinyldopa (Cys-DOPA) is produced from spontaneous oxidation of DOPA and 5-S-cysteinyldopamine (Cys-DA) from spontaneous oxidation of DA.MethodsPost-mortem putamen tissue samples from 17 PD and 25 MSA patients and 30 controls were assayed for endogenous catechols including DA, its cytoplasmic metabolites (Cys-DA, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylethanol, and 3,4-dihydroxyphenylacetaldehyde), and tyrosine hydroxylation products proximal to DA (DOPA and Cys-DOPA).ResultsThe PD and MSA groups did not differ in mean values of parent or cysteinyl catechols, and the data for the two groups were lumped. In the patients an index of vesicular storage of DA (the ratio of DA to the sum of its cytoplasmic metabolites) averaged 54% of control (p = 0.001), and an index of L-aromatic-amino-acid decarboxylase (LAAAD) activity (the ratio of DA and the sum of its cytoplasmic metabolites to the sum of DOPA + Cys-DOPA) averaged 21% of control (p < 0.0001). An index of innervation (the sum of DOPA + Cys-DOPA) averaged 63% of control (p = 0.01).InterpretationBased on patterns of parent and cysteinyl catechols in putamen, PD and MSA involve decreased vesicular uptake and decreased LAAAD activity in the residual dopaminergic terminals. The combination seems to contribute importantly to dopamine depletion in these diseases.     

Effects of movement imitation training in Parkinson's disease: A virtual reality pilot study

BackgroundHypometria is a clinical motor sign in Parkinson's disease. Its origin likely emerges from basal ganglia dysfunction, leading to an impaired control of inhibitory intracortical motor circuits. Some neurorehabilitation approaches include movement imitation training; besides the effects of motor practice, there might be a benefit due to observation and imitation of un-altered movement patterns. In this sense, virtual reality facilitates the process by customizing motor-patterns to be observed and imitated.ObjectiveTo evaluate the effect of a motor-imitation therapy focused on hypometria in Parkinson's disease using virtual reality.MethodsWe carried out a randomized controlled pilot-study. Sixteen patients were randomly assigned in experimental and control groups. Groups underwent 4-weeks of training based on finger-tapping with the dominant hand, in which imitation was the differential factor (only the experimental group imitated). We evaluated self-paced movement features and cortico-spinal excitability (recruitment curves and silent periods in both hemispheres) before, immediately after, and two weeks after the training period.ResultsMovement amplitude increased significantly after the therapy in the experimental group for the trained and un-trained hands. Motor thresholds and silent periods evaluated with transcranial magnetic stimulation were differently modified by training in the two groups; although the changes in the input–output recruitment were similar.ConclusionsThis pilot study suggests that movement imitation therapy enhances the effect of motor practice in patients with Parkinson's disease; imitation-training might be helpful for reducing hypometria in these patients. These results must be clarified in future larger trials.     

Attention modulates step initiation postural adjustments in Parkinson freezers

BackgroundIn view of freezing of gait's circumstances of occurrence in Parkinson's disease, attentional resources appear to be involved in step initiation failure. Anticipatory postural adjustments (APAs) are essential because they allow unloading of the stepping leg and so create the conditions required for progression.Our main objective was to establish whether or not a change in attentional load during step initiation modulates APAs differently in patients with vs. without freezing of gait.MethodsThree groups of 15 subjects were recruited: elderly people and parkinsonian patients with or without freezing of gait. Attention was modulated before step execution by means of an auditory oddball discrimination task with event-related potential recording. The primary endpoint was the occurrence of inappropriate APAs following the attentional task, i.e. APAs not followed by a step after an intercurrent auditory stimulus.ResultsIn parkinsonian patients with freezing of gait, inappropriate APAs were recorded in 63% of the trials and were observed more frequently than in patients without freezing of gait (51%) and elderly controls (48%). Furthermore, inappropriate APAs in freezers were longer and more ample than in parkinsonian non-freezers and controls. Lastly, postural preparation was impaired in the parkinsonian patients.ConclusionOur results indicate that allocation of attentional resources during step preparation influences the release of APAs differently in freezers and non-freezers. Modulating attentional load is partly responsible for triggering an inappropriate motor program. This difficulty in focusing attention or resisting interference may contribute (at least in part) to the gait initiation failure observed in parkinsonian freezers.     

Exploring risk factors for stuttering development in Parkinson disease after deep brain stimulation

BackgroundStuttering is a speech disorder with disruption of verbal fluency, occasionally present in Parkinson's disease (PD). PD co-incident stuttering may either worsen or improve after Deep Brain Stimulation (DBS).MethodsSixteen out of 453 PD patients (3.5%) exhibited stuttering after DBS (PD-S) and were compared with a group of patients without stuttering (PD-NS) using non-parametric statistics.ResultsAfter DBS, stuttering worsened in 3 out of 4 patients with co-incidental stuttering. Most PD-S underwent subthalamic (STN) DBS, but 4 were implanted in the globus pallidus (GPi). Nine out of 16 PD-S (56.3%) reported a positive familial history for stuttering compared to none of the PD-NS. PD-S were mainly male (81.3%) with slight worse motor features compared to PD-NS.ConclusionHerein, we describe a group of PD patients developing stuttering after DBS and report the presence of a positive familial history for stuttering as the most relevant risk factor, suggesting a possible underlying genetic cause. The fact that stuttering occurred after either STN or GPi DBS is an argument against the impact of medication reduction on stuttering.     

Diabetes mellitus is independently associated with more severe cognitive impairment in Parkinson disease

BackgroundThere is increasing interest in interactions between metabolic syndromes and neurodegeneration. Diabetes mellitus (DM) contributes to cognitive impairment in the elderly but its effect in Parkinson disease (PD) is not well studied.ObjectiveTo investigate effects of comorbid DM on cognition in PD independent from PD-specific primary neurodegenerations.MethodsCross-sectional study. Patients with PD (n = 148); age 65.6 ± 7.4 years, Hoehn and Yahr stage 2.4 ± 0.6, with (n = 15) and without (n = 133) comorbid type II DM, underwent [¹¹C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) PET imaging to assess cortical cholinergic denervation, [¹¹C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation, and neuropsychological assessments. A global cognitive Z-score was calculated based on normative data. Analysis of covariance was performed to determine cognitive differences between subjects with and without DM while controlling for nigrostriatal denervation, cortical cholinergic denervation, levodopa equivalent dose and education covariates.ResultsThere were no significant differences in age, gender, Hoehn and Yahr stage or duration of disease between diabetic and non-diabetic PD subjects. There was a non-significant trend toward lower years of education in the diabetic PD subjects compared with non-diabetic PD subjects. PD diabetics had significantly lower mean (±SD) global cognitive Z-scores (−0.98 ± 1.01) compared to the non-diabetics (−0.36 ± 0.91; F = 7.78, P = 0.006) when controlling for covariate effects of education, striatal dopaminergic denervation, and cortical cholinergic denervation (total model F = 8.39, P < 0.0001).ConclusionDiabetes mellitus is independently associated with more severe cognitive impairment in PD likely through mechanisms other than disease-specific neurodegenerations.     

Bradykinesia of posed smiling and voluntary movement of the lower face in Parkinson's disease

ObjectiveImpaired facial expression, including spontaneous and emotional movements such as smiling, has been often reported in Parkinson's disease (PD). There is a general consensus that spontaneous smiling is abnormal in PD. Investigations on posed smiling yield contrasting results. Moreover, no study has yet addressed the relationship between posed smiling and abnormalities of voluntary movements of the lower face, global motor impairment and the effects of dopaminergic medication.MethodsWe investigated the kinematics of posed smiling (mimicking a smile shown in a picture) and those of voluntary movements of the lower face (showing the teeth as fast as possible – voluntary grinning) in 15 patients with PD (ON and OFF therapy) and in 16 healthy controls. Facial movements were recorded using a 3D optoelectronic system and analyzed using dedicated software.ResultsSome kinematic parameters of both posed smiling and voluntary grinning were abnormally lower in PD patients in comparison to healthy subjects. The kinematics of posed smiling correlated with those of voluntary grinning in PD patients but not in healthy controls. Posed smiling and voluntary grinning abnormalities were related to global motor severity but did not significantly improve upon L-dopa administration.ConclusionsThese results suggest that posed smiling and voluntary grinning are both abnormal in PD patients and that they are likely mediated by a common pathophysiological mechanism.     

Spontaneous improvement in both obstructive sleep apnea and cognitive impairment after stroke

BackgroundKnowledge available about the relationship between obstructive sleep apnea (OSA) and cognitive impairment after stroke is limited. The evolution of OSA and cognitive performance after stroke is not sufficiently described.MethodsWe prospectively enrolled and examined acute stroke patients without previously diagnosed OSA. The following information was collected: (1) demographics, (2) sleep cardio-respiratory polygraphy (PG) at 72 h, day seven, month three, and month 12 after stroke, (3) post-stroke functional disability tests at entry and at months three and 12, and (4) cognition (attention and orientation, memory, verbal fluency, language, and visual-spatial abilities) using the revised Addenbrooke's Cognitive Examination (ACE-R) at months three and 12.ResultsOf 68 patients completing the study, OSA was diagnosed in 42 (61.8%) patients. The mean apnea/hypopnea index (AHI) at study entry of 21.0 ± 13.7 spontaneously declined to 11.6 ± 11.2 at month 12 in the OSA group (p < 0.0005). The total ACE-R score was significantly reduced at months three (p = 0.005) and 12 (p = 0.004) in the OSA group. Poorer performance on the subtests of memory at months 3 (p = 0.039) and 12 (p = 0.040) and verbal fluency at months 3 (p < 0.005) and 12 (p < 0.005) were observed in the OSA group compared to non-OSA group. Visual-spatial abilities in both the OSA (p = 0.001) and non-OSA (p = 0.046) groups and the total ACE-R score in the OSA (p = 0.005) and non-OSA (p = 0.002) groups improved.ConclusionsA high prevalence of OSA and cognitive decline were present in patients after an acute stroke. Spontaneous improvements in both OSA and cognitive impairment were observed.     

Levodopa/carbidopa intestinal gel can improve both motor and non-motor experiences of daily living in Parkinson’s disease: An open-label study

BackgroundLevodopa/carbidopa intestinal gel therapy (LCIG) can efficiently improve several motor and non-motor symptoms of advanced Parkinson's disease (PD). The recently developed Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) improved the original UPDRS making it a more robust tool to evaluate therapeutic changes. However, previous studies have not used the MDS-UPDRS and the Unified Dyskinesia Rating Scale (UDysRS) to assess the efficacy of LCIG.ObjectivesOur aim was to determine if the MDS-UPDRS and UDysRS could detect improvement in the experiences of daily living following 1-year LCIG treatment.MethodsIn this prospective, multicenter, open-label study, 34 consecutive patients undergoing LCIG treatment were enrolled. Patients were examined twice: prior to LCIG initiation and 12 months later. Impact of PD-related symptoms and dyskinesia was assessed by the MDS-UPDRS and UDysRS.ResultsNon-motor Experiences of Daily Living part of MDS-UPDRS improved from 20 (median, interquartile-range, IQR:14–23) to 16 points (median, IQR:12–20, p = 0.044) and the Motor Experiences of Daily Living ameliorated from 24 (median, IQR:20–29) to 18 points (median, IQR:13–25, p = 0.025). Health-related quality of life, measured by PDQ-39, also improved from 35.4 (median, IQR:26.9–50.3) to 27.0 (median, IQR:21.3–31.4) points (p = 0.003). The total score of UDysRS decreased from 47 (median, IQR:36–54) to 34 (median, IQR:21–45) points (p = 0.003).ConclusionsAs far as the authors are aware of, our paper is the first to evaluate the impact of LCIG on dyskinesia by the means of UDysRS. Changes in MDS-UPDRS and UDysRS confirm that LCIG treatment can efficiently improve experiences of daily living in advanced PD.