Association between Excessive Daytime Sleepiness and the Cholinergic Ascending Reticular System in Parkinson's Disease.

BACKGROUND: Excessive daytime sleepiness (EDS) in Parkinson's disease (PD) may occur because of dysfunction on the brain areas in controlling wakefulness; however, the pathophysiology of EDS in PD has not been completely clarified. The Pb component of a middle-latency auditory evoked response (MLR) is generated from the cholinergic ascending reticular activating system (ARAS) projecting to the auditory cortex via the thalamus. We examined the association between EDS and the Pb component in patients with PD. METHODS: Participants were 38 patients with nondemented PD and 18 age-matched controls. EDS was evaluated using the Japanese version of the Epworth Sleepiness Scale (JESS). PD patients were classified into the high sleepiness (HS) group and the low sleepiness (LS) group by the score of JESS. MLRs were recorded from the scalp with each earlobe as a reference under presentation of 1-Hz and 65- to 90-dB click sounds. RESULTS: There was no difference in age, duration, and motor function between the HS PD and the LS PD groups. Peak latencies of Pb were not different between PD group and controls; however, Pb amplitudes were significantly increased in the HS PD group compared with the LS PD group and controls. CONCLUSION: One of the mechanisms of EDS in PD was suggested to be dysregulation of cholinergic neurons from the ARAS projecting to cortical cholinergic neurons.

Event-Related Synchronization and Desynchronization of High-Frequency Electroencephalographic Activity during a Visual Go/No-Go Paradigm.

OBJECTIVE: High-frequency electroencephalography (EEG) activity has been observed in association with cognitive processing, including stimulus perception, consciousness and selective attention, in humans. The aim of this study was to compare visual-motor integrated processing between execution and inhibition of a motor response using event-related synchronization (ERS) and desynchronization (ERD) in the 15- to 80-Hz range and to investigate a relationship between event-related potentials (ERPs) and ERS/ERD in 10 normal young subjects. METHODS: EEGs were recorded from 21 scalp sites during a visual go/no-go paradigm. For ERPs, 40 artifact-free trials were averaged off-line referenced to linked ear lobes. In the ß and γ bands, ERS and ERD were calculated by time-frequency analysis. RESULTS: Go N2 and no-go N2 were elicited 200-250 ms after stimuli, and their distributions were predominant at Fz. Go P3 was predominantly elicited 340-360 ms after stimuli at Pz, whereas no-go P3 was predominantly elicited 360-380 ms after stimuli at Cz. ERD of the ß band at Fz and Cz during 300-600 ms showed in the go condition, whereas ERD showed between 39 and 42 Hz at F3 in the no-go condition. CONCLUSION: Oscillatory cortical response-related ß and γ activities differ between the processing of execution and inhibition in motor responses. ß ERDs in the sensorimotor areas with go stimuli may be related to motor responses, and γ ERDs in the left frontal area with no-go stimuli may be involved in the processing of inhibition of motor responses. © 2015 S. Karger AG, Basel.

Pramipexole-induced antecollis in patients with Parkinson's disease: Two cases and literature review.

Antecollis is considered to be relatively rare in Parkinson's disease (PD). Few cases of dopamine agonist-induce antecollis in PD have been reported. We described literature review of 12 PD patients including our 2 cases with pramipexole (PPX)-induced antecollis. The patients were predominantly Japanese, women and above 3 of Hoehn and Yahr stage. PPX-induced antecollis in PD was considered a type of dystonia of flexor neck muscle, and was improved soon after cessation or reduction of PPX. Our two cases improved their antecollis by overnight changing from PPX to ropinirole without deteriorating motor functions. Overnight switching of DA was considered useful as one option in the treatment of antecollis.

[A double-blind comparative study to evaluate the efficacy and safety of NerBloc® (rimabotulinumtoxinB) administered in a single dose to patients with cervical dystonia].

We conducted a single-dose, placebo-controlled, double-blind, dose-response study of NerBloc®(rimabotulinumtoxinB) in patients with cervical dystonia (placebo, 2,500 U, 5,000 U, 10,000 U). The primary endpoint, the change in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-total score at 4 weeks post dose from baseline, showed a significant improvement in all treatment groups (2,500 U, 5,000 U, 10,000 U) compared with the placebo group. As for the secondary endpoints, the change of TWSTRS subscales, severity, disability and pain scores, at 4 weeks post dose in 10,000 U group, showed a significant improvement compared with the placebo group, however, no significant differences were observed between 2,500 U or 5,000 U and placebo group. The subject's and physician's global assessments (visual analog scale; VAS) at 4 weeks post dose also showed significant improvement in all treatment groups relative to the placebo group, whereas subject's pain assessment (VAS) at 4 weeks post dose did not show significant improvement in any of treatment groups. The incidence rate of adverse events was not substantially different between the placebo group and 2,500 or 5,000 U group, but significantly higher in 10,000 U group than in the placebo group. Adverse events frequently observed in active drug groups included dry mouth/thirst and dysphagia, all of which were mild in severity. There were no adverse events that led to death, serious disorders or study discontinuations. The incidence rate of abnormal laboratory values did not show significant difference in any of parameters between the placebo group and any of treatment groups. NerBloc® possessing muscle relaxing effect is expected to be a potential treatment to improve symptoms of cervical dystonia. Clinically recommended dose will range from 2,500 U to 10,000 U. In this study, 10,000 U group was the most effective and the effect lasted the longest. The efficacy and safety profile of NerBloc ® in this study was similar to that in AN072-009 study conducted in the US.

Adversive seizures associated with periodic lateralised epileptiform discharges (PLEDs) after left orbital contusion.

We report a patient who presented with adversive seizures associated with periodic lateralised epileptiform discharges (PLEDs), a month after head trauma. The PLEDs predominantly involving the left frontal contacts became more frequent at the onset of adversive seizures during EEG. Brain MRI demonstrated a contusion scar in the left orbital cortex with reduced diffusion, not only around this orbital lesion but also in the ipsilateral anteromedial thalamus. Single photon emission computed tomography revealed focal cerebral hyperperfusion in the left medial orbitofrontal region, basal ganglia, and thalamus. The abnormal metabolism involving the thalamus and striatum could be associated with the ipsilateral orbital contusion and might have been caused by cortical-subcortical, trans-synaptic hyperactivity. Further studies are warranted to determine the role of subcortical structures in the generation of PLEDs and adversive seizures. [Published with video sequences].

Cardiac sympathetic degeneration correlates with olfactory function in Parkinson's disease.

Autonomic and olfactory dysfunctions are considered markers for preclinical diagnosis in Parkinson's disease (PD), because pathological changes in these systems can start before motor symptoms develop. We investigated whether cardiac sympathetic function and olfactory function are associated in PD. Participants comprised 40 nondemented patients with idiopathic PD, and age-matched controls. Cardiac sympathetic function was evaluated by (123) I-metaiodobenzylguanidine (MIBG) uptake, in terms of the heart to mediastinum (H/M) ratio in both early and delayed images, and the washout rate (WR). Olfactory function was evaluated using the Odor Stick Identification Test for Japanese, which evaluates the detection of 12 odorants familiar to Japanese participants. Smell identification scores were significantly lower (P < 0.001) in patients with PD than in controls. Smell identification scores correlated positively with early (P < 0.05) and delayed H/M ratios (P < 0.01), and inversely with the WR (P < 0.005) especially in patients with early PD (below 5 years of the start of motor symptoms), whereas smell identification scores did not correlate with any parameters of MIBG in the advanced PD (above 5 years of the start of motor symptoms). There was no correlation between motor symptom scores and smell identification scores, H/M ratios, or WR. The results suggest that the cardiac sympathetic nervous system might degenerate in parallel with the olfactory system in patients with early PD, and that these two systems might degenerate at a different rate of speed in advanced PD.

Effects of incense on brain function: evaluation using electroencephalograms and event-related potentials.

To evaluate the effect of the odor of incense on brain activity, electroencephalograms (EEGs) and event-related potentials (ERPs) in a push/wait paradigm were recorded in 10 healthy adults (aged 23-39 years) with normal olfactory function. EEG was recorded from 21 electrodes on the scalp, according to the International 10-20 system, and EEG power spectra were calculated by fast Fourier transform for 3 min before and during odor presentation. ERPs were recorded from 15 electrodes on the scalp before, during and after exposure to incense with intervals of 10 min. In a push/wait paradigm, two Japanese words, 'push' as the go stimulus and 'wait' as the no-go stimulus, appeared randomly on a CRT screen with equal probability. The subjects were instructed to push a button whenever the 'push' signal appeared. Fast alpha activity (10-13 Hz) increased significantly in bilateral posterior regions during incense exposure compared to that during rose oil exposure. The peak amplitudes of no-go P3 at Fz and Cz were significantly greater during incense inhalation. The latencies of go P3 and no-go P3, and the amplitude and latencies of no-go N2 did not change by exposure to the odors of both incense, rose and odorless air. These results suggest that the odor of incense may enhance cortical activities and the function of inhibitory processing of motor response.

[Inter-rater reliability while using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in patients with cervical dystonia].

We examined the inter-rater reliability for the evaluation of patients with cervical dystonia by using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) (translated into Japanese). The TWSTRS is a rating scale that assesses patients with cervical dystonia by grading their symptoms on a subscale of severity, disability, and pain. This study used to TWSTRS-severity scores to examine the inter-rater reliability among 27 evaluators (neurologists) by using videotaped images of 2 patients. Along with the total-severity score on the TWSTRS, the intra-class correlation (ICC) and the lower limit of the 95% confidence interval were calculated as indices of inter-rater reliability. A high ICC of 0.745 was obtained. The ICC obtained from another study conducted outside Japan was 0.763, which is almost equivalent to the result of our study. Thus, the TWSTRS has a favorable inter-rater reliability which suggests that this scale was sufficiently reliable to be used as an accurate and easily available rating tool during the treatment of cervical dystonia.

Smell identification in Japanese Parkinson's disease patients: using the odor stick identification test for Japanese subjects.

OBJECTIVE: The purpose of the present study was to clarify the olfactory functions of Japanese patients with idiopathic Parkinson's disease (IPD) using the odor stick identification test for Japanese (OSIT-J). METHODS: Fifty-four non-demented IPD patients (33 men and 21 women), ranging in age from 43 to 81 years (69.7+/-8.1 years) and 50 age- and gender-matched healthy controls who reported having no olfactory complaints were enrolled. OSIT-J consisted of 12 odorants familiar to Japanese subjects. Each subject sniffed each odor that was applied to paraffin paper. Next the subject chose 1 of 6 answers: 4 pictures associated with the odors labeled with their names, one of which was correct, and 2 other ones ("unknown" and "not detected"). RESULTS: The number of correct answers was significantly lower in the IPD group (4.4+/-2.7) than in the normal group (8.3+/-2.2) (p<0.0001). Even in IPD patients who could smell normal strength odors in subjective symptom, the number of correct answers decreased. The number of correct answers was not correlated with motor function, disease duration, or medication. CONCLUSION: The present study demonstrated that the smell identification ability of Japanese IPD patients was impaired based on the OSIT-J.

[Stiff-person syndrome with elevated anti-Epstein-Barr virus antibody].

Stiff-person syndrome, a relatively rare disease with a poor prognosis, presents as muscle stiffness, rigidity, and spasm. We reported a patient with this syndrome who was treated successfully. The patient was a 56-year-old Japanese man with respiratory infection-like prodromal symptoms. Episodes of painful spasm in both legs on extension and lordosis occurred spontaneously or were triggered with touch or pinprick stimuli at or below spinal level C3, and progressed subacutely. Tendon reflexes were hyperactive, Babinski's sign was positive, and vibration sense was reduced in the legs. Episodes of spasm were alleviated using diazepam. Even after discontinuing diazepam, these symptoms did not exacerbate. In this patient, although anti-glutamic acid decarboxylase (GAD) antibody was negative, anti-EB virus antibody was positive. No previous reports have described stiff-person syndrome with EB virus infection. However, a few cases of this syndrome associated with viral infection were recently reported and viral gene mimicity with GAD has been postulated. Viral infection might be considered as a probable cause of this syndrome.

Arterial hypertension in patients with left primary hemifacial spasm is associated with neurovascular compression of the left rostral ventrolateral medulla.

The aim of the study was to clarify the relationship between neurovascular compression of the rostral ventrolateral medulla and arterial hypertension in patients with primary hemifacial spasm. We enrolled 82 patients with primary hemifacial spasm and 82 age- and sex-matched magnetic resonance imaging (MRI) controls of the posterior cranial fossa. Neurovascular compression of the rostral ventrolateral medulla was assessed by MRI, and its association with arterial hypertension was investigated. No significant differences were found in prevalence of arterial hypertension between patients with primary hemifacial spasm and control subjects (39.0 vs. 29.3%, p=0.19). Thirty-two percent of the patients with left primary hemifacial spasm (n=44) and 47% of the patients with right primary hemifacial spasm (n=38) were hypertensive. Neurovascular compression of the left rostral ventrolateral medulla was observed in 86% of those with left (ipsilateral) primary hemifacial spasm with arterial hypertension (n=14) and 33% of those with left (ipsilateral) primary hemifacial spasm without (n=30). The association between neurovascular compression of the left rostral ventrolateral medulla and arterial hypertension was significant in patients with left (ipsilateral) primary hemifacial spasm (p=0.0012), but not in patients with right (contralateral) primary hemifacial spasm (p=0.18). Neurovascular compression of the left rostral ventrolateral medulla was more frequently observed in hypertensive patients with left primary hemifacial spasm, and neurovascular compression of the left rostral ventrolateral medulla correlated with arterial hypertension in these patients. These results are of potential clinical importance for the treatment of primary hemifacial spasm with arterial hypertension.

[Current status and prospects of medical therapy for dystonia].

The goal of medical therapy for primary dystonia is conservative. While botulinum toxin (BTX) therapy is a first choice for blepharospasm and cervical dystonia, medical therapy is selected as such for other types of dystonia. As oral medications, trihexyphenidyl and benzodiazepines are most frequently used. Muscle relaxants are also commonly used, but dopamine antagonists are not recommended because of the risk of inducing tardive dyskinesia. For childhood-onset generalized dystonia, levodopa should be considered to rule out levodopa-responsive dystonia. Mexiletine is reported to be effective not only for bleharospasm and cervical dystonia but for focal limb dystonia. To improve the therapeutic performance of BTX therapy for blepharospasm, it is recommended that corrugator supercilii and procerus muscles, as well as orbicularis oculi muscle, be added as target muscles. To improve the therapeutic performance of BTX therapy for cervical dystonia, it is recommended that this therapy be started as early as possible, especially within one year of illness, and that levator scapulae muscle be added as target if necessary. To improve usefulness of medical therapy for dystonia, its strategy must be standardized, and more useful therapies must be positively adopted. Algorithm for treatment of dystonia must also be established and generalized.