Kuan-Lin Lai

rTMS Combined With Task-Oriented Training to Improve Symmetry of Interhemispheric Corticomotor Excitability and Gait Performance After Stroke: A Randomized Trial

Background. The model of interhemispheric competition after stroke has been established for the upper but not for the lower extremity. Repetitive transcranial magnetic stimulation (rTMS) of the brain has been shown to modulate cortical excitability. Objective. The purpose of this study was to investigate the effects of rTMS followed by task-oriented training on cortical excitability and walking performance in individuals with chronic stroke. Methods. A total of 24 patients with average Fugl-Meyer lower limb scores of 17.88 ± 5.27 and average walking speeds of 63.81 ± 18.25 cm/s were randomized into an experimental group and a control group. Participants received rTMS (experimental group) or sham rTMS (control group) followed by task-oriented training (30 minutes) for 10 sessions over 2 weeks. Repetitive TMS was applied at a 1-Hz frequency over the leg area of the motor cortex of the unaffected hemisphere for 10 minutes. Outcomes, including motor-evoked potential (MEP), lower-extremity Fugl-Meyer score, and gait performance, were measured before and after training. Results. Decreased interhemispheric asymmetry of the amplitude of the MEP was noted after rTMS and task-oriented training. Improvement in spatial asymmetry of gait was comparable with increased symmetry in interhemispheric excitability. Motor control and walking ability were also significantly improved after rTMS and task-oriented training. Conclusions. rTMS enhances the effect of task-oriented training in those with chronic stroke, especially by increasing gait spatial symmetry and corticomotor excitability symmetry.

Cognitive and neuropsychiatric correlates of EEG dynamic complexity in patients with Alzheimer's disease.

This study assessed the utility of multiscale entropy (MSE), a complexity analysis of biological signals, to identify changes in dynamics of surface electroencephalogram (EEG) in patients with Alzheimers disease (AD) that was correlated to cognitive and behavioral dysfunction. A total of 108 AD patients were recruited and their digital EEG recordings were analyzed using MSE methods. We investigate the appropriate parameters and time scale factors for MSE calculation from EEG signals. We then assessed the within-subject consistency of MSE measures in different EEG epochs and correlations of MSE measures to cognitive and neuropsychiatric symptoms of AD patients. Increased severity of AD was associated with decreased MSE complexity as measured by short-time scales, and with increased MSE complexity as measured by long-time scales. MSE complexity in EEGs of the temporal and occipitoparietal electrodes correlated significantly with cognitive function. MSE complexity of EEGs in various brain areas was also correlated to subdomains of neuropsychiatric symptoms. MSE analysis revealed abnormal EEG complexity across short- and long-time scales that were correlated to cognitive and neuropsychiatric assessments. The MSE-based EEG complexity analysis may provide a simple and cost-effective method to quantify the severity of cognitive and neuropsychiatric symptoms in AD patients.

Combination of rTMS and Treadmill Training Modulates Corticomotor Inhibition and Improves Walking in Parkinson Disease A Randomized Trial

Background. Repetitive transcranial magnetic stimulation (rTMS) of the brain has been shown to modulate cortical excitability. Combinations of rehabilitation therapies with rTMS might enhance the therapeutic effects. Objective. The purpose of this study was to investigate the effects of high-frequency rTMS followed by treadmill training on cortical inhibition and walking function in individuals with Parkinson disease (PD). Methods. A total of 20 patients with PD were randomized into an experimental group and a control group. Participants received rTMS (experimental group) or sham rTMS (control group) followed by treadmill training (30 minutes) for 12 sessions over 4 weeks. Repetitive TMS was applied at a 5-Hz frequency over the leg area of the motor cortex contralaterally to the more affected side for 6 minutes. Outcomes, including corticomotor inhibition and walking performance, were measured before and after training. Results. The results showed significant time effects on almost all corticomotor and functional variables. There are significant interaction effects between group and time of evaluation on the motor threshold, duration of the cortical silent period, and short interval intracortical inhibition of the contralateral hemisphere relatively to the more affected side as well as on the fast walking speed and timed up and go. Conclusions. The findings suggested that combination of rTMS and treadmill training enhances the effect of treadmill training on modulation of corticomotor inhibition and improvement of walking performance in those with PD.

Reduced functional connectivity between salience and visual networks in migraine with aura

Background Migraine with visual aura (MA) is associated with distinct visual disturbances preceding migraine attacks, but shares other visual deficits in between attacks with migraine without aura (MO). Here, we seek to determine if abnormalities specific to interictal MA patients exist in functional brain connectivity of intrinsic cognitive networks. In particular, these networks are involved in top-down modulation of visual processing. Methods Using resting-state functional magnetic resonance imaging, whole-brain functional connectivity maps were derived from seeds placed in the anterior insula and the middle frontal gyrus, key nodes of the salience and dorsal attention networks, respectively. Twenty-six interictal MA patients were compared with 26 matched MO patients and 26 healthy matched controls. Results The major findings were: connectivity between the anterior insula and occipital areas, including area V3A, was reduced in MA but not in MO. Connectivity changes between the anterior insula and occipital areas further correlated with the headache severity in MA only. Conclusions The unique pattern of connectivity changes found in interictal MA patients involved area V3A, an area previously implicated in aura generation. Hypoconnectivity to this and other occipital regions may either represent a compensatory response to occipital dysfunctions or predispose MA patients to the development of aura.

Intermittent theta burst stimulation over primary motor cortex enhances movement-related beta synchronisation

OBJECTIVE The objective of this study is to investigate how transcranial magnetic intermittent theta burst stimulation (iTBS) with a prolonged protocol affects human cortical excitability and movement-related oscillations. METHODS Using motor-evoked potentials (MEPs) and movement-related magnetoencephalography (MEG), we assessed the changes of corticospinal excitability and cortical oscillations after iTBS with double the conventional stimulation time (1200 pulses, iTBS1200) over the primary motor cortex (M1) in 10 healthy subjects. Continuous TBS (cTBS1200) and sham stimulation served as controls. RESULTS iTBS1200 facilitated MEPs evoked from the conditioned M1, while inhibiting MEPs from the contralateral M1 for 30 min. By contrast, cTBS1200 inhibited MEPs from the conditioned M1. Importantly, empirical mode decomposition-based MEG analysis showed that the amplitude of post-movement beta synchronisation (16-26 Hz) was significantly increased by iTBS1200 at the conditioned M1, but was suppressed at the nonconditioned M1. Alpha (8-13 Hz) and low gamma-ranged (35-45 Hz) rhythms were not notably affected. Movement kinetics remained consistent throughout. CONCLUSIONS TBS1200 modulated corticospinal excitability in parallel with the direction of conventional paradigms with modestly prolonged efficacy. Moreover, iTBS1200 increased post-movement beta synchronisation of the stimulated M1, and decreased that of the contralateral M1, probably through interhemispheric interaction. SIGNIFICANCE Our results provide insight into the underlying mechanism of TBS and reinforce the connection between movement-related beta synchronisation and corticospinal output.

A 13-year long-term outcome study of elderly with chronic daily headache

We established a cohort of 60 subjects with chronic daily headache (CDH) out of 1533 community-based elderly in 1993 and finished two short-term follow-ups in 1995 and 1997. All of the 26 survivors without dementia (4 M/22 F, mean age 82.7 ± 3.4 years) finished the follow-up in 2006. The mean headache frequency was 8.4 ± 11.8 days per month in the past year, and seven (27±) had persistent CDH. Based on the International Classification of Headache Disorders, 2nd edn, the CDH subtypes diagnoses were chronic migraine in three subjects, chronic tension-type headache in three, and one with medication-overuse headache. All these seven subjects had CDH during the 1995 and 1997 follow-ups. The diagnosis of CDH with migrainous features increased from 25 to 71± in those with CDH from 1993 to 2006. Migraine was the most common headache type in those with CDH resolution. Aggressive treatment should be applied especially for those with persistent CDH at short-term follow-ups.

Multimodal evoked potentials of Kennedy's disease

BACKGROUND Kennedys disease (KD) is an X-linked recessive polyglutamine disease. Traditionally, it is a lower motor neuron syndrome with additional features such as gynecomastia and tremor. Sensory symptoms are minimal if ever present. We used multimodal evoked potential (EPs) tests to study the distribution of the involvement of the disease. METHODS Visual, brainstem auditory, somatosensory and motor EPs were studied in six KD patients. All of them had typical presentations and had been proved genetically. RESULTS Abnormal findings were noted as follows: prolonged peak latencies of visual EPs, increased hearing threshold level, inconsistent brainstem auditory EPs, decreased amplitudes of cortical potentials of somatosensory EPs, and increased motor threshold to transcranial magnetic stimulation. CONCLUSIONS Our multimodal EP studies showed that KD involved multiple levels of the nervous system. It implies the widespread effects of the mutant androgen receptors.

Hippocampus and amygdala volume in relation to migraine frequency and prognosis

Objectives To investigate the structural changes of hippocampus and amygdala and their relationships with migraine frequency and prognosis. Methods Hippocampus and amygdala volumes were measured by 3-T brain magnetic resonance imaging (MRI) in 31 controls and 122 migraine patients who were categorized into eight groups by headache frequency: group 1 (1–2 headache days/month), 2 (3–4), 3 (5–7), 4 (8–10), 5 (11–14), 6 (15–19), 7 (20–24), and 8 (25–30). Headache frequency was reassessed 2 years later and a frequency reduction ≥50% was regarded a good outcome. Results Hippocampus and amygdala volumes fluctuated in patient groups but did not differ from the controls. In migraine patients, the bilateral hippocampus volumes peaked in group 3. The volumes and headache frequencies correlated positively in groups 2–3 on bilateral sides (L: r = 0.44, p = 0.007; R: r = 0.35, p = 0.037), and negatively in groups 3–7 on the left side (5–24 days/month; L: r = −0.31, p = 0.004) and groups 3–8 on the right side (r = −0.31, p = 0.002). The left amygdala volume also peaked in group 3, and correlated with headache frequency in groups 1–3 (r = 0.34, p = 0.020) and groups 3–6 (r = −0.30, p = 0.012). The volumetric changes of the right amygdala with headache frequency did not reach statistical significance. At 2-year follow-up, the right hippocampus volume was positively associated with a good migraine outcome after adjustment of headache frequency (OR 4.72, p = 0.024). Conclusions Hippocampus and amygdala display a structural plasticity linked to both headache frequency and clinical outcome of migraine.

Brainstem Excitability is Increased in Subjects with Palmomental Reflex

BACKGROUND/PURPOSE The palmomental reflex (PMR) is a brief contraction of the mentalis muscles caused by a scratch over the thenar eminence, i.e. a brainstem reflex to afferents of upper limb. Using electrophysiologic methods, we studied the characteristics of brainstem excitability in PMR subjects. METHODS Ten healthy PMR subjects were included in the study. Brainstem excitability was assessed with electrical stimulation at the trigeminal nerve, median nerve, ulnar nerve, and sural nerve with recordings at the mentalis muscles. A comparison was made by the probability between the mechanical scratch and the electrical stimulation to evoke the visible muscle contraction of mentalis. RESULTS An electrical stimulus was able to elicit mentalis muscle responses (MMR(electrical)) in all the subjects if the stimulus was of sufficient strength. Using electrical stimulation, the median nerve at the wrist was the best site to evoke MMR(electrical). However, in PMR subjects, the probability of MMR(electrical) to median nerve stimulation was less than that of MMR(scratch), i.e. the clinical findings of PMR. Significantly lower thresholds and higher amplitudes were noted in PMR subjects only when the median nerve was stimulated. The onset latency did not show any difference between the two groups despite the stimulation sites. CONCLUSION The facial motor neurons to median nerve stimulation are more sensitive in PMR subjects. In healthy PMR subjects, this indicates that the excitability increases only in the specific neuronal circuits between the lower cervical spinal cord and the facial motor nucleus in the rostral medulla. MMR(electrical) is a physiologic phenomenon, and PMR is a sign of increased brainstem excitability.

Abnormal sensory-motor integration in a patient with anti-NMDA-receptor encephalitis

In this report, we describe the case of patient who showed abnormal corticomotor responses after peripheral afferent stimulation, namely sensory afferent inhibition (SAI) and sensory afferent facilitation (SAF), and its reversibility after treatment in a patient with anti-N-methyl D-aspartate receptor (NMDAR) encephalitis. A 26-year-old woman was admitted to a hospital after experiencing fever and headache for 11 days. Comprehensive serological studies, a brain magnetic resonance imaging scan, and cerebrospinal fluid (CSF) analysis were unremarkable. In the following days, she developed hallucinations and generalized tonic seizures. A repeat CSF analysis showed lymphocytic pleocytosis (261 white blood cells/ mm; 97% lymphocytes) and a normal protein concentration (63 mg/dl). She continued to have hyperkinetic movements and hyper-pyrexia despite receiving antibacterial and antiviral treatments. Electroencephalography showed diffuse slow waves with unremarkable somatosensory evoked potentials and brainstem auditory evoked potentials. After 30 days, she became unresponsive and had respiratory failure, and was then transferred to our hospital. On examination, she presented with dystonic posturing, oro-lingual-facial dyskinesia, and myoclonic movements. A computed tomography scan of the chest and abdomen and a trans-vaginal sonogram disclosed no abnormalities. Her serum and CSF studies were positive for anti-NMDAR antibodies. Transcranial magnetic stimulation (TMS) demonstrated intact corticospinal tracts with normal latencies and thresholds for motor-evoked potentials (MEPs). However, the conditioned peripheral afferent stimulation failed to show an SAI response at inter-stimulus intervals (ISIs) in the range of 15–25 ms, while exaggerated SAF responses were observed at ISIs between 30 and 70 ms. These data are contrasted to data from a healthy control subject in Fig. 1a, b and Table 1. The patient’s condition showed a little improvement in that she started to have some slow responses to verbal stimulation after steroid pulse therapy and plasmapheresis. Intravenous immunoglobulin was then started, and her condition improved dramatically. In a 3-week follow-up SAI/SAF study, the SAF had made notable progress toward normalization, but a normal SAI response was still absent (Fig. 1c; Table 1). NMDARs are expressed at high levels in the central nervous system, and play an important role in excitatory synaptic transmission and synaptic plasticity. Patients with anti-NMDAR antibodies usually present with various neurological symptoms presumably resulting from an AMPA receptor-mediated hyperglutamatergic state [1]. The MEP amplitude and latency of the patient described herein were similar to normal values. Impaired SAI and exaggerated SAF, such as observed in the presently described case, are suggestive of abnormal motor-sensory Y.-H. Dou K.-L. Lai K.-K. Liao S.-P. Chen (&) Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, 112 Taipei, Taiwan e-mail: chensp1977@gmail.com