Navigated transcranial magnetic stimulation in amyotrophic lateral sclerosis

Introduction: Amyotrophic lateral sclerosis (ALS) is a set of disorders associated with preferential degeneration of both upper and lower motor neurons. Navigated transcranial magnetic stimulation (nTMS) is a tool used to perform noninvasive functional brain mapping. We aimed to assess function of upper motor neurons in ALS. Methods: nTMS was performed on 30 patients with ALS (mean age 54.4 ± 12.1 years) and 24 healthy volunteers (mean age 32.7 ± 13.3 years). Results: The resting motor threshold (MT) was significantly higher in ALS patients compared with controls (P < 0.001). The mean map areas were smaller in patients with ALS than in healthy individuals, although some patients with short disease duration had extended maps. Conclusions: Motor area maps serve as markers of upper motor neuron damage in ALS. Further research may elucidate the pathogenic mechanisms of the neurodegenerative process and aid in development of diagnostic and prognostic markers. Muscle Nerve 51 : 125–131, 2015     

Comparison of single motor unit responses to transcranial magnetic and peroneal nerve stimulation in the tibialis anterior muscle of patients with amyotrophic lateral sclerosis

Responses of single tibialis anterior motor units to transcranial magnetic stimulation and to a synchronized la volley evoked by peripheral nerve electrical stimulation were obtained in amyotrophic lateral sclerosis (ALS) patients and normal controls. Whereas the units of normal subjects exhibited rather stereotyped short-latency spike density peaks in response to both types of stimulus, the responses of ALS patient units were much less uniform. All ALS patient units exhibited a response to the synchronized la volley indistinguishable from that of normal subjects, indicating that the investigated spinal motoneurons are capable of normal excitatory responses in ALS patients. More than half of the ALS patient units responded to the transcranial magnetic stimulus with prolonged spike-density peaks appearing at a latency consistent with the notion that these pathological peaks are evoked by some relatively hyperexcitable structures presynaptic to the corticomotoneurons.     

Responses of masseter muscles to transcranial magnetic stimulation in patients with amyotrophic lateral sclerosis

We recorded motor responses evoked by transcranial magnetic stimulation (TMS) in the masseter muscles of 30 patients with amyotrophic lateral sclerosis (ALS), 10 patients with cervical spondylotic myelopathy (CSM) and 22 age-matched normal controls. Responses to direct activation of the trigeminal motor root (R-MEPs) were normal both in ALS and CSM patients. Responses to activation of cortico-bulbar descending fibers (C-MEPs) were absent or delayed in 19 ALS patients (63.3%). Abnormalities of masseter C-MEPs were more frequent than abnormalities of limb MEPs and could be observed both in patients with (77.8%) and without (41.7%) clinical bulbar signs. Masseter C-MEPs were normal in all CSM patients. Recording masseter responses to TMS can reveal the frequent impairment of cortico-bulbar projections in ALS and can be useful in the differential diagnosis of spinal cord compression disorders mimicking ALS because of combination of upper and lower motor neuron signs.     

Modulation of spontaneous motor unit potentials by a new motor cortical magnetic stimulation method in amyotrophic lateral sclerosis

Journal of Neurology - Patients with amyotrophic lateral sclerosis (ALS) show altered cortical excitability. In this study, we measure modulation of spontaneous motor unit potentials (sMUPs) in...     

Double magnetic stimulation of the motor cortex in amyotrophic lateral sclerosis

Objectives: To study the motor cortex circuitry and the motor interhemispheric influences with double magnetic stimulation in patients affected by amystrophic lateral sclerosis.Methods: We investigated the motor cortex in 21 amyotrophic lateral sclerosis patients (ALS, 10 with bulbar and 11 with spinal onset) with double magnetic stimulation (one shock in each hand area) with 2, 4, 6, 11 and 15 ms delay between shocks and paired magnetic stimulation (both shocks in the same area), with 4, 15, 25, 35, 55, 85, 100, 155, 200 and 255 ms delays, and compared the results with those obtained in normal subjects.Results: Double magnetic stimulation showed reduced interhemispheric facilitatory influences (maximal at 4 ms delay between shocks) when the test shock was applied on the left hemisphere in all patients; whereas no significant differences were observed compared to control (P>0.05) when it was applied on the right hemisphere in both forms. Inhibitory effects (maximal at 11 ms delay between shocks) were reduced in all patients for both hemispheres (P<0.05). Paired magnetic stimulations showed decreased inhibitory influences at 100–155 ms delay between shocks. Compared to control, the difference was significant in bulbar (P<0.05) and spinal onset, but not between onset forms (P>0.05). Inhibitory effects recorded with a short delay between shocks (4 ms) were not significantly modified in both forms of onset (P>0.05) as compared to control. There were no facilitatory influences at 15 and 35 ms delays between shocks.Conclusions: The results suggest that under these test conditions inhibition and facilitation were reduced in the motor cortex in ALS. As inhibitory effects were affected differently, two distinct cortical circuitries could be involved for short and long delays. As GABA neurons altered in ALS have been identified as a subpopulation reactive to parvalbumin, and since only inhibitory effects recorded with long delay between shocks were impaired in ALS, we suggest that this subpopulation of GABA neurons may be involved in the genesis of inhibitory effects recorded with a long delay between shocks.     

Inter-hemispheric asymmetry of motor corticospinal excitability in major depression studied by transcranial magnetic stimulation

BACKGROUND: Imaging and electroencephalographic studies have reported inter-hemispheric asymmetries in frontal cortical regions associated with depression. This study aimed at comparing motor corticospinal excitability assessed by methods of transcranial magnetic stimulation (TMS) between the right and left hemispheres in patients with major depression and healthy controls. METHOD: Patients with major depression (n=35) and healthy controls (n=35) underwent a bilateral study of various motor corticospinal excitability parameters, including rest motor threshold (RMT), corticospinal silent period (CSP) duration and intra-cortical inhibition (ICI) and facilitation (ICF). Indexes of asymmetry were calculated, and the relationships between excitability parameters and clinical scores of depression were statistically analyzed. RESULTS: Depressed patients showed a reduced excitability of both excitatory (RMT, ICF) and inhibitory (CSP, ICI) processes in the left hemisphere, compared to the right hemisphere and to healthy controls. CONCLUSION: The present results confirmed the existence of inter-hemispheric asymmetries in frontal cortex activities of depressed patients in favor of a left-sided reduced excitability. This neurophysiological approach may help to guide repetitive TMS procedures in the treatment of depressive disorders.     

Visual and motor cortex excitability: a transcranial magnetic stimulation study.

OBJECTIVES: Phosphene thresholds (PTs) to transcranial magnetic stimulation over the occipital cortex and motor thresholds (MTs) have been used increasingly as measures of the excitability of the visual and motor cortex. MT has been utilized as a guide to the excitability of other, non-motor cortical areas such as dorsolateral prefrontal cortex. The aims of this study were to compare the PTs to MTs; to assess their stability across sessions; and to investigate their relation to MTs. METHODS: PTs and MTs were determined using focal transcranial magnetic stimulation over the visual and motor cortex. RESULTS: PTs were shown to be significantly higher than MTs. Both PTs and MTs were stable across sessions. No correlation between PTs and MTs could be established. CONCLUSIONS: Phosphene threshold is a stable parameter of the visual cortex excitability. MTs were not related to the excitability of non-motor cortical areas.     

Single motor unit variability with threshold stimulation in patients with amyotrophic lateral sclerosis and normal subjects

Repetitive nerve stimulation often shows responses with an abnormal decrement in patients with amyotrophic lateral sclerosis (ALS), suggesting instability of the neuromuscular junction; however, the pathophysiology and response characteristics of this instability are not clear. We evaluated response variability of 47 single motor units from 16 patients with ALS and 51 units from 10 normal subjects, acquired by delivering threshold stimuli sporadically at 0.5 HZ or less. In addition, in 46 other different single motor units obtained from 21 patients with ALS, variability was studied at both 1- and 3-HZ stimulation rates. Motor units from patients with ALS were significantly more variable than those from normal subjects, even when their larger amplitude was accounted for. This increased variability was not rate dependent. Response variability is a critical measure in the statistical method of motor unit number estimation and is attributed to variability in the number of units activated; the fact that variability of single motor units varies with disease state may be a potentially confounding factor in the application of the technique.     

运动单位数目估计在肌萎缩侧索硬化患者随访中的作用

目的 比较多点刺激法和递增法运动单位数目估计在肌萎缩侧索硬化(ALS)患者随访中的作用及差异.方法 120例ALS患者在诊断时,随访3、6、9、12个月时分别进行多点刺激法或递增法运动单位数目估计.多点刺激法:刺激电极分别于腕、腕上6 cm、肘、肘上6 cm,4点刺激正中神经,以超强刺激诱发最大波幅M波;然后从0刺激开始逐渐增加刺激强度直到出现可辨认的单个运动单位电位,逐渐增大刺激强度,记录3个递增的M波.递增法:刺激电极于腕点刺激正中神经,以超强刺激诱发最大M波值,之后自阈强度刺激开始,逐渐增加刺激强度,收集10个递增的M波.比较两种方法在患者随访中所得运动单位数目估计数值的变化及差异.结果 在ALS患者诊断时,随访3、9、12个月时,两种方法所测运动单位数目无差异,均表现为进行性下降;在随访6个月时,多点刺激法所得数值高于递增法(88±6和47±5;t=1.72,P=0.04).结论 多点刺激法和递增法运动单位数目估计可用于ALS患者的随访研究,在疾病不同时期,两种方法所得数值可以不同.     

Cyclical excitability of the motor cortex in patients with catamenial epilepsy: A transcranial magnetic stimulation study

PURPOSE: The pathophysiology of catamenial epilepsy is still unclear. Therefore, we investigated the cortical excitability of women with catamenial epilepsy during different phases of the menstrual cycle. METHODS: Using transcranial magnetic stimulation, six patients suffering from catamenial epilepsy were investigated during ovulatory cycles. On days 8, -14, -7 and 2 of the cycle (day 1 being the first day of menstrual bleeding), resting motor threshold (RMT), cortical silent period (CSP), intracortical inhibition (ICI) and intracortical facilitation (ICF) were investigated. The non-parametric Friedman-test for multiple comparisons and Wilcoxon signed rank test were used for statistical analysis. RESULTS: Five patients suffered from focal epilepsy (three right hemispheric, one bitemporal, one unknown origin) and one patient had idiopathic generalized epilepsy. All patients experienced perimenstrual seizure clustering and two also showed an increased seizure frequency during the luteal phase. In the right hemispheres there was a significant change of CSP duration in the course of the menstrual cycle (chi(2)=8.3, P=0.041), due to a shorter CSP during the luteal phase (Z=-2.0, P=0.043) and menstruation (Z=-2.2, P=0.028) as compared to the follicular phase. There was no significant variation of CSP in the left hemispheres. RMT, ICI and ICF showed no significant changes in the course of the menstrual cycle. CONCLUSIONS: The CSP changes suggest a decreased inhibition involving GABA-ergic neurotransmission during the luteal phase and menstruation. These TMS alterations correlated with the clinical course of the epilepsies and were found in the hemispheres containing the majority of the epileptogenic zones.     

Transcranial magnetic stimulation compared with upper motor neuron signs in patients with amyotrophic lateral sclerosis.

If patients with amyotrophic lateral sclerosis (ALS) present without upper motor neuron signs (UMNS) they do not meet current ALS research criteria. To compare how sensitively degeneration of upper motor neurons is detected clinically and by transcranial magnetic stimulation, 35 patients with ALS were studied. Nineteen patients had definite UMNS, nine patients had probable UMNS, and seven patients had no UMNS. Cortex, cervical nerve roots, and lumbar plexus were stimulated with a magnetic stimulator. Compound muscle action potentials from abductor digiti minimi and from anterior tibial muscles were recorded with surface electrodes. Responses to transcranial magnetic stimulation were considered abnormal if central motor conduction time was above the 99% upper limits or if there was no response to cortical but to peripheral stimulation. In all patients with definite UMNS central motor conduction was abnormal. In patients with probable UMNS it was abnormal in 67%, and in patients without UMNS it was abnormal in 71%. Abnormality of central motor conduction was neither correlated with the duration nor with the severity of the disease. The high rate of abnormalities of central motor conduction found in patients with ALS but without definite UMNS suggests that, in these patients, the diagnosis of ALS can be made more reliably if transcranial magnetic stimulation studies are performed.     

Modulation of corticospinal excitability by repetitive transcranial magnetic stimulation.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is able to modulate the corticospinal excitability and the effects appear to last beyond the duration of the rTMS itself. Different studies, employing different rTMS parameters, report different modulation of corticospinal excitability ranging from inhibition to facilitation. Intraindividual variability of these effects and their reproducibility are unclear. METHODS: We examined the modulatory effects of rTMS to the motor cortex at various frequencies (1, 10, 20 Hz) and at different time-points in twenty healthy volunteers. RESULTS: We observed significant inhibition of MEPs following 1 Hz rTMS and significant facilitation of MEPs following 20 Hz rTMS for both day1 and day 2. Interestingly, at 1 Hz and 20 Hz rTMS, the modulatory effect produced by rTMS was greater on day 2. However, there was no significant change in corticospinal excitability following 10 Hz rTMS neither on day 1 nor day 2. CONCLUSION: Our findings raise questions as to how stimulation parameters should be determined when conducting studies applying rTMS on multiple days, and in particular, studies exploring rTMS as a treatment modality in neuropsychiatric disorders.     

A single motor unit recording technique for studying the differential activation of corticospinal volleys by transcranial magnetic stimulation

The purpose of this method is to establish a single motor unit recording technique to study the differential activation of corticospinal volleys by various types of transcranial magnetic stimulation (TMS). TMS is performed with various coil orientations over the hand or leg motor areas and surface EMG, and single motor unit recordings are made either from the studied hand or leg muscle. Transcranial electrical stimulation (TES) is also performed over the motor cortex as well as at the foramen magnum level to determine the latency of D waves. The intensity of stimulation is set just above the motor threshold for each type of stimulation. This method makes it possible to activate some I volleys (especially I1 and I3 waves) preferentially, if not selectively, from the hand and leg motor areas. The obtained results accord well with recent epidural recording studies, which lends support to the validity of this method.     

帕金森病患者运动皮质兴奋性的经颅磁刺激研究

目的:本研究拟应用低频重复性经颅磁刺激(rTMS)分别刺激帕金森病(PD)患者M1手代表区(M1Hand)及运动前区(PMC),探讨不同干预手段对运动皮质兴奋性的影响,以及M1与PMC间的联系。方法:对18名确诊PD患者先后进行4种不同干预,即口服美多芭、低频rTMS刺激M1Hand(0.5Hz,100%静息阈值,共1600次脉冲)、低频rTMS刺激PMC(0.5Hz,100%静息阈值,共1600次脉冲)以及假刺激。于每次干预前后各进行临床评价并测定运动诱发电位(MEP)相关指标。结果:①口服美多芭后UPDRSⅢ(P=0.001)以及其中有关僵直(P=0.001)、运动迟缓(P<0.001)的评分均较服药前显著改善。三种不同磁刺激干预产生结果不同,M1Hand组UPDRSⅢ减低(P=0.015),僵直(P=0.010)、运动迟缓(P=0.004)亦有所改善;PMC组UPDRSⅢ较干预前减低(P=0.046),僵直评分亦减低,但无显著性意义(P=0.163);②口服美多芭1h后MEP120减低(P=0.002),CSP延长(P=0.006);M1Hand组MEP120无著变,而CSP延长(P=0.015);PMC组MEP120减低(P=0.004),而CSP无著变;假刺激组则均无显著性改变。结论:低频rTMS对不同脑区产生的效应不同:刺激M1可使CSP延长;而刺激PMC可使MEP波幅减低。