**2.1 Motor threshold**

In a study of Di Lazzaro et al. in a small group of DMD patients and a control group (n = 4), the threshold for evoking MEPs using electrical anodal stimulation was the same. Otherwise, the resting motor threshold (RMT) for a stimulation with a circular magnetic coil at the vertex was higher in the DMD patients [7]. The higher threshold was interpreted as a reduced cortical excitability that may be related to an abnormal synaptic function due to the deficiency of brain synaptic dystrophin. However, in a study about the cortical excitability in Duchenne muscular dystrophy investigating central motor conduction time (CMCT), cortical silent periods, and paired-pulse TMS, there were no statistical differences between a group of DMD children and a group of age-matched control children except lower MEP amplitudes in the DMD children. Compared with a control group of healthy adults, the two children groups showed less short interval intracortical inhibition (SICI) and shorter CSP durations [6]. The difference between the two studies can be explained by the applied different methods, since in the study by Di Lazzaro et al., a circular coil was used and an unusual minimum stimulus intensity that evoked an EMG response of at least 100 μV in 100% of 20 consecutive trials was the accepted resting motor threshold. Besides the small sample size in the study of Di Lazzaro et al. can be an explanation for the difference.

Oliveri et al. found that in patients with myotonic dystrophy, the stimulus threshold intensity did not differ between patients and healthy controls, but the mean cortical motor latency and CMCT were significantly prolonged in the patients compared to the controls. This can be interpreted as a central motor delay and a decreased excitability of motor neurons in the myotonic dystrophy patients [12].

**53**

controls [12].

**2.4 Intracortical inhibition**

*Electrophysiological Assessment of CNS Abnormalities in Muscular Dystrophy*

multicore disease) and a group of control subjects [14].

FSHD and LGMD [13, 14] as well as in patients with DMD [6, 7].

In another study Di Lazzaro et al. [13] found that RMT was slightly increased in patients with FSHD as well as in patients with other muscle diseases such as limbgirdle muscle dystrophy (LGMD) and polymyositis [13]. However, Liepert et al. [14] could not show a significant difference in RMT between a group of patients with different myopathies (including FSHD, LGMD, emerinopathy, adhalinopathy,

As mentioned above Oliveri et al. investigated MEPs elicited by cortical and cervical magnetic stimulation in 10 patients with myotonic dystrophy. While MEP cervical latency, absolute or relative amplitude, and RMT did not differ significantly between patients and controls, the mean cortical motor latency and CMCT were significantly prolonged in the patients compared with 10 healthy controls [12]. This central motor delay can be explained by a decreased motoneuron excitability.

In several further studies, it was found that CMCT was normal in patients with

Yayla et al. further described in his study [6] with DMD patients that mean MEP

response amplitudes and areas, as well MEP/compound muscle action potential (CMAP) amplitude ratios, had a tendency to be lower than those of a control group, but only the differences in MEP area values reached a statistical significance [6]. An explanation for the reduced amplitude of CMAPs and MEPs could be the muscle damage in the DMD patients. Otherwise, DMD patients showed an increased ratio of the F-wave and the compound motor action potential (F/CMAP ratio), indicative for an increased α-motoneuron excitability. The mean F-wave amplitudes were not significantly different between DMD patients and controls. Therefore, the reason for a higher F/CMAP ratio in the DMD group is difficult to explain. One explanation may be an increased F-wave amplitude in the DMD patients that did not reach statistical significance especially due to their large variability. Another explanation may be the aforementioned low-amplitude CMAPs in DMD patients or an increased motor cortical excitability due to less SICI and shorter CSP durations in DMD

In the study of Liepert et al., MEP amplitudes of the first dorsal interosseous (FDI) and the deltoid muscle (DM) were increased in patients with different myopathies compared to controls [14]. The recruitment of a larger group of corticospinal neurons by the TMS pulses due to an increased motor cortical excitability with a consecutive increased activation of the α-motoneuron pool may explain this finding. Finally, in the study of Oliveri et al., the first MEP study in patients with myotonic dystrophy, the mean MEP amplitudes did not differ between patients and

In the study of Liepert et al. in myopathy patients with well-defined myopathies,

the patients showed a reduction of SICI compared to an age-matched healthy control group [14]. This reduction of SICI was present in both clinically unaffected and affected muscles. In the patients, both MEP amplitudes and α-motoneuron excitability were enhanced, and, thus, it was concluded that excitability in myopathy patients was enhanced at cortical and subcortical levels in order to compensate for the muscle weakness or because of use-dependent plasticity. In all patients

*DOI: http://dx.doi.org/10.5772/intechopen.86256*

**2.2 Central motor conduction time**

**2.3 MEP amplitudes/areas**

patients with regard to healthy adult controls.

#### *Electrophysiological Assessment of CNS Abnormalities in Muscular Dystrophy DOI: http://dx.doi.org/10.5772/intechopen.86256*

In another study Di Lazzaro et al. [13] found that RMT was slightly increased in patients with FSHD as well as in patients with other muscle diseases such as limbgirdle muscle dystrophy (LGMD) and polymyositis [13]. However, Liepert et al. [14] could not show a significant difference in RMT between a group of patients with different myopathies (including FSHD, LGMD, emerinopathy, adhalinopathy, multicore disease) and a group of control subjects [14].

### **2.2 Central motor conduction time**

*Muscular Dystrophies*

altered short-term synaptic enhancement.

**2.1 Motor threshold**

be an explanation for the difference.

cortical reactivity and plasticity in MD patients.

**2. Electrophysiological markers in muscular dystrophy**

Transcranial magnetic stimulation (TMS) is a proper method to assess brain cortical excitability that is disturbed in muscular dystrophies. A TMS assessment of brain cortical function in DMD patients has yielded contradictory results [6]. While Yayla et al. reported no CNS abnormalities and similar motor threshold (MT) values in DMD patients and healthy controls, Di Lazzaro et al. reported a higher MT for magnetic than for electrical stimulation in four DMD patients [7]. Methodological reasons, as well as the small sample size of the latter study, may account for the discrepancies. Because repetitive TMS (rTMS) modulates cortical excitability, possibly by inducing a short-term increase in synaptic efficacy [8], rTMS can be used to investigate motor cortex excitability in humans. Changes in the size and threshold of motor evoked potentials (MEPs) and cortical silent period (CSP) duration evoked by rTMS delivered in 5 Hz trains of stimuli at suprathreshold intensity have been tested by Golaszewski et al. [9]. The main finding of this study was that 5 Hz-rTMS delivered in trains failed to elicit the normal MEP facilitation over the train in a group of Becker Muscular Dystrophy (BMD) patients with mental retardation or borderline mental retardation and BMD patients with normal intelligence and healthy controls did not show any abnormalities in 5 Hz-rTMS MEPs and CSPs. The lack of MEP facilitation in mentally retarded or borderline BMD patients during the 5 Hz-rTMS train of stimuli may thus reflect an

With the means of transcranial magnetic stimulation, important neurophysiologic and pathophysiologic aspects of cortical involvement in myopathies can be detected [10, 11]. So far, a few studies applying TMS have detected abnormalities in

In a study of Di Lazzaro et al. in a small group of DMD patients and a control group (n = 4), the threshold for evoking MEPs using electrical anodal stimulation was the same. Otherwise, the resting motor threshold (RMT) for a stimulation with a circular magnetic coil at the vertex was higher in the DMD patients [7]. The higher threshold was interpreted as a reduced cortical excitability that may be related to an abnormal synaptic function due to the deficiency of brain synaptic dystrophin. However, in a study about the cortical excitability in Duchenne muscular dystrophy investigating central motor conduction time (CMCT), cortical silent periods, and paired-pulse TMS, there were no statistical differences between a group of DMD children and a group of age-matched control children except lower MEP amplitudes in the DMD children. Compared with a control group of healthy adults, the two children groups showed less short interval intracortical inhibition (SICI) and shorter CSP durations [6]. The difference between the two studies can be explained by the applied different methods, since in the study by Di Lazzaro et al., a circular coil was used and an unusual minimum stimulus intensity that evoked an EMG response of at least 100 μV in 100% of 20 consecutive trials was the accepted resting motor threshold. Besides the small sample size in the study of Di Lazzaro et al. can

Oliveri et al. found that in patients with myotonic dystrophy, the stimulus threshold intensity did not differ between patients and healthy controls, but the mean cortical motor latency and CMCT were significantly prolonged in the patients compared to the controls. This can be interpreted as a central motor delay and a decreased excitability of motor neurons in the myotonic dystrophy patients [12].

**52**

As mentioned above Oliveri et al. investigated MEPs elicited by cortical and cervical magnetic stimulation in 10 patients with myotonic dystrophy. While MEP cervical latency, absolute or relative amplitude, and RMT did not differ significantly between patients and controls, the mean cortical motor latency and CMCT were significantly prolonged in the patients compared with 10 healthy controls [12]. This central motor delay can be explained by a decreased motoneuron excitability.

In several further studies, it was found that CMCT was normal in patients with FSHD and LGMD [13, 14] as well as in patients with DMD [6, 7].

### **2.3 MEP amplitudes/areas**

Yayla et al. further described in his study [6] with DMD patients that mean MEP response amplitudes and areas, as well MEP/compound muscle action potential (CMAP) amplitude ratios, had a tendency to be lower than those of a control group, but only the differences in MEP area values reached a statistical significance [6]. An explanation for the reduced amplitude of CMAPs and MEPs could be the muscle damage in the DMD patients. Otherwise, DMD patients showed an increased ratio of the F-wave and the compound motor action potential (F/CMAP ratio), indicative for an increased α-motoneuron excitability. The mean F-wave amplitudes were not significantly different between DMD patients and controls. Therefore, the reason for a higher F/CMAP ratio in the DMD group is difficult to explain. One explanation may be an increased F-wave amplitude in the DMD patients that did not reach statistical significance especially due to their large variability. Another explanation may be the aforementioned low-amplitude CMAPs in DMD patients or an increased motor cortical excitability due to less SICI and shorter CSP durations in DMD patients with regard to healthy adult controls.

In the study of Liepert et al., MEP amplitudes of the first dorsal interosseous (FDI) and the deltoid muscle (DM) were increased in patients with different myopathies compared to controls [14]. The recruitment of a larger group of corticospinal neurons by the TMS pulses due to an increased motor cortical excitability with a consecutive increased activation of the α-motoneuron pool may explain this finding.

Finally, in the study of Oliveri et al., the first MEP study in patients with myotonic dystrophy, the mean MEP amplitudes did not differ between patients and controls [12].

#### **2.4 Intracortical inhibition**

In the study of Liepert et al. in myopathy patients with well-defined myopathies, the patients showed a reduction of SICI compared to an age-matched healthy control group [14]. This reduction of SICI was present in both clinically unaffected and affected muscles. In the patients, both MEP amplitudes and α-motoneuron excitability were enhanced, and, thus, it was concluded that excitability in myopathy patients was enhanced at cortical and subcortical levels in order to compensate for the muscle weakness or because of use-dependent plasticity. In all patients

irrespective of the type of myopathy, a reduced intracortical inhibition was found. Obviously, this neurobiological mechanism of increased motor cortical excitability for compensation of muscle weakness is independent of a particular muscle pathology in myopathies. However, with regard to the available electrophysiological data, there is no sufficient evidence to conclude that cortical disinhibition is a common feature of myopathies.

In 2004 Di Lazzaro et al. reported significantly reduced SICI in early-onset FSHD patients compared with patients suffering from other muscle diseases (LGMD and polymyositis) and healthy controls. Between polymyositis patients and controls, there was no significant difference in SICI [13].

### **2.5 TMS and fatigue**

During fatiguing muscle exercise, a paired-pulse TMS paradigm can be applied to investigate the central inhibitory and excitatory mechanisms that occur at the motor cortical level. Paired-pulse TMS was already done in patients with multiple sclerosis and in healthy subjects [15, 16]. In a study of Schwenkreis et al., SICI has been applied prior to a fatiguing motor task, immediately post-exercise, and 40 minutes post-exercise in MD patients and patients suffering from fibromyalgia syndrome (FMS) [17]. In the MD and FMS patients, SICI was already reduced pre-exercise. Healthy subjects did not show any pre-exercise SICI decrease but a significant SICI decrease post-exercise. Thus, reduced SICI may be a central compensatory mechanism for peripheral or central fatigue. MD patients may use this neurobiological mechanism of reduced SICI already under baseline conditions, probably due to permanent muscle weakness. Probably due to a ceiling effect, the MD and FMS patients may not be able to further decrease cortical inhibition during the fatiguing exercise. This may be an additional central mechanism to the fatigue in MD and FMS patients. A fatigue syndrome belongs to the typical clinical feature of these patients.

An altered peripheral nerve excitability and reduced SICI at baseline in patients with MD type 1 (DM1) with impaired myoelectric properties (mean power frequency, muscle fiber conduction velocity) have been demonstrated in a study of Boerio et al. [18]. The remaining excitability parameters did not vary post-exercise in patients in contrast to the healthy controls.

In patients with colchicine myopathy with reported fatigue but no significant muscle weakness, Lin et al. investigated central compensatory mechanisms [19]. The patient and control group did not differ in the results. Obviously, there is no change in motor cortical excitability in acquired myopathy due to colchicine, while central reorganization may occur in patients with hereditary myopathy to compensate for muscle weakness.
