Gabapentin for complex regional pain syndrome in Machado-Joseph disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>Chronic pain is a common problem for patients with Machado-Joseph disease. Most of the chronic pain in Machado-Joseph disease has been reported to be of musculoskeletal origin, but now there seems to be different chronic pain in patients with Machado-Joseph disease.</p> <p>Case presentation</p> <p>A 29-year-old man (Han Chinese, Hoklo) with Machado-Joseph disease experienced severe chronic pain in both feet, cutaneous thermal change, thermal hypersensitivity, focal edema, and sweating and had a history of bone fracture. These symptoms were compatible with a diagnosis of complex regional pain syndrome. After common analgesics failed to relieve his pain, gabapentin was added and titrated to 2000 mg/day (500 mg every six hours) in less than two weeks. This relieved 40% of his pain and led to significant clinical improvement.</p> <p>Conclusions</p> <p>The pathophysiology of complex regional pain syndrome includes peripheral and central sensitizations, the latter of which might be associated with the neurodegeneration in Machado-Joseph disease. In this report, we suggest that gabapentin could inhibit central sensitization as an adjunct for complex regional pain syndrome in patients with Machado-Joseph disease.</p

Aberrant Sensory Gating of the Primary Somatosensory Cortex Contributes to the Motor Circuit Dysfunction in Paroxysmal Kinesigenic Dyskinesia

Paroxysmal kinesigenic dyskinesia (PKD) is conventionally regarded as a movement disorder (MD) and characterized by episodic hyperkinesia by sudden movements. However, patients of PKD often have sensory aura and respond excellently to antiepileptic agents. PRRT2 mutations, the most common genetic etiology of PKD, could cause epilepsy syndromes as well. Standing in the twilight zone between MDs and epilepsy, the pathogenesis of PKD is unclear. Gamma oscillations arise from the inhibitory interneurons which are crucial in the thalamocortical circuits. The role of synchronized gamma oscillations in sensory gating is an important mechanism of automatic cortical inhibition. The patterns of gamma oscillations have been used to characterize neurophysiological features of many neurological diseases, including epilepsy and MDs. This study was aimed to investigate the features of gamma synchronizations in PKD. In the paired-pulse electrical-stimulation task, we recorded the magnetoencephalographic data with distributed source modeling and time-frequency analysis in 19 patients of newly-diagnosed PKD without receiving pharmacotherapy and 18 healthy controls. In combination with the magnetic resonance imaging, the source of gamma oscillations was localized in the primary somatosensory cortex. Somatosensory evoked fields of PKD patients had a reduced peak frequency (p &lt; 0.001 for the first and the second response) and a prolonged peak latency (the first response p = 0.02, the second response p = 0.002), indicating the synchronization of gamma oscillation is significantly attenuated. The power ratio between two responses was much higher in the PKD group (p = 0.013), indicating the incompetence of activity suppression. Aberrant gamma synchronizations revealed the defective sensory gating of the somatosensory area contributes the pathogenesis of PKD. Our findings documented disinhibited cortical function is a pathomechanism common to PKD and epilepsy, thus rationalized the clinical overlaps of these two diseases and the therapeutic effect of antiepileptic agents for PKD. There is a greater reduction of the peak gamma frequency in PRRT2-related PKD than the non-PRRT PKD group (p = 0.028 for the first response, p = 0.004 for the second response). Loss-of-function PRRT2 mutations could lead to synaptic dysfunction. The disinhibiton change on neurophysiology reflected the impacts of PRRT2 mutations on human neurophysiology

Electrophysiological characterization of Charcot–Marie–Tooth disease type 1A in Taiwan

Background: Charcot–Marie–Tooth disease type 1A (CMT1A) is the most common type of hereditary neuropathy. The demyelinating pathology of CMT1A results in significant nerve conduction slowing such that a nerve conduction study (NCS) is important in the clinical assessment of CMT1A. In this study, we analyzed and reported the electrophysiological features of a large Taiwanese cohort with CMT1A. Methods: We retrospectively analyzed the NCS data of 106 Taiwanese patients with CMT1A. We also compared the electrophysiological parameters of the CMT1A patients with those of 20 patients with early-onset Charcot–Marie–Tooth disease type 1B (CMT1B). Results: The patients with CMT1A had a significant but variable degree of slowed nerve conduction. The median motor nerve conduction velocities (MNCVs) varied from 10.0 to 37.3 m/s in the entire CMT1A cohort but were more concordant in patients within a family (p<0.001). In each patient, the MNCVs among different nerves were concordant (p<0.001), and the MNCVs tended to remain steady longitudinally. Moreover, younger patients had a slower MNCV than older patients within the CMT1A population (p<0.001). The average median MNCV was significantly faster in the CMT1A patients than in the CMT1B patients (21.8±6.2 m/s and 16.3±3.6 m/s; p<0.001). Conclusion: This study provides basic electrophysiological knowledge about CMT1A in Taiwan. The findings also suggest that the electrophysiological variability in the CMT1A cohort may be at least partially attributable to unknown genetic factors. These data emphasize the role of MNCV in the clinical assessment of CMT1A. A median or ulnar MNCV below 38 m/s can be a sensitive criterion for supporting the diagnosis of CMT1A. A median MNCV can sometimes help to distinguish CMT1A from CMT1B, and CMT1A should be considered in patients with median MNCVs near or above 24 m/s. Moreover, the MNCV may to some degree reflect the severity of CMT1A

Amplitudes of motor evoked potential (% of M-response) during active conditions.

<p>Data are presented as the mean ± SEM.</p>a, b,<p>and^c indicate significant differences between the R FCR task and the R AD task, between the R FCR task and the R RF task, and between the R FCR task and the R TA task, respectively. Significance level was set at <i>P</i><0.05. RMT: resting motor threshold. R: right; AD: anterior deltoid; FCR: flexor carpi radialis; RF: rectus femoris; TA: tibialis anterior.</p

Short-interval intracortical inhibition (%, SICI) during active conditions.

<p>Data are presented as the mean ± SD.</p>a, b,<p>and^c indicate significant differences between the R FCR task and the R AD task, between the R FCR task and the R RF task, and between the R FCR task and the R TA task, respectively. Significance level was set at <i>P</i><0.05. R: right; AD: anterior deltoid; FCR: flexor carpi radialis; RF: rectus femoris; TA: tibialis anterior.</p

Increased corticospinal output and decreased intracortical inhibition of the left rectus femoris (L RF) muscle during unilateral motor task.

<p>(A) Recruitment curves of motor evoked potential (MEP) at rest and during four active conditions that were performed by muscles on the right side. The abscissa shows intensity of transcranial magnetic stimulus expressed relative to the resting motor threshold in each subject. The ordinate shows MEP amplitudes as a percentage of the M-responses collected via femoral nerve magnetic stimulation (M-response_FNMS). Data are presented as the mean ± standard error from all 15 subjects. (B) Ratio of short-interval intracortical inhibition (SICI) at rest and during four active conditions. The size of the conditioned MEP is expressed as a percentage of the amplitude of the test MEP (horizontal dotted line). Data are presented as the mean ± standard deviation from all 15 subjects. Asterisks indicate statistically significant differences from the rest condition (*<i>p</i><0.05) by repeated-measures ANOVA following a post hoc contrast test. R: right; AD: anterior deltoid; FCR: flexor carpi radialis; RF: rectus femoris; TA: tibialis anterior.</p