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Takeshi Shimizu, Koichi Hosomi, Tomoyuki Maruo, Yuko Goto, Masaru Yokoe, Yu Kageyama, Toshio Shimokawa, Toshiki Yoshimine and Youichi Saitoh

OBJECTIVE

Electrical motor cortex stimulation can relieve neuropathic pain (NP), but its use requires patients to undergo an invasive procedure. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) using a figure-8 coil can relieve NP noninvasively, but its ability to relieve lower limb pain is still limited. Deep rTMS using an H-coil can effectively stimulate deep brain regions and has been widely used for the treatment of various neurological diseases; however, there have been no clinical studies comparing the effectiveness of figure-8 coils and H-coils. This study assessed the clinical effectiveness of 5 once-daily stimulations with H-coils and figure-8 coils in patients with NP.

METHODS

This randomized, double-blind, 3-way crossover trial examined 18 patients with NP who sequentially received 3 types of stimulations in the M1 for 5 consecutive days; each 5-day stimulation period was followed by a 17-day follow-up period before crossing over to the next type of stimulation. During each rTMS session, patients received a 5-Hz rTMS to the M1 region corresponding to the painful lower limb. The visual analog scale (VAS) and the Japanese version of the short-form McGill Pain Questionnaire 2 (SF-MPQ2-J) were used to measure pain intensity. The primary outcome was VAS score reduction immediately after and 1 hour after intervention.

RESULTS

Both the VAS and SF-MPQ2-J showed significant pain improvement immediately after deep rTMS with an H-coil as compared with the sham group (p < 0.001 and p = 0.049, respectively). However, neither outcome measure showed significant pain improvement when using a figure-8 coil. The VAS also showed significant pain improvement 1 hour after deep rTMS with an H-coil (p = 0.004) but not 1 hour after rTMS using a figure-8 coil. None of the patients exhibited any serious adverse events.

CONCLUSIONS

The current findings suggest that the use of deep rTMS with an H-coil in the lower limb region of the M1 in patients with NP was tolerable and could provide significant short-term pain relief.

Clinical trial registration no.: UMIN000010536 (http://www.umin.ac.jp/ctr/)

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Suhan Senova, Koichi Hosomi, Jean-Marc Gurruchaga, Gaëtane Gouello, Naoufel Ouerchefani, Yara Beaugendre, Hélène Lepetit, Jean-Pascal Lefaucheur, Romina Aron Badin, Julien Dauguet, Caroline Jan, Philippe Hantraye, Pierre Brugières and Stéphane Palfi

OBJECTIVE

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established therapy for motor symptoms in patients with pharmacoresistant Parkinson's disease (PD). However, the procedure, which requires multimodal perioperative exploration such as imaging, electrophysiology, or clinical examination during macrostimulation to secure lead positioning, remains challenging because the STN cannot be reliably visualized using the gold standard, T2-weighted imaging (T2WI) at 1.5 T. Thus, there is a need to improve imaging tools to better visualize the STN, optimize DBS lead implantation, and enlarge DBS diffusion.

METHODS

Gradient-echo sequences such as those used in T2WI suffer from higher distortions at higher magnetic fields than spin-echo sequences. First, a spin-echo 3D SPACE (sampling perfection with application-optimized contrasts using different flip angle evolutions) FLAIR sequence at 3 T was designed, validated histologically in 2 nonhuman primates, and applied to 10 patients with PD; their data were clinically compared in a double-blind manner with those of a control group of 10 other patients with PD in whom STN targeting was performed using T2WI.

RESULTS

Overlap between the nonhuman primate STNs segmented on 3D-histological and on 3D-SPACE-FLAIR volumes was high for the 3 most anterior quarters (mean [± SD] Dice scores 0.73 ± 0.11, 0.74 ± 0.06, and 0.60 ± 0.09). STN limits determined by the 3D-SPACE-FLAIR sequence were more consistent with electrophysiological edges than those determined by T2WI (0.9 vs 1.4 mm, respectively). The imaging contrast of the STN on the 3D-SPACE-FLAIR sequence was 4 times higher (p < 0.05). Improvement in the Unified Parkinson's Disease Rating Scale Part III score (off medication, on stimulation) 12 months after the operation was higher for patients who underwent 3D-SPACE-FLAIR–guided implantation than for those in whom T2WI was used (62.2% vs 43.6%, respectively; p < 0.05). The total electrical energy delivered decreased by 36.3% with the 3D-SPACE-FLAIR sequence (p < 0.05).

CONCLUSIONS

3D-SPACE-FLAIR sequences at 3 T improved STN lead placement under stereotactic conditions, improved the clinical outcome of patients with PD, and increased the benefit/risk ratio of STN-DBS surgery.

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Hui Ming Khoo, Haruhiko Kishima, Naoki Tani, Satoru Oshino, Tomoyuki Maruo, Koichi Hosomi, Takufumi Yanagisawa, Hiroaki Kazui, Yoshiyuki Watanabe, Toshio Shimokawa, Toshihiko Aso, Atsushi Kawaguchi, Fumio Yamashita, Youichi Saitoh and Toshiki Yoshimine

OBJECT

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder characterized by gait disturbance, cognitive impairment, and incontinence. It is unclear whether the pathophysiology of iNPH is associated with alterations in the default mode network (DMN). The authors investigated alterations in the DMN of patients with iNPH and sought to determine whether a relationship exists between the resting-state functional connectivity of the DMN and a patient’s clinical symptoms.

METHODS

Resting-state functional MRI (rs-fMRI) was performed in 16 preoperative patients with iNPH and 15 neurologically healthy control subjects of a similar age. Independent component and dual-regression analyses were used to quantify DMN connectivity. The patients’ clinical symptoms were rated according to the iNPH grading scale (iNPHGS). Each of their specific clinical symptoms were rated according to the cognitive, gait, and urinary continence domains of iNPHGS, and neurocognitive status was assessed using the Mini-Mental State Examination, Frontal Assessment Battery (FAB), and Trail Making Test Part A. The strength of DMN connectivity was compared between patients and controls, and the correlation between DMN connectivity and iNPHGS was examined using both region of interest (ROI)-based analysis and voxel-based analysis. The correlation between DMN connectivity and each of the specific clinical symptoms, as well as neurocognitive status, was examined using voxel-based analysis.

RESULTS

Both ROI-based and voxel-based analyses revealed reduced DMN connectivity in patients with iNPH. ROI-based analysis showed increased DMN connectivity with worsening clinical symptoms of iNPH. Consistently, voxel-based analyses revealed that DMN connectivity correlated positively with the iNPHGS score, as well as the cognitive and urinary continence domain scores, and negatively with the FAB score. The significant peak in correlation in each case was localized to the precuneus.

CONCLUSIONS

This is the first study to establish alterations in the DMN of patients with iNPH. DMN connectivity may be a useful indicator of the severity of clinical symptoms in patients with iNPH.

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Naoki Tani, Haruhiko Kishima, Hui Ming Khoo, Takufumi Yanagisawa, Satoru Oshino, Tomoyuki Maruo, Koichi Hosomi, Masayuki Hirata, Hiroaki Kazui, Keiko Tokumasu Nomura, Mohamed M. Aly, Amami Kato and Toshiki Yoshimine

OBJECTIVE

Epilepsy surgery is of known benefit for drug-resistant temporal lobe epilepsy (TLE); however, a certain number of patients suffer significant decline in verbal memory after hippocampectomy. To prevent this disabling complication, a reliable test for predicting postoperative memory decline is greatly desired. Therefore, the authors assessed the value of electrical stimulation of the parahippocampal gyrus (PHG) as a provocation test of verbal memory decline after hippocampectomy on the dominant side.

METHODS

Eleven right-handed, Japanese-speaking patients with medically intractable left TLE participated in the study. Before surgery, they underwent provocative testing via electrical stimulation of the left PHG during a verbal encoding task. Their pre- and posthippocampectomy memory function was evaluated according to the Wechsler Memory Scale-Revised (WMS-R) and/or Mini-Mental State Examination (MMSE) before and 6 months after surgery. The relationship between postsurgical memory decline and results of the provocative test was evaluated.

RESULTS

Left hippocampectomy was performed in 7 of the 11 patients. In 3 patients with a positive provocative recognition test, verbal memory function, as assessed by the WMS-R, decreased after hippocampectomy, whereas in 4 patients with a negative provocative recognition test, verbal memory function, as assessed by the WMS-R or MMSE, was preserved.

CONCLUSIONS

Results of the present study suggest that electrical stimulation of the PHG is a reliable provocative test to predict posthippocampectomy verbal memory decline.