Takefumi Hitomi

Low-frequency repetitive transcranial magnetic stimulation for seizure suppression in patients with extratemporal lobe epilepsy-—A pilot study

We evaluated the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on seizure frequency in adult patients with medically intractable extratemporal lobe epilepsy (ETLE). Seven patients with medically intractable ETLE received low-frequency rTMS at 0.9 Hz, basically two sets of 15 min stimulation per day for five days in a week, with the stimulus intensity of 90% of resting motor threshold (RMT). The number of seizures during two weeks before and after the stimulation of one week was compared. Furthermore, RMT and active motor threshold (AMT) were measured before and after rTMS for each daily session. After low-frequency rTMS of one week, the frequency of all seizure types, complex partial seizures (CPSs) and simple partial seizures was reduced by 19.1, 35.9 and 7.4%, respectively. The patients with smaller difference between RMT and AMT before rTMS had higher reduction rate of CPSs. A favorable tendency of seizure reduction, though not statistically significant, during two weeks after low-frequency rTMS was demonstrated in medically intractable ETLE patients. As far as CPSs are concerned, smaller decrease of motor threshold by voluntary muscle contraction was associated with better response to rTMS.

In vivo epileptogenicity of focal cortical dysplasia: a direct cortical paired stimulation study.

Summary:  Purpose: Alternation of the intracortical inhibitory and excitatory mechanisms in focal cortical dysplasia (FCD) has not been well elucidated in vivo in humans. We investigated in vivo alternation of these mechanisms in epileptogenesis of FCD by means of paired‐pulse direct cortical electrical stimulation.

Analysis of systemic and airway inflammation in obstructive sleep apnea

PurposeThe presence of both systemic and airway inflammation has been suggested in obstructive sleep apnea (OSA) by increased levels of inflammatory biomarkers in the circulation and respiratory specimens. We aimed to investigate the relationship between systemic and airway inflammation in OSA.MethodsThis study was conducted by simultaneously measuring various biomarkers both in serum and induced sputum of 43 patients. We compared the relationships of these biomarker levels with polysomnographic data and obesity measurements and also investigated their interrelationships between systemic and local compartments. We also assessed the relation of inflammatory markers with proximal airway resistance measured by impulse oscillometry.ResultsIn multiple regression analyses, each measured serum biomarker [leptin, interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF)] significantly correlated with waist circumference or fat area determined by computed tomography. In contrast, regarding airway inflammation, sputum IL-6, IL-8, TNF-α, and VEGF significantly correlated with OSA severity as indicated by the respiratory disturbance index or oxygen desaturation indices. Sputum IL-6, IL-8, TNF-α, and VEGF were significantly related to sputum neutrophil number, and sputum IL-8 and TNF-α were related to proximal airway resistance independently of body mass index. There were no significant interrelationships between the same biomarkers in serum and induced sputum.ConclusionsSystemic and airway inflammation in OSA might be differently regulated by OSA itself and comorbid obesity, depending on the type of cytokine. Although we did not find apparent interrelationships between systemic and local compartments, further studies are needed to clarify this concept.

Negative motor seizure arising from the negative motor area: Is it ictal apraxia?

Purpose:  Seizure manifesting motor arrest, that is, negative motor seizure (NMS), is a rare epileptic condition in which only inability to conduct voluntary movements or praxis is produced, although consciousness is preserved. The negative motor area (NMA) seems to be responsible, but its generator mechanism has not yet been clarified.

Flexible positive airway pressure improves treatment adherence compared with auto-adjusting PAP.

STUDY OBJECTIVES There are no clinical data comparing adherence and quality of life between auto-adjusting positive airway pressure (APAP) and two different flex positive airway pressure (PAP) devices (A-Flex, C-Flex) in patients with obstructive sleep apnea (OSA). DESIGN AND SETTING Ninety-three patients in whom OSA was newly diagnosed were randomly assigned to receive 3 mo of APAP (n = 31), APAP with C-Flex (n = 31), or APAP with A-Flex (n = 31). Objective adherence was determined after 3 mo of CPAP treatment, and the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Calgary Sleep Apnea Quality of Life Index (SAQLI) were examined at baseline and after 3 mo. After 3 mo, patients in the APAP with A-Flex group and those in the APAP with C-Flex group were crossed over and those in the APAP group were switched to A-Flex for an additional 3 mo. MEASUREMENTS AND RESULTS The groups were similar demographically. Treatment adherence during the first 3 mo was significantly greater in the APAP with C-Flex group (APAP with C-Flex: 5.19 ± 1.84 h/night versus APAP: 3.96 ± 1.66 h/night versus APAP with A-Flex: 4.27 ± 2.12 h/night, P = 0.04). There was a significant improvement in two of four of the SAQLI domain scores and in the ESS and PSQI in the APAP with C-Flex group. Adherence significantly improved among the poor compliers (< 4 h/night of use) in the APAP group after change to APAP with A-Flex (P = 0.01). CONCLUSIONS Of these three modes of PAP delivery, adherence was greatest with APAP with C-Flex. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00873977.

Long-term effect of bone marrow transplantation in adult-onset adrenoleukodystrophy

We report a long‐term outcome of motor function in a patient with adult‐onset adrenoleukodystrophy after bone marrow transplantation (BMT). Clinically motor function gradually improved and became almost normal in 2 years after BMT. Serial transcranial magnetic stimulation showed gradual improvement of central motor conduction until 1 year after BMT, and then it became stable. Central motor conduction time and motor threshold were useful for monitoring the central motor function in this patient.

Dominance of ipsilateral corticospinal pathway in congenital mirror movements

Objective: To clarify the mechanism of congenital mirror movements. Design: The triple stimulation technique (TST) and the silent period were used to investigate a patient with congenital mirror movements. The TST was used to calculate the ratio of ipsilateral to contralateral corticospinal tracts from the two hemispheres to the spinal motor neurones. Results: Transcranial magnetic stimulation over unilateral M1 induced larger ipsilateral than contralateral motor evoked potentials on both sides. Only 9% of spinal motor neurones innervating the abductor digitorum minimi were excited by contralateral primary motor cortex (M1) stimulation, while 94% were excited by the ipsilateral M1 stimulation. The silent period was examined during mirror movements and with voluntary contraction of the right first dorsal interosseus mimicking mirror movements. Left M1 stimulation (through the crossed corticospinal tract) did not show any difference in silent period between the two conditions, while right M1 stimulation (through the uncrossed tract) caused a longer silent period during mirror movements than during voluntary contractions. Conclusions: The results suggest that mirror movements may be caused by a strong connection between ipsilateral M1 and the mirror movements conveyed through a dominant ipsilateral corticospinal pathway.

Association between Plasma Neutrophil Gelatinase Associated Lipocalin Level and Obstructive Sleep Apnea or Nocturnal Intermittent Hypoxia

Background Both obstructive sleep apnea (OSA) and a novel lipocalin, neutrophil gelatinase associated lipocalin (Ngal), have been reported to be closely linked with cardiovascular disease and loss of kidney function through chronic inflammation. However, the relationship between OSA and Ngal has never been investigated. Objectives To evaluate the relationship between Ngal and OSA in clinical practice. Methods In 102 patients, polysomnography was performed to diagnose OSA and plasma Ngal levels were measured. The correlations between Ngal levels and OSA severity and other clinical variables were evaluated. Of the 46 patients who began treatment with continuous positive airway pressure (CPAP), Ngal levels were reevaluated after three months of treatment in 25 patients. Results The Ngal level correlated significantly with OSA severity as determined by the apnea hypopnea index (r = 0.24, p = 0.01) and 4% oxygen desaturation index (ODI) (r = 0.26, p = 0.01). Multiple regression analysis showed that the Ngal level was associated with 4%ODI independently of other clinical variables. Compliance was good in 13 of the 25 patients who used CPAP. Although the OSA (4%ODI: 33.1±16.7 to 1.1±1.9/h, p<0.01) had significantly improved in those with good compliance, the Ngal levels were not significantly changed (60.5±18.1 before CPAP vs 64.2±13.9 ng/ml after CPAP, p = 0.27). Conclusions Plasma Ngal levels were positively associated with the severity of OSA. However, the contribution rate of OSA to systemic Ngal secretion was small and changes in Ngal levels appeared to be influenced largely by other confounding factors. Therefore, it does not seem reasonable to use the Ngal level as a specific biomarker of OSA in clinical practice.

Dynamic change of proximal conduction in demyelinating neuropathies : a cervical magnetic stimulation combined with maximum voluntary contraction

OBJECTIVE To evaluate conduction abnormalities in the nerves innervating the proximal muscles in demyelinating neuropathies (DN) using cervical magnetic stimulation. METHODS We applied cervical root magnetic stimulation in the biceps brachii muscles and examined its activity-dependent conduction changes produced by maximal voluntary contraction (MVC) in 12 DN patients (seven chronic inflammatory demyelinating polyradiculoneuropathy and five multifocal motor neuropathy), six motor neuron disease (MND) patients, and 12 healthy volunteers. RESULTS Defining the upper normal limit of motor threshold (31%) and latency (6.7 ms) of the compound muscle action potential (CMAP) as mean+2SD, most DN patients revealed an abnormality in motor threshold (10/12) and latency (11/12) in contrast to MND patients (motor threshold (1/6) and latency (0/6)). These parameters contribute to the differentiation of DN from MND (P<0.01). Furthermore, the MVC maneuver transiently decreased the CMAP amplitude ratio (after MVC/before MVC x 100) in DN (83+/-18 %) compared with MND (P<0.01). Two of three DN patients who showed normal motor threshold or latency as in MND were successfully differentiated from MND by the MVC maneuver. CONCLUSIONS In DN patients, conduction abnormality in the nerves innervating the proximal muscles was revealed by cervical magnetic stimulation combined with the MVC maneuver. SIGNIFICANCE Our results suggested that conduction abnormalities in the proximal nerves innervating the proximal muscles could be evaluated by this method.

Generators and temporal succession of giant somatosensory evoked potentials in cortical reflex myoclonus: Epicortical recording from sensorimotor cortex

OBJECTIVE To clarify the generator mechanism of giant somatosensory evoked potentials (giant SEPs) and the hyperexcitability of primary somatosensory and motor cortices (SI and MI). METHODS In a patient with intractable focal seizures manifesting cortical reflex myoclonus of the left foot, giant SEPs to left tibial nerve stimulation were epicortically recorded as a part of presurgical evaluation with subdural electrodes. RESULTS In the single pulse SEPs, enlarged P1-N1 components were observed at the foot area of the SI and MI (86.5-258.8 microV, respectively), and the peak latencies were always shorter at SI than at MI by 6 ms. Similar findings were obtained for peroneal and sural nerve stimulation. In the paired pulse SEPs, the second response was less suppressed, as compared to other interstimulus intervals (ISIs), with ISIs of 40 and 200 ms both at SI and MI. CONCLUSIONS In this particular patient, cortical hyperexcitability to somatosensory stimuli seems to originate from SI but subsequently both SI and MI are responsible for the generation of giant SEPs and cortical reflex myoclonus. SIGNIFICANCE Somatosensory and primary motor cortices both generated enhanced early cortical components of SEPs, most likely by enhancing the latter by the former.