Predictors of the usefulness of mirogabalin for neuropathic pain: a single-institution retrospective study.

Mirogabalin is a novel, preferentially selective α2δ-1 ligand to treat neuropathic pain. However, this agent is not always effective for patients with neuropathic pain. We therefore attempted to identify factors that could predict the efficacy of mirogabalin. The study comprised 133 patients given mirogabalin for alleviation of neuropathic pain between April and November 2019 at our hospital. Variables were extracted from medical records for regression analysis of factors associated to alleviation of neuropathic pain. We evaluated the effect of mirogabalin at two weeks after administration. Groups were categorized according to degree of improvement: poor, effective, or very effective. Multivariate ordered logistic regression analysis was conducted to identify predictors for the usefulness of mirogabalin. Threshold measures were analysed using receiver operating characteristic (ROC) curves. Maintenance dose [odds ratio (OR) = 0.90; 95% confidence interval (CI) = 0.84-0.98; P = 0.01], concomitant use of opioids (OR = 0.26, 95% CI = 0.08-0.83; P = 0.023) and Neurotropin® (NTP) (OR = 4.78, 95% CI =1.04-21.93; P = 0.044) were factors significantly correlated to the effect of mirogabalin. ROC curve analysis of the effective group indicated a threshold maintenance dose of≤ 20 mg/day (area under the curve [AUC] = 0.53). In conclusion, maintenance dose (≤ 20 mg), concomitant use of opioids and NTP were identified as predictors for the utility of mirogabalin.

Three cases of suspected sugammadex-induced hypersensitivity reactions.

Neuromuscular blocking agents have been implicated in 60-70% of anaphylactic events associated with anaesthesia. We report two cases of probable hypersensitivity reaction to sugammadex and an additional suspected but less supported case of possible immune-mediated reaction or other adverse reaction. The patients were given a bolus of sugammadex 100 mg immediately before extubation. In all three patients, a possible allergic reaction was suspected within 4 min of sugammadex administration, but with different degrees of severity. Skin testing was positive in two of these patients. Hypersensitivity to sugammadex unaccompanied by cardiovascular or respiratory symptoms might be missed during the course of anaesthesia. Careful monitoring for possible allergic responses is required in patients who have received sugammadex.

Clinical application of radial magnetic resonance imaging for evaluation of rotator cuff tear.

BACKGROUND: Magnetic resonance imaging is useful for evaluating the rotator cuff, but some tendinous insertions cannot be assessed using oblique sagittal, oblique coronal, and axial magnetic resonance (MR) images because of the presence of the partial volume effect. HYPOTHESIS: The purpose of this study was to determine whether radial-slice MR images could reveal normal rotator cuff insertions and rotator cuff tears more clearly than conventional MR images. PATIENTS AND METHODS: The study included 18 subjects with normal rotator cuffs and 30 with rotator cuff tears. MR images of rotator cuff insertions sliced into radial, oblique coronal, and axial sections were obtained. The extent to which normal rotator cuff insertions and rotator cuff tears were visualized in each of the three MR images was evaluated. RESULTS: The top to posterior portions of the rotator cuff insertions from 0° to 120° could be visualized in the radial MR images. In comparison, the posterior portions of the rotator cuff insertions could not be visualized around 45° in both the oblique coronal and axial MR images. DISCUSSION: These findings demonstrate that radial MR images are superior to the oblique coronal and axial MR images regarding their ability to accurately visualize rotator cuff insertions. Radial MR images also revealed greater detail around 45° in the posterior area of the rotator cuff tears than the oblique coronal and axial MR images. Radial MR images are particularly useful for visualizing clinically important posterosuperior rotator cuff tears. LEVEL OF EVIDENCE: Level III - Diagnostic study.

Abnormal cortical motor excitability in dystonia.

To assess the excitability of the motor system, we studied 11 patients with task-specific dystonia and 11 age-matched normal subjects. The dominant side was affected in nine of the patients. We delivered transcranial magnetic stimuli at different stimulus intensities and with different levels of muscle facilitation to the side contralateral to the side of electromyographic recording, and recorded motor evoked potentials (MEPs) from the flexor carpi radialis muscles bilaterally. The threshold intensity for eliciting MEPs at rest did not differ between patients and normal subjects. We compared the affected side in patients with the dominant side in normal subjects. With facilitation, the percentage of the area of the MEP to the M wave (MEP area%) was similar in both groups at low stimulus intensities, but with increasing stimulus intensity the increase in the MEP area% was greater in patients than in normal subjects (ANOVA, p < 0.001). The increase in MEP area% was similar in both groups with increasing facilitation levels. The duration of the silent period was similar in patients and normal subjects. We conclude that cortical motor excitability is increased in dystonia.

Characterization of postexercise facilitation and depression of motor evoked potentials to transcranial magnetic stimulation.

We studied the effects of exercise on motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES). Subjects performed 30-second periods of isometric exercise of the extensor carpi radialis until fatigue, which was defined as the inability to maintain half maximum force. The amplitude of MEPs to TMS recorded from the resting muscle after each exercise period was on average more than twice the pre-exercise value (postexercise MEP facilitation). After fatigue occurred, the MEP amplitudes were approximately 60% of the pre-exercise value (postexercise MEP depression). There was a gradual recovery of the depressed MEPs to pre-exercise values over several minutes of rest. Postexercise MEP facilitation was constant when exercise intensity ranged from 10 to 50% of maximum voluntary contraction and it decayed to baseline over several minutes after the end of exercise. There was no postexercise MEP facilitation to TES. We hypothesize that both postexercise MEP facilitation and MEP depression are due to intracortical mechanisms.

Decreased postexercise facilitation of motor evoked potentials in patients with chronic fatigue syndrome or depression.

We studied the effects of exercise on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in 18 normal (control) subjects, 12 patients with chronic fatigue syndrome, and 10 depressed patients. Subjects performed repeated sets of isometric exercise of the extensor carpi radialis muscle until they were unable to maintain half maximal force. MEPs were recorded before and after each exercise set and for up to 30 minutes after the last set. The mean amplitude of MEPs recorded from the resting muscle immediately after each exercise set was 218% of the mean pre-exercise MEP amplitude in normal subjects, 126% in chronic fatigue patients, and 155% in depressed patients, indicating postexercise MEP facilitation in all three groups. The increases in the patient groups, however, were significantly lower than normal. The mean amplitudes of MEPs recorded within the first few minutes after the last exercise sets in all three groups were approximately half their mean pre-exercise MEP amplitudes. This postexercise MEP depression was similar in all groups. We conclude that postexercise cortical excitability is significantly reduced in patients with chronic fatigue syndrome and in depressed patients compared with that of normal subjects.

Nitric oxide synergistically potentiates interleukin-1 beta-induced increase of cyclooxygenase-2 mRNA levels, resulting in the facilitation of substance P release from primary afferent neurons: involvement of cGMP-independent mechanisms.

We previously demonstrated that cultured rat dorsal root ganglion (DRG) cells respond to stimulation with interleukin-1 beta (IL-1 beta) by releasing substance P (SP), and this response is regulated via the cyclooxygenase (COX)-2 pathway. In this study, to ascertain the interaction between nitric oxide (NO) and prostaglandins in primary afferent neurons, we investigated the effect of NO on the IL-1 beta-induced release of SP in cultured DRG cells. An NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), did not in itself evoke SP release. However, it potentiated the IL-1 beta-induced release of SP. Similarly, while SNAP did not elicit the expression of COX-2 mRNA, it potentiated the expression induced by IL-1 beta in cultured DRG cells, and this potentiation was significantly suppressed by the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO). Moreover, SNAP also potentiated the expression of COX-2 protein induced by IL-1 beta in cultured DRG cells. The stimulatory effect of SNAP on the IL-1 beta-induced release of SP was completely inhibited on co-incubation with a selective COX-2 inhibitor, NS-398. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), a potent inhibitor of soluble guanylate cyclase, did not suppress, and a membrane-permeable cGMP analogue, 8-Br-cGMP, did not mimic the stimulatory effects of SNAP in DRG cells. These results suggest that in cultured DRG cells, NO potentiates the IL-1 beta-induced increase in COX-2 expression via a soluble guanylate cyclase-cGMP-independent pathway, resulting in facilitation of SP release. The interaction between NO and COX in primary afferent neurons might contribute to the change in nociceptive perception in inflammatory hyperalgesia.

(1)H double-quantum filtered MR imaging of joints tissues: bound water specific imaging of tendons, ligaments and cartilage.

The (1)H double-quantum filtered (DQF) NMR and DQF MRI is applied to the joint tissues of rabbits for selective visualization of tendons, menisci and articular cartilage. The (1)H DQF NMR selectively filters double-quantum coherence arising from the (1)H dipolar interaction of the "bound" water in these tissues. The double-quantum creation time dependency of the DQF signal intensity is determined by the molecular environment of the "bound" water. Therefore, each tissue has a unique creation time at which the DQF signal reaches its maximum intensity, tau(max) (Achilles tendon: 0.46 +/- 0.02 ms, patella: 0.55 +/- 0.8 ms, anterior cruciate ligament: 0.60 +/- 0.05 ms, meniscus: 0.78 +/- 0.02 ms, skin: 0.81 +/- 0.07 ms). We have presented the creation-time-contrasted DQF images of the meniscus, patella, foot, and knee joint. Compared with conventional T(2)*-weighted gradient-echo (GRE) MR images, tendons, ligaments, menisci, and articular cartilage were more clearly seen in the DQF MR images. All these tissues were distinctly discriminated from each other by their creation times. DQF MR images of foot and knee joints can selectively demonstrated tendons, ligaments, and cartilage, which make it easier to understand the complicated anatomic structure of joints. Because the DQF NMR signal intensity and tau(max) are sensitive to the order structure of the "bound" water, it might be possible to introduce the creation-time dependent-contrast of (1)H DQF MR images as a new tool for analyzing the changes in the ordered structure of the tissue.

Characteristics of proton NMR T(2) relaxation of water in the normal and regenerating tendon.

The molecular behavior of water in normal and regenerating tendons was analyzed using the transverse relaxation time (T(2)) measured by spin-echo proton nuclear magnetic resonance ((1)H-NMR) spectroscopy at 2.34 T (25 degrees C). A section of the Achilles tendon was dissected from an anesthetized Japanese white rabbit, and its longitudinal axis was oriented at 0, 35, 54.7, 75, and 90 degrees to the static magnetic field. In the normal tendon, the T(2) relaxation of water presented biexponential relaxation and anisotropy in both the long T(2) (5.41 to 6.21 ms) and short T(2) (0.41 to 1.43 ms) components, in which the greatest values were obtained at 54.7 degrees. However, the range of the anisotropy was much narrower than we expected from the (1)H dipolar interaction of water bound to the collagen fibers in the tendon. The apparent fractions of water proton density also varied with orientation: the fraction of the longer T(2) components was at its maximum at 54.7 degrees. These results suggest that a simple two-compartment model could not be applicable to orientational dependency of the T(2) value of the tendon, and the well ordered water in the short T(2) relaxation component may show an elongated T(2) relaxation time that falls in the range of the long T(2) relaxation component at 54.7 degrees. This hypothesis can explain both the narrower range of the T(2) relaxation time and the orientational dependency on the apparent fraction of (1)H density. Regenerating processes of the Achilles tendon were followed for 18 weeks by analyzing the T(2) relaxation time. There is only a long T(2) relaxation time component (21.8 to 28.0 ms) up to 3 weeks after transection. Biexponential relaxation is revealed at 6 weeks and thereafter, whereby (i) the T(2) relaxation times become shorter, (ii) there is anisotropy in the short and long T(2) values, and (iii) the orientational dependency of the apparent fraction of water proton density becomes evident with maturation of the regenerating tendon. From these results, the (1)H T(2) relaxation time of water might be used to monitor the healing process of collagen structures of the tendon non-invasively.

Pulsed magnetic stimulation and F waves in Parkinson's disease.

Twenty-two patients with Parkinson's disease with predominantly unilateral signs in the upper extremities were studied by means of transcranial magnetic stimulation. The mean central motor conduction time (CMCT) on the clinically affected side determined by F wave technique was significantly shorter (p < .01) than that of the other side at rest. However, the mean CMCT during slight voluntary contraction was not significantly different in the two sides. Amplitudes of motor evoked potentials and F waves tended to be higher on the clinically affected side than on the other side. We conclude that reduced CMCT and high F wave amplitudes reflect hyperexcitability of the anterior horn cells in patients with Parkinson's disease.

Central motor conductivity in aged people.

The conductivity of motor neurons in 26 aged females (mean age 79 years) was analyzed by the conventional conduction method and by pulsed magnetic stimulation and compared with that in 14 younger controls. In aged people, slow motor conduction velocities were found in peripheral nerves. Central motor conduction time (CMCT) in relaxed muscle was shorter in the aged people, although CMCT was normal in mildly contracted muscle. These findings coincide with the results studied in Parkinson's disease, although these subjects were not diagnosed as having Parkinson's disease. Aged people generally have an anteflexed posture, slow movements, and poor postural reflexes, and have been reported to have a decrease in the dopamine level which is relatively earlier than that of other transmitters in the basal ganglia. This may account for the present finding that aged people have neurophysiological abnormalities in CNS which are similar to those in Parkinson's disease.

A clinicophysiologic study of central and peripheral motor conduction in hereditary demyelinating motor and sensory neuropathy.

Central and peripheral motor nerve conduction were analyzed in 13 patients with hereditary demyelinating motor and sensory neuropathy using central magnetic stimulation and peripheral electrodiagnostic techniques. All patients showed a marked decrease in peripheral nerve conduction velocity. In 11 patients, the central motor conduction time was slightly prolonged but in 2 it was markedly prolonged suggesting dysfunction of the corticospinal tract. These two patients exhibited marked weakness and atrophy of distal muscles without clinical signs of upper motor neuron dysfunction, which was considered to be masked by the lower motor neuron disorder. This study suggests that in some patients with hereditary demyelinating polyneuropathy central as well as peripheral nerve fibers may be affected.

[Detection of HTLV-I/ATLV by using the culture of lymph node lymphocytes with adult T-cell leukemia/lymphoma].

We cultured the cervical lymph node lymphocytes of a patient suffering from cutaneous T-cell lymphoma. His anti-ATLV antibody was positive by indirect immunofluorescent method (IF). ATLV was detected on these cultured cells by IF. Type C particles were observed in the cultured cells by electron microscopy. These particles were measured to be 60 to 120 nm in diameter with electron dense core, and were considered as ATLV. This case showed a possibility of detecting ATLV by culture of lymph node lymphocytes from such a patient.

[Central motor conduction time (CMCT) in hereditary motor sensory neuropathy type I (HMSN type I)].

The motor system of 13 cases with hereditary motor sensory neuropathy (HMSN) type I were analysed by clinical neurophysiological method. The motor conduction velocity (MCV) and F wave latency in lower motor neurone were markedly delayed. The latency of the muscle evoked potential (MEP) by cortical magnetic stimulation were also markedly delayed. The central motor conduction times (CMCT) were calculated by two methods. CMCT-mag was calculated by subtraction of the MEP by cervical magnetic stimulation from the MEP by cortical magnetic stimulation. CMCT-f was calculated by subtraction of the [(F wave latency -1 + distal latency)/2] from the MEP by cortical magnetic stimulation. There were positive correlation between CMCT-f and CMCT-mag. CMCT of HMSN type I were divided to two groups. CMCT of the first group was markedly delayed. CMCT of the second group was mildly delayed or normal. The former group showed marked weakness in distal muscles clinically. The latter group showed mild or moderate weakness in distal muscles clinically. All these patients did not show any pyramidal tract signs, which could be covered by severe lower motor neurone involvements. The classification of HMSN type I by gene was well known, genetical analysis might be important to these groups in HMSN type I.

[A case of acute multifocal motor neuropathy with conduction block after Campylobacter jejuni enteritis].

The patient was a 25-year-old male with acute multifocal motor neuropathy with conduction block (MMNCB) after Campylobacter jejuni enteritis. After having suffered from diarrhea for 3 days, he rapidly developed asymmetrical distal-dominant muscle weakness in all extremities. Sensory disturbance was unremarkable except for slight disturbance in deep sensation. Deep tendon reflexes were normal throughout the course of present illness. CSF analysis revealed increased protein up to 66 mg/dl without pleocytosis. In electrophysiological examinations, persistant multifocal conduction blocks in the motor nerves were predominantly noted in the distal part of the extremities. Serum titers of anti-Campylobacter jejuni antibody, anti-GM1 antibody and anti-GalNAc-GD1a antibody were elevated. Muscle weakness resolved completely within 7 weeks. The sural nerve biopsy did not reveal either axonal degeneration, nor demyelination. These clinical and laboratory findings suggested that this case was most likely an acute type of MMNCB after Campylobacter jejuni enteritis.