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Background: Iliopsoas hematoma is a rare but serious bleeding event that occurs during anticoagulation therapy. Due to lack of previous reports of clinical data, incidence and characteristics of iliopsoas hematoma during tetanus management, including anticoagulation prophylaxis for venous thromboembolism, remain unclear. Aim: To evaluate the incidence of iliopsoas hematoma in tetanus and identify clinical factors that would help in its detection. Materials and Methods: We conducted a retrospective descriptive study and evaluated the clinical courses of patients with iliopsoas hematoma as a case series. Patient data were collected by reviewing medical charts. Results: Among 21 patients, four (19%) developed iliopsoas hematoma during the clinical course of tetanus. A case series of these four patients revealed that all had progressive anemia; furthermore, D‐dimer levels continued increasing or did not decrease in these patients despite them receiving anticoagulation therapy. Conclusion: The incidence of tetanus‐related iliopsoas hematoma was higher than that of anticoagulation‐related iliopsoas hematoma. Therefore, clinicians should carefully consider the indication of prophylaxis for venous thromboembolism in patients with tetanus. Progressive anemia and increased D‐dimer level may indicate iliopsoas hematoma in patients with tetanus. [ABSTRACT FROM AUTHOR]

Objectives: The triad conditioned facilitation (TCF) technique has been shown to detect motor cortical intrinsic rhythms depending on the functioning of specific cortical layers by measuring motor evoked potential (MEP) enhancement after a triad of conditioning TMS pulses at a certain interval. However, the influence of cortical degeneration on TCF is still undetermined. We therefore studied TCF in patients with amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterised by degeneration of the motor cortex. Methods: Thirteen patients with ALS and 11 age-matched disease control patients with cervical myelopathy (CM) or radiculopathy (CR) participated in the study. We studied short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and TCF using the paired-pulse and triad conditioned TMS paradigm. Results: TCF was significantly reduced in ALS patients compared to CM/CR patients, who had normal TCF. SICI and ICF did not differ between groups. Conclusion: The absence of TCF with preserved SICI and ICF suggests changes in the intrinsic rhythm generation within the motor cortex due to cortical neurodegeneration in ALS patients. In contrast, TCF was normal in patents with CM/CR in whom the motor cortical intrinsic circuits are not involved. This technique may be valuable to differentiate patients with ALS from those with CM/CR. [ABSTRACT FROM AUTHOR]

We report an 81-year-old man with multiple liver metastases after tumorectomy for primary mediastinal malignant melanoma, who experienced limb weakness and sensory disturbance after nivolumab monotherapy. He was diagnosed with nivolumab-induced mononeuropathy multiplex and rhabdomyolysis based on serologic examination, muscle biopsy, magnetic resonance imaging of the limbs, and a nerve conduction study. A course of intravenous methylprednisolone (mPSL) was initiated at 1 g/day for 3 days. After that, oral prednisolone (PSL) was started at 1 mg/kg/day and gradually tapered. Limb muscle strength improved, but when PSL was reduced to 0.3 mg/kg/day, the weakness recurred, and a nerve conduction study showed exacerbation of mononeuropathy multiplex. The patient was again administered intravenous mPSL (0.5 g/day for 3 days) followed by oral PSL at 0.5 mg/kg/day, and his neurological symptoms improved. Nivolumab, an immune checkpoint inhibitor, is used for the treatment of advanced melanoma and other cancers and causes various immune-related adverse events (irAEs). However, neurological irAEs related to nivolumab are rare. Furthermore, there are no reports of simultaneous nerve and muscle impairment. Unexpected irAEs affecting various organs should be recognized and treated appropriately. [ABSTRACT FROM AUTHOR]

To evaluate the spinal cord atrophy that occurs in HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP), we conducted magnetic resonance imaging (MRI) and pathological analyses. In the MRI study, 15 patients with HAM/TSP and 20 age-matched normal control subjects were enrolled. Anteroposterior and transverse distances and cross-sectional areas were measured and calculated at the C2, C4, C6, T2, and T6 vertebral levels. In the pathological study, spinal cord autopsy specimens were compared between a HAM/TSP case and an adult T cell leukemia/lymphoma case. In both the MRI and pathological studies, HAM/TSP spinal cords demonstrated more severe atrophy in the anteroposterior direction than those of controls. The spinal cord atrophy and pathological changes in HAM/TSP occurred predominantly in the white matter, especially in the lateral columns. This is the first report indicating spinal cord atrophy in the anteroposterior direction using MRI. In pathological analysis, atrophy and pathological changes were prominent in areas of the spinal cord with slow blood flow. Hemodynamic and anatomical factors are speculated to be among the main mechanisms of atrophy in the anteroposterior direction. [ABSTRACT FROM AUTHOR]

Background Many patients from Toroku, Japan, who have chronic arsenic exposure demonstrate whole-body sensory disturbance that is slightly more pronounced in the extremities. Although previous research in this population showed a mild peripheral neuropathy, it is unknown whether these patients have central nervous system impairment. To investigate the lesion sites underlying sensory disturbance related to chronic arsenic poisoning, we analyzed somatosensory evoked potentials (SEP). Methods Clinical features, nerve conduction study results, and median and/or tibial SEP were analyzed in patients with chronic arsenic exposure (total, 13 patients; median & tibial, 4; median, 5; tibial, 4) retrospectively. The SEP findings in patients were compared with those in normal controls. Results The median SEP results indicated a conduction delay between the proximal brachial plexus and the primary sensory cortex, and tibial SEP findings indicated a delay between the dorsal gray matter of the lumbosacral cord and the primary sensory cortex. Conclusion This is the first study to identify an impairment of the central somatosensory pathway in patients with chronic arsenic exposure. Sensory disturbance in these patients is related not only to peripheral neuropathy but also to impairment of the central nervous system. [ABSTRACT FROM AUTHOR]

In previous studies of human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), areas of slow blood flow in the spinal cord were related to pathological changes. While the pathological changes in the brain are milder than those in the spinal cord, they are also more significant in sites with slow blood flow. In this study, we investigated brain glucose metabolism in slow blood flow areas using fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET). Clinical features and brain (18)F-FDG-PET parameters were analyzed in six patients with HAM/TSP. For comparison of PET data, eight healthy volunteers were enrolled as normal controls (NLs). Glucose metabolism in the watershed areas of the middle and posterior cerebral arteries, as compared with that in the occipital lobes as a control, was significantly lower in HAM/TSP patients than in NLs. This result confirmed the relationship between slow blood flow areas and hypometabolism in HAM/TSP, and is consistent with previous findings that pathological changes are accentuated in sites with slow blood flow. [ABSTRACT FROM AUTHOR]

Background: Cardiac 123I-metaiodobenzylguanidine scintigraphy (MIBG) previously demonstrated an uptake reduction in patients with Parkinson's disease (PD). However, epidemiologic research showed that electrocardiography (ECG) abnormalities occurred prior to motor signs in PD. Here we investigated whether the electrical conduction system of the heart was impaired in PD. Methods: Clinical features, ECG and MIBG parameters were analyzed in 191 patients with PD, 42 with multiple system atrophy (MSA) and 124 normal controls (NL). Results: The PR interval was significantly longer in patients with PD than in NL. The PR interval was significantly negatively correlated with early and delayed heart-to-mediastinum ratios in MIBG scintigraphy in PD and MSA patients. In 19 PD patients with PR prolongation, 17 patients also had abnormal MIBG findings, and the other 2 showed normal MIBG. Conclusions: The PR prolongation must show some sympathetic system abnormality because it is mainly controlled by the sympathetic nervous system. PR prolongation supports the objective biomarker value of MIBG for PD diagnosis. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate physiological mechanisms underlying ataxia in patients with ataxic hemiparesis. Subjects were three patients with ataxic hemiparesis, whose responsible lesion was located at the posterior limb of internal capsule (case 1), thalamus (case 2), or pre- and post-central gyri (case 3). Paired-pulse transcranial magnetic stimulation (TMS) technique was used to evaluate connectivity between the cerebellum and contralateral motor cortex. The conditioning cerebellar stimulus was given over the cerebellum and the test stimulus over the primary motor cortex. We studied how the conditioning stimulus modulated motor evoked potentials (MEPs) to the cortical test stimulus. In non-ataxic limbs, the cerebellar stimulus normally suppressed cortical MEPs. In ataxic limbs, the cerebellar inhibition was not elicited in patients with a lesion at the posterior limb of internal capsule (case 1) or thalamus (case 2). In contrast, normal cerebellar inhibition was elicited in the ataxic limb in a patient with a lesion at sensori-motor cortex (case 3). Lesions at the internal capsule and thalamus involved the cerebello-thalamo-cortical pathways and reduced the cerebellar suppression effect. On the other hand, a lesion at the pre- and post-central gyri should affect cortico-pontine pathway but not involve the cerebello-thalamo-cortical pathways. This lack of cerebello-talamo-cortical pathway involvement may explain normal suppression in this patient. The cerebellar TMS method can differentiate cerebellar efferent ataxic hemiparesis from cerebellar afferent ataxic hemiparesis. [ABSTRACT FROM AUTHOR]

To evaluate on-line effects of quadripulse stimulation (QPS) over the primary motor cortex (M1) on cortical areas in the contralateral hemisphere. QPS consisted of 24 bursts of transcranial magnetic stimulation (TMS) pulses with an inter-burst interval of 5 s for 2 min (for on-line effect study) or 360 bursts for 30 min (for after-effect study). Each burst consisted of four TMS pulses (i.e. QPS) separated by an interstimulus interval of 5 or 50 ms (QPS-5 or QPS-50). QPSs were delivered over the left M1. Experiment 1 [on-line effect on somatosensory evoked potential (SEP)]: Left median nerve SEPs were recorded before, during and after QPS. Experiment 2 (after effect on SEP): After-effects of QPS were evaluated by following up SEPs after the QPS sessions. Experiment 3 (on-line effect on NIRS): Near infrared spectroscopy (NIRS) was also recorded at the right hemisphere during all QPS paradigms. Both QPS-5 and QPS-50 enlarged a cortical component of the contralateral SEP during stimulation. On the other hand, concerning the after effects, QPS-5 over M1 potentiated the contralateral SEP and QPS-50 tended to depress it. In NIRS study, both QPS-5 and QPS-50 induced a significant oxy-Hb decrease (deactivation pattern) at the right hemisphere during stimulation whereas sham stimulations unaffected them. We have shown the unidirectional on-line effects evoked by QPS-5 and QPS-50 on both SEP and NIRS, and bidirectional after effects on SEP at the contralateral hemisphere. The discrepancy between on-line effect and after effect may be explained by the differences in the underlying mechanisms between them. The former may be mainly explained by pure electrophysiological property changes in the membrane or synapses. The latter may be explained by synaptic efficacy changes which need some protein syntheses at least partly. Another discrepancy shown here is the direction of on-line effects. Electrophysiological (SEP) function was potentiated by both QPSs whereas hemodynamic (NIRS) function was depressed. This may be explained by which sensory areas contribute to NIRS or SEP generation. [ABSTRACT FROM AUTHOR]

We investigated a progression of brain atrophy and somatosensory system dysfunction in multiple system atrophy (MSA). Subjects were 21 MSA patients [12 MSA-C (cerebellar type) and 9 MSA-P (parkinsonism type)]. The relative volumes of cerebrum, brainstem and cerebellum to the intracranial volume were obtained from three-dimensional computed tomography (3D-CT) of the brain. The median nerve somatosensory evoked potentials (SEPs) were recorded, and the latencies and amplitudes of N9, N11, P13/14, N20 and P25 components were measured. We studied correlations between brain volumes, SEP and clinical features. The brainstem and cerebellar atrophies were aggravated with progression of the disease. The central sensory conduction time (CSCT) was progressively prolonged in parallel with the disease duration irrespective of the actual age of the patients. In MSA patients, the volume reductions of cerebellum and brainstem could be one of structural markers of disease progression, and the sensory pathway is progressively involved with the progression of disease processes. [ABSTRACT FROM AUTHOR]

Background: The association between Parkinson's disease (PD) and body mass index (BMI) has not been established. In this study, we investigated the correlation between BMI and autonomic dysfunction in patients with PD. Methods: Clinical features, BMI, cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphy and the coefficient of variation of the electrocardiographic R-R interval (CVRR) were analyzed in 124 patients with PD who were naïve to anti-parkinsonian drugs. Results: BMI was negatively correlated with early heart-to-mediastinum ratio and CVRR in patients with PD, regardless of disease duration and severity. Conclusions: Autonomic dysfunction and BMI increase were associated with each other. Physicians should consider the possibility of autonomic dysfunction in PD patients with high BMI. [ABSTRACT FROM AUTHOR]

Background: We have followed 9 Japanese patients with opticospinal multiple sclerosis (OSMS), some of whom showed longitudinally extensive spinal cord lesions, deep sensory disturbances and resistance to treatment. We investigated the patients for anti-aquaporin 4 (AQP4) antibodies and related this to their neuroimaging, clinical and laboratory features. Methods: We studied the clinical course, neurological findings, cerebrospinal fluid (CSF), and electrophysiological findings, and determined the presence of anti-AQP4 antibody and human leukocyte antigen DPB1 and DRB1 alleles. Results: Five patients (56.6%) had anti-AQP4 antibody. Antibody-positive patients displayed female predominance, longitudinally extensive spinal cord lesions, higher frequency of exacerbations, severe disability, and higher cell counts and total protein content without IgG oligoclonal bands in the CSF. They also showed poor steroid responsiveness and poor therapeutic response to interferon β1b. Conclusions: The presence of anti-AQP4 antibodies correlates with clinical severity and poor prognosis in OSMS. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Using near infrared spectroscopy and repetitive transcranial magnetic stimulation (rTMS), we studied interhemispheric interactions between bilateral motor and sensory cortices in humans. RTMS consisted of a triple-pulse burst (50 Hz) repeated every 200 m for 2 s (10 bursts, 30 pulses); one kind of theta burst TMS (TBS) (Huang et al. in Neuron 45:201–206, ). The hemoglobin concentration changes were recorded at the right prefrontal cortex, premotor area (PM), primary hand motor area (M1) and primary sensory area (S1) during and after TBS over the left PM, M1 and S1 or sham stimulation in eight normal volunteers. In addition, motor evoked potentials (MEPs) to TMS over the right M1 were recorded from the left first dorsal interosseous muscle after the conditioning TBS over left S1. TBS over PM induced a significant oxy-Hb decrease at the contralateral PM. TBS over M1 elicited a significant oxy-Hb decrease at the contralateral S1, and TBS over S1 significant oxy-Hb decreases at the contralateral M1 and S1. MEPs to TMS of the right M1 were significantly suppressed by the conditioning TBS over the left S1. These results suggest that there are mainly inhibitory interactions between bilateral PMs and bilateral sensorimotor cortices in humans. Those are partly compatible with the previous findings. In addition to between the primary motor cortices, bilateral connection is requisite for smooth bimanual coordination between the sensory cortices or premotor cortices. [ABSTRACT FROM AUTHOR]

We measured cortical hemoglobin-concentration changes under the coil induced by single-pulse transcranial magnetic stimulation (TMS) using a technique of simultaneous recording with near-infrared spectroscopy (NIRS). Single-pulse TMS was delivered over the hand area of the left primary motor cortex at an intensity of 100, 120, or 140% of the active motor threshold (AMT). NIRS recordings were also made during sham stimulation. These four different stimulation sessions (TMS at three intensities and sham stimulation) were performed both when the subject slightly contracted the right first dorsal interosseous muscle and when relaxed it (active and resting conditions). Under the active condition with TMS at 100% AMT, we observed a transient increase in oxy-hemoglobin (oxy-Hb), which was significantly larger than sham stimulation. Under the resting conditions with TMS at 120 and 140% AMT, we observed significant decreases in both deoxy-hemoglobin (deoxyHb) and total-hemoglobin (total-Hb) as compared to sham stimulation. We suggest that the increase of oxy-Hb concentration at 100% AMT under the active condition reflects an add-on effect by TMS to the active baseline and that decrease of deoxy-Hb and total-Hb concentrations at 120 and 140% AMT under the resting condition are due to reduced baseline firings of the corticospinal tract neurons induced by a lasting inhibition provoked by a higher intensity TMS. [ABSTRACT FROM AUTHOR]

We used transcranial magnetic stimulation (TMS) in a paired pulse protocol to investigate interhemispheric interactions between the right dorsal premotor (dPM) and left primary motor cortex (M1) using interstimulus intervals of 4, 6, 8, 10, 12, 16 and 20 ms in ten healthy subjects. A conditioning stimulus over right dPM at an intensity of either 90 or 110% resting motor threshold (RMT) suppressed motor-evoked potentials (MEPs) evoked in the first dorsal interosseous (FDI) muscle by stimulation of left M1. Maximum effects occurred for interstimulus intervals (ISIs) of 8–10 ms. There was no effect if the conditioning stimulus was applied 2.5 cm lateral, anterior or medial to dPM. The effect differed from previously described M1 interhemispheric inhibition in that the threshold for the latter was greater than 90% RMT, whereas stimulation of the dPM at the same intensity led to significant inhibition. In addition, voluntary contraction of the left FDI (i.e. contralateral to the conditioning TMS) enhanced interhemispheric inhibition from right M1 but had no effect on the inhibition from right dPM. Finally, conditioning to right dPM at 90% RMT reduced short-interval intracortical inhibition (SICI; at ISI= 2 ms) in left M1 whilst there was no effect if the conditioning stimulus was applied to right M1. We conclude that conditioning TMS over dPM has effects that differ from the previous pattern of interhemispheric inhibition described between bilateral M1s. This may reflect the existence of commissural fibres between dPM and contralateral M1 that may play a role in bimanual coordination. [ABSTRACT FROM AUTHOR]

Single pulses of transcranial magnetic stimulation (TMS) were applied to the right hemisphere over either the hand sensory area, the hand motor area (M1), ventral premotor area (vPM), dorsolateral prefrontal cortex, or 10 cm away from head (sham stimulation) in order to test the effect on motor evoked potentials (MEPs) elicited by single pulse TMS or transcranial electrical stimulus (TES) over the left M1 or the somatosensory evoked potential (SEP) elicited by an electrical stimulus to the right median nerve. The interstimulus intervals (ISIs) for MEP experiments were 50, 100, 150, 200, 300 and 400 ms, with those for SEP experiments being adjusted for the impulse conduction time from the wrist to the cortex. TMS over the right M1 reduced MEPs elicited by TMS of the left motor cortex at ISIs of 50-150 ms, whereas MEPs produced by TES were unaffected. TMS over M1 and vPM facilitated the contralateral cortical median nerve SEPs at an ISI of 100-200 ms, whereas it had no effect on tibial nerve SEPs or paired median nerve stimulation SEP. Based on these results, we conclude that at around 150-ms intervals, TMS over the motor areas (M1 and vPM) reduces the excitability of the contralateral motor area. This has a secondary effect of enhancing the responsiveness of the sensory cortex through cortico-cortical connections. [ABSTRACT FROM AUTHOR]

People who have a Glu487Lys mutation (single nucleotide polymorphism) in the aldehyde dehydrogenase-2 (ALDH2) gene are slow to metabolize the alcohol breakdown product acetaldehyde. The P13/14–N20 interval of the median nerve somatosensory evoked potential was significantly longer in alcoholic patients with a hypoactive ALDH2 (n = 27) than in those with an active ALDH2 (n = 43). This suggests that acetaldehyde accumulation due to hypoactive ALDH2 is associated with a prolongation of the central sensory conduction time between pons and primary sensory cortex. The present result indicates that an elevated blood concentration of acetaldehyde must cause the central sensory tract involvement and that acetaldehyde is one of factors producing brain damage in alcoholics. [Copyright &y& Elsevier]

Selegiline protects nigral dopaminergic neurons and is recommended for the treatment of patients in the early stage of Parkinson''s disease (PD). We treated 112 PD patients and noted that those given selegiline had a high incidence of hallucination. Our objective was to determine which clinical therapeutic factors cause such hallucinations. The Kruskal-Wallis and χ2 test showed that in 94 patients, the severity of the hallucinations was significantly related to the duration of illness, Hoehn and Yahr stage, doses of levodopa and cabergoline, whether or not selegiline was used, and whether or not medication for constipation was required. In addition, patients who were treated with a low dose of levodopa (≤300 mg/day), who had a low Hoehn and Yahr stage, and a short duration of illness (≤8 years) together with a high dose of selegiline or cabergoline also tended to have hallucinations. MRI findings were not related to the incidence of hallucination.When selegiline is given to patients who have PD of long duration and a high Hoehn and Yahr stage, and who already are receiving levodopa and a dopamine agonist, the doses of levodopa and the dopamine agonists given, as well as the presence of constipation, may be related to the incidence of hallucination. [Copyright &y& Elsevier]

Nine alcoholic patients with central pontine myelinolysis (CPM),who showed a favorable prognosis, are reported. The majority of them had taken part in binge drinking and had a subsequent consciousness disturbance for 18.1±10.9 (mean±SD) days. None of the patients had had acute correction of hyponatremia. Truncal ataxia and gait instability were present in most of the patients after recovery from the disturbance of consciousness. Most of them eventually gained independence, and magnetic resonance imaging showed that their pontine lesions tended to shrink. Electrophysiological studies detected prolonged latency between the I and III waves in auditory brainstem responses and between N11 and P13/14 onsets in the somatosensory evoked potentials. These clinical, radiological and electrophysiological findings should be of use in diagnosing CPM. [ABSTRACT FROM AUTHOR]

To evaluate recovery function of and effects of hyperventilation (HV) on high-frequency oscillations (HFOs) of median nerve somatosensory evoked potential (SEP), we recorded SEPs in 8 Parkinson''s disease (PD) patients with enlarged HFOs, 4 myoclonus epilepsy (ME) patients and 10 healthy volunteers (N). SEP was recorded from the hand sensory area contralateral to the median nerve stimulated at the wrist. Responses were amplified with filters set at 0.5 and 3000 Hz. HFOs were obtained by digitally filtering raw SEPs from 500 to 1000 Hz. We measured amplitudes of the N20 onset–peak (N20o–p), N20 peak–P25 peak (N20p–P25p), P25 peak–N33 peak (P25p–N33p), the early (1st–2nd) and late (3rd) HFOs. For the recovery function study, paired-pulse stimuli at various interstimulus intervals (20, 50, 100, 150, 200 and 300 ms) were given. To investigate effects of HV, amplitudes of several components of SEPs recorded after HV were compared with those before HV. In PD and ME, the N20o–p recovery curve showed significantly less suppression as compared with those of N. The P25p–N33p recovery curve of ME showed longer suppression than those of N and PD. There were no significant differences in the early or late HFOs recovery curves among three groups. At the dysinhibited state after HV, the late HFO was reduced in association with a significant enlargement of the N20p–P25p amplitude in normal subjects. This suggests that the late HFOs should reflect bursts of inhibitory interneurons. In the ME patients, the early HFOs significantly decreased by HV. The pattern in ME patients may be explained by a kind of compensation for already enhanced SEPs (giant SEP) in the dysinhibited situation. We conclude that (1) Giant HFOs are normally regulated by inhibitory neuronal systems involving in paired stimulation SEP. (2) The late HFOs must reflect bursts of GABAergic inhibitory interneurons. [Copyright &y& Elsevier]

This paper proposes a new method which produces electric energy by utilizing the density difference of water by means of a “chimney effect.” The density difference of water occurs in two ways, i.e., differences of water temperature and consistency of suitable materials such as salt. For instance, water heated by solar energy is pointed out as an example of the former, while fresh water of a river versus seawater and seawater versus concentrated salt water may account for the latter. This paper also considers the three foregoing cases in a practical way. The analysis estimates that the proposed method generates energy of several hundreds or more, and ten thousands and millions of kilowatts in the respective cases. The amount of energy extracted in the third case is compared with that of the usual electric power stations using nuclear energy. The method is considered as a kind of so-called renewable energy conversion system which is free of CO2, high-energy density and is controllable. © 1997 Scripta Technica, Inc. Electr Eng Jpn, 118 (2): 10–18, 1997 [ABSTRACT FROM AUTHOR]

Highlights • The long-term auditory sequelae after arsenic exposure have never been evaluated. • We evaluated these sequelae in chronically-exposed and control groups. • The results of ABR analysis were similar between the groups. • The exposed group had normal hearing function 40 years after exposure cessation. [ABSTRACT FROM AUTHOR]

A 41-year-old man with multiple sclerosis (MS) complained of nocturnal enuresis at the third exacerbation. Neurological examination revealed echopraxia, forced grasp reflexes and palmo-mental reflexes. The urodynamic studies showed neither spinal cord nor peripheral nerve involvements. His brain magnetic resonance images (MRIs) revealed new lesions at the bilateral medial frontal lobes. The intravenous methylprednisolone therapy improved nocturnal enuresis and made brain MRI lesions smaller and gone. In addition to frequently observed spinal cord lesions, we should consider some medial frontal lesions to be responsible for micturitional disturbance in patients with MS. [ABSTRACT FROM AUTHOR]

• We designed an RT-PCR assay that utilizes newly designed double-quencher probes. • The new assay decreased background fluorescence and improved dynamic range. • Double-quencher probes improved the SARS-CoV-2 detection rate in clinical samples. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in the city of Wuhan, Hubei Province, China, has spread worldwide and is threatening human life. The detection of SARS-CoV-2 is critical for preventing new outbreaks, curbing disease spread, and managing patients. Currently, a reverse-transcription polymerase chain reaction (RT-PCR) assay is used to detect the virus in clinical laboratories. However, although this assay is considered to have high specificity, its sensitivity is reportedly as low as 60–70 %. Improved sensitivity is, therefore, urgently required. We used the primers and single-quencher probes recommended by the CDC (N1, N2 and N3) in the USA and the NIID (N1 and N2) in Japan. In addition, we designed double-quencher probes according to the virus sequence provided by the NIID to develop a further assay (termed the YCH assay [N1 and N2]). Using these assays, we conducted RT-PCR with serially diluted DNA positive controls to assess and compare the detection sensitivity of the three assays. Furthermore, 66 nasopharyngeal swabs were tested to determine the diagnostic performances. The threshold cycle (Ct) value of the RT-PCR was relatively low for the CDC and YCH assays compared with the NIID assay. Serial dilution assays showed that both the CDC and YCH assays could detect low copy numbers of the DNA positive control. The background fluorescence signal at the baseline was lower for the YCH assay compared with the NIID assay. We assessed the diagnostic performance between single- (NIID) and double-quencher (YCH) probes using 66 nasopharyngeal swabs. When the results of YCH-N2 assay were used as a reference, each assay detected SARS-CoV-2 with positive percent agreements of 56 % for NIID-N1, 61 % for YCH-N1, and 94 % for NIID-N2, and 100 % negative percent agreements for NIID-N1, YCH-N1 and NIID-N2. Double-quencher probes decreased the background fluorescence and improved the detection sensitivity of RT-PCR for SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Persons who have the Glu-487→Lys mutation (single nucleotide polymorphism) of the aldehyde dehydrogenase-2 (ALDH2) gene have less ability to metabolize the alcohol breakdown product acetaldehyde. In order to clarify whether acetaldehyde is associated with the pathogenesis of alcoholic polyneuropathy, we compared nerve conduction data as well as clinical signs and symptoms of neuropathy between alcoholics with ALDH2*2 (Lys-487) heterozygotes and those with ALDH2*1 (Glu-487) homozygotes. Alcoholics with ALDH2*2 heterozygotes showed significantly lower sensory nerve action potential amplitudes of the sural and median nerves than those with ALDH2*1 homozygotes, suggesting that the accumulation of acetaldehyde due to ALDH2 inactivity is associated with alcoholic polyneuropathy. [Copyright &y& Elsevier]

Arsenic (As) contamination affects hundreds of millions of people globally. Although the number of patients with chronic As exposure is large, the symptoms and long-term clinical courses of the patients remain unclear. In addition to reviewing the literature on As contamination and toxicity, we provide useful clinical information on medical care for As-exposed patients. Further, As metabolite pathways, toxicity, speculated toxicity mechanisms, and clinical neurological symptoms are documented. Several mechanisms that seem to play key roles in As-induced neurotoxicity, including oxidative stress, apoptosis, thiamine deficiency, and decreased acetyl cholinesterase activity, are described. The observed neurotoxicity predominantly affects peripheral nerves in sensory fibers, with a lesser effect on motor fibers. A sural nerve biopsy showed the axonal degeneration of peripheral nerves mainly in small myelinated and unmyelinated fibers. Exposure to high concentrations of As causes severe central nervous system impairment in infants, but no or minimal impairment in adults. The exposure dose–response relationship was observed in various organs including neurological systems. The symptoms caused by heavy metal pollution (including As) are often nonspecific. Therefore, in order to recognize patients experiencing health problems caused by As, a multifaceted approach is needed, including not only clinicians, but also specialists from multiple fields. [ABSTRACT FROM AUTHOR]

Introduction: Respiratory infections are an ongoing global health challenge. The COVID‐19 pandemic triggered global nonpharmacological measures that reshaped public health. In Japan, the shift from legal to individual discretion in pandemic management started on May 8, 2023. However, it still unknown how the relaxation of measures affects respiratory pathogens across age groups. Methods: We collected 16,946 samples from 13,526 patients between February 2020 and September 2023, analyzing the circulating respiratory pathogen dynamics using FilmArray respiratory panel. Results: Our analysis revealed significant increases in the positivity rates of respiratory pathogens across multiple age groups after relaxation. The pathogens including adenovirus, Bordetella pertussis, parainfluenza 2 and parainfluenza 4 showed increased positivity predominantly in children aged under 10 years. Conversely, some pathogens including human metapneumovirus, rhinovirus/enterovirus, and respiratory virus (RSV) increased in broad range of age groups. SARS‐CoV‐2 positivity rates decreased in children under 10 years but increased in those aged over 60 years. Discussion: Age‐stratified analysis reveals a dynamic pattern of circulating pathogen in each age group after relaxation measures. This study provides essential epidemiologic data that can guide strategies to protect different age groups and effectively respond to respiratory infections in post‐COVID‐19 era. [ABSTRACT FROM AUTHOR]

Objective: To study the presence of liver‐expressed antimicrobial peptide 2 (LEAP2) in human cerebrospinal fluid (CSF) and to measure its concentrations in neurological disorders. Materials & Methods: We identified the presence of LEAP2 in human CSF by chromatographic analysis and a LEAP2‐specific enzyme immunoassay. We measured LEAP2 concentrations in the CSF of 35 patients with neurological disorders. Results: CSF LEAP2 concentrations in the bacterial meningitis group (mean ± SD, 9.32 ± 3.76 ng/ml) were significantly higher (p <.05) than those in the other four groups (psychosomatic disorder, 0.56 ± 0.15 ng/ml; peripheral autoimmune disease, 1.00 ± 0.60 ng/ml; multiple sclerosis, 0.62 ± 0.30 ng/ml; aseptic meningitis, 1.59 ± 0.69 ng/ml). Conclusions: This is the first study to identify the presence of human LEAP2 in the CSF. Levels of LEAP2 were increased in the CSF of patients with bacterial meningitis. LEAP2 may have potential as a biomarker for bacterial meningitis. [ABSTRACT FROM AUTHOR]

• The number of mutations per patient was significantly higher using the molecular barcoding (MB) panel than using the non-MB panel. • Tumor-derived mutations were detected more frequently using the MB panel than the non-MB panel. • Drug-matched mutations were identified in ERBB2 (3 patients with BTC and 1 patient with PC) and PIK3CA (1 patient with BTC). • Liquid biopsy with MB may have utility in providing genomic information for the prognosis of patients with PBCA. Obtaining sufficient tumor tissue for genomic profiling is challenging in pancreaticobiliary cancer (PBCA). We determined the utility of molecular barcoding (MB) of liquid biopsies (bile, duodenal fluid, and plasma) for highly sensitive genomic diagnosis and detection of druggable mutations for PBCA. Two in-house panels of 60 genes (non-MB panel) and 21 genes using MB (MB panel) were used for the genomic analysis of 112 DNA samples from 20 PBCA patients. We measured the yield of DNA and compared the genomic profiles of liquid samples obtained using the non-MB panel and the MB panel. The utility of the panels in detecting druggable mutations was investigated. A significantly greater amount of DNA was obtained from bile supernatants and precipitates compared to tumor samples (P < 0.001 and P = 0.001, respectively). The number of mutations per patient was significantly higher using the MB panel than using the non-MB panel (2.8 vs. 1.3, P = 0.002). Tumor-derived mutations were detected more frequently using the MB panel than the non-MB panel (P = 0.023). Five drug-matched mutations were detected in liquid samples. Liquid biopsy with MB may have utility in providing genomic information for the prognosis of patients with PBCA. [ABSTRACT FROM AUTHOR]

Analyzing RNA samples from formalin‐fixed paraffin‐embedded (FFPE) tissues is essential for precision medicine. We investigated RNA quantity and quality from FFPE tumor tissues fixed in formalin for various times and compared sequencing metrics from next‐generation sequencing (NGS). Hepatocellular carcinoma (HCC) tissues were fixed in 10% neutral buffered formalin (1–240 h) and FFPE blocks were prepared. Total RNA was extracted, and the quantity and quality were assessed using the NanoDrop, Qubit and Bioanalyzer. After preparing sequencing libraries, NGS was performed on the Oncomine Dx Multi‐CDx system. Total RNA yields of all samples met the threshold required for NGS, but longer fixation times resulted in decreased total RNA and long RNA fragment (>200 nt) yields. NGS analysis showed fewer sequencing reads of internal control genes from RNA with longer fixation times. RNA extracted from FFPE blocks stored for 500 days had reduced RNA yield and quality compared with RNA obtained from FFPE blocks prepared immediately. In conclusion, short and over‐fixation should be avoided because of their negative impact on sequencing quality. Fixation process should be finished promptly within recommended guidelines (6–72 h) for cancer patients. [ABSTRACT FROM AUTHOR]

Sensory disturbance is occasionally accompanied with parkinsonism and is sometimes improved by L-DOPA treatment. The abnormalities in cerebral somatosensory neurons were already revealed by neurophysiological methods. However, whether L-DOPA influences the cerebral somatosensory functions is unknown. We evaluated the effect of L-DOPA on the sensory cortex in Parkinson disease (PD) using neurophysiological technique such as high-frequency oscillations (HFOs) and somatosensory evoked potential recovery functions (SEP-Rs), which could detect slight functional abnormalities of cerebral somatosensory interneurons. We examined ten drug-naïve PD patients in pre- and post-L-DOPA treatment. HFOs were obtained by digitally filtering raw SEPs from 500 to 1000 Hz. For SEP-Rs study, paired-pulse stimuli at various interstimulus intervals (ISIs; 20–200 ms) were given. There were no significant differences in the HFO study. The SEP-Rs study demonstrated that patients with disease duration of more than one year ( n = 6) had a significant disinhibition ( P = 0.003) in P25-N33 of post-treatment compared with pre-treatment. L-DOPA may have some effects on the abnormal GABAergic interneuron function in sensory cortex, which could improve sensory disturbance by L-DOPA therapy in PD patients. [ABSTRACT FROM AUTHOR]

Cardiac 123I-metaiodobenzylguanidine scintigraphy (MIBG) has been used to assess the postganglionic presynaptic cardiac sympathetic nerve endings and demonstrated an uptake reduction in patients with Parkinson’s disease (PD). On the other hand, epidemiologic research showed that electrocardiography (ECG) abnormalities occurred prior to motor signs in PD. In this study, we investigated whether the electrical conduction system of the heart was impaired in PD. Clinical features, ECG and MIBG parameters were analyzed in 191 patients with PD, 42 with multiple system atrophy (MSA) and 124 normal controls (NL). PR interval in ECG was significantly longer in patients with PD than in NL, and the PR interval negatively correlated with early and delayed heart-to-mediastinum ratios in MIBG scintigraphy in PD and MSA patients. No significant differences were detected in QTc between the three groups. This study is the first to demonstrate the prolongation of the PR interval in PD and its correlation with MIBG scintigraphy parameters. The PR prolongation must reflect some sympathetic system abnormality since it is mainly controlled by sympathetic nervous system. Repeated measures of PR interval might be one alternative tool to predict autonomic dysfunction in a part of PD patients. [ABSTRACT FROM AUTHOR]

We describe our encounter with a 39-year-old man who exhibited acute painless visual loss and progressive gait disturbance. He had tendinous xanthoma and several neuroophthalmological findings indicative of optic neuropathy in the right eye, including afferent pupillary defect, cecocentral scotoma, and optic disc swelling. Neurological examination showed cerebellar ataxia and pyramidal weakness. Brain magnetic resonance imaging revealed bilateral swelling in the optic nerves with gadolinium-enhancement suggesting optic neuritis, an enlarged fourth ventricle, atrophy of the cerebellum, and hyperintensities in the bilateral dentate nuclei. The patient was diagnosed with cerebrotendinous xanthomatosis (CTX) based on an elevated serum cholestanol level and a homozygous missense mutation in CYP27A1. CTX is a genetic lipid storage disease caused by dysfunction of the mitochondrial enzyme sterol 27-hydroxylase. With respect to ophthalmological manifestations, juvenile cataracts and optic neuropathy are common findings in patients with CTX, but there have been no reports of optic neuropathy with features suggestive of optic neuritis. Thus, this case illustrates that clinicians should consider a diagnosis of CTX in patients with cardinal features of CTX even if the patients show signs indicative of optic neuritis. [ABSTRACT FROM AUTHOR]

Presents a case study of acute axonal polyneuropathy associated with alcoholism. Clinical history of the patient; Signs atypical for Guillain-Barré syndrome; Possible pathomechanisms other than axonal degeneration.

Background and Aim: Little is known about genetic mutations in the regenerated mucosa (RM) after endoscopic resection (ER) of esophageal carcinoma. Thus, this study investigates the status of genetic variation in RM after ER of esophageal squamous cell carcinoma (ESCC). Methods: The study cohort included 19 patients with ESCC. We used an esophageal carcinoma panel to identify target sequences for squamous cell carcinoma (SCC), background mucosa (BM), and RM after ER of ESCC. We used OncoKB to check whether each mutation was a putative driver. Results: We identified 77 mutations of 32 genes in SCC, 133 mutations of 34 genes in BM, and 100 mutations of 29 genes in RM. Putative driver mutations were identified in 20 mutations in 14 cases in SCC, 16 mutations in 10 cases in BM, and 7 mutations in 11 cases in RM. The rate of putative driver mutations to total mutations was significantly lower in RM (26% in SCC vs 12% in BM vs 7% in RM, P = 0.009). Additionally, the rate of cases with TP53 putative driver mutations was significantly lower in RM (63% in SCC vs 37% in BM vs 16% in RM, P = 0.011). The percentage of putative driver mutations and the percentage of cases with a putative driver of TP53 were significantly lower in RM. Conclusion: Esophageal RM after ER of ESCC could have a lower risk of carcinogenesis. [ABSTRACT FROM AUTHOR]

Discusses the case of a patient with Huntington's Disease (HD) presenting with laryngeal chorea. Genetic examination of the patient; Clinical abnormalities confirmed from barium cineradiologic examination of ingestion in patients with HD.

Background and Objective: The Oncomine Dx Target Test (ODxTT) has been used as a companion diagnostic test for lung cancer. Here, we evaluated whether the amount of nucleic acid and the degree of RNA degradation are related to the success of the ODxTT. Methods: This study included 223 samples from 218 patients with lung cancer. For all samples, DNA and RNA concentrations were quantified using Qubit, and the degree of RNA degradation was evaluated using the Bioanalyzer. Results: Of the 223 samples, 219 samples were successfully analyzed in the ODxTT and four were not. DNA analysis failed in two samples, which were attributed to low DNA concentrations and both were cytology specimens. Meanwhile, RNA analysis failed in the other two samples. These samples had sufficient amounts of RNA, but it was highly degraded with DV200 (the percentage of RNA fragments > 200 base pairs) less than 30. Compared with RNA samples with DV200 ≥ 30, analysis of RNA with DV200 < 30 yielded significantly fewer reads for the internal control genes. This test showed actionable mutations were identified in 38% (83/218) of all patients and in 46.6% (76/163) of patients with lung adenocarcinoma. Conclusions: DNA concentration and degree of RNA degradation are key factors determining the success of diagnostic testing by the ODxTT. [ABSTRACT FROM AUTHOR]

Background: Obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling has limitations. Liquid biopsies using plasma do not provide sufficient sensitivity. Thus, this study aimed to determine the effectiveness of liquid biopsy between bile and plasma for identifying oncogenic and drug‐matched mutations. Methods: This study created a panel of 60 significantly mutated genes specific to pancreaticobiliary cancer (PBCA) and used it for genomic analysis of 212 deoxyribonucleic acid (DNA) samples (87 bile supernatant, 87 bile precipitate, and 38 plasma) from 87 patients with PBCA. The quantity of extracted DNA from bile and plasma was compared, as were genomic profiles of 38 pairs of bile and plasma from 38 patients with PBCA. Finally, we investigated 87 bile and 38 plasma for the ability to detect druggable mutations. Results: The amount of DNA was significantly lower in plasma than in bile (p <.001). Oncogenic mutations were identified in 21 of 38 (55%) patients in bile and nine (24%) in plasma samples (p =.005). Bile was significantly more sensitive than plasma in identifying druggable mutations (p =.032). The authors detected 23 drug‐matched mutations in combined bile and plasma, including five ERBB2, four ATM, three BRAF, three BRCA2, three NF1, two PIK3CA, one BRCA1, one IDH1, and one PALB2. Conclusions: Liquid biopsy using bile may be useful in searching for therapeutic agents, and using the obtained genomic information may improve the prognoses of patients with PBCA. Plain Language Summary: Genomic profiling of formalin‐fixed paraffin‐embedded tissues may provide actionable targets for molecular and immuno‐oncological treatment.However, most pancreaticobiliary malignancies are unresectable and formalin‐fixed paraffin‐embedded tissues cannot be obtained.Although comprehensive genomic profiling tests using plasma have been used in recent years, the utility of those using bile is not clear.Our study revealed that bile identified more drug‐matched mutations than plasma in advanced pancreaticobiliary cancer patients.Bile may help widen the patient population benefiting from targeted drugs. Bile contained a large amount of tumor‐derived DNA in pancreaticobiliary cancer. Liquid biopsy using bile may be useful in searching for therapeutic agents. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the validity of pathological diagnosis of early CRC (E‐CRC) from the genetic background by comparing data of E‐CRC to colorectal adenoma (CRA) and The Cancer Genome Atlas (TCGA) on advanced CRC (AD‐CRC). Methods: TCGA data on AD‐CRC were studied in silico, whereas by next‐generation sequencer, DNA target sequences were performed for endoscopically obtained CRA and E‐CRC samples. Immunohistochemical staining of mismatch repair genes and methylation of MLH1 was also performed. The presence of oncogenic mutation according to OncoKB for the genes of the Wnt, MAPK, and cell‐cycle–signaling pathways was compared among CRA, E‐CRC, and AD‐CRC. Results: The study included 22 CRA and 30 E‐CRC lesions from the Chiba University Hospital and 212 AD‐CRC lesions from TCGA data. Regarding the number of lesions with driver mutations in the Wnt and cell‐cycle–signaling pathways, E‐CRC was comparable to AD‐CRC, but was significantly greater than CRA. CRA had significantly more lesions with a driver mutation for the Wnt signaling pathway only, versus E‐CRC. Conclusions: In conclusion, the definition of E‐CRC according to the Japanese criteria had a different genetic profile from CRA and was more similar to AD‐CRC. Based on the main pathway, it seemed reasonable to classify E‐CRC as adenocarcinoma. The pathological diagnosis of E‐CRC according to Japanese definition seemed to be valid from a genetic point of view. [ABSTRACT FROM AUTHOR]

Evaluation of the status of mismatch repair (MMR) in tumors is crucial for determining the application of immune checkpoint inhibitors (ICIs). Conventional PCR (MSI‐PCR) is the gold standard for confirming the MMR status. However, it requires visual confirmation and presents difficulties in determining MMR status. Immunohistochemistry (IHC) is a simple method and can confirming MMR protein expression in the whole tumor. We aim to investigate IHC is more suitable for evaluating MMR status in the tumor. We compared MSI‐PCR and IHC by testing 319 samples from 284 patients across 14 cancer types. In discordant cases, we performed laser‐capture microdissection and microsatellite instability assay by next‐generation sequencing (MSI‐NGS). The concordance rate between IHC and MSI‐PCR testing was 98.1% (313/319). Two reasons for these discrepancies were ambiguous MSI‐PCR results and heterogeneous MSI status within the tumor. Among six cases (1.9%), three were judged as MSI‐H by MSI‐PCR but with proficient MMR by IHC. The results of MSI‐NGS revealed microsatellite stable in these three cases. The remaining three cases, two of three were MSI‐H and one was MSS in whole tumor in MSI‐PCR. IHC showed a "mosaic" pattern containing both proficient MMR and deficient MMR portions by IHC in all three cases. We performed microdissection and MSI‐PCR and found intratumoral heterogeneity of MMR status. These results indicated the advantages of IHC and performed expanded samples (n = 1082) and two additional mosaic cases were identified. Our results clearly indicated that simple IHC is the best choice for determining MMR alterations in critical cases for ICIs treatment. [ABSTRACT FROM AUTHOR]

Presents a correction to the article "An Energy Conversion Method by Using Density Difference of Water," published in Vol. 118, No. 2, 1997 issue of "Electrical Engineering in Japan."