Saiko Nasu

Chiba University, Tiba, Chiba, Japan

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Publications (39)136.82 Total impact

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    ABSTRACT: Objective Combined nerve/muscle biopsy is widely carried out to improve the diagnostic sensitivity for vasculitic neuropathy. However, an additional yield of muscle biopsy is modest. Therefore, we investigated whether skin biopsy in combination with nerve/muscle biopsy increases the detection rate of vasculitis.MethodsA total of 25 combined nerve/muscle/skin biopsy samples from patients with biopsy-proven necrotizing vasculitis (n = 16) or clinically probable vasculitic neuropathy (n = 9) were reviewed. Specimens from the sural nerve, peroneus brevis muscle and skin were obtained simultaneously by a single incision.ResultsSkin biopsy substantially contributed to diagnosis of vasculitic neuropathy. Additional skin biopsy enhanced diagnostic sensitivity from 88% to 100% in patients with pathologically confirmed vasculitis (n = 16). Vasculitis was detected only in skin specimens from two of the entire cohort (n = 25). There were no complications related to skin collection, such as anastomotic leakage or wound infection.Conclusion Combined nerve/muscle/skin biopsy could be a less invasive option to improve the diagnostic sensitivity for vasculitis.
    04/2015; DOI:10.1111/cen3.12213
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    ABSTRACT: Purpose:In current electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy, the cutoff values of distal compound muscle action potential (DCMAP) duration are defined using electromyogram low-cut filter setting of 20 Hz. We aimed to assess effects of low-cut filter on DCMAP duration (10 vs. 20 Hz).Methods:We prospectively measured DCMAP duration in 130 normal controls and 42 patients, fulfilling diagnostic criteria for typical chronic inflammatory demyelinating polyneuropathy by European Federation of Neurological Societies/Peripheral Nerve Society.Results:Distal compound muscle action potential duration was significantly shortened with 20-Hz than 10-Hz filtering. When the cutoff values were defined as the upper limit of normal (ULN, mean + 2.5SD), the sensitivity/specificity was 67%/95% in 10-Hz recordings, and 69%/95% in 20-Hz recordings. This diagnostic accuracy was similar to that defined by receiver operating characteristic analyses.Conclusions:Distal compound muscle action potential duration significantly affected by the low-cut electromyogram filter setting, but with at least 10 and 20 Hz, the diagnostic accuracy is similar.
    Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society 10/2014; 31(5):441-443. DOI:10.1097/WNP.0000000000000045 · 1.60 Impact Factor
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    ABSTRACT: Objective No clinically effective treatment for promoting peripheral axonal regeneration has yet been established. Several experimental studies in vitro and in vivo have shown that a high dose of methylcobalamin (MeCbl), an analogue of vitamin B12, promotes axonal growth in peripheral nerve injury. We herein assessed the safety and efficacy of an ultra-high dose MeCbl treatment for patients with peripheral neuropathy and chronic axonal degeneration. Methods Fourteen patients with immune-mediated or hereditary neuropathy in the chronic progressive or stable phase were enrolled. MeCbl, 25 mg/day for 10 days followed by monthly 25 mg for 5 months, was intravenously administered. The patients were evaluated before and 1 year following treatment. The primary endpoints were safety and improvement in the Medical Research Council (MRC) sum score in at least two muscles of the 20 muscles. This trial is registered with the University Hospital Medical Information Network (UMIN) Center in Japan under the ID: UMIN000009359. Results There were no adverse effects in twelve of the patients, whereas treatment was discontinued in two patients who had seborrheic dermatitis at 3 months and respiratory tract infection at 2 months, respectively. Therefore, twelve patients were evaluated for the primary outcomes; the MRC sum score was improved in seven of the patients and unchanged or worsened in the remaining five patients. Conclusion Intravenous ultra-high dose MeCbl treatment is a safe and potentially efficacious therapy for patients with peripheral neuropathy and chronic axonal degeneration.
    Internal Medicine 01/2014; 53(17):1927-31. DOI:10.2169/internalmedicine.53.1951 · 0.97 Impact Factor
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    ABSTRACT: Bortezomib is a proteasome inhibitor with high efficacy for multiple myeloma but with severe peripheral neurotoxicity, leading to dose modification and severe neurological disability. This study aimed to investigate the pathophysiology of bortezomib-induced neuropathy. Threshold tracking was used to assess the excitability of sensory and motor axons. Measurements were sequentially performed before and after bortezomib treatment in nine patients with newly diagnosed multiple myeloma. In total, 67% of patients finally developed symptomatic neuropathy. Changes in sensory axonal excitability indices readily occurred after the first course of administration. Patterns of changes in excitability indices suggest membrane depolarization (decreased superexcitability, P<0.001; decreased depolarizing threshold electrotonus 90-100ms, P=0.02). Abnormalities in nerve conduction parameters suggestive of axonal degeneration appeared after the second course of treatment. Bortezomib induces a depolarizing shift in resting membrane potential prior to the development of neuropathy. Membrane depolarization could be associated with impairment of electrogenic Na(+)-K(+)-ATPase-dependent pump caused by toxic effects of bortezomib on mitochondria. Axonal depolarization and hyperexcitability might enhance neurodegeneration in bortezomib-induced neuropathy.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 08/2013; 125(2). DOI:10.1016/j.clinph.2013.07.014 · 2.98 Impact Factor
  • Clinical Neurophysiology 08/2013; 124(8):e29-e30. DOI:10.1016/j.clinph.2013.02.074 · 2.98 Impact Factor
  • Clinical Neurophysiology 08/2013; 124(8):e33. DOI:10.1016/j.clinph.2013.02.091 · 2.98 Impact Factor
  • Clinical Neurophysiology 08/2013; 124(8):e33. DOI:10.1016/j.clinph.2013.02.089 · 2.98 Impact Factor
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    ABSTRACT: OBJECTIVES: To clarify whether patients with spinal muscular atrophy (SMA) or spinal and bulbar muscular atrophy (SBMA) suffer disabling muscle fatigue, and whether activity-dependent conduction block (ADCB) contributes to their fatigue. ADCB is usually caused by reduced safety factor for impulse transmission in demyelinating diseases, whereas markedly increased axonal branching associated with collateral sprouting may reduce the safety factor in chronic lower motor neuron disorders. METHODS: We assessed the fatigue severity scale (FSS) in 22 patients with SMA/SBMA, and in 100 disease controls (multiple sclerosis, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy (CIDP), and axonal neuropathy). We then performed stimulated-single fibre electromyography (s-SFEMG) in the extensor digitorum communis (EDC) muscle of 21 SMA/SBMA patients, 6 CIDP patients, and 10 normal subjects. RESULTS: The FSS score was the highest in SMA/SBMA patients [4.9±1.1 (mean±SD)], with 81% of them complaining of disabling fatigue, compared with normal controls (3.5±1.0), whereas patients with multiple sclerosis (4.3±1.6), myasthenia gravis (4.0±1.6) or CIDP (4.3±1.4) also showed higher FSS score. When 2000 stimuli were delivered at 20Hz in s-SFEMG, conduction block of single motor axons developed in 46% of patients with SMA/SBMA, and 40% of CIDP patients, but in none of the normal controls. CONCLUSION: SMA/SBMA patients frequently suffer from disabling fatigue presumably caused by ADCB induced by voluntary activity. SIGNIFICANCE: ADCB could be the mechanism for muscle fatigue in chronic lower motor neuron diseases.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 04/2013; 124(9). DOI:10.1016/j.clinph.2012.12.053 · 2.98 Impact Factor
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    ABSTRACT: BACKGROUND: In amyotrophic lateral sclerosis (ALS), muscle wasting preferentially affects the abductor pollicis brevis (APB) and first dorsal interosseous over the abductor digit minimi (ADM), and this is termed 'split hand'. Previous axonal excitability studies have suggested increased nodal persistent sodium current and reduced potassium current in motor axons in ALS, but the extent of excitability changes in APB and ADM axons in ALS has never been compared. OBJECTIVE: To elucidate the peripheral axonal pathophysiology of split hand. METHODS: In both APB and ADM motor axons of 21 patients with ALS and 17 age-matched normal controls, threshold tracking was used to measure excitability indices such as strength-duration time constant (SDTC; a measure of persistent sodium current) and threshold electrotonus. RESULTS: In normal controls, SDTC was significantly longer for APB than ADM axons, suggesting that axonal excitability is physiologically higher in APB axons. Compared with normal controls, patients with ALS had longer SDTC and greater threshold changes in depolarising threshold electrotonus in both APB and ADM axons. Furthermore, the difference in extent of SDTC prolongation between normal subjects and patients with ALS was greater in APB than ADM axons. CONCLUSIONS: APB axons have physiologically higher excitability than ADM axons, and, in ALS, the hyperexcitability is more prominent in APB axons. Although cortical mechanisms would also be involved, more prominent hyperexcitability of APB axons may contribute to development of split hand, and the altered axonal properties are possibly associated with motor neuronal death in ALS.
    Journal of neurology, neurosurgery, and psychiatry 03/2013; 84(9). DOI:10.1136/jnnp-2012-304109 · 5.58 Impact Factor
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    ABSTRACT: OBJECTIVE: Vascular endothelial growth factor (VEGF) plays an essential role in the pathophysiology of polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome. Anti-VEGF antibody (bevacizumab) appears to be an attractive therapeutic option. The aim of this study is to investigate the effects of bevacizumab for patients with POEMS syndrome. METHODS: We reported six POEMS patients treated with bevacizumab and reviewed the literature. RESULTS: The serum VEGF levels decreased immediately after bevacizumab administration in all six patients. However, four patients had entirely no clinical response, and two of them died. The remaining two showed improvement that could be explained by combined treatments. We also reviewed the literature and found 11 patients treated with bevacizumab; of these, only one was treated with bevacizumab alone. 10 had combined treatments, and four died without any response. CONCLUSIONS: Both our experience and the literature suggest ambiguous effects of bevacizumab; inhibition of VEGF alone may be insufficient because multiple cytokines are upregulated, or aberrant neo-vascularization may have already fully developed in the advanced stage of POEMS syndrome.
    Journal of neurology, neurosurgery, and psychiatry 03/2013; 84(12). DOI:10.1136/jnnp-2012-304874 · 5.58 Impact Factor
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    ABSTRACT: A previously healthy 30-year-old man presented with gradually worsening oscillopsia 2 weeks after an unusual headache; there was ocular flutter on examination (video on the Neurology® Web site at www.neurology.org) without other findings. Brain MRI was unremarkable. CSF showed mild pleocytosis (11 cells/mm(3)), but no evidence of active viral infections (herpes simplex virus, cytomegalovirus, varicella-zoster virus, Epstein-Barr virus, human herpesvirus 6, and measles). Serum antiganglioside antibodies (including anti-GQ1b antibody) were negative. The symptom resolved without treatment within 4 weeks. Ocular flutter is rare and may be isolated, although it is usually accompanied by generalized myoclonus or truncal ataxia.(1,2) Brainstem (omnipause neurons in the paramedian pontine reticular formation(3)) or cerebellar dysfunction may contribute, as may abnormal pause cell control over saccadic burst neurons.
    Neurology 02/2013; 80(9):867. DOI:10.1212/WNL.0b013e31828407a8 · 8.30 Impact Factor
  • Clinical Neurophysiology 09/2012; 123(9):e97. DOI:10.1016/j.clinph.2012.02.046 · 2.98 Impact Factor
  • Clinical Neurophysiology 09/2012; 123(9):e87. DOI:10.1016/j.clinph.2012.02.002 · 2.98 Impact Factor
  • Clinical Neurophysiology 09/2012; 123(9):e91. DOI:10.1016/j.clinph.2012.02.021 · 2.98 Impact Factor
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    ABSTRACT: To systematically study abnormalities in cytokine profiles in polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome, which has been increasingly recognized as a cause of demyelinating neuropathy associated with plasma cell dyscrasia and elevated serum level of vascular endothelial growth factor (VEGF). In this case-control study, we measured serum levels of 27 cytokines in patients with POEMS syndrome using a multiplex suspension array system, and compared them with those of controls. In 10 patients, serial changes after treatment were analyzed. Interleukin (IL)-12 as well as VEGF levels were markedly increased (p < 0.0001) in all the patients (n = 23). Ten kinds of other proinflammatory cytokines such as IL-6 and tumor necrosis factor-α were also significantly increased in the POEMS syndrome group, but in some patients the serum levels of such cytokines remained within the normal ranges. After treatments, the IL-12 as well as VEGF levels significantly decreased with clinical improvements (p > 0.01 and p > 0.05, respectively). Our findings suggest that serum IL-12 is a biomarker of the disease activity in POEMS syndrome. The overproduction of IL-12, as well as VEGF, is likely to play an important role in the pathogenesis of the disorder, and could contribute to the peripheral nerve demyelination in POEMS syndrome.
    Neurology 07/2012; 79(6):575-82. DOI:10.1212/WNL.0b013e318263c42b · 8.30 Impact Factor
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    ABSTRACT: The aim of this study was to investigate whether axonal excitability indices are associated with survival in patients with amyotrophic lateral sclerosis (ALS). Previous nerve excitability studies suggested increased persistent sodium currents in motor axons of patients with ALS, which lead to axonal hyperexcitability and potentially enhance neuronal death. 112 patients with sporadic ALS were followed up until endpoint (death or tracheostomy). Multivariate analyses were performed using the Cox proportional hazard model. Threshold tracking was used to measure multiple axonal excitability indices in median motor axons, such as strength-duration time constant (SDTC; a measure of nodal persistent sodium current). Latent addition was also used to estimate the magnitude of persistent sodium currents. The overall median tracheostomy-free survival from onset was 37 months. Prolonged SDTC was strongly associated with shorter survival (adjusted HR 4.07; 95% CI 1.7 to 9.8; p=0.0018) compared with older onset age (>60 years; HR=1.80) and bulbar onset (HR=1.80). Estimated median survival was 34 months in the longer SDTC group and 51 months in the shorter SDTC group. This index was highly statistically significant even after multiple testing adjustments with age and site of onset (bulbar or limb). Latent addition study results were consistent with these findings. Axonal persistent sodium currents, estimated by SDTC and latent addition, are strong and independent predictors for shorter survival in patients with ALS. Membrane hyperexcitability is possibly associated with motor neuronal death, and modulation of excessive sodium currents could be a novel therapeutic option for ALS.
    Journal of neurology, neurosurgery, and psychiatry 05/2012; 83(7):734-8. DOI:10.1136/jnnp-2011-301782 · 5.58 Impact Factor
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    ABSTRACT: POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes) syndrome, a rare cause of demyelinating neuropathy associated with multiorgan involvement, has been increasingly recognised. Polyneuropathy is often an initial manifestation and therefore the disorder can be misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). Objective To elucidate whether POEMS syndrome and CIDP are differentiated based on profiles of neuropathy. Clinical and electrophysiological data were reviewed in consecutive POEMS syndrome (n=51) and typical CIDP (n=46) patients in a single Japanese hospital between 2000 and 2010. Both POEMS and CIDP patients showed symmetric polyneuropathy, physiological evidence of demyelination (70% of POEMS patients fulfilled the electrodiagnostic criteria for definite CIDP) and albuminocytological dissociation; 49% of the POEMS syndrome patients had neuropathy onset and 60% of them were initially diagnosed as having CIDP by neurologists. Clinically, POEMS neuropathy more frequently showed severe leg pain (76% vs 7%; p<0.001), muscle atrophy (52% vs 24%; p=0.005) and distal dominant muscle weakness. Electrophysiologically, POEMS syndrome was characterised by less prolonged distal motor latency (mean 5.6 ms vs 8.1 ms; p<0.001) and higher terminal latency index (0.42 vs 0.33; p=0.006) in the median nerves, and unrecordable tibial and sural responses (p<0.001), suggesting demyelination predominant in the nerve trunk rather than in the distal nerve terminals, and axonal loss in the lower limb nerves. Before development of typical systemic manifestations, POEMS neuropathy can be distinguished from CIDP by the clinical profile and patterns of nerve conduction abnormalities. Recognition of these features leads to early diagnosis and proper treatment for POEMS syndrome.
    Journal of neurology, neurosurgery, and psychiatry 02/2012; 83(5):476-9. DOI:10.1136/jnnp-2011-301706 · 5.58 Impact Factor
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    ABSTRACT: Whether or not antiganglioside antibodies are related to axonal or demyelinating Guillain-Barré syndrome (GBS) is still a matter of controversy, as detailed in previous studies conducted in Western and Asian countries. To clarify whether antiganglioside antibodies are associated with axonal dysfunction in Japanese and Italian GBS patient cohorts. Clinical and electrophysiological profiles were reviewed for 156 GBS patients collected from Japan (n=103) and Italy (n=53). Serum IgG antibodies against GM1, GM1b, GD1a and GalNAc-GD1a were measured by ELISA in the same laboratory. Electrodiagnostic criteria and results of serial electrophysiological studies were used for classification of GBS subtypes: acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). In both Japanese and Italian cohorts, any of the antibodies were positive in 36% of the patients, and antibody positivity had a significant association with the AMAN electrodiagnosis. Approximately 30% of Japanese and Italian antiganglioside positive patients showed the AIDP pattern at the first examination whereas sequential studies showed that most finally showed the AMAN pattern. Clinically, seropositive patients more frequently had preceding diarrhoea and pure motor neuropathy in both Japanese and Italian cohorts; vibratory sensation was normal in 97% of Japanese and in 94% of Italian seropositive patients. In GBS, clinical and electrophysiological features appear to be determined by antiganglioside antibodies, and the antibodies are associated with motor axonal GBS in both Japan and Italy. Classification of the GBS subtypes as a disease entity should be made, combining the results of antiganglioside assays and serial electrodiagnostic studies.
    Journal of neurology, neurosurgery, and psychiatry 01/2012; 83(1):23-8. DOI:10.1136/jnnp-2011-300309 · 5.58 Impact Factor
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    ABSTRACT: The aim of this study was to investigate differences in excitability properties of human median and superficial radial sensory axons (e.g., axons innervating the glabrous and hairy skin in the hand). Previous studies have shown that excitability properties differ between motor and sensory axons, and even among sensory axons between median and sural sensory axons. In 21 healthy subjects, threshold tracking was used to examine excitability indices such as strength-duration time constant, threshold electrotonus, supernormality, and threshold change at the 0.2 ms inter-stimulus interval in latent addition. In addition, threshold changes induced by ischemia for 10 min were compared between median and superficial radial sensory axons. Compared with radial sensory axons, median axons showed shorter strength-duration time constant, greater threshold changes in threshold electrotonus (fanning-out), greater supernormality, and smaller threshold changes in latent addition. Threshold changes in both during and after ischemia were greater for median axons. These findings suggest that membrane potential in human median sensory axons is more negative than in superficial radial axons, possibly due to greater activity of electrogenic Na(+)/K(+) pump. These results may reflect adaptation to impulses load carried by median axons that would be far greater with a higher frequency. Biophysical properties are not identical in different human sensory axons, and therefore their responses to disease may differ.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 12/2011; 123(7):1440-5. DOI:10.1016/j.clinph.2011.11.002 · 2.98 Impact Factor
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    ABSTRACT: To study the utility of muscle ultrasound (US) for detection of fasciculations and its contribution to diagnosis in amyotrophic lateral sclerosis (ALS). Fasciculations are characteristic features of ALS, and US can detect them easily and reliably. New diagnostic criteria for ALS, the Awaji algorithm, reintroduced fasciculations as evidence of acute denervation equivalent to that of fibrillations and positive sharp waves. In 81 consecutive patients with sporadic ALS, we prospectively performed needle EMG and US in 6 muscles (tongue, biceps brachii, first dorsalis interosseous, paraspinalis, vastus lateralis, and tibialis anterior), and diagnostic category were determined by revised El Escorial criteria and Awaji criteria. Fasciculations were much more frequently detected by US than by EMG in the tongue (60% vs 0%), biceps brachii (88% vs 60%), and tibialis anterior muscles (83% vs 45%). The proportion of the patients with definite or probable ALS was 48% by revised El Escorial criteria and 79% by Awaji criteria using US. Muscle US is a practical and efficient tool to detect fasciculations, particularly in the tongue. A combination of US and EMG substantially increases the diagnostic sensitivity of ALS.
    Neurology 09/2011; 77(16):1532-7. DOI:10.1212/WNL.0b013e318233b36a · 8.30 Impact Factor