Guillain-Barré syndrome in a local area in Japan, 2006-2015: an epidemiological and clinical study of 108 patients.

BACKGROUND AND PURPOSE: Many epidemiological studies of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) have been conducted in Europe and America. In contrast, epidemiological studies are rare in Asia where the GBS subtypes differ from those in Western countries. This study was undertaken to clarify the incidence of GBS and FS in a local area in Japan as well as their seasonal trends. METHOD: Seventy-one GBS and 37 FS patients were recorded from 2006 to 2015 in an area of approximately 1.5 million inhabitants in Japan. The incidence, seasonal trends and clinical features of GBS and FS were examined. RESULTS: The incidence rate of GBS was 0.42 cases per 100 000 person-years and that of FS was 0.22 cases per 100 000 person-years. The incidence of GBS increased with age and FS affected predominantly patients aged from 45 to 64 years old. There was some seasonal clustering of acute motor axonal neuropathy (AMAN) and FS in spring and summer, but it was not significant. AMAN and FS patients had a high frequency of preceding infection (AMAN, 68% gastrointestinal infection; FS, 65% upper respiratory infection). Antecedent respiratory infection was significantly associated with FS as an outcome. Serum antibodies to ganglioside GM1 were detected in 71% of AMAN patients and antibodies to GQ1b were detected in 81% of FS patients. CONCLUSIONS: Our study offers evidence of a lower incidence of GBS and a higher incidence of FS in a local area in Japan than in Western countries.

Preferential changes of skeletal muscle echogenicity in myotonic dystrophy type 1.

BACKGROUND AND PURPOSE: In myotonic dystrophy type 1 (DM1), weakness of distal limb muscles affects quality of life. Non-invasive evaluation of muscular involvement by muscle sonography could be useful for characterizing muscle-specific involvement. METHODS: Sonography of the lower leg and forearm was performed in 19 patients with DM1 and 10 control subjects. The mean echo intensities (EIs) of seven limb muscles were obtained by computer-assisted histogram analysis and compared within DM1 according to the overall clinical severity. RESULTS: The EIs of the muscles were significantly higher in DM1 than in the controls (P < 0.01), except for the soleus (P = 0.4). Comparison of adjacent muscles showed the following: (i) greater EIs in flexor digitorum profundus than flexor carpi ulnaris (P < 0.01) and flexor digitorum superficialis (P = 0.02), and (ii) greater EIs in the medial head of the gastrocnemius than the soleus (P < 0.00001). In a subgroup analysis of DM1 according to the modified Rankin Scale (mRS), the more severe subgroup (mRS = 4-5) had lower mean EIs than the less severe subgroup (mRS from 1-3) (P = 0.01) in the flexor digitorum superficialis but not in other muscles. CONCLUSIONS: Preferential high echogenicity in the medial gastrocnemius and deep finger flexors is suggestive of DM1. Muscle echogenicity is not generally related to functional dysfunction in DM1.

Intramuscular dissociation of echogenicity in the triceps surae characterizes sporadic inclusion body myositis.

BACKGROUND AND PURPOSE: Differential diagnosis of sporadic inclusion body myositis (s-IBM) and polymyositis (PM)/dermatomyositis (DM) is difficult and can affect proper disease management. Detection of heterogeneous muscular involvement in s-IBM by muscle sonography could be a unique diagnostic feature. METHODS: Sonography of the lower leg and forearm was performed in patients with s-IBM, PM/DM and control subjects (n = 11 each). Echo intensities (EIs) of the adjacent muscles [medial head of the gastrocnemius versus soleus and the flexor digitorum profundus (FDP) versus flexor carpi ulnaris (FCU)] were scored by three blinded raters. The mean EIs of these muscles were compared using computer-assisted histogram analysis. RESULTS: Both evaluation methods showed high echoic signals in the gastrocnemius of patients with s-IBM. EIs were significantly different between the gastrocnemius and soleus in patients with s-IBM, but not in those with DM/PM and the controls. In the forearm, although the EI of the FDP was higher in the s-IBM group than in the other groups, the EI differences between the FDP and FCU did not differ significantly between disease groups. The difference in area under the curves to differentiate between s-IBM and DM/PM was greatest between the gastrocnemius-soleus EIs (0.843; P = 0.006). CONCLUSIONS: High echoic signals in the medial gastrocnemius compared with those of the soleus are suggestive of s-IBM over PM/DM.

Activity-dependent conduction block in multifocal motor neuropathy: magnetic fatigue test.

BACKGROUND: Multifocal motor neuropathy (MMN) is often misdiagnosed as motor neuron disease, especially when overt evidence of conduction block (CB) is lacking. Activity-dependent CB (ADCB), defined as transient CB induced by brief exercise, has been recently found in MMN but not in ALS. METHODS: To test the diagnostic utility of ADCB for differentiating MMN from ALS, the authors recorded the compound muscle action potentials (CMAPs) from small hand muscles by magnetically stimulating nerve roots before and after 1 minute of maximal voluntary contraction (magnetic fatigue test). They examined nine patients with MMN with unequivocal clinical responses to IV immunoglobulins (IVIgs), yet lacked CB according to the conventional criteria. RESULTS: Six MMN patients had postexercise CB/temporal dispersion maximum in the immediate postexercise period. ADCB in an MMN patient improved after IVIg. Further analysis revealed that prolongation of the duration from the onset to the positive peak of the CMAP was the most sensitive indicator for MMN, presumably because the phase cancellation obscures the abnormalities of the other parameters. CONCLUSION: The magnetic fatigue test is useful in detecting mild conduction block presumably located in a proximal nerve segment in patients with multifocal motor neuropathy who do not fulfill its conventional electrodiagnostic criteria.

KCNQ channels mediate IKs, a slow K+ current regulating excitability in the rat node of Ranvier.

Mutations that reduce the function of KCNQ2 channels cause neuronal hyperexcitability, manifested as epileptic seizures and myokymia. These channels are present in nodes of Ranvier in rat brain and nerve and have been proposed to mediate the slow nodal potassium current I(Ks). We have used immunocytochemistry, electrophysiology and pharmacology to test this hypothesis and to determine the contribution of KCNQ channels to nerve excitability in the rat. When myelinated nerve fibres of the sciatic nerve were examined by immunofluorescence microscopy using antibodies against KCNQ2 and KCNQ3, all nodes showed strong immunoreactivity for KCNQ2. The nodes of about half the small and intermediate sized fibres showed labelling for both KCNQ2 and KCNQ3, but nodes of large fibres were labelled by KCNQ2 antibodies only. In voltage-clamp experiments using large myelinated fibres, the selective KCNQ channel blockers XE991 (IC50 = 2.2 microm) and linopirdine (IC50 = 5.5 microm) completely inhibited I(Ks), as did TEA (IC50 = 0.22 mm). The KCNQ channel opener retigabine (10 microm) shifted the activation curve to more negative membrane potentials by -24 mV, thereby increasing I(Ks). In isotonic KCl 50% of I(Ks) was activated at -62 mV. The activation curve shifted to more positive potentials as [K+]o was reduced, so that the pharmacological and biophysical properties of I(Ks) were consistent with those of heterologously expressed homomeric KCNQ2 channels. The ability of XE991 to selectively block I(Ks) was further exploited to study I(Ks) function in vivo. In anaesthetized rats, the excitability of tail motor axons was indicated by the stimulus current required to elicit a 40% of maximal compound muscle action potential. XE991 (2.5 mg kg(-1) i.p.) eliminated all nerve excitability functions previously attributed to I(Ks): accommodation to 100 ms subthreshold depolarizing currents, the post-depolarization undershoot in excitability, and the late subexcitability after a single impulse or short trains of impulses. Due to reduced spike-frequency adaptation after XE991 treatment, 100 ms suprathreshold current injections generated long trains of action potentials. We conclude that the nodal I(Ks) current is mediated by KCNQ channels, which in large fibres of rat sciatic nerve appear to be KCNQ2 homomers.

A Bayesian argument against rigid cut-offs in electrodiagnosis of median neuropathy at the wrist.

BACKGROUND: Nerve conduction (NC) tests, using rigid cut-offs separating normal from abnormal test values, are commonly used to confirm median neuropathy at the wrist (MNW). The authors studied patients with clinically defined mild MNW and a normal median distal motor latency to determine 1) how much sensory or mixed NC test results increase (or decrease) the probability of MNW and 2) the NC test values required to confirm (or exclude) MNW for the range of pretest probabilities of MNW. METHODS: Palmar, digit 4 (D4), and digit 2 (D2) median NC tests were reviewed in 125 hands with mild carpal tunnel syndrome (CTS) and 100 control hands with musculoskeletal pain. Receiver operating characteristic curves and interval likelihood ratios were plotted for the three tests. Using Bayes theorem, post-test probability of MNW was then determined for the range of pretest probabilities and NC test values. RESULTS: Receiver operating characteristic curves showed that for a set specificity of 97%, palmar and D4 studies had higher electrodiagnostic utility than D2 studies with cut-off test values (sensitivities of 0.3 msec, 64.0%; 0.4 msec, 71.2%; and 50 m/sec, 44.8%). However, Bayesian analysis showed that to confirm MNW more conservative cut-off values (palmar 0.5 msec, D4 0.7 msec, D2 44 m/sec) were required for pretest probabilities or=75%. Conversely, normal test values could exclude MNW only for pretest probabilities <25%. CONCLUSIONS: For a given NC test value, post-test probability of MNW can be determined from the estimated pretest probability (derived from clinical data), interval likelihood ratios, and Bayes theorem. Use of rigid cut-off values to confirm MNW is problematic, because more conservative cut-offs are required for low pretest probability. Conversely, NC tests with sensitivity <95% cannot exclude MNW when pretest probability is high.

[Hypereosinophilic syndrome associated with antineutrophil cytoplasmic antibody].

A 68-year-old man was admitted to our hospital with complaints of fever, cough, and shortness of breath. He had several erythematous maculae on the trunk and experienced hypesthesia in his lower extremities. Laboratory data showed marked eosinophilia (20,235/mm3) and enhanced hepatobiliary enzymes. Chest X-ray films and computed tomographic scans revealed diffuse patchy infiltrative changes in the lungs. Histologic findings confirmed eosinophilic infiltration of the skin, liver, and lungs. A diagnosis of hypereosinophilic syndrome (HES) was made in accordance with clinical criteria proposed by Chusid et al. The patient was positive for antineutrophil cytoplasmic antibodies (a marker for vasculitis). This suggested a clinical picture resembling Churg-Strauss syndrome (CSS) despite the lack of bronchial asthma. The findings in this report could contribute to a better understanding of the diversity of HES cases, several of which are considered to represent a continuum of pathologies sharing an etiology similar to that of CSS.

[Chronic hypersensitivity pneumonitis due to isocyanate in a patient presenting with acute symptoms 1 month after environmental exposure].

A 51-year-old man who had been working for 10 years with polyurethane paint containing isocyanate (MDI) was admitted to our hospital with complaints of fever and exertional dyspnea. Fine crackles were heard in both bases, and the patient had clubbed fingers. A chest X-ray film and computed tomograms of the lungs revealed patchy infiltrative shadows in both lung fields and subpleural honeycombing associated with irregular linear areas. Examination of bronchoalveolar lavage fluid showed increased T lymphocytes and a decreased CD 4/8 ratio. Specimens obtained by transbronchial lung biopsy revealed lymphoplasmacytic infiltration into the thickened alveolar walls, macrophage accumulation, and micro-epithelioid cell granulomas in the alveolar sacs. Hypersensitivity pneumonitis was suspected although the causative antigen was not identified because the results of short-term environmental provocation tests were negative in the patient's home and workplace. After discharge, the patient continued working as a paint sprayer. His acute symptoms recurred 1 month after exposure to isocyanate. Similar episodes occurred on two separate occasions. In addition, the patient tested positive for antibody to MDI-HSA in bronchoalveolar fluid. From the above observations, the patient was given a diagnosis of chronic hypersensitivity pneumonitis due to isocyanate (MDI). This condition is extremely rare. Furthermore, it is interesting that acute symptoms recurred 1 month after environmental exposure to the causative antigen.

[An elderly woman with chronic pigeon-breeder's disease].

A 64-year-old woman had been feeding more than 60 pigeons in a coop in her back yard for 35 years. Diffuse reticulonodular shadows were found on a chest radiograph obtained as part of an annual check-up eight years before admission to the hospital. She was given a tentative diagnosis of idiopathic pulmonary fibrosis and was observed. She was admitted to our hospital because she noticed dry coughing and shortness of breath. A chest CT scan revealed segmentally distributed honeycombing and bronchi-bronchioloectasis. Tests for IgA and IgG antibodies to extracts of pigeon droppings in serum samples and in samples of bronchoalveolar lavage fluid were strongly positive, as were tests for lymphocyte blastogenic responses to samples of pigeon serum Examination of lung-biopsy specimens obtained by video-assisted thoracoscopic surgery revealed bronchiolitis, alveolitis, and honeycombing in a centrilobular distribution. The patient was given a diagnosis of pigeon-breeder's disease. Chronic hypersensitivity pneumonitis without acute episodes might be misdiagnosed as idiopathic interstitial pneumonia or bronchiectasis, as happened in this case. The possibility of chronic hypersensitivity pneumonitis should be considered when patients are suspected to have pulmonary fibrosis. It is important to obtain the detailed information on past or current avian contact, working history, and the home environment.

Recurrent histiocytic necrotizing lymphadenitis (Kikuchi's disease) in an human T lymphotropic virus type I carrier.

We describe a case of recurrent histiocytic necrotizing lymphadenitis (HNL) with aseptic meningitis. The patient was a 46-year-old male and a carrier of human T lymphotropic virus type I (HTLV-I). The patient had a past medical history of at least three relapses of HNL. In addition, his sister, who was also an HTLV-I carrier, had recurrent clinical episodes consistent with those of HNL, suggesting familial HNL occurrence. This observation suggests the possibility that HTLV-I infection is relevant to the pathogenesis of HNL.

[A case of thymic carcinoma successfully controlled by combined chemotherapy and irradiation].

There is no well established therapeutic protocol for advanced thymic carcinoma, although chemotherapy and irradiation can apparently be used to control the malignancy. Here we report a case of advanced thymic carcinoma successfully controlled by combination of treatment with systemic chemotherapy and irradiation. A 79-year-old man was admitted to the Hiratsuka Kyosai Hospital with complaints of productive cough and dyspnea. Chest roentgenogram and computerized tomography on admission revealed a tumorous lesion in the anterior mediastinum and on accumulation of left pleural and pericardial effusion fluid. The tumor was diagnosed as a thymic squamous cell carcinoma, after percutaneous needle biopsy. Because of extension to the left pleura and cardiac sac, the tumor was considered to be unresectable and systemic chemotherapy (CDDP + VDS + MMC) was begun. After drainage of the pericardial effusion fluid, intrapericardial injection of MMC was also done. The anterior mediastinum was irradiated. The patient has been doing well, with regression of the thymic tumor for 48 months after irradiation. This case provides important information that can be used to establish an effective therapeutic regimen for advanced thymic carcinoma.