Compound muscle action potential of whole-forearm flexors: A clinical biomarker for inclusion body myositis.

Objective: This study aimed to investigate the potential of whole-forearm flexor muscle (WFFM) compound muscle action potential (CMAP) as a quantitative biomarker for inclusion body myositis (IBM) pathology. Methods: We prospectively enrolled 14 consecutive patients (10 men and 4 women) diagnosed with IBM based on muscle biopsies. We evaluated the baseline-to-peak amplitude of the WFFM CMAP and other quantitative parameters, including grip and pinch strength, Inclusion Body Myositis Functional Rating Scale (IBMFRS) score, and other routine muscle CMAP amplitudes. Results: The WFFM CMAP was strongly correlated with disease duration and the IBMFRS score. The WFFM CMAP on the more affected side was lower than that on the less affected side. Furthermore, grip power was strongly correlated with the WFFM CMAP, whereas lateral pinch strength was strongly correlated with the WFFM and first dorsal interosseous CMAPs. The 3-point pinch strength was also correlated with the WFFM CMAP. Conclusions: This study demonstrates that the WFFM CMAP may serve as a biomarker of severity in IBM. Significance: Identification of this biomarker can support drug development, diagnosis, prognosis, and treatment options for patients with IBM.

Challenges in evaluating forearm muscle activity based on the compound muscle action potential of the flexors of the whole forearm.

Objective: Muscle strength, which correlates with the compound muscle action potential (CMAP), can also be estimated by measuring the CMAP. Therefore, we evaluated the CMAP of the flexor muscles of the whole forearm to identify their muscle strength. Methods: Fourteen healthy volunteers were enrolled. The elbow was determined to be the stimulation point, and the recording site for the flexor muscles of the whole forearm was set at approximately 8 cm distal to the elbow. We prospectively evaluated the baseline-to-peak amplitude of the CMAP of the whole forearm flexor muscles (WFFM), including that obtained from the median nerve stimulation (WFFMm), ulnar nerve stimulation (WFFMu), and their sum (WFFMsum). Additionally, we analyzed the relationships between WFFMm and WFFMu amplitudes with other quantitative parameters, including grip strength and routine CMAP amplitudes. Results: The CMAP's test-retest analysis revealed high reliability. Grip power was significantly correlated with WFFMm and WFFMsum and mildly correlated with WFFMu. Tip-pinch strength with WFFMm and flexor pollicis longus (FPL) measurements correlated significantly. Lateral-pinch strength was significantly correlated with the first dorsal interosseous muscle (FDI) measurements but not with WFFM. The abductor digiti minimi (ADM) and abductor pollicis brevis (APB) were not correlated with grip power or pinch strength. Conclusions: By electrophysiology examination, this study demonstrated that WFFMm is involved in grip power and other pinch strengths. This method may serve as a novel tool for measurement of distal muscle strengths. Significance: This is the first study to attempt to evaluate the muscle strength of forearm flexor muscles by measuring the CMAP.

Prognostic value of serum cystatin C concentration in dogs with myxomatous mitral valve disease.

BACKGROUND: Impaired renal function is 1 of the poor prognostic factors in dogs with myxomatous mitral valve disease (MMVD). However, the value of cystatin C (Cys-C), a marker of renal function, as a prognostic marker for MMVD in dogs has not yet been explored. OBJECTIVE: This study aims to investigate the prognostic value of Cys-C in dogs with MMVD. ANIMALS: Fifty client-owned small-breed dogs with MMVD were included in this study. METHODS: This is a retrospective, cross-sectional study. The prognostic value of serum Cys-C concentration was assessed using univariable and multivariable Cox hazard regression analyses. Kaplan-Meier survival curves for MMVD-specific survival in dogs stratified into high and low Cys-C groups were generated and analyzed using the log-rank test. RESULTS: Serum Cys-C concentrations were significantly associated with MMVD-related death (P < .01) in both univariable (hazard ratio [HR], 5.086; 95% confidence interval [CI], 1.950-13.270) and multivariable Cox hazard regression analysis (HR, 4.657; 95% CI, 1.767-12.270). The high Cys-C group (n = 14) had a significantly shorter MMVD-specific survival time than the low Cys-C group (n = 36; P < .01). In dogs with normal blood creatinine concentrations, the high Cys-C group (n = 10) had a significantly shorter MMVD-specific survival time than the low Cys-C group (n = 36; P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: High serum Cys-C concentrations were associated with a worse prognosis of MMVD. Furthermore, serum Cys-C could be a predictor of MMVD prognosis even in dogs with normal blood creatinine concentration.

An Ultrasonographic Evaluation for the Early Detection of Nerve Root Changes in Herpes Zoster-associated Motor Paresis.

We herein report a case of herpes zoster complicated by right-arm paralysis, wherein cervical nerve root ultrasonography enabled the early diagnosis and a therapeutic efficacy evaluation. A 71-year-old man developed progressive weakness in the muscles innervated by the right C5-6 nerve root following the appearance of a painful rash. Cervical nerve root ultrasonography revealed C5-6 nerve root inflammatory swelling. Methylprednisolone pulse therapy and subsequent oral prednisolone therapy gradually improved the muscle weakness. At three weeks following admission, ultrasonography revealed C5-6 nerve root inflammatory swelling improvement. Ultrasonography may aid in the early detection of nerve root inflammatory swelling and help monitor treatment efficacy.

Electromyography varies by stage in inclusion body myositis.

Introduction: Inclusion body myositis (IBM) is a chronic inflammatory muscle disease that is characterized by mixed myogenic and neurogenic electromyography (EMG) findings. We investigated the association between EMG findings and the IBM stage. Methods: We included consecutive patients diagnosed with IBM based on muscle biopsy and had needle EMG performed within 1 month of biopsy. Motor unit potential waveform (MUP) in EMG and pathological findings were compared between patients in early and late phases. Results: In total, 30 patients with biopsy-confirmed IBM and 254 muscles were included. The rate of abnormal discharge did not differ according to disease stage. There was a difference in the frequency of occurrence between myogenic suggestive MUP and neurogenic of biceps and flexor digitorum profundus in the late phase. Abnormal MUP was observed even in muscles without muscle weakness, and myogenic changes were predominant in biceps and gastrocnemius with muscle weakness. The biopsy findings on the contralateral side of the muscle where electromyography was performed revealed a tendency for muscles that exhibited myogenic origin to have more inflammatory cells and RV; however, the difference was not significant. Conclusion: The target muscles for EMG must be selected considering the disease stage as well. In the early stages of IBM, EMG results should be interpreted cautiously, as neurogenic suggestive pattern of MUP might also be exhibited. Contralateral electromyography findings may be helpful in selecting muscles for muscle biopsies, such as biceps and quadriceps.

[A case of the palatal tremor that disappeared during swallowing, thought to be caused by microbleeds of bilateral dentate nucleus].

A 72-year-old female presented with slowly progressive dysphonia, which was a syllable-separated utterance, for three years. She had the rhythmic continues contraction of palatal and uvula muscles during speech with a frequency of about 2 Hz. The videoendoscopy showed that the rhythmic contraction, which synchronized in the nasopharynx and the larynx, did not disappear during vocalization. The swallowing videofluorography showed that the rhythmic contraction disappeared transiently during the swallowing reflex, and there was no aspiration. The MRI revealed olivary pseudohypertrophy and multiple microbleedings including the bilateral dentate nucleus. The degeneration of olivary nucleus secondary to the bilateral asymptomatic dentate nucleus microbleedings within the dentato-rubro-olivary pathway was thought to be a cause of palatal tremor. This is a first report that a dynamic relation between vocalization and swallowing in palatal tremor.

Thoracic Excursion Is a Biomarker for Evaluating Respiratory Function in Amyotrophic Lateral Sclerosis.

Objective: To evaluate the usefulness of thoracic excursion as a biomarker in patients with amyotrophic lateral sclerosis (ALS). Methods: We measured the forced the vital capacity (FVC), thoracic excursion, baseline-to-peak diaphragmatic compound muscle action potential (DCMAP) amplitude, diaphragm thickness at full inspiration (DTfi), Medical Research Council (MRC) sum score for muscle strength, and arterial partial pressures of oxygen and carbon dioxide and administered the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) and modified Medical Research Council (mMRC) Dyspnea Scale. The test-retest reliability of thoracic excursion was determined. Results and Conclusions: Thirty-four patients with ALS and 26 age- and sex-matched healthy participants were enrolled. Thoracic excursion measurement had excellent test-retest reliability (intraclass coefficient: 0.974). Thoracic excursion was more strongly correlated with FVC (r = 0.678, p < 0.001) than DCMAP amplitude (r = 0.501, p = 0.003) and DTfi (r = 0.597, p < 0.001). It was also correlated with ALSFRS-R score (r = 0.610, p < 0.001), MRC sum score (r = 0.470, p = 0.005), and mMRC Dyspnea Scale score (r = -0.446, p = 0.008) and was the most sensitive parameter for assessing dyspnea and FVC. Thoracic excursion decreased as FVC declined in the early and late stages, there were no differences in DCMAP amplitude and DTfi between the early and late stages, and ALSFRS-R score and MRC sum score decreased only in the late stage. Thoracic excursion was well correlated with respiratory function and is useful for predicting respiratory and general dysfunction in patients with ALS regardless of stage.

Effect of age, sex, and breed on serum cystatin C and creatinine concentrations in dogs.

This study investigated the effects of age, sex and breed on serum cystatin C (Cys-C) and creatinine in small breed dogs. This retrospective study included 250 dogs weighing less than 15 kg without azotemia. Serum Cys-C and creatinine concentrations were analyzed, along with their correlation with age, and the difference between sexes or dog breeds. Serum Cys-C concentration correlated with age (P < 0.001), and did not differ between sexes or dog breeds. By contrast, serum creatinine concentration did not correlate with age. Serum creatinine concentration was higher in males than females (P < 0.05), and was lower in Miniature Dachshunds and Chihuahuas, and was higher in Shiba Inus compared to the general study population (P < 0.001). Serum Cys-C concentration correlates with age, and might be more sensitive to aging-associated subclinical renal dysfunction than serum creatinine concentration in dogs. Unlike serum creatinine concentration, serum Cys-C concentration is not affected by sex or dog breed.

Ultrasound-guided computed tomography angiography for the diagnosis of rotational vertebral artery occlusion: 2 case reports and technical notes.

Rotational vertebral artery occlusion is a rare cause of ischemic stroke in the vertebrobasilar arteries. While computed tomography angiography (CTA) is less invasive for the diagnosis of rational vertebral artery occlusion than digital subtraction angiography and more useful for elucidating the correlation between vertebrobasilar arteries and the surrounding structure, carotid ultrasound is noninvasive and more beneficial for the real-time evaluation of the hemodynamic change with neck rotation compared to CTA. Here, we reported 2 cases of rotational vertebral artery occlusion in patients aged 81 and 38 years and proposed a novel technique for its diagnosis using ultrasound-guided CTA. We suggest that the combination of ultrasound and CTA is useful for diagnosing rotational vertebral artery occlusion, which would compensate for the disadvantages of CTA alone.

[A case of hydrocephalus during the course of sporadic Blau syndrome].

Blau syndrome (BS) is a rare granulomatous inflammatory disease presenting in early childhood as dermatitis, arthritis, and uveitis. Here, we describe a case of hydrocephalus in a patient with sporadic BS. A 36-year-old female, with mutations in the NOD2 gene on chromosome 16, who had been diagnosed with BS at the age of 19 years, had visual impairment and required support when walking for a long time. She was admitted to our hospital due to deterioration in her walking ability and an inability to stand by herself. We diagnosed an obstructive hydrocephalus based on head MRI. The aqueductal stenosis and obstructive hydrocephalus associated with granulomatous lesions were considered in this case. After third ventricle fenestration, her standing movement and walking improved immediately.

Gene Expression Profiles of Human Cerebral Organoids Identify PPAR Pathway and PKM2 as Key Markers for Oxygen-Glucose Deprivation and Reoxygenation.

Ischemic stroke is one of the most common neurological diseases. However, the impact of ischemic stroke on human cerebral tissue remains largely unknown due to a lack of ischemic human brain samples. In this study, we applied cerebral organoids derived from human induced pluripotent stem cells to evaluate the effect of oxygen-glucose deprivation/reoxygenation (OGD/R). Pathway analysis showed the relationships between vitamin digestion and absorption, fat digestion and absorption, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and complement and coagulation cascades. Combinational verification with transcriptome and gene expression analysis of different cell types revealed fatty acids-related PPAR signaling pathway and pyruvate kinase isoform M2 (PKM2) as key markers of neuronal cells in response to OGD/R. These findings suggest that, although there remain some limitations to be improved, our ischemic stroke model using human cerebral organoids would be a potentially useful tool when combined with other conventional two-dimensional (2D) mono-culture systems.

Comparison of N-terminal pro-atrial natriuretic peptide and three cardiac biomarkers for discriminatory ability of clinical stage in dogs with myxomatous mitral valve disease.

Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) concentration increases with progression of myxomatous mitral valve disease (MMVD) in dogs. This multicentre, prospective study compared plasma NT-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP), ANP, and cardiac troponin I (cTnI) concentrations in dogs with MMVD for their characteristics and discriminatory ability to detect cardiac dilatation and congestive heart failure (CHF). Thirty-six healthy dogs and 69 dogs with MMVD were included. Clinical variables were obtained via physical examination, thoracic radiography, and echocardiography. The discriminatory ability of each cardiac biomarker (CB) to determine the presence or absence of cardiac dilatation (event 1) and CHF (event 2) was evaluated using the receiver operating characteristic curves. Plasma NT-proANP, NT-proBNP, and ANP concentrations showed a significant association with the left atrium/aorta ratio (P<0.01). The area under the curve of plasma NT-proANP and NT-proBNP concentrations were 0.72 and 0.75, respectively in event1 and 0.72 and 0.76, respectively in event2. Plasma NT-proANP and NT-proBNP concentrations showed sensitivity 80.0 and 80.0%; specificity 67.6 and 64.7% in event1 (cutoff value; 8,497.81 pg/ml and 1,453.00 pmol/l, respectively) and sensitivity 85.7 and 81.0%; specificity 60.4 and 64.6% in event2 (cutoff value; 8,684.33 pg/ml and 1,772.00 pmol/l, respectively). In dogs with MMVD, plasma NT-proANP, NT-proBNP, and ANP concentrations increase with left atrial enlargement. Particularly, plasma NT-proANP and NT-proBNP concentrations appeared to be equally useful in the discriminatory ability to detect cardiac dilatation and CHF.

Evaluation of atrial natriuretic peptide and cardiac troponin I concentrations for assessment of disease severity in dogs with naturally occurring mitral valve disease.

OBJECTIVE: To evaluate and compare the clinical usefulness of plasma atrial natriuretic peptide (ANP) and cardiac troponin-I (cTnI) concentrations for assessment of disease severity in dogs with naturally occurring mitral valve disease (MVD). ANIMALS: 316 dogs with MVD and 40 healthy control dogs. PROCEDURES: Each dog underwent a physical examination and echocardiographic and thoracic radiographic assessments. Blood samples were obtained and processed for measurement of plasma ANP and cTnI concentrations. Dogs with MVD were categorized into 3 groups (stages B1 [no clinical signs or evidence of cardiac enlargement], B2 [no clinical signs with evidence of cardiac enlargement], and C [history of congestive heart failure and pulmonary edema]) on the basis of American College of Veterinary Internal Medicine guidelines. Receiver operating characteristic curve analysis was used to evaluate the accuracy of plasma ANP and cTnI concentrations for assessment of MVD severity. RESULTS: Plasma ANP and cTnI concentrations increased as disease severity increased. Median plasma ANP concentrations for all 3 MVD groups and median plasma cTnI concentrations for the stage B2 and C groups were significantly greater than the corresponding concentrations for the control group. Plasma ANP concentration, but not cTnI concentration, appeared to be useful for detection of dogs with subclinical (stages B1 and B2) MVD, whereas both concentrations appeared useful for detection of dogs with stage C MVD. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that plasma ANP and cTnI concentrations should not be used independently to diagnose MVD but can be used to assess MVD severity and supplement echocardiographic findings.

Long-term management of high-grade atrioventricular block using cilostazol in a cat.

CASE SUMMARY: A 12-year-old neutered female domestic shorthair cat was admitted for syncope. Clinical signs and electrocardiography revealed high-grade atrioventricular (AV) block. Treatment with cilostazol ameliorated the clinical signs and arrhythmia. However, the high-grade AV block recurred on several occasions. After 640 days, the cat presented again with clinical deterioration owing to reoccurrence of the arrhythmia and it died 11 days later. Histopathological examination revealed a loss of conduction cells within the His bundle. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report of high-grade AV block treated with cilostazol in a cat. Treatment with cilostazol prolonged survival for 650 days without pacemaker implantation. Histological findings suggested that the AV block was related to fibrosis of the impulse conduction system.

Evaluation of monitoring methods in asymptomatic dogs with high serum cystatin C concentrations.

This study evaluated the monitoring methods in asymptomatic dogs with high serum cystatin C (Cys-C) concentrations. Ten dogs with high serum Cys-C were divided into two groups based on the owner's choice; one receiving clinical pathology-based monitoring at an animal hospital specialised in chronic kidney disease, and the other receiving symptom-based monitoring at home, partly because they showed no clinical symptoms. The dogs that received the clinical pathology-based monitoring led to an early treatment intervention, resulted in a longer survival period than dogs received the symptom-based monitoring (P<0.05). It became clear that early treatment intervention by clinical pathology-based monitoring extends the renal survival period even in asymptomatic dogs with increased serum Cys-C concentrations.

Increased Signal in the Superior Cerebellar Peduncle of Patients with Progressive Supranuclear Palsy.

OBJECTIVE: The provisional diagnosis of progressive supranuclear palsy (PSP) depends on a combination of typical clinical features and specific MRI findings, such as atrophy of the tegmentum in the midbrain. Atrophy of the superior cerebellar peduncle (SCP) distinguishes PSP from other types of parkinsonism. Histological factors affect the conventional fluid-attenuated inversion recovery (FLAIR) signals, such as the extent of neuronal loss and gliosis. METHODS: We investigated patients with PSP to verify the percentage of patients with various PSP phenotypes presenting a high signal intensity in the SCP. Three interviewers, who were not informed about the clinical data, visually inspected the presence or absence of a high signal intensity in the SCP on the FLAIR images. We measured the pixel value in the SCP of each patient. Clinical characteristics were evaluated using the Mann-Whitney test, followed by the χ2 test. RESULTS: Ten of the 51 patients with PSP showed a high signal intensity in the SCP on FLAIR MRI. Higher pixel values were observed within the SCP of patients with a high signal intensity in the SCP than in patients without a high signal intensity (p < 0.001). The sensitivity and specificity of the high signal intensity in the SCP of patients with PSP was 19.6% and 100%, respectively. This finding was more frequently observed in patients with PSP with Richardson's syndrome (PSP-RS) (25.7%) than other phenotypes (6.2%). CONCLUSION: The high signal intensity in the SCP on FLAIR MRI might be an effective diagnostic tool for PSP-RS.

Serum cystatin C concentration measured routinely is a prognostic marker for renal disease in dogs.

This study examined the predictive value of serum cystatin C (Cys-C) concentration, measured during routine periodic health examinations, in the renal prognosis of dogs. A cohort of 140 dogs weighing <15 kg whose serum Cys-C concentrations were measured during periodic health examinations from December 2013 to March 2016 were prospectively studied, with renal disease-related death the predicted end point. Of the 140 dogs, nine died from renal diseases during the follow-up period (539 ±â€¯249 days). Serum Cys-C concentrations were higher in the dogs that subsequently died of renal disease than in the censored group (0.8 ±â€¯0.25 vs. 0.3 ±â€¯0.1 mg/dl, respectively; P < .01). Dogs with high serum Cys-C concentrations (>0.55 mg/dl) had a shorter (P < .01) renal disease-specific survival period than those with low serum Cys-C concentrations (≤0.55 mg/dl). In conclusion, high serum Cys-C concentrations in periodic health examinations in dogs <15 kg predicted poorer prognosis for renal function.

A Patient With Encephalomyeloradiculoneuropathy Exhibiting a Relapsing-Remitting Clinical Course: Correlation of Serum and Cerebrospinal Fluid Anti-Neutral Glycosphingolipids Antibodies With Clinical Relapse.

Several patients who had a progressive clinical course involving both the central and peripheral nervous systems have been reported, but the diagnostic marker has been remained uncertain. More recently, such patients were reported to have namely "encephalomyeloradiculoneuropathy (EMRN)" associated with anti-neutral glycosphingolipid (GSL) antibodies. These antibodies were reported to disappear from the serum in the recovery phase, but whether this finding applies to the cerebrospinal fluid (CSF) remains uncertain. We describe a 67-year-old man with EMRN in whom we measured anti-neutral GSL antibodies in serial serum and CSF samples. During the disease course, the optical densities of the positive band against the background intensity ratio (-<0.3; ±≥0.3 to <0.6; +≥0.6 to <1.0; 2+≥1.0 to <2.0; 3 +≥2.0) for serum and CSF anti-lactosylceramide (LacCer) antibodies were found to be as follows: 2+ and 1+ at the first admission, ± and - when the consciousness level improved after immunotherapy, - and 1+ at clinical relapse, and ± and - when the consciousness level improved after immunotherapy. This is the first time to document that clinical relapse occurred in EMRN, and at this time the negative anti-LacCer antibodies in CSF after the first course of immunotherapy turned positive, but this was not seen in serum samples.