Muscle MR Imaging in Tubular Aggregate Myopathy

Purpose

To evaluate with Magnetic Resonance (MR) the degree of fatty replacement and edematous involvement in skeletal muscles in patients with Tubular Aggregate Myopathy (TAM). To asses the inter-observer agreement in evaluating muscle involvement and the symmetry index of fatty replacement.

Materials and Methods

13 patients were evaluated by MR to ascertain the degree of fatty replacement (T1W sequences) according to Mercuri''s scale, and edema score (STIR sequences) according to extent and site.

Results

Fatty replacement mainly affects the posterior superficial compartment of the leg; the anterior compartment is generally spared. Edema was generally poor and almost only in the superficial compartment of the leg. The inter-observer agreement is very good with a Krippendorff''s coefficient >0.9. Data show a total symmetry in the muscular replacement (McNemar-Bowker test with p = 1).

Conclusions

MR reveals characteristic muscular involvement, and is a reproducible technique for evaluation of TAM. There may also be a characteristic involvement of the long and short heads of the biceps femoris. It is useful for aimed biopsies, diagnostic hypotheses and evaluation of disease progression.     

Aerobic Training in Patients with Congenital Myopathy

Introduction

Congenital myopathies (CM) often affect contractile proteins of the sarcomere, which could render patients susceptible to exercise-induced muscle damage. We investigated if exercise is safe and beneficial in patients with CM.

Methods

Patients exercised on a stationary bike for 30 minutes, three times weekly, for 10 weeks at 70% of their maximal oxygen uptake (VO_2max). Creatine kinase (CK) was monitored as a marker of muscle damage. VO_2max, functional tests, and questionnaires evaluated efficacy.

Results

Sixteen patients with CM were included in a controlled study. VO_2max increased by 14% (range, 6–25%; 95% CI 7–20; p < 0.001) in the seven patients who completed training, and tended to decrease in a non-intervention group (n = 7; change -3.5%; range, -11–3%, p = 0.083). CK levels were normal and remained stable during training. Baseline Fatigue Severity Scale scores were high, 4.9 (SE 1.9), and tended to decrease (to 4.4 (SE 1.7); p = 0.08) with training. Nine patients dropped out of the training program. Fatigue was the major single reason.

Conclusions

Ten weeks of endurance training is safe and improves fitness in patients with congenital myopathies. The training did not cause sarcomeric injury, even though sarcomeric function is affected by the genetic abnormalities in most patients with CM. Severe fatigue, which characterizes patients with CM, is a limiting factor for initiating training in CM, but tends to improve in those who train.

Trial Registration

The Regional Committee on Health Research Ethics of the Capital Region of Denmark H-2-2013-066 and ClinicalTrials.gov H2-2013-066     

Hydroxyl Radical Formation in Skeletal Muscle of Rats with Glucocorticoid-Induced Myopathy

Steroid myopathy is a well-known adverse effect of glucocorticoids that causes muscle weakness and atrophy; however, its pathogenic mechanism is still unclear. Recently, oxidative stress was reported to contribute to steroid myopathy, but there is no report that actually attempts to measure hydroxyl radical. I developed an animal model of steroid myopathy in rat with dexamethasone (9-Fluoro−11β,17, 21-trihydroxy−16α-methylpregna−1,4-diene−3,20-dione), and measured hydroxyl radical using the salicylate trapping method. There was significant dose-dependent relation between both 2,5- and 2,3-dihydroxybenzoic acids and dexamethasone in the treated group, compared to the control group. These results suggest that hydroxyl radical plays a role in the pathogenesis of steroid myopathy.     

Early Onset of Muscle Atrophy in Women with Chronic Alcoholic Myopathy

This is the first study to observe a 25% atrophy of m. vastus lateralis and a decrease in the size of type I and II muscle fibers (by 35 and 44%, respectively) using magnetic resonance imaging (MRI) in women after five to seven years of alcohol intoxication. The decrease in muscle volume is due to the predominant destruction of contractile apparatus as compared with other components.     

朗格罕细胞组织细胞增生症颅内垂体影像表现及相关临床表现

目的:探讨朗格罕细胞组织细胞增生症累及垂体的MR表现及相关临床表现。方法:搜集了6例确诊为朗格罕细胞组织细胞增生症并垂体表现异常的患儿,男5例,女1例,年龄2～11岁,平均(6±3)岁,对其影像及临床表现进行回顾性分析。结果:临床患儿主要以头面部包块,多饮、多尿等就诊。头颅MR平扫(T1WI)表现6例患儿神经垂体高信号全部消失,垂体柄增粗5例,垂体柄著征1例,垂体饱满1例,其中3例治疗后复查垂体及垂体柄均有变化。结论:神经垂体高信号消失,垂体柄增粗或著征为朗格罕细胞组织细胞增生症累及垂体的头颅MR表现。累及垂体者临床几乎都有多饮、多尿表现。目前,MRI是诊断朗格罕细胞组织细胞增生症累及垂体的唯一可靠的影像学检查方法,并对治疗后病情随访有重要作用。     

Clinical,Haemodynamic, Rheological,and Biochemical Findings in 126 Patients with Intermittent Claudication

Increased blood viscosity has been shown to be an important factor in reducing blood flow in a review and analysis of the history, clinical findings, and haemodynamic, rheological, radiological, and biochemical measurements in 126 patients with intermittent claudication. In some patients increased viscosity seemed to be the determining cause of claudication. A raised plasma fibrinogen was the most common single biochemical abnormality. The results of conventional serum lipid and lipoprotein estimations were abnormal in the series as a whole but did not correlate with clinical findings or flow measurements at individual patient level. There was, however, a significant correlation between some clinical findings and the susceptibility of the red cells to autoxidation.     

An Objective Olfactory Evaluation and its Correlation with Magnetic Resonance Imaging Findings in Asian Indian Patients with Idiopathic Hypogonadotropic Hypogonadism

ObjectiveIdiopathic hypogonadotropic hypogonadism (IHH) can be associated with subnormal sense of smell. The objective of our study was to determine if there is a correlation between the olfactory phenotype (clinical smell test) of IHH patients and structural abnormalities in the olfactory apparatus on magnetic resonance imaging (MRI).MethodsThis was a single-center prospective case control study. Forty-one IHH patients underwent a brief University of Pennsylvania Smell Identification Test (UPSIT) and an MRI of the olfactory apparatus. The size of the olfactory sulcus and bulb were quantified and compared with the normative data of 40 controls. Agreement between UPSIT and MRI results was assessed using the kappa index.ResultsMRI showed that the olfactory apparatus was normal in 17 patients, hypoplastic in 14, and aplastic in 10. All 13 patients who complained of anosmia and 12 of 28 patients who reported normosmia had a low UPSIT score. Thus, 25 patients had Kallmann syndrome (KS) and 16 were normosmic IHH (nIHH). MRI revealedabnormalities in 68% of KS and 37.5% of nIHH patients. The MRI abnormalities in KS patients were aplasia (56%) and hypoplasia (44%). All 6 nIHH patients with abnormal MRI had hypoplasia. A significant positive correlation (r = 0.61; P<.01) between olfactory bulb volume (from MRI) and smell-test score was found, and there was good agreement (kappa index, 0.72) between anosmia and the presence of an aplastic olfactory apparatus.ConclusionSelf-reporting of the sense of smell significantly underestimates olfactory phenotype; hence, we recommend an objective smell test to distinguish KS from nIHH. Olfactory phenotype correlates well with MRI quantification of the olfactory apparatus in IHH. (Endocr Pract. 2013;19:669-674)     

Constitutive Expression of Yes-Associated Protein (Yap) in Adult Skeletal Muscle Fibres Induces Muscle Atrophy and Myopathy

The aim of this study was to investigate the function of the Hippo pathway member Yes-associated protein (Yap, gene name Yap1) in skeletal muscle fibres in vivo. Specifically we bred an inducible, skeletal muscle fibre-specific knock-in mouse model (MCK-tTA-hYAP1 S127A) to test whether the over expression of constitutively active Yap (hYAP1 S127A) is sufficient to drive muscle hypertrophy or stimulate changes in fibre type composition. Unexpectedly, after 5–7 weeks of constitutive hYAP1 S127A over expression, mice suddenly and rapidly lost 20–25% body weight and suffered from gait impairments and kyphosis. Skeletal muscles atrophied by 34–40% and the muscle fibre cross sectional area decreased by ≈40% when compared to control mice. Histological analysis revealed evidence of skeletal muscle degeneration and regeneration, necrotic fibres and a NADH-TR staining resembling centronuclear myopathy. In agreement with the histology, mRNA expression of markers of regenerative myogenesis (embryonic myosin heavy chain, Myf5, myogenin, Pax7) and muscle protein degradation (atrogin-1, MuRF1) were significantly elevated in muscles from transgenic mice versus control. No significant changes in fibre type composition were detected using ATPase staining. The phenotype was largely reversible, as a cessation of hYAP1 S127A expression rescued body and muscle weight, restored muscle morphology and prevented further pathological progression. To conclude, high Yap activity in muscle fibres does not induce fibre hypertrophy nor fibre type changes but instead results in a reversible atrophy and deterioration.     

Incidental Findings on Brain Magnetic Resonance Imaging (MRI) in Pediatric Endocrine Patients

Objective: To explore incidental findings on brain magnetic resonance imaging (MRI) studies of pediatric patients referred due to endocrine disorders.Methods: A retrospective, observational study conducted in a tertiary referral center. The neuroimaging database of 17,445 brain MRI studies of 11,011 pediatric patients were searched for cases with endocrine referrals and without medical history of malignancy, genetic syndromes, and/or neurologic comorbidities. This database was linked to the pediatric neurosurgical database. Clinical data were retrieved from medical files.Results: In total, 524 patients (50.2% males, mean age 8.5 ± 3.5 years) were referred to brain MRI due to growth disturbances (n = 313), pubertal disorders (n = 183), prolactin hypersecretion (n = 18), central diabetes insipidus (n = 8), and obesity (n = 1). Incidental findings were found in 128 (24.4%) cases. Chiari type 1 malformation was more prevalent in patients with growth disturbances (P<.001). Small pituitary cysts were observed in 20 (3.8%) patients, and pineal cysts in 25 (4.8%) patients, mostly girls (68%, P<.001). White matter lesions were diagnosed in 30 (5.7%) patients, none with clinical evidence of neurologic disease. Brain asymmetry without clinical significance and developmental venous anomalies were observed in 14 (2.7%) and 8 (1.5%) patients, respectively. Twelve patients were diagnosed with intracranial tumors, and 5 required surgical intervention for a histopathologic diagnosis of juvenile pilocytic astrocytoma (n = 3), choroid plexus papilloma (n = 1), or inconclusive (n = 1). The rest were managed conservatively.Conclusion: Incidental findings on brain MRIs of pediatric patients referred by endocrinologists are common and raise dilemmas. The spectrum ranges from structural disruptions to tumors. Decision-making is individualized and patient-centered.     

Clinical Course and Changes in High-Resolution Computed Tomography Findings in Patients with Idiopathic Pulmonary Fibrosis without Honeycombing

Some patients with idiopathic pulmonary fibrosis (IPF) do not have honeycombing on high-resolution computed tomography (HRCT) at their initial evaluation. The clinical course and sequential changes in HRCT findings in these patients are not fully understood. We reviewed the cases of 43 patients with IPF without honeycombing on initial HRCT from institutions throughout Japan. All patients were diagnosed with IPF based on a surgical lung biopsy. Multidisciplinary discussions were held five times between 2011 and 2014, to exclude alternative etiologies. We evaluated the sequential changes in HRCT findings in 30 patients with IPF. We classified these 30 patients into three groups based on their HRCT patterns and clarified the clinical characteristics and prognosis among the groups. The patterns of all 30 patients on initial HRCT corresponded to a possible usual interstitial pneumonia (UIP) pattern which was described in the 2011 International Statement. On long-term follow-up (71.0±38.7 standard deviation [SD] months), honeycombing was seen in 16 patients (53%, the HoneyCo group); traction bronchiectasis or cysts without honeycombing was observed in 12 patients (40%, the NoHoneyCo group), and two patients showed no interval change (7%, the NoChange group) on HRCT. The mean survival periods of the HoneyCo and NoHoneyCo groups were 67.1 and 61.2 months, respectively (p = 0.76). There are some patients with IPF whose conditions chronically progress without honeycombing on HRCT. The appearance of honeycombing on HRCT during the follow-up might not be related to prognosis.     

Colonoscopic Findings in Peruvian Patients with Chronic Diarrhea

Objective

To report the colonoscopic and pathological findings in patients with chronic diarrhea from a gastroenterology unit during approximately 3 years in a general teaching hospital located in Lima-Peru.

Materials and Methods

Patients with chronic diarrhea as the motive for colonoscopy from March 2008 to December 2010 were selected from the colonoscopy report computerized database. Colonoscopic findings were registered. Biopsies taken during the procedure were prospectively reviewed.

Results

226 patients were included, of which 162 (71.7%) had a colon biopsy available. The average age of the patients was 53.6±16.36. 85.8% of patients were reported to have a normal colon. 14.8% of patients were found to have a normal colonic mucosa or mucosal edema, 35.8% of patients had lymphocytic colitis and 28.4% had paucicelular colitis.

Conclusions

The majority of colonoscopies were reported with unremarkable macroscopic findings. Lymphocytic colitis was unusually frequent compared to previous reports.     

Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy

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Histological and Clinical Findings in Patients with Post-Transplantation and Classical Encapsulating Peritoneal Sclerosis: A European Multicenter Study

Background

Encapsulating peritoneal sclerosis (EPS) commonly presents after peritoneal dialysis has been stopped, either post-transplantation (PT-EPS) or after switching to hemodialysis (classical EPS, cEPS). The aim of the present study was to investigate whether PT-EPS and cEPS differ in morphology and clinical course.

Methods

In this European multicenter study we included fifty-six EPS patients, retrospectively paired-matched for peritoneal dialysis (PD) duration. Twenty-eight patients developed EPS after renal transplantation, whereas the other twenty-eight patients were classical EPS patients. Demographic data, PD details, and course of disease were documented. Peritoneal biopsies of all patients were investigated using histological criteria.

Results

Eighteen patients from the Netherlands and thirty-eight patients from Germany were included. Time on PD was 78(64–95) in the PT-EPS and 72(50–89) months in the cEPS group (p>0.05). There were no significant differences between the morphological findings of cEPS and PT-EPS. Podoplanin positive cells were a prominent feature in both groups, but with a similar distribution of the podoplanin patterns. Time between cessation of PD to the clinical diagnosis of EPS was significantly shorter in the PT-EPS group as compared to cEPS (4(2–9) months versus 23(7–24) months, p<0.001). Peritonitis rate was significantly higher in cEPS.

Conclusions

In peritoneal biopsies PT-EPS and cEPS are not distinguishable by histomorphology and immunohistochemistry, which argues against different entities. The critical phase for PT-EPS is during the first year after transplantation and therefore earlier after PD cessation then in cEPS.     

Outcomes of Transsphenoidal Surgery in Cushing Disease Patients with Negative Pituitary Magnetic Resonance Imaging Findings: A Single-Center Experience

Objective: Transsphenoidal surgery (TSS) is a first-line treatment for Cushing disease (CD). However, a subset of patients with CD have no visible adenoma on magnetic resonance imaging (MRI), and whether MRI results affect surgical outcomes is controversial. The aim of this study was to compare the surgical outcomes of CD patients with negative MRI findings to those of patients with positive MRI findings.Methods: The clinical features and outcomes of CD patients who underwent TSS between January 2000 and July 2019 at Peking Union Medical College Hospital were collected from medical records. The clinical, endocrinologic, histopathologic, surgical outcomes, and a minimum 12-month follow-up of 125 consecutive CD patients with negative MRI findings were compared with those of 1,031 consecutive CD patients with MRI-visible adenomas.Results: The total remission rate was 73.3% after TSS, and 11.8% of patients experienced recurrence. Of 1,031 patients with MRI-visible adenomas, postoperative remission was achieved in 762 patients (73.9%), and the recurrence of CD was observed in 94 (12.3%) patients. Of the 125 patients with negative MRI findings, postoperative remission was achieved in 85 (68%) patients, and recurrence was observed in 6 (7.1%) patients. The remission rate and recurrence rate were not significantly different between patients with negative MRI findings and those with positive MRI findings (all P>.05). The remission rate was not significantly different between patients who did or did not undergo bilateral inferior petrosal sinus sampling (BIPSS) in patients with negative MRI findings (P>.05). In the patients with negative MRI findings who underwent BIPSS, the remission rate of patients with positive BIPSS results was not different from that in patients with negative BIPSS results (P>.05). The lack of prior TSS, the detection of a tumor during operation, and pathologic confirmation of adenoma were associated with a higher surgical remission rate in patients with negative MRI findings (all P<.05). Similar results were observed in the patients with positive MRI findings (all P<.05). In addition, the major perioperative complications, including intraoperative cerebrospinal fluid leakage, hypopituitarism, and transient diabetes insipidus, were not related to the MRI results (all P>.05).Conclusion: The remission rate and recurrence rate were not different between patients with negative MRI findings and those with positive MRI findings. If CD is clearly diagnosed according to biochemical tests, radiologic examinations, and BIPSS, we recommend TSS as the first-line treatment for patients, even if the MRI results are negative.     

Creatine Kinase Elevation,Lactacidemia, and Metabolic Myopathy in Adult Patients with Diabetes Mellitus

ObjectiveTo determine the frequency of elevated creatine kinase (CK) levels among patients with diabetes mellitus and to determine how often elevated CK is attributable to primary myopathy.MethodsIn this prospective study, we investigated how often CK, aspartate aminotransferase, alanine aminotransferase, and resting lactate were elevated among consecutive diabetic patients attending our clinic. Those with elevated CK values were offered a neurologic workup.ResultsNinety-nine patients with diabetes mellitus, aged 19 to 87 years, were assessed between May 2008 and April 2010. Seven patients had type 1 diabetes and 92 patients had type 2 diabetes. CK, aspartate aminotransferase, alanine aminotransferase, and resting lactate were elevated in 19 of 99, 25 of 99, 22 of 99, and 24 of 98 patients, respectively. Eleven of 19 patients with increased CK were self-injecting insulin. Ten of 24 patients with elevated serum lactate took metformin. Seven of 19 patients with elevated CK consented to neurologic workup. Two of the 7 had elevated resting lactate. In all 7 patients, the findings from neurologic investigation were indicative of a metabolic defect and further diagnostic evaluation was recommended.ConclusionsIn diabetic patients attending our clinic, elevated CK levels occur in one-fifth and lactacidemia occurs in one-quarter. Elevated CK levels are attributable to a primary metabolic myopathy in most cases. Elevated CK levels in the setting of diabetes mellitus require further neurologic evaluation. (Endocr Pract. 2012;18:387-393)