Dyslexia and cognitive impairment in adult patients with myotonic dystrophy type 1: a clinical prospective analysis.

BACKGROUND: Cognitive impairments in patients with myotonic dystrophy type 1 (DM1) have often been described, however, there are only few studies differentiating between partial performance disorders and mental retardation in common. This study focused on the evaluation of reading performance and the frequency of dyslexia in adult DM1 patients. METHODS: We performed a prospective cohort study including genetically confirmed adult DM1 patients registered in the DM registry of Germany or the internal database of the Friedrich-Baur-Institute, Munich, Germany. For the assessment of the patients' reading and spelling performance, we used the standardized and validated test 'Salzburger Lese- und Rechtschreibtest' (SLRT II). The 'CFT-20 R Grundintelligenztest Skala 2' in revised ("R") version (CFT 20-R), determining the intelligence level, was appropriate to differentiate between dyslexia and general mental retardation. The diagnosis of dyslexia, the combined reading and spelling disorder, was based on the guidelines for diagnosis and therapy of children and adolescents with dyslexia 2015 (S3-guideline) providing (1) the criterion of the divergence from age level and (2) the criterion of IQ-divergence. RESULTS: Fifty-seven DM1 patients participated in our study. Evaluating the reading performance, 16 patients fulfilled the divergence criteria of the age level and 2 patients the IQ-divergence criteria. In total, the diagnosis of a reading disorder was given in 18 DM1 patients (31.6 %). In 11 out of these 18 patients with a reading disorder, a relevant impairment of spelling performance was observed with at least three spelling errors. As there are no normative values for adults in spelling performance, we assume a combined reading disorder and dyslexia, in those 11 DM1 patients (19.3 %). Regarding the separate analyses of the test procedures, in the SLRT II the performance was below average in 40.4 % of all patients for 'word reading' and in 61.4 % of all patients for 'pseudoword reading'. There was a significant positive correlation between the CTG expansion size and a reading disorder (p=0.027). The average IQ of 17 examined DM1 patients was in the lower normal range (86.1 ± 19.1). 54.5 % of patients with reading disorder had a normal IQ. CONCLUSION: The calculated prevalence of dyslexia in the DM1 study cohort was 19.3 % and thus considerably increased compared to the normal German population. As dyslexia is not equivalent to a general cognitive impairment, it is important not to miss dyslexic features in cognitive inconspicuous DM1 patients. Case-by-case one should consider a differential diagnostic approach, as individualized therapies can be offered to support dyslexic patients in their performance.

Pathophysiology of Crohn's disease inflammation and recurrence.

Chron's Disease is a chronic inflammatory intestinal disease, first described at the beginning of the last century. The disease is characterized by the alternation of periods of flares and remissions influenced by a complex pathogenesis in which inflammation plays a key role. Crohn's disease evolution is mediated by a complex alteration of the inflammatory response which is characterized by alterations of the innate immunity of the intestinal mucosa barrier together with a remodeling of the extracellular matrix through the expression of metalloproteins and increased adhesion molecules expression, such as MAcCAM-1. This reshaped microenvironment enhances leucocytes migration in the sites of inflammation, promoting a TH1 response, through the production of cytokines such as IL-12 and TNF-α. IL-12 itself and IL-23 have been targeted for the medical treatment of CD. Giving the limited success of medical therapies, the treatment of the disease is invariably surgical. This review will highlight the role of inflammation in CD and describe the surgical approaches for the prevention of the almost inevitable recurrence.

C-reactive protein levels in the perioperative period as a predictive marker of endoscopic recurrence after ileo-colonic resection for Crohn's disease.

The aim of this study was to determine the perioperative behavior of C-reactive protein (CRP) in Crohn's disease (CD) patients undergoing elective ileo-cecal (IC) resection and to identify association between perioperative CRP levels and endoscopic recurrence at 1 year. Study hypothesis was that perioperative CRP changes are disease specific and could detect subset of patients with more aggressive pathopysiology. Seventy-five patients undergoing IC resection for CD were prospectively enrolled. Serial CRP levels were assessed: preoperative, postoperative day 1 (POD1) and day 5 (POD5). CD patients' values were compared against same interval assessments of control groups undergoing right colectomy and appendicectomy. At POD1, the serum concentration increase was significantly higher in CD patients than in controls. Comparing with control groups, CRP levels remained remarkably high and showed a lower reduction in CD at POD5. Difference between groups was statistically significant. Optimal cutoff levels have been identified: serum CRP concentrations of >39.8 mg/l at POD1 and of >23.2 mg/l at POD5 have shown a significant association to endoscopic recurrence when using bivariate correlation. In this preliminary series, binary logistic regression could not demonstrate statistical relationship between endoscopic recurrence and any of the variables evaluated as prognostic factor. This is the only study so far that investigates and confirms a disease-specific upregulation of CRP response in the perioperative period for CD patients undergoing surgery. The postoperative CRP levels and kinetics seem to be related to the grade of mucosal inflammation and recurrence rate according to our 12 months endoscopic evaluation.

[Educational and Professional Qualifications of Adults With Myotonic Dystrophies - A Misleading Perception by the Myopathic Face?]. / Ausbildung und berufliche Qualifikation von Erwachsenen mit Myotonen Dystrophien - eine fehlgeleitete Wahrnehmung durch die Facies myopathica?

BACKGROUND: Myotonic dystrophies types 1 and 2 (DM1 / DM2) are the most frequent inherited progressive, segmental progeroid, multisystemic neuromuscular diseases in adulthood. The executive impairment is one of the key disease features. The myopathic face triggers the general perception of DM1 patients being associated with a low educational level. METHODS: We used a standardized questionnaire to evaluate educational levels in adults with genetically confirmed DM1 and DM2 in comparison to data of the general population. Investigated topics included the level of education, e. g. the highest university degree aquired. RESULTS: Out of a total cohort of 546 DM patients, 125 DM1 and 156 DM2 patients (51 %) participated in this study. There was no statistically significant difference between the two collectives as far as high school levels are concerned. 50.4 % of DM1 and 48.3 % of DM2 patients obtained the higher education entrance qualification compared to 29.6 % of the normal German population. However, there were significant differences between the two collectives in "spelling problems" (DM1 cohort: p = 0.039), "difficulty in mental arithmetic" (p = 0.043), and classification of patients "with learning difficulties" (p = 0.012). DISCUSSION: Misled by a myopathic face, many physicians associate myotonic dystrophy with cognitive deficiency. Based on our study, the minimal deviation between DM1 and DM2 and the normal German population indicates that the multisystemic disease does not significantly influence the maximum attainable level of education in adults with DM1. CONCLUSION: In summary, physicians should be aware that the general educational levels are rather normal in patients with myotonic dystrophy type 1 and rethink their perception of DM1 patients.

Cerebellar ataxia and severe muscle CoQ10 deficiency in a patient with a novel mutation in ADCK3.

Inherited ataxias are a group of heterogeneous disorders in children or adults but their genetic definition remains still undetermined in almost half of the patients. However, CoQ10 deficiency is a rare cause of cerebellar ataxia and ADCK3 is the most frequent gene associated with this defect. We herein report a 48 year old man, who presented with dysarthria and walking difficulties. Brain magnetic resonance imaging showed a marked cerebellar atrophy. Serum lactate was elevated. Tissues obtained by muscle and skin biopsies were studied for biochemical and genetic characterization. Skeletal muscle biochemistry revealed decreased activities of complexes I+III and II+III and a severe reduction of CoQ10 , while skin fibroblasts showed normal CoQ10 levels. A mild loss of maximal respiration capacity was also found by high-resolution respirometry. Molecular studies identified a novel homozygous deletion (c.504del_CT) in ADCK3, causing a premature stop codon. Western blot analysis revealed marked reduction of ADCK3 protein levels. Treatment with CoQ10 was started and, after 1 year follow-up, patient neurological condition slightly improved. This report suggests the importance of investigating mitochondrial function and, in particular, muscle CoQ10 levels, in patients with adult-onset cerebellar ataxia. Moreover, clinical stabilization by CoQ10 supplementation emphasizes the importance of an early diagnosis.

"Orbiting around" the orbital myositis: clinical features, differential diagnosis and therapy.

Orbital myositis (OM) is a rare disease whose clinical heterogeneity and different treatment options represent a diagnostic and therapeutic challenge. We aim to review the state of knowledge on OM, also describing a cohort of patients diagnosed in our centre, to highlight some remarkable clinical features. A literature review was conducted in PubMed and Medline databases. The herein described cohort is composed of seven OM patients, diagnosed according to clinical, laboratory and neuroradiological features, whose clinical data were retrospectively analysed. OM is a non-infectious, inflammatory process primarily involving extraocular eye-muscles. It typically presents as an acute to sub-acute, painful ophthalmoplegia with signs of ocular inflammation, but atypical cases without pain or with a chronic progression have been described. The wide range of OM mimicking diseases make a prompt diagnosis challenging but orbit MRI provides valuable clues for differential diagnosis. Timely treatment is greatly important as OM promptly responds to steroids; nevertheless, partial recovery or relapses often occur. In refractory, recurrent or steroid-intolerant cases other therapeutic options (radiotherapy, immunosuppressants, immunoglobulins) can be adopted, but the most effective therapeutic management is yet to be established. In this review, we provide a detailed clinical description of OM, considering the main differential diagnoses and suggesting the most useful investigations. In light of the currently available data on therapy efficacy, we propose a therapeutic algorithm that may guide neurologists in OM patients' management.

Hepatitis C virus carriers with persistently normal aminotransferase levels: healthy people or true patients?

Since the discovery of hepatitis C virus, the availability of serological hepatitis C virus screening has led to the identification of many subjects with normal aminotransferase levels who are chronically infected by the hepatitis C virus. To date, the epidemiology and natural history of subjects with normal aminotransferase levels are far from being clarified. Further, whether subjects with persistently normal aminotransferase levels should routinely undergo liver biopsy is still extremely controversial, and benefit from interferon treatment in this group of patients is yet to be proven. On account of the consistent normality of aminotransferases, it is not easy to calculate the rate of persons with normal aminotransferase levels among chronic hepatitis C virus carriers, nor their prevalence in the general population. It has been estimated that up to 25% of patients with chronic hepatitis C virus infection have persistently normal aminotransferase levels (10% to 40%, according to different studies). Most studies showed a clear prevalence of females, ranging from 58% to 90%. Liver biopsy shows some degree of chronic liver disease in up to 80% of these subjects, although in the majority, histological damage is mild and probably does not progress to more severe liver disease, moreover, the progression to fibrosis is slower than in patients with elevated aminotransferase levels. Virological features of these subjects (hepatitis C virus genotype distribution, viral load, quasispecies diversity) do not differ with respect to patients with elevated aminotransferase levels although a higher frequency of non 1 hepatitis C virus types has been reported. To date, no biochemical or virological tools to assess the presence and severity of liver damage exist. Antiviral treatment with interferon may induce a long-term response in only a small proportion of hepatitis C virus carriers with persistently normal aminotransferase levels, and many patients develop aminotransferase-flare-up during or shortly after treatment. Thus, interferon or combination antiviral treatment of hepatitis C virus carriers with normal aminotransferase values should be avoided in clinical practice.

Clinical, histological, and virological features of hepatitis C virus carriers with persistently normal or abnormal alanine transaminase levels.

This study was aimed to evaluate demographic, clinical, histological, and virological characteristics of 46 hepatitis C virus (HCV) carriers with persistently normal alanine transaminase (ALT) levels and to compare the results with those obtained in a group of 52 HCV-RNA-positive patients with elevated ALT levels. Subjects with normal ALT were more often females (P < .001), were more likely to be asymptomatic (P < .001), and have a lower incidence of risk factors for HCV transmission (P < .01). All patients with normal ALT had significant histological liver damage. The mean grading and staging did not differ between patients with normal and those with raised ALT concentrations. Moderate to severe hepatitis was more frequently found among subjects with normal than with elevated ALT. HCV genotype 2a was far more common in subjects with normal (43%) than with abnormal ALT levels (6%; P < .002), genotype 1b being more frequent in these latter (50% vs. 17%; P < .001). Patients with normal ALT levels had similar serum HCV-RNA titers than subjects with raised ALT. Neither HCV genotype distribution nor viral load correlated with the severity of liver damage. We conclude that significant liver disease may occur irrespective of clinical symptoms, ALT levels, HCV genotypes, and viral load.

Iron overload in patients with chronic viral hepatitis: how common is it?

OBJECTIVES: To establish the prevalence of increased hepatic iron content in patients with hepatitis C virus-related chronic hepatitis and to assess the accuracy of serum iron and ferritin in detecting tissue iron overload. METHODS: Serum iron, serum ferritin, and hepatic iron content were determined in 81 consecutive patients undergoing liver biopsy for chronic ALT elevation and hepatitis C virus infection. Moreover, in a subgroup of 28 patients, outcome of a 6-month course of interferon (IFN) treatment (6 million U of recombinant IFN, three times weekly) was determined after a mean follow-up of 24 +/- 6 months and the outcome was compared with the pretreatment values of hepatic iron content. RESULTS: Elevated serum iron or ferritin levels were detected in approximately 40% of patients, but elevated hepatic iron content was observed in only eight patients (10%). One of these patients had a hepatic iron index > 1.9, indicating hemochromatosis. Liver iron content and serum iron levels were not correlated. No differences in hepatic iron content were observed among patients with a sustained response to IFN (seven patients), short-term responders (seven patients), or nonresponders (14 patients). CONCLUSIONS: Ten percent of patients with chronic hepatitis C have elevated hepatic iron content. These patients cannot be identified using serum markers of iron status. The relationship between liver iron and response to IFN treatment requires further prospective investigations.

Whole body and regional body composition analysis by dual-energy X-ray absorptiometry in cirrhotic patients.

OBJECTIVES: To compare whole body and regional (arms, legs and trunk) fat mass, fat-free mineral-free mass bone mineral content and bone mineral density, measured by DXA, in cirrhotic patients and age, sex and BMI matched healthy volunteers. DESIGN: Cross-sectional study. SETTING: Two medical research institutions. SUBJECTS: Twenty-two non ascitic cirrhotic patients and 16 age, sex and BMI matched healthy volunteers. INTERVENTIONS: The Lunar DPX whole-body X-ray densitometer with Lunar software version 3.6z (Lunar Radiation Corp., Madison WI, USA) was used. Regional analysis was performed on the arms, legs, trunk and head. RESULTS: Compared to controls, cirrhotic patients showed a significant reduction in percentage body fat. When differentiated by gender, however, the reduction in percentage body fat was evident in female cirrhotics only, particularly in the trunk. In male cirrhotic patients fat-free mineral-free mass was reduced in absolute terms in the whole body and the limbs. For both genders and in each body segment bone mineral content and density were reduced in cirrhotics compared to controls. In cirrhotic patients bone mineral density was significantly correlated to both fat-free, mineral-free mass (r = 0.85; P < 0.001) and to the Physical Activity Index (r = 0.52; P < 0.01). CONCLUSIONS: Two different patterns of soft tissue loss may be found in cirrhotic patients: in women lean tissue is maintained while fat stores are reduced, as in early starvation; in men lean tissue is reduced, as seen under conditions of stress. Moreover, factors influencing lean body mass, such as nutritional depletion and physical inactivity, may contribute to the reduction of bone density frequently observed in cirrhotic patients.