Handan Cakmakci

Nitric oxide as an activity marker in multiple sclerosis

Abstract. Nitric oxide (NO) molecules have one of the most important roles in the pathogenesis of multiple sclerosis (MS). It has been stated that a continuous and high concentration of NO metabolites in CSF and in the serum of MS patients in relapse may cause toxic damage to myelin and oligodendroglia. The aim of this study was to investigate whether NO is a marker of disease activity and is correlated with other disease activity markers such as active lesions on brain magnetic resonance imaging (MRI) and increased immunoglobulin G (IgG) index.Cerebrospinal fluid (CSF) and peripheral serum (PS) samples were taken from patients with definite MS (n = 24) during relapse and remission and from control subjects (n = 18). The Griess reaction was used to measure the NO metabolites, nitrite and nitrate in CSF and PS. Cranial MRI was carried out with triple dose (0,3 mmol/kg) gadolinium and the IgG index was determined.Nitrite and nitrate concentrations (NNCs) of CSF were 11.16 ± 8.60 μmol/ml in relapse and 6.72 ± 3.50 μmol/ml in remission, whereas in PS they were 12.89 ± 7.62 μmol/ml during relapse and 12.35 ± 6.62 μmol/ml during remission. In control subjects NNCs in CSF and PS were 7.42 ± 2.81 μmol/ml and 4.37 ± 1.63 μmol/ml respectively. NNCs in CSF during relapse period were significantly higher than those of both remission phase and control subjects (p = 0.000). Although serum NNCs did not differ in relapse and remission, they were still higher than normal controls. Validity analysis revealed that NNC measurement in CSF was 71 % specific and 66 % sensitive to disease activity. The most important result was the significant correlation of increased NNCs with the existence of active lesion in cranial MRI and an increase in IgG index (p < 0.05).In conclusion, these results add background data to assist in further outlining the possible role of NO in the pathogenesis of MS. Together with the other markers it may be used as an activity marker in relapses of MS.

Mycoplasma pneumoniae: nervous system complications in childhood and review of the literature

Mycoplasma pneumoniae is an important pathogen which causes nervous system disorders during or after the course of a respiratory tract infection. The exact pathogenic mechanism which causes neurological disorders still remains unknown. Although meningoencephalitis and acute disseminated encephalomyelitis are common complications, there are few cases of acute transverse myelitis and isolated abducens nerve palsy associated with M. pneumoniae infection in childhood. The association between ocular myasthenia gravis and M. pneumoniae infection has not been described before. Here, we describe five patients with different nervous system complications associated with M. pneumoniae infection and discuss the pathological features of central nervous system involvement.

Case report of intrafamilial variability in autosomal recessive centronuclear myopathy associated to a novel BIN1 stop mutation

Centronuclear myopathies (CNM) describe a group of rare muscle diseases typically presenting an abnormal positioning of nuclei in muscle fibers. To date, three genes are known to be associated to a classical CNM phenotype. The X-linked neonatal form (XLCNM) is due to mutations in MTM1 and involves a severe and generalized muscle weakness at birth. The autosomal dominant form results from DNM2 mutations and has been described with early childhood and adult onset (ADCNM). Autosomal recessive centronuclear myopathy (ARCNM) is less characterized and has recently been associated to mutations in BIN1, encoding amphiphysin 2. Here we present the first clinical description of intrafamilal variability in two first-degree cousins with a novel BIN1 stop mutation. In addition to skeletal muscle defects, both patients have mild mental retardation and the more severely affected male also displays abnormal ventilation and cardiac arrhythmia, thus expanding the phenotypic spectrum of BIN1-related CNM to non skeletal muscle defects. We provide an up-to-date review of all previous cases with ARCNM and BIN1 mutations.

Comparison of MRI and renal cortical scintigraphy findings in childhood acute pyelonephritis: preliminary experience.

OBJECTIVE The diagnosis of acute pyelonephritis in children remains a clinical challenge. It may cause permanent renal scar formation and results in the chronic renal failure if prompt diagnosis and treatment are delayed. The purpose of this study is to compare magnetic resonance imaging (MRI) and renal cortical scintigraphy (RCS) findings in childhood acute pyelonephritis and to determine pyelonephritic foci in the acute phase. MATERIALS AND METHOD Twenty children (15 females and five males) with symptoms dysuria, enuresis, costovertebral pain, fever of 37.5 degrees C or more and/or positive urine culture were imaged by unenhanced turbo spin echo T2, spin echo T1-weighted, pre- and post-gadolinium inversion recovery MRI and RCS. Both imaging techniques were read independently by two radiologists and nuclear medicine specialists. Sensitivity and specificity of MRI in detecting acute pyelonephritic foci and scar lesions were calculated. Furthermore, in order to calculate the reliability of MRI over RCS in differentiating scar tissue and acute pyelonephritic foci, follow-up MRI studies were done in six patients after treatment of acute pyelonephritis. RESULTS Sensitivity and specificity of MRI in the detection of pyelonephritic lesions were found to be 90.9 and 88.8%, respectively. There is no statistically significant difference in lesion detection between the two diagnostic modalities (P>0.05). CONCLUSION Post-gadolinium MR images show significant correlation with RCS in the determination of renal pathology. Moreover, the ability of discriminating acute pyelonephritic foci and renal scar in early stages of disease is the superiority of MRI.

Diagnostic value of proton MR spectroscopy and diffusion-weighted MR imaging in childhood inherited neurometabolic brain diseases and review of the literature.

The purpose of this study is to evaluate parenchymal diffusion properties and metabolite ratios in affected brain tissues of inherited neurometabolic brain diseases with an overview of the current literature about the diagnostic data of both techniques in childhood inherited metabolic brain diseases. The study group was consisting, 19 patients (15 males, 4 females; mean age, 54 months (4.5 years); age range, 1-171 months (14.25 years)) diagnosed with inherited neurometabolic brain disease. Single- and multivoxel proton MRS was carried out and NAA/Cr, Cho/Cr, mI/Cr, Glx/Cr ratios were calculated. Presence of lactate peak and abnormal different peaks were noted. ADC values were calculated from brain lesions. Results are compared with age and sex matched normal subjects. Elevated NAA/Cr ratio (Canavan disease), galactitol peak (galactosemia) at 3.7 ppm, branched chain amino acids (Maple syrup urine disease-MSUD) at 0.9 ppm were seen on different diseases. In Leigh disease and MSUD restricted diffusion was detected. Different diffusion properties were seen only in one Glutaric aciduria lesions. NAA/Cr ratios and calculated ADC values were significantly different from normal subjects (p<0.05). DWI combined with MRS are complementary methods to routine cranial MRI for evaluating neurometabolic diseases which can give detailed information about neurochemistry of affected brain areas.

Evaluation of serum lipids and carotid artery intima media thickness in epileptic children treated with valproic acid

The aim of this study is to evaluate the carotid artery intima media thickness and serum lipids in pediatric patients with epilepsy treated with valproic acid. The study included 44 pediatric epileptic and 40 healthy children. Intima media thickness of left common carotid artery and fasting lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) were assessed. Although we did not observe any differences regarding serum lipid profiles, intima media thickness of common carotid artery was significantly higher in epileptic patients treated with valproic acid. We suggest that this increase in intima media thickness of common carotid artery may be due to epilepsy and/or valproic acid treatment.

Sturge-Weber syndrome without facial nevus

An 11-month-old patient with Sturge-Weber syndrome with the absence of facial angioma and normal mental development is presented. Noncontrast computed tomography revealed left parieto-occipital atrophy with heavy gyriform calcifications. Axial T(2)-weighed magnetic resonance imaging confirmed the presence of low-signal areas corresponding to the gyral calcifications evident on computed tomography. Contrast-enhanced T(1)-weighted axial and coronal images exhibited high signals in the left parieto-occipital cortical and subcortical areas, representing angiomatous malformations. The clinical appearance and pathologic features of the reported patient were compared with those of similar patients described in published reports.

Diagnostic value of MR arthrography in detection of intrinsic carpal ligament lesions: use of cine-MR arthrography as a new approach

Twenty-five patients with chronic wrist pain and a preliminary diagnosis of carpal instability were examined with conventional MR imaging and MR arthrography with single compartment intra-articular injection. A new cine-MR arthrography technique, with image acquisition at every 5 s during intra-articular injection, was performed in 17 subjects. The purpose of this study was to determine the diagnostic value of MR arthrography in ligamentous lesions of the wrist and to assess the value of cine-MR arthrography in comparison with arthroscopy and/or surgery. Magnetic resonance arthrography, a semi-invasive technique, increased the diagnostic accuracy of intrinsic carpal ligament injuries. Cine-MR arthrography can be considered as a promising technique especially for the evaluation of lunatotriquetral and scapholunate ligament injuries of the wrist.

Molybdenum cofactor deficiency: Review of 12 cases (MoCD and review)

Molybdenum cofactor deficiency is a rare inborn error of metabolism. The major clinical symptoms are intractable neonatal seizures, progressive encephalopathy, facial dysmorphic features and feeding difficulties. Most of the patients are misdiagnosed as hypoxic ischemic encephalopathy. The majority of patients have mutations in the MOCS1 and MOCS2 genes. Although the therapeutic treatment strategies have not been improved, genetic analysis is essential to elucidate the disease. Here, we report a review of 12 patients with Molybdenum cofactor deficiency reported from Turkey.

Fukutin mutations in non-Japanese patients with congenital muscular dystrophy: less severe mutations predominate in patients with a non-Walker-Warburg phenotype.

Six genes including POMT1, POMT2, POMGNT1, FKRP, Fukutin (FKTN) and LARGE encode proteins involved in the glycosylation of α-dystroglycan (α-DG). Abnormal glycosylation of α-DG is a common finding in Walker-Warburg syndrome (WWS), muscle-eye-brain disease (MEB), Fukuyama congenital muscular dystrophy (FCMD), congenital muscular dystrophy types 1C and 1D and some forms of autosomal recessive limb-girdle muscular dystrophy (LGMD2I, LGMD2K, LGMD2M), and is associated with mutations in the above genes. FCMD, caused by mutations in Fukutin (FKTN), is most frequent in Japan, but an increasing number of FKTN mutations are being reported outside of Japan. We describe four new patients with FKTN mutations and phenotypes ranging from: severe WWS in a Greek-Croatian patient, to congenital muscular dystrophy and cobblestone lissencephaly resembling MEB-FCMD in two Turkish patients, and limb-girdle muscular dystrophy and no mental retardation in a German patient. Four of the five different FKTN mutations have not been previously described.