Clinical and Molecular Findings in a Turkish Family Who Had a (c.869- 1G>A) Splicing Variant in PSEN1 Gene with A Rare Condition: The Variant Alzheimer's Disease with Spastic Paraparesis.

BACKGROUND: Early-onset Alzheimer's disease (EOAD) is commonly diagnosed with an onset age of earlier than 65 years and accounts for 5-10% of all Alzheimer's disease (AD) cases. To date, although only 10-15% of familial EOAD cases have been explained, the genetic cause of the vast proportion of cases has not been explained. The variant Alzheimer's disease with spastic paraparesis (var- AD) is defined as a rare clinical entity characterized by early-onset dementia, spasticity of the lower extremities, and gait disturbance. Although the disease was first associated with variants in exon 9 of the PSEN1 gene, it was later shown that variations in other exons were also responsible for the disease. OBJECTIVE: The current study aims to raise awareness of varAD, which occurs as a rare phenotype due to pathogenic variants in PSEN1. In addition, we aimed to evaluate the spectrum of mutations in varAD patients identified to date. METHODS: Detailed family histories and clinical data were recorded. Whole exome sequencing was performed and co-segregation analysis of the family was done by Sanger sequencing. Also, a review of the molecularly confirmed patients with (varAD) from the literature was evaluated. RESULTS: We identified a heterozygous splicing variant (c.869-1G>A) in the PSEN1 gene, in a family with two affected individuals who present with varAD. We reported the clinical and genetic findings from the affected individuals. CONCLUSION: We present the detailed clinical and genetic profiles of a Turkish patient with the diagnosis of varAD together with subjects from the literature. Together, we think that the clinical characteristics and the effect of the (c.869-1G>A) variant will facilitate our understanding of the PSEN1 gene in AD pathogenesis.

Red and White Thrombus Characteristics in Patients Undergoing Carotid Endarterectomy.

OBJECTIVE: The study aimed to compare the characteristics of red and white thrombi in patients undergoing carotid endarterectomy. MATERIAL AND METHODS: The study was conducted in 81 patients with ischemic stroke who underwent carotid endarterectomy for carotid artery stenosis. Carotid plaques were graded by two pathologists. Thrombus materials were divided into two groups: white and red. The parameters of assessment were plaque rupture, lipid core, fibrous cap thickness, inflammation, intraplaque hemorrhage, calcification, necrotic core, and neovascularization. Normally distributed data were evaluated using Mann-Whitney U and Chi-squared tests. RESULTS: The ratio of white and red thrombus was 19.8% and 80.2%, respectively. Lipid core, plaque rupture, necrotic core, neovascularization, intraplaque hemorrhage, obstruction, and inflammation were observed more in red thrombus, which were statistically significant. Calcification and fibrous cap thickness were not statistically significant in the two groups. Moreover, intimal smooth muscle cells were present in all thrombus types. CONCLUSION: In our study, we found that red thrombi had more unstable characteristics than white thrombi. Thus, the risk for ischemic cerebrovascular events is more in red thrombi. However, this finding cannot be generalized due to the small number of patients in this study. Therefore, studies involving more patients are needed.

Two New Cases and Literature Review of CLIPPERS Syndrome with Long-Term Follow-up.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder of the central nervous system. The pathophysiology of CLIPPERS is unknown. The disease has characteristic radiological lesions located in the pons, bulbus, and cerebellum. Here we report two new cases and review the literature on CLIPPERS syndrome. A 35-year-old woman presented with a 2-month history of progressive double vision, vertigo, gait ataxia, nausea, and vomiting. The second case was that of a 40-year-old Iraqi man who presented with a 3-month history of vertigo, headache, and gait ataxia. Diagnosis of CLIPPERS was established based on findings of punctate, nodular enhancing lesions in the pons and bulbus in the first case and in the cerebellum in the second. Our patients responded well to steroid therapy and remained relapse-free for 2 years. CLIPPERS is a rare autoimmune disorder with characteristic radiological findings. Long-term immunosuppressive therapy is necessary for treatment.

A Pericallosal Lipoma Case with Abnormal Vasculature Mimicking Arteriovenous Malformation.

Pericallosal lipomas (PCLs) are rare tumors of the central nervous system. They may be associated with some parenchymal and vascular anomalies of brain. Magnetic resonance imaging is the modality of choice to assess the extent of the PCLs and possible concomitant malformations such as callosal agenesis/disgenesis. Computerized tomography angiography may be indicated to evaluate the vasculature of the lesion. We report here a case of PCL with rare features including asymptomatic callosal agenesis, bilateral choroid plexus lipomas and abnormal vasculature.

Anti-Saccharomyces Cerevisiae as Unusual Antibody in Autoimmune Polyglandular Syndrome Type III: A Case Report.

Backgraund and Objective: Anti-Saccharomyces Cerevisiae Antibodies (ASCA) that are considered to reflect immune response against increased intestinal permeability due to mucosal damage are among the serological markers of Crohn's Disease. METHODS: This microbial seromarker was recently shown to be elevated in several autoimmune disorders such as celiac disease, autoimmune liver diseases, type 1 diabetes, and Graves' disease. Despite that fact, ASCA seropositivity in Autoimmune Polyglandular Syndrome (APS) has never been reported before. RESULTS: Herein, we present a 46-year-old woman who has uveitis, autoimmune thyroiditis, and primary ovarian failure. CONCLUSION: Based on the coexistence of these diseases, the patient was diagnosed with APS type III. Moreover, ASCA seropositivity was detected although she has no overt intestinal disease.

Listeria monocytogenes rhombencephalitis in a patient with multiple sclerosis during fingolimod therapy.

OBJECTIVE: To describe a case of Listeria monocytogenes rhombencephalitis in a patient receiving fingolimod. METHODS: This is a case study. RESULTS: Our patient developed acute rhombencephalitis with hydrocephalus induced with Listeria monocytogenes while on fingolimod. Shunt surgery was performed for the hydrocephalus and patient recovered partially after medical and surgical therapy. CONCLUSION: We describe the first probable case of fingolimod-associated Listeria monocytogenes rhombencephalitis in a patient with multiple sclerosis. Clinicians should be aware of listeriosis and implement measures for its prevention.

Neurological autoantibodies in drug-resistant epilepsy of unknown cause.

BACKGROUND: Autoimmune epilepsy is a rarely diagnosed condition. Recognition of the underlying autoimmune condition is important, as these patients can be resistant to antiepileptic drugs. AIMS: To determine the autoimmune and oncological antibodies in adult drug-resistant epilepsy of unknown cause and identify the clinical, radiological, and EEG findings associated with these antibodies according to data in the literature. METHODS: Eighty-two patients with drug-resistant epilepsy of unknown cause were prospectively identified. Clinical features were recorded. The levels of anti-voltage-gated potassium channel complex (anti-VGKCc), anti-thyroid peroxidase (anti-TPO), anti-nuclear antibody (ANA), anti-glutamic acid decarboxylase (anti-GAD), anti-phospholipid IgG and IgM, anti-cardiolipin IgG and IgM, and onconeural antibodies were determined. RESULTS: Serum antibody positivity suggesting the potential role of autoimmunity in the aetiology was present in 17 patients with resistant epilepsy (22.0%). Multiple antibodies were found in two patients (2.6%). One of these patients (1.3%) had anti-VGKCc and ANA, whereas another (1.3%) had anti-VGKCc and anti-TPO. A single antibody was present in 15 patients (19.5%). Of the 77 patients finally included in the study, 4 had anti-TPO (5.2%), 1 had anti-GAD (1.3%), 4 had anti-VGKCc (5.2%) 8 had ANA (10.3%), and 2 had onconeural antibodies (2.6%) (1 patient had anti-Yo and 1 had anti-MA2/TA). The other antibodies investigated were not detected. EEG abnormality (focal), focal seizure incidence, and frequent seizures were more common in antibody-positive patients. CONCLUSION: Autoimmune factors may be aetiologically relevant in patients with drug-resistant epilepsy of unknown cause, especially if focal seizures are present together with focal EEG abnormality and frequent seizures.

Analysis of Vitamin D Receptor Polymorphisms in Patients with Familial Multiple Sclerosis.

OBJECTIVE: Genetic and environmental factors are important in the development of the multiple sclerosis (MS). Vitamin D shows its effects on the immune system with the vitamin D receptor (VDR) in the nucleus. Single nucleotide polymorphisms (SNPs) in the VDR gene can lead to alterations in vitamin D functions and metabolism.Taq I, Apa I, Fok I and Bsm I polymorphisms and MS associations have been investigated in many studies. VDR gene polymorphism has not been previously studied in patients with familial MS. AIM: We aimed to investigate the relationship between familial MS patients present in Turkish population and VDR genotypes Taq I, Apa I and Fok I polymorphisms. METHODS: 29 patients with a family history of MS and 120 healthy control subjects were included in the present study. We studied present VDR genotypes Taq I, Apa I and Fok I polymorphisms. RESULTS: We observed a significant difference between controls and patient group only in Taq I polymorphism (p: 0.025). Homozygousity of G allele was not seen in the patients whereas in controls frequency of that genotype was p:0.208. When gender was considered males show significant difference for GG genotype. There were no significant association for the Apa I and Fok I polymorphisms. CONCLUSION: Although our findings suggest association between VDR Taq I polymorphism and the familial MS, additional studies are needed to establish detailed relationships.

The association between vitamin D receptor polymorphisms and multiple sclerosis in a Turkish population.

BACKGROUND: Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS). Genetic and environmental factors are important in disease development. Many studies have investigated the relationship between MS and VDR polymorphisms. VDR gene polymorphism has not been previously studied in Turkish MS patients. We aimed to investigate the relationship between MS and VDR genotypes Taq I, Apa I and Fok I polymorphisms in a Turkish population. METHODS: 167 MS patients and 146 healthy control subjects were included in the present study. MS and the VDR TaqI (rs731236), ApaI (rs7975232), and FokI (rs2228570) polymorphisms were investigated. RESULTS: The study enrolled 167 patients (121 females, 46 males) with MS and 146 healthy individuals (88 females, 58 males). The frequency of only the Fok I polymorphism differed significantly between the two groups (p = 0.002). The TaqI (rs731236) and ApaI (rs7975232) genotype distributions were not significantly different between MS patients and healthy controls (p = 0.626 and p = 0.990, respectively). Also there were no significant gender difference between patients and controls for Taq I and Apa I. CONCLUSION: In conclusion, we found a significant association between MS and the FokI polymorphism in our region of Turkey. However, the results may be different in other populations. More epidemiological and genetic studies are needed to explain the association between genetic factors and MS.

A Rare Presentation of Cranial Polyneuropathy Without Rash Caused by Varicella Zoster Virus.

INTRODUCTION: Varicella Zoster Virus (VZV) is associated with many disorders of the central and peripheral nervous systems including neuralgia, meningitis, meningoencephalitis, cerebellitis, vasculopathy, myelopathy, Ramsay-Hunt syndrome, and polyneuritis cranialis. Cranial nerves V, VI, VII, VIII, IX, X, XI, and/or XII may be affected. The neurological disorders caused by VZV usually present with rash, but may rarely present without rash. CASE REPORT: We herein present a case of polyneuritis cranialis without rash caused by VZV affecting cranial nerves VII, VIII, IX, and X. After excluding other causes of the condition, we diagnosed VZV infection based on VZV DNA in the CSF and an elevated anti-VZV IgG level in serum. The patient responded well to antiviral therapy. CONCLUSION: VZV infection should be kept in mind during the differential diagnosis of polyneuritis cranialis; it is important to note that VZV re-activation may occur without rash.

Foveal Thickness Alterations in Patients with Migraine.

AIM: To investigate the alterations in foveal retinal thickness (FT) values in patients with migraine and to reveal the correlations between FT and clinical characteristics of migraine disease. METHODS: This study included sixty-eight eyes of 34 migraine patients [twenty-eight eyes of 14 patients with aura (group 1), and forty eyes of 20 patients without aura (group 2)] and forty eyes of 20 healthy volunteer who served as the control group (group 3). FT values were measured by optical coherence tomography (OCT) in each group. RESULTS: Mean age of patients in group 1, 2, and 3 was 34.0± 6.82, 35.2±10.12, and 35.1± 6.85 years, respectively (p=0.84). Mean FT was 211.07±7.36, 220.0±12.01, and 221.85±12.27 in groups 1, 2, and 3, respectively. There was statistically significance among the group 1-2 and 1-3 (p=0.002 and p< 0.001). There was no statistically significance between group 2-3 (p=0.88). CONCLUSION: This study suggests that in particular migraine with aura may lead to a reduction in FT values. This finding can be explained by the blood flow decrease theory in migraine; however larger studies seem mandatory.

Beneficial effects of ß-glucan against cisplatin side effects on the nervous system in rats 1.

PURPOSE: To investigate the protective effect of Bg on cisplatin (CP)-induced neurotoxicity in rats. METHODS: Twenty eight rats were randomly distributed into four groups. The first group was kept as a control. In the second group, CP was given at the single dose of 7 mg/kg intraperitoneally. In the third group, ßg was orally administered at the dose of 50 mg/kg/day for 14 days. In the fourth group, CP and ßg were given together at the same doses. RESULTS: CP treatment caused significant oxidative damage via induction of lipid peroxidation and reductions antioxidant defense system potency in the brain tissue. In addition, histopathological damage increased with CP treatment. On the other hand, ßg treatment largely prevented oxidative and histopathological negative effects of CP. CONCLUSIONS: Cisplatin has severe neurotoxic effects in rats and ßg supplementation has significant beneficial effects against CP toxicity depending on its antioxidant properties. Thus, it appears that ßg might be useful against CP toxicity in patients with cancer in terms of nervous system.

Chrysin prevents brain damage caused by global cerebralischemia/reperfusion in a C57BL/J6 mouse model.

BACKGROUND/AIM: The present study investigated the neuroprotective effects of chrysin (CRS) following global cerebral ischemia and reperfusion (I/R) in a C57BL/J6 mouse model. MATERIALS AND METHODS: A total of 40 mice were equally divided into four groups: (1) sham-operated (SH = control), (2) global cerebral I/R (I/R), (3) CRS, and (4) CRS + I/R. In the I/R group, the bilateral carotid arteries were clipped for 15 min and the mice were treated with vehicle (corn oil) for 10 days. In the CRS group, CRS (50 mg/kg) was given for 10 days without carotid occlusion. In the CRS + I/R group bilateral carotid arteries were clipped for 15 min and the mice were also treated with CRS (50 mg/kg) for 10 days. All of the rats were sacrificed under anesthesia on day 10, and neurodegenerative histological changes in the brain and tissue levels of oxidants and antioxidants were evaluated. RESULTS: CRS treatment significantly reversed the oxidative effects of I/R and inhibited the development of neurodegenerative histopathologies. In the CRS + I/R group, the decrease in TBARS levels and increase in GSH levels were similar to those in the SH group. CONCLUSION: Treatment with CRS can positively affect the neural system of mice and it can be used for the treatment of global cerebral I/R.

Familial Pompe Disease.

INTRODUCTION: Pompe disorder is a rare glycogen storage disorder that is due to a deficiency of the lysosomal alpha glycosidase enzyme. The heart, skeletal muscle, liver and nervous system can be affected from the lysosomal glycogen accumulation. Symptoms such as muscle weakness, hypotony, myopathy and respiratory failure develop. The onset may be at the infantile, adolescent or adult period depending on the enzyme level. The CK level is high in almost all patients. The diagnosis is made with enzyme level measurement and genetic analysis. CASE REPORT: We present a family with Pompe disease consisting of the asymptomatic mother and two siblings who presented with muscle weakness and respiratory failure and who had been followed-up with a diagnosis of muscular dystrophy for a long time.