[Mitochondrial myopathy, encephalopathy, lactate acidosis with stroke-like episodes syndrome (MELAS): a case report].

INTRODUCTION: Mitochondrial encephalopathy, lactacidosis and stroke-like episodes (MELAS) represent a multisystemic dysfunction due to various mutations in mitochondrial DNA. Here we report a patient with genetically confirmed MELAS. CASE OUTLINE: A patient is presented whose clinical features involved short stature, easy tendency to fatigue, recurrent seizures, progressive cognitive decline, myopathy, sensorineural deafness, diabetes mellitus as well as stroke-like episodes. The major clinical feature of migraine type headache was not present. Neuroimaging studies revealed signs of ischemic infarctions localized in the posterior regions of the brain cortex. Electron microscopy of the skeletal muscle biopsy showed subsarcolemmal accumulation of a large number of mitochondria with paracristal inclusions in the skeletal muscle cells. The diagnosis of MELAS was definitively confirmed by the detection of a specific point mutation A to G at nucleotide position 3243 of mitochondrial DNA. CONCLUSION: When a relatively young patient without common risk factors for ischemic stroke presents with signs of occipitally localized brain infarctions accompanied with multisystemic dysfunction, MELAS syndrome, it is necessary to conduct investigations in order to diagnose the disease.

Joint effect of hypertension and APOE genotype on CSF biomarkers for Alzheimer's disease.

We examined the impact of hypertension on cerebrospinal fluid (CSF) biomarkers amyloid-beta1-42 (Abeta42), total tau (tau), and phosphorylated tau at threonine 181 (ptau-181), and assessed the modifying role of APOE genotype in this relation in 546 patients (mean age 65 +/- 10, 47% female) from our memory-clinic. Of these patients 150 had subjective complaints, 140 were diagnosed with mild cognitive impairment, and 256 with Alzheimer's disease. Linear regression analyses adjusted for age, gender, and diagnosis showed that the association of hypertension with tau and ptau-181 was modified by APOE genotype (p-values for interaction p< 0.05). In APOE epsilon4 homozygotes (n=74), and to a lesser extent in APOE epsilon4 heterozygotes, hypertension was associated with higher tau and ptau-181 levels; beta (95%CI) were 188 (11; 364) pg/mL and 22 (3; 42) pg/mL for the APOE epsilon4 homozygotes. Hypertension was not associated with Abeta42 levels, and APOE genotype did not modify this relation. Our findings suggest that hypertension is directly related to tau pathology in APOE epsilon4 homozygous carriers.

[Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)--three case reports from Serbia].

INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy leading to recurrent strokes and vascular dementia in young and middle-aged patients. The diagnosis of CADASIL is based on typical clinical presentation and characteristic magnetic resonance imaging (MRI) changes, and has to be confirmed by biopsy of the sural nerve, muscle and skin, as well as by genetic analysis. Mutations within the Notch3 gene were identified as the underlying genetic defect in CADASIL. CASE OUTLINE: The clinical manifestations of the first presented patient with migraine from the age of thirteen, stroke without vascular risk factors and stepwise progression of vascular dementia comprising the typical clinical picture of CADASIL, were confirmed after seven years with pathological verification. The second presented case did not satisfy the clinical criteria for CADASIL. His stroke was considered to be related with vascular risk factors--diabetes mellitus and hypertension. The aetiological diagnosis was established only when his brother without vascular risk factors presented with similar clinical manifestations. CONCLUSION: Until the development of the new neuroimaging techniques like MRI, pathologic and genetic analysis, CADASIL was considered as a rare disorder. However, the increasing number of CADASIL families has been identified throughout the world showing that this entity is usually underdiagnosed. This article presents three patients from two Serbian families with clinical suspicion of CADASIL verified by pathologic examination.

[Cerebrospinal fluid amyloid beta and tau protein: biomarkers for Alzheimer's disease].

BACKGROUND/AIM: Introduction of acetylcholine esterase inhibitors as a symptomatic treatment of Alzheimer's disease (AD) has additionally highlighted the importance of diagnostic markers in cerebrospinal fluid (CSF) for early AD diagnosis: low level of 42 amino acid form of amyloid-beta peptide (Abeta42), and levels of tau protein (T-tau) and phosphorylated tau protein (P-tau). The aim of this study was to diagnostic potential of CSF biomarkers T-tau, P-tau and Abeta42 as biochemical markers for AD. METHODS: Lumbar puncture was performed in 63 patients with AD and 26 control subjects who passed orthopedic surgery. The Innotest, ELISA sandwich test (Innogenetics - Belgium) was used for measuring the levels of T-tau, P-tau and Abeta342. RESULTS: The patients and the control group did not differ in age, education and sex. Mean levels of CSF T-tau and P-tau were significantly higher in the patients with AD (p < 0.001) compared to the control group, in contrast to significantely lower CSF Abeta42 in AD group (p < 0.001). A significant progressive decrease of Abeta42, as well as significant progressive increase of T-tau and P-tau was found among AD subgroups (according to MMSE staging) and controls. CONCLUSION: The obtained results suggest that these biomarkers may be supportive in the diagnosis of AD, especially in the early course of the disease and could be used in the routine clinical practice considering the approaching target therapeutics.