Peroxisomal D-bifunctional protein deficiency: First case reports from Slovakia.

D-bifunctional protein deficiency (#OMIM 261515) is a rare autosomal recessive hereditary metabolic disorder causing severe clinical and biochemical abnormalities that are usually fatal in the course of the first years of life. This disease is classified as single enzyme peroxisomal disorder affecting the ß-oxidation pathway in this compartment. In this paper we present a full overview of the clinical presentation, magnetic resonance imaging, biochemical and molecular data of two Slovak D-bifunctional protein deficient patients. In the clinical presentation of both patients severe generalized hypotonia, depression of neonatal reflexes, craniofacial dysmorphism and seizures dominated starting from the second day of life. In both patients, who died up to two years of life, we found elevated plasma levels of very long chain fatty acids and we identified the presence of causative mutations in the HSD17B4 gene. In the first case, we found the homozygous mutation c.46G>A, which is responsible for a defect in the dehydrogenase domain. In the second patient, the heterozygous mutations c.1369A>G and c.1516C>T were present and functionally they are related to the hydratase domain of the protein. This combination of mutations in the second patient is very rare and has not been reported until now. The presence of mutations was examined in all family members, and the resulting data were successfully utilized for prenatal diagnosis.

Optical coherence tomography and its use in optical neuritis and multiple sclerosis.

Optical coherence tomography is a relatively new non-invasive imaging technique used for obtaining the images and quantifying the layers of the retina. It also provides information about optic nerve head topography, peripapillary retinal nerve fiber layer thickness, and macular volume which correlates with axonal loss. Until now, this method was used mainly in ophthalmology; now it has emerged as relevant in neurology as well. RNFL thickness is of particular interest in optic neuropathies and in multiple sclerosis. In sclerosis multiplex, axonal loss occurs as early as the first stages and the quantification of the RNFL thickness by OCT provides an indirect measure of axonal and neuronal loss in the anterior visual pathways. Because OCT is noninvasive, easy to obtain, and highly reproducible, it can be used as a marker of axonal loss and as an endpoint in clinical trials. This paper presents a comprehensive summary of the use of this new diagnostic method in multiple sclerosis patients (Fig. 1, Ref. 58).

The importance of interictal electroencephalography in paroxysmal states.

INTRODUCTION: Electroencephalography (EEG) is a non-invasive investigation method playing an important role in differential diagnostics of seizures. In this article authors point out to its importance, but also limitations. MATERIAL AND METHODS: Native interictal EEG findings were evaluated in inpatients after solitary unprovoked epileptic seizures (n=84), patients with sporadic epileptic seizures (n=179), patients with "chronic" epilepsy (n=324), outpatients with epilepsy (n=300), patients with syncope (n=100), patients with neurocardiogenic syncope (n=70), patients with migraine (n=100) and patients with tetanic syndrome (n=100). EEG findings were evaluated as normal or abnormal and abnormal findings were further divided into epileptic and non-epileptic, focal and generalized. RESULTS: In native EEG, epileptic manifestations were registered in 14.29 % of patients after solitary unprovoked epileptic seizures, in 25.7 % of patients with sporadic epileptic seizures, in 37.34 % of patients with chronic epilepsy and in 32 % of outpatients with epilepsy. Interictal EEG abnormalities (epileptiform and non-epileptiform) in non-epileptic diagnoses were at least registered in patients with syncope, but also in this group abnormal findings occurred in 30 % of them. We registered epileptiform abnormalities in 5 % of patients with migraine, in 4 % of patients with tetanic syndrome and in 2 % of patients with syncope. CONCLUSION: The diagnosis of epilepsy and non-epileptic seizures is a only a clinical diagnosis. EEG is a very important investigational method in this group of patients, but still only additional (Tab. 4, Fig. 2, Ref. 14).

Clinical accuracy of the distinction between Alzheimer's disease and frontotemporal lobar degeneration.

Alzheimer's disease (AD) is the most common cause of dementia. Frontotemporal lobar degeneration (FTLD), although less prevalent overall, is almost as common as AD in patients under the age of 65. AD and FTLD are histopathologically distinct, with AD being characterised by extracellular amyloid plaques and intraneuronal neurofibrillary tangles, and FTLD by the presence of non-AD histological pathology, most commonly either tau-positive inclusions or ubiquitin-positive or TDP 43 positive inclusions. Clinically, AD and FTLD may occur with overlapping symptoms, especially in the early stages of the disease. In the case of Alzheimer's disease, it is represented by isolated decline of recent episodic memory; later on, by the impairment of time and space orientation, whereby the alteration of social behaviour and amnesic aphasia occur predominantly in the advanced phases of the disease. Frontotemporal lobar degeneration is demonstrated in three clinical subunits: 1) The behavioural-dysexecutive variant of FTLD (frontotemporal dementia, the frontal variant of FTLD, {fvFTLD}), 2) Progressive non-fluent aphasia, 3) Semantic dementia (SD) with the profound impairment of social conduct (fvFTLD) or with severe speech impairment (PNFA, SD). Considering the different clinical symptomatology with FTLD diagnostics, it is necessary to use different psychometric tests than in the case of Alzheimer's disease. Therapy and the degree of dependence of the affected person are also different. All three diseases within the FTLD category, mainly the behavioural-dysexecutive variant, require a higher level of nursing care on the part of other persons or institutions in comparison with Alzheimer's disease. The goal of our publication is to point to the differences in clinical manifestation and the findings of auxiliary examinations that are helpful in the clinical accuracy of the distinction between these two types of dementia (Tab. 1, Fig. 3, Ref. 18).