Irish Institute of Clinical Neuroscience

The diagnosis of primary central nervous system (CNS) vasculitis is often difficult. There are neither specific clinical features nor a classical clinical course, and no blood or imaging investigations that can confirm the diagnosis. Contrast catheter cerebral angiography is neither specific nor sensitive, yet still underpins the diagnosis in many published studies. Here we describe an approach to its diagnosis, emphasising the importance of obtaining tissue, and present for discussion a new, binary set of diagnostic criteria, dividing cases into only ‘definite’ primary CNS vasculitis, where tissue proof is available, and ‘possible,’ where it is not. We hope that these criteria will be modified and improved by discussion among experts, and that these (improved) criteria may then be adopted and used as the basis for future prospective studies of the clinical features and diagnosis of this difficult and dangerous disorder, particularly for coordinated multicentre therapeutic trials.

AimsHistopathological tissue samples are being increasingly used as sources of nucleic acids in molecular pathology translational research. This study investigated the suitability of glioblastoma and control central nervous system (CNS) formalin-fixed paraffin embedded (FFPE) tissue-derived RNA for gene expression analyses.MethodsTotal RNA was extracted from control (temporal lobe resection tissue) and glioblastoma FFPE tissue samples. RNA purity (260/280 ratios) was determined and RNA integrity number (RIN) analysis was performed. RNA was subsequently used for RT-qPCR for two reference genes, 18S and GAPDH.ResultsReference gene expression was equivalent between control and glioblastoma tissue when using RNA extracted from FFPE tissue, which has key implications for biological normalisation for CNS gene expression studies. There was a significant difference between the mean RIN values of control and glioblastoma FFPE tissue. There was no significant correlation between 260/280 or RIN values versus total RNA yield. The age of the tissue blocks did not influence RNA yield, fragmentation or purity. There was no significant correlation between RIN or 260/280 ratios and mean qPCR cycle threshold for either reference gene.ConclusionsThis study showed that routinely available CNS FFPE tissue is suitable for RNA extraction and downstream gene expression studies, even after 60 months of storage. Substantial RNA fragmentation associated with glioblastoma and control FFPE tissue blocks did not preclude downstream RT-qPCR gene expression analyses. Cross validation with both archival and prospectively collated FFPE specimens is required to further demonstrate that CNS tissue blocks can be used in novel translational molecular biomarker studies.

Vertigo and dizziness are not independent disease entities, but instead symptoms of various diseases. Accordingly, a variety of treatment approaches are required. Here we review the most relevant drugs for managing dizziness, vertigo, and nystagmus syndromes. It is important to differentiate symptomatic treatment of nausea and vomiting with, for example, dimenhydrinate and benzodiazepines, and prophylactic treatment of motion sickness with scopolamine from a causal therapy of the underlying disorders. Examples of such causal therapy include aminopyridines for downbeat nystagmus and episodic ataxia type 2; carbamazepine for vestibular paroxysmia, paroxsymal dysarthria and ataxia in multiple sclerosis, and superior oblique myokymia; betahistine, dexamethasone, and gentamicin for Menière's disease; gabapentin and memantine for different forms of acquired and congenital nystagmus; corticosteroids for acute vestibular neuritis and Cogan's syndrome; metoprolol and topiramate for vestibular migraine; and selective serotonin reuptake inhibitors such as paroxetine for phobic postural vertigo. The clinical entities are briefly described, the various medications are discussed in alphabetical order, and dosage, major side effects, contraindications, and alternative medications of each drug are displayed in boxes for easy reference.

The aim of the present work was to analyze the age-related dynamics and nature of interindividual differences in performing the A-not-B task, which addresses working memory in children aged 7-12 months. The cohort consisted of 150 children aged 7-12 months from mono- and dizygotic twin pairs. Working memory was assessed in terms of the maximum delay which the children could tolerate in a delayed response test (the A-not-B task). Performance of the task improved with age, such that a sharp change in the ability to tolerate the delay occurred between nine and ten months of age. Mental development as assessed using the Bayley scale showed a significant correlation with the duration of the delay in the task only after a threshold period (9-10 months of age) in the development of working memory. Analysis of intrapair correlations in mono- and dizygotic twins showed that interindividual differences in the A-not-B task delay at age 7-9 months were completely determined by individual environmental factors (including measurement errors), while at age 10-12 months the leading role in the interindividual variability in this measure was taken by the systematic environment. These results show that the abilities to tolerate delays at the beginning and end of the second six months of life are based on different mechanisms.

OBJECTIVESBrain tumours cause considerable concern due to a high mortality and there are increasing efforts to provide adequate care, sometimes outside hospitals. Health care utilisation, direct costs of care, and the indirect social cost of morbidity and early mortality caused by brain tumours in Sweden in the year 1996 was analysed.METHODSQuantification of ambulatory care, care in hospital, long term and palliative/terminal care, drug consumption, temporary as well as long term morbidity, and mortality from comprehensive national data sources. Direct costs were calculated using 1996 charges. Indirect costs were calculated by sex and age specific salaries. A sensitivity analysis considered the impact of alternative estimates of each item.RESULTSIndirect costs were 75% of the total and were caused mainly by early mortality. Direct costs were predominantly for care in hospital, long term care, and home health care. Among direct costs, astrocytomas III-IV and meningiomas accounted for 42% and 30% respectively.CONCLUSIONSThe cost of illness from brain tumours reflects the characteristics of these malignancies. Despite their low incidence rate, the economic impact caused by high mortality among young persons is a predominant trait. Costs of acute hospital care and also long term care and home care are considerable.