Rossana Terlizzi

Spectral analysis of heart rate variability reveals an enhanced sympathetic activity in narcolepsy with cataplexy

OBJECTIVE To test the autonomic control of cardiovascular reflexes and heart rate variability (HRV) at rest and during orthostatic stress in narcolepsy with cataplexy (NC). METHODS Ten NC patients with a hypocretin deficit and 18 control subjects underwent head-up tilt test (HUTT), Valsalva manoeuvre, deep breathing and cold face under controlled laboratory conditions. Heart rate variability (HRV) was analysed during supine rest and HUTT considering the normalized unit of LF and HF power (LFnu; HFnu), using autoregressive (AR) and fast Fourier transform (FFT) algorithms. RESULTS Cardiovascular changes during HUTT, Valsalva manoeuvre, deep breathing, isometric handgrip and cold face were normal and comparable in the two groups. AR and FFT analysis showed an increased LF/HF ratio in NC patients during supine rest. As expected, LFnu increased and HFnu decreased in the control group during HUTT, but did not change in narcoleptics being comparable to values in the supine condition. CONCLUSIONS NC patients showed an increased sympathetic drive on heart rate (HR) in the supine condition that did not further increase during HUTT. SIGNIFICANCE These results suggest the proper functioning of cardiovascular reflexes in NC but support an impairment of HR modulation at rest in favour of an enhanced sympathetic activity.

Reversible postural tachycardia syndrome due to inadvertent overuse of Red Bull

Postural tachycardia syndrome associated with a vasovagal reaction was recorded in a young volleyball player after an excess intake of Red Bull® as a refreshing energy drink. Considering the widespread use of Red Bull® among young people who are often unaware of the drink’s drug content, this case report suggest Red Bull® be considered a possible cause of orthostatic intolerance.

Oneiric stupor: The peculiar behaviour of agrypnia excitata

Agrypnia excitata (AE) is a syndrome characterized by the inability to sleep associated with a generalized motor and autonomic over-activation. AE is caused by a thalamo-limbic system dysfunction and comprises three different conditions: Fatal Familial Insomnia (FFI), Delirium Tremens (DT), and Morvan Syndrome (MS). Oneiric Stupor episodes (OS) are the peculiar motor behaviour of AE. During OS patients perform simple automatic gestures mimicking daily-life activities. This paper is the first description of the different characteristics of OS in two patients with MS and another with FFI, emphasizing the specific clinical features that reliably differentiate OS from REM sleep behaviour disorders.

Nuclear lamins: Functions and clinical implications

GLOSSARYADLD: adult-onset autosomal dominant leukodystrophyCMT: Charcot-Marie-ToothEDMD: Emery-Dreifuss muscular dystrophyLAP: lamin-associated polypeptideLBR: lamin B receptorLGMD1B: autosomal dominant limb-girdle muscular dystrophy

Messenger RNA processing is altered in autosomal dominant leukodystrophy

Adult-onset autosomal dominant leukodystrophy (ADLD) is a slowly progressive neurological disorder characterized by autonomic dysfunction, followed by cerebellar and pyramidal features. ADLD is caused by duplication of the lamin B1 gene (LMNB1), which leads to its increased expression. The molecular pathways involved in the disease are still poorly understood. Hence, we analyzed global gene expression in fibroblasts and whole blood of LMNB1 duplication carriers and used Gene Set Enrichment Analysis to explore their gene signatures. We found that LMNB1 duplication is associated with dysregulation of genes involved in the immune system, neuronal and skeletal development. Genes with an altered transcriptional profile clustered in specific genomic regions. Among the dysregulated genes, we further studied the role of RAVER2, which we found to be overexpressed at mRNA and protein level. RAVER2 encodes a putative trans regulator of the splicing repressor polypyrimidine tract binding protein (PTB) and is likely implicated in alternative splicing regulation. Functional studies demonstrated an abnormal splicing pattern of several PTB-target genes and of the myelin protein gene PLP1, previously demonstrated to be involved in ADLD. Mutant mice with different lamin B1 expression levels confirmed that Raver2 expression is dependent on lamin B1 in neural tissue and determines an altered splicing pattern of PTB-target genes and Plp1. Overall our results demonstrate that deregulation of lamin B1 expression induces modified splicing of several genes, likely driven by raver-2 overexpression, and suggest that an alteration of mRNA processing could be a pathogenic mechanism in ADLD.

Cardiovascular changes during maximal breath-holding in elite divers

During maximal breath-holding six healthy elite breath-hold divers, after an initial “easy-going” phase in which cardiovascular changes resembled the so-called “diving response”, exhibited a sudden and severe rise in blood pressure during the “struggle” phase of the maneuver. These changes may represent the first tangible expression of a defense reaction, which overrides the classic diving reflex, aiming to reduce the hypoxic damage and to break the apnea before the loss of consciousness.

Headache in school age

Headache, especially migraine and tension-type headache, is one of the most frequently reported somatic complaints by children and adolescents. Different population-based studies have been conducted to study the correlation between headache and lifestyles in pediatric age, nevertheless, the obtained results are often controversial and these relationship still remain unclear. Likewise, is still strongly debated the burden of headache during school age, its impact on school performances and on quality of life of children and their families. Consequently, larger studies are necessary to evaluate the degree of disability due to pediatric headache. We summarize the ongoing knowledge about these concepts, with the intent to provide useful data to neurologists but also to primary care providers, to further improve the management of pediatric headaches by preventing the headache progression, the disabling effects associated and improving the long-term outcome.

Tilt-induced cardioinhibitory syncope: a follow-up study in 16 patients

IntroductionThe exact clinical and prognostic significance and the therapeutic implications of asystole induced by head-up tilt test are still a matter of debate.MethodsWe assessed, by means of a semi-structured interview, the long-term outcome of cardioinhibitory syncope in all the patients who presented a tilt-induced sinus arrest of more than 3 s in our Autonomic Unit between 1996 and 2010.ConclusionsAlthough syncopal recurrences were common, tilt-induced asystole did not imply a poor prognosis in terms of death or major therapeutic procedures.

Brain magnetic resonance metabolic and microstructural changes in adult-onset autosomal dominant leukodystrophy.

INTRODUCTION adult-onset autosomal dominant leukodystrophy (ADLD) is a rare inherited disorder due to a duplication of lamin-B1 (LMNB1) gene. The aim of this study was to investigate brain metabolic and microstructural alterations by using advanced MR techniques. METHODS we performed brain MR scans including single-voxel proton-MR Spectroscopy ((1)H-MRS) of the lateral ventricles and parietal white matter and diffusion tensor imaging (DTI) in 4 subjects with LMNB1 gene duplication, 6 non-mutated relatives and 7 unrelated healthy controls. Cervical and thoracic spinal cord MR was performed in three symptomatic subjects with LMNB1 mutation. All participants underwent clinical and neuropsychological evaluation. RESULTS all subjects with LMNB1 gene duplication presented pathological accumulation of lactate in lateral ventricles CSF and no alterations of brain white matter absolute metabolites concentrations or metabolites/Cr ratios. We found increased white matter intra- and extracellular water transverse relaxation times. Tract-based spatial statistics analysis detected a significantly reduced fractional anisotropy in the genu of the corpus callosum in mutated cases compared to unrelated healthy controls and non-mutated relatives. Moreover, we detected different degrees of the typical white matter signal intensity alterations and brain and spinal atrophy at conventional MRI in symptomatic subjects with LMNB1 mutation. A mild impairment of executive functions was found in subjects with LMNB1 gene mutation. CONCLUSION in subjects with LMNB1 gene duplication, we found a pathological increase in CSF lactate, likely due to active demyelination along with glial activation, and microstructural changes in the genu of the corpus callosum possibly underpinning the mild neuropsychological deficits.

A longitudinal study of a family with adult-onset autosomal dominant leukodystrophy: Clinical, autonomic and neuropsychological findings

BACKGROUND AND PURPOSE Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare progressive neurological disorder caused by Lamin B1 duplication (LMNB1). Our aim was to investigate longitudinally the pattern of the autonomic dysfunction and the degree of neuropsychological involvement. METHODS Three related ADLD patients and one asymptomatic carrier of LMNB1 duplication underwent a standardized evaluation of autonomic nervous system, including cardiovascular reflexes, pharmacological testing, microneurography, skin biopsy, Metaiodobenzylguanidine scintigraphy and a complete neuropsychological battery. RESULTS An early neurogenic orthostatic hypotension was detected in all patients and confirmed by a low rise in noradrenaline levels on Tilt Test. However infusion of noradrenaline resulted in normal blood pressure rise as well as the infusion of clonidine. At the insulin tolerance test the increase in adrenaline resulted pathological in two out three patients. Microneurography failed to detect muscle sympathetic nerve activity bursts. Skin biopsy revealed a poor adrenergic innervation, while cardiac sympathetic nerves were normal. None of ADLD patients showed a global cognitive deficit but a selective impairment in the executive functions. CONCLUSION Autonomic disorder in ADLD involves selectively the postganglionic sympathetic system including the sympatho-adrenal response. Cognitive involvement consisting in an early impairment of executive tasks that might precede brain MR abnormalities.