Clinical Neuroscience

[Genetically determined diseases associated with pathological brain iron accumulation and neurodegeneration]

ÁCS Péter1, MOLNÁR Mária Judit2, KLIVÉNYI Péter3, KÁLMÁN Bernadette4

MAY 30, 2016

Clinical Neuroscience - 2016;69(05-06)

DOI: https://doi.org/10.18071/isz.69.0157

[The rare, genetically determined group of diseases characterized by pathological accumulation of iron in the central nervous system and progressive, typically movement disorder’s symptoms are called NBIA (neurodegeneration with brain iron accumulation). By the rapid development of molecular genetics, it has become apparent that different mutations in numerous genes can lead to pathological cerebral iron accumulation. Simultaneously, it has also been recognized that the age of onset, the symptoms and the prognosis of NBIA disorders are much more diverse than it was previously perceived. To our knowledge, a review article on the most recent clinical data of NBIA has not been published in Hungarian. In the first part of this publication, we survey the general clinical characteristics and the diagnostic algorithm of NBIA diseases and address some considerations for differential diagnostics. In the second part of this review, the particular NBIA disorders are presented in details. The purpose of this article is to provide a clinical overview that may be useful for neurologists, pediatricians and any other medical practitioners interested in this field.]

AFFILIATIONS

  1. Pécsi Tudományegyetem, Neurológiai Klinika, Pécs
  2. Semmelweis Egyetem, Genomikai Medicina és Ritka Betegségek Intézete, Budapest
  3. Szegedi Tudományegyetem, Neurológiai Klinika, Szeged
  4. Pécsi Tudományegyetem, ETK, Markusovszky Egyetemi Oktatókórház, Szombathely

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[Objective - We summarize our initial experiences with selective dorsal rhizotomy that we introduced in Hungary to manage the spasticity of patients with cerebral palsy. Patients and methods - Thirty spastic patients were enrolled in our study. All of the patients were operated between July 2014 and June 2015. We performed selective dorsal rhizotomy from a single-level approach at the level of conus medullaris in all cases, with electrophysiological control. Results - We could perform the surgery in all cases safely. Adverse events related either to damage of neurological structures, or to surgery did not occur. The planned rehabilitation courses before and after the operations are in progress in all cases. Conclusion - Selective dorsal rhizotomy is an irreversible surgical intervention to treat spasticity. With sufficient experience and electrophysiological control it can be performed safely, and the early results are promising. ]

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[Background and purpose - Hypothalamic hamartomas are focal, benign congenital malformations that frequently associated with gelastic seizures. Behavioural disturbances, cognitive decline and the appearance of precocious puberty can also be observed. The most effective way to relieve the symptoms is the surgical disconnection between the hamartoma and the hypothalamus. In our study, we retrospectively analyzed the surgical indications and effectiveness of each approach. Methods - Between 1996 and 2014 we operated on 10 hypothalamic hamartomas. Endoscopic assisted resection was performed in three patients. Six patients underwent direct microsurgical resection in various approaches and one patient was treated with Gamma Knife. Results - We achieved significant decrease in the number of seizures in every patient presenting with various seizure types. The surgical resection was effective in the arresting of the puberty praecox as well. However the surgery of these lesions at their special location holds the danger of the appearance of new endocrinological symptoms. According to our observations the operation on hamartoma less effectively ameliorates the psychiatric symptoms than the others. Conclusion - The surgical treatment is effective in the reduction of the initial symptoms and we had no mortality. According to our analysis therapeutic success is anticipated but we couldn’t archive total symptomatic relief in every case. The first approach to these lesions should be the surgery which type must be tailored to each patient.]

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Introduction - Human serum paraoxonase (PON1) and arylesterase (ARE) are lipophilic antioxidant enzymes. PON-1 serum activity diverges in individuals and populations, which might be due to polymorphisms in the PON-1 gene. The PON1 activity phenotyping method, based on the ratio of the stimulated PON activity and the ARE activity, could determine the low-activity homozygotes (QQ), intermediate activity heterozygotes (QR), and high-activity homozygotes (RR) regardless of the genotype. The aim of the present study was to determine the PON1 phenotype distribution and enzymatic activity of PON1 and ARE in multiple sclerosis (MS) patients. Materials and methods - Thirty-four relapsing remitting MS (RRMS) patients (22 females and 12 males; median age 42 (range 20-55) years) in the remission phase and thirty-four age-sex matched healthy controls (19 females and 15 males; median age 37 (21-60) years) were included in this study. All patients had clinically definite MS according to McDonald’s criteria. Results - Serum PON1 and ARE enzyme activities, as well as salt-stimulated PON1, were not significantly different between the patient and control groups. Phenotype distributions were as follows: QQ 58.8%, QR 38.2%, and RR 3% in MS patients (n=34); QQ 44.1%, QR 50%, and RR 5.9% in the control group (n=34). QQ (low activity) phenotypic distribution was more common in MS patients than controls, but this difference was not significant (p=0.14). Conclusions - Our results did not reveal meaningful relationships between PON1 activity or PON1 phenotypes and MS. More studies in larger samples and in all phases of the disease are needed in the future.

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[Decreasing the often-seen multiple disabilities as a consequence of central nervous system impairments requires broadening of the tools of rehabilitation. A promising opportunity for this purpose is the application of physiotherapy robots. The development of such devices goes back a quarter of century. Nowadays several robots are commercially available both for supporting upper and lower limb therapy. The aim is never to replace the therapists, but rather to support and supplement their work. It is worthwhile applying these devices for goal-oriented exercises in high repetition, which one physically fatiguing for the therapist or for the correction of functional movement by various strategies. Robot mediated therapy is also useful for motivation of the patient and making the rehabilitation programme more versatile. Robots can be used for assessment of the neuromotor status as well. Several clinical studies have been executed in this field, all over the world. Meta-analyses based on randomized, controlled trials show that supplementing the traditional physiotherapy with a robot-mediated component presents advantage for the patients. Further studies are necessary to clarify which modality and intensity of the exercises, in which group of patients, in which stage lead to the expected outcome.]

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[Goals - In the present study basic arithmetic induced rearrangements in functional connections of the brain were investigated by using graph theoretical analysis what becomes increasingly important both in theoretical neuroscience and also in clinical investigations. Research questions - During mental arithmetic operations (working) memory plays an important role, but there are only a few studies in which an attempt was made to separate this effect from the process of arithmetic operations themselves. The goal of our study was to separate the neural networks involved in cognitive functions. Methods - As an attempt to clarify this issue the graph-theoretical “minimal spanning tree” method was used for the analysis of EEG recorded during task performance. The effects of passive viewing, number recognition and mental arithmetic on PLI based minimal spanning trees (MST) were investigated on the EEG in young adults (adding task: 17 subjects; passive viewing and number recognition: 16 subjects) in the θ (4-8 Hz) frequency band. Results - Occipital task relevant synchronization was found by using the different methods, probably related to the effect of visual stimulation. With respect to diameter, eccentricity and fraction of leafs different task-related changes were found. Discussion - It was shown that the task related changes of various graph indices are capable to identify networks behind the various relevant dominant functions. Thus the “minimal spanning tree” method is suitable for the analysis of the reorganization of the brain with respect to cognitive functions.]

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