Posterior reversible leukoencephalopathy syndrome in children with hematologic disorders

Objective: Posterior reversible leukoencephalopathy syndrome (PRES) is characterized by headache, altered mental status, cortical blindness, and seizures associated with neuroradiological findings. It involves predominantly white matter of the parieto-occipital lobes. Several medications and disorders play a role in the etiology of PRES. In this study, we aimed to show how the prognosis of PRES in hematological diseases of childhood might be according to the etiological factors.Materials and Methods: Here, we report PRES in six patients, aged 4 to 14 years, with diagnoses of leukemia and aplastic anemia. Results: Suggested causes in our patients were chemotherapeutics, hypertension, infection and antimicrobial drug administration, tumor lysis syndrome, acute renal failure and hemodialysis, immunosuppressive drug administration, and hypomagnesemia. One of the patients died of sepsis, renal failure and pulmonary hemorrhage and another died of relapse after total recovery from PRES. The other four patients are under follow-up without problems. Conclusion: We suggest that PRES can recover fully with early diagnosis and treatment whereas it can show poor prognosis depending on the etiology

ETHE1 and MOCS1 deficiencies : disruption of mitochondrial bioenergetics, dynamics, redox homeostasis and endoplasmic reticulum-mitochondria crosstalk in patient fibroblasts

Ethylmalonic encephalopathy protein 1 (ETHE1) and molybdenum cofactor (MoCo) defciencies are hereditary disorders that afect the catabolism of sulfur-containing amino acids. ETHE1 defciency is caused by mutations in the ETHE1 gene, while MoCo defciency is due to mutations in one of three genes involved in MoCo biosynthesis (MOCS1, MOCS2 and GPHN). Patients with both disorders exhibit abnormalities of the mitochondrial respiratory chain, among other biochemical fndings. However, the pathophysiology of the defects has not been elucidated. To characterize cellular derangements, mitochondrial bioenergetics, dynamics, endoplasmic reticulum (ER)-mitochondria communication, superoxide production and apoptosis were evaluated in fbroblasts from four patients with ETHE1 defciency and one with MOCS1 defciency. The efect of JP4-039, a promising mitochondrial-targeted antioxidant, was also tested on cells. Our data show that mitochondrial respiration was decreased in all patient cell lines. ATP depletion and increased mitochondrial mass was identifed in the same cells, while variable alterations in mitochondrial fusion and fssion were seen. High superoxide levels were found in all cells and were decreased by treatment with JP4-039, while the respiratory chain activity was increased by this antioxidant in cells in which it was impaired. The content of VDAC1 and IP3R, proteins involved in ER-mitochondria communication, was decreased, while DDIT3, a marker of ER stress, and apoptosis were increased in all cell lines. These data demonstrate that previously unrecognized broad disturbances of cellular function are involved in the pathophysiology of ETHE1 and MOCS1 defciencies, and that reduction of mitochondrial superoxide by JP4-039 is a promising strategy for adjuvant therapy of these disorders

Idiopathic vestibular syndrome: methodological approach and descriptive study of nine clinical cases

Orientação: David Orlando Alves FerreiraThe idiopathic vestibular syndrome (IVS) is characterized by a lesion of the vestibular portion of the vestibulocochlear nerve (VIII). There is no known etiology and it usually leads to vestibular clinical signs with an acute onset and severe presentation, which enter in remission in three to four weeks, without any instituted medication. This study intends to analyse and compare the results of the neurological examinations and the respective ancillary diagnostic exams with the disease progression and prognosis of each animal suspected with idiopathic vestibular disorder, followed at Clínica de Referência Veterinária (RRV). In general, the evolution of the described clinical cases was according with the literature. The proposed causes for IVS are early Otitis interna/media, abnormal production, circulation and absorption of the endolymphatic fluid, neuritis of the vestibular portion of the vestibulocochlear nerve, Cuterebra larvae aberrant migration (not present in Portugal) and herpesvirus-1 infection of vestibular labyrinth and ganglion in dogs

Mangaan-efedrooni intoksikatsioonist tingitud neuroloogilise kahjustuse patogenees ja kliiniline sümptomaatika

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Parkinsonistlike sündroomide põhjuseid on palju, neist kõige sagedasem on Parkinsoni tõbi. Muudeks põhjusteks võivad olla teised neurodegeneratiivsed haigused, ravimid, aju koldelised kahjustused, veresoonkonnahaigused, nakkused ja mürkained. Väitekirja eesmärgiks on kirjeldada parkinsonistlikku sündroomi narkomaanidel, kes süstisid n-ö kodumeetodil valmistatud pseudoefedriini, kaaliumpermanganaadi, äädikhappe ja keeva vee segu. Oksüdatsioonireaktsiooni tulemusel tekkis pseudoefedriinist efedroon ehk metkatinoon, mis on amfetamiinilaadne psühhostimulant. Toksilise kõrvalsaadusena sisaldas lahus suures hulgas mangaani, mis veeni manustatuna ületas mangaani soovitusliku päevase normi ligi 2000 korda. Ajavahemikul 2006–2012 uuriti kokku 38 patsienti, kelle keskmine vanus oli 33 aastat. Peamisteks sümptomiteks olid tasakaalu-, kõnnaku- ja kõnehäired, jäsemete lihastoonuse häired ning liigutuste aeglustumine. Kliiniline pilt sarnanes klassikalise mangaanimürgistuse puhusega. Efedrooni kasutamise kestuse ja haiguse kliinilise raskuse vahel puudus seos, s.t ka siis, kui narkootikumi oli tarvitatud väga lühikese perioodi jooksul, võis pärast tekkida raske motoorne defitsiit. Neuroloogiline kahjustus oli pöördumatu ning ka tarvitamise lõpetamise korral esines haiguse progresseerumise tendents. Magnetresonantstomograafilisel uuringul ilmnes mangaaniladestusele iseloomulik signaaliintensiivsuse suurenemine basaaltuumades. Isotoopuuringud näitasid, et dopaminergilised neuronid, mis hävinevad Parkinsoni tõve korral, olid uuritavatel säilinud. Efedrooni tarvitamine on oluline parkinsonistliku sündroomi tekkepõhjus noortel patsientidel Eestis. Narkootilise segu tarvitamise lõpetamise järel puuduvad spetsiifilised muutused, mida oleks võimalik laboratoorsete ja instrumentaalsete uuringutega kindlaks teha, mistõttu on oluline ära tunda mürgistusele omane kliiniline pilt ning küsitleda patsiente efedrooni võimaliku varasema tarvitamise suhtes, et vältida kulukaid ja mittetarvilikke lisauuringuid. Mangaani-efedrooni segu tarvitamine põhjustab olulist füüsilist puuet ja elukvaliteedi halvenemist. Ennetustöö võimaldaks vähendada otseseid ja kaudseid kulutusi rehabilitatsioonile ning sotsiaalhoolekandele.There are many causes of parkinsonian syndromes, among them Parkinson`s disease is the most common. Neurodegenerative diseases, drugs, structural lesions, cerebrovascular diseases, infections and toxicants can all induce parkinsonism. This study describes parkinsonian syndrome in drug addicts, who had injected home-made psychostimulant mixture made of pseudoephedrine, potassium permanganate, acetic acid and boiling water. In the oxidation reaction, pseudoephedrine was converted to ephedrone (methacathinone). As a toxic by-product of the synthesis the final mixture contained high concentration of manganese. The intravenously administered daily manganese load was almost 2000 times higher than recommended. During 2006 till 2012, we examined 38 patients with a mean age of 33 years. The main motor symptoms were postural instability, gait disorder and speech impairment, limb dystonia and bradykinesia. The clinical symptomatology resembled classic manganese intoxication. There was no correlation between the duration of drug abuse and the severity of symptoms, i.e. a severe motor impairment could develop only after a short time of ephedrone abuse. The syndrome was irreversible after cessation of exposure and there was a trend of worsening. Magnetic resonance imaging showed increased signal intensity in globus pallidus and substantia nigra, these findings are specific to manganese exposure. Molecular neuroimaging studies showed the preservation of dopaminergic neurons, which are decreased in Parkinson`s disease. Ephedrone abuse is an imortant cause of parkinonism in young Estonian patients. Identifying the cause of an extrapyramidal syndrome in former ephedrone abusers could be difficult, because there are no specific laboratory or imaging findings. Recognising the typical clinical picture and detailed history taking about previous drug abuse, helps to avoid further expensive and unnecessary investigations. The use of homemade manganese-contaminated ephedrone causes significant motor impairmet and decline in quality of life. Preventive measures could reduce the direct and indirect expenses on rehabilitation and social services

Brain-muscle axis during treatment of minimal hepatic encephalopathy with L-ornithine L-aspartate

Abstract Background: Minimal Hepatic Encephalopathy (MHE) is a fluctuant cognitive deficit, and a common complication of cirrhosis, with significant health and socioeconomic consequences. Oral L-Ornithine L-Aspartate (LOLA) has been proposed to treat MHE but mechanism and efficacy are unknown. This study hypothesises LOLA treatment will correlate with improvements in: 1) Cognitive function (primary endpoints) 2) Relation to Brain-muscle axis (secondary endpoints) Design and methods: This double-blinded placebo-controlled trial included 34 patients (LOLA n=14, placebo n=20) over 12 weeks. All underwent psychometric testing (PHES, CogstateTM, Stroop, Short Form-36). Secondary endpoints included brain volume, white matter microstructure, brain function (proton MR spectroscopy/ functional MRI); muscle power (handgrip strength, 6-minute-walk-test); anthropometry (upper limb skinfold); muscle metabolome (lateral vastus muscle biopsy LC-MS analysis). Results: Significantly more patients receiving LOLA reported improved energy levels, specifically in Vitality (SF36 subdomain). No differences in PHES, Cogstate and Stroop test performance occured. Change-in-biceps skinfold thickness demonstrated significant gain with LOLA compared to placebo, without differences in power. LC-MS experiments were not discriminatory. Whole Brain differences in FA and RD suggested reduced brain oedema (subcortical volume reduction and global white matter changes). No significant group differences in fMRI task/ resting activation were seen. Spectroscopy of ACC showed significantly higher unresolved glutamine-glutamate (Glx) complex levels with LOLA, also correlating with increased PPI use, and may represent LOLA-driven increased Krebs-cycling or a function of altered gut microbiome. Conclusion: No cognitive benefits were demonstrated. Improved quality of life measures maybe a nutritional consequence also relating to increased biceps skinfold thickness with LOLA. Effects on brain oedema are postulated. Future studies need higher powering to allow subanalysis by aetiology, and smaller voxels at basal ganglia are recommended. Attempts to replicate rising ACC Glx with LOLA and regions of interest identified on fMRI subanalysis may be fruitful.Open Acces

Transkraniaalne aju ultraheliuuring Eesti parkinsoni tõve haigetel

Väitekirja elektrooniline versioon ei sisalda publikatsiooneEestis läbiviidud uurimustöö eesmärgiks oli näidata aju ultraheli uuringu abil Parkinsoni tõve korral tekkivaid muutusi keskajus asuvas musttuumas, mis aitaks seda haigust diagnoosida. Täiendavalt uuriti ka ultraheliuuringu tulemuste seoseid depressiivsete sümptomite esinemisega. Tegemist on innovaatilise meetodiga Parkinsoni tõve diagnoosimiseks, mida Eestis pole varem uuritud. Uuringus osales 300 PT patsienti ja 200 kontrollisikut. Aju musttuum sisaldab dopamiinirakke, mis Parkinsoni tõvega haigetel haiguse kulu jooksul hävinevad. Läbi kolju tehtava ultraheliuuringu käigus on võimalik mõõta musttuuma piirkonna suurust ja selle kajarikkuse (hüperehhogeensuse) asümmeetria alusel kinnitada Parkinsoni tõve diagnoosi. Uuringul määrati ultraheli diagnostiline väärtus haigete eristamiseks tervetest, mis ühtib varasemalt teistes riikides leitud tulemustega; kõige olulisemaks tulemuse mõjutajaks on vanus. Lisaks näidati erinevust vasaku ja parema ajupoole vahel, mis on seoses esmassümptomite tekkimise poolega. Lisaks aitab ultraheliuuring kirjeldada depressiivsete sümptomite ilmnemist Parkinsoni tõvega haigetel ajutüves asuvate Raphe tuumade ehhogeensuse esinemise põhjal. Raphe tuumad osalevad virgatsaine serotoniini tootmisel, mille vähenemisel kahjustuse korral võivad tekkida depressiooni sümptomid. Uuring näitas, et ultraheli uuring võimaldab hinnata Raphe tuumade terviklikkust ja on hea meetod varjatud depressiooni sümptomite väljaselgitamiseks. Läbiviidud uuring oli esimene ulatuslik aju ultraheliuuring Eestis, mis kinnitas ultraheliuuringu diagnostilist väärtust Parkinsoni tõve diagnoosimiseks. Lisaks teaduslikule väärtusele on sellel oluline kliiniline tähtsus seoses uue meetodi rakendamisega Parkinsoni tõve käsitluses.The aim of the research carried out in Estonia was to show by transcranial brain sonography the changes in Parkinson's disease in substantia nigra, which would help diagnose the disease. Transcranial brain sonography is an innovative method for diagnosing Parkinson's disease, which has not been studied in Estonia before. By sonography examination of the skull, it is possible to measure the size of the substantia nigra echogenicity and confirm the diagnosis of Parkinson's disease on the basis of its asymmetry in substantia nigra hyperechogenicity. The study determined the diagnostic value of SN+ to distinguish patients from healthy ones, which is consistent with the results previously found in other countries. There was a difference between the left and right sides of the SN+ that are related to the onset of the Parkinson’s disease initial symptoms. In addition, age was the most important factor influencing the asymmetry of SN+. The ultrasound study helps to describe the appearance of depressive symptoms in PD patients based on the occurrence of echogenicity of Raphe nuclei in the brainstem. The study showed that the transcranial brain sonography examination provides an estimate of the integrity of the Raphe nuclei and is a good method for detecting the symptoms of hidden depression. The conducted study was the first extensive transcranial brain sonography study in Estonia confirming the diagnostic value of ultrasound in the diagnosis of Parkinson's disease.  https://www.ester.ee/record=b5250326~S