The cerebellum hosts more than half of all neurons of the human brain, with their organized activity playing a key role in coordinating motor functions. Cerebellar activity has also been implicated in the control of speech, communication, and social behavior, which are compromised in autism spectrum disorders (ASD). Despite major research advances, there is a shortage of mechanistic data relating cellular and molecular changes in the cerebellum to autistic behavior. We studied the impact of tuberous sclerosis complex 2 haploinsufficiency (Tsc2+/-) with downstream mTORC1 hyperactivity on cerebellar morphology and cellular organization in 1, 9, and 18 m.o. Eker rats, to determine possible structural correlates of an autism-like behavioural phenotype in this model. We report a greater developmental expansion of the cerebellar vermis, owing to enlarged white matter and thickened molecular layer. Histochemical and immunofluorescence data suggest age-related demyelination of central tract of the vermis, as evident from reduced level of myelin-basic protein in the arbora vitae. We also observed a higher number of astrocytes in Tsc2+/- rats of older age while the number of Purkinje cells (PCs) in these animals was lower than in wild-type controls. Unlike astrocytes and PCs, Bergmann glia remained unaltered at all ages in both genotypes, while the number of microglia was higher in Tsc2+/- rats of older age. The convergent evidence for a variety of age-dependent cellular changes in the cerebellum of rats associated with mTORC1 hyperactivity, thus, predicts an array of functional impairments, which may contribute to the developmental onset of an autism-like behavioral phenotype in this model. LAY SUMMARY: This study elucidates the impact of constitutive mTORC1 hyperactivity on cerebellar morphology and cellular organization in a rat model of autism and epilepsy. It describes age-dependent degeneration of Purkinje neurons, with demyelination of central tract as well as activation of microglia, and discusses the implications of these changes for neuro-behavioral phenotypes. The described changes provide new indications for the putative mechanisms underlying cerebellar impairments with their age-related onset, which may contribute to the pathobiology of autism, epilepsy, and related disorders.

• Klíčová slova
• Purkinje neurons, autism spectrum disorder, cerebellum, demyelination, mTORC1 signaling, microglia activation, synaptophysin,
• MeSH
• autistická porucha * MeSH
• demyelinizační nemoci * komplikace   metabolismus   MeSH
• epilepsie * komplikace   MeSH
• fenotyp MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mozeček metabolismus   MeSH
• mTORC1 genetika   metabolismus   MeSH
• poruchy autistického spektra * MeSH
• tuberózní skleróza MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• mTORC1 MeSH

BACKGROUND: Neuropsychiatric symptoms and reduced health-related quality of life (HRQoL) are frequent in multiple sclerosis, where are associated with structural brain changes, but have been less studied in clinically isolated syndrome (CIS). OBJECTIVE: To characterize HRQoL, neuropsychiatric symptoms (depressive symptoms, anxiety, apathy and fatigue), their interrelations and associations with structural brain changes in CIS. METHODS: Patients with CIS (n = 67) and demographically matched healthy controls (n = 46) underwent neurological and psychological examinations including assessment of HRQoL, neuropsychiatric symptoms and cognitive functioning, and MRI brain scan with global, regional and lesion load volume measurement. RESULTS: The CIS group had more, mostly mild, depressive symptoms and anxiety, and lower HRQoL physical and social subscores (p≤0.037). Neuropsychiatric symptoms were associated with most HRQoL subscores (β≤-0.34, p≤0.005). Cognitive functioning unlike clinical disability was associated with depressive symptoms and lower HRQoL emotional subscores (β≤-0.29, p≤0.019). Depressive symptoms and apathy were associated with right temporal, left insular and right occipital lesion load (ß≥0.29, p≤0.032). Anxiety was associated with lower white matter volume (ß = -0.25, p = 0.045). CONCLUSION: Mild depressive symptoms and anxiety with decreased HRQoL are present in patients with CIS. Neuropsychiatric symptoms contributing to decreased HRQoL are the result of structural brain changes and require complex therapeutic approach in patients with CIS.

• MeSH
• apatie fyziologie   MeSH
• bílá hmota diagnostické zobrazování   patologie   MeSH
• demyelinizační nemoci komplikace   diagnostické zobrazování   patologie   psychologie   MeSH
• deprese komplikace   diagnostické zobrazování   patologie   psychologie   MeSH
• dospělí MeSH
• kvalita života * MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mladý dospělý MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• neuropsychologické testy MeSH
• posuzování pracovní neschopnosti MeSH
• průzkumy a dotazníky MeSH
• únava komplikace   diagnostické zobrazování   patologie   psychologie   MeSH
• úzkost komplikace   diagnostické zobrazování   patologie   psychologie   MeSH
• velikost orgánu MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Patients with clinically isolated syndrome (CIS), unlike those with multiple sclerosis (MS), have a selective cognitive impairment which is not consistently related to structural brain changes. Our objective was to characterize a profile of cognitive impairment and its association with structural brain changes in patients with CIS who are at high risk of developing MS. Patients with CIS at high risk for MS on interferon-beta (n = 51) and age-, gender-, and education-matched controls (n = 44) underwent comprehensive neuropsychological testing and MRI brain scan with voxel-based morphometry. The CIS group had lower cognitive performance in verbal and nonverbal memory, information processing speed/attention/working memory, and executive and visuo-spatial functions compared to controls (p ≤ 0.040). Lower cognitive performance was present in 18-37 and 14-26% of patients with CIS at high risk for MS depending on the criteria used. Brain volume was reduced predominantly in fronto-temporal regions and the thalamus in the CIS group (p ≤ 0.019). Cognitive performance was not associated with structural brain changes except for the association between worse visuo-spatial performance and lower white matter volume in the CIS group (β = 0.29; p = 0.042). Our results indicated that patients with CIS at high risk for MS may have a pattern of lower cognitive performance and regional brain atrophy similar to that found in patients with MS. Lower cognitive performance may be present in up to one-third of patients with CIS at high risk for MS, but, unlike patients with MS, variability in their cognitive performance may lead to a lack of consistent associations with structural brain changes.

• Klíčová slova
• Clinically isolated syndrome, Cognition, MRI, Multiple sclerosis, Neuropsychology, Voxel-based morphometry,
• MeSH
• atrofie MeSH
• demyelinizační nemoci komplikace   diagnostické zobrazování   psychologie   MeSH
• dospělí MeSH
• kognitivní dysfunkce diagnostické zobrazování   etiologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek diagnostické zobrazování   MeSH
• neuropsychologické testy MeSH
• počítačové zpracování obrazu MeSH
• posuzování pracovní neschopnosti MeSH
• prognóza MeSH
• progrese nemoci MeSH
• rizikové faktory MeSH
• velikost orgánu MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: To investigate the associations between antibody responses to herpesviruses and the development of thalamic, total deep gray matter, cortical and central atrophy in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. METHODS: We analyzed volumetric brain outcomes in 193 CIS patients enrolled in a multi-center study of high-risk CIS. All patients had 2 or more MRI brain lesions and two or more oligoclonal bands in cerebrospinal fluid. Serum samples obtained at the screening visit prior to any treatment were analyzed for IgG antibodies against cytomegalovirus (anti-CMV) and Epstein-Barr virus (EBV) viral capsid antigen (VCA). All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months. RESULTS: Anti-EBV VCA highest quartile status was associated with regional atrophy measures for percent decrease in thalamus. Anti-CMV positivity was associated with greater total deep gray matter atrophy and whole brain atrophy. Anti-EBV VCA highest quartile status was associated as trends with greater whole brain, gray matter atrophy and central atrophy. The associations of anti-EBV VCA antibodies with thalamic atrophy were mediated by its associations with T2 lesions whereas the associations of anti-CMV positivity with deep gray matter atrophy were relatively independent of T2 lesions. CONCLUSIONS: Antibody responses to EBV and CMV are associated with global and regional brain atrophy in CIS patients treated with interferon-beta.

• Klíčová slova
• Cytomegalovirus, Deep gray matter atrophy, Environmental factors, Epstein–Barr virus,
• MeSH
• antigeny virové imunologie   MeSH
• antivirové látky terapeutické užití   MeSH
• atrofie farmakoterapie   etiologie   virologie   MeSH
• časové faktory MeSH
• demyelinizační nemoci komplikace   farmakoterapie   MeSH
• dospělí MeSH
• Herpesviridae imunologie   MeSH
• interferon beta terapeutické užití   MeSH
• leukoencefalopatie etiologie   MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie MeSH
• mladý dospělý MeSH
• neurodegenerativní nemoci etiologie   MeSH
• pozorování MeSH
• protilátky virové krev   MeSH
• thalamus patologie   MeSH
• virové plášťové proteiny imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• antigeny virové MeSH
• antivirové látky MeSH
• Epstein-Barr viral capsid antigen MeSH Prohlížeč
• interferon beta MeSH
• protilátky virové MeSH
• virové plášťové proteiny MeSH

BACKGROUND: Cognitive deficits worsen the quality of life in multiple sclerosis and may be predicted by deep gray matter atrophy, especially thalamic atrophy. This relationship has not been studied in the clinically isolated syndrome (CIS). The aims of this study were to assess cognitive deficits in patients with CIS and relapsing-remitting multiple sclerosis (RRMS) using neuropsychological testing, to search for thalamic atrophy on brain MRI, and to test for their correlations. METHODS: Forty-three patients (19 with CIS and 24 with RRMS) underwent brain MRI and neuropsychological testing involving multiple cognitive domains and the severity of depression. Thalamic volumes automatically segmented from MRI data were compared to 19 healthy controls. Correlations were sought between cognitive performance and thalamic volume. RESULTS: Cognitive impairment was detected in the majority of both CIS and MS patients, most affected in executive functions, auditory memory, lexical verbal fluency, distribution of attention and psychomotor speed. Cognitive impairment and depression were not significantly correlated to disease duration. Both CIS and MS patients demonstrated thalamic atrophy compared to controls, while many cognitive deficits correlated with thalamic volume in both patient groups. CONCLUSION: Cognitive deficits in CIS resemble those found in the later stages of MS and may be directly related to the amount of thalamic damage.

• Klíčová slova
• Clinically isolated syndrome, Cognitive impairment, MRI, Multiple sclerosis, Neuropsychological testing, Thalamic atrophy,
• MeSH
• atrofie patologie   MeSH
• demyelinizační nemoci komplikace   patologie   psychologie   MeSH
• dospělí MeSH
• kognitivní poruchy komplikace   patologie   psychologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• neuropsychologické testy MeSH
• neurozobrazování MeSH
• relabující-remitující roztroušená skleróza komplikace   patologie   psychologie   MeSH
• studie případů a kontrol MeSH
• thalamus patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: Neurological complications of inflammatory bowel diseases (IBDs) are not rare but are under-diagnosed; some are probably immune-mediated. Several previous studies have suggested a higher incidence of demyelinating diseases such as multiple sclerosis in IBD patients. In this single-center, prospective, observational study, the authors focus on T2 focal white-matter lesions of the central nervous system on magnetic resonance imaging (MRI) in IBD patients that may be due to demyelination. MATERIAL AND METHODS: A total of 70 patients with Crohn's disease were examined before beginning anti-TNF-α therapy. These patients were treated with azathioprine, mesalazine or both. Patients were examined by a neurologist to detect possible signs of demyelinating disease, and patients underwent brain MRI (native T1, T2, and FLAIR sequences). RESULTS: Thirty-seven patients (53%) exhibited abnormalities on neurological examination, and 26 patients (37%) displayed abnormalities on MRI. In seven cases, these MRI abnormalities (periventricular lesions) were suspected to be due to demyelination. Cerebral spinal fluid investigation (including polyclonal bands) was completely negative in five cases and was borderline in one case, and multiple sclerosis was confirmed in one case. Pathological MRI findings in 19 other patients were clinically nonsignificant; most were nonspecific sporadic lesions in white matter or mild atrophy. CONCLUSIONS: The results support previous data that the frequency of neurological findings in IBD patients is generally underestimated. With the extension of biological anti-TNF-α treatment for IBD, the possibility of a higher risk of developing multiple sclerosis should be considered.

• MeSH
• Crohnova nemoc komplikace   farmakoterapie   MeSH
• demyelinizační nemoci mozkomíšní mok   komplikace   diagnóza   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mladiství MeSH
• mladý dospělý MeSH
• neurologické vyšetření MeSH
• prospektivní studie MeSH
• senioři MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• TNF-alfa MeSH

The osmotic demyelination syndrome (ODS) has been identified as a complication of the rapid correction of hyponatremia for decades (King and Rosner, 2010). However, in recent years, a variety of other medical conditions have been associated with the development of ODS, independent of changes in serum sodium which cause a rapid changes in osmolality of the interstitial (extracellular) compartment of the brain leading to dehydration of energy-depleted cells with subsequent axonal damage that occurs in characteristic areas (King and Rosner, 2010). Slow correction of the serum sodium concentration and additional administration of corticosteroids seems to be a major prevention step in ODS patients. In the current report we aimed to share a rare case which we observed in our clinic.

• MeSH
• centrální pontinní myelinolýza komplikace   MeSH
• demyelinizační nemoci komplikace   metabolismus   MeSH
• dospělí MeSH
• lidé MeSH
• osmóza MeSH
• syndrom MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Changes in MR images and 1H spectra of 20 patients with hyperphenylalaninaemia were compared with data of controls. Major changes in T2 MR images were found in the periventricular area (20/19). Some patients showed lesions in MR images of basal ganglia (20/7) and in the cerebellum (20/4). The results of proton MR spectroscopy show no significant difference for NAA/Cr ratios but significant ones between the ratios of NAA/Cho (p = 0.97) and Cho/Cr (p = 0.98) of controls and patients with hyperphenylalaninaemia.

• MeSH
• biopteriny nedostatek   MeSH
• cholin analýza   MeSH
• demyelinizační nemoci komplikace   patofyziologie   MeSH
• dítě MeSH
• dospělí MeSH
• fenylalanin analýza   MeSH
• fenylketonurie komplikace   patofyziologie   MeSH
• kreatin analýza   MeSH
• kyselina asparagová analýza   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek - chemie MeSH
• mozek patofyziologie   MeSH
• nemoci mozku diagnóza   etiologie   patofyziologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biopteriny MeSH
• cholin MeSH
• fenylalanin MeSH
• kreatin MeSH
• kyselina asparagová MeSH

The authors describe a case of central pontine myelinolysis in a 43-year-old female alcoholic, confirmed by post-mortem examination, as for technical reasons in lifetime neither CT nor MR examinations could be made. Despite the relatively scarce incidence of the disease, as mentioned in the literature, this possibility must be taken into consideration in particular in young alcoholics.

• MeSH
• alkoholismus komplikace   MeSH
• demyelinizační nemoci komplikace   diagnóza   MeSH
• dospělí MeSH
• lidé MeSH
• pons * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH