RESUMO
OBJECTIVE: To study the prevalence of autoantibodies to synapsin in patients with psychiatric and neurological disorders and to describe clinical findings in synapsin antibody positive patients. METHODS: Sera of 375 patients with different psychiatric and neurological disorders and sera of 97 healthy controls were screened (dilution 1:320) for anti-synapsin IgG using HEK293 cells transfected with rat synapsin Ia. Positive sera were further analyzed by immunoblots with brain tissue from wild type and synapsin knock out mice and with HEK293 cells transfected with human synapsin Ia and Ib. Binding of synapsin IgG positive sera to primary neurons was studied using murine hippocampal neurons. RESULTS: IgG in serum from 23 (6.1%) of 375 patients, but from none of the 97 healthy controls (p=0.007), bound to rat synapsin Ia transfected cells with a median (range) titer of 1:1000 (1:320-1:100,000). Twelve of the 23 positive sera reacted with a protein of the molecular size of synapsin I in immunoblots of wild type but not of synapsin knock out mouse brain tissue. Out of 19/23 positive sera available for testing, 13 bound to human synapsin Ia and 16 to human synapsin Ib transfected cells. Synapsin IgG positive sera stained fixed and permeabilized murine hippocampal neurons. Synapsin IgG positive patients had various psychiatric and neurological disorders. Tumors were documented in 2 patients (melanoma, small cell lung carcinoma); concomitant anti-neuronal or other autoantibodies were present in 8 patients. CONCLUSIONS: Autoantibodies to human synapsin Ia and Ib are detectable in a proportion of sera from patients with different psychiatric and neurological disorders, warranting further investigation into the potential pathophysiological relevance of these antibodies.
Assuntos
Autoanticorpos/sangue , Transtornos Mentais/imunologia , Doenças do Sistema Nervoso/imunologia , Sinapsinas/sangue , Sinapsinas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Feminino , Células HEK293 , Hipocampo/metabolismo , Humanos , Imunoglobulina G/sangue , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/epidemiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/epidemiologia , Neurônios/metabolismo , Prevalência , Ratos , Adulto JovemRESUMO
BACKGROUND: Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder with an extremely variable phenotype. In childhood NF1 can be associated with optic glioma and central precocious puberty; the latter is more common when the optic chiasm is affected. The mutational spectrum of the NF1 gene is wide and complex; R681X is a rare severe mutation of the NF1 gene known to cause truncation of neurofibromin, with only ten reported cases in the literature so far. CASE PRESENTATION: We describe a girl with NF1 associated with early central precocious puberty appearing at 2.5 years of age and optic glioma affecting the optic chiasm as seen on magnetic resonance imaging (MRI). Genetic analysis confirmed the presence of R681X. Therapy with a gonadotropin-releasing hormone agonist was instituted with good response to therapy. The lesions on MRI were stable and no significant vision impairment was present during the 6 years of follow-up. CONCLUSION: Of the ten reported cases of NF1 due to R681X, one has presented with optic glioma and none with precocious puberty. Thus, to our knowledge, this is the first reported case of this mutation presenting with precocious puberty. We believe that this is a contribution to the few reports on the phenotype of this mutation and to the future elucidation of genotype-phenotype correlations of this disease.
Assuntos
Hormônio Liberador de Gonadotropina/agonistas , Mutação , Neurofibromatose 1/patologia , Neurofibromina 1/genética , Glioma do Nervo Óptico/patologia , Puberdade Precoce/tratamento farmacológico , Pamoato de Triptorrelina/uso terapêutico , Arginina , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Neurofibromatose 1/complicações , Neurofibromatose 1/tratamento farmacológico , Neurofibromatose 1/genética , Glioma do Nervo Óptico/tratamento farmacológico , Glioma do Nervo Óptico/genética , Puberdade Precoce/etiologia , Puberdade Precoce/genética , Resultado do TratamentoRESUMO
BACKGROUND: We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer's disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinico-anatomical dissociation in bvAD based on alternative neuroimaging markers. METHODS: We retrospectively included 150 participants, including 29 bvAD, 28 "typical" amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other diagnostic groups on glucose metabolism and metabolic connectivity measured by [18F]FDG-PET, and on subcortical gray matter and white matter hyperintensity (WMH) volumes measured by MRI. A receiver-operating-characteristic-analysis was performed to determine the neuroimaging measures with highest diagnostic accuracy. RESULTS: bvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD than tAD, partially overlapping with bvFTD. bvAD showed greater anterior default mode network (DMN) involvement than tAD, mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with prefrontal regions. Analyses of WMH and subcortical volume showed closer resemblance of bvAD to tAD than to bvFTD, and larger amygdalar volumes in bvAD than tAD respectively. The top-3 discriminators for bvAD vs. bvFTD were FDG posterior-DMN-ratios (bvADAssuntos
Doença de Alzheimer
, Demência Frontotemporal
, Doença de Alzheimer/diagnóstico por imagem
, Demência Frontotemporal/diagnóstico por imagem
, Substância Cinzenta
, Humanos
, Imageamento por Ressonância Magnética
, Estudos Retrospectivos
RESUMO
BACKGROUND: In acute ischemic stroke the status of collateral circulation is a critical factor in determining outcome. We propose a less invasive alternative to digital subtraction angiography for evaluating collaterals based on dynamic-susceptibility contrast magnetic resonance imaging. METHODS: Perfusion maps of Tmax and cerebral blood flow (CBF) were created for 35 patients with baseline occlusion of a major cerebral artery. Volumes of hypoperfusion were defined as having a Tmax delay of > 4 seconds (Tmax4s) and > 6 seconds (Tmax6s) and a CBF drop below 80% of healthy, contralateral tissue. For each patient a ratio between the volume of the CBF and the Tmax based perfusion deficit was calculated. Associations with collateral status and radiological outcome were assessed with the Mann-Whitney-U test, uni- and multivariable logistic regression analyses as well as area under the receiver-operator-characteristic (ROC) curve. RESULTS: The CBF/Tmax volume ratios were significantly associated with bad collateral status in crude logistic regression analysis as well as with adjustment for NIHSS at admission and baseline infarct volume (OR = 2.5 95% CI[1.2-5.4] p = 0.020 for CBF/Tmax 4s volume ratio and OR = 1.6 95% CI[1.0-2.6] p = 0.031 for CBF/Tmax6s volume ratio). Moreover, the ratios were significantly correlated to final infarct size (Spearman's rho = 0.711 and 0.619, respectively for the CBF/Tmax4s volume ratio and CBF/Tmax6s volume ration, all p<0.001). The ratios also had a high area under the ROC curve of 0.93 95%CI[0.86-1.00]) and 0.90 95%CI[0.80-1.00]respectively for predicting poor radiological outcome. CONCLUSIONS: In the setting of acute ischemic stroke the CBF/Tmax volume ratio can be used to differentiate between good and insufficient collateral circulation without the need for invasive procedures like conventional angiography.
Assuntos
Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular , Circulação Colateral , Acidente Vascular Cerebral/fisiopatologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: To identify the specific domains of the presynaptic protein synapsin targeted by recently described autoantibodies to synapsin. METHODS: Sera of 20 and CSF of two patients with different psychiatric and neurological disorders previously tested positive for immunoglobulin (Ig)G antibodies to full-length synapsin were screened for IgG against synapsin I domains using HEK293 cells transfected with constructs encoding different domains of rat synapsin Ia. Additionally, IgG subclasses were determined using full-length synapsin Ia. Serum and CSF from one patient were also screened for IgA autoantibodies to synapsin I domains. Sera from nine and CSF from two healthy subjects were analyzed as controls. RESULTS: IgG in serum from 12 of 20 IgG synapsin full-length positive patients, but from none of the healthy controls, bound to synapsin domains. Of these 12 sera, six bound to the A domain, five to the D domain, and one to the B- (and possibly A-), D-, and E-domains of synapsin I. IgG antibodies to the D-domain were also detected in one of the CSF samples. Determination of IgG subclasses detected IgG1 in two sera and one CSF, IgG2 in none of the samples, IgG3 in two sera, and IgG4 in eight sera. One patient known to be positive for IgA antibodies to full-length synapsin had IgA antibodies to the D-domain in serum and CSF. CONCLUSIONS: Anti-synapsin autoantibodies preferentially bind to either the A- or the D-domain of synapsin I.
Assuntos
Autoanticorpos/sangue , Epitopos/imunologia , Imunoglobulina G/sangue , Sinapsinas/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Células HEK293 , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/classificação , Masculino , Transtornos Mentais/líquido cefalorraquidiano , Transtornos Mentais/patologia , Pessoa de Meia-Idade , Doenças Neurodegenerativas/líquido cefalorraquidiano , Doenças Neurodegenerativas/patologia , Domínios Proteicos/imunologia , Sinapsinas/química , Sinapsinas/metabolismo , Adulto JovemRESUMO
BACKGROUND: Pituitary hyperplasia secondary to primary longstanding hypothyroidism has been reported in the literature in adults and rarely in children. METHODS: Here we present the clinical presentation and diagnostic procedures in eight children with pituitary hyperplasia due to autoimmune thyroiditis, highlighting common findings, such as growth delay, fatigue or gaining weight, but also exceptional findings such as pericardial effusion, rhabdomyolysis, isolated hypertrichosis, and Van Wyk-Grumbach syndrome, which have rarely or never been described. RESULTS AND CONCLUSIONS: Surprisingly no thyroid enlargement was detected. We discuss the unusual presenting signs of autoimmune thyroiditis that should raise the suspicion of pituitary hyperplasia. We suggest that a more elaborate clinical assessment and even modification of the diagnostic approach to autoimmune thyroiditis is needed in order to avoid its serious complications.
Assuntos
Doença de Hashimoto/diagnóstico , Hiperplasia/diagnóstico , Hipotireoidismo/complicações , Doenças da Hipófise/diagnóstico , Tireoidite Autoimune/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Doença de Hashimoto/diagnóstico por imagem , Doença de Hashimoto/etiologia , Humanos , Hiperplasia/diagnóstico por imagem , Hiperplasia/etiologia , Imageamento por Ressonância Magnética , Masculino , Doenças da Hipófise/diagnóstico por imagem , Doenças da Hipófise/etiologia , Prognóstico , Estudos Retrospectivos , Tireoidite Autoimune/diagnóstico por imagem , Tireoidite Autoimune/etiologia , Adulto JovemRESUMO
BACKGROUND: Killian-Pallister syndrome (KPS) is a rare form of chromosomal mosaicism and is defined by the existence of an extra chromosome 12 in some cell lines in one individual. The degree of mosaicism varies among tissues and dictates the clinical presentation of the syndrome. The clinical features of Killian-Pallister syndrome include mental retardation, typical facial dysmorphism and pigmentation defects. CASE PRESENTATION: We present a rare case of Killian-Pallister syndrome with severe form of the disease associated with isolated growth hormone deficiency and low-rate mosaicism on buccal smear. The absence of a marker chromosome 12p in lymphocyte cultures and the low degree of mosaicism lead to frequent misdiagnosis of this condition. CONCLUSIONS: The selection of tissue sampling is crucial in establishing the diagnosis of Killian-Pallister syndrome. Fluorescent in situ hybridisation on buccal smear remains the golden standard as a screening method if a suspicion of the syndrome exists.