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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 922-925, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515791

RESUMO

OBJECTIVE: To report a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifesting as lumbago, hunchback and Parkinson's syndrome. METHODS: A 49-years-old male CADASIL patient was reported. Results of clinical examination, neuroimaging and genetic testing were analyzed. His family members were also subjected to genetic testing. Related literature was reviewed. RESULTS: The patient had no typical symptoms of CADASIL such as headache, repeated stroke, dementia and emotional disorders, but progressive Parkinson's syndrome, late onset lumbago, hunchback, dysphagia, and diplopia. Brain MRI showed left basal ganglia and external capsule lacunar infarction. Genetic testing revealed a point mutation c.1630C>T (p.R544C) in exon 11 of the NOTCH3 gene. A heterozygous mutation was detected in the same gene in his mother, elder sister and younger brother, all of whom showed different clinical phenotypes. CONCLUSION: The clinical features of CADASIL are heterogeneous. Lumbago, humpback, and Parkinson's syndrome may be a rare clinical phenotype of CADASIL.


Assuntos
CADASIL/genética , Dor Lombar/etiologia , Doença de Parkinson/etiologia , CADASIL/complicações , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Receptor Notch3/genética
2.
Psychiatr Danub ; 31(Suppl 3): 591-594, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488796

RESUMO

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare monogenic disorder caused by mutations in the NOTCH3 gene. The clinical features are primarily neurological, which include recurrent transient ischaemic attacks, strokes, and migraines. However, psychiatric manifestations which mainly include mood disturbances have also been reported in CADASIL. Manic symptoms and bipolar disorders are rarely documented in CADASIL and existing reports generally lack detailed descriptions of the psychiatric evaluation. We discuss a case of Bipolar Affective Disorder (BD) in a British woman with a family history of CADASIL. This case provides insight into the diagnosis and management of BD as well as the possible underlying aetiologies that should be considered. The similarities between BD and CADASIL in terms of imaging, genetic, and therapeutic aspects raise the possibility of common dysfunctional pathways. BD in CADASIL may warrant greater consideration by both psychiatrists as well as non-psychiatric specialists and further studies are required to understand the pathological significance.


Assuntos
Transtorno Bipolar/complicações , CADASIL/complicações , Transtorno Bipolar/genética , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , CADASIL/genética , CADASIL/fisiopatologia , CADASIL/psicologia , Feminino , Humanos , Transtornos de Enxaqueca/complicações , Transtornos do Humor/complicações , Mutação , Receptor Notch3/genética , Reino Unido
3.
BMJ Case Rep ; 12(7)2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31324668

RESUMO

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene which maps to the short arm of chromosome 19 and encodes the NOTCH3 receptor protein, predominantly expressed in adults by vascular smooth muscle cells and pericytes. The receptor has a large extracellular domain with 34 epidermal growth factor-like repeats encoded by exons 2-24, the site at which CADASIL mutations are most commonly found. Migraine with aura is often the earliest feature of the disease, with an increased susceptibility to cortical spreading depression suggested as a possible aetiological mechanism. Stroke, acute encephalopathy and cognitive impairment can also occur. Hypertension and smoking are associated with early age of onset of stroke. It diffusely affects white matter, with distinct findings on T2- weighted MRI, involving the external capsule, anterior poles of the temporal lobe and superior frontal gyri, displaying a characteristic pattern of leucoencephalopathy. Affected individuals have a reduced life expectancy. An effective treatment for CADASIL is not available. The authors describe a 35-year-old manwith an unremarkable medical history, presenting to the emergency department with slurred speech and increased confusion 3 days following a fall. He was a smoker and consumed 16 units of alcohol weekly. He was hypertensive and tachycardic. Physical examination confirmed increased tone in his lower limbs and dysarthria. His CT head showed severe cerebral atrophy, multiple small old infarcts and moderate background microvascular disease. Further investigation with an MRI head confirmed multiple white matter abnormalities with microhaemorrhages. The possibility of a hereditary vasculopathy was rendered as the appearances were thought consistent with a diagnosis of CADASIL. Genetic testing identified the NOTCH3 gene thus confirming the diagnosis. This paper provides an overview of the aetiology, clinical presentation, pathogenesis, investigations and management of CADASIL.


Assuntos
CADASIL/diagnóstico , Acidente Vascular Cerebral/diagnóstico por imagem , Adulto , Consumo de Bebidas Alcoólicas , CADASIL/complicações , CADASIL/diagnóstico por imagem , CADASIL/genética , Ecocardiografia , Testes Genéticos , Humanos , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Receptor Notch3/genética , Fumar , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral Lacunar/complicações , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem
4.
BMC Neurol ; 19(1): 106, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146726

RESUMO

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy associated with the NOTCH3 gene. Clinical manifestations include strokes, transient ischaemic events, psychiatric disturbances, dementia, and migraines. We report a case of a Thai man with a severe CADASIL phenotype who presented with recurrent seizures and acute ischaemic stroke and classic vascular risk factors. CASE PRESENTATION: A 50-year-old man with a history of mood disorder and progressive cognitive decline for 20 years as well as well-controlled diabetes mellitus and hypertension presented with recurrent generalized seizures and acute right-sided weakness. An MRI of the brain showed acute infarction of the left pons, a large number of cerebral microbleeds throughout the brain and white matter abnormalities without classic anterior temporal lobe lesions. Molecular genetic testing identified a homozygous pathologic variant, c.1672C > T (p. Arg558Cys), in the NOTCH3 gene. The diagnosis of CADASIL was confirmed. His clinical symptoms deteriorated, and he died of tracheobronchitis with secretion obstruction. CONCLUSION: This case raises awareness of an uncommon cause of acute ischaemic stroke in patients with classic vascular risk factors and emphasizes the need for a complete evaluation in cases with unexpected clinical presentation or unexpected diagnostic study results.


Assuntos
CADASIL/complicações , CADASIL/diagnóstico , Hemorragia Cerebral/etiologia , Convulsões/etiologia , Acidente Vascular Cerebral/etiologia , CADASIL/genética , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Receptor Notch3/genética , Tailândia
5.
Neurologist ; 24(4): 136-138, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31246723

RESUMO

The main clinical manifestations of Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are migraine with aura, ischemic strokes, and progressive cognitive decline. Intracerebral hemorrhage (ICH) has been described in CADASIL, but is not widely recognized. Here we report a case with CADASIL that presented with fatal ICH. A 57-year-old right-handed man of Pakistani descent with history of genetically confirmed CADASIL, hypertension, and mood disorder presented to the emergency department via Emergency Medical Services (EMSs) after he was found down. Initial neurological examination showed a Glasgow Coma Scale (GCS) of 7 (E2, V1, M4), left gaze deviation, pinpoint pupils, and left hemiplegia. His medications included antihypertensive agents and aspirin. He was intubated in the emergency department due to inability to protect his airway. Computed tomographic scan of the head revealed acute hemorrhage in the right pons (ICH score 2) with extension into the right cerebral peduncle, as well as enlargement of the third and lateral ventricles suggesting early obstructive hydrocephalus that required an external ventricular drain placement. He had no improvement of his clinical status, and eventually extubation and comfort care were pursued. He died 6 days after presentation. CADASIL vasculopathy, cerebral microbleeds, hypertension, and antithrombotic agents are factors that could be related to ICH in patients with CADASIL. This case highlights the importance of adequate blood pressure control, magnetic resonance imaging assessment of cerebral microbleed, and careful discussion of the risk and benefits of antiplatelet agents when evaluating and treating patients with CADASIL.


Assuntos
Encéfalo/diagnóstico por imagem , CADASIL/complicações , Hemorragia Cerebral/etiologia , CADASIL/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Evolução Fatal , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
6.
Neurology ; 92(24): 1146-1156, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31142635

RESUMO

CNS small vessel disease (CSVD) causes 25% of strokes and contributes to 45% of dementia cases. Prevalence increases with age, affecting about 5% of people aged 50 years to almost 100% of people older than 90 years. Known causes and risk factors include age, hypertension, branch atheromatous disease, cerebral amyloid angiopathy, radiation exposure, immune-mediated vasculitides, certain infections, and several genetic diseases. CSVD can be asymptomatic; however, depending on location, lesions can cause mild cognitive dysfunction, dementia, mood disorders, motor and gait dysfunction, and urinary incontinence. CSVD is diagnosed on the basis of brain imaging biomarkers, including recent small subcortical infarcts, white matter hyperintensities, lacunes, cerebral microbleeds, enlarged perivascular spaces, and cerebral atrophy. Advanced imaging modalities can detect signs of disease even earlier than current standard imaging techniques. Diffusion tensor imaging can identify altered white matter connectivity, and blood oxygenation level-dependent imaging can identify decreased vascular reactivity. Pathogenesis is thought to begin with an etiologically specific insult, with or without genetic predisposition, which results in dysfunction of the neurovascular unit. Uncertainties regarding pathogenesis have delayed development of effective treatment. The most widely accepted approach to treatment is to intensively control well-established vascular risk factors, of which hypertension is the most important. With better understanding of pathogenesis, specific therapies may emerge. Early identification of pathologic characteristics with advanced imaging provides an opportunity to forestall progression before emergence of symptoms.


Assuntos
Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Anti-Hipertensivos/uso terapêutico , CADASIL/complicações , CADASIL/diagnóstico por imagem , CADASIL/tratamento farmacológico , CADASIL/fisiopatologia , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Angiopatia Amiloide Cerebral/tratamento farmacológico , Angiopatia Amiloide Cerebral/fisiopatologia , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/tratamento farmacológico , Doenças de Pequenos Vasos Cerebrais/fisiopatologia , Demência/etiologia , Demência/fisiopatologia , Imagem de Difusão por Ressonância Magnética , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imagem por Ressonância Magnética , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem , Acidente Vascular Cerebral Lacunar/etiologia , Acidente Vascular Cerebral Lacunar/fisiopatologia
7.
J Pediatr Hematol Oncol ; 41(4): e210-e215, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30883460

RESUMO

OBJECTIVE: The main objectives of this article were to study a severe congenital protein C deficiency (PCD) in a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and analyze the cause of this case. MATERIALS AND METHODS: We had recorded clinical manifestations of the patient, laboratory tests, imaging studies, and gene sequencing of the PROC gene and NOTCH3 gene to study the disease in this family. We checked the change of NOTCH3 protein by immunohistochemistry. RESULTS: Laboratory studies of the patient had revealed that his PC activity was 3%. Magnetic resonance imaging results showed hyperintense lesions in the cerebral white matter of the patient. PROC gene and NOTCH3 gene sequencing was performed among the family members. The patient was confirmed as homozygous for the (A-G)-12 at the transcription initiation site in the promoter region of the PROC gene and heterozygous mutation of the NOTCH3 gene. Immunohistochemical results showed that NOTCH3 protein was positive in the skin vascular smooth muscle of the patient. CONCLUSIONS: We studied a rare case of an infat boy diagnosed with both congenital PCD and CADASIL; congenital PCD was attributable to a compound that was homozygous for (A-G)-12 at the transcription initiation site in the promoter region of the PROC gene, and CADASIL was caused by missense mutation in exon 24 of NOTCH3. He was a sporadic patient with congenital PCD and CADASIL; it maybe that the deficiency of protein C led to early onset of CADASIL. The gene sequencing of PROC gene and NOTCH3 gene may have important value for fertility guidance and prenatal diagnosis.


Assuntos
CADASIL/complicações , Deficiência de Proteína C/congênito , Deficiência de Proteína C/complicações , Grupo com Ancestrais do Continente Asiático , Humanos , Lactente , Masculino
9.
J Clin Neurosci ; 58: 25-29, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30454692

RESUMO

In order to evaluate the usefulness of presymptomatic MRI, we performed 3T brain MRI and Sanger gene sequencing in a proband with suspected but not confirmed CADASIL and her apparently asymptomatic father. The 35-year-old proband presented with migraine with visual aura. Brain MRI showed diffuse leukoencephalopathy, suggesting CADASIL. NOTCH3 gene sequencing (exons 3-6) was negative. Family history was unclear. The MRI study of the father documented severe, diffuse leukoencephalopathy, with involvement of the temporal poles and external capsules (not observed in the proband), and lacunar infarcts in the absence of cardiac disease or risk factors. The MRI findings were in favour of an autosomal dominant mode of transmission and reinforced the hypothesis of CADASIL. Full NOTCH3 gene sequencing uncovered a novel exon 8 mutation (c.1337G>A; p.Cys446Tyr) outside the most commonly mutated region of NOTCH3. The novel mutation leads to a typical MRI pattern but a variable overall phenotype. The study underlines the usefulness of combining full gene sequencing with familial MRI studies.


Assuntos
CADASIL/diagnóstico por imagem , CADASIL/genética , Variação Genética/genética , Imagem por Ressonância Magnética/métodos , Mutação/genética , Receptor Notch3/genética , Adulto , Idoso , Encéfalo/diagnóstico por imagem , CADASIL/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enxaqueca com Aura/complicações , Enxaqueca com Aura/diagnóstico por imagem , Enxaqueca com Aura/genética , Linhagem , Fatores de Risco
10.
BMC Neurol ; 18(1): 134, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-30170552

RESUMO

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized clinically by central nervous system dysfunctions. It is unclear whether CADASIL is involved in peripheral neuropathy. CASE PRESENTATION: A 67-year-old Japanese man with stepwise progression of sensory and motor neuropathy was admitted to our hospital. Peripheral neuropathy of the extremities was detected through electrophysiological and pathological studies, and brain magnetic resonance imaging revealed bilateral periventricular ischemic and thalamic hemorrhagic lesions. We diagnosed CADASIL after detecting granular osmiophilic material in the walls of the endoneurial vessels morphologically and identifying a heterozygous NOTCH3 mutation p.Arg75Pro. CONCLUSIONS: CADASIL is to be included in the work-up of not classified peripheral neuropathies.


Assuntos
CADASIL/complicações , CADASIL/diagnóstico , Doenças do Sistema Nervoso Periférico/etiologia , Idoso , Progressão da Doença , Humanos , Imagem por Ressonância Magnética , Masculino , Mutação , Receptor Notch3/genética
11.
Neurology ; 91(10): e956-e963, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30076273

RESUMO

OBJECTIVE: We aimed to evaluate the role of endothelial-dependent and endothelial-independent vascular reactivity in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), both cerebral small vessel diseases are considered models for stroke, vascular dementia, and migraine. METHODS: RVCL-S (n = 18) and CADASIL (n = 23) participants with TREX1 and NOTCH3 mutations, respectively, were compared with controls matched for age, body mass index, and sex (n = 26). Endothelial function was evaluated by flow-mediated vasodilatation, and endothelial-independent vascular reactivity (i.e., vascular smooth muscle cell function) was assessed by dermal blood flow response to capsaicin application. RESULTS: Flow-mediated vasodilatation was decreased in participants with RVCL-S compared with controls (2.32% ± 3.83% vs 5.76% ± 3.07% change in diameter, p = 0.023) but normal in participants with CADASIL. Vascular smooth muscle cell function was reduced in participants with CADASIL compared with controls (maximal dermal blood flow increase at 40 minutes after capsaicin: 1.38 ± 0.88 vs 2.22 ± 1.20 arbitrary units, p = 0.010) but normal in participants with RVCL-S. CONCLUSIONS: We identified endothelial dysfunction in RVCL-S and confirmed impaired vascular smooth muscle cell relaxation in CADASIL. Our findings may prove to be biomarkers for disease progression in both monogenic cerebral small vessel diseases and improve mechanistic insight in their pathophysiology. This may help in understanding common neurovascular disorders, including stroke, dementia, and migraine.


Assuntos
CADASIL/complicações , CADASIL/diagnóstico , Leucoencefalopatias/complicações , Leucoencefalopatias/diagnóstico , Doenças Vasculares/etiologia , Adulto , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , CADASIL/genética , Capsaicina/efeitos adversos , Exodesoxirribonucleases/genética , Feminino , Humanos , Leucoencefalopatias/genética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Nitroglicerina/uso terapêutico , Fosfoproteínas/genética , Receptor Notch3/genética , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Inquéritos e Questionários , Doenças Vasculares/tratamento farmacológico , Vasodilatadores/uso terapêutico
13.
Cell Transplant ; 27(4): 637-647, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29871518

RESUMO

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a cerebral small vascular disease caused by NOTCH3 mutation-induced vascular smooth muscle cell (VSMC) degeneration, leading to ischemic stroke and vascular dementia. Our previous study has demonstrated that repeated treatment with a combination of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) reduces VSMC degeneration and cerebral endothelial cell (EC) damage and improves cognitive function in a mouse model of CADASIL (TgNotch3R90C). This study aimed to determine whether cerebral thrombosis occurs in TgNotch3R90C mice and whether repeated SCF+G-CSF treatment reduces cerebral thrombosis in TgNotch3R90C mice. Using the approaches of bone marrow transplantation to track bone marrow-derived cells and confocal imaging, we observed bone marrow-derived blood cell occlusion in cerebral small vessels and capillaries (thrombosis). Most thrombosis occurred in the cerebral capillaries (93% of total occluded vessels), and the thrombosis showed an increased frequency in the regions of capillary bifurcation. Degenerated capillary ECs were seen inside and surrounding the thrombosis, and the bone marrow-derived ECs were also found next to the thrombosis. IgG extravasation was seen in and next to the areas of thrombosis. SCF+G-CSF treatment significantly reduced cerebral capillary thrombosis and IgG extravasation. These data suggest that the EC damage is associated with thrombosis and blood-brain barrier leakage in the cerebral capillaries under the CADASIL-like condition, whereas SCF+G-CSF treatment diminishes these pathological alterations. This study provides new insight into the involvement of cerebral capillary thrombosis in the development of CADASIL and potential approaches to reduce the thrombosis, which may restrict the pathological progression of CADASIL.


Assuntos
CADASIL/tratamento farmacológico , Capilares/patologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Trombose Intracraniana/tratamento farmacológico , Fator de Células-Tronco/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Encéfalo/patologia , CADASIL/complicações , CADASIL/patologia , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Fator Estimulador de Colônias de Granulócitos/farmacologia , Proteínas de Fluorescência Verde/metabolismo , Humanos , Imunoglobulina G/metabolismo , Trombose Intracraniana/complicações , Trombose Intracraniana/patologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores Notch/metabolismo , Fator de Células-Tronco/farmacologia
14.
J Stroke Cerebrovasc Dis ; 27(9): e191-e195, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29706439

RESUMO

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) due to mutations of the NOTCH3 gene is the most common cause of inherited cerebral small-vessel disease and one of the genetic causes of migraine with aura. The so-called CADASIL scale has been proposed as a clinical screening tool, and a score of 15 or higher seems useful in identifying patients with high probability of carrying NOTCH3 mutations. We studied a novel Greek family with clinical features compatible with CADASIL. Genetic analysis of NOTCH3 in the 2 living patients revealed the R182C mutation. Both patients had low scores (12 and 14) in the CADASIL scale, probably due to their relatively young age (38 and 37 years, respectively) at which cognitive decline and external capsule involvement have not developed yet. Another unusual feature in the second patient was a venous dysplasia in the parietal lobe. Observations presented here add to the notion that the CADASIL scale, although useful, probably needs a revision, taking into account the patient's age at which the score is calculated.


Assuntos
CADASIL/diagnóstico por imagem , CADASIL/genética , Veias Cerebrais/diagnóstico por imagem , Imagem por Ressonância Magnética , Mutação , Lobo Parietal/irrigação sanguínea , Receptor Notch3/genética , Irmãos , Adulto , CADASIL/complicações , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Grécia , Hereditariedade , Humanos , Linhagem , Fenótipo , Valor Preditivo dos Testes , Prognóstico
16.
Clin Neurol Neurosurg ; 173: 196-199, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29449082

RESUMO

BACKGROUND: Multiple sclerosis (MS) and CADASIL presenting together is exceedingly rare. As more cases of "inflammatory" CADASIL emerge, diagnostic challenges for clinicians increase. We report an individual with MS and CADASIL presenting with cognitive decline at age 25. She presented with gadolinium enhancing lesions on MRI and inflammatory cerebrospinal fluid raising the question of whether these patients should be given a diagnosis of "inflammatory CADASIL" or both MS and CADASIL. METHODS: A literature review was conducted on reports of inflammatory CADASIL or MS and CADASIL, clinical presentations including spinal cord lesions and CSF inflammatory markers. RESULTS: Nine cases in the literature of individuals with CADASIL and inflammatory presentations were found with treatment varying from intravenous steroids to MS immunomodulatory therapy. CONCLUSIONS: If individuals with CADASIL present with immune mediated inflammatory components they may benefit from immunomodulatory therapy. This is discussed with a review of the inflammatory CADASIL/MS cases in the literature and report of a case.


Assuntos
CADASIL/complicações , CADASIL/terapia , Esclerose Múltipla/complicações , Esclerose Múltipla/terapia , Adulto , Biomarcadores/análise , Encéfalo/imunologia , Encéfalo/patologia , CADASIL/diagnóstico , Feminino , Humanos , Imunomodulação/imunologia , Inflamação/terapia , Imagem por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico
17.
PLoS One ; 13(1): e0190878, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29370179

RESUMO

BACKGROUND AND PURPOSE: The frequency, clinical correlates, and risk factors of cerebral microbleeds (CMB) in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) are still poorly known. We aimed at determining the location and number of CMB and their relationship with clinical manifestations, vascular risk factors, drugs, and other neuroimaging features in CADASIL patients. METHODS: We collected clinical data by means of a structured proforma and centrally evaluated CMB on magnetic resonance gradient echo sequences applying the Microbleed Anatomical Rating Scale in CADASIL patients seen in 2 referral centers in Italy and United Kingdom. RESULTS: We evaluated 125 patients. CMB were present in 34% of patients and their presence was strongly influenced by the age. Twenty-nine percent of the patients had CMB in deep subcortical location, 22% in a lobar location, and 18% in infratentorial regions. After adjustment for age, factors significantly associated with a higher total number of CMB were hemorrhagic stroke, dementia, urge incontinence, and statins use (this latter not confirmed by multivariate analysis). Infratentorial and deep CMB were associated with dementia and urge incontinence, lobar CMB with hemorrhagic stroke, dementia, and statins use. Unexpectedly, patients with migraine, with or without aura, had a lower total, deep, and lobar number of CMB than patients without migraine. DISCUSSION: CMB formation in CADASIL seems to increase with age. History of hemorrhagic stroke, dementia, urge incontinence, and statins use are associated with a higher number of CMB. However, these findings need to be confirmed by longitudinal studies.


Assuntos
CADASIL/complicações , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/patologia , Adulto , Idoso , CADASIL/diagnóstico por imagem , CADASIL/tratamento farmacológico , Hemorragia Cerebral/diagnóstico por imagem , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Itália , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Fatores de Risco , Reino Unido
20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 34(6): 821-825, 2017 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-29188608

RESUMO

OBJECTIVE: To investigate a cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy (CADASIL) case with clinical manifestations of baldness, lumbago and Parkinson's symptoms. METHODS: Clinical and imaging data of the patient were analyzed. The patient and his family members were also subjected to genetic testing. RESULTS: The symptoms of the patient included recurrent stroke, dementia, and mood disturbance, in addition with lumbago, baldness and Parkinson's symptoms but no migraine. Cranial MRI of the patient showed bilateral symmetric leukoencephalopathy and multiple small subcortical lacunar infarcts. A point mutation in exon 11 of the NOTCH3 gene (R558C) was discovered in the proband and four asymptomatic relatives. CONCLUSION: CADASIL is characterized by recurrent subcortical ischemic stroke, dementia, pseudobulbar palsy, and mood disturbance. Baldness, lumbago and Parkinson's symptoms may also be seen in such patients.


Assuntos
Alopecia/etiologia , CADASIL/complicações , Dor Lombar/etiologia , Transtornos Parkinsonianos/etiologia , CADASIL/diagnóstico por imagem , CADASIL/genética , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Receptor Notch3/genética
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