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1.
Hum Mol Genet ; 28(18): 3113-3125, 2019 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-31211835

RESUMEN

Oculomotor synkinesis is the involuntary movement of the eyes or eyelids with a voluntary attempt at a different movement. The chemokine receptor CXCR4 and its ligand CXCL12 regulate oculomotor nerve development; mice with loss of either molecule have oculomotor synkinesis. In a consanguineous family with congenital ptosis and elevation of the ptotic eyelid with ipsilateral abduction, we identified a co-segregating homozygous missense variant (c.772G>A) in ACKR3, which encodes an atypical chemokine receptor that binds CXCL12 and functions as a scavenger receptor, regulating levels of CXCL12 available for CXCR4 signaling. The mutant protein (p.V258M) is expressed and traffics to the cell surface but has a lower binding affinity for CXCL12. Mice with loss of Ackr3 have variable phenotypes that include misrouting of the oculomotor and abducens nerves. All embryos show oculomotor nerve misrouting, ranging from complete misprojection in the midbrain, to aberrant peripheral branching, to a thin nerve, which aberrantly innervates the lateral rectus (as seen in Duane syndrome). The abducens nerve phenotype ranges from complete absence, to aberrant projections within the orbit, to a normal trajectory. Loss of ACKR3 in the midbrain leads to downregulation of CXCR4 protein, consistent with reports that excess CXCL12 causes ligand-induced degradation of CXCR4. Correspondingly, excess CXCL12 applied to ex vivo oculomotor slices causes axon misrouting, similar to inhibition of CXCR4. Thus, ACKR3, through its regulation of CXCL12 levels, is an important regulator of axon guidance in the oculomotor system; complete loss causes oculomotor synkinesis in mice, while reduced function causes oculomotor synkinesis in humans.


Asunto(s)
Actividad Motora/genética , Desempeño Psicomotor , Receptores CXCR/genética , Receptores CXCR/metabolismo , Sincinesia/etiología , Sincinesia/metabolismo , Alelos , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Animales Modificados Genéticamente , Biomarcadores , Análisis Mutacional de ADN , Modelos Animales de Enfermedad , Técnica del Anticuerpo Fluorescente , Expresión Génica , Estudios de Asociación Genética , Ligamiento Genético , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Inmunohistoquímica , Ratones , Mutación , Linaje , Polimorfismo de Nucleótido Simple , Transporte de Proteínas , Receptores CXCR/química , Sincinesia/diagnóstico , Sincinesia/fisiopatología
2.
Eye (Lond) ; 26(8): 1095-8, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22627480

RESUMEN

PURPOSE: Adults with facial nerve paresis (FNP) generally develop ectropion, but a recent report of children with syndromatic FNPs implies that entropion may be more common in this setting than ectropion. This study evaluates eyelid position and other periorbital changes in children with isolated, non-syndromatic FNP. METHODS: Charts were reviewed of 10 sequential children who presented to a major national eye referral centre with isolated FNP of variable aetiology. Severity of FNP was assessed according to the House-Brackmann scale. RESULTS: All 10 patients (4 males and 6 females; mean age at presentation, 4 years) had unilateral, isolated FNP. Mild lower-eyelid entropion was present in four patients, and severe lower-eyelid entropion required surgical correction in three patients. All patients had lower eyelid retraction (mean 2.3 mm) and lagophthalmos (mean 2.9 mm). None had enophthalmos, lower eyelid ectropion, or brow ptosis. CONCLUSION: Unlike adults, children with isolated FNP seem prone to develop entropion rather than ectropion. Entropion reported previously in five syndromic children with FNP seems more likely related to patients' age than to their congenital syndromes.


Asunto(s)
Entropión/etiología , Parálisis Facial/complicaciones , Blefaroplastia , Niño , Preescolar , Entropión/cirugía , Parálisis Facial/congénito , Femenino , Humanos , Masculino
3.
Eye (Lond) ; 26(4): 583-92, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22193879

RESUMEN

PURPOSE: To report clinical observations and surgical management in a large series of patients with orbitofacial neurofibromatosis type 1 (OFNF). PATIENTS AND METHODS: Patients were identified and medical records reviewed for demographic data, ophthalmologic examinations, surgical interventions, and procedure outcome to create a retrospective, non-comparative case series of patients with OFNF seen at one medical centre over a 23-year period. RESULTS: Sixty patients with OFNF (31 females and 29 males; mean age, 14 years) were followed for an average of 5.7 years. Presenting signs and symptoms included eyelid swelling in all patients, ptosis in 56 (93.3%), proptosis in 34 (56.6%), dystopia or strabismus in 30 (50%), and decreased visual acuity in 50 (83.3%). Surgical intervention included ptosis repair in 54 (90%; mean 1.6 surgical procedures), facial and orbital tumour debulking in 54 (90%; mean 2.3 surgeries), and canthoplasty in 28 (46.6%) patients. Eleven patients required enucleation or exenteration of a blind eye. CONCLUSION: Patients with OFNF often require multiple procedures to preserve vision, prevent additional disfigurement, and achieve cosmetic rehabilitation. Patients need regular ophthalmological monitoring given the potential for progressive visual and cosmetic consequences.


Asunto(s)
Neoplasias Faciales/cirugía , Neurofibromatosis 1/cirugía , Neoplasias Orbitales/cirugía , Adolescente , Adulto , Niño , Preescolar , Neoplasias Faciales/patología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neurofibromatosis 1/patología , Neoplasias Orbitales/patología , Estudios Retrospectivos , Arabia Saudita , Tomografía Computarizada por Rayos X , Agudeza Visual , Adulto Joven
4.
Br J Ophthalmol ; 93(8): 1101-4, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19286687

RESUMEN

AIM: To investigate whether the prevalence GSTT1 and GSTM1 deletion genotypes (T0M1, T1M0 and T0M0) are increased in certain spontaneous optic neuropathies. METHODS: We compared the prevalence of GSTT1 and GSTM1 deletion genotypes in 108 Arab patients with optic neuritis (ON, 26 patients), LHON-like optic neuropathy (LLON, 35 patients), sporadic bilateral optic neuropathy in children (SBON, 21 patients) and non-arteritic ischaemic optic neuropathy (NAION, 26 patients) to 120 ethnicity-matched controls. Genotypes were determined by multiplex polymerase chain reaction. RESULTS: All three GST deletion genotypes were significantly more prevalent in the entire optic neuropathy group than in controls. When patients were stratified by optic neuropathy type, the prevalence of at least one deletion genotype was significantly increased in each type of optic neuropathy. CONCLUSIONS: These results imply that GST malfunction in the setting of GST deletion genotypes may interfere with metabolism of oxidative intermediates and may exacerbate direct or indirect pathological effects of oxidative stress on the optic nerve in the setting of these spontaneous optic neuropathies. It is possible that these GST polymorphisms are risk factors for the types of optic neuropathies investigated here.


Asunto(s)
Eliminación de Gen , Glutatión Transferasa/genética , Enfermedades del Nervio Óptico/genética , Adolescente , Adulto , Anciano , Árabes/genética , Niño , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
5.
Neurology ; 69(12): 1245-53, 2007 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-17875913

RESUMEN

BACKGROUND: The Bosley-Salih-Alorainy syndrome (BSAS) variant of the congenital human HOXA1 syndrome results from autosomal recessive truncating HOXA1 mutations. We describe the currently recognized spectrum of ocular motility, inner ear malformations, cerebrovascular anomalies, and cognitive function. METHODS: We examined nine affected individuals from five consanguineous Saudi Arabian families, all of whom harbored the same I75-I76insG homozygous mutation in the HOXA1 gene. Patients underwent complete neurologic, neuro-ophthalmologic, orthoptic, and neuropsychological examinations. Six individuals had CT, and six had MRI of the head. RESULTS: All nine individuals had bilateral Duane retraction syndrome (DRS) type 3, but extent of abduction and adduction varied between eyes and individuals. Eight patients were deaf with the common cavity deformity of the inner ear, while one patient had normal hearing and skull base development. Six had delayed motor milestones, and two had cognitive and behavioral abnormalities meeting Diagnostic and Statistical Manual of Mental Disorders-IV criteria for autism spectrum disorder. MRI of the orbits, extraocular muscles, brainstem, and supratentorial brain appeared normal. All six appropriately studied patients had cerebrovascular malformations ranging from unilateral internal carotid artery hypoplasia to bilateral agenesis. CONCLUSIONS: This report extends the Bosley-Salih-Alorainy syndrome phenotype and documents the clinical variability resulting from identical HOXA1 mutations within an isolated ethnic population. Similarities between this syndrome and thalidomide embryopathy suggest that the teratogenic effects of early thalidomide exposure in humans may be due to interaction with the HOX cascade.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Proteínas de Homeodominio/genética , Mutación/genética , Malformaciones del Sistema Nervioso/genética , Malformaciones del Sistema Nervioso/fisiopatología , Factores de Transcripción/genética , Adolescente , Adulto , Arteria Carótida Interna/anomalías , Arteria Carótida Interna/patología , Arteria Carótida Interna/fisiopatología , Niño , Preescolar , Trastornos del Conocimiento/genética , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Sordera/genética , Sordera/patología , Sordera/fisiopatología , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Discapacidades del Desarrollo/fisiopatología , Oído Interno/anomalías , Oído Interno/patología , Oído Interno/fisiopatología , Femenino , Marcadores Genéticos , Humanos , Imagen por Resonancia Magnética , Masculino , Malformaciones del Sistema Nervioso/patología , Trastornos de la Motilidad Ocular/genética , Trastornos de la Motilidad Ocular/fisiopatología , Fenotipo , Arabia Saudita , Base del Cráneo/anomalías , Base del Cráneo/patología , Base del Cráneo/fisiopatología , Síndrome
6.
Br J Ophthalmol ; 90(7): 823-5, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16540486

RESUMEN

AIM: To investigate possible changes in relative mitochondrial DNA (mtDNA) content in patients with non-arteritic anterior ischaemic optic neuropathy (NAION). METHODS: 19 patients with NAION were compared to 32 controls matched for age, sex distribution, and ethnicity. DNA was extracted from leucocytes and competitive multiplex polymerase chain reaction was carried out with two primer pairs (one pair for mtDNA ND1 gene and the other pair for beta actin nuclear gene) in the presence of a fluorescent dye. RESULTS: The mean relative mtDNA content in controls (0.93 (SD 0.11); 95% CI 0.89 to 0.97) was significantly less than in NAION patients (2.40 (1.05); 95% CI 1.90 to 2.91; p < 0.001). Relative mtDNA content was negatively correlated with Snellen visual acuity (Spearman's rho; r = -0.37; p = 0.022). CONCLUSION: Increased relative mtDNA content in NAION patients may imply a response to oxidative stress, possibly in part because of mitochondrial respiratory chain defects. Significantly more non-synonymous mtDNA nucleotide changes, significantly increased relative mtDNA content, and a significant association between relative mtDNA content and visual acuity all imply that mitochondrial abnormalities may be a risk factor for NAION.


Asunto(s)
ADN Mitocondrial/análisis , Leucocitos Mononucleares/ultraestructura , Neuropatía Óptica Isquémica/genética , Adulto , Anciano , Estudios de Casos y Controles , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuropatía Óptica Isquémica/fisiopatología , Reacción en Cadena de la Polimerasa/métodos , Agudeza Visual
9.
Neurology ; 64(7): 1196-203, 2005 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-15824346

RESUMEN

OBJECTIVE: To review the neurologic, neuroradiologic, and electrophysiologic features of autosomal recessive horizontal gaze palsy and progressive scoliosis (HGPPS), a syndrome caused by mutation of the ROBO3 gene on chromosome 11 and associated with defective decussation of certain brainstem neuronal systems. METHODS: The authors examined 11 individuals with HGPPS from five genotyped families with HGPPS. Eight individuals had brain MRI, and six had electrophysiologic studies. RESULTS: Horizontal gaze palsy was fully penetrant, present at birth, and total or almost total in all affected individuals. Convergence, ocular alignment, congenital nystagmus, and vertical smooth pursuit defects were variable between individuals. All patients developed progressive scoliosis during early childhood. All appropriately studied patients had hypoplasia of the pons and cerebellar peduncles with both anterior and posterior midline clefts of the pons and medulla and electrophysiologic evidence of ipsilateral corticospinal and dorsal column-medial lemniscus tract innervation. Heterozygotes were unaffected. CONCLUSIONS: The major clinical characteristics of horizontal gaze palsy and progressive scoliosis were congenital horizontal gaze palsy and progressive scoliosis with some variability in both ocular motility and degree of scoliosis. The syndrome also includes a distinctive brainstem malformation and defective crossing of some brainstem neuronal pathways.


Asunto(s)
Mutación/genética , Malformaciones del Sistema Nervioso/genética , Trastornos de la Motilidad Ocular/fisiopatología , Receptores Inmunológicos/genética , Escoliosis/fisiopatología , Adolescente , Adulto , Tronco Encefálico/anomalías , Tronco Encefálico/fisiopatología , Niño , Preescolar , Trastornos de los Cromosomas/genética , Análisis Mutacional de ADN , Femenino , Genes Recesivos/genética , Pruebas Genéticas , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Malformaciones del Sistema Nervioso/diagnóstico , Malformaciones del Sistema Nervioso/fisiopatología , Vías Nerviosas/anomalías , Vías Nerviosas/fisiopatología , Trastornos de la Motilidad Ocular/diagnóstico , Trastornos de la Motilidad Ocular/genética , Linaje , Receptores de Superficie Celular , Escoliosis/genética , Síndrome
11.
Neurology ; 59(3): 432-5, 2002 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-12177379

RESUMEN

Horizontal gaze palsy with progressive scoliosis (HGPS) is a rare, autosomal recessive disorder characterized by a congenital absence of conjugate horizontal eye movement, with progressive scoliosis developing in childhood or adolescence. The authors identified two unrelated consanguineous families with HGPS. Genomewide homozygosity mapping and linkage analysis mapped the disease locus to a 30-cM interval on chromosome 11q23-25 (combined maximum multipoint lod score Z = 5.46).


Asunto(s)
Mapeo Cromosómico/métodos , Cromosomas Humanos Par 11/genética , Trastornos de la Motilidad Ocular/genética , Escoliosis/genética , Adolescente , Niño , Preescolar , Mapeo Cromosómico/estadística & datos numéricos , Consanguinidad , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Nistagmo Patológico/genética , Enfermedades del Nervio Oculomotor/genética , Linaje
12.
Nat Genet ; 29(3): 315-20, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11600883

RESUMEN

Isolated strabismus affects 1-5% of the general population. Most forms of strabismus are multifactorial in origin; although there is probably an inherited component, the genetics of these disorders remain unclear. The congenital fibrosis syndromes (CFS) represent a subset of monogenic isolated strabismic disorders that are characterized by restrictive ophthalmoplegia, and include congenital fibrosis of the extraocular muscles (CFEOM) and Duane syndrome (DURS). Neuropathologic studies indicate that these disorders may result from the maldevelopment of the oculomotor (nIII), trochlear (nIV) and abducens (nVI) cranial nerve nuclei. To date, five CFS loci have been mapped (FEOM1, FEOM2, FEOM3, DURS1 and DURS2), but no genes have been identified. Here, we report three mutations in ARIX (also known as PHOX2A) in four CFEOM2 pedigrees. ARIX encodes a homeodomain transcription factor protein previously shown to be required for nIII/nIV development in mouse and zebrafish. Two of the mutations are predicted to disrupt splicing, whereas the third alters an amino acid within the conserved brachyury-like domain. These findings confirm the hypothesis that CFEOM2 results from the abnormal development of nIII/nIV (ref. 7) and emphasize a critical role for ARIX in the development of these midbrain motor nuclei.


Asunto(s)
Síndrome de Retracción de Duane/genética , Proteínas de Homeodominio/genética , Homocigoto , Mutación/genética , Estrabismo/genética , Factores de Transcripción/genética , Secuencia de Aminoácidos , Secuencia de Bases , Mapeo Contig , Análisis Mutacional de ADN , Anomalías del Ojo/genética , Femenino , Haplotipos/genética , Humanos , Masculino , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso , Linaje , Fenotipo , Polimorfismo Genético/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia
13.
Neuroradiology ; 43(2): 178-82, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11326568

RESUMEN

We report two patients with abnormal development of the lesser wing of the sphenoid bone, globe, optic nerve and cerebral hemisphere without stigmata of neurofibromatosis type 1. The lesser wing of the sphenoid bone was abnormally formed and was not ossified ipsilateral to the dysmorphic eye and underdeveloped cerebral hemisphere. Maldevelopment of the sphenoid wing may interfere with the normal closure of the optic vesicle and normal growth of encephalic structures, possibly by disturbing developmental tissue interactions. These patients may exhibit a type of restricted primary sphenoid dysplasia, while the sphenoid dysplasia of neurofibromatosis type 1 may be secondary to orbital or ocular neurofibromas and other factors associated with that disease.


Asunto(s)
Microcefalia/diagnóstico por imagen , Microftalmía/diagnóstico por imagen , Hueso Esfenoides/anomalías , Tomografía Computarizada por Rayos X , Niño , Humanos , Masculino , Microcefalia/complicaciones , Microftalmía/complicaciones , Neurofibromatosis 1/diagnóstico
14.
Neuroradiology ; 42(2): 121-3, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10663489

RESUMEN

We report the MRI appearances of an developmental anatomical variant of the basiocciput, with neuroimaging findings (CT and MRI). Such variants are commonly asymptomatic, but may be associated with episodes of meningitis.


Asunto(s)
Imagen por Resonancia Magnética , Hueso Esfenoides/patología , Niño , Fosa Craneal Posterior/patología , Femenino , Estudios de Seguimiento , Humanos , Meningitis/diagnóstico , Meningitis/diagnóstico por imagen , Papiledema/diagnóstico , Tomografía Computarizada por Rayos X , Agudeza Visual
15.
Eye (Lond) ; 14 ( Pt 1): 82-7, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10755107

RESUMEN

PURPOSE: To better describe the clinical and neuroimaging spectrum of abnormalities in clinical anophthalmos. METHODS: We performed a retrospective review of all 17 patients admitted to the King Khaled Eye Specialist Hospital with clinical anophthalmos over a 15 year period who had a complete ophthalmological examination documented and received computed tomographic (CT) imaging of the orbits and brain. RESULTS: Patients with clinical anophthalmos had a high incidence of developmental abnormalities involving both eyes (15/17 patients, 88%), the brain (12/17 patients, 71%) and the body (7/12, 58%). The incidence of central nervous system anomalies reached 100% in patients with bilateral small optic nerves on CT scan. CONCLUSIONS: Patients with clinical anophthalmos share a similar constellation of neurological, somatic and neuroradiological abnormalities as patients with microphthalmos, septo-optic dysplasia and clinical optic nerve hypoplasia. This fact may provide insight into developmental abnormalities of the afferent visual system and brain.


Asunto(s)
Anomalías Múltiples/diagnóstico por imagen , Anoftalmos/diagnóstico por imagen , Encéfalo/anomalías , Adulto , Niño , Preescolar , Anomalías del Ojo/diagnóstico por imagen , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Microftalmía/diagnóstico por imagen , Nervio Óptico/anomalías , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
16.
J Neuroophthalmol ; 19(4): 252-6, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10608680

RESUMEN

OBJECTIVES: The incidence of microvascular ocular cranial nerve palsies may be increasing with the prevalence of diabetes in the developing world. We review this problem for the first time in an Arabic population. MATERIALS AND METHODS: This is a prospective nonrandomized study of all patients with the diagnosis of microvascular cranial mononeuropathy seen in the Neuro-ophthalmology Clinic at the King Khaled Eye Specialist Hospital between September 1997 and April 1998. RESULTS: Forty-seven patients with microvascular palsies of cranial nerves 3, 4, or 6 were seen in this 8-month period. Compared to previous studies, this group had a stronger association with previously diagnosed diabetes mellitus, more males affected, and a longer duration of the cranial nerve palsy before complete resolution. Five patients had an unusual clinical course that included a second microvascular cranial mononeuropathy before the first palsy completely resolved. CONCLUSIONS: Microvascular cranial nerve palsies may occur more frequently in this Arabic population than elsewhere and may have certain unusual features.


Asunto(s)
Enfermedades de los Nervios Craneales/epidemiología , Enfermedades de los Nervios Craneales/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de los Nervios Craneales/etiología , Neuropatías Diabéticas/fisiopatología , Femenino , Humanos , Incidencia , Masculino , Microcirculación , Persona de Mediana Edad , Enfermedad de la Neurona Motora/fisiopatología , Estudios Prospectivos , Factores de Riesgo , Arabia Saudita , Distribución por Sexo , Enfermedades Vasculares/complicaciones
17.
Int Ophthalmol ; 22(1): 59-60, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-10090451

RESUMEN

PURPOSE: To obtain information about the incidence of giant cell arteritis in Saudi Arabia. METHODS: Retrospective review of all temporal artery biopsies performed at the King Khaled Eye Specialist Hospital from December 1982 to January 1998. RESULTS: Seventy-two temporal artery biopsies were performed over this 15 year period, of which four were positive for giant cell arteritis. CONCLUSIONS: The incidence of GCA in Saudi Arabia is probably less than in the United States and Western Europe.


Asunto(s)
Arteritis de Células Gigantes/epidemiología , Anciano , Anciano de 80 o más Años , Biopsia , Reacciones Falso Negativas , Femenino , Arteritis de Células Gigantes/patología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Arabia Saudita/epidemiología , Arterias Temporales/patología
18.
J Neuroophthalmol ; 15(3): 136-40; discussion 140-1, 1995 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8574356

RESUMEN

Ten consecutive patients with acute relative pupillary sparing third nerve palsies were enrolled in a prospective study to determine the prevalence of intracranial aneurysm. All patients were imaged with either cerebral angiography or magnetic resonance angiography. None of the patients demonstrated an intracranial aneurysm. The prevalence of aneurysm in patients with relative pupillary sparing third nerve palsies may be low enough to preclude the use of routine angiography in this condition.


Asunto(s)
Aneurisma Intracraneal/diagnóstico , Enfermedades del Nervio Oculomotor/complicaciones , Pupila , Enfermedad Aguda , Anciano , Arteria Carótida Interna/diagnóstico por imagen , Angiografía Cerebral , Movimientos Oculares , Femenino , Humanos , Aneurisma Intracraneal/complicaciones , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Arteria Vertebral/diagnóstico por imagen
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