RESUMEN
BACKGROUND AND PURPOSE: Pulsatile tinnitus is experienced by most patients with idiopathic intracranial hypertension. The pathophysiology remains uncertain; however, transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence have been proposed as potential etiologies. We aimed to determine whether the prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence was increased in patients with idiopathic intracranial hypertension and pulsatile tinnitus relative to those without pulsatile tinnitus and a control group. MATERIALS AND METHODS: CT vascular studies of patients with idiopathic intracranial hypertension with pulsatile tinnitus (n = 42), without pulsatile tinnitus (n = 37), and controls (n = 75) were independently reviewed for the presence of severe transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence according to published criteria. The prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence in patients with idiopathic intracranial hypertension with pulsatile tinnitus was compared with that in the nonpulsatile tinnitus idiopathic intracranial hypertension group and the control group. Further comparisons included differing degrees of transverse sinus stenosis (50% and 75%), laterality of transverse sinus stenosis/sigmoid sinus diverticulum/dehiscence, and ipsilateral transverse sinus stenosis combined with sigmoid sinus diverticulum/dehiscence. RESULTS: Severe bilateral transverse sinus stenoses were more frequent in patients with idiopathic intracranial hypertension than in controls (P < .001), but there was no significant association between transverse sinus stenosis and pulsatile tinnitus within the idiopathic intracranial hypertension group. Sigmoid sinus dehiscence (right- or left-sided) was also more common in patients with idiopathic intracranial hypertension compared with controls (P = .01), but there was no significant association with pulsatile tinnitus within the idiopathic intracranial hypertension group. CONCLUSIONS: While our data corroborate previous studies demonstrating increased prevalence of sigmoid sinus diverticulum/dehiscence and transverse sinus stenosis in idiopathic intracranial hypertension, we did not establish an increased prevalence in patients with idiopathic intracranial hypertension with pulsatile tinnitus compared with those without. It is therefore unlikely that these entities represent a direct structural correlate of pulsatile tinnitus in patients with idiopathic intracranial hypertension.
Asunto(s)
Senos Craneales/patología , Seudotumor Cerebral/complicaciones , Acúfeno/etiología , Anciano , Constricción Patológica/complicaciones , Constricción Patológica/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Seudotumor Cerebral/patologíaRESUMEN
BACKGROUND: The syndrome of subacute simultaneous peripheral neuropathy and bilateral optic neuropathy is known to occur in tropical countries, probably due to malnutrition or toxicity, but not often seen in developed countries. We report seven patients in London who were not malnourished or alcoholic, and in whom no clear cause was found. METHODS: We retrospectively reviewed the case notes and arranged some further investigations. RESULTS: All patients developed peripheral and bilateral optic neuropathy within 6 months. Patients were aged 30-52, and all of Jamaican birth and race but lived in the UK. Most had subacute, painful ataxic sensory axonal neuropathy or neuronopathy, some with myelopathy. Nerve conduction studies revealed minor demyelinating features in two cases. The optic neuropathy was symmetrical, subacute and monophasic, usually with marked reduction in visual acuity. CSF protein concentration was usually elevated but other laboratory investigations were normal. Patients showed only modest improvement at follow-up. CONCLUSION: These patients share a common clinical and electrophysiological phenotype, age, ethnicity and elevated CSF protein, but otherwise normal laboratory investigations. The syndrome is a cause of significant morbidity in young people. The cause remains uncertain despite thorough investigation.
Asunto(s)
Enfermedades del Nervio Óptico/complicaciones , Enfermedades del Nervio Óptico/etiología , Enfermedades del Sistema Nervioso Periférico/complicaciones , Enfermedades del Sistema Nervioso Periférico/etiología , Adulto , Alcoholismo/epidemiología , Antiinflamatorios/uso terapéutico , Proteínas del Líquido Cefalorraquídeo/análisis , Electromiografía , Electrorretinografía , Potenciales Evocados Visuales/fisiología , Femenino , Humanos , Londres/epidemiología , Masculino , Persona de Mediana Edad , Conducción Nerviosa , Examen Neurológico , Estado Nutricional , Enfermedades del Nervio Óptico/tratamiento farmacológico , Dolor/etiología , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Polineuropatías/complicaciones , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/complicaciones , Estudios Retrospectivos , Esteroides/uso terapéutico , Síndrome , Agudeza VisualRESUMEN
BACKGROUND: The majority of prolactinomas respond to dopamine agonist therapy, but a proportion are resistant, requiring other treatments including surgery and/or radiotherapy. Temozolomide is an oral chemotherapy agent, which has been used as a salvage therapy to treat aggressive pituitary adenomas and carcinomas, including prolactinomas, unresponsive to all conventional treatment. CASE SERIES: We report three patients where temozolomide was used in the treatment of refractory prolactinomas. Case 1 describes a patient with a highly invasive prolactinoma, resistant to all conventional therapy, which responded dramatically to temozolomide used as a salvage treatment. In case 2, temozolomide was used after incomplete surgical resection to relieve chiasmal compression and avoid chiasm exposure to radiotherapy. In case 3, temozolomide enabled radiotherapy to be deferred in a 16-year old with a resistant prolactinoma. In all three cases, the tumours were negative by immunostaining for methylguanine methyltransferase (MGMT). LITERATURE REVIEW AND DISCUSSION: A review of the published literature reveals 51 reported cases of temozolomide treatment for pituitary tumours, including 20 prolactinomas. Fifteen of the 20 prolactinomas showed a good response to temozolomide. Our analysis demonstrates a strong association between MGMT-negative staining and a good response to temozolomide (OR 9.35, P = 0.0030). Current clinical practice is to use temozolomide as a salvage therapy after all conventional modalities of treatment have failed. We suggest that, in selected cases, consideration should be given to using temozolomide earlier in the treatment algorithm.
Asunto(s)
Dacarbazina/análogos & derivados , Agonistas de Dopamina/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Prolactinoma/tratamiento farmacológico , Adolescente , Adulto , Dacarbazina/uso terapéutico , Humanos , Masculino , TemozolomidaRESUMEN
Optic nerve disorders range from the manifestations of life-threatening intracranial or systemic disease, to minor congenital anomalies. Careful clinical assessment, which relies upon a thorough evaluation of symptoms as well as signs, is essential for effective and timely investigation and treatment. Examination methods and pitfalls to be avoided are discussed.
Asunto(s)
Enfermedades del Nervio Óptico/diagnóstico , Percepción de Color/fisiología , Humanos , Disco Óptico/fisiología , Enfermedades del Nervio Óptico/complicaciones , Enfermedades del Nervio Óptico/fisiopatología , Pupila/fisiología , Trastornos de la Visión/etiología , Pruebas de Visión/métodos , Agudeza Visual/fisiología , Campos Visuales/fisiologíaRESUMEN
An overview of possible treatment options for oculomotor disorders that prevent clear vision is given. Downbeat nystagmus, upbeat nystagmus, seesaw nystagmus, periodic alternating nystagmus, acquired pendular nystagmus, and saccadic oscillations such as opsoclonus/ocular flutter are discussed. In addition, superior oblique myokymia and vestibular paroxysmia are reviewed. All treatment recommendations available in the literature are classified as class C only. In general, only some of the patients benefit from the treatment.
Asunto(s)
Comités Consultivos , Nistagmo Patológico/tratamiento farmacológico , Animales , Anticonvulsivantes/uso terapéutico , Europa (Continente) , Agonistas del GABA/uso terapéutico , Humanos , Nistagmo Patológico/fisiopatología , Enfermedades del Nervio Oculomotor/tratamiento farmacológico , Enfermedades del Nervio Oculomotor/fisiopatologíaRESUMEN
The diagnosis of functional visual loss-reduced visual performance in the absence of an organic cause-is usually made by exclusion. We conducted a pilot study to evaluate pupil perimetry in three patients (aged 14, 43 and 50) with visual field loss presumed to be functional on clinical grounds and having no cause identified by visual electrophysiology or magnetic resonance imaging. A modified automated perimeter was used to examine visual and pupil responses to a light stimulus (size 1.7 degrees ) presented at five locations in the visual field (fixation and in each of the four quadrants). In each patient, the pupil responses were normal in those test quadrants which showed apparent visual field loss. Pupil perimetry provides objective evidence for a diagnosis of functional visual field loss in selected patients and may circumvent the need for other investigations.
Asunto(s)
Reflejo Pupilar , Trastornos de la Visión/diagnóstico , Pruebas del Campo Visual/métodos , Campos Visuales , Adolescente , Adulto , Humanos , Persona de Mediana Edad , Proyectos Piloto , Trastornos de la Visión/fisiopatologíaAsunto(s)
Epistaxis/complicaciones , Neuropatía Óptica Isquémica/complicaciones , Hemorragia Uterina/complicaciones , Trastornos de la Visión/etiología , Adulto , Epistaxis/fisiopatología , Femenino , Angiografía con Fluoresceína/métodos , Humanos , Masculino , Persona de Mediana Edad , Neuropatía Óptica Isquémica/fisiopatología , Factores de Riesgo , Trastornos de la Visión/fisiopatología , Campos Visuales/fisiologíaRESUMEN
Leber's hereditary optic neuropathy (LHON) is a common cause of bilateral optic nerve disease. The majority of LHON patients harbour one of three point mutations of the mitochondrial DNA (mtDNA) complex I, or NADH:ubiquinone oxidoreductase (ND) genes (G11778A in ND4, G3460A in ND1, T14484C in ND6). As a consequence, screening for these mutations has become part of the routine clinical investigation of young adults who present with bilateral optic neuropathy, and the absence of these mutations is interpreted as indicating there is a low likelihood that an optic neuropathy is LHON. However, there are many individuals who develop the clinical features of LHON but who do not harbour one of these primary LHON mutations. We describe two LHON pedigrees that harbour the same novel point mutation within the mtDNA ND6 gene (A14495G). This mutation was heteroplasmic in both families, and sequencing of the mitochondrial genome confirmed that the mutation arose on two independent occasions. This is the seventh mutation in the ND6 gene that causes optic neuropathy, indicating that this gene is a hot spot for LHON mutations. Protein modelling studies indicate that all of these pathogenic mutations lie within close proximity to one another in a hydrophobic cleft or pocket. This is the first evidence for a relationship between a specific disease phenotype and a specific structural domain within a mitochondrial respiratory chain subunit. These findings suggest that the mtDNA ND6 gene should be sequenced in all patients with LHON who do not harbour one of the three common LHON mutations.
Asunto(s)
ADN Mitocondrial/genética , Mutación/genética , NADH NADPH Oxidorreductasas/genética , Atrofias Ópticas Hereditarias/diagnóstico , Atrofias Ópticas Hereditarias/genética , Adolescente , Adulto , Sustitución de Aminoácidos , Secuencia Conservada , Análisis Mutacional de ADN , Complejo I de Transporte de Electrón , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mitocondrias/enzimología , Mitocondrias/genética , Linaje , Polimorfismo Genético , Estructura Secundaria de Proteína/genética , Estructura Terciaria de Proteína/genéticaRESUMEN
Congenital or acquired periodic alternating nystagmus (PAN) is characterized by nystagmus occurring in a cycle. The cycle consists of a left-beating nystagmus, a transition phase, a right-beating nystagmus, and a further transition phase. The purpose of this review is to assist the clinician in the recognition of periodic alternating nystagmus (PAN), either as a type of congenital nystagmus or in its acquired form, and to highlight why such identification is important. Recent studies using eye movement recordings are reviewed to point out the frequency of congenital PAN in samples of patients with congenital nystagmus, and to describe the characteristics of the waveforms and the influence of foveation time on the alternation of head turns. Classical and new surgical alternatives are reported. The identification of congenital PAN is essential when surgical treatment is being considered for the correction of anomalous head postures. Acquired PAN is usually due to cerebellar disease and causes oscillopsia. Unlike other forms of acquired nystagmus, it responds well to drug treatment.
Asunto(s)
Nistagmo Congénito/diagnóstico , Baclofeno/uso terapéutico , Técnicas de Diagnóstico Oftalmológico , Movimientos Oculares , Agonistas del GABA/uso terapéutico , Humanos , Nistagmo Congénito/tratamiento farmacológico , Nistagmo Congénito/cirugíaRESUMEN
Epilepsy patients treated with vigabatrin may develop symptomatic or asymptomatic concentric visual field constriction due to GABA-associated retinal dysfunction. The prevalence and course of this side effect are not established yet; in previously reported adult patients the visual disturbances seem to be irreversible. We present two patients with a significant improvement of visual field constriction and retinal function after the discontinuation of vigabatrin. These findings suggest that vigabatrin-associated retinal changes are at least partly reversible in some patients, and that these patients may benefit significantly from a withdrawal of vigabatrin. Larger scale clinical studies are needed to identify predictive factors both for the occurrence and reversibility of vigabatrin-associated visual field defects.
Asunto(s)
4-Aminobutirato Transaminasa/antagonistas & inhibidores , Anticonvulsivantes/efectos adversos , Epilepsia/tratamiento farmacológico , Vigabatrin/efectos adversos , Campos Visuales/efectos de los fármacos , Adulto , Epilepsia/enzimología , Humanos , Masculino , Persona de Mediana Edad , Recuperación de la Función , Retina/efectos de los fármacosRESUMEN
Polymorphism in mitochondrial DNA necessitates careful scrutiny of potentially pathogenic mutations to establish their true pathogenic significance. Research on Leber hereditary optic neuropathy continues to provide insights into the pathogenesis of mitochondrial disease. Interest in the retinal manifestations of mitochondrial disease has highlighted the macular dystrophy of the 3243 mutation, particularly in association with the syndrome of maternally inherited diabetes and deafness. Mitochondrial encephalopathies present in a number of ways, but imaging predominantly shows abnormalities of myelin and grey-matter nuclei. The mitochondrial myopathies provide insights into interactions between nuclear and mitochondrial DNA mutations and parallels between mitochondrial diseases and aging.
Asunto(s)
Miopatías Mitocondriales/complicaciones , Atrofias Ópticas Hereditarias/etiología , Enfermedades de la Retina/etiología , Envejecimiento/genética , ADN Mitocondrial/análisis , ADN Mitocondrial/genética , Diagnóstico Diferencial , Diagnóstico por Imagen , Humanos , Miopatías Mitocondriales/diagnóstico , Miopatías Mitocondriales/genética , Mutación , Atrofias Ópticas Hereditarias/diagnóstico , Atrofias Ópticas Hereditarias/genética , Polimorfismo Genético , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/genéticaRESUMEN
PURPOSE: To compare pupil function with visual function in patients with Leber's hereditary optic neuropathy (LHON) and age-matched normal control subjects. METHODS: Visual function was assessed by measuring the perceptual thresholds at five central locations in the visual field using automated static perimetry. Pupil function was assessed by recording the pupil responses to a standard intensity light stimulus (size equivalent to a Goldmann V target) presented at the same five locations in the visual field. The extent of the pupil afferent defect in LHON patients was quantified by establishing the relationship between stimulus intensity and the size of the pupil response in normal subjects and then interpolating the equivalent luminance deficit in LHON patients from the size of their pupil responses. RESULTS: At all five locations tested, the pupil responses were significantly reduced in amplitude, and the perceptual thresholds were significantly raised in LHON patients compared with normal control subjects. A nonparametric analysis of perceptual and pupil responses to perithreshold stimuli showed that a stimulus that was not perceived was three times more likely to be followed by a pupil response in a LHON patient than in a normal subject (P < 0.001). A quantitative comparison showed that the visual deficits exceeded the pupil deficits by on average 7.5 dB at all tested locations. CONCLUSIONS: Although both visual and pupil function are abnormal in LHON, there appears to be relative sparing of the pupil afferent fibers.
Asunto(s)
Atrofias Ópticas Hereditarias/fisiopatología , Trastornos de la Pupila/fisiopatología , Pupila/fisiología , Trastornos de la Visión/fisiopatología , Percepción Visual/fisiología , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Reflejo Pupilar/fisiología , Agudeza Visual/fisiología , Pruebas del Campo Visual , Campos Visuales/fisiologíaAsunto(s)
Nervio Abducens , Carcinoma de Células Escamosas/secundario , Diplopía/etiología , Neoplasias Pulmonares , Neoplasias Craneales/secundario , Hueso Temporal , Anciano , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/diagnóstico por imagen , Enfermedades de los Nervios Craneales/diagnóstico por imagen , Enfermedades de los Nervios Craneales/etiología , Diplopía/diagnóstico por imagen , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Neoplasias Craneales/complicaciones , Neoplasias Craneales/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Three patients with episodic ocular torsion and skew deviation due to mesodiencephalic lesions were studied by using binocular three-dimensional scleral search coils. The conjugate ocular torsion (upper pole of each eye rotating toward the side of the brainstem lesion) was initiated by a torsional fast eye movement. During prolonged episodes, torsional nystagmus was also present. Cessation of the ocular torsion and skew deviation occurred by slow eye movements with exponentially decreasing velocities in 2 patients, and by multiple fast torsional movements in 1 patient. In 1 patient, the abnormal eye movements were temporally linked to dystonic movements in the limbs on the side opposite the brainstem lesion. The occurrence of skew deviation with conjugate ocular torsion in brainstem lesions has been attributed to functional asymmetry in vestibular pathways responsible for the slow-phase compensatory eye movement response to roll. In comparison, the findings in our patients show that in mesodiencephalic lesions conjugate ocular torsion with skew deviation may be generated by torsional fast eye movements, indicating activation of the burst cells of the rostral interstitial nucleus of the medial longitudinal fasciculus.