Ординатура / Офтальмология / Английские материалы / Imaging of Orbital and Visual Pathway Pathology_Muller-Forell_2005

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CONTENTS

5.1Introduction 127

5.1.1General Remarks 127

5.1.2 Normal Myelination of Optic Pathways 127

5.2Congenital Pathology of Optic Pathways:

Infantile Presentations 128

5.2.1General Remarks 128

5.2.2Microphthalmos/Anophthalmos 128

5.2.3Macrophthalmos/Buphthalmos 129

5.2.4Ocular Tumors 129

5.2.5Spasmus Nutans 130

5.2.6Congenital Nystagmus 130

5.2.8Retinal Blindness 133

5.3.1General Remarks 134

5.3.2Optic Neuritis 134

5.3.3Multiple Sclerosis 135

5.3.4Acute Disseminated Encephalomyelitis (ADEM) 135

5.3.6Intoxications 137

5.3.7 Trauma (Nonaccidental Injury) 137

5.3.8Proptosis 137

5.5.1General Remarks 140

5.5.2Occipital Lobe Lesions Presenting with Epilepsy 142

5.5.3Developmental Delay 142 References 143

E. Boltshauser, MD

Professor, Department of Child Neurology

E. Martin, MD

Professor, Department of Neuroradiology and Magnetic

Resonance, University Children’s Hospital, Steinwiesstrasse 75,

8032 Zürich, Switzerland

5.1 Introduction

5.1.1

General Remarks

The optic pathways can be involved in a large spectrum of congenital as well as acquired conditions in children. In this context, an approach guided by clinical presentations in a pediatric university hospital is preferable over an extensive review. Therefore, we have arbitrarily divided the chapter into:

•congenital pathology/infantile presentations

•acquired optic pathway lesions

•work-up in systemic diseases

•unexpected (incidental) findings

Any neuroimaging procedure should be based on profound clinical (including ophthalmological if appropriate) examination. This should allow the neuroradiologist to formulate specific questions.

We generally refer to standard textbooks for pediatric aspects of neurology (Aicardi 1998), ophthalmology (Brodsky et al. 1995; Nelson et al. 1991), neuroimaging (Barkovich 1995) and for defined syndromes (McKusick 1998).

5.1.2

Normal Myelination of Optic Pathways

Microscopic myelin of the visual system first appears in the optic tract during the 7th month of gestation. It then proceeds both rostrally to the optic chiasm and optic nerves and occipitally along the optic radiation to the occipital lobe. Around term, the intensity of myelin staining in the visual system approaches that of myelin in the mature brain (Yakovlev and Lecours

1967; Gilles et al. 1983; Van Der Knaap and Valk

1995), while the cortical visual system in man is believed to differentiate postnatally (Atkinson 1984). The development of stereopsis and visual topography during infancy is accompanied by changes in visual

evoked potential (VEP) signals and coincides with the most salient phases in the anatomical development of the human visual system (Garey 1984).

On magnetic resonance imaging, myelinated fiber tracts exhibit high signal intensity on short TR/TE and low signal intensity on long TR/TE images (Barkovich 1995; Van Der Knaap and Valk 1995). At birth, the ventrolateral region of the thalamus, the dorsal limb of the internal capsule, the central portion of the centrum semiovale, and the dorsolateral putamen show T1 hyperintense signals, indicating myelinated supratentorial structures. During the first postnatal month, the optic nerve, optic tract and optic radiation appear hyperintense on T1-weighted images, whereas low signal intensity on T2-weighted images is seen in the optic tract by the age of 1 month. During the subsequent 2 or 3 months this T2 hypointensity proceeds posteriorly along the optic radiation, ending in the subcortical white matter of the visual cortex. The occipital white matter of the calcarine area is the earliest subcortical area to be myelinated before the Rolandic area.Increasing signal intensity of the white matter of the primary visual cortex surrounding the calcarine fissure can be observed between 3 and 6 months of life on T1-weighted images and low signal intensity between 4 and 8 months on T2-weighted images.

tagmus can be associated with a number of conditions (such as albinism, aniridia, Leber amaurosis, achromatopsia,congenital dystrophy,stationary night blindness,optic nerve hypoplasia).Ophthalmological assessment often supplemented by electroretinography will assist to delineate most of these conditions.

5.2.2

Microphthalmos/Anophthalmos

Unior bilateral microphthalmos/anophthalmos may be seen in various conditions (Albernaz et al. 1997; Nelson et al. 1991). Neuroimaging is performed to assess orbital anatomy, optic chiasm, and posterior visual pathways as well as possible brain malformations. Typical cases are illustrated in Figs. 5.1–5.4. Aicardi syndrome, observed only in girls, is considered to result from an X-linked mutation that is lethal in boys. The relevant triad consists of a typical optic disc appearance with “chorioretinal lacunae”, infantile spasms, and agenesis of the corpus callosum (Aicardi 1992; Brodsky et al. 1995). In addition, other central nervous system malformations are always present, in particular migration anomalies (heterotopias, polymicrogyria) and midline arachnoid cysts.

5.2

Congenital Pathology of Optic Pathways: Infantile Presentations

5.2.1

General Remarks

In this section, a number of typical presentations will be discussed.

Depending on the situation, a careful ophthalmological examination has to supplement the general pediatric and neurological examination.A few“rules” may help in guiding further diagnostic steps and indicate where to focus on neuroimaging.

Cortical visual impairment (blindness) is not accompanied by nystagmus. Congenital nystagmus is not present at birth but has its onset at 2–3 months. In general, congenital nystagmus points to retinal or anterior optic pathway pathology. Clinical signs of retinal disease in congenital nystagmus are: photophobia,paradoxical pupillary responses,high myopia, oculodigital reflex. Bilateral nystagmus is only seen if the visual acuity is below 20/70. Congenital nys-

Fig. 5.1. T2/FSE axial magnetic resonance image (MRI) of a 5-month-old girl with unilateral anophthalmos (clinically). MRI shows normal orbital anatomy and normal brain

Fig. 5.2. a Axial T2-weighted , b parasagittal T1-weighted MRI of a 7-year-old boy with bilateral microphthalmos, marked mental retardation and epilepsy. Normal brain anatomy

Congenital eye malformations including microphthalmos are part of several genetically determined syndromes associated with neuronal migration disorders, such as Fukuyama congenital muscular dystrophy and Walker-Warburg syndrome (Barkovich 1995, 1998; McKusick 1994). Neuroimaging is essential in delineating these disorders.

Waugh et al. (1998) found a large proportion of additional brain pathology in a series of children with congenital disorders of the peripheral visual system.

5.2.3

Macrophthalmos/Buphthalmos

Buphthalmos may be a rare presentation of SturgeWeber syndrome. In a minority of patients, the typical port-wine trigeminal nevus may be missing.

b

Fig. 5.3a,b. T2 axial MRI of a 3-month-old girl with AICARDI syndrome: bilateral (asymmetric) microphthalmos, vermis hypoplasia, areas of polymicrogyria, multiple gray matter heterotopias, agenesis of corpus callosum and interhemispheric arachnoid cyst. (Reproduced with permission of Ferdinand Enke Verlag: Boltshauser et al. 1992, Fig. 4)

Fig. 5.4. Computed tomography (CT) of newborn with microphthalmos and cataracts: broad communication between lateral ventricles, Dandy-Walker like aspect of posterior fossa (not shown), cortical migration anomalies with polymicrogyria, evident in anterior interhemispheric fissure. Diagnosis: Walker-Warburg syndrome

also called“cat’s eye reflex”. Leukokoria generally represents an advanced stage of the disease. For detailed ophthalmological presentations, diagnostic work-up, and differential diagnosis, we refer to the standard ophthalmological literature. Computed tomography (CT) displays punctate or more homogeneous areas of calcification in 95% of retinoblastomas (Barkovich 1995).Contrast enhancement of tumor tissue is generally found. Contrast enhancement is also demonstrable with MRI. T1-weighted images reveal the tumor as hyperintense, T2-weighted images usually as a hypointense mass (Fig. 5.5). Proton density images may assist in the demarcation of the tumor. MRI can occasionally provide evidence of distal optic nerve infiltration.A large proportion of retinoblastomas are genetically determined,and about a third occurs bilaterally. When tumorous tissue is also demonstrated in the pineal region by neuroimaging, it is termed trilateral/trilocular retinoblastoma. This may already be present on initial evaluation.

5.2.5

Spasmus Nutans

So-called spasmus nutans typically presents at 6–12 months with disconjugate nystagmus, torticollis, and

head titubation. Review of a larger series of patients suggests that the association with optic glioma is extremely low.Neuroimaging of infants initially diagnosed with spasmus nutans may not be immediately necessary (Arnoldi and Trychsen 1995).

5.2.6

Congenital Nystagmus

We refer to 5.2.1 for general remarks about congenital nystagmus.

As outlined above, congenital nystagmus can be due to retinal diseases. Unless a systemic condition affecting both the retina and brain is considered, imaging does not have priority. However, some syndromes with retinal blindness (such as Leber amaurosis and Joubert syndrome) are often associated with cerebellar vermis hypoplasia (see 5.2.8).

5.2.6.1

Pelizaeus-Merzbacher Disease

Congenital nystagmus may be a presenting feature of a dysmyelinating disorder. A prototype is PelizaeusMerzbacher disease (PMD), due to mutations (usually duplication) of the proteolipid protein gene at Xq22. PMD typically has its onset in the first half year with (rotatory/irregular pendular) nystagmus, head nodding, and often congenital stridor, followed by cerebellar dysfunction and spasticity.Although an X-linked condition, a few cases with identical characteristic clinical and imaging findings have been seen in girls; an example is shown in Fig. 5.6. The neuroimaging appearance of PMD is that of a “lack” of myelination.

Fig. 5.5. T1/fat suppression axial MRI. Left intraocular tumor corresponding retinoblastoma. CT (not shown) with dense calcification

b

Fig. 5.6. a Axial, b coronal T2 MRI of an 18-month-old girl with a clinical constellation compatible with Pelizaeus-Mer- zbacher disease. Minimal myelination of the posterior limb of the internal capsule and cerebellar white matter, otherwise almost no myelin

5.2.6.2

Other White Matter Disorders

Apart from PMD, other dysmyelinating conditions can present with congenital nystagmus. The exact genetic/biochemical basis of these rare conditions is still unknown. An example of an infant with this presentation is illustrated in Fig. 5.7.

5.2.6.3

Septo-optic Dysplasia

5.2.6.4

Optic Nerve Hypoplasia

Hypoplasia of the optic nerves may be unior bilateral. It is not a clinical or pathogenetic entity. We have seen several children with unilateral optic nerve hypoplasia presenting to the ophthalmologist with “poor vision”or strabismus.The intracranial anterior optic pathways are usually markedly asymmetric, but additional anomalies are exceptional.

Septo-optic dysplasia (SOD) typically presents as congenital nystagmus. Fundus examination reveals

Fig. 5.7. Axial T2 MRI (mod.) of a 7-month-old girl with pendular nystagmus and hypotonia: “lack” of myelination, etiology unknown

a

b

Fig. 5.8. a Axial, b coronal T2-/FSE MRI of a 3-month-old-girl without visual fixation. Absent septum pellucidum and almost no identifiable optic nerves. Diagnosis: septo-optic dysplasia. Patient clinically blind at 1 year

a

b

Fig. 5.9. a Axial, b coronal T2-/FSE MRI of a 4-year-old boy. Clinically convergent strabismus and bilateral optic nerve hypoplasia. MRI shows absent septum pellucidum. Diagnosis: septo-optic dysplasia. Visual acuity at 6 years: R 1.0, L <0.1

5.2.7

Delayed/Absent Visual Development

5.2.7.1

Periventricular Leukomalacia

Periventricular leukomalacia (PVL) is a well-known complication of prematurity before 34 weeks’ gestational age. PVL affects primarily the posterior part of the hemispheric white matter. Clinically, it may go along with spastic diplegia type of cerebral palsy

and is often accompanied by delayed visual development (Jacobson et al. 1996; Lanzi et al. 1998; Olsen et al. 1997).

As is evident from Figs. 5.10 and 5.11, MRI allows the detection of specific residual findings: variable reduction of periventricular white matter predominantly involving the posterior aspects, increased size of lateral ventricles, often with an irregular contour (e vacuo). The remaining white matter often shows increased T2 signal, presumably corresponding to gliosis.

b

Fig. 5.10a,b. a Axial, b coronal T2-/FSE MRI of an 8-month-old girl who was born prematurely (32 weeks) and subsequently developed tetraspastic cerebral palsy, visual impairment, and infantile spasms. Periventricular leukomalacia is evident: loss of white matter particularly in the posterior parts, irregular ventricular dilatation. There is hemosiderin lateral to the left trigone/posterior horn following periventricular hemorrhage

5.2.7.3

Delayed Visual Maturation

Infants with delayed visual maturation (DVM) as an isolated finding also present with a lack of visual awareness in the first few months. No ocular abnormalities can be found; electroretinography, visual evoked potentials, and MRI are normal (RusselEggitt et al.1998).Exceptionally,children with DVM may also have nystagmus (Bianchi et al. 1998). A confident diagnosis of DVM can only be made in retrospect when normal vision has appeared and is maintained.

5.2.7.2

Postanoxic Cortical Visual Impairment

Perinatal hypoxia may lead to several lesion patterns of CNS injury. Occasionally, but exceptionally, predominant damage occurs in term infants in the cortical/ subcortical occipital lobe with a clinical correlate of delayed visual development, but often in the context of marked spastic cerebral palsy (Casteels et al. 1997). Typical examples are shown in Figs. 5.12 and 5.13.

5.2.8

Retinal Blindness

The prototype of retinal blindness is Leber congenital amaurosis, an autosomal, recessively inherited dystrophy involving rods and cones. It is genetically heterogeneous (Camuzat et al. 1995). It may occasionally go along with cerebellar vermis hypoplasia, but basically the CNS anatomy is normal. Myelination of the optic radiation appears grossly normal, the diagnosis cannot be positively supported by neuroimag-

Fig. 5.12. Axial T2-/FSE MRI at 1 day following severe perinatal asphyxia: blurred anatomy of basal ganglia. Localized signal alteration in right occipital lobe (necrosis)

ing (Steinlin et al. 1992). Recently, Breitenseher et al. (1998) confirmed that the posterior visual pathways and occipital cortex appear normal in patients with congenital peripheral blindness. Congenital amaurosis may be an occasional presenting feature of Joubert syndrome and related syndromes. Neuroimaging is a key investigation to confirm this condition. It reveals cerebellar vermis aplasia and a “molar tooth” appearance of the midbrain (Steinlin et al. 1997; Maria et al. 1997).

5.3

Acquired Optic Pathway Lesions

5.3.1

General Remarks

b

Fig. 5.13. a Axial, b coronal T2-/FSE MRI. Follow-up in 4-year- old term infant following severe perinatal asphyxia, with moderate cerebral palsy and visual impairment. There is a marked asymmetrical loss of occipital white matter, but also signal alteration of the periventricular frontal white matter

5.3.2

Optic Neuritis

In this section, relevant noncongenital disorders often leading to visual impairment will be mentioned. Depending on the underlying pathology, the child may present with nonspecific findings (such as weakness, impaired consciousness) or complain of symptoms clearly pointing to visual system involvement. However, it is often difficult or impossible to obtain an accurate history of the onset in children. Young children may not notice unilateral visual loss, and bilateral visual loss is often only noticed when it becomes incapacitating.

It is controversial whether autoimmune disorders affecting white matter or anterior optic pathways are fundamentally different in adults and children. They are very rare in the pediatric age group. Isolated pediatric optic neuritis is usually considered post-infec- tious following a febrile or “flu-like” illness; it can be “idiopathic”. Figure 5.14 illustrates a case of isolated pediatric optic neuritis occurring subsequently after an interval of several months and resulting in bilateral blindness. All investigations (including brain imaging,CSF examinations,and mitochondrial muta-