Ординатура / Офтальмология / Английские материалы / Handbook of Pediatric Neuro-Ophthalmology_Wright, Spiegel, Thompson_2006

A B

C D

FIGURE 11-1A–D. Progressive nature of progressive hemifacial atrophy (PHA) in a patient at 8 years old (A) and again at 15 years (B), showing left-sided atrophy. Fundus photos of the normal contralateral side (C) and the ipsilateral affected side with hypopigmentary disturbances (D), particularly along the inferior arcade.

trigeminal neuralgia and seizures.60,84 Unilateral trunk, limb, and even visceral changes have been associated in rare cases.91,108,110 Genetic patterns are unclear but, in a review by Rogers, females were affected more than males (3:2) and less than 5% of cases had bilateral involvement.104,110 The acquired progressive nature of hemifacial atrophy differentiates it from the congenital nonprogressive spectrum of Goldenhar’s hemifacial micro-

somia and the branchial arch syndromes.48,49,84

The etiology of PHA remains unclear. Various hypotheses have been proposed that can be largely grouped into four general categories: neurotrophic, vascular, exogenous insult, and autoimmune mediated. Neurotrophic theories implicate a

trigeminal neuritis,80,101 a cerebral deregulation of the peripheral and sympathetic nervous systems through a heredodegenerative process,128 or a sympathetic nerve loss or interruption.84,89 The vascular theory, which itself relates to the trigeminal nerve, stems from work with electron microscopic and cytoimmunological techniques showing the possible role of a “lymphocytic neurovasculitis” deleteriously affecting endothelial regeneration of vessels in close proximity with the trigeminal nerve. This process, in turn, leads to facial atrophy.104 Case studies of PHA with either uveitis and retinal vasculitis, or retinal vascular malformation, suggest that a mechanism for PHA is related to a disruption in the normal angiogenic process.82,100 Possible exogenous insults include a slow virus, which initiates atrophy, as well as other infectious agents and/or trauma, which serve to “trigger” the atrophic process.48,49 Borrelia infection (or Lyme disease) has also been implicated in a case of PHA, the atrophic progression of which was halted with treatment using penicillin.121 An autoimmune mechanism has also been proposed because both linear alopecia (a focal variant of scleroderma) and PHA share many features. However, unlike immune-related scleroderma, PHA is not associated with an elevated antinuclear antibody (ANA) titer, hyperglobulinemia, or circulating immune complexes.73

Ocular Findings

Ocular findings are present in approximately 40% of cases of PHA.84 They may also be grouped into four general categories (Table 11-1). The first, and most clinically evident, involves structural abnormalities. Enophthalmos is the most prominent ocular finding in PHA and is secondary to orbital, lid, and brow atrophy. In rare cases, there is a “monostotic form fruste” with pure maxillary bone atrophy and maxillary sinus implosion.47,57,138 Lid atrophy with madarosis and pseudocolobomatous changes, ptosis, ectropion, blepharophimosis, and extraocular motility disturbances can occur. Ipsilateral upper lid retraction, with subsequent corneal exposure, has also been reported as a late finding.42 A variety of nonspecific abnormalities, including a case of ophthalmoplegia,65 is thought to result from connective tissue atrophy and fibrotic-like changes in the orbit.17,40,124

A second constellation of features is consistent with involvement of sympathetic and trigeminal innervation. The sympathetic features include pupillary disturbances (miosis and

TABLE 11-1. Ocular Findings in Progressive Hemifacial Atrophy.

Structural

Lid atrophy

Madarosis

Ptosis

Ectropion

Blepharophimosis

Lid retraction (late)

Enophthalmos

Innervational

Pupil disturbance

Miosis (Horner’s syndrome)

Mydriasis (Adie’s syndrome)

Corneal anesthesia

Neuroparalytic keratopathy

Autoimmune

Scleroderma

Episcleritis

Iridocyclitis (Fuch’s syndrome)

Uveitic glaucoma

Optic nerve papillitis

Other

Hypopigmentary retinopathy

Lacrimal dysfunction

Progressive hyperopia

Ocular motor palsies

mydriasis), incomplete Horner’s syndrome, Adie’s pupil, Argyll–Robertson pupil, and heterochromia.91 The trigeminal nerve involvement occurs anywhere along the overall distribution of facial atrophy; specific ocular problems such as exposure keratitis are attributed to neuroparalytic keratopathy.84

The third group of ocular signs are consistent with an autoimmune phenomenon and are twofold: those consistent with a form of scleroderma and those reflecting an inflammatory process. Both focal or linear scleroderma and PHA may manifest a classic sabre-like “en coupe de sabre” groove on the forehead at the junction of normal and atrophic tissue.84,91,128 Scleral melting, and even perforation, along this line has also been reported as a late finding of PHA,60 also possibly due to an autoimmune process. Patients with PHA and linear scleroderma may share the findings of enophthalmos, abnormal (often restrictive) ocular motility, heterochromia irides, pupillary changes, and cutaneous hyperpigmentary changes.4,84,117 An autoimmune process may be the underlying cause for inflammatory conditions such as episcleritis, heterochromic cyclitis,

and Fuch’s-like iridocyclitis, which are also seen in PHA. However, a neurovascular defect suggested by electron microscopy,104 and a case study of PHA involving Fuch’s heterochromic cyclitis and retinal vascular abnormalities (macroaneurysms), imply a “common sympathetic defect” linking Fuch’s and PHA.69 Postuveitic glaucoma, cataracts, and papillitis followed by optic atrophy have also been reported.84,85,91,104,124

Certain ocular findings associated with PHA are difficult to place in the foregoing categories. Miller et al reported an ipsilateral hypopigmentary disturbance in the fundi of a series of PHA patients84 (see Fig. 11-1, bottom). This finding was thought to be analogous to uveitic, cutaneous, and iris pigment changes seen in other autoimmune conditions84 such as vitiligo, Vogt–Koyanagi–Harada syndrome, and tuberosclerosis.2,29,76 A disturbance in neural crest cell development has been suggested as another mechanism for this fundus pigmentary abnormality.46 A genetic defect of neural crest origin has also been proposed as a mechanism for primary corneal endothelial failure seen in a case of PHA.37 Ipsilateral lacrimal dysfunction and refractive changes (typically progressive hyperopia as a relatively early finding85), and contralateral oculomotor cranial nerve palsies and uveitis,17,40,65,84 have also been reported.

DISEASES OF CERVICO-OCCIPITAL PROXIMITY OR “BULLNECK ANOMALIES”

This group of entities includes Arnold–Chiari malformation, meningomyelocele, platybasia, basilar impression syndromes, and the Klippel–Feil syndrome. These neurocranial conditions may exist as a primary anomaly or as a result of a systemic bony disease with secondary architectural defects; they often have multiple overlapping and coincident features. Although ocular findings may be a part of the anomaly or syndrome itself, they also occur secondary to cervico-occipital structural defects and altered cerebrospinal fluid (CSF) dynamics.

ARNOLD–CHIARI MALFORMATION

Cleland, Chiari, and later Arnold described an anatomic malformation involving hydrocephalus with hindbrain herniation through the foramen magnum.6,19,25 Later, Chiari refined his description to include four types of malformations.20 The first

FIGURE 11-2. Sagittal MRI of a patient with type II Arnold–Chiari malformation shows cerebellar atrophy, a small posterior fossa, and inferior vermian displacement to the level of C3 with an inferiorly displaced cervicomedullary junction (bottom arrow). Other anomalies present include massive cortical loss, agenesis of the corpus callosum, beaking of the tectum (top arrow), and a large massa intermedia (middle arrow).

tortion) and the dynamics of CSF flow (hydrocephalus). Because of the close association between hydrocephalus and ACM, many ocular findings can be attributed to one or both entities. These findings most typically include optic atrophy, Parinaud’s syndrome, horizontal and downbeating nystagmus, diplopia, and strabismus.127

A classic finding of advanced hydrocephalus in the setting of ACM is vertically downbeating nystagmus (DBN). DBN is associated with craniocervical lesions, most often with basilar impression/platybasia or ACM.28,137 ACMs usually do not directly effect rostral structures associated with vergence movements (midbrain and pretectal areas), although cases have been reported with abnormal convergence and retraction nystag-

mus.90,130 The authors postulate that convergence nystagmus is caused by mechanical brainstem and cerebellar distortion, combined with abnormal transmission of cerebrospinal fluid to the aqueductal region.

Duane’s retraction syndrome has also been found in association with Arnold–Chiari malformation type I.136 Authors postulate a common early embryogenic mechanism between Duane’s and Arnold–Chiari malformation involving aberrant brainstem innervation35,86 and incomplete neural tube closure, causing suboptimal distension of the developing ventricular system.79,83

Attempts have been made to correlate motility disorders with the level of CNS distortion in patients with ACM and meningomyelocele.72 In a clinical series by Lennerstrand, strabismus and nystagmus generally correlated with hydrocephalus and secondary higher cerebral changes more than with lower brainstem structural deformities.72 Oblique muscle motility disorders, horizontal and vertical gaze difficulty, and saccadic control correlated with lower brainstem lesions (tectal plate and medulla oblongata). Convergence defects related to upper brainstem deformities and the level of herniation.70,72

The strabismus most commonly seen with ACM is largely comitant and seldom caused by cranial nerve paralysis.77 It is frequently associated with “A” or “V” patterns, and a possible supranuclear origin has been postulated (see section on Meningomyelocele).72 Acquired esotropia, often with other motility anomalies, may present as an early sign of Arnold– Chiari malformation I. Some authors suggest divergence palsy as a mechanism for which neurosurgical suboccipital and upper cervical decompression is utilized.75 Strabismus surgery may then be performed should proper realignment not be achieved.129 Other associated motility disturbances include horizontal and vertical gaze paresis, saccadic defects, cogwheel pursuits, optokinetic nystagmus (OKN) abnormalities, convergence insufficiencies, and partial sixth nerve palsies,14 which are often attributed to altered CSF dynamics.72 Bilateral and unilateral internuclear ophthalmoplegia (INO),5,96,135 upbeating nystagmus, torsional nystagmus (associated with syringomyelia),16 see-saw nystagmus,139 periodic alternating gaze and skew deviations, saccadic dysmetria, and inappropriate vestibular ocular reflex (VOR) gain have also been reported.44,87,123 “Nystagmus of skew,” whereby one eye demonstrates an upward vertical jerk nystagmus while the other eye has a simultaneous downward beating

jerk nystagmus, has also been seen with Arnold–Chiari malformation.106 It has been suggested that the presentation of nystagmus of skew should prompt an MRI study to rule out Arnold–Chiari malformation. Autonomic dysfunction, including sinus arrhythmia, Horner’s syndrome, and anisocoria (at a greater rate than healthy controls), have also been reported, which suggests a sympathetic lesion at the T1 level of the cord in association with Arnold–Chiari malformation type I.122

Other CNS anomalies associated with ACM appear unrelated to CSF dynamics. These defects include a dysgenetic corpus callosum with absence of the splenium and rostrum,7 defects in the septum pellucidum and falx cerebri, enlargement of the caudate heads and massa intermedia,93 and stenogyria, multiple small gyri of the medial regions of the occipital lobes.133 Recent genetic studies link renal-coloboma syndrome (an autosomal dominant disorder that includes colobomatous eye defects, vesicoureteral reflux, and kidney anomalies) in a patient with hydrocephalus associated with platybasia and Arnold–Chiari malformation. Genetic studies demonstrate the renal-coloboma syndrome results from mutations in PAX 2. The homoguanine tract in PAX 2 is a “hot spot” for spontaneous expansion or contraction mutations and demonstrates the importance of homonucleotide tract mutations in human malformation syndromes.116

Diagnosis

Currently, the best method available for the diagnosis of ACM is magnetic resonance imaging (MRI). Although cranial nerve nuclei and specific CNS pathways may not be imaged, brainstem, cerebellar, and spinal anomalies are clearly visualized.11,16,71,74,115,137 Sagittal imaging provides the most information and allows an overview from ventricular contour, to midand hindbrain placement, down to spinal and vertebral anomalies. Sagittal MRI can also demonstrate the presence of stenogyria, as well as the presence of a “trapped” fourth ventricle, which are both difficult to evaluate on axial sections.8 Axial sections highlight defects that violate the midline as in the corpus callosum, septum pellucidum, and falx cerebri.8,133

Cysternography has been the radiographic gold standard for evaluating CSF flow; however, cine-mode MRI is an alternative for accurate noninvasive assessment of CSF dynamics.126 Computed tomography (CT) also has a role because of its ability to

image particularly bony regions. For example, with axial CT slices, one can appreciate the posterior concavity and scalloped shape of the petrous bones underlying areas of chronic cerebellar pressure often present with ACM.95

Treatment

The treatment of Arnold–Chiari malformation and associated hydrocephalus traditionally has been neurosurgical. Although the severity of anatomic defect does not always correlate with an individual’s clinical presentation,71 patients may require decompression of the deformity and a subsequent valved shunting procedure. Suboccipital craniotomy with sharp dissection into the foramen of Magendie has been described for ACM I with associated hydrosyringomyelia and syringobulbia in the left pons in a case presenting with acute left gaze paralysis.66

In patients with largely dorsal compression, a standard laminectomy with or without resection of the posterior margin of the foramen magnum is performed. Soft tissue excision is also needed when constricting dural bands are present.21 Alternatively, anterior (transoral) decompression may be the method of choice for patients with ventral compression at the cervicomedullary junction in ACM and basilar impression.126 Placement of a ventricular shunt is usually a concomitant or secondary procedure required for patients with ACM and hydrocephalus.

MENINGOMYELOCELE

Failure of the embryologic neural groove to form an intact neural tube results in a spectrum of neurological defects. Lack of vertebral closure is spina bifida, herniation of meninges is a meningocele, and involvement of the spinal cord itself is termed meningomyelocele (MMC).103 MMCs are most commonly located in the midto caudal groove (i.e., lumbar region). More rostral defects in the skull, such as with a midline cleft, may result in protrusion of brain tissue or encephalocele, the majority of which are over the occipital region118 and may occasionally cause cortical blindness.12 Alternatively, if the sacral area is involved, neurogenic bladder and associated urinary tract infections, hydronephrosis, and renal calculi may ensue.119