Cyanotic Congenital Heart Disease

A retinopathy consisting of dilated, tortuous retinal veins, and optic disc elevation has been described in patients with congenital heart disease. Petersen and Rosenthal427 found optic disc elevation in 12 of 52 patients with cyanotic congenital heart disease. The severity of the fundus changes was closely related to the patient’s arterial oxygen saturation and hematocrit, but not to arterial PCO2, pH, central venous pressure, type of cardiac malformation, or the patient’s age. The retinopathy of cyanotic congenital heart disease resembles that seen in patients with polycythemia. Local hypoxemia, which causes retinal vasodilation, may also play a major role.427 The role of elevated intracranial pressure, if any, has not been determined.In one 12-year-old girl with a brain abscess, a congenital superior vena cava draining into the left atrium contributed to the papilledema.195

Craniosynostosis Syndromes

Craniosynostosis syndromes primarily involve the cranium and upper face.543 Each condition involves premature closure of one or more sutures that limits skull growth in the direction perpendicular to the suture. This closure results in compensatory growth in the unrestricted direction to minimize the compressive effect of the growing brain.542 When brain growth exceeds growth of the skull, elevated intracranial pressure develops. It should be remembered, however, that the craniofacial syndromes also comprise a variety of skull base anomalies and can be accompanied by other CNS anomalies such as ventriculomegaly, hydrocephalus, cal-

losal anomalies, hypoplasia/absence of the septum pellucidum, hypoplasia/dysplasia of the hippocampus, dysplasias or distortions of the cerebral cortex, and parenchymal hemorrhage.548

Craniosynostosis syndromes are commonly associated with papilledema and optic nerve atrophy.178,201,237,410 In a series of 244 patients with craniosynostosis, Dufier et al134 found disc edema in 31% with Crouzon’s disease, 23% with oxycephaly, and 9.5% with Apert’s disease. Optic discs were considered either pale or atrophic in 50% with Crouzon’s disease, 34% with oxycephaly, and 24% with Apert’s disease. In some cases, vision-threatening papilledema is the only sign of hydrocephalus,30 while in others, the craniosynostosis may not be clinically apparent.130 Fishman et al160 have stressed that hydrocephalus appears to be independently associated with premature synostosis rather than occurring as a direct consequence of it. Thus, raised intracranial pressure may be present in the absence of reduced intracranial volume.163 Syndromic craniosynostosis patients often have breathing difficulties, and the associated hypercapnia may contribute to raised intracranial pressure.208 Finally, a wide variety of skull base anomalies are present in most patients with craniofacial syndromes.544 Consequently, complex syndromic craniosynostosis can be associated with decreased flow in the sig- moid-jugular sinus complex.410 Consequently, there is a florid collateral circulation through the stylomastoid emissary venous complex.544 Papilledema in these conditions can, therefore, result from elevated intracranial pressure related directly to premature synostosis, from hydrocephalus, or from compromised venous sinus outflow (Fig. 3.10). These abnormalities may help to explain the development of delayed, asymptomatic increases of intracranial pressure with papille-

dema in children who have undergone cranial vault reconstruction for complex craniosynostosis.431

Moreover, the appearance of the optic disc may not correlate with either the presence or absence of elevated intracranial pressure or optic neuropathy.348,552 For example, Bertelsen46 noted that papilledema had not been observed in any of his children who developed optic atrophy. For this reason, some groups obtain baseline VEPs to follow if visual function deteriorates.348,544 The presence of exposure keratopathy, astigmatism, and amblyopia may further complicate any clinical assessment.544

Nonaccidental Trauma (Shaken Baby Syndrome)

The shaken baby syndrome is a unique but common form of child abuse in which intracranial injury and intraocular hemorrhage may coexist in the absence of external signs of direct head trauma. Shaken baby syndrome occurs when a screaming child with elevated jugular venous pressure is squeezed and forcefully shaken. This action produces dramatic acceleration–deceleration forces within the brain, eye, and orbit. The infant brain is particularly prone to whiplash injuries because of the proportionately larger and unsupported head, the pliability of sutures and fonta-

nelles that allows stretching of the calvarium, the greater deformability of the unmyelinated brain, and the greater percentage of CSF. The common finding of subdural hemorrhage in infants with shaken baby syndrome is thought to result from tearing of the bridging cerebral vessels.198 Contusion, laceration, and edema of the brain may also occur.389

It is the characteristic retinal hemorrhages that provide the crucial diagnostic sign and warrants systemic evaluation for other physical signs such as midsternal ecchymosis, boney fractures, inconsistent or absent explanatory history, and other social risk factors.228,389 The finding of multiple hemorrhages surrounding the optic disc that become more sparse toward the retinal periphery favors shaken baby syndrome over the numerous systemic diseases that can also produce retinal hemorrhages (Fig. 3.11). White, ring-shaped retinal folds that encircle the macula outside the vascular arcades are also highly suggestive of shaken baby syndrome.193 The severity of the intraocular hemorrhages correlates with the severity of the acute neurological injury.390,574 The autopsy finding of hemorrhage within the optic nerve sheath seems to be a relatively specific retrospective marker for this mechanism of injury.68,372,588 As there are many causes of retinal hemorrhages in infancy, it is the cumulative clinical evidence along with social factors that enable one to make the diagnosis of shaken

baby syndrome.284 The ophthalmologist should resist the temptation to draw judgmental conclusions prematurely when examining infants with retinal hemorrhages. Although the findings of shaken baby syndrome are fairly specific, it is important to be remember that systemic or neurologic disease can rarely simulate this condition.184,571

Subdural hematoma, the most common intracranial finding in shaken baby syndrome, can be missed on CT scanning because of volume averaging of the hematoma with the overlying bone. In this setting, retinal hemorrhages may precede the subdural hemorrhage by days, so repeat neuroimaging is therefore warranted if clinical deterioration is observed. Diffusion-weighted MR imaging seems to be the optimal neuroimaging study for suspected shaken baby syndrome, demonstrating diffuse or posterior cerebral ischemia in addition to subdural hematomas in most cases.49

In a series of 75 shaken baby syndrome victims with or without impact head trauma, Morad et al390 found subdural hemorrhage in 93%, cerebral edema in 44%, and subarachnoid hemorrhage in 16%. Other, less common, findings included parenchymal contusion, epidural hemorrhage, and vascular infarction. Similar findings have emerged from other studies.310

Postmortem examination shows intradural and subarachnoid (most common near the sclera), and hemorrhages into the orbital fat in the most severe cases.587 The fact that these findings are much more common in shaken baby syndrome than in accidental head trauma without orbital fracture suggest that the unique acceleration–deceleration forces and vitreoretinal interface shearing caused by shaking are the major causes of retinal hemorrhages.587 Other proposed mechanisms such as elevated intracranial or intrathoracic pressure, direct tracking of blood from the intracranial space, or direct impact trauma are now considered unlikely to be responsible for the retinal hemorrhages.390,587 Intracranial vascular malformations, severe systemic hypertension, congenital cytomegalovirus infection, congenital protein C deficiency, subdural hematoma, hemophagocytic lymphohistiocytosis, and glutaric aciduria are rare causes of retinal hemorrhage that should be considered.560,584,521a

For reasons that are poorly understood, papilledema is surprisingly rare in children with shaken baby syndrome.389,390 Furthermore, it appears that the presence or absence of papilledema carries no diagnostic significance except that one must be sure that retinal hemorrhages due to papilledema are not incorrectly attributed to shaken baby syndrome. It has also never been shown that the presence of papilledema per se imparts a worse neurologic prognosis in the child with shaken baby syndrome. Given the strong vitreoretinal shearing forces generated by shaking injuries, it is surprising that vitreopapillary tractional forces have not been implicated as a mechanism of injury.

Because severe CNS injury often coexists, the diagnosis of shaken baby syndrome imparts a poor neurological prognosis.37,56,390 Cortical visual loss and macular pucker, macular hole, and epiretinal membrane formation are common residua that often limit the ultimate visual prognosis.418 Cortical visual loss is the most common cause of permanent visual loss.372 Dilated pupils at presentation and ventilator dependency seem to confer a worse prognosis.372 Mental retardation and other permanent neurological dysfunction are common.75,389,390 Shaken baby syndrome constitutes a major cause of pediatric stroke.389,390 Indeed, Caffey75 emphasized the deleterious effects of even mild whiplash and swinging activities in young children and conjectured that many cases of mental retardation, cerebral palsy, and congenital hydrocephalus represent undiagnosed “shaken baby” injuries to the CNS.

Cysticercosis

Cysticercosis is a common worldwide parasite that affects the CNS.282 Humans serve as intermediate hosts in the life cycle of the pork tapeworm Taenia solium when eggs are ingested with contaminated food.535 The disease is endemic in Mexico, Central and South America, India, and China.118 In Mexico, the prevalence of neurocysticercosis may be as high as 2–3%, based on patients autopsied at general hospitals.118 Neurocysticercosis can develop in children and adults, but symptoms occur most often in young adults. Before modern neuroimaging, neurocysticercosis was included in the differential diagnosis of IIH.432

Many patients remain asymptomatic until degenerating parenchymal cysts produce contiguous inflammation, at which time seizures, increased intracranial pressure, altered mental status, and focal neurological signs develop.118,282,291 Degenerating parenchymal cysts may produce chronic meningitis. Papilledema and pretectal signs (associated with hydrocephalus) are the usual neuro-ophthalmologic manifestations of neurocysticercosis, although other brainstem and cerebellar signs, such as cranial nerve palsies, internuclear ophthalmoplegia, facial myokymia, upbeat nystagmus, periodic alternating nystagmus, and oculopalatal myoclonus, have been reported.52,78,265,266,291,306 Blindness from postpapilledema optic atrophy occurs in some cases.

MR imaging and CT scanning are now considered to be complementary in the diagnosis of neurocysticercosis (Fig. 3.12). Suh et al535 found MR imaging to be more sensitive than CT scanning for visualization of the scolex within the cystic lesions but less sensitive for detection of small calcifications. Because it has been estimated that dead cysticercal larvae take 4–7 years to calcify (and become visible on CT scanning), MR imaging appears to be preferable in children.74 The location of cysticerci can be intraventricular, cisternal, parenchymal, or meningeal.74 In the neurologically symptomatic patient,

Fig. 3.12  Neurocysticercosis. CT scan demonstrates multiple intracranial cysts

the diagnosis of neurocysticercosis is almost always made presumptively on the basis of neuroimaging studies.

An enzyme-linked immunosorbent assay (ELISA) test is available that, when applied to the CSF of people with active disease, has a sensitivity of over 80% and a specificity of over 90%. More recently, the Centers for Disease Control and Prevention developed an immunoblot test that detects both IgM and IgG antibodies to cysticercosis antigens and has a specificity close to 100% and a sensitivity of about 98% in both serum and CSF.118

Treatment of active neurocysticercosis consists of praziquantel, which kills the organism through a mechanism that is poorly understood.118 Patients with inactive disease and dead cysts do not respond to praziquantal. Surgical removal is occasionally indicated for intraventricular cysts, which may have become dislodged and produced obstructive hydrocephalus. Patients with multiple cystic lesions may develop increased CNS symptoms shortly after praziquantel is started, which appears to result from intense reactive inflammation in the surrounding brain following death of the cysticerci. During treatment, patients must therefore be observed closely for worsening of papilledema, which may necessitate acetazolamide and/or optic nerve sheath fenestration.

Mucopolysaccharidosis

Optic disc swelling is a common ocular finding in patients with systemic mucopolysaccharidosis.19 In a study of 108 patients with optic disc edema, Collins et al97 found a greater

Table 3.6  Causes of optic disc elevation with mucopolysaccharidosis (Information from ref193)

Narrowing of the scleral canal by thickened, infiltrated peripapillary sclera Increased intracranial pressure associated with hydrocephalus Accumulation of acid mucopolysaccharides in retinal ganglion cells Compression of the optic nerve by thickened infiltrated meninges

than 40% incidence of optic disc edema in patients with Hurler syndrome, Hurler–Scheie syndrome, Maroteux–Lamy syndrome, and Sly syndrome; 19.7% in Hunter syndrome; and 4.6% in Sanfilippo syndrome. No patient with Scheie syndrome or Morquio syndrome had optic disc edema. Optic disc swelling in mucopolysaccharidosis can result from any one or a combination of several mechanisms97 (Table 3.6).

Beck and Cole40 provided ocular histopathology from a patient with Hunter syndrome who had optic disc swelling without raised intracranial pressure. They confirmed deposition of abnormal mucopolysaccharides within the sclera and lamina cribrosa that produced gross thickening of these structures and compression of the optic nerve. Bone marrow transplant can lead to resolution of optic disc edema.217

Infantile Malignant Osteopetrosis

Osteopetrosis describes a group of hereditary metabolic bone diseases in which osteoclast dysfunction results in abnormal bone resorption, thickened cortical bone, structural skeletal defects, and frequent bone fractures.473 Reduced bone marrow space and replacement of its normal contents by chondroosseous tissue in the sclerotic bones results in anemia, hepatosplenomegaly, thrombocytopenia, leukopenia, and increased susceptibility to infection.473,583 Infantile malignant osteopetrosis is an autosomal recessive subtype of the juvenile-onset variety that develops in utero or in the first months of life.473 Clinical signs in malignant infantile osteopetrosis include reduced vision in the first months of life, an enlarged skull with parietal and frontal bossing, hepatosplenomegaly, recurrent infections, failure to thrive, and bruising.4 Neurologic abnormalities, including extreme irritability, cranial nerve palsies, developmental delay, hydrocephalus, mental retardation, and cerebral atrophy, are often the first manifestation of the disease.473 Hydrocephalus in osteopetrosis may result from obstruction of cerebral venous outflow secondary to narrowed venous foramina.311

Neuro-ophthalmologic findings are common in malignant infantile osteopetrosis. They include optic atrophy, papilledema, nystagmus, strabismus, nasolacrimal duct obstruction, limited extraocular movements, and proptosis. Papilledema in osteopetrosis has been attributed to hydrocephalus, although a IIH mechanism related to venous outflow obstruction also seems plausible. Optic atrophy with severe visual loss is seen