Optic Pathway/Hypothalamic Gliomas

Management

Charles Teo

Optic pathway/hypothalamic gliomas (OPHGs) present a management dilemma. They represent < 1% of brain tumors seen in all age groups and 3 to 5% of all brain tumors in the pediatric age group.1 Patients may present with very subtle or devastating symptoms, have widely diverse imaging, and run either an extremely benign course that may never require intervention or a rapidly progressive course that may result in early death. Predicting the biological nature of these tumors is difficult; therefore, treatment paradigms are poorly defined. It would be wrong to discuss the surgical management of these tumors without first reviewing the different classifications.

Classification

A review of the recent literature is at best confusing. These tumors have been classified according to clinical presentation, radiologic imaging, histologic subtype, anatomical location, and the presence or absence of neurofibromatosis (NF).^2–4 Although each system has certain merits, they result in considerable overlap; subsequently, treatment paradigms are poorly defined. Clearly, if we could predict the biological activity of the tumor, then surgical intervention could be reserved for those aggressive types that result in early visual loss, hydrocephalus, and hypothalamic disturbance. Those with predictable biological inertia could be followed with serial imaging or clinical assessment.

Prognosis by Location

1. Optic nerve involvement only (prechiasmatic): best

2. Optic nerves and chiasm (sparing the hypothalamus): fair

3. Hypothalamic involvement: poor

Prognosis by Age

1. 0 to 5 years of age: poor

2. 5 to 20 years of age: best

3. 20+ years: fair

Prognosis by Histology

1. Juvenile pilocytic astrocytoma: best

2. Fibrillary astrocytoma: fair

3. Pilomyxoid variant: poor

Prognosis by Presentation

1. Unilateral visual loss: best

2. Bilateral visual loss: fair

3. Mostly hypothalamic dysfunction: poor

After a review of the literature, it is clear that there is a consensus that those “anterior” tumors confined to the optic nerve should be discussed separately from true optic chiasmatic-hypothalamic gliomas (OCHGs). The prechiasmatic, optic pathway tumor is usually found in children with neurofibromatosis type 1 (NF1), rarely spreads to the contralateral nerve or chiasm, runs a very indolent course, is mostly of the pilocytic variety and invariably does not progress, and therefore rarely requires treatment. The “posterior” tumors that affect the chiasm and hypothalamus are sometimes classified separately as primarily chiasmatic or primarily hypothalamic, have often been called exophytic, and, most would concede, are hard to distinguish from one another on imaging.

Natural History

The growth rates of optic pathway tumors can vary dramatically. Some are so indolent that they have been called hamartomas. Indeed, spontaneous regression has been seen with the “anterior” located tumors in NF1 patients.⁵ Others are so aggressive that they run a malignant course with rapid recurrence and early death. Rarely, they may even disseminate along the neuraxis.⁶ This is a phenomenon of low-grade gliomas seen in only 5% of all cases, but when present, more than half the cases are the “posterior” located tumors.⁷ Along with the recognized prognosticators listed above, other factors that may play a role in the natural history of optic pathway tumors are the gender of the patient and whether there is a background of NF1. In the surgical series of Ahn et al, only 21% of boys showed tumor progression compared with 71% of girls.6 Listernick et al found progression of tumor in only 2 of 17 patients with NF1 versus 12 of 19 children with glioma not associated with NF1.⁸

Undoubtedly, the worst prognosis is with those patients who present at a very young age with hypothalamic dysfunction. These tumors are often large with secondary hydro-cephalus and intracranial hypertension. Untreated, virtually all of these patients die before 1 year of age.⁹

Pathology

The most common histologic type is the pilocytic astrocytoma (PA). Prechiasmatic tumors are mostly of this type. Other types are low-grade fibrillary astrocytomas, gangliogliomas, and, rarely, malignant gliomas.

Burger’s group¹⁰ described a disturbing variety of astrocytoma that was monomorphous and myxoid in appearance and associated with a more aggressive course (Fig. 7.1). They called this the pilomyxoid astrocytoma (PMA). Other features of this subtype resembled the PA, but there was a clear absence of Rosenthal fibers and very few eosinophilic granular bodies (Fig. 7.2). Those patients with the pilomyxoid variety had a progression-free survival (PFS) rate at 1 year of 38.7% compared with those patients with pilocytic tumors whose PFS rate was 69.2%.¹¹

Microvessel density may be another method of prognosticating. This can be determined by immunostaining with factor VIII. A higher density may be associated with reduced PFS.¹²

Clinical Manifestation

The clinical presentation varies according to the age of the patient and the anatomical location of the tumor. Visual disturbance is common and can be prechiasmatic, chiasmatic, or postchiasmatic. If the patient is younger than 3 years old, visual disturbance is subtle and so insidious that the patient may be near blind at presentation and not have any visual complaints. Of course, if the tumor is prechiasmatic, involving the optic nerve alone, visual disturbance will be confined to the one eye, and examination may demonstrate proptosis. If the tumor is chiasmatic, examination may demonstrate a pendular-type nystagmus and asymmetrical and patchy visual field loss due to confrontation. Fundoscopy often shows optic atrophy, although papilledema may be seen with large tumors or secondary hydrocephalus. If the hypothalamus is affected, patients may present with precocious puberty, short stature, gelastic seizures, and/or the diencephalic syndrome of Russell. This syndrome is found in children younger than 3 years of age and is characterized by emaciation without gastrointestinal abnormalities, euphoria, and a hyperkinetic state. The older child and adult with hypothalamic involvement may present with obesity, diabetes insipidus, hypogonadism, hypopituitarism, headache from secondary hydrocephalus, memory disturbance, and emotional lability. Hypothalamic disturbance is less common in adults than in children.