Neuro-Ophthalmological Manifestations of Gangliogliomas

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Article initiated by:

Andrew Go Lee, MD, Anika Tanwani, Chaow Charoenkijkajorn, M.D., Nagham Al-Zubidi, MD, Peter W. Mortensen, MD, Sami Younes, Subahari Raviskanthan, MBBS

All contributors:

Melanie Shackleford, Nagham Al-Zubidi, MD, Aroucha Vickers, DO, Peter W. Mortensen, MD

Assigned editor:

Aroucha Vickers, DO

Review:

Assigned status Up to Date

 by Aroucha Vickers, DO on May 9, 2024.

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Disease Entity

Disease

Gangliogliomas (GNG) are uncommon, comprising only 0.4% to 1.7% of central nervous system (CNS) tumors. GNG tend to occur in children and young adults and present predominately in the temporal and frontal lobes, with occasional cerebellar and spinal cord involvement. GNG are composed of both neuronal and glial cells.

General Pathology

The histological appearance of GNG consists of both neoplastic glial and ganglion cells. The glial cell components usually include fibrillary astrocytes with varying cellular atypia. The neuronal cells are typically clustered or irregularly oriented. Other common findings include fibrovascular stroma confined to the neuronal component, perivascular lymphocytic infiltrates, small foci of calcification, and positive synaptophysin, neuron-specific enolase, and chromogranin A markers. Aggressive GNG clinical behavior is associated with elevated Ki-67 and p53 labeling index. GNGs may be associated with the BRAF V600E mutation in both adult and pediatric patients.

Diagnosis

History & Physical Examination

A comprehensive history is important when trying to diagnose the presence of an intracranial mass. This involves asking about the time course of symptom development and identifying symptoms of increased intracranial pressure (e.g. headaches, nausea, vomiting, pulsatile tinnitus, transient visual obscurations, diplopia). GNG are generally slow growing and associated with temporal lobe epilepsy, so the presence of these can be helpful when trying to identify the etiology. Although the typical course is gradual and slowly progressive, patients may present acutely with seizure or hydrocephalus.

A complete neuro-ophthalmologic exam is helpful to determine if there may be a mass present and if the GNG is impinging on any part of the afferent or efferent visual pathways. Increased intracranial pressure (ICP) can present with decreased visual acuity, relative afferent pupillary defect, sixth nerve palsy, or papilledema. The clinical features can be localizing (e.g., homonymous hemianopsia) or non-localizing signs of increased intracranial pressure.

Most GNG occur in the frontal or temporal lobe but there also have been at least eight prior reported cases of pineal region GNG. These pineal lesions can obstruct the cerebral aqueduct, resulting in hydrocephalus and can produce the dorsal midbrain syndrome (Parinaud syndrome). Pineal GNG can therefore produce vertical (typically up-gaze) paresis, light near dissociation of the pupils, convergence retraction nystagmus, and lid retraction (Collier sign).

Diagnostic Work-up

When any potential intracranial mass is suspected, it is crucial to perform diagnostic imaging, including a cranial contrast tomography (CT) scan and magnetic resonance imaging (MRI) with gadolinium. The imaging features of GNG are variable and nonspecific but may show a partially cystic mass. Up to 30% of GNG have calcifications and 40% of cases demonstrate a mural enhancing nodule. Associated vasogenic edema is not a typical finding associated with GNG and significant brain edema should suggest either an alternative diagnosis or potential anaplastic transformation of GNG.

Because pineal lesions can be due to germ cell tumors, serum and cerebrospinal fluid (CSF) analysis for tumor markers (e.g., alpha-fetoprotein, beta-human chorionic gonadotropin, placental alkaline phosphatase, and lactose dehydrogenase) may be considered in the differential diagnosis of pineal GNG.

Differential Diagnosis

The differential diagnosis of GNG includes dysembryoplastic neuroepithelial tumor, oligodendroglioma, and pleomorphic xanthoastrocytoma.

Management

Treatment

GNG may be treated with gross total resection alone, gross total resection plus radiotherapy, subtotal resection alone, or subtotal resection plus radiotherapy. Gross total resection is the preferred therapy. Radiation and adjuvant chemotherapy are not typically used in the management of GNG except in cases of high-grade tumor or anaplastic transformation. Lang et al. reported a GNG series showing 5- and 10-year survival rates of 89% and 83% when total resection was achieved. Subtotal resection may be performed if gross total resection is not possible. When resection is not possible, radiation therapy may delay disease progression, although it has not been found to improve overall survival

Prognosis

The prognosis of GNG is generally good. The majority of GNG are histologically benign (WHO grade 1) but up to 5% of GNG are higher grade tumors (WHO grade 3). Older age at diagnosis, male sex, malignant histological features and multifocal disease are poor prognostic factors. Gross total resection is associated with better survival compared to subtotal resection.

Summary

GNG are rare tumors of the CNS which are composed of both glial and neural tissue. Although uncommon, GNG can be considered in the differential diagnosis of patients presenting with afferent or efferent ophthalmologic complaints that may be localizing or non-localizing. Although most GNG occur in the temporal lobe, pineal and cerebellar GNG have also been reported. Gross total surgical resection is the best treatment and adjuvant chemotherapy or radiation therapy are reserved for residual or recurrent higher grade GNG. The prognosis for GNG is generally good and the histopathology is usually WHO Grade 1.