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Optic pathway glioma

Optic pathway gliomas or suprasellar gliomas.

These tumours have sometimes been divided into optic pathway gliomas and hypothalamic gliomas (not to be confused with hypothalamic hamartomas). In cases where the tumour is confined to the optic nerves (Dodge stage 1), they can safely be referred to as optic nerve gliomas. Often, however, they are either centred on or extend to involve the chiasm and optic radiations. In such cases, they are difficult to distinguish from hypothalamic gliomas and such a distinction is in most instances artificial. In such more posterior cases the term hypothalamic-optochiasmatic glioma is perhaps more accurate although it certainly does not roll off the tongue.

As such, generally, the term optic pathway glioma is favoured, recognising that there may be involvement of the hypothalamus 1).

Optic pathway/hypothalamic gliomas (OPHGs) are generally benign but situated in an exquisitely sensitive brain region, and may involve the optic nerves, the optic chiasm, and the optic tracts.

Martin and Cushing (1923) first noted the difficulty of determining the site of origin of optic nerve gliomas, since these tend to extend up and down the optic pathways, often making it impossible to decide even at postmortem examination whether the growth originated in the chiasm and extended to the hypothalamus, or vice versa.


Gliomas of the optic chiasm and hypothalamus account for 10-15% of supratentorial tumors in children. Males and females are approximately equally affected.

Between 20 and 50% of patients with hypothalamic gliomas have a positive family history of neurofibromatosis type 1 (NF-1). Gliomas of the optic chiasm and hypothalamus in children with NF-1 usually have a more indolent course. Tumours may grow more slowly and occasionally regress spontaneously.

A retrospective, single-center, cohort study of 176 patients (93 boys), aged 6 years (range, 0.2-18 years), with hypothalamic-pituitary lesions showed craniopharyngioma (n = 56), optic pathway glioma (n = 54), suprasellar arachnoid cyst (n = 25), hamartoma (n = 22), germ cell tumor (n = 12), and hypothalamic-pituitary astrocytoma (n = 7). The most common presenting symptoms were neurologic (50%) and/or visual complaints (38%), followed by solitary endocrine symptoms (28%). Precocious puberty led to diagnosis in 19% of prepubertal patients (n = 131), occurring earlier in patients with hamartoma than in patients with optic-pathway glioma (P < .02). Isolated diabetes insipidus led to diagnosis for all germ-cell tumors. For 122 patients with neuro-ophthalmic presenting symptoms, the mean symptom interval was 0.5 year (95% CI, 0.4-0.6 year), although 66% of patients had abnormal body mass index or growth velocity, which preceded the presenting symptom interval onset by 1.9 years (95% CI, 1.5-2.4 years) (P < .0001) and 1.4 years (95% CI, 1-1.8 years) (P < .0001), respectively. Among them, 41 patients were obese before diagnosis (median 2.2 years [IQR, 1-3 years] prior to diagnosis) and 35 of them had normal growth velocity at the onset of obesity. The sensitivity of current guidelines for management of childhood obesity failed to identify 61%-85% of obese children with an underlying hypothalamic-pituitary lesion in this series 2).

These masses are, however, rare in adults and require tissue sampling for diagnosis 3).


Dodge classification

The most widely accepted classification of optic pathway gliomas was first proposed by Dodge et al in 1958 and divides these tumours into just three groups based on anatomical localisation:

stage 1: optic nerves only

stage 2: chiasm involved (with or without optic nerve involvement)

stage 3: hypothalamic involvement and/or other adjacent structures

A more recent modification of the Dodge classification has been proposed which further subdivides each stage.


Most are juvenile pilocytic astrocytomas, but their imaging characteristics are not specific with regard to their histologic features. Varying degrees of cystic change and enhancement are demonstrated. The tumours may appear smooth, fusiform, eccentric, or lobulated.

see hypothalamic pilocytic astrocytoma

Clinical features

Optic pathway gliomas (OPG) represent an important cause of visual loss in pediatric population. Visual acuity loss is the most important symptom of disease progression, but children with OPG are frequently unable to complete the testing of visual function.

Clinical features may include:

Decreased visual acuity / optic nerve atrophy ≈50%

Diencephalic syndrome 4) 5) 6).

Obesity; sexual precocity; endocrine dysfunction (short stature)

Diabetes insipidus.


They are characterised on imaging by an enlarged optic nerve seen either on CT or MRI.


Usually showing low T1 and high central T2 signal on MRI images, enhancement is variable.

MR imaging is optimal for showing the relationship of the mass to the hypothalamus, optic chiasm, and infundibulum as well as the intraorbital and intracanalicular components of the mass. Large tumours are typically heterogeneous with cystic and solid components.

T1: almost always hypo intense

T2: hyper intense

FLAIR: hyper intense

T1 C+ (Gd): solid components of large tumours often contrast enhance.

Optical coherence tomography (OCT) was suggested as an objective tool for visual assessment. A literature review was performed in order to determine the role of retinal OCT as a surrogate marker of vision in children with OPG.

Retinal OCT is a promising tool to be considered as a screening or follow-up test in children with OPG, and further multicenter research is encouraged 7).

Differential diagnosis

The main differential is that of optic nerve sheath meningioma, however, the potential list is much longer including most causes of optic nerve enlargement.

The absence of calcification can be used to differentiate optic nerve glioma from optic nerve sheath meningioma.

Additionally, when the bulk of the tumour is located at the chiasm, the differential should include pituitary region masses.

They usually present earlier (first 5 years of age) than craniopharyngioma. Hypothalamic glioma poses a diagnostic dilemma with craniopharyngioma and other hypothalamic region tumors, when they present with atypical clinical or imaging patterns. Neuroimaging modalities especially MRI plays a very important role in scrutinizing the lesions in the hypothalamic region.

The main differentiating features between craniopharyngioma and hypothalamic glioma are the presence of mixed intensity cysts on T1 and calcification in craniopharyngioma and the relative young age of presentation in hypothalamic gliomas. Yet, it is not always possible to differentiate craniopharyngiomas from hypothalamic glioma. Thus, obtaining a tissue diagnosis via biopsy may be the right course of action in planning further management, whenever diagnosis is in doubt. 8).


If it is isolated to one optic nerve and does not extend to the chiasm, then resection is curative (albeit with the loss of vision in that eye). If the tumour extends to the chiasm or more posteriorly, then curative resection is not possible, with resection reserved for treatment of mass effects (proptosis, intracranial mass effect)

En-block removal of intraorbita tumor is recommended in cases with disfiguring exophthalmos and loss of vision.

Surgical resection of intraorbital optic nerve (ON) poses the risks of permanent ptosis and globe atrophy.

Optimal management of optic pathway/hypothalamic glioma (OPHG) remains an ongoing challenge. Little is known about the natural history, management strategies, and outcomes in adolescents.

see Anterior interhemispheric approach

Radiotherapy continues to be the mainstay of progressive OPHG management strategies. In the 2000s, chemotherapy has emerged as a therapeutic option for those <10 years of age aiming to avoid or at least postpone radiation to the immature brain 9).

Carboplatin-based chemotherapy is a useful modality in younger children, delaying radiation to their immature brains. National trials have focused on younger children and excluded adolescents from studies evaluating the role of chemotherapy.

In fact, many institutions continue to consider irradiation as the treatment of choice for progressive OPHGs in patients >10 years of age.

Chemotherapy is a valuable treatment modality for the achievement of disease control even in adolescents; their progression-free survival compares favorably with that in younger children. Chong et al. propose that chemotherapy be considered as a first-line modality in adolescents, avoiding potential radiation-associated morbidities 10).


Case series


A retrospective follow-up study of 40 children with NF1 and OPG evaluated between August 1996 and May 2015 was undertaken. Patients who underwent radiotherapy or surgical resection were excluded and 36 patients were studied. Tumour location was classified according to the Dodge criteria: stage I, optic nerve alone; stage II, optic chiasm with or without optic nerve involvement; and stage III, involvement of the hypothalamus or other adjacent structures.

Endocrinopathies were diagnosed in 20/36 (55.6%) children during a mean follow-up of 9.1 (0.2-13.6) years: 0/4 OPGs were Dodge stage I, 12/21 (57.1%) stage II, and 8/11 (72.7%) stage III. The first endocrinopathy was found at a mean age of 7.4 (5.0-13.2) years, 2.4 (0-6.7) years after tumour diagnosis. We found growth hormone deficiency (GHD; 36.1%), central precocious puberty (33.3%), obesity with insulin resistance/impaired glucose tolerance (11.1%), early puberty (5.5%), GH excess (5.5%), ACTH deficiency (5.5%), hypogonadotropic hypogonadism (2.7%), and thyrotropin deficiency (2.7%). GHD was transient in all of those who were retested.

This population is at high risk of endocrinopathies due to tumour location. Lifelong endocrine follow-up is recommended.


A retrospective case series study was led for 3 patients diagnosed with primary optic nerve and chiasm glioblastoma (GBM), coming from two referral neurosurgical centers. 2) An electronic search was conducted on MEDLINE via PUBMED, COCHRANE, from October 1973 to April 2016. Cohort, case reports, and case series were screened for investigating treatment and overall survivals of malignant optic nerve gliomas. Pooled means and 95% confidence intervals of overall survival for each treatment were generated.

1) From our retrospective case series, all patients had initial visual impairment (2 women and 1 man). The histological diagnosis was done by biopsy. The patients' mean age of was 67.3 years (SD 18.5). The disease was rapidly lethal for all patients: median overall survival (OS) was 5 months (SD: 15.1). Two patients underwent chemotherapy by single cure of temozolomide, while the third one was treated with a radio-chemotherapy protocol. 2) Due to the fact that there is no gold standard treatment as first choice treatment, a large heterogeneity in first-choice oncological treatment is observed. However, we did not find any significant differences for overall survival between WHO grade III and grade IV optic gliomas.

Malignant optic glioma is a rare and fatal disease in adults. Despite the modalities of treatment, the treatment outcomes remain unsatisfactory. There is no significant difference in the median overall survival of patients with malignant optic nerve, as compared to those diagnosed with other supratentorial glioblastoma. Chemoradiotherapy with temozolomide currently remains the best treatment in terms of overall survival. Advances in the understanding of tumor biology have yet failed to translate into effective treatment regimens 12).


Ten patients managed surgically utilising ioMRI at Alder Hey Children's Hospital between 2010 and 2013 were retrospectively identified. Demographic and relevant clinical data were obtained. MRI was used to estimate tumour volume pre-operatively and post-resection. If ioMRI demonstrated that further resection was possible, second-look surgery, at the discretion of the operating surgeon, was performed, followed by post-operative imaging to establish the final status of resection. Tumour volume was estimated for each MR image using the MRIcron software package.

Control of tumour progression was achieved in all patients. Seven patients had, on table, second-look surgery with significant further tumour resection following ioMRI without any surgically related mortality or morbidity. The median additional quantity of tumour removed following second-look surgery, as a percentage of the initial total volume, was 27.79 % (range 11.2-59.2 %). The final tumour volume remaining with second-look surgery was 23.96 vs. 33.21 % without (p = 0.1).

OPHGs are technically difficult to resect due to their eloquent location, making them suitable for debulking resection only. IoMRI allows surgical goals to be reassessed intra-operatively following primary resection. Second-look surgery can be performed if possible and necessary and allows significant quantities of extra tumour to be resected safely. Although the clinical significance of additional tumour resection is not yet clear, we suggest that ioMRI is a safe and useful additional tool, to be combined with advanced neuronavigation techniques for partial tumor resection 13).


Forty-two patients were treated between 1998 and 2011. Their median age at diagnosis was 5 years 7 months. Nineteen patients were positive for neurofibromatosis Type 1 (NF1) and 23 patients were negative for NF1. The median duration of follow-up was 77 months (range 21.8-142.3 months). Presenting symptoms included visual impairment (in 50% of cases), headache (in 24%), and hypothalamic/pituitary dysfunction (in 29%). Twenty-two debulking procedures were performed in 21 patients. Four biopsies (3 open, 1 endoscopic) were also performed. The histological diagnosis was pilocytic astrocytoma in 21 patients and pilomyxoid astrocytoma in 2 patients. Ten patients (Group 1) had primary surgical debulking alone and were then observed. Four patients (Group 2) had surgical debulking, plus planned chemotherapy within 3 months. Seven patients (Group 3) required surgical debulking for progressive disease following a variety of treatments. Patient age had the greatest impact on subsequent tumor progression. In total, 13 patients received chemotherapy, 4 on initial presentation, 4 in combination with surgery, and 5 for further tumor progression. Five patients were treated with radiotherapy, 3 prior to referral to Alder Hey. Eleven patients required shunt insertion for hydrocephalus. Vision was stabilized for 74% of patients. The number of patients with hypothalamic/pituitary dysfunction increased from 12 at presentation to 16 by the end of treatment. The overall survival rate was 93%. Three patients died-1 from tumor progression, 1 from infective complications from tumor biopsy, and 1 from a spontaneous posterior fossa hemorrhage. NF1 was associated with improved outcome-fewer patients required active intervention and rates of visual impairment and/or or hypothalamic/pituitary dysfunction were lower.

Good long-term survival and functional outcomes can be achieved in children with OPHG. Tumor control was achieved through an individualized approach using surgery, chemotherapy, or radiotherapy in varied combinations. The authors aim to limit radiotherapy to cases involving older children in whom other therapies have failed, due to the well-described and often devastating late effects associated with midline cranial irradiation. Surgery has a clear role for diagnosis, tumor control, and relief of mass effect. In particular, primary surgical debulking of tumor (without adjuvant therapy) is safe and effective. Recent advances in intraoperative MRI may add value and need further assessment 14).

Zoli et al. analyze their experience with hypothalamic gliomas treated via the endoscopic endonasal approach. Methods Consecutive cases of hypothalamic gliomas treated since 2007 via an endoscopic endonasal approach were reviewed. Preoperative and postoperative neuroimaging as well as endocrinological, neurological, and visual symptoms were analyzed to assess the surgical outcome. Signs and symptoms of hypothalamic dysfunction including body mass index (BMI), memory, sleep-wake rhythm, and polyphagia were prospectively collected pre- and postoperatively to assess hypothalamic function. Quality of life was evaluated using the Katz scale. Results In the initial phase the endoscopic endonasal approach was adopted in 3 cases with a palliative intent, to obtain a biopsy sample or for debulking of the mass followed by radio- or chemotherapy. In 2 later cases it was successfully adopted to achieve gross-total tumor resection. Complications consisted of 2 postoperative CSF leaks, which required an endoscopic endonasal reintervention. Visual deficit improved in 3 cases and normalized in the other 2. Four patients developed diabetes insipidus, and 3 an anterior panhypopituitarism. All patients had a moderate increase in BMI. No patients presented with any other signs of hypothalamic damage, and their quality of life at follow-up is normal. Conclusions Despite the limitations of a short follow-up and small sample, the authors' early experience with the endoscopic endonasal approach has revealed it to be a direct, straightforward, and safe approach to third ventricle astrocytomas. It allowed the authors to perform tumor resection with the same microsurgical technique: dissecting the tumor with 2 hands, performing a central debulking, and controlling the bleeding with bipolar coagulation. The main limitations were represented by some anatomical conditions, such as the position of the chiasm and the anterior communicating artery complex and, finally, by the challenge of watertight plastic repair. To definitively evaluate the role of this approach in hypothalamic gliomas, a comparison with transcranial series would be necessary, but due to the rarity of these cases such a study is still lacking. The authors observed that more aggressive surgery is associated with a worse endocrinological outcome; thus they consider it to be an open question (in particular in prepubertal patients) whether radical removal is an advisable goal for hypothalamic gliomas. 15).

A retrospective review of patients diagnosed with suprasellar glioma between 2000-October 2012, included patients diagnosed with optic pathway glioma based on radiological features (with or without biopsy) and those who had a biopsy confirming pilocytic astrocytoma.

Fifty-three patients included (sporadic tumours 24 and NF1 related 29). Fifteen sporadic and four NF1 patients were biopsied. Twelve sporadic and 13 NF1 patients were initially treated with chemotherapy while only 1 patient had radiotherapy initially. Progression was noted in 58 % of the sporadic group and 24 % of the NF1 group. The only significant factor for progression was NF1 status (p = 0.026).

Management should be guided by individual patient circumstance. In our cohort, chemotherapy did not significantly improve progression free survival; however, NF1 status significantly correlated with the decreased progression 16).


A total of 101 patients with optic glioma newly diagnosed between 1975 and 2008 were evaluated retrospectively. COPP (cyclophosphamide, vincristine, procarbazine, prednisolone) and cisplatin plus etoposide were the most commonly used chemotherapy regimens. Radiotherapy was administered in patients with progressive or unresponsive disease.

The median age at the time of diagnosis was 6 years, and the male/female ratio was 1.15. The most common referral complaint was strabismus. The most common site of optic glioma was the hypothalamic-chiasmatic region (31.7%). Fifty-three patients (52.5%) had neurofibromatosis type 1 (NF-1). Treatment consisted of surgery, radiotherapy, and chemotherapy. Forty-nine patients (48.5%) underwent surgery, which was predominantly subtotal resection, radiotherapy was administered to 39.4%, and 30 patients received chemotherapy. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 65.8% and 88.4%, respectively, and the 10-year PFS and OS were 54.2% and 83.4%, respectively, with an 8-year median follow-up. OS was significantly lower in patients with hypothalamo-chiasmatic involvement and significantly higher in patients with NF-1. The 5- and 10-year PFS rates were significantly higher in patients 10 years or older at diagnosis (P=0.0001) and in patients with intraorbital involvement (P=0.032). Eighteen patients (17.8%) died of disease.

Patients with NF-l and those older than 10 years have a better prognosis, whereas patients younger than 3 years and those with hypothalamic-chiasmatic optic glioma have a worse outcome. Further studies are needed to find appropriate treatment strategies 17).


Diencephalic syndrome and its relation to opticochiasmatic glioma: review of twelve cases 18).


Twenty children with hypothalamic gliomas from the Hospital for Sick Children, Great Ormond Street, were reviewed in an attempt to determine the appropriate management. If the child's condition at the time of diagnosis is such that survival for several months is likely, the long-term prognosis for good survival is excellent and is enhanced by treatment. It is concluded that radiotherapy has a definite beneficial effect and should be given to every child not presenting in poor or critical condition. These are best left untreated. An exception is a child with the diencephalic syndrome whose general condition is poor but there is little or no impairment of consciousness; such a child should be treated by radiotherapy sometimes preceded by a shunt operation. If there is increased intracranial pressure with radiological evidence to suggest that the obstruction may be relieved by operation, then partial removal should be carried out. If it is judged that obstruction cannot be relieved, a shunting procedure is required. Craniotomy is also indicated if there is anything in the clinical or radiological examination to suggest that the lesion may be extracerebral. Otherwise, biopsy through a burr hole may be adequate for confirmation of the diagnosis 19).

Case reports

Hidalgo et al., present the case of an adult patient with a benign OPG who underwent subtotal resection without adjuvant therapy and has had no tumor progression for more than 20 years. A 50-year-old woman presented with a 2-year history of personality changes, weight gain, and a few months of visual disturbances. Ophthalmological evaluation showed incomplete right homonymous hemianopsia. MRI demonstrated a 2.5 × 2.5 × 2.5-cm enhancing left-sided lesion involving the hypothalamus with extension into the suprasellar cistern, extending along the left optic tract and anterior to the level of the optic chiasm. A biopsy procedure revealed a juvenile pilocytic astrocytoma. A subtotal resection of approximately 80% of the tumor was performed. Postoperatively, the patient experienced complete resolution of her personality changes, and her weight decreased back to baseline. Ophthalmological examination showed increased right homonymous hemianopsia. In the years following her surgery, there was a spontaneous decrease in tumor size without adjuvant therapy. The patient continues to have an excellent quality of life despite a visual field defect, and no further tumor growth has been observed 20).


Loh et al. present here the case of a 4-year-old boy with exophthalmos and near blindness due to an intraorbital OPG. Despite chemotherapy he showed progressive exophthalmos and vision loss. Bony orbital decompression with ON transection temporally reduced his exophthalmos. OPG resection was required later for recurrence of his exophthalmos secondary to tumor progression. Post operatively, he had preserved oculomotor nerve functions but developed globe ischemia. Unusually, his ischemic globe caused him to have pain and severe photophobia, which later lead to enucleation. Photophobia has been reported in blind patients. Animal models and MRI functional imaging showed activation of trigeminal pathway during photophobia in completely transected ON. However, the exact neuro-ophthalmology pathway requires further study.

This is the first described case of photophobia after excision of OPG with ON denervation. Photophobia can be a serious side effect that significantly lowers the patient's quality of life 21).


Cavicchiolo et al. describe the case of a 3-year-old child, diagnosed with familial neurofibromatosis type 1 (NF1) and asymptomatic optic pathway tumor at the age of two, who developed diencephalic syndrome (DS) due to tumor progression 1 year after diagnosis. Magnetic resonance imaging disclosed an enlarging hypothalamic contrast-enhanced mass. Because of the tumor progression, in terms of tumor volume and DS, chemotherapy (CT) treatment was started according to the international protocol for progressive low-grade glioma, with rapid clinical improvement in terms of gain weight and DS resolution. Interestingly, tumor volume was unchanged after CT.

This case report highlights the following facts: (1) optic pathway glioma (OPG) in young children with NF1 may have definitive growth potentials and thus, they are worth an accurate clinical follow-up; (2) also, OPG occurring in NF1 patients can be responsible for DS in case of hypothalamus involvement; (3) consequently, the child's growth pattern must be included among the clinical parameters, which must be specifically evaluated during the follow-up of children, with or without NF1, bearing an OPG; and, finally, (4) that DS can improve after CT, even in face of a stable tumor volume 22).

Vyas et al. report a case of a hypothalamic glioma masquerading as a craniopharyngioma on imaging along with brief review of both the tumors 23).

Diffusion tensor imaging localization of the pyramidal tract and spectroscopy in diencephalic pilocytic astrocytoma: a case report 24).


the authors present an unusual radiographic appearance of a Pilomyxoid astrocytoma (PMA) in an 11-year-old child. Preoperative images suggested a dural-based, homogenously enhancing lesion coupled with an enlarged optic nerve. Surgery revealed an intraparenchymal lesion of the right temporal lobe. There was hyperintensity on T2 MRI sequences, suggesting infiltration of the tumor along the optic tracts 25).

A retrospective, single-center, cohort study of 176 patients (93 boys), aged 6 years (range, 0.2-18 years), with hypothalamic-pituitary lesions was performed. The lesions were craniopharyngioma (n = 56), optic pathway glioma (n = 54), suprasellar arachnoid cyst (n = 25), hamartoma (n = 22), germ cell tumor (n = 12), and hypothalamic-pituitary astrocytoma (n = 7). The most common presenting symptoms were neurologic (50%) and/or visual complaints (38%), followed by solitary endocrine symptoms (28%). Precocious puberty led to diagnosis in 19% of prepubertal patients (n = 131), occurring earlier in patients with hamartoma than in patients with optic-pathway glioma (P < .02). Isolated diabetes insipidus led to diagnosis for all germ-cell tumors. For 122 patients with neuro-ophthalmic presenting symptoms, the mean symptom interval was 0.5 year (95% CI, 0.4-0.6 year), although 66% of patients had abnormal body mass index or growth velocity, which preceded the presenting symptom interval onset by 1.9 years (95% CI, 1.5-2.4 years) (P < .0001) and 1.4 years (95% CI, 1-1.8 years) (P < .0001), respectively. Among them, 41 patients were obese before diagnosis (median 2.2 years [IQR, 1-3 years] prior to diagnosis) and 35 of them had normal growth velocity at the onset of obesity. The sensitivity of current guidelines for management of childhood obesity failed to identify 61%-85% of obese children with an underlying hypothalamic-pituitary lesion in this series.
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optic_pathway_glioma.txt · Last modified: 2019/01/03 12:56 by administrador