Optic Pathway Glioma MRI

Optic Pathway Glioma 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 hypothalamusoptic 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: enlargement, often iso to hypointense compared to the contralateral side

T2: hyperintense centrally

thin low-signal at the periphery representing the dura 1).

FLAIR: hyper intense

T1 C+ (Gd): enhancement is variable

Patients with chiasmatic-hypothalamic low-grade glioma (CHLGG) have frequent MRIs with gadolinium-based contrast agents (GBCA) for disease monitoring. Cumulative gadolinium deposition in the brains of children is a potential concern. The purpose of a study of Malbari et al. was to evaluate whether MRI with GBCA is necessary for determining radiographic tumor progression in children with CHLGG.

Children who were treated for progressive CHLGG from 2005 to 2019 at Texas Children’s Cancer Center were identified. Pre- and post-contrast MRI sequences were separately reviewed by one neuroradiologist who was blinded to the clinical course. Three-dimensional measurements and tumor characteristics were evaluated. Radiographic progression was defined as a 25% increase in size (product of two largest dimensions) compared with baseline or best response after initiation of therapy.

A total of 28 patients with progressive CHLGG were identified with a total of 683 MRIs with GBCA reviewed (mean 24 MRIs/patient; range, 11-43 MRIs). Radiographic progression was observed 92 times, 91 (99%) on noncontrast and 90 (98%) on contrast imaging. Sixty-seven progressions necessitating management changes were identified in all (100%) noncontrast sequences and 66 (99%) contrast sequences. Tumor growth > 2 mm in any dimension was identified in 184/187 (98%) noncontrast and 181/187 (97%) with contrast imaging. Metastatic tumors were better visualized on contrast imaging in 4/7 (57%).

MRI without GBCA effectively identifies patients with progressive disease. When imaging children with CHLGG, eliminating GBCA should be considered unless monitoring patients with metastatic disease 2)

Gadolinium might not be needed for these exams to inform management decisions. Secondary benefits of a non-contrast follow-up protocol include decreased cost and risk to the patient 3).

MR examinations of 91 patients with OPG (47 with NF and 44 without) were reviewed at presentation and during follow-up. The images were evaluated for size and extension of tumor, and imaging parameters. Statistical bivariate analysis was used to compare the patients with and those without NF, and Pearson correlation was used to evaluate the correlation between the different imaging parameters and prognosis. Kappa values were calculated to determine intraobserver and interobserver variability.

Results: The most common site of involvement in the NF group was the orbital nerve (66%), followed by the chiasm (62%). In the non-NF group, the chiasm was the most common site of involvement (91%); the orbital nerves were involved in only 32%. Extension beyond the optic pathway at diagnosis was uncommon in the NF group (2%) but frequent in the non-NF group (68%). In the NF group, the tumor was smaller and the original shape of the optic pathways was preserved (91% vs. 27% in the non-NF group). The presence of cystic components was significantly more common in the non-NF patients (66% vs. 9% in the NF group). During follow-up, half the NF patients remained stable, in contrast to 5% of the non-NF group. No statistical correlation was found between imaging features and biological behavior of the tumor.

Conclusion: NF-OPG is a separate entity from non-NF-OPG, with different imaging features and prognosis, thereby warranting a specific diagnostic, clinical, and therapeutic approach 4).


Müller-Forell WS, Boltshauser E. Imaging of Orbital and Visual Pathway Pathology. Springer Verlag. (2005) ISBN:3540279881.

Malbari F, Chintagumpala MM, Wood AC, Levy AS, Su JM, Okcu MF, Lin FY, Lindsay H, Rednam SP, Baxter PA, Paulino AC, Orzaiz GA, Whitehead WE, Dauser R, Supakul N, Kralik SF. Gadolinium is not necessary for surveillance MR imaging in children with chiasmatic-hypothalamic low-grade glioma. Pediatr Blood Cancer. 2021 Jun 16:e29178. doi: 10.1002/pbc.29178. Epub ahead of print. PMID: 34133064.

Maloney E, Stanescu AL, Perez FA, Iyer RS, Otto RK, Leary S, Steuten L, Phipps AI, Shaw DWW. Surveillance magnetic resonance imaging for isolated optic pathway gliomas: is gadolinium necessary? Pediatr Radiol. 2018 Sep;48(10):1472-1484. doi: 10.1007/s00247-018-4154-4. Epub 2018 May 22. PMID: 29789890.

Kornreich L, Blaser S, Schwarz M, Shuper A, Vishne TH, Cohen IJ, Faingold R, Michovitz S, Koplewitz B, Horev G. Optic pathway glioma: correlation of imaging findings with the presence of neurofibromatosis. AJNR Am J Neuroradiol. 2001 Nov-Dec;22(10):1963-9. PMID: 11733333; PMCID: PMC7973845.

Hippo signaling pathway

Hippo signaling pathway

Hippo signaling pathway, also known as the Salvador/Warts/Hippo (SWH) pathway, controls organ size in animals through the regulation of cell proliferation and apoptosis. The pathway takes its name from one of its key signaling components—the protein kinase Hippo (Hpo). Mutations in this gene lead to tissue overgrowth, or a “hippopotamus”-like phenotype.

A fundamental question in developmental biology is how an organ knows to stop growing after reaching a particular size. Organ growth relies on several processes occurring at the cellular level, including cell division and programmed cell death (or apoptosis). The Hippo signaling pathway is involved in restraining cell proliferation and promoting apoptosis. As many cancers are marked by unchecked cell division, this signaling pathway has become increasingly significant in the study of human cancer.

The Hippo signaling pathway appears to be highly conserved. While most of the Hippo pathway components were identified in the fruit fly (Drosophila melanogaster) using mosaic genetic screens, orthologs to these components (genes that function analogously in different species) have subsequently been found in mammals. Thus, the delineation of the pathway in Drosophila has helped to identify many genes that function as oncogenes or tumor suppressors in mammals.

Results showed the overexpression of YAP1 and Survivin as well as a decreased activity of large tumor suppressor 1 (LATS1) in high-grade glioblastoma versus anaplastic astrocytoma and low-grade glioma. Furthermore, Aguennouz et al. also demonstrated that miR-221 and miR-10b are specifically involved in Hippo signaling pathway via LATS1 regulation and that their knockdown significantly decreased glioma cell proliferation. This preliminary data confirmed the crucial role of the Hippo signaling pathway in cancer and suggested that miR 221 and miR 10b could be potential therapeutic targets for glioma treatment 1).

Increasing studies have revealed that metabolic disorders, especially diabetes, are high risk factors for the development of Alzheimer’s disease (AD) and other neurodegenerative diseases. It has been reported that patients with diabetes are prone to suffer from cognitive dysfunction (CD). Although abnormal glucose metabolism and deposition of amyloid β (Aβ) are proven to have a closely relationship with diabetes-induced CD, its exact mechanism is still undetermined. In this study, a total of 14 mice were intraperitoneally injected with streptozotocin for 5 consecutive days to mimic diabetic models, and then hierarchical cluster analysis was adopted to classify the diabetic mice into CD and Non-CD phenotypes by the results of Morris water maze test (MWMT). Furthermore, we detected Hippo signaling including mammalian sterile 20-like protein kinases1 (MST1), large tumor suppressors 1 (LATS1), Yes-associated protein (YAP) and phosphorylation of YAP (p-YAP) in brain and peripheral tissues. As compared with control mice, the levels of MST1, LATS1 and p-YAP/YAP ratio were increased in medial prefrontal cortex (mPFC), striatum and hippocampus of CD mice, while these proteins were decreased in gut tissue of CD mice. Additionally, there were significant positive correlations between escape latency and p-YAP/YAP ratio in mPFC, anterior cingulate cortex (ACC) and hippocampus, as well as the level of LATS1 in liver, kidney and gut tissues. In conclusion, alterations in Hippo signaling may contribute to CD induced by diabetes. Therefore, therapeutic interventions improving Hippo signaling might be beneficial to the treatment of diabetes-induced CD and other neurodegenerative diseases 2).

The Hippo signaling pathway is functionally conserved in Drosophila melanogaster and mammals, and its proposed function is to control tissue homeostasis by regulating cell proliferation and apoptosis. The core components are composed of a kinase cascade that culminates with the phosphorylation and inhibition of Yes-associated protein 1 (YAP1). Phospho-YAP1 is retained in the cytoplasm. In the absence of Hippo signaling, YAP1 translocates to the nucleus, associates with co-activators TEAD1-4, and functions as a transcriptional factor promoting the expression of key target genes. Components of the Hippo pathway are mutated in human cancers, and deregulation of this pathway plays a role in tumorigenesis. Loss of the NF2 tumor suppressor gene is the most common genetic alteration in meningiomas, and the NF2 gene product, Merlin, acts upstream of the Hippo pathway. Baia et al. show that primary meningioma tumors have high nuclear expression of YAP1. In meningioma cells, Merlin expression is associated with phosphorylation of YAP1. Using an siRNA transient knockdown of YAP1 in NF2-mutant meningioma cells, they show that suppression of YAP1 impaired cell proliferation and migration. Conversely, YAP1 overexpression led to a strong augment of cell proliferation and anchorage-independent growth and restriction of cisplatin-induced apoptosis. In addition, expression of YAP1 in nontransformed arachnoidal cells led to the development of tumors in nude mice. Together, these findings suggest that in meningiomas, deregulation of the Hippo pathway is largely observed in primary tumors and that YAP1 functions as an oncogene promoting meningioma tumorigenesis 3).

Physiologically, The Hippo signaling largely restricts its two downstream effectors, homologous oncoproteins Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), to a low level of activity by the MST1-SAV1 complex-induced kinase cascade. However, how the negative regulation induced by MST1-SAV1 complex is disrupted to exhibit constitutive YAP/TAZ activation in cancer remains unclear.

Zhu et al.report that miR-130b directly repressed MST1 and SAV1 expression in human glioblastoma cells. Overexpression of miR-130b induced hyperactivation of the YAP/TAZ and enhanced expression of the Hippo signaling downstream genes CTGF and the pluripotency associated markers, including CD133, SOX2, Nanog, MYC and BMI1, leading to promotion of glioblastoma stem cell phenotype. Conversely, inhibition of miR-130b attenuated these effects. These findings provide a novel mechanism for Hippo signaling inactivation in cancer, indicating not only a potentially pivotal role for miR-130b in the progression of glioblastoma, but also may represent a new therapeutic target 4).



Aguennouz M, Polito F, Visalli M, et al. microRNA-10 and -221 modulate differential expression of Hippo signaling pathway in human astroglial tumors [published online ahead of print, 2020 Aug 5]. Cancer Treat Res Commun. 2020;24:100203. doi:10.1016/j.ctarc.2020.100203

Yu F, Han W, Zhan G, Li S, Jiang X, Xiang S, Zhu B, Yang L, Hua D, Luo A, Hua F, Yang C. Differential Levels of Hippo Signaling in Selected Brain and Peripheral Tissues in Streptozotocin-Induced Cognitive Dysfunction in Mice. Neuroscience. 2019 Nov 1. pii: S0306-4522(19)30663-3. doi: 10.1016/j.neuroscience.2019.09.018. [Epub ahead of print] PubMed PMID: 31682826.

Baia GS, Caballero OL, Orr BA, Lal A, Ho JS, Cowdrey C, Tihan T, Mawrin C, Riggins GJ. Yes-associated protein 1 is activated and functions as an oncogene in meningiomas. Mol Cancer Res. 2012 Jul;10(7):904-13. doi: 10.1158/1541-7786.MCR-12-0116. Epub 2012 May 22. PubMed PMID: 22618028.

Zhu G, Wang Y, Mijiti M, Wang Z, Wu PF, Jiafu D. Upregulation of miR-130b enhances stem cell-like phenotype in glioblastoma by inactivating the Hippo signaling pathway. Biochem Biophys Res Commun. 2015 Aug 1. pii: S0006-291X(15)30379-X. doi: 10.1016/j.bbrc.2015.07.149. [Epub ahead of print] PubMed PMID: 26241672.

Update: Optic pathway glioma

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

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.

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. 7).


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 8).
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 9).


Presenting at <1 year of age, diencephalic features, non-NF1 status, and location along the posterior pathway have been typically associated with a more aggressive disease course 10) 11).
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. 12).

Case series


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 13).


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 14).


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 15).

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. 16).

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 17).


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 18).


Diencephalic syndrome and its relation to opticochiasmatic glioma: review of twelve cases 19).


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 20).

Case reports


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.

Raelson C, Chiang G. Chiasmatic-hypothalamic masses in adults: a case series and review of the literature. J Neuroimaging. 2015 May;25(3):361-4. doi: 10.1111/jon.12132. Epub 2014 Jul 4. PubMed PMID: 25039315.

Pelc S. The diencephalic syndrome in infants. A review in relation to optic nerve glioma. Eur Neurol. 1972;7(6):321-34. PubMed PMID: 4659145.

Pelc S, Flament-Durand J. Histological evidence of optic chiasma glioma in the “diencephalic syndrome”. Arch Neurol. 1973 Feb;28(2):139-40. PubMed PMID:4683151.

Khan AA, El-Borai AK. Pilomyxoid astrocytoma presenting as diencephalic syndrome. J Ayub Med Coll Abbottabad. 2014 Oct-Dec;26(4):611-5. PubMed PMID: 25672198.
7) , 23)

Vyas S, Prabhakar N, Tewari MK, Radotra BD, Khandelwal N. Hypothalamic glioma masquerading as Craniopharyngioma. J Neurosci Rural Pract. 2013 Jul;4(3):323-5. doi: 10.4103/0976-3147.118790. PubMed PMID: 24250172; PubMed Central PMCID:PMC3821425.

Gnekow AK, Kortmann RD, Pietsch T, Emser A. Low grade chiasmatic-hypothalamic glioma-carboplatin and vincristin chemotherapy effectively defers radiotherapy within a comprehensive treatment strategy—report from the multicenter treatment study for children and adolescents with a low grade glioma—HIT-LGG 1996—of the Society of Pediatric Oncology and Hematology (GPOH) Klin Padiatr. 2004;216(6):331–342.

Chong AL, Pole JD, Scheinemann K, Hukin J, Tabori U, Huang A, Bouffet E, Bartels U. Optic pathway gliomas in adolescence–time to challenge treatment choices? Neuro Oncol. 2013 Mar;15(3):391-400. doi: 10.1093/neuonc/nos312. Epub 2013 Jan 7. PubMed PMID: 23295772; PubMed Central PMCID: PMC3578487.

Laithier V, Grill J, Le Deley MC, et al. Progression-free survival in children with optic pathway tumors: dependence on age and the quality of the response to chemotherapy—results of the first French prospective study for the French Society of Pediatric Oncology. J Clin Oncol. 2003;21(24):4572–4578.

Khafaga Y, Hassounah M, Kandil A, et al. Optic gliomas: a retrospective analysis of 50 cases. Int J Radiat Oncol Biol Phys. 2003;56(3):807–812.
12) , 18)

Varan A, Batu A, Cila A, Soylemezoğlu F, Balcı S, Akalan N, Zorlu F, Akyüz C, Kutluk T, Büyükpamukçu M. Optic glioma in children: a retrospective analysis of 101 cases. Am J Clin Oncol. 2013 Jun;36(3):287-92. doi: 10.1097/COC.0b013e3182467efa. PubMed PMID: 22547006.

Alireza M, Amelot A, Chauvet D, Terrier LM, Lot G, Bekaert O. Poor prognosis and challenging in treatment of optic nerve malignant gliomas: A literature review and case report series. World Neurosurg. 2016 Oct 25. pii: S1878-8750(16)31072-5. doi: 10.1016/j.wneu.2016.10.083. [Epub ahead of print] PubMed PMID: 27793766.

Millward CP, Da Rosa SP, Avula S, Ellenbogen JR, Spiteri M, Lewis E, Didi M, Mallucci C. The role of early intra-operative MRI in partial resection of optic pathway/hypothalamic gliomas in children. Childs Nerv Syst. 2015 Nov;31(11):2055-62. doi: 10.1007/s00381-015-2830-3. Epub 2015 Jul 28. PubMed PMID: 26216059.

Goodden J, Pizer B, Pettorini B, Williams D, Blair J, Didi M, Thorp N, Mallucci C. The role of surgery in optic pathway/hypothalamic gliomas in children. J Neurosurg Pediatr. 2014 Jan;13(1):1-12. doi: 10.3171/2013.8.PEDS12546. Epub 2013 Oct 18. PubMed PMID: 24138145.

Zoli M, Mazzatenta D, Valluzzi A, Marucci G, Acciarri N, Pasquini E, Frank G. Expanding indications for the extended endoscopic endonasal approach to hypothalamic gliomas: preliminary report. Neurosurg Focus. 2014;37(4):E11. doi: 10.3171/2014.7.FOCUS14317. PubMed PMID: 25270130.

Mandiwanza T, Kaliaperumal C, Khalil A, Sattar M, Crimmins D, Caird J. Suprasellar pilocytic astrocytoma: one national centre’s experience. Childs Nerv Syst. 2014 Feb 25. [Epub ahead of print] PubMed PMID: 24566674.

DeSousa AL, Kalsbeck JE, Mealey J Jr, Fitzgerald J. Diencephalic syndrome and its relation to opticochiasmatic glioma: review of twelve cases. Neurosurgery. 1979 Mar;4(3):207-9. PubMed PMID: 460550.

Loh CK, Weis B, van Velthoven V, Reiff C, Rössler J. Photophobia in a blind eye after removal of a progressive orbital optic glioma with denervation. J Neurol Sci. 2015 Nov 15;358(1-2):522-4. doi: 10.1016/j.jns.2015.09.375. Epub 2015 Oct 3. PubMed PMID: 26474792.

Cavicchiolo ME, Opocher E, Daverio M, Bendini M, Viscardi E, Bisogno G, Perilongo G, Da Dalt L. Diencephalic syndrome as sign of tumor progression in a child with neurofibromatosis type 1 and optic pathway glioma: a case report. Childs Nerv Syst. 2013 Oct;29(10):1941-5. doi: 10.1007/s00381-013-2109-5. Epub 2013 Apr 25. PubMed PMID: 23615855.

Knorr Z, Leblond P, Baroncini M, Pruvo JP, Jissendi Tchofo P. Diffusion tensor imaging localization of the pyramidal tract and spectroscopy in diencephalic pilocytic astrocytoma: a case report. J Neuroradiol. 2013 Mar;40(1):68-70. doi: 10.1016/j.neurad.2011.12.002. Epub 2012 Feb 1. PubMed PMID: 22300962.

Edwards JR, Kulwin CG, Martin SE, Wilson S, Ho CY, Fulkerson DH. Temporal and optic pathway pilomyxoid astrocytoma mimicking dural-based lesion: case report and review of the literature. Pediatr Neurosurg. 2012;48(4):253-7. doi: 10.1159/000345634. Epub 2013 Mar 19. Review. PubMed PMID: 23548417.