Answer for BIR CoW 17 July 2022
Neurofibromatosis 1
Findings
Bilateral optic nerve appear diffusely thickened predominantly involving posterior aspect , optic chiasma and thalamo capsular region T2 / FLAIR hyperintensity seen along the optic nerve pathway, optic chiasma and thalamo capsular region causing compression of the aqueduct of sylvius with obstructive hydrocephalus. On contrast administration no significant enhancement noted. ASL perfusion showed no significant increase in perfusion MR spectroscopy at thalamo capsular region showed increase choline integral values and decreased N-acetylaspartate integral values Evidence of multiple patchy illdefined T2 / FLAIR hyperintensities seen involving ,midbrain , left side of pons and bilateral periventricular region with no contrast enhancement
Discussion
The term neurocutaneous syndromes denotes a group of CNS disorders that are characterized by brain malformations or neoplasms and skin/eye lesions. These disorders have also been called phakomatoses NF 1 – MC genetic syndrome - 1:3000 It is AD disorder Mutation of NF1 gene(17q11.2). Mutation inactivate the protein neurofibromin which is tumor supressor – unopposed RAS activation – Hence called Ras-opathy Neurofibromin is expressed in all cells with higher levels in CNS Half cases are familial and half are sporadic(de novo NF1: IMAGING Scalp/Skull, Meninges, and Orbit Dermal neurofibromas ○ Solitary/multifocal scalp nodules Increases with age Localized, well-circumscribed ○ Plexiform neurofibroma Pathognomonic of NF1 (30-50% of cases) Large, bulky infiltrative transspatial lesions Scalp, face/neck, spine ○ Sphenoid wing dysplasia Hypoplasia → enlarged orbital fissure Enlarged middle fossa ± arachnoid cyst Temporal lobe may protrude into orbit ○ Dural ectasia ○ Tortuous optic nerve sheath Patulous Meckel caves Enlarged IACs Brain. FASI/ DYSPLASTIC WM DISEASE Hyperintense T2/FLAIR WM foci ○ Rare in adults Wax in first decade, then wane ○ Astrocytomas Most common: pilocytic Optic pathway, hypothalamus > brainstem LESS COMMON. Malignant astrocytoma (anaplastic astrocytoma, glioblastoma multiforme) Progressive ICA stenosis → moyamoya • Fusiform ectasias, arteriovenous fistulas ○ Vertebral > carotid NF1-ASSOCIATED NEOPLASMS Common 1.Dermal neurofibromas (95% of adults) 2. Plexiform neurofibromas (PNFs) (30-50%) 3.Spinal neurofibromas Less Common 1.Pilocytic astrocytoma (80% of gliomas) 80% in optic pathway (15-20% of NF1 patients) 15% brainstem 5% other locations (cerebellum, cerebral hemispheres) 2.Other astrocytomas (20%) A . Diffusely infiltrating fibrillary astrocytoma (WHO grade II) B. Anaplastic astrocytoma (WHO grade III) Glioblastoma (WHO grade IV) Rare But Important 1. Malignant peripheral nerve sheath tumor Develops in 8-13% of PNFs 2. Juvenile chronic myeloid leukemia 3.Gastrointestinal stromal tumor 4.Pheochromocytoma 5.Rhabdomyosarcoma 6.Juvenile xanthogranuloma 7.Melanoma 8.Thyroid medullary carcinoma 9.Glomus tumors Differential Diagnosis In combination with appropriate clinical findings (see above), the presence of ZMVs on MR with or without OPG is diagnostic of NF1. In and of themselves, multifocal T2/FLAIR hyperintensities are nonspecific and can be seen in a variety of nonneoplastic disorders, including demyelinating disease and viral encephalitis. Unlike NF1, viral encephalitis has an acute clinical course and is usually associated with encephalopathy. Unusually extensive, confluent FASIs can mimic neoplasm (i.e., pilocytic astrocytoma, diffusely infiltrating low-grade astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, or gliomatosis cerebri). Both FASIs and gliomas are part of the NF1 spectrum, so follow-up imaging may be necessary. A recently described disorder parallels NF1 in some ways—multiple café au lait macules, axillary freckling, and macrocephaly—but the causative gene (SPRED1) is different. This disorder has been termed NF1-like syndrome. Patients lack cutaneous neurofibromas or PNFs, typical NF1 bone lesions, and optic pathway gliomas. Difference Between FASI and glioma IN MR SPECTROSCOPY FASI SHOW SIGNIFICANTLY ELEVATED CHOLINE WITH NEAR NORMAL NAA LEVELS WHEREAS IN TUMORS ELEVATED CHOLINE AND NEAR ABSENCE OF NAA LEVELS.
Findings
Bilateral optic nerve appear diffusely thickened predominantly involving posterior aspect , optic chiasma and thalamo capsular region T2 / FLAIR hyperintensity seen along the optic nerve pathway, optic chiasma and thalamo capsular region causing compression of the aqueduct of sylvius with obstructive hydrocephalus. On contrast administration no significant enhancement noted. ASL perfusion showed no significant increase in perfusion MR spectroscopy at thalamo capsular region showed increase choline integral values and decreased N-acetylaspartate integral values Evidence of multiple patchy illdefined T2 / FLAIR hyperintensities seen involving ,midbrain , left side of pons and bilateral periventricular region with no contrast enhancement
Discussion
The term neurocutaneous syndromes denotes a group of CNS disorders that are characterized by brain malformations or neoplasms and skin/eye lesions. These disorders have also been called phakomatoses NF 1 – MC genetic syndrome - 1:3000 It is AD disorder Mutation of NF1 gene(17q11.2). Mutation inactivate the protein neurofibromin which is tumor supressor – unopposed RAS activation – Hence called Ras-opathy Neurofibromin is expressed in all cells with higher levels in CNS Half cases are familial and half are sporadic(de novo NF1: IMAGING Scalp/Skull, Meninges, and Orbit Dermal neurofibromas ○ Solitary/multifocal scalp nodules Increases with age Localized, well-circumscribed ○ Plexiform neurofibroma Pathognomonic of NF1 (30-50% of cases) Large, bulky infiltrative transspatial lesions Scalp, face/neck, spine ○ Sphenoid wing dysplasia Hypoplasia → enlarged orbital fissure Enlarged middle fossa ± arachnoid cyst Temporal lobe may protrude into orbit ○ Dural ectasia ○ Tortuous optic nerve sheath Patulous Meckel caves Enlarged IACs Brain. FASI/ DYSPLASTIC WM DISEASE Hyperintense T2/FLAIR WM foci ○ Rare in adults Wax in first decade, then wane ○ Astrocytomas Most common: pilocytic Optic pathway, hypothalamus > brainstem LESS COMMON. Malignant astrocytoma (anaplastic astrocytoma, glioblastoma multiforme) Progressive ICA stenosis → moyamoya • Fusiform ectasias, arteriovenous fistulas ○ Vertebral > carotid NF1-ASSOCIATED NEOPLASMS Common 1.Dermal neurofibromas (95% of adults) 2. Plexiform neurofibromas (PNFs) (30-50%) 3.Spinal neurofibromas Less Common 1.Pilocytic astrocytoma (80% of gliomas) 80% in optic pathway (15-20% of NF1 patients) 15% brainstem 5% other locations (cerebellum, cerebral hemispheres) 2.Other astrocytomas (20%) A . Diffusely infiltrating fibrillary astrocytoma (WHO grade II) B. Anaplastic astrocytoma (WHO grade III) Glioblastoma (WHO grade IV) Rare But Important 1. Malignant peripheral nerve sheath tumor Develops in 8-13% of PNFs 2. Juvenile chronic myeloid leukemia 3.Gastrointestinal stromal tumor 4.Pheochromocytoma 5.Rhabdomyosarcoma 6.Juvenile xanthogranuloma 7.Melanoma 8.Thyroid medullary carcinoma 9.Glomus tumors Differential Diagnosis In combination with appropriate clinical findings (see above), the presence of ZMVs on MR with or without OPG is diagnostic of NF1. In and of themselves, multifocal T2/FLAIR hyperintensities are nonspecific and can be seen in a variety of nonneoplastic disorders, including demyelinating disease and viral encephalitis. Unlike NF1, viral encephalitis has an acute clinical course and is usually associated with encephalopathy. Unusually extensive, confluent FASIs can mimic neoplasm (i.e., pilocytic astrocytoma, diffusely infiltrating low-grade astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, or gliomatosis cerebri). Both FASIs and gliomas are part of the NF1 spectrum, so follow-up imaging may be necessary. A recently described disorder parallels NF1 in some ways—multiple café au lait macules, axillary freckling, and macrocephaly—but the causative gene (SPRED1) is different. This disorder has been termed NF1-like syndrome. Patients lack cutaneous neurofibromas or PNFs, typical NF1 bone lesions, and optic pathway gliomas. Difference Between FASI and glioma IN MR SPECTROSCOPY FASI SHOW SIGNIFICANTLY ELEVATED CHOLINE WITH NEAR NORMAL NAA LEVELS WHEREAS IN TUMORS ELEVATED CHOLINE AND NEAR ABSENCE OF NAA LEVELS.
Note:
We do not discourage differential diagnosis. But all the differentials must satisfy the findings noted in the case.
If you feel you have answered rightly but cannot find your name in the above list, please call 09551942599.
Did you Know?
The order in which the names appear in this winner's list is based on the time of submission. The first person to send the correct answer gets his/her name on top of the list!
We do not discourage differential diagnosis. But all the differentials must satisfy the findings noted in the case.
If you feel you have answered rightly but cannot find your name in the above list, please call 09551942599.
Did you Know?
The order in which the names appear in this winner's list is based on the time of submission. The first person to send the correct answer gets his/her name on top of the list!