Phakomatosis: Brief overview about Radiological Perspectives

Radiological Presentation/tutorial with introduction to Phakomatoses and most common subtypes and their imaging features. Area of interest Radiology and Neurology residents

1. Dr Waseem Nizamani Senior Registrar Neuroradiology Time: 30 minutes Slides: 49 Phakomatoses : Brief Overview

2. Definition The term “ Phakoma”and its Embryological Connection Clinical Presentation Neuroradiological Presentation Cases Learning Goals

3. The phakomatoses are a heterogeneous group of disorders primarily involving structures derived from the embryologic neuroectoderm . However , they commonly exhibit associated pathology in tissues derived from all three germ cell layers, most notably ectoderm (skin) and mesoderm (connective tissue). Definition

4. All the phakomatoses involve the central nervous system (CNS); some also affect the peripheral nervous system. Most are associated with cutaneous signs, and many have visceral and connective tissue (mesodermal) changes. Since the eye is functionally and developmentally part of the CNS, it is not surprising that ocular/retinal involvement is common in the phakomatoses .

5. The term " phakoma " implies a benign growth of normal or nearly normal cells that are indigenous to the involved tissue; it may be likened to the term "hamartoma." The word phakoma is usually described as being derived from the Greek " phakos "- a word whose meaning is erroneously generalized to include "mother spot" (birthmark?) and "lentil," as well as its true meaning which is "lens" or "eye Phakoma

6. In 1920, the Dutch ophthalmologist van der Hoeve first used " phakoma " to describe two different benign ocular lesions . Neurofibromatosis (NF) Tuberous sclerosis (TS) Calling both these lesions " phakomas ," van der Hoeve then assumed that TS and NF were related diseases, and

7. coined the term " phakomatoses " as the umbrella for congenital disorders affecting the CNS with benign growths . Later , he enlarged this concept to include other conditions characterized by CNS, cutaneous, and often ocular involvement, eg , Sturge -Weber syndrome (SWS) and von Hippel-Lindau disease.

8. Although authorities debate the logic of this grouping, some 20 to 30 other disorders have now been classified as phakomatoses

9. Sturge -Weber Syndrome

10. Sturge -Weber syndrome (SWS) is a congenital disorder of the vasculature of the face, the meninges, the brain, and often the eye. It is sometimes called " encephalofacial " or " encephalotrigeminal " angiomatosis , because the hallmark is the vascular lesion that involves the territory of the trigeminal nerve (CN V) plus the ipsilateral brain and meninges.

11. Typical patients exhibit a dark red or reddish-brown "port-wine" stain or nevus ("nevus flammeus ") on the face in the trigeminal territory The most common clinical manifestation is with childhood seizures, present in 71-89% of cases  2 , that are often refractory to medical therapy  1 . These usually begin in the first few years of life and are often associated with developmental delay and hemispheric symptoms including hemiplegia/hemiparesis and hemianopsia . Clinical Pres

12. Neuroradiology CT detects subcortical calcification at an earlier age than plain film and can also demonstrate associated parenchymal volume loss tram-track sign  of cortical and subcortical calcification 

13. Prominent leptomeningeal enhancement in affected area Much later in life the angioma may 'burn out' losing enhancement  E nlarged ipsilateral choroid plexus MRI

14. Tuberous Sclerosis

15. Tuberous sclerosis (TS) , also known as  tuberous sclerosis complex  or  Bourneville disease,  is a neurocutaneous disorder ( phakomatosis ) characterised by the development of multiple benign tumours of the embryonic ectoderm (e.g. skin, eyes, and nervous system). Definition

16. Tuberous sclerosis was classically described as presenting in childhood with a triad (Vogt triad) of : seizures : absent in one-quarter of individuals mental retardation : up to half have normal intelligence adenoma sebaceum : only present in about three-quarters of patients Clinical Triad

17. Tuberous sclerosis has a significant number of manifestations, involving many organ systems. The most common manifestations are: cortical or subependymal  tubers and white matter abnormalities renal  angiomyolipomas (AML) cardiac rhabdomyoma (s)

18. cortical/subcortical tubers: 50% are in the frontal lobe; high T2 and low T1 with only 10% of tubers showing enhancement; frequently calcify after two years of age subependymal hamartomas 88% are associated with calcification, although calcification absent in early childhood visible within the first six months of age  variable signal, frequently high T1 and iso to high T2 enhancement is variable and is not a useful feature in distinguishing them from subependymal giant cell astrocytomas (SGCA); only serial growth is reliable  5,6 Neurological 

19. subependymal giant cell astrocytomas (SGCA) peak occurrence 8-18 years tend to be large and demonstrate growth  5,6 tend to have intense enhancement white matter abnormalities variable appearance, with nodular, ill-defined, cystic and band-like lesions seen retinal phakomas

20. rarer findings cerebellar atrophy infarcts (due to occlusive vascular disorders) cerebral aneurysms dysgenesis of the corpus callosum Chiari malformations microcephaly arachnoid cysts chordoma

21. Radiology

22. ?

23. Neurofibromatosis type 1 (NF1) , also known as  von Recklinghausen disease , is a multisystem neurocutaneous disorder, the most common  phakomatosis . Also known as peripheral neurofibromatosis Neurofibromatosis 1

24. >6 cafe au lait spots evident during one year two or more  neurofibromas  or one plexiform neurofibroma optic nerve glioma distinctive osseous lesion (such as sphenoid wing dysplasia or thinning of long bone cortex with or without  pseudoarthrosis ) two or more iris hamartomas ( Lisch nodules)    axillary or inguinal freckling primary relative with NF1 with above criteria Diagnostic Crit

25. Breast manifestations Central nervous system manifestations C utaneous manifestations M usculoskeletal manifestations P ulmonary manifestations O rbital manifestations Systemic manifestations

26. FASI  (focal areas of signal intensity): occur in deep white matter and basal ganglia or corpus callosum  5 , areas of T2/FLAIR hyperintensity with no contrast enhancement optic nerve glioma or optic pathway glioma (may manifest as enlarged optic foramen ) progressive sphenoid wing dysplasia CNS manifestations

27. lambdoid suture defects dural calcification at vertex moya moya phenomenon (rare) buphthalmos

28. Imaging

29. Neurofibromatosis type 2   (NF2)  is a rare autosomal dominant neurocutaneous disorder ( phakomatosis ) manifesting as a development of multiple CNS tumours. Unlike  neurofibromatosis type 1 (NF1), it is not associated with neurofibromas .  May be called central neurofibromatosis. Neurofibromatosis 2

30. Instead, patients with this disease have : intracranial schwannoma(s): mostly vestibular schwannoma(s) sometimes patients may have spinal schwannomas intracranial and spinal meningioma(s) intraspinal -intramedullary  ependymoma (s) CNS lesions

31. These features give rise to the acronym  MISME , which describes  Multiple Inherited Schwannomas Meningiomas and Ependymomas   4 .  In fact, labelling this disorder  neurofibromatosis type 2  is a misnomer, because  neurofibromas  are not a part of its constellation of abnormalities  MISME

32. Clinical Menisfestation

33. Bilateral vestibular schwannomas are diagnostic of NF2  but care should be taken because bilateral internal acoustic meatus masses are not specific for vestibular schwannoma and can represent, for example, sarcoid or metastases  . Practical points

34. ataxia telangiectasia von Hippel-Lindau disease  ( retinocerebellar angiomatosis ) incontinentia pigmenti   (Bloch-Sulzberger syndrome) basal cell naevus syndrome  ( Gorlin-Goltz syndrome) Wyburn-Mason syndrome  (Bonnet-Dechaume-Blanc syndrome) encephalocraniocutaneous lipomatosis   hypomelanosis of Ito Other Phakomatosis

35. Nijmegen breakage syndrome epidermal naevus syndrome [+] ​ neurocutaneous melanosis   progressive facial hemiatrophy  (Parry-Romberg syndrome) PHACE syndrome Cowden disease / COLD syndrome Gomez-Lopez-Hernandez syndrome