Neurocutaneous syndromes Flashcards
1
Q
what are neurocutaneous disorders
A
A diverse group of diseases affecting all three germ layers: ectoderm, mesoderm, and endoderm.
2
Q
three key features of sturge-weber syndrome
A
- Facial capillary malformation (port-wine stain)
- Vascular malformation of the brain (leptomeningeal angioma)
- Ipsilateral vascular glaucoma
3
Q
how many variants of sturge-weber syndrome are there
A
3
4
Q
ratio of males to females affected by Sturge weber syndrome
A
1:1
5
Q
incidence of sturge weber syndrome
A
1 in 20,000 to 50,000
6
Q
prevalence of port wine stains
A
3 per 1000
7
Q
what percentage of people with port wine stains have associated eye or brain involvement
A
10-20%
8
Q
pathyphysiology of sturge weber syndrome
A
- Early embryological malformation of the vascular system.
- Failure of primitive cephalic venous plexus to regress and mature during the first trimester.
- Due to GNAQ gene mutation (Guanine nucleotide-binding protein G(q) subunit alpha) whichegulates signaling pathways controlling blood vessel development.
9
Q
are brain angiomas in sturge weber syndrom usually ipsilateral or contralateral to the skin angioma
A
ipsilateral
10
Q
what percentage of brain angiomas occur unilaterally in sturge-weber syndome
A
85%
11
Q
vascular abormalities in sturge weber syndrome (and what they lead to)
A
Dilated and tortuous pial vessels
- Abnormal venous drainage → venous ischemia in the cerebral cortex.
- Reduced arterial flow → cerebral atrophy.
- Neuronal loss, gliosis, and calcification.
12
Q
facial hemangioma presentation in sturge-weber syndrome
A
- Present at birth
- Upper eyelid and frontal region (1st branch of the trigeminal nerve)
- Unilateral in 63% of cases
13
Q
what syndrome may sturge-weber syndrome be associated with
A
Klippel-Trenaunay Syndrome
14
Q
how may sturge-weber syndrome be associated with klipper-trenaunay syndrome
A
Involvement of thorax, abdomen, upper/lower limbs
15
Q
what is the prognosis of sturge-weber syndrome related to
A
the severity of CNS signs
16
Q
common neurological symptoms of sturge weber syndrome
A
- Epilepsy
- Contralateral Spastic Hemiplegia and Hemianopsia
- Cognitive deficits
- Headaches & migraine
17
Q
what percentage of sturge-weber cases have epilepsy
A
75-85%
18
Q
epsilpesy onset in sturge-weber syndrome
A
within the first year
19
Q
factors which indicate severe outcomes of sturge weber syndrome
A
- Bilateral cerebral lesions
- Degree of cerebral atrophy
- Early onset
- Refractory seizures
20
Q
common eye symptoms in sturge weber syndrome
A
- Eyelid hemangioma
- Glaucoma (30-70%)
- Conjunctival and episcleral hemangiomas
- Choroidal hemangiomas (40-50%)
- Heterochromia of the irises
21
Q
what imaging is used to diagnose sturge weber syndrome
A
- MRI with gadolinium: Pial angioma and cerebral atrophy
- CT scan: “Railroad track” calcification
- PET/SPECT scans: Hypometabolism
22
Q
three areas of treatment for sturge weber syndrome
A
- stroke prevention measures
- glaucoma treatment
- seizure management
23
Q
stroke prevention measures in sturge-weber syndrome
A
- Avoid dehydration and fever
- Headache management
24
Q
siezure management in Sturge weber syndrome
A
- Anticonvulsants
- Epilepsy surgery (hemispherectomy) – 81% seizure-free at 1 year
25
tuberous sclerosis inheritance
autosomal dominant
26
tuberous sclerosis pathyphysiology
- TSC1 (Hamartin) and TSC2 (Tuberin) mutations
- Regulate cortical development and growth
- Inhibit mTOR pathway
- Mutation → Hyperactivation of mTOR → Abnormal growth
27
what systems are implicated in tuberous sclerosis
CNS, skin, heart, kidneys, lungs, eyes
28
what percentage of cases with tuberous sclerosis have CNS involvement
85%
29
prevalence of tuberous sclerosis
1 in 12,000 to 14,000
30
brain abormalities in tuberous sclerosis
- **Cortical tubers**
- **Subependymal nodules**
- **Subependymal giant cell astrocytomas (SEGA)**
31
when does SEGA appear
in the first two decades
32
in what percentage of cases does SEGA present
10%
33
what is the main neurological aspect of tuberous sclerosis
epilepsy
34
what percentage of cases of tuberous sclerosis have epilepsy
85%
35
onset of epsilepsy in tuberous sclerosis
first year
36
types of seizures present in tuberous sclerossi
- Focal seizures
- Infantile spasms
- **Lennox-Gastaut syndrome**
37
EEG findings in a patient with CNS implications assocaited with tuberous sclerossi
multifocal abnormalities
38
what does severe epilepsy lead to in tuberous sclerosis
severe cognitive impairment
39
how are seizures managed in tuberous sclerosis
vigabatrin
40
what percentage of cases is vigabartin effective for (tuberous sclerosis)
95%
41
what percentage of people with tuberous sclerosis have an IQ of less than70
50%
42
two neurodevelopmental conditions comorbid with tuberous sclerosis
ASD & ADHD
43
behavioural features of tuberous sclerosis
Aggression, mood instability, and anxiety
44
cutaneous manifestations of tuberous sclerosis
- Facial angiofibromas (late childhood/adolescence)
- Hypomelanotic macules (Ash-leaf spots)
- Ungual and gingival fibromas
- Shagreen patch
45
renal manifestations of tuberous sclerosis
- Angiomyolipomas (80%) – risk of hemorrhage
- Isolated cysts (9-20%)
- Autosomal dominant polycystic kidney disease (2-3%)
- Renal cell carcinoma (2-3%)
46
what cardiac tumour occurs in tuberous sclerosis
Rhabdomyomas (50-60%)
47
when do rhabdomyomas reach their peak size
at birth - tend to regress spontaneously
48
consequences of rhabdomyomas
- Can cause outflow tract obstruction
- Risk of arrhythmia
49
eye manifestations of tuberous sclerosis
Retinal hamartomas (50%)
50
lung involvement of tuberous sclerosis
- Multifocal micronodular pneumocyte hyperplasia
- Pulmonary cysts
- Lymphangioleiomyomatosis (LAM) – seen in 1% of women >30 years
- Can cause pulmonary hypertension and hypercapnia**
51
surveillance of tuberous sclerosis
MRI Brain: Performed before age 2, then annually until 21 years
52
seizure management in tuberous sclerosis
- Antiepileptic drugs (AEDs)
- Epilepsy surgery
- Ketogenic diet or Vagus Nerve Stimulation (VNS)
- mTOR inhibitors (Rapamycin, Everolimus) – used for SEGA
53
three types of neurofibromatosis
1. Neurofibromatosis Type 1 (NF1)
2. Neurofibromatosis Type 2 (NF2)
3. Schwannomatosis
54
prevalence of NF 1
1 in 3000
55
genetic cause of NF1
- Mutation in NF1 gene (chromosome 17q11.2)
- Encodes Neurofibromin, a GTPase-activating protein (GAP)
56
what is a neurofibroma
a benign peripheral nerve tumour
57
features of NF1
- Lisch Nodules - Pigmented hamartomas of the iris
- Neurofibromas - Can be cutaneous or plexiform (deep, invasive)
- Skeletal Dysplasia - Bone abnormalities;, Scoliosis is common
- Optic Gliomas - May cause vision loss
58
what percentage of people with NF1 have optic glioma
15%
59
when do optic gliomas present in people with NF1
the first decade of life
60
diagnostic criteria for NF1
Diagnosis requires two or more of the following:
- ≥6 café-au-lait spots (>5mm in prepubertal children, >15mm in postpubertal)
- ≥2 neurofibromas or 1 plexiform neurofibroma
- Axillary or inguinal freckling
- Optic glioma
- ≥2 Lisch nodules (iris hamartomas)
- Bony dysplasia (sphenoid dysplasia or tibial pseudarthrosis)
- 1st-degree relative with NF1
61
prevalence of NF2
1 in 25,000
62
what type of inheritance is NF2
autosomal dominant
63
pathyphysiology of NF2
mutation on chromosome 22 affecting a tumor supresspr called merlin (shwannomin)
64
key feature of NF2
bilateral vestibular schwannomas
65
tumor assocaitions of NF2
- Vestibular Schwannomas
- Meningiomas
- Ependymomas
66
non tumor symptoms of NF2
- Hearing loss
- Tinnitus
- Facial palsy
67
diagnosis of NF2
- Confirmed by:
- Bilateral vestibular schwannomas on MRI
- Family history and other tumors (meningiomas, ependymomas)
68
schwannomatosis
- Distinct from NF1 and NF2
- Multiple Schwannomas, but no vestibular schwannomas
- Chronic pain is a key feature
69
what is inconinentia pigmenti
multisystem disorder affecting the ectoderm
70
genetic cause of incontinentia pigmenti
x-liked dominant disorder; genetic mutation in the NEMO gene
71
is incontinentia pigmenti lethal for males or females
males
72
skin stages of inconintenia pigmenti
Inflammatory vesicles → Verrucous lesions → Hyperpigmentation → Hypopigmentation
73
non-skin manifestations of incontinentia pigmenti
- **Dental abnormalities (80%)**
- **Ocular involvement (30%)**
- **CNS involvement (33%)** – seizures, spasticity, microcephaly
74
skin features of hypomenanosis of ito
- streaks and whorls of hypopigmentation
- Affects trunk, head, or extremities
75
systemic features of hypomelanosis of ito
- Hemihypertrophy
- Eye abnormalities
- CNS involvement
- Musculoskeletal issues
76
CNS involvement in hypomelanosis of ito
- Cognitive impairment
- Epilepsy
- Psychiatric disorders
- Cortical malformations
77
time course of epidermal nevus syndrome
sporadic
78
key features of epidermal nevus syndrome
facial nevus with neurodevelopmental abnormalities
79
what is the nevus distribution in epidermal nevus syndrome
forhead, nose, scalp, midline
80
two main neurological features occuring in epidermal nevus syndrome
- seizures
CNS deficits
81
what percentage of people with epidermal nevus syndrome have seizures
75%
82
what type of seizures occur in epidermal nevus syndrome
GTCS, tonic seizures, infantile spasms
83
CNS deficits occuring in epidermal nevus syndrome
- CN VI, VII palsies
- Cortical blindness
- Hemiparesis
- Cognitive deficits (70%)
