Headache in children with Sturge-Weber syndrome - Prevalence, associations and impact.

BACKGROUND: Sturge-Weber syndrome (SWS) is a congenital neurovascular disorder characterised by capillary-venous malformations involving the skin, brain and eye. Patients experience headache, however little is known about its characteristics or associations. We aimed to estimate prevalence, associations and the impact of headache in children with SWS. MATERIALS AND METHODS: Case notes of all patients in a national tertiary paediatric SWS clinic were retrospectively reviewed. Patients were categorised into those with or without a history of headache, with an analysis performed of clinical stigmata of their disease and headache symptomology, associations and treatment. A multivariable logistic regression analysis was undertaken to elicit independent predictors of headache. RESULTS: 37% of patients with SWS (n = 84) reported headaches that were variably associated with seizures, a preceding blow to the head and a minority had migraine features. In those reporting headaches, headaches interfered with daily activities of a quarter of the children and 39% experienced headaches frequently (more than 1/month). Headache was associated with glaucoma and aspirin administration while children with monoplegia and hemiplegia were less likely to have headache. CONCLUSIONS: Headache is common in children with SWS, often without classical migraine features and affects daily activities. Awareness of headache and its associations in SWS may improve management of this complex population.

The Bone Does Not Predict the Brain in Sturge-Weber Syndrome.

BACKGROUND AND PURPOSE: It has been hypothesized that skull marrow signal alteration may represent an early disease manifestation of Sturge-Weber syndrome before development of its intracranial manifestations. We alternatively hypothesized that intraosseous changes are associated with the overlying port-wine stain rather than the intracranial stigmata of Sturge-Weber syndrome and hence are not a predictor of brain involvement. MATERIALS AND METHODS: MR imaging of children presenting with port-wine stain and/or Sturge-Weber syndrome between 1998 and 2017 was evaluated by 2 pediatric neuroradiologists for marrow signal abnormality and pial angioma and other Sturge-Weber syndrome features: ocular hemangioma, atrophy, and white matter changes (advanced myelination). Groups were divided into port-wine stain-only (without intracranial Sturge-Weber syndrome features) and Sturge-Weber syndrome (the presence of cerebral pial angioma). The χ2 test was performed to evaluate the association between port-wine stain and bone marrow changes and between osseous change and pial angioma. RESULTS: We reviewed 139 cases: 40 with port-wine stain-only and 99 with Sturge-Weber syndrome with pial angioma. Fifteen of 99 cases of Sturge-Weber syndrome had no port-wine stain. In the port-wine stain-only cohort, 78% had ipsilateral bony changes and 17% had no intraosseous changes. In the Sturge-Weber syndrome cohort, 84/99 had associated port-wine stain, 91% (P < .01) had bony changes ipsilateral to the port-wine stain or had no bone changes in the absence of port-wine stain, and 77% (P = .27) had bony changes ipsilateral to a cerebral pial angioma. Eighty percent of patients with Sturge-Weber syndrome who lacked a port-wine stain also lacked marrow changes. Five patients with bilateral port-wine stain and bilateral marrow changes had only a unilateral pial angioma. CONCLUSIONS: Intraosseous marrow changes are strongly associated with facial port-wine stain; no significant association was found between pial angioma and bone marrow changes.

Classification of neurological abnormalities in children with congenital melanocytic naevus syndrome identifies magnetic resonance imaging as the best predictor of clinical outcome.

BACKGROUND: The spectrum of central nervous system (CNS) abnormalities described in association with congenital melanocytic naevi (CMN) includes congenital, acquired, melanotic and nonmelanotic pathology. Historically, symptomatic CNS abnormalities were considered to carry a poor prognosis, although studies from large centres have suggested a much wider variation in outcome. OBJECTIVES: To establish whether routine MRI of the CNS is a clinically relevant investigation in children with multiple CMN (more than one at birth), and to subclassify radiological abnormalities. METHODS: Of 376 patients seen between 1991 and 2013, 289 fulfilled our criterion for a single screening CNS MRI, which since 2008 has been more than one CMN at birth, independent of size and site of the largest naevus. Cutaneous phenotyping and radiological variables were combined in a multiple regression model of long-term outcome measures (abnormal neurodevelopment, seizures, requirement for neurosurgery). RESULTS: Twenty-one per cent of children with multiple CMN had an abnormal MRI. Abnormal MRI was the most significant predictor of all outcome measures. Abnormalities were subclassified into group 1 'intraparenchymal melanosis alone' (n = 28) and group 2 'all other pathology' (n = 18). Group 1 was not associated with malignancy or death during the study period, even when symptomatic with seizures or developmental delay, whereas group 2 showed a much more complex picture, requiring individual assessment. CONCLUSIONS: For screening for congenital neurological lesions a single MRI in multiple CMN is a clinically relevant strategy. Any child with a stepwise change in neurological/developmental symptoms or signs should have an MRI with contrast of the brain and spine to look for new CNS melanoma.

New vascular classification of port-wine stains: improving prediction of Sturge-Weber risk.

BACKGROUND: Facial port-wine stains (PWSs) are usually isolated findings; however, when associated with cerebral and ocular vascular malformations they form part of the classical triad of Sturge-Weber syndrome (SWS). OBJECTIVES: To evaluate the associations between the phenotype of facial PWS and the diagnosis of SWS in a cohort with a high rate of SWS. METHODS: Records were reviewed of all 192 children with a facial PWS seen in 2011-13. Adverse outcome measures were clinical (seizures, abnormal neurodevelopment, glaucoma) and radiological [abnormal magnetic resonance imaging (MRI)], modelled by multivariate logistic regression. RESULTS: The best predictor of adverse outcomes was a PWS involving any part of the forehead, delineated at its inferior border by a line joining the outer canthus of the eye to the top of the ear, and including the upper eyelid. This involves all three divisions of the trigeminal nerve, but corresponds well to the embryonic vascular development of the face. Bilateral distribution was not an independently significant phenotypic feature. Abnormal MRI was a better predictor of all clinical adverse outcome measures than PWS distribution; however, for practical reasons guidelines based on clinical phenotype are proposed. CONCLUSIONS: Facial PWS distribution appears to follow the embryonic vasculature of the face, rather than the trigeminal nerve. We propose that children with a PWS on any part of the 'forehead' should have an urgent ophthalmology review and a brain MRI. A prospective study has been established to test the validity of these guidelines.

Epilepsy surgery in children under 3 years.

PURPOSE: Resective epilepsy surgery in early childhood has become an important treatment option for selected infants and children with epilepsy. We describe experience and clinical outcomes of children under 3 years undergoing epilepsy surgery at Great Ormond Street Hospital (GOSH). METHODS: All children under 36 months of age who had resective surgery for the purpose of treating epilepsy within the GOSH epilepsy surgery programme were ascertained using a departmental database. Aetiology, post-operative seizure frequency, pre and post-operative cognitive function, long-term complications and re-operation rates were analysed by retrospective examination of clinical records. RESULTS: Forty-two children were included in our cohort with a median age at surgery of 20 months (range 3-36 months). Surgical procedures comprised 25 functional hemispherectomies, two anatomical hemispherectomies, four multilobar resections, seven lobar resections and four focal resections. 7/42 (17%, 95% CI 8-31%) children underwent re-operation. 20/42 (48%, 95% CI 33-62%) children achieved seizure freedom. 18/42 (43%, 95% CI 29-58) demonstrated an improvement in seizure frequency and no children had an increase in seizure frequency. Post-operative complications included subsequent shunt procedure in 5/25 (20%, 95% CI 9-39%) children undergoing hemispherectomy. There were no mortalities. In 23 children pre- and post-operative DQ or IQ was determinable allowing longitudinal comparison. Five children had a decrease in DQ/IQ >15 and two children had an increase DQ/IQ >15. DISCUSSION: Epilepsy surgery in children under 3 years of age offers suitable candidates a good chance of significantly improved seizure outcome which compares with rates in older cohorts.

A spectrum of unusual neuroimaging findings in patients with suspected Sturge-Weber syndrome.

BACKGROUND AND PURPOSE: Sturge-Weber syndrome (SWS) is frequently associated with neurologic complications such as seizures, so diagnosing this condition has important implications for patient management. The purpose of this study was to report unusual neuroimaging findings in patients with facial port-wine stain (PWS) and clinically suspected SWS. MATERIALS AND METHODS: Cranial MR imaging was reviewed for all children with facial port-wine stain (PWS) involving the upper face and eyelids who were referred to Great Ormond Street Hospital between 2003 and 2007 for investigation of suspected SWS. Patients were excluded from further analysis if the imaging findings were normal on initial and subsequent scans and the subject remained free of neurologic disease, or if the imaging showed the well-recognized pattern of exclusively supratentorial pial enhancement representing the pial angioma of SWS. For the remaining patients, the neurologic, dermatologic, and ophthalmologic records were examined and all available imaging was reviewed by a neuroradiologist. We documented the presence and distribution of pial enhancement; corroborative features of SWS, such as atrophy, calcification, choroid plexus changes, and ocular abnormalities; and all other intracranial abnormalities. RESULTS: Of the 62 patients referred for assessment, imaging findings were considered typical of SWS in 32 (52%) and were normal or showed abnormalities attributable to an unrelated pathology in 20 (32%). Of the remaining 10 patients, in 7 (11%), there was evidence of a pial angioma in an unusual distribution involving infratentorial structures, with the angioma in 1 patient being diagnosed at postmortem only; in 2 (3%), there were imaging abnormalities with some features in common with typical SWS, such as subcortical calcification, but with no evidence of pial enhancement; in 1 (1.6%), the initial MR imaging finding was normal, but repeat imaging subsequently revealed pial enhancement. CONCLUSIONS: Involvement of infratentorial structures is common but may be relatively subtle and should be actively sought. Cases in which there are certain patterns of imaging abnormalities but an apparent absence of supratentorial pial enhancement on MR imaging may represent formes frustes of SWS; visualization of pial angiomatosis may also be delayed until later in childhood than expected.

Complications of congenital melanocytic naevi in children: analysis of 16 years' experience and clinical practice.

BACKGROUND: Congenital melanocytic naevi (CMNs) can be associated with abnormalities of the cental nervous system (CNS) and/or with melanoma. Quoted incidences for these complications vary in the literature, as do recommendations for investigations and follow-up. OBJECTIVES: To determine the incidence of complications, and to identify phenotypic features associated with a higher risk of complications. METHODS: We reviewed records of 224 patients with CMNs seen in Dermatology clinic between 1991 and 2007. Patients were excluded if they had a complication at the time of referral. Magnetic resonance imaging (MRI) of the CNS was offered on the basis of CMN phenotype. Follow up was in clinic and/or by postal questionnaires. RESULTS: One hundred and twenty patients (54 boys and 66 girls) who had MRI of the CNS were included in the analysis. Mean age at MRI was 2.46 years (median 1.20). Mean follow up was 8.35 years (median 7.86). Sixty-five per cent had naevi > 20 cm projected adult size or multiple CMNs (40% > 40 cm), and 83% had satellite lesions at birth. Outcome measures were MRI abnormality, clinical neurological abnormality, any tumour, malignant melanoma, and death. No complications were seen in the 16 patients with no satellite lesions at birth. MRI and/or clinical neurological abnormalities were found in 22 patients (18%) and were significantly associated with projected adult size of the CMN (particularly > 40 cm), and independently with male gender. Tumours occurred in five patients, two of which were malignant melanoma (1.7%). Due to small numbers there was no significant association between phenotype and occurrence of tumours. Three patients (2.5%) died (one from neuromelanosis and two from melanoma in patients with normal MRI scans). Death was significantly associated with CMN size > 40 cm. Importantly, there was no significant association between CMN distribution (including posterior axial location) and adverse outcomes. CONCLUSIONS: This is the largest study of CNS imaging in patients with CMNs. We report a newly recognized association between male gender and neurological complications, dispute the previously reported association between CMN site and neurological complications, and quantify the associations between CMN size, satellite lesions and neurological complications. We make recommendations for the management of these patients.

Central nervous system imaging and congenital melanocytic naevi.

AIM: To establish the prevalence of central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) in a population of children with congenital melanocytic naevi (CMN) over the head and/or spine, and to compare this with clinical findings. METHODS: Forty three patients identified from outpatient clinics underwent MRI of the brain and/or spine. These were reported by a paediatric radiologist and findings compared with the clinical picture. RESULTS: Nine patients had abnormal clinical neurology, seven had abnormal findings on MRI, and six had both abnormal clinical and radiological findings. Only three of the abnormal MRIs showed features of intracranial melanosis. Three others showed structural brain abnormalities: one choroid plexus papilloma, one cerebellar astrocytoma, and one posterior fossa arachnoid cyst; the first two of these have not previously been described in association with CMN. The last abnormal MRI showed equivocal changes requiring reimaging. CONCLUSIONS: The prevalence of radiological CNS abnormality in this group of children was 7/43. Six of these developed abnormal clinical neurological signs within the first 18 months of life, but two did not do so until after the MRI. Two of the CNS lesions were operable; for this reason we support the routine use of early MRI in this group.

Sturge-Weber syndrome: cerebral haemodynamics during seizure activity.

The aim of this study was to examine the haemodynamic response to seizures in three infants with Sturge-Weber syndrome by measuring regional cerebral blood flow using transcranial Doppler sonography and 99mTc HMPAO SPECT. Time-locked video/digital EEG recording was carried out for ictal studies. MRI was performed in all subjects. SPECT showed hemispheric hypoperfusion interictally in all three patients and also ictally in one of the three; a small region of hyperperfusion was seen on the same ictal scan in the latter, ie. the patient with interictal and ictal hypoperfusion. In the two older children middle cerebral artery velocity (MCAV) was reduced by between 29 and 62% in the middle cerebral artery of the predominantly affected hemisphere compared with the contralateral side. During seizures, increases of 6 to 30% in MCAV were recorded for the clinically seizing hemisphere compared with 24 to 170% for the contralateral side in four of the seizures recorded. In one infant, MCAV fell bilaterally during a seizure that generalized (-18 and -43% in the predominantly affected and contralateral side respectively). Sequential recordings in one infant suggested that, with time, the haemodynamic response to seizures of the unaffected hemisphere may decrease. These findings suggest that the venous malformation in SWS is associated with an impairment of the cerebral haemodynamic response to seizure activity.

The Kasabach-Merritt syndrome: treatment with intermittent pneumatic compression.

A 6 week old infant presented with a giant angiomatous naevus of the leg complicated by chronic disseminated intravascular coagulation. The bleeding and laboratory abnormalities responded to intermittent pneumatic compression of the affected limb. This innocuous treatment should be considered in the Kasabach-Merritt syndrome.