Late-onset cerebral arteriopathy in a patient with incontinentia pigmenti.

BACKGROUND: Incontinentia pigmenti (IP) is an X-linked neurocutaneous disorder that can present with cerebral arteriopathy during early infancy. However, no previous reports have demonstrated arteriopathic manifestations during postinfantile childhood in patients with IP. PATIENT DESCRIPTION: We describe a case of IP in a 2-year-old girl who developed encephalopathic manifestations associated with influenza A infection. She presented diffuse magnetic resonance imaging abnormalities involving the cortices, subcortical white matter, corpus callosum, basal ganglia, and thalami, resembling the findings in early infantile cases reported in the previous literatures. Magnetic resonance angiography demonstrated attenuation of the cerebral arteries. Proinflammatory cytokines and chemokines were upregulated in the cerebrospinal fluid. Left hemiplegia remained following the remission of the arteriopathic manifestations. Genetic analyses revealed a novel type of mutation in the IKBKG gene. CONCLUSION: Our findings indicate that patients with IP can develop destructive cerebral arteriopathy even after early infancy. The similarities in magnetic resonance imaging abnormalities between our patient and the previously reported infantile patients may be explained by the underlying immunologic pathophysiology of IP.

Neuroimaging in infants and children in select neurocutaneous disorders.

The role of neuroimaging in neurocutaneous disorders is an evolving field. Research can be inconsistent and inconclusive, leading to divergent practice for some disorders. This study provides an overview of the current role of magnetic resonance imaging (MRI) of the brain in select neurocutaneous disorders, namely Sturge-Weber syndrome, congenital melanocytic naevus syndrome, neurofibromatosis type 1, tuberous sclerosis complex, incontinentia pigmenti and basal cell naevus syndrome. Future research assessing new targeted treatments and novel MRI techniques may change current practice.

Multimodal Retinal Imaging in Incontinentia Pigmenti Including Optical Coherence Tomography Angiography: Findings From an Older Cohort With Mild Phenotype.

Importance: Incontinentia pigmenti (IP) is a rare, X-linked dominant disease with potentially severe ocular complications that predominantly affect the peripheral retina. However, little is known about its effects on the macula. Objective: To describe the structural and vascular abnormalities observed in the maculas of patients with IP and to correlate these findings with peripheral pathologies. Design, Setting, and Participants: Prospective, cross-sectional study at Wilmer Eye Institute, Johns Hopkins University. Five participants with a clinical diagnosis of IP were included and underwent multimodal imaging with ultra-wide-field fluorescein angiography (FA), spectral-domain optical coherence tomography (OCT), and OCT angiography. Main Outcomes and Measures: The structural and vascular abnormalities observed on spectral-domain OCT and OCT angiography and their correlation with peripheral pathologies seen on ultra-wide-field FA. Results: A total of 9 eyes from 5 patients (median age, 20.5 years; range, 8.4-54.2 years) were included. Median Snellen visual acuity was 20/32 (range, 20/16 to 20/63). ultra-wide-field FA-identified retinal vascular abnormalities in all 7 eyes in which FA was obtained. These abnormalities included microaneurysms, areas of nonperfusion, and vascular anastomoses, most of which were peripheral to the standard view of 30° FA with peripheral sweeps. Structural abnormalities were observed in 6 eyes on spectral-domain OCT, including inner retinal thinning and irregularities in the outer plexiform layer. Optical coherence tomography angiography abnormalities were noted in all 9 eyes, including decreased vascular density, abnormal vascular loops, and flow loss in the superficial and deep plexuses, which corresponded to areas of retinal thinning on spectral-domain OCT. Conclusions and Relevance: Although our study is limited by the small sample size, the findings suggest that multimodal imaging is useful for detecting structural and vascular abnormalities that may not be apparent on ophthalmoscopy in patients with IP. Macular pathologies, especially a decrease in vascular density on OCT angiography, are common. Further studies are needed to characterize further the association between macular and peripheral abnormalities in patients with IP.

ASSESSMENT OF THE RETINAL STRUCTURE IN CHILDREN WITH INCONTINENTIA PIGMENTI.

PURPOSE: This report aims at expanding the current knowledge of retinal microanatomy in children with incontinentia pigmenti using hand-held spectral domain optical coherence tomography (SDOCT). METHODS: We reviewed OCT scans from 7 children (4 weeks-13 years) obtained either in the clinic or during an examination under anesthesia. The scans were analyzed for anatomical changes in the outer and inner retina, by certified graders. Medical records were assessed for systemic findings. RESULTS: We observed abnormal retinal findings unilaterally in three children. We found inner and outer retinal thinning temporally in two participants. This thinning was present prior to and persisted after treatment. One child showed a distorted foveal contour and significant retinal thickening secondary to dense epiretinal membrane and vitreomacular traction. All other children had normal retinae. CONCLUSION: Hand-held SDOCT imaging of the retina has brought to light additional retinal structural defects that were not previously reported or visualized via routine clinical ophthalmic examination including retinal photography. Despite a normal foveal structure and visual acuity, we identified inner and outer retinal thinning on SDOCT which may benefit from future functional assessment such as visual field testing.

Dental anomalies in 14 patients with IP: clinical and radiological analysis and review.

OBJECTIVES: Current knowledge on dental anomalies in patients with incontinentia pigmenti (IP) has been obtained by examining case reports; however, an overall characterization of such alterations remains lacking. The objective of this study was to determine the frequency, type and location of dental alterations in IP using a case series. METHODS: Fourteen patients (9 children and 5 adults) with a clinical diagnosis of IP who presented dental anomalies were included in this study. All patients were administered a clinical questionnaire, dental examination and radiological investigation. RESULTS: In the present case series, agenesis of primary dentition was present in 60 % of patients and agenesis of permanent tooth was present in 92.8 % of patients. Most cases were missing at least 6 teeth. Second molar agenesis was present in 13 patients (92.8 %). Anomalies in dental crowns occurred in 71.4 % of cases, and the central incisor was most frequently affected. Two adult patients still had primary teeth. Malocclusion was found in 10 patients (71.4 %). High-arched palate was observed in 7 (50 %) patients. CONCLUSIONS: Patients with IP present alterations in both primary and permanent dentition. Because the agenesis of permanent teeth is more common, primary teeth are not always replaced. In addition, the durability of primary dentition appears to be greater in IP. CLINICAL SIGNIFICANCE: This study shows that patients with IP experience significant loss of teeth, especially in permanent dentition, and have an increased risk of high-arched palate compared to the general population. Prophylactic care of primary teeth in IP is relevant for improving functional and aesthetic outcomes until dental prostheses are implanted.

Clinical presentation and spectrum of neuroimaging findings in newborn infants with incontinentia pigmenti.

AIM: To report on the neurological presentation and neuroimaging findings in newborn infants with incontinentia pigmenti. METHOD: The clinical and neurological course including neuroimaging and follow-up data of eight newborn infants with the neurological phenotype of incontinentia pigmenti were retrospectively reviewed. RESULTS: While the clinical picture was polymorphic, the neurological manifestations were defined as encephalopathic and comprised lethargy and seizures in all but one of the infants. Magnetic resonance imaging (MRI) abnormalities were predominantly in the white matter. Diffusion-weighted imaging (DWI) was obtained during the acute phase in seven of the eight infants, showing restricted diffusion in the deep and subcortical white matter but also in the corpus callosum, basal ganglia, thalami, cerebellum, and cerebral peduncles. Susceptibility-weighted imaging (SWI), performed in five infants, showed a variable amount of signal loss, mainly in the white matter, within areas of restricted diffusion. Extensive MRI abnormalities in newborn infants were followed by abnormal neurodevelopment, with significant motor, cognitive, and/or visual problems. INTERPRETATION: To assess the extent of central nervous system involvement, MRI is recommended in the clinical evaluation of infants with incontinentia pigmenti. They have a characteristic pattern of brain lesions seen on MRI, best recognized using DWI and SWI in the acute neonatal phase, which allow the identification of and distinction between ischaemic and haemorrhagic lesions.

Therapy resistant neonatal seizures, linear vesicular rash, and unusually early neuroradiological changes: incontinentia pigmenti: a case report, literature review and insight into pathogenesis.

CASE PRESENTATION: A substance abusing G2P1 mother spontaneously delivered at term an appropriate for gestational age girl. Neonatal seizures appeared at 21 hours and empiric anticonvulsive and antimicrobial treatment was started. At 25 hours, first vesicles appeared. While routine evaluations remained normal, a head CT revealed multifocal ischemic injuries, and a later MRI showed multifocal petechiae and diffusion abnormalities in the corticospinal tracts. The clinical diagnosis of incontinentia pigmenti (stage 1) was secured by histopathology. Follow-up at 13 months showed global developmental delay. DISCUSSION: We discuss the unusually early bilateral, fronto-occipital corticomedullar ischemias (CT day 3). On the MR imaging (day 7) extensive symmetric cerebral corticomedullar destruction and diffusion sequences with corticospinal tracts abnormalities are seen, which then evolve (day 26) to extensive symmetric cerebral destruction. We review the literature, genetics, suspected pathophysiology and possible neonatal manifestation. CONCLUSION: Incontinentia pigmenti is rare and, therefore, diagnosis is frequently delayed. Nevertheless, in the setting of therapy refractory seizures, excluded infections, and linear vesicular rash, a high index of suspicion is needed. This is the first report of simultaneous corticomedullar involvement as early as the third day of life.

[Incontinentia pigmenti: clinical and neuroimaging findings in a series of 12 patients]. / Incontinentia pigmenti. Hallazgos clínicos y radiológicos en una serie de 12 pacientes.

OBJECTIVE: To describe the clinical, neuroimaging 51 with magnetic resonance imaging (MRI) and evolutive findings in 12 patients with incontinentia pigmenti (IP). Five patients show cutaneous and neurological lesions and seven only show cutaneous lesions without neurologic or/ and ophthalmologic abnormalities. MATERIAL AND METHODS: Five mothers and seven daughters from four families were studied and followed between 1965 and 2004. The studies consisted of detailed clinical history since birth, physical examination, family history, EEG recordings and MRI studies. In some patients, at least three MRI studies were performed during our follow-up. All patients were followed-up since their first visit until 2004. Including four patients since birth or early infancy. Skin biopsies were obtained from two infants for histological study. RESULTS: MRI studies revealed brain abnormalities in five girls who had neurologic signs associated with the cutaneous lesions of IP. Brain lesions were bilateral in four and unilateral in one. Cerebellar changes were observed only in one case who also showed severe cerebral lesions. The lesions involved cortex, subcortical and deep white matter, ependymal and subependymal zones of one or both cerebral hemispheres. Lesions usually were localized and extended radially to involve all the cerebral parenchyma between ependyma and cortex. Affected areas did not correspond to territories vascularized by any determined artery. The corpus callosum showed generalized or localized atrophy in the five patients who had cerebral hemispheric lesions. Although parenchymal changes were seen in both the T1 and T2 weighted images, these were most evident in the latter. Parenchymal abnormalities were most severe in patients with neonatal severe cutaneous lesions, especially if these were located in the scalp. Cerebral lesions were present from birth or the first months of life and changed little thereafter. The acute appearance and distribution of cerebral lesions always during the neonatal period, associated with scalp lesions in stage 1, suggest an acute inflammatory origin of unknown etiology and of nonprogressive course. Ocular lesions were directly related with cerebral abnormalities. Patients who only had cutaneous lesions without neurologic symptoms showed no MRI abnormalities. CONCLUSIONS: Neuroimaging studies reveals brain lesions only in patients with neurologic disease in this serie. The brain lesions may involve one or both cerebral hemispheres, corpus callosum, and cerebellum. The brain lesions correlate with the neonatal scalp lesions in stage 1, suggests an inflammatory process of unknown etiology and non-progressive course. The appearance and distribution of the cerebral lesions do not follow the territories vascularized by specific arteries. Ocular lesions are observed only in patients with severe cerebral changes. Early onset of cerebral lesions may be the most reasonable explanation for the progressive microcephaly within the first year of life in IP.

Incontinentia pigmenti with painful subungual tumors: a two-generation study.

We report 2 cases of painful subungual dyskeratotic tumors occurring in a mother and daughter with incontinentia pigmenti (IP) as a late manifestation of the disease. Both patients had a history of similar lesions appearing over a period of years on the digits of both the hands and feet. Biopsy specimens of the current lesions were examined and compared with the previous material available on both patients. The current tumors and the earlier lesions (the latter of which had originally been given diagnoses that included squamous cell carcinoma, keratoacanthoma, and verruca vulgaris) showed similar histopathologic features that were consistent with the late (verrucous) stage of IP. To our knowledge, this is the first reported case of numerous subungual tumors in IP involving more than 1 generation in the same family; the first report of subungual tumors in IP to include a 16-year follow-up; and the first report of a probable recurrence of subungual tumors in IP at the same site of a previously surgically removed tumor.

[Spontaneous abortion of male fetuses with incontinentia pigmenti (apropos of a family)]. / L'interruption spontanée des grossesses de foetus mâles atteints dans l'incontinentia pigmenti (a propos d'une famille).

We report a family with incontinentia pigmenti. One affected woman had seven pregnancies, seven miscarriages; a prenatal diagnosis by molecular biology was undertaken in the last four cases (two males, two females). In the last two males, a miscarriage occurred at the beginning of the second trimester with cystic hygroma in a case. In the first two males a miscarriage was observed also at the beginning of the second trimester after chorionic biopsy or amniocentesis. These two miscarriages would not be a complication of prenatal diagnosis but spontaneous abortion of an affected male. The date of the miscarriage of affected males (the beginning of the second trimester) and the role of a cystic hygroma for the diagnosis of incontinentia pigmenti in this mother of a fetus karyotyped 46,XY are discussed.

Incontinentia pigmenti: clinical and neuroradiologic features.

Developmental brain malformations and destructive processes of unknown etiology were described in incontinentia pigmenti (IP). Two patients, a male and a female, with characteristic skin lesions and central nervous system (CNS) involvement are reported. Neuroradiological examinations revealed hypoplasia of corpus callosum, neuronal heterotopias, and periventricular white matter damage. No specific infectious, inflammatory, or metabolic abnormalities were identified. These neuroradiographic findings may suggest that an ischemic pathogenetic mechanism occurred prenatally. We speculate that the brain damage in IP may occur during CNS development and in successive stages. Magnetic resonance imaging appears more useful to detect white matter lesions and brain malformations in patients with IP.