The clinical and imaging features of cerebrotendinous xanthomatosis: A case report and review of the literature.

RATIONALE: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid deposition disorder characterized by systemic signs and neurological dysfunction. The radiological features of CTX are infrequently summarized in the literature. PATIENT CONCERNS: We described a 40-year-old male patient who repeatedly engaged in wrestling matches and presented with progressive difficulty in walking and reduced balance with egg-sized, hard, smooth, and painless masses in both ankles. DIAGNOSIS: Neuroimaging examination showed abnormalities both supra- and infratentorially. Bilateral ankle joint magnetic resonance imaging showed bilateral xanthomata of the Achilles tendon. The diagnosis was confirmed by the detection of a sterol 27-hydroxylase gene mutation. INTERVENTIONS: The patient was treated with chenodeoxycholic acid (250 mg 3 times per day). OUTCOMES: To date, the patient's bilateral xanthomas of the Achilles tendon have begun to diminish, and his neurological impairment has not deteriorated further but has not yet improved. LESSONS: We report a rare case of CTX and summarize the clinical and imaging features of this disease. Our findings suggest that the abnormal signals in the dentate nucleus or a long spinal cord lesion involving the central and posterior cord, combined with tendon xanthoma, are important clues for the diagnosis of CTX.

Inverse Bell's phenomenon: a rare complication of levator resection surgery in a case of congenital ptosis.

A 27-year-old woman with moderate congenital ptosis and a positive Marcus-Gunn jaw winking reflex underwent levator resection surgery to correct the ptosis. Preoperatively, a normal Bell's reflex was documented. Postoperatively, she developed an inverse Bell's reflex and increased symptoms of ocular surface exposure. The Bell's reflex normalised in a week, with resolution of the corneal exposure. Reversal of the Bell's reflex can be an unforeseen complication following maximal levator resection. The early postoperative care in such cases is crucial, and the cornea must be protected from exposure changes. Accurate documentation of the Bell's phenomenon preoperatively is vital to recognise this rare event and plan management.

Majewski dwarfism type II: an atypical neuroradiological presentation with a novel variant in the PCNT gene.

Microcephalic osteodysplastic primordial dwarfism syndrome II (MOPDII) is microcephalic primordial dwarfism and is a very rare form of disproportionate short stature. This disorder shares common features with other forms of microcephalic primordial dwarfism, including severe prenatal and postnatal growth retardation with marked microcephaly. However, it includes characteristic skeletal dysplasia, abnormal dentition and increased risk for cerebrovascular diseases. Recent reports added more features, including café-au-lait lesions, cutis marmorata, astigmatism, Moyamoya disease, insulin resistance, obesity, abnormal skin pigmentation and acanthosis nigricans around the neck. Clearly, the more MOPDII reports that are produced, the more information will be added to the spectrum of MOPDII features that can improve our understanding of this disorder. In this paper, we reported a new case of MOPDII with more severe clinical features, earlier onset of common features, in addition to a homozygous novel variant in the PCNT gene.

Cytomegalovirus in pregnancy: to screen or not to screen.

BACKGROUND: Cytomegalovirus (CMV) infection is now the commonest congenital form of infective neurological handicap, recognized by the Institute of Medicine as the leading priority for the developed world in congenital infection. In the absence of an effective vaccine, universal screening for CMV in pregnancy has been proposed, in order that primary infection could be diagnosed and- potentially- the burden of disability due to congenital CMV prevented. DISCUSSION: Universal screening for CMV to identify seronegative women at the beginning of pregnancy could potentially reduce the burden of congenital CMV in one of three ways. The risk of acquiring the infection during pregnancy has been shown to be reduced by institution of simple hygiene measures (primary prevention). Among women who seroconvert during pregnancy, CMV hyperimmune globulin (CMV HIG) shows promise in reducing the risk of perinatal transmission (secondary prevention), and CMV HIG and/ or antivirals may be effective in reducing the risk of clinical sequelae among those known to be infected (tertiary prevention). The reports from these studies have re-ignited interest in universal screening for CMV, but against the potential benefit of these exciting therapies needs to be weighed the challenges associated with the implementation of any universal screening in pregnancy. These include; the optimal test, and timing of screening, to maximize detection; an approach to the management of equivocal results, and the cost effectiveness of the proposed screening program. In this article, we provide an overview of current knowledge and ongoing trials in the prevention, diagnosis and management of congenital CMV. Recognising that CMV screening is already being offered to many patients on an ad hoc basis, we also provide a management algorithm to guide clinicians and assist in counseling patients. SUMMARY: We suggest that- on the basis of current data- the criteria necessary to recommend universal screening for CMV are not yet met, but this position is likely to change if trials currently underway confirm that CMV HIG and/ or antivirals are effective in reducing the burden of congenital CMV disease.

[Neurological and psychomotor development of foetuses and children with congenital heart disease--causes and prevalence of disorders and long-term prognosis]. / Neurologische und psychomotorische Entwicklung von Feten und Neugeborenen mit angeborenen Herzfehlern--Ursachen und Prävalenz von Störungen im Langzeitverlauf.

Children with severe congenital heart defects (CHD) requiring open heart surgery in the first year of life are at high risk for developing neurological and psychomotor abnormalities. Depending on the type and severity of the CHD, between 15 and over 50% of these children have deficits, which are usually confined to distinct domains of development, although formal intelligence tends to be normal. Children with mild CHD, who comprise the majority of congenital heart defects, have a far better developmental prognosis than those with complex CHD. This review concentrates on the impact of severe CHD on the developing brain of the foetus and infant. It also provides a summary of recent clinical and neuroimaging studies, and an overview of the long-term neurological prognosis. Advanced neuroimaging modalities indicate that, related to altered cerebral blood flow and oxygenation, foetuses with severe CHD show delayed third trimester brain maturation and increased vulnerability for hypoxic injury. Morphological and neurological abnormalities are present before surgery, commonly affecting the white matter. In the long-term, impaired neurological and developmental outcomes are related to the combination of prenatal, perinatal and additional perioperative risk factors. Therefore, new therapeutic approaches aim to optimise the intra- and perinatal management of foetuses and newborns with congenital heart defects. Identification and avoidance of risk factors, early neurodevelopmental assessment and therapy may optimise the long-term outcome in this high-risk population.

The neurological outcomes of surviving twins in severe twin-twin transfusion syndrome treated by fetoscopic laser photocoagulation at a newly established center.

OBJECTIVE: To evaluate the incidence and predictive factors of poor neurological outcome in survivors of twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP). METHODS: Brain magnetic resonance imaging (MRI) and neurodevelopmental assessment were performed at a corrected age of 1 year in survivors of TTTS treated by FLP. Severe neurological abnormality was defined as either the presence of severe clinical neurodevelopmental disability or severe anomalies, visualized on MRI of the brain. RESULT: In a consecutive series of 46 cases treated by FLP, the total survival rate was 66.3%; survival of at least one was 80.4%. Severe neurodevelopment disability was 6.7 % (4/59) and the presence of a severe anomaly on brain imaging was 8.8% (5/57), which combined to a clinical or MRI abnormality rate of 10.5% (6/57). Univariate analysis revealed that early gestational age at delivery was the most significant predictor. However, the multiple logistic regression model did not identify any significant variables. CONCLUSION: In this small series, we determined a rate of clinical neurologic impairment rate at the age of 1 year of 6.7%, which compares to what has been published.

Non-cardiac manifestations of neonatal lupus erythematosus.

Neonatal lupus erythematosus (NLE) is characterized by the transplacental passage of maternal anti-Ro and/or anti-La antibodies and characteristic illnesses in the foetus/neonate. Most attention has focused on the most serious complication- cardiac involvement. This article will focus on non-cardiac involvement. Skin involvement (cutaneous NLE) is present in 15-25% of children with NLE. The rash of NLE tends to be photosensitive but may be present at birth or in non-sun exposed areas. It is most frequently seen around the eyes, not in the malar area, but also occurs in other parts of the body. The pathology resembles the rash of subacute cutaneous lupus erythematosus. Anti-Ro antibodies are present in >95% with the remaining mothers having anti-U1RNP antibodies only. Asymptomatic elevation of liver function tests, which may be associated with evidence of cholestasis, is seen in 10-25% of cases of NLE. Mild hepatomegaly and less commonly splenomegaly may be present. Liver involvement seen in isolation or associated with other features. The pathology resembles idiopathic neonatal giant cell hepatitis. Any haematological lineage, neutropenia and thrombocytopenia most commonly, may be affected by NLE. Haematological involvement is almost always asymptomatic. There are protean manifestations of neurologic involvement in NLE: hydrocephalus, non-specific white matter changes, calcification of the basal ganglia and a 'vasculopathy'. The most unusual feature of NLE is the radiographic finding of stippling of the epiphyses (chondrodysplasia punctata). Overall, non-cardiac involvement of NLE is more common than cardiac. The study of these manifestations may lead to new insight into how autoantibodies lead to disease.

Rescue of congenital hypomyelination by progenitor cell transplantation.

Replacement of myelin-forming cells is an attractive but unproven therapy for inherited and acquired myelin diseases. In this issue of Cell Stem Cell, Windrem et al. (2008) describe the first progenitor cell transplantation paradigm that rescues the neurological phenotypes and increases life spans of mice with inherited myelin disease.

Congenital osseous anomalies of the upper cervical spine.

BACKGROUND: The developmental anatomy and biomechanics of the upper cervical spine are unique in children. Congenital osseous anomalies in this region may be associated with an increased risk for subsequent neurological compromise from instability and/or spinal cord encroachment. We performed a double-cohort study evaluating congenital osseous anomalies of the upper cervical spine in children who presented with one or more clinical problems, and we attempted to outline the risk of possible neurological compromise. METHODS: We reviewed the medical records and imaging studies of all children seen and treated for osseous anomalies of the upper cervical spine at our institution between 1988 and 2003. Patients were divided into two cohorts on the basis of the presence or absence of associated syndromes. Parameters reviewed included demographic data, clinical presentation, and imaging features. All anomalies involving the central nervous system, the occipitocervical junction, and the upper cervical osseous canal were included. Complicating sequelae such as canal stenosis, segmental instability, and other anomalies of the central nervous system and spine were identified. RESULTS: Sixty-eight consecutive children were identified. Twenty-one patients had an underlying described syndrome. There were 234 osseous anomalies (average, 3.4 per patient). Three or more anomalies were noted in 79% of the patients. There was no significant difference in the mean number of anomalies (p = 0.80) or in the frequency of any specific anomaly (p > 0.20 for all) between syndromic and nonsyndromic patients. The variety of clinical presentations included neck pain (twenty-six patients), neurological changes (twenty-one patients), and torticollis and/or stiffness (twenty-one patients). Twenty-three patients had more than one complaint. Six patients had isolated spinal instability, twenty-eight had isolated spinal cord encroachment, and six had a combination of both. Forty-four (65%) of the sixty-eight patients underwent surgical decompression and/or arthrodesis principally focused from the foramen magnum to the second cervical vertebra. CONCLUSIONS: As a result of these findings, we recommend a thorough evaluation and advanced imaging of the upper cervical spine in all children who present with symptoms related to the upper cervical spine, to identify associated anomalies and further define the nature of canal encroachment including any potential for neurologic compromise.

Hipomielinização em cães Weimaraner: relato de caso / Hypomielination in Weimaraner dogs: case report

Três cães, fêmeas, da raça Weimaraner apresentaram tremores corporais rítmicos generalizados a partir da primeira semana de vida. Outros dois cães, machos, da mesma ninhada não apresentaram alterações. Uma fêmea com quatro semanas de idade foi submetida à eutanásia e necropsiada. Macroscopicamente, observou-se no encéfalo pouca demarcação da substância branca em relação à cinzenta. Histologicamente havia acentuada vacuolização de toda a substância branca subcortical. A mielinização no sistema nervoso periférico estava normal. Os sinais clínicos, a idade de ocorrência e as lesões histológicas são compatíveis com a hipomielinogênese congênita descrita em cães

Three female Weimaraner pups had generalized and rhythmic body tremors since the first week of age. The remaining two male littermates were unaffected. One 4-week-old female was euthanatized and necropsied. On gross examination, poor demarcation between the gray and white matter was observed. Microscopically, there was severe hypomyelination of the brain compatible with congenital hypomyelinogenesis reported in dogs

Focal brain malformations: a spectrum of disorders along the mTOR cascade.

Focal cortical dysplasia with balloon cells (FCDIIB), hemimegalencephaly (HMEG), and ganglioglioma (GG) are sporadic focal malformations of cortical development that are highly associated with epilepsy. Histologically, all three malformations are characterized by disordered cortical lamination and the presence of markedly enlarged cell types known as balloon cells in FCDIIB and HMEG and atypical ganglion cells (AGCs) in GG. These cells are similar to giant cells in the tuberous sclerosis complex (TSC). Recent work has shown that there is enhanced activation of the mTOR cascade in TSC, FCD, HMEG and GG, suggesting a common pathogenesis for these disorders. We propose that these malformation types reflect a spectrum of disorders along the mTOR cascade. The mTOR pathway is known to regulate cell growth and thus is an ideal candidate to study in malformations associated with aberrant cell size. We hypothesize that focal brain malformations form as a consequence of a somatic gene mutation occurring within a progenitor cell during brain development. Our work has implemented several strategies to investigate FCD, HMEG and GG. First, we use single nucleotide polymorphism (SNP) arrays and gene sequencing to identify mutations in candidate genes that would lead to activation of the mTOR cascade. Second, we are using gene and protein expression profile techniques to understand how mTOR activation affects the developing cortex.

A double point mutation in the DNA-binding region of Egr2 switches its function from inhibition to induction of proliferation: A potential contribution to the development of congenital hypomyelinating neuropathy.

Mutations in the DNA-binding domain of EGR2 are associated with severe autosomal dominant forms of peripheral neuropathy. In this study, we show that one such Egr2 mutant (S382R, D383Y), when expressed in Schwann cells in vitro, is not transcriptionally inactive but retains residual wild-type Egr2 functions, including inhibition of transforming growth factor-beta-induced Schwann cell death and an ability to induce the cytoskeletal protein periaxin. More importantly, this mutant Egr2 has aberrant effects in Schwann cells, enhancing DNA synthesis both in the presence and absence of the putative axonal mitogen, beta-neuregulin 1. This is in stark contrast to wild-type Egr2, which causes withdrawal from the cell cycle. Furthermore, mutant Egr2 upregulates cyclin D1 and reduces levels of the cell cycle inhibitor, p27. These observations add significant new evidence to explain how this mutation leads to congenital hypomyelinating neuropathy in humans.

Pesticides and children.

Prevention and control of damage to health, crops, and property by insects, fungi, and noxious weeds are the major goals of pesticide applications. As with use of any biologically active agent, pesticides have unwanted side-effects. In this review, we will examine the thesis that adverse pesticide effects are more likely to occur in children who are at special developmental and behavioral risk. Children's exposures to pesticides in the rural and urban settings and differences in their exposure patterns are discussed. The relative frequency of pesticide poisoning in children is examined. In this connection, most reported acute pesticide poisonings occur in children younger than age 5. The possible epidemiological relationships between parental pesticide use or exposure and the risk of adverse reproductive outcomes and childhood cancer are discussed. The level of consensus among these studies is examined. Current concerns regarding neurobehavioral toxicity and endocrine disruption in juxtaposition to the relative paucity of toxicant mechanism-based studies of children are explored.

Structure of a single-cytidine hairpin loop formed by the DNA triplet GCA.

In certain contexts the DNA triplet GGA, when juxtaposed on opposite strands of a DNA duplex, shows the unusual property of pairing with itself in an antiparallel orientation to form the (GGA)2 motif. In this motif the central guanines do not pair but intercalate and stack between sheared G.A pairs. Similar studies with GCA triplets reveal that they do not form analogous paired (GCA)2 motifs but instead strongly promote formation of a hairpin, the structure of which is now reported here. The GCA hairpin loop consists of a single cytidine residue closed by a sheared G.A pair and this structure is discussed in the context of triplet expansions in triplet-repeat diseases.

[Premature infants weighing less than 1000 grams: mortality, morbidity and short-term neurologic outcome]. / Le prématuré de moins de 1,000 grammes: mortalité, morbidité et devenir neurologique à court terme.

The outcome of 60 premature infants weighing less than 1,000 g at birth and consecutively born during the years 1986 to 1988 is reported. Forty-two (70%) of them were inborn. The overall mortality rate was 42%, but only 26% in the inborn group instead of 78% in the outborn group (P less than 0.001). The mortality rate was higher for the appropriate for gestational age infants (56%) than for the growth retarded infants (14%, P less than 0.01). The main neonatal problems were the following: hyaline membrane disease (63%), patent ductus arteriosus (7%), bronchopulmonary dysplasia (8%), necrotizing enterocolitis (15%), intraventricular hemorrhages (45%) and periventricular leukomalacia (12%). Twenty percent (7/35) of the surviving infants showed abnormal neurodevelopmental outcome, with only one (3%) having major handicap. No correlation was found between gestational age and neuro-developmental outcome.

[Megacystis microcolon intestinal hypoperistalsis syndrome: A neuropathy?]. / Das Megazystis-Mikrokolon-intestinale Hypoperistaltik-Syndrom: Eine Neuropathie?

2 cases of megacystis microcolon intestinal hypoperistalsis are presented. A female newborn was capable of being fed completely enterally after three months. Laparotomy was not performed. A male newborn was subjected to laparotomy after 3 days and an ileal stoma was applied. The infant died after 6 months of complete parenteral feeding without any peristalsis having been initiated. Biopsies of the colon and small intestine of the patient showed normal HE staining findings. Histochemical examination revealed type B neuronal dysplasia with neuronal hypogenesis. The findings of 27 cases described in the literature are discussed with special reference to the histological findings of the intestinal wall.