Inherited ion channel disorders

The inherited ion channel disorders (channelopathies) are a group of disorders caused by mutations in genes encoding ion channels. Ion channel disorders can affect any tissue, but the majority affect skeletal muscle or the central nervous system. These disorders include skeletal muscle sodium channelopathies causing hyperkalaemic periodic paralysis, paramyotonia congenita and potassium-aggravated myotonia. Skeletal muscle calcium channelopathies can cause hypokalaemic periodic paralysis, malignant hyperthermia and central core disease. Skeletal muscle chloride channelopathies can cause Thomsen and Becker myotonia. A neuronal sodium channelopathy causes the generalised epilepsy febrile seizures plus syndrome. Neuronal potassium channelopathies can cause familial benign neonatal convulsions and episodic ataxia type 1. Finally, neuronal calcium channelopathies can cause episodic ataxia type 2, familial hemiplegic migraine and spinocerebellar ataxia type 6. Conclusion The clinical features, aetiology and pathogenesis of inherited voltage-gated ion channel disorders affecting muscle and the central nervous system are reviewed here.     

Langerhans cell histiocytosis: central nervous system involvement treated successfully with 2-chlorodeoxyadenosine

A case of disseminated Langerhans cell histiocytosis with resistant central nervous system (CNS) disease in an adolescent is described. The child presented with visible cranial lesions, emesis, headaches, and short-term memory loss. Diagnostic evaluation revealed multiple osseous lesions in the cranium, ribs, vertebral bodies, and pelvis. The clinical course with complications and response to each therapy are sequentially reviewed. Remission, as evidenced clinically and by magnetic resonance imaging, was ultimately accomplished with 2-chlorodeoxyadenosine (2-CDA). The full course of 2-CDA was not tolerated due to bone marrow suppression. CNS histiocytosis is known to be resistant to therapy. Earlier introduction of 2-CDA for CNS disease might offer more successful treatment with less toxicity than seen in this patient.     

What's new in neuromuscular disorders? The congenital myopathies.

The congenital myopathies are a heterogeneous group of early-onset neuromuscular conditions with characteristic findings on muscle biopsy, comprising central core disease, minicore myopathy (multi-minicore disease), nemaline myopathy and myotubular myopathy. Recent years have seen genetic resolution of a proportion of these conditions. The following review summarizes recent genetic findings in the congenital myopathies and outlines implications for our understanding of their pathophysiological basis and their relation to other neuromuscular disorders.     

The hypotonic infant: case study of central core disease

Causes of hypotonia in the newborn can be broadly categorized into two classifications. Hypotonia with a supraspinal origin may be seen with systemic disease, hypoxic ischemic encephalopathy, cerebral malformations, syndromes (for example: Down, Prader-Willi, Lowe, Zellweger, Smith-Lemli-Opitz), and c-spine injury. Disorders of the motor unit that present with hypotonia in the newborn period include SMA, congenital myotonic dystrophy, congenital myasthenia gravis, and congenital myopathies. Central core disease is one of the classic congenital myopathies that can be differentiated based on characteristic histologic findings. Muscle fiber samples from patients with central core disease possess distinct morphology that can be diagnostic. Many infants may not exhibit muscle weakness in the newborn period, although there have been rare cases of profound hypotonia and respiratory failure. Clearly, muscle biopsy is the gold standard and is indicated for any infant with marked hypotonia that is not thought to be supraspinal in origin.     

Central Nervous System Leukemia and Cushing Syndrome

We treated a child with acute lymphoblastic leukemia who developed central nervous system leukemia and obesity due to Cushing syndrome. The infiltration of leukemic cells was gradually ameliorated with intrathecal nethotrexate therapy. At the same time, clinical symptoms of Cushing syndrome have almost normalized. The relation between central nervous system leukemia and Cushing syndrome is discussed.     

Central diabetes insipidus associated with Caroli syndrome

Caroli disease is a rare congenital malformation characterized by cystic dilatations of large bile ducts. There are two forms of Caroli disease. Simple form entails the bile duct dilatation or ectasia. Complex form is copresence of hepatic fibrosis and portal hypertension. Here is presented a case of central diabetes insipidus (CDI) associated with Caroli disease.     

Central venous catheter sepsis in surgical newborns

We examined central venous catheter (CVC) sepsis in newborn surgical patients, as this group appeared to have a higher incidence of this complication. During a 3-year period 79 patients on the surgical service required a tunneled, cuffed, Broviac CVC. Nineteen patients (24% or 9.9 episodes per 1000 catheter days) had proven sepsis and 8 (10% or 1.9/1000 catheter days) had suspected sepsis. An intestinal stoma was definitely related to CVC sepsis (p<0.001). Other risk factors included lower gestational age, more operations, and younger age at first stoma. Temperature, white blood cell (WBC) count, and platelet count did not correlate with CVC sepsis. We found no better indicator of CVC sepsis than the presentation of an ill child. Certainly temperature, WBC, and platelet count are not reliable indicators. Surgeons have little control over the factors that were found to be related to CVC sepsis. It would appear reasonable from these results to maintain a high index of suspicion in the high-risk groups, to use peripherally inserted central catheters (PIC lines) as the first line of long-term vascular access, and to bring CVCs out of a nonabdominal site, perhaps the scalp, in patients with stomas.     

Spinal muscular atrophy in trizygotic triplets

The clinical, electrophysiological, pathological and genetic findings in trizygotic triplets with spina muscular atrophy (SMA) are reported. The first child was clinically affected shortly after birth and the third one first showed symptoms at 1 month of age. Electromyography and a muscle biopsy provided evidence of lower motor neuron disease. The second child remains clinically normal, but electromyography showed fibrillation potentials and regular spontaneous motor unit activity at rest. Genetic linkage analysis revealed that the two siblings with typical type 1 SMA had the same chromosome 5q haplotype, and that the second child had a different haplotype. It is considered that in this family there is a link to SMA 5q and there is little possibility that the second child is affected. These data emphasize the need to adhere to strict clinical criteria for the diagnosis of chromosome 5q SMA.     

EV71感染致重症手足口病的研究进展

肠道病毒71型(enterovirus 71,EV71)是人类肠道病毒的一种,近30年来,EV71感染在亚太地区广泛流行,是手足口病(HFMD)重症病例的主要病原体.EV71感染引起的重症HFMD病情进展迅速,可表现为中枢神经系统和呼吸系统受累,其发病机制目前尚不十分清楚.研究认为病毒首先通过神经通路侵犯中枢神经系统,导致中枢神经系统的并发症,严重的病例进一步发展为肺水肿、肺出血.研究重症EV71感染的临床特征和发病机制从而采取积极有效的措施阻断其并发症的发生具有重要意义.     

Rotary atlanto-axial subluxation with torticollis following central-venous catheter insertion

Atlanto-axial subluxation with torticollis is an uncommon condition that occurs in children usually as a result of pharyngeal infection, minor trauma, or neck surgery. Passive motion of the head and neck during general anesthesia is probably another etiologic factor. Torticollis is the most common presenting physical finding. Pain may or may not be present, but is commonly present with passive neck motion. Neurologic sequelae are uncommon. Our case illustrates this condition as a complication of central venous catheter (CVC) insertion in a child under general anesthesia. The surgeon should suspect this pathology when a child presents with torticollis following CVC placement. Precautions should be taken in the operating room to avoid aggressive rotation and extension of the child's neck while under general anesthesia whether or not cervical inflammation is present. Special attention to head and neck positioning should be taken in patients with Down's syndrome since they are at increased risk for atlanto-axial subluxation. The prognosis is excellent when diagnosed early. A delay in diagnosis can result in the need for surgical intervention. Accepted: 7 May 1999     

PATHOLOGY TEACH AND TELL: CENTRAL NERVOUS SYSTEM ATYPICAL TERATOID/RHABDOID TUMOR

Atypical teratoid/rhabdoid tumor (AT/RT) is extremely malignant, highly aggressive primitive central nervous systemneoplasm of infancy with very poor prognosis. Histologically, AT/RT is defined as a polymorphous neoplasm often featuring rhabdoid, PNET, mesenchymal, and epithelial components. We report the clinical history, radioligical, and pathological findings in a child affected bycentral nervous system AT/RT.     

Cerebral MRI abnormalities in a premature infant with later confirmed congenital central hypoventilation syndrome

We present a premature infant with an inability to ventilate spontaneously during sleep periods. In addition, the patient showed general hypotonia. The child had a delayed passage of stool and increased anal muscle tone, indicating Hirschsprung’s disease. The combination of these symptoms suggested congenital central hypoventilation syndrome, which was confirmed postmortem by DNA analysis showing a mutation in the PHOX2B gene. MRI of the brain showed damage to the white matter, including the internal capsula. This type of damage to the white matter has not been described before in a premature infant, who did not experience birth asphyxia.     

Experience with central intravenous catheters in a paediatric oncology unit

During a four-year period, 57 children with malignant disease had a central intravenous catheter inserted to facilitate administration of cytotoxic drugs and parenteral nutrition. Despite the fact that all children were immunosuppressed and frequently profoundly neu-tropenic, only three episodes of septicaemia occurred as a direct result of catheter infection. Local damage to the silastic catheter tubing was the most common problem encountered. Education of the parents and child in the techniques of catheter care is probably the main factor in avoiding complications. The availability of a central intravenous catheter reduces psychological and physical trauma to the child and results in a considerable improvement in the child's general care. We now recommend insertion of a central catheter in all children with malignant disease who require intensive therapy.     

Bilhemia: a fatal complication following percutaneous placement of a transhepatic inferior vena cava catheter in a child

A transhepatic central venous catheter was implanted in a 2-year-old child with a history of multiple venous access procedures and superior and inferior vena cava thrombosis. After 2 weeks, inadvertent dislodgement of the catheter was complicated by a biloma. The biloma was percutaneously drained, but a biliary-venous fistula led to a rapidly progressive and fatal bilhemia. We report this case as an infrequent complication of transhepatic catheterization.     

Rare ocular and systemic associations in a case of neurofibromatosis 2

We describe a child with an extensive medical history who presented with extraocular muscle paresis that, on investigation, led to the diagnosis of neurofibromatosis 2. This child had multiple endocrinologic abnormalities and rare ophthalmologic features that could be associated with the disease.     

Acute respiratory failure and oxygen therapy

Acute Respiratory Failure (ARF) results in an inability to maintain gas exchange at a rate commensurate with the demands of the body and results in hypoxemia and/or hypercarbia, the mechanisms of which may be different. Hypoxemia commonly occurs due to Ventilation Perfusion (V/Q) mismatching, intrapulmonary shunt, diffusion defect or hypoventilation. Hypercarpnic respiratory failure may also be multifactorial but is usually due to inhibited central respiratory drive or inefficient respiratory muscle pump. Hypercapnia may occur in upper and lower airways obstruction, respiratory muscle fatigue and occasionally due to excess CO₂ production (burns and excessive glucose administration). Issues in management centre around assessment of severity, determining the need for intervention, establishing diagnosis and etiology and institution of specific treatment. Diagnosis of respiratory failure may be made clinically and confirmed by blood gas analysis. Calculation of oxygenation indices will delineate extent of hypoxemia. When evaluating a child with respiratory failure, one should be aware that a child with prominent respiratory symptoms may have non-respiratory disease (i.e. metabolic acidosis, DKA) and conversly, advanced respiratory failure may be present in a child with no respiratory distress (central hypoventilation secondary to drugs, infection) careful assessment of history, complete physical examination and evaluation of lab parameters may clarify the diagnosis. Serial assessment of sensorium, respiratory symptoms, ABG and response to treatment will provide valuable clues to determine the need for intervention. Oxygen, like any drug, must be administered in a prescribed dose, only when indicated with the potential risks borne in mind. A variety of oxygen delivery devices are available; which ever device is used, the resulting FiO₂ and devisable end points must be clearly determined. Hazards of oxygen therapy range from retinal damage in premature infants, damage to the alveolar capillary membrane with resultant hypoxemia) atelectasis and decreased mucociliary activity.     

Tropical pyomyositis: a case report and review.

Tropical pyomyositis is a disease of skeletal muscle characterized by single or multiple abscesses. The infective organism is most often penicillin-resistant Staphylococcus aureus. Only recently have case reports appeared in the literature from temperate zones; however, this disease is common in the tropics. This report reviews the literature and describes a child from rural North Carolina in whom tropical pyomyositis developed after incision and drainage of a furuncle.     

Accuracy of central venous pressure measurements in the inferior vena cava in the ventilated child

Murdoch IA, Rosenthal E, Huggon IC, Coutinho W, Qureshi SA. Accuracy of central venous pressure measurements in the inferior vena cava in the ventilated child. Acta Pædiatr 1994;83:512–14. Stockholm. ISSN 0803–5253
We compared central venous pressure measurements from three sites, superior vena cava, inferior vena cava and right atrium, in 12 children undergoing cardiac catheterization whilst on assisted ventilation. There was no significant difference between the mean pressures in the superior vena cava and the inferior vena cava. Furthermore, there was also no difference between the mean pressures in the inferior vena cava and the right atrium. Because of the greater safety of the placement of pressure monitoring lines in the inferior vena cava via the femoral vein, this approach should be the preferred route for central venous pressure monitoring in children.     

Prolonged elevation of transaminase concentration in children with unsuspected myopathy

Prolonged elevation of the serum transaminase concentration in an asymptomatic child is usually thought to be secondary to liver disease. Four children with unexplained persistent elevation of serum transaminase concentration were referred to a pediatric gastroenterologist for studies of liver disease. Subsequent evaluation disclosed abnormal muscle biopsy findings in all four patients. This experience suggests that an appropriate workup for occult myopathy is indicated in such patients before invasive diagnostic procedures for evaluation of liver disease are undertaken.     

Intracranial calcification mimicking the Sturge-Weber syndrome A consequence of cerebral folic acid deficiency?

Cerebral cortical calcification identical to that of the Sturge-Weber syndrome was observed in two children. In one child the calcification appeared after intrathecal administration of methotrexate and skull irradiation because of leukemia involving the central nervous system. In the other child, who had coeliac disease and epilepsy, the calcification appeared after treatment with anticonvulsants. This treatment was also contributing to the development of profound megaloblastic anemia. The unspecificity of the Sturge-Weber calcification is stressed and the hypothesis is put forward that the calcification may be secondary to folic acid deficiency interfering with the metabolism in the central nervous system.