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Abstract: The presence of antiphospholipid antibodies is associated with arterial and venous thrombosis. A 14-year-old girl, with systemic lupus erythematosus (SLE), developed headache and cough and was found to have intracranial venous sinus thrombosis with secondary pulmonary embolism associated with antiphospholipid syndrome. Clinical and radiological improvement occurred with anticoagulation therapy. Because SLE is commonly associated with antiphospholipid antibodies, thromboembolic events should be considered in the differential diagnosis of both cough and headache in children with SLE. [ABSTRACT FROM AUTHOR]

Background: Children with severe or persistent back pain and stiffness often have an underlying organic cause but there is a large differential diagnosis, examination may be difficult and the problem is relatively rare in general paediatric practice. These difficulties appeared to lead to delays in diagnosis and management of children with this problem.Objectives: To provide an approach to the diagnosis and management children with severe or persistent back pain or stiffness based on our clinical experience and the literature.Methodology: The case histories of 10 children with severe back pain seen by the authors over a 5-year period were reviewed. They were chosen as illustrative examples of the diagnostic and management problems and did not represent a systematic review of all cases seen by the authors over that time.Results: Underlying causes included infection, inflammation, neoplasm, trauma and vascular malformation. Four of the children had spinal cord compression which required urgent decompression. There was one child with a conversion disorder but three children with organic disease were initially felt to have a conversion disorder. Investigations generally proceeded relatively slowly and the problem was not regarded as a semi-urgent situation carrying the risk of permanent paraplegia. Magnetic resonance imaging (MRI) scan of the spine was the investigation of choice.Conclusion: Children with severe or persistent back pain and stiffness have a wide variety of underlying causes. The possibility of underlying spinal cord compression should always be considered in children with this presentation. If the diagnosis is not obvious, MRI scan of the spine should be arranged without delay. [ABSTRACT FROM AUTHOR]

Functional neurologic disorders (FND) of children have many similarities to those of adults, and there is a potential to learn much from the study of FND in children. In this chapter we discuss multiple aspects of pediatric FND. These include their frequency, historic features, the diagnosis, and controversies over the nature of FND and the "correct" name that should be used. We also discuss methods of informing the child and family of the diagnosis, treatment, and prognosis. FND of children typically affect girls in the 10-14-years age range. The presentation is often polysymptomatic, with pain and lethargy accompanying loss of motor function. A common situation is a perfectionistic child who has taken on too much in her academic, sporting, cultural, and social life. Some children respond readily to treatment, but others have a prolonged illness., (© 2016 Elsevier B.V. All rights reserved.)

Tyrosine hydroxylase deficiency is an autosomal recessive disorder resulting from cerebral catecholamine deficiency. Tyrosine hydroxylase deficiency has been reported in fewer than 40 patients worldwide. To recapitulate all available evidence on clinical phenotypes and rational diagnostic and therapeutic approaches for this devastating, but treatable, neurometabolic disorder, we studied 36 patients with tyrosine hydroxylase deficiency and reviewed the literature. Based on the presenting neurological features, tyrosine hydroxylase deficiency can be divided in two phenotypes: an infantile onset, progressive, hypokinetic-rigid syndrome with dystonia (type A), and a complex encephalopathy with neonatal onset (type B). Decreased cerebrospinal fluid concentrations of homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol, with normal 5-hydroxyindoleacetic acid cerebrospinal fluid concentrations, are the biochemical hallmark of tyrosine hydroxylase deficiency. The homovanillic acid concentrations and homovanillic acid/5-hydroxyindoleacetic acid ratio in cerebrospinal fluid correlate with the severity of the phenotype. Tyrosine hydroxylase deficiency is almost exclusively caused by missense mutations in the TH gene and its promoter region, suggesting that mutations with more deleterious effects on the protein are incompatible with life. Genotype-phenotype correlations do not exist for the common c.698G>A and c.707T>C mutations. Carriership of at least one promotor mutation, however, apparently predicts type A tyrosine hydroxylase deficiency. Most patients with tyrosine hydroxylase deficiency can be successfully treated with l-dopa.

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait. We now report that all affected individuals and obligate carriers in this family are heterozygous for a missense mutation (c.1880C-->T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2). To determine whether this mutation is the susceptibility allele, we screened controls and other patients with ANE who are unrelated to the index family. Patients from 9 of 15 additional kindreds with familial or recurrent ANE had the identical mutation. It arose de novo in two families and independently in several other families. Two other patients with familial ANE had different RANBP2 missense mutations that altered conserved residues. None of the three RANBP2 missense mutations were found in 19 patients with isolated ANE or in unaffected controls. We conclude that missense mutations in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE.

Inborn errors of catecholamine biosynthesis are rare but of great interest as they are genetic disorders, and in some, treatment may completely reverse severe neurological abnormalities. They also provide insights into the action of the biogenic amines in the developing brain. We describe the clinical course of an infant with tyrosine hydroxylase (TOH) deficiency over a 30-month period. The parents are consanguineous, and genetic analysis revealed the infant to be homozygous for the common G698A mutation in the TOH gene. TOH deficiency can be seen as a model of pure catecholamine deficiency. Experimental evidence, reports of other disorders of biogenic amines, and our experience with this infant suggest that the symptoms of catecholamine deficiency in infancy can be broadly subdivided. Signs of dopamine deficiency include tremor, hypersensitivity to levadopa (L-dopa) therapy, oculogyric crises, akinesia, rigidity, and dystonia. Manifestations of norepinephrine deficiency include ptosis, miosis, profuse oropharyngeal secretions, and postural hypotension. Hypersensitivity to L-dopa was a particular management problem in this infant., (Copyright 2002 Movement Disorder Society.)

Two infants presented at 3 weeks and 3 months of age with intractable partial seizures. Extensive investigations failed to identify an underlying cause. There was no response to antiepileptic drug therapy and no developmental progress following the onset of the seizures. In both infants there was a distinctive pattern of seizures that arose independently from multiple regions of both hemispheres. Interictal electroencephalograms revealed multifocal epileptiform activity. The infants died aged 9 and 12 months. One underwent postmortem examination, which was normal with no hippocampal sclerosis. These infants fulfill the diagnostic criteria of the syndrome of migrating partial seizures in infancy described by Coppola and colleagues in 1995.

We reviewed the clinical history, electrophysiologic and pathologic findings, and response to therapy of 16 children with chronic inflammatory demyelinating polyneuropathy. The majority presented with lower limb weakness. Sensory loss was uncommon. The illness was monophasic in seven children, relapsing in six, and three had a slowly progressive course. All patients were treated with immunosuppressive agents. In 11, the initial treatment was prednisolone. All had at least a short-term response but five went on to develop a relapsing course. Intravenous immunoglobulin was the initial treatment in four patients. Three responded rapidly, with treatment being stopped after a maximum of 5 months. In resistant chronic inflammatory demyelinating neuropathy, in addition to prednisolone and immunoglobulin, plasma exchange, azathioprine, cyclosporine, methotrexate, cyclophosphamide and pulse methylprednisolone were tried at different times in different patients. On serial neurophysiologic testing slowing of nerve conduction persisted for long periods after clinical recovery. Follow-up was for an average of 10 years. When last seen 14 patients were asymptomatic, two having mild residual deficits. Childhood chronic inflammatory demyelinating neuropathy responds to conventional treatment and generally has a favourable long-term outcome.

The clinical and neurophysiological findings in six Australian children with generalized tick paralysis are described. Paralysis is usually caused by the mature female of the species Ixodes holocyclus. It most frequently occurs in the spring and summer months but can be seen at any time of year. Children aged 1-5 years are most commonly affected. The tick is usually found in the scalp, often behind the ear. The typical presentation is a prodrome followed by the development of an unsteady gait, and then ascending, symmetrical, flaccid paralysis. Early cranial nerve involvement is a feature, particularly the presence of both internal and external ophthalmoplegia. In contrast to the experience with North American ticks, worsening of paralysis in the 24-48 h following tick removal is common and the child must be carefully observed over this period. Death from respiratory failure was relatively common in the first half of the century and tick paralysis remains a potentially fatal condition. Respiratory support may be required for > 1 week but full recovery occurs. This is slow with several weeks passing before the child can walk unaided. Anti-toxin has a role in the treatment of seriously ill children but there is a high incidence of acute allergy and serum sickness. Neurophysiological studies reveal low-amplitude compound muscle action potentials with normal motor conduction velocities, normal sensory studies and normal response to repetitive stimulation. The biochemical structure of the toxin of I. holocyclus has not been fully characterized but there are many clinical, neurophysiological and experimental similarities to botulinum toxin.

Developmental regression is the presenting symptom of most infants with cobalamin (Vitamin B12) deficiency. We present a report of three infants with cobalamin deficiency in which the infants also developed a movement disorder. In each case the mother was a vegetarian and the infant was exclusively breast-fed. In two of the infants, a striking movement disorder consisting of a combination of tremor and myoclonus particularly involving face, tongue, and pharynx appeared 48 h after the initiation of treatment with intramuscular cobalamin. This was associated with marked changes in plasma amino acid levels. Paradoxically, the onset of the movement disorder coincided with overall neurological improvement. The third infant had a persistent focal tremor, which appeared before the commencement of treatment. The movements slowly abated during a 3-6 week period. The presence of a movement disorder in cobalamin deficiency has received less attention than other features, but in a mild form is probably common. It may offer an early clue to the diagnosis before the onset of profound neurological deterioration. The cause of the severe movement disorder that can appear after treatment is not known.

The case history of a 4-year-old boy with an intraneural ganglion of the common peroneal nerve is presented. These lesions are rare, more commonly affect males, and typically present with a painful foot-drop. A mass is often palpable adjacent to the neck of the fibula. Our patient has made a good recovery after surgery.

Brainstem reflexes were examined in 23 children treated with thiopentone infusion and correlated with serum thiopentone concentrations. The results suggest that if all brainstem reflexes are lost with a serum thiopentone concentration less than 40 mg/l, it is unlikely to be due to the thiopentone alone. Other causes including brain death need to be considered.

Neuropsychological assessment of 65 patients with pituitary tumours revealed impairment of memory and executive function. This did not appear to be related to the size or type of tumour or the effects of radiotherapy or surgery. It is possible that the problems arose from multiple unconnected factors but this observation lends support to the suggestion that pituitary or hypothalamic hormones have a role in the modulation of memory and behavioural pathways. Whatever the cause, neuropsychological impairment is common in patients with pituitary tumours and is an aspect of their disability which has received insufficient attention in the past.

Four cases of delayed radiation necrosis involving the CNS were found in a group of 46 patients irradiated for pituitary tumours over a six year period. This occurred in three of 11 patients with Cushing's disease representing an incidence of 27% in this group. There were no cases among 11 patients with acromegaly or among seven with prolactinomas. One case (6%) was found in the 17 patients with chromophobe adenomas. Standard doses of radiation were delivered to these patients and the findings support suggestions that the metabolic disturbances of Cushing's disease may reduce tolerance to radiation. Our results and a literature review indicate that if radiotherapy is used to treat Cushing's disease, the total dose should be less than 50 Gy at 2 Gy per day fractionation.

Objective: The description of a second case of rabies in Australia, stressing the clinical features and that long incubation periods are possible., Clinical Features: A 10-year-old Vietnamese girl presented with fever, shoulder pain, subcutaneous emphysema, swallowing difficulty and agitation. After a period of maniacal behaviour all peripheral and central nervous system function was lost., Intervention and Outcome: Despite maximal intensive care, the patient died. The diagnosis of rabies was made at autopsy., Conclusions: Rabies occurs in Australia and needs to be considered in the differential diagnosis of acute encephalitis and/or the Guillain-Barré syndrome. Incubation periods of more than six years can occur.

Three patients with Leigh's syndrome developed respiratory failure following general anesthesia. Although all three had respiratory symptoms prior to the anesthetic, the diagnosis was not suspected at the time of the procedure in two of the children. We reviewed the case notes of 16 other patients with Leigh's syndrome. Eight had received anesthetic agents without incident. Although the majority subsequently developed respiratory abnormalities and died with respiratory failure, this problem was not evident at the time of anesthesia. In the presence of respiratory abnormalities, general anesthesia carries significant risks in Leigh's syndrome.

Eight children who presented to two Sydney children's hospitals in 1984 with the neurological complications of measles infection are described. Six of these children have either died or have serious residual neurological abnormalities. Experience in the United States indicates that such complications of measles can be virtually eliminated by a programme of compulsory immunization of pre-school children.

Two children are described who suddenly developed an encephalitic illness with intractable bilateral facial seizures. The seizures subsided over several days, but the children were left with the signs of pseudobulbar palsy and are unable to speak or swallow effectively. Bilateral destructive lesions in the opercular regions evolved on computed tomographic scans. Both children were treated with acyclovir relatively early in the illness, and cerebrospinal fluid and serum antibodies support the diagnosis of herpes simplex virus encephalitis.