Norovirus gastroenteritis and seizures: an atypical case with neuroradiological abnormalities.

We describe an 8-year-old boy admitted because of prolonged seizures during norovirus gastroenteritis without any signs of encephalopathy. Blood tests were normal and cerebrospinal fluid examination resulted negative for both bacteria and viruses. A reverse transcriptase polymerase chain reaction revealed norovirus RNA in a stool sample. A cerebral computed tomography turned out to be normal whereas subsequent cerebral magnetic resonance imaging showed transitory signal abnormalities consistent with vasogenic edema. The post-ictal electroencephalogram revealed normal background activity with sporadic left posterior delta waves. The child was discharged after 10 days with an unremarkable physical examination. A cerebral magnetic resonance imaging and an electroencephalogram after 1 month were both negative. We report a new case of benign infantile convulsions due to norovirus gastroenteritis with neuroradiological abnormalities to the pertinent literature in order to improve knowledge about this disorder and increase the possibility of clarifying its pathogenesis.

Pontocerebellar hypoplasia: clinical, pathologic, and genetic studies.

BACKGROUND: Mutations in genes encoding subunits of the tRNA-splicing endonuclease (TSEN) complex were identified in patients with pontocerebellar hypoplasia 2 (PCH2) and pontocerebellar hypoplasia 4 (PCH4). OBJECTIVE: We report molecular genetic findings in 12 Italian patients with clinical and MRI findings compatible with PCH2 and PCH4. METHODS: We retrospectively selected a cohort of 12 children from 9 Italian families with MRI of hypoplastic pontocerebellar structures and clinical manifestations suggesting either PCH2 or PCH4 and submitted them to direct sequencing of the genes encoding the 4 subunits of the TSEN complex, namely TSEN54, TSEN34, TSEN15, and TSEN2. RESULTS: In a cohort of 12 children, we detected the common p.A307S mutation in TSEN54 in 9/12 available patients from nine unrelated families. We also detected a novel c.1170_1183del (p. V390fs39X) in compound heterozygosity with the common p.A307S in a child with a severe PCH4 phenotype. In another severely affected patient, the second mutant allele was not identified. Two sibs without mutations in the TSEN complex were unlinked to the PCH3 locus. In addition to typical clinical and neuroradiologic features of PCH2, both children were affected by a tubulopathy resembling Bartter syndrome. CONCLUSIONS: We confirm that the common p.A307S mutation in TSEN54 is responsible for most of the patients with a PCH2 phenotype. The presence of a heterozygous in/del variant correlates with a more severe phenotype as PCH4. In addition, we describe a new clinical form of PCH in 2 sibs with clinical and MRI features of PCH2.

Clinical and diagnostic aspects of multiple sclerosis and acute monophasic encephalomyelitis in pediatric patients: a single centre prospective study.

OBJECTIVE: The purpose of the study was to compare and contrast the initial presenting demographic, clinical, neuroimaging, and laboratory features in a cohort of children affected from multiple sclerosis (MS) or acute disseminated encephalomyelitis (ADEM). METHODS: A 12-year prospective study was conducted in 68 pediatric patients (age

Germinoma with synchronous involvement of midline and off-midline structures associated with progressive hemiparesis and hemiatrophy in a young adult.

INTRODUCTION: Cerebral germinomas, the most common and least malignant intracranial germ cell tumors, usually arise in the pineal or suprasellar region and have characteristic clinical and radiological features. Germinomas more rarely occur in the thalamus, basal ganglia, and internal capsule, causing sometimes cerebral hemiatrophy and hemiparesis. More rarely, other clinical features can be fever of unknown origin, visual disturbance, and neuropsychiatric symptoms. Cerebral hemiatrophy can precede the imaging depiction of the off-midline mass. CASE: The authors present the first case of cerebral germinoma with synchronous involvement of the midline and off-midline structures, with unusual clinical and radiological presentation. DISCUSSION: The literature is reviewed, and the pathogenesis, the clinical findings, the imaging, and the therapy are discussed.

Hemiconvulsion-hemiplegia-epilepsy syndrome: early magnetic resonance imaging findings and neuroradiological follow-up.

We describe a case of hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome documented by longitudinal magnetic resonance imaging (MRI). A two-year and nine-month-old boy had a prolonged hemiconvulsion during fever followed by right hemiparesis. Seven days later the imaging abnormality on T2 and diffusion-weighted images (DWI) was limited to the white matter of the left hemisphere. One month later severe gliosis and unilateral brain atrophy were already evident. MRI is useful in the early stages of prolonged seizures and T2 and DWI abnormalities appear to be well correlated with parenchymal damage that results from sustained ictal activity. The neuroradiological findings in our case and in the few HHE patients reported in the literature seem to be very characteristic and, if confirmed in larger series, could permit an early diagnosis.

Infantile encephalomyopathy and nephropathy with CoQ10 deficiency: a CoQ10-responsive condition.

Coenzyme Q10 (CoQ10) deficiency has been associated with various clinical phenotypes, including an infantile multisystem disorder. The authors report a 33-month-old boy who presented with corticosteroid-resistant nephrotic syndrome in whom progressive encephalomyopathy later developed. CoQ10 was decreased both in muscle and in fibroblasts. Oral CoQ10 improved the neurologic picture but not the renal dysfunction.

Acute encephalopathy as a primary manifestation of haemophagocytic lymphohistiocytosis.

Haemophagocytic lymphohistiocytosis (HLH) is characterized anatomically by an infiltration of multiple tissues with lymphocytes and haemophagocytic histiocytes. First symptoms are usually hepatosplenomegaly, pancytopenia, and intractable fever. Up to 73% of those with HLH develop CNS involvement during the disease course. The peculiarity of the two patients presented here, a 20-month-old Italian female and a 4-year-old Moroccan female, is that the initial presenting neurological symptoms mimicked an encephalitis, anticipating the typical systemic symptoms by 1 and 4 months. They developed progressive encephalopathy accompanied by status epilepticus, one child developed a secondary hydrocephalus. In both children it was not possible to detect an underlying infection or malignant disease and there were no other cases in the family that suggested a familial form of HLH. Diagnosis and initiation of treatment was delayed because of the initial encephalopathic clinical picture and the late onset of the typical systemic features. As early diagnosis allows better therapeutical approaches, haemophagocytic lymphohistiocytosis should be considered in children with persistent or progressive findings of encephalopathy, especially in the absence of identification of a plausible pathogen.

Benign paroxysmal vertigo of childhood.

Benign paroxysmal vertigo of childhood (BPV) is a paroxysmal, non-epileptic, recurrent event characterized by subjective or objective vertigo that occurs in neurologically intact children. We recorded the history and the clinical aspects of 19 cases presenting with neurological problems to the outpatient clinic at the Pediatrics Department of Padova University between 1987 and 1998 and re-examined in 1999. Details were collected on the characteristics of their vertigo: age at onset, mode of onset, trigger factors, duration, frequency and recurrence of episodes, duration of symptoms in time and age at disappearance. An attempt was also made to establish any family history of migraine and kinetosis and the most important data were compared, when possible, with those reported in the literature. Differential diagnosis and pathogenetic hypothesis were also reported. It is worth emphasizing that it is important for pediatricians to be aware of these benign events to ensure a correct diagnostic approach, avoiding the child and family any pointless anxiety or costly and sometimes invasive diagnostic procedures.

Benign paroxysmal torticollis of infancy.

Benign paroxysmal torticollis is an episodic functional disorder of unknown etiology that occurs in the early months of life in healthy individuals. The child's head tilts to one side for a few hours or days, usually without any associated symptoms. The disorder, which disappears within the first few years of life, is often misinterpreted and the patient pointlessly undergoes numerous tests. We present our series of 22 patients observed at the pediatric neurology outpatients clinic in Padova with a view to refreshing the pediatrician's memory on this frequent, benign pathology.

Acute quadriplegic myopathy in a 17-month-old boy.

Acute quadriplegic myopathy is a rare condition associated with the use of nondepolarizing muscle-blocking agents and corticosteroids in the course of severe systemic illness. A 17-month-old boy underwent liver transplantation for fulminant hepatitis. He was intubated for 24 days and treated with vecuronium bromide and high-dose methylprednisolone. The child was weaned from the ventilator and presented extreme weakness in the upper limbs and total paralysis of the lower limbs. Serum creatine kinase level was normal and electromyography showed myopathic abnormalities. Muscle biopsy showed severe type-1 fiber atrophy and selective loss of myosin thick filaments was seen on electron microscopy. Scattered regenerating fetal myosin-positive fibers were present, mu calpain was absent, while m calpain was diffusely expressed. Physical therapy was immediately started and the child recovered even though corticosteroids were not discontinued. The pathogenesis of acute quadriplegic myopathy is still unknown. We suggest that it could be due to abnormal protein turnover in the muscle. Several independent factors, such as corticosteroid treatment, immobilization, or cytokines, could take part in a cascade of events that leads to an excessive yet selective degradation of proteins involving myosin thick filaments and possibly components of sarcolemma, causing muscle inexcitability.

Macrocephaly and chromosome disorders: a case report.

We report the case of a young patient with macrocephaly. After excluding the most frequent causes of macrocephaly (hereditary disorders, degenerative, osseous and metabolic diseases, neurocutaneous syndromes and cerebral malformations), the likelihood of a chromosome disorder was investigated, revealing an unbalanced de novo translocation: 46,X,der(X),t(X;7) (q13 or q13.2; q11.23 or q21.11), i.e., a partial trisomy of the long arm of chromosome 7, associated with a partial monosomy of the long arm of chromosome X. Though this chromosome disorder is relatively rare, it should be considered in the differential diagnosis of patients under one year of age presenting with macrocephaly, scoliosis and non-progressive psychomotor retardation.

Intracranial hypertension and cryptococcal meningitis in a girl with AIDS.

A girl with HIV infection acquired at birth by blood transfusion, was admitted at the age of 10 years for diplopia, vomiting, headache and papilledema. CT scan was negative. A lumbar puncture revealed clear CSF, protein 0.40 g/l, glucose 2 mmol/l, 5 mononuclear cells/mm3. The Indian ink preparation and the latex agglutination antigen test were positive for Cryptococcus n. Treatment with amphotericin B and flucytosine was started. After 10 days, since the in vitro susceptibility testing of the isolates showed resistence to both drugs, fluconazolo (400 mg/day) was started. Acetazolamide, furosemide and spironolactone were then added to the antifungal therapy for the persistence of severe intracranial hypertension. Diuretics were maintained for 10 weeks. The patient returned to school two and half months after the admission to the hospital. After 19 months, she is doing well and she is on maintenance of fluconazole (200 mg/day). We hypothesized that the increased intracranial pressure would be due to an impaired CSF reabsorption probably as a consequence of a direct cryptococcal infiltration of the villi.

Cerebrospinal fluid analysis in HIV-1-infected children: immunological and virological findings before and after AZT therapy.

Immunological and viral studies were conducted on cerebrospinal fluid from 31 HIV-1-infected children, of whom 23 were neurologically asymptomatic and 8 had progressive encephalopathy. After AZT treatment, a second cerebrospinal fluid specimen was obtained from 15 children, 11 of whom were neurologically asymptomatic and 4 had progressive encephalopathy. Virus isolation and p24Ag detection were more frequent in children with progressive encephalopathy than in asymptomatic children (66% versus 12%) and were inversely correlated with intrathecal HIV-1-antibody detection (anti-gag AB: 25% versus 70%). High concentrations of interleukin-1 beta (IL-1 beta) and IL-6 were found in children with progressive encephalopathy (50% and 37%, respectively), but low levels were also detected in some asymptomatic children (13% and 9%, respectively). Tumour necrosis factor-alpha (TNF alpha) was not found. AZT treatment induced disappearance of p24Ag in cerebrospinal fluid, as well as a marked reduction in cytokine levels. Cytokine determination may be useful in monitoring AZT treatment in children with progressive encephalopathy.

The use of antibiotics in the treatment and prevention of infection in HIV-infected children.

Children with HIV infection have an unusual susceptibility to bacterial infection, related to several immune abnormalities. Selection of initial antibiotic therapy must be individualized in these children. Patients with community-acquired disease are most likely to have infection by polysaccharide-encapsulated bacterial organism, most commonly Streptococcus pneumoniae and less frequently by Haemophilus influenzae type b. If it is possible to treat the patients at home, the use of amoxicillin-clavulanic acid might be appropriate. Other authors propose management with parenteral ceftriaxone because of the better compliance and the malabsorption. In hospitalized patients, concern for Gram-negative enteric pathogens other than polysaccharide-encapsulated organisms requires initial therapy with a third-generation cephalosporine in combination with an aminoglycoside. Trimethoprim-sulfamethizole is the most common drug used in HIV-infected children because it is recommended for the initial therapy and for prophylaxis of pneumocystis carinii pneumonia, which occurs in as many as 42% of these children.

Neonatal tuberous sclerosis presenting with intractable seizures.

A 2-day old girl with status epilepticus, unresponsive to maximum pharmacological intervention, is reported. Findings of brain and cardiac lesions pointed to the diagnosis of tuberous sclerosis. One of the brain lesions was unusually large, occupying most of the right temporo-parietal lobe.

Congenital muscular dystrophy, brain and eye abnormalities: one or more clinical entities?

Four children with congenital muscular dystrophy (CMD), eye and brain abnormalities are described. Their clinical and neuroradiological features are compatible with a diagnosis of Walker-Warburg syndrome (WWS), according to the criteria proposed by Dobyns et al. (i.e., presence of type II lissencephaly, typical cerebellar and retinal malformations, CMD), who also conclude that WWS is indistinguishable from the muscle-eye-brain disease (MEBD) described by Santavuori. On the basis of our own experience and two recently published series, we emphasize certain features that are different in patients with WWS and patients with MEBD, which make their inclusion in the same syndrome dubious.

Percutaneous ethyl alcohol intoxication in a one-month-old infant.

A one-month-old child was referred to our hospital for unexplained lethargy. She was found to be intoxicated from ethanol-soaked gauze pads which had been applied to the umbilical stump and contiguous skin for several days for the purpose of promoting umbilical cord detachment. We emphasize the importance of considering the risk of percutaneous alcohol absorption, especially in young infants, and the necessity of toxicology screening in every child with drowsiness of unknown etiology.

Immunological markers in the cerebrospinal fluid of HIV-1-infected children.

Several immunological abnormalities were detected in the cerebrospinal fluid (CSF) of human immunodeficiency virus type 1 (HIV-1)-infected children. Intrathecal synthesis of immunoglobulins, free light chains (FLC), IL-1 beta, IL-6, and M-CSF were demonstrated both in asymptomatic children and children with subacute encephalopathy. Our findings further support the hypothesis that an immunopathological subclinical process within the central nervous system (CNS) may be an early manifestation of acquired immunodeficiency syndrome (AIDS). Cytokine detection in the CSF may represent a useful diagnostic tool in evaluating the outcome of HIV-1-infected patients.

Development of language in 18-30-month-old HIV-1-infected but not ill children.

Thirty-six children (age range, 18-30 months) born to HIV-1-infected mothers were studied for speech development by matching 18 infected with 18 non-infected subjects for age, sex and socioeconomic status. All the children were in good health. Each child was given three comprehension and three production tasks. In addition, each child's mean length of utterance (MLU) was obtained by observation of natural child-parent interactions. The development quotients (DQ) were assessed by Brunet-Lézine's tests. Infection significantly affected children's MLU, the infected children being less advanced than those non-infected. Both infected and non-infected children progressed in language acquisition from the second to the third year of age, but infected children had significantly greater production difficulty than non-infected children in the second year of life. The matched subjects design adopted gives some strength to the conclusion that HIV-1 infection impairs the genesis rather than the later development of language in infected but not ill children.