A nationwide study on Sydenham's chorea: Clinical features, treatment and prognostic factors.

OBJECTIVES: Sydenham's Chorea (SC) is a neuropsychiatric disorder and a major manifestation of acute rheumatic fever. The erroneous assumption that SC is a benign and self-limiting disease, has led to a lack of high-quality scientific evidence of the therapeutical and prognostic features of SC. STUDY DESIGN: We retrospectively analyzed the medical records of patients <18-years old with SC in 17 Italian pediatric centers. Recorded data included clinical, instrumental and laboratory parameters. Prognostic risk factors including treatment regimens were assessed with univariate and multivariate sub-analysis. RESULTS: We included 171 patients with SC. 66% had generalized chorea, and 34% hemichorea. 81% had carditis (subclinical in 65%). Additional neurological symptoms were reported in 60% of the patients, mainly dysarthria and dysgraphia. 51% had neuropsychiatric symptoms at onset, which persisted after 12 months in 10%. Among psychiatric manifestations, the most common was anxiety disorder/depression (77%). Neurological remission was reached by 93% of the patients at 6 months; 9% relapsed. Patients were treated as follows: 11% penicillin alone, 37% immunomodulatory therapy, 16% symptomatic drugs (i.e. anti-seizure medication, dopamine antagonists) and 37% both symptomatic and immunomodulatory treatment. Neurological outcome did not differ between groups. Patients receiving symptomatic drugs had a higher risk of relapse on multivariate analysis (p = 0.045). CONCLUSIONS: Treatment of SC was largely heterogeneous. Based on our results, immunomodulatory therapy did not show higher efficacy at medium term, although it was associated to a slightly lower risk of relapse compared to symptomatic therapy. Longitudinal studies are needed to assess specific risk factors and best treatment options.

Long term neurocognitive improvement after "late" right hemispherectomy: case report and review of the literature.

OBJECTIVE: To study the long-term neurocognitive changes of a right-handed girl with intractable epilepsy after late right hemispherectomy and compare them with data in the literature. METHOD: The girl was affected by an epileptic encephalopathy associated with right fronto-temporo-parietal polymicrogyria; she was submitted to right hemispherectomy at the age of 5 and examined with cognitive and neuropsychological tests at the age of 17 years. The girl took advantage of neurocognitive rehabilitation for several years; she is currently seizure-free and off therapy. RESULTS: At the end of the follow-up, the full-scale IQ is stable and within the normal range (p = 88). As the discrepancy between verbal IQ (pp = 120) and performance IQ (pp = 71) is significantly high, the girl was subjected to neurocognitive evaluation with the following results: verbal problem solving, verbal short- and long-term memory, and executive functions are within normal range. The most fragile functional areas are visual and spatial reasoning, verbal working memory, short-term visuospatial memory, visual attention, and processing speed, all > 2 SD. The spatial tests, such as coding, matrix reasoning, picture concepts, and arithmetic reasoning (which are favored by other functions such as associative memory and learning ability), are less severely impaired. CONCLUSIONS: These findings show that good conceptual skills and verbal reasoning can compensate for some deficits in visual-perceptual and visuospatial functions.

A relatively mild phenotype associated with mutation of SCN8A.

Mutations in SCN8A gene have been described in relation to infantile onset epilepsy with movement disorders and developmental delay. Recently various authors have reported patients carrying autosomal dominant heterozygous SCN8A mutations and a milder phenotype expression. We discuss the case of a 6-year-old girl with a positive family history for epilepsy, early benign focal epilepsy, well controlled by Carbamazepine, upper limb tremor since birth, ataxia, slight motor delay and normal cognitive development. Neuroradiological study is normal, waking EEGs are normal, while epileptiform abnormalities on the vertex appear during sleep. The girl carries a de novo mutation of the SCN8A gene with nucleotide substitution of c.3943G > A (p.Val 1315 Met), located in the domain III S4/S5 intracellular linker. In literature two other cases with the same mutation have been reported, both patients have an epileptic encephalopathy. Our patient's milder phenotype could be caused by a modifier effect, possibly a mutation in another gene or a mosaicism. The detailed description of our case should contribute to enlarging the description of the clinical features of SCN8A mutations and to recommending the deepening of genetic investigations to.

LAMA2 stop-codon mutation: merosin-deficient congenital muscular dystrophy with occipital polymicrogyria, epilepsy and psychomotor regression.

Merosin-deficient congenital muscular dystrophy (MD) type 1A (MDC1A) is one of the most frequent forms of CMD in Western countries. The classical form, characterized by a total lack of laminin alpha2 chain expression, usually shows severe clinical features; cases with complete laminin alpha2 deficiency and mild phenotype have also been reported, although the mechanisms underlying the lack of genotype-phenotype correlation have not been elucidated. Epilepsy and focal cortical dysplasia-in addition to the classical diffuse white matter abnormalities-have been described in some of these patients associated with cognitive deterioration. We report on a patient with total laminin alpha2 deficiency due to a homozygous stop-codon mutation in the LAMA2 gene, with mild evolution. When 6.9 years old, she developed focal occipital seizures and absence-like status when awake, with probable relation to an extensive bilateral occipital micropolygyria. Soon afterwards she lost ambulation and developed cognitive deterioration. Our case confirms that the clinical spectrum of MDC1A is more heterogeneous than previously thought.

Danon disease: a novel LAMP2 mutation affecting the pre-mRNA splicing and causing aberrant transcripts and partial protein expression.

LAMP2, the causative gene of Danon disease, located on chromosome Xq24, encodes the lysosome-associated membrane protein-2 (LAMP-2). We describe clinical features and molecular data in an Italian patient with Danon disease. The patient had hyperCKemia, hypertrophic cardiomyopathy, no muscle weakness and slight mental impairment. Muscle biopsy revealed autophagic vacuoles with sarcolemmal features and glycogen storage. Immunohistochemistry and immunoblot revealed traces of LAMP-2 protein in skeletal muscle. Molecular analysis of the LAMP2 gene revealed a novel hemizygous mutation affecting the invariant +1 position of the splice site of intron 8, resulting in aberrant transcripts with skipping of exon 8 in all three LAMP-2 isoforms, skipping of exons 7 and 8 in LAMP-2A and 2C, and a 15 bp deletion in exon 8 of LAMP-2B. Low levels of normal LAMP-2B transcript were also present. Danon disease is an under-recognized and frequently fatal condition, treatable by heart transplantation. Investigation of the primary molecular defect is important for cardiac surveillance and genetic counseling.

Muscle inflammation and MHC class I up-regulation in muscular dystrophy with lack of dysferlin: an immunopathological study.

Muscle inflammation is characteristic of inflammatory myopathies but also occurs in muscular dystrophy with lack of the sarcolemmal protein dysferlin. We quantified inflammatory cells and major histocompatibility complex (MHC) expression in muscle from 10 patients with dysferlinopathy. Infiltrating cells were always present although numbers varied considerably; macrophages were more common than T cells, T cytotoxicity was absent, and MHC class I was overexpressed on muscle fibers. These findings differ from polymyositis (PM) but are closely similar to those in SJL/J mice (which lack dysferlin) and emphasize the relationship between absence of dysferlin and immune system abnormalities in muscle.

Manganese intoxication: the cause of an inexplicable epileptic syndrome in a 3 year old child.

Excess manganese (Mn) can cause several neurotoxic effects, however only a few studies have reported epileptic syndromes related to manganese intoxication. We describe an epileptic syndrome due to manganese intoxication in a 3 year old male child. His blood manganese was elevated, but no other abnormal values or toxic substances were found in blood or urine. The electroencephalogram (EEG) showed a picture of progressive encephalopathy, while brain magnetic resonance was normal. The patient's conditions rapidly worsened to epileptic status despite the use of antiepileptic drugs. Chelating treatment with CaNa(2)EDTA was initiated to remove excess manganese and promptly succeeded in reverting epileptic symptoms. Concurrently, manganese blood levels and electroencephalogram progressively normalized. Thereafter it has been possible to discontinue antiepileptic treatment, and the patient remains in excellent conditions without any treatment.

Hair anomalies as a sign of mitochondrial disease.

UNLABELLED: In 8 out of 25 children with a mitochondrial disorder, slow growing, sparse and fragile hair was observed as an early sign of their disease. Microscopic examination of the hair showed the presence of trichorrhexis nodosa and pili torti. Hair abnormalities can be added to the wide clinical spectrum of mitochondrial disorders. CONCLUSION: Microscopic hair examination is an easy, first level diagnostic tool that can lead to a suspected mitochondrial defect in the early stages of the disease, before symptoms of progressive multi-organ involvement develop.