Biomedical subjects

L Pavone

Publications and source records attributed to L Pavone.

At least 19 recordsLinked to original sources

PubMed2005

Earliest clinical manifestations and natural history of neurofibromatosis type 2 (NF2) in childhood: a study of 24 patients.

BACKGROUND: Neurofibromatosis type 2 (NF2) is an autosomal dominant disease characterised by the development of multiple nervous system tumours, ocular abnormalities, and skin tumours. Although classically considered a disease of adults, initial signs and/or symptoms may be evident in childhood and are often unrecognised. OBJECTIVES: The aim of this study was to identify the earliest clinical presentations of NF2 and to characterise the clinical course and outcome in children with NF2. METHODS: We have performed a retrospective (years 1990-1998) and prospective (years 1998-2004) study of 24 patients (10 males, 14 females; currently aged 4 to 22 years) fulfilling the revised (Manchester) NF2 criteria seen at the Universities of Catania and Rome, Italy. RESULTS: Causes of referral prior to a definitive diagnosis of NF2 were: 1) Ophthalmologic problems: early onset lens opacities (n = 3); strabismus (n = 3) and amblyopia (n = 3) (due to underlying cranial nerves and/or brain tumours); 2) Otolaryngology problems: hearing loss and tinnitus (n = 2) in early teens disregarded or treated as ear infections; hoarse (n = 1) or bitonal (n = 1) voice; 3) Neurological dysfunction: seizures secondary to intracranial meningioma (n = 1) or vestibular schwannomas (VS) (n = 1), neurological dysfunction related to brainstem and/or spinal cord tumours (n = 7), isolated and multiple cranial nerve deficits (n = 10), and peripheral neuropathy secondary to schwannomas (n = 4); 4) Skin manifestations: schwannomas misdiagnosed as neurofibromas because of associated café-au-lait spots (n = 2); café-au-lait spots (n = 8) and skin tumours (n = 3). A family history was relevant in 20 % of the patients. Molecular genetic analysis of the NF2 gene revealed typical truncating mutations in all the 5 familial cases and in 2/10 sporadic cases analysed. CONCLUSIONS: Children with NF2 often first come to medical attention because of ocular, subtle skin, or neurological problems the significance of which is realised when they later present with more classical symptoms due to bilateral VS or other intracranial tumours. The clinical course at this young age is highly variable, depending on tumour burden, early surgical intervention, surgical outcome after tumour resection, and complications.

Adolescent↗

PubMed2004

ENT Wegener's granulomatosis can hide severe central nervous system involvement.

The clinical manifestations of localised or early systemic forms of Wegener's granulomatosis (WG) do not require immediate treatment to save the patient's life and/or the function of a vital organ. The organs mainly involved are the ear, nose, throat (ENT) and lung, and the results of antineutrophil cytoplasmic antibody (ANCA) assays are frequently negative. We here describe three cases of the ANCA-negative early systemic form of WG with prevalent ENT involvement complicated by severe central nervous system (CNS) disease; in two cases, the only symptom was a mild headache. We conclude that, although apparently mild, the localised and early systemic forms of WG can hide CNS involvement and may require immediate treatment. This complication should be suspected and investigated in the case of patients with localised or early systemic disease especially in the presence of ENT involvement and negative ANCA assays.

Adult↗

PubMed2004

Multiple sclerosis in children under 10 years of age.

Despite the consistent amount of information accumulated in recent years on multiple sclerosis (MS) in childhood, many clinicians still view this condition as an exclusively young adult-onset disease and do not consider that it may occur and manifest even during infancy and pre-school age, suggesting that the number of MS cases in the paediatric age group may have been underestimated. Thus, the need to have practical parameters for therapeutic, counselling and educational purposes in such settings as caring for patients whose onset of disease is at very early ages may increasingly arise for practising clinicians. In addition, the clinical and radiographic criteria for the diagnosis of MS have not been validated in a paediatric MS population; accordingly, inclusion age at onset (such as for research purposes) is generally over 10 years. To highlight the peculiarities that characterise MS when it begins at this young age we have reviewed the literature and summarised our preliminary results with the national registry of the Italian Society of Paediatric Neurology (SINP) Study Group on Childhood MS in the group of MS patients with the earliest onset of disease (i.e., <10 years of age).

Adolescent↗

PubMed2004

Application of fuzzy functions for visual presentation of medical data.

While interpretation of medical data is very often an ambiguous process, computers usually display results of recommendations, provided by both human experts and computer algorithms, as concrete data. This study proposes a visual presentation of relative degrees of uncertainty along with "standard" concrete medical data. A medical parameter (mean arterial pressure) is dynamically evaluated during surgery for being too low or too high. Fuzzy membership functions are utilized to display degrees of deviation in the form of a clear and concise pie chart. Thus, in the Operating Room the anesthesiologist can be provided with an easy statistical assessment of uncertainty of existing recommendations.

Algorithms↗

PubMed2002

Congenital muscular dystrophy with adducted thumbs, ptosis, external ophthalmoplegia, mental retardation and cerebellar hypoplasia: a novel form of CMD.

At least six different forms of congenital muscular dystrophy are associated with structural changes of the central nervous system, and three of these have been mapped: merosin-deficient congenital muscular dystrophy on chromosome 6q2, Fukuyama congenital muscular dystrophy on chromosome 9q31, and muscle eye brain disease on chromosome 1p32. Walker-Warburg syndrome, congenital muscular dystrophy with calf hypertrophy, pontocerebellar hypoplasia, and normal eyes, and congenital muscular dystrophy with severe mental retardation and cerebellar cysts are nosologically distinct and have been excluded from the known congenital muscular dystrophy loci with structural changes of the central nervous system. Here, we describe a novel congenital muscular dystrophy syndrome which is phenotypically distinct from the recognized forms of congenital muscular dystrophy with brain involvement. Two siblings, a boy and a girl, were born to consanguineous parents from Sicily. Both children were born with adducted thumbs and toe contractures. They were floppy from birth, walked late, showed profound generalized muscle weakness including facial muscles, elevated creatine kinase levels of 200-700U/l, and histological changes compatible with muscular dystrophy. In addition, both showed ptosis, external ophthalmoplegia, mild mental retardation, and mild cerebellar hypoplasia on MRI. Immunocytochemistry showed normal expression of muscle membrane proteins including laminin alpha 2, laminin beta 2, and alpha-dystroglycan. Linkage analysis excluded the candidate loci on chromosomes 6q2, 9q31, and 1q32. The gene locus for congenital muscular dystrophy 1B, MDC 1B, on chromosome 1q42 was also excluded. Adducted thumbs are a distinct clinical sign that has not been reported in congenital muscular dystrophy before and should facilitate recognition of further patients with this disorder.

Blepharoptosis↗

PubMed2001

Long-term immunotherapy with low-dose interleukin-2 and interferon-alpha in the treatment of patients with advanced renal cell carcinoma.

BACKGROUND: The objective of this study was to evaluate response, toxicity, and immunologic effects of an original immunotherapy schedule based on repeated cycles of low doses of recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFNalpha) in patients with metastatic renal cell carcinoma (mRCC). METHODS: Fifty patients who underwent nephrectomy received therapeutic cycles consisting of subcutaneous rIL-2 for 5 days per week and intramuscular rIFNalpha twice weekly for 4 consecutive weeks. The cycle was regularly repeated indefinitely at 4-month intervals in all patients, irrespective of their response. rIL-2 (1 x 10(6) IU/m(2)) was administered every 12 hours on Days 1 and 2 and once per day on Days 3-5 of each week; rIFNalpha (1.8 x 10(6) IU/m(2)) was given on Days 3 and 5. Toxicity was graded according to the World Health Organization (WHO) criteria. Forty percent of the patients had only one metastatic disease site at the time of treatment. The Kaplan-Meier method was used to estimate survival, and an analysis of variance was used to evaluate the effects on leukocytes and lymphocyte subsets over time. RESULTS: A total of 241 cycles were administered. One patient achieved a complete response, and five patients achieved a partial response. Five patients had stable disease, and 30 patients had progressive disease. Nine patients were not evaluable for response. The overall response rate was 12% (95% confidence interval, 3-21%) on the basis of an intent-to-treat analysis. The 36-month survival probability for all 50 patients was 47%. Treatment-related toxicity was limited to WHO Grades 1 and 2. Both lymphocyte and eosinophil levels significantly increased after all cycles (by 42% and 353%, respectively). The treatment also induced significant increases in the CD25 positive (24%), CD56 positive (28%), and CD3 negative/CD56 positive (54%) lymphocyte subsets. CONCLUSIONS: Long-term, repeated treatment with low doses of rIL-2 and rIFNalpha is feasible in patients with mRCC. The schedule induces clinical response rates and survival probabilities are similar to those obtained using higher doses.

Aged↗

PubMed2001

Long-term treatment with low doses of interleukin-2 and interferon-alpha: immunological effects in advanced renal cell cancer.

PURPOSE: We aimed to determine the immunological effects of low doses of recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) in patients bearing advanced renal cell carcinoma. METHODS: Twenty-seven patients received therapeutic cycles consisting of subcutaneous rIL-2 for 5 days per week and intramuscular rIFN-alpha twice weekly, for 4 consecutive weeks. The cycle was repeated indefinitely at regular 4-month intervals, for all patients. rIL-2 (1 x 10(6) IU/m2) was administered every 12 h on days 1 and 2 and once a day on days 3-5 of each week; rIFN-alpha (1.8 x 10(6) IU/m2) was given on days 3 and 5. In the enrolled patients, total and differential white blood cell counts, phenotypic analysis of some lymphocyte subsets, and soluble IL-2 receptor (sIL-2R), were investigated before and after each of the first six cycles of therapy (about 24 months of follow-up). RESULTS: The cycles of immunotherapy induced a significant increase of total lymphocytes (37%, P < 0.001), eosinophils (222%, P < 0.001), CD25+ cells (27%, P=0.004), sIL-2R (174%, P < 0.001) and natural killer (NK) cells (CD3-CD56+) (61%, P < 0.001); the subset that expresses CD56 with high density (CD56+ bright) expanded more (233%, P < 0.001) than the subset expressing the same marker with low density (CD56+ dimmer) (15%, P = 0.043). Unlike the previous subsets, the treatment decreased significantly T-lymphocytes with NK cell marker (CD3+ CD56+) (28%, P = 0.011). No significant differences of effectiveness were found among the subsequent treatment cycles, except for CD25+ cells and sIL-2R (P = 0.036 and P = 0.005, respectively): the increase induced by immunotherapy was maximum after the first cycle and decreased progressively thereafter. CONCLUSIONS: Long-term repeated cycles of low-dose immunotherapy induced repeated and significant expansion of one of the most important lymphocyte subsets for the non-MHC-restricted immune response to the tumour mass: CD3-CD56+ cells.

Adult↗

PubMed2001

Extraneurologic symptoms as presenting signs of Sanfilippo disease.

Sanfilippo disease, or mucopolysaccharidosis type III, results from the deficiency of lysosomal hydrolases, which impairs heparan sulfate metabolism. Clinically, the disease is characterized by a mild somatic phenotype combined with early severe neurodegenerative illness with prominent behavioral disturbance. We report clinical and molecular findings of a child with Sanfilippo disease type B (alpha-N>-acetylglucosaminidase deficiency) who presented at age 18 months with marked systemic involvement and normal initial psychomotor development. These findings suggest that atypical mucopolysaccharidosis type III patients may present with early somatic changes preceding the onset of overt neurologic symptoms and ensuring an early diagnosis and possible therapeutic intervention.

Acetylglucosaminidase↗

PubMed2001

Acute flaccid paralysis surveillance in Southern Italy.

The purpose of this study was to report the results of the first two years' surveillance programme of acute flaccid paralysis (AFP) in Southern Italy (Calabria). All paediatric, neurology and infectious diseases wards from 23 hospitals were selected. Stool and serum samples to determine the presence of poliovirus were collected. Throat swabs were taken within 10 days of onset of illness. During the period March 1997-April 1999 eight cases of AFP were reported and four of them, three females and one male, occurred in children younger than 15 y of age, although none was confirmed as poliomyelitis. The rate of non-polio AFP in 1997 and 1998 was, respectively, 0.24 and 0.73 per 100 000 persons under 15 y of age. Our results demonstrated that an active surveillance has permitted us to immediately detect AFP cases and to exclude those due to wild polio virus and to vaccine-associated cases and indicated that our area seems to be 'polio-free'.

Adolescent↗

PubMed2000

Pallister-Killian syndrome: case report with pineal tumor.

Pallister-Killian syndrome, an aneuploidy syndrome, comprises a characteristic facial appearance, mental retardation, and multiple other anomalies. It is caused by mosaicism with a supernumerary isochromosome 12p. This chromosomal abnormality has been reported also in human germ cell tumors. We report on a 15-year-old girl with Pallister-Killian syndrome and pineal tumor.

Abnormalities, Multiple↗

PubMed2000

Aggressive behavior in patients with Sotos syndrome.

Sotos syndrome is characterized by peculiar facies, prenatal and postnatal overgrowth, and developmental delay. The course of six patients with psychiatric, neurologic, and magnetic resonance imaging evaluations is reported. Three (50%) of the six patients were observed to have a tendency toward aggressiveness, including one who had pyromania.

Aggression↗

PubMed2000

Diffuse polymicrogyria associated with congenital hydrocephalus, craniosynostosis, severe mental retardation, and minor facial and genital anomalies.

We report an infant boy with an apparently new malformation syndrome. The major anomalies showed by the patient include diffuse polymicrogyria, congenital hydrocephalus, craniosynostosis with severe scaphocephaly, severe mental retardation, intractable epilepsy, and minor facial and genital anomalies. Our review of the literature and two computerized dysmorphology databases found some papers reporting polymicrogyria or lissencephaly associated with craniosynostosis or hydrocephalus. None of the reported patients had a phenotype similar to that of our patient.

Abnormalities, Multiple↗

PubMed2000

Hypomelanosis of Ito: clinical syndrome or just phenotype?

The term hypomelanosis of Ito is applied to individuals with skin hypopigmentation along the lines of Blaschko. Even though originally described as a purely cutaneous disease, subsequent reports have included a 33% to 94% association with multiple extracutaneous manifestations mostly of the central nervous and musculoskeletal systems leading to frequent characterization as a neurocutaneous disorder. A number of reports claimed familial occurrence and supported single gene inheritance for hypomelanosis of Ito, but none has been proved. Miscellaneous chromosomal mosaicisms have been demonstrated in some but not all affected individuals. Thus, it has been suggested that hypomelanosis of Ito is not a single condition but rather a nonspecific manifestation (ie, a phenotype) of chromosomal mosaicism and that this term should now be dropped. In this article, we review these developments focusing on the neurologic and genetic aspects of hypomelanosis of Ito. Our personal experience with 41 hypomelanosis of Ito patients and literature review led us to conclude that (1) the term hypomelanosis of Ito has been often misapplied to individuals with nonspecific "patchy depigmentation of the skin" who had several conditions of different etiologies; (2) the white matter involvement seen at neuroimaging in most of our hypomelanosis of Ito patients was similar to that reported in well-defined neurocutaneous disorders, including Sjögren-Larsson syndrome and incontinentia pigmenti; (3) whatever figures we take for associated central nervous system abnormalities in hypomelanosis of Ito, these represent the most frequent extracutaneous findings and, therefore, the use of the term neurocutaneous disorder for hypomelanosis of Ito might well be appropriate.

Diagnosis, Differential↗

PubMed1999

Multiple sclerosis in children under 6 years of age.

OBJECTIVES: To characterize MS patients with the earliest onset of disease. BACKGROUND: MS-primarily a disease of young adulthood-begins in childhood in 3 to 5% of cases. However, onset before 10 years of age is considered exceptional. Accordingly, inclusion age at onset is generally between 10 and 59 years. METHODS: Information was obtained on patients with MS treated at our institution (n = 6) or from reports in Medline or bibliographies. Onset of disease was before 6 years of age, for a total of 49 patients (29 girls, 20 boys). RESULTS: All patients had clinically defined MS according to Poser's criteria; 22 were also laboratory supported. The female/male ratio (1.4) was lower than that usually recorded for adult onset MS (2.0) and that of MS with onset between 6 and 15 years (2.2 to 3.0). The group of patients (n = 5) with onset before 24 months of age showed the lowest ratio (0.6) and carried the most unfavorable prognosis. Among initial symptoms, ataxia was preponderant (61%). Optic nerve involvement became more frequent with age. Generalized or partial seizures occurred in 22% of cases. First inter-attack interval was less than 1 year in 63% of the cases. The yearly relapse rate ranged from 1.1 at disease onset to 0.2 after 9 years from disease onset. At follow-up (mean length 6.8 years), the disease was relapsing-remitting in 84% patients and the grade of recovery was complete in 64%. CONCLUSIONS: Definite MS can be consistently diagnosed by current criteria for adult onset MS in patients with the earliest onset of disease who show peculiar clinical features and natural history. These findings may suggest a reconsideration of current lower limits for MS diagnostic criteria.

Age of Onset↗

PubMed1999

Plasma chitotriosidase activity in patients with beta-thalassemia.

Chitotriosidase, a macrophage marker, which is extremely increased in plasma of Gaucher patients, was measured in patients with beta-thalassemia, an haematological disorder characterized by the genetic defect of beta-globin chains synthesis resulting in unproductive erythropoiesis and enormous expansion of the reticuloendothelial system. Plasma chitotriosidase was increased to a variable extent in 13 of 70 patients with beta-thalassemia major treated with the intense transfusion regimen and iron chelation therapy. It was normal in 22 and slightly elevated in 3 subjects with beta-thalassemia intermedia which were not transfused. The highest levels of plasma chitotriosidase, as high as in Gaucher patients, were found in 7 (10%) of the beta-thalassemia major patients which also had the highest degree of iron overload as judged by their serum ferritin level (> 3000 ng/ml), high SGPT level and elevated urinary iron excretion. To our knowledge, beta-thalassemia is hitherto the only disorder in which an increase of plasma chitotriosidase, comparable to that seen in Gaucher disease, may occur. The increase of plasma chitotriosidase activity in beta-thalassemia patients with high iron overload, could be related to an iron mediated damage to the lysosomal apparatus. In addition, similarly to Gaucher disease, the increased chitotriosidase production in beta-thalassemia might reflect macrophage activation probably related to the intracellular iron overload, storage of erythrocytes membrane break-down products and oxidation of excess alpha-hemoglobin subunits. Further studies are required to define the role of chitotriosidase evaluation to assess the efficacy of chelation therapy in reducing the macrophage activation due to intracellular iron overload in beta-thalassemia.

Adolescent↗

PubMed1999

Developmental patterns and neuropsychological assessment in patients with carbohydrate-deficient glycoconjugate syndrome type IA (phosphomannomutase deficiency).

Carbohydrate-deficient glycoconjugate (CDG) syndrome type I due to phosphomannomutase deficiency (CDGIA) is the most common among a group of metabolic disorders characterized by a defective glycosylation of glycoconjugates. Clinically it is a multisystem disease with an important involvement of the central nervous system including pontocerebellar atrophy. Here the developmental patterns and results of neuropsychological assessment of four young adults with CDGIA syndrome are reported. The patients, aged 14-26 years, had classical clinical findings of CDGIA syndrome and olivopontocerebellar atrophy of severe degree. They had a marked delay in all areas of psychomotor development and gained to walk with aid, perform manipulative abilities and develop a communicative language after the 7th year. Later on, the acquired abilities remained stable, while self-help skills gradually improved, allowing the patients to join the family life. On neuropsychological assessment, there was mental retardation of variable degree with a special impairment of visuoperceptual skills, visuospatial organization, eye-hand coordination, verbal memory and language. Such findings, may be partially explained by the supratentorial atrophy in our patients and add more evidences to the role of the cerebellum and brainstem in the acquisition of non-motor cognitive functions. This study expands our understanding on the clinical spectrum of CDGIA syndrome and may be helpful for planning rehabilitation and education.

Adolescent↗

PubMed1999

Peripheral lymphocyte subsets and other immune aspects in Rett syndrome.

A possible role of the immune system in the pathogenesis of some neurologic disorders, including infantile autism, was recently postulated. This observation prompted the authors to investigate some immunologic aspects in a group of patients with Rett syndrome, a disorder still not completely clarified but with some points of commonality with infantile autism. Humoral and cell-mediated immunity were investigated in 20 females with Rett syndrome. Peripheral lymphocyte subsets revealed a reduced percentage of CD8+ suppressor-cytotoxic cells in all of the patients with Rett syndrome, resulting in an increased CD4+/CD8+ ratio. In addition, 15 (75%) of the 20 patients had low levels of natural killer cells. Soluble interleukin-2 receptor was elevated in the youngest patients. Antineuronal and antimyelin ganglioside antibodies were absent, as were antinuclear antibodies, antistriated muscle antibodies, and antismooth muscle antibodies. Immunoglobulin fractions and complement were normal for age in all of the patients.

Adolescent↗

PubMed1999

Clinical and neuroradiological follow-up in mucopolysaccharidosis type III (Sanfilippo syndrome).

Mucopolysaccharidosis type III (Sanfilippo syndrome) is an autosomal recessive disorder characterised by progressive nervous system involvement with mental retardation, behavioural problems and seizures. Three patients, of 20 months to 12 years of age, were followed up for 3 years both clinically and by using brain magnetic resonance imaging (MRI). Our results suggest that in MPS III patients MRI findings, including atrophy and abnormal or delayed myelination, may precede the onset of overt neurological symptoms. The increasing neurological morbidity is accompanied by different degrees of progressive atrophic changes, mainly affecting the cerebral cortex and the corpus callosum. However, it appears that, across subjects, the rate of MRI changes is unrelated to the severity of the clinical phenotype. On this basis it could be argued that in MPS III the worsening of the neurological symptoms might not necessarily reflect only the progressive cerebral abnormalities detectable by MRI.

Atrophy↗