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Davide Martino

Publications and source records attributed to Davide Martino.

14 recordsLinked to original sources
PubMed2006

Planning genetic studies on primary adult-onset dystonia: sample size estimates based on examination of first-degree relatives.

Primary adult-onset dystonia is thought to be partly genetic, but families large enough for a genome wide search are difficult to find. We examined the first-degree relatives of 76 primary adult-onset dystonia patients to assess the feasibility of model-free nonparametric methods that allow either screening of candidate loci (case-control design, transmission disequilibrium test [TDT], and sibling-TDT [S-TDT]) or identification of novel genes (affected sib-pair [ASP] method). Among the examined relatives, 1/34 parents, 13/149 siblings and 10/125 offspring were affected by adult-onset dystonia. The predicted sample sizes to detect a gene conferring an Odds ratio of 3.0 were 99 for case-control and TDT methodology, 148 for S-TDT, and 107 to 173 for an ASP study assuming three major loci. Based on our family structure, TDT, S-TDT, and ASP methods would required screening of about 220, 700, and 580 to 939 probands respectively. Analysing subpopulations with different types of dystonia, TDT required fewer probands with cervical/hand dystonia, S-TDT needed fewer probands with cranial dystonia. These sample size estimates suggest that the S-TDT may be feasible, whereas collection of cases for both TDT and ASP approaches would represent a major collaborative challenge.

Adolescent↗
PubMed2006

Head trauma in primary cranial dystonias: a multicentre case-control study.

BACKGROUND: The relationship between prior trauma and primary adult-onset dystonia is not well understood. Previous uncontrolled observations and exploratory case-control studies have yielded contradictory results. OBJECTIVE: To analyse the association between cranial dystonia and prior head trauma. METHODS: An ad hoc multicentre case-control study was performed using a semistructured interview to collect detailed information on the history of head trauma before disease onset in five Italian tertiary referral centres for movement disorders. The presence of a history of head trauma and of post-traumatic sequelae (loss of consciousness, bone fractures, scalp/facial wounds) before disease onset was recorded from 177 patients with primary adult-onset cranial dystonia and from 217 controls with primary hemifacial spasm matched by age strata and sex. Differences between groups were assessed by Mann-Whitney U test and Fisher's exact test, and the relationship between prior head trauma and case/control status was analysed by multivariate logistic regression models. RESULTS: No association was found between vault/maxillofacial trauma and cranial dystonia. Most reported traumas occurred several years before disease onset. None of the main post-traumatic sequelae altered the chance of developing cranial dystonia compared with patients with primary hemifacial spasm, nor did head trauma modify the age at onset of cranial dystonia. CONCLUSIONS: These results do not support prior head trauma as a possible environmental factor modifying the risk of developing late-onset cranial dystonia. The lack of association may have pathogenetic and medical-forensic implications.

Age of Onset↗
PubMed2006

Sensitivity and specificity of a self-administered questionnaire for familial screening of adult-onset dystonia.

We developed a self-administered questionnaire for screening the most common adult-onset dystonias. It was tested in 90 first-degree relatives of 22 adult-onset dystonia patients, yielding 79% sensitivity and 94% specificity. Simulation of a case-finding procedure based on serial application of the questionnaire and clinical examination of both subjects screening positive and subjects screening negative who had < 8 years of schooling increased sensitivity to 95% and specificity to 100%. This questionnaire may be an important screening resource for familial aggregation studies to be used in the context of a complex case-finding procedure.

Aged↗
PubMed2006

Atypical movement disorders in antiphospholipid syndrome.

Movement disorders have only rarely been reported in association with antiphospholipid syndrome (APS). In such cases, chorea is the most common disorder observed, with occasional reports of hemidystonia, Parkinsonism, and hemiballism. We report here on 3 cases of APS (3 women ages 16, 46, and 56 years) who presented with movement disorders, including tics, tremor, myoclonus, and a corticobasal syndrome, never or rarely reported in association with this disease. Mild executive dysfunction was observed in all 3 patients. We also report the successful treatment of two of these patients with mild oral anticoagulation (INR 2-3). Movement disorders in APS seem more clinically heterogeneous than previously thought. Oral anticoagulation should be considered in the treatment of movement disorders associated with APS.

Adolescent↗
PubMed2006

Hyperhomocysteinemia in movement disorders: Current evidence and hypotheses.

Elevated plasma levels of homocysteine (Hcy) are a risk factor for systemic vascular diseases, stroke and vascular dementia. In recent years, increasing Hcy levels have been detected in neurological disorders that are not vascular in origin including Alzheimer's Disease and movement disorders (MD) such as idiopathic Parkinson's Disease (PD), Huntington's Disease (HD) and primary dystonia. Hyperhomocysteinemia (HHcy) in PD results from L-Dopa administration and its O-methylation dependent from catechol-O-methyltransferase and may be implicated in the development of motor complications and non-motor symptoms, such as dementia. In a recent study, HHcy has been evidenced in HD patients, compared to controls. Because mutated Huntington protein influences Hcy metabolism by modulating cystathionine-beta-synthase activity, Hcy could represent a biological marker of neurodegeneration and could explain the leading role of cardiovascular and cerebrovascular diseases as causes of death in HD. Finally, several cases of homocystinuria associated with dystonia, and some recent reports of elevated Hcy in patients with primary adult onset dystonia have been published. Increased Hcy plasma levels may have important implications in patients affected by these basal ganglia disturbances, by exerting neurotoxic effects, contributing to neurotransmitter imbalance in motor circuits, and increasing the risk for vascular insults and cognitive dysfunctions.

Adolescent↗
PubMed2005

Relationship between eye symptoms and blepharospasm: a multicenter case-control study.

Although patients with primary blepharospasm (BSP) commonly report experiencing ocular symptoms before the onset of orbicular spasms, the precise frequency and pathogenic role of this subjective ocular discomfort are poorly understood. We conducted a multicenter case-control study to investigate symptoms related to disorders of the anterior segment of the eye, administering a questionnaire to 165 patients with BSP and 180 age- and gender-matched control patients with hemifacial spasm. On a validation sample, our questionnaire yielded high accuracy in detecting eye diseases (predominantly, dry eye syndrome) using detailed ophthalmological examination as the criterion. Logistic regression analysis indicated a significant association between ocular symptoms at disease onset and BSP. Ocular symptoms starting in the year preceding disease onset (short-latency symptoms) showed a stronger association with BSP than ocular symptoms occurring earlier in time (long-latency symptoms). The association was stronger when short-latency symptoms developed from 40 to 59 years of age, whereas this was not observed for long-latency symptoms. Our findings support the view that eye symptoms associated with BSP result from eye diseases and may be involved in the pathogenesis of BSP. The differential risk of developing BSP, based on age at onset of ocular symptoms, suggests that age and eye diseases may interact in giving rise to BSP.

Age of Onset↗
PubMed2005

Soluble adhesion molecules in acute disseminated encephalomyelitis.

Soluble adhesion molecules are overexpressed in neuroinflammatory disorders. Their synthesis parallels that of their membrane-bound counterparts, which modulate lymphocyte transmigration through the blood-brain barrier. Blood-brain barrier cellular migration may be essential in the evolution of postinfectious inflammatory central nervous system disease. The serum levels of soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and soluble E-selectin were measured in 12 children with acute disseminated encephalomyelitis and in two control groups (35 healthy and 35 affected by noninflammatory neurologic diseases) of similar age. In patients with acute disseminated encephalomyelitis, soluble E-selectin serum levels were significantly higher (median 113 ng/mL, range 54-144) than in both control groups (median 44, range 31-63, and median 58, range 43-89, respectively; one-way analysis of variance, P < 0.0001); a statistical trend for higher levels of soluble intercellular adhesion molecule-1 was observed in acute disseminated encephalomyelitis subjects, whereas soluble vascular adhesion molecule-1 titers did not differ between the three groups. The specific role played by each of these molecules in lymphocyte extravasation and the differential cytokine modulation of their expression might explain the result. Further larger studies are required including serial measurements and cerebrospinal fluid analysis.

Adolescent↗
PubMed2005

Autoaggressive immune-mediated movement disorders.

Poststreptococcal disorders exhibit a remarkable comorbidity of neurologic and psychiatric features. A similar combination of symptoms is also described in other conditions, such as connective tissue or paraneoplastic disorders, albeit less frequently. A better understanding of the underlying mechanisms associated with autoaggressive immune-mediated attack on the basal ganglia is required. This understanding will ideally aid clinicians in diagnosing these conditions and lead to appropriate clinical trials, for example, of chemoprophylaxis strategies to prevent recurrent streptococcal infection and of the use of immunosuppressive treatments.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Validity of family history data on primary adult-onset dystonia.

BACKGROUND: To our knowledge, no study has assessed the validity of family history data provided by probands with adult-onset dystonia. OBJECTIVE: To measure the sensitivity and specificity of interviewing patients with primary adult-onset dystonia as a method for obtaining information on dystonia in first-degree relatives. PARTICIPANTS: Seventy probands with primary adult-onset dystonia were asked to identify first-degree relatives who had dystonia. Available relatives were then directly examined by a trained neurologist. The validity of the probands' reports was tested against the neurologists' diagnoses. RESULTS: Among 300 first-degree relatives who were examined, 26 received a diagnosis of dystonia. Only 7 of the 26 were identified by the probands' reports. Among the 274 relatives free of dystonia, the probands reported 5 as having dystonia. The probands' reports therefore yielded a sensitivity of 27.0% and a specificity of 98.2%. CONCLUSIONS: Because the family history method yields low sensitivity and incurs a risk of misclassification, it is of limited use in family studies of adult-onset dystonia. The only valid means of ascertaining dystonia among relatives remains neurological examination of at-risk subjects.

Adult↗
PubMed2004

Antibasal ganglia antibodies and their relevance to movement disorders.

PURPOSE OF REVIEW: Recently, autoaggressive immunological responses were included among the causative agents of basal ganglia dysfunction. Autoaggressive immune-mediated illnesses secondary to group A beta-haemolytic streptococcal infections present with motor and psychiatric symptoms, due to basal ganglia involvement. These disorders have been associated with serum antineuronal antibodies, relatively specific to human basal ganglia tissue. This review summarizes the most recent studies concerning antibasal ganglia antibodies, focusing on the associated phenotypes and the hypotheses concerning their pathogenicity. RECENT FINDINGS: The spectrum of post-streptococcal neuropsychiatric disorders associated with antibasal ganglia antibodies seems broader than previously recognized. Other than chorea, tics and obsessive-compulsive disorder, which constituted the bulk of previously described disorders associated with antibasal ganglia antibodies, post-streptococcal neuropsychiatric disturbances include a wider range of motor and behavioural abnormalities, in keeping with the multifunctional role of the basal ganglia. An encephalitis lethargica-like illness following streptococcal infection was reported, and unusual adult-onset movement disorders associated with antibasal ganglia antibodies were documented. Moreover, investigators provided preliminary evidence for a pathogenic role of autoantibodies in Sydenham's chorea, the prototypic post-streptococcal neuropsychiatric disorder. SUMMARY: Antibasal ganglia antibodies are relatively specific in identifying post-streptococcal neuropsychiatric disorders, which constitute a wider spectrum of movement disorders than previously recognized. Although their sensitivity in diagnosing Sydenham's chorea seems excellent, it is not yet possible to extrapolate this sensitivity to all the recently identified post-streptococcal neuropsychiatric disorders. The antigens targeted by these autoantibodies and their pathogenic importance are currently under investigation. Preliminary evidence suggests that antibasal ganglia antibodies may be pathogenic.

Autoantibodies↗
PubMed2003

Familial blepharospasm is inherited as an autosomal dominant trait and relates to a novel unassigned gene.

Blepharospasm (BSP) is a common form of primary torsion dystonia (PTD). Although most cases are sporadic, an increased familial incidence of BSP has been reported. Precisely how blepharospasm is inherited remains unclear. We report on two Italian families with adult-onset focal BSP inherited as an autosomal dominant trait with reduced penetrance. None of the affected family members had the 3-bp (GAG) or the 18-bp deletion in the DYT1 gene. In one family, linkage analysis allowed us to exclude segregation of the disease with the known PTD loci (DYT1, DYT6, DYT7, and DYT13). These findings suggest that primary familial adult-onset BSP is a distinct entity among inherited PTD and is caused by a novel, unmapped gene.

Adolescent↗
PubMed2002

Interferon beta-1a counteracts effects of activation on the expression of G-protein-coupled receptor kinases 2 and 3, beta-arrestin-1, and regulators of G-protein signalling 2 and 16 in human mononuclear leukocytes.

Activation regulates the responsiveness of G-protein-coupled receptors (GPCRs) on T cells, and modifications in the activity of GPCRs characterize lymphocytes from some immune disorders such as multiple sclerosis (MS) and rheumatoid arthritis (RA). Some lines of evidence suggest that such an effect is connected with the altered expression of some GPCRs regulatory proteins. Herein we demonstrate that phitoemagglutinin (PHA)-induced activation leads to differential expression of G-protein-coupled receptor kinase (GRK) 2, GRK3, beta-arrestin-1, regulators of G-protein signalling (RGS) 2, and RGS16 and decreases responsiveness of mononuclear leukocytes (MNL) to the beta-adrenergic agonist isoproterenol. Interferon beta-1a (IFN beta-1a), which is known to ameliorate the course of MS, counteracts the activation-induced effects on the expression of these GPCR regulatory proteins in MNL. Furthermore, IFN beta-1a quenches the effects of PHA on the isoproterenol-induced accumulation of cyclic AMP (cAMP). We suggest that regulation of GPCRs responsiveness may be a relevant property of IFN beta-1a in MS.

Adrenergic beta-Agonists↗
PubMed2002

Menopause and menarche in patients with primary blepharospasm: an exploratory case-control study.

We studied the relationships between blepharospasm (BSP) and menopause/menarche in female patients with primary BSP (n = 83) and age-matched healthy (n = 83) and disease controls (n = 83). BSP patients and matched controls had comparable age at menopause, and there was no correlation between age at menopause and age at BSP onset. Thus, menopause probably exerts no significant influence on the age-dependent development of BSP. BSP cases tended to have a later menarche than either group of controls. The association was independent of age, disease duration and education level. Because the higher the age at menarche, the higher the age at BSP onset, later menarche was unlikely to be a risk factor for BSP. Rather, the two conditions may share pathophysiologic mechanisms, for example minor abnormality of neurotransmitter systems controlling both the motor system and the maturation of the hypothalamic-pituitary-gonadal axis responsible for the onset of puberty.

Age of Onset↗