A clinical scoring system for congenital contractural arachnodactyly.

Purpose: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder manifesting joint contractures, arachnodactyly, crumpled ears, and kyphoscoliosis as main features. Due to its rarity, rather aspecific clinical presentation, and overlap with other conditions including Marfan syndrome, the diagnosis is challenging, but important for prognosis and clinical management. CCA is caused by pathogenic variants in FBN2, encoding fibrillin-2, but locus heterogeneity has been suggested.

Factors influencing disease progression in autosomal dominant cerebellar ataxia and spastic paraplegia.

Objectives: To evaluate disease progression and determine validity of clinical tools for therapeutic trials.

Design: Prospective cohort study (36 months).

Setting: Referral center.

Spinocerebellar ataxia types 1, 2, 3 and 6: the clinical spectrum of ataxia and morphometric brainstem and cerebellar findings.

To assess the clinical spectrum of ataxia and cerebellar oculomotor deficits in the most common spinocerebellar ataxias (SCAs), we analysed the baseline data of the EUROSCA natural history study, a multicentric cohort study of 526 patients with either spinocerebellar ataxia type 1, 2, 3 or 6. To quantify ataxia symptoms, we used the Scale for the Assessment and Rating of Ataxia (SARA). The presence of cerebellar oculomotor signs was assessed using the Inventory of Non-Ataxia Symptoms (INAS).

Depression comorbidity in spinocerebellar ataxia.

This is a description of the prevalence and profile of depressive symptoms in dominant spinocerebellar ataxia (SCA). Depressive symptoms were assessed in a convenience sample of 526 genetically confirmed and clinically affected patients (117 SCA1, 163 SCA2, 139 SCA3, and 107 SCA6) using the Patient Health Questionnaire (PHQ). In addition, depressive status according to the examiner and the use of antidepressants was recorded.

Quantitative assessment of the evolution of cerebellar signs in spinocerebellar ataxias.

Background: Responsive ataxia rating scales are essential for determining outcome measures in clinical trials.

Methods: We evaluated the responsiveness over time of the composite cerebellar functional severity score, a quantitative score measuring cerebellar ataxia in 133 patients with autosomal dominant cerebellar ataxias (ADCA), which were prospectively evaluated at inclusion and after one-year of follow-up. A more responsive tool was developed, the Cerebellar Functional Severity score writing, incorporating the writing test at dominant hand to the Cerebellar Functional Severity score.

Missense mutations in the AFG3L2 proteolytic domain account for ∼1.5% of European autosomal dominant cerebellar ataxias.

Spinocerebellar ataxia type 28 is an autosomal dominant form of cerebellar ataxia (ADCA) caused by mutations in AFG3L2, a gene that encodes a subunit of the mitochondrial m-AAA protease. We screened 366 primarily Caucasian ADCA families, negative for the most common triplet expansions, for point mutations in AFG3L2 using DHPLC. Whole-gene deletions were excluded in 300 of the patients, and duplications were excluded in 129 patients.

Self-rated health status in spinocerebellar ataxia--results from a European multicenter study.

Patient-based measures of subjective health status are increasingly used as outcome measures in interventional trials. We aimed to determine the variability and predictors of subjective health ratings in a possible target group for future interventions: the spinocerebellar ataxias (SCAs). A consecutive sample of 526 patients with otherwise unexplained progressive ataxia and genetic diagnoses of SCA1 (117), SCA2 (163), SCA3 (139), and SCA6 (107) were enrolled at 18 European referral centers.

Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6.

Onset of genetically determined neurodegenerative diseases is difficult to specify because of their insidious and slowly progressive nature. This is especially true for spinocerebellar ataxia (SCA) because of varying affection of many parts of the nervous system and huge variability of symptoms. We investigated early symptoms in 287 patients with SCA1, SCA2, SCA3, or SCA6 and calculated the influence of CAG repeat length on age of onset depending on (1) the definition of disease onset, (2) people defining onset, and (3) duration of symptoms.

Composite cerebellar functional severity score: validation of a quantitative score of cerebellar impairment.

Reliable and easy to perform functional scales are a prerequisite for future therapeutic trials in cerebellar ataxias. In order to assess the specificity of quantitative functional tests of cerebellar dysfunction, we investigated 123 controls, 141 patients with an autosomal dominant cerebellar ataxia (ADCA) and 53 patients with autosomal dominant spastic paraplegia (ADSP). We evaluated four different functional tests (nine-hole pegboard, click, tapping and writing tests), in correlation with the scale for the assessment and rating of cerebellar ataxia (SARA), the scale of functional disability on daily activities (part IV of the Huntington disease rating scale), depression (the Public Health Questionnaire PHQ-9) and the EQ-5D visual analogue scale for self-evaluation of health status.

Mental deficiency in three families with SPG4 spastic paraplegia.

Mutations and deletions in the SPG4 gene are responsible for up to 40% of autosomal dominant hereditary spastic paraplegia (HSP). Patients have pyramidal signs in the lower limbs and some present additional features including cognitive impairment such as executive dysfunction or subcortical dementia. We report 13 patients from three SPG4 families, who had spastic paraplegia associated with mental retardation (n=1), extensive social dependence (n=10), or isolated psychomotor delay (n=2).

A novel locus for autosomal dominant "uncomplicated" hereditary spastic paraplegia maps to chromosome 8p21.1-q13.3.

Hereditary spastic paraplegias (HSPs) are genetically and phenotypically heterogeneous. Both "uncomplicated" and "complicated" forms have been described, with autosomal dominant, autosomal recessive, and X-linked inheritance. Hitherto, ten autosomal dominant "uncomplicated" HSP (ADHSP) loci have been mapped.

Psychiatric and cognitive difficulties as indicators of juvenile huntington disease onset in 29 patients.

Background: Juvenile Huntington disease (JHD) is a rare clinical entity characterized by an age at onset younger than 20 years. Patients usually have an expansion of more than 60 CAG repeats in the Huntington disease (HD) gene, and the disease is usually inherited from the father. In general, precise age at onset is difficult to assess in HD because of insidious onset and anosognosia.

Neurological, cardiological, and oculomotor progression in 104 patients with Friedreich ataxia during long-term follow-up.

Background: Friedreich ataxia (FA) is the most frequent autosomal recessive cerebellar ataxia. Although the phenotype is well known, disease progression has not been evaluated in a prospective manner.

Objective: To perform a long-term prospective follow-up of neurological, cardiological, and oculomotor function in patients with FA (FA patients).

Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia.

Background: Point mutations in SPG4, the gene encoding spastin, are a frequent cause of autosomal dominant hereditary spastic paraplegia (AD-HSP). However, standard methods for genetic analyses fail to detect exonic microdeletions.

Methods: 121 mutation-negative probands were screened for rearrangements in SPG4 by multiplex ligation-dependent probe amplification.

A new phenotype linked to SPG27 and refinement of the critical region on chromosome.

Hereditary spastic paraplegias are genetically and clinically heterogeneous. Twenty-six loci have been identified to date. SPG27 was recently mapped to chromosome 10 in a single family with autosomal recessive hereditary spastic paraplegia (AR-HSP) and a pure phenotype.

The S18Y polymorphism in the UCHL1 gene is a genetic modifier in Huntington's disease.

An expanded polyglutamine stretch in the huntingtin protein has been identified as the pathogenetic cause of Huntington's disease (HD). Although the length of the expanded polyglutamine repeat is inversely correlated with the age-at-onset, additional genetic factors are thought to modify the variance in the disease onset. As linkage analysis suggested a modifier locus on chromosome 4p, we investigated the functional relevance of S18Y polymorphism of the ubiquitin carboxy-terminal hydrolase L1 in 946 Caucasian HD patients.

Usefulness of prolonged video-EEG monitoring and provocative procedure with saline injection for the diagnosis of non epileptic seizures of psychogenic origin.

Objectives: To assess the usefulness of long term video-EEG monitoring (VEEGM) and intravenous injection of saline solution (IVISS) for the diagnosis of non epileptic seizures of psychogenic origin (PNES).

Background: PNES are common among patients referred to an epilepsy center. Long term VEEGM remains the gold standard method for assessing the correct diagnosis.

Congenital stationary night blindness: report of an autosomal recessive family and linkage analysis.

Congenital stationary night blindness (CSNB) is a group of rare, non-progressive conditions of the retina characterized by abnormal rod function causing impaired night vision. Among them, the Schubert-Bornschein subgroup, itself divided into a complete and an incomplete form, is characterized by a specific electrophysiological pattern. Complete, Schubert-Bornschein CSNB is usually transmitted as a monogenic trait, and most familial cases result from mutations of the NYX gene located on the X chromosome.

Transient cerebral arteriopathy in infancy associated with enteroviral infection.

We report the case of an 18-month-old boy who presented aphasia and right hemiplegia of acute onset. The neurological deficit completely resolved after a few hours, but identical transient neurological deficits and seizures occurred during the following days. Imaging showed proximal stenosis of the medial cerebral artery and deep ischaemic lesions in the territory of this artery.