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Background: Glycogen storage disease type III (GSDIII) is a rare autosomal recessive disorder due to glycogen debranching enzyme (GDE) deficiency. It results in a multisystemic disease with predominant hepatic and myopathic symptoms. While frequent social maladjustment has been observed in our clinical practice, cognitive and psychological disturbances have never been assessed. The aim of this pilot study was to examine and characterize the cognitive profile of patients with GSDIII. Methods: Seven patients (six women and one man, mean age: 38.7 ± 11.6 years) with GSDIII underwent a neuropsychological set of tests assessing global cognitive efficiency, executive functions, social cognition, apathy, and episodic memory. Results: All patients presented previous psychopathological history. We observed attention fluctuations for each patient, and impaired global cognitive efficiency with deficiencies in executive functions in 5/7 patients. Emotional skills (social cognition) were impaired in five patients. Memory was mostly preserved. Conclusion: The impairment in social cognition (recognition of emotions and ability to attribute mental states to others) and executive functions observed could be a consequence of orbito-frontal dysfunction due to the abnormal glycogen metabolism characteristic of the underlying disease. These results are consistent with the hypothesis of a central nervous system involvement in patients with GSDIII, but need to be confirmed in future research. This could explain the social and economic difficulties, and the lack of compliance to the medical follow-up presented by these patients. It suggests that these disturbances need to be taken into account when planning the medical management of patients with GSDIII. [ABSTRACT FROM AUTHOR]

While the clinical presentation of posterior cortical atrophy is clearly distinct from typical Alzheimer's disease, neuropathological studies have suggested that most patients with posterior cortical atrophy have Alzheimer's disease with an atypical visual presentation. We analysed in vivo pathophysiological markers of Alzheimer's disease such as cerebrospinal fluid biomarkers and positron emission tomography imaging with 11C-labelled Pittsburgh compound-B in posterior cortical atrophy to determine whether biochemical profile and fibrillar amyloid-β burden topography are associated with the clinical presentation. Nine patients with posterior cortical atrophy and nine with typical Alzheimer's disease individually matched for age, duration and severity of the disease and 10 cognitively normal age-matched controls were included. 11C-labelled Pittsburgh compound-B images were analysed both using volumes of interest and on a voxel-wise basis using statistical parametric mapping, taking into account the individual regional cortical atrophy. Cerebrospinal fluid biomarkers did not differ between posterior cortical atrophy and patients with Alzheimer's disease. Compared with normal controls, both posterior cortical atrophy and Alzheimer's disease groups showed increased 11C-labelled Pittsburgh compound-B uptake. No significant difference was found in regional or global 11C-labelled Pittsburgh compound-B binding between posterior cortical atrophy and Alzheimer's disease groups with both volumes of interest and voxel-wise basis using statistical parametric mapping methods. Our findings demonstrate that cerebrospinal fluid biomarkers and positron emission tomography imaging with 11C-labelled Pittsburgh compound-B may be useful in identifying an atypical visual form of Alzheimer's disease. The similar topography of fibrillar amyloid-β deposition between typical Alzheimer's disease and posterior cortical atrophy groups suggests that, although amyloid-β accumulation plays a critical role in the pathogenesis of Alzheimer's disease, other factors such as neurofibrillary tangles may contribute to the different clinical features observed in posterior cortical atrophy. [ABSTRACT FROM AUTHOR]

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). In family FSP-698, 10 affected individuals had both HSP and mental deficiency leading to social dependence in 9 and institutionalization in 5. The mean age at onset of spastic paraplegia was 11±20 years, ranging from 1 to 51 years. This phenotype segregated either with a novel p.Glu442Lys mutation or the two previously described p.Arg459Thr and p.Arg499Cys substitutions in the SPG4 gene. Since two of these mutations were previously reported in families with a pure form of the disease, another genetic factor linked to SPG4 could be responsible for this complex phenotype.European Journal of Human Genetics (2008) 16, 97–104; doi:10.1038/sj.ejhg.5201922; published online 24 October 2007 [ABSTRACT FROM AUTHOR]

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. Onset of motor difficulty signs is usually used to define age at onset. Objectives: To evaluate diagnosis delay in patients with JHD and to analyze the clinical and genetic features of JHD. Design: Retrospective clinical and genetic review. Setting: Referral center for HD at Salpetrière Hospital, Paris, France. Patients: Twenty-nine patients with HD with onset before or at age 20 years who carried an abnormal CAG repeat expansion in the HD gene. Results: The mean ± SD delay before diagnosis was 9 ± 6 years (range, 0-21 years). The most remarkable signs at onset were severe psychiatric and cognitive disturbances (19 of 29 [65.5%]); rigidity was absent. Unusual signs at onset included myoclonic head tremor in 3 patients, severe isolated drug or alcohol addiction in 2, psychotic disorder in 1, and difficulty writing in 1. One patient had progressive cerebellar signs associated with cerebellar atrophy on cerebral magnetic resonance imaging before signs suggestive of HD appeared. During the course of the disease, psychiatric disturbances were severe, with at least 1 suicide attempt in 7 of 29 patients. Transmission was maternal in 25% of patients. Forty-six percent of patients with JHD had fewer than 60 CAG repeats; 6 of these patients inherited the disease from their father. Anticipation (mean ± SD, 18 ± 9 vs 25 ± 11 years; P = .27) and age at onset (mean ± SD, 17.14 ± 2.2 vs 13.29 ± 5.5 years; P = .09) was similar in patients with maternal compared with paternal transmission, respectively. Conclusions: Patients with JHD started showing disease symptoms through nonspecific features, mostly psychiatric and cognitive difficulties. This led to misdiagnosis or diagnosis delay, especially in cases without a familial history of HD. Maternal transmissions and expansions of fewer than 60 CAG repeats were unexpectedly frequent in this series and should not be considered exceptional. [ABSTRACT FROM AUTHOR]

Background: The most frequent form of autosomal dominant hereditary spastic paraparesis is associated with the SPG4 locus, described originally as a pure form of the disease. Mutations of the SPG4 gene have been increasingly associated with reports of cognitive impairment. Objective: To investigate cognitive function in 10 families with hereditary spastic paraparesis due to mutations in the SPG4 gene, using intrafamilial control subjects. Patients and Methods: Neuropsychological examinations, including the Cambridge Cognitive Evaluation, were conducted in 29 carriers with identified SPG4 mutations and 29 intrafamilial controls. Results: Carriers were not demented but had a subclinical cognitive impairment primarily affecting executive functions. The dysfunction was more severe in those carriers older than 50 years, but was correlated with the progression of the disease, not with age. Disease progression and cognitive impairment appeared to be more severe in the carriers of missense mutations than in those with truncating mutations. Conclusion: Asymptomatic cognitive impairment mostly affecting executive functions is present in SPG4 mutation carriers and is more frequent in those with missense mutations. [ABSTRACT FROM AUTHOR]