POLG2 deficiency causes adult-onset syndromic sensory neuropathy, ataxia and parkinsonism

Objective: Mitochondrial dysfunction plays a key role in the pathophysiology of neurodegenerative disorders such as ataxia and Parkinson's disease. We describe an extended Belgian pedigree where seven individuals presented with adult-onset cerebellar ataxia, axonal peripheral ataxic neuropathy, and tremor, in variable combination with parkinsonism, seizures, cognitive decline, and ophthalmoplegia. We sought to identify the underlying molecular etiology and characterize the mitochondrial pathophysiology of this neurological syndrome. Methods: Clinical, neurophysiological, and neuroradiological evaluations were conducted. Patient muscle and cultured fibroblasts underwent extensive analyses to assess mitochondrial function. Genetic studies including genome-wide sequencing were conducted. Results: Hallmarks of mitochondrial dysfunction were present in patients' tissues including ultrastructural anomalies of mitochondria, mosaic cytochrome c oxidase deficiency, and multiple mtDNA deletions. We identified a splice acceptor variant in POLG2, c.970-1G>C, segregating with disease in this family and associated with a concomitant decrease in levels of POLG2 protein in patient cells. Interpretation: This work extends the clinical spectrum of POLG2 deficiency to include an overwhelming, adult-onset neurological syndrome that includes cerebellar syndrome, peripheral neuropathy, tremor, and parkinsonism. We therefore suggest to include POLG2 sequencing in the evaluation of ataxia and sensory neuropathy in adults, especially when it is accompanied by tremor or parkinsonism with white matter disease. The demonstration that deletions of mtDNA resulting from autosomal-dominant POLG2 variant lead to a monogenic neurodegenerative multicomponent syndrome provides further evidence for a major role of mitochondrial dysfunction in the pathomechanism of nonsyndromic forms of the component neurodegenerative disorders

Pengaruh Brand Trust dan Brand Equity terhadap Loyalitas Konsumen pada Produk Kosmetik Wardah (Survey Konsumen pada PT. Paragon Technology And Innovation Cabang Pekanbaru)

The purpose of this study was to determine the influence of brand trust ( X1 ) and brand equity ( X2 ) customer loyalty ( Y ) in cosmetic products Wardah ( consumer survey on PT . Paragon technology and innovation branches pekanbaru ) . The method in this research is quantitatively using SPSS 21 program , where samples were used that consumers using cosmetic products Wardah by respondents as many as 100 people sampling technique is accidental sampling using the formula slovin . The results showed that the test results simultaneously obtained from the F count was 34.888 while the value of F table 3.090 . This means that F count> F table and significant value 0,000 < alpha of 0.05 . This means that brand trust and brand equity simultaneously significant effect on consumer loyalty to cosmetic products Wardah

Le traitement médicamenteux des symptômes moteurs de la maladie de Parkinson

Cet article présente les différentes classes pharmacologiques et les stratégies thérapeutiques aux différents stades de la maladie de Parkinson. Le traitement actuel est uniquement symptomatique. La lévodopa reste le traitement le plus efficace avec la balance bénéfice/risque la plus avantageuse. Elle constitue le traitement de premier choix pour la plupart des patients. Afin de retarder l’apparition de complications motrices comme les dyskinésies ou l’akinésie de fin de dose, les agonistes dopaminergiques ou les inhibiteurs de la monoamine oxydase de type B peuvent être envisagés en première intention chez les patients jeunes avec une forme peu invalidante de la maladie. Les fluctuations motrices peuvent être améliorées en adaptant le nombre de prise de lévodopa ou en y associant un agoniste dopaminergique, un inhibiteur de la monoamine oxydase ou un inhibiteur de la catéchol-O-méthyl transférase. Les dyskinésies invalidantes justifient parfois une réduction du traitement dopaminergique ou l’usage de l’amantadine. Les patients présentant des complications motrices sévères peuvent bénéficier d’un traitement par Duodopa ou apomorphine sous-cutanée.[Pharmacological treatment of motor symptoms of Parkinson's disease] This article presents the different pharmacological classes and therapeutic strategies employed at the different stages of Parkinson's disease. To date, only symptomatic treatments exist. Levodopa remains the most effective treatment with the best benefit-risk ratio. It is the initial treatment of choice for most patients. In order to delay the onset of motor complications, such as dyskinesia or end-of-dose akinesia, dopamine agonists or monoamine oxidase B inhibitors may be proposed as first-line treatment to young patients with mild disability. Motor fluctuations can be improved by adjusting the levodopa dosing frequency or by adding a dopamine agonist, monoamine oxidase inhibitor, or catechol-Omethyltransferase inhibitor. Disabling dyskinesias can be improved by reducing the levodopa dose or using amantadine. Patients with severe motor complications may benefit from a treatment with Duodopa® or subcutaneous apomorphine

Gérer les maladies ; consommateurs et engagements: Le cas des producteurs de pommes et de poires de la Basse Meuse

The authors analyse the construction of a seed fruit market. The conventional market had led to the 'anonymousness' of the fruit and to disconnected temporalities. The process needs new types of coordination and components within the common information channels and actors' network. It also needs the construction of a new contract between producers and consumers, that the conventional market is unable to allow. Producers are experimenting with direct contact with the final consumer to find ways of allowing it. The fruit is replaced in the subject's experience of the final consumer and in the grower's story. The grower's story deals with managing pests, consumers, and commitments through a harmless action: eating a pear or an apple

Managing pests, consumers, and commitments: the case of apple growers and pear growers in Belgium's Lower Meuse region

The authors analyse the construction of a seed fruit market. The conventional market had led to the 'anonymousness' of the fruit and to disconnected temporalities. The process needs new types of coordination and components within the common information channels and actors' network. It also needs the construction of a new contract between producers and consumers, that the conventional market is unable to allow. Producers are experimenting with direct contact with the final consumer to find ways of allowing it. The fruit is replaced in the subject's experience of the final consumer and in the grower's story. The grower's story deals with managing pests, consumers, and commitments through a harmless action: eating a pear or an apple.

Etude de l'impact d'une gastroplastie sur l'image de soi, au moyen du Rorschach

peer reviewe

Symptoms of depression and anxiety after the disclosure of the diagnosis of Alzheimer disease.

Many people fear that the disclosure of the diagnosis of Alzheimer disease (AD) to patients will prompt depressive symptoms or catastrophic reactions. We aimed to prospectively evaluate the modification of anxiety and depressive symptoms 3 months after the disclosure of the diagnosis of AD

Validity of the five-word test for the evaluation of verbal episodic memory and dementia in a memory clinic setting.

BACKGROUND: The five-word test (FWT) uses semantic clues to optimize the encoding and retrieval of 5 items. Our objective was to assess the validity of the FWT as a measure of episodic memory when compared with the Free and Cued Selective Reminding Test (FCSRT), and its ability to distinguish participants with any dementia and especially Alzheimer disease (AD) from those with only subjective complaints. METHODS: Two hundred participants with Mini-Mental State Examination (MMSE) >15 were prospectively evaluated. The sum of the immediate and delayed free recalls of the FWT is called the free recall score (FRS). The sum of the immediate free, immediate cued, delayed free, and delayed cued recalls is called the total recall score (TRS). A total weighted score (TWS) is calculated using this formula: (free recalls × 2) + cued recalls. RESULTS: The correlation between FRS and the free recall scores of the FCSRT and between TRS and the total recall scores of the FCSRT was significant (r (s) ranges from .74-.84, P < .001). Area under the receiver--operating characteristic (ROC) curves of the MMSE, FRS, TRS, and TWS were not statistically different. A TWS at a cutoff value ≤15 could discriminate any dementia from subjective complaints with a sensitivity of 75% and a specificity of 95.9% or AD from subjective complaints with a sensitivity of 90.2% and a specificity of 95.9%. CONCLUSION: The FWT is a valid test of verbal episodic memory. It is useful to discriminate dementia especially AD from isolated subjective complaints

Syndrome MELAS (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes) de révélation tardive

Le syndrome MELAS (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes) est peu fréquent et caractérisé principalement par des accidents vasculaires cérébraux précoces, des crises d'épilepsie et des céphalées d'allure migraineuse. Les premiers symptômes apparaissent le plus fréquemment avant l'âge de 20 ans. Nous rapportons un cas de MELAS diagnostiqué chez une patiente âgée de 49 ans suite à deux épisodes aigus évocateurs d'accidents vasculaires cérébraux. Le syndrome MELAS ne doit pas être omis dans le diagnostic différentiel des accidents vasculaires cérébraux ischémiques chez des adultes d'âge moyen. Les principaux indices permettant d'évoquer le diagnostic sont les particularités de l'IRM cérébrale par rapport à un AVC ischémique classique, l'anamnèse familiale et un taux élevé de lactate dans le sang et dans le liquide céphalo-rachidien. La confirmation définitive du diagnostic de MELAS est apportée par les analyses génétiques à la recherche de mutations de l'ADN mitochondrial. Un traitement par L-arginine peut être utile. Un conseil génétique devrait être proposé