PurposeDrug resistance is a critical issue in the treatment of epilepsy, contributing to clinical emergencies and increasing both serious social and economic burdens on the health system. The wide variety of potential drug combinations followed by often failed consecutive attempts to match drugs to an individual patient may mean that this treatment stage may last for years with suboptimal benefit to the patient. Given these challenges, it is valuable to explore the availability of new methodologies able to shorten the period of determining a rationale pharmacologic treatment. Metabolomics could provide such a tool to investigate possible markers of drug resistance in subjects with epilepsy.MethodsBlood samples were collected from (1) controls (C) (n = 35), (2) patients with epilepsy “responder” (R) (n = 18), and (3) patients with epilepsy “non-responder” (NR) (n = 17) to the drug therapy. The samples were analyzed using nuclear magnetic resonance spectroscopy, followed by multivariate statistical analysis.Key findingsA different metabolic profile based on metabolomics analysis of the serum was observed between C and patients with epilepsy and also between R and NR patients. It was possible to identify the discriminant metabolites for the three classes under investigation. Serum from patients with epilepsy were characterized by increased levels of 3-OH-butyrate, 2-OH-valerate, 2-OH-butyrate, acetoacetate, acetone, acetate, choline, alanine, glutamate, scyllo-inositol (C < R < NR), and decreased concentration of glucose, lactate, and citrate compared to C (C > R > NR).SignificanceIn conclusion, metabolomics may represent an important tool for discovery of differences between subjects affected by epilepsy responding or resistant to therapies and for the study of its pathophysiology, optimizing the therapeutic resources and the quality of life of patients.
Posterior cortical atrophy (PCA) represents a degenerative disorder characterized by the development of higherorder visual deficit. 1 PCA may result from heterogeneous pathologies that make up tauopathies. An increasing number of mutations in the tau gene (microtubule-associated protein tau [MAPT]) causes a wide spectrum of clinical presentations known as frontotemporal dementia with parkinsonism linked to chromosome-17 (FTDP-17). 2 Symptomatology usually involves executive dysfunction and altered personality and behavior, with patients displaying parkinsonian features.We describe the case of a woman with PCA who further developed asymmetric motor signs. A mutation in the MAPT gene was detected, and a diagnosis of FTDP-17 was formulated. To our knowledge, this is the very first report of a patient suffering from FTDP-17 diagnosed with posterior cortical atrophy.
Case ReportA 55-year-old woman started suffering in 2006 from altered perception of human faces. Initially the visual distortion was fluctuating; over the following year it became constant, and she could not recognize her husband and children by their faces anymore. She further developed visuospatial deficits, with difficulty in localizing stimuli, judging distances, or orienting herself in familiar surroundings. A first neurological examination revealed visual agnosia. She had no visual hallucinations or personality changes. Biochemical investigations and CSF analysis were normal. Her mother suffered from dementia that started when she was 80. Genetic tests for Alzheimer's disease genes (betaPP, PS1, PS2) were performed, revealing normal alleles.As the disease progressed, she developed difficulties manipulating objects with her left hand. On further neurological examination, she showed marked ocular apraxia, and she appeared to be cortically blind. Motor signs appeared and were confined to her left arm, with plastic rigidity, bradykinesia, and postural tremor; dopaminergic treatment was not tolerated.Brain magnetic resonance imaging (MRI) showed slight signal alteration in parieto-occipital white matter bilaterally without significant atrophy; an 18F-FDG PET brain study demonstrated decreased metabolism in the posterior parietal and occipital regions, compatible with PCA. To investigate
References1. Depakote (divalproex sodium): http://www.rxabbott.com/pdf/ depakote.pdf 2. Sandson NB, Marcucci C, Bourke DL, Smith-Lamacchia R: An interaction between aspirin and valproate: the relevance of plasma protein displacement drug-drug interactions. Am
Background
Based on our previous finding of the p.A382T founder mutation in ALS patients with concomitant parkinsonism in the Sardinian population, we hypothesized that the same variant may underlie PD and/or other forms of degenerative parkinsonism on this Mediterranean island.
Design
We screened a cohort of 611 patients with PD (544 cases) and other forms of degenerative parkinsonism (67 cases), and 604 unrelated controls for the c.1144G>A (p.A382T) missense mutation of the TARDBP gene.
Results
The p.A382T mutation was identified in 9 patients with parkinsonism. Of these, 5 (0.9% of PD patients) presented a typical PD (2 with familiar forms), while 4 patients (6.0% of all other forms of parkinsonism) presented a peculiar clinical presentation quite different from classical atypical parkinsonism with an overlap of extrapyramidal-pyramidal-cognitive clinical signs. The mutation was found in 8 Sardinian controls (1.3%) consistent with a founder mutation in the island population.
Conclusions
Our findings suggest that the clinical presentation of the p.A382T TARDBP gene mutation may include forms of parkinsonism in which the extrapyramidal signs are the crucial core of the disease at onset. These forms can present PSP or CBD-like clinical signs, with bulbar and/or extrabulbar pyramidal signs and cognitive impairment. No evidence of association has been found between TARDBP gene mutation and typical PD.
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