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2.
Ann Neurol ; 94(3): 470-485, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37243847

RESUMO

OBJECTIVE: The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcomes) across a large number of ataxias, and provide first natural history data for several of them. METHODS: Subitem-level correlation and distribution-based analysis of 1,637 SARA assessments in 884 patients with autosomal recessive/early onset ataxia (370 with 2-8 longitudinal assessments) were complemented by linear mixed effects modeling to estimate progression and sample sizes. RESULTS: Although SARA subitem responsiveness varied between ataxia severities, gait/stance showed a robust granular linear scaling across the broadest range (SARA < 25). Responsiveness was diminished by incomplete subscale use at intermediate or upper levels, nontransitions ("static periods"), and fluctuating decreases/increases. All subitems except nose-finger showed moderate-to-strong correlations to activities of daily living, indicating that metric properties-not content validity-limit SARA responsiveness. SARA captured mild-to-moderate progression in many genotypes (eg, SYNE1-ataxia: 0.55 points/yr, ataxia with oculomotor apraxia type 2: 1.14 points/yr, POLG-ataxia: 1.56 points/yr), but no change in others (autosomal recessive spastic ataxia of Charlevoix-Saguenay, COQ8A-ataxia). Whereas sensitivity to change was optimal in mild ataxia (SARA < 10), it substantially deteriorated in advanced ataxia (SARA > 25; 2.7-fold sample size). Use of a novel rank-optimized SARA without subitems finger-chase and nose-finger reduces sample sizes by 20 to 25%. INTERPRETATION: This study comprehensively characterizes COA properties and annualized changes of the SARA across and within a large number of ataxias. It suggests specific approaches for optimizing its responsiveness that might facilitate regulatory qualification and trial design. ANN NEUROL 2023;94:470-485.


Assuntos
Ataxia Cerebelar , Ataxias Espinocerebelares , Humanos , Atividades Cotidianas , Ataxia , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genética , Extremidade Superior
3.
Acta Neurol Belg ; 123(3): 823-829, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35325434

RESUMO

INTRODUCTION: The key feature that distinguishes mild cognitive impairment (MCI) from dementia is the absence of significant functional decline because of cognitive impairment. In Parkinson's disease patients (PD) with MCI (PD-MCI), the effect of cognitive impairment on complex instrumental daily activities, such as medication management, is not well established. METHOD: 26 patients with PD-MCI (diagnosed to Level 2 Movement Disorders Society diagnostic criteria) and 32 idiopathic PD patients without cognitive impairment participated in the study. A detailed neuropsychological testing battery (including tests for attention and working memory, executive functions, language, visuospatial functions, episodic memory) and various prospective memory tasks were applied to the patients. Medication taking behaviors were evaluated using two different methods based on the performance (medication management ability assessment) and self-reporting (adherence scale). RESULTS: The PD-MCI group obtained significantly lower scores in medication management assessment and made more mistakes on following prescription instructions (e.g., they took more or less tablets and did not use medications as instructed with regard to meal times). Cognitive areas predicting success in medication management performance were language, event-based prospective memory and visuospatial functions. There was no significant difference between the two groups' self-reporting of adherence. CONCLUSION: Mild cognitive impairment in patients with PD adversely affects medication management. Diagnosing MCI in PD is important to ensure that the appropriate measures can be taken to provide support and improve the medication management process. Adherence assessments based on self-reporting may not provide reliable and sensitive information in patients with PD-MCI.


Assuntos
Disfunção Cognitiva , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Conduta do Tratamento Medicamentoso , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Função Executiva , Testes Neuropsicológicos , Cooperação e Adesão ao Tratamento
4.
Dement Geriatr Cogn Disord ; 51(5): 386-395, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36273437

RESUMO

INTRODUCTION: Anticholinergic burden may be an important risk factor for the cognitive impairment. Especially in polypharmacy, even drugs with low anticholinergic effects may contribute to a significant anticholinergic burden. The drugs with anticholinergic effects are used in treatment of motor and nonmotor symptoms of Parkinson's disease (PD). Therefore, it is important to screen for polypharmacy and anticholinergic burden in PD patients with mild cognitive impairment (MCI). METHODS: This cross-sectional study was conducted with 58 patients with PD. PD-MCI was diagnosed according to MDS Level 2 Comprehensive Assessment. Cognitive performance (attention - working memory, executive functions, language, memory, and visuospatial functions) of patients was evaluated. The anticholinergic burden was scored by Anticholinergic Cognitive Burden (ACB) Scale, Anticholinergic Risk Scale (ARS), and Anticholinergic Drug Scale (ADS). RESULTS: There was no significant difference in anticholinergic burden between PD-MCI and PD-normal cognition. A significant concordance was observed between ACB, ARS, and ADS scores (p < 0.001; Kendall's W = 0.653). While the variable predicting anticholinergic burden was the total number of drugs for ACB and ADS scales, it was the number of antiparkinson drugs for ARS scale. CONCLUSION: Patients with PD are at high risk for polypharmacy and anticholinergic burden. Anticholinergic burden should be considered in the selection of drugs, especially for comorbidities in patients with PD. No significant correlation was found between the cognition and anticholinergic burden in patients with PD-MCI. Although the risk scores of antiparkinson and other drugs were different among the 3 scales, significant concordance was observed between scales.


Assuntos
Disfunção Cognitiva , Doença de Parkinson , Humanos , Antagonistas Colinérgicos/efeitos adversos , Estudos Transversais , Polimedicação , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Cognição
5.
Neurosci Lett ; 786: 136799, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35842208

RESUMO

Alzheimer's Disease (AD) is a neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. However, increasing evidence suggests that the pathogenesis of the disease is associated with peripheral inflammation. Here, we aimed to determine plasma concentrations of multiple cytokines and chemokines from moderate-stage AD and age-matched controls. Changes in a total of 20 cytokines and chemokines in plasma of moderate-stage AD were evaluated by using quantitative microarray. Six of them, namely MCP-1, MIP-1a, MIP-1b, MMP-9, RANTES, and VEGF, were found to be significantly reduced in moderate-stage AD patients (n = 25) in comparison to age-matched and non-demented controls (n = 25). However, GM-CSF, GRO-α/ß/γ, IFN- γ, IL-1α, IL-1ß, IL-10, IL-12 p70, IL-13, IL-2, IL- 4, IL-5, IL-6, IL-8, and TNF-α showed no significant differences between the patient and control groups. On the contrary to previous early-stage AD studies that show increased plasma cytokine/chemokine levels, our results indicate that inflammatory plasma molecules are reduced in moderate-stage AD. This finding points out the reduced immune responsiveness, which is known to be directly correlated to the degree of AD.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Alzheimer/patologia , Quimiocinas , Citocinas , Humanos , Imunidade
6.
Parkinsonism Relat Disord ; 93: 35-39, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34781237

RESUMO

INTRODUCTION: The majority of Parkinson's disease (PD) ensue late-onset with a complex spectrum of environmental and genetic risk factors. Awareness of genetic causes in patients with PD is essential for genetic counseling and future genotype-oriented therapeutic developments. METHODS: Large pathogenic changes in eight PD-related genes and small pathogenic sequence variants in 22 PD-related genes were investigated simultaneously in 82 PD patients from 79 families where clinical evaluations were performed. The phenotypic characteristics of the patients with molecular changes were examined for genotype-phenotype relations. RESULTS: Pathogenic variants in SNCA, PRKN, DJ-1, FBXO7, and GBA genes were determined in 25 patients from 24 families (24/79, 30%). Associated variants were found in PRKN in 14, SNCA in three, FBXO7 in two, and DJ-1 in one patient. A novel homozygous deletion (c.491delT, p.(V164Dfs*13) (SCV001733595)) leading to protein truncation in the PRKN gene was identified in two patients from the same family. Furthermore, heterozygous GBA gene variants were detected in five patients from different families. CONCLUSION: It has been shown that the most common cause of genetically transmitted PD is the PRKN gene, while LRRK2 does not play an essential role in this selected population. It has been suggested that even if the autosomal recessive inheritance is expected, genes with autosomal dominant effects such as SNCA should not be overlooked and suggested for investigation. Our study is also the first for evaluating the pathogenic GBA variants' frequency in PD patients from Turkey.


Assuntos
Predisposição Genética para Doença/genética , Doença de Parkinson/genética , Adulto , Proteínas F-Box , Feminino , Variação Genética , Genótipo , Glucosilceramidase , Heterozigoto , Homozigoto , Humanos , Masculino , Linhagem , Fenótipo , Proteína Desglicase DJ-1 , Deleção de Sequência , Turquia , Ubiquitina-Proteína Ligases , alfa-Sinucleína
7.
Noro Psikiyatr Ars ; 58(3): 253-254, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526851

RESUMO

Hiccup is described as the sudden involuntary contraction of the diaphragm, and the intercostal muscles followed by the immediate closure of the glottis. Corticosteroids, benzodiazepines, and antibiotics may cause drug-induced hiccups. Dopamine agonist-induced hiccups were reported in patients diagnosed with Parkinson's Disease (PD) in small number of cases. Here we report a patient diagnosed with PD who had severe hiccups with the use of two dopamine agonists in treatment, however hiccup was not reported with the use of Levodopa. This information may help to manage the treatment of PD, and avoid the unnecessary diagnostic procedures.

8.
Front Neurol ; 12: 677551, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248822

RESUMO

Autosomal recessive cerebellar ataxias (ARCAs) form an ultrarare yet expanding group of neurodegenerative multisystemic diseases affecting the cerebellum and other neurological or non-neurological systems. With the advent of targeted therapies for ARCAs, disease registries have become a precious source of real-world quantitative and qualitative data complementing knowledge from preclinical studies and clinical trials. Here, we review the ARCA Registry, a global collaborative multicenter platform (>15 countries, >30 sites) with the overarching goal to advance trial readiness in ARCAs. It presents a good clinical practice (GCP)- and general data protection regulation (GDPR)-compliant professional-reported registry for multicenter web-based capture of cross-center standardized longitudinal data. Modular electronic case report forms (eCRFs) with core, extended, and optional datasets allow data capture tailored to the participating site's variable interests and resources. The eCRFs cover all key data elements required by regulatory authorities [European Medicines Agency (EMA)] and the European Rare Disease (ERD) platform. They capture genotype, phenotype, and progression and include demographic data, biomarkers, comorbidity, medication, magnetic resonance imaging (MRI), and longitudinal clinician- or patient-reported ratings of ataxia severity, non-ataxia features, disease stage, activities of daily living, and (mental) health status. Moreover, they are aligned to major autosomal-dominant spinocerebellar ataxia (SCA) and sporadic ataxia (SPORTAX) registries in the field, thus allowing for joint and comparative analyses not only across ARCAs but also with SCAs and sporadic ataxias. The registry is at the core of a systematic multi-component ARCA database cluster with a linked biobank and an evolving study database for digital outcome measures. Currently, the registry contains more than 800 patients with almost 1,500 visits representing all ages and disease stages; 65% of patients with established genetic diagnoses capture all the main ARCA genes, and 35% with unsolved diagnoses are targets for advanced next-generation sequencing. The ARCA Registry serves as the backbone of many major European and transatlantic consortia, such as PREPARE, PROSPAX, and the Ataxia Global Initiative, with additional data input from SPORTAX. It has thus become the largest global trial-readiness registry in the ARCA field.

9.
Eur J Neurol ; 28(8): 2603-2613, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33969597

RESUMO

BACKGROUND AND PURPOSE: Nasu-Hakola disease (NHD) is a rare, autosomal recessive disorder characterized by skeletal and neurological symptoms. Behavioral symptoms with cognitive impairment may mimic the behavioral variant of frontotemporal dementia (bvFTD) and other early-onset dementias. Our patients were analyzed and the literature was reviewed to delineate neurological and neuroimaging findings suggestive of NHD. METHOD: Fourteen patients carrying a pathogenic mutation in the TREM2 gene were found in our database. Demographic, clinical, laboratory and radiological data were retrieved and analyzed. RESULTS: The presenting clinical picture was behavioral changes with cognitive decline resembling bvFTD in all patients. The mean age was 37.1 ± 4.97 years and the mean duration of the disease was 8.9 ± 3.51 years. Only two patients had typical bone cysts. Seven patients had bilateral calcification of the basal ganglia in computed tomography of the brain. Magnetic resonance imaging of the brain revealed severe atrophy of the corpus callosum, enlargement of the ventricles, atrophy of the caudate nuclei and periventricular white matter changes in all patients. Symmetrical global atrophy of the brain mainly affecting frontoparietal and lateral temporal regions were observed in all cases, and 13 patients had atrophy of the hippocampus. Cerebrospinal fluid examination of 10 patients showed elevated protein levels in six and the presence of oligoclonal bands in four patients. CONCLUSION: A combination of white matter changes, enlarged ventricles, atrophy of the caudate nuclei and thinning of the corpus callosum in magnetic resonance imaging strongly suggests NHD in patients with FTD syndrome. Molecular genetic analysis should be performed in suspected cases, and families should receive genetic counseling.


Assuntos
Demência Frontotemporal , Lipodistrofia , Glicoproteínas de Membrana/genética , Osteocondrodisplasias , Receptores Imunológicos/genética , Panencefalite Esclerosante Subaguda , Adulto , Encéfalo/diagnóstico por imagem , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/genética , Humanos , Imageamento por Ressonância Magnética , Neuroimagem
10.
Neurol Sci ; 42(7): 2969-2973, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33559790

RESUMO

Loss-of-function mutations in the sacsin (SACS) gene lead to autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), impairing the function of sacsin. Genotype-phenotype correlations are still unclear for the different mutations reported in ARSACS. Here, we present a Turkish ARSACS family in whom the novel homozygous frameshift mutation in SACS c.12461delC (p.Pro4154GlnfsTer20) was detected by next-generation sequencing (NGS). The index patient was admitted with progressive spastic ataxia and dysarthria. Since no common mutation in autosomal recessive (AR) cerebellar ataxias, whole gene sequencing provide an advantage to detect novel mutations and may be more effective for clinical diagnosis.


Assuntos
Proteínas de Choque Térmico/genética , Ataxias Espinocerebelares , Humanos , Espasticidade Muscular/genética , Mutação , Ataxias Espinocerebelares/congênito , Ataxias Espinocerebelares/genética
11.
Neurol Sci ; 42(9): 3829-3834, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33474589

RESUMO

Wilson's disease (WD) is an autosomal recessive genetic disorder of copper metabolism, and WD patients can present with neurologic symptoms. We aimed to report the general characteristics and prognosis of a Turkish series of WD patients with neurological manifestations. A total of 12,352 patients were screened from the patient database, and 53 WD patients were included. Patients were classified based on the predominant neurological syndrome type including tremor, dystonia, parkinsonism, or discrete neurological signs and were classified as having "good outcome," "stable," and "poor outcome" according to their treatment response. There were 32 male and 21 female patients, aged 20-66 years. The mean follow-up was 11.3 ± 4.56 years. Sixty-two percent of patients presented predominantly with neurological symptoms. Neurological WD diagnosis was established after a mean time delay of 2.3 years from the WD diagnosis. The most common neurological manifestation was dystonia, followed by tremor and parkinsonism. Fifteen patients had a family history of WD. Consanguinity was present in 20 patients. Patients were treated with D-penicillamine, trientine, zinc salts, or their combinations. Besides the main treatments, 41 patients were on symptomatic treatment for neurologic symptoms. Thirty-six patients had a "good outcome," five patients were stable, and six patients had "poor outcome." Post-chelation neurological worsening was observed in 11 patients. WD should be considered in differential diagnosis in any patient with unexplained neurologic symptoms. Early diagnosis is important, and appropriate treatment should be promptly initiated to prevent progressive and irreversible damage, with good prognosis and stable disease in the majority of the patients with treatment compliance.


Assuntos
Distonia , Degeneração Hepatolenticular , Cobre , Distonia/diagnóstico , Distonia/epidemiologia , Distonia/etiologia , Feminino , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/tratamento farmacológico , Degeneração Hepatolenticular/epidemiologia , Humanos , Masculino , Penicilamina/uso terapêutico , Tremor/diagnóstico , Tremor/epidemiologia , Tremor/etiologia
12.
Neurol Sci ; 42(4): 1535-1539, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33210227

RESUMO

Autosomal recessive cerebellar ataxias are a group of rare neurological diseases with a genetic origin. Recently, the mutations in the PNPLA6 gene were suggested to lead to ataxia and also to other specific syndromes such as Boucher-Neuhauser (ataxia, hypogonadism, and chorioretinal dystrophy) or Gordon-Holmes Syndromes (ataxia, hypogonadism, and brisk reflexes) within a broad spectrum of neurodegenerative diseases. Here we report three patients from a single-family with a novel pathogenic mutation in the PNPLA6 gene which led to predominantly spastic-ataxia, and intractable Holmes tremor. The PNPLA6-related disease should be considered in the differential diagnosis of spastic-ataxias even in the absence of chorioretinal dystrophy, and hypogonadotropic hypogonadism. Further studies should unravel the factors which account for the phenotypic variability present in patients with PNPLA6 gene mutations.


Assuntos
Espasticidade Muscular , Fosfolipases/genética , Ataxia , Humanos , Hipogonadismo , Deficiência Intelectual , Mutação , Atrofia Óptica , Ataxias Espinocerebelares , Tremor/genética
13.
Parkinsonism Relat Disord ; 66: 228-231, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31431325

RESUMO

OBJECTIVE: Recessive mutations in the Gap Junction Protein Gamma 2 (GJC2) gene cause Pelizaeus-Merzbacher-like disease type 1, a severe infantile-onset hypomyelinating leukodystrophy. Milder, late-onset phenotypes including complicated spastic paraplegia in one family (SPG44), and mild tremor in one case, were reported associated to GJC2 homozygous missense mutations. Here, we report a new family with two siblings carrying a different homozygous GJC2 mutation, presenting with late-onset ataxic and pyramidal disturbances, and parkinsonism in one of them. METHODS: Two affected siblings were studied by neurological examination and brain MRI. Genetic analyses included genome-wide homozygosity mapping in both siblings, and whole exome sequencing in one sib. The resulting candidate gene variant was validated by Sanger sequencing. RESULTS: The affected siblings share a novel homozygous GJC2 missense mutation (c.820G>C, p.Val274Leu), predicted as pathogenic by all used in-silico tools. Brain MRI showed hyperintense signal in T2-weighted images in the internal capsule and subcortical and periventricular white matter, consistent with hypomyelination. CONCLUSIONS: Our findings confirm and further expand the late-onset phenotypes of GJC2 mutations, to include prominent ataxia, pyramidal disturbances and mild parkinsonism, and confirm the distinctive associated MRI pattern.


Assuntos
Ataxia/genética , Conexinas/genética , Transtornos Parkinsonianos/genética , Substância Branca/patologia , Idade de Início , Idoso , Ataxia/patologia , Ataxia/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/fisiopatologia , Linhagem , Fenótipo , Irmãos , Turquia , Substância Branca/diagnóstico por imagem
14.
Neurodegener Dis ; 19(5-6): 218-224, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32349000

RESUMO

OBJECTIVES: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive inborn lipid storage disorder due to various pathogenic mutations in the CYP27A1 gene. Although the symptoms begin commonly in infancy, CTX diagnosis is often delayed. In this study, we report 7 Turkish CTX patients who had a delayed diagnosis despite early clinical signs and belonged to 6 unrelated families. METHODS: We have retrospectively evaluated clinical, laboratory, imaging, and genetic findings of CTX patients, which were collected from 2 centers specialized in movement disorders: the Department of Neurology, Faculty of Medicine, Istanbul University, and the Department of Neurology, Faculty of Medicine, Mersin University. RESULTS: All patients were diagnosed with CTX after neurological symptom development, and their mean age at diagnosis was 38.7 ± 9.6 years, despite a mean onset age of 12.4 ± 10.6 years. The mean follow-up period was 28 months (range: 3-60 months). The most common initial clinical abnormalities in our cohort were unexplained chronic diarrhea (42%), febrile convulsion (42%), juvenile cataract (85%), childhood depression and autism (14%), parkinsonism (14%), and intellectual disability (100%). The most prominent neurological findings were the pyramidal-cerebellar syndrome (85%) and extrapyramidal signs (42%). All patients were genetically confirmed. Serum cholestanol levels were elevated in all patients and decreased after chenodeoxycholic acid (CDCA) treatment in 6 patients. CONCLUSION: This cohort is the largest CTX case series in Turkey. All cases showed improvement in gastrointestinal symptoms as a response to CDCA treatment and stabilization on neurological symptoms, i.e., no further progression of neurological abnormalities were noted during this treatment. Therefore, early diagnosis and treatment is crucial in preventing clinical deterioration.


Assuntos
Xantomatose Cerebrotendinosa/diagnóstico , Adulto , Encéfalo/diagnóstico por imagem , Ácido Quenodesoxicólico/uso terapêutico , Colestanotriol 26-Mono-Oxigenase/genética , Diagnóstico Tardio , Progressão da Doença , Feminino , Seguimentos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Masculino , Estudos Retrospectivos , Xantomatose Cerebrotendinosa/tratamento farmacológico , Xantomatose Cerebrotendinosa/genética , Xantomatose Cerebrotendinosa/fisiopatologia
15.
Parkinsonism Relat Disord ; 39: 64-70, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28347615

RESUMO

INTRODUCTION: Mutations in the C19orf12 gene cause mitochondrial membrane protein associated neurodegeneration (MPAN), an autosomal recessive form of neurodegeneration with brain iron accumulation (NBIA). A limited number of patients with C19orf12 mutations, particularly those with adult onset of symptoms, have been reported. METHODS: We sequenced the entire coding region of C19orf12 in 15 Turkish adult probands with idiopathic NBIA. We also performed haplotype analysis in families with a recurrent C19orf12 mutation. Clinical features were collected using a standardized form. RESULTS: Nine of our 15 probands (60%) carried the homozygous c.32C > T mutation in C19orf12 (predicted protein effect: p.Thr11Met). This homozygous mutation co-segregated with the disease in all affected relatives available for testing (16 homozygous subjects). Haplotypes across the C19orf12 locus were identical for a very small region, closest to the mutation, suggesting an old founder, or, two independent founders. The clinical phenotype was characterized by adult onset in most cases (mean 24.5 years, range 10-36), and broad spectrum, including prominent parkinsonism, pyramidal signs, psychiatric disturbances, cognitive decline, and motor axonal neuropathy, in various combinations. On T2- or susceptibility weighted-MRI images, all patients displayed bilateral hypointensities in globus pallidus and substantia nigra, without an eye-of-the-tiger sign; however, hyperintense streaking of the medial medullary lamina between the external and internal parts of globus pallidus was observed frequently. CONCLUSION: The C19orf12 p.Thr11Met mutation is frequent among adult Turkish patients with MPAN. These findings contribute to the characterization of this important NBIA form, and have direct implications for genetic testing of patients of Turkish origin.


Assuntos
Predisposição Genética para Doença/genética , Proteínas Mitocondriais/genética , Mutação/genética , Doenças Neurodegenerativas/genética , Adolescente , Adulto , Criança , Análise Mutacional de DNA , Saúde da Família , Feminino , Haplótipos , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Metionina/genética , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/diagnóstico por imagem , Treonina/genética , Turquia , Adulto Jovem
16.
J Neurol Sci ; 374: 26-31, 2017 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-28088312

RESUMO

Dementia can occur in a substantial number of patients with Parkinson's disease with a point prevalence close to 30%. The cognitive profile is characterized by predominant deficits in executive, visuospatial functions, attention and memory. Behavioral symptoms are frequent such as apathy, visual hallucinations and delusions. The most prominent associated pathology is Lewy body-type and biochemical deficit is cholinergic. Placebo-controlled randomized trials with cholinesterase inhibitors demonstrated modest but significant benefits in cognition, behavioral symptoms and global functions.


Assuntos
Demência/complicações , Doença de Parkinson/complicações , Inibidores da Colinesterase/uso terapêutico , Demência/tratamento farmacológico , Demência/epidemiologia , Demência/patologia , Humanos , Doença de Parkinson/epidemiologia
17.
Parkinsonism Relat Disord ; 29: 117-20, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26972524

RESUMO

OBJECTIVE: DJ1 mutations (PARK7) are among the monogenic causes of early-onset autosomal recessive parkinsonism. Here, we report clinical and genetic findings in a family with Turkish origin carrying a new DJ1 mutation and presenting with early-onset levodopa responsive parkinsonism and signs of amyotrophic lateral sclerosis (ALS). METHODS: The family consisted of 12 members including 10 offsprings of whom three were affected. All family members underwent detailed clinical examination. DNA samples from the index case, his unaffected sister, and his parents were subjected to whole genome sequencing analysis. RESULTS: The index case 38-year-old man developed left hand tremor at the age of 24 years. He had progressive asymmetrical parkinsonism, depression and developed signs of ALS within 4 years. His two affected sisters had young-onset asymmetrical tremor-dominant parkinsonism with signs of ALS. A new homozygous p.Q45X mutation in exon 3 in DJ1 was found in all three patients. Their unaffected parents and one clinically healthy sibling were found to be heterozygous for this mutation. CONCLUSIONS: This is the second report of DJ1 mutations associated with parkinsonism and ALS. This is relevant for genetic counseling as well as for understanding the pathogenesis of the broad spectrum of parkinsonism-ALS disease complex.


Assuntos
Esclerose Lateral Amiotrófica/genética , Saúde da Família , Mutação/genética , Doença de Parkinson/genética , Proteína Desglicase DJ-1/genética , Adulto , Esclerose Lateral Amiotrófica/complicações , Biologia Computacional , Consanguinidade , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Doença de Parkinson/complicações , Índice de Gravidade de Doença , Turquia
18.
Tumori ; 102(Suppl. 2)2016 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-26481863

RESUMO

PURPOSE: N-methyl-D-aspartate receptor (NMDAR) encephalitis may present as a paraneoplastic syndrome in young women and is often associated with ovarian teratoma. METHODS: We report 2 male cases of NMDAR encephalitis presenting with metastatic cancer of unknown primary origin. RESULTS: Both patients showed cognitive dysfunction as well as other neurological symptoms, slow waves on EEG, and NMDAR antibodies in sera and CSF. Symptoms were effectively treated by pulse steroid and intravenous immunoglobulin treatment. The patients developed metastatic small cell neuroendocrine carcinoma of the parotid gland and inguinal metastatic squamous cell cancer shortly after their neurological episodes. Follow-up PET studies showed small cell lung cancer in the first patient while no primary origin could be found in the second patient. CONLUSIONS: Our cases imply that NMDAR encephalitis may present with metastatic cancers that display slow progression rates and occur after encephalitis attacks.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Neoplasias Primárias Desconhecidas/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Encefalite Antirreceptor de N-Metil-D-Aspartato/cirurgia , Autoanticorpos/líquido cefalorraquidiano , Biópsia , Terapia Combinada , Diagnóstico por Imagem , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Neoplasias Primárias Desconhecidas/cirurgia , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento
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