ABSTRACT
INTRODUCTION: Mutations in presenilin-1 (PSEN1) account for the majority of cases of familial autosomal dominant early-onset Alzheimer's disease (AD) as well as in sporadic forms. Atypical presentations are reported including extrapyramidal signs. In the last years, a pleiotropic effect of some PSEN1 variants has been reported in Parkinson's disease (PD). OBJECTIVE: to report a new PSEN1 mutation characterized by early-onset Parkinsonism (EOPD) without dementia or classical AD biomarkers phenotype. PATIENT AND METHODS: An Argentinian 46 years old woman was diagnosed with EOPD at 35 years old with no family history of neurodegenerative disorders. Her medical history included iron deficiency and anemia since childhood. A brain MRI showed moderate frontal atrophy. 18FDG-PET and PiB-PET as well as CSF biomarkers were inconclusive for AD. Two neuropsychological examinations were compatible with a mild non amnestic cognitive impairment. Whole blood DNA was extracted and whole exome sequencing and analysis was performed. RESULTS AND CONCLUSION: A heterozygous novel missense PSEN1 mutation (position 14:73637540, A > T, pArg41Ser) was identified as a likely causative mutation in this patient. To the best of our knowledge, this case is the first PSEN1 mutation with a l-dopa responsive Parkinsonism lacking distinctive classical AD biomarkers. This case opens a new window to explore the pathophysiological link among PSEN1 and EOPDs and contributes to increase the phenotypes of PSEN1 variants.
Subject(s)
Brain/pathology , Mutation, Missense/genetics , Parkinsonian Disorders/genetics , Presenilin-1/genetics , Alzheimer Disease/diagnosis , Alzheimer Disease/genetics , Female , Humans , Magnetic Resonance Imaging/methods , Middle Aged , Parkinsonian Disorders/diagnosis , PhenotypeABSTRACT
BACKGROUND: Multiple system atrophy (MSA) is an adult-onset and rapidly progressive, neurodegenerative condition that presents with autonomic dysfunction, parkinsonism, cerebellar ataxia and corticospinal deficits. Clinical, demographic and epidemiological data from different regions have provided valuable information concerning the natural history of MSA. There are no published data of Multiple System Atrophy (MSA) in Latin American countries. OBJECTIVE: To describe clinical and epidemiological data of patients with "possible" MSA from seven referral movement disorders centers from Argentina, Chile, Mexico, Peru and United States. METHODS: We conducted a retrospective, observational, cross-sectional Pan-American multicentre cohort study of MSA. RESULTS: The sample was composed of 82 females and 77 men with the diagnosis of "possible" MSA with a mean age at onset of 65 ± 10 years. 67.29% of the individuals had a MSA-P variant with a mean age at onset of 61.47 ± 10.28 years, whereas the mean age at onset in the MSA-C patients was 57.44 ± 10.58 years. Interestingly, MSA-C-was more prevalent in Non-Caucasian (50-Mestizo and 2 Asian patients) than Caucasians (51.92% vs. 20.79%, p = 0.0001). Dysautonomic symptoms were present in 95.6% of the patients, parkinsonism in 85.5%, pyramidal signs in 25.8% and depression in 48.4% of the patients. CONCLUSIONS: Our epidemiological and clinical data appears to be similar to other Western international series, however, of note, the MSA-C phenotype was predominant in Non-Caucasians, more specifically the Mestizo population. This observation opens a new path to explore. Larger prospective epidemiologic studies in Latin America may provide valuable information concerning MSA in the region.
Subject(s)
Multiple System Atrophy/epidemiology , Aged , Americas/epidemiology , Cerebrum/pathology , Cognition Disorders/epidemiology , Cognition Disorders/etiology , Cohort Studies , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Multiple System Atrophy/complications , Multiple System Atrophy/diagnosisSubject(s)
Basal Ganglia/pathology , Cerebral Cortex/pathology , Complex Regional Pain Syndromes/etiology , Neurodegenerative Diseases/complications , Aged , Complex Regional Pain Syndromes/epidemiology , Female , Humans , Magnetic Resonance Imaging/methods , Male , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/epidemiology , Sex FactorsABSTRACT
El 5 por ciento de los aneurismas micóticos (AM) se ubica en el territorio carotídeo y la localización en su sector extracraneal es extremadamente rara...Se presenta un paciente con pseudoaneurisma micótico de la arteria carótida extracraneal secundario a infección parafaríngea, complicado con infarto cerebral y tratado con ligadura de vaso
Subject(s)
Humans , Adenoma , Aneurysm, False , Carotid Artery, Common/pathology , Circle of Willis , Echo-Planar Imaging , Infections/diagnosis , Neck , Pharynx , Tomography, X-Ray ComputedABSTRACT
El 5 por ciento de los aneurismas micóticos (AM) se ubica en el territorio carotídeo y la localización en su sector extracraneal es extremadamente rara...Se presenta un paciente con pseudoaneurisma micótico de la arteria carótida extracraneal secundario a infección parafaríngea, complicado con infarto cerebral y tratado con ligadura de vaso(AU)
