Phenotypical variability in an Argentinian family, with history of frontotemporal lobar degeneration, caused by a mutation in the microtubule-associated protein tau 

Emilia M. Gatto a,b; Ricardo F. Allegri c,i,j; Gustavo Da Prat b; Patricio Chrem Méndez c David S. Hanna d,e; Michael O. Dorschner d,e; Ezequiel I. Surace f i; Ignacio F. Mata g,h 

a Departamento de trastornos del movimiento, Fundación INEBA, Buenos Aires, Argentina. b Sanatorio de la Trinidad Mitre, Buenos Aires, Argentina. c Centro de la memoria y el envejecimiento, Instituto de Investigaciones Neurológicas Dr. Raúl Carrea (FLENI), Buenos Aires, Argentina. d Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, USA. e Department of Pathology, University of Washington, Seattle, USA f Laboratorio de Biología Molecular, Instituto de Investigaciones Neurológicas Dr. Raúl Carrea (FLENI), Buenos Aires, Argentina g Veterans Affairs Puget Sound Health Care System, Seattle, USA h Department of Neurology University of Washington, Seattle, WA USA i Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina j Universidad de la Costa (CUC), Colombia

OBJECTIVES:

To describe the first Argentinian family of Basque ancestry, with MAPT gene (p.P301L) mutation and intrafamilial phenotypical variability (Corticobasal Syndrome and Fronto Temporal Dementia).

BACKGROUND:

BackgroundbvFTD is a genetic disorder related with frontotemporal dementia (FTD), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Gene mutations involving the microtubule-associated protein tau, progranulin and C9orf72 are related

METHODS

The pedigree consists of 26 family members over 6 generations presenting with a history of autosomal dominant bvFTD (previously mentioned as Pick disease). Two different phenotypes were identified among affected members in the living generation, CBS in the proband and FTD in one of his siblings. We performed neurological examination, neuropsychological tests and neuroimaging in 5 individuals. A whole-exome sequencing (WES) was conducted in 5 individuals (Proband, 3 brothers and a cousin). A Sanger sequence was performed to identify candidate variants in all 5 siblings to assess segregation.

RESULTS:

We identify a mutation in the exon 10 of the MAPT gene (p.P301L; rs63751273) in the proband and one affected brother, which was absent in the other three syblings analyzed. This mutation has often been assigned as the cause of FTD, particularly in French populations, but rarely of CBS. The proband and her affected brother presented a CBS and FTD phenotype respectively. This is the first report in Argentina and South America.

CONCLUSIONS:

Our findings contribute to support the wide distribution of this mutation and the high phenotypic variability presented among families, and also within families, carrying the MAPT-p.P301L mutation. This observation emphasize the concept that other environmental or genetic factors could modify the phenotype.

http://www.pascongress2017.org/MDS-PAS-2017-Files/PDFs/PASmiami-FP-v9.pdf

IMPULSE CONTROL DISORDER ON PARKINSON’S DISEASE. A new approach from art?

 Aldinio V., Persi G., Bres Bullrich M., Sánchez de Paz P., Da Prat G., Parisi V., Rojas G., Gatto E.

 Sanatorio de la Trinidad Mitre, Ciudad Autónoma de Buenos Aires, Argentina

Objectives To describe the characteristics of three PD patients, nonprofessional artists who developed an artistic hyper productivity on dopaminergic agonists treatment.

Background On Parkinson's disease (PD), the artistic productivity apparition has been reported with the use of dopaminergic agonists, as an unusual expression of impulse control disorder (ICD). Dopamine is involved into motivation and reward behaviors. The mesolimbic dopaminergic activity has been associated with creative impulse, search of the new and the sensibility for new stimulus.

Methods There were included three patients with PD on pramipexole treatment (2 cases) and ropinirole treatment (1 case): 2 women, 1 man. Literature review.

Results Male patient, 58 years old, 10 years PD, with pramipexole it develops ludopathy. Because of torpid evolution, it's been decided to implement a deep brain stimulator that had to be removed due to an infection. It starts with ropinirole, concomitantly it develops passion for painting. Female patient, 53 years old, 6 years PD, with pramipexole it develops hypersexuality, rotates to rotigotine with no results, restarts pramipexole, it develops skills for painting and dancing salsa. Female patient, 49 years old, 12 years PD, with pramipexole it develops compulsive shopping, and it develops hyper productivity for painting, implementing new artistic techniques.

Conclusion The ICD, related with dopaminergic agonists, is usually reported as a serious adverse event of the therapy, interfering on a negative manner with the quality of life of PD patients and their families. In our study the patients under dopaminergic agonists treatments developed skills for painting and increased their previous ability. This raises the question of whether artistic hyper productivity can be defined like an ICD, because it gave a beneficial effect on our patient’s quality of life.

HEMICHOREA INDUCED BY SERTRALINE

Case Report and Literature Review

Aldinio V., Persi G., Bres Bullrich M., Sánchez de Paz P., Da Prat G., Parisi V., Rojas G., Gatto E.

 Sanatorio de la Trinidad Mitre, Ciudad Autónoma de Buenos Aires, Argentina

Objectives To describe hemichorea in a patient with sertraline treatment

Background Hemichorea (HC) is a unilateral continuous, random and proximal movement on one side of the body. HC is associated with nonketotic hyperglycemia and is less frequently related to stroke involving striatum. Drug induced HC is a rare syndrome related to serotonin selective reuptake inhibitors (SSRIs).

Methods There was included a woman who developed HC after being treated with sertraline. Literature review.

Results A 65 years old woman, with personal history of irritable bowel and smoking, noticed a postural instability and irritability in December 2015. A depressive syndrome was diagnosed on March and she was started on sertraline 50 mg/day. One week later, she developed HC, diarrhea, stomatitis. An extensive investigation to exclude other causes was conducted. Brain MRI revealed no basal ganglia lesions. Laboratory tests, including complete blood count, renal, liver, and thyroid function, vitamin B12, folic acid, VDRL, HIV, prolactin, cortisol, carcinoembryonic antigen, CA 15.3, CA 19.9, CA 125, VSG, PCR, ceruloplasmine, anti-endomysium, Anti RI, Yo, Hu, FAN, P-ANCA , C-ANCA, rheumatoid factor, CSF protein, onconeural antibodies were normal/negative. Echocardiogram, Doppler ultrasound of neck vessels, CT scan of thorax, abdomen and pelvis, normal. High and low video endoscopy with biopsy: negative. Sertraline was withdraw with clinical improvement.

Conclusion The incidence of movement disorders caused by SSRIs is unknown. After a literature review, we failed to identify sertraline induced HC. Fluoxetine was reported associated with HC. In our patient temporal association and an extensive clinical assessment discarded other causes of HC and supported a drug induced involuntary movement. We hypothesized that a serotonergic transmission could impair striatum pathways and induce HC.

MDS 2014

Inverse Association Between Yerba Mate (Ilex Paraguaiensis) Consumption And The Risk Of Parkinson's Disease

Gatto,  E.M., Melcon,  C.M., Parisi,  V., Bartoloni,  L., Gonzalez,  C., Tomoko,  A., Garreto,  N., Pavon,  H., Bueri,  J., Matiazzi,  M.

Yerba Mate tea (YM), an infusion made from the leaves of the small tree Ilex paraguariensis, is a very common beverage in some countries of South America. Its popularity is increasing in the USA, Canada, and Europe. Argentina drinks only moderate amounts of coffee, favoring yerba mate infusion. The bioactive compounds in YM include phenolics, chlorogenic acid, theobromine, caffeine, chlorophyll, condensed tannins and saponins. Experimental studies suggests a neuroprotective role of YM in development and progression of Parkinson disease (PD) probably related to the adenosine A2A receptor antagonism or an augmentation of the expression in the striatum of adenosine A1 receptor.

Methods:

Case-control study on an individual basis from hospital records Data were adjusted by age and sex. Case was defined as a 40 years or older PD individual with ≥ 4 years of disease duration. Other causes of Parkinsonism were excluded. Exposure was measure by YM consumption, coffee, tea, alcohol intake and smoking. Clinical and demographic data were recorded.

Results:

This analysis included cases 180 and 378 control, mean age of PD patients was 68.11 years old. There was an inverse association between YM consumption and PD (coefficient −0.432±0.098; p<0.001). Multivariate analysis with logistic regression adjusted by sex, alcohol intake and smoking showed for YM an OR: 0.65, 95% CI 0.54-0.79; Tea OR: 0.65 CI 95% 0.45-0.94, Coffee OR: 0.53 (95% CI 0.53-0.77). Total xanthines together had an OR 0.69, CI 0.60-0.80.

Conclusions:

YM consumption is inversely associated with PD risk. These results leads us to hypothesize that YM may have a potential protecting role in developing PD, probably related with several mechanisms including Adenosine A2 antagonism.

To cite this abstract, please use the following information:

Gatto, E.M., Melcon, C.M., Parisi, V., Bartoloni, L., Gonzalez, C., Tomoko, A., Garreto, N., Pavon, H., Bueri, J., Matiazzi, M.; Inverse association between Yerba Mate (Ilex paraguaiensis) consumption and the risk of Parkinson's disease [abstract]. Movement Disorders 2014;29 Suppl 1 :1483

MDS 2013

ASSOCIATION BETWEEN YERBA MATE (Ilex paraguaiensis) CONSUMPTION AND RISK OF PARKINSON´S DISEASE. 

 Authors: Emilia M Gatto, Carlos M Melcon, Virginia L Parisi, Leonardo Bartoloni, Tomoko Arakaki, Nelida Garreto, Jose Bueri, Hernan Pavon, Lucía Derosa, Claudio Gonzalez.

Background: Several studies conducted worldwide report an inverse association between caffeine/coffee consumption and the risk of developing Parkinson’s disease (PD). Mate is a beverage, widely consumed in several South American countries, particularly Argentina, Paraguay, Uruguay, and the southern states of Brazil. It is made from dried leaves of the plant Ilex Paraguariensis (Yerba Mate-YM-). Experimental studies suggests that YM could have a neuroprotective rol in development and progression of PD probably related to the adenosine A2A receptor antagonism related with its xanthine alkaloids content.
Objective:  to establish the association between the risk of PD and YM consumption and quantify its magnitude.

Material and Methods: Case-control study on an individual basis from hospital records. Case was defined as ≥ 40 years old PD individual with ≥ 1 years of disease duration. Other causes of parkinsonism were excluded. Exposure was measure by YM consumption, coffee, tea and alcohol intake and smoking.  Clinical and demographic data were recorded.
Multivariate analysis was performed (conditional logistic regression).
Results: This preliminary analysis included 143 cases and 300 controls. Mean age of PD diagnosis 67.88 years, mean disease duration 6.95 years. Multivariate analysis showed an inverse association between YM consumption and risk of PD: OR 0.68 (IC95% 0.55-0.84) (p=0.00029). The rest of associations were: Tea OR: 0.71 (IC95%:0.47-1.05) and Coffee OR: 0.69 (IC95%:0.46-1.02). All infusions considered together had an OR: 0.71 (IC95%: 0.60-0.84) (p=0.00005). A significant linear trend was observed between levels of exposure to YM and the odds estimates, corresponding to a OR of 0.23 (95%CI: 0.11–0.50) per >1 liters /day increase in YM intake.
Conclusions: Our data confirm an inverse association between mate intake and the risk of PD, with a dose-response relation. This leads us to have the hypothesis that YM could have a potential protecting role in developing PD and further studies in this direction should be investigated.

MDS 2011

Apathy in Huntington’s disease from an  Argentinean series of cases.

Authors: Bottini Bonfanti A, Persi G; Parisi V; Gatto EM.

Background:

Huntington’s disease (HD) is a progressive neurodegenerative disease characterized by involuntary movements, cognitive impairment, and neuropsychiatric symptoms including depressed mood, anxiety, irritability and apathy. Prevalence of apathy in HD has been estimated from 34% to 76%. Apathy has been linked with frontal dysfunction and cognitive decline and cause a significant burden for HD patients (HDp) and caregivers.

Objective: To assess the prevalence of apathy in a series of Argentinean HDp and it relationship with depression, executive function impairment and nCAG lenght.

Patients and methods:

Twelve HD outpatients of the Institute of Neuroscience Buenos Aires compose the sample. Written informed consent was obtained from all participants prior to study procedures. All but three individuals have a genetically confirmed diagnosis of HD. Demographic and epidemiological data were analyzed. An extensive battery of test was performed including: INECO Frontal Screening (IFS), Mini Mental State Examination, Apathy Scale (AS) and the Beck Depression Inventory.

Results: The sample included 8 women (66.67%) and 4 men; mean age 48.58 12.23ys; mean age at onset 40±8.89 ys. Mean nCAG repeats in expanded allele were 43.11±2.31. Apathy was present in 2 individuals (16.67%) whereas only 1 patient showed depression (Beck =18) (8.33%). Apathy was associated with depression in one case. All patients but one (91.67%) has an IFS impairment that reflects a frontal cortex involvement.  We failed to demonstrate a correlation between apathy and IFS impairment as well as a correlation between apathy and nCAG lengths.

Conclusions: Although, this is a small sample, our results agree with previous reported in the literature. Frontal impairment is very frequent in HDp; apathy is more prevalent than depression and both disorders appears separable and independently. Due to the major effect of apathy on daily functioning and quality of life it seems a new interesting therapeutic target to explore.