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Resumen Objetivos Caracterizar a los pacientes con trastornos del movimiento (TM) que reportaron el uso de preparados no farmaceuticos no estandarizados de cannabis (NF-C) en un centro especializado en movimientos anormales. Evaluar la relacion entre NF-C, respuesta terapeutica y sintomas asociados al uso (SAU). Material y metodos Cohorte retrospectiva de pacientes ≥ 21 anos que reportasen uso de NF-C en forma de: aceite (37), cigarrillo (2), tintura (1), entre junio 2017 y junio 2018. Fueron analizados datos demograficos, comorbilidades y caracteristicas clinicas. Se recabaron datos subjetivos con respecto a SAU. Resultados La muestra se compuso de 40 pacientes, 67,5%(N = 27) sexo masculino. Edad media al inicio de NF-C 64,08 ± 14,07 (IC95%: 59,52-68,64) con mediana de dias de consumo de 34,5 (21-90). El 67,5% (N = 27) tenian diagnostico de enfermedad de Parkinson. El 55% (N = 22) desconocian el motivo de inicio de NF-C. El 80% (N = 32) reportaron no haber presentado mejoria con NF-C. La frecuencia de SAU fue del 52,5% (N = 21). No se observaron diferencias significativas entre el diagnostico de TM con respecto al tipo de NF-C, respuesta con NF-C y SAU. Conclusion El uso de cannabis medicinal en TM es controvertido. Mas aun, indicar NF-C supone un riesgo no del todo categorizado en pacientes con TM. Nuestra cohorte denota los potenciales riesgos del uso de NF-C en un pool de pacientes con diversos TM.

Background Huntington's disease (HD) is a neurodegenerative disorder that includes motor, psychiatric and cognitive manifestations with typical onset of symptoms is in the forties. A percentage of patients (4.4% - 11.5%) may be exceptions to this and manifest symptoms later (>60 years old). Diagnosis of Late onset HD (LoHD) can be a challenge, due to the low suspicion of the disease at this age. Objective To review the genotype and phenotype of LoHD in an Argentinian cohort. Methods We reviewed the medical records and genetic testing of a total of 95 individuals with clinical and molecular diagnosis of Huntington's disease, based on 2 institution's registry. Results Among our HD cohort, 10 patients (10.52%) had LoHD, with variable results regarding family history. The average of repetitions of the expanded allele was 40 (range 38-44). All cases had mild motor symptoms at onset. Conclusions Late onset HD can be a diagnostic challenge, due to its slow progression, unawareness of manifestations among patients and in many cases, mild symptomatology that does not warrant medical attention.

Huntington's disease (HD) is a genetic, rare and progressive neurodegenerative disorder that causes motor and cognitive impairment in midlife patients. Although retinal damage was observed in animal HD models and in patients with other neurodegenerative diseases, we still need confirmation of impairment in HD patients. Optical coherence tomography (OCT) is a non-invasive methodology that analyses the retinal nerve fibre layers (RNFL) and could reflect processes of neurodegeneration.A cross-sectional study with 14 HD patients who underwent a spectral domain OCT. Results were compared with a control group. Demographic data were also obtained.Temporal and superior RNFL sectors in HD showed a significant RNFL thinning compared with a control group. However, no differences were identified in mean total RNFL thickness between HD patients and controls.OCT is a rapid and non-invasive technique that can be investigated in larger cohorts of patients to assess its potential role as a biomarker in HD patients.

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.

Several epidemiological studies support low cancer rates in patients with neurodegenerative disorders, including Parkinson's disease, Huntington's disease, and Alzheimer's disease. Different mechanisms were raised as possible causes, from mutated tumor suppressor genes (PARKIN, PINK1) to small interfering RNA based on the CAG trinucleotide repeat expansions located in introns or untranslated regions. However, as every rule has an exception, some tumors have an increased incidence in these neurodegenerative diseases such as breast and skin cancer (melanoma). This mini-review aims to establish the epidemiology between these neurodegenerative disorders and cancer to determine the possible mechanisms involved and therefore set eventual therapeutic applications. According to our findings, we conclude the presence of an inverse relationship among most cancers and the aforementioned neurodegenerative disorders. However, this concept needs to be considered cautiously considering specific genetic and extra-genetic linkage factors for particular tumors.

Objectives Precise temporal performance is crucial for several complex tasks. Time estimation in the second-to-minutes range—known as interval timing—involves the interaction of the basal ganglia and the prefrontal cortex via dopaminergic–glutamatergic pathways. Patients with Huntington's disease (HD) present deficits in cognitive and motor functions that require fine control of temporal processing. The objective of the present work was to assess temporal cognition through a peak-interval time (PI) production task in patients with HD and its potential correlation with the Unified Huntington's Disease Rating Scale (UHDRS). Materials and methods Patients with molecular diagnosis of HD and controls matched by age, sex and educational level (n=18/group) were tested for interval timing in short- (3 seconds), medium- (6 seconds) and long (12 seconds)-duration stimuli. Results Significant differences were observed in the PI task, with worse performance in HD compared to controls. Patients underestimated real time (left-shifted Peak location) for 6- and 12-second intervals (P

In the last years, lysosomal storage diseases appear as a bridge of knowledge between rare genetic inborn metabolic disorders and neurodegenerative diseases such as Parkinson’s disease (PD) or frontotemporal dementia. Epidemiological studies helped promote research in the field that continues to improve our understanding of the link between mutations in the glucocerebrosidase (GBA) gene and PD. We conducted a review of this link, highlighting the association in GBA mutation carriers and in Gaucher disease type 1 patients (GD type 1). A comprehensive review of the literature from January 2008 to December 2018 was undertaken. Relevance findings include: (1) There is a bidirectional interaction between GBA and α- synuclein in protein homeostasis regulatory pathways involving the clearance of aggregated proteins. (2) The link between GBA deficiency and PD appears not to be restricted to α⁻synuclein aggregates but also involves Parkin and PINK1 mutations. (3) Other factors help explain this association, including early and later endosomes and the lysosomal-associated membrane protein 2A (LAMP-2A) involved in the chaperone-mediated autophagy (CMA). (4) The best knowledge allows researchers to explore new therapeutic pathways alongside substrate reduction or enzyme replacement therapies.

We read with interest the article by Cubo et al.1 Patients with homozygous Huntington disease (HD) are rare—considering a patient as homozygous when presenting with repetitions greater than 36 in both alleles. Differences in age at onset, clinical characteristics, and evolution have been hypothesized because the gain function of the mutation is due to both alleles. Nevertheless, it has been shown that these patients have a similar clinical evolution. However, a very early study conducted by Squitieri et al.2 reported a more severe and rapid progression in homozygotes.

Huntington's disease is a rare, neurodegenerative disease caused by an expanded CAG repeat mutation in the huntingtin gene. Compared with adult-onset Huntington's disease, juvenile Huntington's disease (onset ≤20 years) is even rarer and has not been studied extensively. We aimed to further characterise juvenile Huntington's disease by examining the effect of CAG repeat size on disease presentation, progression, and survival.We did a retrospective analysis of patients with juvenile Huntington's disease aged 20 years or younger, according to the length of their CAG repeat and who had disabling psychiatric symptoms (with motor symptoms) or motor symptoms alone, and of patients with adult-onset Huntington's disease manifesting aged 30-60 years with 40 or more CAG repeats, from the REGISTRY and ENROLL-HD platforms and from two institutional databases (Lega Italiana Ricerca Huntington Foundation and the Instituto Neurociencias de Buenos Aires and the Sanatorio de la Trinidad Mitre). Patients with psychiatric but no motor symptoms were excluded. We compared symptoms at onset and longitudinally in patients with juvenile Huntington's disease with highly expanded (HE subgroup) or low expansion (LE subgroup) mutations, grouped by hierarchical clustering analysis. We also compared disease progression (longitudinal change in Unified Huntington's Disease Rating Scale-Total Motor Score) and survival of patients with juvenile and adult-onset Huntington's disease.We extracted medical records from 580 patients entered into the studies or databases between June 23, 2004, and March 31, 2018, of whom 36 patients met our definition of juvenile Huntington's disease and 197 for adult-onset Huntington's disease. According to caregiver reports, gait disturbance was more often a first presenting symptom in the HE subgroup (eight [80%] of 10 patients) than in the LE subgroup (seven [27%] of 26 patients; p=0·0071), whereas loss of hand dexterity was more common in the LE subgroup (11 [42%] of 26 patients) than in the HE subgroup (0 [0%] of 10 patients; p=0·0160). Compared with the LE subgroup, development delay (0 [0%] in the LE subgroup vs nine [90%] in the HE subgroup; p0·0001), severe gait impairment (nine [35%] in the LE subgroup vs nine [90%] in the HE subgroup; p=0·0072), and seizures (three [11%] in the LE subgroup vs eight [80%] in the HE subgroup; p0·0001) prevailed over time in the HE subgroup. Disease progression was more rapid in juvenile Huntington's disease (n=14) than in adult-onset Huntington's disease (n=52; generalised estimating equation model, p=0·0003). Of 121 deceased patients, median survival was shorter in the juvenile Huntington's disease (n=17) cohort than in adult-onset Huntington's disease (n=104) cohort (hazard ratio 2·18 [95% CI 1·08-4·40]; p=0·002).Patients with HE juvenile Huntington's disease differ clinically from patients with LE juvenile Huntington's disease or adult-onset Huntington's disease, suggesting reclassification of this particularly aggressive form of Huntington's disease might be required.Lega Italiana Ricerca Huntington Foundation and IRCCS Ospedale Casa Sollievo della Sofferenza.

Heterozygous mutations in the glucocerebrosidase (GBA) gene have been reported as a common risk factor for the development of Parkinson's disease (PD) in Gaucher disease (GD) patients and in heterozygous GBA mutation positive carriers. In this study, we analyzed the occurrence of prodromal markers of PD in an Argentinean cohort with type 1 GD. After signed informed consent, we evaluated 26 patients with type 1 GD under enzymatic replacement therapy from a cohort of the Hospital Ricardo Gutierrez GD Study Group in Buenos Aires City, Argentina. We performed an extensive neurological examination, including cognitive assessment by Montreal Cognitive Assessment (MoCA) and a questionnaire performed ad hoc, to identify non-motor PD symptoms. Parasomnias were reported by 7 patients (26.92%), rapid eye movement behavior disorders in 2 (7.69%), constipation in 2 (7.69%), hyposmia in 1 (3.84%), tremor in 1 (3.84%), and depression in 3 cases (11.53%). MoCA assessment was abnormal in 44.44% of patients. No patient fulfilled PD diagnostic criteria (Queen Square Brain Bank criteria). The identification of prodromal markers of PD in type 1 GD suggests that this population represents a very interesting cohort for identifying potential biomarkers and neuroprotective therapies for PD.