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INTRODUCTION: Tremor is the most common movement disorder. Although clinical examination plays a significant role in evaluating patients with tremor, laboratory tests are useful to classify tremors according to the recent two-axis approach proposed by the International Parkinson and Movement Disorders Society. METHODS: In the present review, we will discuss the usefulness and applicability of the various diagnostic methods in classifying and diagnosing tremors. We will evaluate a number of techniques, including laboratory and genetic tests, neurophysiology, and neuroimaging. The role of newly introduced innovative tremor assessment methods will also be discussed. RESULTS: Neurophysiology plays a crucial role in tremor definition and classification, and it can be useful for the identification of specific tremor syndromes. Laboratory and genetic tests and neuroimaging may be of paramount importance in identifying specific etiologies. Highly promising innovative technologies are being developed for both clinical and research purposes. CONCLUSIONS: Overall, laboratory investigations may support clinicians in the diagnostic process of tremor. Also, combining data from different techniques can help improve understanding of the pathophysiological bases underlying tremors and guide therapeutic management.
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Temblor Esencial , Trastornos del Movimiento , Humanos , Temblor/etiología , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/complicaciones , SíndromeRESUMEN
INTRODUCTION: The recently released classification has revised the nosology of tremor, defining essential tremor (ET) as a syndrome and fueling an enlightened debate about some newly conceptualized entities such as ET-plus. As a result, precise information of demographics, clinical features, and about the natural history of these conditions are lacking. METHODS: The ITAlian tremor Network (TITAN) is a multicenter data collection platform, the aim of which is to prospectively assess, according to a standardized protocol, the phenomenology and natural history of tremor syndromes. RESULTS: In the first year of activity, 679 patients have been recruited. The frequency of tremor syndromes varied from 32% of ET and 41% of ET-plus to less than 3% of rare forms, including focal tremors (2.30%), task-specific tremors (1.38%), isolated rest tremor (0.61%), and orthostatic tremor (0.61%). Patients with ET-plus were older and had a higher age at onset than ET, but a shorter disease duration, which might suggest that ET-plus is not a disease stage of ET. Familial aggregation of tremor and movement disorders was present in up to 60% of ET cases and in about 40% of patients with tremor combined with dystonia. The body site of tremor onset was different between tremor syndromes, with head tremor being most commonly, but not uniquely, associated with dystonia. CONCLUSIONS: The TITAN study is anticipated to provide clinically relevant prospective information about the clinical correlates of different tremor syndromes and their specific outcomes and might serve as a basis for future etiological, pathophysiological, and therapeutic research.
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Distonía , Trastornos Distónicos , Temblor Esencial , Distonía/complicaciones , Humanos , Italia/epidemiología , Estudios Prospectivos , Síndrome , Temblor/complicaciones , Temblor/diagnóstico , Temblor/epidemiologíaRESUMEN
Ischemic stroke is a worldwide major cause of mortality and disability and has high costs in terms of health-related quality of life and expectancy as well as of social healthcare resources. In recent years, starting from the bidirectional relationship between autonomic nervous system (ANS) dysfunction and acute ischemic stroke (AIS), researchers have identified prognostic factors for risk stratification, prognosis of mid-term outcomes and response to recanalization therapy. In particular, the evaluation of the ANS function through the analysis of heart rate variability (HRV) appears to be a promising non-invasive and reliable tool for the management of patients with AIS. Furthermore, preclinical molecular studies on the pathophysiological mechanisms underlying the onset and progression of stroke damage have shown an extensive overlap with the activity of the vagus nerve. Evidence from the application of vagus nerve stimulation (VNS) on animal models of AIS and on patients with chronic ischemic stroke has highlighted the surprising therapeutic possibilities of neuromodulation. Preclinical molecular studies highlighted that the neuroprotective action of VNS results from anti-inflammatory, antioxidant and antiapoptotic mechanisms mediated by α7 nicotinic acetylcholine receptor. Given the proven safety of non-invasive VNS in the subacute phase, the ease of its use and its possible beneficial effect in hemorrhagic stroke as well, human studies with transcutaneous VNS should be less challenging than protocols that involve invasive VNS and could be the proof of concept that neuromodulation represents the very first therapeutic approach in the ultra-early management of stroke.
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Sistema Nervioso Autónomo/fisiopatología , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/terapia , Estimulación del Nervio Vago , Animales , Humanos , Accidente Cerebrovascular Isquémico/etiología , Factores de Riesgo , Resultado del Tratamiento , Estimulación del Nervio Vago/métodosRESUMEN
Progressive supranuclear palsy (PSP) is a rare, rapidly progressive, neurodegenerative disease characterized by falls and ocular movement disturbances. Caring for a partner or relative who suffers from PSP entails a strenuous and demanding task, usually lasting for years that affects carers' everyday life routines and emotional and social well-being. The 26-item Parkinsonism Carers QoL (PQoL Carer) is a self-administered, concise instrument evaluating the quality of life of caregivers of patients with atypical parkinsonism (both PSP and multiple system atrophy). Here, the PQoL Carer was translated into Italian and validated in 162 carers of PSP patients (54.3% women; mean age (standard deviation), 62.4 (15.4)) diagnosed according to the Movement Disorder Society criteria and recruited in 16 third-level movement disorders centers participating in the Neurecanet project. The mean PQoL total score was 40.66 ± 19.46. The internal consistency was excellent (Cronbach's alpha = 0.941); corrected item-total correlation was > 0.40 for all the items. A correlation with other health-related quality of life measures as well as with behavioral assessments was shown suggesting adequate convergent validity of the scale. PQoL also correlated with patients' severity of disease. The discriminant validity of the scale was evidenced by its capacity to differentiate between carers with varying levels of self-reported health (p < 0.001). In conclusion, the Italian version of the PQoL Carer is an easy, consistent, and valid tool for the assessment of the quality of life in carers of PSP patients.
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Cuidadores/psicología , Psicometría/instrumentación , Calidad de Vida/psicología , Encuestas y Cuestionarios , Adulto , Anciano , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Trastornos Parkinsonianos/etiología , Parálisis Supranuclear Progresiva/complicaciones , TraducciónRESUMEN
BACKGROUND: Progressive supranuclear palsy (PSP) is a rare rapidly progressive, neurodegenerative disease characterized by falls and ocular movement disturbances. The use of health-related quality of life (HR-QoL) measures allows assessing changes in health status induced by therapeutic interventions or disease progress in neurodegenerative diseases. The PSP-QoL is a 45-item, self-administered questionnaire designed to evaluate HR-QoL in PSP. METHODS AND RESULTS: Here, the PSP-QoL was translated into Italian and validated in 190 PSP (96 women and 94 men; mean age ± standard deviation, 72 ± 6.5; mean disease duration, 4.2 ± 2.3) patients diagnosed according to the Movement Disorder Society criteria and recruited in 16 third level movement disorders centers participating in the Neurecanet project. The mean PSP-QoL total score was 77.8 ± 37 (physical subscore, 46.5 ± 18.7; mental subscore, 33.6 ± 19.2). The internal consistency was high (Cronbach's alpha = 0.954); corrected item-total correlation was > 0.40 for the majority of items. The significant and moderate correlation of the PSP-QoL with other HR-QoL measures as well as with motor and disability assessments indicated adequate convergent validity of the scale. Gender and geographic location presented a significant impact on the PSP-QoL in our sample with women and patients from the South of Italy scoring higher than their counterparts. CONCLUSION: In conclusion, the Italian version of the PSP-QoL is an easy, reliable and valid tool for assessment of HR-QoL in PSP.
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Psicometría/normas , Calidad de Vida , Parálisis Supranuclear Progresiva/diagnóstico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Italia , Masculino , Psicometría/instrumentación , Reproducibilidad de los Resultados , AutoinformeRESUMEN
In this retrospective study, we evaluated both efficacy and effectiveness of safinamide 50 and 100 mg in the treatment of motor fluctuations and disabling dyskinesias in a cohort of patients with idiopathic Parkinson's disease (PD). Ninety-one PD patients were evaluated during the first year of commercialization of the drug, both prior to starting safinamide and at the last available follow-up. Evaluations were based on the Unified Parkinson's Disease Scale part III (UPDRS III), Hoehn & Yahr (HY), Unified Dyskinesia Rating Scale (UDysRS) walking and balance item 9 score, daily time spent in OFF and in ON with disabling dyskinesias (1 week diary), mean daily dose of levodopa (LD), dopamine-agonists (DA), catechol-O-methyl transferase inhibitor (COMT-I), monoamine oxidase B inhibitor (MAOB-I), and their LD equivalent dose (LEDD). Eight patients withdrew safinamide within the first month for minor side effects. At the follow-up evaluation, after a mean time with safinamide of 7.5 months ± 3.4, all patients showed a significant improvement of all the scale scores, except for HY, and of the daily dosages of the drugs and the LEDD. The same results were shown by PD patients treated with safinamide 50 mg and patients who started safinamide without switching from a previous MAOBI. PD patients with safinamide 100 mg and patients who started safinamide switching from a previous MAOBI significantly improved in time spent in OFF and LEDD. In conclusion, safinamide is safe and effective in improving motor complications in patients with idiopathic PD and can be considered a useful levodopa sparing strategy.
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Alanina/análogos & derivados , Antiparkinsonianos/uso terapéutico , Bencilaminas/farmacología , Inhibidores de la Monoaminooxidasa/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Alanina/farmacología , Agonistas de Dopamina/uso terapéutico , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada/métodos , Femenino , Humanos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Atrofia de Múltiples Sistemas/diagnóstico , Enfermedad de Parkinson/diagnóstico , Retención Urinaria/etiología , Anciano , Enfermedades del Sistema Nervioso Autónomo/etiología , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Hipotensión Ortostática/etiología , Hipotensión Ortostática/fisiopatología , Masculino , Persona de Mediana Edad , Atrofia de Múltiples Sistemas/complicaciones , Enfermedad de Parkinson/complicaciones , Estudios Retrospectivos , Vejiga Urinaria Hiperactiva/etiología , Vejiga Urinaria Hiperactiva/fisiopatología , UrodinámicaRESUMEN
BACKGROUND: Tremor disorders remain as clinical diagnoses and the rate of misdiagnosis between the commonest non-parkinsonian tremors is relatively high. OBJECTIVES: To compare the clinical features of Essential Tremor without other features (pure ET), ET plus soft dystonic signs (ET + DS), and tremor combined with dystonia (TwD). METHODS: We compared the clinical features of patients with pure ET, ET + DS, and TwD enrolled in The ITAlian tremor Network (TITAN). Linear regression models were performed to determine factors associated with health status and quality of life. RESULTS: Three-hundred-eighty-three patients were included. Sex distribution was significantly different between the groups with males being more represented in pure ET and females in TwD. The initial site of tremor was different between the groups with about 40% of TwD having head tremor and ET + DS unilateral upper limb tremor at onset. This pattern mirrored the distribution of overt dystonia and soft dystonic signs at examination. Sensory trick, task-specificity, and position-dependence were more common, but not exclusive, to TwD. Pure ET patients showed the lowest degree of alcohol responsiveness and ET + DS the highest. Midline tremor was more commonly encountered and more severe in TwD than in the other groups. Regression analyses demonstrated that tremor severity, sex, age, and to a lesser degree the variable "group", independently predicted health status and quality of life, suggesting the existence of other determinants beyond tremor. CONCLUSIONS: Pure ET and TwD manifest with a phenotypic overlap, which calls for the identification of diagnostic biomarkers. ET + DS shared features with both syndromes, suggesting intra-group heterogeneity.
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Distonía , Temblor Esencial , Calidad de Vida , Humanos , Masculino , Femenino , Temblor Esencial/fisiopatología , Temblor Esencial/diagnóstico , Temblor Esencial/complicaciones , Distonía/diagnóstico , Persona de Mediana Edad , Anciano , Temblor/diagnóstico , Temblor/fisiopatología , Adulto , Anciano de 80 o más Años , Índice de Severidad de la EnfermedadRESUMEN
Background: To date, there are no large studies delineating the clinical correlates of "pure" essential tremor (ET) according to its new definition. Methods: From the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of "pure" ET and excluded those with other tremor classifications, including ET-plus, focal, and task-specific tremor, which were formerly considered parts of the ET spectrum. Results: Out of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) "pure" ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options. Discussion: The findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of "pure" ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of "pure" ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies.
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Background: Effects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO-B inhibitors (iMAO-B) safinamide and rasagiline are still based on empirical approaches. Objectives: To estimate LED of safinamide 50 and 100 mg. Methods: In this multicenter, longitudinal, case-control study, we retrospectively reviewed clinical charts of 500 consecutive PD patients with motor complications and treated with (i) safinamide 100 mg (N = 130), safinamide 50 mg (N = 144), or rasagiline 1 mg (N = 97) for 9 ± 3 months and a control group of patients never treated with any iMAO-B (N = 129). Results: Major baseline features (age, sex, disease duration and stage, severity of motor signs and motor complications) were similar among the groups. Patients on rasagiline had lower UPDRS-II scores and Levodopa dose than control subjects. After a mean follow-up of 8.8-to-10.1 months, patients on Safinamide 50 mg and 100 mg had lower UPDRS-III and OFF-related UPDRS-IV scores than control subjects, who in turn had larger increase in total LED than the three iMAO-B groups. After adjusting for age, disease duration, duration of follow-up, baseline values and taking change in UPDRS-III scores into account (sensitivity analysis), safinamide 100 mg corresponded to 125 mg LED, whereas safinamide 50 mg and rasagiline 1 mg equally corresponded to 100 mg LED. Conclusions: We used a rigorous approach to calculate LED of safinamide 50 and 100 mg. Large prospective pragmatic trials are needed to replicate our findings.
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Ataxia is not a common feature in Parkinson's disease. Nevertheless, some rare forms of parkinsonism have ataxia as one of the main features in their clinical picture, especially those with juvenile or early-onset. On the other side, in cerebellar degenerative diseases, parkinsonism might accompany the typical symptoms and even become predominant in some cases. Many disorders involving different neurological systems present with a movement phenomenology reflecting the underlying pattern of pathological involvement, such as neurodegeneration with brain iron accumulation, neurodegeneration associated with calcium deposition, and metabolic and mitochondrial disorders. The prototype of sporadic disorders that present with a constellation of symptoms due to the involvement of multiple Central Nervous System regions is multiple system atrophy, whose motor symptoms at onset can be cerebellar ataxia or parkinsonism. Clinical syndromes encompassing both parkinsonian and cerebellar features might represent a diagnostic challenge for neurologists. Recognizing acquired and potentially treatable causes responsible for complex movement disorders is of paramount importance, since an early diagnosis is essential to prevent permanent consequences. The present review aims to provide a pragmatic overview of the most common diseases characterized by the coexistence of cerebellar and parkinsonism features and suggests a possible diagnostic approach for both inherited and sporadic disorders. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.
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Ataxia Cerebelosa , Atrofia de Múltiples Sistemas , Enfermedad de Parkinson , Trastornos Parkinsonianos , Ataxia/complicaciones , Ataxia Cerebelosa/complicaciones , Humanos , Atrofia de Múltiples Sistemas/diagnóstico , Enfermedad de Parkinson/complicaciones , Trastornos Parkinsonianos/complicaciones , Trastornos Parkinsonianos/diagnósticoRESUMEN
Evidence from clinical practice suggests that PD patients with the Glucocerebrosidase gene mutations (GBA-PD) are characterized by more severe dysautonomic symptoms than patients with idiopathic PD (iPD). Therefore, an accurate assessment of cardiovascular autonomic control (CAC) is necessary to clarify the role of GBA mutations in the pathophysiology of PD. We evaluated the CAC at rest and during orthostatic challenge of 15 iPD, 15 GBA-PD and 15 healthy controls (CTR). ECG and respiration were recorded in supine position and during active standing. The analysis of Heart Rate Variability (HRV) was performed on ECG recordings using two different approaches, linear spectral analysis and non-linear symbolic analysis. GBA-PD patients presented more frequently an akinetic-rigid phenotype and cognitive dysfunction than iPD patients. Both iPD and GBA-PD group were characterized by a lower spectral HRV than CTR group. At rest, the GBA-PD group was characterized by a lower parasympathetic modulation and a shift of the sympathovagal balance toward a sympathetic predominance compared to the CTR group. Moreover, the GBA-PD patients presented a lower HR increment and a lower or absent reduction of the vagal modulation in response to the active standing than iPD patients. Lastly, the cardiovascular autonomic dysfunction in PD patients was associated with longer disease duration, and with the occurrence of REM sleep behavior disorder and constipation. Our findings suggest a more severe impairment of the CAC in PD patients with GBA mutations. These results and further studies on the role of GBA mutations could allow a stratification based on cardiovascular risk in PD patients and the implementation of specific prevention programs.
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Multiple System Atrophy (MSA) is a rare neurodegenerative disease, clinically defined by a combination of autonomic dysfunction and motor involvement, that may be predominantly extrapyramidal (MSA-P) or cerebellar (MSA-C). Although dementia is generally considered a red flag against the clinical diagnosis of MSA, in the last decade the evidence of cognitive impairment in MSA patients has been growing. Cognitive dysfunction appears to involve mainly, but not exclusively, executive functions, and may have different characteristics and progression in the two subtypes of the disease (i.e., MSA-P and MSA-C). Despite continued efforts, combining in-vivo imaging studies as well as pathological studies, the physiopathological bases of cognitive involvement in MSA are still unclear. In this view, the possible link between cardiovascular autonomic impairment and decreased cognitive performance, extensively investigated in PD, needs to be clarified as well. In the present study, we evaluated a cohort of 20 MSA patients (9 MSA-P, 11 MSA-C) by means of a neuropsychological battery, hemodynamic assessment (heart rate and arterial blood pressure) during rest and active standing and bedside autonomic function tests assessed by heart rate variability (HRV) parameters and sympathetic skin response (SSR) in the same experimental session. Overall, global cognitive functioning, as indicated by the MoCA score, was preserved in most patients. However, short- and long-term memory and attentional and frontal-executive functions were moderately impaired. When comparing MSA-P and MSA-C, the latter obtained lower scores in tests of executive functions and verbal memory. Conversely, no statistically significant difference in cardiovascular autonomic parameters was identified between MSA-P and MSA-C patients. In conclusion, moderate cognitive deficits, involving executive functions and memory, are present in MSA, particularly in MSA-C patients. In addition, our findings do not support the role of dysautonomia as a major driver of cognitive differences between MSA-P and MSA-C.
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Corticobasal syndrome (CBS) is an atypical parkinsonian presentation characterized by heterogeneous clinical features and different underlying neuropathology. Most CBS cases are sporadic; nevertheless, reports of families and isolated individuals with genetically determined CBS have been reported. In this systematic review, we analyze the demographical, clinical, radiological, and anatomopathological features of genetically confirmed cases of CBS. A systematic search was performed using the PubMed, EMBASE, and Cochrane Library databases, included all publications in English from 1 January 1999 through 1 August 2020. We found forty publications with fifty-eight eligible cases. A second search for publications dealing with genetic risk factors for CBS led to the review of eight additional articles. GRN was the most common gene involved in CBS, representing 28 out of 58 cases, followed by MAPT, C9ORF72, and PRNP. A set of symptoms was shown to be significantly more common in GRN-CBS patients, including visuospatial impairment, behavioral changes, aphasia, and language alterations. In addition, specific demographical, clinical, biochemical, and radiological features may suggest mutations in other genes. We suggest a diagnostic algorithm to help in identifying potential genetic cases of CBS in order to improve the diagnostic accuracy and to better understand the still poorly defined underlying pathogenetic process.
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Enfermedades Neurodegenerativas/diagnóstico , Enfermedades Neurodegenerativas/genética , Trastornos Parkinsonianos/diagnóstico , Trastornos Parkinsonianos/genética , Edad de Inicio , Anciano , Afasia/diagnóstico , Afasia/genética , Proteína C9orf72/genética , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Trastornos del Lenguaje/diagnóstico , Trastornos del Lenguaje/genética , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/genética , Persona de Mediana Edad , Mutación , Proteínas Priónicas/genética , Progranulinas/genética , Síndrome , Resultado del Tratamiento , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/genética , Proteínas tau/genéticaRESUMEN
Since the end of February 2020, Italy has suffered one of the most severe outbreaks of coronavirus disease 2019 (COVID-19). However, what happened just before the Italian index case has not yet been investigated. To answer this question, we evaluated the potential impact of COVID-19 on the clinical features of a cohort of neurological inpatients admitted right before the Italian index case, as compared to the same period of the previous year. Demographic, clinical, treatment and laboratory data were extracted from medical records. The data collected included all inpatients who had been admitted to the Neurology and Stroke Units of the Ospedale Maggiore Policlinico, Milan, Italy, from December 15, 2018 to February 20, 2019 and from December 15, 2019 to February 20, 2020. Of the 248 patients, 97 subjects (39.1%) were admitted for an acute cerebrovascular event: 46 in the 2018/2019 period (mean [SD] age, 72.3 [15.6] years; 22 men [47.8%]), and 51 in the 2019/2020 interval (mean [SD] age, 72.8 [12.4] years; 24 men [47.1%]). The number of cryptogenic strokes has increased during the 2019-2020 year, as compared to the previous year (30 [58.8%] vs. 18 [39.1%], p = 0.05). These patients had a longer hospitalization (mean [SD] day, 15.7 [10.5] days vs. mean [SD] day, 11.7 [7.2] days, p = 0.03) and more frequent cerebrovascular complications (9 [30.0%] vs. 2 [11.1%]), but presented a lower incidence of cardiocerebral risk factors (18 [60.0%] vs. 14 [77.8%]). Right before the Italian index case, an increase in cryptogenic strokes has occurred, possibly due to the concomitant COVID-19.
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Accidente Cerebrovascular Isquémico/clasificación , Accidente Cerebrovascular Isquémico/complicaciones , Anciano , Anciano de 80 o más Años , Análisis de Varianza , COVID-19/complicaciones , COVID-19/epidemiología , COVID-19/fisiopatología , Distribución de Chi-Cuadrado , Estudios de Cohortes , Trazado de Contacto/métodos , Trazado de Contacto/estadística & datos numéricos , Progresión de la Enfermedad , Femenino , Humanos , Accidente Cerebrovascular Isquémico/epidemiología , Italia/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Genetic alterations of leucine-rich repeat kinase 2 (LRRK2), one of the most important contributors to familial Parkinson's disease (PD), have been hypothesized to play a role in cancer development due to demographical and preclinical data. Here, we sought to define the prevalence and prognostic significance of LRRK2 somatic mutations across all types of human malignancies by querying the publicly available online genomic database cBioPortal. Ninety-six different studies with 14,041 cases were included in the analysis, and 761/14,041 (5.4%) showed genetic alterations in LRRK2. Among these, 585 (76.9%) were point mutations, indels or fusions, 168 (22.1%) were copy number variations (CNVs), and 8 (1.0%) showed both types of alterations. One case showed the somatic mutation R1441C. A significant difference in terms of overall survival (OS) was noted between cases harboring somatic LRRK2 whole deletions, amplifications, and CNV-unaltered cases (median OS: 20.09, 57.40, and 106.57 months, respectively; p = 0.0008). These results suggest that both LRRK2 amplifications and whole gene deletions could play a role in cancer development, paving the way for future research in terms of potential treatment with LRRK2 small molecule inhibitors for LRRK2-amplified cases.