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BACKGROUND: Verbal fluency (VF) tasks are known as suitable for detecting cognitive impairment (CI) in Parkinson's disease (PD). This study thus aimed to evaluate the psychometrics and diagnostics of the Alternate Verbal Fluency Battery (AVFB) by Costa et al. (2014) in an Italian cohort of non-demented PD patients, as well as to derive disease-specific cut-offs for it. METHODS: N = 192 non-demented PD patients were screened with the Montreal Cognitive Assessment (MoCA) and underwent the AVFB-which includes phonemic, semantic and alternate VF tests (PVF; SVF; AVF), as well as a Composite Shifting Index (CSI) reflecting the "cost" of shifting from a single- to a double-cued VF task. Construct validity and diagnostics were assessed for each AVFB measure against the MoCA. Internal reliability and factorial validity were also tested. RESULTS: The MoCA proved to be strongly associated with PVF, SVF and AVF scores, whilst moderately with the CSI. The AVFB was internally consistent and underpinned by a single component; however, an improvement in both internal reliability and fit to its factorial structure was observed when dropping the CSI. Demographically adjusted scores on PVF, SVF and AVF tests were diagnostically sound in detecting MoCA-defined cognitive impairment, whilst this was not true for the CSI. Disease-specific cut-offs for PVF, SVF and AVF tests were derived. DISCUSSION: In conclusion, PVF, SVF and AVF tests are reliable, valid and diagnostically sound instruments to detect cognitive impairment in non-demented PD patients and are therefore recommended for use in clinical practice and research.
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Disfunção Cognitiva , Testes Neuropsicológicos , Doença de Parkinson , Psicometria , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/complicações , Masculino , Feminino , Psicometria/normas , Idoso , Itália , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Reprodutibilidade dos Testes , Testes Neuropsicológicos/normas , Pessoa de Meia-Idade , Comportamento Verbal/fisiologia , Testes de Estado Mental e Demência/normasRESUMO
BACKGROUND AND PURPOSE: Fatigue, a disabling symptom in many neuromuscular disorders, has been reported also in Charcot-Marie-Tooth disease (CMT). The presence of fatigue and its correlations in CMT was investigated. METHODS: The Modified Fatigue Impact Scale (MFIS) was administered to CMT patients from the Italian Registry and a control group. An MFIS score >38 indicated abnormal fatigue. The correlation with disease severity and clinical characteristics, the Hospital Anxiety and Depression Scale and Epworth Sleepiness Scale scores, and drug use was analysed. RESULTS: Data were collected from 251 CMT patients (136 women) and 57 controls. MFIS total (mean ± standard deviation 32 ± 18.3, median 33), physical (18.9 ± 9.7, 20) and psychosocial (2.9 ± 2.4, 3) scores in CMT patients were significantly higher than controls. Abnormal fatigue occurred in 36% of the patients who, compared to patients with normal scores, had more severe disease (median CMT Examination Score 9 vs. 7), more frequent use of foot orthotics (22% vs. 11%), need of support for walking (21% vs. 8%), hand disability (70% vs. 52%) and positive sensory symptoms (56% vs. 36%). Patients with abnormal fatigue had significantly increased frequency of anxiety/depression/general distress (Hospital Anxiety and Depression Scale), somnolence (Epworth Sleepiness Scale), obesity (body mass index ≥ 30) and use of anxiolytic/antidepressant or anti-inflammatory/analgesic drugs. CONCLUSIONS: Fatigue is a relevant symptom in CMT as 36% of our series had scores indicating abnormal fatigue. It correlated with disease severity but also with anxiety, depression, sleepiness and obesity, indicating different components in the generation of fatigue. CMT patients' management must include treatment of fatigue and of its different generators, including general distress, sleepiness and obesity.
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Doença de Charcot-Marie-Tooth , Humanos , Feminino , Doença de Charcot-Marie-Tooth/complicações , Doença de Charcot-Marie-Tooth/epidemiologia , Sonolência , Caminhada , Fadiga/epidemiologia , Fadiga/etiologia , Extremidade SuperiorRESUMO
INTRODUCTION: Cluster headache (CH) is usually comorbid to mood spectrum disorders, but the psychopathological aspects are poorly explored. We aimed at identifying discrete profiles of personality traits and their association with clinical features. METHODS: Based on the personality scales of the Millon Clinical Multiaxial Inventory-III, principal component analysis (PCA) identified psychological patterns of functioning of 56 CH patients. PCA outcomes were used for hierarchical cluster analysis (HCA) for sub-groups classification. RESULTS: Eighty-seven percent of patients had personality dysfunctions. PCA found two bipolar patterns: (i) negativistic, sadic-aggressive, borderline, and compulsive traits were distinctive of the psychological dysregulation (PD) dimension, and (ii) narcissistic, histrionic, avoidant, and schizoid traits loaded under the social engagement (SE) component. PD was associated with disease duration and psychopathology. SE was related to educational level and young age. HCA found three groups of patients, and the one with high PD and low SE had the worst psychological profile. CONCLUSIONS: Personality disorders are common in CH. Our data-driven approach revealed distinct personality patterns which can appear differently among patients. The worst combination arguing against mental health is low SE and high PD. Linking this information with medical history may help clinicians to identify tailored-based therapeutic interventions for CH patients.
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Cefaleia Histamínica , Humanos , Cefaleia Histamínica/complicações , Transtornos da Personalidade/complicações , Personalidade , Inventário Clínico Multiaxial de Millon , ComorbidadeRESUMO
BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is a safe and effective procedure for drug-resistant tremor in Parkinson's disease (PD). OBJECTIVE: The aim of this study was to demonstrate that MRgFUS ventralis intermedius thalamotomy in early-stage tremor-dominant PD may prevent an increase in dopaminergic medication 6 months after treatment compared with matched PD control subjects on standard medical therapy. METHODS: We prospectively enrolled patients with early-stage PD who underwent MRgFUS ventralis intermedius thalamotomy (PD-FUS) and patients treated with oral dopaminergic therapy (PD-ODT) with a 1:2 ratio. We collected demographic and clinical data at baseline and 6 and 12 months after thalamotomy. RESULTS: We included 10 patients in the PD-FUS group and 20 patients in the PD-ODT group. We found a significant increase in total levodopa equivalent daily dose and levodopa plus monoamine oxidase B inhibitors dose in the PD-ODT group 6 months after thalamotomy. CONCLUSIONS: In early-stage tremor-dominant PD, MRgFUS thalamotomy may be useful to reduce tremor and avoid the need to increase dopaminergic medications. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Tremor Essencial , Doença de Parkinson , Humanos , Tremor/tratamento farmacológico , Tremor/etiologia , Tremor/cirurgia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/cirurgia , Tremor Essencial/tratamento farmacológico , Tremor Essencial/cirurgia , Projetos Piloto , Levodopa/uso terapêutico , Tálamo/diagnóstico por imagem , Tálamo/cirurgia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Little is known about hypomyelinating leukodystrophies (HLDs) in adults. The aim of this study was to investigate HLD occurrence, clinical features, and etiology among undefined leukoencephalopathies in adulthood. METHODS: We recruited the patients with cerebral hypomyelinating magnetic resonance imaging pattern (mild T2 hyperintensity with normal or near-normal T1 signal) from our cohort of 62 adult index cases with undefined leukoencephalopathies, reviewed their clinical features, and used a leukoencephalopathy-targeted next generation sequencing panel. RESULTS: We identified 25/62 patients (~40%) with hypomyelination. Cardinal manifestations were spastic gait and varying degree of cognitive impairment. Etiology was determined in 44% (definite, 10/25; likely, 1/25). Specifically, we found pathogenic variants in the POLR3A (n = 2), POLR1C (n = 1), RARS1 (n = 1), and TUBB4A (n = 1) genes, which are typically associated with severe early-onset HLDs, and in the GJA1 gene (n = 1), which is associated with oculodentodigital dysplasia. Duplication of a large chromosome X region encompassing PLP1 and a pathogenic GJC2 variant were found in two patients, both females, with early-onset HLDs persisting into adulthood. Finally, we found likely pathogenic variants in PEX3 (n = 1) and PEX13 (n = 1) and potentially relevant variants of unknown significance in TBCD (n = 1), which are genes associated with severe, early-onset diseases with central hypomyelination/dysmyelination. CONCLUSIONS: A hypomyelinating pattern characterizes a relevant number of undefined leukoencephalopathies in adulthood. A comprehensive genetic screening allows definite diagnosis in about half of patients, and demonstrates the involvement of many disease-causing genes, including genes associated with severe early-onset HLDs, and genes causing peroxisome biogenesis disorders.
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Doenças Desmielinizantes , Leucoencefalopatias , Adulto , Feminino , Humanos , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/genética , Imageamento por Ressonância Magnética , Proteínas Associadas aos Microtúbulos , MutaçãoRESUMO
BACKGROUND: Lombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced. METHODS: At the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children. RESULTS: After a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March-September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high. CONCLUSIONS: During the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system.
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COVID-19 , Telemedicina , Adulto , Criança , Humanos , Itália/epidemiologia , Pandemias , Encaminhamento e Consulta , SARS-CoV-2RESUMO
A great deal of studies suggests that cluster headache (CH) patients are usually comorbid to anxiety-mood spectrum disorders and psychopathological symptoms; however, the personality profiles reported in the literature strictly depend on type of assessment used. Psychiatric comorbidities have been extensively studied in migraine and they are recognized to represent a major risk factor associated with poorer outcome, playing a role in the headache chronification process at once as cause and consequence of it. By contrast the incidence and role of psychopathological aspects in CH is still not clarified, insufficiently explored as the striking severity of such a physical pain apparently leaves no room to psychological explanations. The aim of the present study is to describe psychopathological aspects of CH patients by means of the Millon Clinical Multiaxial Inventory-III (MCMI-III), a psychological assessment tool compatible to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) that correlates personality disorders (PDs) and clinical syndromes. We included all consecutive inward patients with CH between January 2014 and December 2016. Patients were evaluated using the MCMI-III a validated inventory assessing 14 PDs Scales (coordinate with DSM-IV Axis II disorders) and ten Clinical Syndrome Scales (coordinate with DSM-IV Axis I disorders). Twenty-six CH patients (24 chronic CH) were tested. Personality disorders were present in 92% of the patients. The most frequent PDs were: obsessive-compulsive (30.8%), histrionic (26.9%), narcissistic (11.5%), paranoid (11.5%) and avoidant (11.5%). According to the MCMI-III, patients with CH showed a high prevalence of personality disorders (Axis II-DSM-IV). PDs in CH patients can play an important role in determining CH course toward chronification. These preliminary results suggest that behavioral treatments can find room to support more conventional drug and neurostimulation therapies in these patients. In addition, the very high prevalence of PDs in our patients suggests that CH could in some cases be considered among the spectrum of somatoform and pain syndromes in patients with PDs.
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Cefaleia Histamínica/diagnóstico , Cefaleia Histamínica/psicologia , Inventário Clínico Multiaxial de Millon , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/psicologia , Adulto , Cefaleia Histamínica/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Personalidade/complicaçõesRESUMO
BACKGROUND: Capgras delusion is a delusional misidentification syndrome, in which the patient is convinced that someone that is well known to them, usually a close relative, has been replaced by an impostor or double. Although it has been frequently described in psychotic syndromes, including paranoid schizophrenia, over a third of the documented cases of Capgras delusion are observed in patients with organic brain lesions or neurodegenerative disease, including Parkinson's Disease. Variants of Capgras involving animals or inanimate objects have also been described. The etiology of Capgras in Parkinson's remains unclear, but may arise from a combination of factors, such as frontal lobe dysfunction and dopaminergic medication. CASE PRESENTATION: We present the case of a 53-year old right-handed female with Parkinson's disease who developed Capgras delusion during treatment with dopamine agonists and Levodopa/Carbidopa. She became convinced that her pet dogs and the plants in her garden had been substituted by identically looking ones. Our patient was initially treated with Quetiapine, with no improvement, and subsequently treated with Clozapine, which lead to partial regression of her symptoms. Neuropsychological Evaluation showed Mild Cognitive Impairment in Executive Functions. CONCLUSIONS: Given the clinical history, onset and evolution of symptoms we believe our patient's delusion resulted from the overlap of dopaminergic medication and Mild Cognitive Impairment in executive functions. Zoocentric Capgras, the variant we describe, has been rarely described in scientific literature, and we believe it is of interest due to its unusual characteristics.
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Síndrome de Capgras/etiologia , Disfunção Cognitiva/psicologia , Doença de Parkinson/psicologia , Animais , Antiparkinsonianos/efeitos adversos , Antipsicóticos/uso terapêutico , Síndrome de Capgras/tratamento farmacológico , Carbidopa/efeitos adversos , Clozapina/uso terapêutico , Delusões/etiologia , Dibenzotiazepinas/uso terapêutico , Cães , Agonistas de Dopamina/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Levodopa/efeitos adversos , Animais de Estimação/psicologia , Plantas , Fumarato de QuetiapinaRESUMO
MRI-guided focused ultrasound (MRgFUS) lesioning is an innovative, safe and effective treatment which provides an innovative development in the field of minimally invasive stereotactic neurosurgery. Based on the application of focused ultrasound energy under full MR planning and thermal imaging control, unilateral lesioning of the thalamus, subthalamic nucleus, and globus pallidus is indicated for the treatment of movement disorders, including essential tremor, Parkinson's disease, and dystonia. We started to apply this technique in February 2019 for the treatment of patients with movement disorders. The authors developed a diagnostic therapeutic care pathway, which is herewith proposed and applied as an explication of standard clinical practice in use. The project was the result of the application of different methods such as Health Technology Assessment (HTA), Strengths, Weaknesses, Opportunities and Threats analysis (SWOT) and Demin -Plan, Do, Check, Act (PDCA) cycle. The aim of this project was to standardize the MRgFUS diagnostic-therapeutic pathway (DTP), describe its application and the appropriateness of different phases (patient selection, intervention phase and follow-up). Here, we described in detail our experience in the DTP application from 2019 up to now in 610 patients with movement disorders.
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BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is increasingly used to treat drug-resistant essential tremor (ET). Data on MRgFUS thalamotomy in dystonic tremor (DT) are anecdotal. OBJECTIVES: To investigate efficacy, safety, and differences in target coordinates of MRgFUS thalamotomy in DT versus ET. METHODS: Ten patients with DT and 35 with ET who consecutively underwent MRgFUS thalamotomy were followed for 12 months. Although in both groups the initial surgical planning coordinates corresponded to the ventralis intermediate (Vim), the final target could be modified intraoperatively based on clinical response. RESULTS: Tremor significantly improved in both groups. The thalamic lesion was significantly more anterior in DT than ET. Considering both ET and DT groups, the more anterior the lesion, the lower the odds ratio for adverse events. CONCLUSIONS: MRgFUS thalamotomy is safe and effective in DT and ET. Compared to classical Vim coordinates used for ET, more anterior targeting should be considered for DT.
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Tremor Essencial , Humanos , Projetos Piloto , Tremor Essencial/diagnóstico por imagem , Estudos Prospectivos , Tremor , Tálamo/diagnóstico por imagemRESUMO
Background: Patients with Parkinson's disease (PD) and GBA gene mutations (GBA-PD) develop nonmotor complications more frequently than noncarriers. However, an objective characterization of both cardiovascular and sudomotor autonomic dysfunction using extensive clinical and instrumental measures has never been provided so far. Survival is reduced in GBA-PD regardless of age and dementia, suggesting that other hitherto unrecognized factors are involved. Objectives: To provide instrumental measures of pattern and severity of autonomic dysfunction in GBA-PD and explore their correlation with other non-motor symptoms and implications for clinical practice. Methods: In this cross-sectional study, 21 GBA-PD and 24 matched PD noncarriers underwent extensive assessment of motor and non-motor features, including neuropsychological testing. Cardiovascular autonomic function was explored through a comprehensive battery of indexes, including power spectral analysis of the R-R intervals and blood pressure short-term variability during resting state and active maneuvers. Dynamic Sweat Test was used to assess post-ganglionic sudomotor dysfunction. Results: Despite minimal or absent clinical correlates, cardiovagal and sympathetic indexes, heart rate variability parameters and sudomotor postganglionic function were more severely impaired in GBA-PD than noncarriers (overcoming relatively preserved compensatory peripheral sympathetic function), suggesting more prominent cardiac sympatho-vagal demodulation, efferent baroreflex failure and peripheral sympathetic dysfunction in GBA-PD. Cardiovascular dysautonomia showed marginal correlations with cognitive impairment. Conclusions: Compared to PD noncarriers, GBA-PD display more severe instrumental autonomic abnormalities, which may be underestimated by purely clinical measures, despite their relevance on morbidity and mortality. This supports the necessity of implementing instrumental autonomic assessment in all GBA-PD, regardless of clinically overt symptoms.
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BACKGROUND: There is little information about neuropsychiatric comorbidities in Charcot-Marie-Tooth disease (CMT). We assessed frequency of anxiety, depression, and general distress in CMT. METHODS: We administered online the Hospital Anxiety-Depression Scale (HADS) to CMT patients of the Italian registry and controls. HADS-A and HADS-D scores ≥ 11 defined the presence of anxiety/depression and HADS total score (HADS-T) ≥ 22 of general distress. We analysed correlation with disease severity and clinical characteristics, use of anxiolytics/antidepressants and analgesic/anti-inflammatory drugs. RESULTS: We collected data from 252 CMT patients (137 females) and 56 controls. CMT patient scores for anxiety (mean ± standard deviation, 6.7 ± 4.8), depression (4.5 ± 4.0), and general distress (11.5 ± 8.1) did not differ from controls and the Italian population. However, compared to controls, the percentages of subjects with depression (10% vs 2%) and general distress (14% vs 4%) were significantly higher in CMT patients. We found no association between HADS scores and disease duration or CMT type. Patients with general distress showed more severe disease and higher rate of positive sensory symptoms. Depressed patients also had more severe disease. Nineteen percent of CMT patients took antidepressants/anxiolytics (12% daily) and 70% analgesic/anti-inflammatory drugs. Patients with anxiety, depression, and distress reported higher consumption of anxiolytics/antidepressants. About 50% of patients with depression and/or general distress did not receive any specific pharmacological treatment. CONCLUSIONS: An appreciable proportion of CMT patients shows general distress and depression. Both correlated with disease severity and consumption of antidepressants/anxiolytics, suggesting that the disease itself is contributing to general distress and depression.
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Ansiolíticos , Doença de Charcot-Marie-Tooth , Feminino , Humanos , Doença de Charcot-Marie-Tooth/complicações , Doença de Charcot-Marie-Tooth/epidemiologia , Depressão/epidemiologia , Depressão/diagnóstico , Ansiolíticos/uso terapêutico , Ansiedade/epidemiologia , Sistema de Registros , Itália/epidemiologia , Antidepressivos/uso terapêuticoRESUMO
BACKGROUND: Sleep abnormalities have been reported in Charcot-Marie-Tooth disease (CMT), but data are scanty. We investigated their presence and correlation in a large CMT patients' series. METHODS: Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were administered to CMT patients of the Italian registry and controls. ESS score > 10 indicated abnormal daytime somnolence, PSQI score > 5 bad sleep quality. We analyzed correlation with disease severity and characteristics, Hospital Anxiety and Depression Scale (HADS), Modified Fatigue Impact Scale (MFIS), Body Mass Index, drug use. RESULTS: ESS and PSQI questionnaires were filled by 257 and 253 CMT patients, respectively, and 58 controls. Median PSQI score was higher in CMT patients than controls (6 vs 4, p = 0.006), with no difference for ESS score. Abnormal somnolence and poor sleep quality occurred in 23% and 56% of patients; such patients had more frequently anxiety/depression, abnormal fatigue, and positive sensory symptoms than those with normal ESS/PSQI. Moreover, patients with PSQI score > 5 had more severe disease (median CMT Examination Score, CMTES, 8 vs 6, p = 0.006) and more frequent use of anxiolytic/antidepressant drugs (29% vs 7%, p < 0.001). CONCLUSIONS: Bad sleep quality and daytime sleepiness are frequent in CMT and correlated with anxiety, depression and fatigue, confirming that different components affect sleep. Sleep disorders, such as sleep apnea and restless leg syndrome, not specifically investigated here, are other factors known to impact on sleep quality and somnolence. CMT patients' management must include sleep behavior assessment and evaluation of its correlated factors, including general distress and fatigue.
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Doença de Charcot-Marie-Tooth , Distúrbios do Sono por Sonolência Excessiva , Transtornos do Sono-Vigília , Humanos , Qualidade do Sono , Sonolência , Doença de Charcot-Marie-Tooth/complicações , Distúrbios do Sono por Sonolência Excessiva/etiologia , Sono , Fadiga/etiologia , Inquéritos e Questionários , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologiaRESUMO
BACKGROUND: Leukodystrophy with vanishing white matter (LVWM) is an autosomal recessive disease with typical pediatric-onset caused by mutations in one of the five EIF2B genes. Adult-onset (AO) cases are rare. METHODS: In this observational study, we reviewed clinical and laboratory information of the patients with AO-LVWM assessed at two referral centers in Italy and Portugal from Jan-2007 to Dec-2019. RESULTS: We identified 18 patients (13 females) with AO-LVWM caused by EIF2B5 or EIF2B3 mutations. Age of neurological onset ranged from 16 to 60 years, with follow-ups occurring from 2 to 37 years. Crucial symptoms were cognitive and motor decline. In three patients, stroke-like events were the first manifestation; in another, bladder dysfunction remained the main complaint across decades. Brain MRI showed white matter (WM) rarefaction in all cases, except two. Diffusion-weighted imaging documented focal hyperintensity in the acute stage of stroke-like events. 1H-spectroscopy primarily showed N-acetyl-aspartate reduction; 18fluorodeoxyglucose-PET revealed predominant frontoparietal hypometabolism; evoked potential studies demonstrated normal-to-reduced amplitudes; neuro-ophthalmological assessment showed neuroretinal thinning, and b-wave reduction on full-field electroretinogram. Interestingly, we found an additional patient with LVWM-compatible phenotype and monoallelic variants in two distinct eIF2B genes, EIF2B1 and EIF2B2. CONCLUSIONS: AO-LVWM presents varying clinical manifestations at onset, including stroke-like events. WM rarefaction is the most consistent diagnostic clue even in the latest onset cases. Spectroscopy and electrophysiological features are compatible with axon, rather than myelin, damage. Cerebral glucose metabolic abnormalities and retinal alterations can be present. LVWM might also be caused by a digenic inheritance affecting the eIF2B complex.
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Doenças Desmielinizantes , Leucoencefalopatias , Doenças por Armazenamento dos Lisossomos , Doenças Neurodegenerativas , Acidente Vascular Cerebral , Substância Branca , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Fator de Iniciação 2B em Eucariotos/genética , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/genética , Imageamento por Ressonância Magnética , Mutação/genética , Estudos Observacionais como Assunto , Substância Branca/diagnóstico por imagemRESUMO
Background: Heterozygous mutations in the GBA gene, encoding the lysosomal enzyme ß-glucocerebrosidase (GCase), are the most frequent genetic risk factor for Parkinson's disease (PD). GBA-related PD (GBA-PD) patients have higher risk of dementia and reduced survival than non-carriers. Preclinical studies and one open-label trial in humans demonstrated that the chaperone ambroxol (ABX) increases GCase levels and modulates α-synuclein levels in the blood and cerebrospinal fluid (CSF). Methods and analysis: In this multicentre, double-blind, placebo-controlled, phase II clinical trial, we randomise patients with GBA-PD in a 1:1 ratio to either oral ABX 1.2 g/day or placebo. The duration of treatment is 52 weeks. Each participant is assessed at baseline and weeks 12, 26, 38, 52 and 78. Changes in the Montreal Cognitive Assessment score and the frequency of mild cognitive impairment and dementia between baseline and weeks 52 are the primary outcome measures. Secondary outcome measures include changes in validated scales/questionnaires assessing motor and non-motor symptoms. Neuroimaging features and CSF neurodegeneration markers are used as surrogate markers of disease progression. GCase activity, ABX and α-synuclein levels are also analysed in blood and CSF. A repeated-measures analysis of variance will be used for elaborating results. The primary analysis will be by intention to treat. Ethics and dissemination: The study and protocols have been approved by the ethics committee of centres. The study is conducted according to good clinical practice and the Declaration of Helsinki. The trial findings will be published in peer-reviewed journals and presented at conferences. Trial registration numbers: NCT05287503, EudraCT 2021-004565-13.
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The aim of this study was to evaluate the efficacy and safety of epidural premotor stimulation in patients with primary focal dystonia. Seven patients were selected: 6 had cervical dystonia and 1 had right upper limb dystonia. In 2 patients, sustained muscle contractions led to a prevalently fixed head posture. Patients with cervical dystonia received a bilateral implant, whereas the patient with hand dystonia received a unilateral implant. Neurological and neuropsychological evaluations were performed before surgery (baseline), and 1, 3, 6, and 12 months afterward. The Burke-Fahn-Marsden scale (BFMS) and the Toronto Western spasmodic torticollis rating scale (TWSTRS) were administered at the same time points. Patients underwent resting (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scans, before and 12 months after surgery. No adverse events occurred. An overall improvement was observed on the BFMS and TWSTRS after surgery. Patients with prevalently fixed cervical dystonia had a reduced benefit. Presurgical neuroimaging revealed a significant bilateral metabolic increase in the sensorimotor areas, which was reduced after surgery.
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Córtex Cerebral/fisiologia , Estimulação Encefálica Profunda/métodos , Distúrbios Distônicos/terapia , Torcicolo/terapia , Adulto , Idoso , Avaliação da Deficiência , Distúrbios Distônicos/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18 , Seguimentos , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Índice de Gravidade de Doença , Torcicolo/diagnóstico por imagem , Resultado do Tratamento , Adulto JovemRESUMO
Adaptive behaviour requires an ability to obtain rewards by choosing between different risky options. Financial gambles can be used to study effective decision-making experimentally, and to distinguish processes involved in choice option evaluation from outcome feedback and other contextual factors. Here, we used a paradigm where participants evaluated 'mixed' gambles, each presenting a potential gain and a potential loss and an associated variable outcome probability. We recorded neural responses using autonomic monitoring, electroencephalography (EEG) and functional neuroimaging (fMRI), and used a univariate, parametric design to test for correlations with the eleven economic parameters that varied across gambles, including expected value (EV) and amount magnitude. Consistent with behavioural economic theory, participants were risk-averse. Gamble evaluation generated detectable autonomic responses, but only weak correlations with outcome uncertainty were found, suggesting that peripheral autonomic feedback does not play a major role in this task. Long-latency stimulus-evoked EEG potentials were sensitive to expected gain and expected value, while alpha-band power reflected expected loss and amount magnitude, suggesting parallel representations of distinct economic qualities in cortical activation and central arousal. Neural correlates of expected value representation were localized using fMRI to ventromedial prefrontal cortex, while the processing of other economic parameters was associated with distinct patterns across lateral prefrontal, cingulate, insula and occipital cortices including default-mode network and early visual areas. These multimodal data provide complementary evidence for distributed substrates of choice evaluation across multiple, predominantly cortical, brain systems wherein distinct regions are preferentially attuned to specific economic features. Our findings extend biologically-plausible models of risky decision-making while providing potential biomarkers of economic representations that can be applied to the study of deficits in motivational behaviour in neurological and psychiatric patients.
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Sistema Nervoso Autônomo/fisiologia , Mapeamento Encefálico , Encéfalo/irrigação sanguínea , Encéfalo/fisiologia , Tomada de Decisões/fisiologia , Adulto , Análise de Variância , Pressão Sanguínea/fisiologia , Eletrocardiografia , Eletroencefalografia , Feminino , Resposta Galvânica da Pele , Jogos Experimentais , Frequência Cardíaca/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Tempo de Reação , Adulto JovemRESUMO
BACKGROUND: The whole hospital system was stressed and at risk in the first phase of the pandemic. This study examined the prevalence of post-traumatic stress disorder (PTSD) in all hospital staff, medical and non-medical, within two months of the pandemic declaration. Survey concerned staff 4510 health workers of Italian Highly Specialized Research Hospitals. METHOD: Subjects were asked to complete an on-line self-reported questionnaire, the PTSD Checklist 5 (PCL-5) and subjective perception of safety related to personal protective equipment (PPE). RESULTS: The sample included staff working in hospitals with or without COVID-19 patient admissions. Overall, 11.56% of the hospitals staff met the symptoms criteria for probable PTSD. The sample included 80.63% (3467) medical staff workers and 19.37% (833) non-medical staff workers. The 31.91% of participants worked in COVID-19 hospitals/wards. The prevalence of positive screening for PTSD symptoms in medical staff was 12.42% (426) and in non-medical staff, 8.59% (70). Among medical staff, anesthesiologists had a significant prevalence of PTSD (22.35%), followed by health care assistants/technicians (15.38%) and physicians (10.11%). Among non-medical staff, personnel involved in cleaning, catering, maintenance, security, and transportation, the symptoms of PTSD reached a rate of 12.24% and in administrative staff 8.47%. Risk factors associated with PTSD included working as an anesthesiologist, perceiving PPE as inadequate, and working in COVID-19 hospitals/wards. CONCLUSIONS: In the present study, as in other studies, the prevalence of PTSD symptoms among hospital workers was significatively higher than the lifetime prevalence of PTSD in the general population, showing the pandemic's incredible impact.
Assuntos
COVID-19 , Transtornos de Estresse Pós-Traumáticos , COVID-19/epidemiologia , Hospitais , Humanos , Pandemias , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Inquéritos e QuestionáriosRESUMO
Continuous high-frequency stimulation of the globus pallidum internum (GPi) is an accepted treatment for patients with primary dystonia. In a series of 18 consecutive dystonia cases that were successfully treated by bilateral GPi stimulation, 1 patient had an adverse event involving the downward migration of the electrodes. He developed remarkable behavioral complications and was found to have dislodgement of the left electrode to a position close to the left amygdala. The patient developed behavioral changes consisting of depression, psychotic symptoms, and heightened pain perception. This syndrome reverted when the left electrode was removed and a new one inserted in the correct position. We describe in detail the clinical features associated with left amygdala dysregulation induced by high-frequency stimulation through the displaced electrode.