RESUMO
BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease characterized by rapidly progressive dementia, motor impairments, and psychiatric symptoms. Sensory disturbances were occasionally reported as well. The study aims to describe the sensory symptoms of the disease. METHODS: The CJD Israeli National Database was screened for patients who presented sensory symptoms throughout the disease course. Symptoms, characteristics, and distribution were reviewed and the demographic and clinical data (sex, etiologies of the disease, age of onset, disease duration, neurological exam finding, tau protein level, EEG and MRI findings) were compared with the demographics and clinical data of CJD without sensory symptoms. Then, the patients with sensory symptoms were divided into patients with symptom distribution consistent with peripheral nervous system (PNS) involvement and central nervous system (CNS) involvement. The demographics and clinical data of the 2 groups were compared. RESULTS: Eighty-four CJD patients with sensory symptoms and 645 CJD patients without sensory symptoms were included in the study. Sensory symptoms were more common in genetic E200K CJD patients (14.6% vs. 5.6% respectively, p = 0.0005) (chi-squared test). Numbness and neuropathic pain were the most common symptoms and distribution of symptoms of "stocking gloves" with decreased deep tendon reflexes suggesting peripheral neuropathy in 44% of the patients. In these patients, the classical EEG findings of Periodic Sharp Wave Complexes were less often found (58% vs. 22%, p = 0.02) (chi-squared test). CONCLUSIONS: Sensory symptoms are more common in E200K patients and often follow peripheral neuropathy distribution that suggests PNS involvement.
Assuntos
Síndrome de Creutzfeldt-Jakob , Doenças Neurodegenerativas , Doenças do Sistema Nervoso Periférico , Humanos , Síndrome de Creutzfeldt-Jakob/complicações , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagem , Doenças Neurodegenerativas/diagnóstico , Imageamento por Ressonância Magnética , Diagnóstico Diferencial , Transtornos de Sensação/etiologia , Transtornos de Sensação/diagnóstico , Doenças do Sistema Nervoso Periférico/diagnósticoRESUMO
BACKGROUND: The largest cluster of genetic Creutzfeldt- Jakob Disease (CJD) exists in Libyan Jews carrying the E200K mutation in the PRNP gene. However, there is another cluster of genetic CJD with E200K mutation in families of Turkish-Jewish origin. AIMS: In this retrospective study, we aim to describe the demographic and clinical features of this population of patients. MATERIAL AND METHODS: The Israeli National CJD database was searched for demographic, clinical, imaging, and laboratory data of genetic CJD patients of Libyan and Turkish ancestry with the E200K mutation. The data of Libyan and Turkish patients were compared with notice similar or different demographic or clinical courses. RESULTS: Four hundred and twenty-three patients with CJD of Libyan (L) ancestry and 27 patients with CJD of Turkish (T) ancestry were identified. There were no significant differences in demographic and clinical data between the two populations (age of onset: T = 62 ± 8.8, L = 60 ± 9.7; age of death: T = 63 ± 8.6, L = 61 ± 9.7; and disease duration: T = 7.8 ± 8.4 months, L = 9.6 ± 13.6 months). Rapidly progressive dementia was the most common presentation in both groups, followed by pure cerebellar onset. The levels of tau protein in CSF did not differ between groups (T = 1290 ± 397.6 pg/ml, L = 1276 ± 594.2 pg/ml). MRI and EEG showed classical CJD features in most patients in both groups. DISCUSSION: The E200K mutation is the most common mutation among gCJD patients and was reported in different ethnical populations, suggesting several independent haplotypes of the mutation. The Turkish-Jew cluster, first described in this study, shares similar demographic and clinical features with the bigger cluster of Libyan-Jews CJD patients. CONCLUSION: E200K gCJD patients of Turkish ancestry share similar demographic and clinical features to patients of Libyan descent, suggesting a common origin of both populations.
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Síndrome de Creutzfeldt-Jakob , Síndrome de Creutzfeldt-Jakob/epidemiologia , Síndrome de Creutzfeldt-Jakob/genética , Demografia , Humanos , Judeus/genética , Mutação/genética , Estudos Retrospectivos , Proteínas tauRESUMO
BACKGROUND: Creutzfeldt-Jacob disease (CJD) is a fatal neuro-degenerative disease, characterized by rapid and intense deterioration, mainly cognitive, leading to death. The typical onset of the disease is around the age of 67. PURPOSE: To characterize the demographic and clinical features of the population of CJD patients with late-onset disease. METHODS: In this retrospective study, the Israeli national database of prion diseases was screened for CJD patients with disease age of onset > 80 years between 1960 and 2016. Patient's demographic and clinical data were collected including sex, type of disease (sporadic/ genetic), clinical presentation, lab results including tau protein level, imaging, and EEG characteristics. Then, the clinical and demographic data of patients with late onset (> 80 years) (L) and patients with usual age of onset (< 80 years) (U) were compared. RESULTS: The study included 728 patients, 23 patients (3.3%) with late-onset disease (82.2.4±4 years, range 80-88) and 705 with usual disease onset (61.31 ± 9.47 years, range 34-80). Sporadic CJD was more common in the late-onset group (18/23 patients (78.2%) (L) vs. 256/705 patients (36.3%) (U)) (p = 0.0001, chi-square test). Classical EEG finding of periodic sharp wave activity were seen more often in the late-onset patients (55% (L) vs. 32.5% (U)) (p = 0.05, chi-square test). The rest of the demographic and clinical features were similar in both groups. CONCLUSION: Late- and usual-onset diseases are similar in most of demographic and clinical features suggesting a common disease type with normal distribution of age of onset.
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Síndrome de Creutzfeldt-Jakob , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/epidemiologia , Síndrome de Creutzfeldt-Jakob/genética , Humanos , Transtornos de Início Tardio , Estudos RetrospectivosRESUMO
Previous studies have suggested that disease duration in Creutzfeldt-Jakob disease (CJD) may be related to the radiological findings or cerebrospinal fluid (CSF) tau levels; however, it is not yet established whether clinical, radiological, and laboratory findings at diagnosis can predict survival or have a prognostic value. The aim of this study was to examine whether the disease duration is correlated with clinical, radiological, and laboratory variables. The study population consisted of consecutive familial CJD (fCJD) patients that were assessed within 1 week from the diagnosis including the CJD neurological scale (CJD-NS), Minimental Status Examination, Frontal Assessment Battery, NIH Stroke Scale, and the expanded disability status scale. In addition, a single MRI study was done and measurements of the extent of the cortical and subcortical involvement were performed. CSF was examined as part of the workout, and tau levels were determined. Sixty-nine fCJD patients were included in the study (43 males, mean age 59.3 ± 8.4, range 44-79 years). The mean disease duration was 7.3 ± 6.9 months (median 5.6 months, range 2-20 months). A significant correlation was found between the disease duration and the CJD-NS, the disease burden as reflected by the degree of cortical involvement by DWI, and the CSF tau levels. The findings of the current study reveal that several findings at disease onset including the disease severity, the cortical changes, and the tau levels are each individually correlated with disease duration and can be used by the clinician as a tool to predict the disease course and prognosis.
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Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/patologia , Proteínas tau/líquido cefalorraquidiano , Adulto , Idoso , Encéfalo/patologia , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Priônicas/genética , PrognósticoRESUMO
INTRODUCTION: Previous studies showed concordance between the typical Periodic Sharp Wave Complex (PSWC) activity in EEG of Creutzfeldt-Jakob Disease (CJD) patients and the MRI findings, while the concordance with slow activity in EEG is less established. The aim of this study was to better characterize the association between MRI findings and EEG changes using quantitative EEG (qEEG) analysis. METHODS: The demographics, clinical features, and the MRI findings of 12 familial E200K patients with CJD were gathered. EEG test was done and reviewed for the typical PSWC and for the non-specific slow activity. A possible association between the MRI findings and the EEG activity was examined. Then, EEG was analyzed using qEEG tool, and the association between the qEEG finding and the MRI was examined. RESULTS: Twelve patients were included in the study (67% women). Cortical MRI lesions finding were seen in 6/12 (50%) of the patients, and deep gray mater lesions were seen in 8/12 patients (67%). EEG showed the classic PSWC in 6/12 (50%) of the patients where slow activity was seen in 10/12 (83%). Slow activity and cortical MRI findings were associated in only 2/6 (33%) where deep gray matter findings and the slow activity had concordance of 4/8 (50%). qEEG analysis improved this concordance between slow activity and cortical findings to 3/6 (50%) and with the deep gray matter findings to 5/8 (63%). CONCLUSIONS: Quantitative EEG analysis modesty but not significantly, improves the association of EEG slow activity in familial E200K CJD patients with MRI findings.
Assuntos
Síndrome de Creutzfeldt-Jakob/fisiopatologia , Eletroencefalografia/métodos , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Síndrome de Creutzfeldt-Jakob/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The use of diffusion MRI improved the accuracy of diagnosis in Creutzfeldt-Jakob disease (CJD) and expanded our knowledge of the changes occurring in the brain during the disease. The aim of this study was to test whether in patients with E200K familial CJD (fCJD) the clinical severity correlates with the disease burden as reflected by the extent of cortical involvement in DWI MRI. Consecutive fCJD patients were examined by a neurologist who performed several tests including the CJD neurological scale (CJD-NS), MiniMental status examination (MMSE), Frontal Assessment Battery (FAB), NIH Stroke Scale (NIHSS), and the expanded disability status scale (EDSS). A simultaneously acquired MRI was analyzed by measuring the extent of cortical involvement in the DWI axial sequence. Correlations were tested for using Pearson test. Fifty-two fCJD patients (35 males, mean age 59.4 ± 5.7 years) were recruited to the study. Significant negative correlation was found between the extent of cortical involvement and the cognitive performance of the patients as reflected by their MMSE and FAB scores. In addition, a significant positive correlation was found between the MRI and the clinical disease severity scales CJD-NS and EDSS. The correlation between clinical scales of severity and cognitive dysfunction and the disease burden confirms the reliability of the CJD-NS scale. Further studies are warranted to examine whether MRI may serve not only for diagnosis but also as a biomarker for follow-up of disease progression and the efficacy of potential treatments.
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Encéfalo/diagnóstico por imagem , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Mutação/genética , Idoso , Encéfalo/patologia , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/etiologia , Síndrome de Creutzfeldt-Jakob/complicações , Síndrome de Creutzfeldt-Jakob/genética , Avaliação da Deficiência , Saúde da Família , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Príons/genética , Estatística como AssuntoRESUMO
BACKGROUND: On May 2017, two generic drugs for fingolimod were introduced into the market in Israel, and most MS patients treated with Gilenya® (Novartis) were switched to fingolimod (Teva), or to Finolim (Rafa). In this study we analyzed the consequences of switching to generic fingolimod in a single MS center. METHODS: Study population included relapsing MS patients who were treated with Gilenya® for at least two year before May 2017, switched to generic fingolimod and remained on treatment for at least 2 years thereafter. Data before and after the switch were compared. RESULTS: Twenty-seven patients fulfilled the inclusion criteria (F = 20, RRMS=20, SPMS=7, average age 49±11.4 years, average disease duration=16.6 ± 7.6 years). Seventeen patients had to be switched back to the original Gilenya® due to intolerable new or worsening clinical adverse events (n = 9), clinical relapse (n = 1), clinical relapse with adverse events (n = 3), elevation of liver enzymes > X3 ULN (n = 3) and elevation of amylase (n = 1). Expanded Disability Status Scale (EDSS) score increased in 4 patients during the year before the switch, and in 12 patients during the year of treatment with generic fingolimod (p = 0.036). CONCLUSION: The tolerability, retention rate and probably efficacy of generic fingolimod seems to be lower than the original Gilenya®.
Assuntos
Cloridrato de Fingolimode , Esclerose Múltipla Recidivante-Remitente , Humanos , Adulto , Pessoa de Meia-Idade , Cloridrato de Fingolimode/efeitos adversos , Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/induzido quimicamente , Medicamentos Genéricos/efeitos adversos , Recidiva , Resultado do TratamentoRESUMO
OBJECTIVES: The onset of Creutzfeldt-Jakob disease (CJD) is usually around the age of 60, but younger patients have been described as well. Our study characterizes the demographic and clinical features of young-onset CJD patients. METHODS: The CJD Israeli National Database was reviewed, and the patients were divided into groups of young (<40-year-old) (Y|) and older disease onset (>40-year-old) (O). Each group was further divided into sporadic (sCJD) and genetic (gCJD) patients. Clinical and demographic parameters were compared between the groups. RESULTS: The study included 731 patients (Y- 18 patients, O- 713 patients). MRI showed classical features more often in the older population (O-76.9%, Y-36%, p = 0.006). Rapidly progressive dementia as a presenting feature was more common in the older group (O = 58%, Y = 27.7%, p = 0.019) whereas cerebellar onset (gait instability, dysarthria) was more common in the younger group (O = 6.7%, Y = 27.7%, p = 0.036)). Among gCJD patients, rapidly progressive dementia was commonly seen in older patients (O = 54%, Y = 21% p = 0.008) whereas cerebellar symptoms were seen in young patients (O = 7%, Y = 30% p = 0.01) Typical MRI findings were seen in 37% of young people compared to 87% of older patients (p = 0.002). No significant differences were between young and older patients in the sCJD group. CONCLUSION: Young-onset gCJD patients have unique disease features including less typical brain MRI changes, a lower prevalence of dementia, and a higher prevalence of cerebellar signs at disease onset.
Assuntos
Síndrome de Creutzfeldt-Jakob , Humanos , Adolescente , Idoso , Adulto , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagem , Síndrome de Creutzfeldt-Jakob/epidemiologia , Imageamento por Ressonância Magnética , Bases de Dados Factuais , Encéfalo/diagnóstico por imagemRESUMO
BACKGROUND: Frontal-type cognitive deficits are common in patients with Parkinson disease (PD). The Frontal Assessment Battery (FAB) was developed to assess frontal lobe functions. However, many studies found that it also correlated with a variety of other general neuropsychological tests. OBJECTIVES: To evaluate whether the FAB has an added value over the Mini-Mental State Examination (MMSE) and other bedside neuropsychological tests in reflecting cognitive deficits in patients with PD. METHODS: Seventy-two consecutive patients with PD underwent cognitive assessment including the FAB, the MMSE, and a variety of other neuropsychological tests. Correlations were examined using the Spearman's r. RESULTS: Highly significant correlations were found between the total FAB score and tests of attention, executive functions, and memory. To evaluate the contribution of the FAB beyond that of the MMSE, partial correlation was used. Analyses revealed that the FAB still correlated with most of the tests. Dividing the patients according to the median MMSE score revealed that the high correlation between the FAB and the MMSE was preserved in the low MMSE group, while in the high MMSE group the correlation was relatively low. In the high MMSE group, the FAB correlated with 11 tests compared to the MMSE that correlated with one (P < .001), while in the low MMSE group the number of correlations was 13 versus 7, respectively (P = .05). CONCLUSIONS: In our sample of patients with PD, the FAB correlated with dysfunction in a variety of cognitive domains including attention, memory, and executive functions. The FAB has an added value over the MMSE, particularly among nondemented patients, an advantage that can be used in clinical practice.
Assuntos
Transtornos Cognitivos/diagnóstico , Lobo Frontal/fisiopatologia , Testes Neuropsicológicos , Doença de Parkinson/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Atenção , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Função Executiva , Feminino , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Doença de Parkinson/psicologiaRESUMO
BACKGROUND: While myoclonus and ataxia are considered common in patients with familial Creutzfeld-Jakob disease (fCJD), other movement disorders are less prevalent. OBJECTIVES: To systemically evaluate the frequency of extrapyramidal signs and movement disorders in patients with fCJD. METHODS: A detailed neurological examination, with special emphasis on movement disorders and extrapyramidal signs, was conducted in 43 consecutive symptomatic CJD patients (26 males and 17 females; mean age 58.7 +/- 8.9 yrs, range 43-77 years) carrying the E200K mutation in the PRNPgene. RESULTS: Limb or gait ataxia was noted in 38 patients (88%) (37 patients, 86%, had ataxia at presentation). Myoclonus was evident in 25/43 patients (58%) (21 patients, 49%, at presentation). In 95% of the patients (41/43) (37/43, 86% at presentation) at least one extrapyramidal sign throughout the disease course was noted, the most prevalent being rigidity (28/43, 65% of the patients; and 22/43, 51% at presentation), followed by the glabellar sign (24/43, 56% of the patients; and 22/43, 51% at presentation), bradykinesia (19/43, 44%; and 15/43, 35% at presentation), dystonia (15/43, 35%; 12/43, 28% at presentation) and tremor (13/43, 30%; 12/43, 28% at presentation). CONCLUSIONS: In this unique population of fCJD patients, myoclonus was less prevalent than previously reported while other extrapyramidal signs were common and occurred at a relatively early stage of the disease. The high prevalence of movement disorders can be added to other phenomena characteristic of this familial disorder among Libyan lews. Whether this is attributable to the E200K mutation itself or to some other mechanism has still to be elucidated.
Assuntos
Doenças dos Gânglios da Base/epidemiologia , Síndrome de Creutzfeldt-Jakob/epidemiologia , Judeus , Transtornos dos Movimentos/epidemiologia , Adulto , Idoso , Doenças dos Gânglios da Base/genética , Síndrome de Creutzfeldt-Jakob/genética , Feminino , Humanos , Israel , Líbia/etnologia , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/genética , Mutação , Mioclonia/epidemiologia , Mioclonia/genética , Prevalência , Proteínas Priônicas , Príons/genética , Estudos ProspectivosRESUMO
Parkinson's disease (PD) is taking a staggering toll on healthcare systems worldwide, with the bulk of the expenditures invested in the late stages of the disease. Considering the rising life expectancy and the increasing prevalence of PD across the globe, a clear understanding of the early signs and treatment options available for advanced PD (APD), will facilitate tailoring management programs and support services. This task is complicated by the lack of both global consensus in defining APD and standardized care guidelines. This perspective prepared by a panel of movement disorder specialists, proposes to extend and optimize currently accepted PD coding to better reflect the diverse disease manifestations, with emphasis on non-motor features. The panel seeks to promote timely diagnosis by adjustment of evaluation tools for use by community neurologists and suggests modification of eligibility criteria for advanced therapy. Moreover, it advocates multidisciplinary assessments of APD patients to drive personalized, patient-centered and holistic management. Overall, earlier and more targeted intervention is expected to markedly improve patient quality of life.
RESUMO
C-reactive protein (CRP) is a plasma protein involved in inflammation. While its levels have been associated with stroke, cognitive impairment and depression, the association with clinical characteristics of Parkinson's disease (PD) is unknown. A total of 73 consecutive patients with PD (46 males, age 68.8 ± 11.5 years) were evaluated regarding motor as well as cognitive and psychiatric features of PD. Plasma CRP levels were determined and tests for associations with disease parameters were performed. The average level of CRP was 3.9 ± 4.1 µmol/L, and 45.2% of the patients (n = 33) had a level above 3.0 µmol/L. Patients in the high CRP group tended to be older (71.4 ± 9.2 vs. 66.7 ± 12.9 years; p = 0.08) and coronary artery disease (CAD) was more common (36 vs. 10%, p < 0.05) in the high CRP group, but no differences were found between the groups regarding gender, disease duration, levodopa dose, motor scores or most of the neuropsychiatric complications such as severity of depression, psychosis, dementia, cognitive decline or frontal lobe dysfunction. Reported depression (at present or in the past) was more common in the high CRP group (54.5 vs. 25%, p = 0.01). CRP levels in patients with PD are associated with a higher prevalence of CAD, but are not associated with PD duration or severity, or with neuropsychiatric complications other than reported depression.
Assuntos
Proteína C-Reativa/metabolismo , Transtornos Cognitivos/sangue , Transtornos Mentais/sangue , Transtornos do Humor/sangue , Transtornos dos Movimentos/sangue , Doença de Parkinson/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/patologia , Comorbidade/tendências , Progressão da Doença , Feminino , Humanos , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/patologia , Pessoa de Meia-Idade , Transtornos do Humor/epidemiologia , Transtornos do Humor/patologia , Transtornos dos Movimentos/epidemiologia , Transtornos dos Movimentos/patologia , Doença de Parkinson/epidemiologia , Doença de Parkinson/psicologia , Estudos ProspectivosRESUMO
OBJECTIVES: Electroencephalogram (EEG) pattern in Creutzfeldt-Jakob disease (CJD) is characterized by diffuse abnormal activity, although lateralization to one hemisphere has been described in the first stages of the disease. This study aimed to determine whether abnormal EEG activity predominantly occurs in anterior versus posterior brain regions. METHODS: As part of a prospective study, the demographics, clinical features and MRI findings of genetic E200K CJD patients were collected. EEG was performed and the recordings reviewed for the typical periodic sharp wave complex (PSWC) and non-specific slow activity. Data were analyzed using the qEEG tool, and the activity in anterior and posterior regions of the brain compared. RESULTS: Eleven genetic E200K CJD patients were included in the study (67% women). The average age was 59.1⯱â¯8.4 SD years and the average disease duration was 2.4⯱â¯2.1 months. EEG showed the classic PSWC pattern in 5/11 (45%) of the patients, and slow activity was seen in 9/11 (82%). EEG was normal in 2 patients. PSWC activity was diffuse in 2/5 patients and unilateral in 3/5 patients; slow activity was diffuse in 9 patients. Quantitative analysis of PSWC and slow activity showed no significant difference between anterior and posterior distribution. CONCLUSION: The abnormal EEG activity in CJD is diffuse with no clear spatial predominance in anterior or posterior brain regions.
Assuntos
Síndrome de Creutzfeldt-Jakob , Idoso , Encéfalo , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: To characterize the demographic, clinical features and disease course of familial Creutzfeldt-Jakob disease (fCJD) patients homozygous to the E200K mutation. METHODS: The Israeli National CJD Database was screened for patients homozygous to the E200K mutation. Patients' demographic data, clinical presentation and neurological findings, tau protein levels in the cerebrospinal fluid (CSF) and EEG, were assessed. RESULTS: Ten homozygous E200K patients were identified (80% males). Average age of onset was 47.5 ± 6.1 years (range 40-56) and the average age of death was 49.3 ± 7. 7 years (range 42-63) with average disease duration of 27.7 ± 9.7 months (range 2-97). Initial clinical presentation included behavioral change in 4/10 patients, cognitive decline in 3/10 patients and focal neurological deficits in 2/10 patients. Throughout the disease course, the clinical signs in descending order of prevalence included cerebellar (70%), brainstem (60%), extrapyramidal (50%), pyramidal (50%), frontal lobe signs (30%), and disturbances of ocular motility (30%) Compared to the 228 heterozygous E200K fCJD patients, the 10 homozygous patients were significantly younger at disease onset (47.5 vs 59.7 years, p < 0.001), had a longer disease duration (27.7 vs 8.5 months, p < 0.001) and presented more frequently with behavioral changes as initial manifestation (4/10 vs. 34/228, p = 0.05). CONCLUSIONS: Homozygous E200K fCJD patients are characterized by a relatively younger age of onset and longer disease duration. Behavioral changes as a presenting symptom were more common in homozygous patients and cerebellar dysfunction was the most common neurological manifestation throughout the disease course.
Assuntos
Síndrome de Creutzfeldt-Jakob , Adulto , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/epidemiologia , Síndrome de Creutzfeldt-Jakob/genética , Progressão da Doença , Feminino , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genéticaRESUMO
Fingolimod was the first oral disease-modifying drug approved for the treatment of relapsing-remitting multiple sclerosis (MS). It has previously been associated with rare cases of lymphoma. Here we describe the first case of mycosis fungoides - a cutaneous lymphoproliferative disorder, in an MS patient treated with fingolimod. who developed histologically confirmed mycosis fungoides 3â¯years after starting fingolimod. The drug was withdrawn and the patient was treated with radiotherapy and surgical excision with remission. This report points to a possible association between fingolimod and skin lymphoproliferative disorder and emphasizes the need for periodic skin examination.
Assuntos
Cloridrato de Fingolimode/efeitos adversos , Cloridrato de Fingolimode/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Micose Fungoide/etiologia , Neoplasias Cutâneas/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Micose Fungoide/radioterapia , Micose Fungoide/cirurgia , Pele/patologia , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/cirurgia , Resultado do TratamentoRESUMO
PURPOSE: To study the effects of a repetitive deep transcranial magnetic stimulation (rDTMS) in patients with Parkinson disease using the H5 coil for the low-frequency stimulation of the primary motor cortex, followed by the high-frequency rDTMS of the prefrontal cortex. METHODS: The main outcome measures were the total and motor scores of the Unified Parkinson's Disease Rating Scale (UPDRS). Secondary measures included rating of depression and quantitative motor tasks. RESULTS: Forty-eight patients were randomized 1:1 into real or sham rDTMS treatment arms. Analyses (n = 42) of both UPDRS scores revealed a significant main effect for time between baseline and day 90 (end of treatment), indicating that there was an improvement of both scores over time in the whole sample. Although effects of treatment and time-by-treatment were insignificant, simple effects analysis of both measures was significant in the rDTMS group and reached a P-value of 0.06 in the sham group. The response rate was higher in patients with longer disease duration and higher motor UPDRS scores. Side effects were more common in the rDTMS group but were transient and tolerable. CONCLUSIONS: Although rDTMS treatment exhibited some motor improvements, we could not demonstrate an advantage for real treatment over sham. Further research is required to establish stimulation parameters that may induce potentially more beneficial outcomes, probably in patients with longer and more sever disease.
Assuntos
Córtex Motor/fisiologia , Doença de Parkinson/terapia , Estimulação Magnética Transcraniana/métodos , Idoso , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
OBJECTIVE: To determine whether plasma homocysteine (Hcy) levels are associated with clinical characteristics, neuropsychological and psychiatric manifestations and cardiovascular comorbidity in patients with Parkinson disease (PD). BACKGROUND: Elevated Hcy levels are linked to atherosclerosis, vascular disease, depression, and dementia. Patients with PD treated with L-dopa have been shown to have elevated Hcy levels. DESIGN/METHODS: Idiopathic PD patients were evaluated using the Unified Parkinson's Disease Rating Scale, Hoehn and Yahr stage, Parkinson Psychosis Rating Scale, Beck Depression Inventory, Frontal Assessment Battery, Mini-Mental Status Examination, and several tests for frontal type cognitive functions. Fasting blood samples were collected for the measurement of Hcy, and carotid B-mode ultrasound was performed to measure intima-media thickness of the common carotid arteries. RESULTS: Seventy-two consecutive PD patients (46 men; average age, 68.7 +/- 11.6 years; average disease duration, 7.0 +/- 4.7 years) were recruited. All but 10 patients were treated with L-dopa. The average level of Hcy was 16.4 +/- 7.8 micromol/L, and 38.9% of the patients had Hcy level above the reference range (>15.0 micromol/L). The Hcy levels were associated with PD duration as they were with L-dopa treatment duration but were not associated with the parameters of disease severity or with L-dopa dose. The Hcy levels were associated neither with the common carotid intima-media thickness nor with cardiovascular morbidity. No association was found between Hcy and the neuropsychiatric features of PD such as depression, cognitive performance, or psychosis. CONCLUSIONS: Hyperhomocystinemia is common in L-dopa-treatedPD patients but was not associated with neuropsychological complications (depression, dementia, and cognitive decline associated with frontal lobe functioning or psychosis), enhanced disease severity, or vascular comorbidity.
Assuntos
Homocisteína/sangue , Doença de Parkinson , Transtornos Psicóticos/etiologia , Túnica Íntima/patologia , Túnica Média/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/uso terapêutico , Progressão da Doença , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/sangue , Doença de Parkinson/complicações , Doença de Parkinson/patologia , Túnica Íntima/efeitos dos fármacos , Túnica Média/efeitos dos fármacosRESUMO
OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS), using standard coils, provided modest symptomatic benefits in patients with Parkinson's disease (PD). In our previous exploratory studies, using the newly developed Hesed coil (providing deeper rTMS; rDTMS) high frequency (HF), excitatory rDTMS over the primary motor cortex (M1), did not achieve sufficient beneficial effect for PD symptoms, while low frequency (LF) inhibitory stimulation, was mildly beneficial. To further investigate the optimal rDTMS stimulation parameters for PD patients, and to assess whether there is an added value for dual stimulation, consisting of HF rDTMS over the prefrontal cortex (PFC) along with LF M1 rDTMS. The rational for the selection of the current stimulation parameters and sites lies on the previous studies that demonstrated an inhibitory effect of 1Hz rTMS on the increased cortical activity in PD as well as dopamine release by PFC stimulation. PATIENTS AND METHODS: An open comparative active study of one month duration (12 sessions) of LF rDTMS over M1 alone (n=9) or combined with HF PFC rDTMS (M1-PFC, n=10). Outcome measures included the total and motor Unified Parkinson's Disease Rating Scale scores (T-UPDRS and M-UPDRS) and other variables, were collected at baseline and on days 30 and 60. RESULTS: For the M1+PFC group, T-UPDRS score improved from baseline to day 30, by 15% (median: 52 points, decreased to 44, p=0.02, effect size: 0.51) and M-UPDRS score improved by 24% (median: 37 points decreased to 28, p=0.04, effect size: 0.47). The corresponding results for the M1 group were insignificant. Additionally, the between groups comparison, was insignificant. CONCLUSION: rDTMS, consisting of M1 excitation with PFC inhibition improved PD motor symptoms but was not significantly superior to M1 rDTMS alone. rDTMS stimulation protocols for M1 should be further evaluated in larger scale controlled studies.
Assuntos
Atividade Motora/fisiologia , Córtex Motor/fisiopatologia , Doença de Parkinson/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Estimulação Magnética Transcraniana , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Magnética Transcraniana/métodosRESUMO
Cerebrospinal fluid (CSF) tau was found to correlate with disease severity and cognitive status in E200K familial Creutzfeldt-Jakob disease (fCJD) patients. The objective of the present study was to test whether tau levels in the CSF also correlate with the disease burden as reflected by the degree of cortical involvement in DWI MRI. Forty-four consecutive E200K fCJD patients (25 males, mean age 58.6±7.5, range 48-75 years) were recruited to the study and had a CSF tau examination as well as measurements of the extent of the cortical involvement in the DWI axial MRI. Correlation was tested using Pearson test. A significant correlation (r=0.617 p<0.0001) was found between CSF tau levels and the extent of cortical involvement. This correlation between tau levels and the disease burden reinforce the notion that tau can be used as a biomarker reflecting the extent of disease in patients with E200K fCJD.
Assuntos
Córtex Cerebral/patologia , Síndrome de Creutzfeldt-Jakob/patologia , Proteínas tau/líquido cefalorraquidiano , Idoso , Biomarcadores/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Familial Creutzfeldt-Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. While carriers are born with this mutation, they usually remain asymptomatic until middle age. Early detection of conversion is crucial for understanding and eventually for the treatment of the disease. The aim of this study was to report longitudinal MRI data in E200K individuals who eventually converted from healthy mutation carriers to clinically symptomatic CJD. As a part of a prospective study, asymptomatic E200K mutation carriers were scanned annually until their conversion to symptomatic disease. Standardized diffusion and anatomical MR sequences were performed before and after clinical conversion in the subjects and those were compared to 15 non-carrier siblings ("healthy controls"). Blinded radiological readings and region of interest analyses were performed. Radiological readings of individual cases failed to detect characteristic changes in the scans taken before the conversion. Region of interest analysis of diffusion changes in pre-symptomatic stage was inconclusive; however, ADC reduction was found in early and late stages of the disease. Computerized volumetric analysis revealed monotonic volume reductions in thalamus, putamen and caudate following conversion, and the lateral ventricles showed dilatation of up to 62 % after clinical conversion. Although the clinical manifestations at disease onset are variable, the diffusion abnormalities and/or volume changes in the thalamus and basal ganglia during conversion may indicate early involvement of the thalamostriatal neuronal circuit.