RESUMO
OBJECTIVE: To compare acute treatment responses and long-term outcome in leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis. METHODS: Retrospective case series of 118 patients with LGI1 antibody encephalitis evaluated at Mayo Clinic across all US sites from 1 May 2008 to 31 March 2019. Patient clinical data were identified and analysed through the neuroimmunology laboratory and electronic medical record. LGI1 antibody detection was by cell-based indirect immunofluorescence assay of serum, cerebrospinal fluid or both. Clinical outcomes were faciobrachial dystonic seizure (FBDS) resolution, modified Rankin Scale (mRS) score, Kokmen Short Test of Mental Status (STMS) score (0-38 point scale) and neuropsychometric testing results. RESULTS: Compared with intravenous immunoglobulin (IVIg) (n=21), patients treated with single-agent acute corticosteroids (intravenous, oral or both) (n=49) were more likely to experience resolution of FBDS (61% vs 7%, p=0.002) and improvements in mRS score (ΔmRS score 2 vs 0, p=0.008) and median Kokmen STMS scores (ΔKokmen STMS score 5 points vs 0 points, p=0.01). In 54 patients with long-term follow-up (≥2 years), the median mRS score was 1 (range 0-6) and the median Kokmen STMS score was 36 (range 24-38) after all combinations of immunotherapy. Neuropsychometric testing in 32 patients with long-term follow-up (≥2 years) demonstrated short-term memory impairments in 37%. CONCLUSIONS: Corticosteroids appeared more effective acutely than IVIg in improving LGI1 antibody encephalitis in this retrospective comparison of immunotherapies. While improvement with immunotherapy is typical and long-term outcome is favourable, short-term memory deficits are noted in approximately a third of the patients.
Assuntos
Corticosteroides/uso terapêutico , Autoanticorpos , Doenças Autoimunes/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Encefalite Límbica/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/imunologia , Feminino , Humanos , Encefalite Límbica/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. METHODS AND RESULTS: Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. CONCLUSIONS: Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Autopsia , Humanos , Imageamento por Ressonância Magnética/métodos , Bainha de Mielina/patologiaRESUMO
Hereditary frontotemporal dementia associated with mutations in the microtubule-associated protein tau gene (MAPT) is a protean disorder. Three neuropathologic subtypes can be recognized, based on the presence of inclusions made of tau isoforms with three and four repeats, predominantly three repeats and mostly four repeats. This is relevant for establishing a correlation between structural magnetic resonance imaging and positron emission tomography using tracers specific for aggregated tau. Longitudinal studies will be essential to determine the evolution of anatomical alterations from the asymptomatic stage to the various phases of disease following the onset of symptoms.
Assuntos
Encéfalo/patologia , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Mutação , Proteínas tau/genética , Encéfalo/diagnóstico por imagem , Feminino , Demência Frontotemporal/diagnóstico por imagem , Humanos , Corpos de Inclusão/metabolismo , Corpos de Inclusão/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fosforilação , Tomografia por Emissão de Pósitrons , Isoformas de Proteínas/genética , Tomografia Computadorizada de Emissão , Proteínas tau/metabolismoRESUMO
BACKGROUND AND PURPOSE: The aim of our study was to determine the utility of longitudinal magnetic resonance imaging (MRI) measurements as potential biomarkers in the main genetic variants of frontotemporal dementia (FTD), including microtubule-associated protein tau (MAPT) and progranulin (GRN) mutations and C9ORF72 repeat expansions, as well as sporadic FTD. METHODS: In this longitudinal study, 58 subjects were identified who had at least two MRI and MAPT mutations (n = 21), GRN mutations (n = 11), C9ORF72 repeat expansions (n = 11) or sporadic FTD (n = 15). A total of 198 serial MRI measurements were analyzed. Rates of whole brain atrophy were calculated using the boundary shift integral. Regional rates of atrophy were calculated using tensor-based morphometry. Sample size estimates were calculated. RESULTS: Progressive brain atrophy was observed in all groups, with fastest rates of whole brain atrophy in GRN, followed by sporadic FTD, C9ORF72 and MAPT. All variants showed greatest rates in the frontal and temporal lobes, with parietal lobes also strikingly affected in GRN. Regional rates of atrophy across all lobes were greater in GRN compared to the other groups. C9ORF72 showed greater rates of atrophy in the left cerebellum and right occipital lobe than MAPT, and sporadic FTD showed greater rates in the anterior cingulate than C9ORF72 and MAPT. Sample size estimates were lowest using temporal lobe rates in GRN, ventricular rates in MAPT and C9ORF72, and whole brain rates in sporadic FTD. CONCLUSION: These data support the utility of using rates of atrophy as outcome measures in future drug trials in FTD and show that different imaging biomarkers may offer advantages in the different variants of FTD.
Assuntos
Encéfalo/patologia , Demência Frontotemporal/patologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Imageamento por Ressonância Magnética/métodos , Proteínas/genética , Proteínas tau/genética , Idoso , Atrofia/patologia , Biomarcadores , Proteína C9orf72 , Feminino , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/genética , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mutação , ProgranulinasRESUMO
BACKGROUND: Recently, a novel mutation in exon 24 of DNAJC13 gene (p.Asn855Ser, rs387907571) has been reported to cause autosomal dominant Parkinson's disease (PD) in a multi-incident Mennonite family. METHODS: In the present study the mutation containing exon of the DNAJC13 gene has been sequenced in a Caucasian series consisting of 1938 patients with clinical PD and 838 with pathologically diagnosed Lewy body disease (LBD). RESULTS: Our sequence analysis did not identify any coding variants in exon 24 of DNAJC13. Two previously described variants in intron 23 (rs200204728 and rs2369796) were observed. CONCLUSION: Our results indicate that the region surrounding the DNAJC13 p.Asn855Ser substitution is highly conserved and mutations in this exon are not a common cause of PD or LBD among Caucasian populations.
Assuntos
Doença por Corpos de Lewy/genética , Chaperonas Moleculares/genética , Doença de Parkinson/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa (Continente) , Éxons , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , MutaçãoRESUMO
BACKGROUND AND PURPOSE: Midbrain atrophy is a characteristic feature of progressive supranuclear palsy (PSP), although it is unclear whether it is associated with the PSP syndrome (PSPS) or PSP pathology. The aim of the present study was to determine whether midbrain atrophy is a useful biomarker of PSP pathology, or whether it is only associated with typical PSPS. METHODS: All autopsy-confirmed subjects were identified with the PSP clinical phenotype (i.e. PSPS) or PSP pathology and a volumetric MRI. Of 24 subjects with PSP pathology, 11 had a clinical diagnosis of PSPS (PSP-PSPS), and 13 had a non-PSPS clinical diagnosis (PSP-other). Three subjects had PSPS and corticobasal degeneration pathology (CBD-PSPS). Healthy control and disease control groups (i.e. a group without PSPS or PSP pathology) and a group with CBD pathology and corticobasal syndrome (CBD-CBS) were selected. The midbrain area was measured in all subjects. [Correction added on 21 June 2013, after first online publication: the abbreviation of corticobasal degeneration pathology was changed from CBD-PSP to CBD-PSPS.] RESULTS: The midbrain area was reduced in each group with clinical PSPS (with and without PSP pathology). The group with PSP pathology and non-PSPS clinical syndromes did not show reduced midbrain area. Midbrain area was smaller in the subjects with PSPS than in those without PSPS (P < 0.0001), with an area under the receiver operator curve of 0.99 (0.88, 0.99). A midbrain area cut-point of 92 mm(2) provided optimum sensitivity (93%) and specificity (89%) for differentiation. CONCLUSION: Midbrain atrophy is associated with the clinical presentation of PSPS, but not with the pathological diagnosis of PSP in the absence of clinical PSPS. This finding has important implications for the utility of midbrain measurements as diagnostic biomarkers for PSP pathology.
Assuntos
Mesencéfalo/patologia , Paralisia Supranuclear Progressiva/patologia , Idoso , Idoso de 80 Anos ou mais , Atrofia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , SíndromeRESUMO
AIMS: Rapid eye movement sleep behaviour disorder (RBD) is characterized by loss of muscle atonia during rapid eye movement sleep and is associated with dream enactment behaviour. RBD is often associated with α-synuclein pathology, and we examined if there is a relationship of RBD with cholinergic neuronal loss in the pedunculopontine/laterodorsal tegmental nucleus (PPN/LDT), compared to catecholaminergic neurones in a neighbouring nucleus, the locus coeruleus (LC). METHODS: This retrospective study utilized human brain banked tissues of 11 Lewy body disease (LBD) cases with RBD, 10 LBD without RBD, 19 Alzheimer's disease (AD) and 10 neurologically normal controls. Tissues were stained with choline acetyl transferase immunohistochemistry to label neurones of PPN/LDT and tyrosine hydroxylase for the LC. The burden of tau and α-synuclein pathology was measured in the same regions with immunohistochemistry. RESULTS: Both the LC and PPN/LDT were vulnerable to α-synuclein pathology in LBD and tau pathology in AD, but significant neuronal loss was only detected in these nuclei in LBD. Greater cholinergic depletion was found in both LBD groups, regardless of RBD status, when compared with normals and AD. There were no differences in either degree of neuronal loss or burden of α-synuclein pathology in LBD with and without RBD. CONCLUSIONS: Whether decreases in brainstem cholinergic neurones in LBD contribute to RBD is uncertain, but our findings indicate these neurones are highly vulnerable to α-synuclein pathology in LBD and tau pathology in AD. The mechanism of selective α-synuclein-mediated neuronal loss in these nuclei remains to be determined.
Assuntos
Tronco Encefálico/patologia , Catecolaminas/metabolismo , Colinérgicos/metabolismo , Transtorno do Comportamento do Sono REM/metabolismo , Transtorno do Comportamento do Sono REM/patologia , Idoso , Idoso de 80 Anos ou mais , Tronco Encefálico/metabolismo , Feminino , Humanos , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/patologia , Locus Cerúleo/metabolismo , Masculino , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Transtorno do Comportamento do Sono REM/diagnóstico , Estudos Retrospectivos , alfa-Sinucleína/metabolismoRESUMO
BACKGROUND AND PURPOSE: Obsessions and compulsive (OC) behaviors are a frequent feature of behavioral variant frontotemporal dementia (bvFTD), but their structural correlates have not been definitively established. METHODS: Patients with bvFTD presenting to the Mayo Clinic Alzheimer's Disease Research Center were recruited. Each patient's caregiver was given the Yale-Brown Obsessive-Compulsive scale (YBOCS) to document the type and presence of OC behaviors and to rate their severity. All subjects underwent standardized magnetic resonance imaging (MRI) that was evaluated using voxel-based morphometry (VBM). Seventeen patients with bvFTD were recruited, and 11 were included in the study and compared with 11 age- and gender-matched controls. Six were excluded for lack of MRI at the time of survey or a pre-existing neurodegenerative condition. RESULTS: Nine of the 11 reported OC behaviors, with the most frequent compulsions being checking, hoarding, ordering/arranging, repeating rituals, and cleaning. In the VBM analysis, total YBOCS score correlated with gray matter loss in the bilateral globus pallidus, left putamen, and in the lateral temporal lobe, particularly the left middle and inferior temporal gyri (P < 0.001 uncorrected for multiple comparisons). CONCLUSIONS: Obsessive-compulsive behaviors were frequent among these patients. The correlation with basal ganglia atrophy may point to involvement of frontal subcortical neuronal networks. Left lateral temporal lobe volume loss probably reflects the number of MAPT mutation patients included but also provides additional data implicating temporal lobe involvement in OC behaviors.
Assuntos
Demência Frontotemporal/complicações , Transtorno Obsessivo-Compulsivo/etiologia , Transtorno Obsessivo-Compulsivo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Demência Frontotemporal/genética , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Transtorno Obsessivo-Compulsivo/genética , Putamen/patologia , Índice de Gravidade de Doença , Proteínas tau/genéticaRESUMO
BACKGROUND AND PURPOSE: Frontotemporal lobar degeneration (FTLD) can be subdivided into those in which the abnormal protein is tau (FTLD-TAU), the TAR DNA binding protein 43 (FTLD-TDP) and the fused in sarcoma protein (FTLD-FUS). We have observed severe caudate atrophy at autopsy in FTLD-FUS, and hence, we aimed to determine whether caudate atrophy on MRI is a feature that can distinguish FTLD-FUS from FTLD-TDP and FTLD-TAU. METHODS: From a cohort of 207 cases of FTLD, we identified all cases of FTLD-FUS that had a volumetric antemortem head MRI (n = 3). Caudate and frontal lobe volumes were measured in all three cases using atlas-based parcellation and SPM5 and were compared to 10 randomly selected cases of FTLD-TDP and 10 randomly selected cases of FTLD-TAU. Total grey matter volumes were also calculated for all cases. RESULTS: The FTLD-FUS cases had significantly smaller caudate volumes (P = 0.02) yet similar frontal lobe grey matter volumes (P = 0.12) compared to FTLD-TDP and FTLD-TAU. Caudate volumes when corrected for total grey matter volume (P = 0.01) or frontal lobe grey matter volume (P = 0.01) were significantly smaller in FTLD-FUS than in FTLD-TDP and FTLD-TAU and showed no overlap with the other two groups. CONCLUSIONS: Caudate atrophy on MRI appears to be significantly greater in FTLD-FUS compared with FTLD-TDP and FTLD-TAU, suggesting that severe caudate atrophy may be a useful clinical feature to predict FTLD-FUS pathology.
Assuntos
Núcleo Caudado/patologia , Proteínas de Ligação a DNA/metabolismo , Lobo Frontal/patologia , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/patologia , Proteína FUS de Ligação a RNA/metabolismo , Idoso , Atrofia , Biomarcadores/metabolismo , Mapeamento Encefálico/métodos , Núcleo Caudado/metabolismo , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Lobo Frontal/metabolismo , Demência Frontotemporal/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Proteínas tau/metabolismoRESUMO
REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of normal skeletal muscle atonia during REM sleep with prominent motor activity accompanying dreaming. The terminology relating to RBD, and mechanisms underlying REM sleep without atonia and RBD based on data in cat and rat are presented. Neuroimaging data from the few published human cases with RBD associated with structural lesions in the brainstem are presented, in which the dorsal midbrain and pons are implicated. Pharmacological manipulations which alter RBD frequency and severity are reviewed, and the data from human neuropathological studies are presented. An anatomic framework and new schema for the pathophysiology of RBD are proposed based on recent data in rat regarding the putative flip-flop switch for REM sleep control. The structure in man analogous to the subcoeruleus region in cat and sublaterodorsal nucleus in rat is proposed as the nucleus (and its associated efferent and afferent pathways) crucial to RBD pathophysiology. The association of RBD with neurological disease ('secondary RBD') is presented, with emphasis on RBD associated with neurodegenerative disease, particularly the synucleinopathies. The hypothesized pathophysiology of RBD is presented in relation to the Braak staging system for Parkinson's disease, in which the topography and temporal sequence of synuclein pathology in the brain could explain the evolution of parkinsonism and/or dementia well after the onset of RBD. These data suggest that many patients with 'idiopathic' RBD are actually exhibiting an early clinical manifestation of an evolving neurodegenerative disorder. Such patients may be appropriate for future drug therapies that affect synuclein pathophysiology, in which the development of parkinsonism and/or dementia could be delayed or prevented. We suggest that additional clinicopathological studies be performed in patients with dementia or parkinsonism, with and without RBD, as well as in patients with idiopathic RBD, to further elucidate the pathophysiology and also characterize the clinical and pathophysiological relevance of RBD in neurodegenerative disease. Furthermore, longitudinal studies in patients with idiopathic RBD are warranted to characterize the natural history of such patients and prepare for future therapeutic trials.
Assuntos
Encéfalo/fisiopatologia , Transtorno do Comportamento do Sono REM/fisiopatologia , Animais , Encéfalo/patologia , Humanos , Imageamento por Ressonância Magnética , Modelos Animais , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/fisiopatologia , Transtorno do Comportamento do Sono REM/patologiaRESUMO
Corticobasal syndrome (CBS) is a phenotypic manifestation of diverse pathologies, including Alzheimer's disease and 4-repeat tauopathies. Predicting pathology in CBS is unreliable and, hence, molecular neuroimaging may prove to be useful. The aim of this study was to assess regional patterns of uptake on [18F] AV-1451 PET in CBS and determine whether patterns of uptake differ according to beta-amyloid deposition or differing clinical presentations. Fourteen patients meeting criteria for CBS underwent Pittsburgh Compound B (PiB) and [18F] AV-1451 PET. Seven patients presented as CBS and seven presented with apraxia of speech (AOS) and later evolved into CBS. A global PiB summary was calculated and used to classify patients as PiB (-) or PiB (+). AV-1451 uptake was calculated in fourteen regions-of-interest, with values divided by uptake in cerebellar crus grey matter to generate standard uptake value ratios. AV-1451 uptake was considered elevated if it fell above the 95th percentile from a group of 476 cognitively unimpaired normal controls. Six of the 14 CBS patients (43%) were PiB (+), with three of these patients showing strikingly elevated AV-1451 uptake across many cortical regions. Of the eight PiB (-) patients, only those with AOS showed elevated AV-1451 uptake in supplementary motor area and precentral cortex compared to controls. No region of elevated AV-1451 uptake were observed in PiB (-) typical CBS patients without AOS. These results suggest that regional [18F] AV-1451 is variable in CBS and depends on the presence of beta-amyloid as well as clinical presentation such as AOS. PiB (+) CBS does not necessarily reflect underlying Alzheimer's disease; however, the possibility some of these patients will evolve into Alzheimer's disease over time cannot be excluded.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/diagnóstico por imagem , Carbolinas , Doenças Neurodegenerativas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina , Apraxias/diagnóstico por imagem , Apraxias/metabolismo , Encéfalo/metabolismo , Mapeamento Encefálico , Estudos de Coortes , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/metabolismo , TiazóisRESUMO
BACKGROUND AND PURPOSE: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia reflecting changes in the brain, but which specific neuronal networks are involved in human RBD pathogenesis has not yet been determined. To date, only one case of idiopathic RBD has undergone autopsy, in which "incidental Lewy body disease" was found. Due to the severe neuronal loss and gliosis in the substantia nigra (SN) and locus ceruleus (LC) in this case, degeneration of brainstem monoaminergic neurons was postulated as the underlying substrate for RBD. Additional cases of idiopathic RBD with neuropathologic examination may help clarify which key brainstem structures are involved. PATIENT AND METHODS: Case report with neuropathologic analysis. RESULTS: A man with polysomnographically proven RBD (onset age 57 years), but no other neurologic signs or symptoms, underwent neuropathologic examination upon his death at age 72. Histopathologic analysis showed Lewy body disease, but no significant neuronal loss or gliosis was present in the SN or LC. CONCLUSIONS: This case represents another example of Lewy body disease associated with RBD. The minimal degenerative changes in the SN and LC call into question the role of these nuclei in RBD, at least in our case. We suggest additional cases of idiopathic RBD undergo neuropathologic analyses to better delineate the neurologic substrate of this intriguing parasomnia.
Assuntos
Tronco Encefálico/fisiopatologia , Dispneia/fisiopatologia , Doença por Corpos de Lewy/fisiopatologia , Sono REM/fisiologia , Idoso , Dispneia/diagnóstico , Eletromiografia , Gliose/metabolismo , Gliose/patologia , Humanos , Doença por Corpos de Lewy/metabolismo , Doença por Corpos de Lewy/patologia , Masculino , Pessoa de Meia-Idade , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Polissonografia , Índice de Gravidade de Doença , alfa-Sinucleína/metabolismoRESUMO
The epidemiology of the diagnosis of Parkinson's disease and dementia with Lewy bodies is still based on clinical criteria and the definition of the different diseases is still a challenge for clinician and researcher. The epidemiologic estimates of prevalence and incidence are highly affected by differences in diagnostic criteria, geographic location, and methodologic limitations. Studies of prevalence and incidence show increases with advancing age and a higher rate of Parkinson's disease and dementia with Lewy bodies in men compared to women.
Assuntos
Doença por Corpos de Lewy/epidemiologia , Doença de Parkinson/epidemiologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por SexoRESUMO
Despite general agreement about the boundaries of Alzheimer disease (AD), establishing a maximum limit for Alzheimer-type pathology in cognitively intact individuals might aid in defining more precisely the point at which Alzheimer pathology becomes clinically relevant. In this study, we examined the neuropathological changes in the brains of 39 longitudinally followed. cognitively normal elderly individuals (24 women, 15 men; age range 74-95, median 85 years). Neuropathological changes of the Alzheimer type were quantified by determining neurofibrillary tangle (NFT) staging by the method of Braak and Braak and by quantification of the abundance of diffuse, cored, and neuritic plaque burden using the scheme developed by the Consortium to Establish a Registry for Alzheimer Disease (CERAD). Vascular, Lewy body, and argyrophilic grain pathology were also assessed. We found 34 subjects (87%) with a Braak stage Assuntos
Envelhecimento/patologia
, Encéfalo/patologia
, Cognição/fisiologia
, Avaliação Geriátrica
, Idoso
, Idoso de 80 Anos ou mais
, Envelhecimento/psicologia
, Apolipoproteínas E/genética
, Infarto Encefálico/patologia
, Distribuição de Qui-Quadrado
, Cristalinas/metabolismo
, Demência Vascular/patologia
, Feminino
, Humanos
, Imuno-Histoquímica
, Corpos de Lewy/patologia
, Masculino
, Entrevista Psiquiátrica Padronizada
, Emaranhados Neurofibrilares/patologia
, Neurópilo/patologia
, Filamentos do Neurópilo/patologia
, Testes Neuropsicológicos
, Placa Amiloide/patologia
, Estudos Prospectivos
, Padrões de Referência
, Índice de Gravidade de Doença
, Proteínas tau/metabolismo
RESUMO
BACKGROUND: To date, to our knowledge, there is no systematic presentation of treatment outcome in large series of patients clinically diagnosed as having corticobasal degeneration. OBJECTIVE: To evaluate the clinical presentation and treatment outcome of patients clinically diagnosed as having corticobasal degeneration. SUBJECTS: We gathered case patients seen in 8 major movement disorder clinics during the last 5 years who were diagnosed as having corticobasal ganglionic degeneration. METHODS: Using a chart review method, we recorded the clinical presentation, medications used, response to medications, and adverse effects. RESULTS: A total of 147 case patients were reviewed, 7 were autopsy proven. Parkinsonian features were present in all, other movement disorders in 89%, and higher cortical dysfunction in 93%. The most common parkinsonian sign was rigidity (92%), followed by bradykinesia (80%), gait disorder (80%), and tremor (55%). Other movement disorders were dystonia in 71% and myoclonus in 55%. Higher cortical dysfunction included dyspraxia (82%), alien limb (42%), cortical sensory loss (33%), and dementia (25%). Ninety-two percent of the case patients received dopaminergic drugs, which resulted in a beneficial effect for 24%. Parkinsonian signs were the elements improving the most and levodopa was the most effective drug. Benzodiazepines, primarily clonazepam, were administered to 47 case patients, which resulted in improvement of myoclonus in 23% and dystonia in 9%. The most frequent disabling adverse effects of drug trials in these case patients were somnolence (n = 24), gastrointestinal complaints (n = 23), confusion (n = 16), dizziness (n =12), hallucinations (n = 5), and dry mouth (n = 5). CONCLUSIONS: Pharmacological intervention was largely ineffective in the management of corticobasal degeneration, and new treatments are needed for ameliorating the symptoms of this syndrome.
Assuntos
Antiparkinsonianos/uso terapêutico , Córtex Cerebral/patologia , Doenças Neurodegenerativas/patologia , Doença de Parkinson/patologia , Antiparkinsonianos/efeitos adversos , Humanos , Londres , Doenças Neurodegenerativas/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Estados UnidosRESUMO
The authors identified patients with the coexistence of narcolepsy and another CNS disorder seen between 1975 and 1998 at their institution. Eighteen patients were identified, nine with narcolepsy commencing within 1 year before or after the other disorder. Seven patients (39%) had hypothalamic-pituitary syndromes. When they occur together, narcolepsy and other CNS disorders frequently emerge at about the same time, suggesting a causative relationship. Hypothalamic-pituitary pathology was the most common association.
Assuntos
Encéfalo/fisiopatologia , Doenças do Sistema Nervoso Central/complicações , Narcolepsia/complicações , Doenças do Sistema Nervoso Central/fisiopatologia , Feminino , Humanos , Masculino , Narcolepsia/fisiopatologiaRESUMO
Five patients, age 54 to 80 years, presented between 3 weeks and 18 months after symptomatic onset of progressive cognitive decline, psychosis, and unsteady gait that proved to be due to a steroid-responsive nonvasculitic autoimmune inflammatory meningoencephalitic syndrome. CSF examination showed elevated immunoglobulin (Ig)G index and IgG synthesis rate in all three patients in whom it was checked, and brain biopsy revealed perivascular lymphocytic infiltrates without vessel wall invasion.
Assuntos
Doenças Autoimunes/diagnóstico , Doenças Autoimunes/fisiopatologia , Meningoencefalite/diagnóstico , Meningoencefalite/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/líquido cefalorraquidiano , Doenças Autoimunes/patologia , Vasos Sanguíneos/patologia , Encéfalo/patologia , Circulação Cerebrovascular , Feminino , Humanos , Imunoglobulina G/biossíntese , Imunoglobulina G/líquido cefalorraquidiano , Masculino , Meningoencefalite/líquido cefalorraquidiano , Meningoencefalite/patologia , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To determine whether the dementia associated with REM sleep behavior disorder (RBD) differs from Alzheimer's disease (AD) and, if so, whether differences in cognitive performance between RBD/dementia and AD resemble reported differences between dementia with Lewy bodies (DLB) and AD. METHODS: This retrospective study compares neurocognitive performance between 31 patients with degenerative dementia and polysomnography-confirmed RBD and 31 patients without brainstem Lewy body pathology who met Consortium to Establish a Registry for Alzheimer's Disease (CERAD) clinical and neuropathologic criteria for AD. The patient groups did not differ in dementia severity (based on Global Deterioration Scale score) or duration. RESULTS: RBD preceded or coincided with the onset of cognitive decline in 94% of the patients. All but one patient with RBD/dementia had one or more of the following clinical features of DLB: visual hallucinations, extrapyramidal signs, or fluctuating cognition/alertness. The data revealed significantly worse performance on attention, perceptual organization, visual memory, and letter fluency for the RBD/dementia group, whereas the AD group showed significantly worse performance on confrontation naming and verbal memory. CONCLUSIONS: Patients with RBD and degenerative dementia demonstrate a significantly different pattern of cognitive performance from patients with AD. Most of the patients in the RBD/dementia sample also meet criteria for possible or probable DLB, and the pattern of cognitive differences from AD is similar to reported comparisons between DLB and AD. The cognitive and clinical data provide evidence to suggest that the dementia associated with RBD may represent DLB.
Assuntos
Doença de Alzheimer/fisiopatologia , Demência/fisiopatologia , Transtornos do Sono-Vigília/fisiopatologia , Sono REM/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Demência/psicologia , Humanos , Testes Neuropsicológicos , Estudos RetrospectivosRESUMO
BACKGROUND: The cognitive continuum in the elderly population can be conceptually divided into those who are functioning normally (control subjects), those with a mild cognitive impairment (MCI), and those with probable AD. OBJECTIVES: To test the hypothesis that the annualized rates of hippocampal atrophy differ as a function of both baseline and change in clinical group membership (control, MCI, or AD). METHODS: The authors identified 129 subjects from the Mayo Clinic AD Research Center/AD Patient Registry who met established criteria for normal control subjects, MCI, or probable AD, both at entry and at the time of a subsequent clinical follow-up evaluation 3 +/- 1 years later. Each subject underwent an MRI examination of the head at the time of the initial assessment and at follow-up clinical assessment; the annualized percentage change in hippocampal volume was computed. Subjects who were classified as controls or patients with MCI at baseline could either remain cognitively stable or could decline to a lower functioning group over the period of observation. RESULTS: The annualized rates of hippocampal volume loss for each of the three initial clinical groups decreased progressively in the following order: AD > MC > control. Within the control and MCI groups, those who declined had a significantly greater rate of volume loss than those who remained clinically stable. The mean annualized rates of hippocampal atrophy by follow-up clinical group were: control-stable 1.73%, control-decliner 2.81%, MCI-stable 2.55%, MCI-decliner 3.69%, AD 3. 5%. CONCLUSION: Rates of hippocampal atrophy match both baseline cognitive status and the change in cognitive status over time in elderly persons who lie along the cognitive continuum from normal to MCI to AD.
Assuntos
Envelhecimento/patologia , Doença de Alzheimer/patologia , Transtornos Cognitivos/diagnóstico , Hipocampo/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Apolipoproteínas E/genética , Atrofia/etiologia , Atrofia/patologia , Transtornos Cognitivos/classificação , Transtornos Cognitivos/etiologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
BACKGROUND: Mild cognitive impairment (MCI) is a recently described transitional clinical state between normal aging and AD. Assuming that amnestic MCI patients had pathologic changes corresponding to an early phase and probable AD patients to a later phase of the disease progression, the authors could approximate the temporal course of proton MR spectroscopic (1H MRS) alterations in AD with a cross-sectional sampling scheme. METHODS: The authors compared 1H MRS findings in the superior temporal lobe, posterior cingulate gyri, and medial occipital lobe in 21 patients with MCI, 21 patients with probable AD, and 63 elderly controls. These areas are known to be involved at different neurofibrillary pathologic stages of AD. RESULTS: The N-acetylaspartate (NAA)/creatine (Cr) ratios were significantly lower in AD patients compared to both MCI and normal control subjects in the left superior temporal and the posterior cingulate volumes of interest (VOI) and there were no between-group differences in the medial occipital VOI. Myoinositol (MI)/Cr ratios measured from the posterior cingulate VOI were significantly higher in both MCI and AD patients than controls. The choline (Cho)/Cr ratios measured from the posterior cingulate VOI were higher in AD patients compared to both MCI and control subjects. CONCLUSION: These findings suggest that the initial 1H MRS change in the pathologic progression of AD is an increase in MI/Cr. A decrease in NAA/Cr and an increase in Cho/Cr develop later in the disease course.