RESUMEN
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.
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Corticoesteroides/uso terapéutico , Autoanticuerpos , Enfermedades Autoinmunes/tratamiento farmacológico , Inmunoglobulinas Intravenosas/uso terapéutico , Péptidos y Proteínas de Señalización Intracelular/inmunología , Encefalitis Límbica/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes/inmunología , Femenino , Humanos , Encefalitis Límbica/inmunología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
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.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Autopsia , Humanos , Imagen por Resonancia Magnética/métodos , Vaina de Mielina/patologíaRESUMEN
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.
Asunto(s)
Encéfalo/patología , Demencia Frontotemporal/genética , Demencia Frontotemporal/patología , Mutación , Proteínas tau/genética , Encéfalo/diagnóstico por imagen , Femenino , Demencia Frontotemporal/diagnóstico por imagen , Humanos , Cuerpos de Inclusión/metabolismo , Cuerpos de Inclusión/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Fosforilación , Tomografía de Emisión de Positrones , Isoformas de Proteínas/genética , Tomografía Computarizada de Emisión , Proteínas tau/metabolismoRESUMEN
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.
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Encéfalo/patología , Demencia Frontotemporal/patología , Péptidos y Proteínas de Señalización Intercelular/genética , Imagen por Resonancia Magnética/métodos , Proteínas/genética , Proteínas tau/genética , Anciano , Atrofia/patología , Biomarcadores , Proteína C9orf72 , Femenino , Demencia Frontotemporal/diagnóstico , Demencia Frontotemporal/genética , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Mutación , ProgranulinasRESUMEN
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.
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Enfermedad por Cuerpos de Lewy/genética , Chaperonas Moleculares/genética , Enfermedad de Parkinson/genética , Adulto , Anciano , Anciano de 80 o más Años , Europa (Continente) , Exones , Femenino , Humanos , Masculino , Persona de Mediana Edad , MutaciónRESUMEN
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.
Asunto(s)
Mesencéfalo/patología , Parálisis Supranuclear Progresiva/patología , Anciano , Anciano de 80 o más Años , Atrofia , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , SíndromeRESUMEN
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.
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Tronco Encefálico/patología , Catecolaminas/metabolismo , Colinérgicos/metabolismo , Trastorno de la Conducta del Sueño REM/metabolismo , Trastorno de la Conducta del Sueño REM/patología , Anciano , Anciano de 80 o más Años , Tronco Encefálico/metabolismo , Femenino , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico , Enfermedad por Cuerpos de Lewy/patología , Locus Coeruleus/metabolismo , Masculino , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/metabolismo , Neuronas/metabolismo , Neuronas/patología , Trastorno de la Conducta del Sueño REM/diagnóstico , Estudios Retrospectivos , alfa-Sinucleína/metabolismoRESUMEN
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.
Asunto(s)
Demencia Frontotemporal/complicaciones , Trastorno Obsesivo Compulsivo/etiología , Trastorno Obsesivo Compulsivo/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Demencia Frontotemporal/genética , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mutación/genética , Trastorno Obsesivo Compulsivo/genética , Putamen/patología , Índice de Severidad de la Enfermedad , Proteínas tau/genéticaRESUMEN
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.
Asunto(s)
Núcleo Caudado/patología , Proteínas de Unión al ADN/metabolismo , Lóbulo Frontal/patología , Demencia Frontotemporal/diagnóstico , Demencia Frontotemporal/patología , Proteína FUS de Unión a ARN/metabolismo , Anciano , Atrofia , Biomarcadores/metabolismo , Mapeo Encefálico/métodos , Núcleo Caudado/metabolismo , Estudios de Cohortes , Diagnóstico Diferencial , Femenino , Lóbulo Frontal/metabolismo , Demencia Frontotemporal/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Proteínas tau/metabolismoRESUMEN
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.
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Encéfalo/fisiopatología , Trastorno de la Conducta del Sueño REM/fisiopatología , Animales , Encéfalo/patología , Humanos , Imagen por Resonancia Magnética , Modelos Animales , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/fisiopatología , Trastorno de la Conducta del Sueño REM/patologíaRESUMEN
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.
Asunto(s)
Péptidos beta-Amiloides/metabolismo , Encéfalo/diagnóstico por imagen , Carbolinas , Enfermedades Neurodegenerativas/diagnóstico por imagen , Tomografía de Emisión de Positrones , Radiofármacos , Anciano , Anciano de 80 o más Años , Compuestos de Anilina , Apraxias/diagnóstico por imagen , Apraxias/metabolismo , Encéfalo/metabolismo , Mapeo Encefálico , Estudios de Cohortes , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Enfermedades Neurodegenerativas/metabolismo , TiazolesRESUMEN
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.
Asunto(s)
Tronco Encefálico/fisiopatología , Disnea/fisiopatología , Enfermedad por Cuerpos de Lewy/fisiopatología , Sueño REM/fisiología , Anciano , Disnea/diagnóstico , Electromiografía , Gliosis/metabolismo , Gliosis/patología , Humanos , Enfermedad por Cuerpos de Lewy/metabolismo , Enfermedad por Cuerpos de Lewy/patología , Masculino , Persona de Mediana Edad , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/patología , Ovillos Neurofibrilares/metabolismo , Ovillos Neurofibrilares/patología , Polisomnografía , Índice de Severidad de la Enfermedad , alfa-Sinucleína/metabolismoRESUMEN
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.
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Enfermedad por Cuerpos de Lewy/epidemiología , Enfermedad de Parkinson/epidemiología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Distribución por SexoRESUMEN
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 Asunto(s)
Envejecimiento/patología
, Encéfalo/patología
, Cognición/fisiología
, Evaluación Geriátrica
, Anciano
, Anciano de 80 o más Años
, Envejecimiento/psicología
, Apolipoproteínas E/genética
, Infarto Encefálico/patología
, Distribución de Chi-Cuadrado
, Cristalinas/metabolismo
, Demencia Vascular/patología
, Femenino
, Humanos
, Inmunohistoquímica
, Cuerpos de Lewy/patología
, Masculino
, Escala del Estado Mental
, Ovillos Neurofibrilares/patología
, Neurópilo/patología
, Hilos del Neurópilo/patología
, Pruebas Neuropsicológicas
, Placa Amiloide/patología
, Estudios Prospectivos
, Estándares de Referencia
, Índice de Severidad de la Enfermedad
, Proteínas tau/metabolismo
RESUMEN
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.
Asunto(s)
Antiparkinsonianos/uso terapéutico , Corteza Cerebral/patología , Enfermedades Neurodegenerativas/patología , Enfermedad de Parkinson/patología , Antiparkinsonianos/efectos adversos , Humanos , Londres , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedad de Parkinson/tratamiento farmacológico , Estados UnidosRESUMEN
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.
Asunto(s)
Encéfalo/fisiopatología , Enfermedades del Sistema Nervioso Central/complicaciones , Narcolepsia/complicaciones , Enfermedades del Sistema Nervioso Central/fisiopatología , Femenino , Humanos , Masculino , Narcolepsia/fisiopatologíaRESUMEN
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.
Asunto(s)
Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/fisiopatología , Meningoencefalitis/diagnóstico , Meningoencefalitis/fisiopatología , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes/líquido cefalorraquídeo , Enfermedades Autoinmunes/patología , Vasos Sanguíneos/patología , Encéfalo/patología , Circulación Cerebrovascular , Femenino , Humanos , Inmunoglobulina G/biosíntesis , Inmunoglobulina G/líquido cefalorraquídeo , Masculino , Meningoencefalitis/líquido cefalorraquídeo , Meningoencefalitis/patología , Persona de Mediana EdadRESUMEN
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.
Asunto(s)
Enfermedad de Alzheimer/fisiopatología , Demencia/fisiopatología , Trastornos del Sueño-Vigilia/fisiopatología , Sueño REM/fisiología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/psicología , Demencia/psicología , Humanos , Pruebas Neuropsicológicas , Estudios RetrospectivosRESUMEN
OBJECTIVE: To test the hypothesis that MRI-based measurements of hippocampal volume are related to the risk of future conversion to Alzheimer's disease (AD) in older patients with a mild cognitive impairment (MCI). BACKGROUND: Patients who develop AD pass through a transitional state, which can be characterized as MCI. In some patients, however, MCI is a more benign condition, which may not progress to AD or may do so slowly. PATIENTS: Eighty consecutive patients who met criteria for the diagnosis of MCI were recruited from the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry. METHODS: At entry into the study, each patient received an MRI examination of the head, from which the volumes of both hippocampi were measured. Patients were followed longitudinally with approximately annual clinical/cognitive assessments. The primary endpoint was the crossover of individual MCI patients to the clinical diagnosis of AD during longitudinal clinical follow-up. RESULTS: During the period of longitudinal observation, which averaged 32.6 months, 27 of the 80 MCI patients became demented. Hippocampal atrophy at baseline was associated with crossover from MCI to AD (relative risk [RR], 0.69, p = 0.015). When hippocampal volume was entered into bivariate models-using age, postmenopausal estrogen replacement, standard neuropsychological tests, apolipoprotein E (APOE) genotype, history of ischemic heart disease, and hypertension-the RRs were not substantially different from that found univariately, and the associations between hippocampal volume and crossover remained significant. CONCLUSION: In older patients with MCI, hippocampal atrophy determined by premorbid MRI-based volume measurements is predictive of subsequent conversion to AD.
Asunto(s)
Enfermedad de Alzheimer/patología , Trastornos del Conocimiento/patología , Hipocampo/patología , Anciano , Anciano de 80 o más Años , Envejecimiento/patología , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/mortalidad , Apolipoproteínas E/genética , Terapia de Reemplazo de Estrógeno , Humanos , Hipertensión/patología , Imagen por Resonancia Magnética , Persona de Mediana Edad , Isquemia Miocárdica/patología , Valor Predictivo de las Pruebas , Análisis de SupervivenciaRESUMEN
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.