RESUMEN
Tolosa Hunt syndrome (THS) is characterized by painful ophthalmoplegia secondary to idiopathic granulomatous inflammation of the cavernous sinus. The characteristic finding on MRI is an enhancing T1 isointense and T2 hypo- or hyperintense cavernous sinus mass lesion, which may result in focal narrowing of the ipsilateral internal carotid artery. Although the incidence is quite rare, it is a common diagnostic consideration in cases that present with multiple cranial neuropathies. However, the differential diagnosis for a unilateral cavernous sinus lesion in adults is broad and includes neoplastic, inflammatory (such as sarcoidosis and immunoglobulin G4-related disease [IgG4-RD]), infectious etiologies (such as syphilis and leprosy), as well as vascular lesions. We describe a patient presenting with neurologic symptoms referable to a persistent unilateral cavernous sinus MRI abnormality, initially thought to be consistent with Tolosa-Hunt syndrome, that was clinically but not radiographically responsive to steroids. Following reevaluation due to the presence of new symptoms, pathology revealed that the abnormality was most consistent with chordoma, a rare skull based tumor. In patients with a presumed diagnosis of Tolosa-Hunt syndrome, close clinical and radiographic follow-up is imperative, with early consideration for biopsy in patients that fail to respond to treatment both clinically and radiographically.
Asunto(s)
Seno Cavernoso/patología , Cordoma/diagnóstico , Cordoma/patología , Neoplasias de la Base del Cráneo/diagnóstico , Neoplasias de la Base del Cráneo/patología , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Esteroides/uso terapéutico , Síndrome de Tolosa-Hunt/diagnósticoRESUMEN
AIM: The p.P301L mutation in microtubule-associated protein tau (MAPT) is a common cause of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We compare clinicopathologic features of five unrelated and three related (brother, sister and cousin) patients with FTDP-17 due to p.P301L mutation. METHODS: Genealogical, clinical, neuropathologic and genetic data were reviewed from eight individuals. RESULTS: The series consisted of five men and three women with an average age of death of 58 years (52-65 years) and average disease duration of 9 years (3-14 years). The first symptoms were those of behavioural variant frontotemporal dementia in seven patients and semantic variant of primary progressive aphasia in one. Three patients were homozygous for the MAPT H1 haplotype; five had H1/H2 genotype. The apolipoprotein E genotype was ϵ3/ϵ3 in seven and ϵ3/ϵ4 in one. The average brain weight was 1015 g (876-1188 g). All had frontotemporal lobar or more diffuse cortical atrophy. Except for one patient, the hippocampus and parahippocampal gyrus had minimal atrophy, whereas there was atrophy of middle and inferior temporal gyri. Dentate fascia neuronal dispersion was identified in three patients, two of whom had epilepsy. In one patient there was extensive white matter tau involvement with Gallyas-positive globular glial inclusions typical of globular glial tauopathy (GGT). CONCLUSIONS: This clinicopathologic study shows inter- and intra-familial clinicopathologic heterogeneity of FTDP-17 due to MAPT p.P301L mutation, including GGT in one patient.
Asunto(s)
Demencia Frontotemporal/genética , Demencia Frontotemporal/patología , Tauopatías/genética , Proteínas tau/genética , Anciano , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mutación , Neuroglía/patología , LinajeRESUMEN
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
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.
Asunto(s)
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
We used double immunocytochemistry for α-synuclein and markers of sympathoexcitatory neurons, oligodendrocytes, iron metabolism, and autophagy to study putative neuropathological interactions in multiple system atrophy. We focused in the rostral ventrolateral medulla as a prototype vulnerable region. We found that loss of C1 neurons and oligodendrocytes related to glial cytoplasmic inclusion accumulation, downregulation of iron transport, and upregulation of autophagy and ferritin expression in these area.
Asunto(s)
Tronco Encefálico/patología , Tronco Encefálico/fisiopatología , Atrofia de Múltiples Sistemas/patología , Atrofia de Múltiples Sistemas/fisiopatología , Anciano , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Beclina-1 , Tronco Encefálico/metabolismo , Estudios de Casos y Controles , Proteínas de Transporte de Catión/metabolismo , Modelos Animales de Enfermedad , Humanos , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Persona de Mediana Edad , Atrofia de Múltiples Sistemas/metabolismo , Neuroglía/metabolismo , Neuroglía/patología , Oligodendroglía/metabolismo , Oligodendroglía/patología , alfa-Sinucleína/metabolismoRESUMEN
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
UNLABELLED: Multiple system atrophy (MSA) is associated with respiratory dysfunction, including sleep apnea, respiratory dysrhythmia, and laryngeal stridor. Neurons of the parabrachial nucleus (PBN) control respiratory rhythmogenesis and airway resistance. OBJECTIVES: The objective of this study is to determine whether there was involvement of putative respiratory regions of the PBN in MSA. METHODS: We examined the pons at autopsy in 10 cases with neuropathologically confirmed MSA and 8 age-matched controls. Sections obtained throughout the pons were processed for calcitonin-gene related peptide (CGRP) and Nissl staining to identify the lateral crescent of the lateral PBN (LPB) and the Kölliker-Fuse nucleus (K-F), which are involved in respiratory control. Cell counts were performed using stereology. RESULTS: There was loss of CGRP neurons in the PBN in MSA (total estimated cell counts for the external LPB cluster was 12,584 ± 1146 in controls and 5917 ± 389 in MSA, p<0.0001); for the external medial PBN (MPB) cluster it was 15,081 ± 1758 in controls and 7842 ± 466 in MSA, p<0.001. There was also neuronal loss in putative respiratory regions of the PBN, including the lateral crescent of the LPB (13,039 ± 1326 in controls and 4164 ± 872 in MSA, p<0.0001); and K-F (5120 ± 495 in controls and 999 ± 308 in MSA, p<0.0001). CONCLUSIONS: There is involvement of both CGRP and putative respiratory cell groups in the PBN in MSA. Whereas the clinical implications of CGRP cell loss are still undetermined, involvement of the LPB and K-F may contribute to respiratory dysfunction in this disorder.
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Atrofia de Múltiples Sistemas/patología , Puente/patología , Centro Respiratorio/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa/patología , Red Nerviosa/fisiología , Puente/fisiología , Centro Respiratorio/fisiologíaRESUMEN
OBJECTIVE: To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder. METHODS: The clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria. RESULTS: 172 cases were identified, of whom 143 (83%) were men. The mean±SD age of onset in years for the core features were as follows - RBD, 62±14 (range, 20-93), cognitive impairment (n=147); 69±10 (range, 22-90), parkinsonism (n=151); 68±9 (range, 20-92), and autonomic dysfunction (n=42); 62±12 (range, 23-81). Death age was 75±9 years (range, 24-96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10±12 (range, 1-61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n=97), Parkinson's disease with or without mild cognitive impairment or dementia (n=32), multiple system atrophy (MSA) (n=19), Alzheimer's disease (AD)(n=9) and other various disorders including secondary narcolepsy (n=2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n=1). The neuropathologic diagnoses were Lewy body disease (LBD)(n=77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n=59), MSA (n=19), AD (n=6), progressive supranulear palsy (PSP) (n=2), other mixed neurodegenerative pathologies (n=6), NBIA-1/LBD/tauopathy (n=1), and hypothalamic structural lesions (n=2). Among the neurodegenerative disorders associated with RBD (n=170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features. CONCLUSIONS: In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.
Asunto(s)
Enfermedad por Cuerpos de Lewy/complicaciones , Enfermedad por Cuerpos de Lewy/patología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/patología , Trastorno de la Conducta del Sueño REM/complicaciones , Trastorno de la Conducta del Sueño REM/patología , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/patología , Encéfalo/patología , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atrofia de Múltiples Sistemas/complicaciones , Atrofia de Múltiples Sistemas/patología , Narcolepsia/complicaciones , Narcolepsia/patología , Parálisis Supranuclear Progresiva/complicaciones , Parálisis Supranuclear Progresiva/patología , Adulto JovenRESUMEN
OBJECTIVES: To describe lesional diffusion-weighted imaging characteristics in a cohort of patients with biopsy-proven CNS inflammatory demyelinating disease (IDD) and compare diffusion characteristics of ring-enhancing CNS IDD lesions vs abscesses and tumors. METHODS: Forty prebiopsy apparent diffusion coefficient (ADC) maps were reviewed from 30 patients with CNS IDD. Lesions were analyzed for size, T2-weighted (T2W) hypointense rim, enhancement, and ADC pattern. ADC patterns of CNS IDD ring-enhancing lesions were compared with a published cohort of 35 patients with ring-enhancing tumors and abscesses. RESULTS: IDD lesions displayed a spectrum of peripheral ADC patterns at the lesion edge: restricted diffusion (low ADC), 33%; increased diffusion (high ADC), 60%; and normal diffusion (homogeneously isointense), 7%. Of biopsied lesions, 93% enhanced (ring, 52%; heterogeneous, 34%; homogeneous, 7%). A hypointense T2W rim was observed in 53%. A ring pattern on ADC (isointense or dark) was associated with T2W hypointense rims (p = 0.02) but not with ring enhancement. On serial imaging, 4 of 7 (57%) patients demonstrated changes in ADC patterns. Peripheral restriction was more common in IDD (p = 0.006) than in tumors or abscesses, whereas central restriction was only observed in abscesses. Restricted lesions in the same stage were more common in the non-IDD cohort (42% vs 20%), with a uniform restricted pattern seen only in abscesses. CONCLUSIONS: In ring-enhancing lesions, peripheral diffusion restriction is more common in IDD than in tumors/abscesses, whereas central restriction is more common among abscesses. Rapid ADC pattern changes in IDD probably reflect dynamic lesion evolution and may distinguish IDD from tumors.
Asunto(s)
Enfermedades Desmielinizantes/diagnóstico , Imagen de Difusión por Resonancia Magnética/métodos , Absceso/diagnóstico , Absceso/patología , Adolescente , Adulto , Anciano , Estudios de Cohortes , Enfermedades Desmielinizantes/inmunología , Enfermedades Desmielinizantes/patología , Femenino , Humanos , Inflamación/clasificación , Inflamación/diagnóstico , Inflamación/patología , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Neoplasias/patología , Estudios Retrospectivos , Método Simple Ciego , Adulto JovenRESUMEN
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.
Asunto(s)
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
OBJECTIVE: To determine whether adding REM sleep behavior disorder (RBD) to the dementia with Lewy bodies (DLB) diagnostic criteria improves classification accuracy of autopsy-confirmed DLB. METHODS: We followed 234 consecutive patients with dementia until autopsy with a mean of 4 annual visits. Clinical diagnoses included DLB, Alzheimer disease (AD), corticobasal syndrome, and frontotemporal dementia. Pathologic diagnoses used the 2005 DLB consensus criteria and included no/low likelihood DLB (non-DLB; n = 136) and intermediate/high likelihood DLB (DLB; n = 98). Regression modeling and sensitivity/specificity analyses were used to evaluate the diagnostic role of RBD. RESULTS: Each of the 3 core features increased the odds of autopsy-confirmed DLB up to 2-fold, and RBD increased the odds by 6-fold. When clinically probable DLB reflected dementia and 2 or more of the 3 core features, sensitivity was 85%, and specificity was 73%. When RBD was added and clinically probable DLB reflected 2 or more of 4 features, sensitivity improved to 88%. When dementia and RBD were also designated as probable DLB, sensitivity increased to 90% while specificity remained at 73%. The VH, parkinsonism, RBD model lowered sensitivity to 83%, but improved specificity to 85%. CONCLUSIONS: Inclusion of RBD as a core clinical feature improves the diagnostic accuracy of autopsy-confirmed DLB.
Asunto(s)
Enfermedad por Cuerpos de Lewy/clasificación , Enfermedad por Cuerpos de Lewy/diagnóstico , Trastorno de la Conducta del Sueño REM/diagnóstico , Actividades Cotidianas , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Enfermedad por Cuerpos de Lewy/complicaciones , Masculino , Estudios Prospectivos , Trastorno de la Conducta del Sueño REM/complicaciones , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To describe a patient presenting with a clinically silent, incidentally found, and pathologically confirmed active demyelinating solitary cortical lesion showing MRI gadolinium contrast enhancement, in whom biopsy was performed before the radiographic appearance of disseminated white matter lesions. METHODS: Neurologic examination, MRI, CSF and serologic analyses, and brain biopsy were performed. Sections of formalin-fixed paraffin-embedded biopsied brain tissue were stained with histologic and immunohistochemical stains. RESULTS: Biopsy revealed an inflammatory subpial lesion containing lymphocytes and myelin-laden macrophages. Recurrent relapses with dissemination of MRI-typical white matter lesions characterized the subsequent course. CONCLUSIONS: Our findings highlight that cortical demyelination occurs on a background of inflammation and suggest that the noninflammatory character of chronic cortical demyelination may relate to long intervals between lesion formation and autopsy. This case provides pathologic evidence of relapsing-remitting MS presenting with inflammatory cortical demyelination and emphasizes the importance of considering demyelinating disease in the differential diagnosis of patients presenting with a solitary cortical enhancing lesion.
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Corteza Cerebral/patología , Enfermedades Desmielinizantes/patología , Esclerosis Múltiple Crónica Progresiva/patología , Adulto , Biopsia , Enfermedades Desmielinizantes/complicaciones , Femenino , Acetato de Glatiramer , Cefalea/etiología , Hemianopsia/complicaciones , Humanos , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Inmunosupresores/uso terapéutico , Inflamación/patología , Imagen por Resonancia Magnética , Trastornos Migrañosos/complicaciones , Esclerosis Múltiple Crónica Progresiva/complicaciones , Adhesión en Parafina , Péptidos/uso terapéutico , Fijación del TejidoRESUMEN
BACKGROUND: Behavioral variant frontotemporal dementia (bvFTD) is a relatively well-defined clinical syndrome. It is associated with frontal and temporal lobe structural/metabolic changes and pathologic findings of a neurodegenerative disease. We have been evaluating patients with clinical and imaging features partially consistent with bvFTD but with evidence also suggestive of brain sagging, which we refer to as frontotemporal brain sagging syndrome (FBSS). METHODS: Retrospective medical chart review to identify all patients seen at our institution between 1996 and 2010, who had a clinical diagnosis of FTD and imaging evidence of brain sag. RESULTS: Eight patients, 7 male and 1 female, were diagnosed with FBSS. The median age at symptom onset was 53 years. All patients had insidious onset and slow progression of behavioral and cognitive dysfunction accompanied by daytime somnolence and headache. Of the 5 patients with functional imaging, all showed evidence of hypometabolism of the frontotemporal regions. On brain MRI, all patients had evidence of brain sagging with distortion of the brainstem; 3 patients had diffuse pachymeningeal enhancement. CSF opening pressure was varied and CSF protein was mildly elevated. A definite site of CSF leak was not identified by myelogram or cisternography, except in one patient with a site highly suggestive of leak who subsequently underwent surgery confirming a CSF leak. In 2 patients with a neuropathologic examination, there was no evidence of a neurodegenerative disease. CONCLUSIONS: This case series demonstrates that FBSS may mimic typical bvFTD but should be recognized as an unusual presentation that is potentially treatable.
Asunto(s)
Trastornos del Conocimiento/etiología , Lóbulo Frontal/patología , Demencia Frontotemporal/complicaciones , Demencia Frontotemporal/diagnóstico , Hipotensión Intracraneal/complicaciones , Lóbulo Temporal/patología , Anciano , Anciano de 80 o más Años , Diagnóstico por Imagen/métodos , Femenino , Estudios de Seguimiento , Lóbulo Frontal/diagnóstico por imagen , Demencia Frontotemporal/líquido cefalorraquídeo , Demencia Frontotemporal/tratamiento farmacológico , Humanos , Imagen por Resonancia Magnética , Masculino , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Fármacos Neuroprotectores/administración & dosificación , Pruebas Neuropsicológicas , Radiografía , Cintigrafía , Estudios Retrospectivos , Lóbulo Temporal/diagnóstico por imagenRESUMEN
OBJECTIVE: To characterize the neuropathologic features of neuromyelitis optica (NMO) at the medullary floor of the fourth ventricle and area postrema. Aquaporin-4 (AQP4) autoimmunity targets this region, resulting in intractable nausea associated with vomiting or hiccups in NMO. METHODS: This neuropathologic study was performed on archival brainstem tissue from 15 patients with NMO, 5 patients with multiple sclerosis (MS), and 8 neurologically normal subjects. Logistic regression was used to evaluate whether the presence of lesions at this level increased the odds of a patient with NMO having an episode of nausea/vomiting. RESULTS: Six patients with NMO (40%), but no patients with MS or normal controls, exhibited unilateral or bilateral lesions involving the area postrema and the medullary floor of the fourth ventricle. These lesions were characterized by tissue rarefaction, blood vessel thickening, no obvious neuronal or axonal pathology, and preservation of myelin in the subependymal medullary tegmentum. AQP4 immunoreactivity was lost or markedly reduced in all 6 cases, with moderate to marked perivascular and parenchymal lymphocytic inflammatory infiltrates, prominent microglial activation, and in 3 cases, eosinophils. Complement deposition in astrocytes, macrophages, and/or perivascularly, and a prominent astroglial reaction were also present. The odds of nausea/vomiting being documented clinically was 16-fold greater in NMO cases with area postrema lesions (95% confidence interval 1.43-437, p = 0.02). CONCLUSIONS: These neuropathologic findings suggest the area postrema may be a selective target of the disease process in NMO, and are compatible with clinical reports of nausea and vomiting preceding episodes of optic neuritis and transverse myelitis or being the heralding symptom of NMO.
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Área Postrema/patología , Náusea/patología , Neuromielitis Óptica/etiología , Neuromielitis Óptica/patología , Vómitos/patología , Adolescente , Adulto , Anciano , Humanos , Persona de Mediana Edad , Náusea/complicaciones , Náusea/etiología , Neuromielitis Óptica/complicaciones , Estudios Retrospectivos , Vómitos/complicaciones , Vómitos/etiología , Adulto JovenRESUMEN
OBJECTIVE: To determine whether TDP-43 type is associated with distinct patterns of brain atrophy on MRI in subjects with pathologically confirmed frontotemporal lobar degeneration (FTLD). METHODS: In this case-control study, we identified all subjects with a pathologic diagnosis of FTLD with TDP-43 immunoreactive inclusions (FTLD-TDP) and at least one volumetric head MRI scan (n = 42). In each case we applied published criteria for subclassification of FTLD-TDP into FTLD-TDP types 1-3. Voxel-based morphometry was used to compare subjects with each of the different FTLD-TDP types to age- and gender-matched normal controls (n = 30). We also assessed different pathologic and genetic variants within, and across, the different types. RESULTS: Twenty-two subjects were classified as FTLD-TDP type 1, 9 as type 2, and 11 as type 3. We identified different patterns of atrophy across the types with type 1 showing frontotemporal and parietal atrophy, type 2 predominantly anterior temporal lobe atrophy, and type 3 predominantly posterior frontal atrophy. Within the FTLD-TDP type 1 group, those with a progranulin mutation had significantly more lateral temporal lobe atrophy than those without. All type 2 subjects were diagnosed with semantic dementia. Subjects with a pathologic diagnosis of FTLD with motor neuron degeneration had a similar pattern of atrophy, regardless of whether they were type 1 or type 3. CONCLUSIONS: Although there are different patterns of atrophy across the different FTLD-TDP types, it appears that genetic and pathologic factors may also affect the patterns of atrophy.
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Encéfalo/metabolismo , Encéfalo/patología , Proteínas de Unión al ADN/metabolismo , Degeneración Lobar Frontotemporal/metabolismo , Degeneración Lobar Frontotemporal/patología , Imagen por Resonancia Magnética , Adulto , Anciano , Anciano de 80 o más Años , Atrofia , Estudios de Casos y Controles , Proteínas de Unión al ADN/clasificación , Femenino , Lóbulo Frontal/metabolismo , Lóbulo Frontal/patología , Humanos , Masculino , Persona de Mediana Edad , Lóbulo Parietal/metabolismo , Lóbulo Parietal/patología , Factores de Riesgo , Lóbulo Temporal/metabolismo , Lóbulo Temporal/patologíaRESUMEN
OBJECTIVE: To asses the presence of cortical demyelination in brains of patients with neuromyelitis optica (NMO). NMO is an autoimmune inflammatory demyelinating disease that specifically targets aquaporin-4-rich regions of the CNS. Since aquaporin-4 is highly expressed in normal cortex, we anticipated that cortical demyelination may occur in NMO. METHODS: This is a cross-sectional neuropathologic study performed on archival forebrain and cerebellar tissue sections from 19 autopsied patients with a clinically and/or pathologically confirmed NMO spectrum disorder. RESULTS: Detailed immunohistochemical analyses of 19 archival NMO cases revealed preservation of aquaporin-4 in a normal distribution within cerebral and cerebellar cortices, and no evidence of cortical demyelination. CONCLUSIONS: This study provides a plausible explanation for the absence of a secondary progressive clinical course in NMO and shows that cognitive and cortical neuroimaging abnormalities previously reported in NMO cannot be attributed to cortical demyelination. Lack of cortical demyelination is another characteristic that further distinguishes NMO from MS.
Asunto(s)
Corteza Cerebral/patología , Neuromielitis Óptica/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Acuaporina 4/metabolismo , Corteza Cerebelosa/metabolismo , Corteza Cerebelosa/patología , Corteza Cerebral/metabolismo , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Corticobasal syndrome (CBS) can be associated with different underlying pathologies that are difficult to predict based on clinical presentation. The aim of this study was to determine whether patterns of atrophy on imaging could be useful to help predict underlying pathology in CBS. METHODS: This was a case-control study of 24 patients with CBS who had undergone MRI during life and came to autopsy. Pathologic diagnoses included frontotemporal lobar degeneration (FTLD) with TDP-43 immunoreactivity in 5 (CBS-TDP), Alzheimer disease (AD) in 6 (CBS-AD), corticobasal degeneration in 7 (CBS-CBD), and progressive supranuclear palsy in 6 (CBS-PSP). Voxel-based morphometry and atlas-based parcellation were used to assess atrophy across the CBS groups and compared to 24 age- and gender-matched controls. RESULTS: All CBS pathologic groups showed gray matter loss in premotor cortices, supplemental motor area, and insula on imaging. However, CBS-TDP and CBS-AD showed more widespread patterns of loss, with frontotemporal loss observed in CBS-TDP and temporoparietal loss observed in CBS-AD. CBS-TDP showed significantly greater loss in prefrontal cortex than the other groups, whereas CBS-AD showed significantly greater loss in parietal lobe than the other groups. The focus of loss was similar in CBS-CBD and CBS-PSP, although more severe in CBS-CBD. CONCLUSIONS: Imaging patterns of atrophy in CBS vary according to pathologic diagnosis. Widespread atrophy points toward a pathologic diagnosis of FTLD-TDP or AD, with frontotemporal loss suggesting FTLD-TDP and temporoparietal loss suggesting AD. On the contrary, more focal atrophy predominantly involving the premotor and supplemental motor area suggests CBD or PSP pathology.
Asunto(s)
Ganglios Basales/patología , Encefalopatías/diagnóstico , Corteza Cerebral/patología , Imagen por Resonancia Magnética , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/patología , Atrofia , Encefalopatías/complicaciones , Encefalopatías/metabolismo , Cadáver , Estudios de Casos y Controles , Proteínas de Unión al ADN/metabolismo , Femenino , Lóbulo Frontal/patología , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/patología , Lóbulo Parietal/patología , Sustancia Gris Periacueductal/patología , Corteza Prefrontal/patología , Parálisis Supranuclear Progresiva/complicaciones , Parálisis Supranuclear Progresiva/patología , Síndrome , Lóbulo Temporal/patologíaRESUMEN
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.