RESUMEN
Ring chromosome 14 (r14) is clinically characterized by early-onset epilepsy, mental retardation, delayed speech, microcephaly, extremely mild facial dysmorphisms and ophthalmologic abnormalities. We report a case presenting with partial seizures and delayed development in infancy in which r14 was diagnosed based on chromosomal analysis. The patient was a girl with a normal family and delivery history. Afebrile generalized convulsions developed at age 9 months, and phenobarbital was started, but was changed to zonisamide due to impaired liver function. Chromosome analysis led to a diagnosis of 46, XX, r(14) (p11.2q32.3). At age 5 years, while under treatment with zonisamide and clobazam, epilepsy was characterized by multiple daily episodes of complex partial seizures. Although there are no consistent brain MRI or electroencephalogram findings, experienced pediatric neurologists can make a diagnosis based on facial dysmorphisms. When refractory epilepsy is encountered in infancy with developmental delay of unknown cause, chromosome analysis should be performed.
Asunto(s)
Trastornos de los Cromosomas/diagnóstico , Discapacidades del Desarrollo/diagnóstico , Epilepsias Parciales/diagnóstico , Anticonvulsivantes/uso terapéutico , Benzodiazepinas/uso terapéutico , Preescolar , Trastornos de los Cromosomas/genética , Cromosomas Humanos Par 14/genética , Clobazam , Discapacidades del Desarrollo/genética , Epilepsias Parciales/tratamiento farmacológico , Epilepsias Parciales/genética , Femenino , Humanos , Lactante , Isoxazoles/uso terapéutico , Fenobarbital/uso terapéutico , Cromosomas en Anillo , Síndrome , ZonisamidaRESUMEN
OBJECTIVE: We conducted a nationwide multicenter study in Japan to elucidate the clinical and laboratory characteristics of acute encephalitis with refractory, repetitive partial seizures (AERRPS). MATERIALS AND METHODS: Clinical and laboratory features, treatment, and outcome were assessed using a structured questionnaire. RESULTS: Twenty-nine children were enrolled in the study. Refractory and repetitive partial seizures accompanied by fever were the cardinal clinical features. Partial seizures consisted principally of eye deviation or facial twitching, being periodically repeated during the acute phase. These seizures were refractory to conventional anticonvulsants and were only suppressed by high-dose intravenous barbiturate administration. Rhythmic activities on electroencephalography and non-specific cerebral atrophy on neuroimaging were common. Serum or cerebrospinal antibodies against GluRepsilon2 were positive in six patients. General prognosis was unfavorable due to intractable epilepsy and cognitive deficits. CONCLUSION: Based on the peculiar and homogenous features, AERRPS can be regarded as a distinct clinical entity.
Asunto(s)
Cerebro , Encefalitis/patología , Encefalitis/fisiopatología , Epilepsias Parciales/fisiopatología , Enfermedad Aguda , Adolescente , Anticonvulsivantes/uso terapéutico , Atrofia , Barbitúricos/uso terapéutico , Cerebro/patología , Cerebro/fisiopatología , Niño , Preescolar , Trastornos del Conocimiento/etiología , Electroencefalografía , Encefalitis/complicaciones , Encefalitis/diagnóstico , Encefalitis/tratamiento farmacológico , Epilepsias Parciales/complicaciones , Femenino , Fiebre/complicaciones , Humanos , Lactante , Masculino , Receptores de N-Metil-D-Aspartato/metabolismo , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Conventional nerve conduction studies (NCS) are not sensitive to detect mild diabetic neuropathy. In order to detect subtle changes, we compared the conventional NCS with the relative refractory period (RRP) measurement of the median sensory nerve action potential by a paired stimulation method. METHODS: Subjects were 29 diabetic patients whose conventional NCS were all normal. They were divided into two groups: neurologically symptomatic and asymptomatic groups. Twenty-eight age-matched control subjects were also studied. RESULTS: The RRP of the symptomatic diabetic patients (5.9 +/- 0.5 ms) and that of the asymptomatic patients (5.6 +/- 0.5 ms) was significantly longer than that of the control subjects (4.9 +/- 0.6 ms). There was no significant difference in RRP between the symptomatic and asymptomatic patients. This may be due to the fact that NCS reflects mainly large myelinated fiber function and early symptoms represent mainly thin myelinated or unmyelinated fiber function. CONCLUSIONS: The RRP measurement could reveal some mild involvement of peripheral nerves undetectable by conventional NCS, even though they caused no clinical symptoms.
Asunto(s)
Neuropatías Diabéticas/fisiopatología , Nervio Mediano/fisiología , Neuropatía Mediana/fisiopatología , Neuronas Aferentes/fisiología , Potenciales de Acción/fisiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Nervio Mediano/citología , Persona de Mediana Edad , Fibras Nerviosas Mielínicas/fisiología , Fibras Nerviosas Amielínicas/fisiología , Conducción Nerviosa/fisiología , Neuronas Aferentes/ultraestructura , Periodo Refractario Electrofisiológico/fisiologíaRESUMEN
Acute encephalopathy is the most serious complication of pediatric viral infections, such as influenza and exanthem subitum. It occurs worldwide, but is most prevalent in East Asia, and every year several hundreds of Japanese children are affected by influenza-associated encephalopathy. Mortality has recently declined, but is still high. Many survivors are left with motor and intellectual disabilities, and some with epilepsy. This article reviews various syndromes of acute encephalopathy by classifying them into three major categories. The first group caused by metabolic derangement consists of various inherited metabolic disorders and the classical Reye syndrome. Salicylate is a risk factor of the latter condition. The second group, characterized by a systemic cytokine storm and vasogenic brain edema, includes Reye-like syndrome, hemorrhagic shock and encephalopathy syndrome, and acute necrotizing encephalopathy. Non-steroidal anti-inflammatory drugs, such as diclofenac sodium and mephenamic acid, may aggravate these syndromes. Severe cases are complicated by multiple organ failure and disseminated intravascular coagulation. Mortality is high, although methylprednisolone pulse therapy may be beneficial in some cases. The third group, characterized by localized edema of the cerebral cortex, has recently been termed acute encephalopathy with febrile convulsive status epilepticus, and includes hemiconvulsion-hemiplegia syndrome and acute infantile encephalopathy predominantly affecting the frontal lobes. Theophylline is a risk factor of these syndromes. The pathogenesis is yet to be clarified, but an increasing body of evidence points to excitotoxicity and delayed neuronal death.
Asunto(s)
Encefalopatías Metabólicas/fisiopatología , Edema Encefálico/fisiopatología , Encéfalo/fisiopatología , Encéfalo/virología , Convulsiones Febriles/fisiopatología , Virosis/complicaciones , Antiinflamatorios/efectos adversos , Encéfalo/efectos de los fármacos , Encefalopatías Metabólicas/etiología , Encefalopatías Metabólicas/inmunología , Edema Encefálico/inmunología , Edema Encefálico/virología , Niño , Preescolar , Humanos , Lactante , Gripe Humana/complicaciones , Convulsiones Febriles/inmunología , Convulsiones Febriles/virología , Teofilina/efectos adversosRESUMEN
Acute encephalopathy is the most serious complication of pediatric viral infections, such as influenza and exanthem subitum. It occurs worldwide, but is most prevalent in East Asia, and every year several hundreds of Japanese children are affected by influenza-associated encephalopathy. Mortality has recently declined, but is still high. Many survivors are left with motor and intellectual disabilities, and some with epilepsy. This article reviews various syndromes of acute encephalopathy by classifying them into three major categories. The first group caused by metabolic derangement consists of various inherited metabolic disorders and the classical Reye syndrome. Salicylate is a risk factor of the latter condition. The second group, characterized by a systemic cytokine storm and vasogenic brain edema, includes Reye-like syndrome, hemorrhagic shock and encephalopathy syndrome, and acute necrotizing encephalopathy. Non-steroidal anti-inflammatory drugs, such as diclofenac sodium and mephenamic acid, may aggravate these syndromes. Severe cases are complicated by multiple organ failure and disseminated intravascular coagulation. Mortality is high, although methylprednisolone pulse therapy may be beneficial in some cases. The third group, characterized by localized edema of the cerebral cortex, has recently been termed acute encephalopathy with febrile convulsive status epilepticus, and includes hemiconvulsion-hemiplegia syndrome and acute infantile encephalopathy predominantly affecting the frontal lobes. Theophylline is a risk factor of these syndromes. The pathogenesis is yet to be clarified, but an increasing body of evidence points to excitotoxicity and delayed neuronal death.
Asunto(s)
Encefalopatías/etiología , Encefalopatías/virología , Gripe Humana/complicaciones , Virosis/complicaciones , HumanosRESUMEN
The prognosis of trisomy 18 is lethal, but recently some long-term survival cases have been recognized. We report here the mortality rate of trisomy 18 based on our hospital data and sporadically published reports in Japan. We collected the 7 previously published reports of mortality and 31 cases from our hospital data with trisomy 18. Our data pool comprised a total of 179 cases of trisomy 18 from 8 institutions. The mortality rates within 24 hours, 7, 28, 60, 180, and 365 days from birth were 14.84% (19/128), 31.01% (40/129), 56.25% (72/128), 64.08% (66/103), 82.17% (106/129), and 90.90% (140/154), respectively. Fourteen of the 154 patients (9.09%) survived for more than 1 year. The Kaplan-Meier survival curves from 78 patients of 5 institutes suggest that trisomy 18 children who have survived over 7 months after birth may have a high probability of long-term survival. We should recognize not only that about 50% of infants with trisomy 18 die within 1 month after birth, but also that about 10% of patients survive over 1 year in Japan. These findings comprise Asia's first clinical statistics concerning trisomy 18, in which the data were collected from multiple institutions. This evidence is valuable in order to perform genetic counseling concerning the natural history of trisomy 18 not only in Japan but also in other countries.
Asunto(s)
Cromosomas Humanos Par 18 , Trisomía/genética , Asesoramiento Genético , Humanos , Japón/epidemiología , Cariotipificación , Análisis de Supervivencia , Sobrevivientes , Trisomía/fisiopatologíaRESUMEN
A genomic DNA containing a rice (Oryza sativa L., cv. Norin-8) gene coding for a pullulanase-type starch debranching enzyme (EC 3.2.1. 41) was sequenced (EMBL/GenBank/DDBJ accession number AB012915). Along the 15, 248 bp DNA, the pullulanase gene is split into 26 exons. The four pullulanase consensus regions are positioned in the middle portion of the sequence and are separated by long introns and 1-3 exons. Comparison of the rice cv. Norin-8 pullulanase genomic structure with that of barley pullulanase (limit dextrinase) (F. Lok et al., EMBL/GenBank/DDBJ accession number AF022725) indicates that most of the pullulanase exons are highly conserved. Alignment of the nucleotide bases of rice exon 8 with those of barley exon 8-intron 8-exon 9 fragment suggests that the 85 bp internal sequence of rice exon 8 was originally an intron, a possibility further indicated by the absence in barley and spinach (A. Renz et al., EMBL/GenBank/DDBJ accession number X83969) pullulanases of amino acid residues encoded by the 85 bp fragment.
Asunto(s)
Genes de Plantas/genética , Glicósido Hidrolasas/genética , Oryza/enzimología , Secuencia de Bases , Clonación Molecular , Secuencia Conservada/genética , Exones/genética , Hordeum/enzimología , Intrones/genética , Datos de Secuencia Molecular , ARN Mensajero/análisis , Mapeo Restrictivo , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
Fluorescence microscopy of rice (Oryza sativa L.) callus sections showed that all of the walls fluoresced blue in water (pH 5.8) and green in ammonia (pH 10.0), both characteristics of feruloyl esters. Such fluorescence in the walls of cells cultured in Gamborg's B5 medium was much stronger than that in amino acid (AA) medium. Laser scanning microscopy showed that the level of fluorescence was higher in the intercellular layer, especially at corner junctions between cells, suggesting that ferulic acid ester derivatives are located in the middle lamella as well as in the wall. Extracellular polysaccharides appearing during cultivation in AA medium were more highly feruloylated than those in B5 medium during cultivation. Both the levels of ferulic and diferulic acid and the relative proportion of diferulic acid in the walls of cells increased on transfer of the cells cultured in AA medium to B5 medium. The walls of cells cultured in B5 medium maintained constant levels and proportions of the phenolic acids. Removal of phenolic acids from wall preparations by carboxylesterase facilitated the solubilization of noncellulosic polysaccharides. Treatment of the cell aggregates grown in AA medium with an enzyme that hydrolyzes feruloyl esters decreased the size of the aggregates to between 20 and 500 [mu]m, compared with an original size between 200 and 1000 [mu]m. These findings suggest that feruloyl and diferuloyl esters between polysaccharides are involved in the aggregation of cultured rice cells.
RESUMEN
We reported a case of a 22-months child with hemolytic uremic syndrome associated with encephalopathy. As the cause of this case, the involvements of verotoxin 1 and 2 caused by O157: the H7 strain of the enterohemorrhagic Escherichia coli and rotavirus were presumed. We administered brain hypothermic therapy and steroid pulse therapy in the intensive care unit, but we were not able to save his life and the child died on the 6th day from the onset.
Asunto(s)
Encefalopatías/diagnóstico , Infecciones por Escherichia coli/diagnóstico , Escherichia coli O157 , Síndrome Hemolítico-Urémico/diagnóstico , Infecciones por Rotavirus/diagnóstico , Enfermedad Aguda , Encefalopatías/etiología , Infecciones por Escherichia coli/complicaciones , Síndrome Hemolítico-Urémico/etiología , Humanos , Lactante , Masculino , Infecciones por Rotavirus/complicacionesRESUMEN
The Eker rat is a model for human tuberous sclerosis (TSC) caused by a mutation in the Tsc2 gene. We describe here histological and immunohistochemical findings of the brain lesions in Eker rats, with emphasis on 2 novel lesions found in this study: a cortical tuber and an anaplastic ganglioglioma. The rat cortical tuber resembled those of humans, and further confirmed the value of this animal model as a tool for investigating the molecular pathology of tuberous sclerosis. On the other hand, the rat anaplastic ganglioglioma had features of a malignant neoplasm that are absent from human subependymal giant cell astrocytomas.
Asunto(s)
Neoplasias Encefálicas/patología , Modelos Animales de Enfermedad , Ganglioglioma/patología , Corteza Motora/patología , Ratas Mutantes , Proteínas Represoras/genética , Esclerosis Tuberosa/patología , Animales , Anticuerpos , Neoplasias Encefálicas/genética , Epéndimo/anomalías , Ganglioglioma/genética , Hamartoma/genética , Hamartoma/patología , Corteza Motora/química , Neostriado/anomalías , Núcleo Accumbens/anomalías , Fenotipo , Ratas , Proteínas Represoras/análisis , Proteínas Represoras/inmunología , Esclerosis Tuberosa/genética , Proteína 2 del Complejo de la Esclerosis Tuberosa , Proteínas Supresoras de TumorRESUMEN
A 73-year-old woman had progressive right hemiparesis, aphasia, and focal motor seizures. EEG showed periodic discharges on the left. She died 8 weeks after onset. At autopsy, there was marked spongiform change, neuronal loss, and severe proliferation of astrocytes predominantly on the left and most prominently in the insular and centroparietal cortex. The changes were consistent with Creutzfeldt-Jakob disease (CJD), but pathology was slight or absent on the right side. This case appears as the first report of what might be called unilateral CJD. Such a condition should be included within the differential diagnosis of progressive unilateral cerebral disorders.
Asunto(s)
Síndrome de Creutzfeldt-Jakob/patología , Anciano , Corteza Cerebral/patología , Femenino , HumanosRESUMEN
We examined brains clinicopathologically from 54 consecutive paroxysmal atrial fibrillation (PAF) patients aged 70 years or older and compared them with those of 59 age-matched controls. Symptomatic cerebral infarctions were present in 29 PAF patients (53.7%) and in 13 controls (22.0%) (p < 0.001). Symptomatic brain infarction was 2.4 times more common in PAF cases than in PAF-free controls; approximately 60% of the infarctions in the PAF cases were judged to be cardioembolic in origin. PAF in the elderly can be an important cause for cardiogenic cerebral embolism.
Asunto(s)
Fibrilación Atrial/complicaciones , Infarto Cerebral/complicaciones , Enfermedad Coronaria/complicaciones , Embolia/complicaciones , Anciano , Anciano de 80 o más Años , Cadáver , Infarto Cerebral/epidemiología , Enfermedad Coronaria/epidemiología , Embolia/epidemiología , Femenino , Humanos , Incidencia , MasculinoRESUMEN
Although CT studies have addressed symptomatic and asymptomatic cerebral infarctions in nonrheumatic atrial fibrillation (NRAF), pathologic verification of the results is lacking. The purpose of this study was to assess the frequency, location, and extent of symptomatic and asymptomatic brain infarction in autopsy specimens from elderly patients with NRAF. We examined autopsy specimens from 136 consecutive NRAF patients 70 years of age or older who received no anticoagulant therapy during their lifetime and compared them with 231 age-matched control subjects with similar health histories except for the absence of NRAF. Symptomatic cerebral infarctions were present in 82 (60.3%) NRAF patients and in 55 (23.8%) control subjects (p < 0.0001). Of symptomatic cerebral infarctions, cardioembolic infarction was present in 53 (64.6%) NRAF patients and in two (3.6%) of the control subjects (p < 0.0001), atherothrombotic infarction in 13 (15.9%) NRAF patients versus 36 (65.5%) control subjects (p < 0.0001), and lacunar infarction in four (4.9%) NRAF patients versus 12 (21.8%) control subjects (p < 0.01). Stroke-related death occurred in 34 (25.0%) NRAF patients and in 18 (7.8%) control subjects (p < 0.0002). Symptomatic cerebral infarction was generally accompanied by asymptomatic infarctions in both NRAF patients and control subjects. Asymptomatic cortical infarctions were more common in NRAF patients, but asymptomatic infarctions in the white matter or deep structures were more common in control subjects. In this autopsy series of individuals over 70 years of age, symptomatic brain infarction was 2.5 times more common in NRAF patients than in NRAF-free control subjects; two-thirds of the infarctions in the NRAF cases were judged to be cardioembolic in origin. Most asymptomatic cerebral infarctions in the NRAF patients were located in the cortices.
Asunto(s)
Fibrilación Atrial/complicaciones , Infarto Cerebral/etiología , Embolia/complicaciones , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/epidemiología , Infarto Cerebral/epidemiología , Embolia/epidemiología , Embolia/etiología , Femenino , Humanos , Masculino , Prevalencia , Cardiopatía ReumáticaRESUMEN
The authors report a patient of pure apraxic agraphia with normal praxis due to left thalamic infarction. 15O-gas-PET showed reduced oxygen metabolism in the left thalamus and the left dorsolateral premotor area, while MRI and 11C-fulumazenil-PET showed no remarkable lesions in the frontal cortex. The patient's word imaging remained normal. The authors hypothesize that thalamic destruction causes pure apraxic agraphia by exerting a remote effect on left dorsolateral premotor area and blocking somewhere between graphemic area and motor programming.
Asunto(s)
Agrafia/etiología , Infarto Encefálico/complicaciones , Núcleo Talámico Mediodorsal/patología , Enfermedades Talámicas/complicaciones , Anciano , Agrafia/diagnóstico , Infarto Encefálico/diagnóstico , Humanos , Pruebas del Lenguaje , Imagen por Resonancia Magnética , Masculino , Núcleo Talámico Mediodorsal/irrigación sanguínea , Núcleo Talámico Mediodorsal/diagnóstico por imagen , Pruebas Neuropsicológicas , Enfermedades Talámicas/diagnóstico , Tomografía Computarizada de EmisiónRESUMEN
The influence of neonatal thyroidectomy (Tx) on GH production was investigated by means of Northern blot analysis. Tx resulted in a significant decrease in pituitary GH mRNA levels after 10, 15 and 20 days. The changes of pituitary GH mRNA were soon reflected in pituitary GH content. There was, however, no significant difference in pituitary GH mRNA levels and GH content between Tx and sham-operated rats at 5 days old. The pituitary GH cells were significantly decreased in number 15 and 20 days after Tx. These data suggest that GH mRNA is transcribed, independent of thyroid hormone, in the rat anterior pituitary gland during early neonatal life. In addition, the present study ascertained that GH dependence on thyroid hormone is acquired between the 5th and 10th day of neonatal life.
Asunto(s)
Animales Recién Nacidos , Hormona del Crecimiento/metabolismo , Hipófisis/metabolismo , Tiroidectomía , Animales , Northern Blotting , Femenino , Hormona del Crecimiento/genética , Inmunohistoquímica , Masculino , Microscopía Inmunoelectrónica , Hipófisis/ultraestructura , ARN Mensajero/análisis , Radioinmunoensayo , Ratas , Ratas Sprague-Dawley , Estadísticas no ParamétricasRESUMEN
The prolactin (PRL) gene expression and PRL accumulation in rat pituitaries during the neonatal period were measured by means of radioimmunoassay and Northern blot analyses. The effects of neonatal thyroidectomy (Tx) on PRL synthesis and release were also investigated. The pituitary PRL mRNA level at 20 fetal days had already reached levels sufficient to detect and was increased markedly in the early neonatal period. The PRL concentrations in sera were at almost the same level during the early neonatal period, but the increases of PRL contents and PRL mRNA levels were marked in this period. Neonatal Tx effectively decreased the PRL mRNA level and PRL contents in the pituitary after 10 postnatal days. A significant decrease in the serum PRL of the Tx group was first observed at 20 postnatal days. These data indicate that thyroid hormone dependent PRL secretion is established in the neonatal period.
Asunto(s)
Prolactina/metabolismo , Tiroidectomía , Animales , Animales Recién Nacidos , Regulación del Desarrollo de la Expresión Génica , Hipotiroidismo/etiología , Hipotiroidismo/metabolismo , Hipotiroidismo/fisiopatología , Prolactina/sangre , Prolactina/genética , Ratas , Ratas Sprague-DawleyRESUMEN
The relationships between overexpression of cyclin D1 or cyclin E and clinicopathological factors were investigated in 157 patients with non-small cell lung cancers (NSCLCs) using immunohistochemical analysis. Fifty-eight cases of NSCLCs (58/157, 37%) showed the overexpression of cyclin D1, and 64 cases (64/157, 41%) were positive for cyclin E. Cyclin E and cyclin D1 were infrequently concurrently overexpressed (17/157, 10.8%). Overexpression of cyclin E was more frequently observed in squamous cell carcinoma (29/57, 51%) compared with that in adenocarcinoma (28/86, 33%) (P<0.05). In addition, overexpression of cyclin E was more frequently observed in poorly or moderately differentiated NSCLCs (52/103, 50%) than in well-differentiated ones (12/54, 22%) regardless of their histological types (P<0.01). On the contrary, there was no statistically significant relationship between cyclin D1 overexpression and histological types or grade of tumor differentiation. These findings suggest that expression of cyclin E was frequently independent of that of cyclin D1 and played some roles in the grade of tumor differentiation in NSCLCs.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/química , Ciclina D1/biosíntesis , Ciclina E/biosíntesis , Neoplasias Pulmonares/química , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Transformación Celular Neoplásica , Femenino , Humanos , Neoplasias Pulmonares/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
A clinicopathologic study was made of 45 elderly persons whose autopsied brains showed the pathologic changes of progressive subcortical vascular encephalopathy (Binswanger type). Progressive subcortical vascular encephalopathy (PSVE) was observed in 3.8 per cent of all autopsied brains of elderly persons and in 6.7 per cent of the brains of those with cerebrovascular diseases. White matter lesions were graded from I to III (slight to severe). Small infarcts in the basal ganglia, thalamus, and pons were common, but the cerebral cortex was usually preserved. Neuropsychiatric symptoms included dementia, urinary incontinence, hemiplegia, pseudobulbar palsy, psychosis, parkinsonism, and mutism. In thge Grade III group there was a high incidence of pseudobulbar palsy, parkinsonism, and mutism. Pathologic study showed marked cerebral arteriosclerosis in almost all cases. Angionecrosis was observed in 60 to 80 per cent. Fibrotic and stenotic changes of the blood vessels in the deep white matter were also noted, particularly in 90 per cent of the Grade III cases. A suggested explanation for the pathogenesis of PSVE is based on the effects of various complications such as hypertension, cardiac disease and malnutrition which may play an important role in PSVE when they occur in elderly persons with a history of long-standing hypertension, marked cerebral arteriosclerosis, and arteriolar changes in the cerebral white matter.