Effect of sailuotong capsule on intervening cognitive dysfunction of multi-infarct dementia in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of Sailuotong capsule (Sailuotong) on learning and memory functions of multi-infarct dementia (MID) rats and its mechanism.</p><p><b>METHOD</b>All SD rats were divided into five groups, namely the sham operation group, the model group, the positive group, the low dosage Sailuotong-treated group and the high dosage Sailuotong-treated group. The multi-infarct dementia model was established by injecting the micro-sphere vascular occlusive agent. On the 10th day after the successful operation, the rats were administered intragastrically with distilled water, memantine hydrochloride (20 mg x kg(-1)) and Sailuotong (16.5 mg x kg(-1) and 33.0 mg x kg(-1)) once a day for 60 days respectively, in order to detect the effect of Sailuotong in different doses on the latent period and route length in Morris water maze and the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) in brain tissues.</p><p><b>RESULT</b>Compared with the sham operation rats, it had been observed that the latent period and route length of MID rats in Morris water maze were significantly increased (P < 0.05 or P < 0.01), and the activity of ChAT in brain tissues was significantly decreased (P < 0.05). After the intervention with Sailuotong for sixty days, the latent period and route length of MID rats in Morris water maze significantly shrank (P < 0.05 or P < 0.01). Additionally, Sailuotong decreased AchE activity, while increasing ChAT activity in brain tissues of MID rats (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>Sailuotong capsule can improve cognitive dysfunction of MID rats to some extent. Its mechanism may be related to its different regulation of activities of ChAT and AchE in brain tissues.</p>

Vascular Dementia

Vascular dementia (VaD) is a dementia syndrome produced by vascular damage to the brain and increases in incidence with advancing age. Early Identification and diagnosis of VaD is particularly importent since its course may be modifiable through controlling vascular risk factors. VaD is heterogeneous and consists of several syndromes : multi-infarct dementia, strategic single infarcts dementia, and subcortical vascular dementia. The diagnosis of VaD is based on several features 1) dementia, 2) evidence of cerebrovascular disease, and 3) temporal relationship between dementia and cerebrovascular disease. Treatment of VaD includes control of vascular risk factors, prevention of further vascular injury and treatment of cognitive impairment. Cholinesterase inhibitors provide symptomatic benefits in treatment of VaD.

Diffusion weighted imaging in acute stroke and stroke mimics: reliability analysis, radiological findings and clinical significance

To assess the reliability and to determine the sensitivity and specificity of Diffusion Weighted Images [DWI] in detection of acute infarcts in patients whose initial CT and conventional MR-sequences did not explain the patients stroke symptoms. The second aim was to find out if DWI provides additional information when it was performed within 2 days of onset of symptoms. MRI and DWI of 59 consecutive patients [66% were male; aged 60 +/- 14 year [Mean +/- SD]] admitted with stroke and stroke like episodes were retrospectively analyzed. The images were independently evaluated by two neuroradiologists. DWI showed acute infarct in 25 patients [42%]. Hemiplegia and dizziness were the most common symptoms in patients with positive and negative DWI, respectively. Lacunar infarcts near the motor cortex were the most common type of infarcts detected by DWI. DWI provided additional information in 89% of patients when performed within 2 days of ictus compared 31% in patients examined =2 days after ictus [Fisher's exact test, P 0.011]. DWI provided relevant information in 26% of patients despite negative DWI. The specificity and sensitivity of DWI in acute stroke was 100% and 89% respectively. DWI is a reliable MR-sequence in the workup of acute and subacute stroke. DWI helps to differentiate acute infarcts from other white matter changes seen on conventional MRI-sequences. In patients with stroke like episodes, a negative DWI provides relevant clinical information and help in future clinical management

Effects of acupuncture on expression CuZnSOD mRNA and protein in hippocampus of the rat with multi-infarct dementia / 中国针灸

<p><b>OBJECTIVE</b>To explore the mechanism of acupuncture in treatment of multi-infarct dementia (MID).</p><p><b>METHODS</b>The multi-infarct dementia model was made by injection of emboli into the internal carotid artery. The dementia rats were randomly divided into 3 groups: model group, acupuncture group and non-acupoint acupuncture group, and a normal group and a sham operation group were set up. The expression of CuZnSOD in the hippocampus of the rats were detected by in situ hybridization and immunohistochemical assay, and effects of acupuncture were analyzed.</p><p><b>RESULTS</b>The expressions of mRNA and protein of CuZnSOD in the hippocampus of the model group were significantly attenuated as compared with that in the normal control group. Both the parameters above were significantly increased in the acupuncture group as compared with the model control group, but with no significant difference between the acupuncture group and the normal control group.</p><p><b>CONCLUSION</b>Acupuncture can up-regulate the expressions of mRNA and protein of CuZnSOD in the rat with MID, so as to strengthen activity of antioxidase and effectively remove free radicals and improve intelligence of MID rats.</p>

Small Vessel Disease and Subcortical Vascular Dementia

Atherothromboembolism and intracranial small vessel disease are considered to be the main causes of cerebrovascular injury, which may lead to cognitive impairment and vascular dementia (VaD). VaD appears to be the second most common type of dementia with prevalence estimates of 10-15%. Cortical or multi-infarct dementia and subcortical vascular dementia (SVD) are suggested to be the two main forms of VaD. The main clinical features of SVD comprise decreased motor performance, early impairment of attention and executive function with slowing of information processing. SVD results from lacunar infarcts or multiple microinfarcts in the basal ganglia, thalamus, brainstem and white matter and are associated with more than 50% of the VaD cases. White matter changes including regions of incomplete infarction are usually widespread in VaD but their contribution to impairment of subcortical regions is unclear. While most of VaD occurs sporadically only a small proportion of cases bear clear familial traits. CADASIL is likely the most common form of hereditary VaD, which arises from subcortical arteriopathy. SVD needs unambiguous definition to impact on preventative and treatment strategies, and critical for selective recruitment to clinical trials.

Encefalopatia traumática crônica do boxeador (dementia pugilistica) / Chronic traumatic encephalopathy (dementia pugilistica) of the box player

A dementia pugilistica é caracterizada clinicamente por declínio cognitivo, alterações de comportamento e sinais parkinsonianos. Do ponto de vista neuropatológico, o achado mais marcante é o de numerosos emaranhados neurofibrilares no córtex cerebral na virtual ausência de placas senis. O objetivo deste artigo é apresentar revisão do tema, enfatizando as alterações cognitivas, epidemiologia, neuropatologia, estratégias de detecção precoce e relação com a doença de Alzheimer.

Presenile dementia--etiology, clinical profile and treatment response at four month follow up.

Dementia is the development of multiple cognitive deficits that includes memory impairment and at least one of the following--Aphasia, apraxia, agnosia or disturbances in executive functioning. The common causes of dementia among the elderly are Alzheimer's disease, vascular dementia, mixed dementia and Lewy body disease. The concept of reversible dementia was introduced in 1980 when a task force sponsored by National Institute of Ageing found 10-12% of dementia cases in older group to have reversible causes such as metabolic-nutritional, drugs, infections, psychiatric disorders etc. In our series of 76 patients in the presenile age group (<65 years), 34.21% (26/76) had a reversible condition underlying the dementia. 43.42% (33/76) had vascular dementia, 13.15% (10/76) had Alzheimer's disease and 9.21% (7/76) had mixed dementia. Hypertension, hyperlipidemia and diabetes mellitus were commoner in the vascular dementia group as compared to the Alzheimer's group. Evaluation of MRI as a tool in diagnosis of dementia showed increased sensitivity of MRI towards detecting lacunes. The potentially reversible dementias comprised infections 14.47% (11/76), metabolic-nutritional 14.47% (11/76) and autoimmune diseases 3.94% (3/76). These were characterized by a subcortical dementia. Four month follow up of MMSE in this group showed significant and sustained improvement in the metabolic nutritional group.

Some observations on the spectrum of dementia.

A study was designed to generate epidemiological and clinical data on dementia, in a teaching hospital in India. It was conducted on 124 (94 male and 30 female) elderly patients (aged more than 60 years) presenting with clinical syndrome of dementia (DSM-3). Their age range was 64-78 (mean 65.7 4.1) years. Detailed clinical, biochemical, radiological and electrophysiological evaluation was done to establish etiology. Patients with psychiatric ailments, cranial trauma and tumors were excluded. The study period was 4.2 years. Multi-infarct dementia (MID) was observed to be commonest cause of dementia and was present in 59 (47.6%) cases. There were 10 (8%) patients each of tuberculosis (TB) and neurocysticercosis (NCC). Alcohol-related dementia was present in 13 (10.5%), while malnutrition (Vitamin B12 deficiency) was present in 9 (7.2%). Alzheimer's Disease (AD) was present (NINCDS-ADRDA criteria) in 6 patients (4.8%). There were 3 (2.4%) cases 1 each of Huntington's disease, Parkinson's and Normal Pressure Hydrocephalus and 2 each of diabetes, hypothyroidism, hyperthyroidism and Creutzfeldt' Jakob Disease. We conclude that AD, which is irreversible and common in the west, is relatively uncommon in India as compared to MID, infections and malnutrition, which are potentially treatable.

Vascular dementia and vascular cognitive impairment / 中国医学科学院学报

Vascular dementia (VaD) subtypes include multi-infarct dementia, subcortical ischemic vascular dementia, strategic-infarct dementia, etc. Poststroke dementia may be related to preexisting cognitive level, and the frequency increased with aging, lower educational level and accompanied vascular risk factors. Vascular cognitive impairment (VCI) forms a spectrum that includes VaD, mixed Alzheimer's disease (AD) with a vascular component, and VCI without dementia. The concept of VCI will improve the early diagnoses and secondary prevention and treatment of VaD, and promote the further research on vascular component in neurodegenrative disorders.

CADASIL: una forma de demencia vascular hereditaria: presentación de un caso clínico aparentemente esporádico / CADASIL: hereditary vascular dementia: description of an apparently sporadic clinical case

Presentamos un caso de CADASIL (acrónimo inglés de arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía), que corresponde al primero de una serie de 4 casos diagnosticados en nuestro servicio desde 1998, con correlato clínico, imageno-lógico y de ultrapatología muscular (microscopia electrónica). Se trata de una paciente mujer con historia de dos crisis isquémicas cerebrales transitorias a los 29 años, sin factores de riesgo tradicionales para patología cerebrovascular, que luego de 7 años desarrolló síntomas de tipo depresivos, asociados a un cuadro de retraimiento sicomotor y parkinsonismo de carácter progresivo y sin respuesta a terapia farmacológica convencional. En su estudio, la resonancia nuclear magnética de cerebro mostró extensas alteraciones en sustancia blanca a nivel fronto-occipital, bilaterales, hiperintensas en T2 e hipointensas en T1, cuya señal no se reforzó con gadolinio, sin efecto de masa, asociadas a leucoaraiosis, compatibles con el diagnóstico de CADASIL. El estudio de una biopsia muscular mediante microscopia electrónica, confirmó una arteriopatia con depósito de material granular osmiofílico en los vasos sanguíneos, tipo CADASIL. No encontramos antecedentes de cuadros demenciales ni cerebrovasculares sintomáticos en otros parientes de la paciente, madre, padre, tíos, abuelos, por lo que es probable que se trate de un cuadro esporádico. No realizamos estudio genético ni biopsico de los parientes asintomáticos. Las características de la paciente ilustran cuando sospechar el diagnóstico de CADASIL, aún frente a un caso aparentemente esporádico.

Mutation of the Notch 3 gene in a Thai cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy family.

The authors report the first Thai family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in which the family members had a classical history of progressive vascular dementia. The proband was a 31-year old Thai male who presented with an acute stroke in the subcortical region. His past history revealed mental disturbance, including poor judgement and regressive behavior as well as mood changes for 1 year. He did not have a history of migraine or any other vascular risk factors except for a strong family history of ischemic stroke and progressive dementia. Magnetic resonance imaging demonstrated multiple small infarctions in the subcortical white matter of the bilateral frontal, parietal and occipital lobes with another small lesion in the pons. Genetic study demonstrated a Notch 3 mutation consisting of the substitution of a nucleotide at position 406 in exon 3 leading to the replacement of an Arginine by Cysteine at position 110 in the 2nd EGF motif, which is compatable with CADASIL.

Observation on efficacy of CT positioning scalp circum-needling combined with Chinese herbal medicine in treating poly-infarctional vascular dementia / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the short-term effect of patients with poly-infarctional vascular dementia (PIVD) treated by CT positioning scalp circum-needling (SCN) combined with Chinese herbal medicine.</p><p><b>METHODS</b>Eighty-nine patients of PIVD were enrolled and divided into the treated group (n = 57) and the control group (n = 32). They were all treated with oral taking of Fuyuan mixture (FYM, consisted of ginseng, medlar, salvia, bitter cardamon, etc). To the treated group, SCN was applied additionally with the unilateral area around the reflecting region (localized by CT) in scalp as main needling points and Ganshu, Shenshu, Zusanli, Hegu as supplementary points. Two courses of SCN were performed. The changes of clinical symptoms, intelligence and hemorrheological characteristics in patients were analysed.</p><p><b>RESULTS</b>After two courses of treatment, the total effective rate in the treated group was 96.5%, which was better than that in the control group (75.0%), with significant difference (u = 2.423, P < 0.01); HDS scores increased in both groups after treatment, showing significant difference as compared with that before treatment (P < 0.01), hemorrheologic parameters were also apparently improved.</p><p><b>CONCLUSION</b>CT positioning SCN combined Chinese herbal medicine treatment has definite therapeutic effect in treating PIVD.</p>

A Novel Mutation (C67Y) in the NOTCH3 Gene in a Korean CADASIL Patient

We report a 52-yr-old Korean woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) whose diagnosis was confirmed by skin biopsy and the presence of a novel mutation in the NOTCH3 gene. The patient's clinical features were rather unusual in that 1) clinical presentations were only two episodes of stroke and mild dementia unaccompanied by mood disturbances or migraine, and 2) there was no family history. Brain MRI showed T2 hyperintensities in both temporal pole areas in line with the recent suggestion by O'Sullivan et al. that the abnormality could be a radiologic marker of CADASIL. FDG-PET also showed a hypometabolism in the temporal pole areas with an abnormal finding on MRI in addition to the hypometabolism in cortical and subcortical regions. We could learn from this case that CADASIL may be included in the differential diagnoses in patients with vascular dementia associated with a small vessel disease, even in the absence of a family history, especially when there are no known stroke risk factors and when the MRI shows T2 hyperintensity in the temporal pole regions.

Arteriopatía autosómica dominante con infartos subcorticales y leucoencefalopatía (CADASIL) / Autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL)

La arteriopatía autosómica dominante con infartos subcorticales y leucoencefalopatía (CADASIL) es una enfermedad vascular cerebral hereditaria que compromete pequeñas arterias y se caracteriza por isquemias recurrentes, parálisis pseudobulbar y demencia. Otras manifestaciones clínicas incluyen migraña y depresión. Reportamos una familia argentina compuesta de VI generaciones con evidencia de enfermedad en IV. De los 262 integrantes vivos de la familia se tomaron 30 sospechosos de enfermedad a los cuales se les realizaron exámenes de rutina para descartar otra causa de ACV. Por consentimiento se logró el estudio genético en 18 y resonancia magnética en 21 de éstos pacientes. Se realizó una biopsia de piel en un enfermo típico para avalar el diagnóstico. De éste grupo de 30 pacientes se eligieron 5 descendientes sanos a los cuales se les practicó RMI y estudios genéticos. Tres de ellos tenían estudios genéticos y RMI normales, los dos restantes tenían alteraciones genéticas y la RMI fue patológica. Los hallazgos en RMI fueron áreas pequeñas, hiperintensas en T2, con características de infartos de sustancia blanca periventricular, tronco cerebral, ganglios basales y talámos. Presentando además áreas confluentes, hipertensas en T2 en sustancia blanca, a menudo simétricas

Vascular Dementia

Vascular dementia (VD) is a dementia syndrome associated with cerebrovascular disease. Among the several subtypes of VD, most common subtypes are multi-infarct dementia, single-infarct dementia, and subcortical vascular dementia. In patients with multi-infarct dementia, dementia occurs with a close temporal relationship to stroke episodes. Brain imaging usually shows multiple territory cortico-subcortical infarcts. Single-infarct dementia, in contrast, is caused by a single infarct in specific regions of the brain such as thalamus, caudate nucleus, capsular genu, angular gyrus, or hippocampus. In subcortical VD, primary lesion is lacunar infacts or ischemic white matter lesions that are located in subcortical regions, i.e., deep nuclei (basal ganglia and thalamus) or white matter (periventricular and deep white matter). The diagnosis of subcortical vascular dementia is challenging, since stroke episodes are often unrecognized, thus temporal relationship between onset of dementia and stroke is lacking. This article describes 1) subtypes of VD, 2) illustrative cases with vascular dementia, 3) research criteria for VD, 4) treatment of VD, and 5) a general guideline on caregiving for patients with VD, which will enable clinicians to provide better diagnosis and management of patients with VD.

Cadasil: um caso com diagnostico molecular / Cadasil: a case with molecular diagnosis

CADASIL include the presence of osmophilic granulateriopathy with Subcortical Infarcts and Leukoencephalopathy) was described in 1991 by Tourmier-Lasserve. Two years later the same authors described its association with chromosome 19; nonetheless, the mutations in gene Notch3 were not described until 1996. Clinical findings depend on the age at onset. The early form of the illness is found in young patients, generally less than 30 years old, and the main clinical manifestation is a migraine headache with subcortical lesions in the white matter, while in the later form ischemic events and behavioral symptoms are predominant. Anatomo-pathological findings in CADASIL include the presence of osmophilic granular deposits in vessel walls, skin, muscles and cerebral arteries. We present a patient with CADASIL and cavernous angioma. We studied a 40-year-old woman who underwent surgery for a left temporal-parietal cavernous angioma, with aphasia as the only symptom, two years before admission. Her family history showed that her father had suffered from vascular dementia. She was admitted to our hospital with right-side hemiparesis and dysarthria. A CT scan showed the presence of ischemic vascular lesions and former surgery sequelae. The duplex scan of the neck vessels and a transesophageal echocardiogram ruled out an embolic source. Laboratory tests including VDRL, HIV, prothrombotic profile and rheumatologic screening tests were normal. An MRI in T2W and FLAIR showed the presence of multiple subcortical cerebral lesions and hyperintensity in the white matter (leukoencephalopaty). We found a left acute putaminal-capsular infarct in the diffusion-MRI. The MRA was normal. Analysis of the cerebrospinal fluid was unremarkable. A molecular DNA test was performed, and a nucleotide substitution in position 583 in exon 4 of gene Notch3 was detected. This mutation was found only in CADASIL patients. The association with cavernous angioma has not been previously reported, and we believe that it was unrelated to CADASIL, either clinically or genetically. To our knowledge, this is the first case of CADASIL diagnosed by molecular DNA test in our country.

Dementia Mortality and Related Clinical Factors at a Nursing Home

OBJECTIVE: This study was designed to evaluate the cause of mortality in patients with dementia, including Alzheimer's disease and multi-infarct dementia, and those without dementia. METHOD: Hospital records of geriatric patients (> or =65) in nursing home having dementia were reviewed retrospectively for 6 years. The total number of patients was 351 (the number of demented patients was 146 and those without dementia was 68). Of the ones with dementia, 146 had dementia of Alzheimer's type, 101 patients had vascular dementia, and 36 patients had non-specific dementia. This study focused on the different complications associated with Alzheimer's disease and cerebrovascular dementia. RESULT: 1) The average age at death of demented patient is higher than the non-demented population;however, there is no difference in age between Alzheimer's disease and vascular dementia. 2) There is no difference in time spent in the nursing home among the non-demented group, Alzheimer's disease and vascular dementia group from admission to death. The life expectancy of male patients with Alzheimer's disease after admission to the nursing home is significant shorter than their female counterpart. 3) Patients with vascular dementia have a higher incidence of hypertension, atherosclerotic disease, and diabetes than the Alzheimer's patients. 4) The main overall causes of the death (in nursing home patients) are infection and sepsis. In Alzheimer's disease's, sepsis is the major cause of death, while in vascular dementia, atherosclerotic disease is the number one cause. CONCLUSION: Knowledge of the causes of the death in demented patients may help the management of the possible complications associated with the different types of dementia. However, long-term research is then needed to analyze the survival rates of demented nursing home patients.

Subtypes of Vascular Dementia

Vascular dementia is defined as a clinical syndrome of acquired intellectual impairment resulting from a brain injury due to a cerebrovascular disorder. It incorporates various vascular pathophysiological mechanisms and changes in the brain, and has diverse cause and clinical manifestations. The main suptypes of vascular dementia include 1) multi-infarct dementia, 2) strategic infarct dementia, and 3) subcortical vascular dementia. Both multi-infarct dementia and strategic infarct dementia show heterogeneity in etiologies, changes of the brain, as well as clinical manifestations. On the contrary, subcortical vascular dementia is suggested to be a more homogenous group. To better understand the clinical features of vascular dementia, cases corresponding to each subtype of vascular dementia are briefly discussed this review.