年龄增长对GRK5基因缺陷小鼠海马内肿胀轴突丛形成与积累的影响

目的研究G蛋白偶联受体(G protein-coupled receptors)激酶5(GPCR kinase-5,GRK5)基因缺陷和老化交互作用对阿尔茨海默病(Alzheimer’s disease,AD)早期的病理改变-海马内肿胀轴突丛(swollen axonal clusters,SACs)出现和积累的影响。方法选取5、6、7、9、12-13、18-19月龄雌性GRK5基因敲除小鼠(GRK5Knockout,GRK5KO)作为观察对象,另选取年龄匹配的雌性野生型(wild type,WT)小鼠为对照,每个年龄段GRK5KO和WT小鼠各4只。用抗人神经原纤维缠结(neurofibrillary tangles,NFTs)特异性抗体的免疫荧光染色方法观察海马内SACs的变化。结果所有小鼠随着年龄增长,海马内SACs逐渐增加;GRK5KO小鼠组海马内NFT+SACs数量较WT型小鼠组显著增加(P<0.01);双因素方差分析显示遗传性GRK5基因缺陷和老化双因素对海马内NFT+SACs的影响有显著协同效应(P<0.01)。结论在促进早期AD病理发生的过程中,GRK5缺陷和老化双因素共同加剧了雌性GRK5KO小鼠海马内SACs的形成与积累。

皮质脊髓束参与肝硬化患者的肝门静脉分流:一项MEP研究

Hepatic myelopathy (HM) is a rare complication of chronic liver diseases usually associated with a portosystemic shunt, causing a progressive spastic parapare sis, and is likely to be overlooked. Thirteen patients with liver cir-rhosis associated with surgical or spontaneous portosystemic shunts were studied to determine the frequency and gravity of HM. Six patients exhibited clearcut signs of spinal cord involvement and four of them exhibited varying degrees of disability. Neurological examination did not reveal any abnormalities in the other patients. Motor evoked potentials (MEPs) were measured in all patients; in five of them the examinations were done before and after orthotopic liver transplantation (OLT). The patients with clinical signs of spinal cord involvement exhibited severe neurophysiological abnormalities, whereas milder but unequivocal MEP abnormalities were found in four of the seven patients with normal clinical examination. The clinical and neurophysiological features of patients with slight MEP abnormalities improved after OLT, whereas the patients with a more advanced stage of disease (severe MEPs abnormalities) did not. Our findings indicate that MEP studies may disclose an impairment of the corticospinal pathways even before HM is clinically manifest and provide evidence that early diagnosis of HM and subsequent immediate liver transplantation have to be recommended.

高血糖型偏盲:可逆转的非酮性高血糖并发症

Four patients each developed a reversible homonymous hemianopia caused by non-ketotic hyperglycemia. In two patients the homonymous hemianopia was the first manifestation of diabetes mellitus type 2. All four patients had abnormal MRI scans; in the three patients who had late follow-up scans the abnormalities resolved completely. In one patient the progressive visual field defect and unusual MRI findings initially caused concern for a tumor.

对舒马普坦治疗反应的预测:舒马普坦和那拉曲坦集合患者数据库

Objective: The efficacy and tolerability profiles of sumatriptan and other 5HT1B/1D agonists (triptans) have been well established. However, the determinants for optimal response to sumatriptan are unknown. The Sumatriptan Naratriptan Aggregate Patient (SNAP) database contains data from 128 clinical trials including 28,407 migraine sufferers treating over 130,000 attacks. The authors analyzed these data to identify factors predicting response (headache relief and pain free response) to sumatriptan. Methods: The authors assessed 24 possible univariate predictors of headache response in 3,706 patients (18 years and older) receiving sumatriptan tablets 100 mg or placebo in a double blind study using recursive partitioning and logistic regression techniques. Results: The authors found seven predictors of headache relief 2 hours postdose. Moderate pain at baseline was the strongest predictor (adjusted p = 3.32× 10- 18), followed by absence of a disability requiring bedrest (adjusted p = 3.11 × 10- 18). Other predictors included absence at baseline of vomiting, pulsating pain, nausea, or photophobia/ phonophobia, and onset of headache during daytime hours. Logistic regression confirmed that treatment with sumatriptan was the strongest predictor of headache relief, with significant baseline covariates being pain severity, level of disability, and presence or absence of vomiting. A similar pattern of results was reported for predictors of pain free response 2 hours after taking sumatriptan. Conclusions: Pretreatment pain seve rity is themost important predicting factor for response to sumatriptan in migraine attacks: the lower baseline severity, the better.

多发性硬化症损害与外观正常白质早发与迟发HHV-6的基因转录

Multiple sclerosis is an inflammatory demyelinating disease of the CNS, the ae tiology of which is believed to have both genetic and environmental components. We have investigated one of the candidate viruses for the environmental componen t of multiple sclerosis, the neurotropic human herpesvirus 6 (HHV-6).Utilizing fluorescent in situ hybridization (FISH) techniques,we have examined human post -mortem tissues for the presence of immediate early and late viral gene express ion in multiple sclerosis patient normal appearing white matter (NAWM), lesional tissue and normal control brain samples. HHV-6 gene transcription was detected in all tissue samples and was restricted to oligodendrocytes, as determined by double mRNA FISH analysis. Quantitative analysis of viral mRNA expression indica ted that both NAWM and lesional multiple sclerosis samples exhibited significant ly higher levels of HHV-6 expression compared with the normal control samples. Lesional samples exhibited the highest levels of viral gene expression,with NAWM exhibiting an intermediate level between lesional and control tissues. Immunofl uorescence against early and late HHV-6 proteins verified active translation of HHV-6 viral mRNA in oligodendrocytes. Southern blot analysis of nested polymer ase chain reactions using extracted genomic DNA and cDNA confirmed the presence of the HHV-6 genome in all individuals,with the active expression profile mirro ring the FISH results. The frequent high level of HHV-6 infection in multiple s clerosis samples suggests a possible role in pathogenesis.

利妥昔单抗治疗IgM单克隆自发感觉神经病

Rituximab, a monoclonal antibody against B-cell membrane marker CD-20, is an effective treatment for immunoglobulinM (IgM) monoclonal anti-myelin-associat ed glycoprotein(MAG) neuropathies. We report a patient with an autonomicand pain ful sensory neuropathy associated with an IgM lambda monoclonal gammopathy, resp onsive to rituximab. Treatment resulted in a decline in total IgM and improvemen t in the patient’s painful neuropathy and dysautonomia. Rituximab maybe an effe ctive and tolerable treatment for autonomic and sensory neuropathy associated wi th IgM monoclonal gammopathy.

ANTI-INFLAMMATORY EFFECTS OF TIANRONG ACUPOINT ON BLOOD VESSELS OF DURA MATER

Although Tianrong acupoint (SI 17) is used for migraine headache, its mechanism of action remains obscure. The effects of Tianrong acupoint therapy on neurogenically-mediated plasma protein extravasation (125I-BSA) in rat dura mater induced by electrical stimulation of the right trigeminal ganglion was studied. When the unilateral trigeminal ganglion was stimulated (5 Hz, 1.2 mA, 5 msec for 5 min), the ratio of stimulated side/ unstimulated side (cpm/mg) was 1.6663 ± 0.0217. The plasma extravasation was blocked by different kinds of treatment in different degrees. The order of the ratio was as follow: Tianrong acupoint therapy (1.0917 ± 0.0266) and Tianrong electrical needle therapy (1.1281 ± 0.0227) 【 Tianrong acupoint injection with normal saline (1.325 ± 0.0444) 【 Quchi acupoint (LI 11) injection with prednisolonum (1.5284 ± 1.1624). The results indicated that Tianrong acupoint therapy could inhibit the neurongenic inflammation on the affected side.

Relationship between Alzheimer′s,Parkinson′s disease and Apolipoprotein E polymorphism in the Chinese

目的 :探讨阿尔茨海默病 (AD)、帕金森病 (PD)及帕金森病痴呆 (PDD)的发病机理和与载脂蛋白 E(Apo E)基因多态性的关系。方法 :对 AD组 (48例 )、PD组 (5 4例 )、PDD组 (43例 )和非痴呆对照组 (2 34例 )的 Apo E基因频率及基因型分布进行对照研究。结果 :非痴呆对照组 Apo Eε3基因频率最高 (0 .887) ,而 AD组 Apo Eε 4基因频率明显升高 (0 .2 19) ,显著高于非痴呆对照组 (0 .0 5 1) (P<0 .0 1)。 PD(0 .0 2 8)和 PDD(0 .0 79)组 Apo Eε 4基因频率与非痴呆对照组相比无显著差异 (P>0 .0 5 )。结论 :Apo Eε4是导致 AD发病的易感或危险基因之一 ,而与 PD和 PDD的发病无关 ,说明 AD和 PD。

The Neurologist in the Emergency Room: Prospective Study of the Neurological Emergency Group in Lombardia

Purpose of the work was to quantify the workloads and the neurologist’s commitment in ER, to verify the management of urgencies and appropriateness of neurological counseling requests. Neurologic emergencies are frequent in elderly patients and are associated with high morbidity and mortality. Due to the aging population, neurologic pathologies in emergency room (ER) are widely expected to increase. The role of the neurologist in this context is controversial. Methods: in 14 operative units of neurology a prospective collection of neurological evaluations in ER was carried out using boards of detection of the most frequent neurological clinical pictures seen in the course of a week. Data were collected from 738 cases. Attention was focused on cerebrovascular diseases (CVD), impairment of consciousness, epilepsy, headache, dizziness, head trauma and disorders of the peripheral nervous system (PNS). Achievements: neurological consultations were on average 5% of total accesses to ER. The most common pathology seen was ischemic stroke. After counseling most patients were discharged home. The CVD required the greatest commitment to the specialist. The usefulness of the specialized neurological “filter” has been confirmed in a non-simple operative context, aimed at optimizing the appropriateness of the hospitalization and the economy of the diagnostic path.

64例包涵体肌炎患者的临床特征与临床病程

The clinical features of inclusion body myositis (IBM) were of minor importance in the design of consensus diagnostic criteria, mainly because of controversial views on the specificity of signs and symptoms, although some authors reported “ typical" signs. To re-assess the clinical spectrum of IBM, a single investigator using a standard protocol studied a cohort of 64 patients cross-sectionally. Symptom onset was before the age of 50 years in 20 % of cases. Only a few patients (14 % ) started with weakness other than that of quadriceps, finger flexor or pharyngeal muscles. The sequence of power loss was erratic, but onset of symptoms with quadriceps weakness predicted an earlier onset of dysphagia in older patients (≥ 56 years) compared with younger ones (< 56 years) (p = 0.02). Despite widespread weakness patients had favourable scores on three commonly used function scales and they kept their employment. Complete wheel-chair dependency was rare (3 % ). A dominant characteristic was the anatomical distribution of afflicted muscles: ventral extremity muscle groups were more affected than dorsal muscle groups and girdle muscles were least affected, the latter preserving postural stability. Ankylosis, especially in extension of the fingers, was frequently present. Together with the sparing of intrinsic hand muscles it was helpful in the preservation of many skilful movements. IBM has a unique distribution of muscle weakness. Ankylotic contractures are common. We feel that their joint impact on daily functioning is characteristic for the disease.

抗Yo阳性伴副瘤性小脑变性患者原发性肿瘤的检出策略

In patients with anti-Yo associated paraneoplastic cerebellar degeneration (P CD) neurological symptoms precede the diagnosis of the underlying cancer in abou t 60%. Ovarian carcinoma, breast cancer and other gynaecological malignancies a re most frequently found as causative malignancies. Antitumour treatment should be applied in an early stage of disease. The identification of the tumour is a d iagnostic challenge in many of these patients. In the first of two patients repo rted here a pelvic tumour was suggested after detection of a pathological lymph node and elevated tumour markers. The intraoperative findings appeared macroscop ically normal during ovariectomy with adnexectomy. Not until microscopic examina tion of the resected tissue was performed was a tubal adenocarcinoma found. If i ntrapelvic gynaecological tumours are suspected a deliberate surgical exploratio n seems to be justified, but only after an intensive diagnostic investigation. T o search for the underlying cancer in patients with paraneoplastic neurological disorders successive CT and[18F]-FDG-PET are widely recommended. Instead of th is in the second reported patient whole-body dualmodality PET/CT was performed revealing enhanced uptake in three regions of the left thorax. By combining func tion and anatomy PET/CT was able to localise the lesions and characterise them a s lymph node metastases of breast cancer. Diagnosis could be confirmed by subseq uently executed needle biopsy. PET/CT seems to be highly applicable in the inves tigation of paraneoplastic disorders with unknown primary cancer. It may help in guidance of needle biopsy or to optimise the results of deliberate surgery and it provides whole-body tumour staging in a single session with higher diagnosti c accuracy than PET alone.

短暂性全面遗忘症患者颈静脉瓣关闭不全的发病率升高

Objective: While transient global amnesia (TGA) is a clinically well defined disorder, its etiology is poorly understood. Cerebral venous hypertension and subsequent damage to hippocampal and diencephalic structures are among the discussed hypothetical causes. Using a direct method for the study of retrograde flow during a Valsalva maneuver, we determined whether jugular valve insufficiency contributes to cerebral venous hypertension in patients with TGA. Methods: Jugular valve closure was assessed by duplex sonography in 20 patients with TGA and 20 age and gender matched controls. The diagnosis of valvular insufficiency was made on the basis of recently established criteria. Results: Valvular insufficiency (either left or right-sided, or bilateral) was identified in 85 % of patients with TGA, and in 45 % of controls (p = 0.008). All patients with involuntary Valsalva episodes immediately prior to TGA developed valvular insufficiency (n = 8; p = 0.13 compared with patients who did not recall such an event). The mean duration of the insufficiency jet did not differ significantly between patients with TGA (3.26s) and controls (2.78s; p = 0.315). However, patients with TGA who experienced a trigger event were characterized by significantly longer insufficiency reflux times (3.84s) than those without (2.55s; p = 0.03). Conclusions: TGA is associated with an increase in the prevalence of jugular insufficiency. Valvular insufficiency may lead to increased venous pressure transmission during a Valsalva maneuver and thus contribute to venous ischemia in TGA. The association of valvular insufficiency and longer reflux times with the occurrence of a trigger event further suggests that cerebral venous congestion is an important etiological factor in transient global amnesia.

一项利妥昔单抗治疗副肿瘤性神经系统综合征相关抗体的非对照试验

Anti-CD20 monoclonal antibody (rituximab) is effectively used in the treatment of B-cell lymphomas. Recent reports in the literature suggest that antibody associated autoimmune disorders may respond to rituximab. We therefore treated nine patients with anti-Hu or anti-Yo associated paraneoplastic neurological syndromes (PNS) with a maximum of four monthly IV infusions of rituximab (375 mg/m2). In this uncontrolled, unblinded trial of rituximab, three patients improved ≥ 1 point on the Rankin Scale (RS). One patient with limbic encephalitis improved dramatically (RS from 5 to 1). Further studies of rituximab in autoantibody associated PNS are warranted.

乙酰胆碱酯酶抑制剂多奈哌齐可改善阿尔茨海默病患者的脑血管动态调节

Background: Alzheimer’s disease (AD) leads to a degeneration of the nucleus basalis of Meynert and thus to decreased cholinergic tonus in the brain. The transcription of endothelial nitric oxide synthase depends on an adequate cholinergic innervation of microvessels and vasoregulative abnormalities have been reported in AD. We investigated activation-flow coupling to study the role of acetylcholine esterase inhibition (AChEI)on vasoregulative function. Methods: A functional transcranial Doppler approach was used to measure the visually evoked flow velocity response in the posterior cerebral artery in AD patients who had no vascular risk factors. The diagnosis of AD was made according to the ICD10/DSMIIIR-criteria. After baseline recording the effect of four weeks 5 mg donepezil and then four weeks 10 mg was investigated. Doppler data were evaluated with a control system approach to obtain dynamic properties of vasoregulation and were compared with a healthy control group. Results: AD patients showed an increased damping (0.64 ± 0.2; p = 0.007 vs. control) in evoked responses and lower resting flow velocity levels (40 ± 13 cm/s; p = 0.06 vs. control), which were restored in a dose-dependent manner under AChEI(0.4 ± 0.2; 44 ± 11 cm/s). Conclusions: AD is associated with a functional vasoregulative deficit possibly due to decreased levels of the endothelial nitric oxide synthase. Augmenting levels with AChEI normalized flow regulation possibly leading to a better blood supply to active neurons.

肌萎缩侧索硬化症患者的情绪反应

Amyotrophic lateral sclerosis (ALS) is a fatal disease, leaving the patient in a partially or completely deafferented state. In an explorative study, we investigated responses to visual socio-emotional stimuli in ALS patients. Pictures from the International Affective Picture System (IAPS) were verbally judged by 12 moderately affected ALS patients with a spinal onset and a slow progression and 18 age-matched controls, and data were compared with psychophysiological responses. Verbal emotional judgments of patients were more positive than ratings of controls. Regarding arousal, patients neutralized extreme pictures, in that they rated calm pictures as more exciting than controls and exciting pictures as more calm. These changes of emotional processing were unrelated to depression or frontal lobe dysfunction. There were no major differences between patients and controls concerning physiological responses to emotional stimuli. We conclude that emotional responses of ALS patients tend to be altered towards positive valence and towards a more balanced arousal state in early stages of the disease. These findings contradict assumptions of a generally negative impact of the disease on the emotional disposition and may indicate compensatory cognitive or neuroplastic changes.

房颤患者的卒中前痴呆:发病率和相关因素

Background and purpose: Prestroke dementia is frequent but usually not identified. Non-valvular atrial fibrillation (NVAF)is independently associated with an increased risk for dementia. However, the frequency and determinants of prestroke dementia in patients with NVAF have never been evaluated. Objective: The aim of this study was to determine the frequency of prestroke dementia and associated factors in patients with a previously known NVAF. Methods: This is an ancillary study of Stroke in Atrial Fibrillation Ensemble II (SAFE II), an observational study conducted in patients with a previously known NVAF, consecutively admitted for an acute stroke in French and Italian centers. Prestroke dementia was evaluated by the IQCODE in patients with a reliable informant. Patients were considered as demented before stroke when their IQCODE score was ≥ 104. Results: of 204 patients, 39 (19.1 % ; 95 % confidence interval [CI]: 13.7 % - 24.5 % ) patients met criteria for prestroke dementia. The only variable independently associated with prestroke dementia was increasing age (adjusted odds ratio for 1 year increase in age: 1.10; 95 % CI: 1.04- 1.17), and there was a non-significant tendency for previous ischemic stroke or TIA and arterial hypertension. Conclusion: One fifth of stroke patients with a previously known NVAF were already demented before stroke. The main determinant of prestroke dementia is increasing age. A large cohort is necessary to identify other determinants.

丘脑底核刺激对帕金森病自发性抑制的影响

Background: Recent animal experiments suggest an important role of descending input from basal ganglia to brainstem and via the reticulospinal tract (RST) to spinal cord in the genesis of motor symptoms in Parkinson disease (PD). In human s, a marker for RST activity is Ib mediated autogenic inhibition, which is reduc ed in PD patients. The authors investigated the effect of high frequency stimula tion of the subthalamic nucleus (STN HFS) on autogenic inhibition in PD. Method s: In 10 controls and 10 PD patients with chronically implanted STN electrodes, the soleus H reflex conditioned by gastrocnemius nerve stimulation (interstimul us interval 2 to 10 msec) was used to examine the effect of STN HFS on the acti vity f Ib spinal interneurons. Results: STN HFS was able to restore the abnorma lly reduced autogenic inhibition. The H reflex changes during STN HFS signific antly correlated with the clinical improvement of gait and posture. Conclusions: Observed changes in spinal autogenic inhibition may allow measurement of the co ntribution of subcortical routes to the STN HFS induced motor benefit in PD.

增加使用静脉rt-PA治疗不影响急性卒中患者的安全

Background: Intravenous thrombolysis with rt-PA improves outcome in acute ischemic stroke. In a prospective study we analyzed the annual frequency of rt-PA treatment, its safety, and early clinical outcome. Methods: All patients admitted to our stroke unit (SU) from 1998 to 2003 were registered in a prospective data base. Documented data included patient age, sex, time interval until admission, initial therapy (e. g., thrombolysis), death, intracerebral hemorrhage, other complications, and score on the National Institute of Health Stroke Scale (NIHSS). Results: From 1998 to 2003, a total of 112 patients were treated with systemic thrombolysis. The number of acute stroke patients admitted within 2.5 hours and therefore eligible for thrombolysis did not substantially change between 1998 and 2003. From 1998 to 2001 the percentage of acute stroke patients that received rt-PA was stable (12.6- 16.9 % ). This percentage increased in 2002 (29.6 % , p < 0.05) and, again, in 2003 (42.1 % , p < 0.01). Of all treated patients, two developed symptomatic intracerebral hemorrhage (1.8 % ) and five died three to seven days after thrombolysis (4.5 % ). The NIHSS score of patients receiving rt-PA significantly decreased during the acute treatment phase (14.2 ± 5.1 to 8.0 ± 5.9, p < 0.001). A comparison of single years revealed that this NIHSS score reduction was stable. Conclusion: In our selected patients, the proportion of acute stroke patients treated with systemic thrombolysis increased almost three-fold from 1998 to 2003. This may be explained by protocol modifications and growing experience with the use of rt-PA. Our data demonstrate that increased use of rt-PA in acute stroke patients can be achieved without adversely affecting safety or clinical benefit.

多发性硬化症社区人群中未被认识的抑郁症状

Background and aims: The association between multiple sclerosis (MS) and depression has been well established but prevalence estimates have varied widely. The aims of this study were to assess the point prevalence of previously unrecognised symptoms of depression in a community-based population with MS and examine their relationship to other disease characteristics. Patients and methods: Three hundred and seventy six patients with clinically definite or probable MS (Poser criteria)were ascertained during the course of an epidemiological study on two counties in Ireland. Of these 211 agreed to participate in the study. Subjects were examined and a Kurtzke Expanded Disability Status Scale Score and Multiple Sclerosis Functional Composite score rated. Participants also completed a Beck’s Depression Inventory-II and a Multiple Sclerosis Impact Scale. Results: In total 60 (28%) patients had moderate or severe symptoms of depression. Only thirty-five of the 211 patients had a history of depression as defined by a medical diagnosis of depression or prescription of an anti-depressant medication at any time prior to enrolment in the present study, of the rem aining 176 patients, 41 (23.3 %) had moderate or severe symptoms of depression as assessed by Beck’s Depression Inventory-II. The only significant clinical difference between the 41 patients with pronounced depressive symptoms and the 135 less affected was shorter disease duration in the former. Conclusions: In this study one in four patients with MS had unrecognised and therefore untreated symptoms of depression. Disability alone is not a good indicator of the likelihood of coexistent depressive symptoms.

特发性震颤患者运动时间的评估

Background: We have observed mild bradykinesia in essential tremor (ET) patients, which do not satisfy the criteria of Parkinson’s disease (PD). Abstract:Objective: To compare the mean movement time for repetitive movements around distal and proximal joints in ET patients with normal controls by using a simple test paradigm. Patients and methods: Seventeen patients with ET and 14 control subjects were instructed to tap with the index finger sequentially on push-button microswitches. Movement times around metacarpophalangeal, wrist, elbow, and shoulder joints of the right side were tested. The data collected were stored on a computer and the time elapsed between sequential taps on two keys (ms) and number of taps on the left key for 15 seconds were evaluated offline. Results: Movement times of the patients with ET were not found to be significantly different from those of the controls at all joints tested despite slight prolongation for movements around the shoulder joint. Conclusion: The simple test paradigm we have used showed that there is no difference in the movement time for repetitive movements around fourjoints of the upper extremity between patients with ET and normal control subjects. The slightly prolonged movement time around the shoulder joint noted in patients with ET may be ascribed to tremor, not bradykinesia. Tremor may cause these patients to pay more attention to the performance of goal-directed finger movements and consequently prolong movement time slightly or it may simply delay the time elapsed to reach the goal in the absence of overt intention tremor.