Background: Randomized trials of thrombolytic stroke treatment have either excluded patients with posterior circulation ischemia or used inclusion criteria making enrollment of these patients less likely. Consequently...Background: Randomized trials of thrombolytic stroke treatment have either excluded patients with posterior circulation ischemia or used inclusion criteria making enrollment of these patients less likely. Consequently, there is less published information on thrombolytic therapy for posterior circulation stroke. Objective: To determine effective thrombolytic treatment times for posterior circulation stroke and factors that might help predict clinical outcome. Design: We describe our experience treating 21 consecutive patients with either intravenous or intra-arterial thrombolytic therapy for posterior circulation ischemic stroke between October 9, 1993, and February 19, 2001. Main Outcome Measures: National Institutes of Health Stroke Scale, Glasgow Coma Scale, and modified Rankin Scale scores were evaluated at baseline, and the modified Rankin Scale was measured 3 months after stroke, with a good outcome being a modified Rankin Scale score of 2 or less. Results: Nine patients received intravenous therapy; 12 patients received intra-arterial therapy. The median National Institutes of Health Stroke Scale score at onset was 20 (range, 2-39), and the median Glasgow Coma Scale score was 9 (range, 3-15). Twelve patients were treated within 8 hours of symptom onset (range, 11/2 hours to 16 days). Nine patients (43%) had a modified Rankin Scale score of 2 or less at 3 months. The initial Glasgow Coma Scale score and treatment within 8 hours of symptom onset were each associated with good outcome, but the initial National Institutes of Health Stroke Scale score was not predictive. Conclusions: Thrombolytic therapy for posterior circulation stroke may be beneficial even when initiated 8 hours after symptom onset. Level of consciousness, as measured by Glasgow Coma Scale score, seems to be a more important predictor of outcome than the initial National Institutes of Health Stroke Scale score.展开更多
Background: An easily accessible and valid surrogate marker for interventional stroke trials is needed. Objective: To investigate the usefulness of various S100B serum measures to predict long-term outcome and infarct...Background: An easily accessible and valid surrogate marker for interventional stroke trials is needed. Objective: To investigate the usefulness of various S100B serum measures to predict long-term outcome and infarct volume in patients with acute stroke. Design: Inception cohort study. Setting: Tertiary care university hospital. Patients: Thirty-nine patients (mean±SD age, 69.1±11.5 years) with acute nonlacunar middle cerebral artery infarction presenting less than 6 hours after symptom onset. Main Outcome Measures: Functional outcome 6 months after stroke (modified Rankin scale score) and final infarct volume on day 7 by means of standardized volumetry of brain images. Serum S100B level was determined at hospital admission and 24, 48, 72, 96, 120, and 144 hours after symptom onset. Results: Single S100B measures obtained 48 and 72 hours after stroke onset demonstrated the highest Spearman rank correlations with modified Rankin scale scores (p=0.68 and p=0.67, respectively; P < .001) and infarct volume (p=0.95 and p=0.94, respectively; P < .001). A 48-hour S100B value of 0.37 μg/L or less revealed a sensitivity of 0.87 and a specificity of 0.78 in predicting an independent functional outcome. In a multivariate model, S100B emerged as an outcome predictor that was independent of age, sex, stroke severity, etiology, lesion side, and risk factors. Conclusions: Single S100B values obtained 48 and 72 hours after stroke onset provide the highest predictive values with respect to functional outcome and infarct volume in nonlacunar middle cerebral artery infarction. More complex measures of the S100B kinetic (ie, area under the curve or peak value) were not superior. Therefore, these single S100B measures appear to be useful surrogate end points in acute interventional stroke trials.展开更多
Background: Apart from diffusion-weighted imaging (DWI)- lesion volume and diffusion-perfusion mismatching, there is limited information about neuroradiological predictors of early prognosis after an ischaemic stroke....Background: Apart from diffusion-weighted imaging (DWI)- lesion volume and diffusion-perfusion mismatching, there is limited information about neuroradiological predictors of early prognosis after an ischaemic stroke. This study sought to identify specific DWI lesion patterns that would help prediction of early prognosis of three different endpoints: unstable hospital course, recurrence of stroke, and poor neurological outcome at 90 days after ischaemic stroke. Methods: A total of 426 patients with acute cerebral infarcts within the middle cerebral artery territory were prospectively studied. Using the DWI data the patients were divided into six groups (territorial, other cortical, small superficial, internal border zone, small deep, and other deep infarcts), and any recurrent strokes and prognosis over the following 90 days were recorded. Results: DWI lesion pattern was a stronger and more consistent independent outcome predictor than DWI lesion volume. The specific DWI lesion patterns associated with each endpoint differed. An unstable hospital course was frequently observed in patients with internal border zone infarcts, whereas recurrent strokes after the index stroke were commoner in those who had small superficial infarcts (p < 0.05 in both cases). Similarly, poor outcome after stroke was associated with older age, severe neurological deficits at admission, and a DWI lesion pattern showing internal border zone infarcts. Conclusions: The results of the present study indicate that the DWI lesion pattern may help in recognition of the likely differences in the early prognostic endpoints after ischaemic stroke, and DWI analysis may guide targeted interventions to prevent negative outcomes.展开更多
Background: Mutations in the NOTCH3 gene are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is an important cause of stroke in young adults. Mu...Background: Mutations in the NOTCH3 gene are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is an important cause of stroke in young adults. Mutations are typically located within epidermal growth factor-like repeat domains in the extracellular part of the Notch3 receptor. Identification of the mutation is critical for genetic counseling and testing of relatives at risk. Objectives: To identify the spectrum of NOTCH3 mutations in CADASIL and to discuss the implications for diagnostic strategies. Design: Screening for NOTCH3 mutations was performed in 125 unrelated German CADASIL patients with biopsy-proven disease by direct sequencing of exons coding for epidermal growth factor-like repeats. Results were compared with those of previously published studies. Results: We detected 54 distinct mutations (117 missense mutations and 3 in-frame deletions) in 120 (96.0%) of the 125 patients. Of the mutations, 58.3%were located in exon 4 and 85.8%in exons 2 through 6. In 5 patients (4.0%), no mutation was identified. Conclusions: Almost 90%of mutations could be detected within a few exons (exons 2-6). Thus, genetic testing should initially be focused on these exons, with some variation depending on the population in whom it is being performed. Yet, genetic testing for CADASIL is associated with a nameable proportion of false-negative results. Cases with a high index of clinical suspicion should be investigated by skin biopsy if genetic testing is negative.展开更多
Background: Transporters, ion pumps, and ion channels are membrane proteins that regulate selective permeability and maintain ionic gradients across cell membranes. Mutations in CACNA1A encoding a neuronal calcium cha...Background: Transporters, ion pumps, and ion channels are membrane proteins that regulate selective permeability and maintain ionic gradients across cell membranes. Mutations in CACNA1A encoding a neuronal calcium channel and ATP1A2 encoding an ion pump cause episodic ataxia, hemiplegic migraine, and seizures. Mutant gene products of both CACNA1A and ATP1A2 may affect neurotransmission of glutamate, the most abundant excitatory amino acid neurotransmitter. Methods: We examined our patient population with episodic ataxia and hemiplegic migraine but with no mutation in either CACNA1A or ATP1A2. We looked for mutations in SLC1A3, which encodes the glutamate transporter excitatory amino acid transporter (EAAT) 1 that is important in removing glutamate from the synaptic cleft. Results: A patient with episodic ataxia, seizures, migraine, and alternating hemiplegia has a heterozygous mutation in SLC1A3 that is not present in his asymptomatic parents and controls. Expression studies of the mutant EAAT1 showed decreased expression of the protein with a markedly reduced capacity for glutamate uptake. When coexpressed, the mutant EAAT1 decreased the activity of wild-type EAAT1 but not of two other transporters EAAT2 or EAAT3, suggesting that mutant EAAT1 specifically multimerizes with wild-type EAAT1 to exert its dominant negative effect. Conclusion: Our data show that a heterozygous mutation in EAAT1 can lead to decreased glutamate uptake, which can contribute to neuronal hyperexcitability to cause seizures, hemiplegia, and episodic ataxia.展开更多
Abstract:Objectives: Cerebral white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) are a recognised risk factor for post-stroke dementia. Their specific relations to cognitive impairment are still ...Abstract:Objectives: Cerebral white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) are a recognised risk factor for post-stroke dementia. Their specific relations to cognitive impairment are still not well known. The purpose of this study was to explore how the severity and location of WMHs predict neuropsychological test performance in the context of other brain lesions in elderly stroke patients. Methods: In the Helsinki Stroke Aging Memory Study, 323 patients, aged from 55 to 85 years, completed a detailed neuropsychological test battery and MRI 3 months after an ischaemic stroke. The demographic and MRI predictors of cognition were studied with sequential linear regression analyses. Results: After age, education and total infarct volume were controlled for, the overall degree of WMHs predicted poor performance in tests of mental speed, executive functions, memory, and visuospatial functions, but not in those of short term memory storage or verbal conceptualisation. However, the contribution of separate white matter regions was relatively low. Only the lesions along the bodies of lateral ventricles were independently associated with speed and executive measures. Additionally, general cortical atrophy clearly predicted a wide range of cognitive deficits while infarct volume had less relevance. Further analyses revealed that executive functions act as a strong mediator between the relationship of WMHs to memory and visuospatial functions. Conclusions: The degree of WMHs is independently related to post-stroke cognitive decline. The most affected cognitive domains seem to be executive functions and speed of mental processing, which may lead to secondary deficits of memory and visuospatial functions.展开更多
Dopamine agonists are increasingly used in the treatment of Parkinson disease, but they may cause serious adverse effects. In December 1983, symptoms of Parkinson disease developed in a 55-year-old man with no history...Dopamine agonists are increasingly used in the treatment of Parkinson disease, but they may cause serious adverse effects. In December 1983, symptoms of Parkinson disease developed in a 55-year-old man with no history of pulmonary disease, smoking, or asbestos exposure. He began treatment with dopamine agonists bromocriptine mesylate (in 1984) and pergolide mesylate (in 1989). In late 2000, pulmonary symptoms developed. Chest radiographs and computed tomographic findings showed a mass in the right upper lobe and effusion. A biopsy specimen showed pleural and parenchymal fibrosis. This syndrome resolved after cessation of pergolide therapy and a switch to pramipexole dihydrochloride. This case draws attention to the association of long-term ergot dopamine agonist therapy with pleuropulmonary fibrosis, which can develop as late as 11 years after the initiation of therapy. We also review evidence that the risk of this complication is substantially lower with the newer nonergot dopamine agonists.展开更多
Early, active multiple sclerosis lesions show four immunopathological patterns of demyelination. Although these patterns differ between patients, multiple active lesions from a given patient have an identical pattern,...Early, active multiple sclerosis lesions show four immunopathological patterns of demyelination. Although these patterns differ between patients, multiple active lesions from a given patient have an identical pattern, which suggests pathogenic heterogeneity. Therapeutic plasma exchange (TPE) has been successfully used to treat fulminant demyelinating attacks unresponsive to steroids. We postulated that patients with pattern II would be more likely to improve after TPE than those with other patterns since pattern II lesions are distinguished by prominent immunoglobulin deposition and complement activation. We retrospectively studied 19 patients treated with TPE for an attack of fulminant CNS inflammatory demyelinating disease. All patients with pattern II (n=10), but none with pattern I (n=3) or pattern III (n=6), achieved moderate to substantial functional neurologicalimprovement after TPE (p < 0.0001). Patients with multiple sclerosis with pattern II pathology are more likely to respond favourably to TPE than are patients with patterns I or III.展开更多
Background: Information on the mechanism of recurrent stroke may help physicians treating patients with ischemic stroke. However, the mechanisms of recurrence in each stroke subtype are not well known, especially in A...Background: Information on the mechanism of recurrent stroke may help physicians treating patients with ischemic stroke. However, the mechanisms of recurrence in each stroke subtype are not well known, especially in Asians. Abstract:Objective: To compare the mechanisms of the index and recurrent stroke. Design: Analysis of data from a prospective acute stroke registry. Setting: University hospital. Patients: Using the clinical syndrome, diffusion-weighted imaging, and vascular studies, we divided 901 patients into 5 groups: large-artery atherosclerosis, cardioembolism, small-artery disease, parent-artery disease occluding the deep perforators, and no determined cause. The patients with large-artery atherosclerosis were subdivided into 2 groups: intracranial and extracranial. Main Outcome Measures: The mechanisms of recurrent vascular events (strokes or coronary heart disease) in subtypes of ischemic stroke were compared. Results: Ninety-three recurrent vascular events (86 strokes and 7 instances of coronary heart disease) were evaluated. The pattern of recurrent stroke differed for the intracranial and extracranial groups; unlike the patients with intracranial large-artery atherosclerosis, recurrent strokes in the extracranial group were often unpredictable with respect to the site of recurrence and degree of preexisting stenosis. None of the patients in the extracranial group had recurrences that were caused by intracranial large-artery atherosclerosis or vice versa. In patients with small-artery disease and stroke with no determined cause, intracranial stenosis was often found at the time of recurrence. Conclusions: From prognostic and therapeutic perspectives, patients with atherosclerosis should be divided into those with intracranial large-artery atherosclerosis and extracranial large-artery atherosclerosis. In addition, intracranial large-artery atherosclerosis may be important in the development of small-artery disease and stroke with no determined cause, especially in the population with a higher frequency of intracranial large-artery atherosclerosis.展开更多
Background: Acute multiple brain infarction (AMBI) pattern on diffusion-weighted imaging (DWI) is associated with arterial and cardiac sources of embolism. The DWI characteristics of patients with stroke due to verteb...Background: Acute multiple brain infarction (AMBI) pattern on diffusion-weighted imaging (DWI) is associated with arterial and cardiac sources of embolism. The DWI characteristics of patients with stroke due to vertebrobasilar arterial dissection and atherosclerotic disease have not been reported in detail. Abstract:Objective: To describe the DWI stroke patterns in patients with posterior circulation occlusive disease to determine mechanisms of ischemia. Design: Retrospective analysis of infarct patterns in patients with symptomatic vertebrobasilar disease. Setting: Large community-based teaching hospital. Patients: Patients admitted with stroke due to vertebrobasilar disease were identified retrospectively.Patients were included if DWI was obtained within 7 days of symptom onset. Main Outcome Measure: Infarct patterns were analyzed according to established templates of vascular territories. Results: Eleven patients with vertebral dissection and 39 patients with atherothrombosis were identified.An AMBI pattern was present in 8 (72%) of 11 patients with arterial dissections and 25 (64%) of 39 patients with atherosclerotic disease (P = .48). Distal embolism to the terminal branches of the basilar artery occurred with equal frequency in both groups and was found in half of all cases. Isolated thalamic infarction did not occur. Pontine infarction was noted in 2 (18%) of 11 patients with dissections and 18 (46%) of 39 patients with atherosclerosis (P = .09). Cerebellar border zone involvement was found in 14 (36%) of 39 patients with atherosclerosis and 4 (37%) of 11 patients with dissections (P = .6). Conclusions: Large arterial disease is frequently associated with AMBI in the posterior circulation. The incidence of AMBI was comparable to that reported in the anterior circulation. This DWI study supports the importance of embolism as the main mechanism of infarction in patients with vertebrobasilar occlusive disease. On the basis of our experience, large-vessel vertebrobasilar disease rarely causes isolated small-vessel thalamic infarction.展开更多
Background: Headache is the most frequent symptom in cerebral venous thrombosis (CVT), and usually the first. However, it has rarely been reported as the only symptom of CVT. Objectives: To study the characteristics o...Background: Headache is the most frequent symptom in cerebral venous thrombosis (CVT), and usually the first. However, it has rarely been reported as the only symptom of CVT. Objectives: To study the characteristics of patients in whom headache was the only presentation of CVT in the absence of intracranial hypertension, subarachnoid haemorrhage (SAH), meningitis, or other intracranial lesion. Methods: From a prospective study of 123 consecutive patients with CVT only those with isolated headache and normal brain computed tomography (CT) scan and cerebrospinal fluid (CSF) examination were included in the present study. All patients underwent an extensive systematic aetiological work-up and were given intravenous heparin followed by oral anticoagulants. A detailed description of the headache was obtained. Results: Headache was only sign of CVT in 17 patients. The lateral sinus was the most frequently involved sinus (n=15). Onset of headache was progressive in 11, acute in 3, and thunderclap in 3 patients. Once established, the headache was continuous in 15, diffuse in four and unilateral in 13, usually ipsilateral to the occluded lateral sinus. No specific risk factor or cause was found. All had a favourable evolution. Conclusion: The pathogenesis of isolated headache in CVT in the absence of intracranial hypertension, SAH, meningitis or intracerebral lesion is unknown but may involve changes in the walls of the occluded sinus. Hence MRI/MRV should be used to look for signs of CVT in all patients with recent headache (progressive or thunderclap) even when the CT scan and CSF examination are normal.展开更多
Using ultrasonography we found multiple sites with nerve enlargement along the course of the brachial plexus, median, ulnar, and radial nerves in the majority of 21 patients with multifocal motor neuropathy. Sonograph...Using ultrasonography we found multiple sites with nerve enlargement along the course of the brachial plexus, median, ulnar, and radial nerves in the majority of 21 patients with multifocal motor neuropathy. Sonography and electrophysiologic studies showed more abnormalities than expected on purely clinical grounds. Moreover, sonography revealed nerve enlargement without clinical or electrophysiologic abnormalities.展开更多
Objective. -To study the frequencies and characteristics of different headache types seen in patients with Behet’s syndrome (BS) in a large cohort of patients. Background. -Patients with BS may present with differe...Objective. -To study the frequencies and characteristics of different headache types seen in patients with Behet’s syndrome (BS) in a large cohort of patients. Background. -Patients with BS may present with different neurological problems, related either directly or indirectly to the disease, with headache being the most common neurological symptom seen in this syndrome, as well as independent from neurologic involvement. Method. -This study was carried out at the multidisciplinary Behet outpatient clinic of the Behet’s Syndrome Research Center. Every fifth admitted patient who had fulfilled the International Study Group for Behet’s Disease classification criteria was recruited for this study. Each patient was interviewed by one of the examining neurologists through a semistructured questionnaire. In case of the presence of more than one headache type, the best defined one was diagnosed and evaluated. All patients received a complete neurological and physical examination. A χ2 test was used to evaluate the differences between frequencies. One sample Mest was used to compare means. The prevalence rates of primary headaches were compared with results of the Turkish Headache Epidemiology study by using goodness-of-fit test. Results. -Two hundred and twenty-eight patients were studied. Headache was reported in 66.2%(151/228) of the study cohort. Primary headaches were seen in 38.6%of the patient population, which corresponds to 58%of BS patients with any type of headache. Tension-type headache (TTHA)-and migraine were seen in 23.6%and 14.9%of the whole study cohort, respectively. In 5.2%of the study cohort, the headache was associated with neurological involvement and in 3.9%to uveal inflammation. A predominantly frontal, bilateral paroxysmal throbbing pain of moderate severity was reported in 18.4%of the study cohort who did not fulfill the criteria of the International Headache Society (IHS) for any of the primary headaches. It was commonly associated with exacerbations of the mucocutaneous symptoms of the syndrome. The neurological examination was normal in all of these patients. This type of headache was categorized as the nonstructural headache of Behet. Conclusion. -Headache is the most common neurological symptom seen in BS, both in patients with and without neurological involvement. The results of our study reveal that headache is seen in a majority of patients with neurological involvement due to BS and in a minority with uveal inflammation. The prevalence of migraine and TTHA are close to the population in general, but a nonstructural migrainous headache, which is commonly associated with exacerbations with some of the systemic symptoms of the syndrome, is noteworthy in patients with BS. This form of headache is not specific for this disorder, but may be explained by a vascular headache triggered by the immunomediated disease activity in susceptible individuals.展开更多
Objectives: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson’s disease (PD). Deep brain stimulation of the STN (STN DB...Objectives: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson’s disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications, has been thought to inhibit STN hyperactivity and therefore decrease progression of PD. Methods: In a prospective two centre study, disease progression was determined by means of serial 18F fluorodopa (F-dopa) positron emission tomography (PET) in 30 patients with successful STN DBS over the first 16 (SD 6) months after surgery. Results: Depending on the method of PET data analysis used in the two centres, annual progression rates relative to baseline were 9.5-12.4%in the caudate and 10.7-12.9%in the putamen. Conclusions: This functional imaging study is the first to demonstrate a continuous decline of dopaminergic function in patients with advanced PD under clinically effective bilateral STN stimulation. The rates of progression in patients with STN DBS were within the range of previously reported data from longitudinal imaging studies in PD. Therefore this study could not confirm the neuroprotective properties of DBS in the STN target.展开更多
Objective. -To investigate the efficacy and tolerability of almotriptan 12.5 mg in migraine patients who respond poorly to sumatriptan 50 mg. Background. -Poor response to sumatriptan therapy for acute migraine attack...Objective. -To investigate the efficacy and tolerability of almotriptan 12.5 mg in migraine patients who respond poorly to sumatriptan 50 mg. Background. -Poor response to sumatriptan therapy for acute migraine attacks has been documented in the literature, but few controlled trials have investigated the efficacy of an alternative triptan in this subgroup of patients. Methods. -Patients with an International Headache Society diagnosis of migraine who self-described as experiencing at least two unsatisfactory responses to sumatriptan treated their first migraine attack with open-label sumatriptan 50 mg. Patients who did not achieve 2-hour pain relief (improvement of headache from moderate/severe to mild/no headache) were then randomized to treat their second attack with almotriptan 12.5 mg or placebo under double-blind conditions. Results. -In the first attack, 221 of 302 participants (73%) did not achieve 2-hour pain relief with sumatriptan and were randomized to treatment of their second attack with almotriptan 12.5 mg or placebo. Of the 198 sumatriptan nonresponders who treated their second attack (99 almotriptan; 99 placebo), 70%had severe headache pain at baseline. Two-hour pain-relief rates were significantly higher with almotriptan compared to placebo (47.5%vs 23.2%; P < .001). A significant treatment effect for almotriptan was also seen in pain-free rates at 2 hours (33.3%vs 14.1%; P < .005) and sustained freedom from pain (20.9%vs 9.0%; P < .05). In the second attack, 7.1%of patients in the almotriptan group experienced adverse events compared to 5.1%in the placebo group (P=.77). Conclusions. -Almotriptan 12.5 mg is an effective and well-tolerated alternative for patients who respond poorly to sumatriptan 50 mg. A poor response to one triptan does not predict a poor response to other agents in that class.展开更多
Objective: To assess the accuracy and clinical usefulness of [ 123I]β-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane)-SPECT in the differential diagnosis of Parkinson’s disease. Subjects: 185 consecutive patients w...Objective: To assess the accuracy and clinical usefulness of [ 123I]β-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane)-SPECT in the differential diagnosis of Parkinson’s disease. Subjects: 185 consecutive patients with symptoms of movement disorder were studied. The diagnoses were Parkinson’s disease (92), essential tremor (16), vascular parkinsonism (15), various Parkinson plus syndromes (P+) (12), dementia with Lewy bodies (DLB) (5), dystonia (5), drug induced movement disorder (12), and other diagnoses (8). A reference group (psychogenic parkinsonism) comprised 20 subjects with complaints suggesting extrapyramidal disease but with no unequivocal signs on clinical examination and no abnormalities on brain imaging. Results: β-CIT uptake was significantly lower in the whole striatum as well as separately in the putamen and in the caudate nucleus in Parkinson’s disease than in the reference group or in drug induced movement disorder, essential tremor, or dystonia. The uptake of β-CIT in the vascular parkinsonism group was heterogeneous and mean β-CIT uptake fell between the reference group and the Parkinson’s disease group. In the P+and DLB groups the striatal uptake ratios overlapped those of the Parkinson’s disease group. Conclusions: [123I]β-CIT SPECT may not be as useful a tool in the clinical differential diagnosis of Parkinson’s disease as was previously believed, but it was 100%sensitive and specific for the diagnosis in younger patients (age < 55 years). In older patients (age > 55 years)-specificity was substantially lower (68.5%). This differential specificity reflected the different distribution of differential diagnostic disorders (P+, DLB, vascular parkinsonism) in the older and younger age groups.展开更多
Myotonic dystrophy (DM) is a multisystem autosomal dominant inherited disease that primarily affects the nervous system, causing myotonia and a characteristic pattern of muscular atrophy and weakness. Careful clinical...Myotonic dystrophy (DM) is a multisystem autosomal dominant inherited disease that primarily affects the nervous system, causing myotonia and a characteristic pattern of muscular atrophy and weakness. Careful clinical description in the late 19th and early 20th centuries separated DM from a similar muscle disease, myotonia congenita, allowing it to emerge as a distinct nosologic disease entity. The electrical characteristics of myotonia were described in the early to mid 20th century. Assiduous study of the clinical features and genetics of DM, including the phenomenon of anticipation, culminated in the discovery of the genetic mutations underlying DM in the early 1990s.展开更多
Context: Basilar artery occlusion(BAO) is an infrequent disease with high morbidity and mortality. Intra-arterial thrombolysis is advocated for treatment but is limited to use at specialized centers. Objective: To eva...Context: Basilar artery occlusion(BAO) is an infrequent disease with high morbidity and mortality. Intra-arterial thrombolysis is advocated for treatment but is limited to use at specialized centers. Objective: To evaluate outcomes for patients with BAO treated with intravenous thrombolytic therapy. Design, Setting, and Participants: During 1995 to 2003, 50 consecutive patients with angiographically proven BAO were treated according to an institutional therapy protocol based on intravenous thrombolysis with recombinant tissue plasminogen activator(alteplase). Patients were treated at an urban university teaching hospital receiving all patients with ischemic stroke who were considered for thrombolysis in a catchment area of 1.5 million inhabitants in Helsinki, Finland. Intervention: Intravenous administration of alteplase(0.9 mg/kg) during a 1-hour infusion. Main Outcome Measures: Basilar artery recanalization determined by magnetic resonance angiography and clinical outcomes at 3 months and at 1 year or longer determined by modified Rankin Scale and Barthel Index scores. Results: Recanalization was studied in 43 patients and verified in 26(52%) of all patients. By 3 months, 20 patients(40%) had died while 11 had good outcomes(modified Rankin Scale score, 0-2); 12(24%) reached independence in activities of daily living(Barthel Index score, 95-100), and 6(16%) were severely disabled(Barthel Index score, 0-50). In the long term(median follow-up 2.8 years), 15 patients(30%) reached good outcomes(modified Rankin Scale score, 0-2) while 23(46%) died. Conclusions: Intravenous administration of alteplase for patients with BAO appears to be associated with rates of survival, recanalization, and independent functional outcome comparable with those reported with endovascular approaches. These data suggest that a randomized trial is needed to compare these approaches for treatment of BAO.展开更多
Background: The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of autosomal dominant ataxias: some mutations, including SCA1, SCA2, and SCA3, are multisystemic disorders characterized by a variet...Background: The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of autosomal dominant ataxias: some mutations, including SCA1, SCA2, and SCA3, are multisystemic disorders characterized by a variety of noncerebellar symptoms while others, like SCA6, give rise to a pure cerebellar syndrome. Abstract:Objective: To identify impairments of the dopaminergic system and regional changes of glucose metabolism in SCA1, SCA2, SCA3, and SCA6. Methods: We used [11C]d-threo-meth- ylphenidate and [18F]-fluorodeoxyglucose positron emission tomography to identify cerebral dopamine terminal loss and specific regional metabolic patterns in SCA1, SCA2, SCA3, and SCA6. Results: The binding potential of [11C]d-threo-methylphenidate was reduced in the striatum in SCA2 and SCA3; in contrast to patients with Parkinson disease, no increased susceptibility of the putamen was evident. Decreased regional cerebral glucose metabolism was found in the cerebellum of all patients with SCA, the brainstem of SCA1, SCA2, SCA3, the thalamus and putamen of SCA3, and the parietal cortex of patients with SCA2. A trend toward increased regional cerebral glucose metabolism was found in the temporal cortex of all patients with SCA, pronounced in SCA6. Conclusions: Specific biochemical patterns point to different mechanisms of neuronal dysfunction in SCA1, SCA2, SCA3, and SCA6; dopamine terminal loss is severe in SCA2 but distinct from Parkinson disease.展开更多
We studied whether a difference exists in the development of symptoms of the Lambert-Eaton myasthenic syndrome (LEMS) between patients with or without small cell lung cancer (SCLC). We assessed symptoms in 38 LEMS pat...We studied whether a difference exists in the development of symptoms of the Lambert-Eaton myasthenic syndrome (LEMS) between patients with or without small cell lung cancer (SCLC). We assessed symptoms in 38 LEMS patients, 13 with SCLC, by interviewing them using a structured checklist, backed up by a review of their clinical records, and compared the frequency and time scale of symptoms during the course of LEMS. Bulbar (87%) and autonomic (95%) symptoms for the whole group were more common than reported in the literature. Frequencies of symptoms did not differ significantly between patients with and without SCLC, but symptoms in patients with SCLC appeared within a shorter time-frame, indicating a more rapid clinical course. The presence of a particular symptom associated with LEMS did not predict the presence of SCLC, but in patients with rapidly progressive LEMS the possibility of underlying lung cancer should be of particular concern.展开更多
文摘Background: Randomized trials of thrombolytic stroke treatment have either excluded patients with posterior circulation ischemia or used inclusion criteria making enrollment of these patients less likely. Consequently, there is less published information on thrombolytic therapy for posterior circulation stroke. Objective: To determine effective thrombolytic treatment times for posterior circulation stroke and factors that might help predict clinical outcome. Design: We describe our experience treating 21 consecutive patients with either intravenous or intra-arterial thrombolytic therapy for posterior circulation ischemic stroke between October 9, 1993, and February 19, 2001. Main Outcome Measures: National Institutes of Health Stroke Scale, Glasgow Coma Scale, and modified Rankin Scale scores were evaluated at baseline, and the modified Rankin Scale was measured 3 months after stroke, with a good outcome being a modified Rankin Scale score of 2 or less. Results: Nine patients received intravenous therapy; 12 patients received intra-arterial therapy. The median National Institutes of Health Stroke Scale score at onset was 20 (range, 2-39), and the median Glasgow Coma Scale score was 9 (range, 3-15). Twelve patients were treated within 8 hours of symptom onset (range, 11/2 hours to 16 days). Nine patients (43%) had a modified Rankin Scale score of 2 or less at 3 months. The initial Glasgow Coma Scale score and treatment within 8 hours of symptom onset were each associated with good outcome, but the initial National Institutes of Health Stroke Scale score was not predictive. Conclusions: Thrombolytic therapy for posterior circulation stroke may be beneficial even when initiated 8 hours after symptom onset. Level of consciousness, as measured by Glasgow Coma Scale score, seems to be a more important predictor of outcome than the initial National Institutes of Health Stroke Scale score.
文摘Background: An easily accessible and valid surrogate marker for interventional stroke trials is needed. Objective: To investigate the usefulness of various S100B serum measures to predict long-term outcome and infarct volume in patients with acute stroke. Design: Inception cohort study. Setting: Tertiary care university hospital. Patients: Thirty-nine patients (mean±SD age, 69.1±11.5 years) with acute nonlacunar middle cerebral artery infarction presenting less than 6 hours after symptom onset. Main Outcome Measures: Functional outcome 6 months after stroke (modified Rankin scale score) and final infarct volume on day 7 by means of standardized volumetry of brain images. Serum S100B level was determined at hospital admission and 24, 48, 72, 96, 120, and 144 hours after symptom onset. Results: Single S100B measures obtained 48 and 72 hours after stroke onset demonstrated the highest Spearman rank correlations with modified Rankin scale scores (p=0.68 and p=0.67, respectively; P < .001) and infarct volume (p=0.95 and p=0.94, respectively; P < .001). A 48-hour S100B value of 0.37 μg/L or less revealed a sensitivity of 0.87 and a specificity of 0.78 in predicting an independent functional outcome. In a multivariate model, S100B emerged as an outcome predictor that was independent of age, sex, stroke severity, etiology, lesion side, and risk factors. Conclusions: Single S100B values obtained 48 and 72 hours after stroke onset provide the highest predictive values with respect to functional outcome and infarct volume in nonlacunar middle cerebral artery infarction. More complex measures of the S100B kinetic (ie, area under the curve or peak value) were not superior. Therefore, these single S100B measures appear to be useful surrogate end points in acute interventional stroke trials.
文摘Background: Apart from diffusion-weighted imaging (DWI)- lesion volume and diffusion-perfusion mismatching, there is limited information about neuroradiological predictors of early prognosis after an ischaemic stroke. This study sought to identify specific DWI lesion patterns that would help prediction of early prognosis of three different endpoints: unstable hospital course, recurrence of stroke, and poor neurological outcome at 90 days after ischaemic stroke. Methods: A total of 426 patients with acute cerebral infarcts within the middle cerebral artery territory were prospectively studied. Using the DWI data the patients were divided into six groups (territorial, other cortical, small superficial, internal border zone, small deep, and other deep infarcts), and any recurrent strokes and prognosis over the following 90 days were recorded. Results: DWI lesion pattern was a stronger and more consistent independent outcome predictor than DWI lesion volume. The specific DWI lesion patterns associated with each endpoint differed. An unstable hospital course was frequently observed in patients with internal border zone infarcts, whereas recurrent strokes after the index stroke were commoner in those who had small superficial infarcts (p < 0.05 in both cases). Similarly, poor outcome after stroke was associated with older age, severe neurological deficits at admission, and a DWI lesion pattern showing internal border zone infarcts. Conclusions: The results of the present study indicate that the DWI lesion pattern may help in recognition of the likely differences in the early prognostic endpoints after ischaemic stroke, and DWI analysis may guide targeted interventions to prevent negative outcomes.
文摘Background: Mutations in the NOTCH3 gene are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is an important cause of stroke in young adults. Mutations are typically located within epidermal growth factor-like repeat domains in the extracellular part of the Notch3 receptor. Identification of the mutation is critical for genetic counseling and testing of relatives at risk. Objectives: To identify the spectrum of NOTCH3 mutations in CADASIL and to discuss the implications for diagnostic strategies. Design: Screening for NOTCH3 mutations was performed in 125 unrelated German CADASIL patients with biopsy-proven disease by direct sequencing of exons coding for epidermal growth factor-like repeats. Results were compared with those of previously published studies. Results: We detected 54 distinct mutations (117 missense mutations and 3 in-frame deletions) in 120 (96.0%) of the 125 patients. Of the mutations, 58.3%were located in exon 4 and 85.8%in exons 2 through 6. In 5 patients (4.0%), no mutation was identified. Conclusions: Almost 90%of mutations could be detected within a few exons (exons 2-6). Thus, genetic testing should initially be focused on these exons, with some variation depending on the population in whom it is being performed. Yet, genetic testing for CADASIL is associated with a nameable proportion of false-negative results. Cases with a high index of clinical suspicion should be investigated by skin biopsy if genetic testing is negative.
文摘Background: Transporters, ion pumps, and ion channels are membrane proteins that regulate selective permeability and maintain ionic gradients across cell membranes. Mutations in CACNA1A encoding a neuronal calcium channel and ATP1A2 encoding an ion pump cause episodic ataxia, hemiplegic migraine, and seizures. Mutant gene products of both CACNA1A and ATP1A2 may affect neurotransmission of glutamate, the most abundant excitatory amino acid neurotransmitter. Methods: We examined our patient population with episodic ataxia and hemiplegic migraine but with no mutation in either CACNA1A or ATP1A2. We looked for mutations in SLC1A3, which encodes the glutamate transporter excitatory amino acid transporter (EAAT) 1 that is important in removing glutamate from the synaptic cleft. Results: A patient with episodic ataxia, seizures, migraine, and alternating hemiplegia has a heterozygous mutation in SLC1A3 that is not present in his asymptomatic parents and controls. Expression studies of the mutant EAAT1 showed decreased expression of the protein with a markedly reduced capacity for glutamate uptake. When coexpressed, the mutant EAAT1 decreased the activity of wild-type EAAT1 but not of two other transporters EAAT2 or EAAT3, suggesting that mutant EAAT1 specifically multimerizes with wild-type EAAT1 to exert its dominant negative effect. Conclusion: Our data show that a heterozygous mutation in EAAT1 can lead to decreased glutamate uptake, which can contribute to neuronal hyperexcitability to cause seizures, hemiplegia, and episodic ataxia.
文摘Abstract:Objectives: Cerebral white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) are a recognised risk factor for post-stroke dementia. Their specific relations to cognitive impairment are still not well known. The purpose of this study was to explore how the severity and location of WMHs predict neuropsychological test performance in the context of other brain lesions in elderly stroke patients. Methods: In the Helsinki Stroke Aging Memory Study, 323 patients, aged from 55 to 85 years, completed a detailed neuropsychological test battery and MRI 3 months after an ischaemic stroke. The demographic and MRI predictors of cognition were studied with sequential linear regression analyses. Results: After age, education and total infarct volume were controlled for, the overall degree of WMHs predicted poor performance in tests of mental speed, executive functions, memory, and visuospatial functions, but not in those of short term memory storage or verbal conceptualisation. However, the contribution of separate white matter regions was relatively low. Only the lesions along the bodies of lateral ventricles were independently associated with speed and executive measures. Additionally, general cortical atrophy clearly predicted a wide range of cognitive deficits while infarct volume had less relevance. Further analyses revealed that executive functions act as a strong mediator between the relationship of WMHs to memory and visuospatial functions. Conclusions: The degree of WMHs is independently related to post-stroke cognitive decline. The most affected cognitive domains seem to be executive functions and speed of mental processing, which may lead to secondary deficits of memory and visuospatial functions.
文摘Dopamine agonists are increasingly used in the treatment of Parkinson disease, but they may cause serious adverse effects. In December 1983, symptoms of Parkinson disease developed in a 55-year-old man with no history of pulmonary disease, smoking, or asbestos exposure. He began treatment with dopamine agonists bromocriptine mesylate (in 1984) and pergolide mesylate (in 1989). In late 2000, pulmonary symptoms developed. Chest radiographs and computed tomographic findings showed a mass in the right upper lobe and effusion. A biopsy specimen showed pleural and parenchymal fibrosis. This syndrome resolved after cessation of pergolide therapy and a switch to pramipexole dihydrochloride. This case draws attention to the association of long-term ergot dopamine agonist therapy with pleuropulmonary fibrosis, which can develop as late as 11 years after the initiation of therapy. We also review evidence that the risk of this complication is substantially lower with the newer nonergot dopamine agonists.
文摘Early, active multiple sclerosis lesions show four immunopathological patterns of demyelination. Although these patterns differ between patients, multiple active lesions from a given patient have an identical pattern, which suggests pathogenic heterogeneity. Therapeutic plasma exchange (TPE) has been successfully used to treat fulminant demyelinating attacks unresponsive to steroids. We postulated that patients with pattern II would be more likely to improve after TPE than those with other patterns since pattern II lesions are distinguished by prominent immunoglobulin deposition and complement activation. We retrospectively studied 19 patients treated with TPE for an attack of fulminant CNS inflammatory demyelinating disease. All patients with pattern II (n=10), but none with pattern I (n=3) or pattern III (n=6), achieved moderate to substantial functional neurologicalimprovement after TPE (p < 0.0001). Patients with multiple sclerosis with pattern II pathology are more likely to respond favourably to TPE than are patients with patterns I or III.
文摘Background: Information on the mechanism of recurrent stroke may help physicians treating patients with ischemic stroke. However, the mechanisms of recurrence in each stroke subtype are not well known, especially in Asians. Abstract:Objective: To compare the mechanisms of the index and recurrent stroke. Design: Analysis of data from a prospective acute stroke registry. Setting: University hospital. Patients: Using the clinical syndrome, diffusion-weighted imaging, and vascular studies, we divided 901 patients into 5 groups: large-artery atherosclerosis, cardioembolism, small-artery disease, parent-artery disease occluding the deep perforators, and no determined cause. The patients with large-artery atherosclerosis were subdivided into 2 groups: intracranial and extracranial. Main Outcome Measures: The mechanisms of recurrent vascular events (strokes or coronary heart disease) in subtypes of ischemic stroke were compared. Results: Ninety-three recurrent vascular events (86 strokes and 7 instances of coronary heart disease) were evaluated. The pattern of recurrent stroke differed for the intracranial and extracranial groups; unlike the patients with intracranial large-artery atherosclerosis, recurrent strokes in the extracranial group were often unpredictable with respect to the site of recurrence and degree of preexisting stenosis. None of the patients in the extracranial group had recurrences that were caused by intracranial large-artery atherosclerosis or vice versa. In patients with small-artery disease and stroke with no determined cause, intracranial stenosis was often found at the time of recurrence. Conclusions: From prognostic and therapeutic perspectives, patients with atherosclerosis should be divided into those with intracranial large-artery atherosclerosis and extracranial large-artery atherosclerosis. In addition, intracranial large-artery atherosclerosis may be important in the development of small-artery disease and stroke with no determined cause, especially in the population with a higher frequency of intracranial large-artery atherosclerosis.
文摘Background: Acute multiple brain infarction (AMBI) pattern on diffusion-weighted imaging (DWI) is associated with arterial and cardiac sources of embolism. The DWI characteristics of patients with stroke due to vertebrobasilar arterial dissection and atherosclerotic disease have not been reported in detail. Abstract:Objective: To describe the DWI stroke patterns in patients with posterior circulation occlusive disease to determine mechanisms of ischemia. Design: Retrospective analysis of infarct patterns in patients with symptomatic vertebrobasilar disease. Setting: Large community-based teaching hospital. Patients: Patients admitted with stroke due to vertebrobasilar disease were identified retrospectively.Patients were included if DWI was obtained within 7 days of symptom onset. Main Outcome Measure: Infarct patterns were analyzed according to established templates of vascular territories. Results: Eleven patients with vertebral dissection and 39 patients with atherothrombosis were identified.An AMBI pattern was present in 8 (72%) of 11 patients with arterial dissections and 25 (64%) of 39 patients with atherosclerotic disease (P = .48). Distal embolism to the terminal branches of the basilar artery occurred with equal frequency in both groups and was found in half of all cases. Isolated thalamic infarction did not occur. Pontine infarction was noted in 2 (18%) of 11 patients with dissections and 18 (46%) of 39 patients with atherosclerosis (P = .09). Cerebellar border zone involvement was found in 14 (36%) of 39 patients with atherosclerosis and 4 (37%) of 11 patients with dissections (P = .6). Conclusions: Large arterial disease is frequently associated with AMBI in the posterior circulation. The incidence of AMBI was comparable to that reported in the anterior circulation. This DWI study supports the importance of embolism as the main mechanism of infarction in patients with vertebrobasilar occlusive disease. On the basis of our experience, large-vessel vertebrobasilar disease rarely causes isolated small-vessel thalamic infarction.
文摘Background: Headache is the most frequent symptom in cerebral venous thrombosis (CVT), and usually the first. However, it has rarely been reported as the only symptom of CVT. Objectives: To study the characteristics of patients in whom headache was the only presentation of CVT in the absence of intracranial hypertension, subarachnoid haemorrhage (SAH), meningitis, or other intracranial lesion. Methods: From a prospective study of 123 consecutive patients with CVT only those with isolated headache and normal brain computed tomography (CT) scan and cerebrospinal fluid (CSF) examination were included in the present study. All patients underwent an extensive systematic aetiological work-up and were given intravenous heparin followed by oral anticoagulants. A detailed description of the headache was obtained. Results: Headache was only sign of CVT in 17 patients. The lateral sinus was the most frequently involved sinus (n=15). Onset of headache was progressive in 11, acute in 3, and thunderclap in 3 patients. Once established, the headache was continuous in 15, diffuse in four and unilateral in 13, usually ipsilateral to the occluded lateral sinus. No specific risk factor or cause was found. All had a favourable evolution. Conclusion: The pathogenesis of isolated headache in CVT in the absence of intracranial hypertension, SAH, meningitis or intracerebral lesion is unknown but may involve changes in the walls of the occluded sinus. Hence MRI/MRV should be used to look for signs of CVT in all patients with recent headache (progressive or thunderclap) even when the CT scan and CSF examination are normal.
文摘Using ultrasonography we found multiple sites with nerve enlargement along the course of the brachial plexus, median, ulnar, and radial nerves in the majority of 21 patients with multifocal motor neuropathy. Sonography and electrophysiologic studies showed more abnormalities than expected on purely clinical grounds. Moreover, sonography revealed nerve enlargement without clinical or electrophysiologic abnormalities.
文摘Objective. -To study the frequencies and characteristics of different headache types seen in patients with Behet’s syndrome (BS) in a large cohort of patients. Background. -Patients with BS may present with different neurological problems, related either directly or indirectly to the disease, with headache being the most common neurological symptom seen in this syndrome, as well as independent from neurologic involvement. Method. -This study was carried out at the multidisciplinary Behet outpatient clinic of the Behet’s Syndrome Research Center. Every fifth admitted patient who had fulfilled the International Study Group for Behet’s Disease classification criteria was recruited for this study. Each patient was interviewed by one of the examining neurologists through a semistructured questionnaire. In case of the presence of more than one headache type, the best defined one was diagnosed and evaluated. All patients received a complete neurological and physical examination. A χ2 test was used to evaluate the differences between frequencies. One sample Mest was used to compare means. The prevalence rates of primary headaches were compared with results of the Turkish Headache Epidemiology study by using goodness-of-fit test. Results. -Two hundred and twenty-eight patients were studied. Headache was reported in 66.2%(151/228) of the study cohort. Primary headaches were seen in 38.6%of the patient population, which corresponds to 58%of BS patients with any type of headache. Tension-type headache (TTHA)-and migraine were seen in 23.6%and 14.9%of the whole study cohort, respectively. In 5.2%of the study cohort, the headache was associated with neurological involvement and in 3.9%to uveal inflammation. A predominantly frontal, bilateral paroxysmal throbbing pain of moderate severity was reported in 18.4%of the study cohort who did not fulfill the criteria of the International Headache Society (IHS) for any of the primary headaches. It was commonly associated with exacerbations of the mucocutaneous symptoms of the syndrome. The neurological examination was normal in all of these patients. This type of headache was categorized as the nonstructural headache of Behet. Conclusion. -Headache is the most common neurological symptom seen in BS, both in patients with and without neurological involvement. The results of our study reveal that headache is seen in a majority of patients with neurological involvement due to BS and in a minority with uveal inflammation. The prevalence of migraine and TTHA are close to the population in general, but a nonstructural migrainous headache, which is commonly associated with exacerbations with some of the systemic symptoms of the syndrome, is noteworthy in patients with BS. This form of headache is not specific for this disorder, but may be explained by a vascular headache triggered by the immunomediated disease activity in susceptible individuals.
文摘Objectives: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson’s disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications, has been thought to inhibit STN hyperactivity and therefore decrease progression of PD. Methods: In a prospective two centre study, disease progression was determined by means of serial 18F fluorodopa (F-dopa) positron emission tomography (PET) in 30 patients with successful STN DBS over the first 16 (SD 6) months after surgery. Results: Depending on the method of PET data analysis used in the two centres, annual progression rates relative to baseline were 9.5-12.4%in the caudate and 10.7-12.9%in the putamen. Conclusions: This functional imaging study is the first to demonstrate a continuous decline of dopaminergic function in patients with advanced PD under clinically effective bilateral STN stimulation. The rates of progression in patients with STN DBS were within the range of previously reported data from longitudinal imaging studies in PD. Therefore this study could not confirm the neuroprotective properties of DBS in the STN target.
文摘Objective. -To investigate the efficacy and tolerability of almotriptan 12.5 mg in migraine patients who respond poorly to sumatriptan 50 mg. Background. -Poor response to sumatriptan therapy for acute migraine attacks has been documented in the literature, but few controlled trials have investigated the efficacy of an alternative triptan in this subgroup of patients. Methods. -Patients with an International Headache Society diagnosis of migraine who self-described as experiencing at least two unsatisfactory responses to sumatriptan treated their first migraine attack with open-label sumatriptan 50 mg. Patients who did not achieve 2-hour pain relief (improvement of headache from moderate/severe to mild/no headache) were then randomized to treat their second attack with almotriptan 12.5 mg or placebo under double-blind conditions. Results. -In the first attack, 221 of 302 participants (73%) did not achieve 2-hour pain relief with sumatriptan and were randomized to treatment of their second attack with almotriptan 12.5 mg or placebo. Of the 198 sumatriptan nonresponders who treated their second attack (99 almotriptan; 99 placebo), 70%had severe headache pain at baseline. Two-hour pain-relief rates were significantly higher with almotriptan compared to placebo (47.5%vs 23.2%; P < .001). A significant treatment effect for almotriptan was also seen in pain-free rates at 2 hours (33.3%vs 14.1%; P < .005) and sustained freedom from pain (20.9%vs 9.0%; P < .05). In the second attack, 7.1%of patients in the almotriptan group experienced adverse events compared to 5.1%in the placebo group (P=.77). Conclusions. -Almotriptan 12.5 mg is an effective and well-tolerated alternative for patients who respond poorly to sumatriptan 50 mg. A poor response to one triptan does not predict a poor response to other agents in that class.
文摘Objective: To assess the accuracy and clinical usefulness of [ 123I]β-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane)-SPECT in the differential diagnosis of Parkinson’s disease. Subjects: 185 consecutive patients with symptoms of movement disorder were studied. The diagnoses were Parkinson’s disease (92), essential tremor (16), vascular parkinsonism (15), various Parkinson plus syndromes (P+) (12), dementia with Lewy bodies (DLB) (5), dystonia (5), drug induced movement disorder (12), and other diagnoses (8). A reference group (psychogenic parkinsonism) comprised 20 subjects with complaints suggesting extrapyramidal disease but with no unequivocal signs on clinical examination and no abnormalities on brain imaging. Results: β-CIT uptake was significantly lower in the whole striatum as well as separately in the putamen and in the caudate nucleus in Parkinson’s disease than in the reference group or in drug induced movement disorder, essential tremor, or dystonia. The uptake of β-CIT in the vascular parkinsonism group was heterogeneous and mean β-CIT uptake fell between the reference group and the Parkinson’s disease group. In the P+and DLB groups the striatal uptake ratios overlapped those of the Parkinson’s disease group. Conclusions: [123I]β-CIT SPECT may not be as useful a tool in the clinical differential diagnosis of Parkinson’s disease as was previously believed, but it was 100%sensitive and specific for the diagnosis in younger patients (age < 55 years). In older patients (age > 55 years)-specificity was substantially lower (68.5%). This differential specificity reflected the different distribution of differential diagnostic disorders (P+, DLB, vascular parkinsonism) in the older and younger age groups.
文摘Myotonic dystrophy (DM) is a multisystem autosomal dominant inherited disease that primarily affects the nervous system, causing myotonia and a characteristic pattern of muscular atrophy and weakness. Careful clinical description in the late 19th and early 20th centuries separated DM from a similar muscle disease, myotonia congenita, allowing it to emerge as a distinct nosologic disease entity. The electrical characteristics of myotonia were described in the early to mid 20th century. Assiduous study of the clinical features and genetics of DM, including the phenomenon of anticipation, culminated in the discovery of the genetic mutations underlying DM in the early 1990s.
文摘Context: Basilar artery occlusion(BAO) is an infrequent disease with high morbidity and mortality. Intra-arterial thrombolysis is advocated for treatment but is limited to use at specialized centers. Objective: To evaluate outcomes for patients with BAO treated with intravenous thrombolytic therapy. Design, Setting, and Participants: During 1995 to 2003, 50 consecutive patients with angiographically proven BAO were treated according to an institutional therapy protocol based on intravenous thrombolysis with recombinant tissue plasminogen activator(alteplase). Patients were treated at an urban university teaching hospital receiving all patients with ischemic stroke who were considered for thrombolysis in a catchment area of 1.5 million inhabitants in Helsinki, Finland. Intervention: Intravenous administration of alteplase(0.9 mg/kg) during a 1-hour infusion. Main Outcome Measures: Basilar artery recanalization determined by magnetic resonance angiography and clinical outcomes at 3 months and at 1 year or longer determined by modified Rankin Scale and Barthel Index scores. Results: Recanalization was studied in 43 patients and verified in 26(52%) of all patients. By 3 months, 20 patients(40%) had died while 11 had good outcomes(modified Rankin Scale score, 0-2); 12(24%) reached independence in activities of daily living(Barthel Index score, 95-100), and 6(16%) were severely disabled(Barthel Index score, 0-50). In the long term(median follow-up 2.8 years), 15 patients(30%) reached good outcomes(modified Rankin Scale score, 0-2) while 23(46%) died. Conclusions: Intravenous administration of alteplase for patients with BAO appears to be associated with rates of survival, recanalization, and independent functional outcome comparable with those reported with endovascular approaches. These data suggest that a randomized trial is needed to compare these approaches for treatment of BAO.
文摘Background: The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of autosomal dominant ataxias: some mutations, including SCA1, SCA2, and SCA3, are multisystemic disorders characterized by a variety of noncerebellar symptoms while others, like SCA6, give rise to a pure cerebellar syndrome. Abstract:Objective: To identify impairments of the dopaminergic system and regional changes of glucose metabolism in SCA1, SCA2, SCA3, and SCA6. Methods: We used [11C]d-threo-meth- ylphenidate and [18F]-fluorodeoxyglucose positron emission tomography to identify cerebral dopamine terminal loss and specific regional metabolic patterns in SCA1, SCA2, SCA3, and SCA6. Results: The binding potential of [11C]d-threo-methylphenidate was reduced in the striatum in SCA2 and SCA3; in contrast to patients with Parkinson disease, no increased susceptibility of the putamen was evident. Decreased regional cerebral glucose metabolism was found in the cerebellum of all patients with SCA, the brainstem of SCA1, SCA2, SCA3, the thalamus and putamen of SCA3, and the parietal cortex of patients with SCA2. A trend toward increased regional cerebral glucose metabolism was found in the temporal cortex of all patients with SCA, pronounced in SCA6. Conclusions: Specific biochemical patterns point to different mechanisms of neuronal dysfunction in SCA1, SCA2, SCA3, and SCA6; dopamine terminal loss is severe in SCA2 but distinct from Parkinson disease.
文摘We studied whether a difference exists in the development of symptoms of the Lambert-Eaton myasthenic syndrome (LEMS) between patients with or without small cell lung cancer (SCLC). We assessed symptoms in 38 LEMS patients, 13 with SCLC, by interviewing them using a structured checklist, backed up by a review of their clinical records, and compared the frequency and time scale of symptoms during the course of LEMS. Bulbar (87%) and autonomic (95%) symptoms for the whole group were more common than reported in the literature. Frequencies of symptoms did not differ significantly between patients with and without SCLC, but symptoms in patients with SCLC appeared within a shorter time-frame, indicating a more rapid clinical course. The presence of a particular symptom associated with LEMS did not predict the presence of SCLC, but in patients with rapidly progressive LEMS the possibility of underlying lung cancer should be of particular concern.
