偏头痛家族聚集性患者临床特点及其一级亲属患病风险因素分析

目的观察偏头痛家族聚集性患者的临床特征,分析其一级亲属的患病风险因素。方法收集资料完整的偏头痛患者72例,根据有无偏头痛家族史分为两组,有偏头痛家族史组及无偏头痛家族史组。利用问卷采集两组患者临床资料,单因素分析筛选出有统计学意义的变量后进行多因素logistic回归分析其一级亲属患病的危险因素。结果 72例中至少有1名一级亲属患有偏头痛者37例,家族史阳性率为51.4%。与家族史阴性的偏头痛先证者比较,家族史阳性的先证者在性别(P=0.675)、年龄(P=0.598)、病程(P=0.419)、先兆(P=0.669)、头痛程度(P=0.837)、发作频率(P=0.465)及头痛伴随症状、头痛部位、头痛性质方面差异无统计学意义;与家族史阴性的头痛先证者比较,家族史阳性的先证者在起病年龄早(16岁)方面的差异(48.6%vs.22.9%,χ~2=5.186,P=0.023)及在头痛发作持续时间长(≥24 h)方面的差异(35.1%vs.14.3%,χ~2=4.170,P=0.041)有统计学意义(P0.05)。多因素回归发现,发病年龄早(OR=2.986,95%CI:1.621~5.503)、头痛发作持续时间长(OR=2.320,95%CI:1.219~4.415)的先证者,其一级亲属患病风险高(P0.05)。结论起病年龄早及头痛持续时间长的偏头痛患者,其一级亲属患偏头痛的风险更高。     

偏头痛慢性转化的临床危险因素分析

目的比较慢性偏头痛(CM)与发作性偏头痛(EM)的病史特征、临床特点等,探究偏头痛慢性转化的危险因素,为其防治提供依据和策略。方法共纳入在中南大学湘雅医院神经内科就诊的CM患者72例及EM患者109例进行回顾性分析。采集患者基本信息,先进行单因素分析,筛选有统计学意义的指标进行相关分析和非条件性多因素logistic回归分析。结果单因素分析发现两组的BMI(P=0.000)、病程(P=0.000)、基线头痛发作频率(P=0.000)、基线头痛持续时间(P=0.037)、匹兹堡睡眠质量指数量表(PSQI,P=0.000)、焦虑自评量表(SAS,P=0.000)及抑郁自评量表(SDS,P=0.001)差异有统计学意义。logistic回归分析显示BMI(OR=1.468,95%CI:1.148～1.876)、病程(OR=1.102,95%CI:1.022～1.188)、基线头痛发作频率(OR=1.461,95%CI:1.247～1.711)、睡眠质量(OR=1.494,95%CI:1.198～1.864)、焦虑状态(OR=1.201,95%CI:1.048～1.376)是偏头痛慢性转化的危险因素。结论控制体重、减少头痛发作频率、缩短病程、改善心境状态与睡眠质量,有可能延缓偏头痛的慢性进展。     

脑微出血与急性缺血性卒中的临床关系分析

目的探讨急性缺血性卒中(AIS)患者脑微出血(CMBs)的危险因素,并进一步探讨CMBs与脑卒中病灶面积和部位的相关性。方法收集2014-1-2015-12在作者医院神经内科住院的AIS患者226例,据是否存在CMBs分为CMBs组(111例)和无CMBs组(115例)。收集研究对象临床资料,采用头颅MRI对其CMBs、脑白质病变(WML)、陈旧腔隙性脑梗死(LI)、AIS病灶面积和部位进行评价,并采用Logistic回归、t检验、χ~2检验等分析影响AIS患者发生CMBs的危险因素。结果多因素Logistic回归分析显示年龄(OR=1.063,95%CI:1.025~1.104,P0.01)、高血压史(OR=3.488,95%CI:1.113~10.927,P0.05)、WML(OR=1.282,95%CI:1.155~1.423,P0.01)及陈旧LI(OR=5.815,95%CI:1.539~21.973,P0.01)是AIS合并CMBs的独立危险因素;CMBs分级与WML分级(r=0.354,P0.01)、陈旧LI分级(r=0.394,P0.01)均呈正相关;不同脑卒中病灶面积患者间CMBs检出率比较有统计学差异(χ~2=7.878,P0.05),其中新发LI患者更易检出CMBs(χ~2=6.084,P=0.0090.017),且CMBs越严重,这种差异越明显(z=-2.832,P=0.0050.017)。结论年龄、高血压史、WML及陈旧LI是AIS合并CMBs的独立危险因素,且CMBs严重程度随WML、陈旧LI的严重程度增加而增高。AIS患者CMBs检出率与梗死灶面积有关,在新发LI中更易被发现。     

帕金森病患者脑微出血相关危险因素分析

目的探讨帕金森病(PD)患者脑微出血(CMBs)的相关危险因素。方法收集128例完成磁敏感加权成像(SWI)序列的原发性PD患者的临床资料,并进行分析。结果 15.6%的PD患者合并CMBs,其中单纯脑叶CMBs占55%,深部或幕下CMBs占45%。CMBs组年龄、高血压及使用抗血小板药物比率显著高于无CMBs组(P0.05～0.01)。二元Logisitic回归分析显示,年龄(OR=1.084,95%CI:1.023～1.149,P=0.007)、高血压(OR=3.210,95%CI:1.129～9.198,P=0.030)是PD合并CMBs的独立危险因素。单纯脑叶CMBs组年龄、病程显著高于非单纯脑叶CMBs组(P0.05～0.01)。二元Logisitic回归分析显示,年龄是PD患者合并单纯脑叶CMBs的独立危险因素(OR=1.121,95%CI:1.035～1.214,P=0.005)。深部或幕下CMBs组高血压比率显著高于非深部或幕下CMBs组(P0.05)。二元Logisitic回归分析显示,高血压是PD患者合并深部或幕下CMBs的独立危险因素(OR=6.027,95%CI:1.459～26.40,P=0.013)。结论年龄、高血压是PD患者CMBs发生的危险因素,控制高血压可能可以减少早中期PD患者CMBs的发生。     

偏头痛脑白质高信号与临床特征及右向左分流的相关分析

目的从临床特征角度探索偏头痛脑白质高信号(WMHs)的危险因素,并研究右向左分流(RLS)是否与偏头痛WMHs有关。方法纳入偏头痛患者,采集头痛资料,进行对比增强TCD检查是否存在RLS以及分流量大小,并行头颅MRI检查评估WMHs。结果共纳入57例偏头痛患者,其中合并WMHs共18例(31.6%),主要位于额、顶叶,病变程度较轻。在对年龄、性别、头痛特征、焦虑抑郁评分以及RLS等因素的分析中,发现合并WMHs组与不合并WMHs组之间,仅年龄(P=0.002)、病程(P=0.046)存在统计学差异。结论偏头痛患者中发现的WMHs,主要位于额、顶叶,年龄、病程可能是其危险因素,未发现先兆、发作频率、持续时间、疼痛程度、焦虑抑郁等临床特征与其相关,也未发现RLS会增加偏头痛患者WMHs的风险。     

发作性偏头痛慢性转化的影响因素

目的探讨发作性偏头痛慢性转化的影响因素。方法收集126例发作性偏头痛(EM)和50例慢性偏头痛(CM)患者的临床资料,并进行比较。采用Logistic多元回归方法分析偏头痛慢性转化的独立危险因素。结果 EM组超重、女性比率,年龄及体重指数(BMI)显著低于CM组(均P0.01),受教育年限显著高于CM组(P0.05)。两组间起病年龄、初发持续时间、初发疼痛程度及有先兆的比率差异无统计学意义(均P0.05)。EM组初发频率、病程、急性期止痛药物过度使用比率以及焦虑自评量表(SAS)、抑郁自评量表(SDS)、匹兹堡睡眠质量指数评分均显著低于CM组(P0.05~0.01)。BMI(OR=1.159,95%CI:1.004~1.338)、SAS(OR=3.100,95%CI:1.360~7.069)、SDS(OR=3.390,95%CI:1.117~10.287)及急性期止痛药物过度使用(OR=2.714,95%CI:1.022~7.204)是EM慢性转化的独立危险因素(均P0.05)。结论伴有抑郁/焦虑、止痛药物过度使用和超重是EM慢性转化的独立危险因素。     

脑白质损害与偏头痛发作频率分析

目的探讨脑白质损害与偏头痛发作频率关系。方法选取重庆市铜梁区中医院接诊的86例偏头痛患者作为研究对象,对患者进行头颅MRI检查以明确脑白质损害程度,根据是否发生脑白质损害分为两组:损害组、未损害组,对比两组的偏头痛发作频率、持续时间。结果脑白质损害病灶位于额叶20个(30.30%)、顶叶13个(23.21%)、基底核区11个(19.64%)、颞枕叶8个(14.29%)、脑干及小脑3个(5.36%)、顶叶1个(1.79%)。两组在冠心病史、高血压病史、糖尿病史、吸烟史、饮酒史、家族病史方面比较,差异均无统计学意义(P>0.05)。损害组的病程明显比未损害组更长(P<0.05)。两组患者在偏头痛类型、发作频率、持续时间方面比较,差异均有统计学意义(P <0.05)。损害组的先兆型偏头痛、发作频率> 3次/月、持续时间> 24h占比均显著高于未损害组(P <0.05)。多因素回归分析显示,除头痛持续时间外,病程、先兆症状、头痛发作频率均是脑白质损害的独立危险因素(均P <0.05)。结论偏头痛患者的脑白质损害好发于额顶叶,偏头痛病程、先兆症状及发作频率都是偏头痛患者发生脑白质损害的独立危险因素。     

女性癫痫患者焦虑、抑郁和失眠发病率及相关因素分析

目的探讨女性癫痫患者焦虑、抑郁和失眠的发病率和相关因素。方法收集428例成人女性癫痫患者的一般资料,并采用汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)、匹兹堡睡眠质量指数量表(PSQI)进行测评,相关因素用逐步逻辑回归进行分析。结果女性癫痫患者并发焦虑、抑郁和失眠的发病率分别是38.7%,21.4%和28.6%。患病影响夫妻关系、患病影响恋爱关系、担心发作、担心影响生育和哺乳、羞耻感、起病年龄和发作频率均与焦虑相关(均P0.05)。患病影响夫妻关系、患病影响恋爱关系、起病年龄、病程和发作频率均与抑郁相关(均P0.05)。职业、性格、人际关系和雌二醇水平均与失眠相关(均P0.05)。Logistic回归分析显示,患病影响夫妻关系(OR=3.103,95%CI:1.097~4.686,P=0.008)、患病影响恋爱关系(OR=2.164,95%CI:0.873~3.752,P=0.005)和发作频率(OR=1.704,95%CI:0.680~2.586,P=0.015)是影响焦虑的独立影响因素。患病影响夫妻关系(OR=3.245,95%CI:1.536~5.108,P=0.003)、患病影响恋爱关系(OR=3.151,95%CI:2.135~5.018,P=0.006)、病程(OR=1.196,95%CI:0.828~2.654,P=0.035)和发作频率(OR=1.661,95%CI:1.033~4.326,P=0.014)是影响抑郁的独立影响因素。性格(OR=2.543,95%CI:1.237~4.686,P=0.003)和人际关系(OR=1.816,95%CI:0.905~3.593,P=0.017)是影响失眠的独立影响因素。结论成人女性癫痫患者焦虑、抑郁和失眠发病率较高。焦虑和抑郁与家庭因素、生育、哺乳、羞耻感及癫痫发作有关,失眠与性格和人际关系有关。     

缺血性脑卒中患者合并脑微出血的危险因素分析

目的探讨缺血性脑卒中(cerebral ischemic stroke,IS)患者合并脑微出血(cerebral microbleeds,CMBs)的危险因素。方法回顾性收集2015年1月至2017年5月作者医院神经内科连续收治的IS住院患者1631例,根据是否存在CMBs分为合并CMBs组703例和未合并CMBs组928例。分析两组间性别构成、年龄、血压、体重、体重指数(body mass index,BMI)、血糖、尿酸、三酰甘油(triglycerides,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-c)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-c)、载脂蛋白A(apolipoproteins A,apoA)、载脂蛋白B(apolipoproteins B,apoB)、吸烟史、饮酒史、高血脂史、糖尿病史、高血压史、心脏疾病史、脑白质高信号(white matter hyperintensity,WMH)的差异,并采用多因素Logistic回归分析影响IS患者发生CMBs的危险因素。结果与未合并CMBs组比较,合并CMBs组患者年龄大,男性、吸烟、饮酒、高血压、糖尿病、WMH构成比例高,空腹血糖、尿酸水平高(均P<0.05),而空腹LDL-c和apoA水平较低(均P<0.05)。多因素Logistic回归分析显示吸烟(OR=5.791,95%CI:3.714~9.031,P<0.01)、饮酒(OR=7.306,95%CI:4.926~10.835,P<0.01)、高血压(OR=2.162,95%CI:1.487~3.143,P<0.01)、WMH(OR=3.249,95%CI:1.594~6.625,P<0.01)、LDL-c(OR=0.789,95%CI:0.630~0.989,P<0.05)、apoA(OR=0.696,95%CI:0.369~0.753,P<0.01)是IS合并CMBs的独立危险因素。结论吸烟、饮酒、高血压、WMH、LDL-c、apoA是IS合并CMBs的独立危险因素,且LDL-c和apoA水平下降与CMBs发生增加相关。     

偏头痛合并卵圆孔未闭的临床特点

目的探讨偏头痛合并卵圆孔未闭(PFO)的临床特点。方法对95例临床确诊的偏头痛患者进行经胸心脏超声检查,根据是否合并PFO进行分组。所有患者给予口服盐酸氟桂利嗪治疗3个月。采集患者的临床资料,记录患者治疗前后头痛发作频率、持续时间和严重程度,对结果进行组间比较并分析。结果经胸心脏超声检查发现合并PFO患者29例,作为PFO组;其余66例患者无PFO,作为非PFO组。偏头痛患者合并PFO的发生率为30.5%。与非PFO组比较,PFO组患者有先兆偏头痛的比例和治疗前头痛发作频率明显增高(均P0.05)。与治疗前比较,PFO组与非PFO组治疗后头痛发作频率明显降低,持续时间明显缩短,严重程度明显减轻(均P0.05)。两组患者治疗后头痛发作频率、持续时间和严重程度的差异无统计学意义。两组患者均无严重不良反应出现。结论偏头痛合并PFO的临床特点为有先兆偏头痛的比例较高,头痛发作频率较高。     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

Anticonvulsant Drugs and Cognitive Function: A Review of the Literature

Summary: Alterations of cognitive function are separate from disturbances of behavior seen in association with epilepsy. The nature of the cognitive disability may to a certain extent depend on the seizure type. Partial seizures, mainly derived from a temporal lobe focus, impair memory tasks, while generalized seizures seem to have more effect on attentional abilities. A number of studies, reviewed in this paper, suggest that anticonvulsant drugs further impair cognitive function. Maximal impairments are seen in patients receiving polytherapy: rationalization of polytherapy improves cognitive abilities. Studies in children and adults have allowed differentiation of the effects of various commonly used antiepileptic agents. Maximal cognitive deficits are seen with. phenytoin, while phenobarbital and sodium valproate induce moderate disturbances, and carbamazepine seems relatively free from such toxicity. Further research is needed on the interrelationship between types of seizure disorders, types of anticonvulsant medications, and cognitive function.     

Dextromethorphan: Cellular Effects Reducing Neuronal Hyperactivity

Summary: Dextromethorphan is a dextrorotary morphinan without affinity for opioid receptors, commonly used as an antitussive medication. During the past 5 years, interest in the compound and its demethylated derivative, dextrorphan, has been revived because additional neuroprotective and an-tiepileptic properties were found in in vitro studies, animal experiments, and a few clinical cases. Both morphinans are able to inhibit N -methyl-D-aspartate (NMDA) receptor channels and voltage-operated calcium and sodium channels with different potencies. The inhibition of the NMDA receptor is believed to be the predominant mechanism of action responsible for the anticonvulsant and neuroprotective properties of the compounds.