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A hamartoma is a benign, noncancerousgrowth consisting of an abnormal mixture of native tissue. Although this tumor-like lesion resembles a neoplasm, it does not exhibit neoplastictendencies such as accelerated growth, local invasion of surrounding tissues,or metastatic spread. 错构瘤由自体组织异常混合组成，呈良性，非癌性生长。尽管这种肿瘤样病变类似于肿瘤，但它没有表现出肿瘤的倾向，例如加速生长、周围组织局部侵犯或转移扩散。 Hypothalamic hamartomas are exceedinglyrare developmental anomalies classically associated with endocrineabnormalities and epilepsy. They consist of a mixture of hyperactive neuronaland glial cells arising from the floor of the third ventricle. 下丘脑错构瘤是非常罕见的发育异常，典型的下丘脑错构瘤伴有内分泌异常和癫痫。它们由起源于三脑室底部的极度活跃的神经元和神经胶质细胞混合组成。 Their true incidence is unknown, but isestimated at one in 50,000 to one in one million. Although classicallyassociated with gelasticseizures, hypothalamic hamartomas are also responsiblefor several other types of more debilitating medically refractory seizures.Endocrine abnormalities, including central precocious puberty, have also beenimplicated. 下丘脑错构瘤确切的发病率不清楚，但估计在1/50，000到1/1，000，000。 尽管下丘脑性错构瘤典型的表现是痴笑样癫痫，但它也是其他几种类型的使人更衰弱的药物治性癫痫的原因。也表现为内分泌异常，包括中枢性性早熟。 下丘脑错构瘤确切的发病率不清楚，但估计在1/50000到1/1000000。 尽管下丘脑性错构瘤典型的表现是痴笑样癫痫，但它也能导致几种其他类型的严重的药物难治性癫痫。下丘脑错构瘤也可表现为内分泌异常，如中枢性性早熟。---不同的译法，请大家一起留言相互学习。 Behavioral, psychiatric, and cognitiveimpairments appear to have a higher incidence in this patient population aswell. In their extreme form, hypothalamic hamartomas lead to disablingepilepsy, severe cognitive deficits, and developmental delay in earlychildhood. 在这种患者群体中，行为、精神和认知障碍有更高的发生率。极端的情况下，下丘脑错构瘤可引起致残性癫痫、严重的认知缺陷和儿童早期的发育迟缓。 Diagnosis诊断 A patient with a hypothalamic hamartomamay present with signs and symptoms of precocious puberty and/or seizures.Gelastic seizures, spells of uncontrollable laughter, were first reported inthe 19th century and are considered a hallmark clinical finding. 下丘脑性错构瘤的患者可表现为性早熟和/或癫痫发作的症状和体征。 痴笑样癫痫，即无法控制的笑声，在19世纪被首次报道，被认为是一个标志性的临床发现。
The laughing events are typically firstnoted in early childhood, and may progress to include other seizure types,including generalized tonic-clonic seizures, partial complex seizures, dropattacks, and atypical absences. As stated before, behavioral, psychiatric, andcognitive changes may also be present. Additionally, gelastic seizures have been reported in the absence of any obvious imaging finding and thus cannot beconsidered a pathognomonic feature. 痴笑往往在儿童早期首先被注意到，并且可能发展成其他类型癫痫，包括全身性强直阵挛发作，部分复杂性发作，跌倒发作和缺乏非典型失神发作。如前所述，也可能存在行为、精神和认知改变。此外，已有报道称痴笑样癫痫可见于没有任何明显的影像学发现的情况下，因此不能被认为是特征性的表现。 Depending on the individual patient’spresentation, the diagnostic workup often includes a full spectrum of labs,electroencephalogram (EEG), and magnetic resonance (MR) imaging. 根据患者的个体表现，诊断检查通常包括全面的实验室检查、脑电图（EEG）和磁共振（MR）成像。 Evaluation评估 Diagnostic workup of patients with seizure disorders includes MR imaging. Hypothalamichamartomas typically demonstrate increased signal on T2-weighted imagesrelative to the brain. MR spectroscopy studies have consistently showndecreased neuronal density and increased gliosis. 检查应有MR成像。下丘脑性错构瘤典型表现在T2加权像上相对于脑实质呈高信号。 MR波谱成像恒定地显示神经元密度降低和神经胶质增多。 Several studies have evaluated the EEGfindings in these patients. Scalp EEG often fails to show ictal or interictalabnormalities if the seizure semiology is confined to gelastic seizures alone.As this disease progresses and secondarily generalized seizures appear, scalpEEG reveals abnormal findings. Multiple seizure types lead to frontal ortemporal multifocal activities. Cortical resection has been ineffective atcontrolling seizures. Depth electrode evaluation has confirmed the hypothalamichamartoma as the ictogenic source. 几项研究评价了下丘脑错构瘤患者的EEG发现。如果癫痫发作的类型仅限于痴笑样癫痫，则头皮脑电图常不能显示发作期或发作间期的异常。随着疾病的进展和出现继发的全面性癫痫发作，头皮脑电图有异常发现。多种发作类型皆可导致额叶或颞叶多灶性活动。皮质切除在控制癫痫发作方面无效。深部电极评估已经证实下丘脑错构瘤为癫痫形成的来源。 There are two subtypes of hypothalamichamartomas, differing on the basis of their anatomic relationship to the normalhypothalamic tissue. Sessile hypothalamic hamartomas harbor a broad base withlocal invasion and displacement of the adjacent surrounding hypothalamictissue. Pedunculated hypothalamic hamartomas, on the other hand, are suspendedby a stalk-like process from the floor of the third ventricle. Sessilehamartomas are more likely to cause epilepsy, whereas pedunculated lesions areassociated with endocrine abnormalities. 下丘脑错构瘤有两种亚型，是根据与正常下丘脑组织的解剖关系而区分。无蒂的下丘脑错构瘤具有宽阔的基底部，局部侵入并取代毗邻周围的下丘脑组织。另一种有蒂的下丘脑错构瘤通过三脑室底发出的茎状突起悬浮着。无蒂的错构瘤更有可能导致癫痫，而有蒂的病变与内分泌异常相关。 Figure 1: A 23-year-old man presentedwith intractable multifocal epilepsy associated with gelastic seizures. MRimaging revealed a T2 hyperintense, nonenhancing mass along the anterior floorof the third ventricle consistent with a sessile hypothalamic hamartoma. 图1：一名23岁的男性患者表现出顽固性多灶性癫痫伴痴笑样发作。MR成像显示T2高信号，沿着第三脑室底前部的非增强占位，符合无蒂的下丘脑错构瘤。 Indicationsfor Surgery手术适应证 Evidence-based management algorithmsare difficult to establish for such rare lesions. In general, surgicalindications include seizures intractable to maximal medical therapy. Precociouspuberty is another indication for intervention that leads to regression ofpreoperative symptoms and signs. 对于这些罕见的病变难以建立循证治疗方案。总的来说，手术适应证包括最大剂量药物难以治疗的癫痫发作。性早熟是手术干预的另一个指标，经治疗可使术前的症状和体征消退。 Several studies have confirmed the primary and secondary epileptogenicity of hypothalamic hamartomas. Thus,patients with an uncontrollable seizure disorder who have a known hypothalamichamartoma are suitable candidates for operative intervention. 几项研究已经证实了下丘脑错构瘤原发性和继发性的致痫灶。因此，具有难以控制的癫痫发作并已明确有下丘脑错构瘤的患者适合手术干预。 PreoperativeConsiderations术前注意事项 Various surgical approaches to theanterior third ventricle have been described in the literature, includingstandard pterional, transcallosal, endoscopic transventricular, endoscopicendonasal, and subfrontal translamina terminalis. A standard pterional approachis familiar to neurosurgeons and offers a relatively direct route to thelesion. However, visualization of the anterior third ventricle is limited bythe critical overlying neurovascular structures with this approach. Thus,significant retraction and manipulation of the normal anatomy may be needed toconduct the resection. 到达第三脑室前部的各种手术入路已经在文献中描述，包括标准翼点入路，经胼胝体入路，内窥镜经脑室入路，内窥镜经鼻入路和额下经终板入路。标准的翼点入路是神经外科医生熟悉的，并可提供到达病变相对直接的路径。但是，经此入路三脑室前部的暴露受到所覆盖的重要的神经血管结构的限制。因此，可能需要对正常解剖结构行显著的牵拉和操作才能进行切除。 A transcallosal approach provides adirect vertical route to the anterior third ventricle and clear visualizationof the intraventricular aspects of the lesion. Limitations of this approachinclude the risks of memory disturbance from forniceal manipulation. 经胼胝体入路提供了抵达第三脑室前部的直接的垂直通道，脑室内病变清晰可见。该入路的局限性在于对穹窿操作有导致记忆障碍的风险。
Endoscopic endonasal access has greatpotential for providing a minimally disruptive option to this lesion, but theexperience for the use of this route is limited. 作为一种微侵袭入路，内镜下经鼻入路有巨大潜力，但是目前使用这种入路的经验有限。
I favor the subfrontal translaminaterminalis approach through a supraorbital craniotomy. Some degree of frontallobe retraction is necessary to reach the lesion via a superior-to-inferioroperative trajectory toward the floor of the third ventricle. Additionally, acontralateral subfrontal pathway creates a more direct surgical corridor to thelateral pole of the mass. 笔者喜欢使用眶上开颅额下经终板入路。此入路需要一定程度的牵拉额叶, 以便于沿着由上至下指向三脑室底部的操作通道到达病变,此外，对侧额下入路可建立更直接的手术通道到达病变的侧面。 Radiosurgery is a viable considerationfor the treatment of hypothalamic hamartomas. The potential limitations ofradiotherapy include a delayed response to treatment and the risk of radiationinjury to the hypothalamus and optic apparatus; thesefactors limit radiotherapeutic dosing and, in turn, can limit treatmenteffectiveness. 放射外科治疗下丘脑错构瘤也是一个可行的方法。放射治疗可能的局限性包括对治疗的反应延迟和对下丘脑和视通路有放射性损伤的风险; 这些因素限制了放射治疗剂量，随之也影响疗效。 OperativeAnatomy手术解剖 Knowledge of the anatomy of the laminaterminalis and the floor of the third ventricle is essential for safe andeffective removal of these lesions. Please refer to the Subfrontal TranslaminaTerminalis Approach chapter for further details. 掌握终板和三脑室底的解剖知识是安全和有效地切除这些病变的关键。请参阅额下经终板入路了解更多详情。
Embryologically, lamina terminalisrepresents the most rostral end of the developing neural tube. This structurerepresents the widest region of the third ventricle and attaches at an acuteangle to the midportion of the optic chiasm, forming the optic recessposteriorly. Anterior to the lamina is its cistern, part of the suprachiasmaticcistern which contains the A1 segments of the anterior cerebral arteries,anterior communicating artery, recurrent arteries of Heubner, frontoorbitalarteries, hypothalamic perforators, proximal A2 segments, anteriorcommunicating vein, and the anterior cerebral vein. 在胚胎学上，终板代表发育中的神经管的最头端。该结构代表第三脑室的最宽区域，并且以锐角附着到视交叉的中部，从而向后形成视隐窝。 终板前方是终板池，是视交叉上池的一部分，内有大脑前动脉A1段，前交通动脉，Heubner回返动脉，额眶动脉，下丘脑穿动脉，大脑前动脉A2段近端，前交通静脉和大脑前静脉。 Figure 2: Note the anatomy of thelamina terminalis in relation to the anterior cerebral arteries and theirseptal and hypothalamic perforating vessels (left image). The boundaries of thelamina terminalis are marked with yellow arrows. Upon opening the laminaterminalis, the floor of the third ventricle is evident (right image). Arelatively acute superior-to-inferior working angle is necessary to reach thefloor via the subfrontal trajectory (images courtesy of AL Rhoton, Jr). 图2：注意终板相对于大脑前动脉及其中隔和下丘脑穿支血管的解剖（左图）。终板的边界用黄色箭头标记。打开终板，三脑室底显而易见（右图）。 需要以由上至下相对锐的工作角度经额下入路到达三脑室底部（图像由AL Rhoton，Jr提供）。 RESECTIONOF HYPOTHALAMIC HAMARTOMA下丘脑错构瘤切除术 Preoperative lumbar puncture orplacement of a lumbar drain affords brain relaxation, thus minimizing the needfor brain retraction regardless of the approach. Intraoperative image guidanceis a useful adjunct, especially for smaller lesions. 术前腰椎穿刺或放置腰大池引流可使大脑松弛，从而不管用何种入路都可以最小程度牵拉脑组织。术中影像导航是有用的辅助，特别对于较小的病变。
Please refer to the SupraorbitalCraniotomy chapter for more detailsregarding the initial steps of the operationand exposure. The patient is positioned supine and the neck is slightlyextended so that the frontal lobes are mobilized away from the skull base underthe influence of gravity. A two-thirds bicoronalor soutar incision is performed; a pericranial flap is elevated,whichmay be used later if the frontal sinus is entered. 有关初始操作和暴露步骤的更多细节，请参阅眶上开颅术章节。患者仰卧位，颈部轻度伸展，使得额叶在重力的作用下离开颅底。执行三分之二的冠状切口或Soutar切口;骨膜瓣向上翻开，如果额窦开放，稍后可以用骨膜瓣进行修补。
The eyebrow incision provides restrictedaccess to the floor of the third ventricle due to the limited vertical reach ofthe craniotomy. 由于垂直方向开颅的限制，眉毛切口提供了有限的进入三脑室底的通道。 Figure 3: The patient is positionedsupine with the head turned only 10 to 15 degrees away from the midline. The neckis extended slightly to allow the frontal lobes to fall away from the anteriorskull base floor. 图3：患者仰卧，头部旋转偏离中线10至15度。颈部稍微伸展以使额叶从前颅底分离。 The surgeon performs a unilateralsupraorbital craniotomy while avoiding the frontal sinus, if possible. As mentionedbefore, the craniotomy is contralateral to the laterality of the mass to allowa “cross-court”direct visualization of the lateral pole of the lesion. The dura is thenincised in a “reverse-U”pattern and based anteriorly. 如果可能，外科医生可行单侧眶上开颅手术，同时避开额窦。如前所述，在病变侧的对侧开颅，可以“斜角线”直视病变的侧面。然后将硬脑膜以前部为基底倒“U”形切开。
Figure 4: I do not remove the orbitalrim for approaching a hypothalamic hamartoma because the operative trajectoryis in the superior-to-inferior direction when I reach the third ventricularchamber. 图4：我不会为了接近下丘脑错构瘤而除去眶缘，因为当我进入三脑室时，手术的轨迹是自上而下的方向。 INTRADURALPROCEDURE硬膜内操作 Cerebrospinal fluid (CSF) drainage viathe lumbar drain facilitates brain mobilization before the opticocarotidcisterns are reached. 通过腰大池引流脑脊液（CSF）有利于在到达视神经颈动脉池之前使脑组织易于移动。 Figure 5: A right-sided supraorbitaltrajectory is shown. The inferior edge of the craniotomy is reduced to thelevel of the orbital roof. I use a piece of rubber glove (cut in the shape of acotton patty) to slide the patty underneath the basal frontal lobe. Gentleelevation of the lobe exposes the ipsilateral optic nerve. 图5：右侧眶上入路手术路径。骨窗下缘低到眶顶水平。 我使用一片橡胶手套（剪成一个棉片的形状），滑入额底下面。轻柔地抬起额叶暴露同侧视神经。 Figure 6: Continued gentle mobilizationof the frontal lobe using dynamic retraction allows additional CSF release fromthe opticocarotid cisterns. The optic nerve is then followed posteriorly to thechiasm. The basal frontal lobe is released from the entire anterior opticapparatus and the anterior cerebral arteries are identified. 图6：应用动态地牵拉持续轻柔地牵拉额叶进一步从视神经颈动脉池释放CSF。先解剖视神经然后视交叉。额叶底部从整个前部视觉装置上游离并辨别大脑前动脉。
The lamina terminalis forms part of theanterior wall of the third ventricle and is attached to the superior opticchiasm. This relationship creates the optic recess within the third ventricleand the lamina terminalis recess in the suprachiasmatic space notable for itsrelationship to the A1 segment and the anterior communicating artery complex,as well as the key perforating arteries, including the recurrent artery of Huebner. 终板形成第三脑室前壁的一部分，并且附着到视交叉上部。 这种关系在三脑室内形成视隐窝，在视交叉上方空间形成终板隐窝，其与大脑前动脉A1段和前交通动脉复合体的关系以及关键的穿动脉，包括Huebner返动脉值得注意。 Figure 7: The exposure of the laminaterminalis and the anterior cerebral artery is shown (the images in the leftcolumn). The lamina is thin and relatively transparent, features that differentiateit from the rest of the chiasm. An incision in the lamina terminalis revealsthe floor of the anterior third ventricle and the lesion (images of the rightcolumn). The perforating arteries arising from the anterior communicatingartery complex and supplying the superior chiasm are preserved. Coagulation iskept to a minimum. 图7：显示终板和大脑前动脉（左栏中的图像）。终板较薄并且相对透明，这是与视交叉其余部分相区别的特征。 在终板的切口显露三脑室底的前部和病变（右侧的图像）。 保留发自前交通动脉复合体的穿动脉，该动脉供应视交叉上部血供。双极电凝保持最小功率。 Figure 8: The working space is deep anddynamic retraction provides limited views of the operative target. I use anarachnoid knife to expand the initial crucial incision in the laminaterminalis. This instrument allows adequate visualization around its tip to avoidblind maneuvers that may lead to inadvertent injury to the surrounding vitalstructures. Next, the operative view is directed inferiorly toward the floor ofthe third ventricle. This superior-to-inferior trajectory around the laminaterminalis requires strategic dynamic mobilization of the frontal lobe to avoidsubfrontal injury. The operative maneuvers must be conducted deliberately andefficiently without uninterrupted excessive retraction on the lobe. Thedynamic force of the suction device exerts only periodic retraction on thesubfrontal area during key maneuvers for removal of the mass. 图8：工作空间很深，动态牵拉对目标病变提供的视野有限。我使用蛛网膜刀扩大终板上最初重要的切口。该器械尖端周围应该能被充分观察到以避免盲目操作，盲目操作可能导致对周围重要结构的无意识的损害。接下来，视线向下朝向三脑室底部。围绕终板的自上而下的操作轨迹需要有策略的动态牵拉额叶，避免额下损伤。手术操作必须谨慎和有效地进行，避免持续过度牵拉脑叶。在切除病灶的关键操作期间，使用吸引器动态牵拉额叶下部区域。 Figure 9: Next, the rubbery and grayishhamartoma is slowly separated and carefully removed from the relatively normalwalls of the hypothalamus using angled dissectors. The perilesional area isleft behind and only the obviously abnormal tissue is disconnected. Pituitaryrongeurs facilitate piecemeal evacuation of the mass. The borders of the massare marked with blue arrows in the left lower photograph. 图9：接下来，缓慢分离质地坚韧呈灰色的错构瘤，并使用有角度的剥离子从下丘脑的相对正常的壁上小心地剥离。病灶周围区域保留，分离明显异常的组织。垂体咬骨钳便于使肿块逐块切除。肿块的边界在左下部照片中用蓝色箭头标记。
Figure10: At the end of resection, the hamartoma-hypothalamic interface is leftuntouched. Aggressive resection is not advised. 图10：切除结束时，错构瘤和下丘脑界面保持不接触。不建议过于积极的切除。 Closure关颅 Closure is conducted in standardfashion. If the frontal sinus was entered, it will be exenterated. 以标准方式进行关颅。如果额窦开放，去除其内容物。
PostoperativeConsiderations术后注意事项 The patient is admitted postoperativelyto the intensive care unit for continuous vital sign monitoring, blood pressurecontrol, and hourly neurologic examinations. Frequent lab draws are obtainedfor close monitoring of the electrolyte and endocrine status. Postoperative MRimaging is usually obtained within the first 48 hours. Supratherapeutic levelsof anticonvulsant medications are advised because the risk of perioperativeseizures is significant. 患者术后转入重症监护室，持续监测生命体征，控制血压并且每小时行神经系统检查。频繁的实验室检查绘制成图用于密切监测电解质和内分泌状态。通常术后48小时内行MR检查。建议使用超过有效治疗浓度的抗惊厥药物，因为围术期癫痫发作的风险是显著的。 Pearlsand Pitfalls经验教训 Hypothalamichamartomas are exceedingly rare lesions associated with precocious puberty andseizures. Cognitive, psychiatric, and behavioral changes may also be present. 下丘脑错构瘤是伴有性早熟和癫痫的非常罕见的病变。也可能表现出认知、精神和行为改变。 Althoughgelastic-type seizures are the hallmark clinical finding with these lesions,they are not pathognomonic. 虽然痴笑样癫痫发作是这些病变的标志性临床发现，但它们不是能明确诊断的病征。 Severalsurgical approaches to the anterior third ventricle are available, each withits own advantages and limitations. 三脑室前部有几种手术入路，每种入路都有自己的优势和局限性。 额下经终板入路方法提供了一个到达病变并可近全切的合理入路。不要尝试过于完全的切除。
Contributors供稿者: Kashif Shaikh, MD, and IanWhite, MD DOI: https:///10.18791/nsatlas.v7.ch06 原著作者: Aaron Cohen 编译者： 杨智，济南市第五人民医院，神经外科，山东大学临床医学硕士，先后于华山医院，北京天坛医院进修。 审校：云强，内蒙古自治区人民医院,神经外科,主任医师, 博士，硕导。发表文章10余篇，SCI收录1篇。获内蒙古自治区医学会科学技术二等奖两项、三等奖一项，内蒙古科技进步三等奖一项。 |
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