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A hamartoma is a benign, noncancerous growth consisting of an abnormal mixture of native tissue. Although this tumor-like lesion resembles a neoplasm, it does not exhibit neoplastic tendencies such as accelerated growth, local invasion of surrounding tissues, or metastatic spread.
Hypothalamic hamartomas are exceedingly rare developmental anomalies classically associated with endocrine abnormalities and epilepsy. They consist of a mixture of hyperactive neuronal and glial cells arising from the floor of the third ventricle.
Their true incidence is unknown, but is estimated at one in 50,000 to one in one million. Although classically associated with gelastic seizures, hypothalamic hamartomas are also responsible for several other types of more debilitating medically refractory seizures. Endocrine abnormalities, including central precocious puberty, have also been implicated.
Behavioral, psychiatric, and cognitive impairments appear to have a higher incidence in this patient population as well. In their extreme form, hypothalamic hamartomas lead to disabling epilepsy, severe cognitive deficits, and developmental delay in early childhood.
A patient with a hypothalamic hamartoma may present with signs and symptoms of precocious puberty and/or seizures. Gelastic seizures, spells of uncontrollable laughter, were first reported in the 19th century and are considered a hallmark clinical finding.
The laughing events are typically first noted in early childhood, and may progress to include other seizure types, including generalized tonic-clonic seizures, partial complex seizures, drop attacks, and atypical absences. As stated before, behavioral, psychiatric, and cognitive changes may also be present. Additionally, gelastic seizures have been reported in the absence of any obvious imaging finding and thus cannot be considered a pathognomonic feature.
Depending on the individual patient’s presentation, the diagnostic workup often includes a full spectrum of labs, electroencephalogram (EEG), and magnetic resonance (MR) imaging.
Diagnostic workup of patients with seizure disorders includes MR imaging. Hypothalamic hamartomas typically demonstrate increased signal on T2-weighted images relative to the brain. MR spectroscopy studies have consistently shown decreased neuronal density and increased gliosis.
Several studies have evaluated the EEG findings in these patients. Scalp EEG often fails to show ictal or interictal abnormalities if the seizure semiology is confined to gelastic seizures alone. As this disease progresses and secondarily generalized seizures appear, scalp EEG reveals abnormal findings. Multiple seizure types lead to frontal or temporal multifocal activities. Cortical resection has been ineffective at controlling seizures. Depth electrode evaluation has confirmed the hypothalamic hamartoma as the ictogenic source.
There are two subtypes of hypothalamic hamartomas, differing on the basis of their anatomic relationship to the normal hypothalamic tissue. Sessile hypothalamic hamartomas harbor a broad base with local invasion and displacement of the adjacent surrounding hypothalamic tissue. Pedunculated hypothalamic hamartomas, on the other hand, are suspended by a stalk-like process from the floor of the third ventricle. Sessile hamartomas are more likely to cause epilepsy, whereas pedunculated lesions are associated with endocrine abnormalities.
Indications for Surgery
Evidence-based management algorithms are difficult to establish for such rare lesions. In general, surgical indications include seizures intractable to maximal medical therapy. Precocious puberty is another indication for intervention that leads to regression of preoperative symptoms and signs.
Several studies have confirmed the primary and secondary epileptogenicity of hypothalamic hamartomas. Thus, patients with an uncontrollable seizure disorder who have a known hypothalamic hamartoma are suitable candidates for operative intervention.
Various surgical approaches to the anterior third ventricle have been described in the literature, including standard pterional, transcallosal, endoscopic transventricular, endoscopic endonasal, and subfrontal translamina terminalis. A standard pterional approach is familiar to neurosurgeons and offers a relatively direct route to the lesion. However, visualization of the anterior third ventricle is limited by the critical overlying neurovascular structures with this approach. Thus, significant retraction and manipulation of the normal anatomy may be needed to conduct the resection.
A transcallosal approach provides a direct vertical route to the anterior third ventricle and clear visualization of the intraventricular aspects of the lesion. Limitations of this approach include the risks of memory disturbance from forniceal manipulation.
Endoscopic endonasal access has great potential for providing a minimally disruptive option to this lesion, but the experience for the use of this route is limited.
I favor the subfrontal translamina terminalis approach through a supraorbital craniotomy. Some degree of frontal lobe retraction is necessary to reach the lesion via a superior-to-inferior operative trajectory toward the floor of the third ventricle. Additionally, a contralateral subfrontal pathway creates a more direct surgical corridor to the lateral pole of the mass.
Radiosurgery is a viable consideration for the treatment of hypothalamic hamartomas. The potential limitations of radiotherapy include a delayed response to treatment and the risk of radiation injury to the hypothalamus and optic apparatus; these factors limit radiotherapeutic dosing and, in turn, can limit treatment effectiveness.
Knowledge of the anatomy of the lamina terminalis and the floor of the third ventricle is essential for safe and effective removal of these lesions. Please refer to the Subfrontal Translamina Terminalis Approach chapter for further details.
Embryologically, lamina terminalis represents the most rostral end of the developing neural tube. This structure represents the widest region of the third ventricle and attaches at an acute angle to the midportion of the optic chiasm, forming the optic recess posteriorly. Anterior to the lamina is its cistern, part of the suprachiasmatic cistern which contains the A1 segments of the anterior cerebral arteries, anterior communicating artery, recurrent arteries of Heubner, frontoorbital arteries, hypothalamic perforators, proximal A2 segments, anterior communicating vein, and the anterior cerebral vein.
RESECTION OF HYPOTHALAMIC HAMARTOMA
Preoperative lumbar puncture or placement of a lumbar drain affords brain relaxation, thus minimizing the need for brain retraction regardless of the approach. Intraoperative image guidance is a useful adjunct, especially for smaller lesions.
Please refer to the Supraorbital Craniotomy chapter for more details regarding the initial steps of the operation and exposure. The patient is positioned supine and the neck is slightly extended so that the frontal lobes are mobilized away from the skull base under the influence of gravity. A two-thirds bicoronal or soutar incision is performed; a pericranial flap is elevated, which may be used later if the frontal sinus is entered.
The eyebrow incision provides restricted access to the floor of the third ventricle due to the limited vertical reach of the craniotomy.
The surgeon performs a unilateral supraorbital craniotomy while avoiding the frontal sinus, if possible. As mentioned before, the craniotomy is contralateral to the laterality of the mass to allow a “cross-court” direct visualization of the lateral pole of the lesion. The dura is then incised in a “reverse-U” pattern and based anteriorly.
Cerebrospinal fluid (CSF) drainage via the lumbar drain facilitates brain mobilization before the opticocarotid cisterns are reached.
The lamina terminalis forms part of the anterior wall of the third ventricle and is attached to the superior optic chiasm. This relationship creates the optic recess within the third ventricle and the lamina terminalis recess in the suprachiasmatic space notable for its relationship to the A1 segment and the anterior communicating artery complex, as well as the key perforating arteries, including the recurrent artery of Huebner.
Closure is conducted in standard fashion. If the frontal sinus was entered, it will be exenterated.
The patient is admitted postoperatively to the intensive care unit for continuous vital sign monitoring, blood pressure control, and hourly neurologic examinations. Frequent lab draws are obtained for close monitoring of the electrolyte and endocrine status. Postoperative MR imaging is usually obtained within the first 48 hours. Supratherapeutic levels of anticonvulsant medications are advised because the risk of perioperative seizures is significant.
Pearls and Pitfalls
- Hypothalamic hamartomas are exceedingly rare lesions associated with precocious puberty and seizures. Cognitive, psychiatric, and behavioral changes may also be present.
- Although gelastic-type seizures are the hallmark clinical finding with these lesions, they are not pathognomonic.
- Several surgical approaches to the anterior third ventricle are available, each with its own advantages and limitations.
- The subfrontal translamina terminalis approach provides a reasonable pathway for reaching the lesion and its radical subtotal removal. Aggressive resection is not attempted.
Contributors: Kashif Shaikh, MD, and Ian White, MD
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