65 Hypothalamic Hamartoma

Abdulrahman J. Sabbagh, Sandeep Mittal, Fahad Eid Alotaibi, and José Luis Montes

Fig. 65.1 T1-weighted magnetic resonance images of the brain with contrast, relevant (A) axial, (B) sagittal, and (C) coronal slices are shown.

Fig. 65.2 T1-weighted sagittal magnetic resonance images of the brain showing depth electrode within the hypothalamic hamartoma.

Clinical Presentation

A 16-year-old boy is referred to you by an epileptologist. He presents with a history of progressive epilepsy that is refractory to medication.

The seizures are described as episodes of short bouts of emotionless laughter with loss of awareness that last only a few seconds at a time and occur several times during the day now.

He also suffers from generalized tonic-clonic seizures several times a month.

Other pertinent findings include cognitive delay. He is able to speak. The remainder of his neurologic exam is normal (including motor, sensory, cerebellar, and gait examination).

A magnetic resonance imaging (MRI) scan is obtained and shown in Fig. 65.1.

Questions

Descr ibe the MR I (Fig. 65.1).
What is the term used for type of seizures this patient is experiencing?
How will you work up this patient?
Briefly describe the anatomy of the hypothalamus; enumerate its nuclei and their functions.
What seizure types are associated with hypothalamic hamartomas (HH)?
What symptoms other than epilepsy are associated with HH?
If this patient has polydactyly and hypopituitarism, what syndrome would you want to confirm?
How do you classify HH? What class does this patient’s hamartoma belong to?
What treatment options can you offer to a patient with HH and intractable seizures? What are their limitations and outcomes?

Answers

Describe the MRI (Fig. 65.1).
- MRI shows a small nonenhancing, isointense lesion in the hypothalamic area.
- The mass occupies the 3rd ventricle and does not cause hydrocephalus.
- This is most consistent with a HH.
What is the term used for type of seizures this patient is experiencing?
- Gelastic seizures
How will you work up this patient?
- Imaging and electrophysiologic investigations include
  - Electroencephalogram (EEG): can show slow spike and wave EEG patterns with or without multifocal epilepticform abnormalities (typically frontal or temporal)¹
  - Computed tomography (CT) scan: may show an isodense nonenhancing lesion
  - MRI: shows an isotense to slightly hypointense lesion compared with gray matter²
  - Depth electrode recording: When the diagnosis is equivocal and EEG is nonspecific, specialized centers may consider this modality for diagnosis (Fig. 65.2).^3,4
  - Positron emission tomography scan: reveals ictal hypermetabolism at the hamartoma site⁵
  - Single photon emission computerized tomography (SPECT) imaging: measures regional cerebral blood flow during seizures. Ictal SPECT scans can be done after injection of the tracer technetium-99m hexamethylpropyleneamine oxime (Tc-99m-HMPAO).
  - Magnetoencephalography (MEG): MEG maps interictal magnetic dipole sources onto MRI to produce a magnetic source image⁶
  - Magnetic resonance spectroscopy: decrease in N-acetyl aspartate/creatine and an increase in myoinositol/creatine (mI/Cr) ratios in tumor tissue when compared with values in normal gray matter of the amygdala. Choline/creatine ratios were also increased when compared with those in normal gray matter controls⁷
- Endocrinologic workup
  - See Case 12, Pituitary Adenoma, for details
Briefly describe the anatomy of the hypothalamus; enumerate its nuclei and their functions.
- The hypothalamus is commonly subdivided into regions along its anteroposterior axis (Fig. 65.3).⁸
  - The preoptic region extends rostrally to the optic chiasm and dorsally to the anterior commissure.
  - The supraoptic region resides above the optic chiasm.
  - The tuberal region lies above and includes the tuber cinereum.
  - The mammillary region includes the mammillary bodies and the posterior hypothalamic nuclei.
What seizure types are associated with HH?
- Seizure types include
  - Gelastic seizures (forced bouts of emotionless laughter) are considered by most authors to be characteristic of HH.
  - Multiple other seizure types exist including
    - Generalized tonic-clonic seizures
    - Partial complex seizures
    - Drop attacks
    - Atypical absences
What symptoms other than epilepsy are associated with HH?
- Other associated symptoms can include
  - Precocious puberty
  - Psychiatric manifestations^9,10
    - Oppositional defiant disorder (83.3%)
    - Attention deficit-hyperactivity disorder (75%)
    - Conduct disorder (33.3%)
    - Affective disorders (16.7%)
    - Progressive cognitive decline
If this patient has polydactyly and hypopituitarism, what syndrome would you want to confirm?
- Pallister–Hall syndrome (PHS)¹¹
- The syndrome is typically characterized by the presence of a HH in association with multisystem malformations.
- The spectrum of features also includes pituitary hypoplasia or dysfunction, central postaxial polydactyly, dysplastic nails, bifid epiglottis, and imperforate anus.
- Additionally, cardiac anomalies, renal defects, and mild mental retardation are seen.
- PHS is often diagnosed at birth. In familial cases it is inherited in an autosomal dominant pattern with variable expressivity.
How do you classify HH? What class does this patient’s hamartoma belong to?
- The most recent and most widely used is the classification of Delalande and Fohlen (Fig. 65.4)¹²
- The present patient’s lesion is classified as intrahypothalamic (3E) according to Delalande and Fohlen’s classification.
What treatment options can you offer to a patient with HH and intractable seizures? What are their limitations and outcomes?
- Microsurgical resection: Seizure outcome is related to completeness of resection.^13,14
  - Pterionaland frontotemporal approach¹⁴
    - Advantage: shortest, most direct route to the suprasellar cistern and hamartoma
    - Disadvantage: Surgical corridor may be narrowed by the internal carotid artery, optic nerve and tracts, oculomotor nerve, and pituitary stalk.
    - Outcome: 23% of patients are seizure free, 87% have significant seizure reduction (in a study of 13 patients).
  - Transcallosal interforniceal approach¹⁵
    - Advantage: provides a wide exposure to the 3rd ventricle and an excellent view of the hamartoma from above; avoidance of cranial nerves and blood vessels in the suprasellar cistern and interpeduncular fossa may further reduce the risk of stroke and oculomotor nerve injury
    - Disadvantage: risk of short-term memory deficits because of potential septal, forniceal, or mammillary body injury
    - Outcome: 52% are seizure free, 24% have significant improvement (in a series of 29 patients)¹⁵
    - Complications: thalamic infarct in 7%, increased appetite in 33% (this is permanent in 16%), and short-term memory deficits in 50%
  - Transcallosal, subchoroidal approach: alternative to the transcallosal interforniceal route; lower risk of short-term memory deficits
  - Endoscopic transventricular approach (Fig. 65.5 for an endoscopic view)
    - Outcome: 31% were able to sustain complete resection (14 of 44 patients), of whom 90% were seizure free.¹⁶
    - Complications: short-term memory difficulties (three patients) and hemiparesis (one patient).¹⁶
- Disconnection procedure (open or endoscopic)¹⁷
  - Outcome: 58% seizure free
  - Complications (in a series of 18 patients)¹⁷: stroke (2 patients), diabetes insipidus (2 patients), meningitis (1 patient)
- Stereotactic radiosurgery¹⁸
  - Gamma knife radiosurgery: good treatment for small- and medium-size hamartomas. The median dose recommended at the marginal isodose is 17 Gy (range is 13–26 Gy).
    - Outcome: 37% seizure free. Most had cognitive and behavioral improvement.
    - Complications: 15% transient worsening of seizures; no permanent complications mentioned.
  - Linear acceleration-based radiosurgery
  - Stereotactic brachytherapy
- Stereotactic radiofrequency ablation
  - Outcome: 25% seizure free, 25% significant improvement (12 patients)¹⁹
  - Complications: 8% mortality (1 patient), 16% memory deficits
- Vagal nerve stimulation: limited role; palliative and seizure freedom is not expected.²⁰
- Corpus callosotomy: limited role