Child's Nervous System

, Volume 34, Issue 9, pp 1663–1673 | Cite as

Open resection of hypothalamic hamartomas for intractable epilepsy revisited, using intraoperative MRI

  • Libby van Tonder
  • Sasha Burn
  • Anand Iyer
  • Jo Blair
  • Mohammed Didi
  • Michael Carter
  • Timothy Martland
  • Conor Mallucci
  • Athanasius Chawira
Original Paper



Hypothalamic hamartomas (HHs) are rare non-neoplastic lesions which cause drug-resistant epilepsy with associated behavioural, psychiatric and endocrine issues. With the development of new minimally invasive techniques for the treatment of HH, there is a need to reappraise the effectiveness and safety of each approach. We review the outcomes of HH patients treated surgically, utilizing intraoperative magnetic resonance imaging (IOMRI), by a team of Alder Hey NHS Foundation Trust tumour and epilepsy neurosurgeons since 2011.


Patient records of all HH cases operated on since 2011 were reviewed to confirm history of presentation and clinical outcomes.


Ten patients have undergone surgery for HH under the dual care of Alder Hey tumour and epilepsy neurosurgeons during this period. Eight cases had a midline transcallosal, interforniceal approach with the remaining 2 having a transcallosal, transforaminal approach. All patients had an IOMRI scan, with 40% needing further tumour resection post-IOMRI. Forty percent had a total resection, 3 patients had near-total resection and 3 patients had subtotal resection (~ 30% tumour residual on post-operative MRI). No new neurological complications developed post-operatively. Hypothalamic axis derangements were seen in 3 cases, including 1 diabetes insipidus with hypocortisolaemia, 1 hypodipsia and 1 transient hyperphagia. Eighty percent are seizure free; the remaining two patients have had significant improvements in seizure frequency.


IOMR was used to tailor the ideal tumour resection volume safely based on anatomy of the lesion, which combined with the open transcallosal, interforniceal route performed by surgeons experienced in the approach resulted in excellent, safe and effective seizure control.


Hypothalamic hamartoma Paediatric Neurosurgery Epilepsy 


Hypothalamic hamartomas (HHs) are rare non-neoplastic focal lesions consisting of normal neurons and glial cells which have undergone aberrant development to form a disorganized mass [1, 2]. They arise from the tuber cinereum at the base of hypothalamus and can extend to involve the mammillary bodies.

HHs manifest clinically with drug-resistant epilepsy as well as behavioural, psychiatric and endocrine disturbances [1]. In this associated epileptic syndrome, which usually begins in early childhood, worsening cognitive decline and rage attacks can co-exist along with the evolving epileptic encephalopathy [3]. Prevalence of hypothalamic hamartomas with gelastic seizures is estimated at 1 in 200,000 [4].

Historically, the management of HHs did not include the surgical modalities that are currently available [5]. Prior to the 1990s, owing to the complex regional anatomy that surrounded these deep-seated lesions, the threat of the severe long-term neurological sequelae that could follow any attempt to surgically resect or disconnect these growths discouraged surgical intervention [5, 6].

At present, there exists a wide array of treatment modalities for the resection and disconnection of HHs [7]. The choice of which approach (or combination of approaches) and which instruments to use depends on the HH anatomy and the experience and resources of the treating team.

Various previously described open surgical approaches include endoscopic transventricular, transcallosal, interseptal, interforniceal, orbitozygomatic and pterional. Other treatment methods include Gamma Knife, stereotactic radiofrequency ablation, stereotactic laser ablation, deep brain stimulation and vagal nerve stimulation [8, 9, 10, 11, 12, 13].

No single uniform approach has been found to be best or appropriate in all cases [7].

With the advent of new minimally invasive techniques for HH (including Visualase® laser ablation) comes the inevitable need to reappraise the effectiveness and safety of each potential treatment.

This paper describes a series of paediatric patients with HHs treated surgically under the dual care of Alder Hey Children’s hospital tumour and epilepsy neurosurgeons using the intraoperative MRI suite since 2009.

The unique aspect of this series represents an evolution of the surgical techniques now available since previously published series [12, 14, 15] including the use of high-field intraoperative magnetic resonance imaging (IOMRI) to maximize safe resection and achieve the pre-stated surgical goal. This is in combination with dedicated neuro-oncology surgeons more familiar with the regular use of the midline approaches to the third ventricle.


A review of all neurosurgical procedures relating to “hypothalamic hamartoma” performed in the Paediatric Neurosurgery Service in Alder Hey Children’s NHS Foundation Trust since the IOMRI scanner was installed in 2009 was performed using MD Analyse software.

Patient electronic medical records were then reviewed to confirm history of presentation and clinical outcomes.

Pre-operative MRI scans were reviewed for Delalande classification and post-operative MRI scans were reviewed to assess completeness of resection (Figs. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12).
Fig. 1

Pre-operative sagittal MRI of case

Fig. 2

Intraoperative sagittal MRI of case 8

Fig. 3

Intraoperative coronal MRI of case 8

Fig. 4

Post-operative coronal MRI of case 8

Fig. 5

Post-operative sagittal MRI of case 8

Fig. 6

Pre-operative coronal MRI of case 1

Fig. 7

Pre-operative sagittal MRI of case 1

Fig. 8

Early intra-operative coronal MRI, to re-establish accurate navigation after drainage of cyst, case 1

Fig. 9

Post-operative coronal MRI of case 1

Fig. 10

Post-operative sagittal MRI of case 1

Fig. 11

Classic type 1 HH pre-op coronal T1 MRI of case 5

Fig. 12

Intra-op MRI coronal T1 of case 5 demonstrating classic interforniceal approach with separation of the fornices to access third ventricle and complete resection of HH—no further surgery required

Patients had routine pre- and post-op evaluations and follow-up by the neuroendocrine team and were assessed and put through the MDT evaluative process as part of the National Children’s Epilepsy Surgery Service (CESS) programme since 2012.

This includes pre- and post-operative neuropsychology evaluations when appropriate depending on age.

A tailored approach was utilized, with 8 cases undergoing a midline transcallosal interforniceal approach and the remaining 2 undergoing a transcallosal transforaminal approach when anatomy suited.

This approach and technique has been used extensively and published on by the neuro-oncology team for surgery for hypothalamic/optic pathway gliomas [16, 17] demonstrating an excellent safety profile.

Surgical method

Patients are positioned supine with neck flexed. A NORAS head frame with adult pins is attached. Registration is then confirmed with neuronavigation. We utilize a curved incision extending over the midline to fashion a small craniotomy over the midline. A dural flap is raised based on the sagittal sinus. Via this opening, we dissect to the corpus callosum, taking due care to identify the pericallosal vessels.

A 1.5-cm incision is made in the corpus callosum defined by neuronavigation just above and running 1.5 cm posterior to the foramina of Munro. The septal and forniceal anatomy/foramina of Munro size and orientation and ventricular size are evaluated pre-operatively on fine cut coronal images and the approach tailored to the optimum anatomy. If there is a split septum in a younger child, then the ideal route is a strict midline through this natural pathway into the third ventricle. In older patients, where the fornices seem more adherent, a transforaminal approach is preferred to introduce the ultrasonic aspirator once in the lateral ventricle.

If there is doubt about the midline, then we advise to enter both lateral ventricles, perform a pellucidotomy and then work posteriorly from the midline and foramina of Munro gently separating the fornices along their natural cleft.

The approach to the third ventricle is made usually between the fornices where they are naturally separated and which tends to be more posterior (this is often easier in younger children). This enables an atraumatic approach and reduces the risk of damage to the fornices and subsequent memory issues. Entry into the third ventricle is via the tela choroidea, and between internal cerebral veins which are often visualized at this point. Careful dissection between the veins allows entry into the third ventricle. At this point, the hamartoma should be seen looking anteriorly as one has usually entered the third ventricle just posterior to the hamartoma with this approach. In the usual case of unilateral HH, careful resection is performed using long thin-tipped ultrasonic aspirator until third ventricular symmetry is observed. At this point, an intraoperative MRI is performed and either closure or further resection thereafter tailoring the final resection to the pre-defined and intraoperative goals thus maximizing a safe and optimized resection.


Summary table of case characteristics and outcomes attached in supplemental documents

Ten patients were identified as having 11 surgical procedures involving HH by Alder Hey Neurosurgeons between 2011 and 2017. Average age at time of surgery was 7 years and 5 months (range 2 years and 1 month to 17 years 8 months). Half of the cohort was less than 5 years old at the time of surgery.

All patients presented with chronic drug-resistant gelastic seizures. Four of these patients had complex partial seizures or tonic clonic seizures in addition to this. Average length of inpatient stay was 7 days (range 5–9 days) and follow-up is ongoing for all cases (mean 34 months, 1–76 months range).

All patients underwent IOMRI, with 4 patients requiring further surgical resection of their HH following the intraoperative imaging.

Total resection of the HH was achieved in 5 patients (all Delalande class II), a further 3 had near-total resection (small layer < 2 mm left against third ventricle wall; 1 Delalande class 1 and 2 class II) and the remaining 2 had subtotal resection (Delalande class III and IV). One of the subtotal resections was a redo of a giant congenital HH that had first had subtotal resection in 2009 with only partial response and came for further major resection in 2016.

Post-operatively, there were no new neurological complications observed.

Seizure outcome

Eight of the 10 patients (80%) in this cohort are now seizure free. The remaining 2 patients have had very significant improvements in their seizure frequency (> 50% reduction in seizure frequency). One hundred percent of patients had either an Engel 1 or 2 outcome.

Endocrine outcome

Acquired ACTH, TSH and gonadotropin deficiencies were seen in 2, 1 and 1 patients, respectively.

A transient diabetes insipidus was observed in 2 patients, which resolved prior to discharge.

There was one case of hypodipsia and the same patient had accelerated weight gain on pre-existing hypothalamic obesity. This responded well to the use of metformin and a fixed fluid intake.

Neuropsychological outcome

Neuropsychological assessments in those children assessed and parent outcome surveys showed an improvement in emotional, cognitive and behavioural well-being. Patients, where possible, have neuropsychological assessments pre-operatively and post-operatively at 1 year and thereafter depending on clinical need. The detailed outcomes of these assessments will be analysed in a future paper. There have been no reports of new short-term memory issues post-operatively in the neurosurgical outpatients department.


Within our series of patients with surgically treated hypothalamic hamartoma, all patients had procedures carried out as a joint effort between a senior paediatric tumour surgeon and a paediatric epilepsy surgeon. This collaborative effort effectively harnessed the skillsets of both subspecialties to achieve the best surgical outcome possible in this technically challenging field.

As IOMRI has been demonstrated to be of significant value in improving resection rates whilst maintaining safety in oncological surgery [18, 19, 20, 21, 22, 23, 24], it follows that for any neurosurgery where the aim is maximizing resection for any MRI identifiable lesion (such as epilepsy surgery) should similarly benefit from IOMRI.

This has been our hypothesis in applying IOMRI to our HH cohort. The utility of IOMRI is seen in the 40% of patients going on for further surgical resection after intraoperative scan (Table 1.).
Table 1

Utility of IOMRI


Date of surgery

Age at surgery

Seizure types

Post-op seizure frequency

Age at onset (years)




Delalande classification; surgical resection



3 years 10 months



Seizure free


15 months



Type III

2nd look surgery

Subtotal resection, 10% remaining



6 years 5 months

Gelastic and complex partial

Gelastic seizure free; ongoing complex partial


26 months



Type II

Near-total resection



12 years 1 month

Gelastic and complex partial


Seizure free


31 months

DI, hypocortisol


Learning difficulties

Type II, Transforaminal approach

Gross total resection



15 years 5 months



Seizure free


36 months

Suboptimal cortisol response LDSST-sick day hydrocortisone


Mild learning disability

Type II

Gross total resection



5 years 10 months

Tonic clonic sz 3–14/day

Absence sz 4–6/day

Tonic clonic sz every 2–3 days

Significant improvement


48 months



Aggressive behaviour

Learning difficulties

< 1st centile for expressive and receptive language

Global developmental delay

Type II

Gross total resection



17 years 8 months

Gelastic complex partial sz 3–4/day

Seizure free


62 months

Post-op DI (resolved)

Secondary ammenhorea-partial gonadotropin deficiency

Short-term verbal memory problems

Type I

Near-total resection



3 years 7 months

Focal nocturnal Sz


Gelastic daytime sz 4/day

Seizure free (not initially sz free but over time)


63 months

Post-op DI (resolved)

Hypothyroidism (thyroxine)

Hyperphagia (metformin)


No behavioural problems

In regular state school

Type II

2nd look surgery

Gross total resection


10/02/2011 and 01/12/2016

3 years 8 months

Gelastic sz

5–10 min

Seizure free


78 months

Precocious puberty

Recently developed ACTH deficiency and hyperphagia (Jan 2016)


Behavioural problems

Aggressive outbursts

Social and communication skills problems

Type IV

Subtotal resection

10/02/2011—30% residual

01/12/2016—combined interforniceal and transforaminal approached, 2nd look surgery, 30% residual but 10% of original tumour bulk remaining



2 years 1 month

Gelastic sz 30/day

Seizure free


14 months



Type II

2nd look surgery

Near-total resection



3 years 3 months

Gelastics 2/day

Significant improvement


5 months


Total resection

Type II

Gross total resection

Kurwale et al. concluded in 2015 that IOMRI increases the extent of resection mainly in lesional epilepsy surgeries translating into good seizure outcomes [25], a point which was repeated in resective epilepsy surgery for peri-eloquent cortex cortical dysplasias and heterotopias in paediatric patients [26] and in an adult HH population by Sommer et al. [27]—we reiterate these findings with the addition of our data.

Ng et al., in their series of 25 patients, found that seizure outcome relates directly with completeness of resection [14]. Complete resection is not always possible or advisable given the risks of permanent neurological or endocrinological deficit; thus, the availability of IOMRI to allow prospective decision making about whether or not to proceed with further resection of any residual hamartoma has played a major role in allowing us to achieve maximal safe resection margins whilst avoiding serious neurological deficits.

Eight of the 10 patients are now seizure free and the remaining 2 have had very significant improvements in their seizure frequency (Engel class 2). Seizure freedom or improvement in seizure frequency has resulted in very significant improvements in our patients’ quality of life. Parents self-report significant improvements in their children’s behaviour, particularly a decrease in rage attacks (which are obviously very disruptive within daily family life and individual child functioning).

Over the last 20–30 years, there have been advances in many neurosurgical techniques, e.g. intraoperative neuronavigation, endoscopic equipment and holders (for navigating the third ventricle) and the emergence of various minimally invasive treatment modalities, such as Gamma Knife, stereotactic radiosurgery and laser ablation, that have propelled efforts in managing these lesions [28]. Evidence remains mainly limited to single institutional experiences for these techniques and long-term and multi-institutional studies will be required. Whilst newer technologies (e.g. Visualase) offer interesting options to how we approach deep-seated lesions like HH, we need to be cognizant of the utility of the open surgical resection for HH in many cases.

The open transcallosal-interforniceal route has previously been recognized as an effective treatment for seizure control in HH [29] with up to 60% of patients achieving seizure freedom [14, 30, 31, 32]. There have been concerns regarding potential complications of the open route and other open surgical approaches particularly with regard to memory, neurological and endocrinological complications when open routes have been used in epilepsy series for HH [31, 33]. We have demonstrated in our series an improved seizure control rate using the open approach combined with IOMRI whilst maintaining a very low complication rate.

Our series compares favourably to other modalities for seizure outcome; Gamma Knife radiosurgery has reported 37% seizure freedom [33] and interstitial brachytherapy 38% seizure freedom, transventricular endoscopic approaches has achieved between 40 and 49% seizure freedom [34, 35, 36], and stereotactic radiofrequency thermocoagulation can achieve 71% seizure freedom [37] and stereotactic laser thermocoagulation 80% [34], but these techniques are limited to smaller lesions.

We have demonstrated an excellent safety profile with this approach with no new neurological deficits and the endocrine sequelae encountered were managed successfully with appropriate endocrine input.

The actual surgical route described in this paper has been a well-established and reported safe route for access to the third ventricle for many years in the context of tumour surgery, the principles of which are no different to this type of HH surgery [16, 17, 35]. Once arrived in the third ventricle safely, the choice of what to do with the hamartoma and whether to resect or disconnect is up for discussion by the MDT and will be determined by the anatomy. We essentially treat it as a tumour with ultrasonic aspirator resection to the edge of mammillary body and to the lateral wall of the third ventricle for unilateral hamartomas or for large/giant sessile tumours, maximal debulk with IOMRI control and disconnection of the relevant attachments has been most effective.

Clearly, for small lesions, the avoidance of an open approach and the use of new minimally invasive technologies (such as Visualase) may prove to be an attractive option.

They have the potential to reduce length of inpatient stay and to minimize the surgical scar. They may have potential to minimize complications associated with a particular approach and in particular minimize the risk of separating the fornices.

However, the aim, as for all other modalities of treatment, is ultimately destruction/ablation/removal of the abnormal tissue in this area and as such there will inevitably be an overlap in complications specific to hypothalamic injury with all these techniques.

The long-term effectiveness of ablation (by heat, laser or radiotherapy) versus actual removal or disconnection needs longer independent outcome studies. It would appear that our approach in attempting maximal removal has provided excellent, safe and highly effective control in this short-term study when compared with the historical case series of open surgical approaches. Longer term follow-up will be needed to ascertain the durability of these results.

Essentially we agree with the conclusions of Regis et al. in their recent review paper in Epilepsia—“The customization of surgical options to the individual patient should accordingly improve treatment results” [36].


No one modality has been accepted as the gold standard for the treatment of HH and it is clear that the approach and methods should be tailored to the anatomical features and position of the HH. Ideally, an array of approaches and treatment modalities should be available to patients using all available expertise and technology in an MDT setting tailoring the most effective treatment to each patient. As these lesions are so rare, this is an inevitable challenge for the NHS and providers where it is often difficult to justify the adoption of expensive new technologies for such small numbers. Careful pre-operative counselling and endocrine involvement in the management of these patients is important.

Our experience using existing experience and technology put in place for the brain tumour service shows that the midline transcallosal approach in experienced hands, combined with IOMRI an effective in seizure control with an excellent safety profile offering patients with HH an effective treatment option to consider.


Compliance with ethical standards

Conflict of interest

The authors ceftify that they have no affiliations with or involvement in any organization or entitiy with any financial interest (such as honoria;educational grants;participation in speakers' bureaus;membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patientlicensing arrangments), or non financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018
corrected publication July/2018

Authors and Affiliations

  • Libby van Tonder
    • 1
  • Sasha Burn
    • 1
  • Anand Iyer
    • 2
  • Jo Blair
    • 3
  • Mohammed Didi
    • 3
  • Michael Carter
    • 4
  • Timothy Martland
    • 5
  • Conor Mallucci
    • 1
  • Athanasius Chawira
    • 1
  1. 1.Department of NeurosurgeryAlder Hey Children’s NHS Foundation TrustLiverpoolUK
  2. 2.Department of Paediatric NeurologyAlder Hey Children’s NHS Foundation TrustLiverpoolUK
  3. 3.Department of EndocrinologyAlder Hey Children’s NHS Foundation TrustLiverpoolUK
  4. 4.Department of NeurosurgeryBristol Royal Hospital for ChildrenBristolUK
  5. 5.Department of Paediatric NeurologyRoyal Manchester Children’s Hospital (RMCH)ManchesterUK

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