Acta Neurochir (2014) 156:1865–1878 DOI 10.1007/s00701-014-2172-z
CLINICAL ARTICLE - BRAIN TUMORS
Intraoperative use of high-field MRI in hypothalamic hamartomas associated with epilepsy: clinico-pathological presentation of five adult patients Bjoern Sommer & Sven-Martin Schlaffer & Roland Coras & Ingmar Blumcke & Hajo Martinus Hamer & Hermann Stefan & Michael Buchfelder
Received: 25 March 2014 / Accepted: 24 June 2014 / Published online: 2 August 2014 # Springer-Verlag Wien 2014
Abstract Background Hypothalamic harmartomas (HHs) are either occasionally associated with medically intractable epileptic syndromes or precocious puberty. Due to the extraordinary location and the expansive intra-axial growth, surgical resection is difficult and challenging without causing severe neurological, hypothalamic or endocrinological deficits, which account for higher mortality and morbidity. Methods We present a series of five adult patients with drugresistant epilepsy who had been operated on for HH using neuronavigation and intraoperative 1.5-T magnetic resonance imaging (MRI). In this retrospective investigation, we compared our surgical strategy and postoperative results to existing series. Results During surgery, we identified remnant HH in the first intraoperative MRI control scan in three out of five patients. After re-segmentation of the residual lesion using neuronavigation, complete resection was achieved in two of the three patients as confirmed by final intraoperative and late follow-up MRI, raising the rate of total resections to four out of five patients. Two patients died during the observation period. One patient suffered from a permanent third nerve palsy and one from a transient monoparesis of the left arm. New endocrinological disturbances included diabetes B. Sommer (*) : S.10 mm), broad-based attachment or invasive growth into the wall of the third ventricle and incomplete resection have a negative impact on seizure control [1, 11, 36]. Gross total resection seems to be a key point in controlling both tumour growth and seizures [37]. However, even under the microscope, boundaries between pathological and healthy brain tissue are often indistinguishable despite an ideal visualisation of the target area. Here, neuronavigation and intraoperative MRI can add valuable information and guidance during surgery.
Impact of neuronavigation and intraoperative MRI Although only few reports exist that describe the use of stereotactic guidance when operating on HH, all of the study groups agree that this additive aids in planning the ideal trajectory, to remain in the midline when performing the callosotomy, and to sharpen the three-dimensional view while performing surgery near the internal carotid artery, optic nerve, chiasm and tracts [9, 10, 13, 33]. By using intraoperative high-field MRI, the degree of resection and/or disconnection of the hamartoma can be assessed by this immediate resection control. Incomplete resections of HH as documented by late postoperative imaging is found in 61 % [5] and 69 % [12] of patients. In a previous report, we presented our experience with 33 paediatric patients operated on with the aid of intraoperative low-field (0.2 T) MRI and neuronavigation [16]. One child suffering from seizures underwent surgery of a suprasellar hamartoma, and intraoperative imaging showed remnant tumour mass after the first intraoperative MRI control scan. After re-segmentation of the remaining tumor, we achieved complete removal of the lesion with neuronavigational guidance, whereas the remnant lesion was not clearly distinguishable as seen through the microscope. In our recent case series, we raised the rate of complete resections from two to four out of five patients using high-field intraoperative MRI and neuronavigation. Keeping in mind that gross total resection is one of the positive predictors of postoperative seizure control, there is a good chance that these patients, who would
Proposed usea Type I (preferred in patients suffering from central precocious puberty) and III lesions (in combination with endoscopic approach)
large Type II lesions; large Type III and IV in midline
Type III (pedunculated) lesions
Type II
Orbitozygomatic: Type I lesions, others: Type III and IV
Surgical approach
Transsylvian: – pterional – fronto-temporal – subtemporal
(Anterior) transcallosal: - transseptal, interforniceal Transcallosal trans-thirdventricular: – midline interforniceal – through foramen of Monro – transchoroideal
Interpeduncular cistern
Lamina terminalis: – subfrontal – bifrontal
Skull base: – orbitozygomatic – subfrontal – supraorbital – pterional
Disadvantages
Typical complications/post-op. neurological deficits
Pterional/frontotemporal: Higher risks of cerebral cannot reach lesions in the ischaemia, leaving remnant third ventricle, no access to tumor mass, nerve palsy, the intrahypothalamic part endocrinological of the HH Subtemporal: disturbances, cannot reach lesions in the thalamic or capsular third ventricle, improved infarction, third and fourth access only with resection nerve paresis of normal frontal or temporal cortex “Classic” and anterior “Classic” transcallosal, transseptal, “Classic” transcallosal, transtranscallosal transseptal interforniceal: wide septal, interforniceal: corpus interforniceal: callosal exposure of the third ventricle callosotomy needed, risk of disconnection syndrome, anterior transcallosal, transbridging vein injury, higher risk short-term memory deficits septal, interforniceal: lower risk of short-term memory due to septal, forniceal or of short-term memory disturbance (especially in older patients), more technical mammillary body injury disturbance compared to the difficulties in patients with while resection of third “classic” approach, better narrow third ventricles and ventricular located lesions overview, sparing of optic lesions that fill/distort the third (could be avoided by chiasm, mamillary bodies, ventricle Anterior transcallosal interventricular approach), pituitary stalk, fewer blood transseptal interforniceal: thalamic infarction, vessels are encountered inability to extend the resection endocrinological changes, compared with transsylvian with wide laterally developed hypothalamic symptoms approach, sparing of the third and attached HHs such as vigilance nerve trans-third ventricular: transforaminal, esp. supra-/ disturbances, lesser incidence of short-term trans-/sub-choroideal: deep diabetes insipidus, abnormal memory deficits, only ipsilateral venous injury, damage to central/core temperature fornix is at risk the fornix regulation, increased appetite, and third cranial nerve palsy Short distance to the lesion, easier Depending on horizontal extent: Infarctions in all major division of the HH’s stalk if vicinity to ICA, PCA, brain stem arterial territories it is narrow arteries, optic chiasm and visual tracts, internale capsule, limited access to larger lesions; HH disconnection is more difficult Greater access to the intrahypothalamic Moderate- to large-sized HH Due to retraction of frontal part of the HH through the third cannot be resected completely, lobe(s): frontal lobe ventricle, resection of the inferior ACA/AcomA is in the line of syndrome, injury to brain an posterior part of the HH approach, much retraction of the tissue, olfactory nerves, optic reaching in the third ventricle is frontal lobe is needed, resection chiasm possible or disconnection of HH attached to the mamillary bodies is more difficult Orbitozygomatic and supraorbital: Cranial nerve palsy (esp. Subfrontal: good access to lesions protruding into the in sessile HH, boundaries are third nerve), thalamic infarct interpeduncular fossa and not as distinguishable, leading with hemiparesis laterally beneath the tuber to incomplete resection cinerum (optionally in Subfrontal and subtemporal:
Good access to the suprasellar cistern and interpeduncular fossa
Advantages
Table 4 Surgical techniques to treat hypothalamic hamartoma: advantages, disadvantages and indications
[12, 35, 38, 50]
[9, 38, 39]
[9, 47]
[1, 4, 11, 14, 35, 37–39]
[12, 13, 33, 35, 38, 39, 47]
References
1874 Acta Neurochir (2014) 156:1865–1878
Seizure control In general, the amount of HH tissue resection has often been incomplete, and the results of seizure control were only satisfying to some extent [33, 38]. As this disease has a predisposition in children, there are only few reports that deal with the “late onset type “in adults. Data indicate that in adults, longterm seizure control is less favourable compared to children. One reason for this could be the long time span between appearance of first seizures and establishment of the correct diagnosis, which is reported to be up to an average of 17 years [5]. However, the published results also indicate that adult patients with HH experience a delayed epilepsy onset with less cognitive and hormonal dysfunctions compared to children [6, 7]. Long-term outcome data of these patients show that the key factors fostering favourable results are: (1) short epilepsy duration, (2) low seizure intensity and frequency and (3) complete resection or disconnection of the HH [12, 26]. Seizure reduction of over 90 % is reported in 24–77 % of published studies, depending on the surgical approach [12, 39, 40]. Seizure freedom rates after surgery range between 12.5 % and 54 % [5, 11, 12, 38, 41]. Our series consists of five adult patients with HH and drugresistant epilepsy, with four out of five being in a favourable Engel class I or II. However, none of our patients was seizurefree after the operation, and all of them were still taking AEDs. It is of note, though, that two of these four patients had a broad-based attachment of the hamartoma, all four of them were adult patients with a long seizure history ranging from 13 to 29 years, as well as a lesion diameter above 10 mm. Thus, our good results were achieved despite the presence of these unfavourable predictive factors of postoperative seizure control (see first paragraph above). Lesions classified according to Delalande and Fohlen [26]
Endoscopic
Small Type II and III lesions with an unilateral attachment
intraventricular component cannot be resected completely, sometimes additional cortical resection is needed for improved access Only useful in small (6 mm thalamic infarct with clearance to the top of the third hemiparesis, ataxia ventricle is needed for decent endoscope operation, narrow working channel through the endoscope, bleeding control more difficult, requires second approach to remove larger lesions, worse vision and tactile feedback compared with open surgery makes differentiation of pathological tissue more difficult combination with transcallosal approach) Subtemporal: especially in lesions with a major prepontine component and patients with precocious puberty Smaller craniotomy/burr hole only; less time needed for surgery, better wound healing/lower infection rate due to small trauma to skin, lower bleeding rate, lower rate of cerebrospinal fluid fistula – subtemporal
otherwise have been resected incompletely, had profited from using this technique.
a
References Typical complications/post-op. neurological deficits Disadvantages Advantages Proposed usea Surgical approach
Table 4 (continued)
1875
[14, 30, 31, 33, 34, 38, 47]
Acta Neurochir (2014) 156:1865–1878
Surgical complications Surgical mortality rates are reported to be around 2–3 % [5]. Permanent neurological deficits occur in 1–7.7 % of the cases, which include mainly third nerve palsy, hemianopsia and hemiparesis (Table 4) [5, 12, 26]. Transient deficits were reported between 3.5 % and 30.8 % [12, 39]. Two of our patients had severe neurological deficits: one with a distinct monoparesis of the left arm, which resolved completely over the next 12 months, and one with a complete ophthalmoplegia, which was absent 6 months after surgery. Other therapy options There are other treatment options which seem to be promising in treating catastrophic epilepsy due to HH. Gamma Knife
1876
radiosurgery has been used mostly in treating this pathology, starting in the early 1990s and evolving as an alternative treatment option in selected cases [42, 43]. It may provide more favourable seizure outcome in patients with small HH and located with enough distance to optical tract, fornices, mamillary bodies and stable seizure burden [11], but has a lower success rate in adults than in children. This method provides high safety and efficacy in treating small, deepseated lesions and is considered as an alternative to microsurgical resection when the risk of surgical complications or functional loss is too high [37]. In the context of this article, Delalande and Fohlen type I lesions are considered as favourable for Gamma Knife surgery. Seizure-freedom rates range from 0% to 37% and 50 % [5, 10, 37]; however, the number of treated patients was very low. As it is reported in the only multicenter study so far, one of the major problems concerning radiotherapy is the collateral damage evoked by a high field dosage on the optical chiasma, optic apparatus and the mamillary bodies as well as the cloudy boundaries which make a distinction between the lesion and surround hypothalamus difficult [40, 44]. We would recommend Gamma Knife therapy as a first line treatment if (1) patients have a high surgical mortality and morbidity, (2) the HH is very small (lesion volume
CLINICAL ARTICLE - BRAIN TUMORS
Intraoperative use of high-field MRI in hypothalamic hamartomas associated with epilepsy: clinico-pathological presentation of five adult patients Bjoern Sommer & Sven-Martin Schlaffer & Roland Coras & Ingmar Blumcke & Hajo Martinus Hamer & Hermann Stefan & Michael Buchfelder
Received: 25 March 2014 / Accepted: 24 June 2014 / Published online: 2 August 2014 # Springer-Verlag Wien 2014
Abstract Background Hypothalamic harmartomas (HHs) are either occasionally associated with medically intractable epileptic syndromes or precocious puberty. Due to the extraordinary location and the expansive intra-axial growth, surgical resection is difficult and challenging without causing severe neurological, hypothalamic or endocrinological deficits, which account for higher mortality and morbidity. Methods We present a series of five adult patients with drugresistant epilepsy who had been operated on for HH using neuronavigation and intraoperative 1.5-T magnetic resonance imaging (MRI). In this retrospective investigation, we compared our surgical strategy and postoperative results to existing series. Results During surgery, we identified remnant HH in the first intraoperative MRI control scan in three out of five patients. After re-segmentation of the residual lesion using neuronavigation, complete resection was achieved in two of the three patients as confirmed by final intraoperative and late follow-up MRI, raising the rate of total resections to four out of five patients. Two patients died during the observation period. One patient suffered from a permanent third nerve palsy and one from a transient monoparesis of the left arm. New endocrinological disturbances included diabetes B. Sommer (*) : S.10 mm), broad-based attachment or invasive growth into the wall of the third ventricle and incomplete resection have a negative impact on seizure control [1, 11, 36]. Gross total resection seems to be a key point in controlling both tumour growth and seizures [37]. However, even under the microscope, boundaries between pathological and healthy brain tissue are often indistinguishable despite an ideal visualisation of the target area. Here, neuronavigation and intraoperative MRI can add valuable information and guidance during surgery.
Impact of neuronavigation and intraoperative MRI Although only few reports exist that describe the use of stereotactic guidance when operating on HH, all of the study groups agree that this additive aids in planning the ideal trajectory, to remain in the midline when performing the callosotomy, and to sharpen the three-dimensional view while performing surgery near the internal carotid artery, optic nerve, chiasm and tracts [9, 10, 13, 33]. By using intraoperative high-field MRI, the degree of resection and/or disconnection of the hamartoma can be assessed by this immediate resection control. Incomplete resections of HH as documented by late postoperative imaging is found in 61 % [5] and 69 % [12] of patients. In a previous report, we presented our experience with 33 paediatric patients operated on with the aid of intraoperative low-field (0.2 T) MRI and neuronavigation [16]. One child suffering from seizures underwent surgery of a suprasellar hamartoma, and intraoperative imaging showed remnant tumour mass after the first intraoperative MRI control scan. After re-segmentation of the remaining tumor, we achieved complete removal of the lesion with neuronavigational guidance, whereas the remnant lesion was not clearly distinguishable as seen through the microscope. In our recent case series, we raised the rate of complete resections from two to four out of five patients using high-field intraoperative MRI and neuronavigation. Keeping in mind that gross total resection is one of the positive predictors of postoperative seizure control, there is a good chance that these patients, who would
Proposed usea Type I (preferred in patients suffering from central precocious puberty) and III lesions (in combination with endoscopic approach)
large Type II lesions; large Type III and IV in midline
Type III (pedunculated) lesions
Type II
Orbitozygomatic: Type I lesions, others: Type III and IV
Surgical approach
Transsylvian: – pterional – fronto-temporal – subtemporal
(Anterior) transcallosal: - transseptal, interforniceal Transcallosal trans-thirdventricular: – midline interforniceal – through foramen of Monro – transchoroideal
Interpeduncular cistern
Lamina terminalis: – subfrontal – bifrontal
Skull base: – orbitozygomatic – subfrontal – supraorbital – pterional
Disadvantages
Typical complications/post-op. neurological deficits
Pterional/frontotemporal: Higher risks of cerebral cannot reach lesions in the ischaemia, leaving remnant third ventricle, no access to tumor mass, nerve palsy, the intrahypothalamic part endocrinological of the HH Subtemporal: disturbances, cannot reach lesions in the thalamic or capsular third ventricle, improved infarction, third and fourth access only with resection nerve paresis of normal frontal or temporal cortex “Classic” and anterior “Classic” transcallosal, transseptal, “Classic” transcallosal, transtranscallosal transseptal interforniceal: wide septal, interforniceal: corpus interforniceal: callosal exposure of the third ventricle callosotomy needed, risk of disconnection syndrome, anterior transcallosal, transbridging vein injury, higher risk short-term memory deficits septal, interforniceal: lower risk of short-term memory due to septal, forniceal or of short-term memory disturbance (especially in older patients), more technical mammillary body injury disturbance compared to the difficulties in patients with while resection of third “classic” approach, better narrow third ventricles and ventricular located lesions overview, sparing of optic lesions that fill/distort the third (could be avoided by chiasm, mamillary bodies, ventricle Anterior transcallosal interventricular approach), pituitary stalk, fewer blood transseptal interforniceal: thalamic infarction, vessels are encountered inability to extend the resection endocrinological changes, compared with transsylvian with wide laterally developed hypothalamic symptoms approach, sparing of the third and attached HHs such as vigilance nerve trans-third ventricular: transforaminal, esp. supra-/ disturbances, lesser incidence of short-term trans-/sub-choroideal: deep diabetes insipidus, abnormal memory deficits, only ipsilateral venous injury, damage to central/core temperature fornix is at risk the fornix regulation, increased appetite, and third cranial nerve palsy Short distance to the lesion, easier Depending on horizontal extent: Infarctions in all major division of the HH’s stalk if vicinity to ICA, PCA, brain stem arterial territories it is narrow arteries, optic chiasm and visual tracts, internale capsule, limited access to larger lesions; HH disconnection is more difficult Greater access to the intrahypothalamic Moderate- to large-sized HH Due to retraction of frontal part of the HH through the third cannot be resected completely, lobe(s): frontal lobe ventricle, resection of the inferior ACA/AcomA is in the line of syndrome, injury to brain an posterior part of the HH approach, much retraction of the tissue, olfactory nerves, optic reaching in the third ventricle is frontal lobe is needed, resection chiasm possible or disconnection of HH attached to the mamillary bodies is more difficult Orbitozygomatic and supraorbital: Cranial nerve palsy (esp. Subfrontal: good access to lesions protruding into the in sessile HH, boundaries are third nerve), thalamic infarct interpeduncular fossa and not as distinguishable, leading with hemiparesis laterally beneath the tuber to incomplete resection cinerum (optionally in Subfrontal and subtemporal:
Good access to the suprasellar cistern and interpeduncular fossa
Advantages
Table 4 Surgical techniques to treat hypothalamic hamartoma: advantages, disadvantages and indications
[12, 35, 38, 50]
[9, 38, 39]
[9, 47]
[1, 4, 11, 14, 35, 37–39]
[12, 13, 33, 35, 38, 39, 47]
References
1874 Acta Neurochir (2014) 156:1865–1878
Seizure control In general, the amount of HH tissue resection has often been incomplete, and the results of seizure control were only satisfying to some extent [33, 38]. As this disease has a predisposition in children, there are only few reports that deal with the “late onset type “in adults. Data indicate that in adults, longterm seizure control is less favourable compared to children. One reason for this could be the long time span between appearance of first seizures and establishment of the correct diagnosis, which is reported to be up to an average of 17 years [5]. However, the published results also indicate that adult patients with HH experience a delayed epilepsy onset with less cognitive and hormonal dysfunctions compared to children [6, 7]. Long-term outcome data of these patients show that the key factors fostering favourable results are: (1) short epilepsy duration, (2) low seizure intensity and frequency and (3) complete resection or disconnection of the HH [12, 26]. Seizure reduction of over 90 % is reported in 24–77 % of published studies, depending on the surgical approach [12, 39, 40]. Seizure freedom rates after surgery range between 12.5 % and 54 % [5, 11, 12, 38, 41]. Our series consists of five adult patients with HH and drugresistant epilepsy, with four out of five being in a favourable Engel class I or II. However, none of our patients was seizurefree after the operation, and all of them were still taking AEDs. It is of note, though, that two of these four patients had a broad-based attachment of the hamartoma, all four of them were adult patients with a long seizure history ranging from 13 to 29 years, as well as a lesion diameter above 10 mm. Thus, our good results were achieved despite the presence of these unfavourable predictive factors of postoperative seizure control (see first paragraph above). Lesions classified according to Delalande and Fohlen [26]
Endoscopic
Small Type II and III lesions with an unilateral attachment
intraventricular component cannot be resected completely, sometimes additional cortical resection is needed for improved access Only useful in small (6 mm thalamic infarct with clearance to the top of the third hemiparesis, ataxia ventricle is needed for decent endoscope operation, narrow working channel through the endoscope, bleeding control more difficult, requires second approach to remove larger lesions, worse vision and tactile feedback compared with open surgery makes differentiation of pathological tissue more difficult combination with transcallosal approach) Subtemporal: especially in lesions with a major prepontine component and patients with precocious puberty Smaller craniotomy/burr hole only; less time needed for surgery, better wound healing/lower infection rate due to small trauma to skin, lower bleeding rate, lower rate of cerebrospinal fluid fistula – subtemporal
otherwise have been resected incompletely, had profited from using this technique.
a
References Typical complications/post-op. neurological deficits Disadvantages Advantages Proposed usea Surgical approach
Table 4 (continued)
1875
[14, 30, 31, 33, 34, 38, 47]
Acta Neurochir (2014) 156:1865–1878
Surgical complications Surgical mortality rates are reported to be around 2–3 % [5]. Permanent neurological deficits occur in 1–7.7 % of the cases, which include mainly third nerve palsy, hemianopsia and hemiparesis (Table 4) [5, 12, 26]. Transient deficits were reported between 3.5 % and 30.8 % [12, 39]. Two of our patients had severe neurological deficits: one with a distinct monoparesis of the left arm, which resolved completely over the next 12 months, and one with a complete ophthalmoplegia, which was absent 6 months after surgery. Other therapy options There are other treatment options which seem to be promising in treating catastrophic epilepsy due to HH. Gamma Knife
1876
radiosurgery has been used mostly in treating this pathology, starting in the early 1990s and evolving as an alternative treatment option in selected cases [42, 43]. It may provide more favourable seizure outcome in patients with small HH and located with enough distance to optical tract, fornices, mamillary bodies and stable seizure burden [11], but has a lower success rate in adults than in children. This method provides high safety and efficacy in treating small, deepseated lesions and is considered as an alternative to microsurgical resection when the risk of surgical complications or functional loss is too high [37]. In the context of this article, Delalande and Fohlen type I lesions are considered as favourable for Gamma Knife surgery. Seizure-freedom rates range from 0% to 37% and 50 % [5, 10, 37]; however, the number of treated patients was very low. As it is reported in the only multicenter study so far, one of the major problems concerning radiotherapy is the collateral damage evoked by a high field dosage on the optical chiasma, optic apparatus and the mamillary bodies as well as the cloudy boundaries which make a distinction between the lesion and surround hypothalamus difficult [40, 44]. We would recommend Gamma Knife therapy as a first line treatment if (1) patients have a high surgical mortality and morbidity, (2) the HH is very small (lesion volume
