Cavernous malformations of the hypothalamus: a single-institution series of 12 cases and review of the literature

View More View Less
  • Department of Neurosurgery and Stanford Stroke Center, Stanford University School of Medicine and Stanford Health Center, Stanford, California
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

OBJECTIVE

There remains a paucity of literature on hypothalamic cavernous malformations (HCMs). Here, the authors present the largest series of HCMs to date and review the literature to gain additional insight into this rare disease subset.

METHODS

A prospectively managed database was retrospectively reviewed for patients diagnosed with symptomatic HCM and treated surgically between 1987 and 2019. Data gathered included demographics, presenting signs, radiological measurements, surgical approach, and postoperative events. Functional outcome was measured using the modified Rankin Scale (mRS) and Glasgow Outcome Scale–Extended (GOSE) pre- and postoperatively. A PRISMA guideline systematic review of HCM in the literature was performed.

RESULTS

Our cohort study consisted of 12 patients with symptomatic, and radiographically confirmed, HCM treated with microsurgery by the senior author (G.K.S.). An additional 16 surgically or conservatively managed patients were also identified from the literature, and the authors analyzed the data of all 28 patients (with 54% of patients being male; mean age 39 ± 16 years, range 10–68 years). Patients harboring HCMs most commonly presented with headache (16/28, 57%), short-term memory impairment (11/28, 39%), and gait disturbance (8/28, 32%). Radiographically, lesions most commonly involved the mammillary region (18/23, 78%), the tuberal/infundibulum region (13/23, 57%), and the preoptic/lamina terminalis region (12/23, 52%), with a mean diameter of 2.5 ± 1.4 cm (range 0.8–7 cm) at presentation. Acute hemorrhage was identified in 96% (23/24) of patients on presentation, with 96% (23/24) intraparenchymal and 29% (7/24) intraventricular. Of 24 patients who were managed surgically, gross-total resection (GTR) was achieved in 88% (21/24) of cases. There were no reports of perioperative infarction or mortality. With a mean follow-up period of 41 months (range 0.5–309 months), 77% (20/26) of patients experienced functional improvement, while 12% (3/26) had no change, and 12% (3/26) experienced increased disability. In our cohort of 12 patients, 83% (10/12) continued to report symptoms at the last follow-up (mean 4.8 years, range 0.1–25.7 years). However, there was a significant improvement in mRS score noted after surgery (mean 1.4 vs 3.1, p = 0.0026) and a trend toward improvement in GOSE score (mean 6.3 vs 5.1, p = 0.09).

CONCLUSIONS

Hemorrhage from HCMs can cause a symptomatic mass effect on adjacent eloquent structures. While patients are unlikely to be deficit free following surgery, GTR allows for functional improvement and reduces recurrent hemorrhage rates. Microsurgery remains a viable option for symptomatic HCMs in experienced hands.

ABBREVIATIONS

CM = cavernous malformation; GOSE = Glasgow Outcome Scale–Extended; GTR = gross-total resection; HCM = hypothalamic CM; IPH = intraparenchymal hemorrhage; IVH = intraventricular hemorrhage; mRS = modified Rankin Scale.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Correspondence Gary K. Steinberg: Stanford University School of Medicine, Stanford, CA. gsteinberg@stanford.edu.

INCLUDE WHEN CITING Published online May 21, 2021; DOI: 10.3171/2020.10.JNS201419.

Disclosures Dr. Steinberg is a consultant for Peter Lazic US, NeuroSave, San-Bio, Audaxion Therapeutics, Zeiss, and Surgical Theater.

A.S.K. and Y.L. contributed equally to this work.

  • 1

    Batra S, Lin D, Recinos PF, et al. . Cavernous malformations: natural history, diagnosis and treatment. Nat Rev Neurol. 2009;5(12):659670.

    • Search Google Scholar
    • Export Citation
  • 2

    Gross BA, Du R. Hemorrhage from cerebral cavernous malformations: a systematic pooled analysis. J Neurosurg. 2017;126(4):10791087.

  • 3

    Pozzati E, Acciarri N, Tognetti F, et al. . Growth, subsequent bleeding, and de novo appearance of cerebral cavernous angiomas. Neurosurgery. 1996;38(4):662670.

    • Search Google Scholar
    • Export Citation
  • 4

    Kondziolka D, Lunsford LD, Kestle JR. The natural history of cerebral cavernous malformations. J Neurosurg. 1995;83(5):820824.

  • 5

    Washington CW, McCoy KE, Zipfel GJ. Update on the natural history of cavernous malformations and factors predicting aggressive clinical presentation. Neurosurg Focus. 2010;29(3):E7.

    • Search Google Scholar
    • Export Citation
  • 6

    Abou-Al-Shaar H, Bahatheq A, Takroni R, Al-Thubaiti I. Optic chiasmal cavernous angioma: a rare suprasellar vascular malformation. Surg Neurol Int. 2016;7(18)(suppl 18):S523S526.

    • Search Google Scholar
    • Export Citation
  • 7

    Cossu G, González-López P, Daniel RT. The transcallosal transchoroidal approach to the diencephalic-mesencephalic junction: how I do it. Acta Neurochir (Wien). 2019;161(11):23292334.

    • Search Google Scholar
    • Export Citation
  • 8

    Enriquez-Marulanda A, Alturki AY, Ascanio LC, et al. . Surgical resection of a cavernous malformation of the anterior perforated substance: 2-dimensional operative video. Oper Neurosurg (Hagerstown). 2019;17(2):E64.

    • Search Google Scholar
    • Export Citation
  • 9

    Han MS, Moon KS, Lee KH, et al. . Cavernous hemangioma of the third ventricle: a case report and review of the literature. World J Surg Oncol. 2014;12:237.

    • Search Google Scholar
    • Export Citation
  • 10

    Hasegawa H, Bitoh S, Koshino K, et al. . Mixed cavernous angioma and glioma (angioglioma) in the hypothalamus—case report. Neurol Med Chir (Tokyo). 1995;35(4):238242.

    • Search Google Scholar
    • Export Citation
  • 11

    Mathiesen T, Edner G, Kihlström L. Deep and brainstem cavernomas: a consecutive 8-year series. J Neurosurg. 2003;99(1):3137.

  • 12

    Mizutani T, Goldberg HI, Kerson LA, Murtagh F. Cavernous hemangioma in the diencephalon. Arch Neurol. 1981;38(6):379382.

  • 13

    Patil PB, Kamalapur MG, Sindhur JC, Joshi SK. Hypothalamic cavernous angioma associated with memory and behavior disturbance attacks: role of imaging in diagnosis. Iran J Radiol. 2012;9(1):4244.

    • Search Google Scholar
    • Export Citation
  • 14

    Rai SPV, Chakraborti S, Chandran P, Pai MV. Blooming in the hypothalamus. J Neurosci Rural Pract. 2019;10(2):339341.

  • 15

    Rheinboldt M, Blase J. Exophytic hypothalamic cavernous malformation mimicking an extra-axial suprasellar mass. Emerg Radiol. 2011;18(4):363367.

    • Search Google Scholar
    • Export Citation
  • 16

    Sasaki T, Hayashi N, Tomura N, et al. . A case of a cerebral cavernous malformation of the third ventricle that caused the syndrome of inappropriate secretion of antidiuretic hormone. Surg Neurol Int. 2017;8:53.

    • Search Google Scholar
    • Export Citation
  • 17

    Toe BP, Ramli NM, Rahmat K. Cavernoma of the hypothalamus. Hong Kong J Radiol. 2011;14(4):234237.

  • 18

    Wang CH, Lin SM, Chen Y, Tseng SH. Multiple deep-seated cavernomas in the third ventricle, hypothalamus and thalamus. Acta Neurochir (Wien). 2003;145(6):505508.

    • Search Google Scholar
    • Export Citation
  • 19

    Barbosa DAN, de Oliveira-Souza R, Monte Santo F, et al. . The hypothalamus at the crossroads of psychopathology and neurosurgery. Neurosurg Focus. 2017;43(3):E15.

    • Search Google Scholar
    • Export Citation
  • 20

    Saper CB, Lowell BB. The hypothalamus. Curr Biol. 2014;24(23):R1111R1116.

  • 21

    Pandey P, Westbroek EM, Gooderham PA, Steinberg GK. Cavernous malformation of brainstem, thalamus, and basal ganglia: a series of 176 patients. Neurosurgery. 2013;72(4):573589.

    • Search Google Scholar
    • Export Citation
  • 22

    Liu JK, Lu Y, Raslan AM, et al. . Cavernous malformations of the optic pathway and hypothalamus: analysis of 65 cases in the literature. Neurosurg Focus. 2010;29(3):E17.

    • Search Google Scholar
    • Export Citation
  • 23

    Sinnamon HM. Preoptic and hypothalamic neurons and the initiation of locomotion in the anesthetized rat. Prog Neurobiol. 1993;41(3):323344.

    • Search Google Scholar
    • Export Citation
  • 24

    Balak N, Balkuv E, Karadag A, et al. . Mammillothalamic and mammillotegmental tracts as new targets for dementia and epilepsy treatment. World Neurosurg. 2018;110:133144.

    • Search Google Scholar
    • Export Citation
  • 25

    Takakusaki K, Chiba R, Nozu T, Okumura T. Brainstem control of locomotion and muscle tone with special reference to the role of the mesopontine tegmentum and medullary reticulospinal systems. J Neural Transm (Vienna). 2016;123(7):695729.

    • Search Google Scholar
    • Export Citation
  • 26

    Mizoi K, Yoshimoto T, Suzuki J. Clinical analysis of ten cases with surgically treated brain stem cavernous angiomas. Tohoku J Exp Med. 1992;166(2):259267.

    • Search Google Scholar
    • Export Citation
  • 27

    Akers A, Al-Shahi Salman R, Awad IA, et al. . Synopsis of guidelines for the clinical management of cerebral cavernous malformations: consensus recommendations based on systematic literature review by the angioma alliance scientific advisory board clinical experts panel. Neurosurgery. 2017;80(5):665680.

    • Search Google Scholar
    • Export Citation
  • 28

    Fritschi JA, Reulen HJ, Spetzler RF, Zabramski JM. Cavernous malformations of the brain stem. A review of 139 cases. Acta Neurochir (Wien). 1994;130(1-4):3546.

    • Search Google Scholar
    • Export Citation
  • 29

    Kim DS, Park YG, Choi JU, et al. . An analysis of the natural history of cavernous malformations. Surg Neurol. 1997;48(1):918.

  • 30

    Kupersmith MJ, Kalish H, Epstein F, et al. . Natural history of brainstem cavernous malformations. Neurosurgery. 2001;48(1):4754.

  • 31

    Porter PJ, Willinsky RA, Harper W, Wallace MC. Cerebral cavernous malformations: natural history and prognosis after clinical deterioration with or without hemorrhage. J Neurosurg. 1997;87(2):190197.

    • Search Google Scholar
    • Export Citation
  • 32

    Robinson JR, Awad IA, Little JR. Natural history of the cavernous angioma. J Neurosurg. 1991;75(5):709714.

  • 33

    Barker FG II, Amin-Hanjani S, Butler WE, et al. . Temporal clustering of hemorrhages from untreated cavernous malformations of the central nervous system. Neurosurgery. 2001;49(1):1525.

    • Search Google Scholar
    • Export Citation
  • 34

    Gross BA, Lin N, Du R, Day AL. The natural history of intracranial cavernous malformations. Neurosurg Focus. 2011;30(6):E24.

  • 35

    Cavalcanti DD, Preul MC, Kalani MY, Spetzler RF. Microsurgical anatomy of safe entry zones to the brainstem. J Neurosurg. 2016;124(5):13591376.

    • Search Google Scholar
    • Export Citation
  • 36

    Kalani MY, Yagmurlu K, Martirosyan NL, et al. . Approach selection for intrinsic brainstem pathologies. J Neurosurg. 2016;125(6):15961607.

    • Search Google Scholar
    • Export Citation
  • 37

    Clatterbuck RE, Bernardo A, Spetzler RF. Discovering the novel surgical approach. Clin Neurosurg. 2003;50:3644.

  • 38

    Chang SD, Lopez JR, Steinberg GK. The usefulness of electrophysiological monitoring during resection of central nervous system vascular malformations. J Stroke Cerebrovasc Dis. 1999;8(6):412422.

    • Search Google Scholar
    • Export Citation
  • 39

    Choudhri O, Karamchandani J, Gooderham P, Steinberg GK. Flexible omnidirectional carbon dioxide laser as an effective tool for resection of brainstem, supratentorial, and intramedullary cavernous malformations. Oper Neurosurg. 2014;10(1)(suppl 1):3445.

    • Search Google Scholar
    • Export Citation
  • 40

    Kurokawa Y, Abiko S, Ikeda N, et al. . Surgical strategy for cavernous angioma in hypothalamus. J Clin Neurosci. 2001;8(suppl 1):106108.

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 689 689 206
Full Text Views 81 81 28
PDF Downloads 45 45 28
EPUB Downloads 0 0 0