Symptomatic Pineal Cysts Without Ventricular Enlargement

Diagnosis and Treament

Background: Pineal cysts that are not associated with ventricular enlargement can lead to manifestations of intracranial hypertension, usually paroxysmal. If these are due to local mass effect or narrowing of the entrance to the aqueduct, surgery may be indicated.

Methods: This is a narrative review based on publications retrieved by a search in PubMed.

Results: Autopsy studies have revealed pineal cysts in 40% of subjects. Pineal cysts that are not associated with ventricular enlargement can cause intermittent attacks of headache; the second most common symptom is visual disturbance. Patients often also report many non-specific symptoms such as dizziness, fatigue, lethargy, drowsiness, a decline in performance, gait disturbances, impaired memory, or sleep disorders. Because the symptoms are often nonspecific and pineal cysts are common, surgery should not be performed on a pineal cyst unless a comprehensive diagnostic work-up for other potential causes has been carried out with the aid of specialists in all relevant disciplines. In multiple clinical studies, the rate of total relief of symptoms by surgery ranged from 46.8% to 96.4%, while the rate of partial relief ranged from 3.6% to 47.6% and that of persistent symptoms from 3.3% to 18.8%. Permanent complications are rare.

Conclusion: If there are manifestations of intracranial hypertension that are clearly attributable to the pineal cyst, such as severe, holocephalic headaches, vomiting (usually projectile), and brainstem signs that can be triggered by the Valsalva maneuver, and if no other cause of these manifestations can be identified, surgery has a high likelihood of success. A prerequisite to surgical treatment is that the MRI reveals that the pineal cyst is exerting mass effect and/or narrowing the entrance to the aqueduct, even if the ventricles are not enlarged. Because pineal cysts are common and have nonspecific manifestations, surgery must only be performed for strict indications. It should be noted that only low-level evidence supports surgical treatment.

Cite this as: Al Mutawa M, Lange I, Kirsch M, Flöel A, Fleck S, Schroeder HWS: Symptomatic pineal cysts without ventricular enlargement: Diagnosis and treatment. Dtsch Arztebl Int 2025; 122: 298–303. DOI: 10.3238/arztebl.m2025.0053

Box

Preoperative symptoms in our published series

Figure 1

Magnetic resonance imaging of a patient with a typical pineal cyst

Figure 2

Magnetic resonance imaging of a symptomatic pineal cyst in a preschool child who presented with headaches, nausea, and vomiting

Figure 3

Magnetic resonance imaging of a symptomatic pineal cyst in a schoolchild complaining of severe headaches, pressure in the head, fatigue, and dizziness

Figure 4

Therapeutic decision-making flowchart for pineal cysts without ventricular enlargement

Table

Published studies on the surgical treatment of pineal cysts without ventricular enlargement

Now that cranial magnetic resonance imaging (MRI) is being performed ever more frequently, pineal cysts are increasingly being diagnosed as incidental findings (1, 2). Pineal cysts are found in as many of 40% of persons at autopsy (3, 4). There is a consensus that pineal cysts causing ventricular enlargement can become symptomatic, and that, in such cases, the surgical fenestration or resection of the cyst is advisable. In the authors’ experience, a pineal cyst that does not cause ventricular enlargement is often considered an incidental finding even if the patient have symptoms that may be explained by the cyst. The resulting failure to diagnose the symptoms correctly, sometimes for many years, may deprive the patient of the opportunity for timely treatment (5, 6).

In this review, we draw attention to the symptoms of pineal cysts without ventricular enlargement and the difficulties pertaining to their diagnostic evaluation.

Methods

We searched for relevant publications in PubMed with the searching terms “pineal cyst,” “pineal cyst surgery,” “pineal cyst treatment,” “pineal cyst symptoms,” and “pineal gland function.” Studies from the last 20 years were primarily considered. No controlled studies on pineal cysts are available; all of the publications are small case series. Studies with more than nine patients who underwent surgery were included for review. The overall level of evidence is low (case series and expert opinion).

Physiology of the pineal gland

The function of the pineal gland in man is incompletely understood. It is known to produce melatonin and to play an important role in the sleep-wake cycle by means of humoral signaling interactions with the suprachiasmatic nucleus (SCN) of the hypothalamus; the SCN, in turn, induces its effects via the sympathetic nervous system. (7, 8). Melatonin is released in darkness and induces sleep (8). Recent animal studies indicate a further major role in the immune response: melatonin stimulates the immune response by activating T lymphocytes (9). In animal experiments, melatonin also lessened age-related arteriosclerosis by maintaining telomere function, which is associated with chromosomal stability and cellular longevity (10). Aging is delayed in animal models by the neutralization of free radicals (11). There is also evidence that, in patients with sepsis, melatonin reduces the inflammatory response and oxidative stress, thereby increasing the probability of survival (12). Melatonin affects prostaglandin activity as well (12, 13, 14, 15). In sum, the pineal gland is not just a major component of the regulation of circadian rhythm; evidence indicates that it is also important for the immune system, healthy blood vessels, neuroprotection, and anti-aging (13, 14, 15).

Diagnostic evaluation

Pineal cysts are best diagnosed with MRI. T1-weighted images typically reveal a roughly spherical structure with a hypointense interior and a contrast-enhancing rim (Figures 1a and b). A fluid level may be seen in the cyst, presumably representing hemorrhage. High-resolution sagittal T2-weighted images, such as a CISS sequence (“constructive interference in steady state”), should be obtained as well to visualize the aqueduct, and flow-sensitive images—T2 or, better, IRTSE (inversion recovery turbo spin echo)—should be obtained to assess the flow of cerebrospinal fluid through it (Figures 1c and d). Axial T2-weighted images are used to measure the width of the third ventricle and the lateral ventricles (Figures 1e and f) (16). Eide et al. were able to detect elevated intravenous pressure in the internal cerebral veins with diffusion-weighted MRI sequences and calculation of ADC (“apparent diffusion coefficient”) maps. These results have not yet been confirmed by other authors (17), and this diagnostic method has therefore not yet been adopted for routine clinical use (18).

Clinical manifestations

Pineal cysts are usually asymptomatic and are usually discovered as incidental findings. Pineal cysts that compress the aqueduct and cause obstructive hydrocephalus can become clinically evident through manifestations of intracranial hypertension, such as headaches, nausea, and vomiting (19, 20). Parinaud syndrome. i.e., vertical gaze palsy (an inability to direct the gaze above the horizontal plane) combined with a deficit of convergence, may arise if the cyst compresses the quadrigeminal plate. Sudden coma and death due to brainstem herniation have been reported only rarely, unlike in cases of colloid cyst of the third ventricle (21, 22, 23); the authors have never encountered such an event.

Pineal cysts can become symptomatic even without ventricular enlargement, mainly with intermittent headache attacks, sometimes accompanied by nausea and vomiting (19). In such cases, the cyst is acting as a ball valve causing intermittent closure of aqueduct with an abrupt increase in intracranial pressure. A buildup of pressure beyond a certain point reopens the narrowed aqueduct and forces the cerebrospinal fluid through it, whereupon the intracranial pressure returns to normal and the symptoms resolve. and causing the symptoms to disappear completely. One of the authors’ patients was a preschool child who suddenly held her hands to her head while playing, cried out “ouch, ouch,” and then vomited profusely and continued playing normally. She was treated for a year and a half in multiple children’s hospitals for a variety of presumed diagnoses; no attention was paid to the pineal cyst, because the ventricles were narrow. She became asymptomatic immediately after the surgical removal of the cyst and has remained so in the ensuing 10 years (Figure 2).

The symptoms are not always so classic. Although most patients complain of holocephalic headaches, these are often hard to distinguish from other types of headache, such as migraine, as their features may overlap. The second most common symptom is visual disturbance (24). Most patients also have nonspecific symptoms such as dizziness, fatigue, exhaustion, lightheadedness, loss of energy, gait disturbance, impaired memory, or sleep disturbance (see Box). When the leading symptoms are nonspecific, the physician may have difficulty distinguishing organic from psychosomatic illness. One of our patients, a schoolgirl, complained of severe headaches, pressure in the head, and dizziness. An MRI scan revealed a pineal cyst without ventricular enlargement, which was considered an incidental finding (Figure 3). Treatment for presumed migraine did not lead to any improvement; cortisone brought only transient relief. Later, she developed an apparently inexplicable gait disorder and general exhaustion, so that she could no longer attend school. A follow-up MRI five months after the first MRI showed no change in the cyst, and she was referred for psychosomatic treatment. After the cyst was surgically removed, the symptoms rapidly subsided and she remains asymptomatic six years later. Surgery should only be considered if the criteria listed in Figure 4 are met.

Surgical treatment

Only a few small case series (11–62 patients) have been published to date (5, 6, 24, 25, 26, 27, 28, 29, 30). The surgical treatment can take one of two forms: endoscopic transventricular cyst fenestration, or craniotomy with open microsurgical cyst fenestration or resection. These operations are carried out under general anesthesia. We prefer microsurgical cyst resection through a paramedian supracerebellar infratentorial approach in the semi-sitting position (31). If the patient has a patent foramen ovale, we use a modified prone position to avoid arterial air embolism. Endoscopic fenestration has been called a “minimally invasive” procedure even though it requires a puncture through the frontal lobe into one of the lateral ventricles. Our endoscopically assisted microsurgical approach enables access to the pineal region through the subarachnoid space without injury to the brain and is therefore, in our opinion, the less invasive option, even if it is technically more demanding than endoscopy. We have also seen cyst recurrence after endoscopic fenestration. In a microsurgical procedure, we attempt to resect the cyst entirely while preserving the pineal gland, although preserving the gland is mostly not possible. The patient is monitored for one night postoperatively in the neurosurgical surveillance unit, and an MRI scan is obtained the next day.

Complications

Fortunately, complications are rare (Table). Transient neurological complications included Parinaud syndrome in 22 patients (8.6%), diplopia in 17 (6.6%), hemianopsia in 6 (2.4%), and facial nerve palsy in 1 patient. 6 patients had transient blurred vision (2.4%), and 1 had nystagmus. There were rare cases of wound infection (2%), meningitis (0.8%), and cerebrospinal fluid leak (2.7%). There was a single case (0.4%) of severe intraventricular hemorrhage, while minor bleeding at the surgical site and intraoperative events with no further clinical consequence, such as air embolism, were occasionally observed as well. Permanent complications include two cases of diplopia (0.8%), one myocardial infarction (0.4%), one postoperative death (0.4%), one case of postoperative epilepsy (0.4%), and one case of Parinaud syndrome (0.4%).

In a meta-analysis published in 2021, permanent complications were reported in 3.6% of patients; these included visual disturbances, incisional pain, paresthesiae, fatigue, neck pain, cerebellar infarction, and death from heart attack (32). We have operated on 104 pineal cysts in our clinic to date. In addition to the complications mentioned in the Table in the study by Fleck et al., we had one patient with permanent diplopia, which improved markedly but not completely. Two children had difficulty falling asleep for several weeks; this was treated with melatonin and later resolved without any further need for medication.

Results of surgical treatment

There is little evidence available on the treatment of pineal cysts. Our literature search only yielded small cohort studies with reporting of the results of surgical treatment in a total of 255 patients with pineal cysts (Table). The most common procedure was microsurgical cyst resection via the supracerebellar infratentorial (SCIT) approach, followed by the occipital transtentorial (OTT) approach. Endoscopic transventricular cyst fenestration accounted for only 7.8% of procedures. The cyst was totally resected in 228 patients (89.4%); subtotal resection and stereotactic biopsy/puncture were performed in 2% and 0.8% of patients, respectively. Hydrocephalus/ventricular enlargement was present in 21% of patients. The rate of complete symptom relief after surgery varied across studies from 46.8% to 96.4% of cases, while the rate of incomplete improvement varied from 3.6% to 47.6%.

In our most recently published series (6), we obtained complete relief of symptoms in 46.8% of patients, partial improvement in 41.9%, and persistent symptoms in 11.3% (6). We are now carrying out a quality-of-life analysis to obtain a further objective measure of success. Even though the surgical results in terms of cyst resection are very good and the complication rates are low, the key prerequisite for a good outcome is surgery for correct indications (proper patient selection). This is often a nontrivial task, particularly when the main symptoms are headache and other nonspecific complaints. Preoperative interdisciplinary assessment is, therefore, essential. Surgical cyst removal is a treatment of last resort when all potential conservative treatments, such as pharmacotherapy for headache, have failed, and only if the criteria listed in the Diagram are met. Our patients are informed in detail that there is no test that can predict whether cyst removal will improve their symptoms. It is frequently asserted that surgical treatment may be effective through a placebo effect, yet this seems an unlikely explanation for the persistent total or partial relief of symptoms, lasting many years, that most of our patients report.

Overview

Symptomatic pineal cysts without ventricular enlargement are often not recognized as the cause of the patient’s symptoms, as the symptoms are often nonspecific and hard to explain with current medical knowledge. Moreover, most pineal cysts are incidental findings of no clinical significance. We therefore recommend, before any patient is selected for surgery according to the criteria listed in the Diagram, that a comprehensive diagnostic evaluation should be carried out by specialists in all of the disciplines through which the symptoms might be explained: in particular, neurology, neuropsychology, psychiatry, ophthalmology, and (in some cases) gastroenterology. The mere size of the cyst is not a determinative factor, but rather its relation to the space between the splenium of the corpus callosum and the quadrigeminal plate. If this space is filled, there is often a certain narrowing of the entrance to the aqueduct; if accompanied by the corresponding clinical symptoms, this constitutes strong evidence for a symptomatic pineal cyst.

Acknowledgment

The authors thank Mr. Marc Matthes for creating the illustrations.

Conflict of interest statement
The authors state that they have no conflict of interest.

Manuscript submitted on 9 July 2024; revised version accepted on
17 March 2025.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
Prof. Dr. med. Henry W. S. Schroeder

References

1. Lum GB, Powell Williams J, Machen BC, Akkaraju V: Benign cystic pineal lesions by magnetic resonance imaging. J Comput Tomogr 1987; 11: 228–35

2. Mamourian AC, Towfighi J: Pineal cysts: MR imaging. Am J Neuroradiol 1986; 7: 1081–6

3. Hasegawa A, Ohtsubo K, Mori W: Pineal gland in old age; quantitative and qualitative morphological study of 168 human autopsy cases. Brain Res 1987; 409: 343–9

4. Cooper ER: The human pineal gland and pineal cysts. J Anat 1932; 67: 28

5. Davidson L: Endoscopic management of pineal cyst-associated aqueductal stenosis. Acta Neurochir 2020; 162: 2975–82

6. Fleck S, Damaty AE, Lange I, et al.: Pineal cysts without hydrocephalus: Microsurgical resection via an infratentorial-supracerebellar approach—surgical strategies, complications, and their avoidance. Neurosurg Review 2022; 45: 3327–37

7. Masters A, Pandi-Perumal SR, Seixas A, Girardin JL, McFarlane SI: Melatonin, the hormone of darkness: From sleep promotion to ebola treatment. Brain DisorTher 2014; 4: 1000151

8. Aulinas A: Physiology of the pineal gland and melatonin. Endotext 2020.

9. Szczepanik M: Melatonin and its influence on immune system. J Physiol Pharmacol 2007; 58: 115–24

10. Xie Y, Lou D, Zhang D: Melatonin alleviates age-associated endothelial injury of atherosclerosis via regulating telomere function. J Inflamm Res 2021; 14: 6799–812

11. Reiter RJ, Tan DX, Poeggeler B, Menendez-Pelaez A, Chen LD, Saarela S: Melatonin as a free radical scavenger: Implications for aging and age-related diseases. Ann N Y Acad Sci 1994; 719: 1–12

12. Hasan ZT, Atrakji MQYMAA, Mehuaiden AK: The effect of melatonin on thrombosis, sepsis and mortality rate in COVID-19 patients. Int J Infect Dis 2022; 114: 79–84

13. Cardinali DP, Ritta MN: The role of prostaglandins in neuroendocrine junctions: Studies in the pineal gland and the hypothalamus. Neuroendocrinol 1983; 36: 152–60

14. Kubiak CA, Grochmal J, Kung TA, Cederna PS, Midha R, Kemp SW: Stem-cell–based therapies to enhance peripheral nerve regeneration. Muscle Nerve 2020; 61: 449–59

15. Lingappa JR, Zigmond RE: Limited recovery of pineal function after regeneration of preganglionic sympathetic axons: Evidence for loss of ganglionic synaptic specificity. JNeurosci 2013; 33: 4867–74

16. Gokce E, Beyhan M: Evaluation of pineal cysts with magnetic resonance imaging. World JRadiol 2018; 10: 65–77

17. Greisert S, Fleck S, Rathmann E, Vollmer M, Schroeder HWS: The role of MRI biomarkers in evaluation of symptomatic pineal cysts—a retrospective analysis. Acta Neurochir 2024; 166: 323

18. Eide PK, Pripp AH, Ringstad GA: Magnetic resonance imaging biomarkers indicate a central venous hypertension syndrome in patients with symptomatic pineal cysts. JNeurol Sci 2016; 363: 207–16

19. El Damaty A, Fleck S, Matthes M, Baldauf J, Schroeder HWS: Pineal cyst without hydrocephalus: Clinical presentation and postoperative clinical course after infratentorial supracerebellar resection. World Neurosurg 2019; 129: e530–e7

20. Choque-Velasquez J, Resendiz-Nieves J, Colasanti R, Hernesniemi J: Management of obstructive hydrocephalus associated with pineal region cysts and tumors and its implication in long-term outcome. World Neurosurg 2021; 149: e913–e23

21. Atallah O, Kumar CR, Das S, Maurya VP, Agrawal A: Sudden death in patients with pineal cyst: Evidence from autopsy studies. JNeurosci Rural Pract 2023; 14: 593–8

22. Barranco R, Lo Pinto S, Cuccì M, et al.: Sudden and unexpected death during sexual activity, due to a glial cyst of the pineal gland. Am J Forensic Med Pathol 2018; 39: 157–60

23. Milroy CM, Smith CL: Sudden death due to a glial cyst of the pineal gland. J Clin Pathol 1996; 49: 267–9

24. Kalani MYS, Wilson DA, Koechlin NO, et al.: Pineal cyst resection in the absence of ventriculomegaly or parinaud‘s syndrome: Clinical outcomes and implications for patient selection. J Neurosurg 2015; 123: 352–6

25. Berhouma M, Ni H, Delabar V, et al.: Update on the management of pineal cysts: Case series and a review of the literature. Neurochirurgie 2015; 61: 201–7

26. Choque-Velasquez J, Resendiz-Nieves JC, Jahromi BR, et al.: The microsurgical management of benign pineal cysts: Helsinki experience in 60 cases. Sur Neurol Int 2019; 10: 10

27. Mena H, Armonda RA, Ribas JL, Ondra SL, Rushing EJ: Nonneoplastic pineal cysts: A clinicopathologic study of twenty-one cases. Ann Diagn Pathol 1997; 1: 11–8

28. Májovský M, Netuka D, Beneš V: Conservative and surgical treatment of patients with pineal cysts: Prospective case series of 110 patients. World Neurosurg 2017; 105: 199–205

29. Koziarski A, Podgórski A, Zieliński GM: Surgical treatment of pineal cysts in non-hydrocephalic and neurologically intact patients: Selection of surgical candidates and clinical outcome. Br J Neurosurg 2019; 33: 37–42

30. Eide PK, Lindstrøm EK, Pripp AH, Valnes LM, Ringstad G: Physiological alterations of pineal recess crowding in symptomatic non-hydrocephalic pineal cysts. Brain Commun 2023; 5: fcad078

31. Rhomberg T, Schroeder HW: Microsurgical resection of a pineal cyst via a paramedian supracerebellar infratentorial approach. World Neurosurg 2024; 185: 113

32. Masina R, Ansaripour A, Beneš V, et al.: Surgical treatment of symptomatic pineal cysts without hydrocephalus—meta-analysis of the published literature. Acta Neurochir 2022; 164: 61–77