Surgical treatment of symptomatic pineal cysts without hydrocephalus-meta-analysis of the published literature

Abstract

Background: To examine published data and assess evidence relating to safety and efficacy of surgical management of symptomatic pineal cysts without hydrocephalus (nhSPC), we performed a systematic review of the literature and meta-analysis.

Methods: Following the PRISMA guidelines, we searched Pubmed and SCOPUS for all reports with the query 'Pineal Cyst' AND 'Surgery' as of March 2021, without constraints on study design, publication year or status (PROSPERO_CRD:42,021,242,517). Assessment of 1537 hits identified 26 reports that met inclusion and exclusion criteria.

Results: All 26 input studies were either case reports or single-centre retrospective cohorts. The majority of outcome data were derived from routine physician-recorded notes. A total of 294 patients with surgically managed nhSPC were identified. Demographics: Mean age was 29 (range: 4-63) with 77% females. Mean cyst size was 15 mm (5-35). Supracerebellar-infratentorial approach was adopted in 90% of cases, occipital-transtentorial in 9%, and was not reported in 1%. Most patients were managed by cyst resection (96%), and the remainder by fenestration. Mean post-operative follow-up was 35 months (0-228).

Presentation: Headache was the commonest symptom (87%), followed by visual (54%), nausea/vomit (34%) and vertigo/dizziness (31%). Other symptoms included focal neurology (25%), sleep disturbance (17%), cognitive impairment (16%), loss of consciousness (11%), gait disturbance (11%), fatigue (10%), 'psychiatric' (2%) and seizures (1%). Mean number of symptoms reported at presentation was 3 (0-9).

Outcomes: Improvement rate was 93% (to minimise reporting bias only consecutive cases from cohort studies were considered, N = 280) and was independent of presentation. Predictors of better outcomes were large cyst size (OR = 5.76; 95% CI: 1.74-19.02) and resection over fenestration (OR = 12.64; 3.07-52.01). Age predicted worse outcomes (OR = 0.95; 0.91-0.99). Overall complication rate was 17% and this was independent of any patient characteristics. Complications with long-term consequences occurred in 10 cases (3.6%): visual disturbance (3), chronic incisional pain (2), sensory disturbance (1), fatigue (1), cervicalgia (1), cerebellar stroke (1) and mortality due to myocardial infarction (1).

Conclusions: Although the results support the role of surgery in the management of nhSPCs, they have to be interpreted with a great deal of caution as the current evidence is limited, consisting only of case reports and retrospective surgical series. Inherent to such studies are inhomogeneity and incompleteness of data, selection bias and bias related to assessment of outcome carried out by the treating surgeon in the majority of cases. Prospective studies with patient-reported and objective outcome assessment are needed to provide higher level of evidence.

Keywords: Headache; Hydrocephalus; Non-hydrocephalic symptomatic pineal cyst; Pineal; Pineal cyst; Symptomatic pineal cyst.

Fig. 1

Prisma flow diagram summarising the systematic review algorithm

Fig. 2

Flow-chart summarising the main decisions taken in the management of patients with nhSPC. This is broadly representative of the contributing series, but individual surgeons have developed their own specific management algorithms—see individual series for details [4, 8, 13, 14, 23, 24, 28, 46]

Fig. 3

Summary of cohort characteristics. A Age at the time of operation. B Cyst size at the time of operation. C Duration of post-operative follow-up. D Symptom progression pre-operatively. E Surgical approach. F Gender at the time of operation. Forest plots report mean (diamonds) ± max/min (error bars). The absence of a diamond or error bars indicate that the information was not available for that study. In all graphs, the final entry represents a summary of all the available data. Yeung2021/Kalani2015 have been grouped together as Kalani’s case series [23] is fully contained within Yeung’s case series [46]. The figure is available in colour online. SCIT, SupraCerebellar Infra-Tentorial approach; OTT, occipital trans-tentorial approach; NR, not reported

Fig. 4

Summary of symptoms at presentation. A Summary of patient-specific demographic (top), presentation (middle) and outcome (bottom) features. Each patient is shown as a vertical segment along the x axis. Different features are labelled according to the legend. B Proportion of patients by presenting symptom. C Proportion of patients by number of symptoms at presentation. Of note, 5 patients reportedly had no symptoms at presentation. These are briefly described below. D Distribution of associated symptoms in patients presenting with only 1, 2 or 3 symptoms (from left to right, respectively). The distribution of patients presenting with 4 and 5 + symptoms is shown in Supplementary Fig. 5. E Co-occurrence of clinical characteristics at presentation. Data represented as correlation matrix, where the correlation coefficient (Pearson) between characteristics X and Y is shown on a colour scale ranging from blue (positive correlation) to red (negative correlation). White corresponds to a correlation coefficient of 0. Statistically significant correlations are marked by one or more ‘*’, according to a conventional notation of statistical significance (* < 0.05; ** < 0.01, *** < 0.005). *5 patients had no reported symptoms at presentation: (1) No symptom reported, surgical indication: ‘progressing cyst size’. (2) 4 years old asymptomatic, surgical indication: ‘cyst with partial solid enhancement’; (3) 54 years old asymptomatic, surgical indication: ‘solid posterior part of the cyst’; (4) 29 years old, no symptoms reported, surgical indication: ‘large cyst unspecified symptoms’; (5) 16 years old, presentation data not available, indication for surgery: not available. The figure is available in colour online. Size_mm_12: cyst size > 12 mm; Visual_sx, visual symptoms; Neurology_NOS, neurology not otherwise specified; Resection_extent, cyst resection, as opposed to cyst fenestration; Sleep, sleep disturbances; Pysch_depression, psychiatric symptoms of depression; Other_sx, any of the following symptoms: ‘Cognitive’, ‘Transient_LoC’, ‘Sleep’, ‘Pysch_depression’, ‘Seizure’, ‘Neurology_NOS’, ‘Fatigue’; LoC, loss of consciousness; HA, headache; V, visual symptoms; NV, nausea and vomiting; DV, dizziness and vertigo; P, psychiatric symptoms; F, fatigue; G, gait abnormalities; N, neurology not otherwise specified; Seiz, seizures; S, sleep disturbances

Fig. 5

Summary of the efficacy profile of surgical management for nhSPC. A Improvement rate for each study and overall cohort. Data shown as mean (diamonds) ± 95% CI (error bars). Eide2017_R refers to the patients of Eide’s cohort that were managed by resection, while Eide2017_F refers to those managed by fenestration. Analogously, Fedorko2018_R refers to the patients in Fedorko’s series that were managed by resection, and Fedorko2018_F to those managed by fenestration. B Proportion of patients presenting with each symptom pre-operatively (red bars), and proportion of patients who did not improve post-operatively (blue bar). C Association between presenting characteristics and post-operative improvement, quantified by univariate logistic regression. Data shown as OR (diamonds) ± 95% CI. Statistically significant associations are shown in red. OR > 1 indicates that the characteristic is associated with better outcomes, while OR < 1 indicates an association with worse outcomes. Raw data is available as scatterplots in Supplementary Fig. 6. In all cases, improvement is defined as reduced symptom-related burden, where both pre-existing and any newly acquired symptoms following surgery are considered. Only data from consecutive case series has been included in the outcome analysis. The figure is available in colour online. Size_mm_12, cyst size > 12 mm; Visual_sx, visual symptoms; Neurology_NOS, neurology not otherwise specified; Resection_extent, cyst resection, as opposed to cyst fenestration; Sleep_fatigue: sleep disturbances or fatigue; Pysch_depression, psychiatric symptoms of depression; Other_sx, any of the following symptoms: ‘Cognitive’, ‘Transient_LoC’, ‘Sleep’, ‘Pysch_depression’, ‘Seizure’, ‘Neurology_NOS’, ‘Fatigue’; LoC, loss of consciousness

Fig. 6

Summary of the safety profile of surgical management for nhSPC. A Complication rate for each study and overall cohort. As for ‘overall improvement’, complication rates were estimated from the subset of the cohort extracted from consecutive case series only (N = 277) to minimise the effect of reporting bias (see Methods). Data shown as mean (diamonds) ± 95% CI (error bars). Eide2017_R refers to the patients of Eide’s cohort that were managed by resection, while Eide2017_F refers to those managed by fenestration. Analogously, Fedorko2018_R refers to the patients in Fedorko’s series that were managed by resection, and Fedorko2018_F to those managed by fenestration. B Proportion of patients presenting with each complication. Here we included all cases (N = 294) to describe all reported complication that occurred during resection of nhSPCs. Complications that resolved by the last follow-up appointment are in blue, while those that persisted are in red. ‘Haematoma’ refers to an episode of bleeding into the 3rd ventricle that occurred in the early post-operative period in a 23-year-old female. EVD was placed for 7 days until the haematoma spontaneously resolved, and the patient had no neurological sequelae [28]. It is unclear whether the case of ‘Cerebellar stroke’ was merely a radiological finding or whether this was associated with clinical manifestations [15]. MI/mortality—mortality due to myocardial infarction [30]. ‘Chronic incisional pain’ refers to 3 cases reported by Yeung in which pain lasted beyond the peri-operative period. Of these, 2 patients underwent neuroma excision that resolved the pain, and 1 resolved spontaneously [29]. C Association between presenting characteristics and post-operative complications, quantified by univariate logistic regression. Data shown as OR (diamonds) ± 95% CI. Statistically significant associations are shown in red. OR > 1 indicates that the characteristic is associated with a higher-than-baseline risk of complications, while OR < 1 indicates an association with a lower risk of complications. Raw data is available as scatterplots in Supplementary Fig. 7. The figure is available in colour online. Size_mm_12, cyst size > 12 mm; Visual_sx, visual symptoms; Neurology_NOS, neurology not otherwise specified; Resection_extent, cyst resection, as opposed to cyst fenestration; Sleep_fatigue, sleep disturbances or fatigue; Pysch_depression, psychiatric symptoms of depression; Other_sx, any of the following symptoms: ‘Cognitive’, ‘Transient_LoC’, ‘Sleep’, ‘Pysch_depression’, ‘Seizure’, ‘Neurology_NOS’, ‘Fatigue’; LoC, loss of consciousness

Fig. 7

Summary of the effects of age on safety and efficacy of nhSPC surgery. A Age distribution across the cohort. B Proportion of improved patients for each age group. C Proportion of cases with complications in each age group. The figure is available in colour online