septum

Cavum septum pellucidum

Cavum septum pellucidum

Cysts of the cavum septi pellucidi (CSP), cavum vergae (CV) and cavum velum interpositum (CVI) are anterior midline intracranial findings which are typically incidental.

They are persistent, primitive, or acquired, midline structures, fluid-filled, generally communicating located between the third ventricle and corpus callosum.

It is sometimes called the fifth ventricle.

Nonneoplastic cysts of the septum pellucidum are of two general forms. The first, the asymptomatic cavum septum pellucidum, is not a malformation or a true cyst and has been recognized since the time of Sylvius 1) 2)

Embriologically the leaves of the septum pellucidum enclose a cavity, the cavum septum pellucidum. This space first appears during the 3rd month of intrauterine growth by secondary cleavage of the banks of fusion of the cerebral hemispheres 3).

Epidemiology

A CSP is present in the normal fetus, but over 85% of them fuse by 3-6 months of age meaning that a CSP persists in ~15% of the adult population.

Gross anatomy

The CSP commonly occurs, and is often confused with the cavum vergae, which is situated posterior to the anterior columns of the fornix. During development, these spaces obliterate postero-anteriorly – the cavum vergae followed by the cavum septum pellucidum – and it is not uncommon that both occur together.

Boundaries

anterior: genu of the corpus callosum

superior: body of the corpus callosum

posterior: anterior limb and pillars of the fornix

inferior: anterior commissure and the rostrum of the corpus callosum

lateral: leaflets of the septum pellucidum

There have been various reports of their association with many behavioral and psychiatric disorders. Infrequently, they have been associated with an obstructive hydrocephalus-like picture. Although the structure and management of CSP has long been known, it has been an enigma as far as functional significance and management indications are concerned.

An absent cavum septum pellucidum in antenatal imaging is a concerning feature and is associated with significant CNS anomalies.

It is frequent among athletes with a history of repeated traumatic brain injury (TBI), such as boxers. Few studies of CSP in athletes, however, have assessed detailed features of the septum pellucidum in a case-control fashion. This is important because prevalence of CSP in the general population varies widely (2% to 85%) between studies. Further, rates of CSP among American pro-football players have not been described previously.

A retrospective study assessed retired American pro-football players presenting with cognitive/behavioral symptoms in whom structural MRI was available with slice thickness ≤2 mm (n=17). Each player was matched to a memory clinic control patient with no history of TBI. Scans were interpreted by raters blinded to clinical information and TBI/football history, who measured CSP grade (0-absent, 1-equivocal, 2-mild, 3-moderate, 4-severe) and length according to a standard protocol. Sixteen of 17 (94%) players had a CSP graded ≥2 compared with 3 of 17 (18%) controls. CSP was significantly higher grade (p<0.001) and longer in players than controls (mean length±standard deviation: 10.6 mm±5.4 vs. 1.1 mm±1.3, p<0.001). Among patients presenting to a memory clinic, long high-grade CSP was more frequent in retired pro-football players compared with patients without a history of TBI 4).

Clinical features

Only rarely do we encounter symptomatic cysts of this type. Only a quite small number of these cysts series have been published 5).

Differential diagnosis

Cavum vergae

Cavum velum interpositum.

Treatment

Symptomatic patients usually present aspecific symptoms. For this reason, the management of these patients is still debated.

TCD in the absence of other objective confirmatory studies, can aid in the diagnosis and provide information about the success of fenestration of the cavum septum 6).

Results suggest that in most of the patients with aspecific symptoms, clinical observation and eventually ICP monitoring are adequate to identify patients for surgery 7).

(1) Endoscopic fenestration of symptomatic CSP cysts is a safe treatment option. (2) Neurocognitive assessment is essential in the evaluation and outcome assessment of CSP 8).

Case series

In a retrospective study of 10 patients treated at 2 clinics between 2002-2018. 9 patients underwent surgery and 1 is under long-term monitoring. Apart from demographic data, the study analyzed symptoms, cyst size and progression over time, ventricle size, complications, and treatment modality.

CSP with CV was found in 8 cases with 1 case each of CSP and CVI. The study comprised 6 men and 4 women, including 4 children. The mean follow-up time was 43.4 months. The average cyst size was 20.4 mm in CSP and 19.8 mm in CV; the CVI was 33 mm. Headache was most commonly reported (70%) followed by behavioral disturbance (30%). Disturbance in memory, psychomotor development, school performance, visual acuity, and vomiting was variously noted in 20%. The prevailing symptom was headache in adults and behavioral and autonomic disturbance in children. Postoperatively, cysts had reduced by an average of 44.3% while the ventricles remained unchanged. Symptoms resolved in all cases with residual problems in patients presenting with memory loss. No complications were noted.

Endoscopic fenestration is the method of choice in the treatment of symptomatic midline cysts. We recommend that any further research focuses on precisely establishing their clinical presentation, particularly neuropsychological symptoms 9).

A retrospective analysis of 3 patients who underwent endoscopic fenestration for CSP with obstructive hydrocephalus between 2012 and 2014 was done in the Division of Paediatric Neurosurgery, Department of Neurosurgery, Amrita Institute of Medical Sciences and Research Centre, Kochi, India.

Data were analyzed for symptomatic clinical improvement in particular behavior.

Pre- and postoperative brain MRI showed a significant decrease in the size of the cyst as well as the ventricles. There were no recurrences during follow-up. All of the patients improved.

(1) Endoscopic fenestration of symptomatic CSP cysts is a safe treatment option. (2) Neurocognitive assessment is essential in the evaluation and outcome assessment of CSP 10).

Case reports

1997

The authors describe the morphological, histological and histo-immunological characteristics of an additional case of septum pellucidum-cavum Vergae cyst in a forty-year-old man who died the day following a ventriculo-peritoneal shunt 11).

1996

A giant CSP and CV cyst in an 18-month-old boy, extending to the posterior cranial fossa and causing hydrocephalus. The literature is reviewed, and the MRI and CT findings of the case are reported 12).

References

1)

Dandy WE: Congenital cerebral cysts of the cavum septi pellucidi (fifth ventricle) and cavum vergae (sixth ventricle). Diagnosis and treatment. Arch Neurol Psychiatry 25: 44–66,1931
2)

Wilson CB, Howieson J: Cysts of the septum pellucidum. Review and report of one case. Neurochirurgia 13: 93–99, 1970
3)

Rakic P, Yakovlev PI. Development of the corpus callosum and cavum septi in man. J Comp Neurol. 1968 Jan;132(1):45-72. PubMed PMID: 5293999.
4)

Gardner RC, Hess CP, Brus-Ramer M, Possin KL, Cohn-Sheehy BI, Kramer JH, Berger MS, Yaffe K, Miller B, Rabinovici GD. Cavum Septum Pellucidum in Retired American Pro-Football Players. J Neurotrauma. 2016 Jan 1;33(1):157-61. doi: 10.1089/neu.2014.3805. Epub 2015 Jul 17. PubMed PMID: 25970145.
5)

Krejčí T, Vacek P, Krejčí O, Chlachula M, Szathmaryová S, Lipina R. Symptomatic cysts of the cavum septi pellucidi, cavum vergae and cavum veli interpositi: A retrospective duocentric study of 10 patients. Clin Neurol Neurosurg. 2019 Aug 19;185:105494. doi: 10.1016/j.clineuro.2019.105494. [Epub ahead of print] PubMed PMID: 31472394.
6)

Bell RS, Vo AH, Dirks MS, Mossop C, Gilhooly JE, Cooper PB, Razumovsky AY, Armonda RA. Transcranial Doppler ultrasonography identifies symptomatic cavum septum pellucidum cyst: case report. J Vasc Interv Neurol. 2010 Jan;3(1):13-6. PubMed PMID: 22518255; PubMed Central PMCID: PMC3317289.
7)

Tamburrini G, Mattogno PP, Narenthiran G, Caldarelli M, Di Rocco C. Cavum septi pellucidi cysts: a survey about clinical indications and surgical management strategies. Br J Neurosurg. 2016 Sep 13:1-4. [Epub ahead of print] PubMed PMID: 27619551.
8)

Udayakumaran S, Onyia CU, Cherkil S. An Analysis of Outcome of Endoscopic Fenestration of Cavum Septum Pellucidum Cyst – More Grey than Black and White? Pediatr Neurosurg. 2017 Jun 10. doi: 10.1159/000474943. [Epub ahead of print] PubMed PMID: 28618406.
9)

Krejčí T, Vacek P, Krejčí O, Chlachula M, Szathmaryová S, Lipina R. Symptomatic cysts of the cavum septi pellucidi, cavum vergae and cavum veli interpositi: A retrospective duocentric study of 10 patients. Clin Neurol Neurosurg. 2019 Aug 19;185:105494. doi: 10.1016/j.clineuro.2019.105494. [Epub ahead of print] PubMed PMID: 31472394.
10)

Udayakumaran S, Onyia CU, Cherkil S. An Analysis of Outcome of Endoscopic Fenestration of Cavum Septum Pellucidum Cyst – More Grey than Black and White? Pediatr Neurosurg. 2017 Jun 10. doi: 10.1159/000474943. [Epub ahead of print] PubMed PMID: 28618406.
11)

Ronsin E, Grosskopf D, Perre J. Morphology and immunohistochemistry of a symptomatic septum pellucidum cavum Vergae cyst in man. Acta Neurochir (Wien). 1997;139(4):366-71; discussion 372. PubMed PMID: 9202780.
12)

Bayar MA, Gökçek C, Gökçek A, Edebali N, Buharali Z. Giant cyst of the cavum septi pellucidi and cavum Vergae with posterior cranial fossa extension: case report. Neuroradiology. 1996 May;38 Suppl 1:S187-9. PubMed PMID: 8811712.

Septum Verum

Septum Verum

Septum Verum (true septum) is a region in the lower medial part of the telencephalon that separates the two cerebral hemispheres.

The human septum consists of two parts: The septum pellucidum (translucent septum), a thin membrane consisting of white matter and glial cells that separate the lateral ventricles, and the lower, precommisural septum verum, which consists of nuclei and grey matter.

The term is sometimes used synonymously with Area Septalis, to refer to the precommisural part of the lower base of the telencephalon. The Septum verum contains the septal nuclei, which are usually considered part of the limbic system.

The septum pellucidum and the subjacent septum verum form the medial wall of the frontal horn of the lateral ventricle. Both structures contain nerve fibers that were organized in 3 groups: 1) the precommissural fibers of the fornix; 2) the inferior fascicle; and 3) the superior fascicle of the septum pellucidum. The area directly rostral to the postcommissural column of the fornix consisted of macroscopically identifiable gray mattercorresponding to the septal nuclei. The histological examinations validated the findings of Barany et al. fiber dissections.

The nerve elements of the septum pellucidum as well as the subjacent septum verum were identified with fiber dissection and verified with histology for the first time. The septal nuclei located just anterior to the fornix and the precommissural fibers of the fornix should be preserved during endoscopic septum pellucidotomy. Considering the venous anatomy as well as the neural architecture of the septum pellucidum, the fenestration should ideally be placed above the superior edge of the fornix and preferably dorsal to the interventricular foramen 1).

1)

Barany L, Meszaros C, Ganslandt O, Buchfelder M, Kurucz P. Neural and vascular architecture of the septum pellucidum: an anatomical study and considerations for safe endoscopic septum pellucidotomy. J Neurosurg. 2019 Aug 2:1-10. doi: 10.3171/2019.5.JNS19754. [Epub ahead of print] PubMed PMID: 31374555.

DNET-like neoplasms of the septum pellucidum

DNET-like neoplasms of the septum pellucidum

Rare midline neoplasms with similar histological features to those found in DNETs have been described near the septum pellucidum and termed ‘DNET-like neoplasms of the septum pellucidum‘. Due to their rarity, these tumors have been described in just a few reports and their genetic alterations sought only in small series

Chiang et al., collected 20 of these tumors for a comprehensive study of their clinical, radiological and pathological features. RNA sequencing or targeted DNA sequencing was undertaken on 18 tumors, and genome-wide DNA methylation profiling was possible with 11 tumors. Published cases (n=22) were also reviewed for comparative purposes.

The commonest presenting symptoms and signs were related to raised intracranial pressure; 40% of cases required cerebrospinal fluid diversion. Epilepsy was seen in approximately one third of cases. All patients had an indolent disease course, despite metastasis within the neuraxis in a few cases. Radiologically, the septum verum / septal nuclei were involved in all cases and are the proposed site of origin for septal DNET (sDNET). sDNET showed a high frequency (~80%) of PDGFRA mutations, and alterations in FGFR1 and NF1 were also identified. In a genomic DNA methylation analysis alongside other neural tumors, sDNETs formed a separate molecular group.

Genetic alterations that are different from those of cerebral DNETs and a distinct methylome profile support the proposal that sDNET is a distinct disease entity. 1).

Gessi et al., described the neuroradiologic, histopathologic, and molecular features of 7 cases (4 female and 3 male; patient age range, 3 to 34 y; mean age, 16.7 y). The tumors, all localized near the supratentorial midline structures in proximity to the foramen of Monro and septum pellucidum, appeared in magnetic resonance imaging as well-delimited cystic lesions with cerebrospinal fluid-like signal on T1-weighted and T2-weighted images, some of them with typical fluid-attenuated inversion recovery ring sign. Histologically, they shared features with classic cortical DNTs but did not display aspects of multinodularity. From a molecular point of view the cases investigated did not show KIAA1549-BRAF fusions or FGFR1 mutations, alterations otherwise observed in pilocytic astrocytomas, or MYB and MYBL1 alterations that have been identified in a large group of pediatric low-grade gliomas. Moreover, BRAF mutations, which so far represent the most common molecular alteration found in cortical DNTs, were absent in this group of rare periventricular tumors 2).

Baisden et al., reported a series of 10 low-grade neoplasms arising in the midline anteriorly in the region of the septum pellucidum with many of the histologic features of dysembryoplastic neuroepithelial tumor (DNT). The patients (five female, five male) ranged in age from 6 to 35 years (mean age, 21.5 years). The most common presenting symptoms were headache, nausea and vomiting, and visual disturbances. Radiographically, the tumors extended into the lateral ventricles from the septal region and obstructed the foramen of Monro. Varying degrees of hydrocephalus were present. The lesions were lobular, well-delineated, hypointense to brain on T1-weighted magnetic resonance imaging, and hyperintense on T2-weighted images. They were uniformly nonenhancing or showed only minimal peripheral enhancement. The tumors, in aggregate, had the histologic features of DNT. These included a mucin-rich background, oligodendrocyte-like cells, “floating neurons,” and a “specific glioneuronal element.” Seven patients underwent gross total resection and two underwent subtotal resection. No patients received adjuvant chemotherapy or radiotherapy. On follow-up (n = 6; median, 14 months), all tumors had either not recurred or were radiologically stable. On the basis of both neuroimaging and histopathology, DNT-like lesions should be considered in the differential diagnosis of midline intraventricular tumors in children and young adults. Distinction from more aggressive neoplasms is essential because these tumors appear to behave in a benign fashion 3).

References

1)

Chiang JCH, Harreld JH, Tanaka R, Li X, Wen J, Zhang C, Boué DR, Rauch TM, Boyd JT, Chen J, Corbo JC, Bouldin TW, Elton SW, Liu LL, Schofield D, Lee SC, Bouffard JP, Georgescu MM, Dossani RH, Aguiar MA, Sances RA, Saad AG, Boop FA, Qaddoumi I, Ellison DW. Septal Dysembryoplastic Neuroepithelial Tumor: A Comprehensive Clinical, Imaging, Histopathologic and Molecular Analysis. Neuro Oncol. 2019 Feb 6. doi: 10.1093/neuonc/noz037. [Epub ahead of print] PubMed PMID: 30726976.
2)

Gessi M, Hattingen E, Dörner E, Goschzik T, Dreschmann V, Waha A, Pietsch T. Dysembryoplastic Neuroepithelial Tumor of the Septum Pellucidum and the Supratentorial Midline: Histopathologic, Neuroradiologic, and Molecular Features of 7 Cases. Am J Surg Pathol. 2016 Jun;40(6):806-11. doi: 10.1097/PAS.0000000000000600. PubMed PMID: 26796505.
3)

Baisden BL, Brat DJ, Melhem ER, Rosenblum MK, King AP, Burger PC. Dysembryoplastic neuroepithelial tumor-like neoplasm of the septum pellucidum: a lesion often misdiagnosed as glioma: report of 10 cases. Am J Surg Pathol. 2001 Apr;25(4):494-9. PubMed PMID: 11257624.