Miyazaki syndrome

Miyazaki syndrome

Miyazaki syndrome is a cervical myelopathy or cervical radiculopathy caused by cervical epidural venous congestion, due to shunt overdrainage. The complex pathophysiology includes CSF pressure-changes consistent with the Monro-Kellie hypothesis and a non-functional Starling resistor, leading to spinal epidural venous plexus enlargement and dilation. This venous congestion may be significant enough to exert compression on the spinal cord or nerve roots. The typical clinical and imaging findings together with a history of ventricular CSF shunting may establish the diagnosis, proven by a successful treatment. The aim of treatment is the abrogation of CSF over-drainage. The eligible interventions may be the followings: the increase of the opening-pressure of the valve system by the insertion of a new programmable valve if necessary, closing or removing the shunt.


In 1997 Miyazaki et al. described a case of intracranial hypotension syndrome due to overdrainage of cerebrospinal fluid presented with hearing loss afterventriculoperitoneal shunting procedure. A 69-year-old man suffering from subarachnoid hemorrhage presented with an angiogram showing two aneurysms, one of the right internal carotid artery and one of the middle cerebral artery. Neck clipping was performed. One month later, he developed normal pressure hydrocephalus (NPH), which was treated by ventriculoperitoneal shunting procedure using low pressure Pudenz valve system. Trias of NPH were improved by insertion of shunt system. However, he complained of hearing loss which was worsened by upright position and improved by lying down. Such kinds of phenomenon were demonstrated by audiogram showing that the transitory decrease of hearing and electrocochleography showing the elongation of N1 latency at upright position. These data suggested that his hearing loss was caused by inner ear or auditory nerve lesion. After the shunt system was replaced into the antisiphon device, his hearing disturbance improved. Axial computed tomography of bone window at the level of orbitomeatal line demonstrated widely perilymphatic duct on both sides. This finding suggested that the fluctuation of intracranial pressure was easily transmitted into the cochlear through the widened perilymphatic duct, resulting in hearing disturbance 1).


Várallyay et al. want to call attention to this rare iatrogenic condition with potentially severe consequences.

They performed a systematic literature-review and presented ther five cases.

Once recognized in time, Miyazaki syndrome can be well taken care of.

Patients with chronic ventricular shunt need monitoring for CSF over-drainage to recognise potential complications such as cervical myelopathy or radiculopathy 2).


In 2018 a 33-year-old patient had undergone placement of a ventriculoperitoneal shunt with a pressure-adjustable valve for communicating hydrocephalus years before presenting to our department with the complaints of constant headache and unsteady gait. On the basis of the clinical picture and her history, plain and contrast-enhanced cranial and whole spine magnetic resonance imaging and magnetic resonance angiography examinations were performed, with the scans revealing signs indicative of cerebrospinal fluid hypotension typical of Miyazaki syndrome 3).


In 2015 Caruso et al. reported one case 4).

References

1)

Miyazaki Y, Tomii M, Sawauchi S, Ikeuchi S, Yuki K, Abe T. [A case of hearing loss caused by overdrainage of cerebrospinal fluid after ventriculo-peritoneal shunting procedure]. No Shinkei Geka. 1997 Apr;25(4):367-71. Japanese. PubMed PMID: 9125722.
2)

Várallyay P, Nagy Z, Szűcs A, Czigléczki G, Markia B, Nagy G, Osztie É, Vajda J, Vitanovics D. Miyazaki syndrome: Cervical myelo/radiculopathy caused by overshunting. A systematic review. Clin Neurol Neurosurg. 2019 Sep 24;186:105531. doi: 10.1016/j.clineuro.2019.105531. [Epub ahead of print] PubMed PMID: 31622897.
3)

Kovács A, Németh T, Csomor A, Novák T, Kövér F, Vörös E. Miyazaki Syndrome due to Ventriculoperitoneal Shunt Treatment. World Neurosurg. 2018 Aug;116:29-34. doi: 10.1016/j.wneu.2018.05.032. Epub 2018 May 31. PubMed PMID: 29775766.
4)

Caruso R, Wierzbicki V, Marrocco L, Pesce A, Piccione E. A Poorly Known Cerebrospinal Fluid Shunt Complication: Miyazaki Syndrome. World Neurosurg. 2015 Sep;84(3):834-8. doi: 10.1016/j.wneu.2015.04.030. Epub 2015 Apr 23. PubMed PMID: 25913430.

Medulloblastoma outcome

Medulloblastoma outcome

All medulloblastomas are WHO grade IV.

Poor prognosticators

● younger age (especially if<3 yrs)

● disseminated (metastatic) disease

● inability to perform gross-total removal(especially if residual > 1.5cm2 in patient with localized disease)

● histological differentiation along glial, ependymal, or neuronal lines

Medulloblastoma is the most common malignant brain tumor that occurs during childhood. Multimodality treatment regimens have substantially improved survival in this disease; however, the tumour is incurable in about a third of patients with medulloblastoma, and current treatment has a detrimental effect on long-term survivors. Drugs that target cell-signaling pathways provide an alternative to conventional cytotoxic approaches to the treatment of cancer. Several pathways have been implicated in medulloblastoma formation, and knowledge of these is now being used to develop new ways of treating children with medulloblastoma 1).

Weil et al. 2) and Prados et al. 3) found female gender to be a significant favorable prognostic factor in medulloblastoma. Sex did not reveal any bearing on the outcome in the series of Kumar et al. 4).

Age, hemispheric location of the tumor, the extent of resection, and adjuvant therapy status were the important clinical prognostic factors for survival in the series of Narayan et al. 5).

Complete resection should be performed if possible as several studies have correlated outcome with the extent of resection and amount of residual tumor 6).

Gene expression profiling is highly predictive of response to therapy, predicting outcome with much greater accuracy than current staging criteria 7).

Long-term survivors of MB are at significant risk for permanent endocrinologic, cognitive, and psychological sequelae of treatments. Infants and very young children with MB remain a di cult therapeutic challenge because they have the most virulent form of the disease and are at the highest risk for treatment-related sequelae. Most common site of recurrence is p-fossa. Collins’law has also been used to define the period of the risk of recurrence (PRR) but exceptions to the law have been reported 8).


Ninety-seven samples of medulloblastoma were collected. Tumor content in samples was judged by frozen section review. Tumor ERBB2 protein and MYCC, MYCN, and TRKC mRNA levels were measured blind to clinical details using Western blotting and real-time polymerase chain reaction, respectively. Histopathologic and clinical review of each case was also performed. All data were subjected to independent statistical analysis.

Sample acquisition and analysis times ranged from 3 to 6 days. Eighty-six samples contained sufficient tumor for analysis, including 38 classic, 30 nodular desmoplastic, and 18 large-cell anaplastic (LCA) medulloblastomas. Protein and mRNA were extracted from 81 and 49 tumors, respectively. ERBB2 was detected in 40% (n=32 of 81) of tumors, most frequently in LCA disease (P=.005), and was independently associated with a poor prognosis (P=.031). A combination of clinical characteristics and ERBB2 expression provided a highly accurate means of discriminating disease risk. One hundred percent (n=26) of children with clinical average-risk, ERBB2-negative disease were alive at 5 years, with a median follow-up of 5.6 years, compared with only 54% for children with average-risk, ERBB2-positive tumors (n=13; P=.0001). TRKC, MYCC, and MYCN expression and histopathologic subtype were not associated with prognosis in this study.

Central and rapid molecular analysis of frozen medulloblastomas collected from multiple institutions is feasible. ERBB2 expression and clinical risk factors together constitute a highly accurate disease risk stratification tool 9).


The purpose of a study of was to determine the relative contributions of biological and clinical predictors of survival in patients with medulloblastoma (MB).

Clinical presentation and survival information were obtained for 119 patients who had undergone surgery for MB at the Hospital for Sick Children (Toronto, Ontario, Canada) between 1985 and 2001. A tissue microarray was constructed from the tumor samples. The arrays were assayed for immunohistochemical expression of MYC, p53, platelet-derived growth factor receptor-alpha, ErbB2, MIB-1, and TrkC and for apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling). Both univariable and multivariable analyses were conducted to characterize the association between survival and both clinical and biological markers. For the strongest predictors of survival, a weighted predictive score was calculated based on their hazard ratios (HRs). The sum of these scores was then used to give an overall prediction of survival using a nomogram.

The four strongest predictors of survival in the final multivariable model were the presence of metastatic disease at presentation (HR, 2.02; P=0.01) and p53 (HR, 2.29; P=0.02), TrkC (HR, 0.65; P=0.14), and ErbB2 (HR, 1.51; P=0.21) immunopositivity. A linear prognostic index was derived, with coefficients equal to the logarithm of these HRs. The 5-year survival rate for patients at the 10th, 50th, and 90th percentiles of the score distribution was 80.0%, 71.0%, and 35.7%, respectively, with radiation therapy and 70.5%, 58.5%, and 20.0%, respectively, without radiation therapy.

In this study, we demonstrate an approach to combining both clinical and biological markers to quantify risk in MB patients. This provides further prognostic information than can be obtained when either clinical factors or biological markers are studied separately and establishes a framework for comparing prognostic markers in future clinical studies 10).


Two rare subtypes at extreme ends of the histologic spectrum, i.e., medulloblastomas with extensive nodularity and large cell/anaplastic medulloblastomas, are associated with better and worse clinical outcomes, respectively. However, there is little data about correlations between histologic features and clinical outcomes for most patients with medulloblastomas that fall between these histologic extremes of nodularity and anaplasia.

Eberhart et al. evaluated the clinical effects of increasing anaplasia and nodularity in a large group of children with medulloblastomas, hypothesizing that increasing nodularity would predict better clinical outcomes and that increasing anaplasia would presage less favorable results.

Medulloblastomas from 330 Pediatric Oncology Group patients were evaluated histologically with respect to extent of nodularity, presence of desmoplasia, grade of anaplasia, and extent of anaplasia. Pathologic and clinical data were then compared using Kaplan-Meier and log-rank analyses.

Increasing grade of anaplasia and extent of anaplasia were associated strongly with progressively worse clinical outcomes (P < 0.0001 for both). Significant anaplasia (moderate or severe) was identified in 24% of medulloblastoma specimens. Neither increasing degrees of nodularity nor desmoplasia were associated significantly with longer survival.

Moderate anaplasia and severe anaplasia were associated with aggressive clinical behavior in patients with medulloblastomas and were detected in a significant number of specimens (24%). Pathologic grading of medulloblastomas with respect to anaplasia may be of clinical utility 11).


Although surgery, radiation and high-dose chemotherapy have led to increased survival, one-third of patients succumb to their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment.

Through analysis of several well-designed multi-institutional trials, much has been learned about the clinical factors that influence outcome in children with medulloblastomas. Age younger than 3 years, bulky residual disease postoperatively, and metastasis constitute adverse prognostic features and indicate patients who are considered “high risk” for recurrence with standard therapy using 3600 cGy craniospinal radiation in conjunction with a posterior fossa dose of 5400 cGy. Patients lacking these features are considered “standard risk.”

Evaluation of biologic predictors of outcome, which may further refine treatment stratification, is in progress.

References

1)

Gilbertson RJ. Medulloblastoma: signalling a change in treatment. Lancet Oncol. 2004; 5:209–218
2)

Weil MD, Lamborn K, Edwards MS, Wara WM. Influence of a child’s sex on medulloblastoma outcome. JAMA. 1998 May 13;279(18):1474-6. PubMed PMID: 9600483.
3)

Prados MD, Warnick RE, Wara WM, Larson DA, Lamborn K, Wilson CB. Medulloblastoma in adults. Int J Radiat Oncol Biol Phys. 1995 Jul 15;32(4):1145-52. PubMed PMID: 7607936.
4)

Kumar LP, Deepa SF, Moinca I, Suresh P, Naidu KV. Medulloblastoma: A common pediatric tumor: Prognostic factors and predictors of outcome. Asian J Neurosurg. 2015 Jan-Mar;10(1):50. doi: 10.4103/1793-5482.151516. PubMed PMID: 25767583; PubMed Central PMCID: PMC4352636.
5)

Narayan V, Sugur H, Jaiswal J, Arvinda HR, Arivazhagan A, Somanna S, Santosh V. Medulloblastoma: Distinctive Histo-Molecular Correlation with Clinical Profile, Radiologic Characteristics, and Surgical Outcome. Pediatr Neurosurg. 2019 Sep 3:1-12. doi: 10.1159/000501913. [Epub ahead of print] PubMed PMID: 31480064.
6)

Chatty EM, Earle KM. Medulloblastoma. A report of 201 cases with emphasis on the relationship of histologic variants to survival. Cancer. 1971 Oct;28(4):977-83. PubMed PMID: 5111749.
7)

Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim JY, Goumnerova LC, Black PM, Lau C, Allen JC, Zagzag D, Olson JM, Curran T, Wetmore C, Biegel JA, Poggio T, Mukherjee S, Rifkin R, Califano A, Stolovitzky G, Louis DN, Mesirov JP, Lander ES, Golub TR. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature. 2002 Jan 24;415(6870):436-42. PubMed PMID: 11807556.
8)

Sure U, Berghorn WJ, Bertalan y H. Collins’ law. Prediction of recurrence or cure in childhood medulloblastoma? Clin Neurol Neurosurg. 1997; 99:113–116
9)

Gajjar A, Hernan R, Kocak M, Fuller C, Lee Y, McKinnon PJ, Wallace D, Lau C, Chintagumpala M, Ashley DM, Kellie SJ, Kun L, Gilbertson RJ. Clinical, histopathologic, and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma. J Clin Oncol. 2004 Mar 15;22(6):984-93. Epub 2004 Feb 17. PubMed PMID: 14970185.
10)

Ray A, Ho M, Ma J, Parkes RK, Mainprize TG, Ueda S, McLaughlin J, Bouffet E, Rutka JT, Hawkins CE. A clinicobiological model predicting survival in medulloblastoma. Clin Cancer Res. 2004 Nov 15;10(22):7613-20. PubMed PMID: 15569993.
11)

Eberhart CG, Kepner JL, Goldthwaite PT, Kun LE, Duffner PK, Friedman HS, Strother DR, Burger PC. Histopathologic grading of medulloblastomas: a Pediatric Oncology Group study. Cancer. 2002 Jan 15;94(2):552-60. PubMed PMID: 11900240.

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

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.
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