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A case report on the relationship between treatment-resistant childhood-onset schizophrenia and an abnormally enlarged cavum septum pellucidum combined with cavum vergae

LIAO, Zheng-luan; HU, Shao-hua; XU, Yi

doi: 10.3760/cma.j.issn.0366-6999.2012.07.029
Case report

The treatment of refractory schizophrenia has been a clinical challenge for most psychiatrists; the possible reasons include diagnostic errors, medical conditions and brain dysgenesis. Here, we described a patient with childhood-onset schizophrenia who had severe psychiatric symptoms such as auditory hallucinations and persecutory delusions, and etc. We reexamined all his possible medical conditions and found that the patient had an abnormally enlarged cavus septum pellucidum (CSP) combined with cavum vergae (CV) (maximum length >30 mm). Some reports suggested that abnormal CSP (length >6 mm) has a significant association with schizophrenia. However, abnormally large CSP or CSP/CV and related prognosis were reported rarely. This case suggested that abnormally enlarged CSP or CSP/CV may worsen the prognosis.

Department of Mental Health, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China (Liao ZL, Hu SH and Xu Y)

Correspondence to: XU Yi, Department of Mental Health, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China (Tel: 86-571-56723002. Fax: 86-571-56723001. Email:

The authors report no conflicts of interest.

(Received May 8, 2011)

Edited by PAN Cheng and JI Yuan-yuan

On the basis of the Kenneth's studies (, refractory schizophrenia was generally regarded as a schizophrenia which was not significantly responsive to two different antipsychotics given in recommended doses and for an adequate period of time. In clinical practice, about 30%-60% of schizophrenia had no adequate response to antipsychotics and was categorized as refractory schizophrenia.

Apart from looking for new breakthroughs in the treatment of refractory schizophrenia, diagnosis is another focus we should consider over. Some underlying or developmental abnormalities may play a decisive role in the etiology and prognosis.

In this case, a 14-year-old boy was treated with five different antipsychotics one after another. However, he did not show adequate clinical response and was diagnosed as having refractory schizophrenia. In the reassessment we unexpectedly found an abnormally enlarged cavum septi pellucidi (CSP) combined with cavum vergae (CV) (>30 mm in length) on magnetic resonance imaging (MRI) scan. Based on this observation we suggest that the abnormally enlarged CSP/CV may be involved in the mechanism of refractory schizophrenia.

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A 14-year-old right-handed boy with three-year history of schizophrenia was admitted with a presenting complaint that he would be “attacked” by three thieves. He often displayed automatic speech, for instance, “I will not go to Taiwan Strait. I love China. Do not bother me, and I hate being alive”. The patient had suffered for 5 months as various people recurrently accused him of his patriotism. His learning performance has deteriorated progressively in the past 5 months. At last, he could not continue studying and had to stay home all day.

He was first hospitalized in 2008 in the local hospital. At the time his primary diagnosis was paranoid schizophrenia according to the DSM-IV-TR (American Psychiatric Association's Diagnostic & Statistical Manual of Mental Disorders (fourth edition, text revision)).1 After being treated with ziprasidone (180 mg/d) and olanzapine (30 mg/d) followed by aripiprazole (20 mg/d) and sodium vedproate (600 mg/d) successively in six months, he still presented with residual auditory hallucinations and delusions of persecution. Six months ago, he was transferred to our hospital for further treatment.

We collected the patient's medical information. His past medical history and developmental milestones, including epilepsy, alcohol ingestion and/or substance abuse, were normal. His family history was also negative for psychiatric illnesses.

We also reviewed all his physical examinations and obtained a MRI scan of his head. Mental status examination revealed sensorial-perceptive disturbances and thought content disorders, in addition to loss of syntonic contact and suspicious attitude. Delusional concepts were primary, focused on complaining that he was being attacked and monitored. Cognitive function was measured with Chinese Intelligence Scale for Children (C-WISC) which showed poor coding and memory deficits. General physical examination on admission was normal. We did not see a Kayser-Fleischer ring at his cornea and so excluded Wilson's disease. All laboratory exanimations and electroencephalogram were normal.

The MRI scan of the head revealed an abnormal enlarged CSP combined with CV, the length of which exceeded 30 mm. There was no evidence of hydrocephalus or trauma.

In our hospital, he was treated with clozapine (700 mg/d) for three months after the treatment with quetiapine (800 mg/d) and olanzapine (30 mg/d) together. However the patient kept presenting with soliloquies and episodes of agitation. In general, his medication was not effective.

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CSP is a space between the two leaflets of the septum pellucidum. In normal prenatal development, the space will disappear with the rapid growth of midline structures including corpus callosum and limbic system structures by six months of life.2 This suggests that dysgenesis of either the hippocampus or the corpus callosum could lead to an arrest of the fusion process, causing CSP to persist.

In 1971, a study found that CSP has a relatively high frequency in variety of neuropsychiatric conditions.2 From then on, more and more investigators went into researching the relationship between CSP and schizophrenia by MRI. A small CSP (length <6 mm) is generally considered as normal, whereas the CSP more than 6 mm in length is defined as an abnormal CSP.3–5 There were such reports declaring that small CSP was common in both healthy comparison subjects and the patients.4,6 However, some studies compared the proportion of abnormal CSP in patients with schizophrenia with that in normal subjects using MRI, and suggested that abnormal CSP might be associated with a higher susceptibility to schizophrenia.7–10 They found that the prevalence of abnormal CSP in schizophrenic patients was significantly higher than that observed in normal subjects. However, not all studies have been able to replicate this finding and very few studies have been conducted in large samples. Takahashi et al11 and Rajarehtinam et al12 found that the prevalence of a large CSP did not differ between patients and normal individuals. They suggested that the CSP is not a neurodevelopmental marker of psychosis.

Little is known about the mechanism of abnormally enlarged CSP. A research concerning in utero infection of progestation found that infected schizophrenic patients have larger CSP than uninfected patients, suggesting that progestational infection may lead to neural development form abnormal which is significantly associated with schizophrenia.13 This report suggestted that abnormal CSP may be regarded as a marker of the severity of neurodevelopmental insult, particularly in prenatal period. This may also form the structural basis for the schizophrenia.

When the size of CSP reached severe degree (length >6 mm), a combined CSP/CV would be formed. This represents the total lack of fusion of the septal leaflets at any time since CV is usually formed in association with a severely enlarged CSP. Some investigators found that the severe CSP or CSP/CV existed particularly in patients with childhood-onset schizophrenia,9 they speculated that schizophrenic patients with no response to medication may have more severe brain abnormalities such as CSP/CV.

Possibly more important than the relationship between larger CSP and schizophrenia is the prognosis of schizophrenic patients with abnormal CSP or CSP/CV. Up to now, only one study suggested that patients with enlarged CSP or CSP/CV, particularly in childhood-onset schizophrenia, may have poorer prognosis than normal controls.4 These patients may present with a total lack of response to medication. However, the mechanism of the resistance to treatment is still unknown. Structural and morphological abnormalities in the limbic system are thought to be associated with schizophrenia.14 Once the abnormalities are formed, medications cannot change the symptoms easily. This may be the explanation of poor response to antipsychotics in refractory schizophrenia.

In this case, the patient with abnormally enlarged CSP/CV presented with thought disturbance and impairment of cognitive functions. He had no significant response to many antipsychotics including olanzapine, clozapine and etc. Therefore this case may be useful to deduce the correlation between abnormally enlarged CSP or CSP/CV and the prognosis of childhood-onset schizophrenia.

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1. American Psychiatric Association Task Force on DSM-IV. American Psychiatric Association's Diagnostic & Statistical Manual of Mental Disorders (DSM-IV-TR), 4 ed Arlington: VA American Psychiatric Association; 2010.
2. Vieira CR, Margues AL, Scaff M, Machado AG, Garcia BN. Agenesis and cavum of septum pellucidum. Arq Neuropsiquiatr 1971; 29: 447-452.
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10. Choi JS, Kang DH, Park JY, Jung WH, Choi CH, Chon MW, et al. Cavum septum pellucidum in subjects at ultra-high risk for psychosis: compared with first-degree relatives of patients with schizophrenia and healthy volunteers. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 1326-1330.
11. Takahashi T, Yung AR, Yücel M, Wood SJ, Phillips LJ, Harding IH, et al. Prevalence of large cavum septi pellucidi in ultra high-risk individual s and patients with psychotic disorders. Schizophr Res 2008; 105: 236-244.
12. Rajarethinam R, Sohi J, Arfken C, Keshavan MS. No difference in the prevalence of cavum septum pellucidum between first-episode schizophrenia patients, offspring of schizophrenia patients and healthy controls. Schizophr Res 2008; 103: 22-25.
13. Brown AS, Deicken RF, Vinogradov S, Kremen WS, Poole JH, Penner JD, et al. Prenatal infection and cavum septum pellucidum in adult schizophrenia. Schizophr Res 2009; 108: 285-287.
14. Bogerts B. The temporolimbic system theory of positive schizophrenic symptoms. Schizophr Bull 1997; 23: 423-435.

schizophrenia; septum pellucidum

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