Late-onset schizophrenia with isolated cavum vergae: Case report and literature review.

Cavum septum pellucidum (CSP) and cavum vergae (CV) have separately and together been associated with an increased risk of neurodevelopmental disorders and psychosis; however, there is little literature on the psychopathological significance of isolated CV, and no previous report of isolated CV in late-onset psychosis. We describe an 80-year-old woman who presented with a 1-month history of psychotic symptoms qualifying for a diagnosis of schizophreniform disorder. Physical (including neurological) examination, bedside cognitive testing, and laboratory investigations were all within normal limits. A magnetic resonance imaging scan of the brain revealed an insignificant CSP with prominent CV. The patient showed almost complete recovery from psychosis after 4-6 weeks of treatment with quetiapine (200 mg/day). She maintained improvement with this medication at an 18-month follow-up; medication taper was associated with re-emergence of hallucinations. We briefly discuss CSP and CV in the context of vulnerability to psychosis. We examine whether isolated CV is a benign and incidental finding versus a biological risk factor for neuropsychiatric illness. We suggest specific studies to resolve the uncertainty.

INTRODUCTION

The septum pellucidum is a thin membranous midline structure which separates the lateral ventricles in the brain. Cavum septum pellucidum (CSP) is a condition characterized by the presence of a gap between the leaflets of the septum pellucidum. This gap results from a failure of the leaflets to fuse during late fetal life and early infancy, as the hippocampus, amygdala, and other midline brain structures develop and grow. Cavum vergae (CV) comprises a posterior extension of CSP, behind the anterior columns of the fornix and below the splenium of the corpus callosum. The two conditions may be seen separately or together.[12]

Although CSP and CV may be present as a normal variation without clinically evident accompaniments or deficits, these have been considered as markers of impaired neurodevelopment.[12] In this context, CSP has been associated with diverse neuropsychiatric syndromes including schizophrenia,[3] bipolar disorder,[4] alcoholism,[5] antisocial behavior,[6] or just susceptibility to psychosis.[7] CSP with co-occurring CV is less common, but has been reported in developmental disorders,[1] schizophrenia,[8] late-onset catatonia necessitating electroconvulsive therapy,[9] and treatment-resistant childhood-onset schizophrenia.[10]

Herein, we describe the incidental detection of CV in an elderly woman with schizophreniform psychosis. We discuss the implications of the finding of CSP with or without CV in such patients.

CASE REPORT

An 80-year-old woman was brought with a 1-month history of restlessness, repeated religious verbalizations, visual hallucinations, third person auditory hallucinations, religious shloka auditory hallucinations, delusions of reference and persecution, persistent irritability, and impaired sleep. She had no awareness of mental illness. Her self-care, however, was adequate.

There was no past, personal, medical, or family history of relevance. She was not receiving medications that might have explained the clinical picture. There was no history or evidence of head injury or toxin exposure.

A general medical and neurological examination yielded results that were within normal limits. Her orientation to time, place, and person was normal. She performed competently on bedside tests of general information, attention, concentration, immediate memory, and recent memory. Her performance on bedside tests of working memory and visuospatial coordination were also adequate.

All laboratory investigations were within normal limits. A brain magnetic resonance imaging (MRI) scan revealed an insignificant CSP but prominent CV [Figure 1]. There were also a few age-consistent periventricular white matter hyperintensities. The MRI findings were otherwise within normal limits, given her age.

Figure 1

T1-weighted magnetic resonance image showing cavum vergae (arrow)

A provisional diagnosis of late-onset schizophreniform disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) was made, and she was treated with quetiapine in a dose that was gradually uptitrated across 1 month to 200 mg/day. She showed almost complete recovery after 4-6 weeks of treatment and has maintained improvement with quetiapine (150 mg/day) at an 18-month follow-up. As auditory hallucinations re-emerge if attempts are made to reduce the medication dose, the diagnosis has been revised from schizophreniform disorder to schizophrenia.

DISCUSSION

Not all studies have found an association between CSP and risk of psychopathology. For example, Takahashi et al.[11] found the prevalence of a large CSP (>5.6 mm) was 9.3% in 162 first-episode psychosis patients, 11.2% in 89 chronic schizophrenia patients, 11.1% in 135 persons at ultra-high risk of psychosis, and 11.5% in 87 control subjects. The length of the CSP was also unassociated with the sulcal morphology of the anterior cingulate cortex. Takahashi et al.,[11] therefore, questioned whether CSP is a neurodevelopmental marker of psychosis and whether it really plays a major role in the neurobiology of psychosis. In this context, in a meta-analysis of 15 MRI studies, Trzesniak et al.[12] showed that relative to healthy controls (n = 866), CSP was significantly associated with schizophrenia spectrum disorders (n = 1054) only when it was large (odds ratio 1.59; 95% confidence interval 1.07-2.38). They suggested that a small CSP may merely be a normal variant.

A large CSP, especially in association with CV, suggests abnormality of the septal nuclei as well as dysgenesis of midline forebrain structures such as the hippocampus and the corpus callosum. If a large CSP or a CSP with CV predispose to schizophrenia, one might expect poor neuroadaptation from an early age, earlier onset of illness, and perhaps poor response to treatment, as well, in affected persons. In line with such a conjecture, Liao et al.[10] reported a 14-year-old boy who had developed schizophrenia at age 11 years. This boy had CSP with CV. He failed treatment with ziprasidone, aripiprazole, olanzapine, quetiapine, and clozapine, all of which had been prescribed in adequate doses. Interestingly, CSP with CV has also been associated with late-onset psychotic symptoms,[13] including late-onset catatonia.[9] There are two possible interpretations of these findings of late-onset psychosis. One is that CSP with or without CV is an incidental MRI finding that has no bearing on psychopathology. The other is that CSP and CV increase the risk of major mental illness across the lifespan of the individual. Late onset, as sometimes reported, can be explained on the basis of compromised neuroadaptation exposed by age-related neurodegenerative changes. These possibilities can be explored through MRI studies in late-onset psychosis patients and matched healthy controls.

The patient we report, however, had isolated CV. Isolated CV is unusual. This is because CSP and CV usually communicate and obliterate from posterior to anterior, during late fetal and early infant life; that is, the CV obliterates first and the CSP, afterward. The presence of isolated CV may, therefore, indicate that midline neurodevelopment in early life did not occur in the expected sequence, or that there was a failure of development of isolated midline structures.[14] Isolated CV has been described in relation to psychosis; for example, Wolf et al.[15] reported a young adult with isolated CV associated with treatment-refractory schizophrenic illness.

There is otherwise little literature on the psychopathological significance of isolated CV, and our patient is probably the first case in the literature of late-onset schizophrenia with isolated CV. In a large study of 249 patients with neurodevelopmental delay and 161 normal individuals, CSP with or without CV discriminated between patient and control group whereas CV alone did not.[1] This seems to suggest that isolated CV may be an incidental finding that does not have neuropsychiatric implications. Importantly, however, this study did not examine elderly subjects nor did it examine subjects with psychosis; the findings, therefore, neither support not refute the possibility that isolated CV, like CSP with or without CV, is associated with a predisposition to psychosis, including psychosis of late-onset. Again, only MRI studies in late-onset psychosis can clarify the issue.

CONCLUSION

We present what may be the first case of isolated CV associated with late-onset schizophrenia. We suggest that there is weak biological plausibility for a cause–effect relationship but that the relationship cannot be considered confirmed (as opposed to being coincidental) without specific study.