Koro delusion in mild cognitive impairment due to Alzheimer’s disease

Introduction:

While neuropsychiatric symptoms (NPS) have been a well-recognized complication of Alzheimer’s disease (AD) in advanced dementia stages, there is increasing interest in the characterization of NPS in early stages such as mild cognitive impairment (MCI) {^1,2}. NPS in MCI not only add to the distress of cognitive deficits, but also may delineate subgroups at higher risk for conversion to dementia {³}. Numerous studies have shown that in MCI, the predominant neuropsychiatric symptoms can include depression, anxiety, and apathy {^1,4}. Psychotic symptoms (delusions and/or hallucinations) typically manifest in the dementia stages {²}, with studies suggesting a direct correlation of the severity of the dementia and emergence of psychotic symptoms {⁴}. Indeed, incidence of psychotic symptoms in MCI is fairly low, estimated to be between 3–14% {⁵}; similarly prevalence rates range only between 1–10% {⁶}. The most common psychotic symptoms observed are persecutory delusions, delusional misidentifications, and visual hallucinations, though prominent psychosis early in the course may in fact be more suggestive of incipient Lewy body disease rather than AD {⁷}.

The Koro delusion, not explicitly described in the DSMV but included in the DSMIV, has been previously defined as having a “sudden and intense anxiety that the penis will recede into the body and possibly cause death” {⁸}. Phenomenologically, it had previously been assigned as a culture-bound syndrome geographically localized to Southeast Asia, Japan, and China, though in the past few decades the syndrome has been reframed to include both a culture-bound epidemic form and a non-culturally bound isolated form {⁹}. This latter isolated form has been observed in numerous case reports across the globe and generally understood to manifest in the context of broader underlying psychiatric pathologies, including body dysmorphic disorders, anxiety/panic disorders, somatoform disorders, dissociative/depersonalization disorders, psychotic depression, or in the psychoanalytic arena, as a form of castration anxiety {^10–13}.

There are scant reports of Koro arising in the setting of non-purely psychiatric situations, i.e. following some form of a direct physiologic insult, examples of which include following a stroke {¹⁴}, in the setting of alcoholic hepatitis {¹⁵}, following abrupt withdrawal of an antipsychotic {¹⁶}, in the setting of a tumor of the corpus callosum {¹⁷}, bronchial carcinoma with metastatic spread to the central nervous {¹⁸}, and in patients with abnormal epileptic activity{¹⁹}. Of these cases with direct CNS involvement, localization studies are limited but highlight the right temporoparietal lobes {¹⁴}, genu of the corpus callosum {¹⁷}, left frontotemporal lobe {¹⁸}, and the bitemporoparietal region {¹⁹}. Importantly, to the best of our knowledge, there are no reports of this delusion in the setting of age-related neurodegenerative disease. Here we present what appears to be the first reported case of Koro syndrome presenting in MCI due to AD.

Case Report:

A 78-year-old man was initially evaluated after being referred from his primary care physician (PC) for memory loss spanning over one year. Past medical history was notable for a distant history of minor stroke (vision loss, resolved). His evaluation at the Memory Disorders clinic demonstrated mild errors in recall as well as deficits in visuoconstruction, resulting in an MMSE of 27/30. This corresponded to a Z-score of −0.869, based on sex, age, and 12 years of education{²⁰}. There were no signs or symptoms of parkinsonism. He reported independence in all of his ADLs and iADLS, corroborated by interview with his relative at a later date, and was living on his own. From this initial evaluation he did not meet criteria for MCI{²¹}, but an initial workup was recommended. Reversible dementia studies revealed normal B12 and TSH levels. A brain MRI was ordered but not initially completed. Follow up five months later revealed mostly stable findings. Three months later, at a routine visit with his PCP, the patient complained that he “heard his penis shrink” and that it had “retracted.” This was causing him a great deal of anxiety. Physical exam of the penis revealed no abnormalities. The patient also reported deleting an email he had written to the PCP after hearing a voice emanating from screen, associated with an incessant “banging” noise. Word finding difficulty was also noted. He was seen urgently in the memory disorders clinic, where he again reiterated that his penis had physically shrunk, despite knowledge of the normal exam, but that he was less anxious about it. He was apologetic about bothering his PCP and showed the neurologist letters of apology he wrote to his PCP. There was some delusional content surrounding these letters as he reported that they were “speaking” to him as well. Neurologic exam at this visit showed mild deficits with registration, recall, and attention/concentration, but with improvement in visuospatial construction. Now 79, MMSE was scored at 24/30, which corresponded to a Z-score of −3.274 {²⁰}. He remained functionally independent, corroborated with family, and thus satisfied criteria for MCI²¹. Brain MRI (Figure 1a,b) was completed, revealing mild supratentorial white matter changes suggestive of microvascular disease and mild bitemporal volume loss concerning for AD. FDG PET (Figure 1c,d) showed decreased uptake in bilateral parietal and temporal lobes, consistent with AD. .

Figure 1. Structural and functional imaging consistent with Alzheimer’s disease in a patient with mild cognitive impairment and Koro delusion.

MRI brain axial FLAIR sequence shows A. mild periventricular and subcortical white matter hyperintensities and B. mild hippocampal atrophy. On axial view, FDG PET CT shows C. parietal and D. temporal hypometabolism.

Discussion:

The above case illustrates what appears to be the first reported case of the Koro syndrome manifesting in a patient with MCI due to AD. The rarity of this presentation is multifactorial; patient’s with MCI have a decreased frequency and severity of NPS as part of their symptom complex relative to patients with major cognitive disorder/dementia {²²}; of the NPS that do manifest in MCI, psychotic symptoms are less frequently observed relative to the more common symptoms of apathy, irritability, depression, and anxiety {^1,4,6}; of the psychotic manifestations that are seen among patients with MCI, the Koro syndrome is exceptional and at this time never previously reported, at least as of this current review.

When considering the typical psychotic presentations in patients with MCI or AD, delusions of misidentification and/or persecution (which, it can be argued, are deeply interrelated) are the most commonly seen {²³}. Delusional misidentification has been typically localized to the right hemisphere, especially the right frontal lobes {²⁴}. Delusions of body image, under which Koro has been previously categorized, have also been attributed to right hemisphere pathology given the right hemisphere’s “role in the construction of the corporeal and psychological self” {²⁵}. Indeed, Gurin has extensively described the relationship of the right hemisphere and delusion formation, essentially assigning four fundamental roles employed by the right hemisphere that affords the individual the “ability to create and maintain accurate appraisals of mental objects holistically and in context – be they simple visuospatial figures, complex narratives, or the self”, the loss of any one of which allows for the eventual formation of delusional content {²⁶}. While no clear area of localization has previously been attributed to the development of the Koro syndrome, the few case reports involving organic CNS lesions seem to settle on temporal lobe involvement, as delineated above.

Why this patient developed this particular delusional syndrome is unclear. His FDG PET revealed bitemporal hypometabolism, though this is a common finding in AD-MCI patients, most of which do not have the Koro delusion. Psychosis is more apparent in early stages of Lewy body dementia, though FDG PET lacks the occipital involvement that is often associated with this neurodegenerative condition. Furthermore, the patient did not display other signs such as Parkinsonism, fluctuation, or dysautonomia. Delusions can be prominent early in frontotemporal dementia associated with the C9ORF72 mutation, thought to localize to frontal disease not apparent in this case {²⁷}. Though isolated Koro has been classically conceptualized as a form of body dysmorphic disorder or depersonalization, perhaps it can be viewed in the context of delusional misidentification, though in this setting it is a misidentification of the self. Such a framework would make the Koro delusion in an AD-MCI patient more understandable, if not at least less bizarre. Similarly, the associated anxiety and panic of this syndrome can be portrayed as a manifestation of underlying paranoid obsession of the loss of the self or, alternatively, the inevitable and demise of the individual.

Beyond etiopathology or nosology, from a clinical standpoint it is evident from this case that, as previously suggested by Anderson, the delusion itself should be taken in as a symptom of a likely larger underlying insult, in our case occurring as part of the symptom complex of AD MCI. And as above, regardless of the nosology and etiopathology of Koro, ultimately the detection of underlying neuropsychiatric symptoms in patients with MCI, including the less common manifestation of delusions and hallucinations, plays an important prognostic role given the greater risk of progression to dementia {¹}.