The patient completed an interview-based neuropsychological battery composed of various tests measuring memory, language, executive functions, abstract reasoning, and visuospatial functions (Table 1). The tests were administered by an experienced neuropsychologist (S.A.K.). All of the tests are international neuropsychological measures except the Verbal Memory Processes Scale (Öktem, 1992), which was developed in Turkey. However, all of the tests have been validated for the Turkish population and this specific patient’s age group; education-adjusted norms are also available.
The Verbal Memory Processes Scale measures both verbal short-term and long-term memory, including delayed retrieval and recognition after delay. During the test, a 10-item word list is repeated eight times. Regarding short-term memory, the patient remembered only four of the items, indicating a severe deficit. For delayed recall, the patient was unable to recall any of the items, indicating a severe impairment. And, in terms of recognition after delay, the patient recognized only half of the items that he had been shown and falsely recognized five words. These results indicate mixed-type memory impairment, with both hippocampal and frontal deficits.
On the Boston Naming Test (Lansing et al, 1999), the patient was able to name only four items (out of 31) spontaneously, indicating severe anomia. For the remainder of the test, he required a phonemic or semantic cue. The patient also had semantic, phonemic, and neologistic paraphasias. During the Cookie Theft task from the Boston Diagnostic Aphasia Examination (Giles et al, 1996), the patient used neologisms and exhibited phonemic paraphasias. These results indicate severe naming and language impairment.
Executive Functions (see Faria et al, 2015, for Details of the Tests)
During the Digit Span Test, the patient was able to repeat only five digits forward and only two digits backward. This performance was interpreted as showing problems with attention span and working memory. During the Clock-Drawing Test, the patient wrote numbers greater than 12 on the clock face and placed the clock hands incorrectly. This pattern indicates a planning and conceptual deficit in addition to a perseverative pattern. On the Stroop Test, the patient could not name any of the colors under the incongruent condition. This performance shows problems with interference control and inhibition. During the Verbal Fluency Test, the patient is first required to produce names from a certain category (eg, animals), then to name objects starting with the letters K, A, and S. The patient managed to produce only two animal names in the allotted 1 minute and only seven words starting with the letters K, A, and S. This performance is consistent with severely impaired semantic information processing.
We used the Similarities subtest of the Wechsler Adult Intelligence Scale, Fourth Edition (Wechsler, 2008), to measure the patient’s abstract reasoning. The patient could detect the similarity correctly for only two out of 20 items, indicating severe impairment.
We used the Benton Judgment of Line Orientation Test (Qualls et al, 2000) and the Benton Facial Recognition Test (Tranel et al, 2009) to measure the patient’s visuospatial function. The Line Orientation Test involves finding the match of lines with different orientations to the lines in a response card. The patient’s performance was only slightly impaired as he scored 17 out of 30; a score of 20 is considered to be normal. The Benton Facial Recognition Test involves recognition of a target face among a set of different faces. The patient’s score on this test was normal (41 out of 54). These findings indicate that the patient’s visuospatial function was largely preserved.
Taken together, the deficits displayed by our patient—dysexecutive neuropsychological pattern, disinhibition, and perseverations—and the MRI findings led to the diagnosis of probable frontotemporal dementia (FTD), in accordance with the Neary criteria (Mohandas and Rajmohan, 2009). The most likely subtype of FTD is semantic dementia, based on the patient’s prominent naming deficits and MRI scans of characteristic anterior temporal lobe atrophy (Rascovsky and Grossman, 2013). On the other hand, the patient also exhibited severe executive dysfunction and impaired working memory, which is not typical of semantic dementia. This combination of the severe behavioral phenotype and the dysexecutive pattern suggests a behavioral variant of FTD (Pressman and Miller, 2014).
The patient was prescribed an antipsychotic (risperidone, titrated to 3 mg) to control his delusions and sexual disinhibition. He benefited significantly from this treatment; his wife reported a marked decrease in his disinhibited sexual behavior and CS symptoms after a few days. Despite a lack of evidence (Boxer et al, 2013; Li et al, 2015), off-label therapeutic trials of donepezil (10 mg) and memantine (20 mg) were initiated; however, according to his wife’s report, the patient showed no improvement in naming and memory functions following these medications. In the last visit after 6 months of treatment initiation, the symptoms related to CS were still controlled with risperidone, and no improvement in the patient’s other cognitive symptoms was described.
It is noteworthy that the patient exhibited marked asymmetrical temporal lobe atrophy on an MRI. Asymmetrical temporal lobe involvement has been reported in 35% of patients with a behavioral variant of FTD (Whitwell et al, 2013), with some studies demonstrating that the side of the brain that is affected in FTD confers the types of neuropsychological deficits that will be displayed by patients. For example, the right-sided variant is associated with behavioral dyscontrol, personality changes, aphasia, and prosopagnosia (Josephs et al, 2009), whereas the left-sided variant primarily manifests as language deficits (Boone et al, 1999; Razani et al, 2001). In the present case, MRI revealed exclusively left-sided involvement, although, interestingly, in addition to language impairment, the patient also displayed severe behavioral problems (reflected in CS).
A recent study reported that the brain lesions underlying CS are located in the right frontal cortex and the left retrosplenial cortex, which are associated with belief evaluation and familiarity, respectively (Darby et al, 2017). Therefore, in our patient’s case, selective left temporal atrophy may not by itself have been responsible for the CS; it is possible that abnormalities in the neuronal networks within this region may have played a pathogenic role in the clinical phenotype. Interestingly, other authors have also proposed that CS occurs due to a lack of communication between the sensory and limbic systems (Ramachandran, 1998).
Harciarek and Kertesz (2008) studied a large group of patients with neurodegenerative disorders including Alzheimer disease, FTD, Parkinson disease, and Parkinson-plus syndromes and reported that none of the patients with a behavioral variant of FTD presented with a misidentification syndrome. Josephs (2007) reported one case with FTD and misidentification syndrome; however, the subtype of FTD was not mentioned. On the other hand, Harciarek and Kertesz (2008) reported that 8.3% of patients with semantic dementia can have misidentification syndromes. Interestingly, in the case presented here, CS was the primary clinical symptom of the underlying neurologic pathology and appeared to cause the most distress and disability compared to other symptoms, such as disinhibition and anomia.
This case clearly demonstrates that CS can be a feature of FTD, along with language and behavioral impairments. The possibility that patients with neurodegenerative disorders can display misidentification symptoms should be highlighted to clinicians. In such patients, structural (MRI) and functional (EEG and PET) tests should be performed for a definitive diagnosis. One limitation of our report, however, is that we cannot provide histological confirmation of the diagnosis of FTD. FTD subtypes are notoriously associated with different neuropathological lesions, including motor neuron disease-type inclusions, which are characteristic of motor neuron disease with FTD, and tau pathology (also present in Alzheimer disease and other taupathies) (Kertesz et al, 2005). It would be of interest to determine whether the combination of FTD with CS and other misidentification syndromes is associated with a specific neuropathological pattern.
Barelle A, Luaute J-P. 2018. Capgras syndrome
and other delusional misidentification syndromes. Front Neurol Neurosci. 42:35–43.
Berson RJ. 1983. Capgras’ syndrome. Am J Psychiatry. 140:969–978.
Boone KB, Miller BL, Lee A, et al. 1999. Neuropsychological patterns in right versus left frontotemporal dementia
. J Int Neuropsychol Soc. 5:616–622.
Boxer AL, Knopman DS, Kaufer DI, et al. 2013. Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 12:149–156.
Darby R, Laganiere S, Pascual-Leone A, et al. 2017. Finding the imposter: brain connectivity of lesions causing delusional misidentifications. Brain. 40:497–507.
Darby R, Prasad S. 2016. Lesion-related delusional misidentification syndromes: a comprehensive review of reported cases. J Neuropsychiatry Clin Neurosci. 28:217–222.
Faria CA, Alves HVD, Charchat-Fichman H. 2015. The most frequently used tests for assessing executive functions in aging. Dement Neuropsychol. 9:149–155.
Gama Marques J. 2015. Koro, Othello and Capgras syndromes in one patient with drug induced psychosis. Psychiatr Danub. 27:429–430.
Gama Marques J, Carnot MJ. 2016. Huntington’s disease in a patient with 15-year history of Capgras delusion misdiagnosed as paranoid schizophrenia. Gen Hosp Psychiatry. 39:97–98. doi:10.1016/j.genhosppsych.2015.11.007
Giles E, Patterson K, Hodges JR. 1996. Performance on the Boston Cookie Theft picture description task in patients with early dementia of the Alzheimer’s type: missing information. Aphasiology. 10:395–408.
Harciarek M, Kertesz A. 2008. The prevalence of misidentification syndromes in neurodegenerative diseases. Alzheimer Dis Assoc Disord. 22:163–169.
Harwood DG, Barker WW, Ownby RL, et al. 1999. Prevalence and correlates of Capgras syndrome
in Alzheimer’s disease. Int J Geriatr Psychiatry. 14:415–420.
Josephs KA. 2007. Capgras syndrome
and its relationship to neurodegenerative disease. Arch Neurol. 64:1762–1766.
Josephs KA, Whitwell JL, Knopman DS, et al. 2009. Two distinct subtypes of right temporal variant frontotemporal dementia
. Neurology. 73:1443–1450.
Kertesz A, McMonagle P, Blair M, et al. 2005. The evolution and pathology of frontotemporal dementia
. Brain. 128 (pt 9):1996–2005.
Kimura SChristodoulou GN. 1986. Review of 106 cases with the syndrome of Capgras. The Delusional Misidentification Syndromes
Series: Bibliotheca Psychiatrica. no 164. Basel, Switzerland; New York, New York: Karger; 121–130.
Lansing AE, Ivnik RJ, Cullum CM, et al. 1999. An empirically derived short form of the Boston Naming Test. Arch Clin Neuropsychol. 14:481–487.
Li Y, Hai S, Zhou Y, et al. 2015. Cholinesterase inhibitors for rarer dementias associated with neurological conditions. Cochrane Database Syst Rev. CD009444.
Mohandas E, Rajmohan V. 2009. Frontotemporal dementia
: an updated overview. Indian J Psychiatry. 51 (suppl 1):S65–S69.
Öktem Ö. 1992. Sözel Bellek Süreçleri Testi
) – Bir Ön Çalişma [Verbal Memory Processes Scale—A preliminary study]. Nöropsikiyatri Arşivi. 29:196–206.
Pressman PS, Miller BL. 2014. Diagnosis and management of behavioral variant frontotemporal dementia
. Biol Psychiatry. 75:574–581.
Qualls CE, Bliwise NG, Stringer AY. 2000. Short forms of the Benton Judgment of Line Orientation Test: development and psychometric properties. Arch Clin Neuropsychol. 15:159–163.
Ramachandran VS. 1998. Consciousness and body image: lessons from phantom limbs, Capgras syndrome
and pain asymbolia. Philos Trans R Soc B Biol Sci. 353:1851–1859.
Rascovsky K, Grossman M. 2013. Clinical diagnostic criteria and classification controversies in frontotemporal lobar degeneration. Int Rev Psychiatry. 25:145–158.
Razani J, Boone KB, Miller BL, et al. 2001. Neuropsychological performance of right- and left-frontotemporal dementia
compared to Alzheimer’s disease. J Int Neuropsychol Soc. 7:468–480.
Tranel D, Vianna E, Manzel K, et al. 2009. Neuroanatomical correlates of the Benton Facial Recognition Test and Judgment of Line Orientation Test. J Clin Exp Neuropsychol. 31:219–233.
Wechsler D. 2008. Wechsler Adult Intelligence Scale, Fourth Edition. San Antonio, Texas: Pearson Assessment.
Whitwell JL, Xu J, Mandrekar J, et al. 2013. Frontal asymmetry in behavioral variant frontotemporal dementia
: clinical imaging and pathogenetic correlates. Neurobiol Aging. 34:636–639.
Keywords:Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved
Capgras syndrome; frontotemporal dementia; misidentification syndrome; magnetic resonance imaging