General Hospital Psychiatry 36 (2014) 760.e5–760.e7
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Impulse control disorders in frontotemporal dementia: spectrum of symptoms and response to treatment☆ Sara Pompanin, M.D. a, Nela Jelcic, Ph.D. b, Diego Cecchin, M.D. c, Annachiara Cagnin, M.D. a, b,⁎ a b c
Department of Neurosciences: Sciences NPSRR, University of Padova, Padova, Italy IRCCS San Camillo Hospital Foundation, Venice, Italy Department of Medicine (DIMED), University of Padova, Padova, Italy
a r t i c l e
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Article history: Received 31 January 2014 Revised 10 June 2014 Accepted 11 June 2014 Keywords: Frontotemporal dementia Impulse control disorder Binge-eating disorder Compulsion Topiramate
a b s t r a c t Objective: To describe a patient with behavioral variant frontotemporal dementia (bvFTD) presenting with impulse control disorders (ICDs) which responded to ﬂuvoxamine and topiramate. Case report: A 64-year-old woman was affected by several ICDs. At disease onset, she suffered from impulsive smoking and overeating which caused a body weight increase of 20 kg in 6 months. Later on she manifested binge-eating behavior and skin-picking compulsion. Presence of progressive frontal cognitive impairment (Mini Mental State Examination 24/30) and evidence of hypoperfusion of the anterior cingulate and dorsolateral frontal cortex with brain single-photon emission computed tomography scan contributed to the diagnosis of bvFTD. Use of combination treatment with selective serotonin reuptake inhibitor drugs and topiramate improved all these symptoms. Conclusion: This case extends the clinical phenotype of repetitive and compulsive habits in bvFTD to encompass symptoms suggestive of ICDs. It is proposed that ﬂuvoxamine and topiramate may be considered as treatment options in these conditions. © 2014 Elsevier Inc. All rights reserved.
2. Case report
Perseverative, stereotyped, or compulsive and ritualistic behaviors are among the clinical core features of behavioral variant frontotemporal dementia (bvFTD) according to recently proposed diagnostic criteria [1,2]. Although stereotyped/repetitive behaviors may have both compulsive and impulsive qualities, only few reports have described the presence of impulse control disorders (ICDs) in bvFTD patients. The essential feature of ICDs is the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the person or to others . A continuum between impulsivity and compulsivity has been framed in the theory of an impulsive–compulsive spectrum disorder [4,5]. As a result, in the new version of the Diagnostic and Statistical Manual of Mental Disorders (DSM) of the American Psychiatric Association, V edition, some clinical manifestations of ICD, such as trichotillomania and skin picking, have been now included in the section dedicated to the obsessive–compulsive spectrum disorders . We here describe the case of a patient who presented with different consecutive ICDs, such as impulsive smoking, binge-eating behavior, and skin picking, as more disturbing manifestations of bvFTD, which responded to ﬂuvoxamine and topiramate.
A 64 year-old woman was referred to the Memory Clinic of the University of Padua for progressive cognitive decline with behavioral disturbances in the past 2 years. No previous relevant medical or family history of neurological and psychiatric disorders was reported. Her husband reported that in the previous 3 years, she had become increasingly more apathetic and that she had been smoking more than 60 cigarettes daily with uncontrollable urge. At the age of 62, after a psychiatrist consultation, she started duloxetine at doses until 90 mg/day in the hypothesis of a depressive disorder. In that period, she was admitted to the emergency room for skin burns on the second and third ﬁngers of the right hand due to prolonged holding of the burnt cigarette's ﬁlter and its hashes (Fig. 1A). She also developed changes in dietary habits, with craving for any type of food, overeating which caused an increased body weight of 20 kg, reaching 98 kg in 6 months. After a second psychiatric consultation, the diagnosis of personality disorder with compulsive behavior was made according to the DSM-IV-TR . The Y-BOCS scale did not reveal the presence of obsessive thoughts, and the compulsive behavior was limited to smoking and overeating. The therapy was changed from duloxetine to ﬂuoxetine tapered to 60 mg/day, with beneﬁt on the impulsive smoking but without impact on the eating disorder, with further increase of body weight until reaching 109 kg over the next 3 months and the development of a binge-eating behavior. At that time, at the age of 64, the patient was ﬁrst seen at the Memory Clinic for cognitive impairment. The Mini Mental State Examination (MMSE) test score was 24/30, suggestive of mild
☆ Founding sources: This research was funded by the Department of Neurosciences, University of Padova. ⁎ Corresponding author at: Department of Neurosciences: Sciences NPSRR, University of Padova Medical School, Via Giustiniani 5, 35128 Padova, Italy. Tel.: +39 49 8213600; fax: +39 49 8751770. E-mail address: [email protected]
(A. Cagnin). http://dx.doi.org/10.1016/j.genhosppsych.2014.06.005 0163-8343/© 2014 Elsevier Inc. All rights reserved.
S. Pompanin et al. / General Hospital Psychiatry 36 (2014) 760.e5–760.e7
Fig. 1. Images of ﬁnger burns from cigarette ashes (A) and leg excoriations from skin-picking behavior (B), returned to normal after treatment with topiramate (C).
cognitive impairment. She was described by her relatives as being increasingly apathetic, detached in familial relationships, and without personal initiatives in everyday life. Episodes of urinary incontinence occurred while she was watching television or in the car during short trips without her being embarrassed or sorry about the circumstances. The neuropsychological assessment demonstrated severe deﬁcits of working memory, attention, and executive functions, with normal performance on tests exploring verbal and visual memory and language abilities (Table 1). At the Frontal Assessment Battery , she scored 12/18 (cutoff for normal performance N 15). Patients' history revealed an impairment of functional status with deﬁcit in scale assessing instrumental daily leaving activities (IADL: 3; cutoff for complete functional dependence ≤ 7). On neurological examination, there was mild axial rigidity with bradykinesia. Reﬂexes were all symmetrically brisk. Strength was normal without a pronator drift. There were no signs of sensory deﬁcits, cerebellar impairment, and cranial nerves deﬁcit. Her speech was slow and with reduced verbal ﬂuency. Routine blood analysis was unremarkable. Brain magnetic resonance imaging (MRI) scan was normal, without signs of cerebrovascular lesions or cortical focal atrophy (Fig. 2A). The study of brain cerebral blood ﬂow with single-photon emission computed tomography (SPECT) revealed the presence of hypoperfusion in the anterior cingulate and left dorsolateral frontal cortex (Fig. 2B). The presence of slowly progressive behavioral disorders in the spectrum of apathy and impulsive/compulsive manifestations, disexecutive cognitive impairment, and neuroimaging evidence of frontal lobe dysfunction satisﬁed the criteria for probable bvFTD [1,2]. A therapeutic attempt to control the binge-eating disorder switching ﬂuoxetine to ﬂuvoxamine (up to 100 mg/day) stabilized the patient's body weight, although the patient was still repetitively asking for food. Therefore, low-dose topiramate (50 mg/day) was
used as add-on therapy, obtaining a persistent beneﬁt on the eating disorder with weight loss of 5 kg in 1 month. However, in the following 6 months, the patient began repetitively scratching and skin-picking her ankles without evidence of dermatological illness. A dermatology examination did not reveal any speciﬁc dermatological disease and excluded an allergic reaction also by means of normal serum level of IgE. For relief of this itchy sensation, she also performed complex rituals such as locally applying of wet-cold packs. She caused herself erythematous and ulcerative lesions, and a diagnosis of psychogenic skin excoriation was made  (Fig. 1B). With increasing doses of topiramate (150 mg/day), a progressive reduction of skin self-mutilations was observed (Fig. 1C). On follow-up, topiramate was reduced to 75 mg/day in add-on to ﬂuvoxamine, with persistent beneﬁt on all the clinical spectrum of the ICDs. At follow-up, clinical assessment performed 2 years later, at age 66, showed a further worsening of the cognitive impairment (MMSE: 19/30) and persistent beneﬁt of the ﬂuvoxamine/topiramate combination therapy on the impulsive symptoms. 3. Discussion Atypical psychiatric symptoms of the compulsive–impulsive spectrum can be present at onset and during the disease course of bvFTD, and manifest sequentially as in the case here described. The presence of compulsive behaviors in bvFTD is well recognized and is among the core features in recently proposed diagnostic criteria [2,9]. In addition, also the semantic variant of FTD may present at onset with obsessive–compulsive disorder as unique feature for several years . As regard to ICD, few reports have described the presence of pathological gambling as isolated symptom [11,12] or in association with abnormal sexual behavior and hoarding  as early
Table 1 Neuropsychological evaluation Cognitive skills
Global cognitive functions Language
MMSE Semantic Fluency Phonemic Fluency Digit Span, Forward Digit Span, Reverse Immediate Story Recall Delay Story Recall Rey's Complex Figure Recall TMT-A TMT-B Digit Cancellation Clock drawing Rey's Complex Figure Copy FAB
24/30 32 21 4/8 3/8 8/28 8/28 7/36 76” Interrupted 25 4/10 17/36 12/18
26 cutoff z=−0.2 z=−0.7 z=−1.8 Pathologicalb z=−0.97 z=−1.4 ES=2 z=−1.6 z=−3 ES=0 z=−2.3 ES=0 15 cutoff
Executive functions and attentions
Visual-executive abilities Frontal lobe functions
MMSE: Mini Mental State Evaluation; TMT-A: Trail Making Test A; TMT-B: Trail Making Test B; FAB: Frontal Assessment Battery. a z-Score: z-scoreN−1.5→normal; −1.5bz-scoreb−2→borderline; z-scoreb−2→pathological. ES: Equivalent Score. ES=2, 3, 4→normal; ES=1→borderline; ES=0→pathological. b Qualitative evaluation (normative data not available).
S. Pompanin et al. / General Hospital Psychiatry 36 (2014) 760.e5–760.e7
Fig. 2. Axial FLAIR-MRI image (A) and corresponding ECD-SPECT scan (B) show cerebral hypoperfusion in the anterior cingulate gyrus and left dorsolateral frontal cortex, without corresponding brain atrophy.
manifestation of bvFTD. Impulsive smoking has never been described in bvFTD, while it has been reported in only one patient with Parkinson's disease . Disturbances of eating behavior, instead, are often present and are included among the core features of bvFTD . There is a signiﬁcant overlap between the neuronal circuits altered in bvFTD and those involved in both compulsive and impulsive disorders. In compulsive repetitive/stereotyped behaviors (stereotypies, rituals, tics, circumscribed interest, perseverations, ﬁxed routines) and in ICDs (skin picking, trichotillomania, binge eating, pathological gambling), a shared pathological mechanism has been suggested involving a dysfunction of frontostriatal neural circuits leading to an impairment of movement inhibitory control . In particular, dysfunction of projections from orbitofrontal and dorsolateral cortex to the caudate nucleus seems to be responsible of driving compulsive activity, while an alteration of the anterior cingulate/ventromedial prefrontal cortex projections to the ventral striatum may be responsible of impulsive actions . In the case reported here, SPECT study conﬁrmed the involvement of these cortical regions, namely, anterior cingulate and dorsolateral frontal cortex. Pharmacological management of compulsive/impulsive behaviors is often challenging for the clinician. Serotoninergic agents have been proved effective to some extent for the control of stereotypies and rituals in bvFTD . Furthermore, topiramate has been recently proposed for treatment of abnormal eating behavior in bvFTD either alone  or in add-on treatment to ﬂuvoxamine . The antiimpulsivity effect of topiramate may be due to its antiglutamatergic action that, in turn, could inﬂuence the hyperactivity of thalamocortical glutamatergic projections. In conclusion, this case report expands the range of bvFTD manifestations that may encompass the features of the compulsive/ impulsive disorder spectrum. Although these behavioral disturbances usually have a poor response to drug treatment, the association of ﬂuvoxamine and topiramate could be considered as a treatment option. References  Piguet O, Hornberger M, Mioshi E, Hodges JR. Behavioral-variant frontotemporal dementia: diagnosis, clinical staging, and management. Lancet Neurol 2011;10:162–72.
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