- Email: [email protected]
Impulse control disorders and punding in Perry syndrome
Parkinsonism and Related Disorders 21 (2015) 1381e1382
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Impulse control disorders and punding in Perry syndrome
Keywords: Perry syndrome Impulse control disorders Punding DCTN1 Frontal lobe dysfunction
Impulse control disorders (ICDs) are psychiatric conditions characterized by poor impulse control such as pathological gambling, hypersexuality, compulsive shopping, compulsive eating, explosive aggressive behavior, reckless driving, and reckless generosity [1,2]. Punding is defined as a complex prolonged, purposeless, and repetitive behavior. It has been increasingly recognized that ICDs and punding are more prevalent in patients with Parkinson's disease (PD) compared with a normal population [1], most likely due to dopaminergic therapy such as levodopa plus pramipexole and ropinirole [3]. Perry syndrome is a rare autosomal dominant neurodegenerative disorder caused by DCTN1 mutations. Parkinsonism is one of the most characteristic features of patients with Perry syndrome, along with apathy/depression, unexpected weight loss, and central hypoventilation [4]. Parkinsonism that occurs in patients with Perry syndrome generally responds well to high dose of dopaminergic therapy; however, to date, neither ICDs nor punding have been reported in patients with Perry syndrome. Herein, we describe two Japanese patients with Perry syndrome who developed ICDs and punding after initiation of dopaminergic therapy. Both patients were from the same family pedigree whom we previously reported (Fig. 1A). 1. Case 1 A 46-year-old man presented with depression. Subsequently, he experienced unexpected weight loss. Neurological examination at age 48 revealed parkinsonism, including bradykinesia, rigidity, and postural instability as well as depressive mood. Head MRI was unremarkable. A single photon emission computed tomography (SPECT) showed hyoperfusion of the frontal and occipital cortexes with occipital lobe predominance (Fig. 1B). He was once diagnosed as having PD and treated with pergolide, pramipexole, and selegiline, but these agents provided no clinical benefit. His gait had been gradually deteriorating. Therapy with levodopa/carbidopa (300 mg/day) was added at age 49, and his motor symptoms were moderately improved. However, he subsequently developed http://dx.doi.org/10.1016/j.parkreldis.2015.09.037 1353-8020/© 2015 Elsevier Ltd. All rights reserved.
prolonged, purposeless, and repetitive behavior, such as continuous touching of a mobile phone and playing video games all day. Repeated SPECT at age 50 revealed hyoperfusion in the frontal and occipital cortexes with more frontal lobe predominance (Fig. 1C) compared with findings at age 49. Genetic sequencing revealed that he had a DCTN1 G71A mutation. 2. Case 2 A 37-year-old woman, a relative of Case 1, developed depression. Neurologic examination at age 38 revealed that she had parkinsonism, including bradykinesia and rigidity. She was once diagnosed as having familial PD and started taking levodopa/carbidopa, which provided moderate benefit. However, as the effects of medication dissipated, she experienced wearing-off, mild dyskinesia and morning dystonia. She was started on pramipexole (3.5 mg/day) in addition to levodopa/carbidopa (650 mg/day), which ameliorated her motor symptoms. At age 39, she developed pathological gambling and compulsive shopping habits. She spent approximately $2000 per month. She also demonstrated compulsive eating and snacking. Her body weight kept increasing, presumably due to the compulsive eating. At age 40, she scored 29 of 30 points on the Mini-Mental State Examination, indicating she had normal cognition. At age 41, she developed repeated episodes of catatonia, which were successfully treated with clomipramine. She also demonstrated paranoia and emotional incontinence such as involuntary crying or uncontrollable episodes of crying and/or laughing. Despite treatment with a combination of antipsychotic drugs, her psychiatric symptoms, including ICDs, gradually deteriorated. Genetic sequencing confirmed to have a DCTN1 G71A mutation. Perry syndrome is often accompanied by behavior and/or personality abnormalities including apathy, lack of initiative, difficulty with attention, loss of interest, and withdrawal. Apathy is the most common behavior and/or personality abnormality in Perry syndrome, neither ICDs nor punding, however, have been reported in patients with Perry syndrome. Dopaminergic medications were reported to be risk factors for the development of ICDs and punding in patients with PD [3]. Both of our patients with Perry syndrome were treated with dopaminergic medications and subsequently developed psychiatric symptoms. The exact mechanism of ICDs and punding in PD remains to be identified; however, frontal lobe dysfunction is thought to be related to development of the symptoms [3]. It has been reported that frontotemporoparietal cortex dysfunction occurs in Perry syndrome [5]. Case 1 showed hypoperfusion of the frontal lobe cortex on the SPECT study. After levodopa replacement therapy, the frontal hypoperfusion was more obvious, indicating that punding seen in our patients could potentially be associated with frontal lobe dysfunction.
1382
Letter to the Editor / Parkinsonism and Related Disorders 21 (2015) 1381e1382
Financial disclosure/conflict of interest Nothing to disclose. Acknowledgments This work was supported by JSPS KAKENHI Grant Number 26860678.
References [1] M. Rodriguez-Violante, P. Gonzalez-Latapi, A. Cervantes-Arriaga, A. CamachoOrdonez, D. Weintraub, Impulse control and related disorders in Mexican Parkinson's disease patients, Park. Relat. Disord. 20 (2014) 907e910. [2] M.B. Callesen, D. Weintraub, M.F. Damholdt, A. Moller, Impulsive and compulsive behaviors among Danish patients with Parkinson's disease: prevalence, depression, and personality, Park. Relat. Disord. 20 (2014) 22e26. [3] A.H. Evans, R. Katzenschlager, D. Paviour, J.D. O'Sullivan, S. Appel, A.D. Lawrence, A.J. Lees, Punding in Parkinson's disease: its relation to the dopamine dysregulation syndrome, Mov. Disord. 19 (2004) 397e405. [4] M.J. Farrer, M.M. Hulihan, J.M. Kachergus, J.C. Dachsel, A.J. Stoessl, L.L. Grantier, S. Calne, D.B. Calne, B. Lechevalier, F. Chapon, Y. Tsuboi, T. Yamada, L. Gutmann, B. Elibol, K.P. Bhatia, C. Wider, C. Vilarino-Guell, O.A. Ross, L.A. Brown, M. Castanedes-Casey, D.W. Dickson, Z.K. Wszolek, DCTN1 mutations in Perry syndrome, Nat. Genet. 41 (2009) 163e165. [5] E.J. Chung, J.H. Hwang, M.J. Lee, J.H. Hong, K.H. Ji, W.K. Yoo, S.J. Kim, H.K. Song, C.S. Lee, M.S. Lee, Y.J. Kim, Expansion of the clinicopathological and mutational spectrum of Perry syndrome, Park. Relat. Disord. 20 (2014) 388e393.
Takayasu Mishima Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan Shinsuke Fujioka Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan
Fig. 1. A pedigree of the family (A) and single photon emission computed tomography (SPECT) images (B, C) of Case 1. For the pedigree (A), standard pedigree symbols were used. Round symbols indicate females; squares indicate males; and diagonal lines indicate that the individual is deceased. Diamonds were used to disguise gender. The solid arrow represents Case 1 and the dashed arrow represents Case 2. Cases 1 and 2 were not described in the original paper reported by Farrer MJ et al. [4]. SPECT (B) captured before initiation of levodopa treatment shows hypoperfusion of the frontal and occipital cortexes with occipital lobe predominance. SPECT (C) captured after initiation of levodopa treatment reveals hypoperfusion of the frontal and occipital cortexes with frontal lobe predominance. The colors used in the SPECT images indicate the degree of depletion of blood: blue represents mild hypoperfusion; yellow represents moderate hypoperfusion; and red represents severe hypoperfusion.
We report two patients with Perry syndrome who developed ICDs and punding during the course of their illness. Perry syndrome and sporadic PD have been classified as distinct proteinopathies; TDP-43 proteinopathy and synucleinopathy, respectively; however, both disorders clinically present with similar phenotype including levodopa responsive parkinsonism and ICDs. Thus, common disease mechanisms could potentially explain the similarities. The information presented here is limited due to the small number of the patients and the retrospective nature of this study. Further investigations are warranted to clarify the mechanisms by which patients with Perry syndrome develop ICDs and punding.
Ryoichi Kurisaki Department of Neurology, National Hospital Organization Kumamoto Minami Hospital, Kumamoto, Japan Shozaburo Yanamoto Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan Masa-aki Higuchi Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan Jun Tsugawa Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan Jiro Fukae Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan Ryuji Neshige Neshige Neurological Clinic, Kurume, Japan Yoshio Tsuboi* Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan * Corresponding author. Department of Neurology, Fukuoka University 7-45-1, Nanakuma, Johnan-ku, Fukuoka-city, Fukuoka 814-0180, Japan. E-mail address: [email protected] (Y. Tsuboi).
11 August 2015
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Impulse control disorders and punding in Perry syndrome
Keywords: Perry syndrome Impulse control disorders Punding DCTN1 Frontal lobe dysfunction
Impulse control disorders (ICDs) are psychiatric conditions characterized by poor impulse control such as pathological gambling, hypersexuality, compulsive shopping, compulsive eating, explosive aggressive behavior, reckless driving, and reckless generosity [1,2]. Punding is defined as a complex prolonged, purposeless, and repetitive behavior. It has been increasingly recognized that ICDs and punding are more prevalent in patients with Parkinson's disease (PD) compared with a normal population [1], most likely due to dopaminergic therapy such as levodopa plus pramipexole and ropinirole [3]. Perry syndrome is a rare autosomal dominant neurodegenerative disorder caused by DCTN1 mutations. Parkinsonism is one of the most characteristic features of patients with Perry syndrome, along with apathy/depression, unexpected weight loss, and central hypoventilation [4]. Parkinsonism that occurs in patients with Perry syndrome generally responds well to high dose of dopaminergic therapy; however, to date, neither ICDs nor punding have been reported in patients with Perry syndrome. Herein, we describe two Japanese patients with Perry syndrome who developed ICDs and punding after initiation of dopaminergic therapy. Both patients were from the same family pedigree whom we previously reported (Fig. 1A). 1. Case 1 A 46-year-old man presented with depression. Subsequently, he experienced unexpected weight loss. Neurological examination at age 48 revealed parkinsonism, including bradykinesia, rigidity, and postural instability as well as depressive mood. Head MRI was unremarkable. A single photon emission computed tomography (SPECT) showed hyoperfusion of the frontal and occipital cortexes with occipital lobe predominance (Fig. 1B). He was once diagnosed as having PD and treated with pergolide, pramipexole, and selegiline, but these agents provided no clinical benefit. His gait had been gradually deteriorating. Therapy with levodopa/carbidopa (300 mg/day) was added at age 49, and his motor symptoms were moderately improved. However, he subsequently developed http://dx.doi.org/10.1016/j.parkreldis.2015.09.037 1353-8020/© 2015 Elsevier Ltd. All rights reserved.
prolonged, purposeless, and repetitive behavior, such as continuous touching of a mobile phone and playing video games all day. Repeated SPECT at age 50 revealed hyoperfusion in the frontal and occipital cortexes with more frontal lobe predominance (Fig. 1C) compared with findings at age 49. Genetic sequencing revealed that he had a DCTN1 G71A mutation. 2. Case 2 A 37-year-old woman, a relative of Case 1, developed depression. Neurologic examination at age 38 revealed that she had parkinsonism, including bradykinesia and rigidity. She was once diagnosed as having familial PD and started taking levodopa/carbidopa, which provided moderate benefit. However, as the effects of medication dissipated, she experienced wearing-off, mild dyskinesia and morning dystonia. She was started on pramipexole (3.5 mg/day) in addition to levodopa/carbidopa (650 mg/day), which ameliorated her motor symptoms. At age 39, she developed pathological gambling and compulsive shopping habits. She spent approximately $2000 per month. She also demonstrated compulsive eating and snacking. Her body weight kept increasing, presumably due to the compulsive eating. At age 40, she scored 29 of 30 points on the Mini-Mental State Examination, indicating she had normal cognition. At age 41, she developed repeated episodes of catatonia, which were successfully treated with clomipramine. She also demonstrated paranoia and emotional incontinence such as involuntary crying or uncontrollable episodes of crying and/or laughing. Despite treatment with a combination of antipsychotic drugs, her psychiatric symptoms, including ICDs, gradually deteriorated. Genetic sequencing confirmed to have a DCTN1 G71A mutation. Perry syndrome is often accompanied by behavior and/or personality abnormalities including apathy, lack of initiative, difficulty with attention, loss of interest, and withdrawal. Apathy is the most common behavior and/or personality abnormality in Perry syndrome, neither ICDs nor punding, however, have been reported in patients with Perry syndrome. Dopaminergic medications were reported to be risk factors for the development of ICDs and punding in patients with PD [3]. Both of our patients with Perry syndrome were treated with dopaminergic medications and subsequently developed psychiatric symptoms. The exact mechanism of ICDs and punding in PD remains to be identified; however, frontal lobe dysfunction is thought to be related to development of the symptoms [3]. It has been reported that frontotemporoparietal cortex dysfunction occurs in Perry syndrome [5]. Case 1 showed hypoperfusion of the frontal lobe cortex on the SPECT study. After levodopa replacement therapy, the frontal hypoperfusion was more obvious, indicating that punding seen in our patients could potentially be associated with frontal lobe dysfunction.
1382
Letter to the Editor / Parkinsonism and Related Disorders 21 (2015) 1381e1382
Financial disclosure/conflict of interest Nothing to disclose. Acknowledgments This work was supported by JSPS KAKENHI Grant Number 26860678.
References [1] M. Rodriguez-Violante, P. Gonzalez-Latapi, A. Cervantes-Arriaga, A. CamachoOrdonez, D. Weintraub, Impulse control and related disorders in Mexican Parkinson's disease patients, Park. Relat. Disord. 20 (2014) 907e910. [2] M.B. Callesen, D. Weintraub, M.F. Damholdt, A. Moller, Impulsive and compulsive behaviors among Danish patients with Parkinson's disease: prevalence, depression, and personality, Park. Relat. Disord. 20 (2014) 22e26. [3] A.H. Evans, R. Katzenschlager, D. Paviour, J.D. O'Sullivan, S. Appel, A.D. Lawrence, A.J. Lees, Punding in Parkinson's disease: its relation to the dopamine dysregulation syndrome, Mov. Disord. 19 (2004) 397e405. [4] M.J. Farrer, M.M. Hulihan, J.M. Kachergus, J.C. Dachsel, A.J. Stoessl, L.L. Grantier, S. Calne, D.B. Calne, B. Lechevalier, F. Chapon, Y. Tsuboi, T. Yamada, L. Gutmann, B. Elibol, K.P. Bhatia, C. Wider, C. Vilarino-Guell, O.A. Ross, L.A. Brown, M. Castanedes-Casey, D.W. Dickson, Z.K. Wszolek, DCTN1 mutations in Perry syndrome, Nat. Genet. 41 (2009) 163e165. [5] E.J. Chung, J.H. Hwang, M.J. Lee, J.H. Hong, K.H. Ji, W.K. Yoo, S.J. Kim, H.K. Song, C.S. Lee, M.S. Lee, Y.J. Kim, Expansion of the clinicopathological and mutational spectrum of Perry syndrome, Park. Relat. Disord. 20 (2014) 388e393.
Takayasu Mishima Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan Shinsuke Fujioka Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan
Fig. 1. A pedigree of the family (A) and single photon emission computed tomography (SPECT) images (B, C) of Case 1. For the pedigree (A), standard pedigree symbols were used. Round symbols indicate females; squares indicate males; and diagonal lines indicate that the individual is deceased. Diamonds were used to disguise gender. The solid arrow represents Case 1 and the dashed arrow represents Case 2. Cases 1 and 2 were not described in the original paper reported by Farrer MJ et al. [4]. SPECT (B) captured before initiation of levodopa treatment shows hypoperfusion of the frontal and occipital cortexes with occipital lobe predominance. SPECT (C) captured after initiation of levodopa treatment reveals hypoperfusion of the frontal and occipital cortexes with frontal lobe predominance. The colors used in the SPECT images indicate the degree of depletion of blood: blue represents mild hypoperfusion; yellow represents moderate hypoperfusion; and red represents severe hypoperfusion.
We report two patients with Perry syndrome who developed ICDs and punding during the course of their illness. Perry syndrome and sporadic PD have been classified as distinct proteinopathies; TDP-43 proteinopathy and synucleinopathy, respectively; however, both disorders clinically present with similar phenotype including levodopa responsive parkinsonism and ICDs. Thus, common disease mechanisms could potentially explain the similarities. The information presented here is limited due to the small number of the patients and the retrospective nature of this study. Further investigations are warranted to clarify the mechanisms by which patients with Perry syndrome develop ICDs and punding.
Ryoichi Kurisaki Department of Neurology, National Hospital Organization Kumamoto Minami Hospital, Kumamoto, Japan Shozaburo Yanamoto Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan Masa-aki Higuchi Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan Jun Tsugawa Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan Jiro Fukae Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan Ryuji Neshige Neshige Neurological Clinic, Kurume, Japan Yoshio Tsuboi* Department of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan * Corresponding author. Department of Neurology, Fukuoka University 7-45-1, Nanakuma, Johnan-ku, Fukuoka-city, Fukuoka 814-0180, Japan. E-mail address: [email protected] (Y. Tsuboi).
11 August 2015