- Email: [email protected]
Resolution of dopamine dysregulation syndrome following cessation of dopamine agonist therapy in Parkinson’s disease
Case Reports / Journal of Clinical Neuroscience 15 (2008) 205–208
205
rysm domes appeared to be composed of spindle-shaped fibrous cells and numerous apoptotic cells.8 The typical degeneration or absence of internal elastic membrane along with apoptosis in the smooth muscle cells in the aneurysm dome indicates a deterioration of the aneurysm wall; that might secondarily rupture. The treatment of these peripherally located aneurysms would include selective occlusion of the aneurysm or parent vessel occlusion, preferably at the site of the aneurysm. It may be done microsurgically or endovascularly. In those patients with associated hematoma, as in our patient, microsurgery would be the preferred method as a single procedure. We emphasize the need of attaining proximal control before approaching a ruptured aneurysm, and it would be natural to attain that on the normal sequence of microsurgical dissection. Fig. 3. Histology of the aneurysm sac.
The three cortical PICA aneurysms in the case series from Lewis had the same pattern.3 Most case reports describe distal PICA aneurysms located at the choroidal or communicating segment. The most common hemorrhage pattern of distal PICA aneurysms is the isolated fourth ventricular hemorrhage. Thus, recognition of a predominant component of fourth ventricular hemorrhage should raise the suspicion of the presence of an underlying aneurysm. Spontaneous cerebellar hemorrhage related to hypertension is classically described as centering over the dentate nucleus; although in clinical practice, vermal hematoma and fourth ventricular hematoma not related to aneurysms and arteriovenous malformation may be found in up to 32% of all spontaneous cerebellar hemorrhage patients.6 Etiologies other than aneurysm, arteriovenous malformation or hypertension, include diabetes, coagulation disorders or liver disease. Mycotic aneurysm is an uncommon cause for posterior fossa peripherally located aneurysms.7 Causes of aneurysm rupture remain to be investigated. In a histological study, the thin wall of the ruptured aneu-
References 1. Locksley HB. Report on the Cooperative Study of Intracranial Aneurysms and Subarachnoid Hemorrhage: Section V, part I. Natural history of subarachnoid hemorrhage, intracranial aneurysms and arteriovenous malformations: based on 6368 cases in the cooperative study. J Neurosurg 1966;25:219–39. 2. Horie N, Takahashi N, Furuichi S, et al. Ruptured aneurysm at the choroidal branch of the posterior inferior cerebellar artery: A case report and review of the literature. Surg Neurol 2003;60:540–4. 3. Lewis SB, Chang JD, Peace DA, et al. Distal posterior inferior cerebellar artery aneurysms: clinical features and management. J Neurosurg 2002;97:756–66. 4. Orakcioglu B, Schuknecht B, Otani N, et al. Distal posterior inferior cerebellar artery aneurysms: Clinical characteristics and surgical management. Acta Neurochir (Wien) 2005;147:1131–9. 5. Lasjaunias P, Berenstein A, ter Brugge KG. Surgical Neuroangiography. 2nd ed. Clinical Vascular Anatomy and Variation, Volume 1. Berlin: Springer Verlag; 2001, p.246–55. 6. Salvati M, Cervoni L, Raco A, et al. Spontaneous cerebellar hemorrhage: clinical remarks on 50 cases. Surg Neurol 2001;55:156–61. 7. Andaluz N, Pensak ML, Zuccarello M. Multiple peripheral aneurysms of the anterior inferior cerebellar artery. Acta Neurochir (Wien) 2005;147:419–22. 8. Pentimalli L, Modesti A, Vignati A, et al. Role of apoptosis in intracranial aneurysm rupture. J Neurosurg 2004;101:1018–25.
doi:10.1016/j.jocn.2006.05.009
Resolution of dopamine dysregulation syndrome following cessation of dopamine agonist therapy in Parkinson’s disease T.E. Kimber *, P.D. Thompson, M.A. Kiley Department of Neurology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia Received 22 February 2006; accepted 27 April 2006
*
Corresponding author. Tel.: +61 8 8222 5289; fax: +61 8 8222 2984. E-mail address: [email protected] (T.E. Kimber).
206
Case Reports / Journal of Clinical Neuroscience 15 (2008) 205–208
Abstract Repetitive and compulsive behaviours can occur in association with the use of dopaminergic medications for the treatment of Parkinson’s disease (PD). This syndrome has been referred to as the ‘dopamine dysregulation syndrome’. The prognosis for patients with this syndrome is unclear. We report five PD patients in whom the abnormal behaviours resolved completely after withdrawal of dopamine agonist therapy. We alert clinicians to the apparent role of dopamine agonists in this syndrome. In addition, we highlight the potential reversibility of the syndrome, its varied phenomenology and its potential pathophysiology. Crown Copyright 2006 Published by Elsevier Ltd. All rights reserved. Keywords: Parkinson’s disease; Dopamine dysregulation syndrome; Punding; Dopamine agonist; Dopaminergic therapy
1. Introduction Cognitive and behavioural phenomena are recognised side effects of dopaminergic therapies for the treatment of Parkinson’s disease (PD). Recent interest has focused on the range of abnormal behaviours exhibited by patients with young-onset PD taking large doses of dopaminergic medication. These behaviours include the repetitive performance of complex motor acts (such as collecting and sorting objects, dismantling and reassembling furniture, household equipment or electronic gadgets), pathological gambling and compulsive walking with akathisia.1,2 Some of these behaviours are similar to ‘punding’ originally described in amphetamine addicts.3,4 It has been suggested that perturbation of cerebral reward systems as the result of alterations in mesolimbic dopaminergic systems may represent a common mechanism. In contrast to reports of an unfavourable prognosis for PD patients who manifest such behaviours,1,5 we describe five PD patients in whom the abnormal behaviours resolved completely after withdrawal of dopamine agonist therapy. 2. Case reports Clinical details of the five cases are presented in Table 1. Case 1 is presented in more detail below as an illustrative case of these phenomena. 2.1. Case 1 A man, now aged 48 years, presented with tremor of the right arm and right leg at 34 years of age. He initially was reluctant to take medication and underwent a left thalamotomy at age 36 followed by left pallidotomy 3 years later. He commenced levodopa at age 39 and pergolide was commenced the following year. Symptoms were initially well controlled on medication. Motor fluctuations with wearing off and dyskinesia developed about 2 years after commencing levodopa. Peak dose dyskinesias were at times severe. He remained on pergolide 4 mg daily and levodopa 1000 mg daily plus a variable number of extra levodopa doses. Around the time that dyskinesias commenced, he developed a range of abnormal behaviours. He began to search his neighbours’ discarded rubbish looking for objects, such as radios and television sets, that he would
repeatedly dismantle and reassemble. He walked long distances without any clear destination or purpose in mind. Interest in sexual matters increased and despite being heterosexual, he felt compelled to loiter outside gay nightclubs. He became a pathological gambler leading to financial difficulties. He was assaulted, his marriage disintegrated and he required treatment for anxiety and depression. Pergolide was changed to cabergoline (4 mg daily). He remained on levodopa/benserazide 250/25 mg five times daily and entacapone 200 mg five times daily. About 4 years after the behavioural symptoms appeared, cabergoline was ceased. Within one month, there was a dramatic improvement in all the obsessive interests and compulsive behaviours without significant deterioration in motor symptoms. 3. Discussion Each of these patients manifested disabling repetitive behaviours that placed considerable strain on personal relationships and, in the case of those with problem gambling, resulted in considerable financial loss. In each case, the abnormal behaviours developed during the combination of levodopa and dopamine agonist therapy and improved promptly after withdrawal of the dopamine agonist. In several of the cases, the behaviours occurred at relatively modest levels of dopaminergic stimulation. All of the patients preferred the state of dopaminergic overstimulation, ostensibly because this optimized motor function, despite concurrent and sometimes severe peakdose dyskinesias, yet in only one case did the severity of parkinsonism deteriorate after cessation of the agonist. A common feature was the sense of dysphoria felt in the ‘off’ motor state (often disproportionate to the degree of off-state motor dysfunction). It seems likely that mood changes were more important than motor state in determining the level of dopaminergic stimulation sought by the patient. As a result, and as reported in previous series, patients begin to self-medicate with dopaminergic drugs, exacerbating both the motor and cognitive side effects of medication.2 In recent years, there has been an increasing awareness of repetitive and compulsive behaviours in association with dopaminergic drug therapy for PD, particularly in male patients with young-onset disease.2
Case Reports / Journal of Clinical Neuroscience 15 (2008) 205–208
207
Table 1 Clinical characteristics of patients and description of abnormal behaviours Age/sex
Age at disease onset
Behaviour
Medications
48/M
34
50/F
43
L-dopa 1250 mg/day, pergolide 4 mg/day (later changed to cabergoline 4 mg/day), entacapone 1000 mg/day L-dopa 800 mg/day, pergolide 3 mg/day
54/M
51
60/M
57
70/M
63
Repeatedly dismantling and reassembling discarded radios and TV sets; purposeless wandering; heightened interest in sex and gambling. Marked improvement after cessation of cabergoline Compulsive gambling (poker machines, punting) resulting in loss of over $200 000 over several years. Urge to gamble completely resolved after cessation of pergolide Preoccupied with placement of stereo speakers in lounge room (continually moving them to improve sound quality); heightened interest in sex causing marital conflict; uncharacteristic interest in gambling (poker machines). Complete resolution after cessation of cabergoline Uncharacteristically preoccupied with buying music CDs (up to 7 per week); repeatedly checking gutters and downpipes of his house, believing them (incorrectly) to be inadequate. Significant improvement after cessation of cabergoline Compulsive eating (resulting in 30-kg weight gain); frequent and inappropriate use of different languages when speaking; flight of ideas; uncharacteristic interest in gambling (poker machines) resulting in considerable financial loss; gave away money inappropriately to people he knew slightly. Complete resolution after cessation of cabergoline. Patient recalls feeling ‘frenetic’ when taking cabergoline
This phenomenon has been variously described as the ‘dopamine dysregulation syndrome’ and the ‘hedonistic homeostatic dysregulation syndrome’. Behaviours manifested by patients with this syndrome vary from so-called ‘appetitive’ behaviours (such as binge eating, hypersexuality, pathological gambling) to repetitive and apparently purposeless motor behaviours, also known as ‘punding’ (such as the repeated ordering or dismantling and reassembling of objects). ‘Punding’ is a Swedish term (meaning ‘blockhead’) originally coined to describe such behaviours in amphetamine addicts.3 These behaviours included manipulation of equipment (as illustrated by case 1 of the present series), and the repetitive tidying and arranging of objects. Authors have differed on the question of how to characterise ‘punding’ behaviours phenomenologically. Rylander characterised such behaviours as ‘automatic behaviours’ rather than compulsions, since the addicts did not generally report a compulsive need to perform the behaviour or relief of anxiety by performing them.3 Others have conceptualised punding as a form of compulsion.6 For our part, we considered the behaviours in the present series, whether appetitive or punding in type, to be ‘compulsions’, in that they were repetitive, uncontrolled and either maladaptive (eg. problem gambling) or purposeless (eg. repetitive dismantling and reassembling of objects). The repertoire of abnormal behaviours manifested by PD patients in the ‘dopamine dysregulation syndrome’ is broader than is typically described in either drug addicts with punding or patients with obsessive-compulsive disorder (OCD). In PD patients, obsessive interest in sex and gambling, not described in the original descriptions of punding, are common features. In PD patients who manifest repetitive and purposeless motor behaviours, the type of
L-dopa 300 mg/day, cabergoline 4 mg/day
L-dopa 400 mg/day, cabergoline 4 mg/day
L-dopa 400 mg/day, cabergoline 8 mg/day
behaviour often reflects the patient’s previous hobbies or occupation, whereas in drug addicts with punding, no such association was reported. Similarly, the compulsions seen in PD patients and those with OCD seem quite distinct. The patients reported here did not report intrusive thoughts in association with their compulsions, nor any sense of relief of anxiety by carrying them out, in contrast to OCD. The pathophysiological basis of these abnormal behaviours in PD patients is a topic of ongoing speculation and study.7 It appears likely they arise from aberrant stimulation of dopamine receptors within mesolimbic circuits that are involved in novelty-seeking and reward-seeking behaviour. The more varied clinical manifestations of this aberrant stimulation in PD patients, compared with drug addicts, may reflect the fact that there is already underlying denervation of these dopaminergic circuits in PD. In summary, it is likely that the ‘dopamine dysregulation syndrome’ is an under-recognised complication of dopaminergic therapy in PD patients, particularly in younger patients receiving a combination of levodopa and a dopamine agonist. Clinicians treating patients with PD should be aware of this syndrome and systematically enquire about symptoms in their patients at risk. In our experience, symptoms improve promptly following weaning and cessation of the dopamine agonist. References 1. Giovannoni G, O’Sullivan JD, Turner K, et al. Hedonistic homeostatic dysregulation in patients with Parkinson’s disease on dopamine replacement therapies. J Neurol Neurosurg Psychiatry 2000;68:423–8. 2. Evans AH, Katzenchlager R, Paviour D, et al. Punding in Parkinson’s disease: its relation to the dopamine dysregulation syndrome. Mov Disord 2004;19:397–405.
208
Case Reports / Journal of Clinical Neuroscience 15 (2008) 208–210
3. Rylander G. Psychoses and the punding and choreiform syndromes in addiction to central stimulant drugs. Psychiatr Neurol Neurochir 1972;75:203–12. 4. Schiørring E. Psychopathology induced by ‘‘speed drugs’’. Pharmacol Biochem Behav 1981;14(Suppl.):109–22.
5. Kurlan R. Disabling repetitive behaviours in Parkinson’s disease. Mov Disord 2004;19:433–69. 6. Stein DJ. Obsessive compulsive disorder. Lancet 2002;360:397–405. 7. Voon V. Repetition, repetition, and repetition: compulsive and punding behaviours in Parkinson’s disease. Mov Disord 2004;19:367–70.
doi:10.1016/j.jocn.2006.04.019
Meningeal extramedullary haematopoiesis mimicking subdural hematoma Kagan Tun a
a,*
, Erkan Kaptanoglu a, Ramazan C. Celikmez a, Oktay Gurcan a, Omer Faruk Turkoglu a, Lale Kutluay b
Ankara Numune Education and Research Hospital, Department of Neurosurgery, Ankara, Turkey b General Pathology Center, Ankara, Turkey Received 7 May 2006; accepted 25 June 2006
Abstract Extramedullary haematopoiesis is a compensatory phenomenon in diseases where erythrocyte production is diminished or destruction is accelerated. The authors describe a rare case of meningeal extramedullary haematopoiesis mimicking subdural hematoma. CT scan revealed a hyperdense subdural lesion at the right frontal region following head injury. The patient was operated on and the pathological examination of the subdural lesion showed extramedullary haematopoiesis. 2007 Elsevier Ltd. All rights reserved. Keywords: Extramedullary haematopoiesis; Subdural hematoma; Radiotherapy
1. Introduction Extramedullary haematopoiesis (EMH) is a response to diseases that results in hemolysis, or in situations when the normal function of bone marrow and formation of red blood cells is impaired.1,2 EMH predominantly affects the reticuloendothelial system including the spleen, liver and lymph nodes, and less frequently, the kidneys, skin, heart, pleura and mesentery.3 Meningeal involvement is rare and in these cases tumor-like masses of EMH usually affect the spinal canal.4,5 Very few cases of intracranial involvement have been reported in the literature.6 We present a patient with EMH who was operated on for an incorrect diagnosis of subdural hematoma. 2. Case report A 51-year-old woman was admitted to emergency services with a head injury. Glasgow Coma Scale score *
Corresponding author. Present address: Hilal Mah, 65, sok, No.: 9/6 06550 Cankaya, Ankara, Turkey. Tel.: +90 312 4414087. E-mail address: [email protected] (K. Tun).
(GCS) of the patient was 10 on hospital admission. Neurological status deteriorated rapidly and noncontrast axial CT scan showed a hyperdense subdural crescent with the appearance of blood at the right frontal region with ventricular compression and brain shift. Brain edema implying an intracranial mass was not observed (Fig. 1). The patient was diagnosed with a subdural hematoma and an emergency operation was performed. Physical examination demonstrated an enlarged spleen. The results of routine hematological tests were a white cell count of 6040/cu.mm, hemoglobin of 11 mg/dL, hematocrit of 37% and platelets of 107 k/Ul (normal 150–450). At operation, an extra-axial subdural mass was observed and totally removed rather than a hematoma. The specimen sent to pathological examination consisted of irregular, hemorrhagic tissues measuring 3 · 1.5 · 1 cm in toto. Microscopic examination showed a nodular lesion consisting of bone marrow cells embedded in a vascular stroma. The cells consisted of erythroid and myeloid cell lines, plasmacytoid cell groups and megakaryocytes. The lesion was diagnosed as extramedullary hematopoiesis (Fig. 2).
205
rysm domes appeared to be composed of spindle-shaped fibrous cells and numerous apoptotic cells.8 The typical degeneration or absence of internal elastic membrane along with apoptosis in the smooth muscle cells in the aneurysm dome indicates a deterioration of the aneurysm wall; that might secondarily rupture. The treatment of these peripherally located aneurysms would include selective occlusion of the aneurysm or parent vessel occlusion, preferably at the site of the aneurysm. It may be done microsurgically or endovascularly. In those patients with associated hematoma, as in our patient, microsurgery would be the preferred method as a single procedure. We emphasize the need of attaining proximal control before approaching a ruptured aneurysm, and it would be natural to attain that on the normal sequence of microsurgical dissection. Fig. 3. Histology of the aneurysm sac.
The three cortical PICA aneurysms in the case series from Lewis had the same pattern.3 Most case reports describe distal PICA aneurysms located at the choroidal or communicating segment. The most common hemorrhage pattern of distal PICA aneurysms is the isolated fourth ventricular hemorrhage. Thus, recognition of a predominant component of fourth ventricular hemorrhage should raise the suspicion of the presence of an underlying aneurysm. Spontaneous cerebellar hemorrhage related to hypertension is classically described as centering over the dentate nucleus; although in clinical practice, vermal hematoma and fourth ventricular hematoma not related to aneurysms and arteriovenous malformation may be found in up to 32% of all spontaneous cerebellar hemorrhage patients.6 Etiologies other than aneurysm, arteriovenous malformation or hypertension, include diabetes, coagulation disorders or liver disease. Mycotic aneurysm is an uncommon cause for posterior fossa peripherally located aneurysms.7 Causes of aneurysm rupture remain to be investigated. In a histological study, the thin wall of the ruptured aneu-
References 1. Locksley HB. Report on the Cooperative Study of Intracranial Aneurysms and Subarachnoid Hemorrhage: Section V, part I. Natural history of subarachnoid hemorrhage, intracranial aneurysms and arteriovenous malformations: based on 6368 cases in the cooperative study. J Neurosurg 1966;25:219–39. 2. Horie N, Takahashi N, Furuichi S, et al. Ruptured aneurysm at the choroidal branch of the posterior inferior cerebellar artery: A case report and review of the literature. Surg Neurol 2003;60:540–4. 3. Lewis SB, Chang JD, Peace DA, et al. Distal posterior inferior cerebellar artery aneurysms: clinical features and management. J Neurosurg 2002;97:756–66. 4. Orakcioglu B, Schuknecht B, Otani N, et al. Distal posterior inferior cerebellar artery aneurysms: Clinical characteristics and surgical management. Acta Neurochir (Wien) 2005;147:1131–9. 5. Lasjaunias P, Berenstein A, ter Brugge KG. Surgical Neuroangiography. 2nd ed. Clinical Vascular Anatomy and Variation, Volume 1. Berlin: Springer Verlag; 2001, p.246–55. 6. Salvati M, Cervoni L, Raco A, et al. Spontaneous cerebellar hemorrhage: clinical remarks on 50 cases. Surg Neurol 2001;55:156–61. 7. Andaluz N, Pensak ML, Zuccarello M. Multiple peripheral aneurysms of the anterior inferior cerebellar artery. Acta Neurochir (Wien) 2005;147:419–22. 8. Pentimalli L, Modesti A, Vignati A, et al. Role of apoptosis in intracranial aneurysm rupture. J Neurosurg 2004;101:1018–25.
doi:10.1016/j.jocn.2006.05.009
Resolution of dopamine dysregulation syndrome following cessation of dopamine agonist therapy in Parkinson’s disease T.E. Kimber *, P.D. Thompson, M.A. Kiley Department of Neurology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia Received 22 February 2006; accepted 27 April 2006
*
Corresponding author. Tel.: +61 8 8222 5289; fax: +61 8 8222 2984. E-mail address: [email protected] (T.E. Kimber).
206
Case Reports / Journal of Clinical Neuroscience 15 (2008) 205–208
Abstract Repetitive and compulsive behaviours can occur in association with the use of dopaminergic medications for the treatment of Parkinson’s disease (PD). This syndrome has been referred to as the ‘dopamine dysregulation syndrome’. The prognosis for patients with this syndrome is unclear. We report five PD patients in whom the abnormal behaviours resolved completely after withdrawal of dopamine agonist therapy. We alert clinicians to the apparent role of dopamine agonists in this syndrome. In addition, we highlight the potential reversibility of the syndrome, its varied phenomenology and its potential pathophysiology. Crown Copyright 2006 Published by Elsevier Ltd. All rights reserved. Keywords: Parkinson’s disease; Dopamine dysregulation syndrome; Punding; Dopamine agonist; Dopaminergic therapy
1. Introduction Cognitive and behavioural phenomena are recognised side effects of dopaminergic therapies for the treatment of Parkinson’s disease (PD). Recent interest has focused on the range of abnormal behaviours exhibited by patients with young-onset PD taking large doses of dopaminergic medication. These behaviours include the repetitive performance of complex motor acts (such as collecting and sorting objects, dismantling and reassembling furniture, household equipment or electronic gadgets), pathological gambling and compulsive walking with akathisia.1,2 Some of these behaviours are similar to ‘punding’ originally described in amphetamine addicts.3,4 It has been suggested that perturbation of cerebral reward systems as the result of alterations in mesolimbic dopaminergic systems may represent a common mechanism. In contrast to reports of an unfavourable prognosis for PD patients who manifest such behaviours,1,5 we describe five PD patients in whom the abnormal behaviours resolved completely after withdrawal of dopamine agonist therapy. 2. Case reports Clinical details of the five cases are presented in Table 1. Case 1 is presented in more detail below as an illustrative case of these phenomena. 2.1. Case 1 A man, now aged 48 years, presented with tremor of the right arm and right leg at 34 years of age. He initially was reluctant to take medication and underwent a left thalamotomy at age 36 followed by left pallidotomy 3 years later. He commenced levodopa at age 39 and pergolide was commenced the following year. Symptoms were initially well controlled on medication. Motor fluctuations with wearing off and dyskinesia developed about 2 years after commencing levodopa. Peak dose dyskinesias were at times severe. He remained on pergolide 4 mg daily and levodopa 1000 mg daily plus a variable number of extra levodopa doses. Around the time that dyskinesias commenced, he developed a range of abnormal behaviours. He began to search his neighbours’ discarded rubbish looking for objects, such as radios and television sets, that he would
repeatedly dismantle and reassemble. He walked long distances without any clear destination or purpose in mind. Interest in sexual matters increased and despite being heterosexual, he felt compelled to loiter outside gay nightclubs. He became a pathological gambler leading to financial difficulties. He was assaulted, his marriage disintegrated and he required treatment for anxiety and depression. Pergolide was changed to cabergoline (4 mg daily). He remained on levodopa/benserazide 250/25 mg five times daily and entacapone 200 mg five times daily. About 4 years after the behavioural symptoms appeared, cabergoline was ceased. Within one month, there was a dramatic improvement in all the obsessive interests and compulsive behaviours without significant deterioration in motor symptoms. 3. Discussion Each of these patients manifested disabling repetitive behaviours that placed considerable strain on personal relationships and, in the case of those with problem gambling, resulted in considerable financial loss. In each case, the abnormal behaviours developed during the combination of levodopa and dopamine agonist therapy and improved promptly after withdrawal of the dopamine agonist. In several of the cases, the behaviours occurred at relatively modest levels of dopaminergic stimulation. All of the patients preferred the state of dopaminergic overstimulation, ostensibly because this optimized motor function, despite concurrent and sometimes severe peakdose dyskinesias, yet in only one case did the severity of parkinsonism deteriorate after cessation of the agonist. A common feature was the sense of dysphoria felt in the ‘off’ motor state (often disproportionate to the degree of off-state motor dysfunction). It seems likely that mood changes were more important than motor state in determining the level of dopaminergic stimulation sought by the patient. As a result, and as reported in previous series, patients begin to self-medicate with dopaminergic drugs, exacerbating both the motor and cognitive side effects of medication.2 In recent years, there has been an increasing awareness of repetitive and compulsive behaviours in association with dopaminergic drug therapy for PD, particularly in male patients with young-onset disease.2
Case Reports / Journal of Clinical Neuroscience 15 (2008) 205–208
207
Table 1 Clinical characteristics of patients and description of abnormal behaviours Age/sex
Age at disease onset
Behaviour
Medications
48/M
34
50/F
43
L-dopa 1250 mg/day, pergolide 4 mg/day (later changed to cabergoline 4 mg/day), entacapone 1000 mg/day L-dopa 800 mg/day, pergolide 3 mg/day
54/M
51
60/M
57
70/M
63
Repeatedly dismantling and reassembling discarded radios and TV sets; purposeless wandering; heightened interest in sex and gambling. Marked improvement after cessation of cabergoline Compulsive gambling (poker machines, punting) resulting in loss of over $200 000 over several years. Urge to gamble completely resolved after cessation of pergolide Preoccupied with placement of stereo speakers in lounge room (continually moving them to improve sound quality); heightened interest in sex causing marital conflict; uncharacteristic interest in gambling (poker machines). Complete resolution after cessation of cabergoline Uncharacteristically preoccupied with buying music CDs (up to 7 per week); repeatedly checking gutters and downpipes of his house, believing them (incorrectly) to be inadequate. Significant improvement after cessation of cabergoline Compulsive eating (resulting in 30-kg weight gain); frequent and inappropriate use of different languages when speaking; flight of ideas; uncharacteristic interest in gambling (poker machines) resulting in considerable financial loss; gave away money inappropriately to people he knew slightly. Complete resolution after cessation of cabergoline. Patient recalls feeling ‘frenetic’ when taking cabergoline
This phenomenon has been variously described as the ‘dopamine dysregulation syndrome’ and the ‘hedonistic homeostatic dysregulation syndrome’. Behaviours manifested by patients with this syndrome vary from so-called ‘appetitive’ behaviours (such as binge eating, hypersexuality, pathological gambling) to repetitive and apparently purposeless motor behaviours, also known as ‘punding’ (such as the repeated ordering or dismantling and reassembling of objects). ‘Punding’ is a Swedish term (meaning ‘blockhead’) originally coined to describe such behaviours in amphetamine addicts.3 These behaviours included manipulation of equipment (as illustrated by case 1 of the present series), and the repetitive tidying and arranging of objects. Authors have differed on the question of how to characterise ‘punding’ behaviours phenomenologically. Rylander characterised such behaviours as ‘automatic behaviours’ rather than compulsions, since the addicts did not generally report a compulsive need to perform the behaviour or relief of anxiety by performing them.3 Others have conceptualised punding as a form of compulsion.6 For our part, we considered the behaviours in the present series, whether appetitive or punding in type, to be ‘compulsions’, in that they were repetitive, uncontrolled and either maladaptive (eg. problem gambling) or purposeless (eg. repetitive dismantling and reassembling of objects). The repertoire of abnormal behaviours manifested by PD patients in the ‘dopamine dysregulation syndrome’ is broader than is typically described in either drug addicts with punding or patients with obsessive-compulsive disorder (OCD). In PD patients, obsessive interest in sex and gambling, not described in the original descriptions of punding, are common features. In PD patients who manifest repetitive and purposeless motor behaviours, the type of
L-dopa 300 mg/day, cabergoline 4 mg/day
L-dopa 400 mg/day, cabergoline 4 mg/day
L-dopa 400 mg/day, cabergoline 8 mg/day
behaviour often reflects the patient’s previous hobbies or occupation, whereas in drug addicts with punding, no such association was reported. Similarly, the compulsions seen in PD patients and those with OCD seem quite distinct. The patients reported here did not report intrusive thoughts in association with their compulsions, nor any sense of relief of anxiety by carrying them out, in contrast to OCD. The pathophysiological basis of these abnormal behaviours in PD patients is a topic of ongoing speculation and study.7 It appears likely they arise from aberrant stimulation of dopamine receptors within mesolimbic circuits that are involved in novelty-seeking and reward-seeking behaviour. The more varied clinical manifestations of this aberrant stimulation in PD patients, compared with drug addicts, may reflect the fact that there is already underlying denervation of these dopaminergic circuits in PD. In summary, it is likely that the ‘dopamine dysregulation syndrome’ is an under-recognised complication of dopaminergic therapy in PD patients, particularly in younger patients receiving a combination of levodopa and a dopamine agonist. Clinicians treating patients with PD should be aware of this syndrome and systematically enquire about symptoms in their patients at risk. In our experience, symptoms improve promptly following weaning and cessation of the dopamine agonist. References 1. Giovannoni G, O’Sullivan JD, Turner K, et al. Hedonistic homeostatic dysregulation in patients with Parkinson’s disease on dopamine replacement therapies. J Neurol Neurosurg Psychiatry 2000;68:423–8. 2. Evans AH, Katzenchlager R, Paviour D, et al. Punding in Parkinson’s disease: its relation to the dopamine dysregulation syndrome. Mov Disord 2004;19:397–405.
208
Case Reports / Journal of Clinical Neuroscience 15 (2008) 208–210
3. Rylander G. Psychoses and the punding and choreiform syndromes in addiction to central stimulant drugs. Psychiatr Neurol Neurochir 1972;75:203–12. 4. Schiørring E. Psychopathology induced by ‘‘speed drugs’’. Pharmacol Biochem Behav 1981;14(Suppl.):109–22.
5. Kurlan R. Disabling repetitive behaviours in Parkinson’s disease. Mov Disord 2004;19:433–69. 6. Stein DJ. Obsessive compulsive disorder. Lancet 2002;360:397–405. 7. Voon V. Repetition, repetition, and repetition: compulsive and punding behaviours in Parkinson’s disease. Mov Disord 2004;19:367–70.
doi:10.1016/j.jocn.2006.04.019
Meningeal extramedullary haematopoiesis mimicking subdural hematoma Kagan Tun a
a,*
, Erkan Kaptanoglu a, Ramazan C. Celikmez a, Oktay Gurcan a, Omer Faruk Turkoglu a, Lale Kutluay b
Ankara Numune Education and Research Hospital, Department of Neurosurgery, Ankara, Turkey b General Pathology Center, Ankara, Turkey Received 7 May 2006; accepted 25 June 2006
Abstract Extramedullary haematopoiesis is a compensatory phenomenon in diseases where erythrocyte production is diminished or destruction is accelerated. The authors describe a rare case of meningeal extramedullary haematopoiesis mimicking subdural hematoma. CT scan revealed a hyperdense subdural lesion at the right frontal region following head injury. The patient was operated on and the pathological examination of the subdural lesion showed extramedullary haematopoiesis. 2007 Elsevier Ltd. All rights reserved. Keywords: Extramedullary haematopoiesis; Subdural hematoma; Radiotherapy
1. Introduction Extramedullary haematopoiesis (EMH) is a response to diseases that results in hemolysis, or in situations when the normal function of bone marrow and formation of red blood cells is impaired.1,2 EMH predominantly affects the reticuloendothelial system including the spleen, liver and lymph nodes, and less frequently, the kidneys, skin, heart, pleura and mesentery.3 Meningeal involvement is rare and in these cases tumor-like masses of EMH usually affect the spinal canal.4,5 Very few cases of intracranial involvement have been reported in the literature.6 We present a patient with EMH who was operated on for an incorrect diagnosis of subdural hematoma. 2. Case report A 51-year-old woman was admitted to emergency services with a head injury. Glasgow Coma Scale score *
Corresponding author. Present address: Hilal Mah, 65, sok, No.: 9/6 06550 Cankaya, Ankara, Turkey. Tel.: +90 312 4414087. E-mail address: [email protected] (K. Tun).
(GCS) of the patient was 10 on hospital admission. Neurological status deteriorated rapidly and noncontrast axial CT scan showed a hyperdense subdural crescent with the appearance of blood at the right frontal region with ventricular compression and brain shift. Brain edema implying an intracranial mass was not observed (Fig. 1). The patient was diagnosed with a subdural hematoma and an emergency operation was performed. Physical examination demonstrated an enlarged spleen. The results of routine hematological tests were a white cell count of 6040/cu.mm, hemoglobin of 11 mg/dL, hematocrit of 37% and platelets of 107 k/Ul (normal 150–450). At operation, an extra-axial subdural mass was observed and totally removed rather than a hematoma. The specimen sent to pathological examination consisted of irregular, hemorrhagic tissues measuring 3 · 1.5 · 1 cm in toto. Microscopic examination showed a nodular lesion consisting of bone marrow cells embedded in a vascular stroma. The cells consisted of erythroid and myeloid cell lines, plasmacytoid cell groups and megakaryocytes. The lesion was diagnosed as extramedullary hematopoiesis (Fig. 2).