Journal of the Neurological Sciences 350 (2015) 103–104
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor
Diagnosis and treatment of restless legs syndrome in progressive supranuclear palsy Marcello Moccia a, Marina Picillo b, Roberto Erro c,d, Roberto Allocca a, Paolo Barone b, Carmine Vitale e,f,⁎ a
Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Naples, Italy Center for Neurodegenerative Diseases (CEMAND), Neuroscience Section, Department of Medicine, University of Salerno, Italy Sobell Department of Motor Neuroscience and Movement Disorders, University College London, London, UK d Department of Neurological and Movement Sciences, University of Verona, Verona, Italy e University of Naples Parthenope, Naples, Italy f IDC Hermitage-Capodimonte, Naples, Italy b c
a r t i c l e
i n f o
Article history: Received 30 September 2014 Received in revised form 11 January 2015 Accepted 20 January 2015 Available online 26 January 2015
a b s t r a c t Restless legs syndrome (RLS) has only been recently investigated in a small cohort of progressive supranuclear palsy (PSP) patients and it has been reported to have variable prevalence (among 3.7–58%). However little is known about its management. Here, we report a case of severe RLS occurring during the course of PSP. Diagnostic issues and therapeutic approaches are discussed. © 2015 Elsevier B.V. All rights reserved.
Keywords: Progressive supranuclear palsy PSP Restless legs syndrome RLS Rotigotine
Progressive supranuclear palsy (PSP) is a heterogeneous clinical syndrome whose diagnosis can be challenging, requiring about 4 years from symptom onset [1]. Considering that early clinical features are often subtle and that many patients with PSP may remain misdiagnosed for much of the course of their disease, PSP-tau pathology is a core feature of a definite PSP diagnosis [1]. Nevertheless, a clinically probable diagnosis can be performed in the presence of a gradually progressive disorder characterized by vertical supranuclear palsy and prominent postural instability with falls within a year of disease onset [2]. However, PSP–parkinsonism (PSP–P), one of possible clinical variants, is characterized by a typical parkinsonism in early phases, and usually takes almost 4–6 years to reveal a typical PSP phenomenology [1]. It is noteworthy that PSP may present non-motor features, some of which have been widely studied (i.e. dysexecutive syndrome), while others deserve further investigation. In particular, restless legs syndrome (RLS) has been reported to occur in PSP with a 3.7–58% range by two different studies, and no further clinical details or therapeutical approaches have been described [3,4]. In this view, we report a case of RLS occurring in PSP–P, discuss its diagnosis and treatment, and propose a possible pathophysiological explanation for such a phenomenon. ⁎ Corresponding author. Tel.: +39 0817462670; fax: +39 0817464348. E-mail address: [email protected] (C. Vitale).
http://dx.doi.org/10.1016/j.jns.2015.01.025 0022-510X/© 2015 Elsevier B.V. All rights reserved.
A 57-year-old man received a diagnosis of Parkinson's disease (PD) because of rest tremor and bradykinesia in his upper right limb. A [123I]beta-CIT SPECT/CT scan showed a striatal DAT reduction mainly in the putamen compared to the caudate (left N right). Dopaminergic treatment was started with rotigotine (8 mg per day) with a slight benefit. As adjunctive treatment due to progressive motor worsening, after 1 year, L-Dopa/Carbidopa was started (up to 800 mg per day), with moderate clinical response. At 60 years, the patient presented a progressive postural instability with frequent falls and was hence sent to our department. On examination, there was an asymmetric bradykinetic-rigid parkinsonism and supranuclear upgaze eye palsy, with a motor score of 21 in the Unified Parkinson's Disease Rating Scale (UPDRS part III). Brain MRI showed a thinning of the anteroposterior diameter of the rostral midbrain tegmentum, with an abnormal shape resembling the “hummingbird sign”. A diagnosis of possible PSP–P was made. Considering previous reports on response to dopaminergic drugs in PSP [1,2], we suggested to progressively withdraw rotigotine and to continue L-Dopa treatment at the previous dosage (800 mg per day). Rotigotine was therefore gradually tapered by 2 mg per week and eventually discontinued. After two weeks of rotigotine progressive reduction, at 4 mg daily dosage, the patient reported an urge to move the legs together with unpleasant sensations of burning and throbbing in the lower limbs. Symptoms were present throughout the day to
104
Letter to the Editor
worsen typically in the evening. They were partly relieved by movement. Essential diagnostic criteria for RLS were fulfilled [5]. Symptoms were severe according to the International RLS Group Rating Scale (27/40), and sleep impairment was scored 10 by the Pittsburgh sleep quality index and 13 by the Epworth sleepiness scale. Secondary causes of RLS were ruled out (i.e. iron deficiency, neuropathy or kidney disease). Rotigotine was started again (up to 6 mg per day) with complete symptom relief, but without any efficacy on motor symptoms. RLS is associated with a modified central dopaminergic neurotransmission and, thus, is expected to be more frequent in neurodegenerative disorders with loss of dopaminergic neurons [5]. Our case showed that RLS occurring in PSP might be severe enough to require specific treatments. Rotigotine (6 mg per day) resulted in a marked benefit, whereas L-Dopa
failed to ameliorate RLS symptoms in our patient. In PSP–P a moderate or good improvement in bradykinesia and rigidity may follow the initiation of dopaminergic drugs. However, secondary unresponsiveness is to be expected within a few years from symptom onset [2]. Notably, our case showed that the dopaminergic benefit for RLS occurring in PSP–P is maintained during disease course, suggesting a functional imbalance more than the neurodegenerative alterations in RLS pathogenesis. Therefore, the efficacy of other dopamine agonists cannot be excluded, and further investigations are needed. Moreover, this benefit from dopamine-agonist treatment can possibly lead to a PD misdiagnosis considering that a poor response to dopaminergic drugs is typical of PSP. In particular, our case complained of a significant worsening after dopamine agonist progressive tapering, and only accurate clinical history and examination showed that it was not strictly related to motor symptoms, but to RLS-related symptoms.
Finally, we have to acknowledge that the main limitation of the current report is the absence of pathology. In conclusion, RLS should be considered in patients with PSP, as it may significantly affect quality of life and is potentially amenable to treatments.
Conflict of interest None of the authors have any conflicts of interest to state.
Acknowledgements The present study received no specific funding.
References [1] Burn DJ, Lees AJ. Progressive supranuclear palsy: where are we now? Lancet Neurol 2000;1:359–69. [2] Williams DR, Lees AJ. Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol 2009;8:270–9. [3] Bhalsing K, Suresh K, Muthane UB, et al. Prevalence and profile of Restless Legs Syndrome in Parkinson's disease and other neurodegenerative disorders: a case– control study. Parkinsonism Relat Disord 2013;19:426–30. [4] Gama RL, Távora DG, Bomfim RC, et al. Sleep disturbances and brain MRI morphometry in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy — a comparative study. Parkinsonism Relat Disord 2010;16:275–9. [5] Allen RP, Picchietti D, Hening WA, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4:101–19.
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor
Diagnosis and treatment of restless legs syndrome in progressive supranuclear palsy Marcello Moccia a, Marina Picillo b, Roberto Erro c,d, Roberto Allocca a, Paolo Barone b, Carmine Vitale e,f,⁎ a
Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Naples, Italy Center for Neurodegenerative Diseases (CEMAND), Neuroscience Section, Department of Medicine, University of Salerno, Italy Sobell Department of Motor Neuroscience and Movement Disorders, University College London, London, UK d Department of Neurological and Movement Sciences, University of Verona, Verona, Italy e University of Naples Parthenope, Naples, Italy f IDC Hermitage-Capodimonte, Naples, Italy b c
a r t i c l e
i n f o
Article history: Received 30 September 2014 Received in revised form 11 January 2015 Accepted 20 January 2015 Available online 26 January 2015
a b s t r a c t Restless legs syndrome (RLS) has only been recently investigated in a small cohort of progressive supranuclear palsy (PSP) patients and it has been reported to have variable prevalence (among 3.7–58%). However little is known about its management. Here, we report a case of severe RLS occurring during the course of PSP. Diagnostic issues and therapeutic approaches are discussed. © 2015 Elsevier B.V. All rights reserved.
Keywords: Progressive supranuclear palsy PSP Restless legs syndrome RLS Rotigotine
Progressive supranuclear palsy (PSP) is a heterogeneous clinical syndrome whose diagnosis can be challenging, requiring about 4 years from symptom onset [1]. Considering that early clinical features are often subtle and that many patients with PSP may remain misdiagnosed for much of the course of their disease, PSP-tau pathology is a core feature of a definite PSP diagnosis [1]. Nevertheless, a clinically probable diagnosis can be performed in the presence of a gradually progressive disorder characterized by vertical supranuclear palsy and prominent postural instability with falls within a year of disease onset [2]. However, PSP–parkinsonism (PSP–P), one of possible clinical variants, is characterized by a typical parkinsonism in early phases, and usually takes almost 4–6 years to reveal a typical PSP phenomenology [1]. It is noteworthy that PSP may present non-motor features, some of which have been widely studied (i.e. dysexecutive syndrome), while others deserve further investigation. In particular, restless legs syndrome (RLS) has been reported to occur in PSP with a 3.7–58% range by two different studies, and no further clinical details or therapeutical approaches have been described [3,4]. In this view, we report a case of RLS occurring in PSP–P, discuss its diagnosis and treatment, and propose a possible pathophysiological explanation for such a phenomenon. ⁎ Corresponding author. Tel.: +39 0817462670; fax: +39 0817464348. E-mail address: [email protected] (C. Vitale).
http://dx.doi.org/10.1016/j.jns.2015.01.025 0022-510X/© 2015 Elsevier B.V. All rights reserved.
A 57-year-old man received a diagnosis of Parkinson's disease (PD) because of rest tremor and bradykinesia in his upper right limb. A [123I]beta-CIT SPECT/CT scan showed a striatal DAT reduction mainly in the putamen compared to the caudate (left N right). Dopaminergic treatment was started with rotigotine (8 mg per day) with a slight benefit. As adjunctive treatment due to progressive motor worsening, after 1 year, L-Dopa/Carbidopa was started (up to 800 mg per day), with moderate clinical response. At 60 years, the patient presented a progressive postural instability with frequent falls and was hence sent to our department. On examination, there was an asymmetric bradykinetic-rigid parkinsonism and supranuclear upgaze eye palsy, with a motor score of 21 in the Unified Parkinson's Disease Rating Scale (UPDRS part III). Brain MRI showed a thinning of the anteroposterior diameter of the rostral midbrain tegmentum, with an abnormal shape resembling the “hummingbird sign”. A diagnosis of possible PSP–P was made. Considering previous reports on response to dopaminergic drugs in PSP [1,2], we suggested to progressively withdraw rotigotine and to continue L-Dopa treatment at the previous dosage (800 mg per day). Rotigotine was therefore gradually tapered by 2 mg per week and eventually discontinued. After two weeks of rotigotine progressive reduction, at 4 mg daily dosage, the patient reported an urge to move the legs together with unpleasant sensations of burning and throbbing in the lower limbs. Symptoms were present throughout the day to
104
Letter to the Editor
worsen typically in the evening. They were partly relieved by movement. Essential diagnostic criteria for RLS were fulfilled [5]. Symptoms were severe according to the International RLS Group Rating Scale (27/40), and sleep impairment was scored 10 by the Pittsburgh sleep quality index and 13 by the Epworth sleepiness scale. Secondary causes of RLS were ruled out (i.e. iron deficiency, neuropathy or kidney disease). Rotigotine was started again (up to 6 mg per day) with complete symptom relief, but without any efficacy on motor symptoms. RLS is associated with a modified central dopaminergic neurotransmission and, thus, is expected to be more frequent in neurodegenerative disorders with loss of dopaminergic neurons [5]. Our case showed that RLS occurring in PSP might be severe enough to require specific treatments. Rotigotine (6 mg per day) resulted in a marked benefit, whereas L-Dopa
failed to ameliorate RLS symptoms in our patient. In PSP–P a moderate or good improvement in bradykinesia and rigidity may follow the initiation of dopaminergic drugs. However, secondary unresponsiveness is to be expected within a few years from symptom onset [2]. Notably, our case showed that the dopaminergic benefit for RLS occurring in PSP–P is maintained during disease course, suggesting a functional imbalance more than the neurodegenerative alterations in RLS pathogenesis. Therefore, the efficacy of other dopamine agonists cannot be excluded, and further investigations are needed. Moreover, this benefit from dopamine-agonist treatment can possibly lead to a PD misdiagnosis considering that a poor response to dopaminergic drugs is typical of PSP. In particular, our case complained of a significant worsening after dopamine agonist progressive tapering, and only accurate clinical history and examination showed that it was not strictly related to motor symptoms, but to RLS-related symptoms.
Finally, we have to acknowledge that the main limitation of the current report is the absence of pathology. In conclusion, RLS should be considered in patients with PSP, as it may significantly affect quality of life and is potentially amenable to treatments.
Conflict of interest None of the authors have any conflicts of interest to state.
Acknowledgements The present study received no specific funding.
References [1] Burn DJ, Lees AJ. Progressive supranuclear palsy: where are we now? Lancet Neurol 2000;1:359–69. [2] Williams DR, Lees AJ. Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol 2009;8:270–9. [3] Bhalsing K, Suresh K, Muthane UB, et al. Prevalence and profile of Restless Legs Syndrome in Parkinson's disease and other neurodegenerative disorders: a case– control study. Parkinsonism Relat Disord 2013;19:426–30. [4] Gama RL, Távora DG, Bomfim RC, et al. Sleep disturbances and brain MRI morphometry in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy — a comparative study. Parkinsonism Relat Disord 2010;16:275–9. [5] Allen RP, Picchietti D, Hening WA, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4:101–19.
