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The dilemma of adult-onset Rasmussen encephalitis clinical assessment: Proposal for a new bedside tool to evaluate disease progression
Epilepsy & Behavior 46 (2015) 249–251
Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Letter to the Editor The dilemma of adult-onset Rasmussen encephalitis clinical assessment: Proposal for a new bedside tool to evaluate disease progression
To the Editor Rasmussen encephalitis (RE) [1] is a rare inflammatory, probably autoimmune-mediated, neurologic disorder characterized by progressive brain hemiatrophy associated with unilateral focal deficits and drugrefractory focal epilepsy with or without epilepsia partialis continua (EPC). The typical onset is in childhood, but an atypical adult-onset RE (a-RE) form has been also described [2]. Rasmussen encephalitis therapy is based on antiepileptic drugs, immunomodulation [1,2], and hemispheric disconnection surgery [3]. The choice and the planning of different treatments (first and second line immunologic drugs or surgery) during the course of the disease are key factors to obtain the best outcome in terms of seizure control and effect on disease progression. Treatment timing is particularly challenging in a-RE presenting with slower and unpredictable evolution [4] since a tool to assess the overall disease severity and the progression of symptoms is lacking. We propose a bedside tool to evaluate a-RE progression by monitoring neurological deficits, seizures, and cognitive and/or behavioral disturbances that contribute to the clinical RE severity. The multiaxis clinical a-RE severity scale (a-RESS) described in Fig. 1A includes and measures all these parameters. The first axis relates to focal deficits, and it includes motor deficits (M) and aphasia (A). An M1 value is attributed when evident neurological signs are present, such as pyramidal signs or pronator drift. An M2 value is assigned for motor deficits that clearly impair self-sufficiency, and M3 is designated to those patients who are not autonomous because of muscle weakness. An A1 value is attributed when an evident speech difficulty is observed (i.e., anomia or phonemic paraphasia), whereas an A2 value should be attributed only when communication is significantly impaired by speech difficulties. The second axis includes epilepsy-related symptoms, such as drugrefractory seizures (S), status epilepticus (SE), and EPC (K — Kojevnikov's epilepsia). The K-score refers to distribution over six muscle segments: upper and lower face, proximal and distal, and upper and lower limbs. For EPC, a score from 0 to 6 is assigned according to the number of segments involved. The third axis pertains to cognitive and behavioral disorders (C). A C1 score should be given to patients who require help in everyday life, whereas a C2 score should be restricted to patients needing continuous care for cognitive and/or behavioral problems.
http://dx.doi.org/10.1016/j.yebeh.2015.04.029 1525-5050/© 2015 Elsevier Inc. All rights reserved.
The assessment using the a-RESS is based exclusively on routine history and neurological examination; instrumental data such as brain MRI, EEG, or neuropsychological tests are not included. Therefore, the a-RESS score is practical not only for the prospective assessment of single patients with a-RE but also for retrospective/prospective evaluations of case series. We applied the a-RESS successfully to prospectively assess our patients with a-RE and to retrospectively evaluate symptom progression in our case series. Fig. 1B exemplifies the development of a-RESS scores for one single patient previously described by our group in a recent paper [5]. In this right-handed female, EPC involving facial muscles, focal seizures, and right pyramidal signs appeared at the age of 19 years (time point (tp) 0). After two years from onset, EPC propagated to the whole right hemibody (tps 1–3) and was later associated with frequent SE episodes and right limb motor deficits (tp 4). Her cognitive abilities also significantly declined, requiring supervision for daily living activities. Six years after disease onset, she presented a superrefractory SE that required deep anesthesia (tp 5). A cortectomy confined to the precentral and postcentral gyri was performed with resolution of the SE and EPC (tp 6). Two years later, her motor deficits improved but aphasia worsened (tps 9–10). At the last follow-up (tp 11), 60 months after surgery, she was still free from epileptic manifestations. The a-RESS recapitulates the clinical status of the patient in a clear, simple, and reproducible way, allowing a more precise follow-up of her clinical condition during and after different treatments. The major advantage of the a-RESS is its ability to provide complete and easily comparable clinical severity scores in longitudinal and transversal studies on patients suffering from RE and similar conditions. The complex assessment of a-RE requires such an easy-to-use assessment tool to gather over time all data necessary to evaluate the efficacy of treatments and, possibly, to choose among therapeutic options. Neurologists involved in the management of this severe and difficultto-treat disorder may benefit from this new bedside tool. A major limitation of the a-RESS is the sensitivity of the assessment only to the most evident changes in the clinical status of the patient. Subtle signs of disease worsening or improvement may be evident only through diagnostic exams such as brain MRI [6], EEG [7], and formal neuropsychological testing. Acknowledgments We are grateful to Dr. Marco de Curtis for critically revising the manuscript. We also thank the Paolo Zorzi Association for Neurosciences for its unconditional support. Conflict of interest statement All authors declare that there are no conflicts of interest.
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Letter to the Editor
Fig. 1. The a-RESS. A. a-RESS item list. B. a-RESS application in the patient described in the text. x-axis: follow-up in years from disease onset. y-axis: a-RESS score. The color legend for each bar component is listed in A. The red arrow indicates the surgical treatment. On the top, the horizontal bars represent the immunological treatments performed over time. The last IV-Ig six-month treatment was performed because of aphasia progression and the appearance of new MRI lesions. A slight improvement in language performance was recognized only after formal neuropsychological testing. pts: points, PEX: plasma exchange, IV-Ig: intravenous immunoglobulin infusion, PAI: protein-A immunoadsorption, and S: acute high-dose steroid infusion.
References [1] Bien CG, Tiemeier H, Sassen R, Kuczaty S, Urbach H, von Lehe M, et al. Rasmussen encephalitis: incidence and course under randomized therapy with tacrolimus or intravenous immunoglobulins. Epilepsia 2013;54:543–50. [2] Bien CG, Granata T, Antozzi C, Cross JH, Dulac O, Kurthen M, et al. Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement. Brain 2005; 128:454–71. [3] Bien CG, Schramm J. Treatment of Rasmussen encephalitis half a century after its initial description: promising prospects and a dilemma. Epilepsy Res 2009;86: 101–12. [4] Villani F, Pincherle A, Antozzi C, Chiapparini L, Granata T, Michelucci R, et al. Adult-onset Rasmussen's encephalitis: anatomical–electrographic–clinical features of 7 Italian cases. Epilepsia 2006;47(Suppl. 5):41–6.
[5] Villani F, Didato G, Deleo F, Tringali G, Garbelli R, Granata T, et al. Long-term outcome after limited cortical resections in two cases of adult-onset Rasmussen encephalitis. Epilepsia 2014;55:e38–43. [6] Wagner J, Schoene-Bake J-C, Bien CG, Urbach H, Elger CE, Weber B. Automated 3D MRI volumetry reveals regional atrophy differences in Rasmussen encephalitis. Epilepsia 2012;53:613–21. [7] Longaretti F, Dunkley C, Varadkar S, Vargha-Khadem F, Boyd SG, Cross JH. Evolution of the EEG in children with Rasmussen's syndrome. Epilepsia 2012;53:1539–45.
Francesco Deleo Clinical Epileptology and Experimental Neurophysiology Unit, Foundation IRCCS “Carlo Besta” Neurological Institute, Milan, Italy E-mail address: [email protected].
Letter to the Editor
Sara Matricardi Department of Pediatric Neuroscience, Foundation IRCCS “Carlo Besta” Neurological Institute, Milan, Italy Department of Pediatrics, University of Chieti, Chieti, Italy E-mail address: [email protected].
Giuseppe Didato Irene Pappalardo Clinical Epileptology and Experimental Neurophysiology Unit, Foundation IRCCS “Carlo Besta” Neurological Institute, Milan, Italy E–mail addresses: [email protected] (G. Didato); [email protected] (I. Pappalardo).
251
Flavio Villani Clinical Epileptology and Experimental Neurophysiology Unit, Foundation IRCCS “Carlo Besta” Neurological Institute, Milan, Italy Corresponding author at: Clinical Epileptology and Experimental Neurophysiology Unit, Foundation IRCCS “Carlo Besta” Neurological Institute, via Celoria 11, Milan, Italy. Tel.: +39 0223942242. E-mail address: [email protected]. 14 April 2015
Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Letter to the Editor The dilemma of adult-onset Rasmussen encephalitis clinical assessment: Proposal for a new bedside tool to evaluate disease progression
To the Editor Rasmussen encephalitis (RE) [1] is a rare inflammatory, probably autoimmune-mediated, neurologic disorder characterized by progressive brain hemiatrophy associated with unilateral focal deficits and drugrefractory focal epilepsy with or without epilepsia partialis continua (EPC). The typical onset is in childhood, but an atypical adult-onset RE (a-RE) form has been also described [2]. Rasmussen encephalitis therapy is based on antiepileptic drugs, immunomodulation [1,2], and hemispheric disconnection surgery [3]. The choice and the planning of different treatments (first and second line immunologic drugs or surgery) during the course of the disease are key factors to obtain the best outcome in terms of seizure control and effect on disease progression. Treatment timing is particularly challenging in a-RE presenting with slower and unpredictable evolution [4] since a tool to assess the overall disease severity and the progression of symptoms is lacking. We propose a bedside tool to evaluate a-RE progression by monitoring neurological deficits, seizures, and cognitive and/or behavioral disturbances that contribute to the clinical RE severity. The multiaxis clinical a-RE severity scale (a-RESS) described in Fig. 1A includes and measures all these parameters. The first axis relates to focal deficits, and it includes motor deficits (M) and aphasia (A). An M1 value is attributed when evident neurological signs are present, such as pyramidal signs or pronator drift. An M2 value is assigned for motor deficits that clearly impair self-sufficiency, and M3 is designated to those patients who are not autonomous because of muscle weakness. An A1 value is attributed when an evident speech difficulty is observed (i.e., anomia or phonemic paraphasia), whereas an A2 value should be attributed only when communication is significantly impaired by speech difficulties. The second axis includes epilepsy-related symptoms, such as drugrefractory seizures (S), status epilepticus (SE), and EPC (K — Kojevnikov's epilepsia). The K-score refers to distribution over six muscle segments: upper and lower face, proximal and distal, and upper and lower limbs. For EPC, a score from 0 to 6 is assigned according to the number of segments involved. The third axis pertains to cognitive and behavioral disorders (C). A C1 score should be given to patients who require help in everyday life, whereas a C2 score should be restricted to patients needing continuous care for cognitive and/or behavioral problems.
http://dx.doi.org/10.1016/j.yebeh.2015.04.029 1525-5050/© 2015 Elsevier Inc. All rights reserved.
The assessment using the a-RESS is based exclusively on routine history and neurological examination; instrumental data such as brain MRI, EEG, or neuropsychological tests are not included. Therefore, the a-RESS score is practical not only for the prospective assessment of single patients with a-RE but also for retrospective/prospective evaluations of case series. We applied the a-RESS successfully to prospectively assess our patients with a-RE and to retrospectively evaluate symptom progression in our case series. Fig. 1B exemplifies the development of a-RESS scores for one single patient previously described by our group in a recent paper [5]. In this right-handed female, EPC involving facial muscles, focal seizures, and right pyramidal signs appeared at the age of 19 years (time point (tp) 0). After two years from onset, EPC propagated to the whole right hemibody (tps 1–3) and was later associated with frequent SE episodes and right limb motor deficits (tp 4). Her cognitive abilities also significantly declined, requiring supervision for daily living activities. Six years after disease onset, she presented a superrefractory SE that required deep anesthesia (tp 5). A cortectomy confined to the precentral and postcentral gyri was performed with resolution of the SE and EPC (tp 6). Two years later, her motor deficits improved but aphasia worsened (tps 9–10). At the last follow-up (tp 11), 60 months after surgery, she was still free from epileptic manifestations. The a-RESS recapitulates the clinical status of the patient in a clear, simple, and reproducible way, allowing a more precise follow-up of her clinical condition during and after different treatments. The major advantage of the a-RESS is its ability to provide complete and easily comparable clinical severity scores in longitudinal and transversal studies on patients suffering from RE and similar conditions. The complex assessment of a-RE requires such an easy-to-use assessment tool to gather over time all data necessary to evaluate the efficacy of treatments and, possibly, to choose among therapeutic options. Neurologists involved in the management of this severe and difficultto-treat disorder may benefit from this new bedside tool. A major limitation of the a-RESS is the sensitivity of the assessment only to the most evident changes in the clinical status of the patient. Subtle signs of disease worsening or improvement may be evident only through diagnostic exams such as brain MRI [6], EEG [7], and formal neuropsychological testing. Acknowledgments We are grateful to Dr. Marco de Curtis for critically revising the manuscript. We also thank the Paolo Zorzi Association for Neurosciences for its unconditional support. Conflict of interest statement All authors declare that there are no conflicts of interest.
250
Letter to the Editor
Fig. 1. The a-RESS. A. a-RESS item list. B. a-RESS application in the patient described in the text. x-axis: follow-up in years from disease onset. y-axis: a-RESS score. The color legend for each bar component is listed in A. The red arrow indicates the surgical treatment. On the top, the horizontal bars represent the immunological treatments performed over time. The last IV-Ig six-month treatment was performed because of aphasia progression and the appearance of new MRI lesions. A slight improvement in language performance was recognized only after formal neuropsychological testing. pts: points, PEX: plasma exchange, IV-Ig: intravenous immunoglobulin infusion, PAI: protein-A immunoadsorption, and S: acute high-dose steroid infusion.
References [1] Bien CG, Tiemeier H, Sassen R, Kuczaty S, Urbach H, von Lehe M, et al. Rasmussen encephalitis: incidence and course under randomized therapy with tacrolimus or intravenous immunoglobulins. Epilepsia 2013;54:543–50. [2] Bien CG, Granata T, Antozzi C, Cross JH, Dulac O, Kurthen M, et al. Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement. Brain 2005; 128:454–71. [3] Bien CG, Schramm J. Treatment of Rasmussen encephalitis half a century after its initial description: promising prospects and a dilemma. Epilepsy Res 2009;86: 101–12. [4] Villani F, Pincherle A, Antozzi C, Chiapparini L, Granata T, Michelucci R, et al. Adult-onset Rasmussen's encephalitis: anatomical–electrographic–clinical features of 7 Italian cases. Epilepsia 2006;47(Suppl. 5):41–6.
[5] Villani F, Didato G, Deleo F, Tringali G, Garbelli R, Granata T, et al. Long-term outcome after limited cortical resections in two cases of adult-onset Rasmussen encephalitis. Epilepsia 2014;55:e38–43. [6] Wagner J, Schoene-Bake J-C, Bien CG, Urbach H, Elger CE, Weber B. Automated 3D MRI volumetry reveals regional atrophy differences in Rasmussen encephalitis. Epilepsia 2012;53:613–21. [7] Longaretti F, Dunkley C, Varadkar S, Vargha-Khadem F, Boyd SG, Cross JH. Evolution of the EEG in children with Rasmussen's syndrome. Epilepsia 2012;53:1539–45.
Francesco Deleo Clinical Epileptology and Experimental Neurophysiology Unit, Foundation IRCCS “Carlo Besta” Neurological Institute, Milan, Italy E-mail address: [email protected].
Letter to the Editor
Sara Matricardi Department of Pediatric Neuroscience, Foundation IRCCS “Carlo Besta” Neurological Institute, Milan, Italy Department of Pediatrics, University of Chieti, Chieti, Italy E-mail address: [email protected].
Giuseppe Didato Irene Pappalardo Clinical Epileptology and Experimental Neurophysiology Unit, Foundation IRCCS “Carlo Besta” Neurological Institute, Milan, Italy E–mail addresses: [email protected] (G. Didato); [email protected] (I. Pappalardo).
251
Flavio Villani Clinical Epileptology and Experimental Neurophysiology Unit, Foundation IRCCS “Carlo Besta” Neurological Institute, Milan, Italy Corresponding author at: Clinical Epileptology and Experimental Neurophysiology Unit, Foundation IRCCS “Carlo Besta” Neurological Institute, via Celoria 11, Milan, Italy. Tel.: +39 0223942242. E-mail address: [email protected]. 14 April 2015