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Clinical improvement of secondary focal limb dystonia in neurodegenerative disease following a five-day lidocaine infusion: A case report
Journal of the Neurological Sciences 277 (2009) 164–166
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Short communication
Clinical improvement of secondary focal limb dystonia in neurodegenerative disease following a five-day lidocaine infusion: A case report D. Irwin, G. Revuelta, C.F. Lippa ⁎ Drexel University College of Medicine, Department of Neurology, Philadelphia, PA, USA
a r t i c l e
i n f o
Article history: Received 25 August 2008 Received in revised form 4 October 2008 Accepted 8 October 2008 Available online 17 November 2008 Keywords: Lidocane Parkinsonism Corticobasal degeneration Treatment Dystonia Neurodegeneration
a b s t r a c t Dystonia associated with neurodegenerative disease has minimal effective treatment options and can be devastating to a patient's ability to perform tasks of daily living. We present a case of a 55 year-old man who had progressive symptoms of an atypical asymmetric parkinsonian neurodegenerative disease. This patient presented with a dystonic left upper extremity that was refractory to treatment. In an attempt to treat worsening pain associated with the dystonia, he was given a five-day lidocaine infusion for associated pain and within 24 h had improvement in mobility of his dystonic extremity. Dystonia was measured by the Burke–Fahn–Marsden (BFM) dystonia rating and disability scales on hospital day five and at an eight week follow up visit. These scores were compared with scores derived from his previous pre-treatment neurologic examination. The BFM dystonia scale score was initially 16 and improved to 12 on both immediate posttreatment and eight-week follow-up. The BFM disability score improved from 16 to 6 post treatment and to 8 on follow-up appointment. Most importantly, the patient could feed and dress himself for the first time in several years. No adverse events of treatment were encountered. Treatment effect lasted three months with a slow return to baseline motor function. This case report raises interesting questions regarding the mechanism of dystonia in neurodegenerative disease and suggests the afferent sensory system as a potential target for therapeutics. © 2008 Elsevier B.V. All rights reserved.
1. Introduction
2. Case report
Secondary focal dystonia is a manifestation of many neurodegenerative diseases including Corticobasal degeneration (CBD), Parkinson's disease, Huntington's disease, and Wilson's disease. Motor impairment from degenerative disease associated dystonia can be devastating as it is accompanied by cognitive impairment and other neurologic manifestations. Dystonia is a major debilitating symptom for many patients with CBD, and can also be associated with pain [1]. The upper extremity is the most frequently affected region, displaying adduction of the arm, and flexion of the hand and forearm, with or without contractures [2]. Treatment options for these patients are limited [2]. Botulinum toxin injection is currently the only effective treatment for relief of these symptoms in CBD [1,3]; however, some studies show limited benefit in gain of functionality [4]. In addition, local weakness and high cost may limit the usefulness of botulinum toxin injections [5].
Patient JR, a 55-year-old male who has been treated at Drexel University College of Medicine Memory Disorders clinic since 1998, originally presented with clinical features suggestive of CBD [6] including: a severely rigid dystonic posture of the left upper extremity with ideomotor apraxia and asymmetric Parkinsonism, including an 8 Hz resting tremor in his left upper extremity. Symptoms were insidious and progressed slowly throughout this time period, with development of rigidity in the left lower extremity and entire right side, and spread of his tremor to the right arm and occasionally the right foot. Cognition was also affected as symptoms of frontal lobe dysfunction, including behavioral changes, became evident over time. Nocturnal myoclonus also developed and was partially responsive to pramipexole. He failed numerous medications for his motor symptoms including carbidopa/levodopa (Max dose = 50 mg/200 mg five times daily, also including a trial of entacapone 200 mg combination). Other medications found to have minimal effect include amantadine and bromocriptine. His only other medication was sertraline for depression. Family history was negative for movement disorder or other neurological disease. Computed tomography (CT) scanning of the head showed global atrophy with frontal lobe predominance (Fig. 1). Laboratory studies including serum antinuclear antibodies, thyroid function, rapid
⁎ Corresponding author. Department of Neurology, Drexel University College of Medicine, New College Building, 245 N 15th St, Philadelphia, PA, USA 19102. Tel.: +1 215 762 4761; fax: +1 215 762 3161. E-mail address: [email protected] (C.F. Lippa). 0022-510X/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2008.10.005
D. Irwin et al. / Journal of the Neurological Sciences 277 (2009) 164–166
165
Fig. 1. Computed tomography (CT) scanning displaying global cerebral atrophy with frontal lobe predominance.
plasma reagin, ammonia, ceruloplasmin, vitamin B-12, erythrocyte sedimentation rate, and cerebrospinal fluid analysis were normal. His initial presentation and previous findings met criteria for the clinical entity “corticobasal syndrome” [7], and lead to his working diagnosis of an atypical parkinsonian syndrome most compatible with CBD. JR presented to the clinic for a follow up appointment in June 2007 with new complaints of pain in his left dystonic hand. The pain corresponded to his dystonia, and did not follow any nerve or root dermatome area. The pain progressed and was not responsive to standard analgesic therapy. 3. Methods JR was admitted for a five-day continuous intravenous lidocaine treatment for neuropathic pain, as previously described [8]. He was placed on cardiac telemetry monitoring and received neurological and vital sign monitoring every 4 h. Daily lidocaine levels were drawn and ranged from 1.8–4 μg/ml. On hospital day two it was noted that his dystonia had improved significantly, both subjectively and on physical exam. To quantify this improvement, Burke–Fahn–Marsden dystonia and disability rating scales [9] were administered on the final day of hospitalization (day 5) and on an eight-week follow-up appointment. These scores were then compared with a score derived from previous pre-treatment neurologic examination. After the five-day infusion, JR received oral mexelitine therapy (150 mg oral twice daily). 4. Results In less than 24 h, JR had a total disappearance of pain symptoms and began to have increased function of his left upper extremity. The BFM dystonia scale score was initially 16 and improved to 12 on both immediate post-treatment and eight week follow-up (Table 1A). The BFM disability score improved from 16 to 6 post treatment and to 8 on follow-up appointment (Table 1B). Most importantly, the patient could feed and dress himself for the first time in several years. No
adverse events of treatment were encountered. At approximately three months past discharge the patient had returned to baseline motor function and discontinued mexelitine treatment. Table 1 (A) BFM dystonia score for left upper extremity before and after treatments, (B) BFM disability score before and after treatment A. Burke–Fahn–Marsden rating scale (BFM) dystonia score: left upper extremity
B. Burke–Fahn–Marsden rating scale (BFM) disability score
Prior to treatment •Provoking factor: Dystonia present at rest = 4 x •Arm: Severe, no useful grasp = 4
Prior to treatment •Speech: easily understood = 1 •⁎Handwriting: slight difficulty = 1 •Feeding: completely dependant = 4 •Eating: no choking = 0 •Hygiene: needs help with all activities = 4 •Dressing: Helpless = 4 •Walking: Moderately abnormal = 2 Total = 16/30
Total: 16
Hospital Day 5 •Provoking factor: Dystonia present at rest = 4 x •Arm: Able to grasp, with some manual function = 3 Total: 12
Eight week follow-up appointment •Provoking factor: Dystonia present at rest = 4 x •Arm: Able to grasp, with some manual function = 3 Total: 12
Hospital Day 5 •Speech: easily understood = 1 •Handwriting: slight difficulty = 1 •Feeding: independent = 1 •Eating: no choking = 0 •Hygiene: clumsy, independent = 1 •Dressing: clumsy, independent = 1 •Walking: slightly abnormal = 1 Total = 6/30
Eight week follow-up appointment •Speech: easily understood = 1 •Handwriting: slight difficulty = 1 •Feeding: can feed/no cut = 2 •Eating: no choking = 0 •Hygiene: clumsy, independent = 1 •Dressing: needs help with some activities = 2 •Walking: slightly abnormal = 1 Total = 8/30 ⁎Patient is right-handed
166
D. Irwin et al. / Journal of the Neurological Sciences 277 (2009) 164–166
5. Discussion This case report describes positive effect of intravenous lidocaine infusion on a central-mediated neurodegenerative focal dystonia. There are several potential mechanisms for the observed therapeutic effect in this case, which also provide insight into the mechanism of dystonia, and more specifically dystonia associated with neurodegenerative disease. The class IB antiarrhythmic drugs, mexelitine and lidocaine, have been reported to have a positive effect in both focal [10–14] and generalized [10] dystonias. These agents are voltage-gated sodium channel antagonists, which preferentially bind activated channels [8]. The mechanism of action for these agents in dystonia most likely involves decreased excitability of the reflex arc [10], with preferential effect on gamma motor neurons [11,13] and Ia afferent fibers [10,15]. Experiments using the tonic vibration reflex indicate abnormal Ia afferent processing of limb velocity in focal dystonia patients [15], which may be inhibited using these agents. Inhibition of smaller C- and A-delta fiber afferents and motor fibers also may be involved in the mechanism of action [14]. Lidocaine and mexelitine may also affect a central process of dystonia, as they can cross the blood-brain barrier [14,15] and affect central nervous tissue sodium channels [8]. This is relevant as focal dystonia can be considered to be due at least in part to abnormal cortical and basal ganglionic sensorimotor processing [15,16], especially in CBD and PD. Intravenous lidocaine or oral mexelitine have not been previously described to alleviate dystonia associated with neurodegenerative disease. The study is limited, as it was retrospective in a single patient after an unexpected benefit of treatment was observed. In addition, the pre-treatment BFM dystonia score was generated from previous neurologic examination. Despite these limitations, these observations demonstrate great symptomatic relief in a patient and disease process that is very resistant to treatment. Ohara and colleagues [14] had similar results in a series of nine patients with spasmodic torticollis, where patients received a 100 mg lidocaine infusion over five minutes, followed by oral mexelitine. These patients required higher doses of mexelitine (mean= 776 mg/day) for prolonged relief at nine months after infusion [14]. To make this treatment more feasible for patients with neurodegenerative disease, more study is needed to determine the appropriate duration and interval of lidocaine infusions, as a five day protocol may not be practical for all affected patients. In addition, perhaps larger doses
of mexelitine, as seen in previous studies [10–12,14] may provide longer duration of relief, with fewer needed lidocaine infusions. This case illustrates a potential treatment strategy that may lead to increased function in activities of daily living for patients afflicted with this debilitating neurological symptom. Acknowledgment Private funding of this study was provided by the Potamkin foundation. References [1] Vanek Z, Jankovic J. Dystonia in corticobasal degeneration. Mov Disord 2001;16(2):251–7. [2] Stover N, Watts R. Corticobasal degeneration. Sem Neurol 2001;21(1):49–58. [3] Müller J, Wenning GK, Wissel J, Seppi K, Poewe W. Botulinum toxin treatment in atypical Parkinsonian disorders associated with disabling focal dystonia. J Neurol 2002;259:300–4. [4] Riley DE, Lang AE, Lewis A, Resch L, Ashby P, Hornykiewicz O, Black S. Cortical– basal ganglionic degeneration. Neurol 1990;40(8):1203–12. [5] Jankovic J, Brin MF. Therapeutic uses of botulinum toxin. N Engl J Med 1991;324(17):1186–94. [6] Litvan I, Agid Y, Goetz C, Jankovic J, Wenning GK, Brandel JP, et al. Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathological study. Neurol 1997;48(1):119–25. [7] Boeve BF, Lang AE, Litvan I. Corticobasal degeneration and its relationship to progressive supranuclear palsy and frontotemporal dementia. Ann Neurol 2003;54(S5):S15–9. [8] Schwartzman RJ, Patel M, Grothusen JR, Alexander GM. Efficacy of five day continuous lidocaine infusion for treatment of refractory complex regional pain syndrome. Pain Med 2008; submitted under review. [9] Burke R, Fahn S, Marsden CD, Bressman SB, Moskowitz C, Friedman J. Validity and reliability of a rating scale for the primary torsion dystonias. Neurol 1985;35:73–7. [10] Lucetti C, Nuti A, Gambaccini G, Bernardini S, Brotini S, Manca ML, Bonucelli U, et al. Mexelitine in the treatment of torticollis and generalized dystonia. Clin Neuropharmacol 2000;23(4):186–9. [11] Ohara S, Miki J, Momoi H, Unno H, Shindo M, Yanagisawa N. Treatment of spasmodic torticollis with mexelitine: a case report. Mov Disord 1997;12(3):466–9. [12] Ohara S, Tsuyuzaki J, Hayashi R. Mexelitine in the treatment of blepharospasm: experience with the first three patients. Mov Disord 1999(1):173–5. [13] Kaji R, Rothwell JC, Katayama M, Ikeda T, Kubori T, Kohara N, et al. Tonic vibration reflex and muscle afferent block in writer's cramp. Ann Neurol 1995;38:155–62. [14] Ohara S, Hayashi R, Momoi H, Miki J, Yanagisawa N. Mexiletine in the treatment of spasmodic torticollis. Mov Disord 1998;13(6):934–40. [15] Grünewald RA, Yoneda Y, Shipman JM, Sagar HJ. Idiopathic focal dystonia: a disorder of muscle spindle afferent processing? Brain 1997;120:2179–89. [16] Breakfield XO, Blood AJ, Li Y, Hallett M, Hanson PU, Standaert DG. The pathophysiological basis of dystonias. Nat Rev Neurosci 2008;9(3):222–34.
Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Short communication
Clinical improvement of secondary focal limb dystonia in neurodegenerative disease following a five-day lidocaine infusion: A case report D. Irwin, G. Revuelta, C.F. Lippa ⁎ Drexel University College of Medicine, Department of Neurology, Philadelphia, PA, USA
a r t i c l e
i n f o
Article history: Received 25 August 2008 Received in revised form 4 October 2008 Accepted 8 October 2008 Available online 17 November 2008 Keywords: Lidocane Parkinsonism Corticobasal degeneration Treatment Dystonia Neurodegeneration
a b s t r a c t Dystonia associated with neurodegenerative disease has minimal effective treatment options and can be devastating to a patient's ability to perform tasks of daily living. We present a case of a 55 year-old man who had progressive symptoms of an atypical asymmetric parkinsonian neurodegenerative disease. This patient presented with a dystonic left upper extremity that was refractory to treatment. In an attempt to treat worsening pain associated with the dystonia, he was given a five-day lidocaine infusion for associated pain and within 24 h had improvement in mobility of his dystonic extremity. Dystonia was measured by the Burke–Fahn–Marsden (BFM) dystonia rating and disability scales on hospital day five and at an eight week follow up visit. These scores were compared with scores derived from his previous pre-treatment neurologic examination. The BFM dystonia scale score was initially 16 and improved to 12 on both immediate posttreatment and eight-week follow-up. The BFM disability score improved from 16 to 6 post treatment and to 8 on follow-up appointment. Most importantly, the patient could feed and dress himself for the first time in several years. No adverse events of treatment were encountered. Treatment effect lasted three months with a slow return to baseline motor function. This case report raises interesting questions regarding the mechanism of dystonia in neurodegenerative disease and suggests the afferent sensory system as a potential target for therapeutics. © 2008 Elsevier B.V. All rights reserved.
1. Introduction
2. Case report
Secondary focal dystonia is a manifestation of many neurodegenerative diseases including Corticobasal degeneration (CBD), Parkinson's disease, Huntington's disease, and Wilson's disease. Motor impairment from degenerative disease associated dystonia can be devastating as it is accompanied by cognitive impairment and other neurologic manifestations. Dystonia is a major debilitating symptom for many patients with CBD, and can also be associated with pain [1]. The upper extremity is the most frequently affected region, displaying adduction of the arm, and flexion of the hand and forearm, with or without contractures [2]. Treatment options for these patients are limited [2]. Botulinum toxin injection is currently the only effective treatment for relief of these symptoms in CBD [1,3]; however, some studies show limited benefit in gain of functionality [4]. In addition, local weakness and high cost may limit the usefulness of botulinum toxin injections [5].
Patient JR, a 55-year-old male who has been treated at Drexel University College of Medicine Memory Disorders clinic since 1998, originally presented with clinical features suggestive of CBD [6] including: a severely rigid dystonic posture of the left upper extremity with ideomotor apraxia and asymmetric Parkinsonism, including an 8 Hz resting tremor in his left upper extremity. Symptoms were insidious and progressed slowly throughout this time period, with development of rigidity in the left lower extremity and entire right side, and spread of his tremor to the right arm and occasionally the right foot. Cognition was also affected as symptoms of frontal lobe dysfunction, including behavioral changes, became evident over time. Nocturnal myoclonus also developed and was partially responsive to pramipexole. He failed numerous medications for his motor symptoms including carbidopa/levodopa (Max dose = 50 mg/200 mg five times daily, also including a trial of entacapone 200 mg combination). Other medications found to have minimal effect include amantadine and bromocriptine. His only other medication was sertraline for depression. Family history was negative for movement disorder or other neurological disease. Computed tomography (CT) scanning of the head showed global atrophy with frontal lobe predominance (Fig. 1). Laboratory studies including serum antinuclear antibodies, thyroid function, rapid
⁎ Corresponding author. Department of Neurology, Drexel University College of Medicine, New College Building, 245 N 15th St, Philadelphia, PA, USA 19102. Tel.: +1 215 762 4761; fax: +1 215 762 3161. E-mail address: [email protected] (C.F. Lippa). 0022-510X/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2008.10.005
D. Irwin et al. / Journal of the Neurological Sciences 277 (2009) 164–166
165
Fig. 1. Computed tomography (CT) scanning displaying global cerebral atrophy with frontal lobe predominance.
plasma reagin, ammonia, ceruloplasmin, vitamin B-12, erythrocyte sedimentation rate, and cerebrospinal fluid analysis were normal. His initial presentation and previous findings met criteria for the clinical entity “corticobasal syndrome” [7], and lead to his working diagnosis of an atypical parkinsonian syndrome most compatible with CBD. JR presented to the clinic for a follow up appointment in June 2007 with new complaints of pain in his left dystonic hand. The pain corresponded to his dystonia, and did not follow any nerve or root dermatome area. The pain progressed and was not responsive to standard analgesic therapy. 3. Methods JR was admitted for a five-day continuous intravenous lidocaine treatment for neuropathic pain, as previously described [8]. He was placed on cardiac telemetry monitoring and received neurological and vital sign monitoring every 4 h. Daily lidocaine levels were drawn and ranged from 1.8–4 μg/ml. On hospital day two it was noted that his dystonia had improved significantly, both subjectively and on physical exam. To quantify this improvement, Burke–Fahn–Marsden dystonia and disability rating scales [9] were administered on the final day of hospitalization (day 5) and on an eight-week follow-up appointment. These scores were then compared with a score derived from previous pre-treatment neurologic examination. After the five-day infusion, JR received oral mexelitine therapy (150 mg oral twice daily). 4. Results In less than 24 h, JR had a total disappearance of pain symptoms and began to have increased function of his left upper extremity. The BFM dystonia scale score was initially 16 and improved to 12 on both immediate post-treatment and eight week follow-up (Table 1A). The BFM disability score improved from 16 to 6 post treatment and to 8 on follow-up appointment (Table 1B). Most importantly, the patient could feed and dress himself for the first time in several years. No
adverse events of treatment were encountered. At approximately three months past discharge the patient had returned to baseline motor function and discontinued mexelitine treatment. Table 1 (A) BFM dystonia score for left upper extremity before and after treatments, (B) BFM disability score before and after treatment A. Burke–Fahn–Marsden rating scale (BFM) dystonia score: left upper extremity
B. Burke–Fahn–Marsden rating scale (BFM) disability score
Prior to treatment •Provoking factor: Dystonia present at rest = 4 x •Arm: Severe, no useful grasp = 4
Prior to treatment •Speech: easily understood = 1 •⁎Handwriting: slight difficulty = 1 •Feeding: completely dependant = 4 •Eating: no choking = 0 •Hygiene: needs help with all activities = 4 •Dressing: Helpless = 4 •Walking: Moderately abnormal = 2 Total = 16/30
Total: 16
Hospital Day 5 •Provoking factor: Dystonia present at rest = 4 x •Arm: Able to grasp, with some manual function = 3 Total: 12
Eight week follow-up appointment •Provoking factor: Dystonia present at rest = 4 x •Arm: Able to grasp, with some manual function = 3 Total: 12
Hospital Day 5 •Speech: easily understood = 1 •Handwriting: slight difficulty = 1 •Feeding: independent = 1 •Eating: no choking = 0 •Hygiene: clumsy, independent = 1 •Dressing: clumsy, independent = 1 •Walking: slightly abnormal = 1 Total = 6/30
Eight week follow-up appointment •Speech: easily understood = 1 •Handwriting: slight difficulty = 1 •Feeding: can feed/no cut = 2 •Eating: no choking = 0 •Hygiene: clumsy, independent = 1 •Dressing: needs help with some activities = 2 •Walking: slightly abnormal = 1 Total = 8/30 ⁎Patient is right-handed
166
D. Irwin et al. / Journal of the Neurological Sciences 277 (2009) 164–166
5. Discussion This case report describes positive effect of intravenous lidocaine infusion on a central-mediated neurodegenerative focal dystonia. There are several potential mechanisms for the observed therapeutic effect in this case, which also provide insight into the mechanism of dystonia, and more specifically dystonia associated with neurodegenerative disease. The class IB antiarrhythmic drugs, mexelitine and lidocaine, have been reported to have a positive effect in both focal [10–14] and generalized [10] dystonias. These agents are voltage-gated sodium channel antagonists, which preferentially bind activated channels [8]. The mechanism of action for these agents in dystonia most likely involves decreased excitability of the reflex arc [10], with preferential effect on gamma motor neurons [11,13] and Ia afferent fibers [10,15]. Experiments using the tonic vibration reflex indicate abnormal Ia afferent processing of limb velocity in focal dystonia patients [15], which may be inhibited using these agents. Inhibition of smaller C- and A-delta fiber afferents and motor fibers also may be involved in the mechanism of action [14]. Lidocaine and mexelitine may also affect a central process of dystonia, as they can cross the blood-brain barrier [14,15] and affect central nervous tissue sodium channels [8]. This is relevant as focal dystonia can be considered to be due at least in part to abnormal cortical and basal ganglionic sensorimotor processing [15,16], especially in CBD and PD. Intravenous lidocaine or oral mexelitine have not been previously described to alleviate dystonia associated with neurodegenerative disease. The study is limited, as it was retrospective in a single patient after an unexpected benefit of treatment was observed. In addition, the pre-treatment BFM dystonia score was generated from previous neurologic examination. Despite these limitations, these observations demonstrate great symptomatic relief in a patient and disease process that is very resistant to treatment. Ohara and colleagues [14] had similar results in a series of nine patients with spasmodic torticollis, where patients received a 100 mg lidocaine infusion over five minutes, followed by oral mexelitine. These patients required higher doses of mexelitine (mean= 776 mg/day) for prolonged relief at nine months after infusion [14]. To make this treatment more feasible for patients with neurodegenerative disease, more study is needed to determine the appropriate duration and interval of lidocaine infusions, as a five day protocol may not be practical for all affected patients. In addition, perhaps larger doses
of mexelitine, as seen in previous studies [10–12,14] may provide longer duration of relief, with fewer needed lidocaine infusions. This case illustrates a potential treatment strategy that may lead to increased function in activities of daily living for patients afflicted with this debilitating neurological symptom. Acknowledgment Private funding of this study was provided by the Potamkin foundation. References [1] Vanek Z, Jankovic J. Dystonia in corticobasal degeneration. Mov Disord 2001;16(2):251–7. [2] Stover N, Watts R. Corticobasal degeneration. Sem Neurol 2001;21(1):49–58. [3] Müller J, Wenning GK, Wissel J, Seppi K, Poewe W. Botulinum toxin treatment in atypical Parkinsonian disorders associated with disabling focal dystonia. J Neurol 2002;259:300–4. [4] Riley DE, Lang AE, Lewis A, Resch L, Ashby P, Hornykiewicz O, Black S. Cortical– basal ganglionic degeneration. Neurol 1990;40(8):1203–12. [5] Jankovic J, Brin MF. Therapeutic uses of botulinum toxin. N Engl J Med 1991;324(17):1186–94. [6] Litvan I, Agid Y, Goetz C, Jankovic J, Wenning GK, Brandel JP, et al. Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathological study. Neurol 1997;48(1):119–25. [7] Boeve BF, Lang AE, Litvan I. Corticobasal degeneration and its relationship to progressive supranuclear palsy and frontotemporal dementia. Ann Neurol 2003;54(S5):S15–9. [8] Schwartzman RJ, Patel M, Grothusen JR, Alexander GM. Efficacy of five day continuous lidocaine infusion for treatment of refractory complex regional pain syndrome. Pain Med 2008; submitted under review. [9] Burke R, Fahn S, Marsden CD, Bressman SB, Moskowitz C, Friedman J. Validity and reliability of a rating scale for the primary torsion dystonias. Neurol 1985;35:73–7. [10] Lucetti C, Nuti A, Gambaccini G, Bernardini S, Brotini S, Manca ML, Bonucelli U, et al. Mexelitine in the treatment of torticollis and generalized dystonia. Clin Neuropharmacol 2000;23(4):186–9. [11] Ohara S, Miki J, Momoi H, Unno H, Shindo M, Yanagisawa N. Treatment of spasmodic torticollis with mexelitine: a case report. Mov Disord 1997;12(3):466–9. [12] Ohara S, Tsuyuzaki J, Hayashi R. Mexelitine in the treatment of blepharospasm: experience with the first three patients. Mov Disord 1999(1):173–5. [13] Kaji R, Rothwell JC, Katayama M, Ikeda T, Kubori T, Kohara N, et al. Tonic vibration reflex and muscle afferent block in writer's cramp. Ann Neurol 1995;38:155–62. [14] Ohara S, Hayashi R, Momoi H, Miki J, Yanagisawa N. Mexiletine in the treatment of spasmodic torticollis. Mov Disord 1998;13(6):934–40. [15] Grünewald RA, Yoneda Y, Shipman JM, Sagar HJ. Idiopathic focal dystonia: a disorder of muscle spindle afferent processing? Brain 1997;120:2179–89. [16] Breakfield XO, Blood AJ, Li Y, Hallett M, Hanson PU, Standaert DG. The pathophysiological basis of dystonias. Nat Rev Neurosci 2008;9(3):222–34.