- Email: [email protected]
Tourettism in Multiple Sclerosis: A case report
Journal of the Neurological Sciences 287 (2009) 288–290
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
Tourettism in Multiple Sclerosis: A case report V. Nociti a,c, A. Fasano a, A.R. Bentivoglio a, G. Frisullo a, T. Tartaglione b, P.A. Tonali a,c, A.P. Batocchi a,c,⁎ a b c
Institute of Neurology, Department of Neuroscience, Catholic University, Rome, Italy Institute of Radiology, Department of Bioimaging and Radiological Sciences, Catholic University, Rome, Italy Fondazione Don Gnocchi, Rome, Italy
a r t i c l e
i n f o
Article history: Received 11 March 2009 Received in revised form 8 July 2009 Accepted 10 July 2009 Available online 19 August 2009 Keywords: Tourettism Multiple Sclerosis Phonic tics Motor tics Behavioural disorders Quetiapine
a b s t r a c t The term Tourettism refers to Tourette Syndrome (TS)-like symptoms which appear secondary to a variety of both acquired and congenital neurological and neuropsychiatric disorders or following an exposure to several drugs. The association between Tourettism and Multiple Sclerosis (MS) is very rare. Only two cases of patients affected by MS who also showed a simple phonic tic and complex vocal tics respectively have been reported. The case here described reports of a 30 year-old woman affected by secondary-progressive MS who developed, 7 years after the onset of the disease, TS-like symptoms which were responsive to quetiapine. At that time her brain MRI, when compared with the previous scan, showed an increased lesion burden and an increased atrophy in the regions around Sylvian fissures. Considering recent findings on TS, the increased atrophy in these strategic brain regions could be responsible for the tics onset in our patient. At the same time, the diffuse involvement of the white matter and the progressive brain atrophy which we observed could have impaired the cortico-striato-thalamo-cortical circuits consistently implicated in the pathogenesis of TS. In conclusion, we can hypothesize that in our case Tourettism and MS could be considered causal related more than coincidentally associated. © 2009 Elsevier B.V. All rights reserved.
1. Introduction Tourette Syndrome (TS) is a childhood-onset chronic and relapsing disorder which is characterised by involuntary motor and phonic tics and by a high co-morbidity with neurobehavioural disturbances such as attention deficit hyperactivity disorders (ADHD) and obsessive– compulsive disorder (OCD) [1]. The term “Tourettism” was introduced by Sacks [2] to describe acquired TS-like symptoms associated to several aetiologies. Tics associated with ADHD and/or OCD have been reported as secondary to a variety of acquired and congenital neurological and neuropsychiatric disorders or following exposure to several drugs [3]. We described here a young woman affected by Multiple Sclerosis (MS) who progressively developed TS-like symptoms.
2. Case report A 30 year-old woman affected by a secondary-progressive MS (SPMS) developed, 7 years after the onset of the disease, simple and complex motor and vocal tics, restlessness and other behaviour disorders.
⁎ Corresponding author. Institute of Neurology, Department of Neuroscience, Catholic University of Rome, L.go A Gemelli 8, 00167 Rome, Italy. Tel.: +39 06 30155390; fax: +39 06 35501909. E-mail address: [email protected] (A.P. Batocchi). 0022-510X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2009.07.009
The patient came to our attention in 1994 for the acute onset of weakness and numbness in the right side of her body. Her past personal and medical history were unremarkable except for a family member, her sister, who was affected by MS; she had neither personal history before the diagnosis of MS neither family history of tics or behavioural disorders nor exposure to drugs capable to induce Tourettism. During her hospitalization, she was diagnosed as relapsing– remitting MS for which she underwent i.v. high dose steroid treatment with improvement of her symptoms. At the first neurological examination the Expanded Disability Status Scale (EDSS) score [4] was 2 and up to 1996 the patient showed a mean annual relapse rate of 3. In 1996, after having started interferon beta 1-b 250 µg s.c. e. o.d., her annual relapse rate showed to have been reduced. In 1999 her disease converted to a secondary-progressive course and at that time the EDSS score was 5.0. In 2001 she started to show changes in her behaviour including restlessness and hyperactivity with stereotypies and mannerisms associated with a poor impulse control, inability to keep her anger under control and sleep disorders. Then, the patient developed progressively motor and phonic tics and a self-injurious behaviour characterised by compulsive, repetitive attempts to damage her skin by scratching herself and by hitting rapidly and repetitively on the ground with the left heel with consequent sore. As for simple motor tics she showed dystonic eyelid tics characterised by increased blink rate at rest with brief and sustained contractions sometimes involving adjacent facial and ocular muscles. On request, the patient was able to
V. Nociti et al. / Journal of the Neurological Sciences 287 (2009) 288–290
289
3. Discussion
Fig. 1. Brain MRI performed one year before the Tourettism onset. T2w (A) and FLAIR (B) axial images before Tourettism onset show small foci of hyperintense signal on the right cerebral peduncle and multiple and confluent hyperintense areas, compatible with demyelinating lesions, in the periventricular white matter of both cerebral hemispheres. Sylvian fissures are dilated related to atrophic parenchymal changes.
temporarily suppress them with the subsequent rebound of tics. She also showed a simple phonic tic characterised by throat clearing and complex phonic tics characterised by coprolalia and palilalia (video in Appendix A). When compared with an MRI performed one year before (Fig. 1), her brain and spinal cord MRI performed at that time showed several demyelinating lesions in the white matter of both cerebral hemispheres, in the brainstem, in the middle cerebellar peduncles and in thalami with increased lesion burden and increased atrophy around Sylvian fissures (Fig. 2). In order to improve her gait she underwent i.v. high dose steroid treatment, obtaining a mild benefit on motor disturbance but no improvement on tics and behavioural disorders. At that time, a diagnosis of Tourettism was made. She started therefore a therapy with risperidone, then suspended it when tremor and rigidity appeared as side effects. Subsequently, she began quetiapine 75 mg/day finding a benefit on behaviour disturbances and a mild improvement on tics. At present, her TS-like symptoms are mostly under control with quetiapine but the patient has developed a severe cognitive impairment and disability. The patient has given her consent to the publication of her case.
Tourettism is very rarely associated with MS [5]. Only two cases of patients affected by MS who showed simple phonic tic [6] and complex vocal tics [7] have been reported. In our patient a diagnosis of Tourettism was made because she did not fulfill the DSM-IV-TR diagnostic criteria [8] for TS. She showed simple and complex motor and phonic tics associated with behaviour disorders but she had neither personal history, nor family history of tics, OCD and other behaviour disorders; she was 30 years old at the time that TS-like symptoms appeared and she seemed to show a specific aetiology for these disturbances. The criteria used to affirm that a movement disorder is secondary to MS –a rapid onset, the presence of strategically located demyelinating lesions and/or an almost complete resolution of the symptoms after steroid treatments [9]– are more specific for relapsing–remitting MS than for secondary-progressive MS. However, some features observed in our SPMS patient suggest a causal relationship between demyelinating disease and Tourettism. Although the neuroanatomic bases of TS and acquired TS-like symptoms are unknown, the basal ganglia (BG) portions of cortico-striato-thalamo-cortical (CSTC) circuits have consistently been implicated in the pathogenesis of TS [10]. Other brain structures too seem to be involved such as the cortical regions [11] and the corpus callosum [12]. Using MRI in TS children, Sowell and colleagues [11], observed thinning of the sensorimotor cortices. The thinning was most prominent in the ventral portions of the sensory and motor homunculi that control the facial, orolingual and laryngeal musculature commonly involved in tic symptoms. They also found a correlation between cortical thickness in sensorimotor regions and tic symptoms suggesting that these brain regions are important in the pathogenesis of TS. At the time of the Tourettism onset, our patient's brain MRI showed enlarged multiple and confluent demyelinating lesions in the white matter of both cerebral hemispheres and some plaques in the brainstem, in the middle cerebellar peduncles and in thalami. When compared with the previous scan, an increased lesion burden and an increased atrophy of the brain regions around Sylvian fissures were observed. Considering the recent findings [11], the increased atrophy in these strategic brain regions could be responsible for the tics onset in our patient. Moreover, the demyelinating lesions in both thalami as well as the diffuse involvement of the brain by confluent demyelinating plaques and the damaged occult tissue which is not detectable
Fig. 2. Brain MRI performed at the time of Tourettism onset. T2w (A,B) and FLAIR (C,D) axial images show multiple and confluent hyperintense areas, compatible with demyelinating lesions, in the white matter of both cerebral hemispheres, with more extensive involvement of the right cerebral peduncle, in the middle cerebellar peduncles and in both thalami. The atrophy of the brain regions around the Sylvian fissures is increased too.
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V. Nociti et al. / Journal of the Neurological Sciences 287 (2009) 288–290
with standard MRI, might contribute to the impairment of CSTC circuits. Some authors [13] showed that, in the progressive phase of MS, diffuse inflammation characterises the whole brain, and it is associated with slowly progressive axonal injury in the normalappearing white matter and cortical demyelination. Another mechanism that could be implicated in the pathogenesis of tics in MS is an aberrant neuronal plasticity, a consequence of the demyelinating plaques, that could involve a specific motor pattern able to induce a movement disorder like tics. Since TS-like symptoms are disabling, we decided to start therapy with risperidone but it was later suspended when tremor and rigidity appeared as side effects. Our patient was therefore treated with quetiapine, an atypical antipsychotic drug that has been shown to have low to moderate affinity for the D1, D2, 5-HT1A and 5-HT2A receptors and moderate to high affinity for the α1- and α2-adrenergic receptor [14], at a dosage of 75 mg/day with benefit on TS-like symptoms. The efficacy of quetiapine has not been systematically investigated in adults with Tourette's disorders, but as it is demonstrated in some case reports [15,16] and in 2 open-label trials, this treatment has revealed to be successful [17,18]. Also our case confirmed these previous data. In our patient, in conclusion, we can hypothesize that Tourettism and MS could be causal related because the diffuse white matter involvement, the irreversible axonal loss and the progressive brain atrophy could impair at multiple levels the CSTC circuits, consistently implicated in the pathogenesis of TS. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jns.2009.07.009. References [1] King RA, Scahill L. Emotional and behavioral difficulties associated with Tourette syndrome. In: Cohen D, Jankovic J, Goetz C, editors. Tourette syndrome. Advances in neurology, 88. Philadelphia: Lippincott Williams and Wilkins; 2001. p. 79–88.
[2] Sacks OW. Acquired Tourettism in adult life. In: Friedhoff AJ, Chase TN, editors. Gilles de la Tourette syndrome. Advances in neurology. New York: Raven Press; 1982. p. 89–92. [3] Mejia NI, Jankovic J. Secondary tics and Tourettism. Rev Bras Psiquiatr 2005;27(1):11–7. [4] Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33:1444–52. [5] Nociti V, Bentivoglio AR, Frisullo G, Fasano A, Soleti F, Iorio R, et al. Movement disorders in multiple sclerosis: causal or coincidental association? Mult Scler 2008;14(9):1284–7. [6] Lana-Peixoto MA, Teixeira AL. Brazilian Committee for Treatment and Research in Multiple Sclerosis. Simple phonic tic in multiple sclerosis. Mult Scler 2002;8(6):510–1. [7] Deutsch SI, Rosse RB, Connor JM, Burket JA, Murphy ME, Fox FJ. Current status of cannabis treatment of multiple sclerosis with an illustrative case presentation of a patient with MS, complex vocal tics, paroxysmal dystonia, and marijuana dependence treated with dronabinol. CNS Spectr 2008;13(5):393–403. [8] American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. 4th edn, text revision. [9] Folgar S, Gatto EM, Raina G, Micheli F. Parkinsonism as a manifestation of multiple sclerosis. Mov Disord 2003;18(1):108–10. [10] Albin RL, Mink JW. Recent advances in Tourette syndrome research. Trends Neurosci 2006;29:175–82. [11] Sowell ER, Kan E, Yoshii J, Thompson PM, Bansal R, Xu D, et al. Thinning of sensorimotor cortices in children with Tourette syndrome. Nat Neurosci 2008;11(6):637–9. [12] Plessen KJ, Grüner R, Lundervold A, Hirsch JG, Xu D, Bansal R, et al. Reduced white matter connectivity in the corpus callosum of children with Tourette syndrome. J Child Psychol Psychiatry 2006;47(10):1013–22. [13] Kutzelnigg A, Lucchinetti CF, Stadelmann C, Brück W, Rauschka H, Bergmann M, et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 2005;128(Pt 11):2705–12. [14] Habermeyer B, Rabovsky K, Jentzsch C, Pinhard K, Müller-Spahn F. Cervical dystonia due to interaction of valproic acid and quetiapine. J Clin Psychopharmacol 2007;27(4):396–7. [15] Matur Z, Uçok A. Quetiapine treatment in a patient with Tourette's syndrome, obsessive–compulsive disorder and drug-induced mania. Isr J Psychiatry Relat Sci 2003;40(2):150–2. [16] Schaller JL, Behar D. Quetiapine treatment of adolescent and child tic disorders. Two case reports. Eur Child Adolesc Psychiatry 2002 Aug;11(4):196–7. [17] Mukaddes NM, Abali O. Quetiapine treatment of children and adolescents with Tourette's disorder. J Child Adolesc Psychopharmacol 2003;13(3):295–9. [18] de Jonge JL, Cath DC, van Balkom AJ. Quetiapine in patients with Tourette's disorder: an open-label, flexible-dose study. J Clin Psychiatry 2007;68(7):1148–50.
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
Tourettism in Multiple Sclerosis: A case report V. Nociti a,c, A. Fasano a, A.R. Bentivoglio a, G. Frisullo a, T. Tartaglione b, P.A. Tonali a,c, A.P. Batocchi a,c,⁎ a b c
Institute of Neurology, Department of Neuroscience, Catholic University, Rome, Italy Institute of Radiology, Department of Bioimaging and Radiological Sciences, Catholic University, Rome, Italy Fondazione Don Gnocchi, Rome, Italy
a r t i c l e
i n f o
Article history: Received 11 March 2009 Received in revised form 8 July 2009 Accepted 10 July 2009 Available online 19 August 2009 Keywords: Tourettism Multiple Sclerosis Phonic tics Motor tics Behavioural disorders Quetiapine
a b s t r a c t The term Tourettism refers to Tourette Syndrome (TS)-like symptoms which appear secondary to a variety of both acquired and congenital neurological and neuropsychiatric disorders or following an exposure to several drugs. The association between Tourettism and Multiple Sclerosis (MS) is very rare. Only two cases of patients affected by MS who also showed a simple phonic tic and complex vocal tics respectively have been reported. The case here described reports of a 30 year-old woman affected by secondary-progressive MS who developed, 7 years after the onset of the disease, TS-like symptoms which were responsive to quetiapine. At that time her brain MRI, when compared with the previous scan, showed an increased lesion burden and an increased atrophy in the regions around Sylvian fissures. Considering recent findings on TS, the increased atrophy in these strategic brain regions could be responsible for the tics onset in our patient. At the same time, the diffuse involvement of the white matter and the progressive brain atrophy which we observed could have impaired the cortico-striato-thalamo-cortical circuits consistently implicated in the pathogenesis of TS. In conclusion, we can hypothesize that in our case Tourettism and MS could be considered causal related more than coincidentally associated. © 2009 Elsevier B.V. All rights reserved.
1. Introduction Tourette Syndrome (TS) is a childhood-onset chronic and relapsing disorder which is characterised by involuntary motor and phonic tics and by a high co-morbidity with neurobehavioural disturbances such as attention deficit hyperactivity disorders (ADHD) and obsessive– compulsive disorder (OCD) [1]. The term “Tourettism” was introduced by Sacks [2] to describe acquired TS-like symptoms associated to several aetiologies. Tics associated with ADHD and/or OCD have been reported as secondary to a variety of acquired and congenital neurological and neuropsychiatric disorders or following exposure to several drugs [3]. We described here a young woman affected by Multiple Sclerosis (MS) who progressively developed TS-like symptoms.
2. Case report A 30 year-old woman affected by a secondary-progressive MS (SPMS) developed, 7 years after the onset of the disease, simple and complex motor and vocal tics, restlessness and other behaviour disorders.
⁎ Corresponding author. Institute of Neurology, Department of Neuroscience, Catholic University of Rome, L.go A Gemelli 8, 00167 Rome, Italy. Tel.: +39 06 30155390; fax: +39 06 35501909. E-mail address: [email protected] (A.P. Batocchi). 0022-510X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2009.07.009
The patient came to our attention in 1994 for the acute onset of weakness and numbness in the right side of her body. Her past personal and medical history were unremarkable except for a family member, her sister, who was affected by MS; she had neither personal history before the diagnosis of MS neither family history of tics or behavioural disorders nor exposure to drugs capable to induce Tourettism. During her hospitalization, she was diagnosed as relapsing– remitting MS for which she underwent i.v. high dose steroid treatment with improvement of her symptoms. At the first neurological examination the Expanded Disability Status Scale (EDSS) score [4] was 2 and up to 1996 the patient showed a mean annual relapse rate of 3. In 1996, after having started interferon beta 1-b 250 µg s.c. e. o.d., her annual relapse rate showed to have been reduced. In 1999 her disease converted to a secondary-progressive course and at that time the EDSS score was 5.0. In 2001 she started to show changes in her behaviour including restlessness and hyperactivity with stereotypies and mannerisms associated with a poor impulse control, inability to keep her anger under control and sleep disorders. Then, the patient developed progressively motor and phonic tics and a self-injurious behaviour characterised by compulsive, repetitive attempts to damage her skin by scratching herself and by hitting rapidly and repetitively on the ground with the left heel with consequent sore. As for simple motor tics she showed dystonic eyelid tics characterised by increased blink rate at rest with brief and sustained contractions sometimes involving adjacent facial and ocular muscles. On request, the patient was able to
V. Nociti et al. / Journal of the Neurological Sciences 287 (2009) 288–290
289
3. Discussion
Fig. 1. Brain MRI performed one year before the Tourettism onset. T2w (A) and FLAIR (B) axial images before Tourettism onset show small foci of hyperintense signal on the right cerebral peduncle and multiple and confluent hyperintense areas, compatible with demyelinating lesions, in the periventricular white matter of both cerebral hemispheres. Sylvian fissures are dilated related to atrophic parenchymal changes.
temporarily suppress them with the subsequent rebound of tics. She also showed a simple phonic tic characterised by throat clearing and complex phonic tics characterised by coprolalia and palilalia (video in Appendix A). When compared with an MRI performed one year before (Fig. 1), her brain and spinal cord MRI performed at that time showed several demyelinating lesions in the white matter of both cerebral hemispheres, in the brainstem, in the middle cerebellar peduncles and in thalami with increased lesion burden and increased atrophy around Sylvian fissures (Fig. 2). In order to improve her gait she underwent i.v. high dose steroid treatment, obtaining a mild benefit on motor disturbance but no improvement on tics and behavioural disorders. At that time, a diagnosis of Tourettism was made. She started therefore a therapy with risperidone, then suspended it when tremor and rigidity appeared as side effects. Subsequently, she began quetiapine 75 mg/day finding a benefit on behaviour disturbances and a mild improvement on tics. At present, her TS-like symptoms are mostly under control with quetiapine but the patient has developed a severe cognitive impairment and disability. The patient has given her consent to the publication of her case.
Tourettism is very rarely associated with MS [5]. Only two cases of patients affected by MS who showed simple phonic tic [6] and complex vocal tics [7] have been reported. In our patient a diagnosis of Tourettism was made because she did not fulfill the DSM-IV-TR diagnostic criteria [8] for TS. She showed simple and complex motor and phonic tics associated with behaviour disorders but she had neither personal history, nor family history of tics, OCD and other behaviour disorders; she was 30 years old at the time that TS-like symptoms appeared and she seemed to show a specific aetiology for these disturbances. The criteria used to affirm that a movement disorder is secondary to MS –a rapid onset, the presence of strategically located demyelinating lesions and/or an almost complete resolution of the symptoms after steroid treatments [9]– are more specific for relapsing–remitting MS than for secondary-progressive MS. However, some features observed in our SPMS patient suggest a causal relationship between demyelinating disease and Tourettism. Although the neuroanatomic bases of TS and acquired TS-like symptoms are unknown, the basal ganglia (BG) portions of cortico-striato-thalamo-cortical (CSTC) circuits have consistently been implicated in the pathogenesis of TS [10]. Other brain structures too seem to be involved such as the cortical regions [11] and the corpus callosum [12]. Using MRI in TS children, Sowell and colleagues [11], observed thinning of the sensorimotor cortices. The thinning was most prominent in the ventral portions of the sensory and motor homunculi that control the facial, orolingual and laryngeal musculature commonly involved in tic symptoms. They also found a correlation between cortical thickness in sensorimotor regions and tic symptoms suggesting that these brain regions are important in the pathogenesis of TS. At the time of the Tourettism onset, our patient's brain MRI showed enlarged multiple and confluent demyelinating lesions in the white matter of both cerebral hemispheres and some plaques in the brainstem, in the middle cerebellar peduncles and in thalami. When compared with the previous scan, an increased lesion burden and an increased atrophy of the brain regions around Sylvian fissures were observed. Considering the recent findings [11], the increased atrophy in these strategic brain regions could be responsible for the tics onset in our patient. Moreover, the demyelinating lesions in both thalami as well as the diffuse involvement of the brain by confluent demyelinating plaques and the damaged occult tissue which is not detectable
Fig. 2. Brain MRI performed at the time of Tourettism onset. T2w (A,B) and FLAIR (C,D) axial images show multiple and confluent hyperintense areas, compatible with demyelinating lesions, in the white matter of both cerebral hemispheres, with more extensive involvement of the right cerebral peduncle, in the middle cerebellar peduncles and in both thalami. The atrophy of the brain regions around the Sylvian fissures is increased too.
290
V. Nociti et al. / Journal of the Neurological Sciences 287 (2009) 288–290
with standard MRI, might contribute to the impairment of CSTC circuits. Some authors [13] showed that, in the progressive phase of MS, diffuse inflammation characterises the whole brain, and it is associated with slowly progressive axonal injury in the normalappearing white matter and cortical demyelination. Another mechanism that could be implicated in the pathogenesis of tics in MS is an aberrant neuronal plasticity, a consequence of the demyelinating plaques, that could involve a specific motor pattern able to induce a movement disorder like tics. Since TS-like symptoms are disabling, we decided to start therapy with risperidone but it was later suspended when tremor and rigidity appeared as side effects. Our patient was therefore treated with quetiapine, an atypical antipsychotic drug that has been shown to have low to moderate affinity for the D1, D2, 5-HT1A and 5-HT2A receptors and moderate to high affinity for the α1- and α2-adrenergic receptor [14], at a dosage of 75 mg/day with benefit on TS-like symptoms. The efficacy of quetiapine has not been systematically investigated in adults with Tourette's disorders, but as it is demonstrated in some case reports [15,16] and in 2 open-label trials, this treatment has revealed to be successful [17,18]. Also our case confirmed these previous data. In our patient, in conclusion, we can hypothesize that Tourettism and MS could be causal related because the diffuse white matter involvement, the irreversible axonal loss and the progressive brain atrophy could impair at multiple levels the CSTC circuits, consistently implicated in the pathogenesis of TS. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jns.2009.07.009. References [1] King RA, Scahill L. Emotional and behavioral difficulties associated with Tourette syndrome. In: Cohen D, Jankovic J, Goetz C, editors. Tourette syndrome. Advances in neurology, 88. Philadelphia: Lippincott Williams and Wilkins; 2001. p. 79–88.
[2] Sacks OW. Acquired Tourettism in adult life. In: Friedhoff AJ, Chase TN, editors. Gilles de la Tourette syndrome. Advances in neurology. New York: Raven Press; 1982. p. 89–92. [3] Mejia NI, Jankovic J. Secondary tics and Tourettism. Rev Bras Psiquiatr 2005;27(1):11–7. [4] Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33:1444–52. [5] Nociti V, Bentivoglio AR, Frisullo G, Fasano A, Soleti F, Iorio R, et al. Movement disorders in multiple sclerosis: causal or coincidental association? Mult Scler 2008;14(9):1284–7. [6] Lana-Peixoto MA, Teixeira AL. Brazilian Committee for Treatment and Research in Multiple Sclerosis. Simple phonic tic in multiple sclerosis. Mult Scler 2002;8(6):510–1. [7] Deutsch SI, Rosse RB, Connor JM, Burket JA, Murphy ME, Fox FJ. Current status of cannabis treatment of multiple sclerosis with an illustrative case presentation of a patient with MS, complex vocal tics, paroxysmal dystonia, and marijuana dependence treated with dronabinol. CNS Spectr 2008;13(5):393–403. [8] American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. 4th edn, text revision. [9] Folgar S, Gatto EM, Raina G, Micheli F. Parkinsonism as a manifestation of multiple sclerosis. Mov Disord 2003;18(1):108–10. [10] Albin RL, Mink JW. Recent advances in Tourette syndrome research. Trends Neurosci 2006;29:175–82. [11] Sowell ER, Kan E, Yoshii J, Thompson PM, Bansal R, Xu D, et al. Thinning of sensorimotor cortices in children with Tourette syndrome. Nat Neurosci 2008;11(6):637–9. [12] Plessen KJ, Grüner R, Lundervold A, Hirsch JG, Xu D, Bansal R, et al. Reduced white matter connectivity in the corpus callosum of children with Tourette syndrome. J Child Psychol Psychiatry 2006;47(10):1013–22. [13] Kutzelnigg A, Lucchinetti CF, Stadelmann C, Brück W, Rauschka H, Bergmann M, et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 2005;128(Pt 11):2705–12. [14] Habermeyer B, Rabovsky K, Jentzsch C, Pinhard K, Müller-Spahn F. Cervical dystonia due to interaction of valproic acid and quetiapine. J Clin Psychopharmacol 2007;27(4):396–7. [15] Matur Z, Uçok A. Quetiapine treatment in a patient with Tourette's syndrome, obsessive–compulsive disorder and drug-induced mania. Isr J Psychiatry Relat Sci 2003;40(2):150–2. [16] Schaller JL, Behar D. Quetiapine treatment of adolescent and child tic disorders. Two case reports. Eur Child Adolesc Psychiatry 2002 Aug;11(4):196–7. [17] Mukaddes NM, Abali O. Quetiapine treatment of children and adolescents with Tourette's disorder. J Child Adolesc Psychopharmacol 2003;13(3):295–9. [18] de Jonge JL, Cath DC, van Balkom AJ. Quetiapine in patients with Tourette's disorder: an open-label, flexible-dose study. J Clin Psychiatry 2007;68(7):1148–50.