- Email: [email protected]
P1.066 Frontal cortex disturbances in focal dystonia
Poster presentations / Parkinsonism and Related Disorders 15S2 (2009) S29–S199
Results: We have identified GCH1 mutations in16 patients (22%), SGCE mutations in 6 patients (8%), Torsin A mutation in 2 patients (3%) and parkin mutation in 1 patient (1%). No mutation was detected in 48 patients (66%). Interestingly, the patient with parkin mutation presented with cervical dystonia only. Dopamine transporter scan showed markedly reduced uptake. He did not respond to levodopa but to trihexyphenidyl. Conclusion: In our series of young onet dystonia, dopa-responsive dystonia is the most common dystonia with genetic origin. Most interesting is the dystonia presentation of parkin mutation which is rare. P1.063 Generalized dystonia treated with pallidal deep brain stimulation B. Brodacki1 , H. Koziara2 , R. Rola3 , T. Tykocki2 , P. Nauman2 , W. Bonicki2 , T. Mandat2 . 1 Neurology, WIM, 2 Neurosurgery, 3 I Neurology, IPiN, Warszawa, Poland One of the most effective treatment modality is pallidal (GPi) Deep Brain Stimulation (DBS). The authors present group of patients with diagnosed generalized dystonia treated with GPi DBS. Materials and Methods: Between 2005 and 2008 four female and three male patients with diagnosed generalized dystonia were treated with GPi DBS. Mean age during implantation was 28±6. Clinical status of the patients was evaluated with Global Dystonia Scale, Fahn-Marsden Movement Scale and Unified Dystonia Rating Scale. One patient was diagnosed with DYT-1 mutation. Using MRI guided frame based stereotactic system GPi was identified using indirect and direct method. One patient was operated under local anesthesia. After macrostimulation the electrodes were implanted. The rest of the patients ware operated under general anesthesia, in those cases the target was verified by microrecording and marcrostimulation. The stimulation was initialized on the first day following implantation of the DBS. Results: All of the patients reported subjective improvement following surgery that was confirmed with previously mentioned scales. Conclusions: GPi DBS is effective and safe method of SGD treatment in selected group of patients. P1.064 The effect of botulinum toxin type A on pain and sleep dysfunction related to cranio-cervical dystonia V. Metta. Kings College Hospital, London, UK Background: There is no information available exploring the occurrence of non-motor symptoms (NMS) associated with the various types of adult onset cranio-cervical dystonia such as torticollis. NMS that are relevant includes pain, sleep disturbance and fatigue. Botulinum toxin injection (BTxA) is a well established treatment for dystonia and is licensed for the treatment of torticollis but so far there are no studies published that explore the effect of BTxA treatment on these NMS. Objective: To assess the effect of BTxA on pain and sleep in a variety of torticollis cases in a OPD set up. Method: Sleep dysfunction and pain related to torticollis was assessed using clinical questionnaires, PDSS for sleep dysfunction and a visual analogue scale for pain ratings. Baseline assessment was carried followed by a re-assessment at follow up to assess sleep or pain dysfunction following BTx therapy in 39 subjects. Results: PDSS values (increased significantly (P < 0.05) from 49.8 (±11.9) to 64 (±17.9). Pain visual analogue scale scores diminished significantly from 6.5 (±3.2) to 3 (±2.3) (P < 0.05). Further to this, the most significant results were evident in the tremulous torticollis group (N = 13) where PDSS values improved by 24.25% from baseline and pain ratings decreased by 52.12%. Similarly, within the rotational torticollis group (N = 10) PDSS values improved by 14.48% and pain ratings decreased by 59.61%.
S45
Conclusions: Therapy with botulinum toxin helps in improvement in pain scores and possibly leads to improvement in several sleep parameters with overall beneficial effect on sleep. P1.065 Cervical dystonia: clinical and therapeutic features in 85 patients R.P. Munhoz1 , H. Teive2 , N. Becker2 , R.H. Scola2 , C.H.F. Camargo2 , L.C. Werneck2 , H. Fameli3 , M. Moscovich3 , L. Filla3 . 1 Neurology, 2 Clinical Hospital, 3 Pontifical University of Parana, Curitiba, Brazil Objective: Identify the clinical profile of 85 patients with cervical dystonia and to analyze their response to treatment with botulinum toxin A (BoNT/A) in terms of the severity of the motor alterations and pain. Background: Dystonia is defined as a syndrome characterized by prolonged muscle contraction causing twisting, repetitive movements or abnormal posture. A wide range of therapies are available for cervical dystonia, from clinical treatment to brain surgery or even peripheral surgery. However, BoNT/A is currently considered the treatment of choice. Methods: The inclusion criteria were: (1) the presence of cervical or segmental dystonia; (2) the presence of generalized dystonia, hemidystonia or multifocal dystonia, with referral for botulinumtoxin-A treatment for cervical dystonia. Patients were assessed on admission and approximately 14, 30 and 120 days after the treatment with BoNT/A had started to compare severity, disability and pain using scales. Results: The average ages at onset of focal dystonia and segmental dystonia were greater than for generalized dystonia (p < 0.0003). The severity of the abnormal head-neck movements were more severe among the patients with generalized dystonia (p < 0.001). Pain in the cervical area was noted in 59 patients. It was not possible to determine the etiology of the disease in 62.3% of patients. Tardive dystonia was the most common secondary etiology. Conclusions: A major improvement in the motor symptoms of CD and pain was observed in patients following treatment with BoNT/A. The tardive dystonia subgroup did not respond to the treatment. Dysphagia was observed in 2.35% of the patients. P1.066 Frontal cortex disturbances in focal dystonia S. Ochudlo1 , K. Wisniewska2 , A. Tarko2 , T. Sadowski3 , G. Opala4 . 1 Neurology, Central Hospital of Medical University of Silesia, 2 Neurology, Student Scientific Group, 3 Epidemiology, 4 Neurology, Medical University of Silesia, Katowice, Poland Objective: Dystonia is a fairly common neurological disorder characterized by abnormal posturing due to sustained muscle contractions, which interferes with the performance of motor tasks. In focal dystonia (FD), a deficient interaction between premotor and motor cortex could impair the ability of the motor cortex to execute a task-specific movement. Background: Prior studies have focused on the motor cortex itself; this investigation is novel in looking at the important contribution of the premotor cortex to both motor execution and abnormalities in FD. We hypothesize that a deficient premotor–motor inhibitory network contributes to the unwanted involuntary movements in dystonia. Methods: We studied 34 control subjects, 39 patients with cervical dystonia (CD), 26 patients with blepharospasm (BPS), 23 patients with Meige Syndrome (MS). Premotor–motor intracortical interactions were analyzed by Frontal Assessment Battery (FAB) and Trial Making Test A and B (TMT-A, TMT-B). Results: Our preliminary results show statistically significant difference between BPS and control in both tests FAB, TMT-A and TMT-B (FAB, p < 0.001; TMT-A p < 0.01; TMT-B p < 0.01); MS and control in both FAB and TMT-A (FAB, p < 0.05; TMT-A p < 0.05); between CD and control in FAB (p < 0.02).
S46
Poster presentations / Parkinsonism and Related Disorders 15S2 (2009) S29–S199
Conclusions: Our preliminary results suggest that executive dysfunctions may reflect an abnormal premotor–motor connections network in FD.
Conclusion: There was essentially no statistical difference in the muscle paralysis resulting from fresh toxin between Botox® (Allergan, Irvine, CA, USA) and BTXA® (Lanzhou Institute, China).
P1.067 Executive dysfunction in hemifacial spasm
P1.069 Genetic spectrum of dopa-responsive dystonia in the Polish families M. Rudzinska1 , M. Bodzioch2 , K. Lapicka-Bodzioch2 , B. Zapała2 , A. Potulska-Chromik3 , P. Janik4 , Z. Jamrozik4 , A. DembinskaKiec2 , A. Szczudlik1 . 1 Department of Neurology, 2 Department of Biochemistry, Jagiellonian University, Krakow, 3 Department of Neurology, Medicial University of Warsaw, Warsaw, 4 Department of Neurology, Medical University of Warsaw, Krakow, Poland
S. Ochudlo1 , K. Wisniewska2 , A. Tarko2 , T. Sadowski3 , G. Opala4 . 1 Neurology, Central Hospital of Medical University of Silesia, 2 Student Scientific Group, 3 Epidemiology, 4 Neurology, Medical University of Silesia, Katowice, Poland Objective: Hemifacial spasm (HFS) is a fairly common neurological disorder characterized by abnormal function of seventh cranial nerve due to repetitive facial muscles contractions, which interferes with the performance of motor tasks. In hemifacial spasm, a deficient interaction between premotor and motor cortex could impair the ability of the motor cortex to execute a task-specific movement. Background: Prior studies have focused on the VII nerv itself; this investigation is novel in looking at the important contribution of the premotor cortex to both motor execution and abnormalities in HFS. We hypothesize that a deficient premotor–motor inhibitory network contributes to the unwanted involuntary movements in HFS. Methods: We studied 34 control subjects adn 41 patients with HFS. Premotor-motor intracortical interactions were analyzed by Frontal Assessment Battery (FAB) and Trial Making Test A and B (TMT-A, TMT-B). Results: Our preliminary results show statistically significant difference between HFS and control in both tests FAB, TMT-A and TMT-B. FAB: 11.2 (2.6), p < 0.05; TMT-A: 75.3 (31.2) p < 0.01; TMT-B: 111.4 (35.7), p < 0.05. Conclusions: Our preliminary results suggest that executive dysfunctions may reflect an abnormal premotor–motor connections network in HFS. P1.068 Comparative study of the botulinum toxin type A potency between Botox® and BTXA® : using human extensor brevis muscle M. Park1 , K. Ahn2 . 1 Neurology, Yeungnam University Medical Center, Daegu, South Korea, 2 Plastic and Reconstructive Surgery, Dr. Ahn’s Aesthetic Clinic, Daegu, Republic of Korea Introduction: Even though the dopaminergic agents are taken adequately in the patients with Parkinson’s disease, focal dystonia of digits is not uncommon. Sometimes local injection of botulinum toxin type A into the target muscles is useful to relieve their focal motor discomfortness. Background: The objective of this study was to compare the potency of botulinum toxin products between Botox® (Allergan, Irvine, CA, USA) and BTXA® (Lanzhou Institute, China). A prospective randomized double blind controlled comparison in the two groups was undertaken. Material and Methods: Using 18 healthy volunteers, we measured decline in extensor digitorum brevis (EDB) compound muscle action potential (CMAP) amplitude following 1 week after injection of fresh reconstituted 2.5 MU Botox® in one side and 2.5 MU BTXA® in the other side of the foot. We also measured EDB CMAP amplitude at post injection 12 weeks. Results: Eighteen (male 9, female 9) volunteers, aged 22 to 29 years old (mean age 24.0±2.3 years), were enrolled and two groups (each side of foot) were evaluated according to their injected commercial preparations. The mean values of EDB amplitude percent paralysis at post injection 1 and 12 week were as follows: 52.9±5.0% in the Botox® group and 54.7±18.1% in the BTXA® group at 1 week after injection, 23.3±24.3%, 25.8±29.6% at 12 weeks after injection in each group.
Introduction: Dopa-responsive dystonia (DRD) is an autosomal dominant disease caused by GCH1 mutations. There have been approximately 100 distinct mutations identified so far. Objective: To present the genetic spectrum of DRD patients in the Polish population. Patients and Methods: We performed mutation analysis of the whole GCH1 coding sequence in 13 DRD patients (11 women) and 28 unaffected family members, representing six DRD families from Poland. Results: We detected six different GCH1 mutations in all 13 clinically confirmed cases and three unsymptomatic carriers. Five of those defects were novel, including two splice site mutations, c.453+1G>A and c.509+5delG, two missense substitutions, c.539A>C (Q180P) and c.680C>A (T227N), and one frameshift mutation in exon 1, resulting in a premature stop codon, c.93delG (G31fsX66). One mutation, c.614T>G (V205G), was reported previously. None of the detected mutations was identified in a control group of 80 sex- and age-matched control individuals without neurological abnormalities. In 10 of 13 patients, the onset was between 4 and 12 years of age but in two others in adulthood (28 and 44 years for age). In all cases the disease presented with foot dystonia, progressing to hemidystonia in one patient, and cervical dystonia in the other. In six patients, dystonia coincided with some other involuntary movements or parkinsonian syndrome. Five patients in one DRD family showed a clinically significant shortening (1.5–4 cm) of a dystonic leg. Conclusion: There is a wide heterogeneity of genetic defects among DRD patients even in patients with similar phenotypes coming from different families. P1.070 Mutations in the THAP1 (DYT6) gene – a cause of generalized dystonia with prominent spasmodic dysphonia S.A. Schneider1 , A. Djarmati1 , K. Lohmann1 , S. Winkler1 , 2 H. Pawlack1 , J. Hagenah2 , N. Bruggemann ¨ , S. Zittel3 , T. Fuchs4 , 1 2 5 A. Rakovic´ , A. Schmidt , H.-C. Jabusch , R. Wilcox6 , V.S. Kostic´ 7 , 3 H. Siebner8 , A. Munchau ¨ , L.J. Ozelius4,9 , C. Klein1 . 1 Neurogenetics, 2 Neurology, University Luebeck, Luebeck, 3 Neurology, University Hamburg, Hamburg, Germany; 4 Genetics and Genomic Science, Mount Sinai School of Medicine, New York, NJ, USA; 5 Institut f¨ ur Musikermedizin, Hochschule f¨ ur Musik Carl Maria von Weber, Dresden, Germany; 6 The Prince Charles Hospital, Chermside, Brisbane, QLD, Australia; 7 Institute of Neurology, CCS, Belgrade, Serbia; 8 Danish Research Centre for Magnetic Resonance, Department of Magnetic Resonance; Copenhagen University Hospital Hvidovre, Copenhagen, Denmark; 9 Department of Neurology, Mount Sinai School of Medicine, New York, NJ, USA DYT6 causes primary early-onset torsion dystonia. Unlike in DYT1 dystonia, symptoms frequently involve the cranio-cervical region. Recently, two mutations in the THAP1 gene have been identified. Methods: We comprehensively screened 160 predominantly German dystonia patients with an early age at onset (n = 64), generalized dystonia (n = 35), a positive family history (n = 56), or
Results: We have identified GCH1 mutations in16 patients (22%), SGCE mutations in 6 patients (8%), Torsin A mutation in 2 patients (3%) and parkin mutation in 1 patient (1%). No mutation was detected in 48 patients (66%). Interestingly, the patient with parkin mutation presented with cervical dystonia only. Dopamine transporter scan showed markedly reduced uptake. He did not respond to levodopa but to trihexyphenidyl. Conclusion: In our series of young onet dystonia, dopa-responsive dystonia is the most common dystonia with genetic origin. Most interesting is the dystonia presentation of parkin mutation which is rare. P1.063 Generalized dystonia treated with pallidal deep brain stimulation B. Brodacki1 , H. Koziara2 , R. Rola3 , T. Tykocki2 , P. Nauman2 , W. Bonicki2 , T. Mandat2 . 1 Neurology, WIM, 2 Neurosurgery, 3 I Neurology, IPiN, Warszawa, Poland One of the most effective treatment modality is pallidal (GPi) Deep Brain Stimulation (DBS). The authors present group of patients with diagnosed generalized dystonia treated with GPi DBS. Materials and Methods: Between 2005 and 2008 four female and three male patients with diagnosed generalized dystonia were treated with GPi DBS. Mean age during implantation was 28±6. Clinical status of the patients was evaluated with Global Dystonia Scale, Fahn-Marsden Movement Scale and Unified Dystonia Rating Scale. One patient was diagnosed with DYT-1 mutation. Using MRI guided frame based stereotactic system GPi was identified using indirect and direct method. One patient was operated under local anesthesia. After macrostimulation the electrodes were implanted. The rest of the patients ware operated under general anesthesia, in those cases the target was verified by microrecording and marcrostimulation. The stimulation was initialized on the first day following implantation of the DBS. Results: All of the patients reported subjective improvement following surgery that was confirmed with previously mentioned scales. Conclusions: GPi DBS is effective and safe method of SGD treatment in selected group of patients. P1.064 The effect of botulinum toxin type A on pain and sleep dysfunction related to cranio-cervical dystonia V. Metta. Kings College Hospital, London, UK Background: There is no information available exploring the occurrence of non-motor symptoms (NMS) associated with the various types of adult onset cranio-cervical dystonia such as torticollis. NMS that are relevant includes pain, sleep disturbance and fatigue. Botulinum toxin injection (BTxA) is a well established treatment for dystonia and is licensed for the treatment of torticollis but so far there are no studies published that explore the effect of BTxA treatment on these NMS. Objective: To assess the effect of BTxA on pain and sleep in a variety of torticollis cases in a OPD set up. Method: Sleep dysfunction and pain related to torticollis was assessed using clinical questionnaires, PDSS for sleep dysfunction and a visual analogue scale for pain ratings. Baseline assessment was carried followed by a re-assessment at follow up to assess sleep or pain dysfunction following BTx therapy in 39 subjects. Results: PDSS values (increased significantly (P < 0.05) from 49.8 (±11.9) to 64 (±17.9). Pain visual analogue scale scores diminished significantly from 6.5 (±3.2) to 3 (±2.3) (P < 0.05). Further to this, the most significant results were evident in the tremulous torticollis group (N = 13) where PDSS values improved by 24.25% from baseline and pain ratings decreased by 52.12%. Similarly, within the rotational torticollis group (N = 10) PDSS values improved by 14.48% and pain ratings decreased by 59.61%.
S45
Conclusions: Therapy with botulinum toxin helps in improvement in pain scores and possibly leads to improvement in several sleep parameters with overall beneficial effect on sleep. P1.065 Cervical dystonia: clinical and therapeutic features in 85 patients R.P. Munhoz1 , H. Teive2 , N. Becker2 , R.H. Scola2 , C.H.F. Camargo2 , L.C. Werneck2 , H. Fameli3 , M. Moscovich3 , L. Filla3 . 1 Neurology, 2 Clinical Hospital, 3 Pontifical University of Parana, Curitiba, Brazil Objective: Identify the clinical profile of 85 patients with cervical dystonia and to analyze their response to treatment with botulinum toxin A (BoNT/A) in terms of the severity of the motor alterations and pain. Background: Dystonia is defined as a syndrome characterized by prolonged muscle contraction causing twisting, repetitive movements or abnormal posture. A wide range of therapies are available for cervical dystonia, from clinical treatment to brain surgery or even peripheral surgery. However, BoNT/A is currently considered the treatment of choice. Methods: The inclusion criteria were: (1) the presence of cervical or segmental dystonia; (2) the presence of generalized dystonia, hemidystonia or multifocal dystonia, with referral for botulinumtoxin-A treatment for cervical dystonia. Patients were assessed on admission and approximately 14, 30 and 120 days after the treatment with BoNT/A had started to compare severity, disability and pain using scales. Results: The average ages at onset of focal dystonia and segmental dystonia were greater than for generalized dystonia (p < 0.0003). The severity of the abnormal head-neck movements were more severe among the patients with generalized dystonia (p < 0.001). Pain in the cervical area was noted in 59 patients. It was not possible to determine the etiology of the disease in 62.3% of patients. Tardive dystonia was the most common secondary etiology. Conclusions: A major improvement in the motor symptoms of CD and pain was observed in patients following treatment with BoNT/A. The tardive dystonia subgroup did not respond to the treatment. Dysphagia was observed in 2.35% of the patients. P1.066 Frontal cortex disturbances in focal dystonia S. Ochudlo1 , K. Wisniewska2 , A. Tarko2 , T. Sadowski3 , G. Opala4 . 1 Neurology, Central Hospital of Medical University of Silesia, 2 Neurology, Student Scientific Group, 3 Epidemiology, 4 Neurology, Medical University of Silesia, Katowice, Poland Objective: Dystonia is a fairly common neurological disorder characterized by abnormal posturing due to sustained muscle contractions, which interferes with the performance of motor tasks. In focal dystonia (FD), a deficient interaction between premotor and motor cortex could impair the ability of the motor cortex to execute a task-specific movement. Background: Prior studies have focused on the motor cortex itself; this investigation is novel in looking at the important contribution of the premotor cortex to both motor execution and abnormalities in FD. We hypothesize that a deficient premotor–motor inhibitory network contributes to the unwanted involuntary movements in dystonia. Methods: We studied 34 control subjects, 39 patients with cervical dystonia (CD), 26 patients with blepharospasm (BPS), 23 patients with Meige Syndrome (MS). Premotor–motor intracortical interactions were analyzed by Frontal Assessment Battery (FAB) and Trial Making Test A and B (TMT-A, TMT-B). Results: Our preliminary results show statistically significant difference between BPS and control in both tests FAB, TMT-A and TMT-B (FAB, p < 0.001; TMT-A p < 0.01; TMT-B p < 0.01); MS and control in both FAB and TMT-A (FAB, p < 0.05; TMT-A p < 0.05); between CD and control in FAB (p < 0.02).
S46
Poster presentations / Parkinsonism and Related Disorders 15S2 (2009) S29–S199
Conclusions: Our preliminary results suggest that executive dysfunctions may reflect an abnormal premotor–motor connections network in FD.
Conclusion: There was essentially no statistical difference in the muscle paralysis resulting from fresh toxin between Botox® (Allergan, Irvine, CA, USA) and BTXA® (Lanzhou Institute, China).
P1.067 Executive dysfunction in hemifacial spasm
P1.069 Genetic spectrum of dopa-responsive dystonia in the Polish families M. Rudzinska1 , M. Bodzioch2 , K. Lapicka-Bodzioch2 , B. Zapała2 , A. Potulska-Chromik3 , P. Janik4 , Z. Jamrozik4 , A. DembinskaKiec2 , A. Szczudlik1 . 1 Department of Neurology, 2 Department of Biochemistry, Jagiellonian University, Krakow, 3 Department of Neurology, Medicial University of Warsaw, Warsaw, 4 Department of Neurology, Medical University of Warsaw, Krakow, Poland
S. Ochudlo1 , K. Wisniewska2 , A. Tarko2 , T. Sadowski3 , G. Opala4 . 1 Neurology, Central Hospital of Medical University of Silesia, 2 Student Scientific Group, 3 Epidemiology, 4 Neurology, Medical University of Silesia, Katowice, Poland Objective: Hemifacial spasm (HFS) is a fairly common neurological disorder characterized by abnormal function of seventh cranial nerve due to repetitive facial muscles contractions, which interferes with the performance of motor tasks. In hemifacial spasm, a deficient interaction between premotor and motor cortex could impair the ability of the motor cortex to execute a task-specific movement. Background: Prior studies have focused on the VII nerv itself; this investigation is novel in looking at the important contribution of the premotor cortex to both motor execution and abnormalities in HFS. We hypothesize that a deficient premotor–motor inhibitory network contributes to the unwanted involuntary movements in HFS. Methods: We studied 34 control subjects adn 41 patients with HFS. Premotor-motor intracortical interactions were analyzed by Frontal Assessment Battery (FAB) and Trial Making Test A and B (TMT-A, TMT-B). Results: Our preliminary results show statistically significant difference between HFS and control in both tests FAB, TMT-A and TMT-B. FAB: 11.2 (2.6), p < 0.05; TMT-A: 75.3 (31.2) p < 0.01; TMT-B: 111.4 (35.7), p < 0.05. Conclusions: Our preliminary results suggest that executive dysfunctions may reflect an abnormal premotor–motor connections network in HFS. P1.068 Comparative study of the botulinum toxin type A potency between Botox® and BTXA® : using human extensor brevis muscle M. Park1 , K. Ahn2 . 1 Neurology, Yeungnam University Medical Center, Daegu, South Korea, 2 Plastic and Reconstructive Surgery, Dr. Ahn’s Aesthetic Clinic, Daegu, Republic of Korea Introduction: Even though the dopaminergic agents are taken adequately in the patients with Parkinson’s disease, focal dystonia of digits is not uncommon. Sometimes local injection of botulinum toxin type A into the target muscles is useful to relieve their focal motor discomfortness. Background: The objective of this study was to compare the potency of botulinum toxin products between Botox® (Allergan, Irvine, CA, USA) and BTXA® (Lanzhou Institute, China). A prospective randomized double blind controlled comparison in the two groups was undertaken. Material and Methods: Using 18 healthy volunteers, we measured decline in extensor digitorum brevis (EDB) compound muscle action potential (CMAP) amplitude following 1 week after injection of fresh reconstituted 2.5 MU Botox® in one side and 2.5 MU BTXA® in the other side of the foot. We also measured EDB CMAP amplitude at post injection 12 weeks. Results: Eighteen (male 9, female 9) volunteers, aged 22 to 29 years old (mean age 24.0±2.3 years), were enrolled and two groups (each side of foot) were evaluated according to their injected commercial preparations. The mean values of EDB amplitude percent paralysis at post injection 1 and 12 week were as follows: 52.9±5.0% in the Botox® group and 54.7±18.1% in the BTXA® group at 1 week after injection, 23.3±24.3%, 25.8±29.6% at 12 weeks after injection in each group.
Introduction: Dopa-responsive dystonia (DRD) is an autosomal dominant disease caused by GCH1 mutations. There have been approximately 100 distinct mutations identified so far. Objective: To present the genetic spectrum of DRD patients in the Polish population. Patients and Methods: We performed mutation analysis of the whole GCH1 coding sequence in 13 DRD patients (11 women) and 28 unaffected family members, representing six DRD families from Poland. Results: We detected six different GCH1 mutations in all 13 clinically confirmed cases and three unsymptomatic carriers. Five of those defects were novel, including two splice site mutations, c.453+1G>A and c.509+5delG, two missense substitutions, c.539A>C (Q180P) and c.680C>A (T227N), and one frameshift mutation in exon 1, resulting in a premature stop codon, c.93delG (G31fsX66). One mutation, c.614T>G (V205G), was reported previously. None of the detected mutations was identified in a control group of 80 sex- and age-matched control individuals without neurological abnormalities. In 10 of 13 patients, the onset was between 4 and 12 years of age but in two others in adulthood (28 and 44 years for age). In all cases the disease presented with foot dystonia, progressing to hemidystonia in one patient, and cervical dystonia in the other. In six patients, dystonia coincided with some other involuntary movements or parkinsonian syndrome. Five patients in one DRD family showed a clinically significant shortening (1.5–4 cm) of a dystonic leg. Conclusion: There is a wide heterogeneity of genetic defects among DRD patients even in patients with similar phenotypes coming from different families. P1.070 Mutations in the THAP1 (DYT6) gene – a cause of generalized dystonia with prominent spasmodic dysphonia S.A. Schneider1 , A. Djarmati1 , K. Lohmann1 , S. Winkler1 , 2 H. Pawlack1 , J. Hagenah2 , N. Bruggemann ¨ , S. Zittel3 , T. Fuchs4 , 1 2 5 A. Rakovic´ , A. Schmidt , H.-C. Jabusch , R. Wilcox6 , V.S. Kostic´ 7 , 3 H. Siebner8 , A. Munchau ¨ , L.J. Ozelius4,9 , C. Klein1 . 1 Neurogenetics, 2 Neurology, University Luebeck, Luebeck, 3 Neurology, University Hamburg, Hamburg, Germany; 4 Genetics and Genomic Science, Mount Sinai School of Medicine, New York, NJ, USA; 5 Institut f¨ ur Musikermedizin, Hochschule f¨ ur Musik Carl Maria von Weber, Dresden, Germany; 6 The Prince Charles Hospital, Chermside, Brisbane, QLD, Australia; 7 Institute of Neurology, CCS, Belgrade, Serbia; 8 Danish Research Centre for Magnetic Resonance, Department of Magnetic Resonance; Copenhagen University Hospital Hvidovre, Copenhagen, Denmark; 9 Department of Neurology, Mount Sinai School of Medicine, New York, NJ, USA DYT6 causes primary early-onset torsion dystonia. Unlike in DYT1 dystonia, symptoms frequently involve the cranio-cervical region. Recently, two mutations in the THAP1 gene have been identified. Methods: We comprehensively screened 160 predominantly German dystonia patients with an early age at onset (n = 64), generalized dystonia (n = 35), a positive family history (n = 56), or