1. COMPREHENSIVE MANAGEMENT OF PARKINSONIAN PATIENTS WITH BOTULINUM TOXIN MAJA TROŠT DEPARTMENT FOR NEUROLOGY

2. PARKINSON’S DISEASE Motor & non motor symptoms impair QoL Many are resistant to conventional treatment

3. Indications for BoNT treatment in PD Limb dystonia Blepharospasm & apraxia of eyelid opening Bruxism Antecollis Camptocormia Tremor (hand and jaw) Painful shoulder (due to rigidity) Freezing of gait Sialorrhea Dysphagia Seborrhea Hyperhidrosis Overactive bladder Constipation

4. DYSTONIA IN PD Affects 60% of patients Risk factors for dystonia in PD: young age, female gender, long disease duration Side effect of levodopa treatment Mechanism? Jankovic and Stacy 2007, Jankovic and Tintner 2001

5. Blepharospasm & lid apraxia More common in PSP Mechanism? Hallett et al 2008, Elston 1992, Krack and Marion 1994

6. BoNT treatment Time form injection to improvement: 3-5 days Duration of benefit: 3-4 months Frowning pre and after BoNT Hirota et al 2008

7. Therapeutics and Technology Assessment Subcommittee of the AAN: level B (probably effective) evidence for its efficacy, and recommended that ‘‘BoNT injection should be considered as a treatment option for blepharospasm’’ Simpson et al 2008

8. Bruxism Focal oromandibular dystonia Study: 18 pts with severe bruxism m. masseter BoNT injection 1 transient dysphagia 3.4 ± 0.9 improvement (0-4) Tan and Jankovic, 2000

9. Limb dystonia Foot dystonia – striatal foot Striatal hand Jankovic 2005

10. Dystonic clenched fist Levodopa related dyskinesia (painful off stage dystonia) Jankovic and Stacy 2007, Pacchetti et al 1995

11. Neck dystonia Antecollis is most common in PD & MSA

13. Axial dystonia & camptocormia Cervical dystonia Abnormal trunk posture (scoliosis, kyphosis, camptocormia, pisa syndrome)

14. Camptocormia BoNT in rectus abdominis: 9/11 pts improved No effect of BoNT of the iliopsoas muscles Azher, Jankovic 2005; von Coelln et al., 2008, Mahjneh e tal. 2009, Colosimo, Salvatori 2009

15. Tremor Re-emergent tremor interferes more with QoL then rest tremor Th: BoNT, DBS

16. Tremor Two double blind, placebo controlled studies with BoNT for essential tremor: safe and effective in reducing of tremor amplitude, but weakness of finger extensors appeared No significant effect in PD tremor Jaw tremor (BoNT in masseter muscles) Jankovic et al 1996, Brin et al 2001, Schneider et al 2006

17. Freezing of gait Mechanism? Dystonic, disinhibited foot grasp (Brown, 1958) BoNT in distal leg muscles was not effective

18. Sialorrhea Affects 75% of PD pts Causes social handicap, skin irritation, infection BoNT in submandibular and parotid glands All types of BoNT are useful Side effects: dysphagia, xerostomia Myobloc side effect: dry mouth… Jankovic, 2008, 2009, Gomez-Caravaca et al. 2014

19.  Egevad et al. 2014

20. Dysphagia/achalasia Mechanism: degeneration of motor nucleus of n. X, Lewy bodies in myenteric plexus of the esophagus, flexed neck, achalasia Th: BoNT in lower esophageal sphincter

21. Overactive bladder Therapeutics and Technology Assessment Subcommittee of the AAN concluded that there is level A evidence for the recommendation that BoNT should be offered as a treatment option for neurogenic detrusor overactivity BoNT into bladder wall to increase bladder capacity and to improve urge and incontinence Patel 2006, Naumann et al 2008, Giannantoni et al 2009, Kulaksizoglu, Parman 2010

22. Constipation Anismus: focal dystonia of striated sphincter muscles at the pelvic outlet Several open-label studies demonstrated the benefic Mathers et al 1988, Albanese et al 2003, Cadeddu et al 2005

23. Thank you!