1 / 37

Drugs and Treatments for Ataxia

Drugs and Treatments for Ataxia. Christopher M. Gomez The University of Chicago. Two types of treatments. Disease-modifying (neuroprotective) Symptomatic. Disease-modifying. Very few options right now. Most will be highly disease specific Some exceptions

marcell-connor
Download Presentation

Drugs and Treatments for Ataxia

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Drugs and Treatments for Ataxia Christopher M. Gomez The University of Chicago

  2. Two types of treatments • Disease-modifying (neuroprotective) • Symptomatic

  3. Disease-modifying • Very few options right now. • Most will be highly disease specific • Some exceptions • AVED, or other disorders of vitamin E deficiency • Hypothyroidism • Immune mediated ataxias • Disorders with some promise • Friedreichs ataxia: anti-oxidants, e.g. CoQ10, vitamin E, HDAC inhib. • Immunological disorders, esp MS: immunotherapies • Many promising avenues and drugs under consideration • e.g. anti-oxidants, kinase inhibitors, protease inhibitors, stem cells

  4. Symptomatic treatments • Target to individual symptoms. • Gold standard examples are: • L-dopa for Parkinson’s • Seizure medicines for epilepsy • May not be disease-specific. • Concept of negative vs positive symptoms • All drugs have some side effects

  5. Symptoms • Ataxia (motor incoordination, gait, limbs, speech) • Ataxic episodes • Tremor • Action • Resting • Vertigo • Blurred vision • Spasticity • Rigidity, slowness of movements • Fatigue

  6. Ataxia • Ataxia (motor incoordination, gait, limbs, speech) • Amantadine (Symmetrel) • Buspirone (Buspar) • Ataxic episodes • Acetazolamide (Diamox) • Topiramide (Topamax) • Valproate (Depakote)

  7. Tremor • Resting • L-dopa (Sinemet) • Intention/Action • Propranolol (Inderal) • Primidone (Mysoline) • Clonazepam (Klonopin) • Levitiracetam (Keppra) • Carbemazemine (Tegretol) • Isonoazid (INH)

  8. Vertigo and Blurred vision • Meclizine (Antivert) • Acetazolamide (Diamox) • Topiramate (Topamax) • Gabapentin (Neurontin) • Baclofen (Lioresal) • 3, 4 Diaminopyridine • Ondansetron (Zofran) • Valproate (Depakote)

  9. Non-ataxia motor symptoms • Spasticity • Baclofen (Lioresal) • Tizanidine (Xanaflex) • Dystonia • Baclofen (Lioresal) • Botulinum (Botox) • Rigidity, slowness of movements • Amantadine (Symmetrel) • L-dopa (Sinemet)

  10. Sleep disorders • Restless legs • L-dopa (Sinemet) • Pramipexole (Mirapex) • Sleep apnea • C-PAP • REM behavior disorder • Clonazepam (Klonopin)

  11. Novel Concept: Potential for Deep brain stimulation (DBS) in the treatment of tremor in ataxia

  12. Deep Brain Stimulation

  13. DBS historydifferent targets in brain • Ventral intermediate nucleus (VIM) DBS for ET and medically refractory parkinsonian tremor in 1997 • Globus pallidus interna (GPi) and subthalamic nucleus (STN) DBS for PD in 2002 • GPi and STN DBS for primary dystonia under humanitarian device exemption program in 2003 • Caudal Zona Incerta (cZi) tremors, dystonia in PD and MS

  14. DBS Anatomy zona incerta

  15. Anatomic Location and Connection of cZi Plaha et al 2006, Brain 129: 1732-1747

  16. Target Sites for DBS Therapy cZI Vim Thalamus: Essential Tremor Subthalamic Nucleus: Parkinson’s diseaseand Dystonia Globus Pallidus: Parkinson’s diseaseand Dystonia

  17. Zona incerta (cZi) • Very effective in controlling various tremors, PD and dystonia • Better than VIM in controlling various tremors by electrode-by-electrode comparison, including intention tremor and proximal tremor. • Better than STN in controlling PD symptoms in direct comparison. • Very effective in controlling various dystonia as well • Possibly less complications than VIM based on current knowledge

  18. DBS Stereotactic Frame:used for image guided target localization

  19. DBS for MS tremor OFF ON

  20. DBS for MS tremor OFF ON

  21. DBS for MS tremor OFF ON

  22. Novel concept • cZi DBS might be a good target to control various symptoms of SCA, particularly debilitating tremors, with a better efficacy and few complications. • A successful case of cZi DBS on SCA2 was reported in the literature (Freund et al, 2007).

  23. Inclusion criteria with SCA for cZi DBS • SCAx • Severe symptoms affecting daily functions • Failed Propranolol at 320mg/d • Failed Primidone (Mysoline) at 250mg/d. • Optional: Failed either Keppra, Sinemet, or Xyrem (if symptoms respond to alcohol) • No significant depression or dementia • Generally healthy • Realistic expectation • Good family support

  24. Surgery and Measurements • DBS Surgery • We place DBS electrodes along the VIM to cZi area, with upper 2 electrodes in VIM and bottom 2 electrodes in cZi area. • Measurements of cZi vs VIM DBS • Fahn-Tolossa-Marin Tremor Rating Scale will be used for the quantitative comparison of the therapeutic outcomes. • UPDRS, ataxia and dystonia scales • Quality of life and mood scales.

  25. Anatomic Location and Connection of cZi Plaha et al 2006, Brain 129: 1732-1747

  26. Deep Brain Stimulation

  27. Zona Incerta Gross Anatomy

  28. Physiologic Target confirmation: Microelectrode Recording Border Sagittal Section Through the Thalamus 10sec 80ms STN 10sec 80ms Border/SN 10sec 80ms

  29. Implantation of Unilateral DBS into the zona incerta, to be connected to a programmable IPG

  30. Demographic and Clinical Characteristics: 4 Case Studies

  31. Tremor Assessment • Activities of Daily Living (ADL) Questionnaire: • Scores 25 activities in terms of severity ranging from 1 to 4; high disability = 100 • 1 = able to do without difficulty • 4 = cannot do without assistance

  32. Tremor Assessment: Global Rating Score • Patient and examiner independently rated the patient’s pre-op vs post-op status • Score ranges from -3 (markedly worse) to +3 (markedly improved) • No change (score = 0)

  33. ADLs pre and post DBS MS

  34. Tremor Global Rating Score Assessor: Patient Physician

  35. SCA • Very debilitating neurodegenerative disease with ataxia, various tremors, dystonia and parkinsonism. • Balance and gait difficulty, dysarthria, clumsy of the hands. • No effective medications so far.

  36. Current targets for DBS are not effective for ataxia. • Current VIM target is not very effective for intention tremor and proximal tremor, commonly seen in SCA • VIM DBS is also associated with tolerance, dysarthria, and disturbance of gait and balance, particularly in bilateral procedures

More Related