Ataxia GW Dec ppt Compatibility Mode Idebenone

Document Sample
Ataxia GW Dec ppt Compatibility Mode  Idebenone Powered By Docstoc
					                                                                                    12/3/2009




         Ataxias and
                                               Ataxias: Clinical Presentation
        Gait Disorders
               Aspen 2009
                                           • Gradual onset and progression
                                           • Balance and gait difficulty
                                           • Dysarthria
                                           • Clumsiness of the hands, including
                                             handwriting
                                           • Miscellaneous other signs from
                                             involvement of other systems




  Classification of the Ataxias                           Sporadic ataxia
                                               •   Degenerative
• Sporadic
                                               •   Stroke
• Genetic                                      •   Tumor
  – Autosomal dominant                         •   Toxic/metabolic
                                                   T i /       b li
  – Autosomal recessive                        •   Paraneoplastic
                                               •   Autoimmune
                                               •   Infectious/post-infectious
                                               •   Demyelinating




       Degenerative ataxia
           (sporadic)                          Strokes that produce ataxia
• Multiple system atrophy (MSA)            •   Ataxic hemiparesis
  – Olivopontocerebellar atrophy (MSA-C)   •   Hemisensory loss and hemiataxia
                             (MSA-P)
  – Strionigral degeneration (MSA P)       •   Isolated gait ataxia
  – Shy-Drager syndrome                    •   Hemiataxia and/or gait ataxia with
• Progressive myoclonic epilepsy               variable cranial nerve involvement




                                                                                           1
                                                                                                  12/3/2009




    Tumors that produce ataxia                         Toxic/metabolic causes of
                                                                ataxia
•   Medulloblastoma
                                                 •   Alcoholism, acute and chronic
•   Astrocytoma
                                                 •   Post-hypoxic, hyperthermia
•   Ependymoma
                                                 •          disease anti-gliadin
                                                     Celiac disease, anti gliadin antibodies
•   Hemangioblastoma
                                                 •   Childhood hyperammonemias
•   Metastatic tumor
                                                 •   Vitamin deficiency
•   Meningioma
                                                 •   Endocrine
•   Cerebellopontine angle schwannoma
                                                 •   Toxins




        Ataxia: Celiac disease                                 Celiac disease
• Celiac disease is a gluten-sensitive
  enteropathy with malabsorption; the            • Intolerance of gluten (wheat, rye, barley
  gastrointestinal disorder is reversed with a
  gluten-free diet
                                                   and oats)
• Anti gliadin antibodies are present
  Anti-gliadin                                   • Immune system response damaging the
    – IgA, but also IgG                            small intestine (atrophy of villi)
    – Other antibody: anti-endomysium
                                                 • Leads to malabsorption of nutrients
• Ataxia ± myoclonus can occur and even
  without an overt enteropathy                   • Affects about 1/250 persons
• In celiac disease, the ataxia can progress
  despite good diet




         Ataxia with Anti-gliadin
                                                     Non-specificity of Anti-gliadin Antibodies
               Antibodies
• Approximately 30% of all patients* with        • Present in a variety of neurologic
  ataxia, sporadic AND genetic                     syndromes
    – There is some controversy about the             – Neuropathy
      incidence                                       – Headache (with white matter changes)
    – *approximately 15% incidence in “normal”        – Mood disorders
      population                                      – Huntington Disease (44%)
• May improve on gluten-free diet
    – All uncontrolled observations so far




                                                                                                         2
                                                                                                                                                  12/3/2009




                                                               IgA and Transglutaminase Staining of Blood Vessels in Gluten Ataxia
                                                                 Here, type 2, but type 6 might be more specific (Hadjivassiliou et al. 2008)

      Ataxia with Anti-ganglioside
              Antibodies
 • Approximately 64% of all patients with
   ataxia, sporadic AND genetic
 • Is there a non-specific increase of many
              non specific
   antibodies in ataxia patients?                        Yellow is
                                                         overlap of
     – There is also an increase in anti-cardiolipin     green and red

       antibodies (Shamim et al. 2005)
                                                                                                                                      L= normal
                                                                                                                                      control

                                                                          Hadjivassiliou, M. et al. Neurology 2006;66:373-377




                                                                                     IVIg therapy
                                                            • IVIg has improved the ataxia in 3
                                                              patients with overt celiac disease and
                                                              ataxia (Souayah et al. 2008)
                                                                     (     y               )
                                                            • IVIg therapy has appeared to help two
                                                              patients (as well as two other patients
                                                              with anti-GAD antibodies) (Nanri et al.
Synapsin I is a cytosolic phosphoprotein found in most        2009)
neurons of the central and peripheral nervous systems.




      Ataxia: Vitamin deficiency                                            Ataxia: Endocrine
 •   Thiamine (Vitamin B1)                                  • Hypothyroidism
 •   Vitamin B12                                            • Hypoparathyroidism
 •   Vitamin E                                              • Hypoglycemia (insulinoma)
 •   Zinc




                                                                                                                                                         3
                                                                                            12/3/2009




               Ataxia: Drugs                               Ataxia: Toxins
• Phenytoin, carbamazepine, barbiturates        • Thallium, Bismuth subsalicylate
  and other antiepileptic drugs                 • Methylmercury, Methylbromide
• Lithium                                       • Toluene
• Serotonin syndrome (MAOI + SSRI)
• Cyclosporin, Methotrexate, 5-FU




        Paraneoplastic Ataxia                        Paraneoplastic Ataxia
•   Anti-Purkinje cell antibodies               • The pattern of disease is a subacute
•   Anti-neuronal antibodies                      course over a period of about 6 months
•   Anti-CV2 antibodies                           with a subsequent p
                                                              q      plateau.
•   Anti-Ma antibodies                          • The ataxia often presents before the
•   Amphiphysin antibodies                        tumor.
•   Antibodies against the glutamate receptor
•   Antibody negative




        Paraneoplastic Ataxia                          Autoimmune ataxia
• Tests currently commercially available        • Antibodies to GAD
  include Hu, Ma, Ta, Yo, Ri and CV2              – Pure ataxia syndrome
                                                  – Associated other autoimmunity
                                                  – Possible peripheral neuropathy
                                                  – Relationship to stiffperson syndrome?
                                                  – Antibody may block GABAergic
                                                    transmission in the cerebellum




                                                                                                   4
                                                                                                                                                                                                                                     12/3/2009




Ataxia with Anti-GAD Antibodies                                                                                      Autosomal Dominant Ataxia
• A study of 14 patients                                                                                           • The cerebellar syndrome is similar in
   – Thirteen patients were women, and 11 had late-                                                                  the different disorders.
     onset IDDM
   – Patients did not have clinical or radiologic
                                                                                                                   • Patients experience the gradual onset
     evidence of brainstem involvement                                                                               of balance and gait difficulty, dysarthria
   – The level of GAD-Ab of these patients was similar                                                               and clumsiness of the hands. There
     to those with stiff person syndrome                                                                             may be visual symptoms such as blurry
                                                                                                                     vision or diplopia. The age of onset is
                                            Honnorat et al. 2001
                                                                                                                     highly variable.




                   The Autosomal Dominant Ataxias
 Name                 Chromosome     Mutation                     Normal repeat number   Range of repeats in the
                                                                                                                               The Autosomal Dominant Ataxias: the Proteins
                                                                                               disorder               Name                                     Protein
 SCA 1                   6p23        CAG expansion                       6-44                   40-83
                                                                                                                      SCA 1                                    Ataxin-1
 SCA 2                   12q24       CAG expansion                       14-31                   34-59                SCA 2                                    Ataxin-2
 SCA 3                   14q32       CAG expansion                       12-38                   56-86                SCA 3 (Machado Joseph Disease)           Ataxin-3
 SCA 4                   16q22                                                                                        SCA 4 (with sensory axonal neuropathy)
 SCA 5                   11q13       Deletion or point mutation                                                       SCA 5 (Lincoln ataxia)                   Beta III Spectrin (SPTBN2)
 SCA 6                   19p13       CAG expansion                       4-20                    21-31                SCA 6                                    α1a component of the voltage-dependent calcium channel:
                                                                                                                                                               CACNL1A4
 SCA 7                   3p14        CAG expansion                       7-17                   38->200
                                                                                                                      SCA 7                                    Ataxin-7
 SCA 8                   13q21       CTG expansion                       15-91                  100-155
                                                                                                                      SCA 8                                    (mutation is in non-coding region)
 SCA 9                 Not Linked                                                                                     SCA 9
 SCA 10                  22q13       ATTCT repeat                        10-22                 800-3800               SCA 10                                   Ataxin-10
 SCA 11                  15q14                                                                                        SCA 11                                   tau tubulin kinase 2 (TTBK2)
 SCA 12                  5q31        CAG expansion                        <29                    66-93                SCA 12                                   Protein phosphatase 2A, regulatory subunit B (PPP2R2B)
 SCA 13                  19q13                                                                                        SCA 13                                   KCNC3
 SCA 14               19q13.4-qter   Point mutation                                                                   SCA14                                    Protein kinase Cγ (PRKCG)
 SCA 15, 16, 29?         3p26        Deletion or point mutation                                                           15 16
                                                                                                                      SCA 15, 16, 29?                          I
                                                                                                                                                               Inositol 1 4 5 t i h   h t       t t
                                                                                                                                                                   it l 1,4,5-triphosphate receptor, type 1 (ITPR1)
 SCA 17                  6q27        CAG expansion                       25-42                   45-63                SCA 17 (also called HDL4)                TATA binding protein (TBP)
 SCA 18                  7q31                                                                                         SCA 18 (with sensorimotor neuropathy)
 SCA 19, 22            1p21-q21                                                                                       SCA 19

 SCA 20                   11                                                                                          SCA 20
                                                                                                                      SCA 21
 SCA 21                  7p21
                                                                                                                      SCA 22
 SCA 23                20p13-12.2
                                                                                                                      SCA 23
 (SCA 24)             Now SCAR4
                                                                                                                      (SCA 24) Now SCAR4
 SCA 25                2p15-p21
                                                                                                                      SCA 25 (with sensory neuropathy)
 SCA 26                  19p13                                                                                        SCA 26
 SCA 27                  13q34       Point mutation                                                                   SCA 27                                   Fibroblast growth factor 14 (FGF14)
 SCA 28                  18p11                                                                                        SCA 28                                   ATPase family gene 3-like 2 (AFG3L2)
 SCA 29                  3p26                                                                                         SCA 29 (congenital, non-progressive)
 SCA 30                  4q34                                                                                         SCA 30
 SCA 31 (SCA 4)          16q22       Point mutation                                                                   SCA 31 (Japanese form of SCA 4)          Pleckstrin homology domain-containing protein, family G,
                                                                                                                                                               member 4 (PLEKHG4, puratrophin-1)
 DRPLA                   12p13       CAG expansion                       3-36                    49-88
                                                                                                                      DRPLA                                    Atrophin-1 or DRPLA protein




                                                                                Schöls et al. 2004

                                                                                                                                                                                                       http://neuromuscular.wustl.edu/ataxia




                                                                                                                                                                                                                                               5
                                                                                                                                                12/3/2009




                                                                                                Distribution of the SCAs

         SCAs masquerading as
            something else
• SCA6 or SCA17 can present as task
  specific focal dystonia
                         p
• SCA2 and SCA3 can present as y       g
                                   young-
  onset dopa-responsive PD
• SCA17 (homozygote), DRPLA, (or
  ataxia with oculomotor apraxia) can
  present as HD


                                                                                                                           Schöls et al. 2004




                      Genetic ataxias                                                  Treatment of SCA1
• Commercial tests are available for SCA1, 2,                                 • Lithium therapy improves neurological
  3, 6, 7, 8, 10, 12, 13, 14,17 and DRPLA                                       function and hippocampal dendritic
  – This list will continue to expand.                                          arborization in a spinocerebellar ataxia type 1
• Genetic testing also available for autosomal                                             d l (Watase et al. 2007)
                                                                                mouse model (W t         t l
  recessive disorders: Friedreich’s ataxia,                                      – Explanation of this effect is unknown but Li
  Ataxia with vitamin E deficiency (AVED),                                         enhances gene expression and in SCA1 there is
                                                                                   downregulation of several genes
  Marinesco-Sjögren Syndrome (SIL1),
  Aprataxin (APTX), POLG1 and ARSACS                                          • The CAG and NINDS are organizing a clinical
                                                                                trial of lithium in SCA1




                        The Episodic Ataxias
  Name                 Chromosome   Mutation   Protein
                                                                                         Episodic ataxia-2
  EA type 1              12p13      Missense   Potassium channel, KCNA1
  (with myokymia)
                                                                              • Attacks of ataxia, dysarthria, nausea, vertigo,
  EA type 2              19p13      Missense   α1a component of the voltage     diplopia, oscillopsia lasting minutes to days
  (with nystagmus)                             dependent calcium channel:
                                               CACNL1A4                       • Interictal nystagmus or mild ataxia
  EA type 3
  (with vertigo and
                          1q42
                                                                              • Provoked by stress and exercise but not
  tinnitus)
                                                                                startle
  EA type 4 (PATX)
  EA type 5               2q22                 CACNB4β4
                                                                              • Attacks may respond to acetazolamide
  EA type 6
  (with migraine)
                          5p13                 SLC1A3
                                                                              • Same gene as SCA6 and familial hemiplegic
  EA type 7              19q13                                                  migraine and overlaps occur
  EA with                  1p
  paroxysmal
  choreoathetosis &
                                                                              • Patients may also have weakness with
  spasticity                                                                    neuromuscular junction abnormalities




                                                                                                                                                       6
                                                                                                                                                                                                           12/3/2009




                                                                                                            Common Autosomal Recessive Ataxias
                                                                                                                Name                              Chromosome   Mutation           Protein

                                                                                                                Friedreich Ataxia (FRDA)          9q13         trinucleotide      Frataxin
                                                                                                                                                               repeat of GAA
                                                                                                                                                               (some point
                                                                                                                                                               mutations)
                                                                                                                Friedreich Ataxia 2 (FRDA2)       9p23

                                                                                                                Ataxia with isolated vitamin E 8q13            Point mutations    α-tocopherol- transfer
                                                                                                                deficiency (AVID)                              and deletions      protein TTP1)

                                                                                                                Abetalipoproteinemia              4q22         Point mutation,    microsomal
                                                                                                                                                               deletion           triglyceride transfer
                                                                                                                                                                                  protein (MTP)
                                                                                                                Ataxia telangiectasia             11q22        Chromosome         ATM gene that codes
                                                                                                                                                               breaks             for the protein kinase
                                                                                                                                                                                  PI-3
                                                                                                                (Early onset) ataxia with         9p13         Insertion,         aprataxin (APTX)
                                                                                                                oculo-motor apraxia type 1                     deletion, point
                                                                                                                (AOA1)                                         mutation
                                                                                                                (Early onset) ataxia with         9q34         Point mutation,    senataxin (SETX)
                                                                                                                oculo-motor apra ia t pe
                                                                                                                oc lo motor apraxia type 2                     deletion
                                                                                                                (AOA2) (SCAR1)
                                                                                                                Autosomal recessive spastic       13q12        Deletions, point   SACS gene that
                                                                                                                ataxia of Charlevoix-                          mutations          codes for sacsin
                                                                                                                Saguenay (ARSACS
                                                                                                                Cayman ataxia (ATCAY)             19p13        Point mutations    ATCAY gene that
                                                                                                                                                                                  codes for caytaxin
                                                                                                                Marinesco-Sjögren Syndrome 5q31                various            SIL1
                                                                                                                (MSS)
                                                                                                                Mitochondrial recessive ataxia 15q25           Point mutation     POLG1, a catalytic
                                                                                                                syndrome (MIRAS)                                                  subunit of the
                                                                                                                                                                                  mitochrondrial DNA
                                                                                                                                                                                  polymerase gamma

                                                                                                                Spinocerebellar ataxia with       14q31        Point mutation     tyrosyl-DNA
                                                                                                                axonal neuropathy (SCAN1)                                         phosphodiesterase
                                                                                                                                                                                  (TDP1)
                                                                                                                ARCA 1 (SCAR8)                    6q25         Point mutation,    Synaptic nuclear
                                                                                                                                                               deletions          envelope protein 1
                                                                                                                                                                                  (SYNE1)
                                                                                                                ARCA 2 (SCAR9)                    1q41         Point mutations    CABC1 (ADCK3)

                                                  http://neuromuscular.wustl.edu/ataxia                         Familial cerebellar ataxia with                                   Some patients have
                                                                                                                muscle coenzyme Q10                                               AOA1 or ARCA2
                                                                                                                deficiency




          Friedreich’s Ataxia                                                                             Friedreich’s Ataxia
• Prevalence of 1 in 50,000 persons                                                       • Genetic abnormality is usually an expanded
• Age of onset is generally before 20 years                                                 trinucleotide repeat of GAA in a gene coding
• Clinical features: ataxia, dysarthria, sensory
                            , y        ,       y                                            for the protein called frataxin; 6% of the time
  loss, corticospinal tract signs with absent                                               th     is     i t    t ti
                                                                                            there i a point mutation.
  reflexes, an axon loss peripheral neuropathy,                                           • Frataxin is a mitochondrial protein encoded
  skeletal abnormalities such as                                                            by nuclear DNA. It is involved in iron
  kyphoscoliosis, cardiomyopathy, and                                                       transport, and its abnormality leads to
  diabetes.                                                                                 mitochondrial dysfunction.




                                                                                                                Treatment of FA with Idebenone

          Friedreich’s Ataxia
• Treatment
  – Idebenone
     • Several trials show reduction in cardiac hypertrophy, but no
       obvious neurological benefit (longer trial might be needed, or
       higher dose, or earlier start of therapy)
     • Dose up to 50 mg/kg can be tolerated (Di Prospero et al. 2007)
       Open label t i l i 9 children: some neurologic b
     • O      l b l trial in hild                           fit (Artuch t
                                                  l i benefit (A t h et
       al. 2002)
     • Other on-going trials in children look promising (NINDS)
  – Co-enzyme Q                                                                           These plots are for
     • Also some cardiac benefit found                                                    the ambulatory
                                                                                          patients only.
  – Other therapies being contemplated
     • Histone deacetylase (HDAC) inhibitors that increase frataxin
       expression
     • An iron chelator that reduce mitochondrial iron
                                                                                                                                                                  Di Prospero et al. 2007




                                                                                                                                                                                                                  7
                                                                                                                                                               12/3/2009




       Other Recessive Ataxias                                                                              Ataxia with isolated vitamin E
• Ataxia with isolated vitamin E deficiency
• Familial cerebellar ataxia with muscle coenzyme Q10                                                            deficiency (AVED)
  deficiency
• Abetalipoproteinemia                                                                                 • Phenotype similar to FA with ophthalmoplegia
• Ataxia telangectasia                                                                                   and retinitis pigmentosa
• (Early onset) ataxia with oculo-motor apraxia                                                        • Due to a defect in the TTP1 gene coding for
                                          Charlevoix-
• Autosomal recessive spastic ataxia of Charlevoix
  Saguenay (ARSACS)                                                                                      α-tocopherol transfer protein, which
• Cayman ataxia                                                                                          incorporates α-tocopherol into lipoproteins
• Spinocerebellar ataxia with axonal neuropathy                                                          secreted by the liver.
  (SCAN1)
• ARCA 1 - SYNE1 mutation                                                                              • This disorder can be treated with vitamin E
• ARCA 2 – CABC1 mutation                                                                                and should not be missed!
• Marinesco-Sjögren Syndrome
• Mitochrondrial recessive ataxia syndrome




Familial cerebellar ataxia with muscle                                                                 Familial cerebellar ataxia with muscle
      coenzyme Q10 deficiency                                                                                coenzyme Q10 deficiency
• Ataxia began in childhood or adolescence,                                                            • In a study of muscle biopsies in 135
  and was accompanied in some cases by
  seizures, cognitive impairment, and distal
                                                                                                         patients with undefined cerebellar
          wasting.
  muscle wasting                                                                                         ataxia, 13 were found to have deficient
                                                                                                                ,
• Administration of CoQ10 (600-3000 mg/day)                                                              CoQ10 (Lamperti et al. 2003)
  led to decreased ataxia in some patients and                                                         • At least some of these patients have
  increased strength (without decreased ataxia)                                                          autosomal recessive cerebellar ataxia type 2
  in others.                                                                                             (ARCA2) with mutation in the CABC1/ADCK3
• Musumeci et al. Neurology 2001;56:849                                                                  gene (Mollet et al. 2008; Lagier-Tourenne et
                                                                                                         al. 2008)




           Common Autosomal Recessive Ataxias
            Name                              Chromosome   Mutation           Protein

            Friedreich Ataxia (FRDA)          9q13         trinucleotide
                                                           repeat of GAA
                                                                              Frataxin                     Frequency of Autosomal Recessive Ataxias
                                                           (some point
                                                           mutations)
            Friedreich Ataxia 2 (FRDA2)       9p23

            Ataxia with isolated vitamin E 8q13            Point mutations    α-tocopherol- transfer
            deficiency (AVID)                              and deletions      protein TTP1)

            Abetalipoproteinemia              4q22         Point mutation,    microsomal
                                                           deletion           triglyceride transfer
                                                                              protein (MTP)
            Ataxia telangiectasia             11q22        Chromosome         ATM gene that codes
                                                           breaks             for the protein kinase
                                                                              PI-3
            (Early onset) ataxia with         9p13         Insertion,         aprataxin (APTX)
            oculo-motor apraxia type 1                     deletion, point
            (AOA1)                                         mutation
            (Early onset) ataxia with         9q34         Point mutation,    senataxin (SETX)
            oc lo motor apraxia type 2
            oculo-motor apra ia t pe                       deletion
            (AOA2) (SCAR1)
            Autosomal recessive spastic       13q12        Deletions, point   SACS gene that
            ataxia of Charlevoix-                          mutations          codes for sacsin
            Saguenay (ARSACS
            Cayman ataxia (ATCAY)             19p13        Point mutations    ATCAY gene that
                                                                              codes for caytaxin
            Marinesco-Sjögren Syndrome 5q31                various            SIL1
            (MSS)
            Mitochondrial recessive ataxia 15q25           Point mutation     POLG1, a catalytic
            syndrome (MIRAS)                                                  subunit of the
                                                                              mitochrondrial DNA
                                                                              polymerase gamma

            Spinocerebellar ataxia with       14q31        Point mutation     tyrosyl-DNA
            axonal neuropathy (SCAN1)                                         phosphodiesterase
                                                                              (TDP1)
            ARCA 1 (SCAR8)                    6q25         Point mutation,    Synaptic nuclear
                                                           deletions          envelope protein 1                            Anheim et al. Neurogenetics 2009
                                                                              (SYNE1)
            ARCA 2 (SCAR9)                    1q41         Point mutations    CABC1 (ADCK3)

            Familial cerebellar ataxia with                                   Some patients have
            muscle coenzyme Q10                                               AOA1 or ARCA2
            deficiency




                                                                                                                                                                      8
                                                                                                       12/3/2009




                                         Fragile-X-associated tremor/ataxia syndrome
                                                           (FXTAS)

                                        • Carriers of premutation alleles (55-200 CGG
                                          repeats) of the fragile-X mental retardation 1
X-linked Ataxia                           (FMR1) gene can present with one (or more)
                                          of three distinct clinical disorders:
                                          – mild cognitive and/or behavioral deficits on the
                                            fragile-X spectrum
                                          – premature ovarian failure
                                          – neurodegenerative disorder of older adult carriers,
                                            FXTAS
                                        • Note that women can be affected




  MRI in FXTAS
                                         Fragile-X-associated tremor/ataxia syndrome
                                                           (FXTAS)

                                        • Although it can look similar to MSA-C, it
                                          is not a common cause of it
                                          – 1 of 77 patients (Biancalana et al. 2005)
                                          – 4 of 426 patients (Kamm et al. 2005)




      Hagerman et al. 2003




                                                     Algorithm for Diagnosis
                                                        Family History
                                                       YES                 NO



                                         Dominant or                   Apparent secondary
                                         Recessive                     cause

                                                                      NO          YES
                                          Genetic                                         Diagnosis
                                          Testing
                                                                       Hunt for non-apparent
                                          YES                NO
                                                                       secondary cause
                                                                            YES          NO


                                         Diagnosis
                                                                  Diagnosis             No Diagnosis
           Hall et al. Neurology 2005




                                                                                                              9
                                                                                                                            12/3/2009




     Cerebellar dysfunction                                                Varenicline
                  Therapy
                                                        • Varenicline is Chantix®, a drug used for
• Added mass (or viscous damping)                         smoking cessation
• Drug effects -- minimally effective                   • 3 patients (FXTAS, SCA 3, SCA 14)
  – TRH, 5-HTP, buspirone, amantadine,                    responded favorably
    physostigmine, N-acetylcysteine,
                                                        • Varenicline is a highly selective partial agonist at α4β2
    isoniazid,branched-chain amino acids, D-              nicotinic acetylcholine receptors and a full agonist at
    cycloserine, piracetam, gabapentin                    α7 nicotinic receptors. There are acetylcholine
  – SeeTrujillo-Martin et al. 2009 for recent             receptors in the cerebellum, and stimulation of α4β2
    systematic review                                     nicotinic acetylcholine receptors can improve alcohol
                                                          induced ataxia in an animal model.
• Surgery directed to Vim for tremor                                     Zesiewicz & Sullivan 2008, Zesiewicz et al. 2009




                                                                         Conclusions
                                                        • Many types of ataxias – still not all
                                                          identified
                                                        • Etiologic therapy uncommon
                                                        • Symptomatic therapy generally
                                                          unsatisfactory



                             Courtesy of T. Zesiewicz




                                                                                                                                  10

				
DOCUMENT INFO
Shared By:
Categories:
Stats:
views:169
posted:7/21/2010
language:English
pages:10
Description: Ataxia GW Dec ppt Compatibility Mode Idebenone