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An introduction to cerebellar ataxia VeoMed

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An introduction to cerebellar ataxia VeoMed Powered By Docstoc
					An introduction to cerebellar
           ataxia
           3/1/2009
           What is ataxia?
• “A-taxia” or “loss of order” is a
  heterogenous group of disorders with
  problems with coordination
• Can involve gait, coordination of the arms
  and speech
• Anatomically ataxia can be localized to the
  cerebellum or its connections
Cerebellar anatomy




            http://www.anatomy.dal.ca
                          Etiology
• Inherited
   – Autosomal dominant: SCA, DRPLA, FXTAS, episodic ataxia
   – Recessive: Friedreich’s ataxia, ARSACS, Ataxia telangiectasia,
     AOA1, AOA2, Vitamin E deficiency, Cayman ataxia
• Sporadic
   –   Nutritional/toxic: EtOH, Mercury
   –   Demyelinating: MS
   –   Inflammatory: Stiff person syndrome, Sprue associated
   –   Degenerative: Kuru
   –   Paraneoplstic
   –   Neoplastic
                  ADCA
• ADCA (Autosomal dominant cerebellar
  ataxia) or SCA (spinocerebellar ataxia)
  – 30 now identified
  – SCA1, SCA2, SCA3, SCA6, SCA7, SCA17,
    and DRPLA are CAG repeat disorders
  Typically late onset conditions with ataxia
    accompanied by variable amounts of brain
    stem dysfunction, extrapyramidal symptoms
    and long tract signs
        List of SCAs (ADCA)
S
S

M
S
S
SCA6
SCA7
SCA8

SCA10
S
S

S
S

S
S
S
S
S

S
S
S
S
S
S
S

S
S


              Soong BW, Paulson HL. Curr Opin Neurol. 2007 ;20:438-46
  CAG repeat disorders with ataxia
• SCA1: Ataxin-1
  Transcriptional corepressor
• SCA2: Ataxin-2
  RNA processing and translational regulation
• SCA3: Ataxin-3
  Deubiquitinating enzyme
• SCA6: P/Q-type calcium-channel
  α1A Voltage-sensitive calcium-channel subunit
• SCA7: Ataxin-7
  Part of histone acetyltransferase complex
• SCA17: TATA-box-binding protein
  Component of core transcriptional complex TFIID
• DRPLA: Atrophin-1
  Possible transcriptional corepressor
   Clinical features of the SCAs
• The most common ADCAs are SCA1, SCA2,
  SCA3, SCA6 and SCA7
• Considerable overlap in clinical features-ataxia
  associated with long tract signs in SCA1 and
  SCA3, peripheral neuropathy in SCA2 (ADCA
  type 1), retinal degeneration in SCA7 (formerly
  classified as a ADCA type 2)
• SCA6 is a relatively “pure” cerebellar
  degeneration (formerly ADCA type 3)
    Sites of neuronal loss in the
      cerebellum in the SCAs
• Many have neuronal loss in the cerebellar
  cotex: i.e. Purkinje neurons
• SCA3, DRPLA: Loss of DCN neurons with
  not as marked Purkinje neuron loss
• SCA6: almost exclusively Purkinje neuron
  loss
          Recessive ataxias
• Friedreich’s ataxia
• Affects the nervous system and heart
• Gait instability, scoliosis with cerebellar
  and sensory ataxia
• Optic atrophy
• Gene: FXN
           Recessive ataxias
•   Ataxia with Vitamin E deficiency (AVED)
•   Ataxia with sensory neuropathy
•   Retinopathy
•   Vitamin E levels <3 mg/L
•   Gene: TTPA
         Recessive ataxias
• AOA1
• Ataxia with peripheral neuropathy
• May or may not have oculomotor apraxia
• Labs: Hypoalbuminemia and
  hypercholesterolemia
• Gene: APTX
           Recessive ataxias
•   AOA2
•   Ataxia with peripheral neuropathy
•   May or may not have oculomotor apraxia
•   Labs: Elevated alpha-fetoprotein
•   Gene: SETX
         Recessive ataxias
• ARSACS
• Autosomal recessive spastic ataxia of
  Charlevaux-Saguenay
• Ataxia with peripheral neuropathy
• Gene: SACS
         Sporadic Ataxias
• Heterogeneous group of disorders
• Most common is ETOH related cerebellar
  atrophy
• Other common causes include multiple
  sclerosis, and cerebellar infarcts
               Treatment
• Symptomatic
• Spasticity
• Parkinsonism may be Levodopa
  responsive
• Idebenone for Friedrich’s ataxia: Mo;ecule
  similar to Coenzyme Q in phase 3 clincal
  trials

				
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