ATAXİA

 

 

ATAXİA
ATAXIA = A (LACK OF) TAXIA
(COORDINATION)

Murat ŞAHİN
CONTENTS
 Ataxia definition
 Types
 Couses
 Wilson’s disease
 Gluten ataxia
 Friedreich’s Ataxia
 Signs and Symptoms
 Genetics of Friedreich’s Ataxia
CONTENTS
 Roles of Frataxin in Mitochondria
 Pathogenesis
 Pathology
 Four Components To An Effective
Physical Therapy Program For
Ataxia
 Characteristic Of An Effective PT
 Outcome Measures
 Characteristics of a
Successful Exercise Program
 Extra slide for people who care
DEFENTION
 Defention: derived from greek word meaning
irregularity
 The coordination of movement depend on:
 Cerebellum & its connection….cerebellar ataxia
( ataxia gait, limb incoordination, tremor,
dysarthria, nystagmus)
 Sensory feed back….sensory ataxia
(ataxia of gait &limb at dark, loss of
proprioception, ve romberg test)
 Cerebrocerenellum:
 Input:cortico pontine
 Output:feedback dentate,thalamus..cortex
motor,premotor
 Lesion: impair complex voluentry movement,
smooth
TYPES
 Vestibulocerebellum”
 Input: vestibular ,visual path
 Out put:feed back to the vestibular nuclie
 Lesion :disturbe equlibrum,wide base gait
,nystagmus
 Spinocerebellum:
 Input ;somatosensory via the spinal cord
 Output: brain stem reticular ,lateral vestibular
nuclie
 Lesion :vermis truncal ataxia, lateral limb ataxia
HEREDITER ATAKSILER
X’e Bağlı Geçiş Gösteren Ataksiler
 Mitokondriyel Hastalıkların Neden Olduğu
Ataksiler
Otozomal Dominan ataksiler
 Spinoserebellar ataksiler
 Epizodik ataksiler
 Herediter spastik ataksi
OTOZOMAL RESESIF ATAKSILER
 Friedreich Ataksisi
 Ataksi- Telanjiektazi
 Vitamin E eksikliğinin neden olduğu ataksi
 Refsum hastalığı
 Serebrotendinöz ksantomozis
 Kseroderma pigmentosa
 Cockayne sendromu
 Cayman ataksisi
 Joubert sendromu
 Spinoserebellar ataksi ve aksonal nöropati
 Sideroblastik Anemi ve ataksi
 Geç Başlangıçlı Tay-Sachs Hastalığı
 Charlevoix- Saguenay OR spastik ataksi
 Marinesco-Sjögren sendromu
 Lökodistrofiler
 Wilson Hastalığı
 Sialidoz
 Seroid lipofusinoz
Edinsel Ataksiler
 Yapısal Serebellum/Medulla Spinalis Lezyonu
 Vasküler hastalıklar
 Primer veya metastatik tümörler
 Multipl skleroz
 Multisistem Atrofi
 Paraneoplastik hastalıklar
 Haşimoto Ensefalopatisi
 Konjenital Deformiteler
 Arnold-Chiari malformasyonu
 Platibazi
 Odontoid kompresyon
 Sifilitik pakimenenjit/Tabes dorsalis
 Subakut kombine dejenerasyon
COUSES
Acquired
 Infection: posterior fosse abscess, cerebellitis
 Vascular:Hge, infarction, TIA
 Demyelinating: MS, Sensory PN( miller fisher)
 Malignancy: tumor
 Toxin &drug: INH, lithium, cyclosporin, cystosine
arabiniside, phyntoin, procainamide
 Paraneoplastic
 Metabolic: vit E deficiency , hypothyroidism
COUSES
 Focal lesions
 Any type of focal lesion of the central nervous
system (such as stroke, brain tumour , multiple
sclerosis) will cause the type of ataxia
corresponding to the site of the lesion: cerebellar if
in the cerebellum, sensory if in the dorsal spinal
cord (and rarely in the thalamus or parietal lobe),
vestibular if in the vestibular system (including the
vestibular areas of the cerebral cortex).
COUSES
 Exogenous substances
 Exogenous substances that cause ataxia
mainly do so because they have a depressant
effect on central nervous system function. The
most common example is ethanol, which is
capable of causing reversible cerebellar and
vestibular ataxia.
COUSES
 Exogenous substances
 A further class of pharmaceuticals which can
cause short term ataxia, especially in high
doses are the benzodiazepines
 Exposure to high levels of methylmercury,
through consumption of fish with high mercury
concentrations, is also a known cause of ataxia
and other neurological disorders.
COUSES
 Radiation poisoning
 Ataxia can be induced as a result of severe
acute radiation poisoning with an absorbed
dose of more than 30 Grays
 Vitamin B
12
deficiency
 Vitamin B
12
deficiency may cause, among
several neurological abnormalities, overlapping
cerebellar and sensory ataxia.
COUSES
 Hypothyroidism
 Symptoms of neurological dysfunction may be
the presenting feature in some patients with
hypothyroidism. These include reversible
cerebellar ataxia, dementia, peripheral
neuropathy , psychosis and coma. Most of the
neurological complications improve completely
after thyroid hormone replacement therapy .
COUSES
 Causes of isolated sensory ataxia
 Peripheral neuropathies may cause generalised
or localised sensory ataxia (e.g. a limb only)
depending on the extent of the neuropathic
involvement. Spinal disorders of various types
may cause sensory ataxia from the lesioned
level below, when they involve the dorsal
columns
COUSES
 Non-hereditary cerebellar degeneration
 Non-hereditary causes of cerebellar
degeneration include chronic ethanol abuse,
head injury , paraneoplastic cerebellar
degeneration, high altitude cerebral oedema,
coeliac disease, normal pressure
hydrocephalus and cerebellitis.
COUSES
 Hereditary ataxias
 Ataxia may depend on hereditary disorders consisting of
degeneration of the cerebellum and/or of the spine; most cases
feature both to some extent, and therefore present with overlapping
cerebellar and sensory ataxia, even though one is often more evident
than the other. Hereditary disorders causing ataxia include
autosomal dominant ones such as spinocerebellar ataxia, episodic
ataxia, and dentatorubropallidoluysian atrophy , as well as autosomal
recessive disorders such as Friedreich’s ataxia (sensory and
cerebellar , with the former predominating) and Niemann Pick
disease, ataxia-telangiectasia (sensory and cerebellar , with the latter
predominating), and abetalipoproteinaemia. An example of X-linked
ataxic condition is the rare fragile X-associated tremor/ataxia
syndrome.
COUSES
 Arnold-Chiari malformation
 Arnold-Chiari malformation is a malformation of
the brain. It consists of a downward
displacement of the cerebellar tonsils and the
medulla through the foramen magnum,
sometimes causing hydrocephalus as a result
of obstruction of cerebrospinal fluid outflow.
COUSES
 Wilson’s disease
 Wilson’s disease is an autosomal-recessive
gene disorder whereby an alteration of the
ATP7B gene results in an inability to properly
excrete copper from the body.
[17]
Copper
accumulates in the nervous system and liver
and can cause ataxia as well as other
neurological and organ impairments
COUSES
 Gluten ataxia
 Gluten ataxia may be a form of gluten sensitivity , a
wide spectrum of disorders marked by an
abnormal immunological response to gluten. With
gluten ataxia, damage takes place in the
cerebellum, the balance center of the brain that
controls coordination and complex movements like
walking, speaking and swallowing. Gluten ataxia is
the single most common cause of sporadic
idiopathic ataxia
FRIEDREICH’S ATAXIA
 Friedreich’s Ataxia is a rare disorder.
 It is estimated that about 140 people in Ireland
have Friedreich’s Ataxia.
 FA, FRDA
 Rare recessively inherited neurodegenerative
disease, does not affect cognitive abilities
(Hereditary ataxia)
 1863 (Nikolaus Friedreich)
 Genetic defect in FXN gene
FRIEDREICH’S ATAXIA
 Hereditary ataxia: poor coordination of hands,
speech, legs (unsteady gait, loss of feeling)
Results from one or more of:
 Cerebellum dysfunction
 Spinal cord lesions
 Sensory loss (Peripheral)
SIGNS AND SYMPTOMS
• Typical age of onset: puberty; Late onset: after 25
• “Degenerative atrophy of the posterior columns of the
spinal cord” – Dr. Friedreich
• Ataxia: gait instability, loss of balance, difficulty in
activities
• Dysarthria: slow and jerky speech unintelligible
• Limb weakness: proximal muscles disability
SIGNS AND SYMPTOMS
 Sensory neuropathy (DRG)
• Loss of sensory fibres
• Degeneration of spinal cord
• Decreased perceptions
 Cardiomyopathy (secondary)
 Diabetes (10%)
 Carbohydrate intolerance (20%)
GENETICS OF FRIEDREICH’S ATAXIA
 Autosomal recessive disease involving the FXN gene on
chromosome 9
 FXN codes for a mitochondrial protein known as frataxin
 Normal allele – “GAA” is repeated 7-22 times
 Mutant allele – “GAA” is repeated hundreds to
thousands of times
 This “triplet repeat extension” blocks transcription of the
FXN gene
 Individuals with the disease have low levels of frataxin,
but it is not completely absent – this would result in
lethality in the embryonic stage of development
ROLES OF FRATAXIN IN MITOCHONDRIA
 Reducing oxidative stress:
 The Fenton reaction (Fe
2+
+ H
2
O
2
+H
+
→ Fe
3+
+ HO• + H
2
O) causes
oxidative stress
 Frataxin protects against the formation of free radicals
 Iron chaperone:
 Heme biosynthesis – frataxin delivers iron to ferrochelatase for insertion
into porphyrin rings
 Iron-sulfur cluster synthesis – low frataxin levels results in diminished
iron-sulfur cluster levels which are needed in proteins involved in
mitochondrial electron transport, thus energy production is reduced
PATHOGENESIS
 Iron overload leads to:
• Free radical production
• Oxidative stress
 Result in damages to:
• CNS/PNS
• Heart
• Pancreas
PATHOLOGY
 Heart damages result in:
 Cardiomyopathy
Hypertrophy of heart leads to heart failure
 Pancreatic damages result in:
 Diabetes Mellitus
Elevated blood sugar
Result from destruction of pancreatic β-cells
due to excess ROS and apoptosis
FOUR COMPONENTS TO AN EFFECTIVE
PHYSICAL THERAPY PROGRAM FOR
ATAXIA
Biraz da biz
fizyoterapistler için
Why Is Physical Therapy and
• Prevent falls
• Maintain function
• Adaptive equipment
• independence
CHARACTERISTIC OF AN EFFECTIVE PT
 • Intense strength training.
 • Dynamic balance training (modified LSVT)
 • Cardiovascular training.
 • Gait training.
 • Stretching
 • Long term participation (HEP, community
 fitness program)
 • Strong pre/post measures (Berg Balance
Scales,
 Timed Up & Go, 6 minute Walk Test)
OUTCOME MEASURES
Berg Balance Scale
 i 14 item scale, rated 0-4 for each item
 i Designed to assess static and dynamic balance
 i Predicts multiple falls in community dwelling and
 institutionalized older adults
 i Strong validity and reliability
 i Maximum score of 56 points
 i Score of <45 = Adults at risk for falls
• TIMED UP AND GO TEST
 i Used to assess balance, functional mobility,
and
 determine fall risk
 i Involves timing individual as they rise from a
 chair, stand, walk 3 meters, return and sit
 i Good intra- and inter-rater reliability
 i Score of 13.5 seconds = fall risk in older
adults
CHARACTERISTICS OF A
SUCCESSFUL EXERCISE PROGRAM
 • Static and dynamic balance
 • Trunk-limb coordination
 • Gait
 • Contracture prevention
PHYSICAL THERAPY PROGRAM
 • 60 minute session.
 • Warm up: 6 mins
 • Balance training: 20 mins
 • Strengthening exercises: 20 mins
 • Stretching: 15 mins
 • Frequency & Duration ( 2 x week for 8 weeks.
 • Outcomes:
 ▫ Ultimate goal: decrease falls, increase safety&
 functional mobility.
WARM UP
 6 Minute walk
 i Increase muscle and body temperature
 i Dilation of blood vessels
 i Increase range of motion
 i Mental preparation
 i Or 6 minutes of a continuous activity, ie: bike,
Nustep,
 arm bike, etc..
STRENGTHENING
 • 20 minutes
 • Target Pelvic Muscles
 • SLR, knee to chest, hip abduction, hip
 adduction, bridging, LAQ, hamstring curls,
 squats.
 • Upper extremity weakness or core: see
 handouts.
Therapeutic exercise to key musculature.
 • Essential components of strength program
 i Individually tailored
 i Increase in difficulty
 i Sustainable at home
 i Include walking program to complement
 strengthening and balance activities
 • Evidenced-based research suggests:
 i Muscle strength decreased with age
 i Weakness = important risk factor for falls
 i High intensity strength training program
 1- significantly ’d LE strength and 2- resulted in
 significantly ’d functional balance ability
 i Addition of resistance training to an existing
 program of balance & flexibility lead to
 improvements in balance & functional ability
 Strengthening
 • 20 minutes of total 60 minute treatment time
 • Most beneficial strengthening activities
 i Leg Press
 i Hip Abduction/Adduction
 i Calf Press
 i Seated Row
 i Plank
 i Bridging
 i Abdominal bracing
 • Intensity
 i 3 sets of 8 reps
 i week 1 @ 50% RM
 i week 2-10 @ 80% RM
BALANCE
 • 20 minutes
 • Modified LVST
 • Romberg
 • Unilateral stance
 Target neuromuscular systems that control
 balance through various levels of challenges
 i Control center of gravity (COG) over the base of
 support (BOS)
 i Increase challenge by engaging visual, vestibular,
 somatosensory and cognitive systems
 i Elicit postural reactions and balance strategies by
 altering stimuli, surfaces, etc
FLEXIBILITY
 • 15 minutes
 • Hamstrings
 • Heel cords
 • Hip flexors
 • Quads
 • 5 reps, hold 30 seconds
REFRENCE
 http://en.wikipedia.org/wiki/Ataxia
 http://www.mayoclinic.com/health/ataxia/DS00910
 http://www.ninds.nih.gov/disorders/ataxia/ataxia.htm
 http://www.ninds.nih.gov/disorders/friedreichs_ataxia/friedreichs_ataxia.htm
 http://www.nhs.uk/conditions/ataxia/Pages/Introduction.aspx
 http://www.ataxia.org/
 www.mertnihat.com/00_main/main/dokuman/enzootik_ataksi
 www.parkinsondernegi.org
 http://www.ataxia.org National Ataxia Foundation web site
 http://www.ataxia.org/resources/caregivers.aspx Resources for caregivers
 http://www.ataxia.org/forum/toast.asp Ataxia forum
 http://www.ataxiaconnect.org Webcasted ataxia information
 http://www.ncbi.nlm.nih.gov/books/NBK1138/ Detailed information about ataxias (technical)
 http://ghr.nlm.nih.gov/handbook: Genetics home reference
 http://www.clinicaltrials.gov – clinical trials information
 Dr Garbern: james_garbern@urmc.rochester.edu
 Sohnee Ahmed: sohnee_ahmed@urmc.rochester.edu
 http://www.studyblue.com/notes/note/n/pnb-exam-3/deck/107773

EXTRA SLIDE FOR PEOPLE WHO CARE
 50 % risk of passing disease for
each child
 Disease appears in every
generation
• Except if:
• new mutation
• ascertainment error or
oversight
• Each child of an affected parent
has a 50 % chance of inheriting
the trait
• Male-to-male transmission
essentially confirms the mode of
transmission
• Males and females equally likely
to be affected

GENES AND DNA
 Genes
 ~25,000 in humans
 Instructions for making
proteins to carry out
bodily functions
 DNA
 Bases A,C,G, T

HOW POLYGLUTAMINE EXPANSIONS ARE
THOUGHT TO CAUSE TROUBLE
RNA SILENCING: TURNING OFF A BAD GENE
SPINOCEREBELLAR ATAXIA I (SCA I)
 Clinical features: Adult (mean age 35) onset
progressive ataxia, peripheral neuropathy,
Babinski signs, bulbar palsies, probably
accounts for 10-15 % of inherited ataxias
 Inheritance: Autosomal dominant, with paternal
anticipation
 Chromosome: 6p23
 Mutation: Expansion of CAG repeat region in
ataxin gene, which encodes a protein of
unknown function
 Testing: NCV, gene testing available
X-LINKED ATAXIAS
Mom Dad
Unaffected Female Unaffected Male Affected Female
Affected Male
 Fragile X-tremor and ataxia
 Usually seen in some of the maternal grandfathers of
boys/med with Fragile X mental retardation syndrome
 Occurs in men with an intermediate trinucleotide repeat
expansion of the FMR1 gene
 X-linked sideroblastic anemia and ataxia (XLSA/A)
 Early-onset ataxia, dysmetria, and dysdiadochokinesis.
 Usually slowly progressive.
 Mutations are present in ABC7
○ ABC7 encodes a protein involved with mitochondrial iron
transport, similar to Friedreich ataxia