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