Transcript Huntington`s disease

Movement disorder
Chorea
Chorea is derived from the Greek word ‘choreia’ meaning a
dance. are rapid, purposeless, irregular, jerky movements that
seem to flow randomly from one part of the body to another.
Causes
Chorea has many causes which can be simply divided into
inherited and acquired :
1-Inherited causes
Huntington’s disease
Wilson’s disease
2-Acquired causes
Stroke
Drug induced:(Levodopa and other dopaminergic drugs,
Antipsychotic drugs, Oral contraceptives, Phenytoin)
Chorea gravidarum(during pregnancy)
Thyrotoxicosis
Systemic lupus erythematosus/antiphospholipid syndrome
Post-infective Sydenham’s chorea
Huntington’s disease
Huntington’s disease (HD) is a slowly progressive autosomal
dominant neurodegenerative disorder and the most
important inherited cause of chorea discovered by George
Huntingtonin 1872. In 1993, the causative gene defect was
identified as a CAG triplet repeat expansion mutation in the
HD gene on chromosome 4. Onset is usually in adult life with
a mean age of about 40 years It progresses inexorably, with
death occurring 15–20 years from HD.
Clinical features
 Motor features
Subtle motor abnormalities seen early in the disease include
general restlessness, abnormal eye movements, and fidgety
movements of fingers, hands and toes during stress or when
walking. Also Dysarthria.
Cognitive features
Cognitive abnormalities are variable but universal in HD. The
key cognitive abnormalities seen are impaired executive
function with poor planning and judgment, disorganized
actions.
Psychiatric features
Psychiatric symptoms are common, particularly depression
and anxiety. Irritability is also very common and some
patients become aggressive.
Investigation
MRI imaging to exclude stroke
Wilson screen(Serum caeruloplasmin, serum copper ,Urinary
copper level and KF ring)
Pregnancy test
Anti-dsDNA,ANA
Thyroid function tests
Antistreptolysin O (ASO) titre
Treatment
No intervention currently slows or halts the degenerative
process.
Drug used to treat chorea
Chorea usually responds to treatment with dopamine receptor
blockers or dopamine depleting agents:
dopamine receptor blockers
eg.,Olanzapine,Risperidone,Quetiapine
Dopamine-depleting agents eg.Reserpine,Tetrabenazine
Benzodiazepines eg. Clonazepam
.
Drugs Used to Treat Depression and irritability in Huntington’s
Disease:
Selective serotonin reuptake inhibitors eg.Fluoxetine
Tricyclic anti depressants eg.Nortriptyline
Sydenham’schorea (SC):
One of the major manifestations of rheumatic fever, appears
months after the index streptococcal infection in children
with rheumatic fever,The usual clinical picture of SC is the
insidious development of choreic movements in a girl during
childhood or adolescence. The chorea evolves over weeks,
then recedes within 6 months .
Treatment: is valproicacid .
Dystonia
is a disorder marked by the presence of involuntary, sustained
muscle contractions causing abnormal postures. Pain may
accompany the motor symptoms of dystonia.
Classification of Dystonia
Body Distribution
Focal: single body region
Segmental: contiguous body regions
Generalized: both legs and at least one other body region
Multifocal: noncontiguous body regions
Hemidystonia: involving one half of the body
Etiology
Primary: Dystonia is only sign; may be sporadic or inherited
Secondary: Dystonia occurring associated with a defined
etiology or associated with other neurologic abnormalities
Primary dystonia
Young onset dystonia (before the age of 26 years) most
commonly manifests with limb onset dystonia, followed by
subsequent generalization In severe cases, patients can suffer
disabling postural deformities and was referred to in the
older literature as dystonia musculorum deformans or
Oppenheim’s dystonia It has an autosomal dominant
inheritance. This condition is more common in Ashkenazi
Jewish, with a possible founder in Eastern Europe about 3
centuries ago.
Focal Dystonias
These are the most common forms of dystonia. They typically
present in the fourth to sixth decades and affect women more
than men. The major types are
blepharospasm—dystonic contractions of the eyelids with
increased blinking that can interfere with reading, watching
TV, and driving.
Oromandibular dystonia (OMD)
Cervical dystonia—dystonic contractions of neck muscles
causing the head to deviate to one side (torticollis), in a
forward direction (anterocollis), or in a backward direction
(retrocollis).
task-specific dystonia such as handwriting (writer's cramp),
playing a musical instrument (musician's cramp)
Secondary Dystonias
These develop as a consequence of drugs or other neurologic
disorders eg: Wilson disease ,levodopa,meticlopromide etc...
Investigation:
MRI of brain and cervical spin
 Wilson screen eg(serum copper ,serum ceruloplasmin ,KF
ring)
Genetic study
Treatment
Treatment of dystonia are:
treatment of a primary underlying condition is available
eg: Wilson's disease
anticholinergics (e.g., trihexyphenidyl)
Baclofen(muscle relaxant)
Clonazepam (bezodiazepin)
Tetrabenazine(dopamin depleting drug)
Botulinum toxin has become the preferred treatment
for patients with focal dystonia
DBS of the pallidum can provide dramatic benefits for
patients with primary dystonia.
Oculogyric crisis
Is the name of a dystonic reaction to certain drug or
medical condition .the term "oculogyric " refer to rotating
of eyeballs also crisis associated with backwards and
lateral flexion of the neck ,widely opened mouth,
toungue protrusion and agitation
Causes :some eg:
•Neuroleptic drugs eg: olanzapin
•Metoclopramid and domperidon
Treatment
•antimuscarinic eg:procyclidin ,benzatropin
•diphenhydramine
•diazepam
Tic
Brief, repeated, stereotyped muscle contractions that are
often suppressible. Can be simple and involve a single
muscle group or complex and affect a range of motor
activities.
Tourette's Syndrome (Ts)
TS is a neurobehavioral disorder named after the French
neurologist Georges Gilles de la Tourette, It
predominantly affects males, TS is characterized by
multiple motor tics often accompanied by vocalizations
(phonic tics). Associated behavioral disturbances include
anxiety,
depression, attention deficit hyperactivity
disorder, and obsessive-compulsive disorder.
Treatment
Patients with mild disease often only require education
and counseling (for themselves and family members).
Drug treatment is indicated when the tics are disabling
and interfere with quality of life. Therapy is generally
initiated with the
alpha-agonist eg: clonidine and
Guanfacine also atypical antipsychotic can be used ,the
DBS(deep brain stimulation) is going on .
Hemifacial spasm
This is a benign, usually painless but often distressing
condition, characterized by unilateral, involuntary, irregular
tonic or clonic contractions of muscles supplied by the facial
nerve. It is now generally accepted that hemifacial spasm is
usually caused by extrinsic compression of the root entry
zone of the facial nerve, generally by vascular structures such.
as the vertebral or basilar arteries or their branches .
Drug treatment with carbamazepine, gabapentin,
clonazepam and baclofen are rarely very effective and seldom
result in resolution of symptoms
Botulinum toxin injection into affected muscles is now the
first line for those patients who want treatment
Surgical decompresion.
Hemiballismus
Hemiballismus is a violent form of chorea composed of
wild, flinging, large-amplitude movements on one side of
the body. Proximal limb muscles tend to be
predominantly affected. The movements may be so
severe as to cause exhaustion, dehydration, local injury,
and in extreme cases, death. The most common cause
is a partial lesion (infarct or hemorrhage) in the
subthalamic nucleus (STN).
Athetosis
Slow, distal, writhing, involuntary movements with a
propensity to affect the arms and hands.
causes :the same as chorea.