Approach to diagnosis and treatment of dystonia

Terence D. SangerUniversity of Southern California

Dept. Biomedical Engineering, Child Neurology, Biokinesiology

Types of Dystonia

Hypertonic (stiff)

Hyperkinetic (too much movement)

Hypertonia: Hypertonia: Resistance to passive Resistance to passive movementmovement

•Spasticity: velocity-dependent, asymmetric and/or a catch

•Dystonia: sustained or intermittent muscle contractions cause twisting and repetitive movements or abnormal postures

•Spasticity: velocity-dependent, asymmetric and/or a catch

•Dystonia: sustained or intermittent muscle contractions cause twisting and repetitive movements or abnormal postures

Reflexes in SpasticityReflexes in Spasticity

PhasicPhasicPhasicPhasic TonicTonicTonicTonicCharacterized by Characterized by catchcatch: Sudden : Sudden ONSETONSET determined by position and velocity; not determined by position and velocity; not

proportional.proportional.

Characterized by Characterized by catchcatch: Sudden : Sudden ONSETONSET determined by position and velocity; not determined by position and velocity; not

proportional.proportional.

Van Van Doornik Doornik

and and Sanger, Sanger,

20092009

Tonic stretch reflexes maintain Tonic stretch reflexes maintain fixed dystonic postures.fixed dystonic postures.

DystoniaDystonia is defined as a movement disorder in is defined as a movement disorder in which involuntary which involuntary sustained or intermittentsustained or intermittent muscle muscle contractions cause twisting and repetitive contractions cause twisting and repetitive movements, abnormal postures, or both.movements, abnormal postures, or both.ChoreaChorea is a random-appearing sequence of is a random-appearing sequence of movements or movement fragments with movements or movement fragments with continuously variable timing, duration, direction, continuously variable timing, duration, direction, and anatomic location.and anatomic location.AthetosisAthetosis is a continuous flowing or writhing is a continuous flowing or writhing movements that prevent maintenance of a stable movements that prevent maintenance of a stable posture. posture.

Hyperkinetic disorders:Excess involuntary

movement

Hyperkinetic disorders:Excess involuntary

movement

Hyperkinetic DystoniaHyperkinetic DystoniaHyperkinetic DystoniaHyperkinetic Dystonia

Where does dystonia come from?

We are not really sure

Best guess is often basal ganglia

How the Basal Ganglia WorkHow the Basal Ganglia Work

Motor command in the cortex...Motor command in the cortex...... is amplified in basal ganglia...... is amplified in basal ganglia......and sent back to the cortex....and sent back to the cortex.

Dopamine controls whether Dopamine controls whether the signal is increased or the signal is increased or decreased.decreased. Over time, dopamine Over time, dopamine “teaches” the basal ganglia “teaches” the basal ganglia which signals to increase which signals to increase and which to decrease.and which to decrease.

What goes wrong?What goes wrong?

Too little dopamine, or Too little dopamine, or injury to basal ganglia, and injury to basal ganglia, and the output may be too the output may be too much or too little.much or too little.

Too little output -> Too little output -> ParkinsonsParkinsons

Too much output -> Too much output -> DystoniaDystonia

Involuntary and continual Involuntary and continual activation of a region of activation of a region of cortex.cortex.

Long pulse trains to cortex trigger stable multijoint

postures

Graziano, Taylor, Moore 2002Graziano, Taylor, Moore 2002

What causes dystonia?

Inserted postures in dystonia...

... are caused by involuntary stimulation of motor cortex...

... by the basal ganglia (or anything else).

Approach to Treatment

• Etiology-specific: treatment of underlying disease

• Anatomy-specific: treat sensory, basal ganglia, frontal, or cerebellar origin

• Nonspecific: reduce stretch reflexes

Approach to Treatment

• Etiology-specific: treatment of underlying disease

For AHC: Flunarizine, or treat underlying genetic

disorder.

Approach to Treatment

• Anatomy-specific: treat sensory, basal ganglia, frontal, or cerebellar origin

Levodopa, Trihexyphenidyl, Deep-Brain Stimulation

Medicines for Dystonia

•Artane: takes months to work; may affect attention; works in many types of dystonia

•Sinemet: works quickly; naturally-occurring neurotransmitter; only works if dopamine deficit

•Clonazepam: works for hyperkinetic dystonia; can cause drowsiness and drooling

•Tetrabenazine: works only for chorea

Approach to Treatment

• Nonspecific: reduce stretch reflexes

Baclofen, Intrathecal Baclofen, Benzodiazepines, Botulinum Toxin

Medicines for stretch reflexes

•Baclofen: primarily for spasticity; may help dystonia at high doses; may cause trunk and neck weakness

•Botox: localized to targeted muscles; effect lasts 3 months; requires repeated injections

•Tizanidine: probably no better than baclofen

•Dantrolene: causes permanent changes to muscle

Treatment

Often need a combination of treatments.

Botulinum toxin if only a small number of muscles are the problem.

Trihexyphenidyl (Artane) and Levodopa (Sinemet) affect the whole body.

Deep-brain stimulationDeep-brain stimulation

Wire in basal ganglia blocks abnormal activity and reduces excessive stimulation of the motor cortex.

Wire in basal ganglia blocks abnormal activity and reduces excessive stimulation of the motor cortex.

Pacemaker is in the chest. Can be programmed externally. Batteries last 2-5 years.

Pacemaker is in the chest. Can be programmed externally. Batteries last 2-5 years.

Taskforce on childhood Taskforce on childhood motor disordersmotor disorders

Multi-disciplinaryMulti-disciplinaryFunded by NIHFunded by NIHConsensus definitions and measurement Consensus definitions and measurement technologytechnology

ConclusionConclusionConclusionConclusion

Treatments for dystonia target multiple places in the chain from the disease to the symptoms.

Need more research to find new treatments that are less invasive.

Need to understand the details of dystonia in AHC

short-term rescue treatment

prevention of progression

Treatments for dystonia target multiple places in the chain from the disease to the symptoms.

Need more research to find new treatments that are less invasive.

Need to understand the details of dystonia in AHC

short-term rescue treatment

prevention of progression