Childhood Onset Dystonia: Movement Disorders: Definitions / Diagnosis Objectives

11/4/2015

Disclosure Information AACPDM 69 th Annual Meeting | October 21-24, 2015

Speaker Name: Mark Gormley Jr. MD Relevant Financial Relationships: Research support from Allergan and Ipsen Disclosure of Off-Label and/or investigative uses : IC 35: An Overview of Childhood I will discuss Botulinum toxin off label use and/or investigational use in my Onset Dystonia: Evaluation, presentation. Diagnosis and Treatment Speaker Name: Peter D. Kim, MD, PhD Relevant Financial Relationships: None Disclosure of Off-Label and/or investigative uses : I will discuss DBS under the humanitarian device exemption for dystonia Mark Gormley, Jr., MD – Pediatric Physiatrist, Gillette Children's Specialty Healthcare Peter D. Kim, MD, PhD – Pediatric Neurosurgeon, Speaker Name: Tim Feyma MD Gillette Children's Specialty Healthcare Relevant Financial Relationships: None Tim Feyma, MD – Pediatric Neurologist, Gillette Disclosure of Off-Label and/or investigative uses : Children's Specialty Healthcare I will discuss off label uses of medicines because I treat kids.

• Learn about the spectrum of etiologies seen in • A movement disorder is any condition that childhood dystonia affects volitional well coordinated movements or causes excess involuntary movements.

• Establish a diagnostic algorithm

• Can be Primary (genetic / idiopathic), or • Discuss the spectrum of treatments that can be Secondary (toxins, psychogenic, stroke …) offered

• Hyperkinetic Movement Disorders: Movement Disorders: Definitions / Diagnosis – Dystonia – Chorea Definitions / Diagnosis – Tremor – Tics • Divided into being either hypokinetic (too little), or – Ballismus • Hypokinetic hyperkinetic (too much) with generalized versus focal – Stereotypies – Bradykinesia (Parkinsonism manifestation – Abdominal dyskinesia / Parkinson’s) – Akathitic / Tardive movements – Apraxia – Asynergia/ataxia – Blocking tics – Athetosis – Cataplexy / drop attacks • Movement characteristics to consider: – Dysmetria – Hemifacial spasm – Catatonia – Speed of movement – Hyperekplexia – Freezing phenomena – Amplitude of movement – Hypnogenic dyskinesia – Hesitant gaits – Force of movement – Jumpy stumps – Hypothyroid slowness – Moving fingers/toes – Suppressible – Rigidity – Complexity – Myoclonus – Myokymia – Stiff muscles – Continuous / paroxysmal (awake versus sleep) – Myorhythmia – Distractibility – Paroxysmal dyskinesia – Restless legs

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Dystonia: Definition

In the course of the last five years I have repeatedly observed an affliction, whose meaning and classification caused great difficulties. When examining the first cases I was trying to decide between a Focusing on Dystonia… diagnosis of hysteria, and idiopathic bilateral athetosis; but then I soon realized that neither of these diagnoses was appropriate, and that this was a new condition . . . I have selected the titles dysbasia lordotica progressiva and dystonia musculorum deformans and would prefer the latter .

Oppenheim H.: Neurol Centrabl. 30:1090-1107 1911

Dystonia: Definition Dystonia: Definition

• A Hyperkinetic movement disorder • There are well described subgroups within the diagnosis of Dystonia: • Dystonia: – Movements sustained at the peak of movement – Blepharospasm (eyelids) – Usually twisting and oft repetitive – Adult cervical torticollis (neck) – Can progress to sustained prolonged abnormal postures – Spasmodic dysphonia (vocal cords) – Patterned to often involve the same muscle groups – Writer’s / Musician’s / Occupational cramps (hands and arms)

Dystonia: Anatomy Dystonia: Anatomy • Dysfunction occurs when an imbalance in Cerebral Hemispheres Telencephalic / Cerebral + lateral ventricles vesicle becomes motor control arises: cerebral hemisphere

Optic vesicle Thalamus becomes retina + neurohypophysis + optic nerve + 3rd ventricle Midbrain + Aqueduct Pons + Cerebellum + upper 4 th ventricle Medulla + lower 4 th ventricle

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Dystonia: Anatomy Dystonia: Anatomy • Dysfunction occurs when an imbalance in motor control arises:

Kandel, Schwartz, and Jessell 2000

Supreme Court Justice Potter Stewart Dystonia: Diagnosis about pornography in 1964 • Etiology workup is guided by the history + exam and can include: “ I shall not today attempt further – Imaging to define the kinds of material I understand to be embraced…, – Blood for metabolic + genetic studies but I know it when I see it.”

– Cerebrospinal fluid

Dystonia: Diagnosis Dystonia: Diagnosis • Hyperkinetic: dystonia, focal, idiopathic • Hyperkinetic: hemi-dystonia, post stroke

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Dystonia: Diagnosis Dystonia: Diagnosis • Hyperkinetic: dystonia, focal, tardive • Hyperkinetic: dystonia, generalized, kernicterus

Dystonia: Diagnosis Dystonia: Workup • Hyperkinetic: dystonia, generalized, HIE Imaging

Dystonia: Workup Genetic: Non-Genetic: Dystonia: Quantification? • Hereditary DAT deficiency • Nutritional (Vitamin E, Copper) • Tyrosine Hydroxylase deficiency • Autoimmune • Dystonia genes (DYT1-21 – the primary • Medication induced + Tardive syndrome dystonias include 1, 5, 6, 7, 13, 17, 21) • Stroke • Diagnosis is based upon observation, but • SCA 6, 17, 2, 3, 17 • Trauma • Childhood Huntington’s Disease • Infection • GLUT-1 deficiency rating scales do exist. • Pterin disorders ( Sepiapterin Reductase deficiency is 1 of 4 types described) • AADC deficiency – Unified Dystonia Rating Scale • Ataxia telangiectasia • Gangliosidoses – Fahn-Marsden Scale • Glutaric Aciduria • Homocystinuria – Hypertonia Assessment Tool • Juvenile Parkinson’s • Metachromatic Leukodystrophy • Methylmalonic Aciduria – Barry-Albright Dystonia Scale • Niemann-Pick type C • NBIA (PKAN, PLAN, FAHN, – Movement Disorder-Childhood Rating Scales Aceruloplasminemia, Neuroferritinopathy, Kufor-Rakeb, SENDA) • Wilson’s disease • X-linked dystonia deafness • Lesch Nyhan disease • Pelizaeus Merzbacher • Rett Syndrome • Mitoch ondrial

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Dystonia: Treatment Goal of Treating Pediatric Dystonia • Disease Specific

• Physical Improve function • Medications

• Surgical

Treatment Goals Treatment Options in Pediatric Dystonia • Dystonia impairs movement, swallowing, •Therapy articulation, etc. •Physical, occupational, speech therapy • Often a differential between motor function •Assistive technologies •Oral medication and cognition, i.e. cognition higher than •Bracing and casting motor skills •Neurolytic blocks •Botulinum toxin • Because of the difficulties of treating •Phenol blocks •Orthopaedic surgery dystonia goals often basic, but still difficult •Neurosurgical treatments to achieve •Intrathecal baclofen pump •Selective dorsal rhizotomy • Communication and independent mobility •Deep brain stimulator common goals

Combination therapy most PT/OT/SP typical • Typically children with dystonia receive

Therapy and ongoing PT/OT/SP focused on specific equipment functional goals • Contractures less of an issue in pure dystonia, however most patients with mixed tone and contractures still common Oral Procedures medications • Positioning particularly important since postural correction often easily altered

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Bracing for dystonia Dystonia treatment • Still commonly used, but less so than with spasticity Some dystonias improve with light touch • Ambulatory patients often find braces on the involved part (geste antagoniste) uncomfortable because of posturing and not helpful • Trial and error like much of dystonia Tarsy and Simon, NEJM treatment 2006 • Assistive technology otherwise common

Communication Communication • In patients with severe dystonia and GMFCS IV- V dysarthria and dysphagia common • Often, unless the dystonia is controlled • Many patients and their families would be happy success with augmentative communication just with independent communication isn’t possible • Improvement of articulation by improving • Oral Rx, focal tone management, bracing, dystonia often difficult neurosurgical procedures often used • Speech and occupational therapy a mainstay • Use of augmentative systems common but often not successful • Rehabilitation engineer and seating specialist key to success

Dysphagia in dystonia Phenol/botulinum toxins • Trials of phenol/botulinum toxins common • Dysphagia common in pediatric dystonia • Very goal specific, i.e. one upper extremity for • Even in patients with pure dystonia but joystick access, multiple injections in lower GMFCS IV-V still can eat orally extremities for walking or cares • Usually a modified diet, i.e. pureed with • Start low doses, multiple muscles, use EMG or thickened liquids U/S; E-stim may not work if posturing during injections • Gastrostomy tubes still common, but • Pain relief a very common indication usually some oral intake • Treatment intervals often shorter than spasticity • Treatments less likely ongoing than in spasticty

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Botulinum toxin to treat Orthopedic surgery in dystonia dystonia in CP • Less successful in pure dystonia than • Hemidystonic cerebral palsy spasticity • GMFCS II • Posturing often continues limiting • Cognitively normal functional improvement • Bracing not helpful • If contractures present often return in a • Oral Rx not helpful • Poor orthopedic surgery few years candidate because of • Hip dysplasia less common in pure posturing dystonia • Botulinum toxin R gastroc q 4months

Hip Subluxation in CP Hip Subluxation by GMFCS

Normal hips CP quad 7 y/o

Hip displacement ≈ MP >30 %

CP quad 9 y/o CP quad 9+ y/o, post VDO

Hip Subluxation and Spasticity Hip subluxation in Dystonia

• Spasticity of hip adductors, hamstrings, and hip flexors increases the risk of subluxation

AE 4 mon post AE 8 mon post

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Hip dysplasia in Dystonia Dystonia: Treatment

• Oral Pharmacotherapy: – Levodopa – Anticholinergics (trihexyphenidyl) – Baclofen – Tetrabenazine – Anticonvulsants (carbamazepine, pregabalin, levetiracetam, zonisamide) – Benzodiazepines – Tizandine – Anti-Psychotics

Dystonia: Treatment

• What dose the evidence look like?

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Dystonia: Deep Brain Stimulation

Dystonia: Deep Brain Stimulation Dystonia: Deep Brain Stimulation

• Technical challenges – Size – Anatomic placement – Complication avoidance – Stimulation settings – Ability to manipulate field shape in vivo

Dystonia: Deep Brain Stimulation Dystonia: Deep Brain Stimulation

• Technical challenges • Technical challenges – Size – Size Putamen – Anatomic placement – Anatomic placement

– Complication 3 – Complication avoidance GPe 2 avoidance 1 – Stimulation settings 0 – Stimulation settings – Ability to manipulate GPi – Ability to manipulate field shape in vivo field shape in vivo

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Dystonia: Deep Brain Stimulation Dystonia: Deep Brain Stimulation

• Technical challenges • Technical challenges – Size – Size – Anatomic placement – Anatomic placement – Complication – Complication avoidance avoidance – Stimulation settings – Stimulation settings – Ability to manipulate – Ability to manipulate field shape in vivo field shape in vivo

Dystonia: Selective Peripheral Dystonia: Baclofen Pump Neurectomy • GABA B agonist • Intraventricular vs intrathecal with high cervical catheter • Simple • More potency than oral • Cheap • Effective treatment for spasticity and • Durable result dystonia • Numbness, irreversible

Dystonia: Rhizotomy

• Ventral Rhizotomy – Cut 80% of ventral (motor) roots intradurally – For dystonia • Dorsal Rhizotomy – Cut 30% of dorsal roots intradurally – For spasticity

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Dystonia: Patient Cases • Hyperkinetic: dystonia (focal), tardive

Dystonia: Patient Cases Dystonia: Patient Cases • Hyperkinetic: dystonia, focal, idiopathic

Autoimmune basal ganglia encephalopathy

Questions?