ATHETOSIS AND DYSTONIA

Dr PS Deb MD, DM

Director Neurology

GNRC Hospitals ,Guwahati Assam , India

ATHETOSIS “Irregular, slow, forceful writhing movement,

generally of extremities, very often characterized by finger movement.”

Associated Rigidity due to corticospinal involvement Hypotonia - choreoathetosis

Pattern of movement Flexion extension, supination pronation of hand and finger Eversion inversion of foot, Retraction and pursing of lips Twisting of neck Winking and relaxation of face Rate: slow to rapid like chorea Voluntary movement slow due to overflow of spasm to

antagonist.

PATHOPHYSIOLOGY

Denny Brown: Medial frontal lesion → grasp Lateral parietal lesion → avoidance reaction A sequence of grasp and avoidance reaction →

athetosis Corticospinal relay station in putamen is damaged Athetoid movements are unstable rivalry of

grasping and avoiding reactions, released by the loss of frontal and parietal lobe inhibition through the putaminal lesion

Athetosis is peculiar reaction of childhood, rarely seen in brain damaged adult. Infantile brain has the ability to employ a variety of motor pathway in an attempt to replace those destroyed by disease.

PATHOPHYSIOLOGY CONT..

1. Lack of reciprocal inhibition by striatum and co-contraction of antagonist overflow

2. Grasping pattern of impulse in EMG3. Fluctuation of tone in the affected muscle

during movement Similar to dystonia, athetosis and dystonia

are closely related. Use of one term rather the other is more a matter of situation and semantics than different movements.

Choric movement may be associated or follow one other (attempted voluntary movement → tonic contraction of antagonistic muscle

AETIOLOGY: ATHETOSIS Childhood (double athetosis)

Anoxic brain damage Kernicterus Post encephalitic Status mormorotus – usually

acquired lesion Status dysmylinatous Hallivordon Spatz disease Pheylketonuria Hyperuricemia (Leih Nyhan) Progressive pallidal atrophy Pelzius Merzbacker disease Diffuse cerebral sclerosis Tuberous sclerosis

Adult (double athetosis) Wilson’s disease and other

hepatolenticular disease Huntington’s chorea Anoxic encephalopathy, CO

poisoning Phenothiazine and L dopa

Hemiathetosis in childhood Same as above Birth trauma Asphyxia Neonatal infection Exenthema Dyphtheria C. embolism

Hemiathetosis in adult Vascular accident Infection

Encephalitis TB, Syphilis

Thalamic glioma Trauma Presenile dementia

DYSTONIA

“ Distorted state of movement due to abnormality of tone of skeletal muscle, most frequently

occurring as hypertonia without evidence of pyramidal tract involvement.”

Oppenheim and Vogats 1911“ Abnormality of any attitude owing to sustained

muscle contraction”Danny Brown

Flexion dystonia of Parkinsonism Spastic dystonia of hemiplegia, paraplegia Torsion dystonia Segmental dystonia Decerebrate rigidity

DEFINITION

“Dystonia is slow, long sustained contracting movements and posture involving mainly the

proximal appendicular and axial muscle.”St. Fahn 1976

The movements are generally slow but may be rapid termed as dystonic spasm. Dystonic spasm may be repetitive, jerky and even tic like (sustained for more than 1sec)

“Dystonia is a syndrome of sustained muscular contraction frequently causing twisting and repetitive movement of abnormal posture”

Ad.hoc committee: Scientific advisory board of the dystonia research foundation 1984

MOTOR PHENOMENOLOGY RELEVANT TO DYSTONIA

Voluntary action

Purposeful, anticipated, goal-directedmovement produced by will. Dystonia istypically influenced by voluntarymovement or voluntarily maintainedposture, as in antigravity support.

Dystonic tremor

A spontaneous oscillatory, rhythmical,although often inconstant, patternedmovement produced by contractions ofdystonic muscles often exacerbated by anattempt to maintain primary (normal)posture. The dystonic tremor may not berelieved by allowing the abnormal dystonicposture to fully develop without resistance(“null point”). Dystonic tremor may bedifficult to distinguish from essential-typetremor.39,45

MOTOR PHENOMENOLOGY RELEVANT TO DYSTONIA CONT..

Overflow Motor overflow commonly found in dystoniais unintentional muscle contraction whichaccompanies, but is anatomically distinctfrom the primary dystonic movement.46,47It commonly occurs at the peak ofdystonic movements.

Mirror dystonia

Mirror dystonia is a unilateral posture ormovement that is the same or similar incharacter to a dystonic feature that canbe elicited, usually in the more severelyaffected side, when contralateralmovements or actions are performed.47

Alleviating maneuvers(sensory tricks orgestes antagonistes)

Voluntary actions that specifically correct theabnormal posture or alleviate the dystonicmovements. These are usually simplemovements (“gestes”) involving, ordirected to, the body region affected bydystonia,23 but not consisting in a forcefulopposition to the phenomenology ofdystonia.

PSEUDODYSTONIAS Dystonic (tonic) tics Head tilt (vestibulopathy, trochlear nerve palsy) Bent spine, camptocormia, scoliosis Atlanto axial and shoulder subluxation Arnold-Chiari malformation Soft tissue neck mass Congenital muscular torticollis Congenital Klippel-Feil syndrome Satoyoshi syndrome Dupuytren’s contractures Trigger digits Neuromuscular causes (Isaacs syndrome, etc.) Spasms (hypocalcemia, hypomagnesemia, alkalosis) Orthopedic and rheumatological causes Sandifer syndrome Deafferentiation (pseudoathetosis)

NEW DEFINITION : MOVEMENT DISORDER SOCIETY 2013

“Dystonia is a movement disorder characterized by sustained or intermittent

muscle contractions causing abnormal, often repetitive, movements, postures, or both.

Dystonic movements are typically patterned, twisting, and may be tremulous. Dystonia is

often initiated or worsened by voluntary action and associated with overflow muscle

activation.”

DYSTONIA NEW CLASSIFICATION

DYSTONIA NEW CLASSIFICATION

PATHOLOGY

Not consistent Putamen, Globus Pallidus (GP), Subthalamus

(ST), Caudate Nucleus (CN) GABA in putamen and GP reduced In monkey electrolytic lesion of putamen or GP →

dystonia (Denny Brown ) Intracuadal injection of carbacol eliciting

dystonic torticolis in monkey

TYPES

Generalized Segmental Focal Action

Muscular cramp Writer’s cramp Oromandibuar dystonia Spasmodic dysphonia

AETIOLOGY: PRIMARY HEREDITARY Symbol OMIM Gene Locus Alt Name

DYT1 128100 TOR1A 9q34 Early-onset torsion dystonia

DYT2 224500 unknown unknown Autosomal recessive torsion dystonia

DYT3 314250 TAF1 Xq13 X-linked dystonia-parkinsonism

DYT4 128101 TUBB4[3] 19p13.12-13 Autosomal dominant whispering dysphonia

DYT5a 128230 GCH1 14q22.1-q22.2 Autosomal dominant dopamine-responsive dystonia

DYT5b 191290 TH[disambiguation needed] 11p15.5 Autosomal recessive dopamine-responsive dystonia

DYT6 602629 THAP1 8p11.21 Autosomal dominant dystonia with cranio-cervical predilection

DYT7 602124 unknown 18p (questionable) Autosomal dominant primary focal cervical dystonia

DYT8 118800 MR1 2q35 Paroxysmal nonkinesigenic dyskinesia

DYT9 601042 SLC2A1 1p35-p31.3 Episodic choreoathetosis/spasticity (now known to be synonymous with DYT18)

DYT10 128200 PRRT2 16p11.2-q12.1 Paroxysmal kinesigenic dyskinesia

AETIOLOGY: PRIMARY HEREDITARY

DYT11 159900 SGCE 7q21 Myoclonic dystonia

DYT12 128235 ATP1A3 19q12-q13.2Rapid onset dystonia parkinsonism and alternating hemiplegia of childhood

DYT15 607488 unknown 18p11[5] Myoclonic dystonia not linked to SGCE mutations

DYT16 612067 PRKRA 2q31.3 Autosomal recessive young onset dystonia parkinsonism

DYT17 612406 unknown, near D20S107[6] 20p11.2-q13.12 Autosomal recessive dystonia in one family

DYT18 612126 SLC2A1 1p35-p31.3 Paroxysmal exercise-induced dyskinesia

DYT19 611031 probably PRRT2 16q13-q22.1 Episodic kinesigenic dyskinesia 2, probably synonymous with DYT10

DYT20 611147 unknown 2q31 Paroxysmal nonkinesigenic dyskinesia 2

DYT21 614588 unknown 2q14.3-q21.3 Late-onset torsion dystonia

DYT23 610110 ANO3[7] 11p14.2 Autosomal dominant cranio-cervical dystonia with prominent tremor

HEREDITARY DYSTONIA - AD

Type Clinical Features Epidemiology Age of Onset

Dystonia 1.  Dystonia musculorum deformans; idiopathic torsion dystonia; Oppenheim's dystonia

Dystonia may present as focal dystonia, usually in the limbs; often generalizes especially if early-onset

50% of early-onset dystonia in non-Jews, 90% in Jews; prevalence of 1:10000-1:15000 in non-Jews, 1:3000-1:5000 in Jews

Usually childhood, may be later (most <26 years)

Dystonia 4Laryngeal and cervical dystonia

Single large Australian family

13-37 years

Dystonia 6Focal or generalized; cranial, cervical, or limb dystonia

Two Mennonite families

Average 19 years

Dystonia 7

Focal dystonia (cervical and laryngeal dystonia) and postural tremor

Single German family 28-70 years

Dystonia 13

Cranial or cervical dystonia; some focal, some generalized

Single Italian familyFive years to adulthood

Non hereditary – idiopathic torsion dystonia

1. Generalized2. Segmental3. Focal – Torticollis, writer’s cramp,

oromandibular dystonia, blepherospasm

SECONDARY DYSTONIAS

1. Associated with other hereditary neurologic syndrome

1. Wilson’s disease2. Huntington’s chorea3. Progressive pallidal atrophy4. Parkinson’s disease5. Hallevorden Spatz disease6. Frederick's ataxia7. Batten Speilmayer Vogt disease8. Juvenile neuronal ceroid lipofuscinosis9. Dystonia with neural deafness10. Dystonia with subcapsular catarect11. Myoclonic dystonia with nasal malformation12. Leigh disease13. Mg poisoning (dopa responsive)

SECONDARY DYSTONIAS

2. Due to known environmental factors1. Perinatal brain injury –

1. Status mormorotus2. Status demylinatous3. Other basal ganglia lesion

2. Inflammatory1. Lethargic encephalitis2. Non specific encephalitis3. Tubercular meningitis4. Syphilis

3. Craniocerebral trauma, Surgical lesion4. CVA

1. Cerebral atherosclerosis2. Striatopallidonigral calcification3. Rheumatic brain disease

5. Brain tumor6. Toxin

1. Mn, CO, CS2, Phenothiazine

7. Hysteric - rare

CHARACTERISTICS Extensive cocontraction of antagonist muscles during voluntary

movement Failure of reciprocal inhibition Overflow of contraction to remote muscles, not normally

employed in voluntary movement Spontaneous spasm of co-contraction EMG burst in antagonistic muscle –overflow phenomenon 100-

300ms CD Marsden

Tremor rigidity and involuntary movement of limb can be abolished by surgical lesion in the medial segment of globus pallidus or preferably in the VCN of thalamus, without causing paresis of voluntary movement contralaterally

This VC nucleus probably through its connection with pre-motor cortex and cortico-spinal tract is essential link in the expression of extra-pyramidal syndrome both striatonigral and cerebellar type.

Mayer Cooper

TREATMENT

1. Anticholinergic2. Ldopa3. Dopa depletor4. DOPA agonist5. Baclofen6. Benzodiazepine7. Carbamazepine8. Phenytoin9. Alcohol10. Clonidine11. Lithium

12. GABArgic13. Botulin toxin14. Thalamotomy

(bilateral complication high)

15. Paroxysmal kinesogenic dystonia – Anticonvulsant responsive

16. Non- kinesogenic – Benzodiazepine responsive

FOCAL DYSTONIA1. Orofacial dystonia

2. Blepherospasm

3. Spasmodic dysphonia

4. Spasmodic torticolis

5. Writer’s cramp

OROFACIAL DYSTONIA (MEIG SYNDROME)BRUGEL SYNDROME Aetiology

Occur in middle age, elderly women Phenothiazine With other dystonic disorder

Clinical Orofacial dyskinesia, Blepherospasm, may be

associated torticolis or truncal dystonia Pathogenesis

Activation of mesolimbic DA receptors Inhibition of mesolimbic NE receptors Inhibition of GABAergic fibers within the zona

incerta an output station of mesolimbic DA region

* Subject of Brugel painting

OROMANDIBUAL DYSTONIA CON…

Pathology : Neuronal loss of striatum Treatment:

Dopa antagonist – Tetrabenazine GABAergic – Clonazepam Anticholinergic – Trihexiphenydil Lithium

BLEPHAROSPASM AND BLEPHEROCLONUS

Isolated or with other MD or dystonias Elderly person Due to dopaminergic predominance in the

striatum Rx

Botulinum toxin Anticholinergic Baclofen Benzodiazepine Tetrabenazine Halloparidol

SPASMODIC DYSPHONIA

Tremulous forced voice with a low tone and volume and often associated with facial grimicing

SPASMODIC TORTICOLLIS

Intermittent arrhythmic brief or prolonged spasm of neck muscle resulting in more or less sustained movement or abnormal posture of head

Benign idiopathic form Age 30-40y male Painful contraction, worse on standing and

walking, psychogenic stimuli Reduce by contathal stimuli and relaxation No consistent neuropathology –

Extrapyramidal system of diencephalon / mesencephalon

Secondary form associated with other dystonias

SPASMODIC TORTICOLLIS D/D

Fixed orthopedic form (wry neck) – Congenital sternocleidomastoid shortening Acquired : root, cord lesion, muscle disease

Treatment Drug resistant –

Anticholinergic Beclofen Carbamazepine Benzodiazepine Tetrabenizine Dopamine blocker Botulinum toxin

Behavioral relaxation, biofeedback – recur Electrical stimulation of cervical cord, cerebellum – not

sustained effect Selective peripheral denervation

WRITER’S CRAMP Spasm, cramps, ache and occasional tremor of the hand

muscle on writing, may disappear on continuous writing Other focal dystonias may be present and during other

acts Onset 20-50 y both sexes Once started persist for long time Discreet movement are impaired by spreading

innervation of un-needed muscles (intension spasm) a feature common to other tonic state

Pathophysiology : unknown Treatment:

De-conditioning : Delivering shock during spasm Biofeedback Anticholinergic Botulinum toxin

THANKS