The Symptomatic Treatment of Acquired Dystonia

The Symptomatic Treatment of Acquired Dystonia: A SystematicReview

Corina N.A.M. van den Heuvel, MSc, Marina A.J. Tijssen, MD, PhD, Bart P.C. van de Warrenburg, MD, PhD, Catherine C.S. Delnooz, MD, PhD

Karina Fontánez L.

Residente Psiquiatría

Introducción

• Distonía Adquirida (DA) es aquella cusada por un evento exógeno oadquirido.

• En la práctica clínica el arsenal terapéutico utilizado es similar alusado para distonías hereditarias o idiopáticas.

• Se requiere evidencia formal sobre la eficacia de estasintervenciones.

• Fahn y Eldridge (1976) realizaron la primera distinción entredistonía primaria y adquirida.

• En 2013, se logró un consenso actualizado sobre la clasificación delas distonías de acuerdo a características clínicas y etiológicas.

Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of

Acquired Dystonia: A Systematic Review. Movement Disorders (2016)

Introducción

Según etiología:-Patología del sistema nervioso.-Hereditarias-Adquiridas-Idiopáticas

Albanese et al (consenso): distonía no genética secundaria a causaespecífica conocida.

no hereditaria y con origen exógeno o adquirido

conocido.

Aunque el tratamiento no difiere mayormente, existe evidencia de

una respuesta diferencial de acuerdo al origen de las distonías

(Keychev V. et al, 2011).

Causas de DAgg



Objetivo del estudio

Realizar una revisión sistemática comprensiva de evidencia actual sobre estrategias de tratamiento de distonías adquiridas.



Metodología

Revisión de bases de datos: PubMed, Cochrane Library, web of Sciencie,PiCarta, PsycINFO.Publicaciones en inglés de 1983 a 2015.

MeSH:“secundary dystonia” “tardive dystonia” “cerebral palsy and dystonia”

+Búsqueda por fármacos (por familia y nombre genérico) -anticolinérgicos, benzodiacepinas, dopaminérgicos, anticonvulsivantes,vitaminas, bloqueadores de canales de calcio, antipsicóticos, propofol,toxina botulínica; DBS, cirugías, TCMS, rehabilitación, terapiaelectroconvulsiva y otras técnicas.



Metodología

Se clasificó los estudiosrecolectados de acuerdoal “Evidencie-basedGuideline Development”(Dutch Cochrane Center)EBRO.

S1: nro de pacientes en grupode tratamiento igual o menor a5 y estudios no clasificables entipo B o superior.



Resultados y Discusión

Tratamiento

Médico

Neuroestimulación

Abordaje Quirúrgico

Allied Health Care

I Tratamiento Médico: Toxina Botulínica

PARÁLISIS CEREBRAL DISTÓNICA

• 5 estudios• Evidencia nivel 3 para Toxina A y B• Serie de caso (n=7) con toxina B

mostró mejoría clínica sin efectos adversos serios, sin relación dosis - eficacia.

• Serie con distonía y distonía + espasticidad (n=10) mostró algunos efectos adversos (paresia, desarrollo de Ac)

DISTONÍA TARDÍA

• 2 reportes de caso y 4 series• Mejoría de distonías focales y

segmentarias con toxina A, evidencia nivel 3.

• Series (distonía focal) de mejoría moderada a marcada en 76 a 96% de las áreas.

• Efectos adversos comunes transitorios (disfagia, afonía, fatiga, otros)





Supplementary Table 1. Studies of BoNT therapy in acquired dystonia

Reference, year of

publication

Design No. (aetiology) Localization of dystonia (no.) Intervention (dosage) Effect EBRO

Cerebral palsy

Arens LJ, 1997 (8) Case series 5 (dystonic CP), 5

(dystonic-spastic CP)

; total 15 patients

Dystonic CP: hemiplegia (4),

quadriplegia (1); mixed

dystonic-spastic CP:

hemiplegia (1), diplegia (1),

quadriplegia (3)

BoNT A (4 - 6 U/kg, 1

repetition)

Improvement in achievement

of the defined goal in 80% of

patients in all groups

C

Gallien P, 2004 (S1) Case report 1 (CP) Focal, lumbar BoNT A (200 U, 1

repetition)

Subjective improvement in

pain and posture

C

Racette BA, 1998 (S3) Case series 2 (CP) Focal, cervical BoNT A (500-700 U, 1-2

repetitions)

Elimination of all involuntary

neck movements

C

Worley G, 2003 (S2) Case report 1 (CP)

; total 3 patients

Focal, laryngeal BoNT A (2-3 U, every 3-

4 m during 2 yr)

Relief of inspiratory stridor;

transient overparalysis of

muscles

C

Sanger TD, 2007 (9) Prospective case

series

7 (CP) Focal, arm (6); hemidystonia

(1)

BoNT B (50, 100, 200

U/kg with 3 m in

between)

Significant improvement UDRS

proximal and distal scores,

BFMDRS upper extremity score

, UPDRS rigidity and finger

taps, maximum reaching speed

of hand movements; no

improvement Ashworth score.

C



Supplementary Table 1. Studies of BoNT therapy in acquired dystonia

Reference, year of

publication


Tardive dystonia

Brashear A, 1998 (13) Case series 7 (tardive)

; total 156 patients

Focal, cervical BoNT A (237-415 U, 4-17

repetitions)

Improvement severity score

40%

C

Chatterjee A, 1997 (14) Retrospective case series 19 (tardive) Focal, neck (9), eyes (8), vocal cords (1), jaw

(6), facial (4)

BoNT A (2.5-161.2 IU, >1

repetitions)

Improvement in 96% of

affected body regions, rated

on a clinical scale

C

Dressler D, 2014 (S4) Case report 1 (tardive)

; total 2 patients

Segmental, blepharospasm + mandibular +

cervical + pharyngolaryngeal

BoNT (dose NA) Reduced symptoms C

Kanovsky P, 1999 (S6) Case series 4 (tardive) Focal, facial/orolinguomandibular BoNT A (100-300 MU, 2-

8 repetitions)

Improvement AIMS >50% in

all cases; longlasting effect

in 2 patients (6 and 18 m)

C

Kaufman DM, 1994 (S5) Case report 3 (tardive) Focal, cervical BoNT A (75-200 U, 1-2

repetitions)

Subjective improvement of

pain and dystonic symptoms

in 2 patients, complete relief

of symptoms in 1 patient;

effect lasted for 2-3 m

C

Tarsy D, 1997 (15) Retrospective case series 34 (tardive) Focal, cervical (24), blepharospam (6),

oromandibular (3), laryngeal (2), lingual (1),

lower extremity (1), lumbar (1)

BoNT A (mean 227.0 U,

1 repetition)

Marked or moderate

improvement in 76% of

affected body regions (global

scale)

C

Other

Vasileiadis GI, 2012 (S7) Case report 1 (trauma) Focal, shoulder BoNT A (190 IU, 2

repetitions)

Improvement constant score

60%

C

AIMS, abnormal involuntary movement scale; BFMDRS, Burke-Fahn-Marsden dystonia rating scale; BoNT, botulinum neurotoxin; CP, cerebral palsy; NA, not available; UDRS, Unified Dystonia Rating Scale;

UPDRS, Unified Parkinson's Disease Rating Scale.

I Tratamiento Médico: Farmacoterapia oral

• 38 estudios• Controversia en uso de trihexifenidilo y levodopa para PC

distónica.• En otras subpoblaciones pacientes sólo existen series de caso

pequeñas o reportes de caso (evidencia clase C)




ANTICOLINÉRGICOS

Estudio con 23 pacientes (Randall et al, 2001) distinguió que ensubgrupo con hiperkinesia el trihexifenidilo empeoró síntomas.

Pacientes con distonía generalizada mostró mejoría en síntomasmotores de EESS y no motores, con relación inversa a la edad (Hoonet al, 2001)

Series y reportes con efecto positivo en 94% de pacientes (n=109).



Supplementary Table 2. Studies of oral drug therapy in acquired dystonia

Reference, year of

publication

Design No. (aetiology) Localization of dystonia

(no.)

Intervention (dosage) Effect EBRO

Anticholinergic agents

Carranza-del Rio J, 2011

(24)

Retrospective case series 101 (CP) NA Trihexyphenidyl (initial dose

0.01-0.414 mg/kg/d, gradually

increased to 0.03-3.13 mg/kg/d;

duration 0-10.8 yr)

Improvement upper (59.4% of patients) and lower

(37.6% of patients) extremities, sialorrhea (60.4% of

patients), and speech (24.7% of patients) (scale NA);

91% of patients tolerated medication well; side

effects in 69.3% of patients

C

Hoon AH, 2001 (23) Retrospective case series 22 (CP) Generalized Trihexyphenidyl (0.04-0.3

mg/kg, mean duration of

treatment 9 m)

Parental rating of change in function: great change in

speech/arms, moderate change in legs/drooling.

C

Pidcock FS, 1999 (S10) Case report 1 (putaminal hemorrhage) Generalized Trihexyphenidyl (gradual

increase from 2 mg to 14 mg, 11

m)

Improvement in fine motor control, language, oral

motor skills

C

Rice K, 2009 (20) Pilot study, randomized,

double blind, cross-over

16 (CP) Generalized Trihexyphenidyl (dose-escalation

from 0.2 mg/kg/d to 2.5

mg/kg/d in 12 w, duration 16 w)

vs. placebo

No improvement BADS, QUEST, GAS, COPM;

significant order effects on GAS, COPM-P

B

Sanger TD, 2007 (22) Prospective case series 23 (CP) Focal, dominant upper

extremity

Trihexyphenidyl (0.05 mg/kg 2

times/d-0.25 mg/kg 3 t.i.d.,

duration 15 w)

Significant improvement MAULF (mean change 2.97,

scale 0-100); trihexyphenidyl may worsen symptoms

in children with hyperkinetic forms of dystonia (10)

C

Wolf ME, 1985 (S12) Case series 3 (tardive) Dystonic posturing Trihexyphenidyl (15-20 mg/d, 1-

4 w)

>50% improvement in 2 patients (generalized dystonia

scale); increased choreatic movements

C



X


GABAÉRGICOS

Baclofeno: 3 series de casos con resultados positivos, en general en asociación.

Benzodiacepinas: se requiere estudio que distinga entre distintas bdz. Reportes de caso con efectos positivos (clonazepam) y otros negativos (diazepam).




Reference, year of

publication


GABA-mimetic agents

Gospe SM, 1986

(S13)

Case report 1 (tardive) Generalized Baclofen (gradual increase from

15 mg/d to 45 mg/d, 1 w then

tapering/discontinuation)

Symptom-free after 2 m C

Worley G, 2003 (S2) Case series 3 (CP) Generalized+laryngeal Baclofen+gabapentin (dose NA) Improvement dystonia

and inspiratory stridor;

recurrence of symptoms

in 1 patient (scale NA)

C

Yassa R, 1986 (25) Case series 7 (tardive) Focal (5) Discontinuation neuroleptics (3),

baclofen 60-90 mg/d (2)

No improvement (scale

NA)

C

Generalized (2) Discontinuation neuroleptics (2),

baclofen 60 mg/d (1)

Improvement (scale NA)

Diazepam 300 mg/d (1) No improvement (scale

NA)

Kaplan Z, 1991 (S16) Case report 1 (tardive) Focal, oromandibular Diazepam (40 mg IV) No effect C



X

XX


DOPAMINÉRGICOS

• L-dopa: estudio controlado negativo para distonía en PC (Pozin et al) y reporte de paciente con lesión bilateral de GB con efecto positivo a dosis bajas.

• Aripiprazol: 5 reportes positivos para distonía tardía, uno en combinación con trihexifenidilo (1,5 a 30 mg día).

• Tetrabenazina: Serie con efecto positivo en 80% de 92 pacientes con distonía tardía (Jankovic J, 1997) y una serie sin efectos (Shapleske J, 1996) (37,5-400 mg dia)

• Clozapina: mayor evidencia positiva y de largo plazo, mayor en asociación a benzodiacepinas (67,5-200 mg dia).

• Quetiapina: Serie positiva y prolongada con 19 pacientes (Gourzis P, 2015) y reportes positivos (600-800 mg día)

• Olanzapina: Mejoría en serie de 4 pacientes con seguimiento a 4 meses y un caso con recidiva luego de 5 años.




Reference, year of

publication


Dopamine-altering agents

Bernard G, 2010 (S17) Case report 1 (bilateral T2 hyperintensities

globus pallidus, unknown cause)

Multifocal, lower extremities+right upper extremity Levodopa (exact dose NA, 2

yr)

Control of dystonic symptoms C

Pozin I, 2014 (31) Pilot study, randomized,

double blind, cross-over

9 (CP) Focal, upper extremities Levodopa (mean dose 6.65

mg/kg/d vs. placebo)

No improvement QUEST,

dynamometer grip strength

and the 9-hole pegs in/out

test; worsening box-and-

blocks test

B

Lucetti C, 2002 (S31) Pilot study, single blind 4 (tardive) Focal, cervical (3); segmental, orofacial+cervical (1) Olanzapine (5 mg/d increased

up to 7.5 mg/d, 12 w)

Improvement TWSTRS 26.4%;

improvement VAS 42.6%

C

Garcia-Lado I, 2005 (S23) Case report 1 (tardive) Focal, left foot Olanzapine (10 mg/d, 5 yr) Symptom-free after 1 m;

recurrence after 5 yr

C

Clozapine (200 mg/d) Symptom-free; effects

maintained up to 2 yr

Charfi F, 2004 (S22) Case report 1 (tardive) Multifocal, cervical+axial+upper limbs Clozapine (200 mg/d, 6 w) Improvement AIMS 100% C

Grover S, 2014 (S24) Case series 4 (tardive)

; total 5 patients

Segmental, cervical+orofacial (2); multifocal,

blepharospasm+cervical+extremities (1), cervical+lumbar (1)

Clozapine (62.5-175 mg/d, 8

w-6 yr)

Response rate of 50-100%;

sustained effects over 6 yr

C

Joe S, 2015 (S25) Case report 1 (tardive) Focal, cervical Clozapine (12.5 mg/d titrated

up to 87.5 mg/d, 3 m)

Symptom-free C

Kwan Y, 2010 (S26) Case report 1 (tardive) Multifocal, facial+axial+upper extremities Clozapine (200 mg/d, 21 m) Symptom-free C

Pinninti NR, 2012 (S27) Case report 1 (tardive) Multifocal, facial+cervical+axial+upper extremities Clozapine (250 mg/d, duration

of treatment 3 yr)

Improvement AIMS 90%;

improvement BFMDRS 98%;

improvement started after 3

m of treatment and

maintained up to 3 yr

C


Reportes anecdóticos

Positivos con pregabalina, midazolam, pimozide, verapamilo, gabapentina, levetiracetam y vitamina E.

Negativos con biperideno, propanolol y clonidina.




Reference, year of

publication


Other oral drug

therapy

Abad V, 1993 (S34) Case report 1 (tardive) Generalized Verapamil (40 mg increased to 120 mg t.i.d.) Nearly symptom-free C

Dannon PN, 1997

(S36)

Case report 1 (tardive) Generalized Vitamin E (1200 IU)+carbamazepine (600 mg/d, 15

m)

Improvement AIMS 95% within 2 m; no exacerbation up to 15 m C

Nisijima K, 1998

(S33)

Case report 1 (tardive) Segmental, upper half of

body

Eperisone (150 mg/d increased up to 300 mg/d, 2

m)

Symptom-free C

Karosin C, 2012

(S32)

Case report 1 (subarachnoidal and

cerebral hemorrhage;

dystonic foot)

Multifocal, right foot+hip Pregabalin (75 mg 2 times/d, duration of treatment

3 w)

Disappearance of dystonia within 2 days C

Kaplan Z, 1991 (S16) Case report 1 (tardive) Focal, oromandibular Biperiden (5 mg IV) No effect C

Propranolol (up to 280 mg/d, 2 w) Improvement movement score 67% (scale 0-5)

Clonidine (up to 0.3 mg/d) Worsening movement score 75% (scale 0-5) C

Yassa R, 1986 (25) Case series 3 (tardive)

; total 7 patients

Focal (1) Haloperidol (10 mg/d) No improvement (scale NA) C

Focal (2) Lithium (900 mg/d) No improvement (scale NA)

Focal (1) Propranolol (40 mg/d) No improvement (scale NA)

Generalized (1) Lecithin (60 mg/d) No improvement (scale NA)


Reference, year of

publication


(no.)

Intervention (dosage) Effect EBRO

Combinational therapy

Grosso S, 2012 (S9) Case report 2 (CP, status

dystonicus)

; total 3 patients

Generalized Midazolam (5 mg q4h)+pimozide (6 mg/d)+trihexyphenidyl (8 mg/d) Complete resolution of

status dystonicus

C

Midazolam (10 µg/kg/min cIV)+tetrabenazine+baclofen+trihexyphenidyl (doses NA) Partial improvement

Bavle AD, 2013 (S8) Case report 1 (tardive) Focal, TOC Trihexiphenidyl (4 mg/d)+aripiprazole (10 mg/d); discontinuation olanzapine Gradual disappearance of

TOC over 3 months

C

Shapleske J, 1996 (S11) Case report 1 (tardive) Generalized Trihexyphenidyl (increasing up to 8 mg/d, 6 w)+diazepam (increasing up to 15

mg/d, 6 w)

No improvement C

Clozapine (550 mg/d)+clonazepam (3 mg/d) Nearly symptom-free with

restoration of normal gait

Blake LM, 1991 (S14) Case report 2 (tardive) Focal, cervical (1), oral (1) Clozapine (900 mg/d)+clonazepam (3 mg/d) Improvement DISCUS score

63%

C

Mangot A, 2014 (S35) Case report 1 (tardive) Focal, craniocervical Levetiracetam (gradually increased up to 1000 mg)+tetrabenazine (100

mg)+clonazepam (1.5 mg)

Improvement AIMS 36% C

Yamamoto N, 2007 (S15) Case report 1 (tardive) Focal, cervical Clonazepam (5.5 mg/d)+risperidone (6 mg/d)+biperiden (1 mg/d) Improvement DIEPSS 50% C

Aukst-Margetic B, 2008 (S28) Case report 1 (tardive) Generalized Clozapine (350 mg/d)+diazepam (30 mg/d, duration of treatment 6 m) Improvement BFMDRS-D

85%; improvement BFMDRS-

M 96%

C

AIMS, abnormal involuntary movement scale; BADS, Barry-Albright dystonia scale; BFMDRS, Burke-Fahn-Marsden dystonia rating scale (BFMDRS-D, disability; BFMDRS-M, movement); cIV; continuous intravenous infusion; COPM, Canadian

occupational performance measure (COPM-P, performance); CP, cerebral palsy; DISCUS, Dyskinesia Identification System: Condensed User Scale; DIEPSS, drug-induced extra-pyramidal symptoms scale; GAS, goal attainment scale; NA, not

available; PANSS, positive and negative syndrome scale; QUEST, quality of upper extremity skills test; SARS, Simpson-Angus Rating Scale; TOC, tardive oculogyric crises; TWSTRS, Toronto western spasmodic torticollis rating scale; VAS, visual

analogue scale; q4h, every 4 hours.

II Cirugía

BACLOFENO INTRATECAL E INTRAVENTRICULAR.

Ventajas: reversible, ajuste de dosis, concentraciones mayores que oral, menos efectos adversos.

-ITB

11 estudios.

Recomendación nivel 3 para PC, además de distonía tardía y distonía post hipoxia perinatal o traumatismo. Algunos estudios con efecto mayor a 11 años

-IVB

Permite mayores concentraciones cerebrales y menos efectos adversos que ITB.

2 series con recomendación nivel 3



Supplementary Table 3. Studies of intrathecal or intraventricular baclofen therapy in acquired dystonia

Reference, year of

publication

Design No. (aetiology) Localization of dystonia (no.) Intervention (dosage) Effect EBR

O

Intrathecal baclofen therapy

Arishima H, 2015 (S37) Case report 1 (CP) NA ITB (50 µg/d) Effective control of dystonia C

Bonouvrié LA, 2011 (39) Case controlled trial,

randomized, double blind

4 (CP) Generalized ITB bolus/continuous

(increased to individual

optimal dose, max 200 µg/d,

3d), followed by 4d ITB or IT

placebo

Initial BADS improvement (72%) during ITB

trial. ITB vs placebo: comparable BADS

scores (improvement 63% and 54%,

respectively); improvement in pain and

comfort after ITB treatment

B

Grosso S, 2012 (S9) Case report 1 (CP) Generalized ITB (100 µg/d)+pimozide (2

mg t.i.d.)+trihexyphenidyl (5

mg t.i.d., 14 m)

Complete resolution of status dystonicus

from day 10 onwards

C

McCarty SF, 2001 (S40) Case report 1 (CP) NA Continuous ITB (details NA) Improvement Ashworth score 50% C

Motta F, 2009 (40) Case series 11 (CP) Dystonic tetraplegy Continuous ITB (individual

optimal dose, 1 yr)

Improvement BADS 15%; improvement MAULF

dominant upper extremity 9%, non-dominant

upper extremity 8%

C

Ross DA, 2005 (S41) Case report 1 (CP) NA Continuous ITB (NA) Excellent response (scale NA); paraspinal

pump placement may eliminate repeated

catheter migration

C

Woon K, 2007 (S43) 2 (CP)

; total 8 patients

NA Continuous ITB (400-500 µg/d) Subjective improvement in dystonia C

Dressler D, 1997 (S38) Case report 1 (tardive) Segmental, cervical+axial Continuous ITB (100 µg/d, 6

m)

Symptom-free C

Walker RH, 2000 (S42) Case series, single blind 2 (tardive), 1 (perinatal

hypoxia)

; total 14 patients

Generalized (2); focal, upper extremities (1) Continuous ITB (individual

optimal dose, max 1000 µg/d,

15-60 m)

Worsening BFMDRS (tardive, generalized, 1),

improvement BFMDRS 93% (tardive, focal, 1),

improvement BFMDRS 10% (perinatal hypoxia,

generalized, 1)

C



Intraventricular baclofen therapy

Albright AL,

2009 (41)

Case series 5 (CP) Generalized Continuous IVB (120-2012

µg/d, duration of treatment 3-

21 m)

Mean improvement BADS

20%

C

1 (striatal lesions

of unknown

origin)

Generalized Continuous IVB (900 µg/d,

duration of treatment 6 m)

No improvement BADS

1 (traumatic

brain injury)

Generalized Continuous IVB (250 µg/d,


Improvement BADS 58%

1 (anoxia) Generalized Continuous IVB (675 µg/d,


Improvement BADS 100%

; total 10 patients

Bollo RJ, 2012

(S45)

Case series 1 (CP), 1

(hypoxic-ischemic

encephalopathy)

; total 3 patients

Generalized Continuous IVB (50-100 µg/d

increased over 3 days to 525-

980 µg/d, 5.5-7 m)

Improvement BADS 36-40% C



II Cirugía

DENERVACIÓN QUIRÚRGICA

No se ha estudiado diferencialmente las técnicas utilizadas.

Recomendación nivel 3 (estudios clase C).

Distonía cervical por asfixia perinatal (Albright AL, 2007), distonía y espasticidad en niños (Tyler – Kabara, Albright)

Rehabilitación postqirúrgica mejora los resultados.



Supplementary Table 4. Studies of surgical denervation in acquired dystonia

Reference,

year of

publication

Design No.

(aetiology)

Localization of

dystonia (no.)

Intervention Effect EBRO

Albright AL,

2007 (42)

Case series 6 (CP,

cerebral

infection,

anoxia)

Focal, upper

extremities (2);

generalized (3);

unknown (1)

Combined

ventral+dorsal

rhizotomy

Variable improvement

BADS 50-100%

C

Sitthinamsuw

an B, 2010

(S46)

Case report 1 (CP) Focal, cervical Peripheral

denervation

Symptom-free C

BADS, Barry-Albright dystonia scale; CP, cerebral palsy.



II Cirugía

LESIÓN CON GUÍA ESTEREOTÁXICA

Once estudios (recomendación nivel 3).

Efecto positivo de talamotomía y palidotomía, en especial en hemidistonías

Estudio negativo en PC para lesión bilateral de tálamo y GPi.

Reportes negativos en lesiones postencefalíticas, stroke e hipoxia perinatal.

Yoshor (2001) comparó intervención talámica versus de GP (n=17 pacientes) sin encontrar diferencia significativa.

Complicaciones fueron usualmente transitorias.



Supplementary Table 5. Studies of stereotactic lesioning in acquired dystonia

Reference, year of

publication

Design No. (aetiology) Localization of dystonia (no.) Intervention Effect EBRO

Thalamotomy

Broggi G, 1983 (43) Case series 8 (CP) Hemiparesis (6) Thalamotomy 50% good improvement, 33% fair

improvement, 17% minimal

improvement

C

Tetraparesis (2) Thalamotomy Minimal improvement

1 (trauma) Hemiparesis Thalamotomy Minimal improvement

1 (post-embolisation

syndrome), 1 (removal

of right parietal

ependymoblastoma)

Hemiparesis Thalamotomy Good improvement

; total 33 patients

Speelman JD, 1989

(S48)

Retrospective case

series

12 (CP)

; total 18 patients

Generalized (7); posturing (5) Thalamotomy General improvement of dystonia C

Cardoso F, 1995 (44) 1 (cardiovascular

arrest), 1 (seizure), 6

(stroke), 2 (perinatal

cerebral injuries);

total 17 patients

NA Thalamotomy GOS short-term = 2.20; GOS long-

term = 1.90

C

Fonoff ET, 2011 (S47) Case report 1 (bacterial

meningitis)

Hemidystonia Thalamotomy

posterior ZI

Improvement UDRS 89.08%;

improvement GRS 91.4%;

improvement BFMDRS 97.43%;

sustained effects up to 6 yr

C

Yoshor D, 2001 (45) Case series 11 (insult to the

central or peripheral

nervous system)

; total 32 patients

NA Thalamotomy GOS = 2.00 C

Pallidotomy

Lin JJ, 1999 (S51) Case report 1 (CP) Generalized Bilateral

pallidotomy

Improvement BFMDRS 34%,

only in cervical and

oromandibular dystonia (no

improvement in dystonia of

extremities or axial)

C

Speelman JD, 1989

(S48)

Retrospective case

series

3 (CP)

; total 18 patients

Dystonic posturing Pallidotomy Improvement locomotion 75-

80% (ADL)

C

Eltahawy HA, 2004

(S50)

Case series 1 (encephalitis) Hemidystonia Unilateral

pallidotomy

Improvement BFMDRS 0%; GOS

= 0

C

1 (stroke) Hemidystonia Improvement BFMDRS 0%; GOS

= 1

; total 15 patients

Sanghera MK, 2003

(S49)

Case series 4 (brain damage,

details NA)

; total 15 patients

Generalized (2) Posteroventral

pallidotomy

Improvement BFMDRS 21%;

improvement UDRS 19%

C

Hemidystonia (2) Improvement BFMDRS 61%;

improvement UDRS 65%

Yoshor D, 2001 (45) Case series 6 (insult to the

central or

peripheral nervous

system)

; total 32 patients

NA Pallidotomy GOS = 2.50 C

II Cirugía

NEUROESTIMULACIÓN

DBS:

45 estudios, todos clase C (nivel 3), con mejoría además en calidad de vida y dolor.

Área más estudiada corresponde al GPi.

Mayor respuesta en distonías tardías (hasta 97% de pacientes).

Efecto casi inmediato y de larga duración.

DA parecen responder menos que las primarias (Eltahawy et al)

Reportes favorables en cerebelo anterior y NST, y negativos para tálamo VLP y VIM.



II Cirugía

NEUROESTIMULACIÓN: DBS

Predictores de buena respuesta: ausencia de anomalía estructural cerebral o de trastornos concomitantes, menor edad y menor tiempo de evolución de la enfermedad.

Predictores negativos son la presencia de deformidad musculoesquelética, posiciones fijas anormales, inmadurez ósea, severidad de la distonía.

En general se describe mejoría prolongada, pero existen 3 reportes con empeoramiento posterior.

Efectos adversos tienden a desaparecer luego de ajustar el dispositivo.



Supplementary Table 6. Studies of deep brain stimulation in acquired dystonia

Reference, year of

publication


GPi-DBS

Air EL, 2011 (59) Retrospective case series 5 (CP) NA GPi bilateral Mean improvement BFMDRS-M 8%;

mean improvement BFMDRS-D 21%

C

1 (CP), 1 (encephalitis), 2

(stroke)

NA GPi unilateral Improvement BFMDRS-M 9-52%;

improvement BFMDRS-D 4-69%

; total 31 patients

Apetauerova D, 2010

(S65)

Case report 2 (CP) Generalized GPi bilateral Persistent suppression of dystonic

movements

C

Gimeno H, 2012 (S67) Case series 4 (CP)

; total 6 patients

Generalized GPi bilateral Improvement BFMDRS-M <10%; no

effect on BFMDRS-D; improvement PPP

55%; improvement NRS 73%;

improvement CPCHILD 27%; mean

change COPM-P 3.1; mean change

COPM-S 2.9; GAS goals achievement

74%

C

Gimeno H, 2014 (58) Prospective case series 14 (CP)

; total 30 patients

Generalized GP bi/unilateral Median change COPM-P 5.6; median

change COPM-S 5.8; median change

BFMDRS 4

C

Keen JR, 2014 (S68) 5 (CP) Generalized GPi bilateral Mean improvement BADS 16%; mean

improvement BFMDRS-M 28.5%;

patients stimulated 23 m or more

improved 18.3% and 30.5%,

respectively

C

Kim JP, 2012 (47) Retrospective case series 4 (CP)

; total 10 patients

Generalized GPi bilateral Improvement BFMDRS-M 32%;

improvement BFMDRS-D 14.3%

C

Kim AR, 2014 (64) Case series 7 (CP)

; total 12 patients

Generalized GPi bilateral Mean improvement BFMDRS-M: 50%

after 1 year, 40% after 2 years; no

improvement BFMDRS-D; worsening

satisfaction scale score 27%

C

Marks WA, 2011 (60) Prospective case series 14 (CP) NA GPi bi/unilateral Improvement BFMDRS-M 37.84%;

improvement BFMDRS-D 14.44%;

improvement BADS 19.48%

C

Marks WA, 2013 (61) Prospective case series,

single blind

9 (CP)

; total 17 patients

Generalized GPi Improvement BFMDRS-M 21.8%;

improvement BFMDRS-D 15.8%;

improvement BADS 16.8%

C

II Cirugía

NEUROESTIMULACION

MOTOR CORTEX STIMULATION

Serie de caso (10 pacientes) con distonía de distinta causa mostró mejoría tras 6 meses de tratamiento.

Serie de 5 pacientes con distonía por lesión vascular no mostró mejoría y presentó efectos adversos reversibles.

No es posible establecer una recomendación en base a la evidencia.



Supplementary Table 7. Studies of motor cortex stimulation in acquired dystonia

Reference, year

of publication


(no.)

Intervention Effect EBRO

Messina G, 2012

(74)

Case series 10 (anoxia,

brain trauma,

encephalitis,

iatrogenic

postsurgical

syndome,

stroke, tardive)

Focal, upper extremity Unilateral

epidural MCS

Improvement DASH 11-

68%; improvement SF-36

physical activity

subscale 25-95/100;

improvement SF-36

mental state subscale

12-96/100;

improvement VAS 66-

73%

C

Rieu I, 2014

(S77)

Randomized,

double blind,

cross-over

5 (focal

vascular basal

ganglia lesion)

Hemidystonia Bipolar epidural

MCS;

(neurostimulato

r ON/OFF, 3m,

1 m wash-out

period)

No effects on BFMDRS,

Ashworth score, SF-36,

VAS

B

BFMDRS, Burke-Fahn-Marsden dystonia rating scale; DASH, disability of arm, shoulder, and hand; MCS, motor cortex stimulation;

SF-36, short form-36; VAS, visual analogue scale; QoL, quality of life.



III NEUROESTIMULACIÓN NO INVASIVA

TEC

7 reportes de casos con distonía tardía.

En dos pacientes, mejoría tras 3 o 4 sesiones de TEC bilateral y mejoría parcial en 1 paciente.

Reportes de efectividad con TEC unilateral

Duración del efecto de meses a años.



III NEUROESTIMULACIÓN NO INVASIVA

EST. MAGNÉTICA TRANSCRANEAL

Un reporte de 3 pacientes (encefalitis viral, daño neonatal, intoxicación).

Estimulación repetitiva premotora.

Efectos positivos en todos los pacientes.



Supplementary Table 8. Studies of noninvasive neurostimulation in acquired dystonia

Reference, year of

publication


Electroconvulsive therapy

Adityanjee, 1990

(S78)

Case report 1 (tardive) Focal, cervical ECT Little improvement after 6

sessions, marked after 11

sessions; deterioration within

months

C

Kaplan Z, 1991 (S16) Case report 1 (tardive) Segmental, craniocervical ECT bilateral Improvement on 3 separate

occasions, all within 3 sessions;

2x relapse

C

Kwentus JA, 1984

(S79)

Case report 1 (tardive) Multifocal,

craniocervical+axial+upper

extremities

ECT unilateral Improvement after 4 sessions;

no relapse up to 7 m

C

Manteghi A, 2009

(S80)

Case report 1 (tardive) Focal, cervical ECT bilateral

frontotemporal

Improvement in 4th-6th session;

no relapse in 4 yr follow-up

C

Nisijima K, 1998

(S33)

Case report 1 (tardive) Segmental, upper half of body ECT No effect C

Postolache TT, 1995

(S81)

Case report 1 (tardive) Segmental, cervical+back ECT 3x unilateral, 8x

bilateral

Improvement severity score 35%

after 6 sessions; deterioration

after 2 m

C

Sienaert P, 2005

(S82)

1 (tardive) Focal, facial ECT bitemporal Improvement AIMS 67%; back to

baseline within 3 m after

stopping continuation-ECT

C

Transcranial magnetic stimulation

Lefaucheur J, 2004

(S83)

Case series 3 (encephalitis,

intoxication,

neonatal brain

injury)

Generalized Premotor rTMS No to slight improvement

BFMDRS-M; no improvement

BFMDRS-D; great improvement

of frequency and intensity of

dystonic spasms

C

AIMS, abnormal involuntary movement scale; BFMDRS, Burke-Fahn-Marsden dystonia rating scale (BFMDRS-D, disability; BFMDRS-M, motor); ECT, electroconvulsive

therapy; rTMS, repetitive transcranial magnetic stimulation; TENS, transcutaneous electrical nerve stimulation.Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of


IV OTRAS DISCIPLINAS

• “Extracorporeal shock wave therapy” en 3 pacientes con lesión de ganglios basales. Sin efectos adversos.

• Ortesis para estabilidad de la marcha y dolor en distonía generalizada (un paciente).

• Feedback visual y haptico para control motor y escritura en un niño con PC.



CONCLUSIONES

CONCLUSIONES

1. Conflictos metodológicos.

2. El uso de toxina botulínica y DBS en GPi son opciones a considerar para distonía tardía y PC distónica.

3. La información es insuficiente sobre el efecto (y riesgo) de otras intervenciones farmacológicas.-Posiblemente, el ITB para PC distónica es la excepción.

4. No se ha explorado lo suficiente otras formas de neuroestimulación.



Health & Medicine

The Symptomatic Treatment of Acquired Dystonia