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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
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
Objetivo del estudio
Realizar una revisión sistemática comprensiva de evidencia actual sobre estrategias de tratamiento de distonías adquiridas.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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)
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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
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)
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
I Tratamiento Médico: Farmacoterapia oral
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).
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
X
I Tratamiento Médico: Farmacoterapia oral
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).
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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
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
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
X
XX
I Tratamiento Médico: Farmacoterapia oral
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.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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
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
I Tratamiento Médico: Farmacoterapia oral
Reportes anecdóticos
Positivos con pregabalina, midazolam, pimozide, verapamilo, gabapentina, levetiracetam y vitamina E.
Negativos con biperideno, propanolol y clonidina.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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
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)
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
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
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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,
duration of treatment 11 m)
Improvement BADS 58%
1 (anoxia) Generalized Continuous IVB (675 µg/d,
duration of treatment 7 m)
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
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
Supplementary Table 6. Studies of deep brain stimulation in acquired dystonia
Reference, year of
publication
Design No. (aetiology) Localization of dystonia (no.) Intervention Effect EBRO
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.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
Supplementary Table 7. Studies of motor cortex stimulation in acquired dystonia
Reference, year
of publication
Design No. (aetiology) Localization of dystonia
(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.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
Supplementary Table 8. Studies of noninvasive neurostimulation in acquired dystonia
Reference, year of
publication
Design No. (aetiology) Localization of dystonia (no.) Intervention Effect EBRO
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
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)
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.
Van den Heuvel C., Tijssen M., Van de Warrenburg B., Delnooz C. The Symptomatic Treatment of
Acquired Dystonia: A Systematic Review. Movement Disorders (2016)