DEEP$BRAIN$STIMULATION$IN$CHILDREN$ - … anesthetic release, involuntary movements are much less...
Transcript of DEEP$BRAIN$STIMULATION$IN$CHILDREN$ - … anesthetic release, involuntary movements are much less...
DEEP BRAIN STIMULATION IN CHILDREN
Unité des Pathologies Cérébrales Rés is tantes
Unité de Recherche sur les Comportements et Mouvements Anormaux
CHRU Montpell ier ; Univers ité Montpe ll ier ; France
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
Laura Cif, Montpellier, France
PHENOMENOLOGIC CLASSIFICATION OF PEDIATRIC MOVEMENT DISORDERS
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
Schlaggar, Mink 2003
DIAGNOSIS
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
Koy, 2016
PEDIATRIC MOVEMENT DISORDERS
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
oTransient/Permanent
oAge-‐dependent
oAge at onset, phenomenologyand extent orientate towards etiology
oComplexe dystonia rather in acquired and progressive disorders
oOften unremitting (most frequent lasting movement disorder in children)
oEarly spread of symptoms (generalized)
oÌncreasingdisability
oEventually life-‐threatening conditions
oNo efficient pharmacological therapy
oSide effects of medication/cognitive impact insufficiently assessed
DYSTONIA
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
MEDICAL TREATMENToLittle evidence from controlled trials on the best therapeuticstrategies (Trihexyphenidyl, Fahn , 1983)
oHeterogeneity in the pharmacological management of pediatricdystonia
oMostly related to personal experience, drugs availability, …
oThe higher number of treatment -‐proxy measure for nonresponsiveness and severity of the movement disorder
oL-‐dopa trial mainly for isolated dystonia and patients with symptomfluctuations not to miss a DRD
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
MEDICAL TREATMENT
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
Koy, 2016
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
o Baclofene 42,5%o Trihexyphenidyl 35,3%o L-‐DOPA 20,5%
MEDICAL TREATMENT
DYSTONIA CLASSIFICATIONAXIS I :CLINICAL CARACTERISTICS
Associated featuresBody
distribution Age of onset Temporal patternIsolated /combined withother movement disorders
Focal Infancy (0-‐2) Disease course
Combined dystonia
Segmental Childhood (3-‐12)
ProgressiveMultifocal Adolescence (13-‐20)
Occurrence of otherneurological or systemicmanifestations
Hemi dystonia Early adulthood (21-‐ 40)Temporal variability
Generalized Late adulthood (>40)
PersistentAction-‐specificDiurnalParoxysmal
Isolated dystonia Static
Albanese, 2013
MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 201708/07/2017
CLASSIFICATION AXIS II-‐ETIOLOGY
A. Nervous system pathologyoEvidence of degenerationoEvidence structural (often static) lesionsoNo degeneration or structural lesion
B. Inherited or acquiredInheritedoAutosomal dominantoAutosomal recessiveo X-‐linked recessiveoMitochondrial
Acquiredo Perinatal brain injuryo Infectiono Drugo Toxico Vascularo Neoplastico Brain injuryo Psychogenic
C. Idiopathico Sporadico Familial
MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 201708/07/2017
DEEP BRAIN STIMULATION IN DYSTONIAoFollowing ablative surgeries (thalamotomy, pallidotomy)
oFollowing DBS in adults for PD (suppression of dyskinesia in the GPi)and ET
o1996: 1st child with isolated generalized dystonia receiving GPi DBS inMontpellier (Coubes, 1999 Neurochirurgie)
oSimultaneously, DBS proposed for other forms of dystonia in adultsKumar, Neurology, 1999, and Krauss, Lancet, 1999
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
THE CASE OF SOPHIE-‐first patient with DBS treated childhood onset generalized dystonia
Coubes, Neurochirurgie, 1999
« Although her future remains uncertain, we believe thatchronic bilateral pallidal stimulation may prove to be thetreatment of choice for early onset generalized dystonia,especially in children.Electrical stimulation is a conservative, adaptable,reversible neurosurgical procedure, and seemsparticularly worthwhile in children because of theirongoing brain development »
MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 201708/07/2017
21 years of follow-‐up with DBS
oAt anesthetic release, involuntary movements are much less severe, no pain,breathing is autonomous
oRecovery is very progressive
oOral feeding is again possible and PEG tube is removed one month after DBSonset.
oIPG early depleted, with recurrence of symptoms, controlled within one weekafter IPG replacement
oNo immediate effect on dystonic symptoms
oIt could be possible to propose this therapy also to severe forms of secondarydystonias
MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 201708/07/2017
Coubes, Neurochirurgie, 1999
08/07/2017MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE,
FRANCE ·∙ JULY 6-‐8, 2017
SUPERIOR INITIAL RESULTS IN PEDIATRIC ISOLATED DYSTONIA VERSUS ADULTS (AGE AT DBS ADMINISTRATION)
Coubes et al, JNS 2004
TARGETS
Starr, JNS, 2006
ALTERNATIVE TARGETS FOR DBS IN DYSTONIAPOSTERO-‐LATERAL AND VENTRAL PART OF THE GPI
STNWhen GPi structurally impairedPKAN, Ge, 2011To avoid side effects related to GPi DBS; Kleiner Fisman, 2007; Ostrem, 2011; Blahak, 2011; Ostrem 2017
Thalamic motor nuclei+VimDystonic tremor Carvalho, 2013Myoclonus dystonia Grüber, 2010
DYT6 dystonia Mure H, 2014+Ventral lateral anterior (VLa) nucleus
MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 201708/07/2017
INDICATIONSoMedical therapy refractoriness
oSymptoms severe enough to producedisability
oPain Moro et al., 2013
oBetter response in the hyperkinetic forms (but not always)
oBetter response in children (in isolated cases) Vidailhet, 2013
But most frequently dystonia in children is acquired/degenerative (and complexe…)
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
INDICATIONS
oNo validated criteria for DBS in children (severity, refractoriness to conventional therapy…)
oNo cut-‐off related to symptom severity
oNo predictor such as levodopa challenge in PD
oChalenging task especially in acquired /progressive dystonias
MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 201708/07/2017
INDICATIONS
ISOLATED (PRIMARY) DYSTONIA
opositive outcome in pediatric and adult populations
oDYT1 dystonia (TOR1A gene)
o DYT6 (THAP1 gene)
oOther forms of idiopathic dystonia
COMBINED DYSTONIA
o DYT11 (epsilon sarcoglycan gene) myoclonus dystonia
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
THAP1 GENE RELATED DYT6 DYSTONIA
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
oGeneralized dystonia and dyskinesia
oSevere axial symptoms (neck, trunk)
oDysarthria, oromandibular dystonia
oSpread of the symptoms Cranial –caudal
Decrease of dystonia a at early FU (32%; p = 0.046) and 42/ at late follow-up.
The rate of responders considerably lower in DYT6 vs DYT1(57% vs >90%; p = 0.017)
Brüggemann, 2015
COMBINED DYSTONIA DYT11 MYOCLONUS DYSTONIAoEpsilon sarcoglycane gene related
Myoclonus-‐dystonia
Myoclonusand dystonia improvement>80%
Pediatric cases
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
Cif L, 2004, Kühn A, 2014
ACQUIRED DYSTONIA
oDyskinetic/dystonic cerebral palsy ; Hemidystonia (post traumatic, vascular )Two different phenotypes of HIE related CPFirst-‐delayed onset dystonic/dyskinetic CP-‐very good outcomeSecond case-‐dyskinetic CP; axial decreased tone; mild response to DBS
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
PROGRESSIVE FORMS (EVIDENCE FOR DEGENERATION)
oPantothenate kinase associatedneurodegeneration, PANK2 gene mutations Castelnau, 2005; Krause M, 2006
o Atypical PLA2G6-‐neurodegeneration (PLAN)
MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
08/07/2017
Cif, 2014
EMERGENCIESo GNAO1 gene related dystonia/choreaWaak, M, 2017
MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
08/07/2017
SPECIFICITIES OF PROGRAMMING IN CHILDREN WITH DYSTONIA
oClinical improvement not immediate (vs tremor)
oMonotonic time course of improvement (days, weeks, months)
oOften monopolar stimulation (in our experiencemost frequentlydouble monopolar)
oHigh frequency stimulation (almost exclusively)
oBut settings no different from adults
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
oMore often generalized anesthaesia suitable/requested
oHigher risk for clinical worseningdespite ongoing efficient DBS
oWithout efficient treatment, higher risk of life threateningconditions
oPossible influence on growth and development
oRechargeable systems suitable
MANAGEMENT OF PEDIATRIC VS. ADULT DYSTONIA POPULATIONS
MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
08/07/2017
PROGNOSISoRelated to the underlying disorder
oUsual good maintain of the clinical benefit on long term in isolated and combined dystonias
oHowever some variability (initial and long term clinical benefit)
oBradykinesia/gait impairment induced versus control of dystonia/dysphagia
oRebound at DBS interruption in some patients
oDisease progression
oTolerance in some patients Miyagi, 2013-‐Two DYT1 cases
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
RISK RELATED TO DBS: OPERATE LATE
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
o Status Dystonicus in a case of fast progression of dystonic symptoms (delayed DBS indication)
o Spontaneous femoral fracture because of dystonic spasms
MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
RISK RELATED TO DBS: DISCONTINUE TREATMENT BECAUSE OF NON AVAIALBILITY
o Severeworsening of dystonia because of IPG depletion in a patient coming from abroad(no possibility of IPG to be replaced in the Country and no financial support for doing it)
o Disease can become an emergency
RISK RELATED TO DBS: NOT CONTROLLING ALL THE TARGETED SYMPTOMS: DYSPHONIA
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
THAP1 gene related (DYT6) dystonia: excellent control of cervicaland trunk dystoniabut no improvement of laryngeal dystonia
COMPLICATIONSosurgical site infections 10.3% for new implants and revisionsomalfunction in 7.7% N= 129 patients; mean FU =3.3yoshort extension 3.8% oelectrode migration in 2.3%oskin erosions (2.3%)obleeding (1 patient)o unexpected switching off in 18.7% of Soletra/Kinetra and3.4% of Activa RC, otransient seroma at IPG site in postoperative period (8%)
Kaminska, 2017
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
WHEN TO OPERATE?
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
o Childhood onset TOR1A gene related DYT1 dystoniao Surgery in adulthood; excellent control of dystonia but severe scoliosis requesting arthrodesis
RELATIONSHIP BETWEEN ETIOLOGY, SYMPTOM DURATION AND PROGRESSION OF MUSCULOSKELETAL DEFORMITY
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
RUNNING FAST INTO STATUS DYSTONICUSoDystonic storm (independentlyof the etiology)
oTOR1A gene related DYT1 dystonia
oDBS scheduled; Status Dystonicus two day previous to planned DBS
MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 201708/07/2017
o Monitor evolution and ANTICIPATE when needed
FREQUENT FAILURESo Complexe forms (dystonia associated with pyramidal signs, ataxia, …)
o Mitochondrial encephalopathy (frequently but not always)
o Other Progessive disorders (glutaric aciduria type 1…)
o Static forms with severe structural alterations (thalamic, motor cortex)
o DYT12 rapid onset dystonia parkinsonismMDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE,
FRANCE ·∙ JULY 6-‐8, 201708/07/2017
FACTORS OF GOOD PROGNOSISophasic component of dystonia
o short disease duration
o absence of skeletal deformities
oDYT1 genemutation in isolated dystonia
o no associated weakness and spasticity in acquired forms
Isaias, 2008, Vasques, 2009, Cif, 2017
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
CONCLUSIONSoDBS in pediatric movement disorders refers mainly to dystonia
oObjective depends on the type of dystonia (etiology and phenotype)
oObjective must be defined and validated together with the childand his family
oComplications are related mainly to DBS system and treatmentinterruption
oDBS is a life time treatment dealing sometimes with progressivedisorders (inform patient and family)
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
CONCLUSION DBS administration in pediatrics requires a multidisciplinary team to
o select candidates
o identify reasonable target symptoms
o perform the procedure
o cope with complications related to therapy and devices
ooptimize DBS administration
o support the patients and families over the changing life
08/07/2017 MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 2017
University Hospital in MontpellierOver the last 20 years…
Neurology/PediatricNeurologyL. Cif, V Gonzalez, I de Antonio, M Azais, B Biolsi, A Roubertie, B Echenne, F Rivier
Neurosurgery
P Coubes, S Gil Robles, H Elfertit, T Roujeau, S James, E Chan Seng
ICU: A Boularan, F Gréco, G Cambonie, C Milési
Psychiatry: A Seychelle, A Ionita, D Capdevielle, F Cyprien
Neuropsychology: E Sanrey
Genetics: C Coubes, G Collod-‐Beroud, M Claustres
Rehabilitation: I Laffont, F Coroian, V Carre, C Jourdan
MDS-‐ES 1ST SUMMER SCHOOL ON NEUROMODULATION FOR MOVEMENT DISORDERS GRENOBLE, FRANCE ·∙ JULY 6-‐8, 201708/07/2017