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F.J. Liégeois, A.T. Morgan / Neuroscience andBiobehavioral Reviews 36 (2012) 439–458 441

sound production, that is, across the domains of articulation,

resonance, vocal quality, prosody and respiration. For instance,dysarthric speech may sound imprecise or ‘slurred’ due to afailure of execution of the lips or tongue, or severely distortedas regards nasal resonance due to velopharyngeal dysfunction.

Various sub-types of dysarthria have been reported to occur in iso-lation or combination depending on the neuroanatomical lesionsite, as early as 1943 (Froeschels, see Duffy and Kent, 2001,for a historical perspective and Duffy, 2005, for an update on

the widely used Mayo classification by Darley et al., 1969). Incontrast, apraxia of speech is a disorder of planning and program-ming , where execution of individual speech sounds is reportedlymostly preserved but coarticulation and sequencing may be

impaired.

1.2.1. Neural correlates of dysarthriaAlthough “not a rare disorder . . . in paediatric neurology” (Van

Mourik et al., 1997b, p. 299), dysarthria in conjunction with neu-roimaging has mainly been reported in the adult population.Consistent with recent functional imaging studies during overtspeech (see Price, 2010, f or a recent review), unilateral damage to

the pyramidal or extrapyramidal system and associated pathways

is sufficientto resultin dysarthria in adults(see reviewin Kent et al.,2001). A recent report (Urban et al., 2006) indicated that extracere-bellarinfarcts to the left hemisphere (irrespective of location) were

notonlymore likelyto resultin dysarthria,but also resulted in moresevere dysarthria than right hemisphere infarctions, especially forarticulation and prosody, in the acute stage (within 72h). Alto-gether, the findings therefore suggesta left hemisphere dominance

for articulatory functions in the mature brain.

1.2.2. Neural correlates of apraxia of speechApraxia of speech is the main symptom noted in adults with

Broca’s aphasia, resulting from infarcts to the left hemisphere and

involving the inferior frontal region, including the posterior part of

Broca’s area (Hilliset al., 2004; Jordanand Hillis, 2006) andthe insu-lar cortex (Dronkers, 1996; Nagao et al., 1999) or adjacent whitematter( Jaffe et al., 2003; seereviews Ackermannand Riecker, 2010;

Ogar et al., 2005). It is also a feature of neurological degenerativediseases (e.g., Josephs et al., 2006), such as corticobasal degenera-tion ( Josephs and Duffy, 2008), where pathology is bilateral. Sincethere is little evidence to suggest that right hemisphere damage

alone is sufficientto resultin apraxia of speech, theliterature there-fore suggests that the planning/programming of speech may alsobe predominantly subserved by left hemisphere networks in themature brain.

Given that conditions such as infarcts and neurodegenera-tive diseases are rare in childhood, motor speech outcomes inchildren and adults with similar aetiologies have not been com-

pared. Despite recent advances in neuroimaging data acquisitionand analysis techniques that allow the detection of functional(e.g., functional MRI, PET) and subtle structural (e.g., voxel-brainmorphometry or VBM, Ashburner and Friston, 2000) brain abnor-malities, no neuroanatomical model of paediatric motor speech

disorders is available. As a result, the question of a left hemisphericdominance for motor speech functions throughout developmentremains unanswered, and the potential for post-lesional functionalreorganization remains difficult to predict in childhood.

In order to address these questions, theaim of thepresent articlewas to systematically review and describe recent evidence report-ing on a link between motor speech disorders (apraxia of speechand dysarthria) and brain abnormalities in children and adoles-

cents (16 years or younger) with developmental, progressive, orchildhood-acquired neurological conditions.

2. Methods

2.1. Search strategy

Articles were searched using the OvidSP interface, which pro-

vides access to the following biomedical and health relateddatabases: AMED; Biotechnology Abstracts; EMBASE; Health andPsychosocial Instruments; HMIC; Maternity and Infant Care; MED-LINE; PsycEXTRA; PsycINFO; PsycCRITIQUES; Social Policy and

Practice.For inclusion purposes, children and adolescents were defined

asaged 16 orunder,although adult cases were included ifpathologyonset was at or before the age of 16. The term brain abnormality

was used here in the broad sense, encompassing overt damage,dysfunction, or morphological abnormality (i.e., detectable usingquantitative MRI analysis methods) to grey or white matter struc-tures. We examined articles published after a seminal review on

acquired childhood dysarthria by Van Mourik et al. (1997b), that is,between January 1997 and January 2010.

2.2. Step 1: search criteria and abstract extraction

Thirty-six search terms were used for neuropathology (includ-ing developmental, progressive and acquired disorders, seeAppendix 1 f or complete list), three search term to encompass

the paediatric population (see Appendix 2), and six search termsdescribing motorspeech disorders (dysarthriaand CAS with all syn-onyms, see Appendix 3). Abstracts fulfilling selection criteria (i.e.,abstracts available, English language, published between January

1997 and January 2010) that included one or more terms fromAppendix 1 AND one or more terms from Appendix 2 AND oneor more terms from Appendix 3, were retrieved.

2.3. Step 2: abstract selection

The 3730 abstracts generated from Step 1 were reviewed inde-pendently by both authors to exclude those that (i) were not data

driven, (ii) did not mention motor speech disorders (see Appendix3 f or included terms),or (iii)included adult-onset conditions.Therewas disagreement on 4% (154), solved by mutual agreement. Themain reasonfor exclusionwas that terms such as “speechdisorder”

or “speech delay” were used generically to refer to impairmentsof language comprehension or production, rather than of motorspeech. Where views were not in accordance, and the content of the abstract did not provideenough information to make an agreed

upon decision,the authors erred on the sideof caution andselectedthe abstract forfurther examination in Step 3 (106abstracts, 2.8%of total). Of the 3730 titles and abstracts identified via the computer-generated search strategy, 260 potentiallyeligible full articles were

retrieved.

2.4. Step 3: article selection

The 260 retrieved articles were reviewed independently by theauthors to exclude thosewithout neuroimaging evidence or explicitmention of a motor speech disorder diagnosis in the full text.Reviews not containing original data were also identified at this

stage and were excluded. All articles containing routine clinical ormore sophisticated CT and MRI scan reports were included, evenwhere only brief mention of neurological status was made such as‘CTreports were normal’. Disagreementswere discussedin onefur-

ther round of review where consensus was reached. Seventy-twoarticles were selected for the present review.



442 F.J. Liégeois, A.T. Morgan / Neuroscience and Biobehavioral Reviews 36 (2012) 439–458

Fig. 2. Proportion of cases with childhood apraxia of speech (A)and childhooddysarthria (B)falling into each neurological condition listed in thepresent review.

3. Results

Only 12 reports of CAS were accompanied by neuroimaginginvestigations. CAS was either associated with epilepsy disor-ders (five reports), metabolic disorders (two reports), syndromicconditions (two reports), idiopathic forms arising from FOXP2 dis-

ruption (tworeports), orwas of unknown origin(one report). Whenexamining the number of cases (Fig. 2A), epilepsy and metabolicdisorders accounted for about 70% of cases (31 individuals) alto-gether.

Neuroimaging correlates of dysarthria were reported in chil-dren with known clinical syndromic entities (16 reports), tumours(mainly of the posterior fossa, ten reports), infarcts (six reports),metabolic disorders (eight reports), traumatic brain injury (seven

reports), degenerative diseases (four reports), epilepsy disorders

(three reports), and other conditions not falling into the abovementioned categories (“miscellaneous”, six reports). The highestproportion of cases with dysarthria (Fig.2B) experienced metabolic

disorders, accounting for about one quarter (74 individuals) of allcases.

4. Discussion

Within the past 13 years, seventy-two articles have reportedon motor speech disorder in the paediatric population togetherwith neuroimaging data. Dysarthria and CAS were reported fornumerous categories of neurological conditions (ten including our

“miscellaneous” category). The human motor speech systemthere-fore appears vulnerable to a wide range of neurological events

arising in the pre- and post-natal period, although motor speechdisorders were rarely the only symptoms for the cases listed in the

present review (i.e., frequent co-morbidities included motor andlanguage impairments). The main findings will be summarized anddiscussed below for each condition.

4.1. Neural bases of childhood apraxia of speech

It is perplexing that withinthe past 13 years,onlytwelvearticles

(reporting on 45 cases, see Table 1) have reported neural findingsassociated with CAS. Around 60% (27 cases)had MRI scans reportedto be radiologically normal. These negative MRI findings suggestthat brain abnormalities may be present at the sub-macroscopic

level, compromising for instance white matter integrity or grey

matter density. They could also indicate that CAS is associated with

brain functional anomalies at the metabolic or neurotransmitter

level.Such evidence for subtle abnormalities in CAS differs strikingly

from the adult cases where apraxia of speech is overwhelminglyreported as being associated with frank lesions to the left hemi-sphere, mainly due to infarcts (see Section 1). This aetiological

difference highlights the fact that neither CAS associated withneural abnormality nor the developmental idiopathic form of thedisorder may be comparable to its adult-acquired counterpart (assuggested by Maassen, 2002).

4.1.1. Genetic disorders (idiopathic form)The scarcity of studies examining the neural basis of CAS is par-

ticularly surprising with regard to the idiopathic form given that,

since the discovery of the FOXP2 gene in 2001 (the only knowngene associated with CAS), a considerable amount of studies haveinvestigated the possible genetic basis for the disorder (Fisher andScharff, 2009;MacDermot et al., 2005;Vernes et al., 2009). In addi-tion, the clinical diagnostic markers of CAS have been extensively

researched during this time period (Shriberg et al., 1997a,b,c).Neuroimaging investigations in the affected members of a

British family (“KE” family), who have a FOXP2 gene mutation(Belton et al., 2003), and other studies on the same individuals not

included in the present review (Watkins et al., 2002; see Vargha-Khadem et al., 2005, for a review) have revealed bilateral greymattermorphological abnormalities in the perisylvian and rolandiccortices, basal ganglia and cerebellum (Fig. 3; see Liégeois et al.,

2003 f or functionalabnormalitiesin overlapping regions). It is note-

worthythat these structuralabnormalities in the affected membersof the KE family were detected with a more sensitive quantitativeimaging analysis technique (voxel-based morphometry, or VBM),

while the routine clinical MRI scans appeared radiologically nor-mal. Normal structural MRI was also reported for the other casewith a genetic abnormality identified in the present review, whosedeletion encompasses FOXP2 (single case study, Lennon et al.,

2007), but no quantitative imaging analysis technique was used. Inthecase of genetic disruption, therarity ofCAS (1–2/1000 accordingto Shriberg et al., 1997a; 3–4% in Delaney and Kent, 2004) makesit difficult to identify large families or homogeneous samples with

the disorder. This is a major hurdle when quantitative MRI meth-ods must be used,as these methods require large samples to detectsubtle differences between the brains of affected and unaffected

individuals.




Fig. 3. Schematic illustration of lesions or morphological abnormalities associated with childhood apraxia of speech. Red, bilateral reduced grey matter in cases withFOXP2

gene mutation(VBM analyses, fromBelton et al.,2003). Blue, epilepsydisorders (rolandicepilepsy in Probands1 and2, Roll etal.,2006). Yellow,thin corpus callosumreported

in one case with unknown aetiology(Le Normand et al., 2000) and in onecasewith creatine transporter deficit(Battini et al., 2007). Green,cerebellaratrophyin 7 cases with

galactosemia (Hughes et al., 2009). Other neuroimaging results from the latter article are not illustrated since abnormalities were reported throughout the cerebral whitematter. See Table 1 f or details. (For interpretation of thereferences to color in this figure legend, the readeris referred to theweb version of the article.)

4.1.2. Epilepsy disordersIn children suffering from CAS associated with epilepsy,

including the rolandic form, MRIs were reported normal for

most cases (12/18 cases). In the remainder, bilateral perisylvianhypometabolism or polymicrogyria (Fig. 3) was reported. These

scarce findings suggest that bilateral disruption of the speech plan-ning/programming cortices (possibly the premotor and Broca’s

regions, see Fig. 1) may be at the root of epilepsy-related CAS.This disruption is however difficult to detect using routine clinicalinvestigations as it may involve dysfunction arising from epilep-tic activity, which is not necessarily associated with underlying

structural abnormality. Overall, again only limited neuroimagingevidence is currently available for this sub-group of children withCAS.

4.1.3. Metabolic disorders

A total of 13 individuals with CAS associated with metabolicdisorders were included in the present review, with 12 hav-ing classical galactosaemia. Neuroimaging revealed white matter

anomalies (including delayed or absent myelination) and cerebel-lar atrophy, suggesting that developmental disruption of the whitematter structures may be at the root ofCAS inthose cases. Becauseabnormalities were reported in the corpus callosum, periventric-ular region, as well as in the deep white matter, it is difficult to

establish a causal link between damage to a particular white mat-ter tract and speech symptoms. Furthermore, only a proportion(up to 50%—Nelson et al., 1991) of cases diagnosed with clas-sic galactosaemia present with a diagnosis of “verbal dyspraxia”.

Future studies directly comparing children with and without CASare therefore needed to improve our understanding of the vari-ability in speech outcome for those children. In conclusion, furtherresearch is needed to understand theneural basis of CASin children

with metabolic disorders. Despite the rarity of metabolic disorders

(about 1 per 60,000 births for classic galactosaemia), those studiesmay shed light on brain structures that arecrucial to normalspeechplanning during development.

4.1.4. Syndromes of unknown originThree single-case studiesreported CAS in Floating Harbour syn-

drome, Klinefeler syndrome, and of unknown origin, respectively.MRIs were reported normal in the first two cases, whereas incom-

plete myelination was reported for the third case. The sparseevidence in those cases makes it difficult to establisha link betweenneural disorder and CAS symptoms. As concluded in the cases of metabolic disorders, further neuroimaging data will be necessary

to understand the neural mechanisms that explain the phenotypic

speech variability within each syndromic entity reported here.

4.1.5. InfarctsThe lack of studies reporting on CAS in childhood stroke is note-

worthy given the well-documented association between Broca’s

aphasia and apraxia of speech in adults. Although childhood strokeis rare (2–3 per 100,000 persons-year, Beslow and Jordan, 2010),

the condition has long been recognized, and numerous outcomestudies are now available for language skills (e.g., Raja Beharelle

et al., 2010). Motor speech outcome has not been reported in thosestudies, making it difficult to compare childhood and adult cases,and to assess the consequences of left vs. right hemisphere infarcts.The question of hemispheric specialization for the planning and

programming of speech will be discussed further below.The study of motor speech outcome in children who have expe-

rienced a unilateral hemispheric neurological event should helpclarify whether the adult left hemispheric dominance for speech

planning is also present in childhood. If so, such studies shouldalso help elucidate whether the right hemisphere can compen-sate for these functions after left hemisphere insult. Unfortunately,such evidence is not available, and the fact that within the last

13 years no report of CAS and left hemisphere infarct or tumourhas been reported remains surprising. Our current interpretationis that the intact left and right hemispheres can alone compen-sate for speech planning/programming functions, so that even if

CAS is observed, it is only transient. This interpretation wouldbe consistent with the fact that young people who underwentleft or right hemispherectomy (that is, who have only one func-tioning hemisphere) in childhood do not present with CAS long

term (Liégeois et al., 2010). However, until a large sample of chil-dren post left and right hemisphere infarct is screened for CAS inthe acute stage, the hypothesis of a left hemispheric dominancefor speech planning in childhood can neither be confirmed nor

refuted.

4.1.6. Childhood apraxia of speech: concluding commentsIn summary, it seems that the neural basis for CAS remains

poorly understood, and rarely examined. Several reasons can beproposed. First, the brain structural abnormalities associated withCAS may be too subtle to be detected with clinical MRI sequences,

and quantitative methods are required to reveal morphologicalchanges in the grey and white matter. Another possibility is thatCAS is mainly the result of functional, metabolic or neurotransmis-sion defects, which again can only be detected by methods that

are not always available as part of routine clinical examinations.Thirdly, it should be noted that a general consensus on the diag-nostic features of CAS has been reached only recently (AmericanSpeech-Language-Hearing Association, 2007) and remains under

debate. This diagnostic issue probably makes CAS difficult to iden-

tify in paediatric settings.



Table 2

Neuroimaging findings in childhood dysarthria associated with metabolic disorders.

Article Aetiology Sample size (gender) Age/age range Description of speech

disorder

Neuroim

Pellecchia et al. (2003) Wilson’s disease N = 5 with both dysarthriaand neuroimaging (2

m)/series of 30 (15m)

? (inwholeseries, onset5–30 yrs) “Cerebellar dysarthria” in6 MRI “inrecovery

Alajoki et al. (2004) Salla disease N =15 with

neuroimaging/series of 41

(22 m)

11mthsto 63yrs (mean 24

yrs)

Expressive speech

impairment; “motor

difficulties connected to

dyspraxiaand dysarthria”

4 cannot speak

MRI

Golombet al. (2004) Pelizaeus–Merzbacher

disease

10 with

neuroimaging/series of 11

(10 m)

10 mths to 20 yrs All those who speak:

dysphoniaand dysarthria

MRI

Gootjes et al.(2004) Peroxisome biogenesis

disorder

N = 1 (f) 22 yrs at last investigation Dysarthria diagnosed at

age 5

CT

Muthane et al.(2004) Adult GM1 Gangliosidosis N = 2 (2 m)/series of 3 16 and 17 yrs (onset of

symptoms within 1st

decade)

Case1: at 16, speech

gradually worsened and

wasdifficultto

comprehend

MRI

Case2: lost his ability to

speak bythe age of 15

(anarthria)

Iturriaga et al. (2006) Niemann-Pick C disease N = 27 (?) 4 days to 43 yrs (onset of

symptoms from birth)

Dysarthriab (diagnosis

2–19yrs)

MRI

Fuijkschot et al. (2009) Sjögren–Larsson syndrome N = 13 (8 m)/series of 16 1;9–34;11 yrs Pseudobulbar (10),

hypokinetic (2), or both (1)

dysarthriaSeverity:3 severe, 2

moderate-severe, 5

moderate, 3 mild

MRI

Gupta and Nagarkar (2009) Nijmegen breakage

syndrome

N = 1 (f) 13 yrs Reduced loudness

Articulatory errors:distortion of velars and

dentals, omissions; “not

CAS”

MRI

Abbreviations as in Table 1.a Individual results are not reported in thearticle.b From Table 3, page 3 in original article.




Fig. 4. Schematic illustration of locations of lesions/abnormalities associated with childhood dysarthria for each neurological condition. See Tables 2–8 f or details. (A)

Metabolicdisorders. Red,Wilson’sdisease(Pellecchiaet al.,2003). Blue, gangliosidosis(Muthaneet al.,2004). Yellow, cerebellar atrophyin Niemann-PickC disease(Iturriaga

et al., 2006). Other reports are not illustrated as atrophy and white matter changes are reported throughout the brain. (B) Syndromic conditions: Green, bilateral perisylvian

and opercularsyndromes(overview of findings fromTable 3). Red,suprabulbar palsy (Suresh andDeepa,2004). Blue, cerebellar andvermal atrophyin bothJoubert syndrome

(Andermannet al., 1999) and opsoclonus-myoclonus syndrome (Klein et al., 2007). Yellow, congenital non-progressive cerebellar ataxia (Dudding et al., 2004). (C) Infarcts:

Yellow, middle cerebral artery territory (Agrawal et al., 2007); white, brainstem (Miyakita et al., 1999); Green, cases 4 and 5 from Gout et al. (2005); pink, single case from

Golomb et al., 2002; red, basal ganglia (two left- and three right-sided cases from Rowan et al., 2007). Data from Horton et al. (1997) are only illustrated in the thalami

(blue) as the location of multipleinfarcts within thecerebellum is notspecified. (D)Neurodegenerative and progressivediseases: red, Charcot Marie Tooth disease (Siskind

et al., 2009); blue, PKAN (pantothenate kinase-associated neurodegeneration, Mikati et al., 2009); green, juvenile Huntingdon’s disease (Papapetropoulos et al., 2005). (For

interpretation of thereferences to color in this figure legend, the readeris referred to theweb version of the article.)

Therefore, we cannot rule out that numerous other neurolog-ical conditions exist that are associated with CAS in childhood,but that the diagnostic criteria are so contentious that CAS is

impossible to sensitively diagnose by health professionals not

trained in the specific diagnostic features of the condition (i.e.,not Speechand Language Therapists/Pathologists). Finally, the puz-zling absence of a single report of CAS following childhood stroke,

supratentorial tumour, or unilateral brain injury in the last decade




strongly suggests that unilateral hemispheric lesion/damage is

not sufficient to result in CAS during development (as previouslyhypothesized by Vargha-Khadem et al.,1998; seealsoLiégeois et al.,2008; Morgan et al., 2010a). This hypothesis is corroborated byrecent findings indicating that even complete removal of a cere-

bral hemisphere in childhood does not result in apraxia of speech(Liégeois et al., 2010).

4.2. Neural bases of childhooddysarthria

Neuroimaging evidence in childhood dysarthria was better doc-umented than for CAS, with a total of 60 articles, reporting on 254cases. Given the heterogeneity of aetiologies associated withchild-

hood dysarthria, the possible neural basis for this speech disorderwill be discussed separately for each condition.

4.2.1. Metabolic disorders

Although representing only eight reports (Table 2), childrenwith dysarthria associated with metabolic conditions represent thelargest proportion of cases.As reported forCAS, neuroimagingfind-ings included white matter changes and hypomyelination across

the cerebral hemispheres (including periventricular regions) andthe cerebellum, with little regional specificity. In two conditions,

namely gangliosidosis and Wilson’s diseases, the basalganglia wereaffected bilaterally (Fig. 4A). Overall, dysarthria associated with

metabolic disorders therefore seems to disrupt brain structuresbilaterally, affecting both white matter integrity and basal gangliafunction. The mechanisms underlying such neural dysfunction of the speech systems remain to be explored.

4.2.2. Syndromic conditionsThe majority of articles (16 reports, 46 cases representing

18% of the total) included here reported on long-term childhood

dysarthria in children and adolescents with syndromic conditions(Table 3), withover two thirds (31 cases) presenting with Worster-Drought, bilateral perisylvian, and bilateral operculum syndromes.There is an ongoing debate as to whether these separate syn-

dromes represent a clinical continuum (Clark et al., 2000), but froma neuroimaging perspective they form a cohesive group in thatthey all affect the perisylvian or perirolandic cortices bilaterally(Fig. 4B). Aetiologies include anomalies of cortical development,

such as polymicrogyria or schizencephaly (see Spalice et al., 2009,for a review on migration disorders), and acquired neurologicalinsults, such as encephalopathy or infarct. Youngpeople presentingwith these syndromes most commonly suffer from severe forms

of dysarthria or anarthria (complete lack of speech). Altogether,results from this group suggest that when there is neuroimagingevidence of bilateral structural abnormality within the perisylvianand perirolandic cortices in childhood, motor speech prognosis is

poor, and spontaneous compensation is unlikely.Dysarthria was also reported in syndromes affecting the cere-

bellum, namely Joubert syndrome, congenital non-progressivecerebellar ataxia, and opsoclonus-myoclonus syndrome. In allcases, either agenesis or atrophy/hypoplasia of the cerebellar ver-mis was reported. The role of the cerebellum in speech productionwill be discussed further in a separate section (“posterior fossa

tumours”), but these few reports suggest that the cerebellarvermismay play a crucial role in normal speech execution.

4.2.3. Traumatic brain injury

As predicted, lesions associated with traumatic brain injury inthe series of cases reported here (10% of all cases with dysarthria)were highly heterogeneous (Table 4). Moreover, white and greymatter structures were affected at multiple sites. Cortical regions

affected included the frontal, parietal, and occipital cortices, while

subcortically lesions to the basal ganglia and cerebellum were T

a b l e

6

N

e u r o i m a g i n g fi n d i n g s i n c h i l d h o o d d y s a r t h r i a a s s o c i a t e d w i t h e p i l e p t i c d i s o r d e r s .

A r t i c l e

A e t i o l o g y

S a m p l e s i z e ( g e n d e r )

A g e / a g e r a n g e

D e s c r i p t i o n o f

s p e e c h

d i s o r d e r

N e u r o i m a g i n g

t e c h n i q u e

R e p o r t e d

n e u r o i m a g i n g

a b n o r m a l i t i e s

K r a m e r e t a l . ( 2 0 0 1 )

B C E C T S

N = 4 ( 3 m )

7 ; 6 – 1 5 y r s ( o n s e t o f

s y m p t o m s 4 – 1 0 ; 5 y r s )

I c t a l d y s a r t h r i a

M R I i n 4

N o r m a l i n a l l

P a r k e t a l . ( 2 0 0 5 )

B e n i g n r o l a n d i c

e p i l e p s y

N = 1 1 ( 8 m )

5 – 1 2 y r s ( s z o n s e t 4 – 1 1

y r s )

I n t e r i c a t a l h y p

o k i n e t i c

p a t t e r n o f a r t i c u l a t i o n ;

w o r s e n e d a f t e r C B Z

t r e a t m e n t

M R I


S e r r a e t a l . ( 2 0 0 8 )

C a t a p l e x y i n c h i l d

h o o d

n a r c o l e p s y

N = 3 ( ? ) / s e r i e s o f 2 3

( 1 3 m )

6 – 1 7 y r s ( s z o n s e t 6 – 1 6

y r s )

S l u r r e d s p e e c h

i n 1 3 %

d u r i n g c a t a p l e

c t i c

a t t a c k s

M R I


A

b b r e v i a t i o n s : B C E C T S , B e n i g n C h i l d h o o d E p i l e p s y w i t h C e n t r a l T e m p o r a l S p i k e s ; C B Z , c a r b a m a z e p i n e . O t h e r a b b r e v i a t i o n s a s i n T a b l e 1 .



Table 7

Neuroimaging findings in childhood dysarthria associated with infarcts.

Article Aetiology Sample size (gender) Age/age range Description of speech

disorder

Neuroimaging

technique

Hortonet al.(1997) Brainstem infarct

(basilar artery

occlusion)

N = 1 (m) 9 yrs (infarctat 5 yrs) 2 mthspost: slurred

speech then mutism

for2 mths, then severe

dysarthria

At9 yrs:

moderate-severedysfunction at all

levelsa

CT (2mthspost)

MRI (10days later)

CT (3yrs post)

Miyakita et al.(1999) Brainstem infarct N = 1 (f) 3;7 yrs Mute for 10 days, then

dysarthria

CT

MRI

Golomb et al. (2002) Infarct (possible

arteriopathy)

N =1 (m) 15 yrs Mild dysarthria

Difficulty forming

complex syllables

CT

DW MRI

Gout et al. (2005) Subcortical stroke 3 (?)/series of 9 5;4–10;6 yrs Case 4: mild at +1 mth;

resolved at +3mths

Case5: atday 1:resolved at +48mths

Case6: mutism for 12

days then slurred

speech; not mentioned

at+19 days

MRI

Agrawal et al.(2007) Ischemic infarct N =1 (m) 16 yrs Sudden mild slurring of

speech

CT

Contrast-enhanced

MRI

Rowan et al.(2007) Basal ganglia stroke (10

L, 7 R)

N =5 (1 m)/series of 17

(5m)

6;10–19;11 yrs (infarct

at 1;1–15;0 yrs)

Acute “slurred speech”

in 5 cases

MRI

Abbreviations:IC, internal capsule; MCA, middle cerebralartery; LH cases,left infarct cases;RH cases,right infarct cases; DW, diffusion-weighted; GP, globus pallidus. Othera For detailed reportof speech features seeoriginal article.




reported on patients with left hemisphere infarcts (cortical or sub-

cortical, Fig. 4C). These latter findings raise the question of whethera bias exists in mainly reporting or examining motor speech out-come in children with left hemisphere infarcts. With regard to thelong-term speech outcome, it is noteworthy that only two articles

reported motor speech outcome more than one month post infarct.One case suffered from severe dysarthria four years after multi-ple infarcts caused by basilar artery occlusion (Horton et al., 1997).In contrast, dysarthria had resolved at 3 months and 4 years post

subcortical strokes in the two other cases, respectively (Gout et al.,2005, see Table7 for details).Importantly, in thecase with longtermdysarthria, both thalami were affected.

Regarding hemispheric differences, no cases with right hemi-

sphere basal ganglia strokes were recruited in the study by Goutet al.(2005). The studyby Rowan et al.(2007), which examined lan-guage (not motor speech) outcome after left or right basal gangliastroke, anecdotally reported on “slurred” speech in the acute phase

forfive cases, two with left and three with right hemisphere stroke.Whether these motor speech deficits were also present long-termwas not examined. In conclusion, from the sparse evidence avail-able we may conclude that (i) there is no hemispheric difference

for articulation in childhood, (ii) only transient dysarthria occursafter childhood unilateral stroke, and that (iii) longterm dysarthria

only occurs after bilateral stroke to speech-related neural systems.These claims however will need further substantiation.

4.2.7. Neurodegenerative and progressive diseasesIn adults, neurodegenerative diseases such as Parkinson’s dis-

ease(PD, Pintoetal.,2004), Huntington’s disease (HD, e.g.,Hartelius

et al., 2003) and corticobasal degeneration (e.g., Josephs and Duffy,2008) are closely associated with motor speech disorders. Giventhe natural prevalence of these conditions in the ageing popu-lation, a comparison with childhood-onset equivalents must be

approached with caution. Overall, both HD and PD fall howeverinto the category of basal ganglia dysfunction, and have their owndysarthria classifications aligned with hypokinetic or hyperkineticmotor symptoms, respectively in the model originally proposed by

Darley et al. (1969). In the present review a total of only 7 caseswere reported alongside neuroimaging evidence (Table 8), consis-tent with the rarity of the disorders. Apart from four cases withno reported abnormalities, two cases had bilateral abnormalities

in the basal ganglia (Fig. 4D), namely the caudate nucleus for juve-nile HD, and the globus pallidus and surrounding white matter inpantothenate kinase-associatedneurodegeneration. In the remain-ing case, white matter changes were reported across the brain, in

periventricular and cerebellar white matter, the posterior limb of the internal capsule, and cerebral peduncles (Fig. 4D). Altogether,the limited evidence therefore suggests that bilateral disruption tothebasalganglia circuits may be at theroot of dysarthria in children

with these neurodegenerative diseases, as seen in adults. Furtherinvestigations will be needed however to draw firm conclusions on

the role of the basal ganglia control circuits and their disruption inneurodegenerative conditions that affect children.

4.2.8. Miscellaneous conditionsA significant proportion of cases (17%) with conditions not

falling into the above categories had neuroimaging data alongsidedysarthria diagnosis (Table 9). The majority of cases (38/43, onereport) had the pyramidal form of infantile cerebral palsy. In thisreport, the extent of changes was reported to correlate with the

severity of the disorder, but no information was provided as to thelocation of brain abnormalities (Otapowicz et al., 2007). In one case(Brugnolettiet al.,2009), whitematter abnormalities were detectedwithin the centrum semiovale and frontal lobes bilaterally, to a

greater extent in the left hemisphere. In the remainder of cases,

the cerebellum and brainstem were affected bilaterally. Overall

therefore, these reports indicate bilateral abnormality at different

levels of the speech neural systems.

4.2.9. Dysarthria types in relation to neuroimaging evidenceUse of correct terminology in relation to dysarthria was poor in

the articles reviewed here. Six of the 60 reviewed studies used only

the term ‘slurred’ speech (or other such terms “impaired speecharticulation,” “speech less smooth”) in place of dysarthria itself.Of the 54 studies reporting on dysarthria as such, only 12 (mainlyin the areas of TBI and posterior fossa tumour resection) reported

specific diagnoses of dysarthria sub-types using the Darley et al.(1969) classification. Specific diagnoses were highly mixed bothwithin and across the various populations of interest, as is typicallyseen in use of the scale with adults (Simmons and Mayo, 1997),

partly reflecting the heterogeneity of the underlying neural basesfor the problems. This heterogeneity also reflects a main criticismof the Darley and colleagues’ scale, in that few clear associationscan be made between speech outcome and disruption of underly-

ingneural function,in which case clinicians typicallyreport ‘mixed’dysarthria diagnoses (e.g., ataxic-spastic dysarthria, Simmons andMayo, 1997). These findings, taken together with the lack of CASresultingfrom left hemispherestroke, suggest that it may be timely

for development of a child-specific neuro-anatomical classification

system for motor speech disorders (Van Mourik et al., 1997b; seeMorgan and Liégeois, 2010, f or further discussion on this topic).

4.3. Childhood speechdisorders: a window into the developing

neural systems involved in speech

Neuroimaging correlates of CAS reviewed here are not incon-sistent with the adult model of speech planning (illustrated in

Fig. 1), with dysfunction involving the basal ganglia and the infe-rior frontal cortices. This speech planning network might thereforebe functional early in development. Similarly, neuroimaging cor-relates of childhood dysarthria are not inconsistent with current

neuroanatomical models of adult speech execution (Fig. 1). Indeed,childhood dysarthria was associated with white matter lesions

located along the corticobulbar and corticospinal tracts (coronaradiata, central semiovale, internal capsule, midbrain), and with

grey matter lesions within the perisylvian and peri-rolandic cor-tices, basal ganglia (putamen, caudate nucleus) thalamus, andcerebellum (Fig. 4). It seems therefore that the adult speech execu-tion systemsmay be in place early in development. Altogether, data

from the present review suggest that the neuroanatomical basesfor speech production in adults and children overlap, but that thepotential for functional compensation after unilateral lesion differsbetween the two age groups.

5. Concluding remarks

Thepresent reviewconfirms that the conditionsassociated with

speech disorders differ between adults and children. However cur-rent adult models of the neural basis for speech seem to applyin childhood, whereby the perisylvian and perirolandic cortices,the basal ganglia, and the cerebellum all play a major role in bothspeech execution and planning. Yet one major difference is of crit-

ical note. Where uni-hemispheric damage in the adult populationseems to be sufficient to result in chronic speech disorders, bilat-eral disruption of these systems in childhood seems necessary toresult in the most severe and long-lasting deficits (see also Vargha-

Khadem et al., 1985 f or a similar conclusion regarding languagedevelopment). This suggests that either hemisphere has the poten-tial to subserve speech functions in childhood. Further, in the caseof unilateral lesion/disruption, the evidence for a left hemispheric

dominance for speech functions, including articulation, was sparse.

Additional scientific evidence is therefore needed to improve our




understanding of the neuralbasis of speech disordersduringdevel-

opment.Such evidence would provide a major stepforward for thedevelopment of a clinicoanatomical classification of motor speechdisorders in children and adolescents.

Conflict of interest

The authors reported no conflict of interest.

Acknowledgements

We thank Cristina Mei for her assistance in retrieving andarchiving abstracts and articles. We also thank Dr. Baldeweg andDr. Vogel for their helpful comments on an earlier version of the

manuscript, and Dr. Schulze for her assistance with illustrations.Dr. Morgan is supported by NHMRC Career Development Award607315.

Appendix 1.

Search terms for neuropathology

1. Brain Injuries/ or Brain Diseases, Metabolic/ or Hypoxia, Brain/or Brain Damage, Chronic/ or Brain/ or Hypoxia-Ischemia,Brain/ or Brain Injury, Chronic/ or Brain Hemorrhage, Trau-matic/ or Brain Ischemia/ or Brain Diseases, Metabolic, Inborn/or “Pick Disease of the Brain”/ or Brain Stem Neoplasms/ or

Brain Infarction/ or Brain Stem Hemorrhage, Traumatic/2. Brain Neoplasms/ or Tumor Necrosis Factor-alpha/ or Carcinoid

Tumor/ or tumour.mp. or tumor.mp. or Wilms Tumor/3. infarct.mp. or exp Infarction/

4. Neurology/ or neuropathology.mp. or neurodevelopmen-tal.mp.

5. Developmental Disabilities/ or Nervous System Diseases/ orChildDevelopment Disorders,Pervasive/or developmental dis-

order.mp.

6. Magnetic Resonance Imaging/ or Neocortex/ or Cerebral Cor-tex/ or migration disorder.mp.

7. polymicrogyria.mp. or “Malformations of Cortical Develop-

ment”/8. Infant/ or Tomography, X-Ray Computed/ or Microcephaly/ or

lissencephaly.mp. or Abnormalities, Multiple/ or CobblestoneLissencephaly/ or Lissencephaly/ or Syndrome/

9. pachygiria.mp.10. schizencephaly.mp.11. heterotopia.mp. or Cerebral Ventricles/ or Brain Neoplasms/ or

Periventricular Nodular Heterotopia/

12. cortical dysplasia.mp.13. hemimegalencephaly.mp.14. exp Epilepsy/ or epilepsy.mp.

15. cerebral palsy.mp. or Cerebral Palsy/16. traumatic brain injury.mp.17. Encephalitis/ or Encephalitis.mp.18. Brain Diseases, Metabolic/ or Metabolic Diseases/ or

metabolic.mp. or Brain Diseases, Metabolic, Inborn/

19. galactosaemia.mp. or Galactosaemias/20. Perisylvian syndrome/ or perisylvian.mp.21. moebius.mp. or Mobius Syndrome/22. Bulbar Palsy, Progressive/ or worster-drought.mp.

23. exp Williams Syndrome/ or william.mp. or Child/24. exp Down Syndrome/ or down.mp.25. foix-chavany-marie.mp.26. Brain Diseases/ or Magnetic Resonance Imaging/ or opercular

syndrome.mp. or Speech Disorders/ or Syndrome/ or Epilepsy,Frontal Lobe/

27. sturge-weber.mp.

28. juvenile Parkinson*.mp.29. juvenile Huntington*.mp.30. encephalopathy.mp.31. myotonic dystrophy.mp.

32. muscular dystrophy.mp.33. multiple sclerosis.mp.34. Friedrich ataxia*.mp.35. spinocerebellar ataxia.mp.

36. Niemann Pick.mp.

Appendix 2.

Search terms for paediatric population

37. exp Child/ or Infant/38. exp Pediatrics/ or paediatric.mp.

39. Adolescent/ or exp Adolescent/

Appendix 3.

Search terms for motor speech disorders

40. Speech/ or Speech Therapy/ or Speech Disorders/ or Aphasia/or Dysarthria/

41. Speech Articulation Tests/ or Articulation Disorders/ or Speechintelligibility/

42. verbal dyspraxia.mp.43. Language Disorders/

44. Verbal Behavior Language Development Disorders/45. (oral dyspraxia or speech dyspraxia).mp

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