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The Relaonship Between Regulaon Disorders of Sensory Processing (RDSP)
and White Maer Abnormalies
Vanadia E1, Di Renzo M1, Trapolino D2, Racinaro L1 and Rea M1
1Instute of Ortofonologia (IdO), Via Tagliamento Salaria, Rome, Italy
2Child Neuropsychiatry School, University of Palermo, Piazza Nicola Leoa, 4, 90127 Palermo, Italy
Corresponding author: Elena Vanadia, Instute of Ortofonologia (IdO), Via Tagliamento Salaria 30, 00198, Rome, Italy, Tel: 0039-068542038;
Fax: 0039-3281421235; E-mail: e.vanadia@ortofonologia.it
Received: Apr 30, 2016; Accepted: May 30, 2016; Published: June 02, 2016
Abstract
Background: The Regulatory-Sensory Processing Disorder
(RSPD), dened on the diagnosc manual DC: 0-3 R as
"the child's dicules to regulate his own behaviour, his
physiological, sensory, aenon, motor or aecve
processes and dicules in organizing a state of calm, of
alert or a posive aecve state", is a
neurodevelopmental disorder of the early infancy for
which it has not yet been determined a clear eo-
pathology. Clinical pracce has led us to hypothesize an
associaon between "minor" injuries of the white maer,
in parcular periventricular hyperyntensies (PVHs) and
RSPD.
Method: We conducted a prospecve clinical and
neuroradiological study of 20 children aged between 2
and 4 years; the sample was divided into children with
RDSP (N = 10) and healthy children (N = 10).
Findings: The MRI revealed the presence of a low-grade
non-cysc diuse hyperintensity of the periventricular
white maer in 8 of the 10 children with RSPD. In none of
the healthy children these anomalies were found.
Conclusion: The ndings of our study revealed that the
RSPD may be associated with periventricular
hyperyntensies (PVHs), so demonstrang a probable
neurobiological origin of the disorder. An interesng fact
is that in the children with RSPD we analyzed, we found a
posterior-anterior gradient in the localizaon of the
altered PVWM areas, in two cases with involvement of
the deep WM of temporal and parietal areas, and this
seems to be in accordance with the esmated dysfuncon
of the associave posterior and limbic areas, with an
inevitable impact on the child's emoonal sphere too.
However, further studies will be necessary to dene the
specicity of those neuroimaging ndings that can be
used as RSPD markers.
Keywords: Regulaon disorders of sensory processing;
Periventricular hyperyntensies; Neurodevelopmental
disorder; Child neurological dysfuncons
Introducon
In developmental neuroscience, the most recent ndings
conrm the wide plascity of the nervous system in the early
years of life, both in the case of typical development and in the
presence of genec abnormalies or lesions. The plascity is
greater during the so-called "crical periods" in which the
environment has a beer chance to play a posive inuence,
but also potenally negave ("maladapve plascity") on the
development of the nervous system [1]. As regards the scope
of clinical research and healthcare organizaon, these
discoveries make it increasingly important the weight of early
diagnosis and mely treatment of developmental disabilies,
starng from psychomotor and sensory disorders ll to those
mental and relaonal.
Research in the eld of child mental health has led to an
important transformaon in the knowledge of early
psychopathological disorders.
At the same me, great aenon has been paid to the so-
called “minor” disorders of perceptual-motor development
such as the Developmental Coordinaon Disorder (DCD) and
the disorders of “new denion” such as the Decit in
Aenon, Motor control and Percepon (DAMP) and the
Regulaon Disorders of Sensory Processing (RDSP),
aributable in most, if not in all cases, to a dysfuncon in the
processing and/or integraon of sensory-percepve
informaon [2]. This aspect refers to the concepts of
"connecvity" and "system", to the extent that it does not
require a macroscopic lesion to the onset of the disorders, but
it is quite conceivable a malfuncon of circuits and bundles of
intra- and interhemispheric bers that underlie them [3].
In 2002, Hadders-Algra’s team published an interesng work
on minor neurological dysfuncons asserng the certain
existence of a correlaon between these and adverse perinatal
factors, the descripon of which, however, remained
unspecic [4].
The current hypothesis is that a minimal brain damage
origins the minimum brain dysfuncon that determines the
minor neurological dysfuncon. The quesons that remain
unresolved are: what is meant by minimal brain damage
and/or dysfuncon? How much the individual vulnerability,
presumably genec, it is crucial in the presentaon of a clinical
Case Report
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framework rather than another for the same period of onset
and topography of the lesion? Moreover, how much the
environment aects through epigenec mechanisms?
Currently the majority of neuroradiological and clinical
neuropsychiatric studies are aimed at idenfying
intensiometric and morphological features which allow to
associate specic neuroimaging characteriscs to certain
developmental disorders, with the ulmate goal of increasing
the predictability of injuries and the ancipate both diagnosis
and therapy [5-7]. At the same me great aenon is paid to
the research of the so-called "suscepbility genes" that are
typical of certain diseases [8]. In the context of
neurodevelopmental disorders lies a clinical framework whose
diagnosis is steadily increasing, that is the Regulaon Disorders
[9].
As part of neurodevelopmental disorders, there is another
disorder of early childhood, the Regulatory-Sensory Processing
Disorder (RSPD) dened on the diagnosc manual DC: 0-3R as
"the child's dicules to regulate his own behaviour, his
physiological, sensory, aenonal, motor or aecve
processes and dicules in organizing a state of calm, of alert
or a posive aecve state". For the diagnosis must be present
sensory processing and motor dicules and a specic paern
of behaviour, characteriscs that allow the denion of the
"type" hypersensive, hyposensive (with the relave
subtypes) or impulsive/disorganized [10].
At the base of the RSPD denion, there are the works of Dr.
Anne Jean Ayres, an occupaonal therapist with a PhD in
developmental psychology, who had always worked at the
Brain Research Instute at the University of California in Los
Angeles. In the course of her research at this instuon, she
coined the term "sensory integraon dysfuncon" to describe
what she considered the basis of learning disabilies of which
she was dealing. These works precisely inuenced the sort of
the publishing of the diagnosc manual DC: 0-3 and then of its
review DC: 03R in which the regulaon disorders clearly refer
to the abnormal processing and sensory integraon. Another
sphere of inuence concerns the presence and nature of
sensory percepon disorders in ausm spectrum as well as on
the development of dierent methods of treatment of
children "with special needs" [11].
Clinical pracce has led us to hypothesize an associaon
between "minor" injuries of the white maer (WM) and
neurodevelopmental disorders with early onset, which will be
the object of the research detailed below.
The main goal of our work was to demonstrate the
associaon between low grade non-cysc diuse lesions of the
periventricular white maer (PVWM) presumably aributable
to a prenatal onset and specic neuropsychiatric paerns with
onset in early childhood.
The hypothesis is that these abnormalies of the PVWM can
determine an alteraon in brain connecvity systems with a
pathogenic role in certain neurodevelopmental disorders with
onset in the rst years of life, parcularly in RDSP. In favour of
this hypothesis, there are many scienc works that, through
the use of neuroimaging techniques, such as the high-
resoluon MRI and tractography, show the existence of a
dense network of intracerebral bers and alteraons of traits
or bundles of bers corresponding to convenonal MRI
pictures as diuse hyperintensity of the PVWM in FLAIR
sequences (Fluid Aenuated Inversion Recovery). FLAIR is a
pulse sequence used in MRI that allow to visualize the brain in
T2 weighted images and to suppress cerebrospinal uid eects
on the images, so it is used to bring out the periventricular
hyperintense lesions.
It also seems interesng to speculate that early insults,
presumably hypoxic / ischemic, borne by the subplate can
determine not so much macroscopical alteraons but rather
funconal, aecng mulple neural circuits that in the
subplate neurons nd an important relay point between
thalamic, brainstem and subcorcal aerent bers and mainly
directed to the cortex eerent bers.
Methods
Parcipants
We conducted a prospecve clinical and neuroradiological
study of 20 children (15 males and 5 females) aged between 2
and 4 years (mean = 25.5; SD = 6.5). The sample was divided
into children with RDSP (N = 10) and healthy children (N = 10).
All children were born between the 37th and 40th gestaonal
week, with a birth weight appropriate for gestaonal age.
None of the children had a documented perinatal distress,
with an Apgar index ranging from 8 to 10 at the rst and the
h minute.
Procedures
The diagnosis of RDSP was formulated according to the DC:
0-3R, by excluding specic visual or hearing pathologies in
accordance with the inclusion criteria; the clinical evaluaon
was integrated with neurophysiological tests: the visual and
acousc Evoked Potenals (EP) of the sperimental group of
children resulted aected in most cases by a modest increase
of latencies, while in only 1 child epilepform EEG
abnormalies were present. In healthy children no
neurophysiological anomaly was found.
All the MRI analyses were performed using the RM Philips
Full 1.5 T equipment; the images were acquired in SE technical
(spin-echo) and FAST-SE with mulplanar axial, sagial and
coronal weighngs in T1 and T2, with and without infusion of
paramagnec contrast.
Results
As shown in Table 1, in 8 of the 10 children with RDSP the
MRI revealed the presence of a low grade non-cysc diuse
hyperintensity of the periventricular white maer typically
noceable in FLAIR sequences, not associated with
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morphological and structural abnormalies of the lateral
ventricles (LV); this value was signicantly higher than that
found in the group of healthy children (p<0.001). In 5 of the 8
children the PVHs showed a posterior-anterior grading, with
involvement of the deep temporo-parietal area in 2 of them; in
6 of the 8 children with posive MRI, the PVHs was associated
with hypoplasia of the corpus callosum. In none of the healthy
children these anomalies were found. In Table 1 the
informaon of both groups are shown.
Table 1 MRI normal and pathologic ndings of the sample, with the specic typology of pathologic ndings.
RDSP children Healthy children
MRI Normal Findings N = 2 N = 10
MRI Pathologic Findings N = 8 N = 0
Typology of MRI Pathologic Findings
Patient 1
PVH (> post.); CCH
Patient 2 PVH (> ant.); CCH
Patient 3 PVH (> temporo-parietal)
Patient 4 PVH (ant.)
Patient 5 PVH; CCH
Patient 6 PVH (> temporo-parietal); CCH
Patient 7 PVH (> post.); CCH
Patient 8 PVH (> post.); CCH
RDSP: Regulation Disorders of the Sensory Processing; PVH: Periventricular Hyperintensity; CCH: Corpus Callosum Hypoplasia.
Figures 1 to 4, show some of the ndings highlighted in 3
children of the RDSP group and in 1 of the control group
children (Figure 4).
Figure 1 Paent 1: Hyperintense aspect of the PVWM and in parcular of the back secons. Hypoplasc CC.
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Figure 2 Paent 2: Mild hyperintensity of the PVWM adjacent to the frontal horns of LV. Modestly hypoplasc CC.
Figure 3 Paent 3: Hyperintensity of the PVWM and parcularly deep temporo-parietal. Mild hypoplasia of the posterior
poron of the CC.
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Figure 4 Paent 9: Normal MRI aspect.
Discussion
The RDSP is a neurodevelopmental disorder with onset in
early childhood. In literature, there is only one study [12] in
which the associaon between the RDSP and neuroimaging is
invesgated. Owen and colleagues explored the role of white
maer microstructural abnormalies in Sensory Processing
Disorders (SPD) using Diusion Tensor Imaging (DTI), nding a
signicant decrease in Fraconal Anisotropy (FA) and increase
in Mean Diusivity (MD) and Radial Diusivity (RD) in the SPD
cohort compared to controls, primarily involving posterior
white maer including the posterior corpus callosum,
posterior corona radiata and posterior thalamic radiaons.
These ndings were correlated with stascal signicance with
behavioural measures, parcularly with auditory, mulsensory
and inaenon scores.
These data are in line with what we found through MRI
pictures and the hypotheses about anatomical and funconal
correlaons that will be stated below. Compared with Owen’s
work, whose sample consists of children aged 8 to 11 years,
our study focuses on pre-school children, according to the
concepts of early diagnosis and plascity. To have found a
stascal signicance between behavioral paern aributable
to RSPD and neuroimaging data is, in our view, an important
starng point for further studies on the possible
neurobiological or epigenec vulnerabilies of some children
respect to RSPDs but, in terms of development, especially on
the posive eects of a therapy centered on the specic needs
of each child.
Therefore only few data concerning the neuroanatomical
and neurofunconal basis of the disorder are currently
available.
Recent studies related to other neurodevelopmental
pathologies, such as Ausm Spectrum Disorders (ASD) and
intellectual disabilies of genec origin, have shown the
presence of alteraons in the neural connecvity systems
[13,14], as was the case in the epileptologic eld with the new
denion of “system epilepsy” (SystE) [15].
The ndings of our study revealed that the RDSP may be
associated with periventricular hyperyntensies (PVHs), and in
our sample this happens in the 80% of cases. According to the
results of the research in eld of neuroscience and
neuropathology about the relaon between psychiatric
diseases and PVHs, it is hypothesized that PVHs could be due
to one of the three main causes: ependymal loss, diering
degrees of myelinaon in adjacent bre tracts and cerebral
ischaemia with associated demyelinaon [16].
A more accurate analysis of the topography of the WM next
to LV paves the way for anatomical and funconal correlaon
studies in our opinion very interesng:
• The lateral poron of the frontal horn of LV is covered by
inferior fronto-occipital fasciculus (IFOF) that ‘can be
considered as a “mul-funcon” bundle, with each
anatomical subcomponent subserving dierent brain
processing The supercial layer and the posterior
component of the deep layer, which connects the occipital
extra-striate, temporo-basal and inferior frontal corces,
might subserve semanc processing. The middle
component of the deep layer could play a role in
mulmodal sensory–motor integraon. Finally, the anterior
component of the deep layer might be involved in
emoonal and behavioural aspects’ [17];
• The upper poron of the frontal horn of LV is covered by
the corpus callosum (CC), that is the major neural pathway
that connects homologous corcal areas of the two
cerebral hemispheres [18];
• The body of the LV is laterally covered by the bers of the
internal capsule formed by bundles of bers called
“projecon bers” because they start from or arrive to the
cortex, leading informaons from thalamus and basal
ganglia, with the funcon to control the voluntary motor
skills and receive the sensivity of the body, and from the
arcuate fasciculus, which connects the areas of Broca and
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Wernike and transmits auditory-verbal messages aer they
have reached the associave parietal-temporal-occipital
area; frontal-subcorcal cognive and limbic feedback
loops modulate higher cognive funconing [19];
• The lower poron of the LV is in relaon to the body of
fornix, which is an interhemispheric commissural formaon
in the shape of a "C" that puts the hippocampus in
communion with the mammillary bodies and then with the
thalamic nuclei and the cingulate gyrus (posterior bers)
and the amygdala (anterior bers); it is involved in
cognive funcons such as memory and complex visual
percepon;
• The temporal horn of LV is covered by opcal radiaon in
the depths of the middle temporal gyrus. The auditory
radiaons cross the opcal radiaons to the level of the
roof of the lower horn.
It therefore seems clear the importance of the bundles of
periventricular, associave and commissural bers in sensory-
perceptual processing and integraon, that is the basis for
mulple funcons including learning, visual-spaal, motor
planning, social behaviour and language.
The second interesng fact is that in children with RDSP we
analysed, we found a posterior-anterior gradient in the
localizaon of the altered PVWM areas, in two cases with
involvement of the deep WM of temporal and parietal areas,
and this seems to be in accordance with the esmated
dysfuncon of the associave posterior and limbic areas, with
an inevitable impact on the child's emoonal sphere too [20].
Moreover, the fact that the widespread periventricular
hyperintensity was not associated with morphological and
structural abnormalies of the LV gives evidence of a prenatal
origin of the damage, in accordance with the hypothesis that
intrauterine repeated insults in early gestaonal ages can
determine a damage to the WM (being aected the precursors
of oligodendrocytes and potenally the IVZ) of subplate and
neural circuits that depend on it [21].
In parcular, the intensiometric characteriscs (non-cysc
widespread hyperintensity of the PVWM in FLAIR images) lay
for glioc lesions with loss of oligodendrocytes and axonal
damage.
It should also be remembered that the neurons of the
subplate show both glutamatergic and GABAergic acvity and
are involved in the early formaon of funconal circuits not
only at a local level of the subplate itself, but also at a distance
with cortex and thalamus.
Although the subplate is a transional structure, which will
gradually disappear aer the birth, its role is crucial as it forms
a hub between aerent projecons from the brainstem, the
thalamus and subcorcal nuclei and eerent projecons
mainly addressed to the thalamus, the cortex and the spinal
cord; however, most of the thalamic axons not establish
synapses at the level of subplate, remaining "on hold" to enter
the corcal plate around the 24th GW [22].
A very interesng fact is that some thalamocorcal bers
move to the level of corcal plaque in the visual,
somatosensory, auditory and associave areas constung a
connecvity "sensory-driven" framework, while others remain
engaged in the formaon of endogenous circuits at the level of
the subplate. The laer undergoes to a gradual disappearance
around the 36th GW; however, it is present as a band below
the corcal VI layer and represents an important indicator of
the growth of corcocorcal and callosal circuits [23].
It seems plausible to assume that insults to the subplate can
thus determine an alteraon in the formaon of mulple
neural circuits that remain over its disappearance.
Finally also the nding of hypoplasia of the corpus callosum,
and in parcular of the posterior third, is in accordance with
the clinical presentaon of our paents, as in the Witelson
division [24], it would contain the connecng bers between
the upper temporal, parietal and occipital regions closely
related with auditory-verbal and visual-perceptual funcons.
Our hypothesis, which deserves funconal neuroimaging
and ber tracking invesgaons, then is that intensiometric
alteraons of the WM, and in parcular the non-cysc
periventricular leukomalacia should be underpinned by
abnormalies borne by the intra and interhemispheric
connecon bers so determining the formaon of dis-
funconal circuits which above all alter the percepon and
sensory integraon processes. This leads to the inevitable
consequences on motor planning and control, but also and
especially on the behaviour on the relaonship and emoon.
In fact, complex cognive-emoonal behaviours have their
basis in dynamic coalions of networks of brain areas, none of
which should be conceptualized as specically aecve or
cognive. ‘Central to cognive-emoonal interacons are
brain areas with a high degree of connecvity, called hubs,
which are crical for regulang the ow and integraon of
informaon between regions [25].
The future perspecve is to integrate the instrumental
studies with single-voxel spectroscopy evaluaon and with the
applicaon of the diusion ber tracking tensor in order to
idenfy quantave and quality changes of bundles of bers
and of the specic areas aected by the damage in relaon to
the clinical presentaon and as markers that support the
diagnosis [26].
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