NEUROIMAGING IN CEREBRAL PALSY

ABSTRACT:

Cerebral palsy represents a group of early onset, nonprogressive, persistent (but not necessary unchanged) disturbances of movement, posture, tonus, motor functions, due to non-progressive impairments, happening on an immature or in development brain (prenatal, perinatal, postnatal in the first 3-4 years of life). [1] It is variabily associated with: cognitive disorder, epilepsy, sensitive deficit, behavioural disorders. Cerebral palsy aetiology is sometimes hard to identify, and neuroimagistic plays an important role in this. Most of the children (83%) with CP have neuro-radiologic anomalies. Imagistic investigations are contributing at the understanding of the aetiology and pathogenicity of CP, setting a prognosis, and, in the future, finding the prophylaxis.

INTRODUCTION 

Even if cerebral palsy diagnosis is mainly a clinical diagnosis, neuro-radiologic imagistic exams are indicated for all CP patients. There are used: ultrasonography, cerebral CTscan, cerebral or spinal conventional MRI. New techniques of DWI (diffusion weighted imaging), DTI (diffusion tensor imaging), MR spectroscopy, Functional MRI, have brought new data that are completing the understanding of CP pathogenesis. DTI is a non-invasive nuclear magnetic resonance technique that uses the variability of water diffusion in different directions for mapping the white substance fibre tracts, while DWI uses water diffusion to map the whole brain. RM spectroscopy uses the suppressing of water signals to show the metabolites present in the tissue as a spectrum. The mapping of marker metabolites in pathogenic processes, ex. Coline and glutamate, are offering helpful etiopatogenic proofs. Functional RM is using the paramagnetic effect of deoxihemoglobine to study the brain structure and the biochemistry of functional pathways in movement or speech. 

Specific  indications for imagistic in cerebral palsy are as follows:

-Cerebral palsy of unclear etiology

-Presence of hemiplegia

-Cerebral palsy ataxic or hypotonic form 

Purpose of imagistic:

1. Establishing etiology – together with the history and clinical examination. In 2004 the practice parameters of American Academy of Neurology are recommending neuro-imaging for children with cerebral palsy to establish if there is a brain structure anomaly that could suggest an aetiology and hence a prognosis [3].

2. Prenatal diagnosis, in some cases like malformations, hydrocephaly, ischemic brain disease.

3. Establishing the moment of immature brain injury: prenatal, perinatal, postnatal. After Barcovich, the presence of neuronal migration disorder indicates injuries in the first half of pregnancy, while the presence of glial response indicates injuries in the second half of the pregnancy [ 4].

4. Differential diagnosis: excluding neurometabolic or degenerative disorders, that may have a similar clinical picture with the CP.

5. Excluding spinal palsy: in children with spastic paraparesis and progressive sphincterian disturbances, a spinal MRI should be done to exclude spina bifida occulta [3].

6. Advancing a prognosis by following the newborn at risk, or in patients with CP , by offering indications regarding the future motor, mental, visual function development, risks for epilepsy.

7. Planning the recovery program with realistic phases.

Early imagistic: What? When?

For investigating newborns at risk, most eligible is brain MRI, done as early neo-natal as possible, associated with ultrasonography. According to US guidelines, early ultrasonography is very useful in small instable infants that cannot be transported for MRI. Ultrasonography can show structural anomalies and hemorrhagic signs or hypoxic-ischemic lesions. [3] 

Cerebral CT scan or MRI early postnatal, by showing established lesions are useful for diagnosing a prenatal lesion.

RM imaging is indicated early in congenital microcephaly cases or when we suspect a brain malformation, in front of a dysmorphia, a multiorgan malformative syndrome, or a congenital or with early debut hemiplegia. It can play a role in neuro-developmental prognosis in preterm newborns. [3]

Cerebral CT scan is more useful in diagnosing vascular lesions, haemorrhages and congenital infections (TORCH). CT helps identifying congenital malformations and periventricular leukomalacia more clearly than ultrasnography (77% cases of abnormality).[ 3]

Ultrasonography, cerebral CT and MRI are useful in detecting and following hydrocephaly.[3] 

Ultrasonography (US) is useful in newborns to diagnose ischemic/hypoxic lesions, especially in preterm newborns, because the dominant lesions for them are peri/intraventricular haemorrhage and/or white matter lesions – periventricular leukomalacia, have a brain more full of water, the lesions are more destructive and have a bigger fontanel. US explores very good ventricular and periventricular regions, is easy to perform, has low costs and can be repeated frequently, so it allows the follow up of the evolution. It can show cystic periventricular leukomalacia, peri/intra-ventricular haemorrhage, hemorrhagic vein infarction, development of active or ex vacuo (secondary to cerebral peri-ventricular atrophy) hydrocephaly. Although, the disappearance of some peri ventricular hyperechogne lesions does not allow a motor prognosis because cellular lesions are not visible at echography, especially pathologic gliosis (noncystic periventricular leukomalacia is less visible at echography). American Academy of Neurology and Child Neurology Society in 2002 were recommending (Ment şi colab, 2002), routine cranial ultrasonography screening for all newborns of 30 weeks, between 7-10 days from the birth, and then repeated in between 36-40 weeks gestational age.

At term newborn the lesions are cortical/subcortical more frequent, and so more difficult to see through fontanel window, the brain tissue is more dense, the necrosis is less destructive than at premature, US showing especially the constriction of the ventricles following the cerebral oedema and periventricular sub cortical leukomalacia. Selective neuronal necrosis is not visible in the acute phase and poorly visible in the sequelar phase, as the arterial infarction.

-Imagistic signs are fore sure before birth: atrophy, porencephalic cysts and ventriculomegalia, already present at birth.

-Perinatal signs: normally echographic at birth, then increased echogenity intra and periventricular in the first week of life, or peryventricular hyperecognity in the first week and the development of cysts in 2-6 days.

-For neonatal aetiology are pleading: periventricular echogenities developed after 7 days and cysts after 3 weeks.

Echographic grading of perivntricular leukomalacia signs (after De Vries L, 2001)[10].

1 – Increasing peri-ventricular echodensity (24-48h) not evolving into cysts.

2 – Small cysts located frontal-parietal.

3 – Parietal-occipital extensive cysts, with development in 2-3 month of the ex vacuo ventricular expansion (sign of periventricular white matter atrophy).

4 – Extensive cystic lesions subcortically in the white matter.

There are 5 degrees according to other classification [14]:

1 – Periventricular hyperechognities with duration under 7 days.

2 – Periventricular hyperechognities with duration over 7 days, not evolving into cysts.

3 – Periventricular hyperechognities evolving in localised small cysts (week 2-6).

4 – Periventricular hyperechognities evolving into extensive peri-ventricular cystic lesions.

5 – Hyperechogenities that are extending in the subcortical white substance evolving into extensive ventricular and subcortical cystic lesions.

Early periventricular leukomalacia can be shown also on MRI in preterm newborns.

MRI at term newborn, after a hypoxic-ischemic event, in the first week of life can show:

-focal or diffuse cerebral oedema, with the loss of differentiation between white and gray matter (shown in T2 weighted sequences), attenuation of sulcus and gyri, small ventricles- cleft type. This non-specific aspect is shown also on CTscan as decrease of density of the cerebral parenchyma, loss of differentiation between white and gray matter, attenuation of the brain gyri , small ventricles, and on ultrasography – small ventricles and of attenuation of brain structure.

-loosing the normal signal of rear stratum of internal capsule (present after week 37).

-brain stem lesions (rear part of midbrain and pons).

-gyriform cortical hyperintense signal T1/ hypointense signal T2 in the lower part of cortex, more explicit at the bottom of the sulcus (it is representing the ischemia of cortical layers leading to laminar necrosis).

-triangular infarction area, marginally, in parasagital area as hyperintense signal T2 and hypointense signal T1. These lesions are appearing early as increased echogenicity in ultrasonography or as hypodensities at CT scan.

-after severe anoxia, from day 1 until day 7- 10 are distinguished T1 hyper-signal in basal ganglia or thalamus (with T2 normal signal). Subsequently is obtained signal hyper/heterogenous focal T1, and hyposignal T2, and in chronic phase we have gliosis area shown in T2 as hyper-signal, with normal signal or discrete hypo-signal in T1, or cystic necrosis area.

-RM spectroscopy can show abnormal spectra with the decrease of NAA (N-acetylaspartate), increase of glutamat/glutamin, presence of lactate doublets [2,7].

Also, in global pre/perinatal hypoxi-ischemic lesions, may exist lesions of basal ganglia, more frequent the thalamus and rear part of midbrain and pons.

Peri/intra-ventricular haemorrhage is more frequent in preterm newborns with low weight under 1000 g at birth (60% beside 20% in children with high weight at birth – Perlman and Volpe, 1986), being rare in term newborns [14].

Usually is peri or postnatal, exceptionally being prenatal (if the mother has coagulation disturbances) with outpouring in the first 72 hours from birth.

Diagnosis is easy to make with ultrasonography (92% cases with intra-ventricular bleeding, 82% with ependimal bleeding Szimonowicz, 1984, after Aicardi) [1] or CS (hyperdensity intra and periventricular). Ultrasonography has the advantage that allows also the follow up in time of these patients.

A 3 stages classification was made with the help of imagistic (Papile and colab 1978), (Volpe,1995): [14]

1 – Haemorrhage limited to the subependimal germinal zone (or under 10% of the ventricle with blood).

2 – Haemorrhage is progressing towards the lateral ventricle without the enlarement of those (10-50% from the ventricle surface with blood).

3 – Bilateral intra-ventricular haemorrhage with ventricular enlargement (over 50% from the ventricular surface with blood) (Figure 2).

4 – Extended necrotic haemorrhagic lesions in the white matter are associated with massive intraventricular haemorrhage – which are shown as unilateral lesions in 2/3 of cases or are prevailing on one side, on the side of the most dilated ventricle.

Figure 1. Neonatal CTscan-intraventricular hemorrhage grade 3 of prematurity

Periventricular leukomalacia can appear in haemorrhages, is usually symmetric and is most probable of ischemic origin. As later sequels we are mentioning hydrocephaly (Figure 2):

Figure 2. Later CT scan – ventricular enlargement

LATER NEUROIMAGING 

MRI is the election examination for older children because is better differentiating the cortex and white matter and their abnormalities. (evidence level A according to US guidelines). Also it allows to asses the degree of myelination according to the age. Literature data are suggesting structural abnormalities founded at MRI in 83% of children with cerebral palsy. [3]

Cerebral MRI should be performed at 2-3 years of age when is easier to see cerebral myelination and you can easier identify cerebral discrete dysgenesis. (At this age sechelar lesions are detected.)

In preterm baby, posthypoxic lesions are predominating in the white matter, the characteristic aspect being of periventricular leukomalacia. Clinical correspondence is spastic diparesis/or bilateral spastic cerebral palsy affecting more the lower limbs. The more the lesion of white matter is extended, the more severe is the motor lesion – tetraparetic aspect.

Later MRI signs in periventricular leukomalacia in preterm infants: [2]

-ventricular expansion, ventricular rough contour– lateral ventricles in butterfly wings

-reducing the depth of periventricular white matter, mostly posterior, with the deepening of the sulcuses and gyri.

-delay of myelination

-periventricular T2 hyperintense signal /hypointense signal T1, indicating gliosis

-calosal hypoplasia associated cortical lesions

Figure 3. Periventricular leukomalacia MRI aspect T2 and FLAIR sequences

Cerebral CT Scan aspect of periventricular leukomalacia(Figure 4):

-ventricular dilatation, rough ventricular borders– lateral ventricles in butterfly wings.

-reducing the depth of peri-ventricular white substance, mostly posterior, with deepening the sulcuses and gyri.

Figure 4. CT scan aspect of periventricular leukomalacia

Perinatal lesions through prolonged or intermittent hypoxia at term newborn are predominating in the gray matter in the parasagital cerebral regions – parasagital infarction – in the border territories between the distribution areas of the cerebral arteries (wathershed areas). They are shown imagistic as triangular area of encephalomalacia.

When the lesions are extended, affecting large areas of cortex and subjacent white matter, the gyri have characteristic mushroom aspect and carry the name of ulegyria. Cortical-subcortical atrophy associated to these lesions is shown on MRI late, while the multicystic encephalomalacia can be shown also on CS. (Figure 5, 6).

Figure 5. CT- severe multicystic ecephalomalacia

Figure 6. MRI– multicystic ecephalomalacia

Hypoxia associated with hyperbilirubinemia in the term newborn/total short term anoxia in the term newborn and preterm newborn are determining lesions in grey matter predominating in basal ganglia, brain stem, thalamus, perirolandic regions: [5, 11]

Imagistic MRI can indicate cystic and/or gliotic lesions in the putamen and/or thalamus, associated or not with cortical damage signs (Figure 7, 8, 9). If in the neonatal period lesions are visible in T1-wheighted sequences, later, in the second year of age, T2 sequences is showing it better. There are associated with lesions in central regions (ex. pre/postcentral gyrus), in which case there are associated pyramidal signs. Prolonged anoxia is determining extended lesions of multi-cystic encephalomalacia, shown also on CT scan.

Figure 7. MRI –hyper-signal T2 bilaterally in putamen and thalamus

Figure 8. IRM–hyposignal T1, same patient with extrapiramidal CP

Figure 9. FLAIR hyperintense signal byllateraly in thalamus, in an extrapiramidal CP patient

In preterm newborn there are shown signs of periventricular leukomalacia associated with thalamic and basal ganglia lesions.

Kernicterus is shown as hyperintense signal T2 bilateral in posterior-medial region of globus palidus; sometimes, they may not be visible.[4] 

Cerebral infarction are more frequent in term newborn but they may be possible also in preterm newborn: they are interesting big arteries, usually middle cerebral artery (left more than right), or the border areas (watershed) between the arterial distribution territories, parasagital areas. There are shown on CTscan or MRI as lesions interesting a vascular territory (Figure 10).

As late images there are seen porencephaly or multicystic encephalomalacia or even hydranencephaly.

Figure 10. CS aspect of middle cerebral artery infarction – left parietal-temopral-frontal porencephalic lesion

Figure 11. Cerebral CT scan of hydranencephalia of prenatal causes

Later images from cerebral palsy in existent studies in speciality literature were grouped as follows [8, 9, 12, 13, 15]:

1. Congenital malformation. Malformations that are more frequent determining cerebral palsy are migration disturbances: lissencephaly (Figure 13), schizencephaly (Figure 14), cortical dysplasia, polymicrogyria (Figure 15), hemimegalencephaly (Figure 12), but also holoprosencephaly and microcephaly. They are more frequent in term newborn then in preterm newborn, and are more frequent hemiplegias. They are produced prenatal in the first half of gestation.

Figure 12. Left hemimegalencephaly MRI

Figure 13. Lissencephaly CT scan

Figure 14. Bilateral schizencephaly MRI

2. Pure gray matter lesions are rare and were reported in about 6% of the patients – lesions in cortex, basal ganglia, thalamus, diencephalon and they are produced at the end of gestation (end of third trimester), peri or neonatal, being seen predominant in term newborn. Parasagital lesions, multicystic encephalomalacia, porencephaly, midle cerebral artery infarction are combined lesions of white and grey matter. Encephaloclastic porencephaly is a well defined cavity in the white and/or grey matter, surrounded by minimal glial reaction. Encephalomalacia is referring at uni/multifocal cerebral necrosis and it is differentiating by porencephaly by the presence of astrogliosis.

3. White matter lesions are produced at the beginning of third trimester of pregnancy or in preterm newborn, such as periventricular leukomalacia, lesions after intraventricular haemorrhage (ventricular enlarging) or hemorrhagic infarction (communicating porencephaly).

Figure 15. Bilateral perisilvian polymicrogyria – MRI

Figure 16. MRI – sagital sequence T1 – porencephalic lesion in cerebellum in an ataxic CP patient

4. Ventriculomegaly, cortical atrophy or abnormalities of LCR containing spaces

5. Nonspecific aspects, for example calcification, enlarging of Virchow-Robin spaces, delaying of myelination

6. Infections. Radiologic signs suggestive for citomegalic virus infections: peri-ventricular calcification easier detectable on CT scan as focal hyperdensity, migration abnormalities, delaying of myelination (present whatever the gestational age), cerebellum hypoplasia, present especially in the 2 gestational trimester. (fig. 7)

Figure 17. Cerebral CT scan – congenital infection with CMV

Congenital toxoplasmosis before 20 weeks is severe, and cerebral CTscan shows ventricular enlargements, porencephaly areas, extensive calcifications especially in the basal ganglia. Between 20-30 weeks CT shows multiple periventricular calcifications and ventricular enlargements. After 30 weeks the clinical form is easier and CT shows small periventricular and intracerebral calcifications, rarely accompanied by ventricular enlargements. A feature that is differentiating them from CMV infection is the absence of cortical malformations.

7. Normal- more frequent in the ataxic form – about 60%, and 9-20% in spastic and diskinetic forms. A normal cerebral MRI (17% of cases) does not exclude the CP diagnosis, but should be completed the tests with investigations for to exclude metabolic, neurodegenerative or genetic disorders (according to US guidelines) [3].

CONCLUSIONS 

Neuroimaging is necessary in the cerebral palsy to identify the etiology, to help the differential diagnosis, to evaluate the severity of damage and to formulate a prognosis. With the help of new imaging techniques we will better understand the etiopathogenity of these disorders and we hope that in the future to have new data that will contribute to the prophylaxis.

A.N: The images used in this article belong to the author’s personal archive and Neuropsychiatry Clinic Hospital „Alexandru Obregia” of Bucharest

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