Deep Grey Matter Haematoma

Summary

Haemorrhage in the neonatal brain results from blood leakage through vessels, and can be caused by ischaemic stroke, venous thrombosis, haemorrhagic diathesis, as well as vascular anomalies. Haemorrhage in deep grey matter is predominantly driven by venous pathology. This includes medullary vein compression caused by germinal matrix haemorrhage in preterm infants, and venous thrombosis across all gestational ages. Rarely it can also be caused by arterial perforator stroke. The venous congestion - mostly of the great vein of Galen, basal vein of Rosenthal and/or the internal cerebral vein and its branches - or the retrograde propagation of the thrombus from the superior sagittal sinus, leads to deep venous infarction associated with a haemorrhagic necrotic lesion of the thalamus, and, when there is extensive injury, also in the grey nuclei (caudate nucleus, globus pallidus) or in periventricular white matter. This phenomenon is nearly always associated with intraventricular haemorrage. Another mechanism can be primary venous thrombosis due to a prothrombotic risk factor, mainly factor V Leiden mutation or deficiencies in Protein C, Protein S, or Anti-Thrombin III, the PT G20210A variant, Lupus Anticoagulant and Plasminogen activator inhibitor-1 mutations. Finally, prolonged congestion from difficult delivery or asphyxia, hyperviscosity from polycythaemia or cyanotic heart disease, and infections like leptomeningitis and ventriculitis, significantly predispose to deep venous thrombosis. Clinical presentation, management. Unexpected seizures and irritability are the typical presenting signs, following a symptom-free period after birth. Eye signs can be present but are not pathognomonic. There is no established immediate surgical or medical treatment. Nearly half of the patients will develop posthaemorrhagic hydrocephalus. Most will experience long-term sequelae, including cerebral palsy, epilepsy, cognitive delay or persistent oculomotor deficit. Thrombosis of internal cerebral versus basal vein. Unilateral thalamic haemorrhage is a distinct entity that typically presents after the third day of life or into the late neonatal period. Imaging links this condition directly to thrombosis of the internal cerebral vein, that triggers this sequence of events: initial congestion, choroid plexus or subependymal bleeding, intraventricular haemorrhage, subsequent brain edema leading with haemorrhagic infarction and necrosis. This damage can extend to the head of the caudate nucleus, the corpus callosum, and the periventricular white matter. If thrombosis involves the basal vein of Rosenthal, globus pallidus and inferolateral thalamus are included in a lesion of temporal white matter. Imaging findings. Cranial ultrasound characteristically reveals unilateral or asymmetric hyperechoic lesions within the thalamus, often accompanied by intraventricular haemorrhage and variable involvement of the caudate nucleus, periventricular white matter or globus pallidus. In some, thrombosed veins present as short linear echoes. Given the potential for concurrent sinus involvement, screening for superior sagittal sinus thrombosis is strongly indicated. MRI allows visualization of cerebral venous thrombosis with associated white matter changes and restricted diffusion. These lesions characteristically undergo cavitation by the second week. Thalamus lesions and epilepsy. Neonates with thalamic haemorrhage are at high risk of developing electrical status epilepticus in slow wave sleep (ESES), sleep induced epileptic activity or focal epilepsy. Children affected by ESES(-spectrum) exhibit reduced thalamic volumes at three months of age; conversely, a lower residual thalamic volume at three months correlates with lower IQ/DQ.

Mechanisms and clinical presentation

Haemorrhage follows leakage of blood from a vessel. Intact vessels may cause haemorrhage following infarction (arterial ischaemic stroke or venous thrombosis) or due to haemorrhagic diathesis (often bleeding from capillaries and small veins). Anomalous vessels (in vascular anomalies or a tumour) are prone to disruption. These patterns occur all over the cerebrum and cerebellum. In thalamus and striatum it is possible, but very rare, that arterial perforator stroke leeds to haemorrhage. But most often haemorrhage in deep grey matter is related to a venous problem:
- GMH with venous compression in preterm infants
- deep venous thrombosis at any stage of maturation. Manifest congestion, mostly with thrombosis of the great vein of Galen, basal vein of Rosenthal and/or the internal cerebral vein and its branches, will put fragile tributaries under pressure that can be found even in the term baby in the vicinity of residual germinal matrix or in choroid plexus. This will lead to deep venous infarction with a haemorrhagic necrotic zone in the thalamus but also in the adjoining gray nuclei (caudate nucleus or globus pallidus) when there is extensive injury. The phenomenon is nearly always associated with IVH, mostly low grade. The infarct related to internal cerebral vein thrombosis may stretch as far as the corpus callosum and periventricular white matter, without affecting subcortical areas. When a single branch of the internal cerebral vein is thrombosed, the most striking phenomenon may be unilateral haemorrhagic infarction in thalamus or caudate nucleus. Besides propagation from thrombosis in the superior sagittal sinus, along the straight sinus to the deep venous system, presenting with a free interval of days before presentation with thalamic haemorrhage, another mechanism is possible: primary thrombosis due to high prothrombotic risk. Prothrombotic risk (Govaert et al. 2009): factors are anti-thrombin III deficiency, Protein C deficiency, Factor V Leiden mutation, protein S deficiency, hyperlipoproteinemia and defects in fibrinogen and plasminogen. The factor V Leiden mutation (G 1691 A) is in adults as well as in children the most common risk factor of venous thrombosis. The lupus anticoagulant contributes to arterial as well as venous thrombosis. Plasminogen activator inhibitor-1 mutation was described in a neonate with thrombosis of the deep cerebral veins. The PT G20210A variant is a recently recognized risk factor. Vascular malformations may cause deep haemorrhage looking like deep venous thrombosis. Parenchymal lesions with IVH are the consequence of venous infarction in medullary veins compressed at the foramen of Monro by an expanding matrix haemorrhage or by a major clot in the lateral ventricle. Prolonged venous congestion (as in difficult delivery with or without asphyxia), leptomeningitis and ventriculitis, and hyperviscosity (cyanotic heart disease, polycythaemia) may predispose to deep venous thrombosis/occlusion. Clinical setting: seizures and irritability are the presenting signs, often surprising because of an uneventful interval between birth and thrombosis (Burger et al. 1978, Palma et al. 1979, Mitchell and O'Tuama 1980, Trounce et al. 1985, Hurst et al. 1989, Roland et al. 1990, Govaert et al. 1992). Pure intraventricular haemorrhage at term has the same bifid presentation. Several instances of early (day 1-2) thalamoventricular haemorrhage are also on record. Special attention was paid by Trounce et al. 1985 to eye signs, attributed to damage of the frontomesencephalic optic pathway in subthalamus: vertical upward gaze palsy, deviation of the eyes towards the lesion, ipsilateral saccadic paresis and a flat visual evoked response. These do not seem to be pathognomonic (Roland et al. 1990).

Clinical features in primary thalamo-ventricular haemorrhage at term (26 cases) (Govaert 1993)

irritability	11
seizures focal	8
seizures general	10
intracranial hypertension	8
opisthotonus	6
lethargy	5
high cry	3
contralateral hemiparalysis	3
eye signs: sunsetting	5
eye signs: saccadic paresis	3
eye signs: nystagmus	1

There is no established immediate surgical or medical treatment. Posthaemorrhagic hydrocephalus is common in view of the incidence of ventricle bleeding or possibly due to associated superficial venous thrombosis. It complicates recovery in about half the survivors, in contrast to about one in four pure IVHs at term. A minority of infants, with limited thalamic involvement and without hydrocephalus or white matter softening may turn out to be 'neurologically intact' (Govaert et al. 1992). Others will suffer from epilepsy, mental retardation and (usually hemiplegic or diplegic) cerebral palsy. Persistence of abnormal eye signs was reported by Mitchell and O'Tuama 1980 in an infant with hypometric saccadic eye movements still present at the age of five months.

Shrunken left thalamus with evidence of prior haemorrhage and ipsilateral ventricular dilatation (Schwartz 1961)

Multiple haemangiomata in deep grey matter (courtesy dr Pryds, Aarhus)

Term, focal right clonic seizures day 2; haemorrhage bordered by ischaemia in left thalamus

Haemorrhagic infarction due to occlusion of both internal cerebral veins and the great cerebral vein of Galen

Imaging findings

Early reports commented on the diagnosis with ultrasound (Trounce et al. 1985) and CT. CUS in case of internal cerebral vein thrombosis will initially show asymmetric or unilateral particularly hyperechoic lesions in the thalamus or caudate nucleus, close to the plexus of the lateral ventricle (Naidich 1986). Thalamic involvement is essential. Thalamic haemorrhage is irregular and asymmetrical or unilateral, with restriction to the medio-dorsal thalamus in minor thromboses. Red softening of the head of the caudate nucleus may not be readily differentiated from subependymal haemorrhage or limited IVH. Caudate does not seem to be involved all the time, understandable because of its separate venous drainage. Extension of the venous infarct into the globus pallidus is rare. Most patients seem to have important IVH. A coronal section clearly shows a hyperechogenicity abutting the midline, immediately under the fornix and the cavity of the septum pellucidum. The hyperechoic area connects to the internal cerebral vein. Associated periventricular white matter infarction shows up as irregular and asymmetric hyperechogenicites in white matter. Veins caught in the process of congestion or thrombosis may appear as short linear echos. Given the haemorrhagic nature, the lesion already cavitates in the second week. Cavitation may occur in white matter, along lines set out by the involved medullary veins. Around these veins there may be areas of decreased water diffusion on MRI in the (sub)acute stage. It would be an ommission not to screen for superior sagital sinus thrombosis by insonating from both the anterior and posterior fontanelles. In a limited number of early observations failure of direct angiography to visualize the deep cerebral veins suggested venous occlusion (Johnsen et al. 1973, Mitchell and O'Tuama 1980, Trounce et al. 1985, Roland et al. 1990). MRI provides easy diagnosis of the presumable primary thrombosis of (tributaries of) the great cerebral vein (Hurst et al. 1989, Govaert et al. 1992). Even minor vessels, like the anastomotic vein of Labbé, can be shown to contain thrombi with this technique and associated white matter softening is equally recognizable.

Graphic display of a cohort of cases (Govaert 1993)

Deep venous thrombosis: typical imaging

Thrombosis of internal cerebral versus basal vein

Already in 1936 Ehlers and Courville reviewed the available literature on thrombosis of the deep cerebral veins in early childhood and established this sequence of events: thrombosis of the internal cerebral vein -> choroid plexus bleed and possibly intraventricular haemorrhage and -> thalamic haemorrhage. Following initial congestion, most marked in the choroid plexus, there is a phase of brain oedema and subsequent red or pale softening. The red softening is due to venous haemorrhagic infarction with bleeding throughout the affected region or most pronounced around its margins. Thrombosed veins, with possibly simultaneous involvement of separate vessels, stand out as black cords in the parenchyma or protrude from the ventricle walls. Subarachnoid haemorrhage is an additional finding in case of thrombosis of superficial venous channels as well. If the basal vein of Rosenthal is occluded, either directly or as a corolary to thrombosis of the great cerebral vein of Galen, variable softening of the globus pallidus and inferolateral thalamus complete the picture. Several reports described unilateral thalamic haemorrhage in at or near term neonates as a separate entity. It usually presents after the third day of life, not infrequently well into the late neonatal period (Burger et al. 1978, Palma et al. 1979, Mitchell and O'Tuama 1980, Trounce et al. 1985, Hurst et al. 1989, Roland et al. 1990). The existing literature links this entity to thrombosis of the internal cerebral vein(s) (Govaert et al. 1992, 1993). With modern imaging techniques the salient features are unilateral or clearly asymmetrical and irregular haemorrhagic infarction of the thalamus associated with a variable degree of ipsilateral intraventricular bleeding. Additional structures involved are (i) the head of the caudate nucleus, (ii) the periventricular white matter of frontal, parietal and mesial occipital lobe sparing only a rim of subcortical white matter of about 2 cm, and (iii) the corpus callosum. Thalamic necrosis can be extensive or focal, near the upper midline in the latter instance. The ventricular coagula sprout from a ruptured subependymal or choroid plexus bleed (Mitchell and O'Tuama 1980). Internal cerebral vein thrombosis Mild. On occasion there is deep venous thrombosis without thalamic bleeding but clear perivenous haemorrhage in frontal white matter or mixed IVH and caudate bleeding. Perhaps the process of venous occlusion was slow enough for collateral veins to develop or occlusion was only partial. Moderate. Venous infarction affects a large part of thalamus. IVH is minimal or absent. Severe. Venous infarction affects the entire thalamus. The internal capsule is displaced. Basal vein thrombosis. This rare event enters the differential diagnosis of a haemorrhage with feathered margins in the centre of the temporal lobe and extending upward into lateral and inferior striatum.

Related structures and vessels, amongst others outlining the separate venous drainage of thalamus and head of caudate, thus explaining their differential involvement (Stein and Rosenbaum 1974, Larroche 1977, Pape and Wigglesworth 1979)

The normal ICV and GCV in doppler

Superior thalamic vein primary thrombosis

Thalamus lesions and epilepsy

Neonatal thalamic injury and sleep associated epilepsy: Neonates with thalamic haemorrhage are at high risk of developing electrical status epilepticus in slow wave sleep (ESES) (35%), sleep induced epileptic activity (14%) or focal epilepsy (14%) (Kersbergen et al. 2013). 30 Neonates with thalamic injury (the majority haemorrhagic), were scanned again around three months and during childhood (van den Munckhof et al. 2020). Sleep EEGs distinguished into ESES (spike-wave index SWI >85%), ESES-spectrum (SWI 50–85%) or no ESES (SWI < 50%). In a subcohort 19/23 (83%) developed ESES(-spectrum) after a mean follow-up of 96 months. The majority with perinatal thalamic injury eventually develop epilepsy with classic ESES (SWI > 85%) or ESES spectrum (SWI 50–85%), and affected children have a lower thalamic volume at 3 months compared to those without ESES(-spectrum). Higher residual thalamic volume at three months of age correlates with higher IQ/DQ.

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