Non-traumatic brain injuries (nTBI) can result in long-term adverse consequences and should be carefully recognized. The most common causes of nTBI include hypoxic insult, vascular insults, toxicity, tumors, infective, and metabolic encephalopathy. The impact of nTBI on the health service among adults is currently available, and it was found that the direct cost of healthcare services for nTBI was higher than that of TBI. The impacts of nTBI among the pediatric population are important to study because they are often overlooked with regard to the potential for long-lasting consequences with its need for prolonged healthcare services post-injury [14, 15]. The current study included patients with non-traumatic, non-infectious brain insult that necessitated NICU/PICU admission owing to the importance to study such group of patients in agreement with the previous study [14].
The leading cause of cerebral palsy and death among children is the hypoxic-ischemic injury occurring in about 2–9 of 1000 live births. HII is more common among preterm infants occurring in 5% of infants born below 32 weeks of gestation. Reduced cerebral blood oxygenation (hypoxemia) and cerebral blood flow (ischemia) are the frequent pathophysiologic processes resulting in HII [16].
Mild to moderate HII in the premature brain may lead to germinal matrix hemorrhage, PVL, or both, while severe HII to the premature brain usually causes injury to the thalamus, dorsal brainstem, and anterior part of the vermis with occasional extension to the basal ganglia, cerebellum, hippocampus, and corticospinal tracts. The basal ganglia injury is frequently less severe than thalamic injury [16].
Depending on the severity and the duration of the HII, variable clinical and imaging findings are seen. Mild episodes of hypoxia or ischemia for short duration (< 10 min) are common in the perinatal setting and frequently have no major neurologic consequences. However, HII with greater severity and longer duration are usually associated with clinical and imaging drawbacks. The peripheral pattern (or the parasagittal, watershed, or border zone pattern) is the most frequent pattern and caused by partial hypoxia with prolonged duration or mild to moderate hypotension. The basal ganglia-thalamic pattern is less frequent and caused by severe hypotensive or severe hypoxic insult within shorter duration. Overlap between both patterns is frequently seen. When the insult is severe and of longer duration, the resultant injury is more grave, with involvement of the whole cerebral cortex and dorsal brainstem and resulting in total brain injury pattern [16, 17].
This retrospective study included 60 selected patients according to the study inclusion and exclusion criteria. The final diagnosis revealed that hypoxic ischemia injury (HII) was the most common encountered cause found in 65% in agreement with Manohar et al. [1] and Sonia et al. [16] who mentioned that hypoxic-ischemic injury is the most common cause of neonatal encephalopathy.
Mild to moderate grades of HII (peripheral pattern) was found in 76.9% of patients with HII, while 23.1% of the patients were severe grade in agreement with Sonia et al. [16] who mentioned that the peripheral pattern is the most common pattern.
In the mild to moderate grade cases (n = 30), the MRI revealed peripheral ischemic pattern (water shed areas) in all cases, displaying high T2 and FLAIR signal in agreement with Sonia et al. [16] who mentioned that the peripheral pattern of HII is frequently seen in the cerebral cortex and subcortical white matter, with predilection to the parieto-occipital and posterior temporal regions more injured than the anterior regions with corresponding restricted diffusion in the acute phase.
In the current study, severe HII showed extension of the white matter high T2 and FLAIR signal lesions into the basal ganglia, thalami, hippocampus, and corticospinal tracts, and all cases showed restricted diffusion, in agreement with Sonia et al. [16] who mentioned that the basal ganglia-thalamic pattern is less common and usually seen in the case of severe hypoxic or severe hypotensive insult within a short duration.
Restricted diffusion was found in DWI in all cases of HII, while one case post-chocking with resultant prolonged asphyxia showed free diffusion, and this could be explained by the delay in performing MRI due to bad general condition of the patient, so MRI was done 8 days after the incident revealing free diffusion (pseudonormalization) in agreement with Manohar et al. [1] and Sonia et al. [16] who mentioned that DWI became falsely negative about 1 week after the ischemic or hypoxic event; this phenomenon is known as pseudonormalization; so, it is vital to know the time of the onset of encephalopathy.
The present study included 6 patients (10%) with a final diagnosis of metachromatic leukodystrophy; all patients were infantile in form, and 3 of them had a family history of death in brother/sister at the same early age. Laboratory investigation revealed low levels of arylsulfatase A in urine and in peripheral blood leukocytes in accordance with Cheon et al. [2], Mohannad et al. [3], and Karimzadeh [4] studies who reported that metachromatic leukodystrophy has 3 different types according to the age of the patient at the onset which are late infantile, juvenile form, and adult form, and the most frequent type is late infantile.
The clinical presentations of this group of patients in the current study were motor signs of acute peripheral neuropathy, speech, gait and coordination disturbance, intellect deterioration, quadriplegia in 2 patients, and blindness in 1 patient. Death occurred in 2 of them after 6 months of initial admission in agreement with Cheon et al. [2] who mentioned that the late infantile form of metachromatic leukodystrophy usually manifested in children between the ages of 12 and 18months and is manifested by peripheral neuropathy motor signs usually followed by coordination and speech deterioration. Gait disturbance, blindness, quadriplegia, and decerebrate posturing may be seen within 2 years. The disease may progress, and death occurs within 6 months to 4 years after the onset of disease.
In the current study, MRI of metachromatic leukodystrophy patients revealed bilateral symmetrical confluent foci of high T2 and FLAIR signal intensity in the periventricular white matter with sparing of the subcortical U-fibers with no enhancement. The periventricular white matter and centrum semiovale showed tigroid patterns of demyelination, suggesting sparing of the perivascular white matter. Extension of the abnormality into the corpus callosum and the internal capsule as well as corticospinal tracts also were noted. This was in concordance with Cheon et al. [2], Mohannad et al. [3] and Karimzadeh [4] studies who reported similar imaging findings.
The current study included 4 patients (6.7%), with a final diagnosis of BTBGD; the age of the patients ranged from 2 to 4 years, all with positive consanguinity and positive family history, manifested by febrile illness progressing to acute encephalopathy which ultimately progressed to dystonia, ataxia, and seizures in agreement with Alabdulqader et al. [5] who mentioned a similar clinical presentation.
MRI reveals high signal at T2 and FLAIR affecting both basal ganglia and thalami as well as the white matter with diffusion restriction. The brain stem and cerebellum were relatively spared. The follow-up MRI after 1–6 months showed resolved lesions after treatment. Genetic testing in those patients revealed mutation of the SLC19A gene in agreement with Karimzadeh [4], Alabdulqader et al. [5], and Sremba et al. [7] who reported similar MRI imaging findings and genetic testing results and concluded that the typical MRI finding, lack of clinical improvement, and the clinical suspicion should raise the possibility of BTBGD, so empirical treatment should started.
This study included 4 patients (6.7%) with Leigh disease; all patients had positive family history and presented with hypotonia, ataxia, ptosis, ophthalmoplegia, and dystonia in agreement with Cheon et al. [2] and Mohannad et al. [3] who reported that Leigh disease is a progressive, inherited, neurodegenerative disease of infancy/early childhood with variable disease course and prognosis. Affected infants/children frequently presented with psychomotor deterioration, hypotonia, ophthalmoplegia, dystonia, ataxia, ptosis, and difficulty in swallowing.
MRI revealed high T2WI and FLAIR signal at both basal ganglia, thalami, dorsal brainstem, and the white matter with diffusion restriction in acute phase in agreement with Cheon et al. [2] and Mohannad et al. [3] who reported that the typical MR imaging findings include bilateral symmetric involvement of the putamen and may be associated with abnormalities in the caudate nuclei, globus pallidi, brainstem, thalami, and less frequently the cerebral cortex with rare affection of the cerebral white matter.
The present study included 3 patients (5%) with MRI diagnosis of PVL; all of them were premature (33–36 weeks) and showed delayed milestones, 2 of them showed cerebral cyst with small hematoma within at ante-natal US, and all presented with delayed milestones. MRI revealed intra-axial cystic lesions with small hemorrhagic component within (high T1 and T2 signal with minimal blooming at T2*) in 2 patients and abnormal periventricular white matter signal displaying high signal at T2 and FLAIR with no restricted diffusion as well as markedly thinned corpus callosum. This was in consistent with Manohar et al. [1] who reported that PVL has two variants, the cystic one which is characterized by areas of focal necrosis at the deep white matter or non-cystic variant which shows more diffuse insult to the premyelinating oligodendrocytes. The lesions in PVL do not show or show minimal blooming at T2* susceptibility-weighted sequence, unlike hemorrhagic lesions. DWI show early diffusion restriction and normalize within 5–7 days. Corpus callosum thinning especially its posterior body and splenium is a frequently associated feature.
This study included 2 patients (3.3%) with a final diagnosis of MELAS, presented with recurrent vomiting, seizures, and recurrent cerebral strokes. Laboratory investigations revealed elevated serum lactate levels in agreement with Cheon et al. [2] and Karimzadeh et al. [4] who mentioned that MELAS syndrome patients are usually seen healthy at birth with early normal development, then show growth delay, seizures, episodic vomiting, and recurrent cerebral stroke-like injuries. Cerebrospinal fluid and serum lactate levels are frequently usually elevated.
MRI of this group in the current study showed multiple cortical and subcortical infarct-like lesions extending to the basal ganglia and both thalami and cerebral hematoma, together with a variable degree of generalized cerebellar and cerebral atrophy. DWI showed marked restricted diffusion at the previous sites, and T2* showed minimal blooming at the site of the hematoma. The follow-up MR showed resolution and newly developed similar foci in agreement with Cheon et al. [2], Mohannad et al. [3], and Karimzadeh [4] who reported similar imaging findings.
Current study included 2 patients (3.3%) with final diagnosis of non-ketotic hyperglycinemia presented shortly after delivery by acute encephalopathy with neurologic impairment in agreement with Manohar et al. [1] and Mohammad [10] who reported that NKH is an autosomal recessive neurometabolic disease causing neurologic impairment usually evident soon after delivery.
The MR imaging findings of this group in the current study included mildly dilated ventricular system with corpus callosum agenesis as well as high T2 and FLIAR signal of the deep white matter with diffusion restriction at DWI in agreement with Manohar et al. [1], Karimzadeh [4], Nicholas et al. [9], and Mohammad et al. [10] who reported similar imaging findings.
The limitation of the study was the small number of patients with possible bias due to the narrow selection criteria, but this can be explained by the fact that these types of brain abnormalities are not frequently seen; a large multicenter study is recommended with additional MRI sequences, e.g., MR spectroscopy for better characterization and possible differentiation of various causes of non-traumatic, non-infective brain encephalopathy among NICU/PICU patients.
