Discussion
The locked-in syndrome is a neurological disorder that is characterized by quadriplegia and anarthria with preserved cognitive functioning. Patients usually retain eye movements, thereby facilitating non-verbal communication. This clinical diagnosis may prove challenging, given that the children are often considered as being in coma or in an unresponsiveness state, or as displaying akinetic mutism. A normal electroencephalogram (EEG) should alert the physician1. This condition is mostly caused by a brainstem lesion; in 61% of cases, the etiology in children is ventral pontine stroke due to a vertebrobasilar artery thrombosis1. The syndrome’s prognosis depends on the underlying cause. Around 35% of patients experienced some motor recovery, 26% exhibited good recovery, 23% died, and 16% remained quadriplegic and anarthric1. Motor recovery is earlier and superior in locked-in syndrome non-vascular cases. Intensive rehabilitative care has been shown to improve motor outcome1.
As illustrated by our case, differential diagnosis of brainstem lesions can be challenging. We reviewed the brainstem disorders in pediatric patients in an effort to guide the clinician in this difficult yet essential differential diagnosis. Usually, brainstem lesions tend to become quickly symptomatic. A small and single lesion can produce severe and mixed deficits related to the large number of essential structures localized within this area including cranial nerves nuclei, the reticular formation, ascending, descending, and cerebellar pathways. Brain MRI is generally carried out early in the diagnostic approach. The resulting findings can help clinicians in regard to differential diagnosis.
Among the causes of brainstem pathologies in children, vascular, toxic, metabolic, infectious, inflammatory, or neoplasia processes appear to play a role, as previously reported. As degenerative diseases are rather rare in this specific area, they will not be discussed here. The clinical presentation of brainstem lesions is roughly uniform with multiple cranial nerve palsy, motor deficiencies and headaches, whereas the clinical context, brain MRI features, and laboratory testing results may be quite useful in further directing the clinicians (table 1)2.
In our case, the diagnosis was difficult, given that the lesion progression let us to suspect the presence of a tumor, within the NF2 setting.
NF2 is an autosomal dominant disorder, caused by a variant inactivating the NF2 gene encoding the protein merlin whose main function is to regulate cellular proliferation3. Its loss of function is associated with several neurological tumors including peripheral, spinal and cranial nerve schwannomas, meningiomas, as well as ependymomas, in addition to skin anomalies like NF2 skin plaques, subcutaneous and cutaneous schwannomas, along with visual symptoms, including cataracts, retinal hamartomas, or optic nerve sheath meningiomas. Bilateral vestibular schwannomas in children, adolescents, and young adults are pathognomonic of the condition. The most common entry in the disease is through unilateral or bilateral hearing impairment, which usually occurs in the second decade of life. The presence of sudden or rapidly worsening onset of neurological deficits in NF2 patients should evoke a brainstem ischemic syndrome, which is an under-recognized entity4. This syndrome occurs in teenagers without any previously known NF2 diagnosis, presenting as an acute, usually monophasic event, which involves the midbrain or pons. A gradual evolution, as seen in our case, is similarly possible4. In clinical terms, patients start to suffer from cranial nerve palsy, dysarthria, hemiparesis, or a locked-in syndrome. The brain MRA, cardiac echocardiogram, and thrombophilia screen usually prove to be non-contributive. Several cases have been described exhibiting vascular stenosis, which cannot explain the stroke in anatomical terms. So far, the etiology remains unclear. According to one of the hypotheses, the tumor suppressor protein merlin possibly plays a role in regulating physiological angiogenesis, whereas its inactivation may induce vascular dysplasia that could induce an ischemic event5. Genetically, any distinct variant inNF2 has been associated with brainstem ischemia. Another hypothesis raises the possibility of a digenic process, given that this syndrome is relatively rare in NF2 patients4. Concerning treatment, aspirin can be employed, which is the case in ischemic events. The prognosis is variable. While some patients have fully recovered after 6 months, others did exhibit some motor recovery, and still others remained in a locked-in syndrome4,6. The evolution likely depends on both the ischemia extension and the quality of rehabilitative care.