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.