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Paediatric patients with sudden vision impairment – An overview of MRI findings
Accepted Manuscript Paediatric patients with sudden vision impairment Dr. med. Stephanie Lescher, Cand. Med. Valerie Wickmann, Dr. Peter Hofstetter, PD Dr. med. Luciana Porto PII:
S1090-3798(16)00047-7
DOI:
10.1016/j.ejpn.2016.03.001
Reference:
YEJPN 2023
To appear in:
European Journal of Paediatric Neurology
Received Date: 11 January 2016 Revised Date:
22 February 2016
Accepted Date: 2 March 2016
Please cite this article as: Lescher S, Wickmann V, Hofstetter P, Porto L, Paediatric patients with sudden vision impairment, European Journal of Paediatric Neurology (2016), doi: 10.1016/j.ejpn.2016.03.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Paediatric patients with sudden vision impairment – An overview of MRI findings –
Dr. med. Stephanie Lescher1 – [email protected] Dr. Peter Hofstetter2 - [email protected] PD Dr. med. Luciana Porto1 – [email protected]
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Cand. Med. Valerie Wickmann1 - [email protected]
Institute of Neuroradiology, Hospital of Goethe University, Frankfurt am Main, Germany
2
Department of Paediatric Neurology, Hospital of Goethe University, Frankfurt am Main,
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1
Corresponding author: Dr. med. Stephanie Lescher Institute of Neuroradiology Hospital of Goethe University
60528 Frankfurt am Main Germany [email protected]
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Schleusenweg 2 – 16
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Germany
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Conflict of interest and Fundings
We wish to confirm that there are no known conflicts of interest associated with this
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publication and there has been no significant financial support or fundings for this work that could have influenced its outcome.
Keywords
vision impairment, paediatric patients, MRI
Short Title Sudden vision impairment in children
ACCEPTED MANUSCRIPT Paediatric patients with sudden vision impairment – An overview of MRI findings – Abstract Purpose: Sudden visual impairment in children occurs sporadically but, when
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present, needs urgent attention. Optimal management strategies and timely recognition are required. Often psychogenic disorders are the cause in school-age children; however, this is a diagnosis of exclusion. Therefore, MRI plays an important
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role in ruling out pathology along the optic pathways or helping with the diagnosis of underlying life threatening diseases, such as hydrocephalus or intracranial mass. The
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purpose of this study was first to evaluate non-traumatic (tumoural and non-tumoural) causes of acute vision impairment; and, second, to assess whether conventional cerebral and orbital MR imaging is helpful for children with sudden visual impairment. Patients and Methods: We retrospectively analysed the MRI scans and clinical
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findings of 95 children (47 male, 48 female; mean age: 12.5 years, range: from 2 to 17 years) who presented symptoms of monocular or bilateral acute vision impairment.
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Results: Patients with acute visual impairment were usually older than 7 years. In 36% of the patients a correlation between the MRI findings and the clinical symptoms
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was found. The most common causes of visual impairment were: infectious diseases (16%), migraine (12%), autoimmune diseases (11%), optic nerve neuritis with unknown aetiology (8%), neoplasms (8%), idiopathic intracranial hypertension (5%) and orthostatic hypotension (4%). Still, in 23% of the patients the cause remained unclear. Conclusion: Acute vision impairment is frequently caused by infectious diseases, migraine, autoimmune diseases or tumours in children. MRI is highly recommended,
ACCEPTED MANUSCRIPT especially in the case of children younger than 5 years of whom clinical assessment can be difficult.
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Introduction
Sudden impairment of vision is a rare but serious symptom in paediatric patients and indicates an emergency situation. The visual impairment can be monocular or
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bilateral. Regarding children, it is important first to rule out traumatic causes of visual impairment. In the present study, we have restricted ourselves to the non-traumatic
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spectrum; this is far less common but still important to consider in the absence of trauma. The cause of visual impairment can be found along all the afferent visual systems, i.e. not only diseases affecting the orbit and optic nerve itself; but also involvement of sellar and parasellar region, optic tracts, and retrogeniculate visual pathways should be ruled out1. Therefore, neuroimaging studies provide an important
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and useful tool for the clinician to evaluate a child with visual impairment.
In this study, the incidence of the main non-traumatic causes of visual impairment in
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paediatric patients with acute vision impairment was evaluated. We defined a wide range of vision loss an impairment, including other clinical symptoms such as
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constriction of visual fields, flashes, blurred vision or pain during eye movement. Causes were structured into two categories: tumoural and non-tumoural. We hypothesised that a significant part of the so-called non-traumatic causes in paediatric patients were related to inflammatory diseases; for instance demyelinating diseases or post-infectious causes, such as neuritis or even a banal sinusitis with subsequent functional vision impairment. MRI is of main importance in the differential diagnosis due to not only ruling out inflammatory diseases but also helping to recognize acute life threatening diseases such as acute hydrocephalus or tumours.
ACCEPTED MANUSCRIPT Our goals were, first, to determine non-traumatic causes of acute visual impairment in children and, second, to evaluate to which extent MRI is helpful in patients with non-traumatic visual impairment in a tertiary care paediatric hospital.
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Patients and Methods
This study was approved by the institutional review board. The study design was retrospective. A search of the electronic medical records was conducted for
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paediatric patients who were seen by the paediatric department with acute vision
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impairment.
Patients
We retrospectively analysed the cerebral and orbital MRI scans and clinical findings of 95 children who presented symptoms of monocular or bilateral acute i.e. new
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vision impairment in the children’s emergency department in a tertiary care paediatric hospital between January 2008 and December 2013. Inclusion criteria for the subsequent analyses were a lack of previous tumour history and a non-existent
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history of trauma or accident. Only patients who underwent MRI of the brain and
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orbital region were included in the study. All patients’ data were pseudonymised.
Analysis of MRI findings and Data assessment
MRI scans were obtained at 3 Tesla (Magnetom Verio, Siemens Medical Solutions, Erlangen, Germany) with an 8-channel phased array head coil using a standard protocol consisting of axial T2-/FLAIR- and Diffusion weighted images as well as T1weighted images pre- and post-contrast over the whole cerebrum in addition to special orbital sequence protocol consisting of T2-weighted images with fat
ACCEPTED MANUSCRIPT saturation in coronal slice and thin axial and sagittal T1-weighthed images with fat saturation.
Using a dedicated PACS workstation, two neuroradiologists, one with more than ten
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years of experience in paediatrics neuroimaging, analysed the anonymous MRI scans. The MRI results were divided in conspicuous and normal findings. Conspicuous findings were defined as possible causes, which might explain the
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clinical disturbance of the acute vision impairment.
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Clinical findings
In a next step, the two raters compared the MRI findings with the clinical examinations of each patient after critical review of the patients’ electronic records with the help of an experienced neuro-paediatric colleague (P. H.). Then, the clinical
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findings were correlated with the patients’ age and sex. Therefore, the patients were classified into four age categories: patients between 2 and 5 years (toddler/ preschooler), patients between 5 and 7 years (preschool age), patients between 7
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and 13 years (school-aged child) and patients older than 13 years (adolescent). The clinical findings were subdivided into nine categories. The categories are briefly
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discussed in the following:
Differential diagnosis within the different categories:
1. Neoplasm - Tumoural lesions included rhabdomyosarcoma involving the orbital region, medulloblastoma, optic glioma, germ cell tumour, pituitary tumours and craniopharyngioma. 2. Infectious causes - Patients with inflammation of the eyes or primary or secondary inflammatory optic neuritis due to orbital phlegmon, sinusitis,
ACCEPTED MANUSCRIPT bacterial infections including Lyme disease, cat-scratch fever and syphilis or viruses such as measles, mumps and herpes. 3. Idiopathic intracranial hypertension (IIH) - By definition, IIH is characterised by signs and symptoms of raised intracranial pressure, elevated opening
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pressure on lumbar puncture, and normal cerebrospinal fluid (CSF) studies and imaging. The exact aetiology of the disease remains unclear in many cases2.
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4. Migraine – One of the most common causes for transient vision impairment in children3.
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5. Orthostatic hypotension – This category includes patients with acute vision impairment due to orthostatic dysfunction.
6. Optic neuritis associated with other demyelinating conditions - This category describes disorders going together with demyelination of the cerebral nerve
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system including acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS) or neuromyelitis optica (NMO). 7. Isolated Optic neuritis of unknown etiology – Acute inflammation of the optic
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nerve typically presents as rapidly progressive, painful, monocular vision impairment without associated demyelinating conditions. The exact cause of
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the optic neuritis is unknown. Nevertheless, optic neuritis is believed to develop when the immune system targets the myelin of the optic nerve,
resulting in inflammation and damage.
8. Other organic, non-organic or ophthalmological causes – Other organic causes, as mentioned before, include visual disturbances due to toxic substances, underlying haematological diseases with haemorrhage along the visual pathway or vascular malformations. Non-organic causes are most often of psychogenic reasons without cerebral or ocular disease including hysterical
ACCEPTED MANUSCRIPT blindness, functional vision impairment, and psychogenic amaurosis. Other ophthalmological causes can be astigmatism, uncorrected defective vision or a retinal nevus. 9. Unknown etiology - In a number of patients, no cause could be identified for
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the vision impairment, and it was not possible to assign the patients to the categories mentioned above. This group of patients will be explained in more
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detail in the following section.
Results
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Patients’ characteristics
We retrospectively evaluated MRI data sets of 95 patients (mean age 12.5 years, range from 2 years 5 months to 17 years 10 months) who presented acute vision
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impairment. The gender distribution was balanced in our collective with 47 male and 48 female patients. 76 of the 95 children (80%) were older than 7 years. Acute vision impairment mostly occurred in patients older than 13 years (46.3 %), and it was
years).
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relatively rare in younger patients (only 20% of the patients were younger than 7
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All patients underwent initial MRI of the brain and/or orbital region depending on the clinical symptoms and the MRI findings in the first performed T2 weighted sequence in axial orientation of the cerebrum. If the first sequence was suspicious for cerebral pathologies, a MRI scan of the brain was performed. If no intracranial pathologies were suspected, a MRI scan of the orbit was done. In 38 of the 95 patients (40 %), MRI was conspicuous. In 34 of the 95 patients (36 %), MRI was helpful in determining the cause for the acute vision impairment. 4 of the 38 children with
ACCEPTED MANUSCRIPT conspicuous MRI had incidental findings which did not explain the visual disturbances, and the reason for the visual symptomatology remained unclear.
Causes of vision impairment
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Table 1 provides an overview of the distribution of the clinical findings in paediatric patients with acute vision impairment.
The most frequent known cause for acute vision impairment in childhood was first-
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episode optic neuritis. This was the case in 17 out of 95 patients (18%), 10 females (59%) and 7 males (41%), and children were usually older than 7 years (94%). In 5
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patients (29%) the optic nerve neuritis was isolated and caused by infection with a spirochete of the genus Borrelia. In 4 patients (24%), the optic nerve neuritis was part of an autoimmune disease: multiple sclerosis in 2 patients and a clinically isolated syndrome in 2 patients, which is defined as a first episode of neurologic symptoms
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which lasts at least 24 hours and is caused by inflammation and demyelination in one or more sites in the central nervous system. In 8 cases (47%) isolated optic nerve
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neuritis was obvious, but the cause remained unclear.
The second largest group of visual disturbances included infectious causes (16%).
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Most of the children with infectious causes were older than 7 years (80%). In this group, 3 out of 15 (3/15) patients suffered from sinusitis (20%), 5/15 patients had infectious optic nerve neuritis (33%), and the remaining 7/15 patients had other infectious reasons, for example an orbital phlegmon in 3 patients. The patients with sinusitis complained about unspecific symptoms such as headaches, dizziness, tiredness, disturbed vision (double vision) or decrease in vision. Each of those three patients presented an acute sphenoid sinusitis.
ACCEPTED MANUSCRIPT 12% of the patients suffered from migraine with visual aura. Migraine affected usually “older children” (55% older than 13 years of age). In 11% of the patients, an underlying autoimmune disease was responsible for the
patients were older than 7 years.
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vision impairment. In this group, most of the patients were female (80%), and all
In 8% of the patients, MRI showed a tumour (including: medulloblastoma, rhabdomyosarcoma of the orbit, choriocarcinoma, craniopharyngioma, germinoma,
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optic glioma, and pituitary macroadenoma).
5% of the children suffered from IIH. In contrast to the autoimmune disease, all but
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one patient with IHH were male (80%) and 40% younger than 5 years. 4 out of 95 patients had orthostatic hypotension, most of them were female (3 of 4), and all patients were older than 7 years.
In 13% of the patients, there were other organic e.g. acutely ruptured cerebral
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arteriovenous malformations, or papillary bleeding in a patient with Von Willebrand's disease, or ophthalmological causes such as conjunctivitis, uncorrected strabismus, or astigmatism.
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Psychogenic disorders were present in only 4 of the 95 patients (5%). In this group, the patients did not show any clinically manifest psychogenic disorder. Most of the
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children (59%) were older than 13 years. The patients of this group had unspecific symptoms such as blurred vision, vertigo and headaches. This leads to the suspicion that these symptoms were due to emotional disorders or psychosomatic superimposition, and that some of the patients tried to arouse attention through an imagined visual disturbance. Still, visual disturbances remained unclear in 23% of the patients. Some of these patients showed clinical improvement without any therapy. Others signed out against medical advice. But, a higher percentage of psychogenic disorders can be suspected
ACCEPTED MANUSCRIPT in this subgroup. In all children with visual disturbances, a psychogenic disorder should
be
assumed
when
neurological,
radiological
and
ophthalmological
examinations are inconspicuous and when there are clear signs of psychological
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problems of the familiar or social environment.
MRI findings
In 57 of the 95 patients (60%) the MRI study was normal. In the other 38 patients
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(40%) the MRI presented abnormal findings and pathologies. Of these, MRI could determine the cause of the visual impairment in 34 patients. In 4 patients, the MRI
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findings were unrelated to the vision impairment, i.e. incidental finding. Table 2 Around 26% (10 out of 38) of the patients with positive MRI findings showed abnormalities suggesting an autoimmune disease along with a demyelination process such as acute disseminated encephalomyelitis, MS or neuromyelitis optica.
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Most of the patients with autoimmune disease were female (80%) and 70% of the cases older than 13 years of age. (Fig. 1)
The second most common MRI finding was a neoplasm in 8 out of 38 patients (21%),
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including two medulloblastomas, one rhabdomyosarcoma of the orbit, one choriocarcinoma, one craniopharyngioma, one germinoma, one optic glioma, and
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one pituitary macroadenoma. This group showed a light male predominance (62.5%), and patients were usually older than 13 years of age. (Fig. 2) In 7 of the 57 patients, an infectious disease (such as orbital phlegmon, sinusitis and inflammatory optic neuritis) was the underlying reason for the vision impairment. In patients with neuritis nervi optici, the MRI showed abnormalities such as swelling and contrast enhancement of the optic nerve in 7 out of 17 patients (41%).
ACCEPTED MANUSCRIPT In 4 out of 5 patients (80%) with IHH the MRI was conspicuous. The typical MRI changes are: empty sella, optic nerve sheath enlargement and reversal of optic nerve head (Fig. 3). In four patients, the MRI showed pathologies which did not explain the clinical
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finding. Two of the four patients (50%) presented white matter lesions of the corpus callosum suggesting an underlying demyelination disease such as MS but without any clinical correlation. In these patients, no MRI findings indicating presence of optic
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neuritis were obvious. Thus, these patients had probably the so-called “radiologically isolated syndrome” (RIS), which is an incidentally discovered, clinically silent disease
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state of MS. In both patients, a migraine was one possible differential diagnosis due to their clinical presentations. The other two patients presented suspected signal inhomogeneity of the pituitary gland but without any clinical, laboratory and/or imaging evidence of a pituitary microadenoma. In these patients, the reason for the
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acute vision impairment remained unclear. In all patients (10 out of 10 patients) with confirmed autoimmune disease, MRI revealed pathological findings which included
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white matter lesions, optic neuritis or transverse myelitis.
Correlation of the clinical findings with patients’ age and sex
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Only 20% of the patients in our collective were younger than 7 years. In younger patients with acute visual impairment three main differential diagnoses should be considered: tumour, infection and IHH. Interestingly, we did not find any infectious causes in patients younger than 5 years. In patients older than 7 years, the cause for visual disturbances often remained unclear. Other causes in decreasing incidence were: infection, migraine, autoimmune disease and neoplasm.
ACCEPTED MANUSCRIPT Overall, gender distribution of our collective was balanced. Regarding the differential diagnosis, the gender distribution was most remarkable in the group of autoimmune diseases showing a female predominance (80 %). A slight predominance of male
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patients was apparent in children with IHH (4 male to one female patient).
Correlation between pathological MRI findings and patient’s age
Younger children were more prone to having pathological findings on MRI. Newborn
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babies were not included.
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Discussion
Acute vision impairment in children requires a quick diagnostic approach. Unfortunately, children may not present unless they experience significant impairment of vision. In very young children, parents’ awareness for the behavioral
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symptoms of visually impaired children could help recognizing the condition at an early stage. The child might show an exceptional delay of developing skills, which might show in everyday situations. For instance, the child might be inhibited in
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coordinately reaching and transferring objects such as toy blocks or a spoon. The
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later the vision impairment is noticed, the lower is the chance for recovery. Therefore, a favourable outcome depends on a fast diagnosis. Consequently, vision loss is an emergency situation and MRI examination should be performed within the first 24 hours after the clinical manifestation of symptoms. Be aware that “acute” visual impairment can be a misleading description in children. A systematic approach must follow. First, an ophthalmological and/or traumatic cause must be ruled out. Traumatic reasons are known to be the most frequent cause of visual impairment in childhood3.
ACCEPTED MANUSCRIPT In our retrospective evaluation, only children with non-traumatic visual disturbance were included. These consist of different organic and functional disturbances. In addition, the clinical assessment of children is more challenging due to the lack of cooperation. Therefore, MRI plays an important role in the differential diagnosis.
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In our study, gender distribution was balanced. Most of the 95 children with acute visual impairment (80%) were older than 7 years with predominance in children older than 13 years (46%). Acute vision impairment was relatively rare in younger patients
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(only 20% of the patients were younger than 7 years).
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While in 77% of our patients the cause of vision impairment could be determined, in 23% the symptoms remained unclear.
As reported before, psychogenic visual disturbances including hysterical blindness, functional vision impairment, psychogenic amaurosis (conversion phenomenon with headaches, which can simulate migraine) are common in school-age children4. In our
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collective, psychogenic disorders were present in only 4 of the 95 patients (5%) and were therefore less common than suspected. Yet, in almost a quarter of the patients (23%) the cause of the visual disturbances remained unclear due to reasons
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mentioned above; therefore, it is to be assumed that the incidence of psychogenic
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disorders could have been much higher. This theory is supported by the fact that younger children were more prone to having pathological findings on MRI, whereas in older children the cause often remained unclear.
As we hypothesized, one common reason for acute vision impairment in childhood was infectious causes, which were present in 16% of the patients. In this group, patients were usually older than 7 years. 3 patients suffered from sinusitis of the sphenoid sinus (20%), 5 patients had optic nerve neuritis (33%), and the remaining 7 patients had other infectious reasons such as orbital phlegmon, varicella zoster
ACCEPTED MANUSCRIPT meningoencephalitis, mycoplasma encephalitis, enterovirus encephalitis. The relation between acute sphenoid sinusitis and painless vision loss was reported by Reynolds et al.5. According to the authors of this case report, the second most common symptom in acute sinusitis is visual disturbance due to the very close anatomical
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relation to the adjacent cranial nerves II – VI. They emphasised that concerning patients with acute vision loss presenting to the emergency department a sinusitis of the sphenoid sinus has to be considered.
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Optic nerve neuritis can be caused by different disease processes, which will all lead to an acute inflammatory demyelination of the optic nerve, resulting in rapid,
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progressive, painful, monocular vision impairment3. According to Patel et al., 15% to 20% of the patients with optic nerve neuritis will later develop multiple sclerosis3. In 17 out of 95 children (18%), optic nerve neuritis was responsible for visual disturbances. In 5 out of 17 patients (29%), the optic nerve neuritis was due to
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infection, in 4 out of 17 patients (24%) due to autoimmune disease such as multiple sclerosis. In 8 out of 17 cases (47%), the optic nerve neuritis remained unclear. Regarding these patients, optic neuritis could have been the first manifestation of a
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future autoimmune disease, such as MS or NMO, but long term follow-ups are missing in these cases.
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The most common cause reported in previous literature on transient vision impairment in children is migraine headaches defined as a fully reversible monocular visual
disturbance,
associated
with
migraine
headache
and
a
normal
neuroophthalmologic examination between the attacks3. In our collective, 12% of the patients suffered from migraine headache with visual aura. In 11% of the patients, an underlying autoimmune disease was responsible for the vision impairment with a female predominance (80%). Autoimmune diseases included acute disseminated encephalomyelitis, MS or NMO, all of them resulting in
ACCEPTED MANUSCRIPT a demyelination of the cerebral nerve system, but the incidence might have been higher if a long term follow-up had been performed. In the case of intracranial tumours, visual impairment can be caused by compression of the visual pathways (for example, if a craniopharyngeoma involves the optic tracts,
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chiasm, or nerves) or be secondary to an increased intracranial pressure (as in the case of posterior fossa tumours). In our collective, 8 out of 95 patients (8 %) presented vision loss, i.e. impairment secondary to a neoplastic disease; which
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included two medulloblastomas, one rhabdomyosarcoma of the orbit, one choriocarcinoma, one craniopharyngioma, one germinoma, one optic glioma, and
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one pituitary macroadenoma. Ophthalmic complications of childhood due to medulloblastoma have been reported in 66% of the children, and patients usually present with diplopia6. Rhabdomyosarcoma involves primarily the orbit, resulting in unilateral proptosis, swelling, and restricted ocular motility7. Prieto et al. reported
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vision impairment/loss in 69% of the patients with craniopharyngiomas prior to surgery8. Visual impairment is reported in up to 54% of patients with optic gliomas at presentation9. Optic nerve glioma or visual pathway gliomas involving the optic nerve,
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chiasm, or optic tract are very typical for neurofibromatosis type 110. This should be considered for differential diagnosis in this group of patients.
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5 out of 95 children suffered from IIH. All but one patient with IHH were male (80%); 2 out of 5 patients were younger than 5 years old. In patients with IHH, visual impairment or blindness occurs as an initial symptom in severe cases. The speed of symptom development is variable, but severely or rapidly progressive vision impairment due to high-grade papilledema, macular oedema, and venous sinus thrombosis has been reported before2, 11. MRI helps to rule out tumours, meningeal infiltration and cerebral venous sinus thrombosis.
ACCEPTED MANUSCRIPT 4% out of the patients had orthostatic hypotension, most of them were female (75%), and all patients were older than 7 years. Temporal arteritis, which is the most frequent cause of vision impairment in adults, was not a cause in our group of patients. In the existing literature, only 11 cases of 13
. None of our patients
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temporal arteritis in children have been documented12,
suffered from occipital lobe seizures, a rare cause for visual disturbances14. Moreover, various drugs should be included in the differential diagnosis of visual
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disorders such as sildenafil, anticholinergics, antibiotics (linezolid), immune modulators (cyclosporine, tacrolimus, inflinximab) resulting in an optic neuropathy
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with acute vision impairment15. Despite the absence in our collective, there are still some important symptoms along with acute loss of vision which the reader should be aware of. Some metabolic disorders (acute metabolic crisis in methylmalonic academia and propionic academia) may trigger visual loss16. Another metabolic
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disorder is the ornithine transcarbamylase deficiency which might be accompanied by acute reversible cortical blindness17 as well as Vitamin B12 deficiency18. Acute lymphoblastic leukemia may come along with a rapidly enlarging and vision-
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threatening orbital mass19.
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On the one hand, given the large spectrum of neurological disorders resulting in vision impairment, the challenge for the paediatric neurologist and/or ophthalmologist is to recognize acute life threatening causes such as hydrocephalus as early as possible. On the other hand, they should avoid unnecessary investigations and treatment procedures. MRI is the imaging modality of choice due to the fact that it serves to rule out neurological causes. As has been previously reported in the literature, imaging techniques, especially MRI studies, are valuable tools for the clinician attempting to distinguish between causes of visual loss1. However, the
ACCEPTED MANUSCRIPT incidence of pathological MRI findings in children with vision loss has not been fully reported in the literature before. In our sample, MRI could determine the cause of visual impairment in 34 out of 95 patients. In 4 patients with functional visual disturbance, MRI findings were abnormal but unrelated to the vision impairment.
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Nearly one third of the patients with abnormal MRI showed abnormalities being suggestive of an autoimmune disease, along with a demyelination process such as MS, NMO and optic neuritis, which correlates with the findings in the existing
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literature that described pathologic enhancement in up to 95% of cases of acute optic neuritis20. In the final review of longitudinal data from the Optic Neuritis Treatment
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Trial (ONTT), 25% of patients without lesions on MRI developed MS at the age of 15, while 72% of patients with one or more brain lesions developed clinically definite MS at 15 years of age21. Compared with idiopathic demyelinating optic neuritis or optic neuritis associated with MS, imaging findings in NMO more commonly include
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bilateral optic nerve enlargement and enhancement1, which was also present in our patients. In patients with optic neuritis, the MRI showed abnormalities such as swelling and enhancement of the optic nerve in 7 out of 17 of our patients (41%).
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The second most common MRI finding, especially in patients older than 13 years of age, was a neoplasm, that was visible in all cases with MRI, as has been previously
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described in the literature1.
Almost all patients (4 out of 5 patients) with IHH, MRI revealed a conspicious empty sella or swelling of the optic nerve. Mallery et al. recommended in cases of suspected pseudotumour cerebri the performance of MRI/MR venous time of flight angiographie to rule out an intracranial lesion or venous sinus thrombosis. In their study, MRI could demonstrate several common MRI findings including dilated optic nerve sheaths, an “empty sella” and/ or narrowing of one or both transverse sinuses1.
ACCEPTED MANUSCRIPT Therefore, upon suspicion of an underlying cause such as neoplasm, autoimmune disease, infectious disease and IHH in paediatric patients with acute non-traumatic vision impairment a MRI study is highly recommended. Furthermore, MRI should always be performed in younger children (< 5 years), because visual impairment,
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although less common (only 7% of the patients), showed a higher percentage of abnormal findings (71%). In comparison, in the age category of 5 – 7 year-olds, in 50% of the cases the MRI revealed abnormal findings; in the group of school-age
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children, MRI was usually normal (78%), and during puberty MRI was abnormal in 45.5% of the patients.
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In order to get an understanding of the issue of vision impairment in children we would recommend a systematic approach: First, the children should be seen by a specialist pediatrician and a specialist ophthalmologist for ruling out any traumatic or ophthalmological causes such as astigmatism that may cause the vision impairment.
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Then, MRI examination should be performed within 24 hours. The MRI protocol should include a standard protocol for brain examination including axial T2-weighted sequence, axial FLAIR sequence, T2*- and Diffusion weighted images. Axial T1-
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weighted spin echo sequences should be performed before and after intravenous application of a standard dose of Gd-DTPA. Further, for the orbit examination coronal
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T2w SPIR sequence and T1w sequence after contrast agent with FATSAT and 3 mm slice thickness should be added to the protocol. By combining both examinations in one session, we are able to save time, contrast agent and time under anesthesia in younger children. In children older than 7 years and inconspicuous MRI, a follow up MRI should be performed when the clinical symptoms persist or recur so as to rule out chronic inflammatory disorder. Figure 4 shows a diagnostic algorithm for the evaluation of children with acute vision impairment.
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Limitation The limitation of this study is its retrospective character. Therefore, a consistent clinical documentation of symptoms is missing. Regarding the evaluated data, it
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remained unclear whether the vision loss was uni- or bilateral. However, this would be an interesting topic for further evaluation and for comparison with MRI findings for both groups. Further, in a prospective study, follow-up visits could be terminated for
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and the causes remained also unclear.
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patients with unexplained vision impairment, as most of those patients dropped out
Conclusion
When faced with a child presenting with an acute visual impairment, the paediatrician should first keep in mind that, in the lack of a traumatic cause a MRI can be very
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helpful, since it rules out most neurological causes. In our sample, MRI helped to differentiate between neurological and psychological causes in one third of the children.
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Second, beyond the newborn period; in children without previous history of trauma, the most common cause of acute vision impairment was an infectious disease,
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followed by an autoimmune disease, tumours and intracranial hypertension. Therefore, MRI is highly recommended, especially in the case of children younger than 5 years of whom clinical assessment can be difficult. Third, an initial normal MRI imaging may not exclude early stages of neurodegenerative disorders or autoimmune diseases. Furthermore, without thin slices dedicated to the orbits, one cannot rule out optic neuropathy. Fourth, while neuroimaging plays a key role in elucidating the cause of acute visual impairment in children, it is, however, of note that the final diagnosis is a combination
ACCEPTED MANUSCRIPT of history and examination findings, especially concerning patients for whom a
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psychological cause should be considered.
ACCEPTED MANUSCRIPT Literature
1. Mallery RM, Prasad S. Neuroimaging of the afferent visual system. Semin Neurol. 2012; 32:273-319.
options. Indian J Ophthalmol. 2014; 62:996-998.
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2. Dave SB, Subramanian PS. Pseudotumor cerebri: an update on treatment
3. Patel KN. Acute vision loss. Clin Pediatr Emerg Med. 2010; 11: 137–142.
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4. Doummar D, Roussat B, Pelosse B, Le Pointe HD, Iba-Zizen M, Roubergue A, Rodriguez D, de Villemeur TB. Management of acute visual loss in children.
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[Article in French] Arch Pediatr. 2004; 11:1384-1388.
5. Reynolds SC, Evans EM. Acute sphenoid sinusitis induced blindness: a case report. J Emerg Med. 2012; 43: 123-124.
6. Cassidy L, Stirling R, May K, Picton S, Doran R. Ophthalmic complications of
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childhood medulloblastoma. Med Pediatr Oncol. 2000; 34:43-47. 7. Breen LA, Kline LB, Hart WM Jr, Burde RM. Rhabdomyosarcoma causing
188.
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rapid bilateral visual loss in children. J Clin Neuroophthalmol. 1984; 4:185-
8. Prieto R, Pascual JM, Barrios L. Optic chiasm distortions caused by
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craniopharyngiomas: clinical and magnetic resonance imaging correlation and influence on visual outcome. World Neurosurg. 2015; 83:500-529.
9. Greenwell TH, Anderson PJ, Madge SK, Selva D, David DJ. Long-term visual outcomes in patients with orbitotemporal neurofibromatosis. Clin Experiment Ophthalmol. 2014; 42:266-270. 10. Listernick R, Charrow J, Greenwald MJ, Esterly NB. Optic gliomas in children with neurofibromatosis type 1. J Pediatr. 1989; 114:788-792. 11. Friedman DI. Pseudotumor cerebri. Neurol Clin. 2004; 22: 99-131.
ACCEPTED MANUSCRIPT 12. Vortman M, Schnieder I. Acute monocular visual loss. Emerg Med Clin North Am. 2008; 26:73-96. 13. Melachrinou M, Andonopoulous AP. Juvenile temporal arteritis. In Orphanet. Available
at
http://www.orpha.net/data/patho/GB/uk-juvenile-temporal-
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arteritis.pdf. 2005. Accessed 4/2010.
14. Shahar E, Barak S. Favorable outcome of epileptic blindness in children. J Child Neurol. 2003; 18:12-16.
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15. Kerrison JB. Optic neuropathies caused by toxins and adverse drug reactions. Ophthalmol Clin North Am. 2004; 17:481-488.
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16. Alvarez L, Jameson E, Parry NR, Lloyd C, Ashworth JL. Optic neuropathy in methylmalonic acidemia and propionic academia. Br J Ophthalmol. 2016; 100: 98-104.
17. Prasun P, Altinok D, Misra VK. Ornithine transcarbamylase deficiency
782-785.
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presenting with acute reversible cortical blindness. J Child Neurol. 2015; 30:
18. Jalil A, Usmani HA, Khan MI, Blakely EL, Taylor RW, Vassallo G, Ashworth J.
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Bilateral paediatric optic neuropathy precipitated by vitamin B12 deficiency and a novel mitochondrial DNA mutation. Int Ophthalmol. 2013; 33: 687-690.
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19. Vrcek I, Finnerty K, Ford P, Hogan RN, Mancini R. Relapsing acute lymphoblastic leukemia presenting with a rapidly enlarging and visionthreatening orbital mass. Int Ophthalmol. 2015; 35: 257-260.
20. Fazzone HE, Lefton DR, Kupersmith MJ. Optic neuritis: correlation of pain and magnetic resonance imaging. Ophthalmology. 2003; 110:1646–1649. 21. Optic Neuritis Study Group. Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial follow-up. Arch Neurol. 2008; 65:727–732.
ACCEPTED MANUSCRIPT Figure Legends
Figure 1: Typical MRI findings in a female patient with multiple sclerosis (MS). Cerebral MRI shows multiple white matter lesions (arrows) involving the corpus
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callosum, subcortical U-fibres, temporal lobes and brainstem. Contrast enhanced T1 weighted imaging shows an enhancing lesion (asterisk) on the left frontal lobe. The
space.
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Fig. 2: Female patient with craniopharyngioma.
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lesions met the McDonald criteria for MS due to their dissemination in time and
The tumour (asterisk) has a significant suprasellar component and involves both the suprasellar and intrasellar spaces. After Gadolinium an enhancing nodule is obvious (arrow). The tumour is mostly of cystic components. On CT images, note the typical
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calcifications within the tumour (ellipse).
Fig. 3: Male patient with idiopathic intracranial hypertension
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Note the bilateral optic disc swelling caused by increased cerebrospinal fluid pressure on the optic nerve (arrows) as well as a partially empty sella turcica
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(asterisk): The pituitary fossa is largely empty of tissue and replaced by CSF.
Figure 4: The figure illustrates a diagnostic algorithm for the evaluation of children with acute vision impairment.
ACCEPTED MANUSCRIPT Tables Table 1: Clinical findings in paediatric patients with acute vision impairment Incidence
Percentage (%)
Neoplasm
8
8.4
Infectious causes
15
15.8
Idiopathic intracranial hypertension
5
Migraine
11
Orthostatic hypotension
4
Autoimmune disease
10
Optic nerve neuritis with unknown aetiology
8
Other reasons
12
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Differential diagnosis
5.3
11.6 4.2
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Unknown aetiology Total
10.5 8.4 12.6
22
23.2
95
100
Table 2: MRI findings in paediatric patients with acute vision impairment Percentage (%)
Normal Findings - total
57
60
Pathological Findings - total
38
40
Autoimmune disease
10
26
8
21
7
18
Optic Nerve Neuritis of unknown aetiology
2
5
Idiopathic intracranial hypertension
4
11
Other reasons
3
8
Incidental Findings
4
11
Neoplasm
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Incidence
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MRI Findings
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Infectious causes
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ACCEPTED MANUSCRIPT “Highlights” •
Cerebral MRI is highly recommended in children with acute vision impairment, especially in children younger than 5 years. MRI can rule out the causes for the visual disturbance in one third of the children.
•
Reasons for the vision impairment can be found along all the afferent visual system.
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•
S1090-3798(16)00047-7
DOI:
10.1016/j.ejpn.2016.03.001
Reference:
YEJPN 2023
To appear in:
European Journal of Paediatric Neurology
Received Date: 11 January 2016 Revised Date:
22 February 2016
Accepted Date: 2 March 2016
Please cite this article as: Lescher S, Wickmann V, Hofstetter P, Porto L, Paediatric patients with sudden vision impairment, European Journal of Paediatric Neurology (2016), doi: 10.1016/j.ejpn.2016.03.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Paediatric patients with sudden vision impairment – An overview of MRI findings –
Dr. med. Stephanie Lescher1 – [email protected] Dr. Peter Hofstetter2 - [email protected] PD Dr. med. Luciana Porto1 – [email protected]
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Cand. Med. Valerie Wickmann1 - [email protected]
Institute of Neuroradiology, Hospital of Goethe University, Frankfurt am Main, Germany
2
Department of Paediatric Neurology, Hospital of Goethe University, Frankfurt am Main,
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1
Corresponding author: Dr. med. Stephanie Lescher Institute of Neuroradiology Hospital of Goethe University
60528 Frankfurt am Main Germany [email protected]
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Schleusenweg 2 – 16
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Germany
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Conflict of interest and Fundings
We wish to confirm that there are no known conflicts of interest associated with this
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publication and there has been no significant financial support or fundings for this work that could have influenced its outcome.
Keywords
vision impairment, paediatric patients, MRI
Short Title Sudden vision impairment in children
ACCEPTED MANUSCRIPT Paediatric patients with sudden vision impairment – An overview of MRI findings – Abstract Purpose: Sudden visual impairment in children occurs sporadically but, when
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present, needs urgent attention. Optimal management strategies and timely recognition are required. Often psychogenic disorders are the cause in school-age children; however, this is a diagnosis of exclusion. Therefore, MRI plays an important
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role in ruling out pathology along the optic pathways or helping with the diagnosis of underlying life threatening diseases, such as hydrocephalus or intracranial mass. The
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purpose of this study was first to evaluate non-traumatic (tumoural and non-tumoural) causes of acute vision impairment; and, second, to assess whether conventional cerebral and orbital MR imaging is helpful for children with sudden visual impairment. Patients and Methods: We retrospectively analysed the MRI scans and clinical
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findings of 95 children (47 male, 48 female; mean age: 12.5 years, range: from 2 to 17 years) who presented symptoms of monocular or bilateral acute vision impairment.
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Results: Patients with acute visual impairment were usually older than 7 years. In 36% of the patients a correlation between the MRI findings and the clinical symptoms
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was found. The most common causes of visual impairment were: infectious diseases (16%), migraine (12%), autoimmune diseases (11%), optic nerve neuritis with unknown aetiology (8%), neoplasms (8%), idiopathic intracranial hypertension (5%) and orthostatic hypotension (4%). Still, in 23% of the patients the cause remained unclear. Conclusion: Acute vision impairment is frequently caused by infectious diseases, migraine, autoimmune diseases or tumours in children. MRI is highly recommended,
ACCEPTED MANUSCRIPT especially in the case of children younger than 5 years of whom clinical assessment can be difficult.
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Introduction
Sudden impairment of vision is a rare but serious symptom in paediatric patients and indicates an emergency situation. The visual impairment can be monocular or
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bilateral. Regarding children, it is important first to rule out traumatic causes of visual impairment. In the present study, we have restricted ourselves to the non-traumatic
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spectrum; this is far less common but still important to consider in the absence of trauma. The cause of visual impairment can be found along all the afferent visual systems, i.e. not only diseases affecting the orbit and optic nerve itself; but also involvement of sellar and parasellar region, optic tracts, and retrogeniculate visual pathways should be ruled out1. Therefore, neuroimaging studies provide an important
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and useful tool for the clinician to evaluate a child with visual impairment.
In this study, the incidence of the main non-traumatic causes of visual impairment in
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paediatric patients with acute vision impairment was evaluated. We defined a wide range of vision loss an impairment, including other clinical symptoms such as
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constriction of visual fields, flashes, blurred vision or pain during eye movement. Causes were structured into two categories: tumoural and non-tumoural. We hypothesised that a significant part of the so-called non-traumatic causes in paediatric patients were related to inflammatory diseases; for instance demyelinating diseases or post-infectious causes, such as neuritis or even a banal sinusitis with subsequent functional vision impairment. MRI is of main importance in the differential diagnosis due to not only ruling out inflammatory diseases but also helping to recognize acute life threatening diseases such as acute hydrocephalus or tumours.
ACCEPTED MANUSCRIPT Our goals were, first, to determine non-traumatic causes of acute visual impairment in children and, second, to evaluate to which extent MRI is helpful in patients with non-traumatic visual impairment in a tertiary care paediatric hospital.
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Patients and Methods
This study was approved by the institutional review board. The study design was retrospective. A search of the electronic medical records was conducted for
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paediatric patients who were seen by the paediatric department with acute vision
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impairment.
Patients
We retrospectively analysed the cerebral and orbital MRI scans and clinical findings of 95 children who presented symptoms of monocular or bilateral acute i.e. new
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vision impairment in the children’s emergency department in a tertiary care paediatric hospital between January 2008 and December 2013. Inclusion criteria for the subsequent analyses were a lack of previous tumour history and a non-existent
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history of trauma or accident. Only patients who underwent MRI of the brain and
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orbital region were included in the study. All patients’ data were pseudonymised.
Analysis of MRI findings and Data assessment
MRI scans were obtained at 3 Tesla (Magnetom Verio, Siemens Medical Solutions, Erlangen, Germany) with an 8-channel phased array head coil using a standard protocol consisting of axial T2-/FLAIR- and Diffusion weighted images as well as T1weighted images pre- and post-contrast over the whole cerebrum in addition to special orbital sequence protocol consisting of T2-weighted images with fat
ACCEPTED MANUSCRIPT saturation in coronal slice and thin axial and sagittal T1-weighthed images with fat saturation.
Using a dedicated PACS workstation, two neuroradiologists, one with more than ten
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years of experience in paediatrics neuroimaging, analysed the anonymous MRI scans. The MRI results were divided in conspicuous and normal findings. Conspicuous findings were defined as possible causes, which might explain the
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clinical disturbance of the acute vision impairment.
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Clinical findings
In a next step, the two raters compared the MRI findings with the clinical examinations of each patient after critical review of the patients’ electronic records with the help of an experienced neuro-paediatric colleague (P. H.). Then, the clinical
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findings were correlated with the patients’ age and sex. Therefore, the patients were classified into four age categories: patients between 2 and 5 years (toddler/ preschooler), patients between 5 and 7 years (preschool age), patients between 7
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and 13 years (school-aged child) and patients older than 13 years (adolescent). The clinical findings were subdivided into nine categories. The categories are briefly
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discussed in the following:
Differential diagnosis within the different categories:
1. Neoplasm - Tumoural lesions included rhabdomyosarcoma involving the orbital region, medulloblastoma, optic glioma, germ cell tumour, pituitary tumours and craniopharyngioma. 2. Infectious causes - Patients with inflammation of the eyes or primary or secondary inflammatory optic neuritis due to orbital phlegmon, sinusitis,
ACCEPTED MANUSCRIPT bacterial infections including Lyme disease, cat-scratch fever and syphilis or viruses such as measles, mumps and herpes. 3. Idiopathic intracranial hypertension (IIH) - By definition, IIH is characterised by signs and symptoms of raised intracranial pressure, elevated opening
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pressure on lumbar puncture, and normal cerebrospinal fluid (CSF) studies and imaging. The exact aetiology of the disease remains unclear in many cases2.
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4. Migraine – One of the most common causes for transient vision impairment in children3.
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5. Orthostatic hypotension – This category includes patients with acute vision impairment due to orthostatic dysfunction.
6. Optic neuritis associated with other demyelinating conditions - This category describes disorders going together with demyelination of the cerebral nerve
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system including acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS) or neuromyelitis optica (NMO). 7. Isolated Optic neuritis of unknown etiology – Acute inflammation of the optic
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nerve typically presents as rapidly progressive, painful, monocular vision impairment without associated demyelinating conditions. The exact cause of
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the optic neuritis is unknown. Nevertheless, optic neuritis is believed to develop when the immune system targets the myelin of the optic nerve,
resulting in inflammation and damage.
8. Other organic, non-organic or ophthalmological causes – Other organic causes, as mentioned before, include visual disturbances due to toxic substances, underlying haematological diseases with haemorrhage along the visual pathway or vascular malformations. Non-organic causes are most often of psychogenic reasons without cerebral or ocular disease including hysterical
ACCEPTED MANUSCRIPT blindness, functional vision impairment, and psychogenic amaurosis. Other ophthalmological causes can be astigmatism, uncorrected defective vision or a retinal nevus. 9. Unknown etiology - In a number of patients, no cause could be identified for
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the vision impairment, and it was not possible to assign the patients to the categories mentioned above. This group of patients will be explained in more
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detail in the following section.
Results
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Patients’ characteristics
We retrospectively evaluated MRI data sets of 95 patients (mean age 12.5 years, range from 2 years 5 months to 17 years 10 months) who presented acute vision
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impairment. The gender distribution was balanced in our collective with 47 male and 48 female patients. 76 of the 95 children (80%) were older than 7 years. Acute vision impairment mostly occurred in patients older than 13 years (46.3 %), and it was
years).
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relatively rare in younger patients (only 20% of the patients were younger than 7
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All patients underwent initial MRI of the brain and/or orbital region depending on the clinical symptoms and the MRI findings in the first performed T2 weighted sequence in axial orientation of the cerebrum. If the first sequence was suspicious for cerebral pathologies, a MRI scan of the brain was performed. If no intracranial pathologies were suspected, a MRI scan of the orbit was done. In 38 of the 95 patients (40 %), MRI was conspicuous. In 34 of the 95 patients (36 %), MRI was helpful in determining the cause for the acute vision impairment. 4 of the 38 children with
ACCEPTED MANUSCRIPT conspicuous MRI had incidental findings which did not explain the visual disturbances, and the reason for the visual symptomatology remained unclear.
Causes of vision impairment
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Table 1 provides an overview of the distribution of the clinical findings in paediatric patients with acute vision impairment.
The most frequent known cause for acute vision impairment in childhood was first-
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episode optic neuritis. This was the case in 17 out of 95 patients (18%), 10 females (59%) and 7 males (41%), and children were usually older than 7 years (94%). In 5
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patients (29%) the optic nerve neuritis was isolated and caused by infection with a spirochete of the genus Borrelia. In 4 patients (24%), the optic nerve neuritis was part of an autoimmune disease: multiple sclerosis in 2 patients and a clinically isolated syndrome in 2 patients, which is defined as a first episode of neurologic symptoms
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which lasts at least 24 hours and is caused by inflammation and demyelination in one or more sites in the central nervous system. In 8 cases (47%) isolated optic nerve
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neuritis was obvious, but the cause remained unclear.
The second largest group of visual disturbances included infectious causes (16%).
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Most of the children with infectious causes were older than 7 years (80%). In this group, 3 out of 15 (3/15) patients suffered from sinusitis (20%), 5/15 patients had infectious optic nerve neuritis (33%), and the remaining 7/15 patients had other infectious reasons, for example an orbital phlegmon in 3 patients. The patients with sinusitis complained about unspecific symptoms such as headaches, dizziness, tiredness, disturbed vision (double vision) or decrease in vision. Each of those three patients presented an acute sphenoid sinusitis.
ACCEPTED MANUSCRIPT 12% of the patients suffered from migraine with visual aura. Migraine affected usually “older children” (55% older than 13 years of age). In 11% of the patients, an underlying autoimmune disease was responsible for the
patients were older than 7 years.
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vision impairment. In this group, most of the patients were female (80%), and all
In 8% of the patients, MRI showed a tumour (including: medulloblastoma, rhabdomyosarcoma of the orbit, choriocarcinoma, craniopharyngioma, germinoma,
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optic glioma, and pituitary macroadenoma).
5% of the children suffered from IIH. In contrast to the autoimmune disease, all but
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one patient with IHH were male (80%) and 40% younger than 5 years. 4 out of 95 patients had orthostatic hypotension, most of them were female (3 of 4), and all patients were older than 7 years.
In 13% of the patients, there were other organic e.g. acutely ruptured cerebral
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arteriovenous malformations, or papillary bleeding in a patient with Von Willebrand's disease, or ophthalmological causes such as conjunctivitis, uncorrected strabismus, or astigmatism.
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Psychogenic disorders were present in only 4 of the 95 patients (5%). In this group, the patients did not show any clinically manifest psychogenic disorder. Most of the
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children (59%) were older than 13 years. The patients of this group had unspecific symptoms such as blurred vision, vertigo and headaches. This leads to the suspicion that these symptoms were due to emotional disorders or psychosomatic superimposition, and that some of the patients tried to arouse attention through an imagined visual disturbance. Still, visual disturbances remained unclear in 23% of the patients. Some of these patients showed clinical improvement without any therapy. Others signed out against medical advice. But, a higher percentage of psychogenic disorders can be suspected
ACCEPTED MANUSCRIPT in this subgroup. In all children with visual disturbances, a psychogenic disorder should
be
assumed
when
neurological,
radiological
and
ophthalmological
examinations are inconspicuous and when there are clear signs of psychological
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problems of the familiar or social environment.
MRI findings
In 57 of the 95 patients (60%) the MRI study was normal. In the other 38 patients
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(40%) the MRI presented abnormal findings and pathologies. Of these, MRI could determine the cause of the visual impairment in 34 patients. In 4 patients, the MRI
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findings were unrelated to the vision impairment, i.e. incidental finding. Table 2 Around 26% (10 out of 38) of the patients with positive MRI findings showed abnormalities suggesting an autoimmune disease along with a demyelination process such as acute disseminated encephalomyelitis, MS or neuromyelitis optica.
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Most of the patients with autoimmune disease were female (80%) and 70% of the cases older than 13 years of age. (Fig. 1)
The second most common MRI finding was a neoplasm in 8 out of 38 patients (21%),
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including two medulloblastomas, one rhabdomyosarcoma of the orbit, one choriocarcinoma, one craniopharyngioma, one germinoma, one optic glioma, and
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one pituitary macroadenoma. This group showed a light male predominance (62.5%), and patients were usually older than 13 years of age. (Fig. 2) In 7 of the 57 patients, an infectious disease (such as orbital phlegmon, sinusitis and inflammatory optic neuritis) was the underlying reason for the vision impairment. In patients with neuritis nervi optici, the MRI showed abnormalities such as swelling and contrast enhancement of the optic nerve in 7 out of 17 patients (41%).
ACCEPTED MANUSCRIPT In 4 out of 5 patients (80%) with IHH the MRI was conspicuous. The typical MRI changes are: empty sella, optic nerve sheath enlargement and reversal of optic nerve head (Fig. 3). In four patients, the MRI showed pathologies which did not explain the clinical
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finding. Two of the four patients (50%) presented white matter lesions of the corpus callosum suggesting an underlying demyelination disease such as MS but without any clinical correlation. In these patients, no MRI findings indicating presence of optic
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neuritis were obvious. Thus, these patients had probably the so-called “radiologically isolated syndrome” (RIS), which is an incidentally discovered, clinically silent disease
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state of MS. In both patients, a migraine was one possible differential diagnosis due to their clinical presentations. The other two patients presented suspected signal inhomogeneity of the pituitary gland but without any clinical, laboratory and/or imaging evidence of a pituitary microadenoma. In these patients, the reason for the
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acute vision impairment remained unclear. In all patients (10 out of 10 patients) with confirmed autoimmune disease, MRI revealed pathological findings which included
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white matter lesions, optic neuritis or transverse myelitis.
Correlation of the clinical findings with patients’ age and sex
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Only 20% of the patients in our collective were younger than 7 years. In younger patients with acute visual impairment three main differential diagnoses should be considered: tumour, infection and IHH. Interestingly, we did not find any infectious causes in patients younger than 5 years. In patients older than 7 years, the cause for visual disturbances often remained unclear. Other causes in decreasing incidence were: infection, migraine, autoimmune disease and neoplasm.
ACCEPTED MANUSCRIPT Overall, gender distribution of our collective was balanced. Regarding the differential diagnosis, the gender distribution was most remarkable in the group of autoimmune diseases showing a female predominance (80 %). A slight predominance of male
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patients was apparent in children with IHH (4 male to one female patient).
Correlation between pathological MRI findings and patient’s age
Younger children were more prone to having pathological findings on MRI. Newborn
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babies were not included.
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Discussion
Acute vision impairment in children requires a quick diagnostic approach. Unfortunately, children may not present unless they experience significant impairment of vision. In very young children, parents’ awareness for the behavioral
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symptoms of visually impaired children could help recognizing the condition at an early stage. The child might show an exceptional delay of developing skills, which might show in everyday situations. For instance, the child might be inhibited in
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coordinately reaching and transferring objects such as toy blocks or a spoon. The
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later the vision impairment is noticed, the lower is the chance for recovery. Therefore, a favourable outcome depends on a fast diagnosis. Consequently, vision loss is an emergency situation and MRI examination should be performed within the first 24 hours after the clinical manifestation of symptoms. Be aware that “acute” visual impairment can be a misleading description in children. A systematic approach must follow. First, an ophthalmological and/or traumatic cause must be ruled out. Traumatic reasons are known to be the most frequent cause of visual impairment in childhood3.
ACCEPTED MANUSCRIPT In our retrospective evaluation, only children with non-traumatic visual disturbance were included. These consist of different organic and functional disturbances. In addition, the clinical assessment of children is more challenging due to the lack of cooperation. Therefore, MRI plays an important role in the differential diagnosis.
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In our study, gender distribution was balanced. Most of the 95 children with acute visual impairment (80%) were older than 7 years with predominance in children older than 13 years (46%). Acute vision impairment was relatively rare in younger patients
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(only 20% of the patients were younger than 7 years).
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While in 77% of our patients the cause of vision impairment could be determined, in 23% the symptoms remained unclear.
As reported before, psychogenic visual disturbances including hysterical blindness, functional vision impairment, psychogenic amaurosis (conversion phenomenon with headaches, which can simulate migraine) are common in school-age children4. In our
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collective, psychogenic disorders were present in only 4 of the 95 patients (5%) and were therefore less common than suspected. Yet, in almost a quarter of the patients (23%) the cause of the visual disturbances remained unclear due to reasons
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mentioned above; therefore, it is to be assumed that the incidence of psychogenic
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disorders could have been much higher. This theory is supported by the fact that younger children were more prone to having pathological findings on MRI, whereas in older children the cause often remained unclear.
As we hypothesized, one common reason for acute vision impairment in childhood was infectious causes, which were present in 16% of the patients. In this group, patients were usually older than 7 years. 3 patients suffered from sinusitis of the sphenoid sinus (20%), 5 patients had optic nerve neuritis (33%), and the remaining 7 patients had other infectious reasons such as orbital phlegmon, varicella zoster
ACCEPTED MANUSCRIPT meningoencephalitis, mycoplasma encephalitis, enterovirus encephalitis. The relation between acute sphenoid sinusitis and painless vision loss was reported by Reynolds et al.5. According to the authors of this case report, the second most common symptom in acute sinusitis is visual disturbance due to the very close anatomical
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relation to the adjacent cranial nerves II – VI. They emphasised that concerning patients with acute vision loss presenting to the emergency department a sinusitis of the sphenoid sinus has to be considered.
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Optic nerve neuritis can be caused by different disease processes, which will all lead to an acute inflammatory demyelination of the optic nerve, resulting in rapid,
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progressive, painful, monocular vision impairment3. According to Patel et al., 15% to 20% of the patients with optic nerve neuritis will later develop multiple sclerosis3. In 17 out of 95 children (18%), optic nerve neuritis was responsible for visual disturbances. In 5 out of 17 patients (29%), the optic nerve neuritis was due to
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infection, in 4 out of 17 patients (24%) due to autoimmune disease such as multiple sclerosis. In 8 out of 17 cases (47%), the optic nerve neuritis remained unclear. Regarding these patients, optic neuritis could have been the first manifestation of a
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future autoimmune disease, such as MS or NMO, but long term follow-ups are missing in these cases.
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The most common cause reported in previous literature on transient vision impairment in children is migraine headaches defined as a fully reversible monocular visual
disturbance,
associated
with
migraine
headache
and
a
normal
neuroophthalmologic examination between the attacks3. In our collective, 12% of the patients suffered from migraine headache with visual aura. In 11% of the patients, an underlying autoimmune disease was responsible for the vision impairment with a female predominance (80%). Autoimmune diseases included acute disseminated encephalomyelitis, MS or NMO, all of them resulting in
ACCEPTED MANUSCRIPT a demyelination of the cerebral nerve system, but the incidence might have been higher if a long term follow-up had been performed. In the case of intracranial tumours, visual impairment can be caused by compression of the visual pathways (for example, if a craniopharyngeoma involves the optic tracts,
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chiasm, or nerves) or be secondary to an increased intracranial pressure (as in the case of posterior fossa tumours). In our collective, 8 out of 95 patients (8 %) presented vision loss, i.e. impairment secondary to a neoplastic disease; which
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included two medulloblastomas, one rhabdomyosarcoma of the orbit, one choriocarcinoma, one craniopharyngioma, one germinoma, one optic glioma, and
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one pituitary macroadenoma. Ophthalmic complications of childhood due to medulloblastoma have been reported in 66% of the children, and patients usually present with diplopia6. Rhabdomyosarcoma involves primarily the orbit, resulting in unilateral proptosis, swelling, and restricted ocular motility7. Prieto et al. reported
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vision impairment/loss in 69% of the patients with craniopharyngiomas prior to surgery8. Visual impairment is reported in up to 54% of patients with optic gliomas at presentation9. Optic nerve glioma or visual pathway gliomas involving the optic nerve,
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chiasm, or optic tract are very typical for neurofibromatosis type 110. This should be considered for differential diagnosis in this group of patients.
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5 out of 95 children suffered from IIH. All but one patient with IHH were male (80%); 2 out of 5 patients were younger than 5 years old. In patients with IHH, visual impairment or blindness occurs as an initial symptom in severe cases. The speed of symptom development is variable, but severely or rapidly progressive vision impairment due to high-grade papilledema, macular oedema, and venous sinus thrombosis has been reported before2, 11. MRI helps to rule out tumours, meningeal infiltration and cerebral venous sinus thrombosis.
ACCEPTED MANUSCRIPT 4% out of the patients had orthostatic hypotension, most of them were female (75%), and all patients were older than 7 years. Temporal arteritis, which is the most frequent cause of vision impairment in adults, was not a cause in our group of patients. In the existing literature, only 11 cases of 13
. None of our patients
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temporal arteritis in children have been documented12,
suffered from occipital lobe seizures, a rare cause for visual disturbances14. Moreover, various drugs should be included in the differential diagnosis of visual
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disorders such as sildenafil, anticholinergics, antibiotics (linezolid), immune modulators (cyclosporine, tacrolimus, inflinximab) resulting in an optic neuropathy
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with acute vision impairment15. Despite the absence in our collective, there are still some important symptoms along with acute loss of vision which the reader should be aware of. Some metabolic disorders (acute metabolic crisis in methylmalonic academia and propionic academia) may trigger visual loss16. Another metabolic
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disorder is the ornithine transcarbamylase deficiency which might be accompanied by acute reversible cortical blindness17 as well as Vitamin B12 deficiency18. Acute lymphoblastic leukemia may come along with a rapidly enlarging and vision-
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threatening orbital mass19.
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On the one hand, given the large spectrum of neurological disorders resulting in vision impairment, the challenge for the paediatric neurologist and/or ophthalmologist is to recognize acute life threatening causes such as hydrocephalus as early as possible. On the other hand, they should avoid unnecessary investigations and treatment procedures. MRI is the imaging modality of choice due to the fact that it serves to rule out neurological causes. As has been previously reported in the literature, imaging techniques, especially MRI studies, are valuable tools for the clinician attempting to distinguish between causes of visual loss1. However, the
ACCEPTED MANUSCRIPT incidence of pathological MRI findings in children with vision loss has not been fully reported in the literature before. In our sample, MRI could determine the cause of visual impairment in 34 out of 95 patients. In 4 patients with functional visual disturbance, MRI findings were abnormal but unrelated to the vision impairment.
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Nearly one third of the patients with abnormal MRI showed abnormalities being suggestive of an autoimmune disease, along with a demyelination process such as MS, NMO and optic neuritis, which correlates with the findings in the existing
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literature that described pathologic enhancement in up to 95% of cases of acute optic neuritis20. In the final review of longitudinal data from the Optic Neuritis Treatment
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Trial (ONTT), 25% of patients without lesions on MRI developed MS at the age of 15, while 72% of patients with one or more brain lesions developed clinically definite MS at 15 years of age21. Compared with idiopathic demyelinating optic neuritis or optic neuritis associated with MS, imaging findings in NMO more commonly include
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bilateral optic nerve enlargement and enhancement1, which was also present in our patients. In patients with optic neuritis, the MRI showed abnormalities such as swelling and enhancement of the optic nerve in 7 out of 17 of our patients (41%).
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The second most common MRI finding, especially in patients older than 13 years of age, was a neoplasm, that was visible in all cases with MRI, as has been previously
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described in the literature1.
Almost all patients (4 out of 5 patients) with IHH, MRI revealed a conspicious empty sella or swelling of the optic nerve. Mallery et al. recommended in cases of suspected pseudotumour cerebri the performance of MRI/MR venous time of flight angiographie to rule out an intracranial lesion or venous sinus thrombosis. In their study, MRI could demonstrate several common MRI findings including dilated optic nerve sheaths, an “empty sella” and/ or narrowing of one or both transverse sinuses1.
ACCEPTED MANUSCRIPT Therefore, upon suspicion of an underlying cause such as neoplasm, autoimmune disease, infectious disease and IHH in paediatric patients with acute non-traumatic vision impairment a MRI study is highly recommended. Furthermore, MRI should always be performed in younger children (< 5 years), because visual impairment,
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although less common (only 7% of the patients), showed a higher percentage of abnormal findings (71%). In comparison, in the age category of 5 – 7 year-olds, in 50% of the cases the MRI revealed abnormal findings; in the group of school-age
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children, MRI was usually normal (78%), and during puberty MRI was abnormal in 45.5% of the patients.
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In order to get an understanding of the issue of vision impairment in children we would recommend a systematic approach: First, the children should be seen by a specialist pediatrician and a specialist ophthalmologist for ruling out any traumatic or ophthalmological causes such as astigmatism that may cause the vision impairment.
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Then, MRI examination should be performed within 24 hours. The MRI protocol should include a standard protocol for brain examination including axial T2-weighted sequence, axial FLAIR sequence, T2*- and Diffusion weighted images. Axial T1-
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weighted spin echo sequences should be performed before and after intravenous application of a standard dose of Gd-DTPA. Further, for the orbit examination coronal
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T2w SPIR sequence and T1w sequence after contrast agent with FATSAT and 3 mm slice thickness should be added to the protocol. By combining both examinations in one session, we are able to save time, contrast agent and time under anesthesia in younger children. In children older than 7 years and inconspicuous MRI, a follow up MRI should be performed when the clinical symptoms persist or recur so as to rule out chronic inflammatory disorder. Figure 4 shows a diagnostic algorithm for the evaluation of children with acute vision impairment.
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Limitation The limitation of this study is its retrospective character. Therefore, a consistent clinical documentation of symptoms is missing. Regarding the evaluated data, it
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remained unclear whether the vision loss was uni- or bilateral. However, this would be an interesting topic for further evaluation and for comparison with MRI findings for both groups. Further, in a prospective study, follow-up visits could be terminated for
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and the causes remained also unclear.
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patients with unexplained vision impairment, as most of those patients dropped out
Conclusion
When faced with a child presenting with an acute visual impairment, the paediatrician should first keep in mind that, in the lack of a traumatic cause a MRI can be very
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helpful, since it rules out most neurological causes. In our sample, MRI helped to differentiate between neurological and psychological causes in one third of the children.
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Second, beyond the newborn period; in children without previous history of trauma, the most common cause of acute vision impairment was an infectious disease,
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followed by an autoimmune disease, tumours and intracranial hypertension. Therefore, MRI is highly recommended, especially in the case of children younger than 5 years of whom clinical assessment can be difficult. Third, an initial normal MRI imaging may not exclude early stages of neurodegenerative disorders or autoimmune diseases. Furthermore, without thin slices dedicated to the orbits, one cannot rule out optic neuropathy. Fourth, while neuroimaging plays a key role in elucidating the cause of acute visual impairment in children, it is, however, of note that the final diagnosis is a combination
ACCEPTED MANUSCRIPT of history and examination findings, especially concerning patients for whom a
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psychological cause should be considered.
ACCEPTED MANUSCRIPT Literature
1. Mallery RM, Prasad S. Neuroimaging of the afferent visual system. Semin Neurol. 2012; 32:273-319.
options. Indian J Ophthalmol. 2014; 62:996-998.
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2. Dave SB, Subramanian PS. Pseudotumor cerebri: an update on treatment
3. Patel KN. Acute vision loss. Clin Pediatr Emerg Med. 2010; 11: 137–142.
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4. Doummar D, Roussat B, Pelosse B, Le Pointe HD, Iba-Zizen M, Roubergue A, Rodriguez D, de Villemeur TB. Management of acute visual loss in children.
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[Article in French] Arch Pediatr. 2004; 11:1384-1388.
5. Reynolds SC, Evans EM. Acute sphenoid sinusitis induced blindness: a case report. J Emerg Med. 2012; 43: 123-124.
6. Cassidy L, Stirling R, May K, Picton S, Doran R. Ophthalmic complications of
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childhood medulloblastoma. Med Pediatr Oncol. 2000; 34:43-47. 7. Breen LA, Kline LB, Hart WM Jr, Burde RM. Rhabdomyosarcoma causing
188.
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rapid bilateral visual loss in children. J Clin Neuroophthalmol. 1984; 4:185-
8. Prieto R, Pascual JM, Barrios L. Optic chiasm distortions caused by
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craniopharyngiomas: clinical and magnetic resonance imaging correlation and influence on visual outcome. World Neurosurg. 2015; 83:500-529.
9. Greenwell TH, Anderson PJ, Madge SK, Selva D, David DJ. Long-term visual outcomes in patients with orbitotemporal neurofibromatosis. Clin Experiment Ophthalmol. 2014; 42:266-270. 10. Listernick R, Charrow J, Greenwald MJ, Esterly NB. Optic gliomas in children with neurofibromatosis type 1. J Pediatr. 1989; 114:788-792. 11. Friedman DI. Pseudotumor cerebri. Neurol Clin. 2004; 22: 99-131.
ACCEPTED MANUSCRIPT 12. Vortman M, Schnieder I. Acute monocular visual loss. Emerg Med Clin North Am. 2008; 26:73-96. 13. Melachrinou M, Andonopoulous AP. Juvenile temporal arteritis. In Orphanet. Available
at
http://www.orpha.net/data/patho/GB/uk-juvenile-temporal-
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arteritis.pdf. 2005. Accessed 4/2010.
14. Shahar E, Barak S. Favorable outcome of epileptic blindness in children. J Child Neurol. 2003; 18:12-16.
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15. Kerrison JB. Optic neuropathies caused by toxins and adverse drug reactions. Ophthalmol Clin North Am. 2004; 17:481-488.
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16. Alvarez L, Jameson E, Parry NR, Lloyd C, Ashworth JL. Optic neuropathy in methylmalonic acidemia and propionic academia. Br J Ophthalmol. 2016; 100: 98-104.
17. Prasun P, Altinok D, Misra VK. Ornithine transcarbamylase deficiency
782-785.
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presenting with acute reversible cortical blindness. J Child Neurol. 2015; 30:
18. Jalil A, Usmani HA, Khan MI, Blakely EL, Taylor RW, Vassallo G, Ashworth J.
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Bilateral paediatric optic neuropathy precipitated by vitamin B12 deficiency and a novel mitochondrial DNA mutation. Int Ophthalmol. 2013; 33: 687-690.
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19. Vrcek I, Finnerty K, Ford P, Hogan RN, Mancini R. Relapsing acute lymphoblastic leukemia presenting with a rapidly enlarging and visionthreatening orbital mass. Int Ophthalmol. 2015; 35: 257-260.
20. Fazzone HE, Lefton DR, Kupersmith MJ. Optic neuritis: correlation of pain and magnetic resonance imaging. Ophthalmology. 2003; 110:1646–1649. 21. Optic Neuritis Study Group. Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial follow-up. Arch Neurol. 2008; 65:727–732.
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Figure 1: Typical MRI findings in a female patient with multiple sclerosis (MS). Cerebral MRI shows multiple white matter lesions (arrows) involving the corpus
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callosum, subcortical U-fibres, temporal lobes and brainstem. Contrast enhanced T1 weighted imaging shows an enhancing lesion (asterisk) on the left frontal lobe. The
space.
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Fig. 2: Female patient with craniopharyngioma.
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lesions met the McDonald criteria for MS due to their dissemination in time and
The tumour (asterisk) has a significant suprasellar component and involves both the suprasellar and intrasellar spaces. After Gadolinium an enhancing nodule is obvious (arrow). The tumour is mostly of cystic components. On CT images, note the typical
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calcifications within the tumour (ellipse).
Fig. 3: Male patient with idiopathic intracranial hypertension
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Note the bilateral optic disc swelling caused by increased cerebrospinal fluid pressure on the optic nerve (arrows) as well as a partially empty sella turcica
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(asterisk): The pituitary fossa is largely empty of tissue and replaced by CSF.
Figure 4: The figure illustrates a diagnostic algorithm for the evaluation of children with acute vision impairment.
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Percentage (%)
Neoplasm
8
8.4
Infectious causes
15
15.8
Idiopathic intracranial hypertension
5
Migraine
11
Orthostatic hypotension
4
Autoimmune disease
10
Optic nerve neuritis with unknown aetiology
8
Other reasons
12
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Differential diagnosis
5.3
11.6 4.2
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Unknown aetiology Total
10.5 8.4 12.6
22
23.2
95
100
Table 2: MRI findings in paediatric patients with acute vision impairment Percentage (%)
Normal Findings - total
57
60
Pathological Findings - total
38
40
Autoimmune disease
10
26
8
21
7
18
Optic Nerve Neuritis of unknown aetiology
2
5
Idiopathic intracranial hypertension
4
11
Other reasons
3
8
Incidental Findings
4
11
Neoplasm
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Incidence
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MRI Findings
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Infectious causes
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ACCEPTED MANUSCRIPT “Highlights” •
Cerebral MRI is highly recommended in children with acute vision impairment, especially in children younger than 5 years. MRI can rule out the causes for the visual disturbance in one third of the children.
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Reasons for the vision impairment can be found along all the afferent visual system.
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