Successful Management of Acute Streptococcal Meningoencephalitis Complicated by Bilateral Third-Nerve Palsies, Wall-Eyed Bilateral Internuclear Ophthalmoplegia, Blindness, and Deafness: Case Report Open Access

Streptococcal meningoencephalitis (SME) is a rare and frequently lethal acute inflammation of the central nervous system parenchyma, with involvement of meningeal structures. Meningoencephalitis due to Streptococcus pneumoniae may result in severe postinfection sequelae, with fatality rates of between 19 and 37%. SME occurs most commonly in association with head trauma, chronic sinusitis, and neurosurgical procedures [1].

In 1971, Lubow first coined the term wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) [2, 3]. WEBINO is a rare neuro-ophthalmological disorder, and most commonly occurs in demyelinating disease such as multiple sclerosis but may also occur in patients with cerebral inflammation or ischaemia [4, 5].

Bacterial meningoencephalitis (BME) is frequently associated with bacterial meningitis in both children and adults [6]. Nevertheless, direct extension of pneumococcal infection into the parenchyma of the central nervous system has been only rarely reported [6, 7]. Early diagnosis and antimicrobial intervention are essential for reducing mortality and disability associated with BME. While some case reports have demonstrated that S. pneumoniae may cause subdural abscesses, the underlying mechanism is poorly understood [1, 8]. The authors’ bedside assessment of saccadic velocity [9] was helpful in diagnosing a bedridden, visually and hearing impaired patient with WEBINO and bilateral third-nerve palsies.

The authors employed Multidisciplinary Teamwork (MDT) to diagnose and manage this patient. Specialists included Neurologists, Infectious Disease Physicians, Neurosurgeons, a Neuroradiologist, and a Neuro-Ophthalmologist. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000538821).

A previously well, 49-year-old Australian man presented to the authors’ Tertiary Referral Teaching Hospital with sudden onset severe headache, fevers, neck stiffness, agitation, and reduced consciousness. There was no significant past medical or surgical history, and the patient was on no regular medications.

At lumbar puncture, CSF opening pressure was greater than 35 cm H₂O, with CSF protein significantly elevated at 4.38 g/L (normal range [NR] 0.15–0.45 g/L). CSF cell count demonstrated red cells (11 × 10⁶/L). CSF glucose was 4.4 mmol/L (NR-2.5–3.5). The CSF polymorphonuclear cells were elevated, at 69 × 10⁶/L (NR <2 × 10⁶/L). The white cell count was 23.9 (NR: 4.0–11.0 × 10⁹/L), and C-reactive protein was 186 (NR <5 mg/L).

CSF streptococcal antigen and PCR were both positive. CSF cultures confirmed a growth of pan-sensitive S. pneumoniae.

The patient was immunocompetent, with a normal immunodeficiency screen. In particular, human immunodeficiency virus, and hepatitis B and C viruses were not detected. QuantiFERON Gold and Chemiluminescent Microparticle Immunoassay (previously FTA-ABS) were negative, excluding TB and Lues Disease, respectively.

Transthoracic echocardiography revealed normal left ventricular function, with no valvular or septal abnormalities suggestive of infective endocarditis. Non-contrast CT Brain demonstrated gross cerebral oedema, necessitating placement of an External Ventricular Drain by the attending Neurosurgeons (R.C. and J.P.). The MRI Brain diffusion-weighted axial sequence demonstrated multiple foci of restricted diffusion and cytotoxic oedema in the cerebral cortex, Sylvian fissures, midbrain, and basal cisterns, with pus in the occipital horns of both lateral ventricles (Fig. 1a). Leptomeningeal enhancement at the base of the brain involving cranial nerves was present in the post contrast sagittal T2 FLAIR sequence (Fig. 1b). Further, there were multiple scattered foci of diffusion restriction in the supratentorial brain and cerebellum, representing acute infarctions.

MRI changes were noted bilaterally in the Medial Longitudinal Fasciculi (MLF). There was enhancement in the interpeduncular cistern, and of both oculomotor nerves, consistent with localised neuritis (Fig. 1c).

Intravenous benzylpenicillin 2.4 g four times daily and linezolid 600 mg twice daily were commenced. However, as the admission day of the patient progressed, his level of consciousness deteriorated to GCS 3, with fixed and dilated pupils. The patient was intubated and underwent emergent external ventricular drain insertion.

The neuro-ophthalmological examination at this point demonstrated the patient’s visual acuity as hand movements in the right eye and light perception in the left eye. The patient had a complete right upper lid ptosis, and a marked but incomplete left upper lid ptosis, with the elevating saccadic velocity of the left upper lid being reduced.

Both eyes were abducted in the primary position (Fig. 2), a clinical appearance consistent with both bilateral third-nerve palsies and WEBINO. Consistent with both bilateral internuclear ophthalmoplegia (INO) and bilateral third-nerve palsies, slow adducting saccades were readily identified.

Bilateral abducting nystagmus of both contralateral eyes was observed, consistent the patient’s bilateral INO. The abducting saccadic velocity of each eye was normal, thereby excluding bilateral sixth nerve palsies and bilateral horizontal gaze palsies. While the bilateral abducting nystagmus could potentially have been associated with the gaze-paretic nystagmus of bilateral sixth nerve palsies and bilateral horizontal gaze palsies, these were excluded because of the normal bilateral abducting saccadic velocities.

Ductions, versions, and vestibulo-ocular testing demonstrated no vertical eye movements. Further, as there was no evidence, on attempted downgaze, of intorsion of the depressing eye, bilateral fourth nerve palsies were also diagnosed.

Bilateral pupil-involving third-nerve palsies were present, with complete loss of vertical movements, in association with bilateral severe ptosis and widely dilated pupils that were non-reactive to light. A complete right lower motor neuron facial nerve palsy (House-Brackmann grade 6/6) was present. Moderate bilateral deafness was present.

Upper motor neuron signs were also present, including bilateral upper and lower limb hyperreflexia, and extensor plantar responses, reflecting the inflammatory changes within the brainstem. The patient was referred to definitive specialist rehabilitation. On re-examination at week 14, substantial improvement in the patient’s neurological and neuro-ophthalmological findings had occurred. Right visual acuity had improved from hand movement to 6/18 and left visual acuity from light perception to 6/12. The patient’s bilateral ptosis had resolved, and the velocity of the left upper lid elevating saccade had normalised. Ocular rotations were now full, but slow adducting saccades were still present in the left eye. Bilateral abducting nystagmus persisted. Pupillary areflexia to light was still present, but light-near dissociation was now present. The right lower motor neuron facial palsy had improved to House-Brackmann 4/6. Confrontation visual field testing at 14 weeks demonstrated dense bitemporal hemianopias with variable nasal field loss to 5–20°. By 24 weeks, the patient’s visual acuity had improved to 6/6 in both eyes, but the visual fields demonstrated persisting tunnel vision (Fig. 3a). Further systemic rehabilitation is continuing.

The term WEBINO was considered by Lubow to be secondary to midbrain lesions that involved the medial rectus subnuclei of the Oculomotor nerve and the two MLFs [2]. The MLF changes in this patient’s MRI were consistent with the recently reported high resolution MRI studies out of India [4]. Nevertheless, despite this Indian study and others, there is still no clear pathophysiological explanation for exotropia in WEBINO [2, 10].

Demyelinating disease is the most common cause of bilateral INO. However, brainstem stroke may present with unilateral INO, and WEBINO may also be associated with inflammation or ischaemia [4, 5]. Consistent with the ischaemic mechanism, a recent literature review of WEBINO revealed 14 cases caused by stroke, of which six involved the pons, five involved the midbrain, and three affected both areas [5]. On the other hand, several alternative theories for the pathophysiology of WEBINO have been suggested. Preexisting latent divergent squint, or an imbalance of the two eyes in the yaw plane resulting from interruption of ascending otolithic projections, has been proposed [10]. Studies performed in mice showed that WEBINO may be associated with damage to the motor neurons found within the MLF, causing wide-angled exotropia [2]. Despite these studies, there still remains no clear pathophysiological explanation for exotropia in WEBINO.

Cranial nerve palsies are reported to occur in 4–11% of cases of BME and are associated with a poor prognosis. The most affected cranial nerves are the oculomotor, abducens, facial, and trochlear nerves. Fortunately, in this patient the abducens nerve was spared.

After 40 days of high dose intravenous benzylpenicillin, the infectious diseases team recommended the addition of intravenous corticosteroids, consistent with the appropriate management of the inflammatory component of meningoencephalitis affecting the extra-axial intracranial cranial nerves [3]. Gradual improvement of the patient’s symptoms and signs followed. It is noteworthy that the systematic review performed by Brouwer et al. [3] in 2015 revealed that corticosteroids reduced mortality in S. pneumoniae meningitis (RR: 0.84, 95% CI: 0.72–0.98), although not in Haemophilus influenzae or Neisseria meningitidis meningitis.

The lack of vertical movement of both eyes was consistent with the patient’s bilateral third-nerve palsies and bilateral fourth nerve palsies. The current report has documented a case of acute SME complicated by bilateral pupil-involving third-nerve palsies, WEBINO, bilateral blindness, bilateral deafness, a right lower motor neuron facial palsy, and upper motor neuron signs. It appears to be the first reported case of SME with this rare collection of neuro-ophthalmological abnormalities. Fortunately, administration of the necessary antibiotic to treat the patient’s SME, along with corticosteroids, contributed to this patient’s marked neurological and neuro-ophthalmological improvement.

Ethical approval is not required for this study in accordance with local or national guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

The authors report there are no competing interests to declare.

The authors received no financial support for the research, authorship, and/or publication of this article. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Dr. Amitouj Sidhu, Dr. Thomas Riisfeldt, and Professor Ian Francis assessed and managed the patient. They also, with Dr. Charles Walker, reviewed the medical records, wrote the draft of the case report, and revised intellectual content. Mr. Peter Tweedie, Dr. Natasha Gerbis, Dr. Emily Sutherland, Professor Neil Simon, Dr. Lucy Somerville, Dr. Ross Bradbury, Dr. Raymond Cook, Dr. Jonathon Parkinson, and Dr. Robert Goetti clinically managed the patient and critically revised the manuscript and intellectual content.

All data generated or analysed during this study are included in this article and supporting images. Further enquiries can be directed to the corresponding author.