Cranial neuritis is a general term for diseases in which inflammation of the cranial nerves leads to nerve destruction or demyelination. It can affect a single cranial nerve or multiple cranial nerves simultaneously. The latter is called polyneuritis cranialis (PNC).
PNC is considered a rare subtype of Guillain-Barré syndrome (GBS). In the GBS classification proposed by Wakerley et al. in 2014, PNC is defined as presenting only with ocular motor disturbances and bulbar symptoms, without limb weakness or ataxia 1).
A literature review of PNC reported a median age of 40 years in 20 cases, with 75% being male 3). Facial weakness was present in 70%, and normal deep tendon reflexes in 50% 3). When cranial nerves involved in eye movement (III, IV, VI) are affected, diplopia and ophthalmoplegia become the main symptoms.
Cranial neuritis is a general term for inflammation of the cranial nerves. When a single cranial nerve is affected, it is called cranial neuritis; when multiple cranial nerves are affected simultaneously, it is called multiple cranial neuritis (polyneuritis cranialis). Multiple cranial neuritis is classified as a rare subtype of GBS.
The subjective symptoms of cranial neuritis vary depending on which cranial nerve is affected. The main symptoms are as follows.
Ocular motor disorders
Oculomotor nerve palsy (III): Downward and outward deviation of the eye, dilated pupil, and ptosis.
Trochlear nerve palsy (IV): Causes vertical diplopia or torsional diplopia.
Abducens nerve palsy (VI): Causes horizontal diplopia due to limited abduction.
Lower cranial nerve disorders
Facial nerve palsy (VII): Presents with facial asymmetry, incomplete eye closure, and taste disturbance. Severity is assessed using the House-Brackmann classification 2).
Hypoglossal nerve palsy (XII): Shows tongue atrophy, deviation, and fasciculations 1).
Bulbar palsy (IX, X): Causes dysphagia, hoarseness, and soft palate deviation.
In multiple cranial neuritis, deep tendon reflexes are often decreased or absent 1)3). If meningeal signs are present, it suggests an underlying meningitis.
The causes of cranial neuritis are diverse. The main causes are classified below.
| Category | Representative causes |
|---|---|
| Infectious | Varicella-zoster virus, EBV, Lyme disease, tuberculosis, syphilis, SARS-CoV-2 |
| Autoimmune | GBS/MFS, sarcoidosis, SLE, Behçet’s disease, MOG-AD |
| Neoplastic | Leptomeningeal tumor, metastatic tumor, immune checkpoint inhibitors |
| Vascular | Diabetes, aneurysm |
| Idiopathic | Idiopathic multiple cranial neuropathy, hypertrophic pachymeningitis |
Among infectious causes, Lyme disease (Borrelia burgdorferi infection) is important. Neuroborreliosis develops in 10–15% of untreated Lyme disease patients and presents with the triad of lymphocytic meningitis, cranial neuritis, and radiculitis 4).
Cranial neuritis after SARS-CoV-2 infection has also been reported. In two cases of multiple cranial neuritis predominantly involving the hypoglossal nerve after severe COVID-19 pneumonia, marked improvement was observed after IVIG administration 1). The mechanism is suggested to be immune-mediated rather than direct neural invasion 1).
In PNC as a subtype of GBS, serum anti-GQ1b IgG antibodies are detected in 47% of cases 3). The most common preceding infection is Mycoplasma pneumoniae 3).
A case of PNC in a 16-year-old after COVID-19 vaccination (BNT162b2) has also been reported 2). However, the risk of vaccine-related neurological complications is much lower than that of COVID-19 infection itself 2).
Multiple cases of cranial neuritis (especially multiple cranial neuritis) following SARS-CoV-2 infection have been reported 1)5). The pathogenesis is thought to be primarily an immune-mediated reaction after infection rather than direct viral invasion. Cases after COVID-19 vaccination have also been reported, but the risk is lower than that from infection itself 2).
The diagnosis of cranial neuritis combines clinical findings with imaging, cerebrospinal fluid analysis, and electrophysiological studies.
Contrast-enhanced MRI is the most important examination. In cranial neuritis, contrast enhancement of the affected cranial nerve is a characteristic finding. MRI sequences using CISS (constructive interference in steady state) can depict cranial nerves more clearly.
Key points for MRI acquisition are as follows:
If a vascular etiology is suspected, CTA, MRA, or catheter angiography should be added. CT is useful as an emergency screening tool.
Cerebrospinal fluid analysis via lumbar puncture is essential for identifying underlying diseases.
| Test | Main significance |
|---|---|
| Contrast-enhanced MRI | Enhancement of affected cranial nerves |
| Cerebrospinal fluid examination | Albuminocytologic dissociation, exclusion of infection |
| Nerve conduction study | Assessment of demyelination and axonal damage |
| Antibody testing | Detection of anti-ganglioside antibodies |
In nerve conduction studies, loss of F-waves is an important early sign of proximal demyelination2). Blink reflex testing evaluates abnormalities in R1 and R2 responses3).
Measurement of anti-ganglioside antibodies (anti-GM1, anti-GQ1b, anti-GD1a, etc.) is useful for diagnosing GBS subtypes3). However, a negative antibody test does not rule out PNC.
As part of the search for infectious causes, serological tests for Lyme disease, syphilis, anti-AQP4 antibodies, and anti-MOG antibodies are performed as appropriate.
Treatment of cranial neuritis is based on specific treatment of the underlying disease.
Before systemic steroid administration, it is essential to rule out infections such as hepatitis B.
Identification of the underlying cause and appropriate treatment can lead to improvement of neurological symptoms in many cases. In the GBS subtype PNC, many reports show marked improvement after IVIG administration 1)3). However, in cases with visual impairment, recovery of visual function may be incomplete 3).
The pathophysiology of cranial neuritis varies depending on the cause, but the main mechanisms include the following.
Demyelination is the destruction of the myelin sheath surrounding the axon of myelinated nerves. When the myelin sheath is destroyed, saltatory conduction becomes impossible, leading to nerve conduction impairment. In the GBS subtype PNC, the demyelinating type is predominant, and electrophysiologically, loss of F-waves, conduction block, and prolonged distal latency are observed 2)5). On the other hand, the axonal type is characterized by reduced amplitude of compound muscle action potentials 5).
In post-infectious cranial neuritis, molecular mimicry is an important pathology. Due to structural similarity between glycolipids carried by the preceding infectious pathogen and gangliosides present in the myelin sheath of cranial nerves, cross-reactive autoantibodies are produced 3).
The main anti-ganglioside antibodies detected in PNC are anti-GQ1b IgG (47%), followed by anti-GT1a and anti-GD1a IgG antibodies 3). These antibodies target the myelin sheath of cranial nerves and trigger complement-mediated demyelination.
The mechanism of cranial neuritis after COVID-19 is not fully understood.
De Gennaro et al. (2021) reported two cases of multiple cranial neuritis after severe COVID-19 pneumonia. In both cases, neurological symptoms appeared about one month after infection, and SARS-CoV-2 PCR tests had become negative. Since marked improvement was observed after IVIG administration, they concluded that post-infectious immune-mediated mechanisms, rather than direct neural invasion, were the main cause 1).
Candidate mechanisms are as follows 1).
Molecular mimicry is considered the main mechanism in post-infectious cranial neuritis. Structural similarity between pathogen glycolipids and gangliosides of the cranial nerve myelin leads to production of cross-reactive autoantibodies, triggering demyelination of cranial nerves3). The good response to IVIG also supports this immune-mediated mechanism1).
Manganotti et al. (2021) reported GBS/PNC complications in 5 COVID-19 patients. Four received IVIG (0.4 g/kg for 5 days) with improvement in neurological symptoms. Elevated CSF IL-8 was found in 3 cases, suggesting immune-mediated peripheral neuropathy associated with SARS-CoV-2 infection5).
Kulsirichawaroj et al. (2022) reported a case of a 16-year-old Thai woman who developed PNC 3 hours after the first dose of BNT162b2 mRNA vaccine. She presented with right-sided cranial nerve V, VII, IX, and X deficits, with absent F-waves and contrast enhancement of the right facial nerve. After IVIG, all symptoms except facial palsy recovered within 4 weeks2).
Li et al. (2023) reported a rare case of a 54-year-old man with PNC complicated by visual impairment. Serum anti-GM1 and anti-GD1a IgG antibodies were positive, and rapid neurological improvement occurred after IVIG. Visual recovery required additional steroid therapy, but complete recovery to 6/6 vision in both eyes was achieved after one month3). In a literature review of 32 cases of GBS combined with optic neuritis, poor visual prognosis was 47%, while neurological prognosis was generally favorable.
