Neurology: A case report of anti-MA2 encephalitis with main complaints of vertigo, ptosis and red eye

Recently, a case report published in Neutology reported acute vestibular syndrome in a 48-year-old woman with breast cancer who was eventually confirmed to have anti-MA2-associated encephalitis
.

Although the initial diagnosis was vestibular neuritis elsewhere, as symptoms progressed, the patient had bilateral ptosis and marginal injections, and slowed vertical saccades, leading to a final diagnosis of midbrain injury

Recently, a case report published in Neutology reported acute vestibular syndrome in a 48-year-old woman with breast cancer who was eventually confirmed to have anti-MA2-associated encephalitis

A 48-year-old female patient was admitted with "spontaneous vertigo and nausea for 2 weeks"
.

The patient complains of persistent visual rotation regardless of the change in posture

A 48-year-old female patient was admitted with "spontaneous vertigo and nausea for 2 weeks"

Past history: Diagnosed 2 years ago with invasive lobular carcinoma of the right breast and underwent modified radical mastectomy followed by chemotherapy and tamoxifen

Physical examination: perilimbic lesions and ptosis in both eyes (Fig.

Questions to consider: 1.
Which findings do not support the diagnosis of vestibular neuritis? 2.
Which advanced vestibular function tests can help identify central versus peripheral involvement?

Questions to consider: 1.
Which findings do not support the diagnosis of vestibular neuritis? 2.
Which advanced vestibular function tests can help identify central versus peripheral involvement?

Vestibular neuritis is characterized by acute spontaneous vertigo, nausea/vomiting, and balance disturbance due to unilateral vestibular deafferents
.

Vestibular neuritis is characterized by acute spontaneous vertigo, nausea/vomiting, and balance disturbance due to unilateral vestibular deafferents
.

Vestibular neuritis is characterized by acute spontaneous vertigo, nausea/vomiting, and balance disturbance due to unilateral vestibular deafferents

The patient presented with spontaneous horizontal torsion nystagmus, a positive HITS test, spontaneous neural tube palsy, and a tendency to fall on the side of the lesion

Taking these factors into consideration, the physician performed a thorough vestibular evaluation of the patient

Questions to consider: 1.
How does a laboratory test change your differential diagnosis? 2.
Based on these findings, what is the localization of the lesion? 3.
What are the possible reasons for these findings? 4.
What will be your next inspection?

Questions to consider: 1.
How does a laboratory test change your differential diagnosis? 2.
Based on these findings, what is the localization of the lesion? 3.
What are the possible reasons for these findings? 4.
What will be your next inspection?

Abnormal HITS tests of the bilateral vertical neural canal make the diagnosis of vestibular neuritis the least likely
.

Conversely, impaired torsional VOR and reduced torsional fast phase combined with slowed vertical saccade and impaired convergence suggest that midbrain rostral lesions primarily involve the rostral mesenchymal nucleus of the medial longitudinal fascicle (RiMLF) and the interstitial nucleus of Cajal (Inc )

Abnormal HITS tests of the bilateral vertical neural canal make the diagnosis of vestibular neuritis the least likely

Excitatory burst neurons that generate vertical and torsional saccades are present within RiMLFs that project to ocular motor neurons of the levator muscle bilaterally but ipsilaterally to the ocular motor neurons of the hypotensive muscle

Several disorders involving the rostral midbrain exhibit vertical supranuclear eye movement abnormalities
.
The subacute attacks observed in this patient raise the suspicion of an inflammatory, infectious, or demyelinating disease involving the rostral midbrain, such as anti-MA2-associated encephalitis, viral rhomboencephalitis, Creutzfeldt-Jakob disease or Whipple disease
.
It can also be caused by neurodegenerative diseases such as progressive supranuclear ophthalmoplegia, Niemann-Pick type C, midbrain infarction, or even pineal tumors compressing the cranial midbrain tectum
.
The above information requires brain MRI and cerebrospinal fluid (CSF) analysis
.
Brain MRI and angiography were normal, and there were no obvious findings on orbital fat suppression images
.
Analysis of cerebrospinal fluid showed a cellularity rate of 114/mm~3 (75%) and a protein content of 69 mg/dL
.
Cerebrospinal fluid cytology and venereal disease research laboratory tests were negative
.
Serum anti-MA2 antibody was positive, and other paraneoplastic antibodies were negative
.
Serum was also negative for autoimmune and viral markers
.
Breast ultrasound, mammography, and CT of the chest, abdomen, and pelvis were all normal
.
18F-deoxyglucose positron emission tomography (FDG-PET) did not reveal any evidence of metastasis or tumor recurrence
.
The patient received intravenous methylprednisolone 1 g daily for 5 consecutive days, followed by intravenous tacrolimus 1 g daily for 1 month
.
The patient reported an improvement in dizziness and the ability to walk without support
.
Right-click nystagmus and HITS tests improved significantly, and the patient's ptosis and uveitis disappeared after 1 month
.

References: 1.
What is the diagnosis and prognosis?

References: 1.
What is the diagnosis and prognosis?

Patients with anti-MA2-related encephalitis showed slowed vertical beat, abnormal vertical semicircular canal HITS test, impaired torsional VOR, disappearance of torsional fast phase, and anterior uveitis
.

Patients with anti-MA2-related encephalitis showed slowed vertical beat, abnormal vertical semicircular canal HITS test, impaired torsional VOR, disappearance of torsional fast phase, and anterior uveitis
.

MA1 and MA2 are intracellular proteins expressed in the testis and brain, especially in the limbic and brainstem regions
.
Therefore, patients with anti-MA2-associated encephalitis may experience memory impairment, sleep disturbance, and abnormal eye movements
.
Most of these symptoms are associated with testicular tumors, but sometimes lung, breast, or ovarian cancer
.
Unlike other paraneoplastic syndromes that develop rapidly over 6–8 weeks, anti-MA2-associated encephalitis progresses slowly, complicating diagnosis
.
Rituxan, mycophenolate mofetil, and cyclophosphamide are more widely used for immunomodulation in paraneoplastic syndromes, although tacrolimus was chosen for this patient's economic status
.
Overall, the treatment of anti-MA2-related paraneoplastic syndromes is challenging because neurological deterioration can be observed in nearly half of patients
.
But in patients younger than 45 years, those with limited involvement of the limbic, brainstem, and cerebellar nervous systems, or those with a good tumor response, a favorable outcome is expected
.
Furthermore, since anti-MA2-related encephalitis is often accompanied by abnormal eye movements, analysis of eye movement function can aid in early detection, leading to favorable outcomes
.
Again, vertical gaze palsy was most prominent in this patient
.
Anti-MA2-related encephalitis with other eye movement abnormalities such as ptosis, vertical ophthalmoplegia, opsoclonus, nystagmus or nystagmus, and strabismus
.

MA1 and MA2 are intracellular proteins expressed in the testis and brain, especially in the limbic and brainstem regions
.
Therefore, patients with anti-MA2-associated encephalitis may experience memory impairment, sleep disturbance, and abnormal eye movements
.
Most of these symptoms are associated with testicular tumors, but sometimes lung, breast, or ovarian cancer
.
Unlike other paraneoplastic syndromes that develop rapidly over 6–8 weeks, anti-MA2-associated encephalitis progresses slowly, complicating diagnosis
.
Rituxan, mycophenolate mofetil, and cyclophosphamide are more widely used for immunomodulation in paraneoplastic syndromes, although tacrolimus was chosen for this patient's economic status
.
Overall, the treatment of anti-MA2-related paraneoplastic syndromes is challenging because neurological deterioration can be observed in nearly half of patients
.
But in patients younger than 45 years, those with limited involvement of the limbic, brainstem, and cerebellar nervous systems, or those with a good tumor response, a favorable outcome is expected
.
Furthermore, since anti-MA2-related encephalitis is often accompanied by abnormal eye movements, analysis of eye movement function can aid in early detection, leading to favorable outcomes
.
Again, vertical gaze palsy was most prominent in this patient
.
Anti-MA2-related encephalitis with other eye movement abnormalities such as ptosis, vertical ophthalmoplegia, opsoclonus, nystagmus or nystagmus, and strabismus
.

Acute unilateral peripheral vestibular lesions may have initially been speculated on the basis of horizontal nystagmus and abnormal HITS tests
.
However, red eye may be an inflammatory alarm and was not limited to vestibular afferents in our patient
.
Although patients present with neurological symptoms of unilateral peripheral vestibulopathy, other oculomotor manifestations should be adequately sought, especially those with atypical presentations
.

Acute unilateral peripheral vestibular lesions may have initially been speculated on the basis of horizontal nystagmus and abnormal HITS tests
.
However, red eye may be an inflammatory alarm and was not limited to vestibular afferents in our patient
.
Although patients present with neurological symptoms of unilateral peripheral vestibulopathy, other oculomotor manifestations should be adequately sought, especially those with atypical presentations
.

A combination of ocular inflammation and vestibular lesions may also raise suspicions about Cogan syndrome, an inflammatory disorder caused by autoantibodies to the cornea and inner ear
.
However, in Cogan syndrome, red eye is attributed to nonsyphilitic interstitial keratitis
.
In addition, the patient had no hearing loss, which is characteristic of Cogan syndrome
.
Not to mention the central oculomotor signs due to midbrain dysfunction, this case suggests the importance of detecting subtle signs of systemic inflammation in patients presenting with acute/subacute vestibular syndrome
.

A combination of ocular inflammation and vestibular lesions may also raise suspicions about Cogan syndrome, an inflammatory disorder caused by autoantibodies to the cornea and inner ear
.
However, in Cogan syndrome, red eye is attributed to nonsyphilitic interstitial keratitis
.
In addition, the patient had no hearing loss, which is characteristic of Cogan syndrome
.
Not to mention the central oculomotor signs due to midbrain dysfunction, this case suggests the importance of detecting subtle signs of systemic inflammation in patients presenting with acute/subacute vestibular syndrome
.

This patient showed no evidence of breast cancer recurrence
.
In fact, paraneoplastic syndromes may appear with tumor recurrence
.
This may be attributed to the limited diagnostic efficacy of traditional screening tests
.
Since the smallest breast tumor size detectable by mammography is 2.
1 mm, and the sensitivity of FDG-PET to detect breast tumors smaller than 2 cm is less than 50%, recurrence may be missed
.
Considering the mean tumor volume doubling time of 280 days for breast cancer, it is recommended that this patient have a breast MRI and mammogram every 6 months for at least 4 years
.

This patient showed no evidence of breast cancer recurrence
.
In fact, paraneoplastic syndromes may appear with tumor recurrence
.
This may be attributed to the limited diagnostic efficacy of traditional screening tests
.
Since the smallest breast tumor size detectable by mammography is 2.
1 mm, and the sensitivity of FDG-PET to detect breast tumors smaller than 2 cm is less than 50%, recurrence may be missed
.
Considering the mean tumor volume doubling time of 280 days for breast cancer, it is recommended that this patient have a breast MRI and mammogram every 6 months for at least 4 years
.

Source: Kim KT, Baek SH, Lee SU, Kim JB, Kim JS.
Clinical Reasoning: A 48-Year-Old Woman Presenting With Vertigo, Ptosis and Red Eyes [published online ahead of print, 2022 Feb 28].
Neurology.
2022;10.
1212/WNL.
0000000000200141.
doi:10.
1212/WNL.
0000000000200141

Source: Kim KT, Baek SH, Lee SU, Kim JB, Kim JS.
Clinical Reasoning: A 48-Year-Old Woman Presenting With Vertigo, Ptosis and Red Eyes [published online ahead of print, 2022 Feb 28].
Neurology.
2022;10.
1212/WNL.
0000000000200141.
doi:10.
1212/WNL.
0000000000200141 Kim KT, Baek SH, Lee SU, Kim JB, Kim JS.
Clinical Reasoning: A 48-Year-Old Woman Presenting With Vertigo, Ptosis and Red Eyes [published online ahead of print, 2022 February 28].
Neurology.
2022;10.
1212/WNL.
0000000000200141 .