Case Report:
A 26-year-old male presented with a 3-year history of dysphagia, along with intermittent neck stiffness, giddiness, and neck pain persisting over the past 2 years.
Initial investigations included MRI brain and spine, which revealed:
Posterior fossa: A solid-cystic lesion at the level of the fourth ventricle with proximal
hydrocephalus, suggestive of an ependymoma.
Cerebellopontine angles: Bilateral heterogeneous lesions with internal auditory canal
(IAC) extension, likely vestibular schwannomas.
Cervical spine: T2-weighted/STIR hyperintensity at C2-C3 level consistent with cord edema.
Thoracic spine: STIR hyperintense lesion at the D1-D2 level in the left paravertebral region, possibly a neurogenic tumor.
Cauda equina: Multiple small T2 hypointense lesions with homogeneous enhancement, consistent with schwannomas.
The patient’s initial presentation with hydrocephalus warranted urgent CSF diversion. A left ventriculoperitoneal (VP) shunt was placed and postoperative MRI suggested effective CSF decompression.
The patient was subsequently shifted to the ICU due to desaturation. A CT chest revealed multifocal scattered patchy consolidation, ground-glass opacities with ill defined centrilobular nodules in both lung fields, Prominent subcentimeter mediastinal lymphadenopathy was also noted.Recurrent aspiration prompted ENT and speech therapy evaluations which revealed bilateral vocal cord paralysis.
Following neurosurgical review, the patient underwent midline suboccipital craniectomy and total excision of the posterior fossa tumor with
tracheostomy. Postoperative biopsy confirmed posterior fossa ependymoma. The patient had a protracted hospital stay complicated by recurrent febrile episodes
with Blood and Et cultures growing Serratia marcescens and Stenotrophomonas maltophilus, and the patient responded to targeted intravenous antibiotics.
Due to recurrent aspiration and nutritional concerns, a PEG tube was placed following medical gastroenterology consultation The patient also received physiotherapy and rehabilitation throughout the hospital stay.
Follow-up contrast MRI of brain and spine showed:
* Suboccipital craniotomy changes with residual heterogeneous signal in the surgical bed (possible residual tumor vs post-procedural changes).
* Persistent bilateral vestibular schwannomas.
* No definitive new lesions in the spine.
Radiation oncologist opinion was obtained and Radiotherapy was deferred to allow for adequate recovery and rehabilitation.
The patient was clinically stabilized and transitioned from acute hospital care to a dedicated rehabilitation centre for ongoing multidisciplinary management.
Discussion
Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder characterized by the development of multiple benign tumors in the nervous system, particularly affecting the vestibulocochlear nerve. The hallmark of NF2 is the development of bilateral vestibular schwannomas, which often lead to hearing loss, tinnitus, and balance issues. Other common tumors associated with NF2 include meningiomas, gliomas, and ependymomas. Ophthalmological manifestations such as cataracts and retinal hamartomas are also prevalent. The condition typically manifests between the ages of 18 and 24, with most patients developing bilateral vestibular schwannomas by 30 years of age. Approximately 50% of cases are inherited from an affected parent, while the remainder result from de novo mutations.
The NF2 gene, located on chromosome 22q, encodes a tumor suppressor protein called merlin. It is involved in regulating cell proliferation, motility, and adhesion. Merlin exerts its effects by interacting with various signaling pathways, including the PI3K/Akt, Raf/MEK/ERK, and mTOR pathways. Loss of merlin function due to NF2 gene mutations leads to dysregulation of these pathways, promoting tumorigenesis.
Truncating mutations (nonsense and frameshift) are the most common germline events and are associated with more severe disease phenotypes. Missense mutations and large deletions are also observed and may correlate with milder clinical presentations.
Diagnosis of NF2 is based on clinical criteria, imaging studies, and genetic testing. Magnetic resonance imaging (MRI) is highly sensitive and can readily detect schwannomas, meningiomas, and gliomas. Genetic testing for mutations in the NF2 gene is available and can confirm the diagnosis.
The Children’s Tumor Foundation (CTF) and updated the diagnostic criteria of neurofibromatosis type 2 (NF2) and schwannomatosis (SWN)
A diagnosis of NF2 can be established if any one of the following conditions is met:
- Bilateral Vestibular Schwannomas (VS):
- Presence of VS on both sides of the body, confirmed by MRI.NINDS
- Pathogenic NF2 Variant in Multiple Tumors:
- Identification of the same disease-causing NF2 gene variant in at least
two different NF2-related tumors (e.g., schwannoma, meningioma, or
ependymoma).NINDS
- Identification of the same disease-causing NF2 gene variant in at least
- Combination of Clinical Criteria:
- Presence of either:
- Two major criteria, or
- One major and two minor criteria
- Presence of either:
Major Criteria:
- Unilateral vestibular schwannoma
- First-degree relative diagnosed with NF2
- Two or more meningiomas
- Pathogenic NF2 variant identified in blood or saliva
Minor Criteria:
- Ependymoma
- Schwannoma
- Juvenile cataract
- Retinal hamartoma
- Epiretinal membrane
Management of NF2 is multidisciplinary and depends on the size and location of tumors, as well as the presence and severity of symptoms. Treatment options include surgical removal of tumors, radiation therapy, and symptom management with medications.
The prognosis for individuals with NF2 varies. Factors such as early age at onset, the number and size of tumors, and the presence of certain genetic mutations can influence disease progression and outcomes. While there is currently no cure for NF2, ongoing research into targeted therapies holds promise for improving management and quality of life for affected individuals.
In summary, NF2 is a complex disorder requiring a comprehensive, multidisciplinary approach to management. Advancements in genetic testing and targeted therapies offer hope for improved outcomes. Ongoing research into the molecular mechanisms of NF2 will be instrumental in developing novel therapeutic strategies.
References
- Harrison’s Principles of Internal Medicine, 22th Edition.
- Children’s Tumor Foundation. (2022). Revised diagnostic criteria for NF2-related schwannomatosis, and SMARCB1/LZTR1-related schwannomatosis. https://www.ctf.org/wpcontent/uploads/2023/11/CTF_2022_DiagnosticCriteria.pdf
- https://pmc.ncbi.nlm.nih.gov/articles/PMC2708144/?utm_source=chatgpt.com “Neurofibromatosis type 2 (NF2): A clinical and molecular review PMC”
- https://pubmed.ncbi.nlm.nih.gov/23931824/?utm_source=chatgpt.com” Neurofibromatosis type 2 (NF2): diagnosis and management PubMed”
Dr. Madhumitha R M, MBBS,
DNB General Medicine Resident
Kauvery Hospital Chennai
Dr. Sivaram Kannan, MD (General Medicine), FRCP
Senior Consultant Internal Medicine
Kauvery Hospital Chennai
Dr. Ranganathan Jothi, MCh, DNB (Neuro Surgery),
Director of Neurosciences,
Kauvery Hospital, Chennai
Dr. S. Vadivel Kumaran
Senior Consultant Gastroenterologist
Kauvery Hospital Chennai
Dr. Preethi P, DLO, DNB(ENT), Consultant,
Department of ENT, Head and Neck Surgery
Kauvery Hospital, Chennai
