Neurofibromatosis (NF) is a genetic disorder of the nervous system mainly affecting nerve cell formation and growth. Tumors often form on the nerves and though typically benign, these tumors sometimes become malignant.1
There are three types of neurofibromatosis:
Type 1 (NF1): Causes skin changes and deformed bones; usually starts in childhood; symptoms often present at birth; learning disabilities are present in at least 50% of individuals2
Type 2 (NF2): Causes hearing loss, ringing in the ears, and poor balance; symptoms often manifest in young adulthood2
Schwannomatosis: Causes intense pain; rarest type2
Electroneurodiagnostic (END) procedures are important in identifying and evaluating the neurological impacts of NF.
NF1
NF1 is the most common type of neurofibromatosis with an incidence of approximately 1 in 3,000 individuals.3 Approximately half of the cases are inherited.3 Diagnosis is typically made through clinical findings. Molecular genetic testing of NF1 is rarely required.
The hallmarks of NF1 are multiple café-au-lait macules and multiple cutaneous neurofibromas.About half of people with NF1 also have plexiform neurofibromas, which unlike benign cutaneous neurofibromas, may become cancerous, developing into a malignant peripheral nerve sheath tumor (MPNST).2
Serious though less common NF1 issues include optic nerve and other central nervous system gliomas, scoliosis, tibial dysplasia and vasculopathy.2
The mean age of death for people NF1 is 54.4 years and the median age 59, below the general population ages of 70.1 and 74 years, respectively.4 Because more serious optic and CNS issues can develop over time, ongoing monitoring and care is required throughout the lives of patients with NF1.
NF2
NF2 is an autosomal dominant disorder characterized by the development of multiple tumors involving the central nervous system.5 The pronounced cutaneous tumors of NF1 are less common in NF2.5 Patients typically present with tinnitus, hearing loss, and balance problems.5 The average age of onset is 18-24.5
Bilateral vestibular schwannomas are present in 90 to 95 percent of patients with NF2, while meningiomas are seen in about half of patients.3 Affected individuals may also develop schwannomas in different cranial and peripheral nerves.3
Though NF2 is considered an adult-onset disease, it may be underrecognized in children. Children who present with skin tumors, ocular issues (e.g., retinal hamartoma, thickened optic nerves) or mononeuropathies (e.g., persistent facial palsy or hand/foot drop) should be evaluated for the disease.3
The NF2 patient care team includes oncologists, ophthalmologists, geneticists, nurse practitioners and neurology professionals including neurologists, neuroradiologists, neurosurgeons and neurodiagnostic techs.
Electroneurodiagnostics: Contributions to NF Care
With both optical and auditory abnormalities and complications occurring in both NF1 and NF2, electroneurodiagnostic exams including visual and auditory evoked potentials are critical assessment and surveillance tools.
Visual evoked potentials (VEP)
The use of VEP may indicate abnormalities in the absence of clinical symptoms. A study of 39 adult patients with NF1 reported that more than half (51.3%) had abnormal VEPs, even though no clinical manifestations were previously reported.6 Another study of children with NF1 reported abnormal findings in at least one of the evoked potentials (particularly visual and auditory) for two-thirds of the study participants though no clinical signs of impairment were noted.7
Optic pathway glioma (OPG) is the most common brain tumor in children with NF1, occurring in 15%–20% of patients.8VEP has high sensitivity (90%–100%) in identifying OPGs but moderate specificity (60%–69%).8 It has not shown utility in distinguishing symptomatic from asymptomatic OPGs.
Another study examined children with and without NF1 who were affected by optic pathway low-grade gliomas (OPLGG). Full-field transient pattern-reversal visually evoked potentials (PRVEP) with 15’ and 60’ check sizes demonstrated reduced amplitude and delayed latencies in patients with OPLGG with and without NF1.9 Visual dysfunction was identified in two-thirds of the study participants.9
Without reliable clinical indicators to predict the development of symptomatic NF1-OPG, careful surveillance for early signs of vision loss is important. Subclinical evidence of visual loss may be useful in expediting treatment before optic atrophy is otherwise detected. VEP’s ability to predict visual impairment sufficiently to affect treatment decisions, though, is an area of ongoing study.
Auditory evoked potentials (AEP)
NF2 patients are susceptible to cochlear nerve function loss due to growth and/or removal of bilateral vestibular schwannomas.10 Patients affected with hearing loss or damage may be candidates for auditory brainstem implants (ABIs). AEP monitoring helps the surgeon identify the optimal position of the electrode in the cochlear nucleus.11 Implant function can first be checked by the stimulus artifact,11then closer analysis of AEP latencies helps guide placement of the ABI in an optimal location.12 No potentials should occur later than 5ms. AEPs are deployed because anatomical landmarks alone may not provide sufficient guidance for good placement.11
The Future of NF Care
Currently, there is no standard treatment approach for patients with NF. As a complex genetic condition that affects individuals differently, NF patients will likely benefit from advances in genetic research and genomic medicine. Electroneurodiagnostic testing can provide insights into the current and future status of patients with NF, particularly when clinical symptoms are not yet apparent or reported. The neurodiagnostic team is an important contributor to creating treatment paths for people living with the disease.
LifeSync Neuro is a leading provider of neurodiagnostic and neuromonitoring products that deliver patient comfort, excellent signal quality and accurate test results. For more information, visit the LifeSync Neuro website or call 1-800-328-5544 to request more information or a product catalog.
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References
1. https://medlineplus.gov/neurofibromatosis.html
2 Evans DG, Howard E, Giblin C, et al. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A 2010; 152A:327.
3. Rasmussen SA, Yang Q, Friedman JM. Mortality in neurofibromatosis 1: an analysis using U.S. death certificates. Am J Hum Genet 2001; 68:1110.
4. Friedman JM, Adam MP, Ardinger HH, et. al. Neurofibromatosis 1. GeneReview. Seattle (WA): University of Washington, Seattle; 1993–2021. 1998 Oct 2[updated2019 Jun 6]; 1993–2021.
5. Tiwari R, Singh AK. Neurofibromatosis Type 2. StatPearls. Treasure Island (FL): StatPearls Publishing; Updated 2020 Aug 10.Available from: https://www.ncbi.nlm.nih.gov/books/NBK470350/
6. YerdelenD, Koc F, Durdu M, Karakas M. Electrophysiological findings in neurofibromatosis type Neurol Sci. 2011 Jul 15;306(1-2):42-8.
7.Ammendola A, Ciccone G, Ammendola E. Utility of multimodal evoked potentials study in neurofibromatosis type 1 of childhood. Pediatr Neurol. 2006 Apr;34(4):276-80.
8. de Blank PMK, Fisher MJ, Liu GT, et. al. Optic Pathway Gliomas in Neurofibromatosis Type 1: An Update: Surveillance, Treatment Indications, and Biomarkers of Vision. J Neuroophthalmol. 2017 Sep; 37 (Suppl 1): 523-532.
9.de Freitas Dotto P, Berezovsky A, Cappellano AM. Visual function assessed by visually evoked potentials in optic pathway low-grade gliomas with and without neurofibromatosis type 1. Doc Ophthalmol.2018 Jun;136(3):177-189.
10. Deep NL, Choudhury B, Roland JT. Auditory Brainstem Implantation: An Overview. J Neurol Surg B Skull Base.2019 Apr; 80(2): 203–208.
11. Frohne C, Matthies C, Lesinksi-Scheidat A, Battmer RD, Samil M, Lenarz T. Extensive monitoring during auditory brainstem implant surgery. J Laryngol Otol Suppl. 2000;(27):11-4.
12.Matthies C, Tomas S, Moshrefi M, Lesinksi-Scheidat A, et al. Auditory brainstem implants: current neurosurgical experiences and perspective. J Laryngol Otol Suppl. 2000;(27):32-6.