malignant peripheral nerve sheath tumor (MPNST) has been reported. NF1 patients have a 7–13% lifetime risk of developing MPNST [25]. MPNSTs metastasize widely and carry a poor prognosis.

7.2.3.3  CNS Abnormality

Cognitive impairment, behavior problems, and epilepsy are well recognized in NF1 patients. Cognitive disability is the most common neurological symptom in NF1 patients [25–27].

Characteristically, the intelligent quotient (IQ) is in the low-average range and mental retardation (IQ < 70) is uncommon. Children with NF1 have specific learning difficulties that include visual spatial problems, impaired visual motor integration with language deficits, and disorder of executive function [26–28]. Attention-deficit hyperactivity disorder and poor socialization are common behavior problems [26, 28].

Diagnosis and Diagnostic Aids

The diagnosis of NF1 is essentially based on the clinical findings supplemented by appropriate imaging studies. The NIH consensus criteria are useful in establishing the diagnosis in adults as well as young children. In a large series of children less than 6 years of age, 94% could be correctly diagnosed as affected or unaffected on initial examination correctly using the NIH consensus criteria. Café-au-lait spots were the most frequent finding (97%) with Lisch nodules in 30% and neurofibroma only in 15% of the affected children [29]. Those children whose diagnosis remains uncertain on initial diagnosis should be monitored carefully.

Imaging studies such as computed tomography (CT) scan or MRI are helpful in establishing the diagnosis of optic nerve glioma. These lesions appear as intraconal, fusiform enlargement of the optic nerve with or without chiasmal mass. The nerve may appear kinked with cystic spaces. MRI screening for known optic glioma every 2 years is recommended.

Eyelid and orbital neurofibromas are homogenous, well-circumscribed lesions with a density similar to brain on CT scans with contrast enhancement. CT scan may demonstrate bony expansion, particularly of the superior orbital fissure [30].

A characteristic finding of “bright lesions” on MRI studies is seen in about 15% of patients with NF1. The hyperintense T2 lesions are present in the cerebral hemispheres, brainstem, and cerebellum. The lesions revolve over time and may represent abnormal myelination or gliosis [31]. The bright lesions are more commonly seen in children and may relate to the region-specific effects of the NF1 gene product [32]. The presence of T2 hyperintensity in childhood has been advocated by some researchers as a biological marker of cognitive impairment in NF1 [28].

Treatment

Once the diagnosis of NF1 is made, patients need detailed counseling regarding the prognosis, genetic, and psychological aspects of the disease. First-degree relatives should be evaluated. For malignant tumors, excision, chemotherapy, and radiotherapy may be indicated.

The management of optic nerve glioma remains controversial. The likelihood of visual loss depends on the extent and location of the tumor and is particularly associated with postchiasmal tumors [33]. Optic nerve glioma associated with NF1 is less likely to progress as compared with sporadic cases [34]. Therapy is limited to symptomatic gliomas showing progression. Excision, radiotherapy, and chemotherapy have been used, but the visual acuity in the affected eye often gets worse despite treatment [24, 35].

Treatment is reserved for symptomatic plexiform neurofibroma. Surgical excision often sacrifices the involved nerve and is complicated by excessive bleeding. Complete resection is rarely possible as the lesion is diffusely intertwined with the normal surrounding tissue.

Social and Family Impact

Patients with NF1 are at risk of increased malignancy and shortened life span [15]. Cosmetic issues related to multiple plexiform neurofibromas are also a concern for most patients. Children and adolescents with NF1 have social and emotional problems such as attention problems, anxiety, depression, and aggressive behavior [23]. Early screening and increased level of intervention is necessary to prevent and treat psychological problems.