Page 409 - Read Online

Almedallah et al. Neuroimmunol Neuroinflammation 2018;5:48 I http://dx.doi.org/10.20517/2347-8659.2018.55 Page 5 of 6

Neurologic paraneoplastic disorders are believed to result from an immune cross-reactivity between
[6]
the tumor cells and components of the nervous system PLE has been associated with auto-antibodies
[7,8]
produced against neuronal cell surfaces and synaptic bodies, expressed in nervous tissue and tumors .
Their presence indicates an underlying tumor and often allows early detection of the associated tumor, thus
[9]
aiding the diagnosis. However, these antibodies are detected in only 60% of patients diagnosed with PLE .
Commonly encountered antibodies include anti-NMDA, anti-Ma2, anti-Hu, anti-Ta, anti-LG1, anti-CASPR2
[8]
and anti-VGKC .
PLE is a spectrum of heterogeneous neuropsychiatric manifestations, described as a result of the inflamma-
tion of the limbic system. The constellation of symptoms include acute or subacute mental confusion, im-
pairment of recent memory, cognitive dysfunction, hallucinations, depression, personality changes, complex
[10]
partial seizures and sleep disturbances . Hyperthermia, somnolence, and endocrine abnormalities may
[4]
also occur as a result of hypothalamic involvement . Although the inflammation is localized to the limbic
[8]
system, Newman et al. explains the clinical and pathologic findings are not confined to these anatomical
areas, and symptoms of brainstem and cerebellar dysfunctions commonly occur, as exhibited by the unbal-
anced gait of our patient.

The non-specific nature of neuropsychiatric manifestations often precedes the detection of cancer in 80%
[11]
of patients , presents a diagnostic challenge. In addition, its mimicry of other presentations such as viral
[2]
encephalomyelitis or rapidly progressive neurodegenerative disease, broaden the differential diagnosis .
Therefore, tumor screening via imaging and electroencephalography (EEG) is paramount when unexplained
paraneoplastic neurologic symptoms are encountered. This uncovered the masked diagnosis of testicular
mixed germ cell tumor in our patient, despite the unrevealing results of auto-antibodies.

Although imaging results are often nonspecific, MRI with T2/FLAIR remains the most sensitive tool to di-
[4]
agnose PLE. Medial temporal lobe hyperintensities are seen with infrequent contrast enhancement . EEG
supports the diagnosis by showing focal or generalized slowing and/or epileptiform activity, also maximal in
the temporal regions. It is useful for determining alterations in consciousness due to postictal states or par-
[5]
tial complex seizures .
Diagnostic dependence on antibody testing and immunotherapy response might delay proper detection ac-
[7]
cording to Graus et al. , since several antibody tests may not be widely available in facilities. These tests re-
quire a long duration to produce results, and interestingly, the absence of the antibodies does not exclude the
[6,7]
diagnosis and vice versa .

[2]
Lancaster argues the use of response to immunotherapy as an indicator of the diagnosis can also be mis-
leading as some patients may require intensive treatments not available in all centers or may not respond at
all. Moreover, patients with other diagnoses may show clinical improvement. The growing consensus advises
[7]
to start empiric immunotherapy before antibody testing in suspected autoimmune encephalitis .
Given the novelty and variation in responses, definitive treatment is not yet available. Early diagnosis aids
in the eradication of the underlying cause and antigen source, and in turn provides the highest chance of
neurological improvement, with the best prognosis. Suppression of this overactive immune response is also a
cornerstone in treatment; achieved by an array of medical modalities, including steroids, cyclophosphamide,
[8]
IVIG, and plasma exchange .
Despite the successful eradication of the tumor in our patient, neurologic improvement was not guaranteed
because the causative agents were not produced by the tumor cells, and the possible permanent damage
accrued by the immune response. This emphasizes that all efforts should be extended in finding the hidden