Facial pain as first manifestation of anti-Hu paraneoplastic syndrome

Trigeminal nerve involvement is a frequent cause of facial pain. In our patient, cheek numbness and further trigeminal hypoesthesia strongly suggested symptomatic trigeminal neuropathy. A structural lesion involving the fifth cranial nerve was excluded by the normality of the brain MRI. Vasculitis and connective tissue diseases associated with trigeminal neuropathy were then considered. The association of xerophthalmia and xerostomia suggested a Sjögren’s syndrome, which is associated with a sensory trigeminal involvement in 16% [2]. However, the absence of anti-Ro/anti-SS-A, anti-SS-B antibodies and the normality of the labial salivary gland biopsy argued against this diagnosis. Trigeminal neuropathy has been also reported in association with other connective tissue diseases, such as scleroderma or mixed connective tissue diseases [3], but the lack of joint, renal, eye, skin involvement, and the normality of the immunologic tests prompted us to reject these diagnoses. There was no evidence of infection on serological screening.

Facial pain as a first manifestation of a cancer was also considered. Trigeminal neuropathic pain can be associated with cancer, either by a direct compression of the nuclei in the brainstem or of the peripheral branches by the tumour or by a meningeal carcinomatosis. In our patient, we did not disclose any evidence of metastatic invasion nor contiguity spread of a tumour lesion to the trigeminal nerve. Conversely, the CSF oligoclonal bands and the detection of anti-Hu antibody confirmed the hypothesis of a paraneoplastic syndrome.

Cranial nerve involvement represents one of the manifestations of anti-Hu-associated brainstem encephalitis [4] which is associated with a small-cell lung carcinoma in the majority of patients. Brainstem symptoms can be isolated or associated during paraneoplastic encephalomyelitis with signs of widespread dysfunction of the nervous system [1, 5, 6]. The frequency of trigeminal involvement in patients with anti-Hu antibodies is unknown. Facial numbness was described in 2 out of 23 patients with brainstem encephalitis reported by Dalmau et al [6]. Trigeminal involvement can emerged early in the course of paraneoplastic syndrome with anti-Hu antibodies in association with multiple cranial nerve palsies [7] or with progressive dysautonomia [8]. To our knowledge, only one previous study has reported trigeminal involvement as the first manifestation of an anti-Hu neuropathy [9]. However, we suggest that trigeminal paraneoplastic involvement may be underestimated. 33 cases of facial pain as the first manifestation of lung cancers have been collected in literature in 2003 [10]. In these patients, the mean delay between the onset of facial pain and the diagnosis of lung cancer was 9 months. In most cases, the pain was described as severe and aching and commonly affected the jaws and temporal region. In two patients, the diagnosis of trigeminal neuralgia was previously made. Several mechanisms were proposed to explain facial pain, such as local invasion, compression of the nerve or a paraneoplastic syndrome. To our knowledge, screening for paraneoplastic antibodies was not performed in these studies.

In conclusion, trigeminal neuropathy is a well-known symptom occurring during the evolution of patients with anti-Hu-associated encephalomyelitis/sensory neuropathy, but can also represent the first isolated manifestation of a paraneoplastic syndrome.