Numb cheek syndrome as the first manifestation of anti–Hu paraneoplastic neuronopathy

Abstract

Sirs: Unilateral numb cheek syndrome (NCS) has rarely been described as the first manifestation of malignancy due to neoplastic involvement of the trigeminal nerve, more specifically the maxillary branch [1, 2]. NCS as the first symptom of subacute paraneoplastic sensory neuronopathy has, to the best of our knowledge, never been reported. We present this case because its rarity led to a diagnostic delay of several months. A 47-year-old man presented with a one month history of numbness in the left cheek, both inner and outer surfaces. The area of numbness corresponded with the mandibular division of the left trigeminal nerve (V3). His medical history was unremarkable. Neurological examination was normal including the left V3 area. As the main part of the cheek is innervated by the buccal nerve we considered that our patient had a mandibular sensory neuropathy probably due to compression or infiltration of the nerve by local malignancy, as seen in other types of trigeminal mononeuropathy [3]. Ancillary investigations including contrast enhanced brain MRI, thorax CT and extensive laboratory examinations of the blood and urine were normal. Cerebrospinal fluid (CSF) examination revealed mild lymphocytic pleocytosis, slightly elevated protein of 0.69 g/l (0.2–0.5) and no malignant cells or oligoclonal bands. Although intracranial malignancy could not be ruled out an expectant policy was chosen by the patient. Two months later he complained of slightly unsteady gait. A second MRI of the brain and skull base was normal. Another 4 months later he noticed numbness of his left hand and foot. Neurological examination showed only left sided facial hypalgesia. Nerve conduction studies were consistent with a non uniformly distributed, predominantly axonal, sensorimotor neuropathy, most pronounced in the left extremities. Repeated conventional CSF examination only showed an increased protein level of 0.86 g/l. Anti-Hu antibodies in CSF were detected with indirect immunofluorescence and Western blotting techniques. A second thorax CT and whole body PET-scan eventually showed a solitary lesion in the right hilus, which proved to be a metastasis of an anaplastic small cell carcinoma on histological examination. Although the primary tumour remained unrevealed, a paraneoplastic multifocal mainly sensory neuronopathy associated with presumed primary small cell lung carcinoma was diagnosed and combined chemotherapy started. Fifteen months after the initial complaint the primary tumour remained undetected and no metastases were found. The neuropathy progressed resulting in very severe sensorimotor neuropathy with asymmetric painful paresthesias, diffuse proprioceptive loss and weakness in all extremities. In patients with paraneoplastic anti-Hu associated neuropathy (AHN) involvement of the cranial nerves may be present but is very rarely the presenting symptom. AHN most commonly presents as a subacute sensory neuropathy, less frequently as a sensorimotor neuropathy [5, 6]. These neurological symptoms typically antedate the diagnosis of cancer and most commonly involve the extremities [4–7]. In 306 patients with malignancy and associated anti-Hu antibodies, 50 % of the patients had a sensory neuropathy [4–6]. Three of them had trigeminal nerve involvement, but in no one was cheek numbness described as the only presenting symptom. As initially no primary tumour was found, we did not consider AHN as a potential cause of the unilateral cheek numbness in our patient. The final diagnosis was reached because of the extension of the sensory symptoms and eventually the evidence of an asymmetric sensorimotor neuropathy. The diagnostic delay between the NCS and final diagnosis was 6 months, which lies within the range of reported diagnostic delays in AHN patients [4–7]. As early treatment of the underlying malignancy is the mainstay of treatment, we report this patient in order to add NCS to the list of presenting symptoms of AHN.