Anti-Hu associated paraneoplastic neuropathy simulating an axonal variant of Guillain-Barré syndrome

Dear Editor:

Acute motor/motor-sensory axonal neuropathy (AMAN/AMSAN) is a rare, severe form of Guillain-Barré syndrome (GBS).¹ Although it is usually triggered by infection, on exceptional occasions it may present as a paraneoplastic syndrome.² We present one such case of paraneoplastic neuropathy simulating axonal GBS.

Our patient was a 53-year-old man with personal history of arterial hypertension and smoking (100 packs/year). Two weeks before admission to hospital he presented dysaesthesia in a glove and stocking pattern, subsequently extending up to the elbows and knees; as dysaesthesia progressed, the patient also presented weakness, diplopia, and urinary retention. The neurological examination revealed paresis of both lateral rectus muscles, left tonic pupil, paresis of the distal muscles of the lower limbs, and hypoaesthesia to proprioceptive and nociceptive stimuli. The patient also displayed generalised hyporeflexia with normal plantar reflexes, postural instability during the Romberg test, and ataxic gait. He did not display anhidrosis.

A blood test revealed no alterations, with normal erythrocyte, leucocyte, and platelet counts; normal kidney and liver function; and tumour marker levels (CEA, Ca 19.9, AFP, and PSA) within the normal range. Immune tests yielded negative results, except for an antinuclear antibody titre of 1/160. A chest and abdomen CT scan revealed right hilar adenopathy and isodense nodular lesions in the liver parenchyma. The initial neurophysiological study revealed signs of predominantly sensory axonal involvement. A CSF analysis revealed albuminocytologic dissociation, with high protein levels (202.80 mg/dL) and no red blood cells; the remaining CSF findings were normal. Anti-Hu antibodies were detected in the CSF and serum (Western blot and indirect immunofluorescence). Transbronchial biopsy was performed to obtain a sample of the hilar adenopathy, and the patient was diagnosed with small-cell lung cancer.

Immunoglobulin treatment (5 days’ duration) was ineffective. The symptoms worsened, with the patient presenting permanent dysaesthesia, allodynia, increased weakness of distal muscles, bilateral tonic pupils (with response to pilocarpine), ophthalmoparesis, and severe dysautonomia (orthostatic hypotension, constipation, urinary retention, nocturnal hyperhidrosis, and recurrent syncope). Ten days after immunoglobulin treatment, he received 5 cycles of plasmapheresis, which stabilised the neurological symptoms. However, the patient died of respiratory complications a month after diagnosis.

GBS is usually caused by a demyelinating polyneuropathy. Since its initial description, several rare forms have been reported, including the axonal subtype, encompassing AMAN and AMSAN, with the latter being the more severe form.^1,3

From a neurophysiological viewpoint, the axonal subtype is characterised by axonal degeneration and reversible nerve conduction block, which progress in parallel with clinical symptoms over the course of days to weeks.^1,4

The literature includes very few reports of axonal forms of GBS associated with antineuronal antibodies and presenting as a paraneoplastic syndrome.^5–7 Anti-Hu antineuronal antibodies are usually associated with small-cell lung cancer, but have also been detected in such other cancers as breast and prostate tumours.⁸ Anti-Hu antibodies can be determined in the serum or the CSF.⁹ Unlike GBS, sensory and sensorimotor neuropathies are often associated with presence of anti-Hu antibodies due to direct immune-mediated damage to the neuronal cell body.^8,10,11 In these cases, a sural nerve biopsy reveals axonal degeneration and occasionally inflammatory cells in the epineurial space.⁴ Dysautonomia secondary to paraneoplastic neuropathies, as in the case presented here, may present in isolation or combined with other symptoms.¹² It is frequently associated with anti-Hu antibodies and may be a key finding in screening for paraneoplastic syndromes: paraneoplastic origin should be suspected when the initial symptoms are severe.^2,13,14 Presence of dysautonomic symptoms suggests poorer prognosis given the potential for severe complications.

As in other paraneoplastic syndromes, management of paraneoplastic neuropathies focuses on treating the underlying neoplasia. Plasmapheresis and various immunosuppressants have been tested, including corticosteroids, rituximab, and intravenous immunoglobulins; these treatments seem to be effective in demyelinating forms.¹ In cases of axonal degeneration, however, they are often ineffective or may stabilise progression with severe sequelae due to the aggressive course of axonal forms, especially when associated with anti-Hu antibodies. Non-responders may benefit from cyclophosphamide or rituximab pulse therapy, although the effectiveness of these approaches has only been tested in isolated cases.¹⁴