A 69-year-old man was referred to our Clinic with a 4-month history of progressive pain and paresthesias of distal lower limbs. No other cognitive, systemic or autonomic symptoms were reported before his admission to our Clinic. Patient’s body mass index (BMI) was 23,66 and he had a 30-year history of alcohol abuse and smoking (38 pack years). He initiated drinking red wine at the age of 27 and his daily alcohol consumption was 160 g for the last 30 years. His family history was negative for neurological diseases and he reported no other medical issues.

Nerve conduction studies performed up to one month before his reference to our Clinic (Table 1) were suggestive of a sensory axonal neuropathy of the lower limbs (Fig. 1a). The patient had already undergone extensive laboratory testing (blood sugar, urea, creatinine, ferritin, liver enzymes, vitamin B12, thiamine, folate, TSH, protein and immune electrophoresis, anti-nuclear antibody, serology for hepatitis B virus, hepatitis C virus and human immunodeficiency virus), as well as Magnetic Resonance Imaging (MRI) of the cervical and lumbosacral spine; None of the above revealed any abnormalities. Our differential diagnosis included toxic causes, systemic and autoimmune diseases, infections, and cancer. Alcoholic neuropathy was considered the most likely diagnosis, due to his medical history of alcohol abuse and no other reported possible cause of neuropathy, as well as due to his clinical and neurophysiological evaluation, compatible with a length- and dose-dependent toxic neuropathy.

Nerve conduction studies: sensory nerve action potentials in sural nerve. a One month before his admission to our clinic, b upon his admission. Compound motor nerve action potentials in c peroneal, and d tibial nerve, upon his admission. Motor and sensory distal latencies were measured from the onset of the potentials

The patient’s neurological examination revealed distally pronounced symmetric superficial and deep sensory loss in the lower extremities, reduced Achilles tendon reflexes and wide based gait. No motor, autonomic or systemic symptoms and signs were reported, at that time. A new electrophysiological testing was performed (Table 1), with nerve conduction studies revealing markedly reduced sensory nerve action potentials in sural nerves (Fig. 1b), and mildly reduced compound motor nerve action potentials in peroneal (Fig. 1c) and tibial motor nerves (Fig. 1d), suggesting axonal sensory-motor polyneuropathy. The patient was also tested for small fiber involvement. Sympathetic skin response (SSR) could not be recorded from the left plantar surface and thermal threshold (TT) was abnormal, with heat and cold threshold (HT and CT) values exceeding the mean control data, suggesting also small fiber neuropathy [7].

Patient was referred to a 3-week program in a Detoxification Clinic and was administrated vitamin B complex supplements.

He was reevaluated 1 month later, and even though he had not consumed any alcoholic beverage, his gait impairment had worsened and he reported postural dizziness. His examination revealed slight overall worsening compared to his last evaluation as regards pain and numbness of distal lower limbs and, in addition, bilateral plantar dorsiflexion weakness and postural hypotension. Diagnosis of alcoholic neuropathy was reconsidered due to his clinical worsening and a lumbar puncture was performed at that time. Cerebrospinal fluid (CSF) contained slightly elevated protein at 52 mg/dl without pleocytosis. Further examinations, including cryoglobulins, antineutrophil cytoplasmic antibodies (ANCA), angiotensin converting enzyme (ACE), IgM and IgG antibodies for herpes simplex virus 1 and 2, varicella zoster virus, cytomegalovirus, West Nile virus, Epstein–Barr virus, enterovirus, adenovirus, influenza, echovirus, mumps, measles, rubella, Chlamydia pneumoniae, Mycoplasma pneumoniae and Borrelia burgdorferi, anti-CRMP5 and anti-Yo antibodies, were negative. Testing for serum anti-Hu antibody, however, was positive with a titer of 1:6400. Full body computerized tomography (CT) with contrast and positron emission tomography (PET-SCAN) scanning were performed according to EFNS proposal for tumor screening [8], without malignancy findings. Treatment with prednisone, plasma exchange and intravenous immunoglobulin (IVIg) showed no benefit and symptoms gradually worsened, with pronounced muscle weakness of lower limbs.

Repeated evaluation for cancer detection was performed 3 months later, and chest CT revealed an 8 mm nodule at the left lower lobe of lungs. PET-SCAN confirmed CT’s findings, revealing diseased tissue and peribronchial nodules at the left lower lobe. Bronchoscopy was performed soon after PET-SCAN, and biopsy results were indicative for small cell lung cancer. The patient died of respiratory infection 2 weeks after bronchoscopy.