PNS of the Peripheral Nervous System

The SN often associated with the Hu antibody is characterized by primary damage to the nerve cell body. The patient suffers from progressive, painful sensory disturbances evolving subacutely, usually with a Rankin score of 3 within 12 weeks of the onset of symptoms [14]. Presenting symptoms include paresthesia, hypoestesia, and very often proprioceptive loss in the affected areas sensory ataxia is common. The upper limbs are often involved [97], The distribution of the SN is often atypical for peripheral neuropathy. The involvement is usually asymmetrical, especially at the onset of symptoms, and may affect the face or upper limbs only. SN is often the presenting symptom of the PEM/SN syndrome, but signs of CNS involvement usually evolve, and autonomic disturbances are common [36]. 

Although the sensory ganglia and roots are the primary affected area in SN, demyelination and axonal degeneration combined with inflammatory infiltrates consisting of CD8+ cells and macrophages also extend to peripheral nerves [102]. Simultaneous affection of the CNS and autonomic ganglia is common [42]. 

Paraneoplastic autonomic neuropathy is primarily seen with SCLC [103]. Lymphoma, non-small cell lung cancer, and ovarian cancer are also associated with autonomic disturbances [104]. Autonomic dysfunction affects 23-30% of Hu antibody positive patients [36, 98] and is the predominant symptom at presentation in up to 9% of the patients [90]. The onset of symptoms is usually subacute. A prominent clinical manifestation in patients with paraneoplastic autonomic neuropathy is gastrointestinal dysmotility and intestinal pseudo-obstruction, which can occur as part of the PEM/SN syndrome or as the sole symptom of Hu antibody related PNS. Ortostatic hypotension and erectile dysfunction are other common features [37, 105, 106], Autonomic neuropathy is also commonly associated with the CRMP-5 antibody and have been detected in more than 30% of CRMP-5 antibody positive patients [30], Inflammation in autonomic ganglia and infiltration of B and T cells have been demonstrated at autopsy [107], and Hu antibodies have been shown to induce neuronal apoptosis in cultured myenteric neurons [105], 

Antibodies specific for neuronal nicotinic acetylcholine receptors in the autonomic ganglia have been identified in some patients with both idiopathic and paraneoplastic autonomic neuropathy, and high levels of these antibodies were correlated with more severe disease, suggesting that the antibodies may be of functional importance [108], 

Finally, autonomic dysfunction is a common feature of LEMS with and without malignant disease. In LEMS patients, the most frequent symptoms are cholinergic, including dry mouth, erectile failure, constipation, blurred vision, and impaired sweating, suggesting that major involvement is the parasympathetic nerves [109]. 

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