Acquired sensory neuronopathies depend on a primary involvement of sensory neurons in dorsal root ganglia leading eventually to a definitive and irreversible degeneration of the cell body (34; 68; 28). They include toxic, infectious, and dysimmune mechanisms, although an important proportion remains idiopathic after an extensive workup. The differential diagnosis includes genetic sensory neuronopathies and sensory ataxic neuropathies that may resemble acquired sensory neuronopathies. A short therapeutic window before definitive neuron degeneration warrants that all effort should be made to obtain an early diagnosis of these disorders.
• Most acquired sensory neuronopathies are probably immune-mediated.
• An early diagnosis is warranted to treat the patient before neuron cell death.
Historical note and terminology
The concept of sensory neuronopathy or ganglionopathy was first developed by Dereck Denny-Brown in 1948 in his seminal description of the first pathologically identified cases of sensory neuronopathies here due to a remote effect of cancer (18). The term “neuronopathy” is used to indicate that the neuron cell body is the target of the disorder at the difference of “peripheral neuropathy”, which designates diseases involving the axon or myelin sheath of the neuron peripheral process.
The main difficulty with sensory neuronopathies is that the direct exploration of sensory ganglia is very difficult and that we can only rely on indirect arguments to ascribe a given disorder to a degeneration of sensory neurons because dorsal root ganglia biopsy cannot be performed in routine. Another difficulty is that depending on the etiology, the lesioning process may sometimes extend to other part of the nervous system so that the disorder may not be purely sensory. Beyond the dorsal root ganglia, the most frequently affected structures are the autonomic nervous system, motor neurons, peripheral nerves, and the cerebellum. Of course, this clearly depends on the etiology of the sensory neuronopathy. In particular in genetic diseases, sensory neuronopathy is frequently only 1 component of the disorder. On another side, inflammatory or paraneoplastic sensory neuronopathies are often associated with autonomic nervous system involvement.
The last level of complexity is that the sensory neuron population is heterogeneous, with at least 2 distinct morphological and functional groups of neurons: those involved in thermal and pain sensation whose axon is unmyelinated and those involved in proprioception and superficial tact with a myelinated axon. However, it is now established that there exist at least 11 subtypes of sensory neurons based on their function, fiber type, receptors, developmental pathway, and molecular expression in the adult (76). This explains that some disorders may specifically or predominantly target 1 group of neurons, resulting in a purely or predominantly ataxic or painful neuropathy.
Here, we will focus on acquired sensory neuronopathies and only mention the hereditary forms that may be difficult to distinguish from acquired sensory neuronopathies.