Science News: Sensory Neuronopathies: A Case Series and Literature Review

Submitted by: Bryan X. DeSouza, MD & Niranjan N. Singh, MD, DM
Edited by: Hristelina Ilieva, MD, PhD   

Sancho Saldaña A, Mahdi-Rogers M, Hadden RD. Sensory neuronopathies: A case series and literature review. J Peripher Nerv Syst. 2021;26(1):66-74. doi:10.1111/jns.12433

Summary: Sensory neuronopathies also called sensory ganglionopathies are important disorders to understand especially in the setting of COVID-19 infections, which are characterized by clinical features of acute and subacute loss of smell and taste sensation. In the first article, Drs. Amato and Ropper provide an elegant review of sensory neuronopathies. The article is limited to the acquired sensory ganglionopathies and not the rare hereditary ganglionopathies.

Amato and Ropper describe the important anatomical and physiological characteristics of the sensory ganglia showing how it is different from the common peripheral nerves, but how they may be vulnerable to autoimmune attack because of fenestrated endothelial cells forming a permeable blood nerve barrier. These features provide clues as to their strong association and susceptibility to paraneoplastic, immune mediated, infection-related, and drug- or toxicity related diseases and conditions.

The clinical features of the sensory ganglionopathies, causes, diagnostic evaluations and treatment options are described. There are 3 key distinguishing features of the sensory ganglionopathies: 1 - that they do not cause weakness because they are confined to the sensory neurons. 2 - ganglionopathies are not length dependent and symptoms can appear in the face, oral mucosa, scalp, trunk and proximal limbs. 3 - most sensory ganglionopathies affect large fiber neurons and are associated with loss of touch, vibration, proprioception pseudoathetoid posturing, Romberg's sign, loss of tendon reflexes. Less commonly, the small sensory fibers are affected resulting in dysesthesias, but preserved large fiber functions. Other features include involvement of autonomic ganglia and may cause dysautonomia.

The types of ganglionopathy and causes of are categorized as paraneoplastic, systemic autoimmune, infection-related, drug- or toxicity and idiopathic. The most common causes are paraneoplastic and inflammatory, but at least 50% are idiopathic and involve large and small fiber ganglia. The most common malignancy associated is small-cell lung cancer, but associations have also been reported with breast, ovarian, prostate, colon, gastric lymphoma, and neuroendocrine. Sensory symptoms can be acute or insidious and precede the diagnosis of cancer. Other causes listed include, Sjogren's syndrome, SLE, MCTD, or RA. Infections include HIV, HTLV-1, EBV, Zika, enterovirus, HVZ and leprosy. Drugs and toxicity include Platinum-based chemotherapies, Vitamin B6 toxicity and Checkpoint inhibitors.

Diagnostic evaluations are well described. Electrodiagnostically, the sensory nerve conduction studies in the common large fiber sensory ganglionopathies show reduced amplitudes of sensory-nerve action potentials (SNAPs) with relative sparing of sensory latencies and conduction velocities, but these tests may be normal early in the disorder. The reduced SNAPs can be asymmetric or generalized corresponding to the clinical presentation. The important characteristic of the NCV pattern of a sensory ganglionopathy is that it is not length dependent and could show involvement in the arms, (radial, median or ulnar) or blink reflex (assessing trigeminal sensory ganglion) but normal lower legs sural and superficial peroneal nerves. EMG is normal. The sensory NCV are normal in the small fiber ganglionopathies. Autonomic testing may show abnormalities in sudomotor function, or abnormal HR and BP responses. MRI may show swelling with increased signal on T2-weighted images or enhancement in the DRG and degeneration of the posterior columns of the spinal cord. Small fiber skin biopsy may show a reduction of the IENFD in the arm and thigh than the distal leg.
Treatment of immune mediated sensory ganglionopathies may occasionally halt the disease progression, but it has not been successful in treating or reversing the ganglionopathies. Treating the cancer also fails to cause remission in the ganglionopathy.
 
In the second article, Sancho et al report a case series of 54 patients with sensory ganglionopathies, 18 male, median age 54.5, most common initial symptoms were hypoesthesia paresthesia ataxia and pain.  Etiology as possibly immune mediated 33% paraneoplastic 15% and idiopathic 11%.  About 31 patients has received immune therapy where 11 improved or stabilized.  Corticosteroid where the most used treatment.  Response rate was 50%.  Worst outcome seen in the patient with areflexia, pseudo athetosis.

Comments: In summary, the sensory ganglionopathies are disabling disorders that have unique clinical anatomical and pathophysiological features that distinguish this type of ganglionic sensory loss from sensory loss due to peripheral sensory neuropathies. The distinguishing features can localize to the face, trunk and arms before they appear in the distal legs. There is no weakness and sensory ataxia is common in the large fiber ganglionopathies while burning dysesthesia are less common and involve small fiber ganglionopathies. Evaluation for underlying causes such as cancer and Sjogren's are insufficient and 50% are idiopathic. Therapy such as immunotherapy is limited.