In this post I link to and excerpt from emedicine.medscape.com‘s June 14, 2018 review Autonomic Neuropathy.
My blog posts are my study notes on topics I review. Excerpting helps me fix the learning in my mind. But I often just go directly to the linked resource when reviewing the topic.
Here are excerpts:
Background
Autonomic neuropathies are a collection of syndromes and diseases affecting the autonomic neurons, either parasympathetic or sympathetic, or both. Autonomic neuropathies can be hereditary or acquired in nature. Most often, they occur in conjunction with a somatic neuropathy, but they can also occur in isolation.
The autonomic nervous system modulates numerous body functions; therefore, autonomic dysfunction may manifest with numerous clinical phenotypes and various laboratory and neurophysiologic abnormalities. Although a patient may present with symptoms related to a single portion of the autonomic system, the physician must be vigilant for other affected parts of the autonomic system.
Pathophysiology
The pathophysiology of autonomic neuropathies is variable and depends upon the underlying medical conditions. We have chosen to classify the autonomic neuropathies into hereditary and acquired. The acquired autonomic neuropathies may then be subsequently subdivided into primary or secondary.
Inherited Autonomic Neuropathies [See link for details]
All forms of inherited autonomic neuropathies are rare. Familial amyloid polyneuropathy, the hereditary sensory autonomic neuropathies, Fabry disease, and the porphyrias are genetic diseases in which autonomic neuropathy is a common feature.
Acute intermittent porphyria and variegate porphyria*
*See Porphyria Overview from emedicine.medscape.com
Acute intermittent porphyria and variegate porphyria can both have forms of peripheral neuropathy. Attacks can be triggered by exposure to particular drugs. During episodes, affected individuals present with acute polyneuropathy that may mimic Guillain-Barré syndrome. Autonomic dysfunction, particularly cardiac and vascular in nature, can be prominent.
Acquired Autonomic Neuropathies
The acquired autonomic neuropathies are much more prevalent than the inherited ones. Here, we subclassify the acquired autonomic neuropathies into primary and secondary disorders. Primary autonomic neuropathies are disorders that are idiopathic or that have autonomic neuropathy as a characteristic feature of the disease process itself. In the secondary autonomic neuropathies, an identifiable cause, such as a nutritional deficiency, may lead to autonomic neuropathy, but does not have autonomic neuropathy as a defining feature of the disease process. Subclassification can be somewhat artificial as the true mechanism of action is not clear in all cases, although it can be helpful when trying to develop an understanding of autonomic neuropathy.
Primary acquired autonomic neuropathies
- Pandysautonomia
- Idiopathic distal small-fiber neuropathy
- Holmes-Adie syndrome and Ross syndrome
- Chronic idiopathic anhidrosis
- Amyloid neuropathy: Amyloid neuropathy can be inherited as noted above; however, it can also be associated with hematologic disease, such as multiple myeloma, leading to accumulation of immunoglobulins kappa or lambda light chains. [14] Another acquired amyloidosis occurs with dialysis, with β2-microglobulin deposits in the nervous system. In syndromes of amyloidosis, the development of generalized autonomic failure significantly worsens the overall prognosis. Of all autonomic neuropathies, amyloidosis probably causes the most severe forms, with universal autonomic dysfunction common. A somatic neuropathy is often coexistent. [15]
- Postural orthostatic tachycardia syndrome: Postural orthostatic tachycardia syndrome (POTS) is a syndrome most common in young females with orthostatic intolerance characterized by palpitations with excessive orthostatic sinus tachycardia, sensation of lightheadedness, and near-syncope. POTS may be associated with an infectious prodrome and thus may represent the chronic sequelae of a forme fruste of postviral pandysautonomia. [16] Antibodies against ganglionic receptors are found in 9% of patients with POTS. [17]
Secondary acquired autonomic neuropathies
Metabolic derangements that may have an associated autonomic neuropathy are as follows:
Diabetes mellitus
- Diabetes mellitus is the most common cause of autonomic neuropathy. Neuropathy is the most common complication of diabetes mellitus and may have both somatic and autonomic features. [18, 19, 20, 21] See Medscape Reference’s article on Diabetic Neuropathy. Parasympathetic abnormalities are thought to precede sympathetic abnormalities, but this has not been verified.
- A disorder called acute diabetic autonomic neuropathy appears as an acute pandysautonomia and may be associated with ganglionic antibodies in some patients. Diabetic radiculoplexopathy is associated with prominent autonomic dysfunction, which may have an immunologic cause with destruction of both large and small nerve fibers. [18]
- Diabetes affects autonomic neurons differently; sympathetic neurons from the celiac/superior mesenteric ganglia develop pathological changes, while sympathetic superior cervical ganglion neurons do not. This selectivity may be related to increased sensitivity to oxidative stress. [22]
Hepatic disease–related neuropathy
Vitamin deficiencies, toxins, and drugs that may have an associated autonomic neuropathy are as follows:
Vitamin deficiency and nutrition-related neuropathy: Deficiency of vitamin B12 neuropathy may also be associated with autonomic dysfunction. [25]
Toxic and drug-induced autonomic neuropathy: Toxic and drug-induced autonomic neuropathies may occur with a large variety of chemotherapeutic medications such as vincristine, cisplatin, carboplatin, vinorelbine, paclitaxel, and suramin. Other therapeutic agents associated with a toxic autonomic neuropathy include acrylamide, pyridoxine, thallium, amiodarone, perhexiline, and gemcitabine. [7]
- Alcohol may be associated with an autonomic neuropathy, possibly related to directly toxic effects of alcohol, although thiamine deficiency may also play a role. [26]
Infectious diseases that may have an associated autonomic neuropathy are as follows:
Lyme disease: Patients with Lyme disease have shown lymphoplasmocellular infiltrates in the autonomic ganglia. [27]
Chagas disease: Chagas disease due to infection with Trypanosoma cruzi is occasionally associated with autonomic neuropathy during the chronic stage of infection. [30] Parasympathetic dysfunction tends to be greater than sympathetic dysfunction. [31] Autoimmune destruction of the peripheral nervous system and autonomic nervous system may occur, especially of autonomic nerves supplying the cardiovascular and gastrointestinal systems.
Diphtheria: Diphtheria has been associated with an autonomic neuropathy. Although the mechanism of action is not clear, the parasympathetic nervous system may be more affected than the sympathetic. [33]
Autoimmune conditions that may have an associated autonomic neuropathy are as follows:
Celiac disease: Autonomic neuropathy may occur in approximately 50% of adults with celiac disease, leading to clinical features of presyncope and postural nausea. [36] Autonomic denervation may be related to antineuronal antibodies; the neuropathy does not appear to respond to a gluten-free diet. [37]
Sj ö gren syndrome: Sj ö gren syndrome may lead to peripheral and autonomic neuropathy without characteristic systemic symptoms. A small-fiber neuropathy associated with Sj ö gren syndrome can be associated with widespread anhidrosis. Also, a sensory neuronopathy due to Sj ö gren syndrome can be associated with autonomic dysfunction. The cause of neuropathy in these patients is likely to be autoimmune, but this remains unclear. [38]
Rheumatoid arthritis, systemic lupus erythematosus, and connective tissue disorders: Abnormalities of sympathetic postganglionic function may be seen in rheumatoid arthritis, systemic lupus erythematosus, and other connective tissue disorders. Some of these patients may have autoantibodies to ganglionic acetylcholine receptors. Autoimmune thyroiditis, such as chronic thyroiditis and Hashimoto thyroiditis, can be associated with some features of Sj ö gren syndrome such as xerostomia. Patients with systemic sclerosis and mixed connective tissue disorder may have abnormalities of autonomic functioning of esophageal motor activity. [7]
Guillain-Barré syndrome: Guillain-Barré syndrome (GBS), or acute inflammatory demyelinating polyneuropathy (AIDP), is an acute autoimmune somatic neuropathy commonly associated with prominent autonomic dysfunction that can lead to both morbidity and mortality. [39, 40] Autoantibodies can be found against gangliosides, such as with anti-GM1 antibodies. Pathologic studies of the autonomic nervous system in GBS may demonstrate edema and inflammation of autonomic ganglia and destruction of peripheral ganglion cells. Chromatolysis, mononuclear cell infiltration, and nodules of Nageotte can be found within sympathetic ganglia. [39]
Lambert-Eaton myasthenic syndrome: Lambert-Eaton myasthenic syndrome (LEMS) is an acquired neuromuscular transmission disorder with antibodies present against presynaptic voltage-gated P/Q-type Ca2+ channels. LEMS is frequently associated with clinical and electrophysiologic evidence of dysautonomia, which can be severe in 20% of patients with LEMS. [41] In 50% of cases, LEMS is associated with a neoplasm, most commonly small cell carcinoma of the lung.
Paraneoplastic autonomic neuropathy
- Paraneoplastic autonomic neuropathy may occur as a component of paraneoplastic neuronopathy with anti-Hu antibodies in 23% of patients. Autonomic dysfunction appears to result from autoimmune destruction of autonomic postganglionic and myenteric neurons. [42]
- A variant of paraneoplastic autonomic neuropathy is an enteric neuronopathy that exists with antibodies directed against the myenteric plexus (anti-enteric neuronal antibodies). [43] Other paraneoplastic autonomic syndromes may have autoantibodies against neuronal cytoplasmic proteins of the collapsin response–mediator family (CRMP-5) and against Purkinje cell cytoplasm (PCA-2). [44]
Inflammatory bowel disease: Inflammatory bowel disease–related disorders may rarely have an associated autonomic neuropathy, particularly involving the pupillary nerves. [45]
Mortality/Morbidity
Falls and loss of consciousness are significant contributors to morbidity associated with autonomic neuropathies. They may lead to injury, particularly in the elderly. Often, an autonomic neuropathy manifests with orthostatic hypotension, which has been associated with increased mortality in the middle aged and elderly. [46] As the autonomic nervous system is involved in involuntary control of almost every organ system, patients may have many other complaints that are discussed below.
