Sensory neuronopathy

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Sensory neuronopathy
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Nerves in the dorsal root ganglion (also known as the spinal ganglion) are damaged in sensory neuronopathy/sensory ganglionopathy
Specialty Neurology
Symptoms Loss of sensation, pain, parasthesias, ataxia, dysesthesia
Usual onsetVariable
DurationLifetime
Diagnostic method Clinical diagnosis combined with nerve conduction studies, MRI, spinal fluid analysis
Differential diagnosis Other forms of peripheral neuropathy
TreatmentImmunomodulators

Sensory neuronopathy (also known as sensory ganglionopathy) is a type of peripheral neuropathy that results primarily in sensory symptoms (such as parasthesias, pain or ataxia) due to destruction of nerve cell bodies in the dorsal root ganglion. [1] The causes of nerve damage are grouped into categories including those due to paraneoplastic causes (neuropathy secondary to cancer), immune mediated, infectious, inherited or degenerative causes and those due to toxin exposure. In idiopathic sensory neuronopathy no cause is identified. Idiopathic causes account for about 50% of cases. [2] Sensory neuronopathy differs from the more common length dependent axonal polyneuropathies (such as diabetic sensorimotor polyneuropathy) in that the symptoms do not progress in a distal to proximal pattern (starting in the feet and progressing to the legs and hands), rather symptoms develop in a multifocal, asymmetric, and non-length dependent manner (often involving all 4 limbs at onset). [3] [4] Ataxia (lack of coordination) is a prominent symptom early in the disease course. The trigeminal nerve ganglion is also commonly affected leading to facial numbness. Motor nerves are usually not affected however some cases do have mild motor involvement in the form of weakness. Symptoms tend to develop sub-acutely, over weeks, in acquired sensory neuronopathy and more slowly in inherited or primary degenerative cases. In cases of paraneoplastic or infectious sensory neuropathy, treatment is directed at the underlying cancer or infectious cause respectively. Immunomodulatory and anti-inflammatory therapies are also commonly used however their effectiveness is limited.

Contents

Signs and symptoms

The dorsal root ganglion contains cell bodies for sensory nerves including large, myelinated Aβ fibers which carry proprioception and tactile touch sensation to the brain via the dorsal column–medial lemniscus pathway and small, unmyelinated C fibers which carry thermal and pain sensation to the brain via the spinothalamic tract. [2] The destruction of nerve bodies in the dorsal root ganglia in sensory ganglionopathies thus leads to symptoms of ataxia, decreased sensation, pain, dysesthesia, paresthesias and allodynia that characteristically occurs in a multifocal, asymmetric distribution and in a non-length dependent manner. [1] [4] Symptoms usually start in the upper and lower extremities at onset and often also involve the face. [2] [4] This is in contrast to diabetic peripheral polyneuropathy and other length-dependent axonal polyneuropathies in which symptoms start in the feet and then progress proximally to affect the legs, hands, arms, thighs and trunk. Strength is usually normal, but sometimes can be mildly affected. [2] The symptom onset in acquired sensory neuronopathy is subacute with symptoms developing over weeks, however idiopathic and inherited causes often follow a more chronic, indolent course with symptoms developing over years. [2]

Cause

Sensory neuronopathy is thought to be primarily a T-cell mediated inflammatory process that leads to destruction of nerve cell bodies in the dorsal root ganglion. [1] The dorsal root ganglion is not separated by a blood brain barrier as it contains fenestrated capillaries which are highly permeable. This allows antibodies, T-cells, toxins and other substances to enter, causing damage to the nerve cell bodies. [2] Paraneoplastic sensory neuropathy occurs in the setting of cancer and is thought to involve anti-cancer antibodies cross reacting with antigens that are expressed by neurons and cancer cells. The most common auto-antibodies are those of the T-cell mediated anti-Hu antibodies being taken up by nerve cells and attaching to ELAV-like protein 1 (ELAVL-1), ELAVL-2 and ELAVL-3 which are mRNA binding proteins. [2] Small cell lung cancer is the most common anti-Hu antibody associated paraneoplastic syndrome associated sensory neuropathy. [1] But other cancers which may cause paraneoplastic sensory neuropathy include bronchogenic carcinoma, breast cancer, ovarian cancer, Hodgkin lymphoma, prostate cancer, bladder cancer, neuroendocrine tumors, mixed Mullerian tumor and sarcomas. [2] Symptoms of sensory neuropathy may sometimes precede the cancer diagnosis by several months.

Immune mediated sensory neuronopathy is commonly associated with Sjogrens syndrome. [5] Sjogren's is most commonly affected by a length dependent axonal sensorimotor neuropathy characterized by symptoms in the extremities. However, people with Sjogren's may also develop a sensory neuronopathy with progressive numbness in the face, trunk, limbs in a non-length dependent manner. [5] In Sjogren's sensory neuronopathy, vibratory and proprioceptive sensations are profoundly affected, leading to a severe ataxia. [5] Sensory neuronopathy is thought to involve 40% of neuropathies in Sjogren's syndrome and 5% of all cases of Sjogren's overall, it is usually subacute in onset. Other immune mediated causes of sensory neuronopathy include systemic lupus erythematosus, autoimmune hepatitis and celiac disease. [4]

Toxin exposure can also lead to sensory neuronopathies. Platinum-based antineoplastic chemotherapeutic agents are particularly toxic to the dorsal root ganglion. [1] And long term vitamin B6 toxicity has also been implicated, with severe ataxia due to large fiber proprioceptive involvement. Vitamin B6 is thought to lead to neuropathy due to its cytoskeletal and microtubule toxicity leading to nerve cell loss with prolonged overdosing. [2]

Possible infectious causes of sensory neuronopathy include HIV (in which lymphocyte infiltrates have been observed in the dorsal root ganglion), Human T-lymphotropic virus 1, Epstein-Barr virus and varicella zoster virus. [2]

Several inherited neurodegenerative disease have also been shown to have dorsal root ganglion destruction leading to sensory ganglionopathy (in addition to other central and peripheral nervous system aberrations). These include Friedrich ataxia, Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS), and Facial onset sensory and motor neuronopathy (FOSMN). [2]

Diagnosis

Sensory neuronopathy is diagnosed clinically, based on signs and symptoms, along with nerve conduction studies. [1] Ataxia in the upper and lower extremities at onset or at full development, asymmetric distribution of sensory loss, sensory loss not being restricted to the lower limbs (as in length dependent axonal polyneuropathy) are specific to sensory neuronopathies. [4] Nerve conduction studies will show absent or reduced sensory nerve conduction action potentials in the upper and lower limbs with preserved conduction velocity. [4] Motor nerve action potentials and conduction are usually unaffected, but in a subset of cases may have limited dysfunction. [2] Analysis of the cerebrospinal fluid may show increased protein, pleocytosis and oligoclonal bands but this is non-specific. [2] [1] Biopsy of the dorsal nerve root ganglions show a characteristic CD8+ T-cell inflammation pattern, but this is not required for diagnosis and is technically difficult to complete, only sometimes being done on autopsy. [4] [1]

Treatment

Treatment in sensory neuronopathy is usually ineffective. Immunomodulation has been used in with varying levels of success. This includes steroids, immunoglobulin therapy, plasma exchange, cyclophosphamide, rituximab and sirolimus. Immunomodulatory treatments are more efficacious if started early in the disease process (less than 2 months after symptom onset). [1] Treating the underlying cancer in paraneoplastic disease usually does not alleviate the symptoms. [2] [1]

Tricyclic antidepressants such as amitriptyline, Serotonin–norepinephrine reuptake inhibitors such as duloxetine or venlafaxine and gabapentinoids such as gabapentin or pregabalin may be used for the symptomatic treatment of pain including dysesthesias or hyperalgesia. [2]

Prognosis

Anti-Hu paraneoplastic associated sensory neuronopathy carries a poor prognosis, with median survival of less than 1 year and a 20% 36 month survival. [2]

Idiopathic sensory neuronopathy usually does not respond to immunotherapy and the prognosis regarding symptoms control is poor. [2]

Related Research Articles

Neuromyotonia (NMT) is a form of peripheral nerve hyperexcitability that causes spontaneous muscular activity resulting from repetitive motor unit action potentials of peripheral origin. NMT along with Morvan's syndrome are the most severe types in the Peripheral Nerve Hyperexciteability spectrum. Example of two more common and less severe syndromes in the spectrum are cramp fasciculation syndrome and benign fasciculation syndrome. NMT can have both hereditary and acquired (non-inherited) forms. The prevalence of NMT is unknown.

<span class="mw-page-title-main">Peripheral neuropathy</span> Nervous system disease affecting nerves beyond the brain and spinal cord

Peripheral neuropathy, often shortened to neuropathy, is a general term describing damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerves are affected. Neuropathy affecting motor, sensory, or autonomic nerves result in different symptoms. More than one type of nerve may be affected simultaneously. Peripheral neuropathy may be acute or chronic, and may be reversible or permanent.

<span class="mw-page-title-main">Polyneuropathy</span> Medical condition

Polyneuropathy is damage or disease affecting peripheral nerves in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. It usually begins in the hands and feet and may progress to the arms and legs and sometimes to other parts of the body where it may affect the autonomic nervous system. It may be acute or chronic. A number of different disorders may cause polyneuropathy, including diabetes and some types of Guillain–Barré syndrome.

<span class="mw-page-title-main">Alcoholic polyneuropathy</span> Medical condition

Alcoholic polyneuropathy is a neurological disorder in which peripheral nerves throughout the body malfunction simultaneously. It is defined by axonal degeneration in neurons of both the sensory and motor systems and initially occurs at the distal ends of the longest axons in the body. This nerve damage causes an individual to experience pain and motor weakness, first in the feet and hands and then progressing centrally. Alcoholic polyneuropathy is caused primarily by chronic alcoholism; however, vitamin deficiencies are also known to contribute to its development. This disease typically occurs in chronic alcoholics who have some sort of nutritional deficiency. Treatment may involve nutritional supplementation, pain management, and abstaining from alcohol.

<span class="mw-page-title-main">POEMS syndrome</span> Paraneoplastic syndrome

POEMS syndrome is a rare paraneoplastic syndrome caused by a clone of aberrant plasma cells. The name POEMS is an acronym for some of the disease's major signs and symptoms, as is PEP.

<span class="mw-page-title-main">Neuritis</span> Inflammation of a nerve or generally any part of the nervous system

Neuritis, from the Greek νεῦρον), is inflammation of a nerve or the general inflammation of the peripheral nervous system. Inflammation, and frequently concomitant demyelination, cause impaired transmission of neural signals and leads to aberrant nerve function. Neuritis is often conflated with neuropathy, a broad term describing any disease process which affects the peripheral nervous system. However, neuropathies may be due to either inflammatory or non-inflammatory causes, and the term encompasses any form of damage, degeneration, or dysfunction, while neuritis refers specifically to the inflammatory process.

Polyneuropathy in dogs and cats is a collection of peripheral nerve disorders that often are breed-related in these animals. Polyneuropathy indicates that multiple nerves are involved, unlike mononeuropathy. Polyneuropathy usually involves motor nerve dysfunction, also known as lower motor neuron disease. Symptoms include decreased or absent reflexes and muscle tone, weakness, or paralysis. It often occurs in the rear legs and is bilateral. Most are chronic problems with a slow onset of symptoms, but some occur suddenly.

<span class="mw-page-title-main">Chronic inflammatory demyelinating polyneuropathy</span> Medical condition

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disease of the peripheral nervous system characterized by progressive weakness and impaired sensory function in the legs and arms. The disorder is sometimes called chronic relapsing polyneuropathy (CRP) or chronic inflammatory demyelinating polyradiculoneuropathy. CIDP is closely related to Guillain–Barré syndrome and it is considered the chronic counterpart of that acute disease. Its symptoms are also similar to progressive inflammatory neuropathy. It is one of several types of neuropathy.

<span class="mw-page-title-main">Rheobase</span>

Rheobase is a measure of membrane potential excitability. In neuroscience, rheobase is the minimal current amplitude of infinite duration that results in the depolarization threshold of the cell membranes being reached, such as an action potential or the contraction of a muscle. In Greek, the root rhe translates to "current or flow", and basi means "bottom or foundation": thus the rheobase is the minimum current that will produce an action potential or muscle contraction.

A paraneoplastic syndrome is a syndrome that is the consequence of a tumor in the body. It is specifically due to the production of chemical signaling molecules by tumor cells or by an immune response against the tumor. Unlike a mass effect, it is not due to the local presence of cancer cells.

Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation or pain often in the back along with muscle weakness, beginning in the feet and hands, often spreading to the arms and upper body. The symptoms may develop over hours to a few weeks. During the acute phase, the disorder can be life-threatening, with about 15% of people developing weakness of the breathing muscles and, therefore, requiring mechanical ventilation. Some are affected by changes in the function of the autonomic nervous system, which can lead to dangerous abnormalities in heart rate and blood pressure.

Acute motor axonal neuropathy (AMAN) is a variant of Guillain–Barré syndrome. It is characterized by acute paralysis and loss of reflexes without sensory loss. Pathologically, there is motor axonal degeneration with antibody-mediated attacks of motor nerves and nodes of Ranvier.

Antiganglioside antibodies that react to self-gangliosides are found in autoimmune neuropathies. These antibodies were first found to react with cerebellar cells. These antibodies show highest association with certain forms of Guillain–Barré syndrome.

<span class="mw-page-title-main">Hereditary motor and sensory neuropathy</span> Medical condition

Hereditary motor and sensory neuropathies (HMSN) is a name sometimes given to a group of different neuropathies which are all characterized by their impact upon both afferent and efferent neural communication. HMSN are characterised by atypical neural development and degradation of neural tissue. The two common forms of HMSN are either hypertrophic demyelinated nerves or complete atrophy of neural tissue. Hypertrophic condition causes neural stiffness and a demyelination of nerves in the peripheral nervous system, and atrophy causes the breakdown of axons and neural cell bodies. In these disorders, a patient experiences progressive muscle atrophy and sensory neuropathy of the extremities.

Neuropathy may refer to:

Anti-MAG peripheral neuropathy is a specific type of peripheral neuropathy in which the person's own immune system attacks cells that are specific in maintaining a healthy nervous system. As these cells are destroyed by antibodies, the nerve cells in the surrounding region begin to lose function and create many problems in both sensory and motor function. Specifically, antibodies against myelin-associated glycoprotein (MAG) damage Schwann cells. While the disorder occurs in only 10% of those afflicted with peripheral neuropathy, people afflicted have symptoms such as muscle weakness, sensory problems, and other motor deficits usually starting in the form of a tremor of the hands or trouble walking. There are, however, multiple treatments that range from simple exercises in order to build strength to targeted drug treatments that have been shown to improve function in people with this type of peripheral neuropathy.

Multifocal motor neuropathy (MMN) is a progressively worsening condition where muscles in the extremities gradually weaken. The disorder, a pure motor neuropathy syndrome, is sometimes mistaken for amyotrophic lateral sclerosis (ALS) because of the similarity in the clinical picture, especially if muscle fasciculations are present. MMN is thought to be autoimmune. It was first described in the mid-1980s.

<span class="mw-page-title-main">Autoimmune autonomic ganglionopathy</span> Medical condition

Autoimmune autonomic ganglionopathy is a type of immune-mediated autonomic failure that is associated with antibodies against the ganglionic nicotinic acetylcholine receptor present in sympathetic, parasympathetic, and enteric ganglia. Typical symptoms include gastrointestinal dysmotility, orthostatic hypotension, and tonic pupils. Many cases have a sudden onset, but others worsen over time, resembling degenerative forms of autonomic dysfunction. For milder cases, supportive treatment is used to manage symptoms. Plasma exchange, intravenous immunoglobulin, corticosteroids, or immunosuppression have been used successfully to treat more severe cases.

Peripheral mononeuropathy is a nerve related disease where a single nerve, that is used to transport messages from the brain to the peripheral body, is diseased or damaged. Peripheral neuropathy is a general term that indicates any disorder of the peripheral nervous system. The name of the disorder itself can be broken down in order to understand this better; peripheral: in regard to peripheral neuropathy, refers to outside of the brain and spinal cord; neuro: means nerve related; -pathy; means disease. Peripheral mononeuropathy is a disorder that links to Peripheral Neuropathy, as it only effects a single peripheral nerve rather than several damaged or diseased nerves throughout the body. Healthy peripheral nerves are able to “carry messages from the brain and spinal cord to muscles, organs, and other body tissues”.

Megavitamin-B6 syndrome is a collection of symptoms that can result from chronic supplementation, or acute overdose, of vitamin B6. While it is also known as hypervitaminosis B6, vitamin B6 toxicity and vitamin B6 excess, megavitamin-b6 syndrome is the name used in the ICD-10.

References

  1. 1 2 3 4 5 6 7 8 9 10 Amato, Anthony A.; Ropper, Allan H. (22 October 2020). "Sensory Ganglionopathy". New England Journal of Medicine. 383 (17): 1657–1662. doi:10.1056/NEJMra2023935.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Gwathmey, Kelly Graham (January 2016). "Sensory neuronopathies". Muscle & Nerve. 53 (1): 8–19. doi:10.1002/mus.24943.
  3. ↑ "Length-Dependent Polyneuropathies". Peripheral Neuropathies: A Practical Approach. Cambridge University Press. 2018. p. 135. ISBN   978-1-107-09218-1.
  4. 1 2 3 4 5 6 7 Camdessanche, J.-P.; Jousserand, G.; Ferraud, K.; Vial, C.; Petiot, P.; Honnorat, J.; Antoine, J.-C. (1 July 2009). "The pattern and diagnostic criteria of sensory neuronopathy: a case-control study". Brain. 132 (7): 1723–1733. doi:10.1093/brain/awp136.
  5. 1 2 3 Amato, Anthony; Barohn, Richard. Harrison's Principles of Internal Medicine (19 ed.). McGraw Hill. p. 2683. ISBN   1260128857.
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