Rigid-person syndrome ( SPS ), also known as rigid-male syndrome ( SMS ), is a rare disorder neurological causes are not clearly characterized by progressive rigidity and stiffness. Stiffness primarily affects the trunkal muscles and is superimposed by seizures, resulting in postural deformity. Chronic pain, impaired mobility, and lumbar hyperlordosis are common symptoms.
SPS occurs in about one in a million people and is most commonly found in middle-aged people. A small percentage of patients have variations in paraneoplastic conditions. Variant conditions, such as stiff-limb syndromes that primarily affect specific limbs, are often seen.
SPS was first described in 1956. The diagnostic criteria were proposed in 1960 and refined two decades later. In the 1990s and 2000s the role of antibodies in the condition became more apparent. SPS patients generally have GAD antibodies, which are rare in the general population. In addition to blood tests for GAD, electromyography tests can help confirm the presence of the condition.
Benzodiazepine group drugs are the most common treatment; they are used to relieve symptoms of stiffness. Other common treatments include baclofen, intravenous immunoglobin and rituximab. There is limited therapeutic experience but encourages hematopoietic stem cell transplantation for SPS.
Video Stiff-person syndrome
Signs and symptoms
Patients with stiff-person syndrome (SPS) suffer from progressive stiffness in their truncal muscles, which become stiff and stiff because the lumbar and abdominal muscles engage in constant contraction. Initially, stiffness occurs in the paraspinal and thoracolumbar abdominal muscles. This then affects the proximal muscles and the abdominal wall. Stiffness causes changes in posture, and the patient develops a rigid walking style. Persistent lumbar hyperchlorosis often occurs as it progresses. Muscle stiffness initially fluctuates, sometimes for days or weeks, but eventually begins to consistently impair mobility. As the disease progresses, the patient sometimes becomes unable to walk or bend. Chronic pain is common and worsens over time but sometimes acute pain also occurs. Stress, cold weather, and infection lead to increased symptoms, and sleep reduces them.
SPS patients experience seizures and very high sensitivity to touch and sound. These seizures occur mainly in the proximal and axial limb muscles. There is a co-contraction of muscle agonists and antagonists. Spasm usually lasts for several minutes and can recur for hours. Seizures are unpredictable and are often caused by rapid movements, emotional distress, or sudden sound or touch. In rare cases, facial, hand, foot, and chest muscles can be affected and unusual eye movements and vertigo occur. There is a quick stretch reflex and clonus occurs in the patient. Late in the progression of this disease, hypnagogic myoclonus may occur. Tachycardia and hypertension are sometimes also present.
Because of seizures, patients may become increasingly fearful, need help, and lose the ability to work, leading to depression, anxiety, and phobias, including agoraphobia and dromophobia. Most patients are psychologically normal and respond to their situation fairly.
Paraneoplastic SPS tends to affect the neck and arms more than other variations. It lasts very quickly, is more painful, and is more likely to include distal pain than the classic SPS. Patients with paraneoplastic SPS generally have no other autoimmune problems but may have other paraneoplastic conditions.
Stiff-limb syndrome is a variant of SPS. This syndrome develops into full SPS about 25 percent of the time. Rigidity and seizures are usually confined to the limbs and hyperlordoisis generally does not occur. Stiffness begins with one leg and remains most prominent there. Sphincter and brainstem problems often occur with rigid-limb syndrome. Progressive encephalomyelitis with rigidity, other variants of the condition, including SPS symptoms with brainstem problems and autonomic disorders. It involves polio-encephalomyelitis in the spine and brainstem. There is cerebellar involvement and brain stem. In some cases, the limbic system is also affected. Most patients have upper motoneuron problems and autonomic disorders. Human jolting syndrome or jerking SPS is another subtype of this condition. It starts like a classic SPS and lasts for several years, up to 14 in some cases. This is then distinguished by the development of myoclonus as well as seizures and ataxia in some cases.
Maps Stiff-person syndrome
Cause
Patients with SPS generally have high levels of high glutamic acid decarboxylase titer antibody. About 80 percent of SPS patients have GAD antibodies, compared with about one percent of the general population. The majority of people who have GAD antibodies do not contract with SPS, suggesting that systematic antibody synthesis is not the only cause of SPS. GAD, presinaptic autoantigen, is generally considered to play a key role in this condition, but the precise details of how autoantibodies affect SPS patients are unknown. Most SPS patients with high titres GAD antibodies also have antibodies that inhibit proteins associated with GABA receptors (GABARAP). Autoantibodies against amphiphysin and gephyrin are also occasionally found in SPS patients. Antibodies appear to interact with antigens in brain neurons and spinal synapses, causing functional blockade with gamma-aminobutyric acid. This causes GABA disorders, which may cause stiffness and seizures characteristic of SPS. There is a low GABA rate in the motor cortex of SPS patients.
It is not known why GAD autoimmunity occurs in SPS patients, and whether SPS qualifies as a neuro-autoimmune disorder has been questioned. It is also unknown whether these antibodies are pathogenic. The number of antibody titers of GAD found in SPS patients is not correlated with the severity of the disease, indicating that titer levels do not need to be monitored. It has not been proven that GAD antibodies are the only cause of SPS, and it is possible that they are the markers or epiphenomenon that causes the condition.
In SPS patients, the motor unit neurons fire unconsciously in a way that resembles a normal contraction. Potential motor units light up when the patient is resting, especially in the stiff muscles. Excessive firing of motor neurons may be caused by malfunctions in spinal and supra-segmental inhibitory tissue utilizing GABA. Unconscious action arises voluntarily on the EMG scan; even when the patient tries to relax, there is contraction of agonist and antagonist.
In a small proportion of patients with SPS, breast, ovary, or lung cancer manifest paraneoplastis as proximal muscle stiffness. This cancer is associated with synaptic proteins amphiphysin and gephyrin. Paraneoplastic SPS with amphiphysin antibodies and breast adenocarcinoma tend to coexist. These patients are less likely to have GAD antibodies. Passive transfer of disease by plasma injections has been shown in paraneoplastic SPS but not classical SPS.
There is evidence of SPS genetic risk. Class II HLA focuses makes the patient susceptible to the condition. Most SPS patients have DQB1 * 0201 alleles. The allele is also associated with type 1 diabetes.
Diagnosis
SPS is diagnosed by evaluating clinical findings and excluding other conditions. There are no special laboratory tests that confirm its existence. Underdiagnosis and misdiagnosis are common.
The presence of antibodies against GAD is the best indication of conditions that can be detected by blood and cerebrospinal fluid (CSF) tests. Anti-GAD65 is found in about 80 percent of SPS patients. Anti-thyroid, anti-intrinsic, anti-nuclear, anti-RNP, and anti-gliadin factors are also present in blood tests. Electromyography (EMG) demonstrates the removal of spontaneous motor units in SPS patients. EMG can confirm the diagnosis by noting seizures in the distant muscles as a result of subnocular stimulation of the skin nerves or mixtures. Responsiveness to diazepam helps ensure that patients suffer from SPS, as this reduces the stiffness and potential of motorized motor units.
The same general criteria are used to diagnose paraneoplastic SPS as a normal form of the condition. Once SPS is diagnosed, a poor response to conventional therapy and the presence of cancer suggests that it may be paraneoplastic. CT scans are indicated for SPS patients who respond poorly to therapy to determine if this is the case.
Various conditions have symptoms similar to SPS, including myelopathies, dystonias, spinocerebellar degeneration, primary lateral sclerosis, neuromyotonia, and some psychogenic disorders. Tetanus, malignant neuroleptic syndrome, malignant hyperpirexia, chronic spinal interneuronitis, serotonin syndrome, Multiple sclerosis, Parkinson's disease, and Isaacs syndrome should also be excluded.
Fear and phobic patients often mistakenly lead doctors to think that their symptoms are psychogenic, and sometimes they are suspected of illness. It takes an average of six years after the onset of symptoms before the disease is diagnosed.
Treatment
There is no evidence-based criterion to treat SPS, and no large controlled care trial for this condition. The scarcity of disease makes it difficult to set guidelines.
GABA A agonist, usually diazepam but occasionally other benzodiazepines, is the main treatment for SPS. Drugs that increase GABA activity reduce muscle stiffness caused by lack of GABAergic tones. They increase pathways that depend on GABA and have muscle relaxant and anticonvulsant effects, often providing symptomatic relief. Because the condition worsens over time, patients generally require increased doses, which causes more side effects. For this reason, a gradual increase in benzodiazepine dosage is indicated. Baclofen, GABA agonist B , is commonly used when individuals taking high-dose benzodiazepines have high side effects. In some cases it has shown improvement in electrophysiological and muscle rigidity when administered intravenously. Administration of intrathecal baclofen may not have long-term benefits, and there are potentially serious side effects.
Treatments that target the autoimmune response are also used. Intravenous immunoglobin is the best second-line treatment for SPS. It often decreases stiffness and improves quality of life and surprises reflexes. Generally safe, but there are potentially serious and expensive side effects. The European Federation of Neurological Societies suggests it is used when disabled patients do not respond well to diazepam and baclofen. Steroids, rituximab, and plasma exchange have been used to suppress the immune system in SPS patients, but the efficacy of this treatment is unclear. Botulinum toxin has been used to treat SPS, but it does not seem to have long-term benefits and has potentially serious side effects. In the case of paraneoplastik, the tumor should be managed for the condition to be conceived. Opiates are sometimes used to treat severe pain, but in some cases they aggravate symptoms.
Hematopoietic stem cell transplantation (HSCT) with high-intensity conditioning protocol has been performed in some cases with severe anti-GAD-positive SPS, resulting in clinical remission. In carefully chosen cases, refractory SPS treatment, HSCT may be an effective therapeutic option.
Prognosis
The development of SPS depends on whether it is a typical or abnormal shape of the condition and the presence of comorbidities. Early recognition and neurological care can limit its development. SPS is generally responsive to treatment, but the condition usually develops and is stable periodically. Even with treatment, the quality of life generally decreases as stiffness prevents many activities. Some patients require mobility assistance because of the risk of falling. Approximately 65 percent of SPS patients can not function independently. About ten percent of SPS patients require intensive care at some point; sudden death occurs in approximately the same number of patients. This death is usually caused by metabolic acidosis or autonomic crisis.
Epidemiology
SPS is estimated to have a prevalence of about one per million. Underdiagnosis and misdiagnosis inhibit epidemiological information about the condition and may cause its prevalence to be underestimated. In the UK, 119 cases were identified between 2000 and 2005. This did not occur in any racial or ethnic group. The age of onset varies from about 30 to 60, and it is most common in people in their 40s. Five to ten percent of patients with SPS have a paraneoplastic variant of this condition. In one group of 127 patients, only 11 of them had paraneoplatic symptoms. About 35 percent of SPS patients have type I diabetes.
History
SPS was first described by Moersch and Woltman in 1956. Their description of the disease is based on 14 cases they have observed for 32 years. Using electromyography, they note that the combustion of motor units indicates that voluntary muscle contractions occur in their patients. Previously, the SPS case had been dismissed as a psychogenic problem. Moersch and Woltman were originally termed "rigid-human syndrome" conditions, but the first female patients were confirmed in 1958 and a boy was confirmed to have them in 1960. The clinical diagnostic criteria were developed by Gordon et al. in 1967. They observed "persistent tonic contractions reflected in constant shooting, even at rest" after giving the patient muscle relaxants and examining them with electromyography. In 1989, criteria for SPS diagnosis were adopted which included episodic axial rigidity, development of stiffness, lordosis, and triggered spasms. The name of the disease shifted from "stiff-man syndrome" to "gender-neutral syndrome" in 1991.
In 1988, Solimena et al. found that autoantibodies to GAD played a key role in SPS. Two years later, Solimena found antibodies in 20 of 33 patients examined. In the late 1980s, it also showed that serum SPS patients would bind GABAergic neurons. In 2006, the role of GABARAP in SPS was found. The first case of paraneoplastic SPS was discovered in 1975. In 1993, antiamphipicin proved to play a role in paraneoplastic SPS, and seven years later antigephyrin was also found to be involved in this condition.
Source of the article : Wikipedia
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