Stiff person syndrome
Encyclopedia
Stiff person syndrome (or stiff-man syndrome; also known as Stiffperson's Syndrome or Moersch-Woltman Condition) is a rare neurologic
disorder of unknown etiology
characterized by progressive rigidity and stiffness, primarily of the axial musculature, that is superimposed by spasms, resulting in postural deformities. There are also sub-variants: Stiff Baby Syndrome and Stiff Limb Syndrome. Other forms or types of the disease include focal SPS, jerking SPS, and progressive encephalomyelitis with rigidity
and myoclonus
.
, which begin in this stage. Exaggerated lumbar lordosis
becomes more evident in the patients. Depression can be comorbid with SPS at this stage due to the patient’s quality of life decreasing. In the end stage, activities of daily living such as eating and simple movements become hard to perform. Skeletal fractures and muscle ruptures occur quite often along with joint deformities.
Those with the illness experience progressive, fluctuating tonic muscle contractions, particularly the axial musculature. These spasms occur in response to environmental stimuli such as voluntary or passive movements, and unexpected somatosensory or auditory stimulation. Often changes in emotion or stress can trigger spasms as well. Common signs of SPS found during assessment are hypertonia
, hyperreflexia
and rigidity
of muscles.
Reflexive integrity in individuals with Stiff Person Syndrome can be assessed via deep tendon reflexes as well as resistance to passive stretch. Deep tendon reflexes are graded using a 0 to 4+ scale. 0 indicates absent reflexes, 1+ indicates hypoactive (decreased) reflexes, 2+ indicates normal reflexes, 3+ indicates hyperactive (increased) reflexes without clonus and 4+ indicates hyperactive reflexes with clonus. During the examination, individuals with stiff person’s syndrome are likely to have deep tendon reflexes which are graded at 2+ (normal) or 3+ (increased reflexes). Furthermore, they are likely to exhibit increased startle reflex as well as an increased head retraction reflex (HRR).
Symptoms begin in the region of the trunk and the lower extremities before moving proximally in the upper limbs, and eventually affecting facial and laryngeal muscles used for swallowing and speech.
Depression
and anxiety
are often noted although this may be a result of discomfort due to stiffness, rather than underlying neurochemical
abnormalities.
MRI detection of GABA
in the brain have demonstrated reduced levels in stiff-person syndrome.
In the variant Stiff-limb syndrome, symptoms present focally affecting one or more limbs. Motor symptoms occur predominantly in distal limb muscles rather than axial muscles. However, when patients experience severe spasms, motor symptoms can be seen in the trunk, upper extremities and face. Increased distal limb stiffness in ankles and feet leads to feet being in constant plantar flexion. This in turn affects posture during gait
and increases fall risks for the patient.
possess anti-GAD antibodies, yet the frequency of SPS among Type I diabetics is 1 in 10,000. Approximately 60% of patients diagnosed with SPS have anti-GAD antibodies present, while 40% do not and therefore rely on clinical testing for diagnosis. The GAD protein regions (epitopes) recognized by these antibodies may differ in each disease(GAD65ab). A mutation in GLRA1
(glycine receptor
) is responsible for some cases of stiff person syndrome. Apart from antibodies to GAD65 seen in the serum, these antibodies are also found in the cerebrospinal fluid of stiff-person syndrome patients.
rarely sps is also seen associated with cancer of breast and hodgkins lymphoma.
action, such as benzodiazepines. These treatments lose their effectiveness as the illness progresses.
In the absence of double-blind
, placebo
-controlled trials to determine treatment efficacy, some authorities recommend human trials of immunosuppressive therapy, plasmapheresis
or intravenous immunoglobulin infusion. A recent study funded by the NINDS
demonstrated the effectiveness of intravenous immunoglobulin (IVIg) treatment in reducing stiffness and lowering sensitivity to noise, touch, and stress in people with SPS.
Monoclonal antibody rituximab
has produced long-lasting remissions. Clinical trials of this treatment have been completed. NINDS also recently tested plasmapherisis as another treatment option.
One case found symptoms improved unexpectedly from propofol
administration.
Physical therapy
is another treatment option for people with stiff person syndrome. It may help attenuate spasms
in some patients, but physiotherapy should be used cautiously in patients for whom passive
movements trigger spasms. Some physical therapy treatment approaches may include therapeutic exercise, functional retraining
, and training family members..) Therapeutic exercises for people with stiff man syndrome would likely include a stretching program to help patients gain range of motion
by reducing muscle spasms and muscle stiffness. Functional retraining would have a large emphasis on gait training
to increase endurance
, independence, and the ability to climb stairs. Practicing sitting to standing, in a variety of situations, would aid a person in becoming more independent, especially with activities of daily living
. Training the patient’s family would allow the family to help with home stretches and situations where the person is dependent on another person (ie wheelchair transfers, getting dressed, ambulating long distance, etc.) Physical therapy may not change the disease course in the long-term, however, it may help optimize current function as well as have some positive short term effects.
Prognosis is variable and there is no reliable predictor of speed and severity of disease onset. Muscle tetany
may lead to muscle rupture and broken bones, or problems swallowing and breathing in severe cases.
Neurology
Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...
disorder of unknown etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
characterized by progressive rigidity and stiffness, primarily of the axial musculature, that is superimposed by spasms, resulting in postural deformities. There are also sub-variants: Stiff Baby Syndrome and Stiff Limb Syndrome. Other forms or types of the disease include focal SPS, jerking SPS, and progressive encephalomyelitis with rigidity
Rigidity
Rigid or rigidity may refer to:*Stiffness, the property of a solid body to resist deformation, which is sometimes referred to as rigidity*Structural rigidity, a mathematical theory of the stiffness of ensembles of rigid objects connected by hinges...
and myoclonus
Myoclonus
Myoclonus is brief, involuntary twitching of a muscle or a group of muscles. It describes a medical sign and, generally, is not a diagnosis of a disease. Brief twitches are perfectly normal. The myoclonic twitches are usually caused by sudden muscle contractions; they also can result from brief...
.
Signs and symptoms
People with stiff person syndrome tends to present in 3 different stages: early, late and end stage. In the early stages, there are few objective findings indicating SPS during the initial assessment. SPS will begin insidiously in the axial muscles. Patients will present with an exaggerated upright posture and have stiffness and pain in the whole back. Sleep disturbances are also common due to muscle spasms waking them. In the late stages, proximal limb muscle become involved and the patient tends to move slower as fast movements will cause the severe spasms. Emotions such as anger have been shown to have a link to causing the spasmsSpasms
-Plot:Jason Kincaid has this massive serpent captured and brought to the US because it killed his brother and he now shares some kind of psychic link with it...
, which begin in this stage. Exaggerated lumbar lordosis
Lordosis
Lordosis is a medical term used to describe an inward curvature of a portion of the lumbar and cervical vertebral column. Two segments of the vertebral column, namely cervical and lumbar, are normally lordotic, that is, they are set in a curve that has its convexity anteriorly and concavity...
becomes more evident in the patients. Depression can be comorbid with SPS at this stage due to the patient’s quality of life decreasing. In the end stage, activities of daily living such as eating and simple movements become hard to perform. Skeletal fractures and muscle ruptures occur quite often along with joint deformities.
Those with the illness experience progressive, fluctuating tonic muscle contractions, particularly the axial musculature. These spasms occur in response to environmental stimuli such as voluntary or passive movements, and unexpected somatosensory or auditory stimulation. Often changes in emotion or stress can trigger spasms as well. Common signs of SPS found during assessment are hypertonia
Hypertonia
Hypertonia a condition marked by an abnormal increase in muscle tension and a reduced ability of a muscle to stretch. It is caused by lesions to upper motor neurons in the central nervous system, which carry information from the central nervous system to the muscles and control posture, muscle...
, hyperreflexia
Hyperreflexia
Hyperreflexia is defined as overactive or overresponsive reflexes. Examples of this can include twitching or spastic tendencies, which are indicative of upper motor neuron disease as well as the lessening or loss of control ordinarily exerted by higher brain centers of lower neural pathways...
and rigidity
Rigidity
Rigid or rigidity may refer to:*Stiffness, the property of a solid body to resist deformation, which is sometimes referred to as rigidity*Structural rigidity, a mathematical theory of the stiffness of ensembles of rigid objects connected by hinges...
of muscles.
Reflexive integrity in individuals with Stiff Person Syndrome can be assessed via deep tendon reflexes as well as resistance to passive stretch. Deep tendon reflexes are graded using a 0 to 4+ scale. 0 indicates absent reflexes, 1+ indicates hypoactive (decreased) reflexes, 2+ indicates normal reflexes, 3+ indicates hyperactive (increased) reflexes without clonus and 4+ indicates hyperactive reflexes with clonus. During the examination, individuals with stiff person’s syndrome are likely to have deep tendon reflexes which are graded at 2+ (normal) or 3+ (increased reflexes). Furthermore, they are likely to exhibit increased startle reflex as well as an increased head retraction reflex (HRR).
Symptoms begin in the region of the trunk and the lower extremities before moving proximally in the upper limbs, and eventually affecting facial and laryngeal muscles used for swallowing and speech.
Depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
and anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
are often noted although this may be a result of discomfort due to stiffness, rather than underlying neurochemical
Neurochemical
A neurochemical is an organic molecule, such as serotonin, dopamine, or nerve growth factor, that participates in neural activity. The science of neurochemistry studies the functions of neurochemicals.-Prominent neurochemicals:...
abnormalities.
MRI detection of GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
in the brain have demonstrated reduced levels in stiff-person syndrome.
In the variant Stiff-limb syndrome, symptoms present focally affecting one or more limbs. Motor symptoms occur predominantly in distal limb muscles rather than axial muscles. However, when patients experience severe spasms, motor symptoms can be seen in the trunk, upper extremities and face. Increased distal limb stiffness in ankles and feet leads to feet being in constant plantar flexion. This in turn affects posture during gait
Gait
Gait is the pattern of movement of the limbs of animals, including humans, during locomotion over a solid substrate. Most animals use a variety of gaits, selecting gait based on speed, terrain, the need to maneuver, and energetic efficiency...
and increases fall risks for the patient.
Causes
Because many patients with SPS have circulating antibodies to the enzyme glutamic acid decarboxylase (GAD), an autoimmune cause of the disease has been postulated. However, GAD antibodies cannot be the sole cause, as most Type I diabeticsDiabetes mellitus type 1
Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose...
possess anti-GAD antibodies, yet the frequency of SPS among Type I diabetics is 1 in 10,000. Approximately 60% of patients diagnosed with SPS have anti-GAD antibodies present, while 40% do not and therefore rely on clinical testing for diagnosis. The GAD protein regions (epitopes) recognized by these antibodies may differ in each disease(GAD65ab). A mutation in GLRA1
GLRA1
Glycine receptor subunit alpha-1 is a protein that in humans is encoded by the GLRA1 gene.-Further reading:...
(glycine receptor
Glycine receptor
The glycine receptor, or GlyR, is the receptor for the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current...
) is responsible for some cases of stiff person syndrome. Apart from antibodies to GAD65 seen in the serum, these antibodies are also found in the cerebrospinal fluid of stiff-person syndrome patients.
rarely sps is also seen associated with cancer of breast and hodgkins lymphoma.
Treatment
Treatment is mostly palliative with muscle relaxants which potentiate GABAGabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
action, such as benzodiazepines. These treatments lose their effectiveness as the illness progresses.
In the absence of double-blind
Double-blind
A blind or blinded experiment is a scientific experiment where some of the people involved are prevented from knowing certain information that might lead to conscious or subconscious bias on their part, invalidating the results....
, placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
-controlled trials to determine treatment efficacy, some authorities recommend human trials of immunosuppressive therapy, plasmapheresis
Plasmapheresis
Plasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...
or intravenous immunoglobulin infusion. A recent study funded by the NINDS
National Institute of Neurological Disorders and Stroke
The National Institute of Neurological Disorders and Stroke is a part of the U.S. National Institutes of Health . It conducts and funds research on brain and nervous system disorders and has a budget of just over US$1.5 billion...
demonstrated the effectiveness of intravenous immunoglobulin (IVIg) treatment in reducing stiffness and lowering sensitivity to noise, touch, and stress in people with SPS.
Monoclonal antibody rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
has produced long-lasting remissions. Clinical trials of this treatment have been completed. NINDS also recently tested plasmapherisis as another treatment option.
One case found symptoms improved unexpectedly from propofol
Propofol
Propofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine...
administration.
Physical therapy
Physical therapy
Physical therapy , often abbreviated PT, is a health care profession. Physical therapy is concerned with identifying and maximizing quality of life and movement potential within the spheres of promotion, prevention, diagnosis, treatment/intervention,and rehabilitation...
is another treatment option for people with stiff person syndrome. It may help attenuate spasms
Spasms
-Plot:Jason Kincaid has this massive serpent captured and brought to the US because it killed his brother and he now shares some kind of psychic link with it...
in some patients, but physiotherapy should be used cautiously in patients for whom passive
Passive
Passive may refer to:* "Passive" , by A Perfect Circle* Passive voice, a grammatical voice common in many languages* Passive house, a standard for energy efficiency in buildings* Passive psi, psychic abilities involving cognition...
movements trigger spasms. Some physical therapy treatment approaches may include therapeutic exercise, functional retraining
Retraining
Vocational rehabilitation or retraining is the process of learning a new skill or trade, often in response to a change in the economic environment. Generally it reflects changes in profession rather than an "upward" movement in the same field....
, and training family members..) Therapeutic exercises for people with stiff man syndrome would likely include a stretching program to help patients gain range of motion
Range of motion
Range of motion , is the distance that a movable object may normally travel while properly attached to another object. It is also called range of travel, particularly when talking about mechanical devices and in mechanical engineering fields...
by reducing muscle spasms and muscle stiffness. Functional retraining would have a large emphasis on gait training
Gait training
In its most general form, Gait training is the act of learning how to walk. However, the term is more often used in reference to a person learning how to walk again after injury or with a disability...
to increase endurance
Endurance
Endurance is the ability for a human or animal to exert itself and remain active for a long period of time, as well as its ability to resist, withstand, recover from, and have immunity to trauma, wounds, or fatigue. In humans, it is usually used in aerobic or anaerobic exercise...
, independence, and the ability to climb stairs. Practicing sitting to standing, in a variety of situations, would aid a person in becoming more independent, especially with activities of daily living
Activities of daily living
Activities of Daily Living is a term used in healthcare to refer to daily self-care activities within an individual's place of residence, in outdoor environments, or both...
. Training the patient’s family would allow the family to help with home stretches and situations where the person is dependent on another person (ie wheelchair transfers, getting dressed, ambulating long distance, etc.) Physical therapy may not change the disease course in the long-term, however, it may help optimize current function as well as have some positive short term effects.
Prognosis
Patients with Stiff-person syndrome usually respond well to muscle relaxants and their condition can stabilize after months to years of progression. Those with Stiff-limb syndrome have a poorer prognosis, as they do not respond well to medications. These patients often require a wheelchair.Prognosis is variable and there is no reliable predictor of speed and severity of disease onset. Muscle tetany
Tetany
Tetany has two meanings, though both are related to the muscular system.* Tetany * Tetany The terms "tetany" and "tetanus" are distinct....
may lead to muscle rupture and broken bones, or problems swallowing and breathing in severe cases.
Epidemiology
This rare autoimmune disease shows no specific prevalence in either sex, has no known genetic predisposition and has no cure. Age of onset is usually 30–50 years of age, but can occur in children aged 3 years old and younger. At this age it is known as Stiff Baby Syndrome.Differential Diagnoses
The following differential diagnoses should also be considered when suspecting stiff person syndrome.- TetanusTetanusTetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani...
- HyperekplexiaHyperekplexiaHyperekplexia is a neurologic disorder classically characterised by pronounced startle responses to tactile or acoustic stimuli and hypertonia. The hypertonia may be predominantly truncal, attenuated during sleep and less prominent after a year of age...
- Strychnine poisoningStrychnine poisoningStrychnine poisoning can be fatal to humans and other animals and can occur by inhalation, swallowing or absorption through eyes or mouth. It produces some of the most dramatic and painful symptoms of any known toxic reaction...
- Isaac's syndrome also known as NeuromyotoniaNeuromyotoniaNeuromyotonia , also known as Isaacs' syndrome, is a form of peripheral nerve hyperexcitability that causes spontaneous muscular activity resulting from repetitive motor unit action potentials of peripheral origin.-Causes:...
- Spinal multiple sclerosisMultiple sclerosisMultiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
- Paraneoplastic Myelitis
- Latent autoimmune diabetesLatent autoimmune diabetesLatent Autoimmune Diabetes of Adults , also known as, Diabetes Type 1.5, is a term coined by Tuomi et al. in 1993 to describe slow-onset Type 1 autoimmune diabetes in adults...
of adults (LADA) - Spinal Arteriovenous malformationArteriovenous malformationArteriovenous malformation or AVM is an abnormal connection between veins and arteries, usually congenital. This pathology is widely known because of its occurrence in the central nervous system, but can appear in any location. An arteriovenous malformation is a vascular anomaly. It is a...
External links
- A site about the link between GAD and SPS at University of Birmingham Medical SchoolUniversity of Birmingham Medical SchoolThe University of Birmingham Medical School is one of Britain's largest and oldest medical schools with over 400 Medics graduating each year. It is based at the University of Birmingham in Edgbaston, Birmingham, England...
- Article at Cleveland ClinicCleveland ClinicThe Cleveland Clinic is a multispecialty academic medical center located in Cleveland, Ohio, United States. The Cleveland Clinic is currently regarded as one of the top 4 hospitals in the United States as rated by U.S. News & World Report...
- Article at eNotes
- GAD antibodies at antibodypatterns.com
- Amphiphysin antibodies at antibodypatterns.com
- SMS Support Group - the official UK and Ireland Support Group
- http://clinicaltrials.gov/ct2/results?cond=%22Stiff-Person+Syndrome%22 SPS Clinical Trials
- http://www.stiffpersonsyndrome.net/ Study of 33 SPS'ers and link for additional SPS'ers to submit reports on symptoms
- http://www.jimmunol.org/cgi/content/abstract/175/11/7755 Free abstract on GAD65ab eiotope for SPS diagnoses
- http://www.springerlink.com/content/kt6865774t1001v7/ 1990 article on SPS and sudden death (SPS+)
- http://www.hopkinsmedicine.org/neurology_neurosurgery/specialty_areas/neuroimmunology_and_neurological_infections/conditions/stiff_person_syndrome.html John Hopkins Neurology site for SPS
- http://www.eurordis.org/content/stiff-man-syndrome-still-dancing-inside - Eurodis Rare Diseases Europe article and link to SMS support group
- http://www.braintalkcommunities.org has Stiff Person Syndrome discussion threads, and information posts.