Paroxysmal dyskinesia | |
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Other names | Paroxysmal dystonic choreoathetosis |
Specialty | Neurology |
The paroxysmal dyskinesias (PD) are a group of movement disorders characterized by attacks of hyperkinesia with intact consciousness. [1] Paroxysmal dyskinesia is a rare disorder, however the number of individuals it affects remains unclear. There are three different subtypes of PD that include paroxysmal kinesigenic dyskinesia (PKD), paroxysmal nonkinesigenic dyskinesia (PNKD), and paroxysmal exercise-induced dyskinesia (PED). Other neurological diseases have similar symptoms to PD, such as epilepsy and Parkinson's. The different subtypes make accurate and quick diagnosis of PD challenging. Thus, PD is often under reported and misdiagnosed, making it difficult to accurately study its prevalence in human populations. Onset of PD is usually in late childhood to early adolescence. New drug regimens help treat symptoms of PD, but no cure for the disorder is known.
These movement disorders are classified into three main types based on their triggers and the duration and frequency of the attacks.
This is characterized by attacks of involuntary movements (dystonia, chorea, or ballism), which are typically triggered by sudden voluntary movements, but can also be triggered by involuntary movements as well (for example, hyperventilating). These voluntary movements usually involve whole body activity such as standing, walking, and running. The age of onset is typically in childhood or early adolescence with most cases reporting improvement or complete remission with aging. [2] Attacks last from seconds to minutes and are known to be at higher risk of occurring during stress, fear, cold, heat, or menstruation.
This is similar to PKD, characterizing as an episodic movement disorder, but is not triggered by voluntary movements. The attacks for PNKD are spontaneous and last from hours to days. It is an autosomal dominant disorder passing to nearly 50% of the offspring. Some predisposing factors include stress, excitement, alcoholic beverages, tea, and beverages with caffeine.
This is an extremely rare type of paroxysmal dyskinesia characterized by sudden, involuntary, dystonic movements, often including repetitive twisting motions and painful posturing. The attacks are triggered by exercise and other physical exertion, and usually last from minutes to an hour. Attacks usually appear in the body part that is being exercised or exerted over a period of time, perhaps 10 to 15 minutes. [2]
The symptoms for PKD are varied from case to case, however, typically they consist of involuntary movements. Such contractile movements include dystonia, chorea, athetosis, and ballism. For example, “Her attacks were characterized as sudden unilateral stiffness of upper and lower limbs followed by an involuntary extrarotation of the arm and leg.” [3] Another frequently occurring symptom is the presence of an aura before the attack. These sensations manifest in several forms, usually described as a tingling in the target limb. [3]
A single limb is the most frequently affected area; however it is possible for an attack to affect more than one limb. When more than one limb is affected, the two limbs are usually unilateral (same side), even though cases of bilateral (opposite sides) symptoms have also been observed. [3] Another frequently affected area is the torso, with some PKD patients twisting their body. [4]
Attacks experienced by PKD patients typically last less than a minute; [5] however, longer attacks can also occur. To further distinguish between PKD and epilepsy, patients typically retain consciousness during their attacks, and are able to recall the attacks even after they have ended. Despite retaining consciousness, patients are usually incapable of speech during the attack and may experience great pain in the affected area. [4] The frequency of attacks vary greatly. Some patients have been noted as having hundreds of attacks per day, while others go months without an attack. [3]
The attacks consist of dystonia, chorea, and athetosis just like PKD. They are mostly of the limbs, and are usually unilateral or asymmetric. What sets PNKD apart from PKD is that the attacks can last anywhere from four minutes to four hours, but shorter and longer attacks have been reported as well.
The attacks also affect the limbs, usually unilaterally, but bilateral symptoms have also been experienced. PNKD patients usually report the presence of an aura before an attack as well; however they are usually different from those of PKD patients. Once again the aura varies, but is typically felt in the target limb. Another frequently noted aura is dizziness [3]
PNKD patients experience attacks that last much longer than those of PKD. These attacks vary in length and can last anywhere between four minutes and four hours. Similar to the difference between length of attacks, the intervals between attacks are much longer. The Interval between PNKD patients’ attacks is from one day to several months. [3]
PED attacks are characterized in multiple ways. One distinguishing characteristic of PED patients is that they typically experience longer durations of dystonia during their attacks. The most frequent target of attacks are both legs bilaterally, rather than unilateral symptoms. [3] The attacks have also been known to affect the upper half of the body as well. In some cases, patients have had attacks that affected the posturing of their neck and shoulder. [6] Usually there is not an indicative aura symptom prior to a PED attack, which has to do with the nature of the onset of attacks.
The duration and frequency of PED attacks fall between those of PKD and PNKD. The attacks can be relieved with rest, typically taking about 10 minutes from cessation of the exercise. [6] Attacks usually do not last longer than 30 minutes. [3] Attacks typically occur at intervals of between a day and a month, however, there is a great deal of variability here. This variability can be contributed to the nature of the onset of attacks.
All PD associated subtypes have genetic contributions and are likely to run in a families genetic history due to dominant allele mutations. Mutations of identified genes have been leading areas of research in the study and treatment of paroxysmal dyskinesia. PKD, PNKD, and PED are classified as separate subtypes because they all have different presentations of symptoms, but also, because they are believed to have different pathologies.
Studies on diseases that are similar in nature to PD have revealed insights into the causes of movement disorders. Hypnogenic paroxysmal dyskinesia is a form of epilepsy affecting the frontal lobe. Single genes have been identified on chromosomes 15, 20, and 21, which contribute to the pathology of these epilepsy disorders. [4] Utilizing new knowledge about pathologies of related and similar disease can shed insight on the causal relationships in paroxysmal dyskinesia.
Numerous causes have been proposed for PKD, such as genetic mutations, multiple sclerosis, brain trauma, and endocrine dysfunction. This is not an exhaustive list; many other causes are being proposed and studied. Until causal genes can be identified, the pathology of PKD will not be fully understood. Researchers have identified specific loci in chromosomes 16 and 22, which have been reported to have a genotype–phenotype correlation. [4]
Research on the pathology for PNKD suggests that mutations to specific nucleotide sequences in chromosome 2, MR-1 (myofibrililogenesis regulator - 1) may be linked to PNKD. [4] Studies on MR-1 reveal that it serves as a detoxifying agent. PNKD is sometimes induced by the consumption of alcohol or coffee. Individuals with a mutation in the MR-1 gene sequence may have problems detoxifying the body when alcohol or caffeine is ingested, perhaps resulting in the onset of PNKD.
Other studies have revealed a possible mutation on the calcium sensitive potassium (BK) channel. [4] A mutation affecting the influx and efflux of potassium and calcium can cause large scale changes in a neuron. This specific mutation leads to increased excitability of the neuron, often inducing rapid depolarization eliciting numerous action potentials.
The pathogenesis of PKND is partially defined by the identification of mutations in the myofibrillogenesis regulator 1 (MR-1), whose gene product is an enzyme involved in the detoxification of methylglyoxal (a compound present in coffee, cola, and alcoholic beverages). [2]
Long periods of continuous physical exercise is often considered the causal factor involved in a PED diagnosis. It is important to note that PED a is sometimes co-diagnosed with epilepsy and young-onset Parkinson's disease. Correlations between the causes of young-onset Parkinson's disease and PED may be due to a similar problem, specifically a mutation of a potassium channel gene on chromosome 1. [4]
The pathogenesis of PED has also been linked to mutations in the GLUT1 glucose transporter which can result in transient energy deficits in the basal ganglia. [2] See GLUT1 deficiency syndrome.
Diagnosis is similar, but slightly different for each type of PD. Some types are more understood than others, and therefore have more criteria for diagnosis.
The guidelines for diagnosing PKD were reviewed and confirmed by Unterberger and Trinka. [3] PKD consists of unexpected forms of involuntary movements of the body. The patient is usually diagnosed sometime before their 20s, and is more likely diagnosed during childhood than early adulthood. Almost all PKD's are idiopathic, but there have been examples of autosomal dominant inheritance as well. [3] Physical examination and brain imaging examinations show normal results, and an EEG shows no specific abnormalities as well. However, the negative synchronous EEG results can be used to prove that PKD is not a sort of reflex epilepsy, but a different disease. [4]
PKD is the most prevalent subtype of paroxysmal dyskinesia, encompassing over 80% of all given PD diagnosis. PKD is more prevalent in boys, usually as high as 3.75:1. [4]
PNKD has a set guideline for diagnosis that is slightly different from PKD. PNKD usually occurs unexpectedly, and is not brought on by sudden movements or exercise. Instead the attacks are brought on by stresses such as emotional stress, fatigue, alcohol, or caffeine consumption. [3] Just like PKD, PNKD also shows autosomal dominance in family history. [3] Physical examination and brain imaging examinations show normal results, and EEG shows no specific abnormalities as well. [4]
PNKD is more prevalent in boys, with ratios of 1.4:1. [4]
PED has a set guideline for diagnosis that is similar, but slightly different from both PKD and PNKD. PED attacks consist of dystonic and bilateral movements usually in the lower limbs of the body. [3] These attacks are usually brought about only by exercise and physical exhaustion. PED patients do not feel an aura-like sensation before an attack occurs, unlike PKD and PNKD. These attacks usually last from 5 to 30 minutes, and can occur once a day or once a month. [3] Physical examination and brain imaging examinations show normal results, and EEG shows no specific abnormalities as well. [4]
PED is the rarest paraoxysmal dyskinesia subtype.
PKD patients usually show a good response to anticonvulsants. Most commonly used medications are sodium blockers, carbamazepine and phenytoin. During a drug-testing study, patients reported a decreasing response to the latter use of anticonvulsants and switched to carbamazepine or phenytoin. [2] Refraining from established triggers such as sudden movement has been shown to lessen attacks occurrences. Avoidance of predisposing factors such as stress, excitement, and fatigue also help manage attacks.
Treatment for PKND is more difficult than other Paroxysmal Dyskinesias. The majority of patients experience some relief from low dosages of clonazepam, a muscle relaxant and anticonvulsant. Similar to PKD, avoidance of stress, excitement, and fatigue will lower the frequency of PNKD attacks. Many patients also avoid known methyglyoxal containing foods and beverages such as alcohol, coffee, tea, and chocolate.
PED patients usually avoid prolonged, continuous exertion to prevent occurrence of attacks. Use of anticonvulsants such as benzodiazepines show little to no success in PED patients. A few cases have shown that patients were able to lessen their attacks with a high carbohydrate snack. A new approach to managing PED is the ketogenic diet, which alters the primary cerebral energy metabolism from glucose to ketone bodies. Reports have shown that the ketonic diet protects against seizures in epilepsy. [2] In PED, it is probable that ketones will provide sufficient energy for the basal ganglia, which is normally deficient in patients with PED. [2]
Paroxysmal Dyskinesia is not a fatal disease. Life can be extremely difficult with this disease depending on the severity. The prognosis of PD is extremely difficult to determine because the disease varies from person to person. The attacks for PKD can be reduced and managed with proper anticonvulsants, but there is no particular end in sight for any of the PD diseases. PKD has been described to cease for some patients after the age of 20, and two patients have reported to have a family history of the disease where PKD went into complete remission after the age of 23. [7] With PNKD and PED, at this time, there is no proper way to determine an accurate prognosis.
A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term convulsion is often used as a synonym for seizure. However, not all epileptic seizures result in convulsions, and not all convulsions are caused by epileptic seizures. Non-epileptic convulsions have no relation with epilepsy, and are caused by non-epileptic seizures.
Myoclonus is a brief, involuntary, irregular twitching of a muscle, a joint, or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus describes a medical sign and, generally, is not a diagnosis of a disease. These myoclonic twitches, jerks, or seizures are usually caused by sudden muscle contractions or brief lapses of contraction. The most common circumstance under which they occur is while falling asleep. Myoclonic jerks occur in healthy people and are experienced occasionally by everyone. However, when they appear with more persistence and become more widespread they can be a sign of various neurological disorders. Hiccups are a kind of myoclonic jerk specifically affecting the diaphragm. When a spasm is caused by another person it is known as a provoked spasm. Shuddering attacks in babies fall in this category.
Dyskinesia refers to a category of movement disorders that are characterized by involuntary muscle movements, including movements similar to tics or chorea and diminished voluntary movements. Dyskinesia can be anything from a slight tremor of the hands to an uncontrollable movement of the upper body or lower extremities. Discoordination can also occur internally especially with the respiratory muscles and it often goes unrecognized. Dyskinesia is a symptom of several medical disorders that are distinguished by their underlying cause.
Hyperkinesia refers to an increase in muscular activity that can result in excessive abnormal movements, excessive normal movements, or a combination of both. Hyperkinesia is a state of excessive restlessness which is featured in a large variety of disorders that affect the ability to control motor movement, such as Huntington's disease. It is the opposite of hypokinesia, which refers to decreased bodily movement, as commonly manifested in Parkinson's disease.
Corticobasal degeneration (CBD) is a rare neurodegenerative disease involving the cerebral cortex and the basal ganglia. CBD symptoms typically begin in people from 50 to 70 years of age, and the average disease duration is six years. It is characterized by marked disorders in movement and cognition, and is classified as one of the Parkinson plus syndromes. Diagnosis is difficult, as symptoms are often similar to those of other disorders, such as Parkinson's disease, progressive supranuclear palsy, and dementia with Lewy bodies, and a definitive diagnosis of CBD can only be made upon neuropathologic examination.
Frontal lobe epilepsy (FLE) is a neurological disorder that is characterized by brief, recurring seizures arising in the frontal lobes of the brain, that often occur during sleep. It is the second most common type of epilepsy after temporal lobe epilepsy (TLE), and is related to the temporal form in that both forms are characterized by partial (focal) seizures.
Neuroacanthocytosis is a label applied to several genetic neurological conditions in which the blood contains misshapen, spiculated red blood cells called acanthocytes.
Alternating hemiplegia of childhood (AHC) is an ultra-rare neurological disorder named for the transient episodes, often referred to as "attacks", of hemiplegia from which those with the disorder suffer. It typically presents before the age of 18 months. These hemiplegic attacks can cause anything from mild weakness to complete paralysis on one or both sides of the body, and they can vary greatly in duration. Attacks may also alternate from one side of the body to the other, or alternate between affecting one or both sides during a single attack. Besides hemiplegia, symptoms of the disorder include an extremely broad range of neurological and developmental impairments which are not well understood. Normally, hemiplegia and other associated symptoms cease completely with sleep, but they may recur upon waking.
Paroxysmal nonkinesigenic dyskinesia (PNKD) is an episodic movement disorder first described by Mount and Reback in 1940 under the name "Familial paroxysmal choreoathetosis". It is a rare hereditary disease that affects various muscular and nervous systems in the body, passing to roughly fifty percent of the offspring.
GLUT1 deficiency syndrome, also known as GLUT1-DS, De Vivo disease or Glucose transporter type 1 deficiency syndrome, is an autosomal dominant genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier. Glucose Transporter Type 1 Deficiency Syndrome has an estimated birth incidence of 1 in 90,000 to 1 in 24,300. This birth incidence translates to an estimated prevalence of 3,000 to 7,000 in the U.S.
Progressive Myoclonic Epilepsies (PME) are a rare group of inherited neurodegenerative diseases characterized by myoclonus, resistance to treatment, and neurological deterioration. The cause of PME depends largely on the type of PME. Most PMEs are caused by autosomal dominant or recessive and mitochondrial mutations. The location of the mutation also affects the inheritance and treatment of PME. Diagnosing PME is difficult due to their genetic heterogeneity and the lack of a genetic mutation identified in some patients. The prognosis depends largely on the worsening symptoms and failure to respond to treatment. There is no current cure for PME and treatment focuses on managing myoclonus and seizures through antiepileptic medication (AED).
Paroxysmal kinesigenic choreoathetosis (PKC) also called paroxysmal kinesigenic dyskinesia (PKD) is a hyperkinetic movement disorder characterized by attacks of involuntary movements, which are triggered by sudden voluntary movements. The number of attacks can increase during puberty and decrease in a person's 20s to 30s. Involuntary movements can take many forms such as ballism, chorea or dystonia and usually only affect one side of the body or one limb in particular. This rare disorder only affects about 1 in 150,000 people, with PKD accounting for 86.8% of all the types of paroxysmal dyskinesias, and occurs more often in males than females. There are two types of PKD, primary and secondary. Primary PKD can be further broken down into familial and sporadic. Familial PKD, which means the individual has a family history of the disorder, is more common, but sporadic cases are also seen. Secondary PKD can be caused by many other medical conditions such as multiple sclerosis (MS), stroke, pseudohypoparathyroidism, hypocalcemia, hypoglycemia, hyperglycemia, central nervous system trauma, or peripheral nervous system trauma. PKD has also been linked with infantile convulsions and choreoathetosis (ICCA) syndrome, in which patients have afebrile seizures during infancy and then develop paroxysmal choreoathetosis later in life. This phenomenon is actually quite common, with about 42% of individuals with PKD reporting a history of afebrile seizures as a child.
Paroxysmal exercise-induced dystonia or PED is a rare neurological disorder characterized by sudden, transient, involuntary movements, often including repetitive twisting motions and painful posturing triggered by exercise or other physical exertion. PED is in the class of paroxysmal dyskinesia which are a group of rare movement disorders characterized by attacks of hyperkinesia with intact consciousness. The term paroxysmal indicates that the episodes are sudden and short lived and usually unpredicted, and return to normal is rapid. The number of reported cases of people with PED is very small leading to difficulty in studying and classifying this disease and most studies are limited to a very small number of test subjects.
Dopamine-responsive dystonia (DRD) also known as Segawa syndrome (SS), is a genetic movement disorder which usually manifests itself during early childhood at around ages 5–8 years.
Neuroferritinopathy is a genetic neurodegenerative disorder characterized by the accumulation of iron in the basal ganglia, cerebellum, and motor cortex of the human brain. Symptoms, which are extrapyramidal in nature, progress slowly and generally do not become apparent until adulthood. These symptoms include chorea, dystonia, and cognitive deficits which worsen with age.
Sepiapterin reductase deficiency is an inherited pediatric disorder characterized by movement problems, and most commonly displayed as a pattern of involuntary sustained muscle contractions known as dystonia. Symptoms are usually present within the first year of age, but diagnosis is delayed due to physicians lack of awareness and the specialized diagnostic procedures. Individuals with this disorder also have delayed motor skills development including sitting, crawling, and need assistance when walking. Additional symptoms of this disorder include intellectual disability, excessive sleeping, mood swings, and an abnormally small head size. SR deficiency is a very rare condition. The first case was diagnosed in 2001, and since then there have been approximately 30 reported cases. At this time, the condition seems to be treatable, but the lack of overall awareness and the need for a series of atypical procedures used to diagnose this condition pose a dilemma.
Alternating hemiplegia is a form of hemiplegia that has an ipsilateral cranial nerve palsies and contralateral hemiplegia or hemiparesis of extremities of the body. The disorder is characterized by recurrent episodes of paralysis on one side of the body. There are multiple forms of alternating hemiplegia, Weber's syndrome, middle alternating hemiplegia, and inferior alternating hemiplegia. This type of syndrome can result from a unilateral lesion in the brainstem affecting both upper motor neurons and lower motor neurons. The muscles that would receive signals from these damaged upper motor neurons result in spastic paralysis. With a lesion in the brainstem, this affects the majority of limb and trunk muscles on the contralateral side due to the upper motor neurons decussation after the brainstem. The cranial nerves and cranial nerve nuclei are also located in the brainstem making them susceptible to damage from a brainstem lesion. Cranial nerves III (Oculomotor), VI (Abducens), and XII (Hypoglossal) are most often associated with this syndrome given their close proximity with the pyramidal tract, the location which upper motor neurons are in on their way to the spinal cord. Damages to these structures produce the ipsilateral presentation of paralysis or palsy due to the lack of cranial nerve decussation before innervating their target muscles. The paralysis may be brief or it may last for several days, many times the episodes will resolve after sleep. Some common symptoms of alternating hemiplegia are mental impairment, gait and balance difficulties, excessive sweating and changes in body temperature.
People with epilepsy may be classified into different syndromes based on specific clinical features. These features include the age at which seizures begin, the seizure types, and EEG findings, among others. Identifying an epilepsy syndrome is useful as it helps determine the underlying causes as well as deciding what anti-seizure medication should be tried. Epilepsy syndromes are more commonly diagnosed in infants and children. Some examples of epilepsy syndromes include benign rolandic epilepsy, childhood absence epilepsy and juvenile myoclonic epilepsy. Severe syndromes with diffuse brain dysfunction caused, at least partly, by some aspect of epilepsy, are also referred to as epileptic encephalopathies. These are associated with frequent seizures that are resistant to treatment and severe cognitive dysfunction, for instance Lennox-Gastaut syndrome and West syndrome.
Occipital epilepsy is a neurological disorder that arises from excessive neural activity in the occipital lobe of the brain that may or may not be symptomatic. Occipital lobe epilepsy is fairly rare, and may sometimes be misdiagnosed as migraine when symptomatic. Epileptic seizures are the result of synchronized neural activity that is excessive, and may stem from a failure of inhibitory neurons to regulate properly.
Tyrosine hydroxylase deficiency (THD) is a disorder caused by disfunction of tyrosine hydroxylase, an enzyme involved in the biosynthesis of dopamine. This condition is one of the causes of dopa-responsive dystonia.