Pleurothotonus

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Pleurothotonus
Other namesPisa syndrome

Pleurothotonus, commonly known as Pisa syndrome, is a rare neurological disorder which occurs due to prolonged exposure to antipsychotic drugs (which may also be referred to as neuroleptics). It is characterized by dystonia, and abnormal and sustained involuntary muscle contraction. This may cause twisting or jerking movements of the body or a body part. Although Pisa syndrome develops most commonly in those undergoing long-term treatment with antipsychotics, it has been reported less frequently in patients receiving other medications, such as an acetylcholinesterase inhibitor. However, it has also been seen in those with other diseases causing neurodegeneration and in those who are not receiving any medication (idiopathic Pisa syndrome). The characteristic development of Pisa syndrome consists of two types of dystonia: acute dystonia and tardive dystonia (also known as tardive dyskinesia). The underlying pathology of drug-induced Pisa syndrome is very complex, and development may be due to an underlying dopaminergic-cholinergic imbalance, or serotonergic/noradrenergic dysfunction. [1] [2] [3]

Contents

Symptoms

The predominant symptom of Pisa syndrome is dystonia. Dystonia is a neurological movement disorder characterized by sustained muscle contraction leading to abnormal posture, twisting, and repetitive movement. In Pisa Syndrome specifically there is commonly a tonic flexion of the trunk of the body to one side, leading to a slight lean (reminiscent of the Leaning Tower of Pisa, hence the name "Pisa syndrome"). This is usually associated with a backward axial rotation of the spine and indifferent to markedly abnormal posture. Patients diagnosed with Pisa Syndrome usually experience either acute dystonia or tardive dystonia, also known as tardive dyskinesia. Differential diagnosis between the two may be hard to accomplish without a complete patient history, since both types of dystonia may occur simultaneously in a patient. These symptoms generally disappear after discontinuation of the antipsychotic drug. The time of onset of symptoms may vary depending on drug being administered and the neurological characteristics of the patient in question. [2]

Acute dystonia

Acute dystonia nearly always develops a few weeks after a dopamine blocking agent/medication has begun or a substantial increase in antipsychotic dosage. An acute dystonic reaction consists of sustained, painful muscular spasms, producing twisting of the trunk/body and abnormal posture. The most frequent occurrences of these spasms have been reported in the neck, tongue, and jaw. Oculogyric crisis and opisthotonus are also very common. Acute effects of dopamine antagonists also include Parkinsons-like symptoms, manifested by bradykinesia, pin rolling tremor, and rigidity of the body. These movements may fluctuate over hours and temporarily dissipate in response to reassurance, and the individual episodes may last minutes to hours. Acute reactions are more common in older patients and females. The pathophysiology underlying these reactions is unknown, but the movements usually occur during the period when blood medication level is dropping. The acute syndromes which occur due to prolonged exposure to a dopamine antagonist are collectively termed extrapyramidal symptoms, EPS.

Tardive dyskinesia

Tardive dyskinesias are involuntary movements of the lips, tongue, face, trunk, and extremities which occur in patients with prolonged exposure to dopamine antagonists or antipsychotic medications. Clinical findings have provided evidence that adenosine, a major inhibitory neurotransmitter in the central nervous system, plays a role in the development of tardive dykinesias. [4] Tardive dykinesias have also been associated with polymorphism in the dopamine receptor D2 gene, dopamine receptor D3 gene, dopamine transporter (DAT) gene, and manganese superoxide dismutase (MnSOD) gene. [5] [6] Tardive dyskinesias are chronic compared to acute dystonia, which occur in an episodic fashion.

Causes

Pisa syndrome is predominantly caused by a prolonged administration or an overly dosed administration of antipsychotic drugs. Although antipsychotic drugs are known to be the main drugs that are concerned with this syndrome, several other drugs are reported to have caused the syndrome as well. Certain antidepressants, psychoactive drugs, and antiemetics have also been found to cause Pisa syndrome in patients. [7]

Drugs found to have caused Pisa Syndrome:

Based on the drugs that caused Pisa syndrome, it has been implicated that the syndrome may be due to a dopaminergic-cholinergic imbalance or a serotonergic or noradrenergic dysfunction.[ citation needed ] For the development of Pisa syndrome that cannot be alleviated by anticholinergic drugs, it has been considered that asymmetric brain functions or neural transmission may be the underlying mechanism.[ citation needed ] How these drugs interact with the biochemistry of the brain to cause the syndrome is unknown and a topic of current research.[ citation needed ]

Risk factors

Typically, females and older patients with organic brain changes are more likely to develop Pisa syndrome. Organic brain changes are physical changes in the brain which lead to neurological dysfunction, including dementia and frontal lobe syndrome. This includes the presence of neurodegenerative illnesses such as Alzheimer's disease and Parkinson's disease. [9]

Diagnosis

Treatment and Medication

There are two lines of treatment for Pisa syndrome. The first line entails discontinuation or reduction in dose of the antipsychotic drug(s). The second line of treatment is an anticholinergic medication. A pharmacological therapy for Pisa syndrome caused by prolonged use of antipsychotic drugs has not been established yet. [10]

Reduction of drug dosage

Reducing the dosage of the antipsychotic drugs resulted in gradual improvement in the abnormal posture. In some cases, discontinuing the use of those drugs resulted in complete disappearance of the syndrome. The time it took for the improvement and the disappearance of the syndrome depended on the type of drug being administered or the specific cause of the syndrome itself. [10]

Anticholinergic drugs

Anticholinergic drugs have been reported to be extremely effective in 40% of the patients with the Pisa syndrome.[ citation needed ] Patients with Pisa syndrome that is resistant to anticholinergic drugs is mostly resolved by the reduction of the administration of the antipsychotic drugs as previously mentioned. While the specific pathology underlying idiopathic Pisa syndrome is unknown, the administration of anticholinergic drugs has provided resolution in known cases. [10]

History

Pisa syndrome was discovered by Karl Axel Ekbom, a Swedish neurologist, in the early 1970s. Cases of the syndrome were first observed in three elderly female patients with presenile dementia. Each of these women were undergoing treatment with the antipsychotic drug methylperone, haloperidol or a combination of the two. The use of neuroleptic drugs caused the patients to exhibit a lateral flexion along with a rotation of the trunk. As the patients walked they experienced an increase in rotation. The postural and gait disturbances symptoms is what set this apart from any other form of acute dystonia previously observed. These symptoms proved to be the making of a new dystonic reaction, which was termed pleurothotonus or Pisa syndrome. [11]

The first patient, a 59-year-old woman with no family history of neuroleptic disease, was put through two periods of treatment with methylperone. The first trial of the drug was administered in February 1971. In the beginning the patient demonstrated no symptoms of dystonia. However, within the first few days the patient began to exhibit a tilting to right upon walking. The women was then taken off the methylperone treatment and as a result progressively regressed back to her previous state of exhibiting no symptoms within the first two months. The patient started a second trial of methylperone treatment in late October 1971. After a little over a week of the drug treatment, she began to express previous symptoms that including a bending of the trunk towards the right along with a rotation. The patient also experienced a pulling away from her direction of walking and a difficulty of turning. Within a couple of days of exhibiting symptoms, the patient was then treated with orphenadrine. This treatment helped regress the expressed symptoms quicker than the first time. By the end of the week the patient was able to return to her normal state. [11]

The second patient to undergo methylperone treatment was a 63-year-old woman with presenile dementia, which caused her to experience restlessness and paranoid hallucinations. The methylperone treatment was able to alleviate the woman's problems induced by her dementia. It did not take long for the woman to begin to experience symptoms of Pisa syndrome and as a result she was taken off of the methylperone treatment. Like the first patient, she was able to overcome the induced symptoms of Pisa syndrome within a month. The patient was again treated with methylperone after two months from the first treatment. Soon after the patient began to lean toward the right when standing or walking. She was then administered orphenadrine, which soon stopped the patient's tilting posture. [11]

The final patient was a 69-year-old woman, diagnosed with presenile dementia after she expressing symptoms of memory dysfunction, depression and urinary incontinence. As a result, the woman was put under a methylperone treatment, which soon caused a bending and rotation to her left. These symptoms disappeared soon after being taken off of methylperone. Unlike the other two patients, when the woman was again administered methylperone she did not exhibit any previous dystonic symptoms after two weeks of treatment. The patient was then switched to a small dosage of haloperidol along with the typical dosage of orphenadrine used on the previous patients. Instead of not having symptoms of Pisa syndrome, the woman began to experience a leaning to her left side and a particular rotation of her shoulder towards the left. Once haloperidol was eliminated from the treatment the patient no longer had these symptoms. [11]

As more cases of the syndrome came about, research discovered that the switching of drug treatments can be debated as a possible inducer of the disease.[ citation needed ] Other cases of the disease have been proven to be caused by medications other than neuroleptic drugs.[ citation needed ] These patients were observed exhibiting symptoms of Pisa syndrome as a result of having a prior neurodegenerative disease.[ citation needed ]

Further research

Current research has been focusing on discovering the underlying mechanisms of Pisa syndrome, since little is known about the biological and pharmacological reasons Pisa syndrome occurs (although theories about dopaminergic dysfunction have been suggested). While Pisa syndrome is mostly associated with antipsychotic drugs, there have been incidents of idiopathic Pisa Syndrome, the development of Pisa syndrome in those with other neurological disorders, and Pisa syndrome in those with intellectual disability. [12] Future research aims to pinpoint the essential neurological disorder or disorders underlying the development of Pisa syndrome so more that more effective medication and treatment may be created and/or administered.[ citation needed ]

See also

Related Research Articles

<span class="mw-page-title-main">Antipsychotic</span> Class of medications

Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay together with mood stabilizers in the treatment of bipolar disorder.

<span class="mw-page-title-main">Neuroleptic malignant syndrome</span> Medical condition

Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fast heart rate. Complications may include rhabdomyolysis, high blood potassium, kidney failure, or seizures.

<span class="mw-page-title-main">Trifluoperazine</span> Chemical compound

Trifluoperazine, marketed under the brand name Stelazine among others, is a typical antipsychotic primarily used to treat schizophrenia. It may also be used short term in those with generalized anxiety disorder but is less preferred to benzodiazepines. It is of the phenothiazine chemical class.

<span class="mw-page-title-main">Haloperidol</span> Typical antipsychotic medication

Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosis, and hallucinations from alcohol withdrawal. It may be used by mouth or injection into a muscle or a vein. Haloperidol typically works within 30 to 60 minutes. A long-acting formulation may be used as an injection every four weeks by people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.

<span class="mw-page-title-main">Typical antipsychotic</span> Class of drugs

Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis. Typical antipsychotics may also be used for the treatment of acute mania, agitation, and other conditions. The first typical antipsychotics to come into medical use were the phenothiazines, namely chlorpromazine which was discovered serendipitously. Another prominent grouping of antipsychotics are the butyrophenones, an example of which is haloperidol. The newer, second-generation antipsychotics, also known as atypical antipsychotics, have largely supplanted the use of typical antipsychotics as first-line agents due to the higher risk of movement disorders in the latter.

<span class="mw-page-title-main">Benzatropine</span> Group of stereoisomers

Benzatropine (INN), known as benztropine in the United States and Japan, is a medication used to treat movement disorders like parkinsonism and dystonia, as well as extrapyramidal side effects of antipsychotics, including akathisia. It is not useful for tardive dyskinesia. It is taken by mouth or by injection into a vein or muscle. Benefits are seen within two hours and last for up to ten hours.

<span class="mw-page-title-main">Thioridazine</span> Chemical compound

Thioridazine is a first generation antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis. The branded product was withdrawn worldwide in 2005 because it caused severe cardiac arrhythmias. However, generic versions are still available in the US.

<span class="mw-page-title-main">Tardive dyskinesia</span> Neurological disorder featuring involuntary, repetitive body movements

Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movements. In about 20% of people with TD, the disorder interferes with daily functioning.

<span class="mw-page-title-main">Dystonia</span> Neurological movement disorder

Dystonia is a neurological hyperkinetic movement disorder in which sustained or repetitive muscle contractions result in twisting and repetitive movements or abnormal fixed postures. The movements may resemble a tremor. Dystonia is often intensified or exacerbated by physical activity, and symptoms may progress into adjacent muscles.

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.

<span class="mw-page-title-main">Hyperkinesia</span> Excessive movements due to basal ganglia dysfunction

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.

<span class="mw-page-title-main">Prochlorperazine</span> Medication for nausea, psychosis, and anxiety

Prochlorperazine, formerly sold under the brand name Compazine among others, is a medication used to treat nausea, migraines, schizophrenia, psychosis and anxiety. It is a less preferred medication for anxiety. It may be taken by mouth, rectally, injection into a vein, or injection into a muscle.

<span class="mw-page-title-main">Progabide</span> Pharmaceutical drug

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<span class="mw-page-title-main">Sulpiride</span> Atypical antipsychotic

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<span class="mw-page-title-main">Meige's syndrome</span> Medical condition

Meige's syndrome is a type of dystonia. It is also known as Brueghel's syndrome and oral facial dystonia. It is actually a combination of two forms of dystonia, blepharospasm and oromandibular dystonia (OMD).

<span class="mw-page-title-main">Biperiden</span> Group of stereoisomers

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Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side effects (EPSE). The symptoms can be acute (short-term) or chronic (long-term). They include movement dysfunction such as dystonia, akathisia, parkinsonism characteristic symptoms such as rigidity, bradykinesia, tremor, and tardive dyskinesia. Extrapyramidal symptoms are a reason why subjects drop out of clinical trials of antipsychotics; of the 213 (14.6%) subjects that dropped out of one of the largest clinical trials of antipsychotics, 58 (27.2%) of those discontinuations were due to EPS.

<span class="mw-page-title-main">Zuclopenthixol</span> Chemical compound

Zuclopenthixol, also known as zuclopentixol, is a medication used to treat schizophrenia and other psychoses. It is classed, pharmacologically, as a typical antipsychotic. Chemically it is a thioxanthene. It is the cis-isomer of clopenthixol. Clopenthixol was introduced in 1961, while zuclopenthixol was introduced in 1978.

<span class="mw-page-title-main">Antipsychotic switching</span> Process of transferring between antipsychotics

Antipsychotic switching refers to the process of switching out one antipsychotic for another antipsychotic. There are multiple indications for switching antipsychotics, including inadequate efficacy and drug intolerance. There are several strategies that have been theorized for antipsychotic switching, based upon the timing of discontinuation and tapering of the original antipsychotic and the timing of initiation and titration of the new antipsychotic. Major adverse effects from antipsychotic switching may include supersensitivity syndromes, withdrawal, and rebound syndromes.

References

  1. ↑ Van Harten: Ned Tijdschr Geneeskd. 1997 Jul 26;141(30):1471-4
  2. 1 2 Nishimura, K: Pisa Syndrome Resolved After Switching to Olanzapine. Journal of Neuropsychiatry and Clinical Neuroscience 2007; 19:202-203
  3. ↑ M. Amore, M. Cerisoli, S. Campanile, A. Campanile: Pisa Syndrome. Report of a Case. Italian Journal of Neurological Sciences 1988; 9:273-274.
  4. ↑ Bishnoi M, Chopra K, Kulkarni SK. Involvement of adenosinergic receptor system in an animal model of tardive dyskinesia and associated behavioural, biochemical and neurochemical changes. Eur J Pharmacol. Dec 15 2006;552(1-3):55-66.
  5. ↑ Lafuente A, Bernardo M, Mas S, et al. Dopamine transporter (DAT) genotype (VNTR) and phenotype in extrapyramidal symptoms induced by antipsychotics. Schizophr Res. Feb 2007;90(1-3):115-22.
  6. ↑ Liou YJ, Lai IC, Liao DL, et al. The human dopamine receptor D2 (DRD2) gene is associated with tardive dyskinesia in patients with schizophrenia. Schizophr Res. Sep 2006;86(1-3):323-5
  7. ↑ Suzuki et al., 1997 T. Suzuki, H. Kurita, T. Hori, M. Sasaki, A. Baba and H. Shiraishi, et al. The Pisa syndrome (pleurothotonus) during antidepressant therapy. Biol Psychiatry, 41 (1997), pp. 234–236.
  8. 1 2 Cossu et al., 2004 G. Cossu, M. Melis, G. Melis, E. Maccioni, V. Putzu, O. Catte, PF. Putzu, Reversible Pisa syndrome (pleurothotonus) due to the cholinesterase inhibitor galantamine: case report. Department of Neuroscience, Oct;19(10):1243-4.
  9. ↑ Lamparska A, Smoczyński S. Psychotic syndromes in patients with organic brain damage in the light of clinical analysis. Psychiatr Pol. 1990 Jul-Aug;24(4):1-6.
  10. 1 2 3 Suzuki et al., 2002 T. Suzuki, H. Matsuzaka, et al. Drug-induced Pisa syndrome (pleurothotonus): epidemiology and management. Department of Psychiatry, 16(3) (2002), pp. 165-74.
  11. 1 2 3 4 K. Ekbom, H. Lindholm and L. Ljungerberg, New dystonic syndrome associated with butyrophenone therapy. Z Neurol, 202 (1972), pp. 94–103.
  12. ↑ Ulhaq, Inam, et al. Case Report: Pisa Syndrome in Patients with Intellectual Disability. Mental Health and Learning Disabilities: Research and Practice. 2010, v.7, pg. 59-63.
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