Toxic encephalopathy | |
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Specialty | Neurology |
Toxic encephalopathy is a neurologic disorder caused by exposure to neurotoxic organic solvents such as toluene, following exposure to heavy metals such as manganese, as a side effect of melarsoprol treatment for African trypanosomiasis, adverse effects to prescription drugs, or exposure to extreme concentrations of any natural toxin such as cyanotoxins found in shellfish or freshwater cyanobacteria crusts. Toxic encephalopathy can occur following acute or chronic exposure to neurotoxicants, which includes all natural toxins. Exposure to toxic substances can lead to a variety of symptoms, characterized by an altered mental status, memory loss, and visual problems. Toxic encephalopathy can be caused by various chemicals, some of which are commonly used in everyday life, or cyanotoxins which are bio-accumulated from harmful algal blooms (HABs) which have settled on the benthic layer of a waterbody. Toxic encephalopathy can permanently damage the brain and currently treatment is mainly just for the symptoms.
"Encephalopathy" is a general term describing brain malfunctions and "toxic" asserts that the malfunction is caused by toxins on the brain. The most prominent characteristic of toxic encephalopathy is an altered mental status. Acute intoxication is a reversible symptom of exposure to many synthetic chemical neurotoxicants. Acute intoxication symptoms include lightheadedness, dizziness, headache and nausea, and regular cumulative exposure to these neurotoxicants over a number of years puts the individual at high risk for developing toxic encephalopathy. Chronic exposure to low levels of neurotoxic chemicals can also cause reversible changes in mood and affect which resolve with cessation of exposure. Acute and chronic toxic encephalopathy on the other hand, are persistent changes in neurological function that typically occur with exposure to higher concentrations and longer durations respectively. The symptoms of acute and chronic toxic encephalopathy do not resolve with cessation of exposure and can include memory loss, dementia, small personality changes/increased irritability, insidious onset of concentration difficulties, headache, lightheadedness, ataxia, involuntary movements (parkinsonism), fatigue, seizures, arm strength problems, and depression. [1] A paper by Feldman and colleagues described neurobehavioral effects in a 57-year-old house painter with regular exposure to large amounts of solvents. [2]
Magnetic Resonance Imaging (MRI) analyses have also demonstrated increased rates of dopamine synthesis in the putamen, reduced anterior and total corpus callosum volume, demyelination in the parietal white matter, basal ganglia, and thalamus, as well as atypical activation of frontal areas of the brain due to neural compensation. [ citation needed ]
The regions of interest on SPECT brain imaging include a majority of all cortical regions, and the globus pallidus in carbon monoxide poisoning. Based on medical literature on SPECT brain imaging, signature patterns for toxic encephalopathy is a nonspecific patchy, diffuse pattern on the cortex, and sometimes is shown in subcortical regions, if exposure was severe.[ citation needed ]
A thorough and standard diagnostic process is paramount with toxic encephalopathy, including a careful occupational, medication and medical history, standardized imaging and neuropsychological testing.[ citation needed ]
In addition, chemicals, such as lead, that could instigate toxic encephalopathy are sometimes found in everyday products such as prescription drugs, cleaning products, building materials, pesticides, air fresheners, and even perfumes. These harmful chemicals can be inhaled (in the case of air fresheners) or applied (in the case of perfumes). [3] [4] The substances diffuse into the brain rapidly, as they are lipophilic and readily transported across the blood–brain barrier. This is a result of increased membrane solubility and local blood flow, with central nervous system (CNS) solvent uptake being further increased with high levels of physical activity. [5] When they are not detoxified immediately, the symptoms of toxic encephalopathy begin to emerge. [4] However, in chronic situations, these effects may not become severe enough to be noticed until much later. Increased exposure time and increased concentration of the chemicals will worsen the effects of toxic encephalopathy, due to the associated structural CNS damage and direct functional impairment consequences. [5]
Subacute toxic encephalopathies are challenging to identify due to their often insidious tempo of evolution, nonspecific manifestations, relative infrequency as individual entities, and frequent lack of specific diagnostic testing. Yet they are crucial to recognize in aggregate, subacute toxic encephalopathies are a common problem that can lead to severe, irreversible harm if not diagnosed and treated efficiently. This article reviews the clinically relevant aspects of some of the more important subacute toxic encephalopathy syndromes caused by inorganic toxins, carbon monoxide (CO), anti- biotics, antineoplastic agents, and psychiatric medications. [6]
All therapeutic interventions are double-edged swords with benefits and adverse effects, and pharmacotherapy is not an exception. Shortly after the introduction of conventional antipsychotic drugs into clinical practice, relatively rare but serious complications with hyperthermia, muscle rigidity, autonomic instability, and disturbed mental status were recognized to develop in some patients treated with antipsychotics. This type of encephalopathy induced by the use of antipsychotics was referred to as neuroleptic malignant syndrome (NMS), and almost all physicians prescribing antipsychotics are nowadays aware of this adverse phenomenon. Another well-known type of encephalopathy associated with psychotropic drug therapy is serotonin toxicity (ST) or serotonin syndrome (SS), which is characterized by autonomic and neuromuscular symptoms and altered mental status. In contrast with the idiosyncratic nature of NMS, ST is a spectrum pathophysiological state assumed to derive from excess serotonergic neural transmission caused by serotonin-related psychotropic agents. In these two decades, pharmacotherapy with psychotropic drugs for patients with mental illness has been dramatically changed, and classical prototypal antipsychotics and antidepressants have been replaced with atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs), respectively. These newly developed psychotropic drugs are generally safer and more tolerable than older drugs. However, atypical antipsychotics are not free of the risk of development of NMS, and the explosive prevalence of SSRIs prescribed not only for depression but also for a number of psychiatric diagnoses such as anxiety, eating disorders, impulse-control, and personality disorders may increase the incidence of ST. Therefore, these two pathological states still remain as major adverse effects of psychotropic drugs involving altered functioning of the central nervous system (CNS), to which all clinicians prescribing psychoactive drugs should pay attention. The popularity of SSRIs also increased the case reports of patients with discontinuation syndrome, which sometimes includes CNS symptoms like anxiety and irritability. In this chapter, the author provides a comprehensive overview of the above- mentioned adverse effects affecting the CNS function associated with psychotropic pharmacotherapy. In addition, several other pathological conditions potentially causing encephalopathic symptoms in psychiatric patients treated with psychotropic drugs, e.g., hyponatremia, valproate-induced hyperammonemia, transient splenial lesion of the corpus callosum, and so on, are also described.[ citation needed ]
Fume events on aircraft have been linked to cases of toxic encephalopathy, for example in the case of JetBlue Captain Andrew Myers, who as a result of exposure needed a cane to walk, experienced tremors and struggled to speak. In the following year, the Federal Aviation Administration revoked Myers' medical certificate; the workers compensation board agreed that Myers experienced brain damage as a result of the event. [7]
Rapid diagnosis is important to attempt to prevent further damage to the brain and further neurologic deficits. It is a diagnosis of exclusion, so a full work up for other possible etiologies (hepatic, uremic, infectious, oncologic) should be performed. In addition to the neurological examination, diagnostic testing could include MRI, PET or SPECT brain imaging, EEG, QEEG and most importantly, neuropsychological testing. Screening for heavy metals, as well as other toxins, should be done immediately as those are some of the most common causes and the patient can then remove themselves from the dangerous environment. In addition, a full examination of blood (CBC) and metabolites (CMP) should be done.[ citation needed ]
Treatment is mainly for the symptoms that toxic encephalopathy causes, and vary depending on how severe the case is. Diet changes and nutritional supplements may help some patients. To reduce or halt seizures, anticonvulsants may be prescribed. Dialysis or organ replacement surgery may be needed in some severe cases. [8]
Lifelong abstinence from alcohol, a well-established neurotoxin and cause of the condition, is encouraged to prevent further loss of neurocognitive function.[ citation needed ]
Management of affected individuals consists of immediate removal from exposure to the toxic substance(s), treatment of the common clinical manifestation of depression if present, and counselling for the provision of life strategies to help cope with the potentially debilitating condition. [5]
Toxic encephalopathy is often irreversible. If the source of the problem is treated by removing the toxic chemical from the system, further damage can be prevented, but prolonged exposure to toxic chemicals can quickly destroy the brain. [9] Long-term studies have demonstrated residual cognitive impairment (primarily attention and information-processing impairment resulting in dysfunction in working memory) up to 10 years following cessation of exposure. [5] Severe cases of toxic encephalopathy can be life-threatening. [10]
Research is being done by organizations such as NINDS (National Institute of Neurological Disorders and Stroke) on what substances can cause encephalopathy, why they do this, and eventually how to protect, treat, and cure the brain from this condition. [11]
An anxiolytic is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiety disorders and their related psychological and physical symptoms.
Psychopharmacology is the scientific study of the effects drugs have on mood, sensation, thinking, behavior, judgment and evaluation, and memory. It is distinguished from neuropsychopharmacology, which emphasizes the correlation between drug-induced changes in the functioning of cells in the nervous system and changes in consciousness and behavior.
A psychiatric or psychotropic medication is a psychoactive drug taken to exert an effect on the chemical makeup of the brain and nervous system. Thus, these medications are used to treat mental illnesses. These medications are typically made of synthetic chemical compounds and are usually prescribed in psychiatric settings, potentially involuntarily during commitment. Since the mid-20th century, such medications have been leading treatments for a broad range of mental disorders and have decreased the need for long-term hospitalization, thereby lowering the cost of mental health care. The recidivism or rehospitalization of the mentally ill is at a high rate in many countries, and the reasons for the relapses are under research.
Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar disorder, severe behavioral problems in children including those with attention deficit hyperactivity disorder, nausea and vomiting, anxiety before surgery, and hiccups that do not improve following other measures. It can be given orally, by intramuscular injection, or intravenously.
Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.
Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back and forth, or pace, while some may just have an uneasy feeling in their body. The most severe cases may result in poor adherence to medications, exacerbation of psychiatric symptoms, and, because of this, aggression, violence, and/or suicidal thoughts. Akathisia is also associated with threatening behaviour and physical aggression in mentally disordered patients. However, the attempts to found potential links between akathisia and emerging suicidal or homicidal behaviour were not systematic and were mostly based on a limited number of case reports and small case series. Apart from these few low-quality studies, there is another more recent and better quality study that concludes «akathisia cannot be reliably linked to the presence of suicidal behaviour in patients treated with antipsychotic medication».
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 chorea or slow writhing movements. In about 20% of people with TD, the disorder interferes with daily functioning. If TD is present in the setting of a long-term drug therapy, reversibility can be determined primarily by severity of symptoms and how long symptoms have been present before the long-term drug has been stopped.
Encephalopathy means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome has many possible organic and inorganic causes.
Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifically, a neurotoxin or neurotoxicant– alters the normal activity of the nervous system in such a way as to cause permanent or reversible damage to nervous tissue. This can eventually disrupt or even kill neurons, which are cells that transmit and process signals in the brain and other parts of the nervous system. Neurotoxicity can result from organ transplants, radiation treatment, certain drug therapies, recreational drug use, exposure to heavy metals, bites from certain species of venomous snakes, pesticides, certain industrial cleaning solvents, fuels and certain naturally occurring substances. Symptoms may appear immediately after exposure or be delayed. They may include limb weakness or numbness, loss of memory, vision, and/or intellect, uncontrollable obsessive and/or compulsive behaviors, delusions, headache, cognitive and behavioral problems and sexual dysfunction. Chronic mold exposure in homes can lead to neurotoxicity which may not appear for months to years of exposure. All symptoms listed above are consistent with mold mycotoxin accumulation.
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. It belongs to the hyperkinetic movement disorders, among tremor and chorea for example. 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.
A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.
Psychoorganic syndrome (POS), also known as organic psychosyndrome, is a progressive disease comparable to presenile dementia. It consists of psychopathological complex of symptoms that are caused by organic brain disorders that involve a reduction in memory and intellect. Psychoorganic syndrome is often accompanied by asthenia.
Sulpiride, sold under the brand name Dogmatil among others, is an atypical antipsychotic medication of the benzamide class which is used mainly in the treatment of psychosis associated with schizophrenia and major depressive disorder, and sometimes used in low dosage to treat anxiety and mild depression. Sulpiride is commonly used in Asia, Central America, Europe, South Africa and South America. Levosulpiride is its purified levo-isomer and is sold in India for similar purpose. It is not approved in the United States, Canada, or Australia. The drug is chemically and clinically similar to amisulpride.
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.
Protriptyline, sold under the brand name Vivactil among others, is a tricyclic antidepressant (TCA), specifically a secondary amine, indicated for the treatment of depression and attention-deficit hyperactivity disorder (ADHD). Uniquely among most of the TCAs, protriptyline tends to be energizing instead of sedating, and is sometimes used for narcolepsy to achieve a wakefulness-promoting effect.
Toxic leukoencephalopathy is a rare condition that is characterized by progressive damage (-pathy) to white matter (-leuko-) in the brain (-encephalo-), particularly myelin, due to causes such as exposure to substance use, environmental toxins, or chemotherapeutic drugs. The prevalence of this disease is infrequent and often goes unreported, especially in cases resulting from substance use. Magnetic resonance imaging (MRI) is a popular method to study and diagnose the disease. However, even with technological advances, the exact mechanism and underlying pathophysiology of toxic leukoencephalopathy remains unknown and is thought to vary between sources of toxicity. The clinical severity of toxic leukoencephalopathy also varies among patients, exposure time, concentration, and purity of the toxic agent. Some reversibility of the condition has been seen in many cases when the toxic agent is removed.
Chronic solvent-induced encephalopathy (CSE) is a condition induced by long-term exposure to organic solvents, often—but not always—in the workplace, that lead to a wide variety of persisting sensorimotor polyneuropathies and neurobehavioral deficits even after solvent exposure has been removed. This syndrome can also be referred to as psycho-organic syndrome, organic solvent syndrome, chronic painter's syndrome, occupational solvent encephalopathy, solvent intoxication, toxic solvent syndrome, painters disease, chronic toxic encephalopathy, or neurasthenic syndrome. The multiple names of solvent-induced syndromes combined with inconsistency in research methods makes referencing this disease difficult and its catalog of symptoms vague.
Certain lithium compounds, also known as lithium salts, are used as psychiatric medication, primarily for bipolar disorder and for major depressive disorder. In lower doses, other salts such as lithium citrate are known as nutritional lithium and have occasionally been used to treat ADHD. Lithium is taken orally.
Lithium toxicity, also known as lithium overdose, is the condition of having too much lithium. Symptoms may include a tremor, increased reflexes, trouble walking, kidney problems, and an altered level of consciousness. Some symptoms may last for a year after levels return to normal. Complications may include serotonin syndrome.
Antimanic drugs are psychotropic drugs that are used to treat symptoms of mania. Though there are different causes of mania, the majority is caused by bipolar disorder, therefore antimanic drugs are mostly similar to drugs treating bipolar disorder. Since 1970s, antimanic drugs have been used specifically to control the abnormal elevation of mood or mood swings during manic episodes. One purpose of antimanic drugs is to alleviate or shorten the duration of an acute mania. Another objective is to prevent further cycles of mania and maintain the improvement achieved during the acute episode. The mechanism of antimanic drugs has not yet been fully known, it is proposed that they mostly affect chemical neurotransmitters in the brain. However, the usage of antimanic drugs should be consulted with a doctor or pharmacist due to their side effects and interactions with other drugs and food.