As of 2015 there was no cure for CJD; some of the symptoms like twitching can be managed but otherwise treatment is palliative care.

As of 2017, there was no cure for BSE; some of the symptoms like twitching can be managed but otherwise treatment is palliative care.

An experimental treatment was given to a Northern Irish teenager, Jonathan Simms, beginning in January 2003. The medication, called pentosan polysulphate (PPS) and used to treat interstitial cystitis, is infused into the patient's lateral ventricle within the brain. PPS does not seem to stop the disease from progressing, and both brain function and tissue continue to be lost. However, the treatment is alleged to slow the progression of the otherwise untreatable disease, and may have contributed to the longer than expected survival of the seven patients studied. Simms died in 2011. The CJD Therapy Advisory Group to the UK Health Departments advises that data are not sufficient to support claims that pentosan polysulphate is an effective treatment and suggests that further research in animal models is appropriate. A 2007 review of the treatment of 26 patients with PPS finds no proof of efficacy because of the lack of accepted objective criteria.

Scientists have investigated using RNA interference to slow the progression of scrapie in mice. The RNA blocks production of the protein that the CJD process transforms into prions. This research is unlikely to lead to a human therapy for many years.

Both amphotericin B and doxorubicin have been investigated as potentially effective against CJD, but as yet there is no strong evidence that either drug is effective in stopping the disease. Further study has been taken with other medical drugs, but none are effective. However, anticonvulsants and anxiolytic agents, such as valproate or a benzodiazepine, may be administered to relieve associated symptoms.

Scientists from the University of California, San Francisco are currently running a treatment trial for sporadic CJD using quinacrine, a medicine originally created for malaria. Pilot studies showed quinacrine permanently cleared abnormal prion proteins from cell cultures, but results have not yet been published on their clinical study. The efficacy of quinacrine was also assessed in a rigorous clinical trial in the UK and the results were published in Lancet Neurology,

and concluded that quinacrine had no measurable effect on the clinical course of CJD.

In a 2013 paper published in the Proceedings of the National Academy of Sciences, scientists from The Scripps Research Institute reported that Astemizole, a medication approved for human use, has been found to have anti-prion activity and may lead to a treatment for Creutzfeldt–Jakob disease.

Variant Creutzfeldt–Jakob disease (vCJD) or new variant Creutzfeldt–Jakob disease (nvCJD) is a transmissible spongiform encephalopathy which was identified in 1996 by the National CJD Surveillance Unit in Edinburgh, Scotland. It is always fatal and is caused by prions, which are mis-folded proteins. Over 170 cases of vCJD have been recorded in the United Kingdom, and around 30 cases in the rest of the world. The fact that the epidemiology of the disease coincided with an epidemic of bovine spongiform encephalopathy led to the hypothesis that consumption of BSE-infected beef caused the disease. It is a different disease from Sporadic and Familial Creutzfeldt–Jakob disease, though it is believed to be caused by the same pathogenic agent, a mis-folded protein, known as a prion.

Despite the consumption of contaminated beef in the UK being reckoned to be quite high, vCJD has infected a comparatively small cohort of people. One explanation for this can be found in the genetics of patients with the disease. The human PRNP protein which is subverted in prion disease can occur with either methionine or valine at amino acid 129, without any apparent difference in normal function. Of the overall Caucasian population, about 40% have two methionine-containing alleles, 10% have two valine-containing alleles, and the other 50% are heterozygous at this position. Only a single vCJD patient tested was found to be heterozygous; most of those affected had two copies of the methionine-containing form. Additionally, for unknown reasons, those affected are generally under the age of 40. It is not yet known whether those unaffected are actually immune or only have a longer incubation period until symptoms appear.

A ban on feeding meat and bone meal to cattle has resulted in a strong reduction in cases in countries where the disease was present. In disease-free countries, control relies on import control, feeding regulations, and surveillance measures.

In UK and US slaughterhouses, the brain, spinal cord, trigeminal ganglia, intestines, eyes, and tonsils from cattle are classified as specified risk materials, and must be disposed of appropriately.

An enhanced BSE-related feed ban is in effect in both the United States and Canada to help improve prevention and elimination of BSE.

In late 1983, Italian neurologist/sleep expert Dr. Ignazio Roiter received a patient at the University of Bologna hospital's sleep institute. The man, known only as Silvano, decided in a rare moment of consciousness to be recorded for future studies and to donate his brain for research in hopes of finding a cure for future victims. As of 2017, no cure or treatment has yet been found for FFI. Gene therapy has been thus far unsuccessful. While it is not currently possible to reverse the underlying illness, there is some evidence that treatments that focus solely upon the symptoms may improve quality of life.

It has been proven that sleeping pills and barbiturates are unhelpful; on the contrary, in 74% of cases, they have been shown to worsen the clinical manifestations and hasten the course of the disease.

One of the most notable cases is that of Michael (Michel A.) Corke, a music teacher from New Lenox, Illinois (born in Watseka, Illinois). He began to have trouble sleeping before his 40th birthday in 1991; following these first signs of insomnia, his health and state of mind quickly deteriorated as his condition worsened. Eventually, sleep became completely unattainable, and he was soon admitted to University of Chicago Hospital with a misdiagnosis of clinical depression due to multiple sclerosis. Medical professionals Dr. Raymond Roos and Dr. Anthony Reder, at first unsure of the nature of his illness, initially diagnosed multiple sclerosis; in a bid to provide temporary relief in the later stages of the disease, physicians attempted to induce a coma with the use of sedatives, to no avail as his brain still failed to shut down completely. Corke died in 1993, a month after his 42nd birthday, by which time he had been completely sleep-deprived for six months.

One person was able to exceed the average survival time by nearly one year with various strategies, including vitamin therapy and meditation, using different stimulants and hypnotics, and even complete sensory deprivation in an attempt to induce sleep at night and increase alertness during the day. He managed to write a book and drive hundreds of miles in this time but nonetheless, over the course of his trials, the person succumbed to the classic four-stage progression of the illness.

In the late 2000s, a mouse model was made for FFI. These mice expressed a humanized version of the PrP protein that also contains the D178N FFI mutation. These mice appear to have progressively fewer and shorter periods of uninterrupted sleep, damage in the thalamus, and early deaths, similar to humans with FFI.

As of 2016, studies are investigating whether doxycycline may be able to slow or even prevent the development of the disease.

Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of progressive, invariably fatal, conditions that affect the brain (encephalopathies) and nervous system of many animals, including humans. According to the most widespread hypothesis, they are transmitted by prions, though some other data suggest an involvement of a "Spiroplasma" infection. Mental and physical abilities deteriorate and myriad tiny holes appear in the cortex causing it to appear like a sponge (hence spongiform) when brain tissue obtained at autopsy is examined under a microscope. The disorders cause impairment of brain function, including memory changes, personality changes and problems with movement that worsen chronically.

Prion diseases of humans include Creutzfeldt–Jakob disease—which has four main forms, the sporadic (sCJD), the hereditary/familiar (fCJD), the iatrogenic (iCJD) and the variant form (vCJD)—Gerstmann–Sträussler–Scheinker syndrome, fatal familial insomnia, kuru, and the recently discovered variably protease-sensitive prionopathy. These conditions form a spectrum of diseases with overlapping signs and symptoms. TSEs in non-human mammals include scrapie in sheep, bovine spongiform encephalopathy (BSE)—popularly known as 'mad cow's disease'—in cattle and chronic wasting disease (CWD) in deer and elk. The variant form of Creutzfeldt–Jakob disease is caused by exposure to bovine spongiform encephalopathy prions.

Unlike other kinds of infectious disease, which are spread by agents with a DNA or RNA genome (such as virus or bacteria), the infectious agent in TSEs is believed to be a prion, thus being composed solely of protein material. Misshapen prion proteins carry the disease between individuals and cause deterioration of the brain. TSEs are unique diseases in that their aetiology may be genetic, sporadic, or infectious via ingestion of infected foodstuffs and via iatrogenic means (e.g., blood transfusion). Most TSEs are sporadic and occur in an animal with no prion protein mutation. Inherited TSE occurs in animals carrying a rare mutant prion allele, which expresses prion proteins that contort by themselves into the disease-causing conformation. Transmission occurs when healthy animals consume tainted tissues from others with the disease. In the 1980s and 1990s, bovine spongiform encephalopathy (BSE) spread in cattle in an epidemic fashion. This occurred because cattle were fed the processed remains of other cattle, a practice now banned in many countries. In turn, consumption (by humans) of bovine-derived foodstuff which contained prion-contaminated tissues resulted in an outbreak of the variant form of Creutzfeldt–Jakob disease in the 1990s and 2000s.

Prions cannot be transmitted through the air or through touching or most other forms of casual contact. However, they may be transmitted through contact with infected tissue, body fluids, or contaminated medical instruments. Normal sterilization procedures such as boiling or irradiating materials fail to render prions non-infective.

The degenerative tissue damage caused by human prion diseases (CJD, GSS, and kuru) is characterised by four features: spongiform change, neuronal loss, astrocytosis, and amyloid plaque formation. These features are shared with prion diseases in animals, and the recognition of these similarities prompted the first attempts to transmit a human prion disease (kuru) to a primate in 1966, followed by CJD in 1968 and GSS in 1981. These neuropathological features have formed the basis of the histological diagnosis of human prion diseases for many years, although it was recognized that these changes are enormously variable both from case to case and within the central nervous system in individual cases.

The clinical signs in humans vary, but commonly include personality changes, psychiatric problems such as depression, lack of coordination, and/or an unsteady gait (ataxia). Patients also may experience involuntary jerking movements called myoclonus, unusual sensations, insomnia, confusion, or memory problems. In the later stages of the disease, patients have severe mental impairment (dementia) and lose the ability to move or speak.

Early neuropathological reports on human prion diseases suffered from a confusion of nomenclature, in which the significance of the diagnostic feature of spongiform change was occasionally overlooked. The subsequent demonstration that human prion diseases were transmissible reinforced the importance of spongiform change as a diagnostic feature, reflected in the use of the term "spongiform encephalopathy" for this group of disorders.

Prions appear to be most infectious when in direct contact with affected tissues. For example, Creutzfeldt–Jakob disease has been transmitted to patients taking injections of growth hormone harvested from human pituitary glands, from cadaver dura allografts and from instruments used for brain surgery (Brown, 2000) (prions can survive the "autoclave" sterilization process used for most surgical instruments). It is also believed that dietary consumption of affected animals can cause prions to accumulate slowly, especially when cannibalism or similar practices allow the proteins to accumulate over more than one generation. An example is kuru, which reached epidemic proportions in the mid-20th century in the Fore people of Papua New Guinea, who used to consume their dead as a funerary ritual. Laws in developed countries now ban the use of rendered ruminant proteins in ruminant feed as a precaution against the spread of prion infection in cattle and other ruminants.

There exist evidence that prion diseases may be transmissible by the airborne route.

Note that not all encephalopathies are caused by prions, as in the cases of PML (caused by the JC virus), CADASIL (caused by abnormal NOTCH3 protein activity), and Krabbe disease (caused by a deficiency of the enzyme galactosylceramidase). Progressive Spongiform Leukoencephalopathy (PSL)—which is a spongiform encephalopathy—is also probably not caused by a prion, although the adulterant that causes it among heroin smokers has not yet been identified. This, combined with the highly variable nature of prion disease pathology, is why a prion disease cannot be diagnosed based solely on a patient's symptoms.

Kuru is a very rare, incurable neurodegenerative disorder that was formerly common among the Fore people of Papua New Guinea. Kuru is caused by the transmission of abnormally folded prion proteins, which leads to symptoms such as tremors, loss of coordination, and neurodegeneration.

The term kuru derives from the Fore word kuria or guria ("to shake"), due to the body tremors that are a classic symptom of the disease and kúru itself means "trembling". It is also known as the "laughing sickness" due to the pathologic bursts of laughter which are a symptom of the disease. It is now widely accepted that kuru was transmitted among members of the Fore tribe of Papua New Guinea via funerary cannibalism. Deceased family members were traditionally cooked and eaten, which was thought to help free the spirit of the dead. Females and children usually consumed the brain, the organ in which infectious prions were most concentrated, thus allowing for transmission of kuru. The disease was therefore more prevalent among women and children.

While the Fore people stopped eating human meat in the early 1960's, when it was first speculated to be transmitted via endocannibalism, the disease lingered due to kuru’s long incubation period of anywhere from 10 to over 50 years. The epidemic declined sharply after discarding cannibalism, from 200 deaths per year in 1957 to 1 or no deaths annually in 2005, with sources disagreeing on whether the last known kuru victim died in 2005 or 2009.

Treatment varies according to the type and severity of the encephalopathy. Anticonvulsants may be prescribed to reduce or halt any seizures. Changes to diet and nutritional supplements may help some patients. In severe cases, dialysis or organ replacement surgery may be needed.

Sympathomimetic drugs can increase motivation, cognition, motor performance and alertness in patients with encephalopathy caused by brain injury, chronic infections, strokes, brain tumors.

Kuru is largely localized to the Fore people and people with whom they intermarried, and was transmitted through ritualistic cannibalism. The Fore people ritualistically cooked and consumed body parts of their family members following their death to symbolize respect and mourning. Because the brain is the organ enriched in the infectious agent prion, women and children, who consumed brain and viscera, had much higher likelihood of being infected than men, who preferentially consumed muscles.

Treating the underlying cause of the disorder may improve or reverse symptoms. However, in some cases, the encephalopathy may cause permanent structural changes and irreversible damage to the brain. These permanent deficits can be considered a form of stable dementia. Some encephalopathies can be fatal.

Fatal familial insomnia (FFI) is an extremely rare autosomal dominant inherited prion disease of the brain. It is almost always caused by a mutation to the protein PrP, but can also develop spontaneously in patients with a non-inherited mutation variant called sporadic fatal insomnia (sFI). FFI has no known cure and involves progressively worsening insomnia, which leads to hallucinations, delirium, confusional states like that of dementia, and eventually, death. The average survival time for patients diagnosed with FFI after the onset of symptoms is 18 months.

The mutated protein, called PrP, has been found in just 40 families worldwide, affecting about 100 people; if only one parent has the gene, the offspring have a 50% risk of inheriting it and developing the disease. With onset usually around middle age, it is essential that a potential patient be tested if they wish to avoid passing FFI on to their children. The first recorded case was an Italian man, who died in Venice in 1765.

Some degree of control of the fasciculations may be achieved with the same medication used to treat essential tremor (beta-blockers and anti-seizure drugs). However, often the most effective approach to treatment is to treat any accompanying anxiety. No drugs, supplements, or other treatments have been found that completely control the symptoms. In cases where fasciculations are caused by magnesium deficiency, supplementing magnesium can be effective in reducing symptoms.

In many cases, the severity of BFS symptoms can be significantly reduced through a proactive approach to decrease the overall daily stress. Common ways to reduce stress include: exercising more, sleeping more, working less, meditation, and eliminating all forms of dietary caffeine (e.g. coffee, chocolate, cola, and certain over-the counter medications).

If pain or muscle aches are present alongside fasciculations, patients may be advised to take over-the-counter pain medications such as ibuprofen or acetaminophen during times of increased pain. Other forms of pain management may also be employed. Prior to taking any over-the-counter medications, individuals should initiate discussions with their health care provider(s) to avoid adverse effects associated with long-term usage or preexisting conditions.

Concerning more serious afflictions, the complex origins of myoclonus may be treated with multiple drugs, which have a limited effect individually, but greater when combined with others that act on different brain pathways or mechanisms. Treatment is most effective when the underlying cause is known, and can be treated as such. Some drugs being studied in different combinations include clonazepam, sodium valproate, piracetam, and primidone. Hormonal therapy may improve responses to antimyoclonic drugs in some people.

Some studies have shown that doses of 5-hydroxytryptophan (5-HTP) leads to improvement in patients with some types of action myoclonus and PME. These differences in the effect of 5-HTP on patients with myoclonus have not yet been explained.

Many of the drugs used for myoclonus, such as barbiturates, phenytoin and primidone, are also used to treat epilepsy. Barbiturates slow down the central nervous system and cause tranquilizing or antiseizure effects. Phenytoin and primidone are effective antiepileptics drugs, although phenytoin can cause liver failure or have other harmful long-term effects in patients with PME. Sodium valproate is an alternative therapy for myoclonus and can be used either alone or in combination with clonazepam. Some people have adverse reactions to clonazepam and/or sodium valproate.

When patients are taking multiple medications, the discontinuation of drugs suspected of causing myoclonus and treatment of metabolic derangements may resolve some cases of myoclonus. When pharmacological treatment is indicated anticonvulsants are the main line of treatment. Paradoxical reactions to treatment are notable. Drugs which most people respond to may in other individuals worsen their symptoms. Sometimes this leads to the mistake of increasing the dose, rather than decreasing or stopping the drug. Treatment of myoclonus focuses on medications that may help reduce symptoms. Drugs used include sodium valproate, clonazepam, the anticonvulsant levetiracetam, and piracetam. Dosages of clonazepam usually are increased gradually until the patient improves or side effects become harmful. Drowsiness and loss of coordination are common side effects. The beneficial effects of clonazepam may diminish over time if the patient develops a tolerance to the drug.

In forms of myoclonus where only a single area is affected, and even in a few other various forms, Botox injections (OnabotulinumtoxinA) may be helpful. The chemical messenger responsible for triggering the involuntary muscle contractions is blocked by the Botulinum toxins of the Botox.

Surgery is also a viable option for treatment if the symptoms are caused by a tumor or lesion in the brain or spinal cord. Surgery may also correct symptoms in those where myoclonus affects parts of the face or ear. While DBS is still being studied for use with myoclonus, Deep Brain Stimulation has also been tried in those with this and other movement disorders.

Research on myoclonus is supported through the National Institute of Neurological Disorders and Stroke (NINDS). The primary focus of research is on the role of neurotransmitters and receptors involved in the disease. Identifying whether or not abnormalities in these pathways cause myoclonus may help in efforts to develop drug treatments and diagnostic tests. Determining the extent that genetics play in these abnormalities may lead to potential treatments for their reversal, potentially correcting the loss of inhibition while enhancing mechanisms in the body that would compensate for their effects.

The precise cause of BFS is unknown, and it is not known if it is a disease of the motor nerves, the muscles, or the neuromuscular junction.

Though twitching is sometimes a symptom of serious diseases such as spinal injury, muscular dystrophy, Lyme disease, Creutzfeldt–Jakob disease (CJD), neurofibromatosis or amyotrophic lateral sclerosis (ALS), causes like over-exertion are more common. Mitsikostas "et al." found that fasciculations "were slightly correlated to the body weight and height and to the anxiety level" in normal subjects.

BFS can also be attributed to long term use of anticholinergics such as diphenhydramine and opiates such as morphine, but the latter case is usually when withdrawal symptoms are present.

Magnesium deficiency can cause both fasciculations and anxiety. A vitamin D deficiency may also cause fasciculations, stemming from reduced ionized calcium in the blood (hypocalcemia).

Recent studies have found an association between widespread fasciculations and/or paresthesias with small fiber neuropathy in up to 82% of cases which have a normal EMG and nerve conduction study.