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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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The treatment of dysautonomia can be difficult; since it is made up of many different symptoms, a combination of drug therapies is often required to manage individual symptomatic complaints. Therefore, if an autoimmune neuropathy is the case, then treatment with immunomodulatory therapies is done, or if diabetes mellitus is the cause, control of blood glucose is important. Treatment can include proton-pump inhibitors and H2 receptor antagonists used for digestive symptoms such as acid reflux.
For the treatment of genitourinary autonomic neuropathy medications may include sildenafil (a guanine monophosphate type-5 phosphodiesterase inhibitor). For the treatment of hyperhidrosis, anticholinergic agents such as trihexyphenidyl or scopolamine can be used, also intracutaneous injection of botulinum toxin type A can be used for management in some cases.
Balloon angioplasty, a procedure referred to as transvascular autonomic modulation, is specifically not approved for the treatment of autonomic dysfunction.
Proper treatment of autonomic dysreflexia involves administration of anti-hypertensives along with immediate determination and removal of the triggering stimuli. Often, sitting the patient up and dangling legs over the bedside can reduce blood pressures below dangerous levels and provide partial symptom relief. Tight clothing and stockings should be removed. Straight catheterization of the bladder every 4 to 6 hrs, or relief of a blocked urinary catheter tube may resolve the problem. The rectum should be cleared of stool impaction, using anaesthetic lubricating jelly. If the noxious precipitating trigger cannot be identified, drug treatment is needed to decrease elevating intracranial pressure until further studies can identify the cause.
Drug treatment includes the rapidly acting vasodilators, including sublingual nitrates or oral clonidine. Ganglionic blockers are also used to control sympathetic nervous system outflow. Topical nitropaste is a convenient and safe treatment—an inch or two can be applied to the chest wall, and wiped off when blood pressures begin to normalize. Autonomic dysreflexia is abolished temporarily by spinal or general anaesthesia. These treatments are used during obstetric delivery of a woman with autonomic dysreflexia.
Pharmacological methods of treatment include fludrocortisone, midodrine, somatostatin, erythropoietin, and other vasopressor agents. However, often a patient with pure autonomic failure can mitigate his or her symptoms with far less costly means. Compressing the legs and lower body, through crossing the legs, squatting, or the use of compression stockings can help. Also, ingesting more water than usual can increase blood pressure and relieve some symptoms.
Management of neuropsychiatric lupus is similar to the management of neuropsychiatric disease in patients without lupus. Treatment depends on the underlying causes of a patient’s disease, and may include immunosuppressants, anticoagulants, and symptomatic therapy.
Antidepressants are "associated with improvements in pain, depression, fatigue, sleep disturbances, and health-related quality of life in people with FMS." The goal of antidepressants should be symptom reduction and if used long term, their effects should be evaluated against side effects. A small number of people benefit significantly from the SNRIs duloxetine and milnacipran and the tricyclic antidepressants (TCAs), such as amitriptyline. However, many people experience more adverse effects than benefits. While amitriptyline has been used as a first line treatment, the quality of evidence to support this use is poor.
It can take up to three months to derive benefit from the antidepressant amitriptyline and between three and six months to gain the maximal response from duloxetine, milnacipran, and pregabalin. Some medications have the potential to cause withdrawal symptoms when stopping so gradual discontinuation may be warranted particularly for antidepressants and pregabalin.
There is tentative evidence that the benefits and harms of SSRIs appear to be about similar.
If people are found to have a tumor, the long-term prognosis is generally better and the chance of relapse is much lower. This is because the tumour can be removed surgically, thus eradicating the source of autoantibodies. In general, early diagnosis and aggressive treatment is believed to improve patient outcomes, but this remains impossible to know without data from randomized controlled trials. Given that the majority of patients are initially seen by psychiatrists, it is critical that all physicians (especially psychiatrists) consider anti-NMDA receptor encephalitis as a possible cause of acute psychosis in young patients with no past neuropsychiatric history.
- If a tumor is detected, its removal should occur in conjunction with first-line immunotherapy. This involves steroids to suppress the immune system, intravenous immunoglobulin, and plasmapheresis to physically remove autoantibodies. A study of 577 patients showed that over four weeks, about half the patients improved after receiving first-line immunotherapy.
- Second-line immunotherapy includes rituximab, a monoclonal antibody that targets the CD20 receptor on the surface of B cells, thus destroying the self-reactive B cells. Cyclophosphamide, an alkylating agent that cross-links DNA and is used to treat both cancer and autoimmune diseases, has sometimes proven useful when other therapies have failed.
- Other medications, such as alemtuzumab, remain experimental.
The anti-convulsant drugs gabapentin and pregabalin may be used to reduce pain. Gabapentin may be of significant benefit for pain relief in about 35% of people with fibromyalgia. It is not possible to predict who will benefit, and a short trial may be recommended to test the effectiveness of this type of medication. Approximately 6/10 people who take gabapentin to treat pain related to fibromyalgia experience unpleasant side effects such as dizziness, abnormal walking, or swelling from fluid accumulation. Pregabalin demonstrates a substantial benefit in about 9% of people. Pregabalin reduced time off work by 0.2 days per week.
There is a wide range of treatments for central nervous system diseases. These can range from surgery to neural rehabilitation or prescribed medications.
Medications offered can include the immunosuppressant prednisone, intravenous gamma globulin (IVIG), anticonvulsants such as gabapentin or Gabitril and antiviral medication, depending on the underlying cause..
In addition to treatment of the underlying disorder, palliative care can include the use of topical numbing creams, such as lidocaine or prilocaine. Care must be taken to apply only the necessary amount, as excess can contribute to the condition. Otherwise, these products offer extremely effective, but short-lasting, relief from the condition.
Paresthesia caused by stroke may receive some temporary benefit from high doses of Baclofen multiple times a day. HIV patients who self-medicate with cannabis report that it reduces their symptoms.
Paresthesia caused by shingles is treated with appropriate antiviral medication.
The medication that may be prescribed to someone who has a mental breakdown is based upon the underlying causes, which are sometimes more serious mental disorders. Antidepressants are given to treat depression. Anxiolytics are used for those with anxiety disorders. Antipsychotics are used for schizophrenia and mood stabilizers help with bipolar disorder. Depending upon what caused a person’s mental breakdown, any of these treatments can be helpful for them.
There are several different kinds of therapy that a patient can receive. The most common type of therapy is counseling. This is where the patient is able to talk about whatever is on their mind without worrying about any judgments. Psychotherapy is a very common type of therapy that addresses the current problems in someone’s life and helps them to deal with them. Past experiences may also be explored in this type of therapy. In psychoanalysis therapy, the main focus is a patient’s past experiences so that they can confront these issues and prevent breakdowns in the future. Cognitive behavioral therapy explores how a person behaves and what they are thinking and feeling. If there is anything negative in these three different categories, then this therapy will try to turn them around into positives. Hypnotherapy is where hypnosis is performed and used to help the patient relax. Hypnosis can also be used to figure out why a person acts or feels a certain way, by examining past events that may have caused the breakdown. Expressive therapy focuses on how the patient is able to express their feelings. If the patient has a hard time doing this, expression through the arts is highly recommended. There is also aromatherapy, which consists of herbs to help the patient relax and to try to relieve stress. Yoga and massage may also be included in this therapy that will help the muscles to relax. Meditation is also often recommended. All of these therapies help a person to relax and de-stress and also help to prevent future breakdowns.
Treatment also involves central nervous system penetrating chemotherapy. Options include intrathecal, intraventricular, and systemic chemotherapy. These must penetrate the blood-brain barrier in order to be effective. Sometimes mixing multiple forms of treatment with chemotherapy seems to be the best route. For example, some significant improvement has been shown as a result of cranial radiation treatment preceding a brief course of intrathecal chemotherapy. Although this is an effective treatment to do, penetrating the blood-brain barrier can cause side effects due to the toxicity in the nervous system. These would include dizziness, confusion, and changes in mental status. Another form could be the use of pharmaceuticals, which have all shown positive results for treatment but should always be consulted with a physician to asses risks.
Autologous stem-cell transplants are shown to be an effective treatment. However, this should be only considered for certain people due to toxicity concerns. It is possible that the transplant may cause problems like septic shock.
The recovery process from anti-NMDA encephalitis can take many months. The symptoms reappear in reverse order: The patient may begin to experience psychosis again, leading many people to falsely believe the patient is not recovering. As the recovery process continues on, the psychosis fades. Lastly, the person's social behavior and executive functions begin to improve.
Treatment typically involves improving the patient's quality of life. This is accomplished through the management of symptoms or slowing the rate of demyelination. Treatment can include medication, lifestyle changes (i.e. quit smoking, adjusting daily schedules to include rest periods and dietary changes), counselling, relaxation, physical exercise, patient education and, in some cases, deep brain thalamic stimulation (in the case of tremors). The progressive phase of MS appears driven by the innate immune system, which will directly contribute to the neurodegenerative changes that occur in progressive MS. Until now, there are no therapies that specifically target innate immune cells in MS. As the role of innate immunity in MS becomes better defined, it may be possible to better treat MS by targeting the innate immune system.
Treatments are patient-specific and depend on the symptoms that present with the disorder, as well as the progression of the condition.
Since each case is different, the following are possible treatments that patients might receive in the management of myelitis.
- Intravenous steroids
High-dose intravenous methyl-prednisolone for 3–5 days is considered as a standard of care for patients suspected to have acute myelitis, unless there are compelling reasons otherwise. The decision to offer continued steroids or add a new treatment is often based on the clinical course and MRI appearance at the end of 5 days of steroids.
- Plasma exchange (PLEX)
Patients with moderate to aggressive forms of disease who don’t show much improvement after being treated with intravenous and oral steroids will be treated with PLEX. Retrospective studies of patients with TM treated with IV steroids followed by PLEX showed a positive outcome. It also has been shown to be effective with other autoimmune or inflammatory central nervous system disorders. Particular benefit has been shown with patients who are in the acute or subacute stage of the myelitis showing active inflammation on MRI. However, because of the risks implied by the lumbar puncture procedure, this intervention is determined by the treating physician on a case-by-case basis.
- Immunosuppressants/Immunomodulatory agents
Myelitis with no definite cause seldom recurs, but for others, myelitis may be a manifestation of other diseases that are mentioned above. In these cases, ongoing treatment with medications that modulate or suppress the immune system may be necessary. Sometimes there is no specific treatment. Either way, aggressive rehabilitation and long-term symptom management are an integral part of the healthcare plan.
The cause of autonomic dysreflexia itself can be life-threatening, and must also be completely investigated and treated appropriately to prevent unnecessary morbidity and mortality.
The Consortium for Spinal Cord Medicine has developed evidence-based clinical practice guidelines for the management of autonomic dysreflexia in adults, children, and pregnant women. There is also a consumer version of this guideline.
Since interleukin 1β plays a central role in the pathogenesis of the disease, therapy typically targets this cytokine in the form of monoclonal antibodies (such as canakinumab), binding proteins/traps (such as rilonacept), or interleukin 1 receptor antagonists (such as anakinra). These therapies are generally effective in alleviating symptoms and substantially reducing levels of inflammatory indices. Case reports suggest that thalidomide and the anti-IL-6 receptor antibody tocilizumab may also be effective.
Caffeine is the most widely consumed stimulant in North America. In small doses, caffeine can improve endurance. Recently, it has also been shown to delay the onset of fatigue in exercise. The most probable mechanism for the delay of fatigue is through the obstruction of adenosine receptors in the central nervous system. Adenosine is a neurotransmitter that decreases arousal and increases sleepiness. By preventing adenosine from acting, caffeine removes a factor that promotes rest and delays fatigue.
Amphetamine is a stimulant that has been found to improve both physical and cognitive performance. Amphetamine blocks the reuptake of dopamine and norepinephrine, which delays the onset of fatigue by increasing the amount of dopamine, despite the concurrent increase in norepinephrine, in the central nervous system. Amphetamine is a widely used substance among collegiate athletes for its performance enhancing qualities, as it can improve muscle strength, reaction time, acceleration, anaerobic exercise performance, power output at fixed levels of perceived exertion, and endurance.
Methylphenidate has also been shown to increase exercise performance in time to fatigue and time trial studies.
Treatment requires a firm and transparent diagnosis based on positive features which both health professionals and patients can feel confident about. It is essential that the health professional confirms that this is a common problem which is genuine, not imagined and not a diagnosis of exclusion.
Confidence in the diagnosis does not improve symptoms, but appears to improve the efficacy of treatments such as physiotherapy which require altering established abnormal patterns of movement.
A multi-disciplinary approach to treating functional neurological disorder is recommended.
Treatment options can include:
- Physiotherapy and occupational therapy
- Medication such as sleeping tablets, painkillers, anti-epileptic medications and anti-depressants (for patients suffering with depresssion co-morbid or for pain relief)
Physiotherapy with someone who understands functional disorders may be the initial treatment of choice for patients with motor symptoms such as weakness, gait (walking) disorder and movement disorders. Nielsen et al. have reviewed the medical literature on physiotherapy for functional motor disorders up to 2012 and concluded that the available studies, although limited, mainly report positive results. Since then several studies have shown positive outcomes. In one study, up to 65% of patients were very much or much improved after five days of intensive physiotherapy even though 55% of patients were thought to have poor prognosis. In a randomised controlled trial of physiotherapy there was significant improvement in mobility which was sustained on one year follow up. In multidisciplinary settings 69% of patients markedly improved even with short rehabilitation programmes. Benefit from treatment continued even when patients were contacted up 25months after treatment.
For patients with severe and chronic FND a combination of physiotherapy, occupational therapy and cognitive behavioural therapy may be the best combination with positive studies being published in patients who have had symptoms for up to three years before treatment.
Cognitive behavioural therapy (CBT) alone may be beneficial in treating patients with dissociative (non-epileptic) seizures. A randomised controlled trial of patients who undertook 12 sessions of CBT which taught patients how to interrupt warning signs before seizure onset, challenged unhelpful thoughts and helped patients start activities they had been avoiding found a reduction in the seizure frequency with positive outcomes sustained at six month follow up. A large multicentre trial of CBT for dissociative (non-epileptic) seizures started in 2015 in the UK.
For many patients with FND, accessing treatment can be difficult. Availability of expertise is limited and they may feel that they are being dismissed or told 'it's all in your head' especially if psychological input is part of the treatment plan. Some medical professionals are uncomfortable explaining and treating patients with functional symptoms. Changes in the diagnostic criteria, increasing evidence, literature about how to make the diagnosis and how to explain it and changes in medical training is slowly changing this
After a diagnosis of functional neurological disorder has been made, it is important that the neurologist explains the illness fully to the patient to ensure the patient understands the diagnosis.
Some, but not all patients with FND may experience low moods or anxiety due to their condition. However, they will often not seek treatment due being worried that a doctor will blame their symptoms on their anxiety or depression.
It is recommended that the treatment of functional neurological disorder should be balanced and involve a whole-person approach. This means that it should include professionals from multiple departments, including neurologists, general practitioners (or primary health care providers), physiotherapists, occupational therapists. At the same time, ruling out secondary gain, malingering, conversion disorder and other factors, including the time and financial resources involved in assessing and treating patients who demand hospital resources but would be better served in psychological settings, must all be balanced.
Although the FD-causing gene has been identified and it seems to have tissue specific expression, there is no definitive treatment at present.
Treatment of FD remains preventative, symptomatic and supportive. FD does not express itself in a consistent manner. The type and severity of symptoms displayed vary among patients and even at different ages on the same patients. So patients should have specialized individual treatment plans. Medications are used to control vomiting, eye dryness, and blood pressure. There are some commonly needed treatments including:
1. Artificial tears: using eye drops containing artificial tear solutions (methylcellulose)
2. Feeding: Maintenance of adequate nutrition, avoidance of aspiration; thickened formula and different shaped nipples are used for baby.
3. Daily chest physiotherapy (nebulization, bronchodilators, and postural drainage): for Chronic lung disease from recurrent aspiration pneumonia
4. Special drug management of autonomic manifestations such as vomiting: intravenous or rectal diazepam (0.2 mg/kg q3h) and rectal chloral hydrate (30 mg/kg q6h)
5. Protecting the child from injury (coping with decreased taste, temperature and pain perception)
6. Combating orthostatic hypotension: hydration, leg exercise, frequent small meals, a high-salt diet, and drugs such as fludrocortisone.
7. Treatment of orthopedic problems (tibial torsion and spinal curvature)
8. Compensating for labile blood pressures
There is no cure for Familial Dysautonomia.
CNS depression is treated within a hospital setting by maintaining breathing and circulation. Individuals with reduced breathing may be given supplemental oxygen, while individuals who are not breathing can be ventilated with bag valve mask ventilation or by mechanical ventilation with a respirator. Sympathomimetic drugs may be used to attempt to stimulate cardiac output in order to maintain circulation. CNS Depression caused by certain drugs may respond to treatment with an antidote.
There are two antidotes that are frequently used in the hospital setting and these are Naloxone and Flumazenil. Naloxone is an opioid antagonist and reverses the central nervous depressive effects seen in opioid overdose. In the setting of a colonoscopy, Naloxone is rarely administered but when it is administered, its half life is shorter than some common opioid agonists. Therefore, the patient may still exhibit central nervous system depression after Naloxone has been cleared. Typically, Naloxone is administered in short intervals with relatively small doses in order to prevent the occurrence of withdrawal, pain, and sympathetic nervous system activation. Flumazenil is a benzodiazepine antagonists and blocks the binding of benzodiazepines to GABAa. Similarly to Naloxone, Flumazenil has a short half life, and this needs to be taken into account because the patient may exhibit central nervous depression after the antidote has been cleared. Benzodiazepines are used in the treatment of seizures and subsequently, the administration of Flumazenil may result in seizures. Therefore, slow administration of Flumazenil is necessary to prevent the occurrence of a seizure. These agents are rarely used in the setting of a colonoscopy as 98.8% of colonoscopies use sedatives but only 0.8% of them result in the administration of one of these antidotes. Even if they are rarely used in colonoscopies they are important in preventing the patient from entering a coma or developing respiratory depression when sedatives are not properly dosed. Outside of the colonoscopy setting, these agents are used for other procedures and in the case of drug overdose.
There is currently no cure for FD and death occurs in 50% of the affected individuals by age 30. There are only two treatment centers, one at New York University Hospital and one at the Sheba Medical Center in Israel. One is being planned for the San Francisco area.
The survival rate and quality of life have increased since the mid-1980s mostly due to a greater understanding of the most dangerous symptoms. At present, FD patients can be expected to function independently if treatment is begun early and major disabilities avoided.
A major issue has been aspiration pneumonia, where food or regurgitated stomach content would be aspirated into the lungs causing infections. Fundoplications (by preventing regurgitation) and gastrostomy tubes (to provide nonoral nutrition) have reduced the frequency of hospitalization.
Other issues which can be treated include FD crises, scoliosis, and various eye conditions due to limited or no tears.
An FD crisis is the body's loss of control of various autonomic nervous system functions including blood pressure, heart rate, and body temperature. Both short-term and chronic periodic high or low blood pressure have consequences and medication is used to stabilize blood pressure.
There is no current cure for superficial siderosis, only treatments to help alleviate the current symptoms and to help prevent the development of further symptoms. If a source of bleeding can be identified (sources are frequently not found), then surgical correction of the bleeding source can be performed; this has proved to be effective in halting the development of further symptoms in some cases and has no effect on symptoms that have already presented.
Patients with superficial siderosis are often treated with deferiprone, a lipid-soluble iron chelator, as this medication has been demonstrated to chelate iron in the central nervous system.
While on this drug you will need a frequent blood test (weekly) to keep an eye on the blood levels as this drug is known to lower certain blood levels such as the neutrophils and WBC (white blood count) and etc. While it is ok if these levels go low in the average person, if they go low while taking Deferiprone Ferriprox it can cause life threatening infections that can result in death.
Alleviation of the most common symptom, hearing loss, has been varyingly successful through the use of cochlear implants. Most people do not notice a large improvement after successful implantation, which is most likely due to damage to the vestibulocochlear nerve (cranial nerve VIII) and not the cochlea itself. Some people fare far better, with a return to near normal hearing, but there is little ability to detect how well a person will respond to this treatment at this time.
The prognosis of dysautonomia depends on several factors; individuals with chronic, progressive, generalized dysautonomia in the setting of central nervous system degeneration such as Parkinson's disease or multiple system atrophy have a generally poorer long-term prognosis. Consequently, dysautonomia could be fatal due to pneumonia, acute respiratory failure, or sudden cardiopulmonary arrest.
Autonomic dysfunction symptoms such as orthostatic hypotension, gastroparesis, and gustatory sweating are more frequently identified in mortalities.