Based on anecdotal evidence, the drugs of choice are those used for other idiopathic generalized epilepsies. Valproate alone, or most probably in combination with clonazepam, levetiracetam, lamotrigine or ethosuximide, appears to be the most effective regimen. The choice of the second drug depends on the main seizure type. Clonazepam is highly efficacious in eyelid myoclonia and myoclonic jerks. Of the newer antiepileptic drugs, levetiracetam may be the most effective, because of its anti myoclonic and anti photosensitive properties. Lamotrigine is very effective in absence seizures but may exaggerate myoclonic jerks.

Contra-indicated drugs are: Carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine and vigabatrin.

Lifestyle and avoidance of seizure precipitants are important. Non-pharmacological treatments used for photosensitive patients (such as wearing special glasses or the newly commercially available blue Z1 lenses) should be employed in Jeavons syndrome when photosensitivity persists.

Valproic acid is the first line drug choice for reducing generalised seizures and myoclonus. Levetiracetam is also effective for both generalised seizures and myoclonus. Clonazepam and high-dose piracetam can alleviate myoclonus. Phenytoin can worsen seizures and may speed up neurodegeneration; carbamazepine, oxcarbazepine, tiagabine, vigabatrin, gabapentin and pregabalin may worsen myoclonus and myoclonic seizures. Other common medications to treat ULD include topiramate and zonisamide. If an individual with Unverricht–Lundborg disease is particularly sensitive to a certain type of stimulus, it is also beneficial to reduce the patient's exposure to that stimulus in order to reduce the likelihood of seizures. Since ULD is progressive and may not get better over time, depression has been documented in many cases, so providing a strong support group of friends, family, and even other individuals with ULD is very beneficial.

While there is no current cure to repair the mutated CSTB gene, several antiepileptic drugs are effective in reducing seizures and helping patients with ULD to manage the symptoms. In addition, new research is being performed to examine the effectiveness of other types of treatments.

Patients with ICOE-G need prophylactic treatment mainly with carbamazepine or other antiepileptic drugs licensed for focal seizures. A slow reduction in the dose of medication 2 or 3 years after the last visual or other minor or major seizure should be advised, but if visual seizures reappear, treatment should be restored.

Jeavons syndrome is a lifelong disorder, even if seizures are well controlled with antiepileptic drugs. Men have a better prognosis than women. There is a tendency for photosensitivity to disappear in middle age, but eyelid myoclonia persists. It is highly resistant to treatment and occurs many times a day, often without apparent absences and even without demonstrable photosensitivity.

The prognosis of ICOE-G is unclear, although available data indicate that remission occurs in 50–60% of patients within 2–4 years of onset. Seizures show a dramatically good response to carbamazepine in more than 90% of patients. However, 40–50% of patients may continue to have visual seizures and infrequent secondarily generalized convulsions, particularly if they have not been appropriately treated with antiepileptic drugs.

No cure is available for PSE, although the sensitivity of some patients may diminish over time. Medical treatment is available to reduce sensitivity, with sodium valproate being commonly prescribed. Patients can also learn to avoid situations in which they might be exposed to stimuli that trigger seizures and/or take steps to diminish their sensitivity (as by covering one eye) if they are unavoidably exposed. These actions together can reduce the risk of seizures to almost zero for many PSE patients.

Some PSE patients have trigger stimuli that are so specific that they are never likely to encounter them in real life. Their PSE may only be discovered by accident in an unusual situation or during examination for other complaints.

Because most patients respond to steroids or immunosuppressant treatment, this condition is now also referred to as steroid-responsive encephalopathy.

Initial treatment is usually with oral prednisone (50–150 mg/day) or high-dose IV methylprednisolone (1 g/day) for 3–7 days. Thyroid hormone treatment is also included if required.

Failure of some patients to respond to this first line treatment has produced a variety of alternative treatments including azathioprine, cyclophosphamide, chloroquine, methotrexate, periodic intravenous immunoglobulin and plasma exchange. There have been no controlled trials so the optimal treatment is not known.

Seizures, if present, are controlled with typical antiepileptic agents.

The opioid antagonist naloxone allowed a woman with congenital insensitivity to pain to experience it for the first time. Similar effects were observed in Na1.7 null mice treated with naloxone. As such, opioid antagonists like naloxone and naltrexone may be effective in treating the condition.

Hemicrania continua generally responds only to indomethacin 25–300 mg daily, which must be continued long term. Unfortunately, gastrointestinal side effects are a common problem with indomethacin, which may require additional acid-suppression therapy to control.

In patients who are unable to tolerate indomethacin, the use of celecoxib 400–800 mg per day (Celebrex) and rofecoxib 50 mg per day (Vioxx - no longer available) have both been shown to be effective and are likely to be associated with fewer GI side effects. There have also been reports of two patients who were successfully managed with topiramate 100–200 mg per day (Topamax) although side effects with this treatment can also prove problematic.

Greater Occipital Nerve [GON] block comprising 40 mg Depomedrone and 10mls of 1% Lignocaine injected into the affected nerve is effective, up to a period of approximately three months. Changing the 'cocktail' to include [for example] 10mls of .5% Marcaine and changing to 2% Lignocaine, whilst in theory should increase the longevity, renders the injection completely ineffective. See 4.2 Posology and method of administration [flocculation]

Occipital nerve stimulation may be highly effective when other treatments fail to relieve the intractable pain.

Attacks are self-limiting, and require analgesia and NSAIDs (such as diclofenac). Colchicine, a drug otherwise mainly used in gout, decreases attack frequency in FMF patients. The exact way in which colchicine suppresses attacks is unclear. While this agent is not without side effects (such as abdominal pain and muscle pains), it may markedly improve quality of life in patients. The dosage is typically 1–2 mg a day. Development of amyloidosis is delayed with colchicine treatment. Interferon is being studied as a therapeutic modality. Some advise discontinuation of colchicine before and during pregnancy, but the data are inconsistent, and others feel it is safe to take colchicine during pregnancy.

Approximately 5–10% of FMF cases are resistant to colchicine therapy alone. In these cases, adding anakinra to the daily colchicine regimen has been successful.

The first line of treatment are corticosteroids and other medicines used to suppress the immune system such as tacrolimus and sirolimus.

A intravenous nutrition such as total parenteral nutrition and/or a special diet may be necessary. Hematopoietic stem cell transplantation may be curative.

Should the viral progression be diagnosed during stage 1 (even during late stage 1 when stage 2 symptoms start to manifest themselves) then treatment to combat the infection can be administered successfully—there is no cure for SSPE but if it is caught early enough then the sufferer can respond to the treatment and prevent symptom recurrence by taking the medication for the rest of their life. The treatment for the SSPE infection is the immunomodulator interferon and specific antiviral medication—ribavirin and inosine pranobex are specifically used to greater effect than antivirals such as amantadine.

For those who have progressed to stage 2 or beyond, the disease is incurable. For patients in the terminal phase of the disease there is a palliative care and treatment scheme—this involves anticonvulsant therapy (to help with the body's progressive loss of control of the nervous system causing gradually more intensive spasms/convulsions) alongside supportive measures to help maintain vital functioning. It is fairly standard as the infection spreads and symptoms intensify that feeding tubes need to be inserted to keep a nutritional balance. As the disease progresses to its most advanced phase, the patient will need constant nursing as normal bodily function declines to the complete collapse of the nervous system.

Combinations of treatment for SSPE include:

- Oral inosine pranobex (oral isoprinosine) combined with intrathecal (injection through a lumbar puncture into the spinal fluid) or intraventricular interferon alpha.

- Oral inosine pranobex (oral isoprinosine) combined with interferon beta.

- Intrathecal interferon alpha combined with intravenous ribavirin.

Duration of treatment is usually between 2 and 25 years. Earlier reports suggested that 90% of cases stay in remission after discontinuation of treatment; however, this is at odds with more recent studies which suggest that relapse commonly occurs after initial high-dose steroid treatment. Left untreated, this condition can result in coma and death.

Corticosteroids such as prednisone are often prescribed along with a blood pressure medication, typically an ACE inhibitor such as lisinopril. Some nephrologists will start out with the ACE inhibitor first in an attempt to reduce the blood pressure's force which pushes the protein through the cell wall in order to lower the amount of protein in the urine. In some cases, a corticosteroid may not be necessary if the case of minimal change disease is mild enough to be treated just with the ACE inhibitor. Often, the liver is overactive with minimal change disease in an attempt to replace lost protein and overproduces cholesterol. Therefore, a statin drug is often prescribed for the duration of the treatment. When the urine is clear of protein, the medications can be discontinued. Fifty percent of patients will relapse and need further treatment with immunosuppressants, such as cyclosporine and tacrolimus.

Minimal change disease usually responds well to initial treatment and over 90% of patients will respond to oral steroids within 6–8 weeks, with most of these having a complete remission. Symptoms of nephrotic syndrome (NS) typically go away; but, this can take from 2 weeks to many months. Younger children, who are more likely to develop minimal change disease, usually respond faster than adults. In 2 out of 3 children with minimal change disease; however, the symptoms of NS can recur, called a relapse, particularly after an infection or an allergic reaction. This is typical and usually requires additional treatment. Many children experience 3 to 4 relapses before the disease starts to go away. Some children require longer term therapy to keep MCD under control. It appears that the more time one goes without a relapse, the better the chances are that a relapse will not occur. In most children with minimal change disease, particularly among those who respond typically, there is minimal to no permanent damage observed in their kidneys.

With corticosteroid treatment, most cases of nephrotic syndrome from minimal change disease in children will go into remission. This typically occurs faster, over 2 to 8 weeks, in younger children, but can take up to 3 or 4 months in adults. Typically, the dose of corticosteroids will initially be fairly high, lasting 1or 2 months. When urine protein levels have normalised, corticosteroids are gradually withdrawn over several weeks (to avoid triggering an Addisonian crisis). Giving corticosteroids initially for a longer period of time is thought to reduce the likelihood of relapse. The majority of children with minimal change disease will respond to this treatment.

Even among those who respond well to corticosteroids initially, it is common to observe periods of relapse (return of nephrotic syndrome symptoms). 80% of those who get minimal change disease have a recurrence. Because of the potential for relapse, the physician may prescribe and teach the patient how to use a tool to have them check urine protein levels at home. Two out of 3 children who initially responded to steroids will experience this at least once. Typically the steroids will be restarted when this occurs, although the total duration of steroid treatment is usually shorter during relapses than it is during the initial treatment of the disease.

There are several immunosuppressive medications that can be added to steroids when the effect is insufficient or can replace them if intolerance or specific contraindications are encountered.

Diagnosis

Originally NEMO deficiency syndrome was thought to be a combination of Ectodermal Dysplasia (ED) and a lack of immune function, but is now understood to be more complex disease. NEMO Deficiency Syndrome may manifest itself in the form of several different diseases dependent upon mutations of the IKBKG gene such as Incontinentia pigmenti or Ectodermal dysplasia.

The clinical presentation of NEMO deficiency is determined by three main symptoms:

1. Susceptibility to pyogenic infections in the form of severe local inflammation

2. Susceptibility to mycobacterial infection

3. Symptoms of Ectodermal Dysplasia

To determine whether or not patient has NEMO deficiency, an immunologic screen to test immune system response to antigen may be used although a genetic test is the only way to be certain as many individuals respond differently to the immunological tests.

Commonly Associated Diseases

NEMO deficiency syndrome may present itself as Incontinentia pigmenti or Ectodermal dysplasia depending on the type of genetic mutation present, such as if the mutation results in the complete loss of gene function or a point mutation.

Amorphic genetic mutations in the IKBKG gene, which result in the loss of gene function, typically present themselves as Incontinetia Pigmenti (IP). Because loss of NEMO function is lethal, only heterozygous females or males with XXY karyotype or mosaicism for this gene survive and exhibit symptoms of Incontinetia Pigmenti, such as skin lesions and abnormalities in hair, teeth, and nails. There are a variety of mutations that may cause the symptoms of IP, however, they all involve the deletion of exons on the IKBKG gene.

Hypomorphic genetic mutations in the IKBKG gene, resulting in a partial loss of gene function, cause the onset of Anhidrotic ectodermal dysplasia with Immunodeficiency (EDA-IP). The lack of NEMO results in a decreased levels of NF-κB transcription factor translocation and gene transcription, which in turn leads to a low level of immunoglobulin production. Because NF-κB translocation is unable to occur without proper NEMO function, the cell signaling response to immune mediators such as IL-1β, IL-18, and LPS are ineffective thus leading to a compromised immune response to various forms of bacterial infections.

Treatment

The aim of treatment is to prevent infections so children will usually be started on immunoglobulin treatment. Immunoglobulin is also known as IgG or antibody. It is a blood product and is given as replacement for people who are unable to make their own antibodies. It is the mainstay of treatment for patients affected by primary antibody deficiency. In addition to immunoglobulin treatment, children may need to take antibiotics or antifungal medicines to prevent infections or treat them promptly when they occur. Regular monitoring and check-ups will help to catch infections early. If an autoimmune response occurs, this can be treated with steroid and/or biologic medicines to damp down the immune system so relieving the symptoms.

In some severely affected patients, NEMO deficiency syndrome is treated using a bone marrow or blood stem cell transplant. The aim is to replace the faulty immune system with an immune system from a healthy donor.

There is currently no definitive evidence that support altering the course of the recovery of minimally conscious state. There are currently multiple clinical trials underway investigating potential treatments.

In one case study, stimulation of thalamus using deep brain stimulation (DBS) led to some behavioral improvements. The patient was a 38-year-old male who had remained in minimally conscious state following a severe traumatic brain injury. He had been unresponsive to consistent command following or communication ability and had remained non-verbal over two years in inpatient rehabilitation. fMRI scans showed preservation of a large-scale, bi-hemispheric cerebral language network, which indicates that possibility for further recovery may exist. Positron emission tomography showed that the patient's global cerebral metabolism levels were markedly reduced. He had DBS electrodes implanted bilaterally within his central thalamus. More specifically, the DBS electrodes targeted the anterior intralaminar nuclei of thalamus and adjacent paralaminar regions of thalamic association nuclei. Both electrodes were positioned within the central lateral nucleus, the paralaminar regions of the median dorsalis, and the posterior-medial aspect of the centromedian/parafasicularis nucleus complex. This allowed maximum coverage of the thalamic bodies. A DBS stimulation was conducted such that the patient was exposed to various patterns of stimulation to help identify optimal behavioral responses. Approximately 140 days after the stimulation began, qualitative changes in behavior emerged. There were longer periods of eye opening and increased responses to command stimuli as well as higher scores on the JFK coma recovery scale (CRS). Functional object use and intelligible verbalization was also observed. The observed improvements in arousal level, motor control, and consistency of behavior could be a result of direct activation of frontal cortical and basal ganglia systems that were innervated by neurons within the thalamic association nuclei. These neurons act as a key communication relay and form a pathway between the brainstem arousal systems and frontal lobe regions. This pathway is crucial for many executive functions such as working memory, effort regulation, selective attention, and focus.

In another case study of a 50-year-old woman who had symptoms consistent with MCS, administration of zolpidem, a sedative hypnotic drug improved the patient's condition significantly. Without treatment, the patient showed signs of mutism, athetoid movements of the extremities, and complete dependence for all personal care. 45 minutes after 5 to 10 mg of zolpidem was administered, the patient ceased the athetoid movements, regained speaking ability, and was able to self-feed. The effect lasted 3–4 hours from which she returned to the former state. The effects were repeated on a daily basis. PET scans showed that after zolpidem was administered, there was a marked increase in blood flow to areas of the brain adjacent to or distant from damaged tissues. In this case, these areas were the ipsilateral cerebral hemispheres and the cerebellum. These areas are thought to have been inhibited by the site of injury through a GABA-mediated mechanism and the inhibition was modified by zolpidem which is a GABA agonist. The fact that zolpidem is a sedative drug that induces sleep in normal people but causes arousal in a MCS patient is paradoxical. The mechanisms to why this effect occurs is not entirely clear.

There is recent evidence that transcranial direct current stimulation (tDCS), a technique that supplies a small electric current in the brain with non-invasive electrodes, may improve the clinical state of patients with MCS. In one study with 10 patients with disorders of consciousness (7 in VS, 3 in MCS), tDCS was applied for 20 minutes every day for 10 days, and showed clinical improvement in all 3 patients who were in MCS, but not in those with VS. These results remained at 12-month follow-up. Two of the patients in MCS that had their brain insult less that 12 months recovered consciousness in the following months. One of these patients received a second round of tDCS treatment 4 months after his initial treatment, and showed further recovery and emerged into consciousness, with no change of clinical status between the two treatments. Moreover, in a sham-controlled, double-blind crossover study, the immediate effects of a single session of tDCS were shown to transiently improve the clinical status of 13 out of 30 patients with MCS, but not in those with VS

Several approaches have been taken to address tumor hypoxia. Some companies tried to develop drugs that are activated in hypoxic environments (Novacea, Inc. Proacta, Inc, and Threshold Pharmaceuticals, Inc), while others are currently seeking to reduce tumor hypoxia (Diffusion Pharmaceuticals, Inc. and NuvOx Pharma, LLC).

Several companies have tried to develop drugs that are activated in hypoxic environments. These drug candidates target levels of hypoxia that are common in tumors but are rare in normal tissues. The hypoxic zones of tumors generally evade traditional chemotherapeutic agents and ultimately contribute to relapse. In the literature, hypoxia has been demonstrated to be associated with a worse prognosis, making it a determinant of cancer progression and therapeutic response. Several review articles summarize the current status of hypoxic cytotoxins (hypoxia activated prodrugs). Companies that have tried drugs that are activated in hypoxic environments included Novacea, Inc. Proacta, and Threshold Pharmaceuticals. Novacea Inc discontinued development of its hypoxia activated drug. Proacta’s drug PR610 failed a Phase I clinical trial due to toxicity. Threshold Pharmaceuticals discontinued the hypxia activated prodrug, TH-302, after Phase III trials failed to show statistically significant overall survival.

Niacinamide, the active form of vitamin B, acts as a chemo- and radio-sensitizing agent by enhancing tumor blood flow, thereby reducing tumor hypoxia. Niacinamide also inhibits poly(ADP-ribose) polymerases (PARP-1), enzymes involved in the rejoining of DNA strand breaks induced by radiation or chemotherapy. As of August 2016, no clinical trials appear to be in progress for this indication.

Another approach to the treatment of tumor hypoxia is the use of an oxygen diffusion-enhancing compound to reoxygenate the hypoxic zones of tumors. The developer of oxygen diffusion-enhancing compounds, Diffusion Pharmaceuticals, tested its lead compound, trans sodium crocetinate (TSC), in a Phase II clinical trial in 59 patients newly diagnosed with glioblastoma multiforme. The results of the Phase II showed that 36% of the full-dose TSC patients were alive at 2 years, compared with historical survival values ranging from 27% to 30% for the standard of care. The main endpoint of the trial was survival at two years, not overall survival.

Another drug in development that is designed to reduce tumor hypoxia is NuvOx Pharma’s NVX-108. NVX-108 is a formulation of the perfluorocarbon, dodecafluoropentane (DDFPe). NVX-108 is injected intravenously, flows through the lungs and picks up oxygen, then flows through the arteries and releases oxygen in the precense of hypoxic tissue. A Phase Ib/II clinical trial is in progress for newly diagnosed glioblastoma multiforme. Early results have shown reversal of tumor hypoxia, and the trial continues to progress.

When functioning correctly, mains-powered fluorescent lighting has a flicker rate sufficiently high (twice the mains frequency, typically 100 Hz or 120 Hz) to reduce the occurrence of problems. However, a faulty fluorescent lamp can flicker at a much lower rate and trigger seizures. Newer high-efficiency compact fluorescent lamps (CFL) with electronic ballast circuits operate at much higher frequencies (10–20 kHz) not normally perceivable by the human eye, though defective lights can still cause problems.

The Job Accommodation Network lists reduction or elimination of fluorescent lighting as an appropriate accommodation for many conditions including epilepsy. The Canadian Department of Labour states that the newer lights are problematic for fewer people.

The treatment hospitals use on comatose patients depends on both the severity and cause of the comatose state. Although the best treatment for comatose patients remains unknown, hospitals usually place comatose patients in an Intensive Care Unit (ICU) immediately. Attention must first be directed to maintaining the patient's respiration and circulation, using intubation and ventilation, administration of intravenous fluids or blood and other supportive care as needed. Once a patient is stable and no longer in immediate danger, the medical staff may concentrate on maintaining the health of patient’s physical state. The concentration is directed to preventing infections such as pneumonias, bedsores (decubitus ulcers), and providing balanced nutrition. Infections may appear from the patient not being able to move around, and being confined to the bed. The nursing staff moves the patient every 2–3 hours from side to side and depending on the state of consciousness sometimes to a chair. The goal is to move the patient as much as possible to try to avoid bedsores, atelectasis and pneumonia. Pneumonia can occur from the person’s inability to swallow leading to aspiration, lack of gag reflex or from feeding tube, (aspiration pneumonia). Physical therapy may also be used to prevent contractures and orthopedic deformities that would limit recovery for those patients who awaken from coma.

A person in a coma may become restless, or seize and need special care to prevent them from hurting themselves. Medicine may be given to calm such individuals. Patients who are restless may also try to pull on tubes or dressings so soft cloth wrist restraints may be put on. Side rails on the bed should be kept up to prevent the patient from falling.

Methods to wake comatose patients include reversing the cause of the coma (i.e., glucose shock if low sugar), giving medication to stop brain swelling, or inducing hypothermia. Inducing hypothermia on comatose patients provides one of the main treatments for patients after suffering from cardiac arrest. In this treatment, medical personnel expose patients to “external or intravascular cooling” at 32-34 °C for 24 hours; this treatment cools patients down about 2-3 °C less than normal body temperature. In 2002, Baldursdottir and her coworkers found that in the hospital, more comatose patients survived after induced hypothermia than patients that remained at normal body temperature. For this reason, the hospital chose to continue the induced hypothermia technique for all of its comatose patients that suffered from cardiac arrest.

This cancer is typically aggressive, presents at an advanced stage when the cancer has already metastasized, and is resistant to chemotherapy. It therefore poses a significant management challenge. Current treatment options include surgical resection and chemotherapy with a variety of agents, including (but not limited to) ifosfamide, etoposide, carboplatin, and topotecan. A recent study looked at the use of methotrexate, vinblastine, doxorubicin, and cisplatin in 3 patients and saw a partial response and longer survival than historical reports. Carboplatin, gemcitibine, and paclitaxel provided a complete response in a patient with advanced disease. The role of radiation is unclear; some tumors have shown a response to radiation. Due to the apparent propensity for the tumor to spread to the central nervous system, it has been suggested that prophylactic craniospinal irradiation should be considered.

Bioreductive prodrugs play a significant part in dealing with these kinds of cells: they can kill the oxygen-deficient tumor cells selectively as hypoxia-activated prodrugs. Example drugs include Tirapazamine and Evofosfamide. The study of tumors in such conditions was pioneered by Dr L. H. Gray.

Corticosteroids are the mainstay of therapy with a 90% response rate in some studies. Appropriate duration of steroid treatment is unknown and relapse often necessitates long term treatment. Various steroid sparing agents e.g. sodium cromoglycate (a stabilizer of mast cell membranes), ketotifen (an antihistamine), and montelukast (a selective, competitive leukotriene receptor antagonist) have been proposed, centering on an allergic hypothesis, with mixed results. An elimination diet may be successful if a limited number of food allergies are identified.

mTOR inhibitors :

- Everolimus

- Temsirolimus

mTOR is a kinase enzyme inside the cell that regulates cell growth, proliferation, and survival. mTOR inhibitors lead to cell cycle arrest in the G1 phase and also inhibits tumor angiogenesis by reducing synthesis of VEGF.

A Phase II trial of Evorolimus on relapsed DLBCL patients showed a 30% Overall Response Rate (ORR).

No specific cure is known. Treatment is largely supportive. Nonsteroidal anti-inflammatory drugs (NSAIDs) are indicated for tender lymph nodes and fever, and corticosteroids are useful in severe extranodal or generalized disease.

Symptomatic measures aimed at relieving the distressing local and systemic complaints have been described as the main line of management of KFD. Analgesics, antipyretics, NSAIDs, and corticosteroids have been used. If the clinical course is more severe, with multiple flares of bulky enlarged cervical lymph nodes and fever, then a low-dose corticosteroid treatment has been suggested.