An average clinical profile from published studies shows that the median onset age for HDLS patients is 44.3 years with a mean disease duration of 5.8 years and mean age of death at 53.2 years. As of 2012, there have been around 15 cases identified with at least 11 sporadic cases of HDLS. HDLS cases have been located in Germany, Norway, Sweden, and the United States, showing an international distribution focusing between Northern Europe and the United States.

Through the study of numerous kindred, it was found that the disease did not occur among just males or females, but rather was evenly distributed indicative of an autosomal rather than a sex-linked genetic disorder. It was also observed that the HDLS cases did not skip generations as it would occur with a recessive inheritance, and as such has been labeled autosomal dominant.

Treatment of ALS2-related disorders includes physical therapy and occupational therapy to promote mobility and independence and use of computer technologies and devices to facilitate writing and voice communication.

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare adult onset autosomal dominant disorder characterized by cerebral white matter degeneration with demyelination and axonal spheroids leading to progressive cognitive and motor dysfunction. Spheroids are axonal swellings with discontinuous or absence of myelin sheaths. It is believed that the disease arises from primary microglial dysfunction that leads to secondary disruption of axonal integrity, neuroaxonal damage, and focal axonal spheroids leading to demyelination. Spheroids in HDLS resemble to some extent those produced by shear stress in a closed head injury with damage to axons, causing them to swell due to blockage of axoplasmic transport. In addition to trauma, axonal spheroids can be found in aged brain, stroke, and in other degenerative diseases. In HDLS, it is uncertain whether demyelination occurs prior to the axonal spheroids or what triggers neurodegeneration after apparently normal brain and white matter development, although genetic deficits suggest that demyelination and axonal pathology may be secondary to microglial dysfunction. The clinical syndrome in patients with HDLS is not specific and it can be mistaken for Alzheimer's disease, frontotemporal dementia, atypical Parkinsonism, multiple sclerosis, or corticobasal degeneration.

As of 2010, there was no cure for MMND. People with MMND are given supportive care to help them cope, which can include physical therapy, occupational therapy, counselling, and hearing aids.

People with MMND become progressively more weak with time. Generally, affected individuals survive up to 30 years after they are diagnosed.

Management Corticosteroids may be effective in some patients. Additional treatment options are beta-interferon or immunosuppressive therapy. Otherwise management is supportive and includes physiotherapy, occupational therapy and nutritional support in the later stages as patients lose their ability to eat.

Juvenile Primary Lateral Sclerosis is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, parents of affected individuals each carry one copy of the altered gene, but do not show any signs or symptoms.

Mutations in the ALS2 gene, found on Chromosome 2, are responsible for causing Juvenile Primary Lateral Sclerosis. The ALS2 gene provides instructions for making a protein called alsin. Alsin is abundant in motor neurons, but its function is not fully understood. Mutations in the ALS2 gene in this disorder disrupt the instructions for producing alsin. As a result, alsin is unstable and decays rapidly, or it is disabled and cannot function properly. It is currently unknown how the loss of functional alsin protein causes the death of motor neurons and the symptoms of juvenile primary lateral sclerosis.

Early and aggressive treatment is important to prevent irreversible neurological damage, hearing loss, or vision loss. Medications used include immunosuppressive agents and corticosteroids such a prednisone, or intravenous immunoglobulins (IVIG). Other drugs that have been used are mycophenolate mofetil (Cellcept), azathioprine (Imuran), cyclophosphamide, rituximab, and anti-TNF therapies.

Hearing aids or cochlear implants may be necessary in the event of hearing loss.

Pharmacologic treatments for MS include immunomodulators and immunosuppressants which reduce the frequency and severity of relapses by about 35% and reduce the lesion growth. Unfortunately they are mainly tested for RRMS and its effect in tumefactive lesions is unknown. The main ones are Interferon beta (IFN-beta), Glatiramer acetate and Mitoxantrone

Plasma exchange has been reported to work at least in some cases

The prognosis of this disease is very variable and can take three different courses: a monophasic, not remitting;

remitting;

and finally, progressive, with increase in deficits.

Treatment is symptomatic, often addressing indicators associated with peripheral pulmonary artery stenosis. Laryngotracheal calcification resulting in dyspnea and forceful breathing can be treated with bronchodilators including the short and long-acting β2-agonists, and various anticholinergics. Prognosis is good, yet life expectancy depends on the severity and extent of diffuse pulmonary and arterial calcification.

Riluzole has been found to modestly prolong survival by approximately two to three months. It may have a greater survival benefit for those with a bulbar onset. It is approved by the US Food and Drug Administration (FDA) and recommended by the National Institute for Health and Care Excellence (NICE) (England and Wales). Riluzole does not reverse damage already done to motor neurons but affects neurons by reducing their activity through blocking Na+ entrance into the neurons and thus blocking the release of the chemicals that causes the activity of the motor neurons. The reduction in activity prevents the ruining of the neuronal muscle and so the drug can act as a protective chemical. Studies have shown that the function of this drug is dependent on the amount taken at a given time. The higher the concentration, the better the drug will protect the neurons from ruin. The recommended dosage of Riluzole is 50 mg, twice a day for people with known ALS for more than 5 years.

There are a number of side effects caused by the drug including the feeling of weakness in muscles but this is normal due to the function of the drug. Studies have shown that people on the drug are not likely to stop responding to it or develop symptoms that might cause the activity of neurons to rise again, making Riluzole an effective drug for prolonging survival.

In 2015, edaravone was approved in Japan for treatment of ALS after studying how and whether it works on 137 people with ALS and has obtained orphan drug status in the EU and USA. On May 5, 2017, the FDA approved edaravone to extend the survival period of people with ALS. It costs about 145,000 USD per year in the US and 35,000 USD per year in Japan.

Other medications may be used to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Drugs also are available to help people with pain, such as non-steroidal and anti-inflammatory drugs and opioids, depression, sleep disturbances, dysphagia, and constipation. Baclofen and diazepam are often prescribed to control the spasticity caused by ALS, and trihexyphenidyl, amitriptyline or most commonly glycopyrrolate may be prescribed when people with ALS begin having trouble swallowing their saliva. There is no evidence that medications are effective at reducing muscle cramps experienced by people with ALS.

Management of ALS attempts to relieve symptoms and extend life expectancy. This supportive care is best provided by multidisciplinary teams of healthcare professionals working with the person and their caregivers to keep them as mobile and comfortable as possible.

Typical tumefactive lesions have been found to be responsive to corticosteroids because of their immunosuppressive and anti-inflammatory properties. They restore the blood-brain barrier and induce cell death of T-cells.

No standard treatment exists, but practitioners seem to apply intravenous corticosteroids, followed by plasmapheresis and cyclophosphamide in non-responsive cases High dose intravenous corticosteroids (methylprednisolone 1 g for 3–5 days) followed by oral tapering hasten clinical and radiological improvement in approximately 80% of patients

Plasmapheresis has been reported to work even in the absence of response to corticosteroids

Neurodegeneration is the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases – including amyotrophic lateral sclerosis, Parkinson's, Alzheimer's, and Huntington's – occur as a result of neurodegenerative processes. Such diseases are incurable, resulting in progressive degeneration and/or death of neuron cells. As research progresses, many similarities appear that relate these diseases to one another on a sub-cellular level. Discovering these similarities offers hope for therapeutic advances that could ameliorate many diseases simultaneously. There are many parallels between different neurodegenerative disorders including atypical protein assemblies as well as induced cell death. Neurodegeneration can be found in many different levels of neuronal circuitry ranging from molecular to systemic.

Some hypotheses as to the cause of the disease include genetics, cycad seeds, and ingested beta-Methylamino-L-alanine (BMAA) from the consumption of fruit bats.

The process of neurodegeneration is not well understood, so the diseases that stem from it have, as yet, no cures. In the search for effective treatments (as opposed to palliative care), investigators employ animal models of disease to test potential therapeutic agents. Model organisms provide an inexpensive and relatively quick means to perform two main functions: target identification and target validation. Together, these help show the value of any specific therapeutic strategies and drugs when attempting to ameliorate disease severity. An example is the drug Dimebon (Medivation). This drug is in phase III clinical trials for use in Alzheimer's disease, and also recently finished phase II clinical trials for use in Huntington's disease. In March 2010, the results of a clinical trial phase III were released; the investigational Alzheimer's disease drug Dimebon failed in the pivotal CONNECTION trial of patients with mild-to-moderate disease. With CONCERT, the remaining Pfizer and Medivation Phase III trial for Dimebon (latrepirdine) in Alzheimer's disease failed in 2012, effectively ending the development in this indication.

In another experiment using a rat model of Alzheimer's disease, it was demonstrated that systemic administration of hypothalamic proline-rich peptide (PRP)-1 offers neuroprotective effects and can prevent neurodegeneration in hippocampus amyloid-beta 25–35. This suggests that there could be therapeutic value to PRP-1.

Protein degradation offers therapeutic options both in preventing the synthesis and degradation of irregular proteins. There is also interest in upregulating autophagy to help clear protein aggregates implicated in neurodegeneration. Both of these options involve very complex pathways that we are only beginning to understand.

The goal of immunotherapy is to enhance aspects of the immune system. Both active and passive vaccinations have been proposed for Alzheimer's disease and other conditions, however more research must be done to prove safety and efficacy in humans.

Keutel syndrome (KS) is a rare autosomal recessive genetic disorder characterized by abnormal diffuse cartilage calcification, hypoplasia of the mid-face, peripheral pulmonary stenosis, hearing loss, short distal phalanges (tips) of the fingers and mild mental retardation. Individuals with KS often present with peripheral pulmonary stenosis, brachytelephalangism, sloping forehead, midface hypoplasia, and receding chin. It is associated with abnormalities in the gene coding for matrix gla protein (MGP). Being an autosomal recessive disorder, it may be inherited from two unaffected, abnormal MGP-carrying parents. Thus, people who inherit two affected MGP genes will likely inherit KS.

It was first identified in 1972 as a novel rare genetic disorder sharing similar symptoms with chondrodysplasia punctata. Multiple forms of chondrodysplasia punctata share symptoms consistent with KS including abnormal cartilage calcification, forceful respiration, brachytelephalangism, hypotonia, psychomotor delay, and conductive deafness, yet peripheral pulmonary stenosis remains unique to KS.

No chromosomal abnormalities are reported in affected individuals, suggesting that familial consanguinity relates to the autosomal recessive mode of inheritance. Also, despite largely abnormal calcification of regions including the larynx, tracheobronchial tree, nose, pinna (anatomy), and epiglottis, patients exhibit normal serum calcium and phosphate levels.

Frontotemporal lobar degeneration (FTLD) is a pathological process that occurs in frontotemporal dementia. It is characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes.

Common proteinopathies that are found in FTLD include the accumulation of Tau proteins and TARDBPs. Mutations in the C9orf72 gene have been established as a major genetic contribution of FTLD, although defects in the GRN and MAPT genes are also associated with it.

Renal failure is the major cause of morbidity and mortality in complete LCAT deficiency, while in partial deficiency (fish eye disease) major cause of morbidity is visual impairment due to corneal opacity. These patients have low HDL cholesterol but surprisingly premature atherosclerosis is not seen. However, there are some reported cases.

Currently, there is no specific treatment to correct the LCAT deficiency so therapy is focused on symptom relief. Corneal transplant may be considered for patients presenting with severely impaired vision caused by cholesterol corneal opacities. Dialysis may be required for patients presenting with renal failure, and kidney transplant may be considered.

Lytico-bodig disease, sometimes spelled Lytigo-bodig, is the name of a disease in the language of Chamorro. It is referred to by neuroscientists as amyotrophic lateral sclerosis-parkinsonism-dementia (ALS-PDC), a term coined by Asao Hirano and colleagues in 1961. It is a neurodegenerative disease of uncertain etiology that exists in the United States territory of Guam.

The disease resembles Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease, and Alzheimer's. First reports of the disease surfaced in three death certificates on Guam in 1904. These death certificates made some mention of paralysis. The frequency of cases grew amongst the Chamorro people on Guam until it was the leading cause of adult death between 1945 and 1956. The incidence rate was 200 per 100,000 per year and it was 100 times more prevalent than in the rest of the world.

Neurologist Oliver Sacks detailed this disease in his book "The Island of the Colorblind"

. Sacks and Paul Alan Cox subsequently wrote that a local species of flying fox, which is now extinct due to overhunting, had been feeding on cycads and concentrating β-methylamino--alanine (BMAA), a known neurotoxin, in its body fat. The hypothesis suggests that consumption of the fruit bat by the Chamorro exposed them to BMAA, contributing to or causing their condition. Decline in consumption of the bats has been linked to a decline in the incidence of the disease.

There is ongoing research looking for more effective, convenient, and tolerable treatments for relapsing-remitting MS; creation of therapies for the progressive subtypes; neuroprotection strategies; and effective symptomatic treatments.

During the 2000s and 2010s, there has been approval of several oral drugs that are expected to gain in popularity and frequency of use. Several more oral drugs are under investigation, including ozanimod, laquinimod, and estriol. Laquinimod was announced in August 2012 and is in a third phase III trial after mixed results in the previous ones. Similarly, studies aimed to improve the efficacy and ease of use of already existing therapies are occurring. This includes the use of new preparations such as the PEGylated version of interferon-β-1a, which it is hoped may be given at less frequent doses with similar effects. Estriol, a female sex hormone found at high concentrations during late pregnancy, has been identified as a candidate therapy for women with relapsing-remitting MS and has progressed through Phase II trials. Request for approval of "peginterferon beta-1a" is expected during 2013.

Monoclonal antibodies have also raised high levels of interest. As of 2012 alemtuzumab, daclizumab, and CD20 monoclonal antibodies such as rituximab, ocrelizumab and ofatumumab had all shown some benefit and were under study as potential treatments, and the FDA approved ocrelizumab for relapsing and primary MS in March, 2017. Their use has also been accompanied by the appearance of potentially dangerous adverse effects, the most important of which being opportunistic infections. Related to these investigations is the development of a test for JC virus antibodies, which might help to determine who is at greater risk of developing progressive multifocal leukoencephalopathy when taking natalizumab. While monoclonal antibodies will probably have some role in the treatment of the disease in the future, it is believed that it will be small due to the risks associated with them.

Another research strategy is to evaluate the combined effectiveness of two or more drugs. The main rationale for using a number of medications in MS is that the involved treatments target different mechanisms and, therefore, their use is not necessarily exclusive. Synergies, in which one drug improves the effect of another are also possible, but there can also be drawbacks such as the blocking of the action of the other or worsened side-effects. There have been several trials of combined therapy, yet none have shown positive enough results to be considered as a useful treatment for MS.

Research on neuroprotection and regenerative treatments, such as stem cell therapy, while of high importance, are in the early stages. Likewise, there are not any effective treatments for the progressive variants of the disease. Many of the newest drugs as well as those under development are probably going to be evaluated as therapies for PPMS or SPMS.

Over 50% of people with MS may use complementary and alternative medicine, although percentages vary depending on how alternative medicine is defined. The evidence for the effectiveness for such treatments in most cases is weak or absent. Treatments of unproven benefit used by people with MS include dietary supplementation and regimens, vitamin D, relaxation techniques such as yoga, herbal medicine (including medical cannabis), hyperbaric oxygen therapy, self-infection with hookworms, reflexology, acupuncture, and mindfulness. Regarding the characteristics of users, they are more frequently women, have had MS for a longer time, tend to be more disabled and have lower levels of satisfaction with conventional healthcare.

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.