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Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND) or Lou Gehrig's disease, is a disease that causes the death of neurons controlling voluntary muscles.[4][9] Some also use the term motor neuron disease for a group of conditions of which ALS is the most common.[2] ALS is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscles decreasing in size.[2] It may begin with weakness in the arms or legs, or with difficulty speaking or swallowing.[10] About half of the people affected develop at least mild difficulties with thinking and behavior and most people experience pain.[11][12] Most eventually lose the ability to walk, use their hands, speak, swallow, and breathe.[5]

The cause is not known in 90% to 95% of cases,[4] but is believed to involve both genetic and environmental factors.[13] The remaining 5–10% of cases are inherited from a person's parents.[3] About half of these genetic cases are due to one of two specific genes.[4] The underlying mechanism involves damage to both upper and lower motor neurons.[2] The diagnosis is based on a person's signs and symptoms, with testing done to rule out other potential causes.[4]

No cure for ALS is known.[4] The goal of treatment is to improve symptoms.[11] A medication called riluzole may extend life by about two to three months.[6] Non-invasive ventilation may result in both improved quality and length of life.[5] Mechanical ventilation can prolong survival but does not stop disease progression.[14] A feeding tube may help.[15] The disease can affect people of any age, but usually starts around the age of 60 and in inherited cases around the age of 50.[3] The average survival from onset to death is two to four years, though this can vary, and about 10% survive longer than 10 years.[5][16][4] Most die from respiratory failure.[3] In Europe, the disease affects about two to three people per 100,000 per year.[8] Rates in much of the world are unclear.[17] In the United States, it is more common in white people than black people.[18]

Descriptions of the disease date back to at least 1824 by Charles Bell.[19] In 1869, the connection between the symptoms and the underlying neurological problems was first described by Jean-Martin Charcot, who in 1874 began using the term amyotrophic lateral sclerosis.[19] It became well known in the United States in the 20th century when in 1939 it affected baseball player Lou Gehrig and later worldwide following the 1963 diagnosis of cosmologist Stephen Hawking.[20][21] The first ALS gene was discovered in 1993 while the first animal model was developed in 1994.[22][23] In 2014, videos of the Ice Bucket Challenge went viral on the Internet and increased public awareness of the condition.[24]

Anxiety disorders are a group of mental disorders characterized by significant feelings of anxiety and fear.[2] Anxiety is a worry about future events, while fear is a reaction to current events.[2] These feelings may cause physical symptoms, such as increased heart rate and shakiness.[2] There are several anxiety disorders, including generalized anxiety disorder, specific phobia, social anxiety disorder, separation anxiety disorder, agoraphobia, panic disorder, and selective mutism.[2] The disorder differs by what results in the symptoms.[2] An individual may have more than one anxiety disorder.[2]

The cause of anxiety disorders is thought to be a combination of genetic and environmental factors.[5] Risk factors include a history of child abuse, family history of mental disorders, and poverty.[4] Anxiety disorders often occur with other mental disorders, particularly major depressive disorder, personality disorder, and substance use disorder.[4] To be diagnosed, symptoms typically need to be present for at least 6 months, be more than what would be expected for the situation, and decrease a person's ability to function in their daily life.[2][4] Other problems that may result in similar symptoms include hyperthyroidism; heart disease; caffeine, alcohol, or cannabis use; and withdrawal from certain drugs, among others.[4][6] Anxiety disorders differ from normal fear or anxiety by being excessive or persisting.[2]

Without treatment, anxiety disorders tend to remain.[2][5] Treatment may include lifestyle changes, counselling, and medications.[4] Cognitive behavioral therapy is one of the most common counselling techniques used in treatment of anxiety disorders.[4] Medications, such as antidepressants, benzodiazepines, or beta blockers, may improve symptoms.[5]

About 12% of people are affected by an anxiety disorder in a given year, and between 5% and 30% are affected over a lifetime.[4][7] They occur in females about twice as often as in males and generally begin before age 25.[2][4] The most common are specific phobias, which affect nearly 12%, and social anxiety disorder, which affects 10%.[4] Phobias mainly affect people between the ages of 15 and 35, and become less common after age 55.[4] Rates appear to be higher in the United States and Europe than in other parts of the world.[4]

 Autism is a developmental disorder characterized by difficulties with social interaction and communication, and by restricted and repetitive behavior.[6] Parents often notice signs during the first three years of their child's life.[1][6] These signs often develop gradually, though some children with autism experience worsening in their communication and social skills after reaching developmental milestones at a normal pace.[17]

Autism is associated with a combination of genetic and environmental factors.[7] Risk factors during pregnancy include certain infections, such as rubella, toxins including valproic acid, alcohol, cocaine, pesticides, lead, and air pollution, fetal growth restriction, and autoimmune diseases.[18][19][20] Controversies surround other proposed environmental causes; for example, the vaccine hypothesis, which has been disproven.[21] Autism affects information processing in the brain and how nerve cells and their synapses connect and organize; how this occurs is not well understood.[22] The Diagnostic and Statistical Manual of Mental Disorders (DSM-5), combines autism and less severe forms of the condition, including Asperger syndrome and pervasive developmental disorder not otherwise specified (PDD-NOS) into the diagnosis of autism spectrum disorder (ASD).[6][23]

Early behavioral interventions or speech therapy can help children with autism gain self-care, social, and communication skills.[9][10] Although there is no known cure,[9] there have been cases of children who recovered.[24] Some autistic adults are unable to live independently.[15] An autistic culture has developed, with some individuals seeking a cure and others believing autism should be accepted as a difference to be accommodated instead of cured.[25][26]

Globally, autism is estimated to affect 24.8 million people as of 2015.[16] In the 2000s, the number of people affected was estimated at 1–2 per 1,000 people worldwide.[27] In the developed countries, about 1.5% of children are diagnosed with ASD as of 2017,[28] from 0.7% in 2000 in the United States.[29] It occurs four-to-five times more often in males than females.[29] The number of people diagnosed has increased dramatically since the 1960s, which may be partly due to changes in diagnostic practice.[27] The question of whether actual rates have increased is unresolved.[27]

 Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body.[2][8] These contrast with benign tumors, which do not spread.[8] Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements.[1] While these symptoms may indicate cancer, they can also have other causes.[1] Over 100 types of cancers affect humans.[8]

Tobacco use is the cause of about 22% of cancer deaths.[2] Another 10% are due to obesity, poor diet, lack of physical activity or excessive drinking of alcohol.[2][9][10] Other factors include certain infections, exposure to ionizing radiation and environmental pollutants.[3] In the developing world, 15% of cancers are due to infections such as Helicobacter pylori, hepatitis B, hepatitis C, human papillomavirus infection, Epstein–Barr virus and human immunodeficiency virus (HIV).[2] These factors act, at least partly, by changing the genes of a cell.[11] Typically, many genetic changes are required before cancer develops.[11] Approximately 5–10% of cancers are due to inherited genetic defects from a person's parents.[12] Cancer can be detected by certain signs and symptoms or screening tests.[2] It is then typically further investigated by medical imaging and confirmed by biopsy.[13]

The risk of developing certain cancers can be reduced by not smoking, maintaining a healthy weight, not drinking too much alcohol, eating plenty of vegetables, fruits and whole grains, vaccination against certain infectious diseases, not eating too much processed and red meat and avoiding too much sunlight exposure.[14][15] Early detection through screening is useful for cervical and colorectal cancer.[16] The benefits of screening in breast cancer are controversial.[16][17] Cancer is often treated with some combination of radiation therapy, surgery, chemotherapy and targeted therapy.[2][4] Pain and symptom management are an important part of care.[2] Palliative care is particularly important in people with advanced disease.[2] The chance of survival depends on the type of cancer and extent of disease at the start of treatment.[11] In children under 15 at diagnosis, the five-year survival rate in the developed world is on average 80%.[18] For cancer in the United States, the average five-year survival rate is 66%.[5]

In 2015, about 90.5 million people had cancer.[6] As of 2019, about 18 million new cases occur annually.[19] It caused about 8.8 million deaths (15.7% of deaths).[7] The most common types of cancer in males are lung cancer, prostate cancer, colorectal cancer and stomach cancer.[20] In females, the most common types are breast cancer, colorectal cancer, lung cancer and cervical cancer.[11] If skin cancer other than melanoma were included in total new cancer cases each year, it would account for around 40% of cases.[21][22] In children, acute lymphoblastic leukemia and brain tumors are most common, except in Africa where non-Hodgkin lymphoma occurs more often.[18] In 2012, about 165,000 children under 15 years of age were diagnosed with cancer.[20] The risk of cancer increases significantly with age, and many cancers occur more commonly in developed countries.[11] Rates are increasing as more people live to an old age and as lifestyle changes occur in the developing world.[23] The financial costs of cancer were estimated at $1.16 trillion USD per year as of 2010.[24]

 Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract from the mouth to the anus.[2] Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension, and weight loss.[1][2]

Other complications outside the gastrointestinal tract may include anemia, skin rashes, arthritis, inflammation of the eye, and tiredness.[1] The skin rashes may be due to infections as well as pyoderma gangrenosum or erythema nodosum.[1] Bowel obstruction may occur as a complication of chronic inflammation, and those with the disease are at greater risk of colon cancer and small bowel cancer.[1]

While the causes of Crohn's disease are unknown, it is believed to be caused by a combination of environmental, immune, and bacterial factors in genetically susceptible individuals.[6][7][8][2] It results in a chronic inflammatory disorder, in which the body's immune system attacks the gastrointestinal tract, possibly targeting microbial antigens.[7][9] While Crohn's is an immune-related disease, it does not appear to be an autoimmune disease (in that the immune system is not being triggered by the body itself).[10] The exact underlying immune problem is not clear; however, it may be an immunodeficiency state.[9][11][12]

About half of the overall risk is related to genetics, with more than 70 genes having been found to be involved.[1][13] Tobacco smokers are twice as likely to develop Crohn's disease as nonsmokers.[3] It also often begins after gastroenteritis.[1] Diagnosis is based on a number of findings including biopsy and appearance of the bowel wall, medical imaging, and description of the disease.[1] Other conditions that can present similarly include irritable bowel syndrome and Behçet's disease.[1]

There are no medications or surgical procedures that can cure Crohn's disease.[1][2] Treatment options are intended to help with symptoms, maintain remission, and prevent relapse.[1] In those newly diagnosed, a corticosteroid may be used for a brief period of time to rapidly improve symptoms, alongside another medication such as either methotrexate or a thiopurine used to prevent recurrence.[1] Stopping smoking is recommended in people with Crohn's disease.[1] One in five people with the disease is admitted to hospital each year, and half of those with the disease will require surgery for the disease at some point over a ten-year period.[1] While surgery should be used as little as possible, it is necessary to address some abscesses, certain bowel obstructions, and cancers.[1] Checking for bowel cancer via colonoscopy is recommended every few years, starting eight years after the disease has begun.[1]

Crohn's disease affects about 3.2 per 1,000 people in Europe and North America.[5] It is less common in Asia and Africa.[14][15] It has historically been more common in the developed world.[16] Rates have, however, been increasing, particularly in the developing world, since the 1970s.[15][16] Inflammatory bowel disease resulted in 47,400 deaths in 2015[17] and those with Crohn's disease have a slightly reduced life expectancy.[1] It tends to start in the teens and twenties, though it can occur at any age.[1][2][18] Males and females are equally affected.[2] The disease was named after gastroenterologist Burrill Bernard Crohn, who in 1932, together with two colleagues at Mount Sinai Hospital in New York, described a series of patients with inflammation of the terminal ileum of the small intestine, the area most commonly affected by the illness.[19]

 Central nervous system diseases, also known as central nervous system disorders, are a group of neurological disorders that affect the structure or function of the brain or spinal cord, which collectively form the central nervous system (CNS).[1][2][3] 

 Epilepsy is a group of neurological disorders characterized by recurrent epileptic seizures.[10][11] Epileptic seizures are episodes that can vary from brief and nearly undetectable periods to long periods of vigorous shaking.[1] These episodes can result in physical injuries, including occasionally broken bones.[1] In epilepsy, seizures have a tendency to recur and, as a rule, have no immediate underlying cause.[10] Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy.[12] People with epilepsy may be treated differently in various areas of the world and experience varying degrees of social stigma due to their condition.[1]

The underlying mechanism of epileptic seizures is excessive and abnormal neuronal activity in the cortex of the brain.[12] The reason this occurs in most cases of epilepsy is unknown.[1] Some cases occur as the result of brain injury, stroke, brain tumors, infections of the brain, or birth defects through a process known as epileptogenesis.[1][2][3] Known genetic mutations are directly linked to a small proportion of cases.[4][13] The diagnosis involves ruling out other conditions that might cause similar symptoms, such as fainting, and determining if another cause of seizures is present, such as alcohol withdrawal or electrolyte problems.[4] This may be partly done by imaging the brain and performing blood tests.[4] Epilepsy can often be confirmed with an electroencephalogram (EEG), but a normal test does not rule out the condition.[4]

Epilepsy that occurs as a result of other issues may be preventable.[1] Seizures are controllable with medication in about 70% of cases;[7] inexpensive anti-seizure medications are often available.[1] In those whose seizures do not respond to medication, surgery, neurostimulation or dietary changes may then be considered.[5][6] Not all cases of epilepsy are lifelong, and many people improve to the point that treatment is no longer needed.[1]

As of 2015, about 39 million people have epilepsy.[8] Nearly 80% of cases occur in the developing world.[1] In 2015, it resulted in 125,000 deaths, an increase from 112,000 in 1990.[9][14] Epilepsy is more common in older people.[15][16] In the developed world, onset of new cases occurs most frequently in babies and the elderly.[17] In the developing world, onset is more common in older children and young adults due to differences in the frequency of the underlying causes.[18] About 5–10% of people will have an unprovoked seizure by the age of 80,[19] and the chance of experiencing a second seizure is between 40 and 50%.[20] In many areas of the world, those with epilepsy either have restrictions placed on their ability to drive or are not permitted to drive until they are free of seizures for a specific length of time.[21] The word epilepsy is from Ancient Greek ἐπιλαμβάνειν, 'to seize, possess, or afflict'.[22]

 Glaucoma is a group of eye diseases which result in damage to the optic nerve and cause vision loss.[1] The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye remains open, with less common types including closed-angle (narrow angle, acute congestive) glaucoma and normal-tension glaucoma.[1] Open-angle glaucoma develops slowly over time and there is no pain.[1] Peripheral vision may begin to decrease, followed by central vision, resulting in blindness if not treated.[1] Closed-angle glaucoma can present gradually or suddenly.[2] The sudden presentation may involve severe eye pain, blurred vision, mid-dilated pupil, redness of the eye, and nausea.[1][2] Vision loss from glaucoma, once it has occurred, is permanent.[1] Eyes affected by glaucoma are referred to as being glaucomatous.

Risk factors for glaucoma include increased pressure in the eye, a family history of the condition, and high blood pressure.[1] For eye pressures, a value of greater than 21 mmHg or 2.8 kPa is often used, with higher pressures leading to a greater risk.[2][5] However, some may have high eye pressure for years and never develop damage.[2] Conversely, optic nerve damage may occur with normal pressure, known as normal-tension glaucoma.[6] The mechanism of open-angle glaucoma is believed to be slow exit of aqueous humor through the trabecular meshwork, while in closed-angle glaucoma the iris blocks the trabecular meshwork.[2] Diagnosis is by a dilated eye examination.[1] Often, the optic nerve shows an abnormal amount of cupping.[2]

If treated early, it is possible to slow or stop the progression of disease with medication, laser treatment, or surgery.[1][7] The goal of these treatments is to decrease eye pressure.[2] A number of different classes of glaucoma medication are available.[2] Laser treatments may be effective in both open-angle and closed-angle glaucoma.[2] A number of types of glaucoma surgeries may be used in people who do not respond sufficiently to other measures.[2] Treatment of closed-angle glaucoma is a medical emergency.[1]

About 6 to 67 million people have glaucoma globally.[2][4] The disease affects about 2 million people in the United States.[2] It occurs more commonly among older people.[1] Closed-angle glaucoma is more common in women.[2] Glaucoma has been called the "silent thief of sight", because the loss of vision usually occurs slowly over a long period of time.[8] Worldwide, glaucoma is the second-leading cause of blindness after cataracts.[2][9] Cataracts caused 51% of blindness in 2010, while glaucoma caused 8%.[10] The word "glaucoma" is from Ancient Greek glaukos, which means "shimmering".[11] In English, the word was used as early as 1587 but did not become commonly used until after 1850, when the development of the ophthalmoscope allowed people to see the optic nerve damage.[12]

 Human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV).[9][10][11] Following initial infection a person may not notice any symptoms, or may experience a brief period of influenza-like illness.[4] Typically, this is followed by a prolonged period with no symptoms.[5] If the infection progresses, it interferes more with the immune system, increasing the risk of developing common infections such as tuberculosis, as well as other opportunistic infections, and tumors which are otherwise rare in people who have normal immune function.[4] These late symptoms of infection are referred to as acquired immunodeficiency syndrome (AIDS).[5] This stage is often also associated with unintended weight loss.[5]

HIV is spread primarily by unprotected sex (including anal and oral sex), contaminated blood transfusions, hypodermic needles, and from mother to child during pregnancy, delivery, or breastfeeding.[12] Some bodily fluids, such as saliva, sweat and tears, do not transmit the virus.[13] HIV is a member of the group of viruses known as retroviruses.[14]

Methods of prevention include safe sex, needle exchange programs, treating those who are infected, and pre- & post-exposure prophylaxis.[4] Disease in a baby can often be prevented by giving both the mother and child antiretroviral medication.[4] There is no cure or vaccine; however, antiretroviral treatment can slow the course of the disease and may lead to a near-normal life expectancy.[5][6] Treatment is recommended as soon as the diagnosis is made.[15] Without treatment, the average survival time after infection is 11 years.[7]

In 2018, about 37.9 million people were living with HIV and it resulted in 770,000 deaths.[8] An estimated 20.6 million of these live in eastern and southern Africa.[16] Between the time that AIDS was identified (in the early 1980s) and 2018, the disease caused an estimated 32 million deaths worldwide.[8] HIV/AIDS is considered a pandemic—a disease outbreak which is present over a large area and is actively spreading.[17] HIV made the jump from other primates to humans in west-central Africa in the early-to-mid 20th century.[18] AIDS was first recognized by the United States Centers for Disease Control and Prevention (CDC) in 1981 and its cause—HIV infection—was identified in the early part of the decade.[19]

HIV/AIDS has had a large impact on society, both as an illness and as a source of discrimination.[20] The disease also has large economic impacts.[20] There are many misconceptions about HIV/AIDS, such as the belief that it can be transmitted by casual non-sexual contact.[21] The disease has become subject to many controversies involving religion, including the Catholic Church's position not to support condom use as prevention.[22] It has attracted international medical and political attention as well as large-scale funding since it was identified in the 1980s.[23]

 Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine. Crohn's disease and ulcerative colitis are the principal types of inflammatory bowel disease.[3] Crohn's disease affects the small intestine and large intestine, as well as the mouth, esophagus, stomach and the anus, whereas ulcerative colitis primarily affects the colon and the rectum.[4][5][6]

IBD also occurs in dogs and is thought to arise from a combination of host genetics, intestinal microenvironment, environmental components and the immune system. There is an ongoing discussion however the term chronic enteropathy might be a better term to use than Inflammatory bowel disease in dogs because it differs from IBD in humans in how the dogs respond to treatment. For example, many dogs respond to only dietary changes compared to humans with IBD who often need immunosuppressive treatment. Some dogs may also need immunosuppressant or antibiotic treatment when dietary changes are not enough. After having excluded other diseases that can lead to vomiting, diarrhea and abdominal pain in dogs, intestinal biopsies are often performed to investigate what kind of inflammation that is occurring (lymfoplasmacytic, eosinophilic or granulomatous). In dogs, low levels of cobalamin in the blood have shown to be a risk factor for negative outcome.[7][8][9]

 Seizure types most commonly follow the classification proposed by the International League Against Epilepsy (ILAE) in 1981.[1] These classifications have been updated in 2017.[2] Distinguishing between seizure types is important since different types of seizure may have different causes, outcomes and treatments. 

This classification is based on observation (clinical and EEG) rather than the underlying pathophysiology or anatomy.

I Focal seizures (Older term: partial seizures)A Simple partial seizures – consciousness is not impaired1 With motor signs2 With sensory symptoms3 With autonomic symptoms or signs4 With psychic symptomsB Complex partial seizures – consciousness is impaired (*Note: impaired does not necessarily mean [fully] lost) (Older terms: temporal lobe or psychomotor seizures)1 Simple partial onset, followed by impairment of consciousness2 With impairment of consciousness at onsetC Partial seizures evolving to secondarily generalized seizures1 Simple partial seizures evolving to generalized seizures2 Complex partial seizures evolving to generalized seizures3 Simple partial seizures evolving to complex partial seizures evolving to generalized seizuresII Generalized seizuresA Absence seizures (Older term: petit mal, meaning 'small, or smaller, bad')1 Typical absence seizures2 Atypical absence seizuresB Myoclonic seizuresC Clonic seizuresD Tonic seizures,E Tonic–clonic seizures (Older term: grand mal, meaning 'great, or greater, bad')F Atonic seizuresIII Unclassified epileptic seizures

In terms of their origin within the brain, seizures may be described as either partial (focal) or generalized. Partial seizures only involve a localized part of the brain, whereas generalized seizures involve the whole of both hemispheres. The term 'secondary generalisation' may be used to describe a partial seizure that later spreads to the whole of the cortex and becomes generalized.

Whilst most seizures can be neatly split into partial and generalized, there exists some that don't fit. For example: the seizure may be generalized only within one hemisphere. Alternatively there may be many focal points (multifocal seizures) that are distributed in a symmetrical or asymmetrical pattern.

 Neurodegeneration is the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases – including amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, fatal familial insomnia, and Huntington's disease – occur as a result of neurodegenerative processes. Such diseases are incurable, resulting in progressive degeneration and/or death of neurons.[1] 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.[2][3] Neurodegeneration can be found in many different levels of neuronal circuitry ranging from molecular to systemic.

Comparison of brain tissue between healthy individual and Alzheimer's disease patient, demonstrating extent of neuronal deathMain article: Alzheimer's disease

Alzheimer's disease (AD) is a chronic neurodegenerative disease that results in the loss of neurons and synapses in the cerebral cortex and certain subcortical structures, resulting in gross atrophy of the temporal lobe, parietal lobe, and parts of the frontal cortex and cingulate gyrus.[4]

AD pathology is primarily characterized by the presence of senile plaques and neurofibrillary tangles. Plaques are made up of small peptides, typically 39–43 amino acids in length, called beta-amyloid (also written as A-beta or Aβ). Beta-amyloid is a fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that penetrates through the neuron's membrane. APP appears to play roles in normal neuron growth, survival and post-injury repair.[5][6] APP is cleaved into smaller fragments by enzymes such as gamma secretase and beta secretase.[7] One of these fragments gives rise to fibrils of beta-amyloid which can self-assemble into the dense extracellular deposits known as senile plaques or amyloid plaques.[8][9]

Main article: Parkinson's disease

Parkinson's disease (PD) is the second most common neurodegenerative disorder.[10] It typically manifests as bradykinesia, rigidity, resting tremor and posture instability. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries.

PD is primarily characterized by death of dopaminergic neurons in the substantia nigra, a region of the midbrain. The cause of this selective cell death is unknown. Notably, alpha-synuclein-ubiquitin complexes and aggregates are observed to accumulate in Lewy bodies within affected neurons. It is thought that defects in protein transport machinery and regulation, such as RAB1, may play a role in this disease mechanism.[11] Impaired axonal transport of alpha-synuclein may also lead to its accumulation in Lewy bodies. Experiments have revealed reduced transport rates of both wild-type and two familial Parkinson's disease-associated mutant alpha-synucleins through axons of cultured neurons.[12] Membrane damage by alpha-synuclein could be another Parkinson's disease mechanism.[13]

The main known risk factor is age. Mutations in genes such as α-synuclein (SNCA), leucine-rich repeat kinase 2 (LRRK2), glucocerebrosidase (GBA), and tau protein (MAPT) can also cause hereditary PD or increase PD risk.[14]

Main article: Huntington's disease

Huntington's disease (HD) is a rare autosomal dominant neurodegenerative disorder caused by mutations in the huntingtin gene. HD is characterized by loss of medium spiny neurons and astrogliosis.[15][16][17] The first brain region to be substantially affected is the striatum, followed by degeneration of the frontal and temporal cortices.[18] The striatum's subthalamic nuclei send control signals to the globus pallidus, which initiates and modulates motion. The weaker signals from subthalamic nuclei thus cause reduced initiation and modulation of movement, resulting in the characteristic movements of the disorder, notably chorea.[19]

HD is caused by polyglutamine tract expansion in the huntingtin gene, resulting in the aggregation-prone mutant huntingtin (mHtt). mHtt aggregates may be directly toxic. Additionally, they may damage molecular motors and microtubules to interfere with normal retrograde transport along the axon, leading to impaired transport of important cargoes such as BDNF.[12]

Main article: Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) is a disease in which motor neurons are selectively targeted for degeneration. In 1993, missense mutations in the gene encoding the antioxidant enzyme Cu/Zn superoxide dismutase 1 (SOD1) were discovered in a subsets of patients with familial ALS. This discovery led researchers to focus on unlocking the mechanisms for SOD1-mediated diseases. However, the pathogenic mechanism underlying SOD1 mutant toxicity has yet to be resolved. More recently, TDP-43 and FUS protein aggregates have been implicated in some cases of the disease, and a mutation in chromosome 9 (C9orf72) is thought to be the most common known cause of sporadic ALS.

Recent independent research by Nagai et al.[20] and Di Giorgio et al.[21] provide in vitro evidence that the primary cellular sites where SOD1 mutations act are located on astrocytes. Astrocytes then cause the toxic effects on the motor neurons. The specific mechanism of toxicity still needs to be investigated, but the findings are significant because they implicate cells other than neuron cells in neurodegeneration.[22]

Main article: Batten disease

Batten disease is a rare and fatal recessive neurodegenerative disorder that begins at birth.

 Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland or organ function depending on which nerves are affected; in other words, neuropathy affecting motor, sensory, or autonomic nerves result in different symptoms. More than one type of nerve may be affected simultaneously. Peripheral neuropathy may be acute (with sudden onset, rapid progress) or chronic (symptoms begin subtly and progress slowly), and may be reversible or permanent.

Common causes include systemic diseases (such as diabetes or leprosy), hyperglycemia-induced glycation,[1][2][3] vitamin deficiency, medication (e.g., chemotherapy, or commonly prescribed antibiotics including metronidazole and the fluoroquinolone class of antibiotics (Ciprofloxacin, Levaquin, Avelox etc.)), traumatic injury, including ischemia, radiation therapy, excessive alcohol consumption, immune system disease, coeliac disease, non-celiac gluten sensitivity, or viral infection. It can also be genetic (present from birth) or idiopathic (no known cause).[4][5][6][7] In conventional medical usage, the word neuropathy (neuro-, "nervous system" and -pathy, "disease of")[8] without modifier usually means peripheral neuropathy.

Neuropathy affecting just one nerve is called "mononeuropathy" and neuropathy involving nerves in roughly the same areas on both sides of the body is called "symmetrical polyneuropathy" or simply "polyneuropathy". When two or more (typically just a few, but sometimes many) separate nerves in disparate areas of the body are affected it is called "mononeuritis multiplex", "multifocal mononeuropathy", or "multiple mononeuropathy".[4][5][6]

Neuropathy may cause painful cramps, fasciculations (fine muscle twitching), muscle loss, bone degeneration, and changes in the skin, hair, and nails. Additionally, motor neuropathy may cause impaired balance and coordination or, most commonly, muscle weakness; sensory neuropathy may cause numbness to touch and vibration, reduced position sense causing poorer coordination and balance, reduced sensitivity to temperature change and pain, spontaneous tingling or burning pain, or skin allodynia (severe pain from normally nonpainful stimuli, such as light touch); and autonomic neuropathy may produce diverse symptoms, depending on the affected glands and organs, but common symptoms are poor bladder control, abnormal blood pressure or heart rate, and reduced ability to sweat normally.[4][5][6]

 Opioid use disorder (OUD) is a substance use disorder relating to the use of an opioid. Any such disorder causes significant impairment or distress.[3] Signs of the disorder include a strong desire to use opioids, increased tolerance to opioids, difficulty fulfilling obligations, trouble reducing use, and withdrawal symptoms with discontinuation.[4][5] Opioid withdrawal symptoms may include nausea, muscle aches, diarrhea, trouble sleeping, agitation, and a low mood.[5] Addiction and dependence are components of a substance use disorder.[13] Complications may include opioid overdose, suicide, HIV/AIDS, hepatitis C, and problems at school, work, or home.[4][5]

Opioids include substances such as heroin, morphine, fentanyl, codeine, oxycodone, and hydrocodone.[5][6] In the United States, a majority of heroin users begin by using prescription opioids, that may also be bought illegally. [14][15] Risk factors for misuse include a history of substance use, substance use among family and friends, mental illness, low socioeconomic status, and race.[16][17] Diagnosis may be based on criteria by the American Psychiatric Association in the DSM-5.[4] If more than two of eleven criteria are present during a year, the diagnosis is said to be present.[4] If a person is appropriately taking opioids for a medical condition, issues of tolerance and withdrawal do not apply.[4]

Individuals with an opioid use disorder are often treated with opioid replacement therapy using methadone or buprenorphine.[7] Being on such treatment reduces the risk of death.[7] Additionally, individuals may benefit from cognitive behavioral therapy, other forms of support from mental health professionals such as individual or group therapy, twelve-step programs, and other peer support programs.[8] The medication naltrexone may also be useful to prevent relapse.[10] Naloxone is useful for treating an opioid overdose and giving those at risk naloxone to take home is beneficial.[9]

In 2013, opioid use disorders affected about 0.4% of people.[4] As of 2016, about 27 million people are affected.[11] Long term opioid use occurs in about 4% of people following their use for trauma or surgery related pain.[18] Onset is often in young adulthood.[4] Males are affected more often than females.[4] It resulted in 122,000 deaths worldwide in 2015,[12] up from 18,000 deaths in 1990.[19] In the United States during 2016, there were more than 42,000 deaths due to opioid overdose, of which more than 15,000 were the result of heroin use.[20]

 Intractable pain, also known as Intractable Pain Disease or IPD, is a severe, constant, relentless and debilitating pain that is not curable by any known means and which causes a house-bound or bed-bound state ... and early death ... if not adequately treated, usually with opioids and/or interventional procedures. It is not relieved by ordinary medical, surgical, nursing, or pharmaceutical measures. Unlike the more common chronic pain, it causes adverse biologic effects on the body's cardiovascular, hormone, and neurologic systems. Patients experience changes in testosterone, estrogen, cortisol, thyroid hormones, and/or pituitary hormones. Both men and women require testosterone, however many doctors neglect to test women for low testosterone. Untreated Intractable Pain can cause death.[1] 

 Parkinson's disease (PD), or simply Parkinson's [9] is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly and, as the disease worsens, non-motor symptoms become more common.[1][4] The most obvious early symptoms are tremor, rigidity, slowness of movement, and difficulty with walking,[1] but cognitive and behavioral problems may also occur. Parkinson's disease dementia becomes common in the advanced stages of the disease. Depression and anxiety are also common, occurring in more than a third of people with PD.[2] Other symptoms include sensory, sleep, and emotional problems.[1][2] The main motor symptoms are collectively called "parkinsonism", or a "parkinsonian syndrome".[4]

While the cause of PD is unknown, it is believed to involve both inherited and environmental factors. Those with a family member affected are more likely to get the disease themselves. There is also an increased risk in people exposed to certain pesticides and among those who have had prior head injuries, while there is a reduced risk in tobacco smokers and coffee or tea drinkers.[4][10] The motor symptoms of the disease result from the death of cells in the substantia nigra, a region of the midbrain, leading to a dopamine deficit.[1] The cause of this cell death is poorly understood, but involves the build-up of proteins into Lewy bodies in the neurons.[4]

Diagnosis of typical cases is mainly based on symptoms, with tests such as neuroimaging used to rule out other diseases.[1] Parkinson's disease typically occurs in people over the age of 60, of whom about one percent are affected.[1][3] Males are more often affected than females at a ratio of around 3:2.[4] When it is seen in people before the age of 50, it is called early-onset PD.[11] In 2015, PD affected 6.2 million people and resulted in about 117,400 deaths globally.[7][8] The average life expectancy following diagnosis is between 7 and 15 years.[2]

There is no cure for PD; treatment aims to improve the symptoms.[1][12] Initial treatment is typically with the medication levodopa (L-DOPA), followed by dopamine agonists when levodopa becomes less effective.[2] As the disease progresses, these medications become less effective, while at the same time producing a side effect marked by involuntary muscle movements.[2] Diet and some forms of rehabilitation have shown some effectiveness at improving symptoms.[13][14] Surgery to place microelectrodes for deep brain stimulation has been used to reduce motor symptoms in severe cases where drugs are ineffective.[1] Evidence for treatments for the non-movement-related symptoms of PD, such as sleep disturbances and emotional problems, is less strong.[4]

The disease is named after the English doctor James Parkinson, who published the first detailed description in An Essay on the Shaking Palsy, in 1817.[15][16] Public awareness campaigns include World Parkinson's Day (on the birthday of James Parkinson, 11 April) and the use of a red tulip as the symbol of the disease.[17] People with Parkinson's who have increased the public's awareness of the condition includes the boxer Muhammad Ali, actor Michael J. Fox, Olympic cyclist Davis Phinney, and actor Alan Alda.[18][19][20][21]

 Post-traumatic stress disorder (PTSD)[note 1] is a mental disorder that can develop after a person is exposed to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, or other threats on a person's life.[1][6] Symptoms may include disturbing thoughts, feelings, or dreams related to the events, mental or physical distress to trauma-related cues, attempts to avoid trauma-related cues, alterations in how a person thinks and feels, and an increase in the fight-or-flight response.[1][3] These symptoms last for more than a month after the event.[1] Young children are less likely to show distress, but instead may express their memories through play.[1] A person with PTSD is at a higher risk of suicide and intentional self-harm.[2][7]

Most people who experience traumatic events do not develop PTSD.[2] People who experience interpersonal trauma such as rape or child abuse are more likely to develop PTSD as compared to people who experience non-assault based trauma, such as accidents and natural disasters.[8] About half of people develop PTSD following rape.[2][9][disputed – discuss] Children are less likely than adults to develop PTSD after trauma, especially if they are under 10 years of age.[10] Diagnosis is based on the presence of specific symptoms following a traumatic event.[2]

Prevention may be possible when counselling is targeted at those with early symptoms but is not effective when provided to all trauma-exposed individuals whether or not symptoms are present.[2] The main treatments for people with PTSD are counselling (psychotherapy) and medication.[3][11] Antidepressants of the selective serotonin reuptake inhibitor type are the first-line medications used for PTSD and are beneficial for about half of people.[4] Benefits from medication are less than those seen with counselling.[2] It is not known whether using medications and counselling together has greater benefit than either method separately.[2][12] Medications, other than SSRIs, do not have enough evidence to support their use and, in the case of benzodiazepines, may worsen outcomes.[13][14]

In the United States, about 3.5% of adults have PTSD in a given year, and 9% of people develop it at some point in their life.[1] In much of the rest of the world, rates during a given year are between 0.5% and 1%.[1] Higher rates may occur in regions of armed conflict.[2] It is more common in women than men.[3] Symptoms of trauma-related mental disorders have been documented since at least the time of the ancient Greeks.[15] During the World Wars, the condition was known under various terms including "shell shock" and "combat neurosis".[16] The term "post-traumatic stress disorder" came into use in the 1970s in large part due to the diagnoses of U.S. military veterans of the Vietnam War.[17] It was officially recognized by the American Psychiatric Association in 1980 in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III).[18]

 Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents.[2] The most common type is known as sickle cell anaemia (SCA).[2] It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blood cells.[2] This leads to a rigid, sickle-like shape under certain circumstances.[2] Problems in sickle cell disease typically begin around 5 to 6 months of age.[1] A number of health problems may develop, such as attacks of pain ("sickle cell crisis"), anemia, swelling in the hands and feet, bacterial infections and stroke.[1] Long-term pain may develop as people get older.[2] The average life expectancy in the developed world is 40 to 60 years.[2]

Sickle cell disease occurs when a person inherits two abnormal copies of the β-globin gene that makes haemoglobin, one from each parent.[3] This gene occurs in chromosome 11.[9] Several subtypes exist, depending on the exact mutation in each haemoglobin gene.[2] An attack can be set off by temperature changes, stress, dehydration, and high altitude.[1] A person with a single abnormal copy does not usually have symptoms and is said to have sickle cell trait.[3] Such people are also referred to as carriers.[5] Diagnosis is by a blood test, and some countries test all babies at birth for the disease.[4] Diagnosis is also possible during pregnancy.[4]

The care of people with sickle cell disease may include infection prevention with vaccination and antibiotics, high fluid intake, folic acid supplementation, and pain medication.[5][6] Other measures may include blood transfusion and the medication hydroxycarbamide (hydroxyurea).[6] A small percentage of people can be cured by a transplant of bone marrow cells.[2]

As of 2015, about 4.4 million people have sickle cell disease, while an additional 43 million have sickle cell trait.[7][10] About 80% of sickle cell disease cases are believed to occur in Sub-Saharan Africa.[11] It also occurs relatively frequently in parts of India, the Arabian Peninsula, and among people of African origin living in other parts of the world.[12] In 2015, it resulted in about 114,800 deaths.[8] The condition was first described in the medical literature by American physician James B. Herrick in 1910.[13][14] In 1949, its genetic transmission was determined by E. A. Beet and J. V. Neel.[14] In 1954, the protective effect against malaria of sickle cell trait was described.[14]

 Terminal illness or end-stage disease is a disease that cannot be cured or adequately treated and is reasonably expected to result in the death of the patient. This term is more commonly used for progressive diseases such as cancer or advanced heart disease than for trauma. In popular use, it indicates a disease that will progress until death with near absolute certainty, regardless of treatment. A patient who has such an illness may be referred to as a terminal patient, terminally ill or simply terminal. There is no standardized life expectancy for a patient to be considered terminal, although it is generally months or less. Life expectancy for terminal patients is a rough estimate given by the physician based on previous data and does not always reflect true longevity.[1] An illness which is lifelong but not fatal is a chronic condition.

Terminal patients have options for disease management after diagnosis. Examples include caregiving, continued treatment, hospice care, and physician-assisted suicide. Decisions regarding management are made by the patient and his or her family, although medical professionals may give recommendations or more about the services available to terminal patients.[2][3]

Lifestyle after diagnosis varies depending largely on management decisions and also the nature of the disease, and there may be living restrictions depending on the condition of the patient. Oftentimes, terminal patients may experience depression or anxiety associated with oncoming death, and family and caregivers may struggle with psychological burdens as well. Psycho-therapeutic interventions may help alleviate some of these burdens, and is often incorporated in palliative care.[2][4]

Because terminal patients are aware of their oncoming deaths, they have more time to prepare advance care planning, such as advance directives and living wills, which have been shown to improve end-of-life care. While death cannot be avoided, patients can still strive to die a good death.[5][6][7]

 Tourette syndrome or Tourette's syndrome (abbreviated as TS or Tourette's) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) tic. Common tics are blinking, coughing, throat clearing, sniffing, and facial movements. These are typically preceded by an unwanted urge or sensation in the affected muscles, can sometimes be suppressed temporarily, and characteristically change in location, strength, and frequency. Tourette's is at the more severe end of a spectrum of tic disorders. The tics often go unnoticed by casual observers.

Tourette's was once regarded as a rare and bizarre syndrome and has popularly been associated with coprolalia (the utterance of obscene words or socially inappropriate and derogatory remarks). It is no longer considered rare; about 1% of school-age children and adolescents are estimated to have Tourette's,[1] and coprolalia occurs only in a minority. There are no specific tests for diagnosing Tourette's; it is not always correctly identified, because most cases are mild, and the severity of tics decreases for most children as they pass through adolescence. Therefore, many go undiagnosed or may never seek medical attention. Extreme Tourette's in adulthood, though sensationalized in the media, is rare, but for a small minority, severely debilitating tics can persist into adulthood. Tourette's does not affect intelligence or life expectancy.

There is no cure for Tourette's and no single most effective medication. In most cases, medication for tics is not necessary, and behavioral therapies are the first-line treatment. Education is an important part of any treatment plan, and explanation alone often provides sufficient reassurance that no other treatment is necessary.[1] Among those who are referred to specialty clinics, other conditions like attention deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD) are more likely than in the broader population of persons with Tourette's. These co-occurring diagnoses often cause more impairment to the individual than the tics; hence it is important to correctly distinguish co-occurring conditions and treat them.

Tourette syndrome was named by French neurologist Jean-Martin Charcot for his intern, Georges Gilles de la Tourette, who published in 1885 an account of nine patients with a "convulsive tic disorder". While the exact cause is unknown, it is believed to involve a combination of genetic and environmental factors. The mechanism appears to involve dysfunction in neural circuits between the basal ganglia and related structures in the brain.