Diseases

Cerebral Amyloid Angiopathy

Cerebral amyloid angiopathy (CAA) is a neurological condition in which amyloid protein is deposited onto the walls of the arteries of the brain (and less frequently, veins). Although CAA often does not cause symptoms, it may cause bleeding into the brain (hemorrhagic stroke), dementia, or neurologic episodes in some patients. The majority of CAA cases occur in individuals who do not have a family history.

It is not associated with systemic amyloidosis. CAA has been recognized as one of the morphologic hallmarks of Alzheimer disease (AD), but it is also often found in the brains of elderly patients who are neurologically healthy. While often asymptomatic, CAA may lead to dementia, intracranial hemorrhage (ICH), or transient neurologic events. ICH is the most recognized result of CAA. Most affected individuals die within a decade after signs and symptoms first appear, although some people with the disease have survived longer.

There are many different types of hereditary cerebral amyloid angiopathy. The different types are distinguished by their genetic cause and the signs and symptoms that occur. The various types of hereditary cerebral amyloid angiopathy are named after the regions where they were first diagnosed.

The Dutch type of hereditary cerebral amyloid angiopathy is the most common form. Stroke is frequently the first sign of the Dutch type and is fatal in about one third of people who have this condition. Survivors often develop dementia and have recurrent strokes. About half of individuals with the Dutch type who have one or more strokes will have recurrent seizures (epilepsy).

People with the Flemish and Italian types of hereditary cerebral amyloid angiopathy are prone to recurrent strokes and dementia. Individuals with the Piedmont type may have one or more strokes and typically experience impaired movements, numbness or tingling (paresthesias), confusion, or dementia.

The first sign of the Icelandic type of hereditary cerebral amyloid angiopathy is typically a stroke followed by dementia. Strokes associated with the Icelandic type usually occur earlier than the other types, with individuals typically experiencing their first stroke in their twenties or thirties.

Strokes are rare in people with the Arctic type of hereditary cerebral amyloid angiopathy, in which the first sign is usually memory loss that then progresses to severe dementia. Strokes are also uncommon in individuals with the Iowa type. This type is characterized by memory loss, problems with vocabulary and the production of speech, personality changes, and involuntary muscle twitches (myoclonus).
Two types of hereditary cerebral amyloid angiopathy, known as familial British dementia and familial Danish dementia, are characterized by dementia and movement problems. Strokes are uncommon in these types. People with the Danish type may also have clouding of the lens of the eyes (cataracts) or deafness.

 

Cerebral aneurysm

Cerebral aneurysm is a common cerebrovascular disorder caused by a weakness in the wall of a cerebral artery or vein.

Cerebral cavernous hemangioma

Another name for Cerebral cavernous hemangioma isCerebral cavernous malformations .(CCMs) are collections of small blood vessels (capillaries) in the brain that are enlarged and irregular in structure. These capillaries have abnormally thin walls that are prone to leak. They also lack other support tissues, such as elastic fibers, which normally make them stretchy. As a result, when the capillaries fill with blood, they stretch out and may not return to their normal size when the blood vessels empty. Cavernous malformations can occur anywhere in the body, but usually produce serious signs and symptoms only when they occur in the central nervous system (the brain and spinal cord).

Cerebral palsy, spastic diplegic

Brain damage that involves muscle rigidity that occurs either in both arms or in both legs. The brain damage is often the result of a birth defect or some sort of trauma to the brain.

Cerebral palsy, spastic tetraplegic

Spastic tetraplegic cerebral palsy: A rare disorder characterized by the association of spasticity -muscle tightness of the arms and legs, as well as cerebral palsy.

Cerebral ventricle neoplasm

A tumor that occurs in the fluid-filled spaces of the brain called the ventricles. Symptoms vary depending on the size and exact location of the tumor and whether it is cancerous or not.

Cerebro-costo-mandibular syndrome

A rare genetic disorder characterized by a very small jaw, abnormal rib development and a small thorax as well as other abnormalities.

Cerebrospinal fluid leak

A cerebrospinal fluid leak (CSFL) is a medical condition where the cerebrospinal fluid in the brain leaks out of the dura mater. This can be due to a spontaneous cerebrospinal fluid leakor result from different causes such as a lumbar puncture or physical trauma. While high CSF pressure can make lying down unbearable, low CSF pressure due to a leak is often relieved somewhat by lying flat on the back.

Cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis is a fat (lipid) storage disorder that affects many areas of the body. People with this disorder cannot break down certain lipids effectively, specifically different forms of cholesterol, so these fats accumulate in various areas of the body. Xanthomatosis refers to the formation of fatty yellow nodules (xanthomas). Cerebrotendinous refers to the typical locations of the xanthomas (cerebro- meaning the brain and -tendinous meaning connective tissue called tendons that attach muscle to bone).

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. 

Other features of cerebrotendinous xanthomatosis include chronic diarrhea during infancy, clouding of the lens of the eye (cataracts) developing in late childhood, progressively brittle bones that are prone to fracture, and neurological problems in adulthood, such as dementia, seizures, hallucinations, depression, and difficulty with coordinating movements (ataxia) and speech (dysarthria). The neurological symptoms are thought to be caused by an accumulation of fats and an increasing number of xanthomas in the brain. Xanthomas can also accumulate in the fatty substance that insulates and protects nerves (myelin), disrupting nerve signaling in the brain. Disorders that involve the destruction of myelin are known as leukodystrophies. Degeneration (atrophy) of brain tissue caused by excess lipid deposits also contributes to the neurological problems.

Xanthomas in the tendons (most commonly in the Achilles tendon, which connects the heel of the foot to the calf muscles) begin to form in early adulthood. Tendon xanthomas may cause discomfort and interfere with tendon flexibility. People with cerebrotendinous xanthomatosis are also at an increased risk of developing cardiovascular disease. If untreated, the signs and symptoms related to the accumulation of lipids throughout the body worsen over time; however, the course of this condition varies greatly among those who are affected.

Ceroid lipofuscinosis – Neuronal 1

Ceroid lipofuscinosis - Neuronal 1 (also known as CLN1, Classic Infantile NCL, INCL and Santavuori-Haltia) is a rare inherited biochemical disorder involving the progressive accumulation of lipopigments (lipofuscins) in neuronal cells and many organs, including the liver, spleen, myocardium, and kidneys due to deficiency of an enzyme (protease tri-peptidyl-peptidase) needed to process it. CLN1 is often caused by a mutation in the PPT1 (palmitoyl- protein thioesterase 1) gene or more rarely from mutations in the KCTD7 (Potassium channel tetramerisation domain containing 7 ) gene. The age of onset is usually between 6-24 months. 

All individuals with a ceroid lipofuscinosis neuronal disorder have progressive decline, an evolving cognitive and motor disorder, and seizures.

Ceroid lipofuscinosis – Neuronal 10

Ceroid lipofuscinosis - Neuronal 10 (also known as CLN10, Congenital neuronal ceroid lipofuscinosis and Cathepsin D deficiency disease) is a rare, severe metabolic disorder that primarily affects the nervous system and is characterized by the deposits of lipopigments (lipofuscin). CLN10 involves a deficiency of cathepsin D and involves an initial period of normal development with neurodegenerative symptoms starting during the early school years. 

Individuals with this condition typically show signs and symptoms soon after birth. These signs and symptoms can include muscle rigidity, respiratory failure, and prolonged episodes of seizure activity that last several minutes (status epilepticus). It is likely that some affected individuals also have seizures before birth while in the womb. Infants with CLN10 disease have unusually small heads (microcephaly) with brains that may be less than half the normal size. There is a loss of brain cells in areas that coordinate movement (the cerebellum) and control thinking and emotions (the cerebral cortex). Nerve cells in the brain also lack a fatty substance called myelin, which protects them and promotes efficient transmission of nerve impulses. Infants with CLN10 disease often die hours to weeks after birth.

In some individuals with CLN10 disease, the condition does not appear until later in life, between late infancy and adulthood. These individuals have a gradual loss of brain cells and often develop problems with balance and coordination (ataxia), loss of speech, a progressive loss in intellectual functioning (cognitive decline), and vision loss. Individuals with later-onset CLN10 disease have a shortened lifespan, depending on when their signs and symptoms first started.

Ceroid lipofuscinosis – Neuronal 4

Ceroid lipofuscinosis - Neuronal 4 (also known as Kufs disease and CLN4) is one of a group of rare inherited biochemical disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype. 

There are two types of CLN4 disease: Type A and Type B. Type A causes seizures, myoclonic epilepsy (muscle jerks), dementia, ataxia (compromised muscle coordination), tremors and tics, dysarthria (speech difficulties), confusion, and psychotic behaviour. Although similar to Type A, patients with Type B do not suffer from myoclonic epilepsy or dysarthria, and they do display changes in personality. It is occasional that patients present with skin disorders causing dryness, roughness, and scaliness. The signs and symptoms of CLN4 disease typically appear around age 30, but they can develop anytime between adolescence and late adulthood. In addition, the signs and symptoms of CLN4 disease worsen over time, and affected individuals usually survive about 15 years after the disorder begins.

Ceroid lipofuscinosis – Neuronal 5

Ceroid lipofuscinosis - Neuronal 5 (also known as CLN5, Neuronal ceroid lipofuscinosis Finnish variant and Finnish variant late infantile neuronal ceroid lipofuscinosis) is a rare metabolic disorder that affects the nervous system.  It is characterised by the deposits of lipopigments (lipofuscin). CLN5-NCL is caused by changes (mutations) in the CLN5 gene and is inherited in an autosomal recessive manner. 

Although the incidence of CLN5 disease is unknown; more than 85 cases have been described in the scientific literature. CLN5 disease was originally thought to affect only the Finnish population as they were the first individuals to be diagnosed with the condition. However, research has since shown that CLN5 disease affects populations worldwide. CLNs, including CLN5 disease, are still most common in Finland, where approximately 1 in 12,500 individuals are affected. Collectively, all forms of NCL affect an estimated 1 in 100,000 individuals worldwide.

Signs and symptoms of the condition generally develop between ages 4.5 and 7 years, although later onset cases have been reported. Affected people may experience loss of muscle coordination (ataxia), seizures that do not respond to medications, muscle twitches (myoclonus), visual impairment, and cognitive/motor decline. Treatment options are limited to therapies that can help relieve some of the symptom(s).

Ceroid lipofuscinosis – Neuronal 6

Ceroid lipofuscinosis - Neuronal 6 (also known as CLN6 and Variant late infantile neuronal ceroid lipofuscinosis) is a rare metabolic disorder that affects the nervous system. It is characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. CLN6 disease is caused by changes (mutations) in the CLN6 gene and is inherited in an autosomal recessive manner. The lipopigment patterns observed most often in CLN6 comprise mixed combinations of granular, curvilinear, and fingerprint profiles. It occurs predominantly in people of Portuguese, Indian, Pakistani, or Czech ancestry. The incidence of CLN6 disease is unknown; more than 125 cases have been described in the scientific literature.

Signs and symptoms of the condition generally develop between ages 18 months and 8 years, although later onset cases have been reported. Affected people may experience loss of muscle coordination (ataxia), seizures that do not respond to medications, muscle twitches (myoclonus), visual impairment, and developmental regression (loss of previously acquired skills). Treatment options are limited to therapies that can help relieve some of the symptoms. 

Ceroid lipofuscinosis – Neuronal 8

Ceroid lipofuscinosis - Neuronal 8 (also known as CLN8, vLINCL, EPMR and Turkish Late Infantile Variant NCL disease) is a rare metabolic disorder that affects the nerve cells of the body and is characterized by the deposits of lipopigments (lipofuscin). Type 8 is distinguished from other types by the origin of the genetic defect.

CLN8 disease is an inherited disorder that varies in severity and primarily affects the nervous system. The condition is generally separated into less-severe and more-severe forms, based on the types of signs and symptoms that develop and life expectancy. The less-severe form of CLN8 disease appears to affect only individuals of Finnish ancestry, particularly those from the Kainuu region of northern Finland, which is why it is sometimes called Northern epilepsy. Approximately 1 in 10,000 individuals in this region have the condition. The prevalence of the more-severe form of CLN8 disease is unknown. Collectively, all forms of NCL affect an estimated 1 in 100,000 individuals worldwide.

The less-severe form of CLN8 disease, sometimes referred to as Northern epilepsy, is characterized by recurrent seizures (epilepsy) and a decline in intellectual function that begins between ages 5 and 10. The seizures in this form may be resistant to treatment and are often the generalized tonic-clonic type, which involve muscle rigidity, convulsions, and loss of consciousness. Some people with this form of CLN8 disease also experience partial seizures, which do not cause a loss of consciousness. The seizures occur approximately one to two times per month until adolescence; by early adulthood the frequency decreases to about four to six times per year. By middle age, seizures become even less frequent. In addition to seizures, affected individuals experience a gradual decline in intellectual function and develop problems with coordination and balance. Vision problems may occur in early to mid-adulthood. Individuals with the less-severe form of CLN8 disease often live into late adulthood.

The more-severe form of CLN8 disease typically begins between ages 2 and 7.The seizures in this form involve uncontrollable muscle jerks (myoclonic epilepsy). Individuals with the more-severe form have a more pronounced decline in intellectual function and usually lose the ability to speak. Vision loss is also common. People with this form of CLN8 disease have increasing difficulty walking and coordinating movements (ataxia), eventually becoming immobile. Individuals with the more-severe form of CLN8 disease usually survive only into late childhood or adolescence.

Ceroid lipofuscinosis – Neuronal 9

Ceroid lipofuscinosis - Neuronal 9 (also known as CLN9) is a rare metabolic disorder that affects the nerve cells of the body and is characterized by the deposits of lipopigments (lipofuscin). Signs and symptoms of the condition generally develop in early childhood (average age 4 years) and may include loss of muscle coordination (ataxia), seizures that do not respond to medications, muscle twitches (myoclonus), visual impairment, and developmental regression (the loss of previously acquired skills). The underlying genetic cause of CLN9 is unknown but it appears to be inherited in an autosomal recessive manner. Treatment options are limited to therapies that can help relieve some of the symptoms.

Ceroid storage disease

A rare metabolic storage disease characterized by the abnormal deposits of a waxy substance called ceroid lipfuscin in various parts of the body such as the liver, spleen and intestinal lining.

Cerulean cataract

A type of cataract that occurs at birth or soon after and has a characteristic blue color with spoke-like opacities radiating from the centre of the lens.