Cerebellar degeneration

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Cerebellar degeneration
Cerebrum lobes.svg
Cerebellum (labeled bottom right) of the human brain. It is located above the brain stem, posterior to the brain.
Specialty Neurology

Cerebellar degeneration is a condition in which cerebellar cells, otherwise known as neurons, become damaged and progressively weaken in the cerebellum. [1] There are two types of cerebellar degeneration; paraneoplastic cerebellar degeneration, and alcoholic or nutritional cerebellar degeneration. [2] As the cerebellum contributes to the coordination and regulation of motor activities, as well as controlling equilibrium of the human body, any degeneration to this part of the organ can be life-threatening. Cerebellar degeneration can result in disorders in fine movement, posture, and motor learning in humans, due to a disturbance of the vestibular system. This condition may not only cause cerebellar damage on a temporary or permanent basis, but can also affect other tissues of the central nervous system, those including the cerebral cortex, spinal cord and the brainstem (made up of the medulla oblongata, midbrain, and pons). [2]

Contents

Cerebellar degeneration can be attributed to a plethora of hereditary and non-hereditary conditions. More commonly, cerebellar degeneration can also be classified according to conditions that an individual may acquire during their lifetime, including infectious, metabolic, autoimmune, paraneoplastic, nutritional or toxic triggers. [3]

Signs and symptoms

Diplopia is a symptom that individuals with cerebellar degeneration may experience. Diplopia3hjke.jpg
Diplopia is a symptom that individuals with cerebellar degeneration may experience.

Patients with cerebellar degeneration experience a progressive loss of nerve cells (Purkinje cells) throughout the cerebellum. As well as this, it is common to incur an elevated blood protein level and a high volume of lymph cells within the cerebrospinal fluid, resulting in swelling and enlargement of the brain. The most characteristic signs and symptoms experienced by patients with cerebellar degeneration include: [2] [4]

Scientific studies have revealed that psychiatric symptoms are also common in patients with cerebellar degeneration, [5] [6] where dementia is a typical psychiatric disorder resulting from cerebellar damage. Approximately 50% of all patients experience dementia as a result of paraneoplastic cerebellar degeneration. [2]

Causes

The root cause of incurring a cerebellar degenerative condition can be due to a range of different inherited or acquired (non-genetic and non-inherited) conditions, including neurological diseases, paraneoplastic disorders, nutritional deficiency, and chronic heavy alcohol use. [7]

Neurological diseases

A neurological disease refers to any ailment of the central nervous system, including abnormalities of the brain, spinal cord and other connecting nerve fibres. [8] Where millions of people are affected by neurological diseases on a worldwide scale, [8] it has been identified that the number of different types of neurological diseases exceeds six hundred, [9] any of which an individual can incur. Some of the most prevalent types include Alzheimer's disease, cerebral palsy, epilepsy, Parkinson's disease and stroke. [10] More specifically, the neurological diseases that can cause cerebellar degeneration include: [11]

Diagram of two different nerve cells. The diagram on the left shows a nerve cell that is healthy and normally-functioning. The diagram on the right shows a nerve cell with a damaged myelin sheath, being the cause of multiple sclerosis. Myelin sheath damage in multiple sclerosis.png
Diagram of two different nerve cells. The diagram on the left shows a nerve cell that is healthy and normally-functioning. The diagram on the right shows a nerve cell with a damaged myelin sheath, being the cause of multiple sclerosis.

Inherited

  • Spinocerebellar ataxia (SCA), which refers to a group of conditions caused by mutations in the genes of a human, and are characterised by degenerative changes to many parts of the central nervous system, inclusive of the cerebellum, brain stem, and spinal cord. [12] If a parent is affected by SCA, each of their children will have a 50% risk of inheriting the mutated gene. [12]

Non-inherited

  • Multiple sclerosis (MS), a progressive and incurable condition caused by the combination of an individual's genetic influences and environmental circumstances. [4] It occurs when the myelin sheath of the nerve cells becomes damaged. [13] As the myelin sheath is responsible for protecting the nerves and conducting rapid impulses between them, any damage to this lipid-rich layer will result in delayed and interrupted nerve impulses to and from the brain. [14]
  • Transmissible spongiform encephalopathies (TSEs), which refers to a combination of diseases caused by the subsistence of foreign proteins in the blood, called prions. [15] Prions originate in the bloodstream via ingestion of contaminated foods or through contact with contaminated medical instruments, body fluids, or infected tissue. This causes severe inflammation of the brain, impairing one's memory, personality and muscular coordination.[ citation needed ]
  • Acute & haemorrhagic stroke, resulting in the death of neurons in the cerebellum due to a disrupted flow of oxygen to the brain. [16] This disrupted flow may be due to one of two causes; either a narrowing or blocked artery which derives from a build-up of plaque in the inner walls of the coronary arteries, or a ruptured blood vessel, commonly deriving from high blood pressure or head trauma. [17]

Paraneoplastic disorders

Paraneoplastic disorders are a combination of non-inherited conditions that are activated by an individual's autoimmune response to a malignant tumour. These disorders prevail when T-cells (also known as white blood cells) begin to harm familiar cells in the central nervous system rather than the cancerous cells, [2] resulting in degeneration of neurons in the cerebellum. Other signs and symptoms that commonly result from the incursion of a paraneoplastic disorder include an impaired ability to talk, walk, sleep, maintain balance and coordinate muscle activity, as well as experiencing seizures and hallucinations. [18] Paraneoplastic disorders are prevalent among middle-aged individuals, typically those with lung, lymphatic, ovarian or breast cancer. [19]

Nutritional deficiency

Nutritional deficiency relates to an insufficient amount of macronutrients and micronutrients being provided to the body. Nutrient deficiencies are most prevalent among infants, the elderly, the poverty-stricken, and individuals with eating disorders. [20] Alcohol use disorder is the diagnosis of which an individual frequently consumes excessive amounts of alcohol, and thus becomes dependent on the intoxicating substance. Studies show that men of every age group consume more alcohol than women, where the prevalence is higher in some regions of the world than others, such as across Western Europe and Australia. [21] [22] Nutritional deficiency is a non-inherited condition that lead to impaired absorption or utilisation of the vitamin thiamine (B-1) by the body, thus causing temporary or permanent damage to cerebellar cells. [2] Alcoholic degeneration of cerebellar cells is the most common trigger of spinocerebellar ataxia. [23]

Diagnosis

Magnetic resonance imaging scans of two different brains. The scan of the brain on the left indicates a weakened, deteriorated cerebellum of a human with cerebellar degeneration. The scan of the brain on the right indicates a healthy, normally-functioning cerebellum of a human. Cerebellar Degeneration.png
Magnetic resonance imaging scans of two different brains. The scan of the brain on the left indicates a weakened, deteriorated cerebellum of a human with cerebellar degeneration. The scan of the brain on the right indicates a healthy, normally-functioning cerebellum of a human.

To select an appropriate and accurate diagnostic test for cerebellar degeneration, it is crucial that a range of factors specific to each patient are taken into consideration. These include; the patient's age, acuity of their signs and symptoms, associated neurological conditions, and family history of hereditary forms of cerebellar degeneration. [3] A diagnosis for cerebellar degeneration is regarded after any of the aforementioned signs and symptoms surface. For genetically classified forms of cerebellar degeneration, genetic testing can be carried out in order to confirm or deny the diagnosis, where this form of testing is only possible if the gene responsible for the cause of the condition is recognised. [24] In saying this, for most conditions the genetic cause of cerebellar degeneration is unidentified, hence these patients cannot proceed with genetic testing. [1] In cases where cerebellar degeneration is acquired, a diagnosis can be established using imaging methods such as computerised tomography (CT scans) and magnetic resonance imaging (MRI), necessary to detect brain abnormalities in patients with cerebellar degeneration. [25]

Treatment

Like any other disease, treatment for cerebellar degeneration is contingent on the underlying cause, unique to each patient. As of present time, hereditary forms of cerebellar degeneration are incurable, though they can be managed. Management is centred around coping with symptoms and improving a patient's quality of life. In these cases, immediate management of inherited cerebellum damage should involve consultation with a neurologist, followed by specific management approaches based on the signs and symptoms experienced by each unique patient. [3] These management approaches aim to provide supportive care to the patient, consisting of physical therapy to strengthen muscles, occupational therapy, and speech pathology. Long-term management of inherited cerebellar degeneration involves an ongoing commitment to supportive care therapies, as well as a longitudinal relationship with a neurologist. In some instances adjustments need to be made in the patients home, to improve accessibility and mobility in and around their living environment, to optimise safety. [3] The cerebellum is highly reactive to transcranial direct current stimulation, a technique which may improve ataxia. [26]

For non-hereditary types of cerebellar degeneration, some physical and mental indicators can be reversed by treating the fundamental cause. [27] For instance, the signs and symptoms of paraneoplastic cerebellar degeneration can be managed by initially terminating the underlying cancer with treatments such as surgery, radiation therapy and chemotherapy. In cases of nutritional or alcoholic cerebellar degeneration, symptoms of these conditions can be relieved by initially consuming a balanced diet and discontinuing the consumption of alcohol respectively, followed by dietary supplementation with thiamine. [2]

Prognosis

The long-term prospect for patients with cerebellar degeneration differs according to the underlying cause of the disease. [1] Each inherited or acquired disease that results in cerebellar degeneration has its own specific prognosis, however most are generally poor, progressive and often fatal. [3]

Epidemiology

Cerebellar degeneration continues to carry a considerable burden on the health of the world population, as well as on health agencies and governing bodies across the globe. Cerebellum-related disorders generally transpire in individuals between the ages of 45 to 65 years, however the age of symptomatic onset differs in accordance with the underlying cause of the degenerative disorder. [1] For paraneoplastic cerebellar degeneration, the average age of onset is 50 years, generally affecting a greater population of males than females. [2] Nutritional and alcoholic cerebellar degeneration, being more prevalent than paraneoplastic cerebellar degeneration, affects individuals with a thiamine deficiency and dipsomaniacs, respectively. [2] Recent epidemiological studies on cerebellar degeneration estimated a global prevalence rate of 26 per 100,000 cases of cerebellar degeneration in children. [28]

Related Research Articles

Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements, that indicates dysfunction of parts of the nervous system that coordinate movement, such as the cerebellum.

<span class="mw-page-title-main">Abetalipoproteinemia</span> Medical condition

Abetalipoproteinemia is a disorder characterized by abnormal absorption of fat and fat-soluble vitamins from food. It is caused by a mutation in microsomal triglyceride transfer protein resulting in deficiencies in the apolipoproteins B-48 and B-100, which are used in the synthesis and exportation of chylomicrons and VLDL respectively. It is not to be confused with familial dysbetalipoproteinemia.

<span class="mw-page-title-main">Wernicke–Korsakoff syndrome</span> Combined presence of Wernickes encephalopathy (WE) and Korsakoffs syndrome

Wernicke-Korsakoff syndrome (WKS) is the combined presence of Wernicke encephalopathy (WE) and Korsakoff syndrome. Due to the close relationship between these two disorders, people with either are usually diagnosed with WKS as a single syndrome. It mainly causes vision changes, ataxia and impaired memory.

<span class="mw-page-title-main">Olivopontocerebellar atrophy</span> Medical condition

Olivopontocerebellar atrophy (OPCA) is the degeneration of neurons in specific areas of the brain – the cerebellum, pons, and inferior olivary nucleus. OPCA is present in several neurodegenerative syndromes, including inherited and non-inherited forms of ataxia and multiple system atrophy (MSA), with which it is primarily associated.

<span class="mw-page-title-main">Friedreich's ataxia</span> Rare autosomal-recessive human disease

Friedreich's ataxia is an autosomal-recessive genetic disease that causes difficulty walking, a loss of coordination in the arms and legs, and impaired speech that worsens over time. Symptoms generally start between 5 and 20 years of age. Many develop hypertrophic cardiomyopathy and require a mobility aid such as a cane, walker, or wheelchair in their teens. As the disease progresses, some affected people lose their sight and hearing. Other complications may include scoliosis and diabetes mellitus.

<span class="mw-page-title-main">Spinocerebellar ataxia</span> Medical condition

Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of spinocerebellar ataxia at any given time. SCA is hereditary, progressive, degenerative, and often fatal. There is no known effective treatment or cure. SCA can affect anyone of any age. The disease is caused by either a recessive or dominant gene. In many cases people are not aware that they carry a relevant gene until they have children who begin to show signs of having the disorder.

<span class="mw-page-title-main">Machado–Joseph disease</span> Genetic neurodegenerative disease

Machado–Joseph disease (MJD), also known as Machado–Joseph Azorean disease, Machado's disease, Joseph's disease or spinocerebellar ataxia type 3 (SCA3), is a rare autosomal dominantly inherited neurodegenerative disease that causes progressive cerebellar ataxia, which results in a lack of muscle control and coordination of the upper and lower extremities. The symptoms are caused by a genetic mutation that results in an expansion of abnormal "CAG" trinucleotide repeats in the ATXN3 gene that results in an abnormal form of the protein ataxin which causes degeneration of cells in the hindbrain. Some symptoms, such as clumsiness and rigidity, make MJD commonly mistaken for drunkenness or Parkinson's disease.

<span class="mw-page-title-main">Aceruloplasminemia</span> Medical condition

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<span class="mw-page-title-main">Spinocerebellar ataxia type 6</span> Medical condition

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<span class="mw-page-title-main">Autosomal recessive cerebellar ataxia type 1</span> Hereditary ataxia that has material basis in autosomal recessive inheritance

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Oculomotor apraxia (OMA) is the absence or defect of controlled, voluntary, and purposeful eye movement. It was first described in 1952 by the American ophthalmologist David Glendenning Cogan. People with this condition have difficulty moving their eyes horizontally and moving them quickly. The main difficulty is in saccade initiation, but there is also impaired cancellation of the vestibulo-ocular reflex. Patients have to turn their head in order to compensate for the lack of eye movement initiation in order to follow an object or see objects in their peripheral vision, but they often exceed their target. There is controversy regarding whether OMA should be considered an apraxia, since apraxia is the inability to perform a learned or skilled motor action to command, and saccade initiation is neither a learned nor a skilled action.

<span class="mw-page-title-main">Autosomal dominant cerebellar ataxia</span> Medical condition

Autosomal dominant cerebellar ataxia (ADCA) is a form of spinocerebellar ataxia inherited in an autosomal dominant manner. ADCA is a genetically inherited condition that causes deterioration of the nervous system leading to disorder and a decrease or loss of function to regions of the body.

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Familial Danish Dementia is an extremely rare, neurodegenerative disease characterized by progressive cataracts, loss of hearing, cerebellar ataxia, paranoid psychosis, and dementia. Neuropathological hallmarks include extensive atrophy of all areas of the brain, chronic diffuse encephalopathy, and the presence of exceedingly thin and nearly totally demyelinated cranial nerves.

Autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCADN) is a rare progressive genetic disorder that primarily affects the nervous system and is characterized by sensorineural hearing loss, narcolepsy with cataplexy, and dementia later in life. People with this disorder usually start showing symptoms when they are in their early-mid adulthoods. It is a type of autosomal dominant cerebellar ataxia.

References

  1. 1 2 3 4 "Cerebellar degeneration". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. U.S. National Institutes of Health. Retrieved 2018-10-09.
  2. 1 2 3 4 5 6 7 8 9 "Cerebellar Degeneration, Subacute". NORD (National Organization for Rare Disorders). Retrieved 2018-10-09.
  3. 1 2 3 4 5 "Cerebellar degeneration". Clinical Advisor. 2016-12-20. Retrieved 2018-10-09.
  4. 1 2 "Cerebellar degeneration". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. U.S. National Institutes of Health. Retrieved 2018-10-09.
  5. ↑ Liszewski CM, O'Hearn E, Leroi I, Gourley L, Ross CA, Margolis RL (February 2004). "Cognitive impairment and psychiatric symptoms in 133 patients with diseases associated with cerebellar degeneration". The Journal of Neuropsychiatry and Clinical Neurosciences. 16 (1): 109–12. doi:10.1176/jnp.16.1.109. PMID   14990766.
  6. ↑ Phillips JR, Hewedi DH, Eissa AM, Moustafa AA (2015). "The cerebellum and psychiatric disorders". Frontiers in Public Health. 3: 66. doi: 10.3389/fpubh.2015.00066 . PMC   4419550 . PMID   26000269.
  7. ↑ Agamanolis D. "Ataxia and cerebellar degeneration". neuropathology-web.org. Retrieved 2018-10-09.
  8. 1 2 Liszewski CM, O'Hearn E, Leroi I, Gourley L, Ross CA, Margolis RL (2004). "Cognitive impairment and psychiatric symptoms in 133 patients with diseases associated with cerebellar degeneration". J Neuropsychiatry Clin Neurosci. 16 (1): 109–12. doi:10.1176/jnp.16.1.109. PMID   14990766.
  9. ↑ Phillips JR, Hewedi DH, Eissa AM, Moustafa AA (2015). "The cerebellum and psychiatric disorders". Front Public Health. 3: 66. doi: 10.3389/fpubh.2015.00066 . PMC   4419550 . PMID   26000269.. [ verification needed ]
  10. ↑ Agamanolis D. "Ataxia and cerebellar degeneration". neuropathology-web.org. Retrieved 2018-10-09. [ verification needed ]
  11. ↑ "Spinocerebellar ataxia". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. U.S. National Institutes of Health. Retrieved 2018-10-09. [ verification needed ]
  12. 1 2 "Spinocerebellar ataxia". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. U.S. National Institutes of Health. Retrieved 2018-10-09.
  13. ↑ "Multiple sclerosis (MS)". Australian Department of Health & Human Services. Retrieved 2018-10-09.
  14. ↑ "Myelin Sheath - Definition and Function | Biology Dictionary". Biology Dictionary. 2017-02-10. Retrieved 2018-10-19.
  15. ↑ "Transmissible Spongiform Encephalopathies (TSEs)". European Food Safety Authority. Retrieved 2018-10-09.
  16. ↑ "About Stroke". Stroke Foundation - Australia. Retrieved 2018-10-09.
  17. ↑ "Stroke - Symptoms and causes". Mayo Clinic. Retrieved 2018-10-19.
  18. ↑ "Paraneoplastic syndromes of the nervous system - Symptoms and causes". Mayo Clinic. Retrieved 2018-10-19.
  19. ↑ "Paraneoplastic Neurologic Disorders | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-10-19.
  20. ↑ "Nutritional Deficiencies". www.clinicaladvisor.com. Retrieved 2018-10-19.
  21. ↑ Ritchie, Hannah; Roser, Max (16 April 2018). "Alcohol consumption". Our World in Data. Retrieved 2018-10-19.
  22. ↑ Wilsnack RW, Wilsnack SC, Kristjanson AF, Vogeltanz-Holm ND, Gmel G (September 2009). "Gender and alcohol consumption: patterns from the multinational GENACIS project". Addiction. 104 (9): 1487–500. doi:10.1111/j.1360-0443.2009.02696.x. PMC   2844334 . PMID   19686518.
  23. ↑ Shanmugarajah PD, Hoggard N, Currie S, Aeschlimann DP, Aeschlimann PC, Gleeson DC, Karajeh M, Woodroofe N, Grünewald RA, Hadjivassiliou M (2016-10-03). "Alcohol-related cerebellar degeneration: not all down to toxicity?". Cerebellum & Ataxias. 3 (1): 17. doi: 10.1186/s40673-016-0055-1 . PMC   5048453 . PMID   27729985.
  24. ↑ "Autosomal Dominant Hereditary Ataxia". NORD (National Organization for Rare Disorders). Retrieved 2018-10-09.
  25. ↑ "UpToDate". www.uptodate.com. Retrieved 2018-10-09.
  26. ↑ Manto, M. Neuromodulation of the cerebellum: the importance of the assessment of the cerebellar reserve. J Neurol (2022) https://doi.org/10.1007/s00415-022-11455-7
  27. ↑ "Cerebellar Disorders - Neurologic Disorders". Merck Manuals Professional Edition. Retrieved 2018-10-09.
  28. ↑ Salman MS (February 2018). "Epidemiology of Cerebellar Diseases and Therapeutic Approaches". Cerebellum. 17 (1): 4–11. doi:10.1007/s12311-017-0885-2. PMID   28940047. S2CID   46763077.
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