Spinocerebellar ataxia

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Spinocerebellar ataxia
Other namesSpinocerebellar atrophy or Spinocerebellar degeneration
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Cerebellum (in blue) of the human brain
Specialty Neurology   OOjs UI icon edit-ltr-progressive.svg

Spinocerebellar ataxia (SCA) is a progressive, degenerative, [1] 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. [2]

Contents

Signs and symptoms

Spinocerebellar ataxia (SCA) is one of a group of genetic disorders characterized by slowly progressive incoordination of gait and is often associated with poor coordination of hands, speech, and eye movements. A review of different clinical features among SCA subtypes was recently published describing the frequency of non-cerebellar features, like parkinsonism, chorea, pyramidalism, cognitive impairment, peripheral neuropathy, seizures, among others. [3] As with other forms of ataxia, SCA frequently results in atrophy of the cerebellum, [4] loss of fine coordination of muscle movements leading to unsteady and clumsy motion, and other symptoms. Ocular deficits can be quantified using the SODA scale. [5]

The symptoms of an ataxia vary with the specific type and with the individual patient. In many cases a person with ataxia retains full mental capacity but progressively loses physical control.[ citation needed ]

Cause

The hereditary ataxias are categorized by mode of inheritance and causative gene or chromosomal locus. The hereditary ataxias can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner.[ citation needed ]

Diagnosis

Classification

A few SCAs remain unspecified and can not be precisely diagnosed, but in the last decade[ as of? ] genetic testing has allowed precise identification of dozens of different SCAs and more tests are being added each year. [8] In 2008, a genetic ataxia blood test developed to test for 12 types of SCA, Friedreich's ataxia, and several others. However, since not every SCA has been genetically identified some SCAs are still diagnosed by neurological examination, which may include a physical exam, family history, MRI scanning of the brain and spine, and spinal tap. [9]

Many SCAs below fall under the category of polyglutamine diseases, which are caused when a disease-associated protein (i.e., ataxin-1, ataxin-3, etc.) contains a large number of repeats of glutamine residues, termed a polyQ sequence or a "CAG trinucleotide repeat" disease for either the one-letter designation or codon for glutamine respectively. The threshold for symptoms in most forms of SCA is around 35, though for SCA3 it extends beyond 50. Most polyglutamine diseases are dominant due to the interactions of resulting polyQ tail.[ citation needed ]

The first ataxia gene was identified in 1993 and called "Spinocerebellar ataxia type 1" (SCA1); later genes were called SCA2, SCA3, etc. Usually, the "type" number of "SCA" refers to the order in which the gene was found. At this time, there are at least 49 different gene mutations that have been found.[ citation needed ]

The following is a list of some of the many types of Spinocerebellar ataxia.

SCA TypeAverage Onset
(Range in Years)		Average Duration
(Range in Years)		What the patient experiencesCommon originProblems
with DNA
SCA1 [10] (ATXN1)4th decade
(<10 to >60)		15 years
(10–35)		Hypermetric saccades, slow saccades, upper motor neuron
(note: saccades relates to eye movement)		 CAG repeat, 6p (Ataxin 1)
SCA2 [11] (ATXN2)3rd–4th decade
(<10 to >60)		10 years
(1–30)		Diminished velocity saccades
areflexia (absence of neurologic reflexes)		 Cuba CAG repeat, 12q
SCA3 [12] (MJD) (ATXN3)4th decade
(10–70)		10 years
(1–20)		Also called Machado-Joseph disease (MJD) [13]
Gaze-evoked nystagmus (a rapid, involuntary, oscillatory motion of the eyeball)
upper motor neuron
slow saccades		 Azores
(Portugal)		CAG repeat, 14q
SCA4 (PLEKHG4)4th–7th decade
(19–72)		Decadesareflexia (absence of neurologic reflexes)  Chromosome 16q
SCA5 (SPTBN2)3rd–4th decade
(10–68)		>25 yearsPure cerebellar   Chromosome 11
SCA6 [14] (CACNA1A)5th–6th decade
(19–71)		>25 yearsDownbeating nystagmus, positional vertigo
Symptoms can appear for the first time as late as 65 years old.		 CAG repeat, 19p
Calcium channel gene
SCA7 [15] (ATXN7)3rd–4th decade
(0.5–60)		20 years
(1–45; early onset correlates with shorter duration)		 Macular degeneration, upper motor neuron, slow saccades CAG repeat, 3p (Ataxin 7)
SCA8 [16] (IOSCA)39 yrs
(18–65)		Normal lifespan Horizontal nystagmus (a rapid, involuntary, oscillatory motion of the eyeball), instability, lack of coordination CTG repeat, [17] 13q
SCA10 [18] (ATXN10)36 years9 years ataxia, seizures Mexico Chromosome 22q linked
pentanucleotide repeat
SCA11 (TTBK2)30 yrs
(15–70)		Normal lifespanMild, remain ambulatory (able to walk about on one's own) 15q
SCA12 [19] (PPP2R2B)33 yrs
(8–55)		  Head and hand tremor,
akinesia (loss of normal motor function, resulting in impaired muscle movement)		 CAG repeat, 5q
SCA13 (KCNC3)Childhood or adulthood depending on mutationDepending on KCNC3 (a kind of gene) Intellectual disability  19q
SCA14 [20] (PRKCG)28 yrs
(12–42)		Decades
(1–30)		 Myoclonus (a sudden twitching of muscles or parts of muscles, without any rhythm or pattern, occurring in various brain disorders) 19q
SCA16 (ITPR1)39 yrs
(20–66)		1–40 years Head and hand tremor  8q
SCA17 (TBP) CAG repeat, 6q (TATA-binding protein)
SCA19, SCA22 (KCND3 [21] )  Mild cerebellar syndrome, dysarthria   
SCA25 1.5–39 yrsUnknown ataxia with sensory neuropathy, vomiting and gastrointestinal pain. 2p
SCA27 [22] (FGF14 [21] )15–20 yrsUnknown ataxia with poor cognition, dyskinesias and tremor. FGF14 13q34
SCA35 40–48 yearsUnknowngait and limb ataxia, dysarthria, ocular dysmetria, intention tremor, pseudobulbar palsy, spasmodic torticollis, extensor plantar responses, reduced proprioception and hyperreflexia China transglutaminase 6 (TGM6) located at chromosome 20p13
SCA365th and 6th decade (adulthood)Decadesataxia, hyperrheflexia, dysarthria, fasciculations of the tongue with subsequent wasting of the tongue NOP56
SCA37AdulthoodDecadesdysarthria, slowly progressive gait and limb ataxia with severe dysmetria in the lower extremities, mild dysmetria in the upper extremities, dysphagia, and abnormal ocular movements DAB1

Others include SCA18, SCA20, SCA21, SCA23, SCA26, SCA28, and SCA29.

Four X-linked types have been described ( 302500, 302600, 301790, 301840), but only the first of these has so far been tied to a gene (SCAX1).

Name OMIM RareDiseases Other
Anemia, sideroblastic spinocerebellar ataxia; Pagon Bird Detter syndrome 301310 Disease ID 668 at NIH 's Office of Rare Diseases
Friedreich's ataxia; Spinocerebellar ataxia, Friedreich 229300 Disease ID 6468 at NIH 's Office of Rare Diseases
Infantile onset Spinocerebellar ataxia 605361 Disease ID 4062 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 1 164400 Disease ID 4071 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 2 183090 Disease ID 4072 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 3; Machado Joseph disease 109150 Disease ID 6801 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 4 600223 Disease ID 9970 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 5 600224 Disease ID 4953 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 7 164500 Disease ID 4955 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 8 603680 Disease ID 4956 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 13 605259 Disease ID 9611 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 18 607458 Disease ID 9976 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 19 607346 Disease ID 9969 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 20 608687 Disease ID 9997 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 21 607454 Disease ID 9999 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 23 610245 Disease ID 9950 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 25 608703 Disease ID 9996 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 26 609306 Disease ID 9995 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 28 610246 Disease ID 9951 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 30 117360 Disease ID 9975 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia 35 613908 Disease ID at NIH 's Office of Rare Diseases
Spinocerebellar ataxia amyotrophy deafness syndrome Disease ID 2451 at NIH 's Office of Rare Diseases ORPHA:2074 at Orphanet
Spinocerebellar ataxia, autosomal recessive 1 606002 Disease ID 4949 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia, autosomal recessive 3 271250 Disease ID 9971 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia, autosomal recessive 4 607317 Disease ID 4952 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia, autosomal recessive 5 606937 Disease ID 9977 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia, autosomal recessive 6 608029 Disease ID 4954 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia, autosomal recessive 21 - mutation in SCYL1 Online Mendelian Inheritance in Man (OMIM): 616719 ORPHA:466794
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 607250 Disease ID 10000 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia, X-linked, 2 302600 Disease ID 9978 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia, X-linked, 3 301790 Disease ID 9981 at NIH 's Office of Rare Diseases
Spinocerebellar ataxia, X-linked, 4 301840 Disease ID 9980 at NIH 's Office of Rare Diseases

Treatment

Medication

There is no cure for spinocerebellar ataxia, which is currently considered to be a progressive and irreversible disease, although not all types cause equally severe disability. [23]

In general, treatments are directed towards alleviating symptoms, not the disease itself. Many patients with hereditary or idiopathic forms of ataxia have other symptoms in addition to ataxia. Medications or other therapies might be appropriate for some of these symptoms, which could include tremor, stiffness, depression, spasticity, and sleep disorders, among others. Both onset of initial symptoms and duration of disease are variable. If the disease is caused by a polyglutamine trinucleotide repeat CAG expansion, a longer expansion may lead to an earlier onset and a more radical progression of clinical symptoms. Typically, a person with this disease will eventually be unable to perform daily tasks (ADLs). [24] However, rehabilitation therapists can help patients to maximize their ability of self-care and delay deterioration to certain extent. [25] Researchers are exploring multiple avenues for a cure including RNA interference (RNAi) technology, the use of stem cells, and several other avenues. [26]

On January 18, 2017, BioBlast Pharma announced completion of Phase 2a clinical trials of their medication, trehalose, in the treatment of SCA3. BioBlast has received FDA Fast Track status and orphan drug status for their treatment. The information provided by BioBlast in their research indicates that they hope this treatment may prove efficacious in other SCA treatments that have similar pathology related to PolyA and PolyQ diseases. [27] [28]

In addition, Dr. Beverly Davidson has been working on a methodology using RNAi technology to find a potential cure for over 2 decades. [29] Her research began in the mid-1990s and progressed to work with mouse models about a decade later and most recently has moved to a study with non-human primates. The results from her most recent research "are supportive of clinical application of this gene therapy". [30]

Finally, another gene transfer technology discovered in 2011 has also been shown by Boudreau et al. to hold great promise and offers yet another avenue to a potential future cure. [31]

N-Acetyl-Leucine

N-Acetyl-Leucine is an orally administered, modified amino acid that is being developed as a novel treatment for multiple rare and common neurological disorders by IntraBio Inc (Oxford, United Kingdom). [32]

N-Acetyl-Leucine has been granted multiple orphan drug designations from the U.S. Food & Drug Administration (FDA) [33] and the European Medicines Agency (EMA) [34] for the treatment of various genetic diseases, including spinocerebellar ataxias. N-Acetyl-Leucine has also been granted Orphan Drug Designations in the US and EU for the related inherited cerebellar ataxia ataxia-telangiectasia U.S. Food & Drug Administration (FDA) [35] and the European Medicines Agency (EMA). [36]

Published case series studies have demonstrated the effects of acute treatment with N-Acetyl-Leucine for the treatment of inherited cerebellar ataxias, including spinocerebellar ataxias. [37] [38] These studies further demonstrated that the treatment is well tolerated, with a good safety profile.[ citation needed ] A multinational clinical trial investigating N-Acetyl-L-Leucine for the treatment of a related inherited cerebellar ataxia, ataxia-telangiectasia, began in 2019. [39]

IntraBio is also conducting parallel clinical trials with N-Acetyl-L-Leucine for the treatment of Niemann-Pick disease type C [40] and GM2 gangliosidosis (Tay-Sachs and Sandhoff disease). [41] Future opportunities to develop N-Acetyl-Leucine include Lewy body dementia, [42] amyotrophic lateral sclerosis, restless leg syndrome, multiple sclerosis, and migraine. [43]

Rehabilitation

Physical therapists can assist patients in maintaining their level of independence through therapeutic exercise programmes. One recent research report demonstrated a gain of two SARA points (Scale for the Assessment and Rating of Ataxia) from physical therapy. [44] In general, physical therapy emphasises postural balance and gait training for ataxia patients. [45] General conditioning such as range-of-motion exercises and muscle strengthening would also be included in therapeutic exercise programmes. Research showed that spinocerebellar ataxia 2 (SCA2) patients [46] with a mild stage of the disease gained significant improvement in static balance and neurological indices after six months of a physical therapy exercise training program. [47] Occupational therapists may assist patients with incoordination or ataxia issues through the use of adaptive devices. Such devices may include a cane, crutches, walker, or wheelchair for those with impaired gait. Other devices are available to assist with writing, feeding, and self care if hand and arm coordination are impaired. A randomised clinical trial revealed that an intensive rehabilitation program with physical and occupational therapies for patients with degenerative cerebellar diseases can significantly improve functional gains in ataxia, gait, and activities of daily living. Some level of improvement was shown to be maintained 24 weeks post-treatment. [48] Speech language pathologists may use both behavioral intervention strategies as well as augmentative and alternative communication devices to help patients with impaired speech.[ citation needed ]

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.

Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder. The disease presents with progressive stiffness (spasticity) and contraction in the lower limbs. HSP is also known as hereditary spastic paraparesis, familial spastic paraplegia, French settlement disease, Strumpell disease, or Strumpell-Lorrain disease. The symptoms are a result of dysfunction of long axons in the spinal cord. The affected cells are the primary motor neurons; therefore, the disease is an upper motor neuron disease. HSP is not a form of cerebral palsy even though it physically may appear and behave much the same as spastic diplegia. The origin of HSP is different from cerebral palsy. Despite this, some of the same anti-spasticity medications used in spastic cerebral palsy are sometimes used to treat HSP symptoms.

<span class="mw-page-title-main">Ataxia–telangiectasia</span> Rare, neurodegenerative, autosomal recessive human disease causing severe disability

Ataxia–telangiectasia, also referred to as ataxia–telangiectasia syndrome or Louis–Bar syndrome, is a rare, neurodegenerative, autosomal recessive disease causing severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease. A–T affects many parts of the body:

<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">Gerstmann–Sträussler–Scheinker syndrome</span> Human neurodegenerative disease

Gerstmann–Sträussler–Scheinker syndrome (GSS) is an extremely rare, always fatal neurodegenerative disease that affects patients from 20 to 60 years in age. It is exclusively heritable, and is found in only a few families all over the world. It is, however, classified with the transmissible spongiform encephalopathies (TSE) due to the causative role played by PRNP, the human prion protein. GSS was first reported by the Austrian physicians Josef Gerstmann, Ernst Sträussler and Ilya Scheinker in 1936.

<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.

Cerebellar ataxia is a form of ataxia originating in the cerebellum. Non-progressive congenital ataxia (NPCA) is a classical presentation of cerebral ataxias.

The GM2 gangliosidoses are a group of three related genetic disorders that result from a deficiency of the enzyme beta-hexosaminidase. This enzyme catalyzes the biodegradation of fatty acid derivatives known as gangliosides. The diseases are better known by their individual names: Tay–Sachs disease, AB variant, and Sandhoff disease.

Ataxin 7 (ATXN7) is a protein of the SCA7 gene, which contains 892 amino acids with an expandable poly(Q) region close to the N-terminus. The expandable poly(Q) motif region in the protein contributes crucially to spinocerebellar ataxia (SCA) pathogenesis by the induction of intranuclear inclusion bodies. ATXN7 is associated with both olivopontocerebellar atrophy type 3 (OPCA3) and spinocerebellar ataxia type 7 (SCA7).

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

Cerebrotendinous xanthomatosis, also called cerebral cholesterosis, is an autosomal recessive form of xanthomatosis. It falls within a group of genetic disorders called the leukodystrophies.

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

Spinocerebellar ataxia type 6 (SCA6) is a rare, late-onset, autosomal dominant disorder, which, like other types of SCA, is characterized by dysarthria, oculomotor disorders, peripheral neuropathy, and ataxia of the gait, stance, and limbs due to cerebellar dysfunction. Unlike other types, SCA 6 is not fatal. This cerebellar function is permanent and progressive, differentiating it from episodic ataxia type 2 (EA2) where said dysfunction is episodic. In some SCA6 families, some members show these classic signs of SCA6 while others show signs more similar to EA2, suggesting that there is some phenotypic overlap between the two disorders. SCA6 is caused by mutations in CACNA1A, a gene encoding a calcium channel α subunit. These mutations tend to be trinucleotide repeats of CAG, leading to the production of mutant proteins containing stretches of 20 or more consecutive glutamine residues; these proteins have an increased tendency to form intracellular agglomerations. Unlike many other polyglutamine expansion disorders expansion length is not a determining factor for the age that symptoms present.

<span class="mw-page-title-main">Spinocerebellar ataxia type-13</span> Medical condition

Spinocerebellar ataxia type 13 (SCA13) is a rare autosomal dominant disorder, which, like other types of SCA, is characterized by dysarthria, nystagmus, and ataxia of gait, stance and the limbs due to cerebellar dysfunction. Patients with SCA13 also tend to present with epilepsy, an inability to run, and increased reflexes. This cerebellar dysfunction is permanent and progressive. SCA13 is caused by mutations in KCNC3, a gene encoding a voltage-gated potassium channel KV3.3. There are two known mutations in this gene causative for SCA13. Unlike many other types of SCA, these are not polyglutamine expansions but, rather, point mutations resulting in channels with no current or altered kinetics.

<span class="mw-page-title-main">Ataxin-2</span> Mammalian protein found in Homo sapiens

Ataxin-2 is a protein that in humans is encoded by the ATXN2 gene. Mutations in ATXN2 cause spinocerebellar ataxia type 2 (SCA2).

<span class="mw-page-title-main">Ataxin 10</span> Protein-coding gene in the species Homo sapiens

Ataxin-10 is a protein that in humans is encoded by the ATXN10 gene.

Ataxin 8 opposite strand, also known as ATXN8OS, is a human gene.

<span class="mw-page-title-main">Marinesco–Sjögren syndrome</span> Medical condition

Marinesco–Sjögren syndrome (MSS), sometimes spelled Marinescu–Sjögren syndrome, is a rare autosomal recessive disorder.

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

Autosomal recessive cerebellar ataxia type 1 (ARCA1) is a condition characterized by progressive problems with movement. Signs and symptoms of the disorder first appear in early to mid-adulthood. People with this condition initially experience impaired speech (dysarthria), problems with coordination and balance (ataxia), or both. They may also have difficulty with movements that involve judging distance or scale (dysmetria). Other features of ARCA1 include abnormal eye movements (nystagmus) and problems following the movements of objects with their eyes. The movement problems are slowly progressive, often resulting in the need for a cane, walker, or wheelchair.

<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.

<span class="mw-page-title-main">Spinocerebellar ataxia type 1</span> Rare neurodegenerative disorder

Spinocerebellar ataxia type 1 (SCA1) is a rare autosomal dominant disorder, which, like other spinocerebellar ataxias, is characterized by neurological symptoms including dysarthria, hypermetric saccades, and ataxia of gait and stance. This cerebellar dysfunction is progressive and permanent. First onset of symptoms is normally between 30 and 40 years of age, though juvenile onset can occur. Death typically occurs within 10 to 30 years from onset.

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

Cerebellar degeneration is a condition in which cerebellar cells, otherwise known as neurons, become damaged and progressively weaken in the cerebellum. There are two types of cerebellar degeneration; paraneoplastic cerebellar degeneration, and alcoholic or nutritional cerebellar degeneration. 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.

References

  1. ↑ " spinocerebellar ataxia " at Dorland's Medical Dictionary
  2. ↑ "Ataxias and Cerebellar or Spinocerebellar Degeneration Information Page". National Institute on Neurological Disorders and Stroke.
  3. ↑ Rossi, M; Perez-Lloret, S; Doldan, L; Cerquetti, D; Balej, J; Millar Vernetti, P; Hawkes, H; Cammarota, A; Merello, M (2014). "Autosomal dominant cerebellar ataxias: A systematic review of clinical features". European Journal of Neurology. 21 (4): 607–15. doi:10.1111/ene.12350. hdl: 11336/30194 . PMID   24765663. S2CID   74661673.
  4. ↑ "Spinocerebellar ataxia". Genes and Disease [Internet]. Bethesda MD: National Center for Biotechnology Information. 1998. NBK22234. — Gives a concise description of SCA, along with a picture of shrunken degenerated cerebellum.
  5. ↑ Shaikh, A; Ji Soo, Kim (2022). "Scale for Ocular motor Disorders in Ataxia (SODA)". Journal of the Neurological Sciences. 443: 120472. doi:10.1016/j.jns.2022.120472. PMID   36403298. S2CID   253156325.
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  11. ↑ sca2 at NIH / UW GeneTests
  12. ↑ sca3 at NIH / UW GeneTests
  13. ↑ machado_joseph at NINDS
  14. ↑ sca6 at NIH / UW GeneTests
  15. ↑ sca7 at NIH / UW GeneTests
  16. ↑ sca8 at NIH / UW GeneTests
  17. ↑ Mosemiller, A.K.; Dalton, J.C.; Day, J.W.; Ranum, L.P.W. (2003). "Molecular genetics of spinocerebellar ataxia type 8 (SCA8)". Cytogenetic and Genome Research. 100 (1–4): 175–83. doi:10.1159/000072852. PMID   14526178. S2CID   2292926.
  18. ↑ sca10 at NIH / UW GeneTests
  19. ↑ sca12 at NIH / UW GeneTests
  20. ↑ sca14 at NIH / UW GeneTests
  21. 1 2 Perlman, Susan L. (2016). Evaluation and Management of Ataxic Disorders: An Overview for Physicians. Minneapolis: National Ataxia Foundation. p. 6. ISBN   978-0-943218-14-4. LCCN   2007923539.
  22. ↑ Online Mendelian Inheritance in Man (OMIM): 609307
  23. ↑ Jiang, Bingcheng; Glover, J.N. Mark; Weinfeld, Michael (January 2017). "Neurological disorders associated with DNA strand-break processing enzymes". Mechanisms of Ageing and Development. 161 (Pt A): 130–140. doi:10.1016/j.mad.2016.07.009. PMC   5266678 . PMID   27470939.
  24. ↑ Cruts, Marc; Engelborghs, Sebastiaan; van der Zee, Julie; Van Broeckhoven, Christine (1993). "C9orf72-Related Amyotrophic Lateral Sclerosis and Frontotemporal Dementia". In Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E.; Bean, Lora J.H.; Stephens, Karen; Amemiya, Anne (eds.). GeneReviews. Seattle (WA): University of Washington, Seattle. PMID   25577942.
  25. ↑ Synofzik, Matthis; Ilg, Winfried (2014). "Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames". BioMed Research International. 2014: 583507. doi: 10.1155/2014/583507 . PMC   4022207 . PMID   24877117.
  26. ↑ "Archived copy". Archived from the original on 2016-11-19. Retrieved 2017-01-26.{{cite web}}: CS1 maint: archived copy as title (link)
  27. ↑ "Bioblast Announces Phase 2a Results of Trehalose in Patients with Spinocerebellar Ataxia Type 3 (SCA3)". Investors Hub. Retrieved 14 October 2017.
  28. ↑ "The Orphan Genetic Disease Company: Bioblast Pharma Ltd. June 2016" (PDF). Bioblast Pharma Ltd. Retrieved 14 October 2017.
  29. ↑ Veritas, Gene (17 August 2013). "RNA Interference for Treating Huntington's Disease: An Interview with Dr. Beverly Davidson". Vimeo. Retrieved 14 October 2017.
  30. ↑ Keiser, M. S.; Kordower, J. H.; Gonzalez-Alegre, P; Davidson, B. L. (2015). "Broad distribution of ataxin 1 silencing in rhesus cerebella for spinocerebellar ataxia type 1 therapy". Brain. 138 (12): 3555–3566. doi:10.1093/brain/awv292. PMC   4840549 . PMID   26490326.
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  38. ↑ Schniepp, Roman; Strupp, Michael; Wuehr, Max; Jahn, Klaus; Dieterich, Marianne; Brandt, Thomas; Feil, Katharina (December 2016). "Acetyl-DL-leucine improves gait variability in patients with cerebellar ataxia—a case series". Cerebellum & Ataxias. 3 (1): 8. doi: 10.1186/s40673-016-0046-2 . PMC   4828858 . PMID   27073690.
  39. ↑ Clinical trial number NCT03759678 for "N-Acetyl-L-Leucine for Ataxia-Telangiectasia (A-T)" at ClinicalTrials.gov
  40. ↑ Clinical trial number NCT03759639 for "N-Acetyl-L-Leucine for Niemann-Pick Disease, Type C (NPC)" at ClinicalTrials.gov
  41. ↑ Clinical trial number NCT03759665 for "N-Acetyl-L-Leucine for GM2 Gangliosdisosis (Tay-Sachs and Sandhoff Disease)" at ClinicalTrials.gov
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  44. ↑ Synofzik, Matthis; Ilg, Winfried (2014). "Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames". BioMed Research International. 2014: 583507. doi: 10.1155/2014/583507 . PMC   4022207 . PMID   24877117.
  45. ↑ Marsden, J.; Harris, C. (2011). "Cerebellar ataxia: Pathophysiology and rehabilitation". Clinical Rehabilitation. 25 (3): 195–216. doi:10.1177/0269215510382495. PMID   21321055. S2CID   40374830.
  46. ↑ "SCA2 information sheet from www.ataxia.org" (PDF). Archived from the original (PDF) on 2012-07-12. Retrieved 2012-05-10.
  47. ↑ Trujillo-Martín, M.Mar; Serrano-Aguilar, Pedro; Monton-Álvarez, Fernando; Carrillo-Fumero, Romen (2009). "Effectiveness and safety of treatments for degenerative ataxias: A systematic review". Movement Disorders. 24 (8): 1111–24. doi:10.1002/mds.22564. PMID   19412936. S2CID   11008654.
  48. ↑ Miyai, I.; Ito, M.; Hattori, N.; Mihara, M.; Hatakenaka, M.; Yagura, H.; Sobue, G.; Nishizawa, M.; Cerebellar Ataxia Rehabilitation Trialists Collaboration (2011). "Cerebellar Ataxia Rehabilitation Trial in Degenerative Cerebellar Diseases". Neurorehabilitation and Neural Repair. 26 (5): 515–22. doi: 10.1177/1545968311425918 . PMID   22140200. S2CID   23764699.

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