Spinocerebellar ataxia type 1 is an autosomal dominant genetic disease in which progressive central nervous system degeneration (primarily of the cerebellum) results in the appearance of gait disorders, dysarthria, and severe motor impairment. The severity of the disorder and clinical progression markedly varies from patient to patient. The diagnosis is made on clinical grounds, findings obtained from a detailed family history, and genetic testing to confirm ataxin-1 mutations.
Spinocerebellar ataxias (SCAs) are a group of more than 40 distinct disorders of progressive neuronal degeneration, principally involving the cerebellum and the motor tracts involved in signaling to and from this part of the central nervous system    . Each type arises due to a specific genetic mutation and in the case of spinocerebellar ataxia type 1 (SCA1), the ataxin-1 gene (located on chromosome 6) is expanded by trinucleotide repeats (CAG)   , which through still unexplained mechanisms, leads to a variable degree of central nervous system damage. The onset of symptoms is reported to be around 30-40 years of age in the majority of patients, while gender predilection has not been established  . Symptoms related to the function of the cerebellum are the cornerstone of spinocerebellar ataxia type 1, with the inability to control body movements (ataxia) resulting in gait impairment and an improper balance being the main complaints  . In addition, dysarthria and ocular symptoms (diplopia, difficulties with focusing objects, saccadic nystagmus, gaze palsies, blepharospasm, and ptosis) are frequently encountered in this patient population   . Some reports have identified cognitive dysfunction (memory impairment, defects in executive functioning) and focal dystonias (writer's cramp) in the clinical presentation  . Unfortunately, ataxia eventually affects all four limbs and necessitates the use of wheelchairs within 15-20 years in virtually all individuals who suffer from this condition .
Jaw & Teeth
- Eye Movements Abnormal
Schmahmann, Eye Movement Abnormalities Are Ubiquitous in the Spinocerebellar Ataxias, The Cerebellum, 10.1007/s12311-019-01044-2, (2019). [doi.org]
Eye movement abnormalities correlate with genotype in autosomal dominant cerebellar ataxia type I. Ann Neurol. 1998 Mar;43(3):297-302. Review. Stricker S, Oberwahrenbrock T, Zimmermann H, Schroeter J, Endres M, Brandt AU, Paul F. [disorders.eyes.arizona.edu]
movements abnormal: SCA 6 ; 26 ; 30 ; 37 Maculopathy (Visual loss): SCA 7 Pseudoexophthalmos: SCA 1, 2, 3 Ptosis: SCA 7, 28 Oculomotor apraxia: Saccades slow Orthostatism ; Recessive Motor Motor neuron & Fasciculations: SCA 3, 36 Cramps: 2, 3 UMN signs [neuromuscular.wustl.edu]
movement abnormalities Axial myoclonus, dystonia, vibratory loss Late onset can be pure ataxia -- 19q13.4 Protein kinase C gamma type (PRKC) Spinocerebellar ataxia (SCA15/SCA 16) OMIM #606658 Pure ataxia with slow progression Tremor Mutations or deletions [emedicine.com]
We describe the unusual case of a 51-year-old woman with spinocerebellar ataxia type 1 (SCA1) who showed choreiform movements in addition to cerebellar ataxia. [ncbi.nlm.nih.gov]
Sørensen, The molecular diagnosis of spinocerebellar ataxia type 1 in patients with ataxia, European Journal of Neurology, 4, 6, (586), (1997). James F. Gusella, Francesca Persichetti and Marcy E. [doi.org]
- Cerebellar Ataxia
Cerebellar ataxia was found in 25 individuals belonging only to the former community (7.2%). [ncbi.nlm.nih.gov]
The results were correlated with the disease duration and severity of the clinical deficit assessed with the International Cerebellar Ataxia Rating Scale (ICARS) and Inherited Ataxia Clinical Rating Scale (IACRS). [doi.org]
All patients underwent a video‐oculographic recording of fixation abnormalities, gaze‐evoked nystagmus, positional and head‐shaking nystagmus, and dysmetric saccades. [doi.org]
Disease definition Spinocerebellar ataxia type 1 (SCA1) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term) characterized by dysarthria, writing difficulties, limb ataxia, and commonly nystagmus and saccadic abnormalities [orpha.net]
Neurological examination 5 years after onset revealed slow eye movement with nystagmus as well as limb and truncal ataxia. Magnetic resonance imaging showed atrophy of the cerebellum and brainstem. [ncbi.nlm.nih.gov]
Among SCA2 patients, bradykinesia was the most frequent (35.3%), followed by reduced facial expression, postural tremor and dystonia (29.4% each), rest tremor, titubation and rigidity (23.5% each), and lip/jaw tremor and chorea (11.8% each). [ncbi.nlm.nih.gov]
Rarely, rigidity, tremors, and involuntary jerking movements (chorea) have been reported in people who have been affected for many years. [ghr.nlm.nih.gov]
There was no evidence of dystonia at rest or extrapyramidal manifestations such as bradykinesia, rigidity, or tremor in any other part of the body. [ruralneuropractice.com]
Characteristic features of SCA1 such as dysphagia, pale discs, intention tremor and pyramidal signs were present in the four SCA1 individuals with short expansions (mean age was 71.0 13.1 years). [doi.org]
- Cerebellar Disease
Frohman, Neuro-ophthalmic Manifestations of Cerebellar Disease, Neurologic Clinics, 10.1016/j.ncl.2014.07.002, 32, 4, (1009-1080), (2014). Angela Jinsook Oh, Tiffany Chen, Mohammad Ali Shariati, Naz Jehangir, Thomas N. [doi.org]
However in cerebellar disease this response is completely absent causing to limb to continue moving in the desired direction. (Be careful that you protect the patient from the unarrested movement causing them to strike themselves.) [stanfordmedicine25.stanford.edu]
Long-term effects of coordinative training in degenerative cerebellar disease. [ncbi.nlm.nih.gov]
Because of the rare occurrence of spinocerebellar ataxia type 1 in clinical practice (1-2 per 100,000 individuals) , the diagnosis may be difficult to establish without a comprehensive clinical investigation. One of the most important components of the workup is a thorough patient history, during which the familial presence of symptoms can be the first sign pointing toward an inherited disorder. The age of onset, as well as the progression of symptoms, should be noted. A detailed physical examination must follow and the physician must particularly focus on the neurological exam and evaluation of the cerebellum. A wide stance, gait difficulties, and tremor (intentional) on finger-nose testing are some of the main findings in patients with spinocerebellar ataxia type 1 , whereas assessment of speech and eye movement to identify dysarthria and associated anomalies, respectively, are equally important steps. Once sufficient evidence toward this disorder is attained, genetic testing may be indicated  . Confirmation of trinucleotide repeats on the ataxin-1 gene through various molecular methods are a definite measure for establishing a diagnosis of spinocerebellar ataxia type 1  .
[…] of Spinocerebellar Ataxia Medical research yet now unable to discover the curative treatment for spinocerebellar ataxia, even the available treatment is not able to control the disease progression. [healthsaline.com]
Research to develop treatments is ongoing and in addition to conventional pharmaceutical treatment, SCA1 has been the subject of research into more advanced treatment options such as gene therapy and stem cell therapy. [en.wikipedia.org]
Moreover, these studies will pave the way for nanomedicine based treatments to be used to replace other neurotrophic factors, with broad ramifications for potential therapies for many diseases. [grantome.com]
We occasionally observe long-term remission of cervical dystonia after several botulinum toxin treatments. However, botulinum toxin transiently acts on neuromuscular junctions. [ncbi.nlm.nih.gov]
Abstract We occasionally observe long-term remission of cervical dystonia after several botulinum toxin treatments. However, botulinum toxin transiently acts on neuromuscular junctions. [doi.org]
Prognosis Prognosis is poor. In the late stages of the disease, usually 10 to 15 years following onset, bulbar dysfunction secondary to affection of lower medullary nuclei results in aspiration which is life-threatening. [orpha.net]
The prognosis is bleak, with a gradual progression to disability and death within 10-20 years. Ref: Orr, H.T. et al. (1993). Expansion of an unstable CAG trinucleotide repeat in spinocerebellar ataxia type I. Nature Genet. 4, 221-26. [gpnotebook.co.uk]
Etiology SCA1 is caused by CAG repeat expansions in the ATXN1 gene region on chromosome 6p23. Prognosis Prognosis is poor. [orpha.net]
Given that these were cases of sporadic ataxia, acquired causes would be predicted to be more common etiologies in this population (Fogel and Perlman, 2006 ; Klockgether, 2010 ; Fogel and Perlman, 2011 ). [doi.org]
Summary Epidemiology Prevalence is estimated to be 1-2 in 100,000 with significant geographical and ethnic variations. Clinical description The disease typically presents in the 4th decade (age range 4-74 years). [orpha.net]
An epidemiological study of cerebellar ataxia was done in two villages in the Indian state of Tamilnadu where its prevalence was observed to be high. All the people were screened and the clinical characteristics of those with ataxia were recorded. [ncbi.nlm.nih.gov]
This suggests a possible pathophysiologic relationship between SCA1 and familial occurrence of spontaneous pneumothorax. [ncbi.nlm.nih.gov]
However, both the sporadic and inherited cases of cerebellar ataxia exhibit common pathophysiological characteristics such as the specific degeneration of the main cerebellar neurons; the Purkinje cells. [neurodegenerationresearch.eu]
Ruegsegger C et al (2016) Impaired mTORC1-dependent expression of homer-3 influences SCA1 pathophysiology. Neuron 89(1):129–146 CrossRef Google Scholar 25. [doi.org]
Clinical, genetic, molecular, and pathophysiological insights into spinocerebellar ataxia type 1. Cerebellum. 2008;7(2):106-14. doi: 10.1007/s12311-008-0009-0. Review. Zoghbi HY, Orr HT. [ghr.nlm.nih.gov]
Notably, MitoQ slowed down the appearance of SCA1-linked neuropathology such as lack of motor coordination as well as prevented oxidative stress-induced DNA damage and PC loss. [ncbi.nlm.nih.gov]
- Ashizawa T, Figueroa KP, Perlman SL, et al. Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study. Orphanet J Rare Dis. 2013;8:177.
- Rüb U, Bürk K, Timmann D, et al. Spinocerebellar ataxia type 1 (SCA1): new pathoanatomical and clinico-pathological insights. Neuropathol Appl Neurobiol. 2012;38(7):665-680.
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- Khwaja GA, Srivastava A, Ghuge VV, Chaudhry N. Writer’s cramp in spinocerebellar ataxia Type 1. J Neurosci Rural Pract. 2016;7(4):584-586.
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- Jacobi H, Bauer P, Giunti P, et al. The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: A 2-year follow-up study. Neurology. 2011;77(11):1035-1041.