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 [1] [2] [3] [4]. 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) [3] [4] [5], 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 [1] [6]. 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 [3] [4]. 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 [3] [4] [5]. Some reports have identified cognitive dysfunction (memory impairment, defects in executive functioning) and focal dystonias (writer's cramp) in the clinical presentation [4] [5]. 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 [3].

• Difficulty Walking

  People between 18 and 65 years of age with SCA1 who have only difficulty walking or who have difficulty walking as well as tremor, hand incoordination or speech problems, may be eligible for this study. [clinicaltrials.gov]

  Signs and symptoms of AT can include: difficulty walking – most children need to use a wheelchair by 10 years of age increasingly slurred, slow and unclear speech (dysarthria) difficulty swallowing (dysphagia) small spider-like clusters of red blood vessels [nhs.uk]

• Developmental Disorder

  We conducted sensitivity analyses for Aim 2 that expanded the definition of a negative family history as also excluding family history of developmental disorder or early death. [doi.org]

• Aspiration

  The mean number of aspiration pneumonia events per month prior to the DPEJ placement was 3.39 and postplacement was 0.42 ( P < .001). DPEJ placement appears to decrease recurrent aspiration pneumonia in patients with history of aspiration pneumonia. [doi.org]

  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]

• Abnormal Eye Movement

  Ileok Jung and Ji-Soo Kim, Abnormal Eye Movements in Parkinsonism and Movement Disorders, Journal of Movement Disorders, 10.14802/jmd.18034, 12, 1, (1-13), (2019). [doi.org]

  This form of hereditary cerebellar ataxia was clinically distinct from that described by Friedreich and was characterized by adult onset, abnormal eye movements, increased tendon reflexes, marked atrophy of the cerebellum and an autosomal dominant inheritance [scielo.br]

  In addition to ataxia, an abnormal eye movement known as nystagmus may appear on the neurological examination. SCA7 SCA7 only comprises 2 to 5 percent of autosomal dominant spinocerebellar ataxias. [verywell.com]

• Incontinence

  […] stiffness and cramps loss of sensation in the hands and feet (peripheral neuropathy) memory loss and difficulties with spoken language slow eye movement, which means people have to move their head to compensate reduced bladder control (urinary urgency or incontinence [nhs.uk]

• Ataxia

  A family with spinocerebellar ataxia type 8 expansion and vitamin E deficiency ataxia [18]. [wikigenes.org]

  Abstract Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by expansion of a CAG trinucleotide repeat.We analyzed CAG repeat expansion in 25 families in the northeast of Japan with hereditary ataxia of Menzel type. [neurology.org]

  Cerebellar ataxia was found in 25 individuals belonging only to the former community (7.2%). [doi.org]

  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]

• Cerebellar Ataxia

  Cerebellar ataxia was found in 25 individuals belonging only to the former community (7.2%). [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]

  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]

• Nystagmus

  All patients underwent a video‐oculographic recording of fixation abnormalities, gaze‐evoked nystagmus, positional and head‐shaking nystagmus, and dysmetric saccades. [doi.org]

  All patients underwent a video-oculographic recording of fixation abnormalities, gaze-evoked nystagmus, positional and head-shaking nystagmus, and dysmetric saccades. [ncbi.nlm.nih.gov]

  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]

  Spinocerebellar ataxia 1 See the list below: Clinical features Onset in the fourth decade of life Gait ataxia, dysarthria, dysmetria, nystagmus, peripheral neuropathy, muscle wasting, and dystonia in late stages of the disease Gain of function mutation [emedicine.com]

• Tremor

  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]

  Rating Scale: Part A Tremor location/severity rating Part B Handwriting and drawings Part C Functional disabilities resulting from tremor Questionnaires related to sleep, depression (Beck Depression Inventory) (BDI), alertness (Computerized Continuous [clinicaltrials.gov]

  A slowly progressive cerebellar syndrome with various combinations of oculomotor disorders, dysarthria, dysmetria/kinetic tremor, and ataxic gait are key presenting features. [emedicine.com]

  Tremor in SCA-12 might respond to medications used for essential tremor. SCA12 is caused by a repeat expansion. If both genes have 4-32 repeats, then the individual does not have SCA12. [ataxiacenter.umn.edu]

• Cerebellar Disease

  Duration of disease was similar in the Huntington’s disease and degenerative cerebellar diseases groups. [doi.org]

  NOTE: THE ROMBERG TEST IS NOT A SIGN OF CEREBELLAR DISEASE. It is a sign of a disturbance of proprioception, either from neuropathy or posterior column disease. The patient does not know where their joint is in space and so uses their eyes. [stanfordmedicine25.stanford.edu]

  Hereditary cerebellar ataxia NOS Hereditary cerebellar degeneration Hereditary cerebellar disease Hereditary cerebellar syndrome specified NEC G11.8 ICD-10-CM Codes Adjacent To G11.8 G07 Intracranial and intraspinal abscess and granuloma in diseases [icd10data.com]

Because of the rare occurrence of spinocerebellar ataxia type 1 in clinical practice (1-2 per 100,000 individuals) [5], 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 [3], 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 [3] [5]. 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 [3] [5].

• MRI Shows Cerebellar Atrophy

  […] are described on brain MRI: pure cerebellar atrophy, olivopontocerebellar atrophy, and global brain atrophy. [emedicine.com]

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]

[…] 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]

However, multiple potential therapeutic methods are under investigation and show promising implications for clinical implementation including RNAi suppression of the mutant gene and stem cell treatments. Bibliography 1. Orr, HT. [neurowiki2014.wikidot.com]

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]

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]

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]

Consequently, they are often approached together in epidemiological studies. [doi.org]

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]

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]

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]

The CAG-polyglutamine repeat diseases: a clinical, molecular, genetic, and pathophysiologic nosology Stoyas CA, La Spada AR Handbook of clinical neurology, 2018, 147, p 143 Coronary adventitial cells are linked to perivascular cardiac fibrosis via TGFbeta1 [myobase.org]

Therefore, synthesis and review of research from the SCA1 field is valuable for future clinical and diagnostic work in the treatment and prevention of SCA1. [ncbi.nlm.nih.gov]

1. 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.
2. 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.
3. Paulson HL. The Spinocerebellar Ataxias. J Neuroophthalmol. 2009;29(3):227-237.
4. 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.
5. Subramony SH, Ashizawa T. Spinocerebellar Ataxia Type 1. 1998 Oct 1 [Updated 2014 Jul 3]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
6. 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.