Presentation
We describe three genetically confirmed myoclonus dystonia (M-D) patients and one spinocerebellar ataxia type 14 (SCA14) patient, presenting with a combination of trunk tremor, multifocal myoclonus and axial dystonia as predominant clinical features. [ncbi.nlm.nih.gov]
Onset of permanent gait ataxia – presenting symptom in all but three – varied between 4 and 50 years (mean±SD 38±15y). Five subjects reported minor or episodic motor difficulty of gait or speech already present in childhood. [mdsabstracts.org]
Entire Body System
- Epilepsy
Child Neurology Fellow and epilepsy genetics researcher at the Children’s Hospital of Philadelphia (CHOP), USA and Department of Neuropediatrics, Kiel, Germany [epilepsygenetics.net]
We ascertained 366 unrelated patients with spinocerebellar ataxia, either pure or with associated features such as epilepsy, mental retardation, seizures, paraplegia, and tremor. [ncbi.nlm.nih.gov]
Epilepsy, familial temporal lobe, 1: Leucine-rich, glioma inactivated 1 gene (LGI1); Autosomal dominant nocturnal frontal lobe epilepsy - ADFNLE: Cholinergic receptor, nicotinic, alpha 4 (CHR- NA4) and Cholinergic receptor, nicotinic, beta 2 (CHRNB2 [cnr.it]
Some patients have cognitive impairment, parkinsonism characterized by rigidity, as well as focal dystonia, axial myoclonus, facial myokymia, choreic movement of hands and epilepsy. [orpha.net]
- Movement Disorder
Movement disorders in neurology concern involuntary movements of parts of the body. Many movement disorders are caused by nerve diseases such as Parkinson’s disease. [books.google.de]
(c) 2006 Movement Disorder Society. [ncbi.nlm.nih.gov]
[…] to gait ataxia, including sensory or motor neuropathies, extraocular movement disorders, dystonia, parkinsonism, sleep disorders, autonomic dysfunction, and others. • On occasion the non-ataxic signs may precede the ataxia. • Individuals in the same [medlink.com]
Schnitzler, Institute of Clinical Neuroscience and Medical Psychology / Center for Movement Disorders and Neuromodulation, Heinrich-Heine-University Düsseldorf, Germany • Prof.D Dr. Ricarda I. [fz-juelich.de]
Dementia 17, DRPLA 2, 13, 19, 21 Psychosis DRPLA, 17 3, 27 (Episodic) Epilepsy 10, DRPLA 17 Movement disorders Chorea DRPLA, 17 1 (Late stage) Myoclonus DRPLA 2, 19 Tremor 2, 8, 12 15, 21, 27 Parkinsonism 3, 9, 12, 17 2, 21 Dystonia 3 17 Ocular disorders [neuromuscular.wustl.edu]
- Falling
MANAGEMENT: Treatment of manifestations: Clonazepam or valproic acid to help improve axial myoclonus; canes and walkers to help prevent falls; modification of the home (grab bars, raised toilet seats, ramps for motorized chairs); weighted eating utensils [ncbi.nlm.nih.gov]
Evaluation at 1 month (plus or minus 5 days) and 3 months (plus or minus 5 days) Outcome Measures Primary Outcomes Incidence of side effects Side effect profile Secondary Outcomes Timed-up-and-go test ICARS score SARA score Modified Falls Efficacy Scale [clinicaltrials.gov]
As the risk of falls becomes increasingly apparent with disease progression, it is important that the patient’s safety in day-to-day activity becomes a priority. [10] It may be necessary that the patient be evaluated for appropriate physical aids such [physio-pedia.com]
This falls under the category of genetic anticipation. [ citation needed ] Several types of SCA are characterized by repeat expansion of the trinucleotide sequence CAG in DNA that encodes a polyglutamine repeat tract in protein. [en.wikipedia.org]
[…] in a family with an ADCA that has not been assigned an SCA number. 17 SCA 14 is due to mutation (missense, small deletion, splice site) in the PRKCG gene. 2, 3, 6, 7 Most mutations have been in the cysteine rich region of the gene, and most of these fall [jnnp.bmj.com]
- Asymptomatic
In fact, inflammatory genes were upregulated in cell lines and patient brains of SCA3 [ 8 ], and a secretion of eotaxin was elevated in astrocyte in brains of asymptomatic SCA3 carries [ 9 ]. [karger.com]
The one somatically asymptomatic affected subject was excluded from the neuropsychological group analyses to avoid bias. [bmcneurol.biomedcentral.com]
- Pathologist
Some level of improvement was shown to be maintained 24 weeks post-treatment. [34] Speech language pathologists may use both behavioral intervention strategies as well as augmentative and alternative communication devices to help patients with impaired [en.wikipedia.org]
Gastrointestinal
- Vomiting
[…] 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 [19] ) Mild cerebellar syndrome, dysarthria SCA25 1.5–39 yrs Unknown ataxia with sensory neuropathy, vomiting [en.wikipedia.org]
Eyes
- Abnormal Eye Movement
SCA 16 14 is associated with horizontal gaze evoked nystagmus, but other specific details of eye movement abnormalities are not mentioned. [jnnp.bmj.com]
Egan RA, Camicioli R, Popovich BW: A small 55-repeat MJD1 CAG allele in a patient with Machado-Joseph disease and abnormal eye movements. Eur Neurol 2000; 44: 189-190. [scabase.eu]
Neurologic
- Hyperreflexia
Affiliated tissues include eye, brain and cerebellum, and related phenotypes are progressive cerebellar ataxia and hyperreflexia OMIM : 56 Autosomal recessive spinocerebellar ataxia-14 is a neurologic disorder characterized by delayed psychomotor development [malacards.org]
In addition to cerebellar signs, hyperreflexia and decreased vibration sense are frequently observed. [orpha.net]
All had at least mild hyperreflexia, with evidence of abnormal reflex spread in the upper and/or lower limbs in four of the six subjects. [jnnp.bmj.com]
mild SCA12 (autosomal dominant type 12) 5q31-q33, > 66 CAG repeats in the promotor region, coding for protein phosphatase 2A Tremor, bradykinesia, parkinsonism, dementia, hyperreflexia SCA13 (single French family) 19q13.3-q13.4 (6q27 with CAG repeats [bcm.edu]
FGF14 13q34 SCA35 40-48 years Unknown gait and limb ataxia, dysarthria, ocular dysmetria, intention tremor, pseudobulbar palsy, spasmodic torticollis, extensor plantar responses, reduced proprioception and hyperreflexia China transglutaminase 6 ( TGM6 [en.wikipedia.org]
- Spastic Paraplegia
225 16 Spinal Muscular Atrophy 237 An Update on Animal Models Frataxin Function and Therapies 247 18 Genetics and Pathogenesis of Inherited Ataxias and Spastic Paraplegias 262 9 The Role of Mitochondrial Network Dynamics in the Pathogenesis of CharcotMarieTooth [books.google.de]
Hereditary Spastic Paraplegia Information Page National Institute of Neurological Disorders and Stroke. 2017. USA. Spinocerebellar Ataxia Type 1 ( SCA 1 ) National Ataxia Foundation. 2014. USA. [infoneuro.mcgill.ca]
paraplegia G11.8 Other hereditary ataxias G11.9 Hereditary ataxia, unspecified G12 Spinal muscular atrophy and related syndromes G12.0 Infantile spinal muscular atrophy, type I [Werdnig-Hoffman] G12.1 Other inherited spinal muscular atrophy G12.2 Motor [icd10data.com]
The Global Epidemiology of Hereditary Ataxiaand Spastic Paraplegia: A systematic review of prevalence studies. Neuroepidemiology 2014; 24:174-183. Ashizawa T, Figueroa KP, Perlman SL, et al. [rarediseases.org]
View Article PubMed Google Scholar Erichsen AK, Koht J, Stray-Pedersen A, Abdelnoor M, Tallaksen CM: Prevalence of hereditary ataxia and spastic paraplegia in southeast Norway: a population-based study. [bmcneurol.biomedcentral.com]
- Cerebellar Disease
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]
diseases can be difficult to manage. [7] Unlike ataxia following a stroke, which may permit unaffected, intact areas of the cerebellum to compensate for deteriorating areas, degenerative cerebellar diseases begin to affect essentially all parts of the [physio-pedia.com]
Transcranial direct current stimulation (tDCS) is used to modulate cerebellar function in healthy subjects and patients with cerebellar disease. [dagmar-timmann.de]
"Cerebellar Ataxia Rehabilitation Trial in Degenerative Cerebellar Diseases". Neurorehabilitation and Neural Repair. 26 (5): 515–22. doi : 10.1177/1545968311425918. PMID 22140200. Further reading [ edit ] Bird, Thomas D (23 January 2014). [en.wikipedia.org]
- Dysmetria
Mild or moderate cerebellar ataxia was present in the upper and lower limbs, with all affected patients showing signs of dysmetria, overshoot on ballistic tracking movements, abnormal ramp tracking in the upper limbs, and dyssynergia and dysmetria in [jnnp.bmj.com]
FGF14 13q34 SCA35 40-48 years Unknown gait and limb ataxia, dysarthria, ocular dysmetria, intention tremor, pseudobulbar palsy, spasmodic torticollis, extensor plantar responses, reduced proprioception and hyperreflexia China transglutaminase 6 ( TGM6 [en.wikipedia.org]
During the last two decades there has been a growing interest for the cerebellum’s role also in non-motor functions, with the introduction of the “dysmetria of thought”-hypothesis and the clinically described Cerebellar Cognitive Affective Syndrome (CCAS [bmcneurol.biomedcentral.com]
- Hyporeflexia
dementia SCA22 (one Chinese family) 1q21-q23 Chinese family, age at onset 10-46, gait ataxia, dysarthria, hyporeflexia, slowly progressive pure cerebellar ataxia and atrophy; might be allelic with SCA19 SCA23 (one Dutch family) 20p13-p12.3 Ataxia, decreased [bcm.edu]
SCA 1 is often associated with supranuclear gaze palsy, spasticity, sensory loss, and dysphagia as a reflection of brain stem atrophy. 9 SCA 2 is more usually associated with slow saccades 9 and hyporeflexia. [jnnp.bmj.com]
Treatment
Science & Business Media, 11.03.2010 - 304 Seiten This reference on the state-of-the-art of neuromuscular diseases as a whole offers a current review of inherited neuromuscular diseases under different approaches: genetics, pathomechanisms, therapies and treatments [books.google.de]
Seventeen states have approved medical marijuana for the treatment of spasms, which are commonly associated with spinocerebellar ataxia. [medicalmarijuanainc.com]
Lithium treatment Start treatment and remain in hospital until the blood level of the drug is stabilized; continue treatment at home after hospital discharge. Admission 2 (2-4 days, 4 weeks after hospital discharge). [clinicaltrials.gov]
Treatment of Ataxia There is currently no medicine that specifically treats Ataxia, however the NAF is funding cutting-edge research to develop treatments. [sandiegomagazine.com]
Prognosis
Prognosis Prognosis is good. Some patients need supportive devices such as a cane or wheelchair for gait impairment. However, several affected patients have lived beyond 80 years of age. [orpha.net]
Prognosis - Spinocerebellar ataxia 14 Not supplied. Treatment - Spinocerebellar ataxia 14 Not supplied. Resources - Spinocerebellar ataxia 14 Not supplied. [checkorphan.org]
(See 'Prognosis' above and 'Treatment' above.) SCA3, also known as Machado-Joseph disease, is the most common type of SCA (table 1). SCA types 9 through 36 are rare and less well characterized. [es.slideshare.net]
They most likely affected the clinical severity and also the cause of the poor prognosis. SCA31 is an autosomal dominant disorder with adult onset and a slowly progressive pure cerebellar ataxia. [karger.com]
Etiology
These results indicate that SCA14 mutations make gammaPKC form cytoplasmic aggregates, suggesting the involvement of this property in the etiology of SCA14. [ncbi.nlm.nih.gov]
Beginning with an examination of the cerebellar region, and then progressing to a fresh perspective on the clinical aspects of the various forms of ataxia, this handbook gives clinicians a state-of-the-art reference for the management of the many etiologies [books.google.de]
Etiology SCA14 is caused by missense mutations in the PRKCG gene (19q13.4) encoding protein kinase C gamma (PKC-gamma). Prognosis Prognosis is good. Some patients need supportive devices such as a cane or wheelchair for gait impairment. [orpha.net]
Epidemiology
Summary Epidemiology The disease has been reported in more than twenty families from Europe, the United States, and Australia. [orpha.net]
The Global Epidemiology of Hereditary Ataxiaand Spastic Paraplegia: A systematic review of prevalence studies. Neuroepidemiology 2014; 24:174-183. Ashizawa T, Figueroa KP, Perlman SL, et al. [rarediseases.org]
[…] repeated CAG code only partially explains the effects of MJD. [4] MJD is the most common form of spinocerebellar ataxia (SCA). [4] On a global scale, spinocerebellar ataxia disorders are considered rare with a prevalence of 0.2-0.3 per 100,000. [5] The epidemiology [physio-pedia.com]
Pathophysiology
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 Cajal bodies in neurons Lafarga M, Tapia O, Romero AM, et al. [myobase.org]
Advances in molecular biology are helping to form a better picture of the underlying pathophysiology, and this better understanding has contributed to the development of multiple experimental strategies for symptomatic improvement and to slowing the progression [medlink.com]
"Cerebellar ataxia: Pathophysiology and rehabilitation". Clinical Rehabilitation. 25 (3): 195–216. doi : 10.1177/0269215510382495. PMID 21321055. ^ "SCA2 information sheet from www.ataxia.org" (PDF). Archived from the original (PDF) on 2012-07-12. [en.wikipedia.org]
Prevention
Prevention of secondary complications: Dietary modifications when dysphagia becomes troublesome to reduce the risk for aspiration and maintain caloric intake. Surveillance: Annual evaluation of gait, coordination, and speech. [ncbi.nlm.nih.gov]
Collaborative Meta-Analysis of Randomised Trials of Antiplatelet Therapy for Prevention of Death, Myocardial Infarction, and Stroke in High Risk Patients. [books.google.es]
Prevention - Spinocerebellar ataxia 14 Not supplied. Diagnosis - Spinocerebellar ataxia 14 The signs and symptom information on this page attempts to provide a list of some possible signs and symptoms of Spinocerebellar ataxia 14. [checkorphan.org]