Disease relevance of Cerebellar Ataxia

• In 1891, Luigi Luciani published his famous monograph on the cerebellum and formulated his triad of the cerebellar symptoms: atonia, asthenia and astasia, which explained all troubles provoked by cerebellar lesions; later he added a fourth sign, dysmetria [1].
• They consisted of tremor, hyperreflexia, dysmetria, unsteady gait, and dizziness [2].
• Recurrence of the T666M calcium channel CACNA1A gene mutation in familial hemiplegic migraine with progressive cerebellar ataxia [3].
• X-linked sideroblastic anemia and ataxia (XLSA/A) is a recessive disorder characterized by an infantile to early childhood onset of non-progressive cerebellar ataxia and mild anemia with hypochromia and microcytosis [4].
• Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1; MIM 254800) is an autosomal recessive disorder characterized by seizures, myoclonus and progression to cerebellar ataxia [5].

Psychiatry related information on Cerebellar Ataxia

• We performed a study of the distribution of PrP27-30, the proteinase-K-resistant form of prion protein, in the central and peripheral nervous system of a patient with a Glu200Lys mutation of the prion protein gene, cerebellar ataxia, subcortical dementia, rigidity, and demyelinating peripheral neuropathy [6].
• We have tested the role of PAX6 mutations in three families with Gillespie syndrome, a rare autosomal recessive condition consisting of partial aniridia, cerebellar ataxia, and mental retardation [7].
• Familial Creutzfeldt-Jakob disease with D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia [8].
• Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is an autosomal recessive form of cerebellar ataxia that occurs most commonly in Japan but is also frequently seen in Europe. This disease is caused by mutations in the aprataxin gene, but the functions of the gene product and the pathogenic mechanism remain unclear [9].
• These disorders include hypotonia, developmental delay, learning disorders and ADHD, headache, and cerebellar ataxia [10].

High impact information on Cerebellar Ataxia

• Large, expanded repeats in SCA8 are not confined to patients with cerebellar ataxia [11].
• Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel [12].
• The gene for autosomal dominant cerebellar ataxia with pigmentary macular dystrophy maps to chromosome 3p12-p21.1 [13].
• Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1; MIM 254800) is an autosomal recessive disorder with onset between 6 and 13 years followed by variable progression to mental deterioration and cerebellar ataxia [14].
• Treatment of cerebellar ataxia with buspirone: a double-blind study [15].

Chemical compound and disease context of Cerebellar Ataxia

• Cerebrospinal fluid gamma-aminobutyric acid variations in cerebellar ataxia [16].
• Acetazolamide responsive hereditary paroxysmal cerebellar ataxia (APCA) is a rare autosomal dominant disorder characterized by attacks of cerebellar ataxia and dysarthria with normal or near normal neurologic function between attacks [17].
• Autosomal dominant cerebellar ataxia with progressive macular degeneration is caused by a CAG/glutamine repeat expansion in the SCA7 gene/protein [18].
• Persistent cerebellar ataxia after exposure to toluene [19].
• Using these two tracers, the integrity of the presynaptic striatal dopaminergic system has been studied with positron emission tomography (PET) in 10 subjects with multiple system atrophy (MSA, Shy-Drager syndrome) who had an akinetic-rigid syndrome that was poorly responsive to L-dopa, autonomic failure, and cerebellar ataxia [20].

Biological context of Cerebellar Ataxia

• The prevalence and wide clinical spectrum of the spinocerebellar ataxia type 2 trinucleotide repeat in patients with autosomal dominant cerebellar ataxia [21].
• Missense mutations in the regulatory domain of PKC gamma: a new mechanism for dominant nonepisodic cerebellar ataxia [22].
• Forty-one patients suffering from autosomal dominant cerebellar ataxia type I (ADCA-I) were subjected to a genotype-phenotype correlation analysis using molecular genetic assignment to the spinocerebellar ataxia type 1, 2 or 3 (SCA1, -2 or -3) genetic locus, clinical examination and nerve conduction as well as evoked potential studies [23].
• The combination of cerebellar ataxia, dystonia, abnormal eye movements, and prominent eyes has been reported only in ADMSD [24].
• OBJECTIVE: To search for mutations in the calcium channel gene CACNA1A and to study the genotype-phenotype correlation in a family with a severe familial hemiplegic migraine (FHM) phenotype and a slowly progressive cerebellar ataxia [25].

Anatomical context of Cerebellar Ataxia

• Otolith function in cerebellar ataxia due to mutations in the calcium channel gene CACNA1A [26].
• SCA-6 has recently been identified genetically and characterized as pure cerebellar ataxia that affects the cerebellar cortex selectively [27].
• The GAD-Ab levels of the three patients with cerebellar ataxia were compared with those of five with SMS, 49 with IDDM, 64 with cerebellar ataxia of probable degenerative origin without associated autoimmune features, 14 non-IDDM islet cell antibody-positive first-degree relatives of IDDM patients, and 91 normal subjects [28].
• Three siblings in their sixth and seventh decade with hexosaminidase A and B deficiency (adult form of GM2-gangliosidosis, variant O) developed early and severe sensory loss in addition to chronic motor neuron disease and cerebellar ataxia [29].
• T-cell reactivity to glutamic acid decarboxylase in stiff-man syndrome and cerebellar ataxia associated with polyendocrine autoimmunity [30].

Gene context of Cerebellar Ataxia

• Two genes implicated in the disease, SCA1 (spinal cerebellar ataxia 1) and SCA2, are already localized [31].
• Frequency analysis of autosomal dominant cerebellar ataxias in Taiwanese patients and clinical and molecular characterization of spinocerebellar ataxia type 6 [32].
• RESULTS: Two patients carried FMR1 premutations of 110 and 135 repeats: a man with a familial form of cerebellar ataxia and a woman diagnosed as having MSA-cerebellar type [33].
• Identification of a novel SCA locus ( SCA19) in a Dutch autosomal dominant cerebellar ataxia family on chromosome region 1p21-q21 [34].
• Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant cerebellar ataxia associated with the expansion of an unstable CAG repeat in the 5' region of the PPP2R2B gene on chromosome 5q31-5q32 [35].

Analytical, diagnostic and therapeutic context of Cerebellar Ataxia

• Reevaluation of the exact CAG repeat length in hereditary cerebellar ataxias using highly denaturing conditions and long PCR [36].
• CONCLUSION: Intravenous immunoglobulin therapy is worth considering in acute cerebellar ataxia that does not respond to high-dose steroid therapy [37].
• We performed a double-blind cross-over study with amantadine hydrochloride in 12 patients with Friedreich's disease and 2 with autosomal dominant cerebellar ataxia [38].
• We present an unusual case of cerebellar ataxia in a 2 year old girl several days after treatment with piperazine citrate for suspected worm infestation [39].
• The neurological examination was consistent with cervical myelopathy: upper thoracic spinothalamic sensory level (83%), hyperreflexia (64%), inversion of the radial periosteal reflex (57%), positive Romberg sign (28%), ankle clonus (25%), positive Hoffman sign (26%), impaired tandem walk (23%), dysmetria (15%) and dysdiadochokinesia (13%) [40].

References