Paroxysmal Cerebellar Ataxia Research Articles

СЛУЧАЙ ИЗ ПРАКТИКИ: ЭПИЗОДИЧЕСКАЯ ПАРОКСИЗМАЛЬНАЯ МОЗЖЕЧКОВАЯ АТАКСИЯ 2 ТИПА

Instability walking is a fairly common complaint made by patients who come to be examined by a neurologist in polyclinics and hospitals. From a medical point of view, this symptom is included in the concept of "ataxia". Neurologists distinguish four types of ataxia depending on the localization of the pathological process: cortical, cerebellar, vestibular, and sensitive. There are often combinations of different types of ataxia in the same patient, for example, cortical-vestibular, sensitive-cerebellar. In addition to establishing the variant of the atactic syndrome, there is an urgent question of verifying the etiological factor that led to this pathology. Pathological heredity becomes the least obvious. In this article, we draw attention to a similar case from practice in order to form the alertness of doctors regarding hereditary coordination disorders. Episodic ataxia is a group of rare hereditary diseases of the nervous system, the main clinical manifestation of which are paroxysms of cerebellar ataxia of varying duration and frequency. The most studied from a genetic and clinical point of view are episodic cerebellar ataxia of the first and second types. The authors present a clinical case of episodic paroxysmal cerebellar ataxia type 2 in a 22-year-old patient. The diagnosis of the disease was based on a typical clinical picture and confirmed by a molecular genetic study that revealed a mutation in the CACNA1A gene. The article discusses aspects of the pathogenesis of the main forms of episodic paroxysmal ataxia, age of onset, frequency and duration of seizures, features of the clinical picture, neurological status. This clinical observation draws the attention of practitioners to the possibilities of modern methods of molecular genetic diagnosis and treatment of these conditions.

Autoimmune episodic ataxia in patients with anti-CASPR2 antibody-associated encephalitis.

Objective:To report paroxysmal episodes of cerebellar ataxia in a patient with anti–contactin-associated protein-like 2 (CASPR2) antibody-related autoimmune encephalitis and to search for similar paroxysmal ataxia in a cohort of patients with anti–CASPR2 antibody-associated autoimmune encephalitis.Methods:We report a patient with paroxysmal episodes of cerebellar ataxia observed during autoimmune encephalitis with anti-CASPR2 antibodies. In addition, clinical analysis was performed in a retrospective cohort of 37 patients with anti-CASPR2 antibodies to search for transient episodes of ataxia. Paroxysmal symptoms were further specified from the referral physicians, the patients, or their relatives.Results:A 61-year-old man with limbic encephalitis and anti-CASPR2 antibodies developed stereotyped paroxysmal episodes of cerebellar ataxia, including gait imbalance, dysarthria, and dysmetria, 1 month after the onset of the encephalitis. The ataxic episodes were specifically triggered by orthostatism and emotions. Both limbic symptoms and transient ataxic episodes resolved after treatment with steroids and IV cyclophosphamide. Among 37 other patients with anti-CASPR2 antibodies, we identified 5 additional cases with similar paroxysmal ataxic episodes that included gait imbalance (5 cases), slurred speech (3 cases), limb dysmetria (3 cases), and nystagmus (1 case). All had concomitant limbic encephalitis. Paroxysmal ataxia was not observed in patients with neuromyotonia or Morvan syndrome. Triggering factors (orthostatism or anger) were reported in 4 patients. Episodes resolved with immunomodulatory treatments in 4 patients and spontaneously in 1 case.Conclusions:Paroxysmal cerebellar ataxia must be added to the spectrum of the anti-CASPR2 antibody syndrome.

Acetazolamide responsive episodic ataxia treated with methazolamide: a case report

Acetazolamide-responsive ataxia is a rare episodic ataxia (EA) disorder characterized by paroxysmal cerebellar ataxia. Many of the symptoms with EA can be treated with the carbonic anhydrase inhibitor acetazolamide. EA is a family of channelopathies each with its own unique mutation. We report a case of EA treated with methlazolamide in a 37 year old man who experienced dysguesia with acetazolamide. Methazolamide has higher rates of diffusion into the tissue and a longer half-life compared with acetazolamide. It should be considered for episodic ataxia.

New calcium channel mutations predict aberrant RNA splicing in episodic ataxia

Episodic ataxia type 2 (EA2) is an autosomal dominant channelopathy characterized by paroxysmal cerebellar ataxia. Previous studies suggest that most EA2 cases are associated with mutations in the alpha1A subunit of the P/Q-type voltage-gated calcium channel gene CACNA1A. In a UK national study, the authors analyzed 15 index cases with typical EA2 and identified two unreported intronic mutations that predict aberrant splicing.

Episodic ataxia type 2

Episodic ataxia type 2 is an autosomal dominant paroxysmal cerebellar ataxia characterized by acetazolamide-responsive recurrent attacks with interictal nystagmus. This disease is caused by mutations (mainly truncating mutation) within the alpha1(A) subunit of P/Q type voltage-dependent calcium channel gene, CACNA1A. Further researches would establish the genotype/phenotype correlation and clarify the mechanism of this disorder.

Sporadic late onset paroxysmal cerebellar ataxia in four unrelated patients: a new disease?

We describe a peculiar form of late onset paroxysmal cerebellar ataxia including clinical features similar to episodic ataxia type 2 (EA2) but unresponsive to acetazolamide. Four unrelated patients were clinically investigated. Neuropathological examination was performed in one patient and molecular analysis in all four. All 47 exons of CACNA1A were screened by a combination of single-strand conformer polymorphism and sequencing analysis in three patients. In addition, the length of the CAG repeat was determined in all four patients. The four patients were in their 60s at the onset of the disease, which was characterized by cerebellar ataxia attacks lasting from a few minutes to 1-2 h and occurring mainly in the morning. In the interictal period a nystagmus was present together with a slowly progressive cerebellar ataxia over the years. The neuropathological examination disclosed a dramatic loss of Purkinje cells mainly in the vermis. Moreover, certain cerebellar granular neurons had a strong cytoplasmic staining at immunopathological examination with an anti-tau protein serum. Search for truncating mutations or CAG repeat expansion in CACNA1A was negative. This late-onset paroxysmal cerebellar ataxia with neuropathological lesions restricted to Purkinje cells and with negative results both for truncating mutations and CAG expansion in the CACNA1A gene represents a new entity. Further studies are needed to delineate the underlying process.

Familial hemiplegic migraine, nystagmus, and cerebellar atrophy

Familial hemiplegic migraine (FHM) is an autosomal dominant disorder characterized by transient hemiplegia during the aura phase of a migraine attack. Nystagmus has been reported in individuals affected with this disorder, but the origin of the ocular motility findings is unknown. A three-generation family with FHM is described and clinical histories are outlined. Ocular motility evaluations were performed on 7 family members, 5 with a history of hemiplegic migraine and 2 without history of migraine. All affected family members had abnormal eye movements consistent with vestibulocerebellar dysfunction. Magnetic resonance imaging scans in affected family members revealed cerebellar vermian atrophy. DNA linkage analysis revealed a common marker in all the affected family members on chromosome 19. We suggest that the hemiplegic migraine attacks and the cerebellar degeneration are linked genetically and that the eye movements are not the ischemic sequelae of recurrent migraine. Strikingly similar ocular motility findings and cerebellar degeneration are reported in both FHM and a genetically related disorder, hereditary paroxysmal cerebellar ataxia (HPCA). The significance of these similarities is discussed along with a proposed pathophysiology for FHM.

A gene for hereditary paroxysmal cerebellar ataxia maps to chromosome 19p

Hereditary paroxysmal cerebellar ataxia (HPCA) is an autosomal dominant disorder characterized by the recurrence of intermittent attacks of vestibulocerebellar ataxia lasting from 15 minutes to a few days. The number of attacks is often significantly decreased by acetazolamide treatment. Neurological examination shows a permanent gaze-evoked nystagmus, as well as a mild cerebellar ataxia in most patients. The paroxysmal feature of this condition is shared by another autosomal dominant neurological condition, familial hemiplegic migraine (FHM), a condition in which permanent cerebellar signs have also been reported in some families. Although hemiplegic migraine has never been reported in patients with HPCA, we hypothesized, based on the latter observations, that HPCA and FHM may be allelic disorders. We previously mapped a gene responsible for FHM on the short arm of chromosome 19. We performed linkage analysis with 6 markers spanning the FHM interval on a large HPCA family. Significant lod scores were obtained with 3 markers: D19S244 (LS = 3.71), D19S221 (3.60), and D19S226 (3.54) at theta = 0. Haplotype and multipoint linkage analysis established that the most likely location was the same interval of 30 cM encompassing the chromosome 19 FHM locus.

Mapping the gene for acetazolamide responsive hereditary paryoxysmal cerebellar ataxia to chromosome 19p.

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. A genome-wide search using polymorphic di- and tri-nucleotide repeats was initiated and the APCA locus was found to be linked to the short arm of chromosome 19 in two large kindreds. The microsatellite marker UT705 was found to be linked to the APCA locus with two point analysis yielding a maximum lod score of 8.20 at theta max = 0.000 in a five generation pedigree. Linkage to this region was confirmed in a second kindred. The absence of known candidate genes in the region may necessitate a positional cloning approach in order to identify the gene for this disorder.

Paroxysmal cerebellar ataxia: use of phenytoin as a provocation test

Paroxysmal cerebellar ataxia: use of phenytoin as a provocation test

Paroxysmal cerebellar ataxia

Australian and New Zealand Journal of MedicineVolume 20, Issue 1 p. 103-103 Paroxysmal cerebellar ataxia P. J. GOADSBY, P. J. GOADSBY Clinical Neurophysiology Registrar.Search for more papers by this authorG. BOYCE, G. BOYCE Assistant-in-Neurology, Department of Neurology, The Prince Henry and Prince of Wales Hospitals, Little Bay, NSW.Search for more papers by this author P. J. GOADSBY, P. J. GOADSBY Clinical Neurophysiology Registrar.Search for more papers by this authorG. BOYCE, G. BOYCE Assistant-in-Neurology, Department of Neurology, The Prince Henry and Prince of Wales Hospitals, Little Bay, NSW.Search for more papers by this author First published: February 1990 https://doi.org/10.1111/j.1445-5994.1990.tb00388.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume20, Issue1February 1990Pages 103-103 RelatedInformation