Marcus Vinicius Cristino Albuquerque

Should spinocerebellar ataxias be included in the differential diagnosis for Huntington's diseases-like syndromes?

In this article, we describe three patients with different spinocerebellar ataxia (SCA) subtypes presenting with unusual movement disorders predominantly characterized by choreoathetosis, which, together with their autosomal dominant pattern of inheritance, resembled the Huntington-like syndromes. From a large SCA cohort, we have observed chorea in 1/35 SCA2, 1/112 SCA3/MJD, and 1/30 SCA7 patients. Twenty-eight patients with SCA1, 11 patients with SCA6, and 3 patients with SCA10 were also evaluated, and none of them presented chorea. We provide a brief report of the three cases, with a video demonstrating chorea. Although a debate regarding the frequency of chorea in SCA patients is a fact, its occurrence, together with the autosomal dominant pattern of inheritance, clearly imposes SCA in the differentials of Huntington-like syndromes. There is some debate about what to include in a list of Huntington-like disorders, with several review articles about Huntington-like syndromes not including SCA in the differential diagnosis, except for SCA17. We believe that SCAs-at least SCA1, SCA2, SCA3/MJD, SCA7 and DRPLA-should be thought in the diagnostic workout of at least the atypical cases, such as those presented in this report.

Adult onset sporadic ataxias: a diagnostic challenge

Patients with adult onset non-familial progressive ataxia are classified in sporadic ataxia group. There are several disease categories that may manifest with sporadic ataxia: toxic causes, immune-mediated ataxias, vitamin deficiency, infectious diseases, degenerative disorders and even genetic conditions. Considering heterogeneity in the clinical spectrum of sporadic ataxias, the correct diagnosis remains a clinical challenge. In this review, the different disease categories that lead to sporadic ataxia with adult onset are discussed with special emphasis on their clinical and neuroimaging features, and diagnostic criteria.

SCA1 patients may present as hereditary spastic paraplegia and must be included in spastic-ataxias group.

INTRODUCTION The combination of cerebellar ataxia and spasticity is common. However, autosomal dominant genetic diseases presenting with spastic-ataxia are a smaller group. Pyramidal signs have been frequently observed in several SCA subtypes, particularly in spinocerebellar ataxia type 1. METHODS We prospectively evaluated the pyramidal signs and spasticity in SCA1 patients, and correlated the data with genetic and clinical features. RESULTS In this study, we observed that spasticity may be an early and presenting feature of SCA1, since 3 patients had pyramidal signs and spasticity as the first neurological sign. SCA1 patients with spasticity were significantly younger. CONCLUSION SCA1 may rarely present with pure spastic paraplegia, resembling hereditary spastic paraplegia, before the appearance of cerebellar signs. This observation may confuse the neurologist when a genetic testing is requested for an autosomal dominant spastic paraplegia, directing research to hereditary spastic paraplegia group.

Unusual movement disorders in spinocerebellar ataxias.

Spinocerebellar ataxias (SCA) are a group of neurodegenerative diseases that may affect the cerebellum and its connections. Although the clinical spectrum of SCA is mostly characterized by progressive cerebellar ataxia, phenotypic variability has often been reported. Moreover, a wide range of non-ataxia features can be observed during disease progression. Among non-ataxia features, several types of movement disorders may be found in SCA, and are not uncommon [1]. Almost all types of movement disorders can be detected in patients with SCA, and may be related to basal ganglia involvement. Up to this moment, 36 subtypes of SCA are known. The most common related movement disorders with SCA subtype are: myoclonus in SCA2 and SCA14; dystonia in SCA2, SCA3 and SCA17; eyelid dystonia in SCA3; chorea in SCA3 and SCA17; parkinsonism in SCA2, SCA3 and SCA17; akathisia in SCA3; action tremor SCA12 and SCA27; palatal tremor in SCA20 [1–4]. Thus, the observed movement disorder, when present in combination with cerebellar ataxia, could point to the underlying SCA. Conversely, some patients with SCA may present with complex and unusual movement disorders. Herein, we describe four patients presenting with unusual movement disorders in three different subtypes of SCA. We also comment on phenomenology and underlying pathophysiology involved.

Clinical spectrum of early onset cerebellar ataxia with retained tendon reflexes: an autosomal recessive ataxia not to be missed.

Autosomal recessive cerebellar ataxias are a heterogeneous group of neurological disorders. In 1981, a neurological entity comprised by early onset progressive cerebellar ataxia, dysarthria, pyramidal weakness of the limbs and retained or increased upper limb reflexes and knee jerks was described. This disorder is known as early onset cerebellar ataxia with retained tendon reflexes. In this article, we aimed to call attention for the diagnosis of early onset cerebellar ataxia with retained tendon reflexes as the second most common cause of autosomal recessive cerebellar ataxias, after Friedreich ataxia, and also to perform a clinical spectrum study of this syndrome. In this data, 12 patients from different families met all clinical features for early onset cerebellar ataxia with retained tendon reflexes. Dysarthria and cerebellar atrophy were the most common features in our sample. It is uncertain, however, whether early onset cerebellar ataxia with retained tendon reflexes is a homogeneous disease or a group of phenotypically similar syndromes represented by different genetic entities. Further molecular studies are required to provide definitive answers to the questions that remain regarding early onset cerebellar ataxia with retained tendon reflexes.

Phenotype variability and early onset ataxia symptoms in spinocerebellar ataxia type 7: comparison and correlation with other spinocerebellar ataxias

The spinocerebellar ataxias (SCA) are a group of neurodegenerative disorders characterized by heterogeneous clinical presentation. Spinocerebellar ataxia type 7 (SCA7) is caused by an abnormal CAG repeat expansion and includes cerebellar signs associated with visual loss and ophthalmoplegia. Marked anticipation and dynamic mutation is observed in SCA7. Moreover, phenotype variability and very early onset of symptoms may occur. In this article, a large series of Brazilian patients with different SCA subtypes was evaluated, and we compared the age of onset of SCA7 with other SCA. From the 26 patients with SCA7, 4 manifested their symptoms before 10-year-old. Also, occasionally the parents may have the onset of symptoms after their children. In conclusion, our study highlights the genetic anticipation phenomenon that occurs in SCA7 families. Patients with very early onset ataxia in the context of a remarkable family history, must be considered and tested for SCA7.

When should we test patients with familial ataxias for SCA31? A misdiagnosed condition outside Japan?

The autosomal dominant spinocerebellar ataxias (SCAs) are a highly heterogeneous group of genetic diseases characterized by progressive gait ataxia and variable degrees of extracerebellar symptoms and signs. SCAs comprise a large number of unusual genetic disorders, and may be considered a diagnostic challenge. Genetics has a significant role to play in the etiology, and up to now, approximately 40 SCA subtypes have been described, and at least 32 different loci were identified [1]. As the knowledge of clinical and genetic features of SCAs is growing, the “What type of SCA should this patient tested for?” question becomes important before ordering a SCA diagnostic panel. Although wholeexome sequencing is a promising approach to search simultaneously for a large number of genetic conditions, it is usually ineffective to identify some SCA subtypes, since their mutations may lie in a noncoding genomic region or consist of large repeat expansions. Spinocerebellar ataxia type 31 (SCA31), a late-onset cerebellar ataxia with or without hearing loss, is one of the most common inherited ataxia in Japan. To date, only two cases of SCA31 were described in other countries [2,3] and large European [4] and Taiwanese [5] population studies showed no SCA31 cases. Thus, SCA31 could be a misdiagnosed condition outside Japan. In this article, we aimed to describe a Brazilian family with SCA31 and to provide clinical clues in order to request a specific genetic testing for this unusual SCA subtype outside Japan.

Non-progressive cerebellar ataxia and previous undetermined acute cerebellar injury: a mysterious clinical condition

Cerebellar ataxias represent a wide group of neurological diseases secondary to dysfunctions of cerebellum or its associated pathways, rarely coursing with acute-onset acquired etiologies and chronic non-progressive presentation. We evaluated patients with acquired non-progressive cerebellar ataxia that presented previous acute or subacute onset. Clinical and neuroimaging characterization of adult patients with acquired non-progressive ataxia were performed. Five patients were identified with the phenotype of acquired non-progressive ataxia. Most patients presented with a juvenile to adult-onset acute to subacute appendicular and truncal cerebellar ataxia with mild to moderate cerebellar or olivopontocerebellar atrophy. Establishing the etiology of the acute triggering events of such ataxias is complex. Non-progressive ataxia in adults must be distinguished from hereditary ataxias.

Superior cerebellar hyperintense sign on FLAIR-weighted magnetic resonance imaging in paraneoplastic cerebellar degeneration

A 59 year-old woman presented with 15 days history of progressive gait instability and slurred speech. She had recurrence of breast cancer diagnosed five years before. Neurological examination showed dysarthria and ataxia. Brain magnetic resonance imaging (MRI) presented hyperintense sign in the superior cerebellar vermis and upper cerebellar hemispheres, without atrophy (Figure). Cerebrospinal fluid (CSF) revealed lymphocytic pleocytosis. Cerebellar degeneration is one of the most common neurological paraneoplastic syndromes. The most frequently associated tumors are: breast, ovary and lung cancer, and also lymphoma1. Early brain MRI is frequently normal or shows a diffuse enlargement of cerebellar hemispheres; rarely, there are signal changes in the cerebellar cortex2. After a few months, atrophy of the brainstem and cerebellum may appear.

Clinical and epidemiological profiles of non-traumatic myelopathies

Non-traumatic myelopathies represent a heterogeneous group of neurological conditions. Few studies report clinical and epidemiological profiles regarding the experience of referral services. Objective To describe clinical characteristics of a non-traumatic myelopathy cohort. Method Epidemiological, clinical, and radiological variables from 166 charts of patients assisted between 2001 and 2012 were compiled. Results The most prevalent diagnosis was subacute combined degeneration (11.4%), followed by cervical spondylotic myelopathy (9.6%), demyelinating disease (9%), tropical spastic paraparesis (8.4%) and hereditary spastic paraparesis (8.4%). Up to 20% of the patients presented non-traumatic myelopathy of undetermined etiology, despite the broad clinical, neuroimaging and laboratorial investigations. Conclusion Regardless an extensive evaluation, many patients with non-traumatic myelopathy of uncertain etiology. Compressive causes and nutritional deficiencies are important etiologies of non-traumatic myelopathies in our population.