Adult-onset Alexander disease mimicking multiple system atrophy predominant cerebellar ataxia

Adult-onset Alexander disease (AOAD) is an autosomal dominant progressive astrogliopathy caused by pathogenic variants in glial fibrillary acidic protein (<i>GFAP</i>). Individuals with this disorder often present with a typical neuroradiologic pattern, including frontal white matter abnormality with contrast enhancement, atrophy and signal intensity changes of the medulla oblongata and upper cervical cord on MRI. Focal lesions are rarely seen in AOAD, which causes concern for primary malignancies. This study aimed to present the case of a 37-year-old male patient initially diagnosed with an astrocytoma in the lateral ventricle that was later identified as GFAP mutation-confirmed AOAD. <i>GFAP</i> sequencing revealed a heterogeneous missense mutation point c.236G>A. Hence, AOAD should be considered in patients with tumor-like lesion brain lesion in association with atrophy of medulla oblongata and upper cervical spinal cord, and frontal white matter abnormality with contrast enhancement.

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Adult onset Alexander disease presenting with progressive spastic paraplegia

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2013.10.014 ◽

2014 ◽

Vol 20 (2) ◽

pp. 241-242 ◽

Cited By ~ 1

Author(s):

José Luiz Pedroso ◽

Salmo Raskin ◽

Orlando Graziani Povoas Barsottini ◽

Acary S.B. Oliveira

Keyword(s):

Alexander Disease ◽

Adult Onset ◽

Spastic Paraplegia

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Prevalence of Fragile X-Associated Tremor/Ataxia Syndrome in Patients with Cerebellar Ataxia in Japan

The Cerebellum ◽

10.1007/s12311-021-01323-x ◽

2021 ◽

Author(s):

Yujiro Higuchi ◽

Masahiro Ando ◽

Akiko Yoshimura ◽

Satoshi Hakotani ◽

Yuki Koba ◽

...

Keyword(s):

Multiple System Atrophy ◽

Cerebellar Ataxia ◽

Fragile X ◽

Genetic Diagnosis ◽

Japanese Patients ◽

High Signal ◽

Intranuclear Inclusion ◽

Neuronal Intranuclear Inclusion ◽

Male Patients ◽

Ataxia Syndrome

AbstractThe presence of fragile X mental retardation 1 (FMR1) premutation has been linked to patients with a certain type of cerebellar ataxia, the fragile X-associated tremor/ataxia syndrome (FXTAS). However, its prevalence in Japan has yet to be clarified. The aim of the present study is to determine the prevalence of FXTAS in Japanese patients with cerebellar ataxia and to describe their clinical characteristics. DNA samples were collected from 1328 Japanese patients with cerebellar ataxia, referred for genetic diagnosis. Among them, 995 patients with negative results for the most common spinocerebellar ataxia subtypes were screened for FMR1 premutation. Comprehensive clinical and radiological analyses were performed for the patients harbouring FMR1 premutation. We herein identified FMR1 premutation from one female and two male patients, who satisfied both clinical and radiological criteria of FXTAS (0.3%; 3/995) as well. Both male patients presented with high signal intensity of corticomedullary junction on diffusion-weighted magnetic resonance imaging, a finding comparable to that of neuronal intranuclear inclusion disease. The female patient mimicked multiple system atrophy in the early stages of her disease and developed aseptic meningitis with a suspected immune-mediated mechanism after the onset of FXTAS, which made her unique. Despite the lower prevalence rate in Japan than the previous reports in other countries, the present study emphasises the necessity to consider FXTAS with undiagnosed ataxia, regardless of men or women, particularly for those cases presenting with similar clinical and radiological findings with multiple system atrophy or neuronal intranuclear inclusion disease.

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Genetic Rhabdomyolysis within the Spectrum of the Spinocerebellar Ataxia Type 2 Responsive to Pregabalin

10.21203/rs.3.rs-125754/v1 ◽

2021 ◽

Author(s):

Fabian Rossi ◽

Joe Ma ◽

Nina Tsakadze ◽

Lourdes Benes-Lima ◽

Julio Araque Gonzalez ◽

...

Keyword(s):

Cerebellar Ataxia ◽

Spinocerebellar Ataxia ◽

Clinical Presentation ◽

Spinocerebellar Ataxia Type ◽

Adult Onset ◽

Spinocerebellar Ataxia Type 2 ◽

First Report ◽

Recurrent Rhabdomyolysis

Abstract BackgroundSpinocerebellar Ataxia type 2 is a slowly progressive adult onset ataxia with a broad clinical presentation. Case presentationWe describe a man with Spinocerebellar Ataxia type 2 with chronic, severe, and recurrent rhabdomyolysis, as part of the cerebellar ataxia genetic spectrum. Initially rhabdomyolysis was refractory to multiple medications, but entirely resolved and remained in chronic remission with pregabalin. ConclusionThis is the first report of Spinocerebellar Ataxia type 2 associated with chronic, severe, recurrent rhabdomyolysis as part of its genetic phenotype responsive to pregabalin.

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Human alpha-synuclein overexpressing MBP29 mice mimic functional and structural hallmarks of the cerebellar subtype of multiple system atrophy

Acta Neuropathologica Communications ◽

10.1186/s40478-021-01166-x ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Lisa Mészáros ◽

Markus J. Riemenschneider ◽

Heiko Gassner ◽

Franz Marxreiter ◽

Stephan von Hörsten ◽

...

Keyword(s):

Mouse Model ◽

Multiple System Atrophy ◽

Cerebellar Ataxia ◽

Purkinje Cells ◽

Alpha Synuclein ◽

Significant Loss ◽

Disease Stage ◽

Cytoplasmic Inclusions ◽

Unsteady Gait ◽

Advanced Disease Stage

AbstractMultiple system atrophy (MSA) is a rare, but fatal atypical parkinsonian disorder. The prototypical pathological hallmark are oligodendroglial cytoplasmic inclusions (GCIs) containing alpha-synuclein (α-syn). Currently, two MSA phenotypes are classified: the parkinsonian (MSA-P) and the cerebellar subtype (MSA-C), clinically characterized by predominant parkinsonism or cerebellar ataxia, respectively. Previous studies have shown that the transgenic MSA mouse model overexpressing human α-syn controlled by the oligodendroglial myelin basic protein (MBP) promoter (MBP29-hα-syn mice) mirrors crucial characteristics of the MSA-P subtype. However, it remains elusive, whether this model recapitulates important features of the MSA-C-related phenotype. First, we examined MSA-C-associated cerebellar pathology using human post-mortem tissue of MSA-C patients and controls. We observed the prototypical GCI pathology and a preserved number of oligodendrocytes in the cerebellar white matter (cbw) accompanied by severe myelin deficit, microgliosis, and a profound loss of Purkinje cells. Secondly, we phenotypically characterized MBP29-hα-syn mice using a dual approach: structural analysis of the hindbrain and functional assessment of gait. Matching the neuropathological features of MSA-C, GCI pathology within the cbw of MBP29-hα-syn mice was accompanied by a severe myelin deficit despite an increased number of oligodendrocytes and a high number of myeloid cells even at an early disease stage. Intriguingly, MBP29-hα-syn mice developed a significant loss of Purkinje cells at a more advanced disease stage. Catwalk XT gait analysis revealed decreased walking speed, increased stride length and width between hind paws. In addition, less dual diagonal support was observed toward more dual lateral and three paw support. Taken together, this wide-based and unsteady gait reflects cerebellar ataxia presumably linked to the cerebellar pathology in MBP29-hα-syn mice. In conclusion, the present study strongly supports the notion that the MBP29-hα-syn mouse model mimics important characteristics of the MSA-C subtype providing a powerful preclinical tool for evaluating future interventional strategies.

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