Dopaminergic response in Parkinsonian phenotype of Machado‐Joseph disease

Abstract

We report on a patient with genetically proven Machado-Joseph Disease (MJD) presenting with signs indistinguishable from Parkinson's disease (PD), including levodopa response and typical levodopa-induced motor fluctuations. Only after 10 years of prolonged benefit from levodopa and different dopamine agonists (DA), the patient developed cerebellar ataxia and pyramidal signs. Preferential D3-receptor-stimulating dopamine agonists especially showed a benefit at the time, when D2 receptor binding was reduced in IBZM SPECT. This is the first report of a meaningful response to DA in MJD.

Dramatic levodopa responsiveness of dystonia in a sporadic case of spinocerebellar ataxia type 3

“…In a Ghanaian patient with Machado-Joseph disease, the manifestation of dopamine agonist responsive parkinsonian phenotype was associated with levodopa induced motor fluctuation (in the form of freezing and wearing off phenomenon), while dystonia was not the predominant feature. 4 Severe generalised dystonia was the presenting feature in a German patient reported by Munchau et al 1 Like the case reported here, he was heterozygous for SCA 3 gene mutation, but showed only a mild improvement of his dystonia after starting levodopa. The response lasted for two weeks only, unlike the significant benefit seen for two years in our patient.…”

Dramatic levodopa responsiveness of dystonia in a sporadic case of spinocerebellar ataxia type 3

“…In a Ghanaian patient with Machado-Joseph disease, the manifestation of dopamine agonist responsive parkinsonian phenotype was associated with levodopa induced motor fluctuation (in the form of freezing and wearing off phenomenon), while dystonia was not the predominant feature. 4 Severe generalised dystonia was the presenting feature in a German patient reported by Munchau et al 1 Like the case reported here, he was heterozygous for SCA 3 gene mutation, but showed only a mild improvement of his dystonia after starting levodopa. The response lasted for two weeks only, unlike the significant benefit seen for two years in our patient.…”

TGM6 variants in Parkinson’s disease: clinical findings and functional evidence

“…Moreover, PET imaging conducted in an SCA2 family showed results similar to that found in idiopathic PD (Furtado et al, 2004). Some SCA3 patients have been found to initially present with a phenotype indistinguishable from PD, as well as responding positively to levodopa (Bettencourt et al, 2011;Buhmann et al, 2003). However, cerebellar signs have been reported to manifest in some of these patients after several years of disease progression (Lu et al, 2004).…”

Spinocerebellar ataxia type 3: subphenotypes in a cohort of brazilian patients

“…We emphasize the fact that levodopa usually is an effective form of treatment in this group of SCA3 patients 14 . In addition, other described phenotypes, such as type 5, were rare in our sample.…”

Dramatic levodopa responsiveness of dystonia in a sporadic case of spinocerebellar ataxia type 3

“…In a Ghanaian patient with Machado-Joseph disease, the manifestation of dopamine agonist responsive parkinsonian phenotype was associated with levodopa induced motor fluctuation (in the form of freezing and wearing off phenomenon), while dystonia was not the predominant feature. 4 Severe generalised dystonia was the presenting feature in a German patient reported by Munchau et al 1 Like the case reported here, he was heterozygous for SCA 3 gene mutation, but showed only a mild improvement of his dystonia after starting levodopa. The response lasted for two weeks only, unlike the significant benefit seen for two years in our patient.…”

TGM6 variants in Parkinson’s disease: clinical findings and functional evidence

“…Moreover, PET imaging conducted in an SCA2 family showed results similar to that found in idiopathic PD (Furtado et al, 2004). Some SCA3 patients have been found to initially present with a phenotype indistinguishable from PD, as well as responding positively to levodopa (Bettencourt et al, 2011;Buhmann et al, 2003). However, cerebellar signs have been reported to manifest in some of these patients after several years of disease progression (Lu et al, 2004).…”

Spinocerebellar ataxia type 3: subphenotypes in a cohort of brazilian patients

“…We emphasize the fact that levodopa usually is an effective form of treatment in this group of SCA3 patients 14 . In addition, other described phenotypes, such as type 5, were rare in our sample.…”

Dramatic levodopa responsiveness of dystonia in a sporadic case of spinocerebellar ataxia type 3

“…In a Ghanaian patient with Machado-Joseph disease, the manifestation of dopamine agonist responsive parkinsonian phenotype was associated with levodopa induced motor fluctuation (in the form of freezing and wearing off phenomenon), while dystonia was not the predominant feature. 4 Severe generalised dystonia was the presenting feature in a German patient reported by Munchau et al 1 Like the case reported here, he was heterozygous for SCA 3 gene mutation, but showed only a mild improvement of his dystonia after starting levodopa. The response lasted for two weeks only, unlike the significant benefit seen for two years in our patient.…”

TGM6 variants in Parkinson’s disease: clinical findings and functional evidence

“…Moreover, PET imaging conducted in an SCA2 family showed results similar to that found in idiopathic PD (Furtado et al, 2004). Some SCA3 patients have been found to initially present with a phenotype indistinguishable from PD, as well as responding positively to levodopa (Bettencourt et al, 2011;Buhmann et al, 2003). However, cerebellar signs have been reported to manifest in some of these patients after several years of disease progression (Lu et al, 2004).…”

Spinocerebellar ataxia type 3: subphenotypes in a cohort of brazilian patients

“…We emphasize the fact that levodopa usually is an effective form of treatment in this group of SCA3 patients 14 . In addition, other described phenotypes, such as type 5, were rare in our sample.…”