Transcranial sonography in patients with Parkinson's disease with glucocerebrosidase mutations

Kresojević, Nikola; Mijajlović, Milija; Perić, Stojan; Pavlović, Aleksandra M.; Svetel, Marina; Janković, Milena; Dobričić, Valerija; Novaković, Ivana; Lakočević, Milan; Klein, Christine; Kostić, Vladimir

doi:10.1016/j.parkreldis.2012.12.006

Cited by 15 publications

(23 citation statements)

References 28 publications

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“…In agreement with previous studies [17][18][19], we show that an enlarged SN hyperechogenicity area occurs in the majority of patients with GBA-related PD (>0.2 cm 2 in >90% of the individuals). However, this study reveals that the mean area of hyperechogenicity is also enlarged in both GBA mutation carriers and patients with GD who do not have PD.…”

Section: Discussionsupporting

confidence: 93%

Prodromal substantia nigra sonography undermines suggested association between substrate accumulation and the risk for GBA‐related Parkinson's disease

Arkadir

Dinur

Cohen

et al. 2019

Euro J of Neurology

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Background and purpose Individuals with GBA (glucocerebrosidase) mutations are at increased risk of Parkinson's disease (PD). It is still debated, however, whether this increased risk results from impaired glucocerebrosidase activity leading to substrate accumulation. Comparing the presence of prodromal PD marker in GBA mutation carriers and patients with Gaucher disease (GD) (in which substrate accumulation is extensive) can assist in clarifying this issue. Methods In this cross‐sectional study, we compared the hyperechogenic area of the substantia nigra, a prodromal PD marker, in large cohorts of GBA mutation carriers (n = 71) and patients with GD (n = 145). Our control populations were healthy, non‐carriers (n = 49) and patients with GBA ‐related PD (n = 11). Substrate accumulation was assessed from dry blood spot levels of glucosylsphingosine. Results Our findings indicate no contribution of substrate accumulation, as the area of hyperechogenicity is similarly enlarged relative to healthy controls in both GBA mutation carriers and patients with GD. Moreover, this similarity between GBA carriers and patients with GD persists when comparing only carriers of the N370S (c.1226A>G) mutation (n = 38) with untreated patients with GD who were homozygotes for the same mutation (n = 47). In addition, measurements of hyperechogenic area did not correlate with levels of glucosylsphingosine in the untreated patients with GD. Conclusion The presence of a marker of prodromal PD (substantia nigra hyperechogenicity) is independent of substrate accumulation in a population with mutated GBA . Although further longitudinal studies are needed to determine the precise predictive value of this marker for GBA ‐related PD, our findings raise doubts regarding the contribution of substance reduction strategies to PD prevention.

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Section: Discussionsupporting

confidence: 93%

Prodromal substantia nigra sonography undermines suggested association between substrate accumulation and the risk for GBA‐related Parkinson's disease

Arkadir

Dinur

Cohen

et al. 2019

Euro J of Neurology

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“…This finding, together with earlier data suggests that BR hypoechogenicity may be present already several years prior to the onset of the motor stage of PD . Interestingly, BR hypoechogenicity has been detected with higher frequency in patients with glucocerebrosidase (GBA)‐associated PD as compared to idiopathic PD in several studies which correlates with higher frequency of depressive symptoms in GBA‐related PD …”

Section: Tcs In Depressed Patients With Association To Neurodegeneratsupporting

confidence: 55%

“…20 Interestingly, BR hypoechogenicity has been detected with higher frequency in patients with glucocerebrosidase (GBA)-associated PD as compared to idiopathic PD in several studies which correlates with higher frequency of depressive symptoms in GBA-related PD. [42][43][44] To summarize, the association between abnormal BR findings and depression in patients with PD has been confirmed by a number of independent groups, reporting reduced BR echogenicity in about 63% (35-92%) of depressed but only in ca. 27% (10-62%) of nondepressed PD patients (Table 1).…”

Section: Tcs In Depressed Patients With Association To Neurodegeneratmentioning

confidence: 74%

Transcranial Sonography Findings in Depression in Association With Psychiatric and Neurologic Diseases: A Review

Krogias

Walter

2016

Journal of Neuroimaging

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The transcranial sonography (TCS) finding of reduced echogenicity of brainstem raphe (hypoechogenic BR) has been associated with depressive states. Here, we review the TCS studies in subjects with depressive disorders and with depression related to degenerative brain diseases, and compare the frequency and clinical correlates of hypoechogenic BR in these reports. Summarizing the data published so far, hypoechogenic BR is present in 67% (range, 37-95%) of depressed but only in 15% (5-36%) of nondepressed subjects without history of neurodegenerative disease. The finding of hypoechogenic BR in these subjects is associated with a relative risk of 3.03 (95% CI, 2.44-3.75; P < .001) of being diagnosed with depression. In patients with Parkinson's disease, hypoechogenic BR is present in 63% (35-92%) of depressed but only in 27% (10-62%) of nondepressed patients, resulting in a relative risk of 2.18 (95% CI, 1.80-2.66; P < .001) of being diagnosed with depression. Hypoechogenic BR is associated with depression in a number of neurological disorders such Huntington's disease, idiopathic Rapid Eye Movement (REM) sleep behavior disorder, myotonic dystrophies, and cerebral small vessel disease. Although some studies did not show any relationship between BR echogenicity and severity of depression, others suggest an association with higher severity of depression, or even with suicidal ideation. In one study BR hypoechogenicity was found to be associated with better responsivity to serotonin reuptake inhibitors. Further studies are warranted to compare the TCS findings of BR alteration with post-mortem histopathological findings, and with genetic variants related to cerebral serotonin metabolism.

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“…It is also seen in heterozygous GBA carriers with PD 46 , 52 , and gene dose (one vs. two GBA mutations) did not affect the degree of nigral echogenicity 52 . Interestingly, TCS in GD1 patients without PD is normal 53 . Hypoechogenicity of the brainstem raphe, reported in PD with depression 51 , may reflect structural damage to the serotonergic system, and is more prevalent in PD patients with GBA mutations compared to IPD patients 46, 53 and to controls 53 , and may correspond with the increased rate of depression among GBA-PD 46 .…”

Section: Neuroimaging In Gba-pdmentioning

confidence: 95%

The Association Between ß-Glucocerebrosidase Mutations and Parkinsonism

Swan

Saunders‐Pullman

2013

Curr Neurol Neurosci Rep

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Mutations in the ß-glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme ß-glucocerebrosidase, have traditionally been implicated in Gaucher disease, an autosomal-recessive lyososomal storage disorder. Yet the past two decades have yielded an explosion of epidemiological and basic-science evidence linking mutations in GBA with the development of Parkinson disease as well. Although the specific contribution of mutant GBA to the pathogenesis of parkinsonism remains unknown, evidence suggests both loss of function and toxic gain-of-function by abnormal ß-glucocerebrosidase may be important, and a close relationship between ß-glucocerebrosidase and α-synuclein. Furthermore, multiple lines of evidence suggest that while GBA-associated PD closely mimics idiopathic PD (IPD), it may present at a younger age, and is more frequently complicated by cognitive dysfunction. Understanding the clinical association between GBA and PD, and the relationship between ß-glucocerebrosidase and α-synuclein, may enhance understanding of the pathogenesis of IPD, improve prognostication and treatment of GBA carriers with parkinsonism, and may furthermore inform therapies for IPD not due to GBA mutations.

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Transcranial sonography in patients with Parkinson's disease with glucocerebrosidase mutations

Cited by 15 publications

References 28 publications

Prodromal substantia nigra sonography undermines suggested association between substrate accumulation and the risk for GBA‐related Parkinson's disease

Prodromal substantia nigra sonography undermines suggested association between substrate accumulation and the risk for GBA‐related Parkinson's disease

Transcranial Sonography Findings in Depression in Association With Psychiatric and Neurologic Diseases: A Review

The Association Between ß-Glucocerebrosidase Mutations and Parkinsonism

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