Gaucher disease ascertained through a Parkinson's center: imaging and clinical characterization.

Among the genes implicated for parkinsonism is glucocerebrosidase (GBA), which causes Gaucher disease (GD). Despite a growing literature that GD may present as parkinsonism, neuroimaging, olfaction, and neuropsychological testing have not been extensively reported. We describe transcranial sonography (TCS), 18F-fluorodopa (F-dopa) and fluorodeoxyglucose (FDG) Positron emission tomography, olfaction testing, neuropsychological testing, and clinical features in homozygous and compound heterozygous GBA mutation carriers identified through screening of 250 Ashkenazi Jewish parkinsonian individuals treated at a tertiary care center. We identified two individuals with N370S/R496H compound heterozygous mutations and two with N370S homozygous mutations; one individual died before completing detailed evaluation. TCS (n = 3) demonstrated nigral hyperechogenicity that was greater than controls [median area maximal substantia nigra echogenicity (aSNmax) = 0.28 cm(2) vs. 0.14 cm(2), P = 0.005], but similar to idiopathic PD (aSNmax = 0.31 cm(2)). FDG PET (n = 2) demonstrated hypermetabolism of the lentiform nuclei, and F-fluorodopa PET (n = 2), bilateral reduction in striatal F-dopa uptake. Olfaction was markedly impaired in the two tested cases, including onset of smell disturbance in adolescence in one. Neuropsychological features (n = 3) were consistent with Parkinson's disease (PD) or diffuse Lewy body disease (DLB). The imaging, neuropsychological and olfactory markers suggest the GD phenotype includes PD with and without features of DLB, marked olfactory loss, nigral hyperechogenicity on TCS, and F-dopa and FDG PET abnormalities.

Life-long increase of substantia nigra hyperechogenicity in transcranial sonography.

Transcranial ultrasound of the substantia nigra (SN) shows a distinct hyperechogenicity in the majority of patients with Parkinson's disease. Recent studies indicate a larger area of hyperechogenicity in elderly healthy adult subjects. The present study aimed to determine the size of the SN hyperechogenicity and of the mesencephalic brainstem in children and adults without evidence of movement disorders. The areas of echogenicity in the substantia nigra (aSN) and the area of the ipsilateral midbrain (aMid) were assessed in 121 healthy infants and children as well as in 64 healthy adults. Furthermore, the ratio of aSN and aMid was calculated (S/M ratio). We found a positive correlation between age and aSN and between age and the S/M ratio. The values for aSN and S/M ratio were smaller in infants and children compared to healthy adults (aSNmax 0.06+/-0.05 cm2 vs. 0.13+/-0.08 cm2). The aSN and S/M ratio grew with increasing age in an almost linear progression. The increase of SN hyperechogenicity over time suggests that the biological process underlying this ultrasound finding may be more dynamic and possibly progressive than previously thought.

Clinical utility of computed tomography in the assessment of dementia: a memory clinic study.

OBJECTIVE: To define the influence of computed tomography (CT) on clinical decision-making in the outpatient evaluation of dementia. DESIGN: A case series in which two physicians reviewed standardised data extracted from clinical records, first blind to CT results, and then with CT results. Clinical decisions made with and without the input of CT were compared. The study was based in an outpatient referral centre for the assessment of memory disorders and dementia. The study involved 146 participants who were diagnosed with dementia after their first clinic visit, had Mini Mental State Examination scores >12, were aged >65 years, and had no history of neurologic disease. RESULTS: CT impacted on diagnosis in an average of 12% (+/-2), and on treatment plan in 11% (+/-2) of cases. Physicians predicted a priori which cases CT may influence with an average sensitivity of 28% (+/-2), and specificity of 78.5% (+/-1.5). There was no statistically significant relationship between diagnostically uncertain cases and helpful CT scans [average chi(2) = 1.121 (+/-1.116), p = ns]. Blind to CT physicians appropriately identified cerebrovascular disease with an average sensitivity of 63% (+/-3), and specificity of 93.5% (+/-3.5). CONCLUSIONS: In the outpatient setting, CT may be expected to impact on diagnosis and treatment of dementia in 10% to 15% of cases. Memory clinic physicians recognise and treat cerebrovascular risk factors with reasonable sensitivity and specificity without the input of CT.

Prediction rules for computed tomography in the dementia assessment: do they predict clinical utility of CT?

Neuroimaging is widely employed in the dementia assessment in refining clinical decision-making. However, with rising interest in cost-effective medical practice, efforts have been made in the literature to define clinical prediction rules that select for a subgroup of patients who would most likely benefit from neuroimaging. This short study examined the ability of a group of published clinical predictors to identify patients whose diagnoses or management would be influenced by CT scan results. The study finds that none of the published predictors bears a significant relationship to actual influence of CT scans in a group of memory clinic patients, highlighting the need for the development of clinical predictors for neuroimaging that will impact patient care.