The specificity and sensitivity of transcranial ultrasound in the differential diagnosis of Parkinson's disease: a prospective blinded study

BACKGROUND: Increased echogenicity of the substantia nigra (SN), as determined by transcranial sonography (TCS), is characteristic of idiopathic Parkinson's disease (iPD). The results of initial retrospective studies indicate that this ultrasound sign is specific for iPD and can help to differentiate it from atypical parkinsonian syndromes (aPS); however, these early studies were done in patients with later disease stages and known clinical diagnosis. We aimed to determine the diagnostic value of TCS in the early stages of parkinsonian syndromes, when the clinical symptoms often do not enable a definite diagnosis to be made. METHODS: 60 patients who presented with the first, but still unclear, clinical symptoms of parkinsonism had TCS in this prospective blinded study. Investigators were blinded to the results of the clinical investigations, the ultrasound findings, and the diagnosis at time of investigation. The patients were followed-up every 3 months for 1 year to assess and re-evaluate the clinical symptoms. The patients in whom a clinical diagnosis could not be made with certainty were investigated with raclopride PET or dopamine transporter single-photon emission computed tomography (SPECT), or both. FINDINGS: A clinical diagnosis of parkinsonism could not be established at baseline in 38 patients. At 12 months, 39 patients were clinically categorised as having iPD. Compared with endpoint diagnosis, the sensitivity of TCS at baseline was 90%7% and the specificity was 82.4%; the positive predictive value of TCS for iPD was 92.9% and the classification accuracy was 88.3%. INTERPRETATION: TCS is an easy to implement, non-invasive, and inexpensive technique that could help in the early differential diagnosis of parkinsonian syndromes. The routine use of TCS in the clinic could enable disease-specific therapy to be started earlier. FUNDING: Michael J Fox Foundation for Parkinson's Research.     

Echogenicity of substantia nigra determined by transcranial ultrasound correlates with severity of parkinsonian symptoms induced by neuroleptic therapy.

BACKGROUND: Increased echogenicity of the substantia nigra (SN) detected by transcranial sonography is a characteristic ultrasound feature of Parkinson's disease. This ultrasound feature can also be detected in a subgroup of healthy adults. In recent studies, healthy subjects with this ultrasound feature showed a reduced [(18)F]-Dopa uptake on positron emission tomography (PET), indicating a subclinical alteration of the nigrostriatal system. This study was designed to evaluate whether the severity of neuroleptic side effects is related to the echo-feature of the SN. METHODS: In the retrospective part of the study, 93 psychiatric patients with either definite and severe parkinsonism after neuroleptic treatment (n = 52) or with no or minimal parkinsonian symptoms (n = 41) were included and underwent transcranial sonography to measure the extension of hyperechogenic areas at the SN. In addition, in the prospective part 11 patients with an acute psychotic episode requiring first-ever neuroleptic treatment underwent ultrasound examination. Subsequently, neuroleptic-induced parkinsonian signs were assessed prospectively. RESULTS: In the retrospective part of the study, patients with severe neuroleptic-induced parkinsonism had more extended echogenic signals at the SN than those with low echogenic SN (U-test; p <.01). The prospective part of the study showed that the severity of parkinsonian symptoms correlated with the echogenicity of the substantia nigra (Spearman's rank: p <.01). CONCLUSIONS: Increased echogenicity of the substantia nigra is associated with impaired function of the nigrostriatal system that can be disclosed by neuroleptic drugs.     

The impact of familial structure on Parkinson's disease in Istanbul Medical School, Turkey

The prevalence and family structure of idiopathic Parkinson disease (iPD) in Turkey is not known. Patients with iPD were recruited consecutively at the Medical School of Istanbul University over an 18-month period. Clinical details were assessed with standardized forms. Of the 219 iPD patients, 136 had sporadic iPD [26 with parental consanguinity (cs)], 20 autosomal recessive PD (9 with cs) and 63 autosomal dominant or pseudo-dominant inheritances (20 with cs). Age at onset was 49.1 ± 17.1 years (range 3-83) and age at examination 56.4 ± 16.5 years (range 4-93). Ages at examination and at clinical onset of PD were significantly greater in sporadic iPD than in familial iPD patients, but disease duration was similar. Patients with familial PD had significantly lower basal UPDRS III and Hoehn and Yahr scores than sporadic PD patients and brisk reflexes in the lower limbs were significantly more frequent, but they suffered less from mictional problems. The frequency of familial PD and consanguinity in Turkey is higher and age at onset of iPD earlier than in Western countries. Molecular diagnoses and genetic counseling will therefore have a very important impact on the medical, psychological, and familial handling of PD in Turkey.     

Substantia nigra echogenicity correlated with clinical features of Parkinson's disease

BackgroundTranscranial sonography can display structural alterations in the substantia nigra (SN) of patients with Parkinson's disease (PD), and is considered to be a potential useful tool for the diagnosis of PD. The aim of this study was to assess the correlation between SN echogenicity and clinical features in Chinese patients with PD.MethodsA total of 420 subjects including 290 patients with PD and 130 controls were recruited from the neurological clinic or the community. Transcranial sonographic evaluations of the SN were performed in all subjects, and motor and non-motor symptoms were thoroughly assessed by a series of rating scales in PD patients.ResultsTwo hundred and one patients were successfully assessed by transcranial sonography. SN hyperechogenicity was found to be associated with male sex (p = 0.004), higher scores on the Unified Parkinson's Disease Rating Scale (UPDRS) part II (p = 0.001) and autonomic symptoms scores (p = 0.003). Moreover, regression analysis revealed that UPDRS part II scores (odds ratio = 1.141, p < 0.001) and gender (odds ratio = 2.409, p = 0.007) could be the independent predictors for SN hyperechogenicity; in addition, among all items of UPDRS part II, speech, dressing, hygiene, and turning in bed and adjusting bed clothes significantly correlated with SN hyperechogenicity.ConclusionsThis is the first report suggesting the correlation between SN echogenicity and UPDRS part II, and we conclude that increased SN echogenicity might reflect more severe disease disability or poorer medical response.     

Enlarged hyperechogenic substantia nigra is related to motor performance and olfaction in the elderly

Enlarged substantia nigra hyperechogenicity (SN+) assessed by transcranial sonography (TCS) may be associated with Parkinson's disease (PD) risk markers such as impaired motor performance and hyposmia. The aim of this multicenter cross‐sectional study was to define the association between SN+ and these risk markers in a large population older than 50 years without the diagnosis of PD. In three centers (Tuebingen, Homburg, and Innsbruck), 1,839 individuals were examined. The echostatus of the SN was assessed by TCS, motor performance by the Unified Parkinson's Disease Rating Scale (UPDRS) motor score, and olfactory function with Sniffin' Sticks. From the 1,603 subjects included in the analysis, 16.2% were SN+, 23.0% scored above zero in the UPDRS motor section, and 28.0% were hyposmic as defined by less than 75% correctly classified Sniffin' Sticks. SN+ was associated with a UPDRS motor score above zero (OR 1.45, 95% CI 1.08–1.96) and with a lower odor identification capability (OR 1.48, 95% CI 1.12–1.96). The combination of these two features (OR 1.98, 95% CI 1.25–3.15) and UPDRS motor scores ≥3 lead to higher OR. It is concluded that SN+, impaired motor performance, and hyposmia are frequently observed in the elderly and in isolation are unspecific and of limited use to predict a subject's risk for PD. Whether the association of SN+ with both impaired motor performance and hyposmia as seen in this study predicts an increased risk for the development of PD needs to be evaluated in the follow‐up investigations. © 2010 Movement Disorder Society     

An Absent Ophthalmic Artery or Carotid Siphon Signal on Transcranial Doppler Confirms the Presence of Severe Ipsilateral Internal Carotid Artery Disease

Transcranial Doppler ultrasound provides a useful adjunct to extracranial ultrasound in the diagnosis of carotid bifurcation disease. Previous studies have shown that collateral flow patterns and diminished flow velocities in the ipsilateral middle cerebral artery correlate with hemodynamically significant carotid disease. In a series of 7,054 carotid duplex and transcranial Doppler examinations, 12.5% (95% confidence interval [CI]: 8.7, 16.4) of 287 ophthalmic arteries ipsilateral to an apparent carotid occlusion had no detectable flow signal, compared with 0.5% (95% Cl: 0.3, 0.7) of 6,767 ophthalmic arteries ipsilateral to a nonoccluded carotid artery (p < 0.001 ). Carotid siphon signals were not detectable in 24.4% (95% Cl: 19.4, 29.4) of arteries ipsilateral to the carotid occlusion, versus 1.0% (95% Cl: 0.8, 1.3) ipsilateral to nonoccluded carotid arteries (p < 0.001 ). A significant number of absent ophthalmic artery and carotid siphon signals (5.7 and 8.7%, respectively) were also found in patients with 80 to 99% extracranial carotid stenosis. A subset of 216 studies with angiographic correlation confirmed the high association of these transcranial Doppler findings with severe stenosis or occlusion of the internal carotid artery. Primary ophthalmological disease or siphon occlusion did not explain these findings. An absent ophthalmic artery or carotid siphon signal on transcranial Doppler examination is believed to represent a failure to detect slow flow distal to severe carotid bifurcation lesions. As a sign of ipsilateral carotid occlusion, the sensitivities of absent ophthalmic artery and carotid siphon signals are quite low (12.5 and 24.4%, respectively). The high specificities of 99.5 and 99.0%, however, make these findings useful in confirming the diagnosis of presumptive carotid occlusion by carotid duplex ultrasound.     

Relationship of substantia nigra echogenicity and motor function in elderly subjects

BACKGROUND: Patients with Parkinson's disease (PD) exhibit an increased echogenicity of the substantia nigra (SN) on transcranial sonography. Some healthy adults with the same echo characteristics showed a reduced 18fluorodopa uptake on PET, indicating a subclinical alteration of the nigrostriatal system. OBJECTIVES: To determine whether the sonographic phenotype of hyperechogenic SN has any relevance for motor function in elderly subjects and whether an increased echogenicity of the SN is associated with an impaired motor function. METHOD: In a population-based, cross-sectional study, 93 subjects older then 60 years without history of extrapyramidal disorder underwent sonographic and neurologic examinations, with a quantitative motor assessment. RESULTS: Elderly healthy subjects without prediagnosed extrapyramidal disorder but with SN hyperechogenicity had more frequent and more severe parkinsonian symptoms and a slower finger tapping than those with a regular echogenicity of the SN (p < 0.05, U test). CONCLUSION: With increasing age, subjects with SN hyperechogenicity develop a more substantial slowing of movements than subjects without this echo pattern, stressing the functional relevance of this sonographic finding. The authors speculate that hyperechogenicity of the SN may be detected by transcranial sonography early in life and may serve as a risk marker for nigral injury, although only a minority of these subjects will develop the full clinical picture of PD.     

In vivo detection of iron and neuromelanin by transcranial sonography – a new approach for early detection of substantia nigra damage

Summary. In more than 90% of patients with idiopathic Parkinson’s disease (PD) hyperechogenicity of the substantia nigra (SN) can be found by transcranial sonography (TCS) as a typical, stable sign. Animal experiments provided first evidence that SN hyperechogenicity may be associated with increased tissue iron levels. Two consecutive studies revealed the same association in human brain. Postmortem brains of 60 subjects without clinical signs for Parkinson’s disease during life time at different ages were scanned by ultrasound with planimetric measurement of the echogenic area of the SN. Afterwards the SN was dissected and used for histological examination and determination of iron content in all brains as well as ferritin and neuromelanin content in 40 brains. A significant positive correlation was found between the echogenic area of the SN and the concentration of iron, H- and L-ferritins. A multivariate analysis performed considering the iron content showed a significant negative correlation between echogenicity and neuromelanin content of the SN. Iron staining confirmed the biochemical findings. In PD a typical loss of neuromelanin and increase of iron is observed in this brain area. However, it is not clear yet, whether iron accumulation is a primary cause or a secondary phenomenon in the disease process. Screening of genes involved in brain iron metabolism showed a significant association of some sequence variations of the ceruloplasmin gene with PD. Others were associated with the ultrasound marker for increased iron levels in both PD patients and control subjects. As SN hyperechogenicity is typical for PD or subjects with a preclinical impairment of the nigrostriatal system, these findings indicate that TCS enables the detection of increased iron and decreased neuromelanin levels at the SN, even before the clinical manifestation of PD.     

Ultrasound in the (premotor) diagnosis of Parkinson's disease

A number of independent studies provide evidence that transcranial sonography (TCS) is helpful in the diagnosis of idiopathic and monogenetic Parkinson's disease (PD). In the clinical setting, it may exclude a number of secondary or atypical parkinsonian syndromes at very early stages. TCS may additionally depict morphological alterations of symptoms associated with PD motor features like midline alterations in PD-associated depression. Importantly, substantia nigra (SN) hyperechogenicity, the typical ultrasound marker of PD, can also be found in approximately 9% of healthy subjects. PET studies and conditions challenging the dopaminergic system indicate that this stable ultrasound feature has a functional relevance. Ongoing longitudinal studies test the hypothesis that SN hyperechogenicity is a risk marker for nigrostriatal vulnerability.     

Relationship of substantia nigra hyperechogenicity to risk of Lewy body disease in idiopathic REM sleep behavior disorder patients: a longitudinal study

BackgroundWe examined the relationship between baseline substantia nigra (SN) echogenicity on transcranial sonography (TCS) images and medium-to long-term developments of Parkinson's disease (PD) and dementia with Lewy bodies (DLB) in idiopathic RBD (IRBD) patients.MethodsFrom 2007–2009, TCS and odor identification tests were performed in 34 consecutive IRBD patients (67.9 ± 6.1 years). A medical chart review was conducted in August 2019 to investigate the development of PD or DLB.ResultsOf the 34 IRBD patients, 14 (41.2%) showed SN hyperechogenicity (SN+) on TCS at baseline. There were no significant differences in age, Unified Parkinson's Disease Rating Scale (UPDRS) score, Mini-Mental State Exam (MMSE) score, or odor identification (OSIT-J) score between the SN+ and SN normoechogenicity (SN−) groups at baseline. The phenoconversion rate was 57.4% (n = 8) in the SN+ group (mean 5.8 years from baseline TCS), and 25.0% (n = 5) in the SN− group (mean 8.6 years from baseline TCS). Of those with phenoconversions, there were five PD patients and three DLB patients in the SN+ group, and one PD patient and four DLB patients in the SN− group. The SN+ group had a higher estimated risk for disease development than the SN− group. The coexistence of SN+ with functional anosmia may predict a short-term Lewy body disease onset risk.ConclusionA single baseline TCS for IRBD patients may be a suitable test for screening and predicting groups at high-risk for developing PD or DLB. This may help to select appropriate IRBD patients in clinical trials for disease modifying therapy to prevent progression to PD or DLB.     

A Biomarker Study in Patients with GBA1-Parkinson's Disease and Healthy Controls

Background

Molecules related to glucocerebrosidase (GCase) are potential biomarkers for development of compounds targeting GBA1-associated Parkinson's disease (GBA-PD).

Objectives

Assessing variability of various glycosphingolipids (GSLs) in plasma, peripheral blood mononuclear cells (PBMCs), and cerebrospinal fluid (CSF) across GBA-PD, idiopathic PD (iPD), and healthy volunteers (HVs).

Methods

Data from five studies were combined. Variability was assessed of glucosylceramide (various isoforms), lactosylceramide (various isoforms), glucosylsphingosine, galactosylsphingosine, GCase activity (using fluorescent 4-methylumbeliferryl-β-glucoside), and GCase protein (using enzyme-linked immunosorbent assay) in plasma, PBMCs, and CSF if available, in GBA-PD, iPD, and HVs. GSLs in leukocyte subtypes were compared in HVs. Principal component analysis was used to explore global patterns in GSLs, clinical characteristics (Movement Disorder Society – Unified Parkinson's Disease Rating Scale Part 3 [MDS-UPDRS-3], Mini-Mental State Examination [MMSE], GBA1 mutation type), and participant status (GBA-PD, iPD, HVs).

Results

Within-subject between-day variability ranged from 5.8% to 44.5% and was generally lower in plasma than in PBMCs. Extracellular glucosylceramide levels (plasma) were slightly higher in GBA-PD compared with both iPD and HVs, while intracellular levels were comparable. GSLs in the different matrices (plasma, PBMCs, CSF) did not correlate. Both lactosylceramide and glucosylsphingosine were more abundant in granulocytes compared with monocytes and lymphocytes. Absolute levels of GSL isoforms differed greatly. GBA1 mutation types could not be differentiated based on GSL data.

Conclusions

Glucosylceramide can stably be measured over days in both plasma and PBMCs and may be used as a biomarker in clinical trials targeting GBA-PD. Glucosylsphingosine and lactosylceramide are stable in plasma but are strongly affected by leukocyte subtypes in PBMCs. GBA-PD could be differentiated from iPD and HVs, primarily based on glucosylceramide levels in plasma. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity

Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson's disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50–70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN− and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10–12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson's disease.     

Differential progression of motor impairment in levodopa-treated Parkinson's disease.

OBJECTIVE: To monitor comparative progression of clinical impairment over 4 years in patients with Parkinson's disease (PD) who present on levodopa at two different levels of Hoehn and Yahr (HY) stages, II and III. BACKGROUND: The rate of clinical impairment progression in patients with PD being treated with levodopa has not been studied in detail using current, standardized assessment tools. Sample size estimates for all levodopa adjunctive treatment studies and proper definition of study groups require a solid estimate of longitudinal motor impairment progression. DESIGN/METHODS: From our computer database, we identified two groups of patients with PD being treated with levodopa based on their initial HY stage at presentation to our center (II or III). Fifty randomly selected subjects in each stage were monitored in the ON state with annual Unified Parkinson's Disease Rating Scale (UPDRS) motor scores, dyskinesia ratings, and antiparkinsonian medication doses using a repeated measures analysis of variance. RESULTS: The stage II and stage III subjects had similar disease duration. In stage II subjects, parkinsonian impairment was maintained without progression over 4 years, but in association with significantly higher dyskinesia scores and dopaminergic medication doses. In stage III subjects, UPDRS motor scores deteriorated despite more medication and increased dyskinesias. Of the established six factors comprising the UPDRS motor scale, bradykinesia accounted for the increased impairment. Initial UPDRS motor score and disease duration did not influence progression of motor impairment. CONCLUSION: In subjects with similar disease duration, progression of PD motor impairment differs significantly between stage II and stage III subjects over 4 years. Whereas in stage II subjects, parkinsonian impairment can be stabilized at the expense of increased dyskinesia and dopaminergic drugs, once subjects reach stage III, motor impairment progresses. Power estimates and sample size calculations for these groups of patients should be calculated separately.     

Striatal silent lacunar infarction is associated with changes to the substantia nigra in patients with early-stage Parkinson’s disease: A diffusion kurtosis imaging study

A recent study has shown that striatal silent infarction may occur secondary to the degeneration of dopaminergic neurons in the substantia nigra (SN) of mice. However, it is uncertain whether this phenomenon occurs in patients with early-stage Parkinson’s disease (PD) and can be detected by diffusion kurtosis imaging (DKI). A total of 72 untreated patients with early-stage PD underwent conventional MRI and DKI. Participants were divided into control and striatal silent lacunar infarction (SSLI) groups. The differences in mean kurtosis (MK) values of the SN, Hoehn–Yahr (H–Y) staging, and Unified Parkinson’s Disease Rating Scale (UPDRS) III score between groups, were analyzed. Linear regression analysis was used to correlate age, SSLI count, silent lacunar infarction count in other brain areas and age-related white matter change score with MK values of the SN. Spearman correlation coefficient analysis was used to correlate MK values of the SN and SSLI count with H–Y staging and UPDRS III score. There was no significant difference in the severity of disease between two groups; however, MK values of the SN with SSLI present were significantly higher than in SN without SSLI. In addition, SSLI count had linear correlation with MK values of the SN, which had positive correlation with H–Y-staging and UPDRS III score. SSLI is associated with structural changes to the SN in patients with early-stage PD, detectable by DKI, and may aggravate their motor impairments.     

Sonographic abnormalities in idiopathic restless legs syndrome (RLS) and RLS in Parkinson's disease

We aimed to investigate and compare sonographic abnormalities in the substantia nigra (SN) in patients with idiopathic restless legs syndrome (iRLS), those with RLS and Parkinson's disease (RLS-PD), those with idiopathic Parkinson's disease (iPD), and healthy controls. Study participants totaled 60 patients with RLS (41 iRLS, 19 RLS-PD), 25 iPD patients, and 35 age-matched healthy controls. Comparing all groups, the SN region's echogenicity area in the iRLS patients was significantly decreased compared with that in the PD-RLS, iPD, and control groups (p < 0.0001), and the PD-RLS group demonstrated a significantly increased echogenicity area compared with the control group (p < 0.05) and iRLS group (p < 0.0001). We found that the RLS-PD group's sonological results and clinical findings were different from those of the iRLS group.     

Repetitive transcranial magnetic stimulation of the primary motor cortex in the treatment of motor signs in Parkinson's disease: A quantitative review of the literature

Parkinson's disease (PD) is a progressive disorder characterized by the emergence of motor deficits. In light of the voluminous and conflicting findings in the literature, the aim of the present quantitative review was to examine the effects of repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1) in the treatment of motor signs in PD. Studies meeting inclusion criteria were analyzed using meta‐analytic techniques and the Unified Parkinson's Disease Rating Scale (UPDRS) sections II and III were used as outcome measures. In order to determine the treatment effects of rTMS, the UPDRS II and III scores obtained at baseline, same day, to 1 day post rTMS treatment (short‐term follow‐up) and 1‐month post stimulation (long‐term follow‐up) were compared between the active and sham rTMS groups. Additionally, the placebo effect was evaluated as the changes in UPDRS III scores in the sham rTMS groups. A placebo effect was not demonstrated, because sham rTMS did not improve motor signs as measured by UPDRS III. Compared with sham rTMS, active rTMS targeting the M1 significantly improved UPDRS III scores at the short‐term follow‐up (Cohen's d of 0.27, UPDRS III score improvement of 3.8 points). When the long‐term follow‐up UPDRS III scores were compared with baseline scores, the standardized effect size between active and sham rTMS did not reach significance. However, this translated into a significant nonstandardized 6.3‐point improvement on the UPDRS III. No significant improvement in the UPDRS II was found. rTMS over the M1 may improve motor signs. Further studies are needed to provide a definite conclusion. © 2015 International Parkinson and Movement Disorder Society     

Substantia nigra hyperechogenicity as a marker of predisposition and slower progression in Parkinson's disease.

Increased echogenic size (hyperechogenicity) of the substantia nigra (SN) is a characteristic transcranial sonography finding in patients with Parkinson's disease (PD). The SN echogenic size does not change in the course of the disease. In order to see whether this stable ultrasound marker may give any implications for the rate of PD progression, we sonographically investigated 16 PD patients in whom the rate of progression had been determined by serial 18-fluorodopa positron emission tomography over a follow-up period of 65.7+/-26.7 months. We found a significant negative correlation between the right-to-left averaged SN echogenic size and the rate of disease progression in the caudate nucleus and in the putamen. There was a tendency towards a younger age at symptom onset in patients with SN hyperechogenicity. It may therefore be hypothesized that a differing influence of factors determining SN echogenicity early in life and impairing forces occurring later in life may account for different pathogenetic subgroups of idiopathic PD.     

Abnormalities of motor cortical excitability are not correlated with clinical features in atypical parkinsonism.

OBJECTIVE: To evaluate the specificity of motor cortical excitability changes in parkinsonian syndromes and their relevance to the pathophysiology of cardinal parkinsonian features. METHODS: Paired transcranial magnetic stimulation (TMS) was used to assess cortico-cortical inhibition (CCI) and facilitation (CCF) in the opponens pollicis muscle of patients with atypical, non-L-dopa- (LD) responsive parkinsonism. RESULTS: Compared with age-matched normal control subjects, CCI (interstimulus interval [ISI], 3 ms) was significantly reduced in 10 patients with predominantly parkinsonian multiple system atrophy (MSA-P) and in seven with vascular parkinsonism (VP), but not in four with predominantly cerebellar MSA. No significant change of CCF (ISI, 12 ms) was observed. No correlation was found between the amount of CCI and clinical status as evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS). In 10 patients (5 MSA-P, 5 VP), CCI was significantly increased by LD acute administration without concurrent clinical changes. CONCLUSIONS: Abnormalities of CCI are not peculiar to idiopathic Parkinson's disease and seem unlikely to underlie any specific parkinsonian feature, but rather possibly reflect a nonspecific imbalance of inhibitory and facilitatory motor cortical circuits.     

Sonographic discrimination of dementia with Lewy bodies and Parkinson's disease with dementia

Objective To study the use of transcranial sonography (TCS) in discriminating between patients with dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). Methods Fourteen patients with DLB, 31 with PDD and 73 with PD without dementia (PDnD) were studied with TCS. Results All assessable patients with DLB, 97% with PDD, and 94% with PDnD showed at least unilateral hyperechogenicity of substantia nigra (SN). However, bilateral marked SN hyperechogenicity was present in 80% of DLB patients but only in one third of PDD and PDnD patients, and was associated with younger age at disease onset in PD but not in DLB. An asymmetry index ≥ 1.15 of bilateral SN echogenic sizes, estimated by division of larger size by smaller size, was found in 69% of PDD patients but only 20% of DLB patients. Combination of SN echogenic sizes, asymmetry indices and onset age discriminated PDD from DLB with a sensitivity of 96%, a specificity of 80% and a positive predictive value of 93%. TCS of brainstem raphe, thalami, lenticular nuclei, caudate nuclei and ventricle widths did not discriminate between DLB and PDD. Compared with PDnD patients, DLB and PDD patients exhibited significantly larger widths of third ventricle and of frontal horns. In PDD patients, scores on the Unified Parkinson's Disease Rating Scale correlated with widths of third ventricle and of frontal horns. Conclusions SN hyperechogenicity is typical for PDD and DLB.However, size, asymmetry and relation of SN hyperechogenicity to age at disease onset discriminate PDD from DLB.     

Region‐specific disturbed iron distribution in early idiopathic Parkinson's disease measured by quantitative susceptibility mapping

In Parkinson's disease (PD), iron elevation in specific brain regions as well as selective loss of dopaminergic neurons is a major pathologic feature. A reliable quantitative measure of iron deposition is a potential biomarker for PD and may contribute to the investigation of iron‐mediated PD. The primary purpose of this study is to assess iron variations in multiple deep grey matter nuclei in early PD with a novel MRI technique, quantitative susceptibility mapping (QSM). The inter‐group differences of susceptibility and R2^* value in deep grey matter nuclei, namely head of caudate nucleus (CN), putamen (PUT), global pallidus (GP), substantia nigra (SN), and red nucleus (RN), and the correlations between regional iron deposition and the clinical features were explored in forty‐four early PD patients and 35 gender and age‐matched healthy controls. Susceptibility values were found to be elevated within bilateral SN and RN contralateral to the most affected limb in early PD compared with healthy controls (HCs). The finding of increased susceptibility in bilateral SN is consistent with work on a subgroup of patients at the earliest clinical detectable state (Hoehn and Yahr [1967]: Neurology 17:427–442; Stage I). However, increased R2^* values were only seen within SN contralateral to the most affected limb in the PD group when compared with controls. Furthermore, bilateral SN magnetic susceptibility positively correlated with disease duration and UPDRS‐III scores in early PD. This finding supports the potential value of QSM as a non‐invasive quantitative biomarker of early PD. Hum Brain Mapp 36:4407–4420, 2015. © 2015 Wiley Periodicals, Inc .