Transcranial Brain Sonography Research Articles

Transcranial brain sonography for Parkinsonian syndromes.

Substantia nigra (SN) hyperechogenicity has been proved to be a characteristic finding for idiopathic Parkinson's disease (PD), occurring in more than 90% of the patients. This echofeature is owed to increased amounts of iron in the SN region and reflects a functional impairment of the nigrostriatal dopaminergic system. In a prospective blinded study in which a group of patients with early mild signs and symptoms of unclear Parkinsonism were followed until a definite clinical diagnosis of PD, the hyperechogenicity of the SN was demonstrated to be highly predictive of a final diagnosis of PD. For the diagnosis of PD in individuals with early motor symptoms, both the sensitivity and positive predictive value of SN hyperechogenicity were higher than 90% and both the specificity and negative predictive value were higher than 80%. For early differential diagnosis between PD and atypical Parkinsonian syndromes, the sensitivity and positive predictive value of SN hyperechogenicity were higher than 90%, and both the specificity and negative predictive value were higher than 80%. The diagnostic specificity is increased if combining the TCS findings of SN, lenticular nucleus and third ventricle. In asymptomatic adult subjects, SN hyperechogenicity, at least unilaterally, indicates a subclinical functional insufficiency of the nigrostriatal dopaminergic system. Recent papers revealed that SN hyperechogenicity might suggest preclinical PD. Reduced echogenicity of midbrain raphe indicates increased risk of depression in PD patients. Caudate nucleus hyperechogenicity has been associated with drug-induced psychosis, and frontal horn dilatation >20 mm with dementia. Transcranial brain sonography can be a valuable tool for managing patients with Parkinsonian signs and symptoms.

Sonographic alteration of substantia nigra is related to parkinsonism-predominant course of X-linked dystonia-parkinsonism

IntroductionX-linked recessive dystonia-parkinsonism (XDP, DYT3) is highly prevalent in the Philippines and manifests with varying phenotype. We sought to evaluate the significance of transcranial brain sonography as a biomarker for parkinsonism-predominant phenotype. Methods90 Filipino participants were enrolled into a cross-sectional study: 39 patients with XDP, 21 asymptomatic first-degree relatives of XDP patients, and 30 healthy control subjects. Echogenicity of the substantia nigra and the lenticular nuclei was digitally quantified. Brain sonography data were compared with video-based clinical assessment, genetic status and pedigree charts. ResultsThe majority of patients had hyperechogenicity of the substantia nigra (79%) and/or the lenticular nuclei (81%). Disease duration correlated with echointensity of lenticular nuclei (Pearson test, r = 0.55, p = 0.029) but not substantia nigra (p = 0.31). Abnormal substantia-nigra hyperechogenicity was more frequent in patients with prominent parkinsonism (100%) compared to those without (68%; χ2 test, p = 0.035). The grading of substantia-nigra echogenicity (normal/increased) in patients was in all cases identical to that in their respective asymptomatic relatives. All patients with “familial” substantia-nigra normoechogenicity presented with a phenotype of predominant dystonia and only mild parkinsonism. In turn, “familial” substantia-nigra hyperechogenicity indicated a phenotype with moderate to severe parkinsonism (sensitivity, 100%; specificity, 67%; Fisher test, p = 0.021). ConclusionFindings imply early alteration of the substantia nigra in XDP mutation carriers prone to develop parkinsonism. Thus, substantia-nigra hyperechogenicity may be regarded as a preclinical risk marker of parkinsonism-predominant XDP. Furthermore, this biomarker is clustered in some families suggesting the existence of one or more genetic co-factors influencing the phenotype of the disease.

Transcranial Brain Sonography in Parkinson's Disease and Other Parkinsonian Disorders: a Hospital Study from Tuzla, Bosnia and Herzegovina.

Introduction:Transcranial sonography (TCS) is a relatively new ultrasound modality which could display echogenicity of human brain tissue through the intact skull. TCS may be useful in differentiation of idiopathic Parkinson’s disease (PD) from other parkinsonian disorders. Therefore, we studied different ultrasound markers by TCS in individuals with Parkinson’s disease.Patients and Methods:We performed TCS in 44 patients with PD and 22 patients with other parkinsonian disorders. Echogenic sizes of the substantia nigra (SN) and the lentiform nuclei (LN), as well as the width of the third ventricle and the frontal horns of the lateral ventricle, were measured. We also analyzed the echogenicity of the brainstem raphe (BR).Results:An unilateral hyperechogenic SN was observed in 31 (70%) patients with PD and only in 2 patients (9%) with other parkinsonian disorders (P<0.0001). Hyperechogenicity of the LN was no observed in patients with PD; however, it was present in 7 (32%) patients with other parkinsonian disorders (P=0.0002). Diameter of third ventricle (8.6+/-2.2 mm vs. 6.9+/-1.7mm, P=0.001), right (18.5+/-2.6 mm vs. 16.5+/-2.3 mm, P=0.003) and left frontal horn of lateral ventricle (19.0+/-3.7 mm vs. 16.2+/-2.6 mm, P=0.0006) was significantly wider in patients with other parkinsonian disorders compared with patients with PD. There was no difference in presence of hypoechogenic or interrupted BR in patients with PD and patients with other parkinsonian disorders (39% vs. 27%, P=0.4).Conclusion:TCS is a promising diagnostic technique and can be very helpful in differentiating between idiopathic Parkinson’s disease and other parkinsonian disorders.

Transcranial sonography in dopa-responsive dystonia.

Mutations in the GCH1 gene, encoding GTP cyclohydrolase 1, the enzyme critically important for dopamine production in nigrostriatal neurons, are the most common cause of dopa-responsive dystonia (DRD), characterized predominantly by limb dystonia, although parkinsonian features may also be present. It has been suggested that DRD is a neurochemical rather than neurodegenerative disorder. Transcranial brain sonography, which might be a risk marker for nigral injury, was obtained from 141 subjects divided into four groups: (i) 11 patients with genetically confirmed DRD; (ii) 55 consecutive patients with Parkinson's disease (PD); (iii) 30 patients diagnosed as isolated adult-onset focal dystonia; and (iv) 45 healthy controls (HCs). Substantia nigra hyperechogenicity was present in 63.6% of patients with DRD, which was significantly different in comparison to patients with dystonia (20%) and HCs (6.7%), but not in comparison to the PD group (87.3%). Also, values of the maximal areas of substantia nigra hyperechogenicity in patients with DRD were higher in comparison to HCs, but significantly lower than among the PD group. We suggested that the observed transcranial brain sonography features in patients with DRD might primarily be risk markers for particular clinical features (parkinsonism, dystonia) occurring in the specific genetic context (i.e. GCH1 mutations), or might reflect compensated neurodegenerative processes triggered by the long-lasting dopamine deficiency due to the profound delay in levodopa treatment in our patients with DRD.

Frequency and profile of Parkinson's disease prodromi in patients with malignant melanoma

ObjectiveThe results of register studies suggest an association between Parkinson's disease (PD) and melanoma. We studied the frequency and profile of early markers of PD in patients with malignant melanoma.Methods100...

Lenticular nucleus hyperechogenicity in Wilson’s disease reflects local copper, but not iron accumulation

In patients with Wilson's disease (WD) transcranial brain sonography typically reveals areas of increased echogenicity (hyperechogenicity) of the lenticular nucleus (LN). Correlation with T2-hypointensity on magnetic resonance images suggested that LN hyperechogenicity in WD is caused by trace metal accumulation. Accumulation of both, copper and iron, in the brain of WD patients has been reported. The present study was designed to elucidate whether LN hyperechogenicity in WD reflects accumulation of copper or iron. Post-mortem brains of 15 WD patients and one non-WD subject were studied with ultrasonography in an investigator-blinded fashion. LN hyperechogenicity was measured planimetrically by manual tracing as well as using digitized image analysis. The putaminal copper content was determined in samples of 11 WD brains and the non-WD brains using inductively coupled plasma mass spectrometry, and iron content was assessed using flame atomic absorption spectroscopy. LN was normal on ultrasonography only in the non-WD brain, but abnormal (hyperechogenic) in all WD brains. Digitized image analysis measures of LN hyperechogenicity and, by trend, manual measures correlated with putaminal copper content (Pearson test; digitized: r = 0.77, p = 0.04; manual: r = 0.57, p = 0.051) but not with iron content (each, p > 0.18). LN hyperechogenicity measures were unrelated to age at death of patients, age at onset of WD, WD duration, age of brain specimen, serum copper or serum ceruloplasmin (each, p > 0.1). We conclude that LN hyperechogenicity in WD reflects copper, but not iron accumulation. Further studies are warranted to elucidate the use of transcranial brain sonography for monitoring therapeutic effects of chelating agents in WD patients.

Asymmetric Postural Tremor Preceding DOPA-Responsive Parkinsonism – the Transition Disease

Tremulous Parkinson's disease (PD) and essential tremor are well known to be associated, but characteristics of progression of pure tremor state to PD remain unclear. In this prospective study a cohort of 16 patients suffering from a suggested new disease entity was clinically, pharmacologically, and sonographically analyzed to evaluate whether characteristics giving rise to a new entity in this field can be detected. All patients had a history of asymmetric postural tremor (aPT) who either already had developed surplus Parkinsonism (PARK group), or were still in the state of a pure asymmetric postural tremor syndrome (APT group). Asymmetry of aPT was assessed by tremor scores including an asymmetry index. DOPA-responsivity was analyzed by tremor scores and the score of the motor part of the Unified Parkinson's disease rating scale. Transcranial brain sonography was performed to evaluate echogenicity of the substantia nigra. Mean age at onset of asymmetric postural tremor was 57 ± 8.5 years without significant differences between both groups. Family history was compatible with an autosomal-dominant inheritance pattern in the majority of patients of both the APT and PARK group. All patients in the PARK group and 3 out of 8 patients in the APT group (38%) with respect to their asymmetric postural tremor were DOPA-responsive. All patients of both groups eligible to transcranial brain sonography showed hyperechogenicity of substantia nigra. In both groups, there was no correlation between tremor severity and duration of asymmetric postural tremor. Our data indicate that patients with an initial asymmetric and sometimes DOPA-responsive postural tremor syndrome and PARK patients are at various stages within the transition from aPT to a later developed DOPA-responsive Parkinsonian syndrome. It is postulated that the described group of patients may represent a separate disease entity with a hereditary background.

Combining Testing Methods

The authors deserve thanks for their explanation of the diagnostic value of hyposmia in neurodegenerative disorders (1). The recommendation of olfactory testing from the American Academy of Neurology, which the authors adopted, as a potential sole instrument to distinguish idiopathic Parkinson’s disease (IPD) from progressive supranuclear palsy (PSP) (2) needs comment. This recommendation is based on studies that investigated a total of only 16 PSP patients with a blinded study design by using olfactory testing; only one PSP patient was studied using “Sniffin’ Sticks”. In this setting, guidelines for the type and extent of olfactory testing and threshold values are lacking. In our experience, the olfactory identification tests based on Sniffin’ Sticks, which are commonly used in Germany’s neurological hospitals, have insufficient sensitivity and specificity in differentiating PSP from IPD. Only their combination with other non-invasive testing methods, such as transcranial brain sonography and motor examination (3), is of high diagnostic value. The authors rightly pointed out that slowly progressing olfactory dysfunction is an often unnoticed early symptom of IPD. On the other hand, 30% of IPD patients experience olfactory dysfunction as a prodromal symptom, but fewer than 5% of these report their symptoms to their doctor (our own investigation, manuscript submitted for publication). The common complete lack of perception of, or subjective lack of attention to, olfactory dysfunction may be a reason why idiopathic hyposmia or anosmia diagnosed by an otorhinolaryngologist is mostly an incidental diagnosis. Educating the wider population about the potential relevance of olfactory dysfunction in the early detection of IPD makes sense only once effective treatment methods become available that can delay the progression of IPD in its early phase.

Transcranial brain sonography findings in two main variants of progressive supranuclear palsy

Progressive supranuclear palsy (PSP) can occur with two main clinical presentations, classified as classical Richardson's syndrome (PSP-RS) and as PSP-parkinsonism (PSP-P), the most common atypical PSP variant. The differential diagnosis between them is challenging. Therefore, we studied different ultrasound markers by transcranial sonography in individuals with PSP-RS and PSP-P, to test their value in the diagnostic work up of these patients. Transcranial sonography was performed in 21 patients with PSP-RS and 11 patients with PSP-P. Echogenic sizes of the substantia nigra (SN) and the lenticular nuclei (LN), as well as the width of the third ventricle, were measured. Among the patients with PSP-RS and PSP-P, three (14%) and eight (73%) patients had a hyperechogenic SN (P = 0.020), respectively. Uni- or bilateral hyperechogenicity of the LN was observed in 67% and 36% of patients with PSP-RS and PSP-P, respectively (P = 0.101). Third ventricle was significantly wider in patients with PSP-RS (11.2 ± 2.3 mm) when compared with patients with PSP-P (7.5 ± 1.4 mm; P = 0.001). Our data, possibly reflecting pathological differences, primarily contribute supporting the view that the neurodegenerative process differs in the two PSP variants.

Hirnsonografie, Riechtestung und motorische Testverfahren in der Frühdiagnose des idiopathischen Parkinson-Syndroms

The early diagnosis of idiopathic Parkinson's disease, preferably already at premotor disease stages, promises a greater benefit of upcoming neuroprotective therapies. While genetic, biochemical, radiotracer and other specialised imaging methods have their specific place value in the diagnostic confirmation of a suspected premotor Parkinson's disease, for the broad screening of risk populations non-invasive, low-cost diagnostic methods are more suitable. The present article gives an overview on the results of recently published studies and of our own investigations on the use of transcranial brain sonography, olfactory testing and motor assessment tools including their combined use for the detection of individuals at high risk for the later development of Parkinson's disease.

Evaluation of basal ganglia, brainstem raphe and ventricles in bipolar disorder by transcranial sonography

Transcranial brain sonography (TCS) has become a reliable and sensitive diagnostic tool in the evaluation of extrapyramidal movement disorders. Alterations of brainstem raphe (BR) have been depicted by TCS in major depression but not in bipolar disorder. The aim of our study was to evaluate BR echogenicity depending on the different conditions of bipolar patients. Echogenicities of dopaminergic basal ganglia structures were assessed for the first time in bipolar disorder. Thirty-six patients with bipolar I disorder (14 depressed, 8 manic, 14 euthymic) were compared to 35 healthy controls. Echogenicities were investigated according to the examination protocol for extrapyramidal disorders using a Siemens Sonoline® Elegra system. The sonography examiner was blinded for clinical rating scores. Six patients (16.7%) showed hyperechogenicity of the substantia nigra. The raphe was hypoechogenic in 13 (36.1%) of the patients. No significant differences were seen between the subgroups. Compared to the control group, frequency of altered echogenicities did not reach statistical significance. The width of third ventricle was significantly larger in the patient group (3.8±−2.1 mm vs. 2.7±1.2 mm). Depressed bipolar patients with reduced BR echogenicity showed significantly higher scores on the Hamilton Depression Rating Scale as well as the Montgomery-Åsberg Depression Rating Scale. In contrast to unipolar depression, sonographic findings of bipolar patients may generally indicate structural integrity of mesencephalic raphe structures. If bipolar disorder coexists with hypoechogenic raphe structure, depressive symptoms are more severe.

Transcranial sonography findings in spinocerebellar ataxia type 3 (Machado–Joseph disease): A cross-sectional study

Few studies on transcranial brain sonography have been performed in hereditary and non-hereditary ataxias. The objective of the present study was to report transcranial brain sonography findings in a sample of clinically and molecularly proven Machado–Joseph disease patients and to compare these data against those of an age- and gender-matched control group. A cross-sectional study on transcranial brain sonography was conducted in 30 Machado–Joseph disease patients. Transcranial brain sonography was performed by an experienced sonographer blinded to the clinical, genetic, and neuroimaging data. The results were compared with those of a control group of 44 healthy subjects matched for age and gender. The sonographic findings were also correlated with clinical features and genetic data in Machado–Joseph disease group. A significantly higher frequency of substantia nigra and lenticular nucleus hyperechogenicity was found in the Machado–Joseph disease group compared to an age- and gender-matched healthy control group (p<0.001). The substantia nigra echogenic area proved to be the best predictor for differentiating cases from controls. Third and lateral ventricles were significantly larger in the Machado–Joseph disease patients than in the control subjects. No significant correlations were found between transcranial brain sonography findings and Machado–Joseph disease demographic/clinical data. Transcranial brain sonography findings in Machado–Joseph disease patients differed significantly to those in age- and gender-matched controls. Substantia nigra hyperechogenicity occurred frequently in Machado–Joseph disease patients and was found to be the best predictor for differentiating cases from controls. Additionally, this data describes the occurrence of brain atrophy in Machado–Joseph disease group.

Transcranial brain sonography in Parkinson's disease with restless legs syndrome

Substantia nigra (SN) hyperechogenicity assessed by transcranial brain sonography (TCS) is a characteristic finding in idiopathic Parkinson's disease (PD). In contrast, SN hypoechogenicity on TCS has been recently demonstrated in restless legs syndrome (RLS). RLS is one of the most common sleep problems in PD, but the pathophysiologic relationship between these two disorders has not been thoroughly elucidated. We compared the SN echogenicities of PD patients with and without RLS to investigate whether comorbid RLS in PD affects SN echogenicity and to explain the echogenic differences between idiopathic RLS (iRLS) and secondary PD-related RLS (pRLS). Sixty-three PD patients (median age 64.6 +/- 10.6 years), 40 iRLS patients (53.1 +/- 11.7 years), and 40 healthy controls (69.1 +/- 2.3 years) were enrolled in our study. All subjects answered a sleep questionnaire and underwent TCS. PD patients were subdivided into two groups, PD with RLS (PD+RLS, n = 26) and PD without RLS (PD-RLS, n = 37), and the sonographic findings of each group were compared. Although significant hyperechogenicity was detected in both the SN and SN/midbrain ratios in both PD subgroups compared with the controls and the iRLS group (P < 0.001), there were no significant differences in SN echogenicity between the PD+RLS and PD-RLS groups. Meanwhile, iRLS patients showed significant SN hypoechogenicity. In conclusion, comorbid RLS in PD did not have an impact on the sonographic SN findings. These results suggest that the pathogenesis of pRLS and iRLS involve different mechanisms. Further study will be required to clarify the association between RLS and PD.

Substantia nigra hyperechogenicity in Parkinson’s disease

Dear Editor Over the past 15 years, the visualization of brain structures, mainly the mesencephalon and the basal ganglia, has been possible by transcranial sonography (TCS) in patients with intact skull. Since then, several papers concerning TCS in movement disorders have been published, nevertheless, to the best of our knowledge, none of them in neurosurgical journals. In order to update the neurosurgical community on this subject, the authors report a characteristic finding of Parkinson’s disease (PD), the hyperechogenicity of the substantia nigra (SN) disclosed by TCS [1–10, 12], and discuss the significance of this ultrasound sign in clinical neurosurgery. A 59-year-old man with advanced PD, severe motor fluctuations, and incapacitating levodopa-induced dyskinesias underwent bilateral deep brain stimulation (DBS) of the subthalamic nucleus with excellent results. He presented with a relatively early onset of PD symptoms (50 years of age). Transcranial brain sonography disclosed a marked hyperechogenicity of the SN (0.36 cm on the right SN, and 0.39 cm on the opposite side; Fig. 1a), and a normal echogenicity lentiform nucleus. Hyperechogenic images of the DBS electrodes were also shown clearly (Fig. 1b). SN hyperechogenicity has been considered characteristic for idiopathic PD, occurring in 91-100% of the patients [3, 8]. It was demonstrated to be caused by increased amounts of iron bound to protein other than ferritin in the SN, and reflects a functional impairment of the nigrostriatal dopaminergic system [2, 7]. For most authors, echogenic areas in the SN region ≤0.19 cm are classified as normal, while areas ≥0.20 cm are considered as hyperechogenic [1–10, 12]. SN echogenic size tends to be larger contralateral to the clinically more affected side, and larger SN echogenic sizes correlate with younger age at the disease onset [3, 8]. The diagnosis of PD is a challenge since several other conditions resemble the idiopathic form of the disease. SN hyperechogenicity associated with normal lentiform nucleus echogenicity may discriminate idiopathic PD from atypical Parkinsonian syndromes (multiple system atrophy and progressive supranuclear palsy) with a positive predictive value ≥90% [3, 8, 9]. In a prospective blinded study, the sensitivity of SN hyperechogenicity for idiopathic PD versus atypical Parkinsonian syndromes was 94.8%, the specificity was 90%, the positive predictive value was 97.4%, and the negative predictive value was 81.8% [4]. In asymptomatic adult subjects, SN hyperechogenicity, at least unilaterally, indicates a subclinical functional impairment of the nigrostriatal dopaminergic system. Recent papers revealed that SN hyperechogenicity might suggest preclinical PD [2, 3, 7, 8], and SN hyperechogenicity correlates with severity of Parkinsonian symptoms induced by neuroleptic therapy [1]. Reduced echogenicity of midbrain raphe indicates increased risk of depression and urinary incontinence in PD patients. Caudate nucleus hyperechogenicity is associE. Bor-Seng-Shu (*) :M. J. Teixeira Division of Neurological Surgery, Laboratory for Neurosonology, Cerebral Hemodynamics and Neurocritical Care, Hospital das Clinicas, University of Sao Paulo School of Medicine, Rua Loefgreen, 1272, CEP 04040-001 Sao Paulo, Brazil e-mail: edsonshu@hotmail.com

Transcranial brain sonography in Huntington's Disease: depression correlates with the detection of hypoechogenic mesencephalic raphe structures

Transcranial sonography (TCS) has become a new diagnostic tool in the evaluation of extrapyramidal disorders. Furthermore, recent studies report alterations of mesencephalic raphe structures in unipolar depression and in depressed Parkinson patients. Aim of this study was to evaluate TCS findings in patients with Huntington's disease in correlation with their neurological and psychiatric status.

Recent imaging advances in the diagnosis and management of Parkinson's disease

In this review we report novel sensitive imaging biomarkers for Parkinson’s disease (PD) and its atypical variants. Diffusion tensor imaging and transcranial brain sonography are potentially promising techniques that can differentiate typical PD from atypical variants (multiple system atrophy and progressive supranuclear palsy) and from benign tremor disorders. Non-motor symptoms, such as dementia, depression, and sleep disruption, are often more distressing to PD patients than their slowness and stiffness. Dopamine replacement treatment can also lead to complications such as dyskinesias, impulse control disorders, and psychosis. Recent positron emission tomography studies have helped to clarify the physiopathological mechanisms underlying dementia and compulsive gambling in PD and provide a rationale for therapeutic strategies.

This week in Neurology ®

### Transcranial brain sonography findings predict disease progression in multiple sclerosis The authors performed transcranial sonography in patients with multiple sclerosis and frequently detected increased echogenicity of substantia nigra and basal ganglia, thought to reflect iron accumulation. Substantia nigra echogenicity correlated with rate of further disease progression. These findings suggest that the course of multiple sclerosis correlates with changes in iron metabolism. See p. 1010; Editorial, p. 1006 ### Increased neuronal proliferation in human bacterial meningitis This retrospective study examined the records of 16 patients who underwent autopsy subsequent to bacterial meningitis. Diagnosis of bacterial meningitis was …

Transcranial brain sonography findings predict disease progression in multiple sclerosis

In multiple sclerosis (MS), an early neurodegenerative affection of subcortical gray matter has been suggested. Transcranial sonography (TCS) shows hyperechogenic lesions of substantia nigra (SN) and basal ganglia, thought to reflect iron accumulation, in a number of primary neurodegenerative diseases. The present study deals with the question of whether TCS can also display deep gray matter lesions in patients with MS and whether sonographic findings relate to severity and progression of MS. We prospectively studied 75 patients with different courses of MS and 55 age-matched healthy subjects clinically and with TCS. Twenty-three patients additionally had 1.5-T MRI at the time of TCS. Disease progression was assessed clinically 2 years after TCS. Abnormal hyperechogenicity of SN, lenticular nucleus (LN), caudate nucleus, and thalamus was found in 41%, 54%, 40%, and 8% of the patients with MS, with similar frequency in patients with relapsing-remitting and primary or secondary progressive MS if corrected for disease duration, but only in 13%, 13%, 5% (each, p < 0.001), and none (p = 0.028) of the control subjects. Hyperechogenicity of SN and LN correlated with more pronounced MRI T2 hypointensity, thought to reflect iron deposition. Larger bilateral SN echogenic area was related to higher rate of disease progression, whereas small SN echogenic area (SN hypoechogenicity) predicted a disease course without further progression within 2 years. Neurodegenerative disease-like deep gray matter lesions can be frequently detected by transcranial sonography (TCS) in patients with multiple sclerosis (MS). Findings suggest that TCS shows changes of brain iron metabolism which correlate with future progress of MS.

Transcranial brain sonography findings in Parkinson’s disease: implications for pathogenesis, early diagnosis and therapy

In Parkinson’s disease (PD) transcranial sonography (TCS) reveals changes of several deep brain structures that are related to distinct motor and nonmotor features. Approximately 90% of PD patients exhibit substantia nigra (SN) hyperechogenicity, which is stable over time and discriminates PD from atypical parkinsonian disorders. Since this TCS feature is also present in 9% of healthy adults aged 18–80 years, and is associated with a subclinical malfunction of the nigrostriatal dopaminergic system, it is considered to be a risk marker for PD. SN hyperechogenicity is caused by increased amounts of iron, probably in abnormal protein bindings, and could be related in some cases to mutations of genes involved in iron metabolism. Influencing the disturbances of iron metabolism reflected by SN hyperechogenicity early in life might become a future therapeutic target for PD. Longitudinal studies currently assess the value of SN hyperechogenicity in combination with clinical and other neuroimaging findings in predicting an individual high risk of PD. TCS has the potential of a cost–effective, quick and mobile screening tool for risk populations within a stepwise diagnostic scheme to select individuals for upcoming neuroprotective therapies. This review summarizes TCS findings, shedding light on the pathophysiology of PD, and discusses their potential therapeutic relevance.

Transcranial Brain Sonography Findings in Discriminating Between Parkinsonism and Idiopathic Parkinson Disease

In several pilot studies, transcranial brain sonography findings of substantia nigra and lenticular nucleus discriminated between idiopathic Parkinson disease (PD) and atypical parkinsonian disorders. To study the use of transcranial brain sonography in excluding the diagnosis of idiopathic PD in patients with sporadic parkinsonism. All patients with parkinsonism admitted to our movement disorder clinic from January 1, 2003, through December 31, 2005, who fulfilled clinical diagnostic criteria for definite PD, probable parkinsonian variant of multiple-system atrophy (MSA-P), or probable progressive supranuclear palsy (PSP) were prospectively studied with transcranial brain sonography by an investigator blinded to clinical diagnoses. Patients Eligible patients included 138 with sporadic idiopathic PD (82 men and 56 women; mean +/- SD age, 67.1 +/- 9.8 years; mean +/- SD disease duration, 7.5 +/- 6.3 years; mean +/- SD motor score on the Unified Parkinson Disease Rating Scale, 32.6 +/- 18.1), 21 with MSA-P (10 men and 11 women; mean +/- SD age, 65.4 +/- 9.5 years; mean +/- SD duration of disease, 3.1 +/- 2.0 years; mean +/- SD motor score, 33.5 +/- 16.1), and 22 with PSP (13 men and 9 women; mean +/- SD age, 71.2 +/- 5.5 years; mean +/- SD duration of disease, 3.4 +/- 2.4 years; mean +/- SD motor score, 46.2 +/- 18.9). In 7 patients, transcranial brain sonography was not possible owing to insufficient temporal acoustic bone windows. Sensitivity, specificity, and predictive value of transcranial brain sonography in indicating an atypical parkinsonian syndrome rather than idiopathic PD in patients with sporadic parkinsonism. Normal echogenic substantia nigra indicated MSA-P rather than PD (sensitivity, 90%; specificity, 98%; positive predictive value, 86%), whereas third-ventricle dilatation of more than 10 mm in combination with lenticular nucleus hyperechogenicity indicated PSP rather than PD (sensitivity, 84%; specificity, 98%; positive predictive value, 89%). Normal echogenic substantia nigra combined with lenticular nucleus hyperechogenicity indicated MSA-P or PSP (sensitivity, 59%; specificity, 100%; positive predictive value, 100%). In parkinsonism with age at onset younger than 60 years, normal echogenic substantia nigra alone indicated MSA-P or PSP (sensitivity, 75%; specificity, 100%; positive predictive value, 100%). Distinct transcranial brain sonography findings can exclude the diagnosis of PD in patients with sporadic parkinsonism. Sonographic discrimination of atypical parkinsonian syndromes from PD is clearer in patients with onset of parkinsonism at younger than 60 years.