Distinguishing Parkinson's disease and essential tremor with transcranial sonography

Objectives – Until today there is no reliable test that can clearly distinguish Parkinson’s disease (PD) from the essential tremor (ET). Our aim was to determine the usefulness of the transcranial sonography (TCS) in the differential diagnosis of the PD and ET as well as the interobserver reliability for this method. Methods – Transcranial sonography of substantia nigra and clinical examination were performed on 80 PD patients, 30 ET patients, and 80 matched controls by two independent physicians. Results – Bilateral SN hyperechogenicity over the margin of 0.20 cm² was found in 91% of PD patients, 10% of healthy subjects, and in 13% patients with ET. Interobserver agreement for this method was significant (Student’s t‐test, P = 1.000). Conclusions – Substantia nigra hyperechogenicity on TCS is a highly specific finding of PD, where in healthy individuals or in ET patients, it might correspond to an increased risk of developing PD later in life or might also be because of the impairment of nearby area of nucleus ruber in ET patients, as suggested by positron emission tomography studies. TCS may serve as a practical and sufficiently sensitive neuroimaging tool in PD diagnoses and in distinguishing it from ET; its repeatability and accuracy might add to its practical value.     

Transcranial brain sonography findings in clinical subgroups of idiopathic Parkinson's disease.

To investigate whether transcranial brain sonography (TCS) discriminates different courses of idiopathic Parkinson's disease (PD), 101 patients with clinically definite PD were studied. In four patients, TCS was not possible due to insufficient acoustic temporal bone windows. Substantia nigra (SN) hyperechogenicity was found in 96% of assessable patients. Larger SN echogenic size correlated with younger age at PD onset (Spearman correlation, r = -0.383; P < 0.001), but not with age, PD duration, or severity. Marked bilateral SN hyperechogenicity indicated early-onset rather than late-onset PD, and akinetic-rigid (AR) or mixed-type (MX) PD rather than tremor-dominant PD. SN echogenic sizes were larger contralateral to the clinically more affected side in AR PD and MX PD patients. Reduced echogenicity of brainstem raphe was associated with depression (RR = 1.61; 95% CI = 1.05-2.46; P = 0.044) but not with other clinical features. Caudate nucleus hyperechogenicity was, independently from PD duration, related to drug-induced psychosis (RR = 2.40; CI = 1.36-4.22; P = 0.001), but not to motor fluctuations. Lenticular nucleus hyperechogenicity indicated AR PD rather than tremor-dominant PD (RR = 1.44; CI = 1.11-1.86; P = 0.040). Frontal horn dilatation > 15.4 mm (mean of bilateral measurements) indicated increased risk of dementia (RR = 4.11; CI = 1.51-11.2; P = 0.001). We conclude that TCS displays characteristic changes of deep brain structures in different clinical manifestations of PD.     

Emotional processing in Parkinson's disease. A study using functional transcranial doppler sonography

This study evaluated the use of transcranial Doppler ultrasonography for detecting selective changes in cerebral blood flow velocity during emotional processes. The aim was to investigate the possibility of obtaining functional information on the neuropsychology of emotions in patients with Parkinson's disease (PD). For this reason, blood flow velocity changes were investigated in both middle cerebral arteries (MCA) during a rest condition and when viewing non emotional (tasks 1 and 3) and emotional (task 2) slide sequences. The study included 12 PD patients and 12 healthy subjects. All patients were in treatment with levodopa or dopamine agonist. Investigation of PD patients was performed during an on-phase. The three tasks produced significantly different effects on the right and left side in the PD patients compared with the control group. During the two non emotion-related tasks the increase of mean flow velocity (MFV) compared with the basal values was similar in the two middle cerebral arteries in both groups [(PD Patients: Task 1: left MCA = 3.95 % 2.2, Right MCA = 4.33 % ± 2.3, Task 3: left MCA = 3.04 % ± 1.9, Right MCA = 2.71 % ± 2.2) (control group: Task 1: left MCA = 4.57 % ± 1.4, Right MCA = 4.46 % ± 1.7, Task 3: left MCA = 2.32 % ± 0.9, Right MCA = 2.52 % ± 1.2)] The negative emotional task was accompanied by a significantly higher increase in the right (10.53 % ± 3.2) than in the left middle cerebral artery (4.52 % ± 1.51) only in the control group. The PD patients showed a bilateral and symmetrical increase of MFV (left MCA = 4.28 % ± 2.3 and right MCA 5.77 % ±3.8). To determine whether there was a dysfunction in cerebrovascular reactivity and a deficit in the ability to activate both hemispheres in response to non emotion-related stimuli in the PD patients, the protocol study included a cerebrovascular reactivity test to apnea, a motor task (thumb-to-finger opposition), a cognitive task (word fluency and visual discrimination of objects), performed by both patients and controls. The pattern of MFV changes during these tasks was not statistically significantly different in the two experimental groups. In order to evaluate the possible influence of drug treatment on cerebrovascular reactivity, seven patients were also evaluated during an off-phase, after a 48-hour wash-out period. Changes in MFV during every task were similar to that observed during the on-phase. These findings show the possibility of obtaining specific functional information from bilateral transcranial Doppler and suggest the selective and specific deficit of PD patients in emotional processing. Received: 23 July 2001 Received in revised form: 28 January 2002 Accepted: 1 February 2002     

Transcranial sonography findings in welding‐related Parkinsonism in comparison to Parkinson's disease

The pathogenetic relationship of welding‐related Parkinsonism (WP) and idiopathic Parkinson's disease (PD) is a matter of debate. In the present study, we compared transcranial sonography (TCS) findings in patients with WP and PD. Two male patients with WP, who had developed levodopa‐resistant akinetic‐rigid Parkinsonism without ongoing progression after having worked as welders for many years in Chilean mines in confined spaces without adequate ventilation, and three age‐matched male patients with clinically definite akinetic‐rigid PD were studied with TCS in a random order by two investigators blind to clinical diagnoses. In both WP patients, normal echogenicity of substantia nigra was found whereas all PD patients exhibited marked substantia nigra hyperechogenicity, previously reported as a characteristic TCS finding in idiopathic PD. In contrast, lenticular nucleus was hyperechogenic in both WP patients but only in one of the PD patients. TCS findings suggest a different pathophysiology of Parkinsonism in WP and PD patients. © 2007 Movement Disorder Society     

Transcranial color-coded sonography helps differentiation between idiopathic Parkinson's disease and vascular parkinsonism

Abstract Background Recently, transcranial color-coded sonography (TCCS) has been found to have a diagnostic value in patients with idiopathic Parkinson's disease (IPD), which displays increased hyperechogenicity at the substantia nigra (SN). Objective To use TCCS, to assess the difference in SN hyperechogenicity and intracranial hemodynamics among subjects with IPD, vascular parkinsonism (VP) and controls. Methods Eighty IPD and 30 VP patients, and 60 controls were recruited into this study. The hyperechogenicity area at the SN and midbrain were calculated by encircling the outer circumference from the ipsilateral temporal window, using TCCS in each subject. The hemodynamics of intracranial large arteries, including flow velocity and pulsatility index (PI), were also measured. Results The presence of SN hyperechogenicity was significantly higher in the IPD patients than in the VP patients and controls (84% vs. 20% & 5%, respectively, p < 0.001). In IPD patients, the SN hyperechogenicity was correlated with the neurological severity and disease duration. Twenty-five (66.7%) VP patients had obvious vascular abnormality, as seen in TCCS study. The mean PI was significantly more elevated in the VP patients than those in the IPD patients and controls (all p < 0.05), but there was no significant difference of flow velocities among the VP, IPD patients and controls. Conclusion TCCS, combining B-mode imaging for SN echogenicity and trancranial Doppler for intracranial hemodynamics, is a useful diagnostic tool in the differentiation between IPD and VP. These findings also suggest that multiple subcortical vascular lesions may damage the basal ganglia and thalamocortical circuit and result in parkinsonism features in VP patients.     

Midbrain transcranial sonography in Korean patients with Parkinson's disease.

Transcranial sonography (TCS) is potentially useful for the diagnosis of Parkinson's disease (PD). However, studies on TCS have so far been restricted to European populations. To investigate the efficacy of TCS in Korean PD patients and its correlation with the clinical features, we carried out midbrain TCS in 43 PD patients and 35 normal controls and evaluated the area of the substantia nigra (SN) hyperechogenicity and its ratio to the area of the whole midbrain. In 16 subjects (21%), TCS was unsuccessful due to insufficient acoustic temporal bone windows. The mean area of bilateral SN hyperechogenicity and its ratio to the midbrain area were greater in the PD patients than that in the controls (P < 0.01). In the PD patients, the area of SN hyperechogenicity and its ratio to the individual midbrain area were moderately correlated with the PD duration (r = 0.526 and 0.536, P = 0.01, respectively) but not with the age, UPDRS motor scores or H-Y stage. There was no difference in the SN hyperechogenicity between the tremor-dominant, akinetic-rigid, and mixed-type PD patients. In conclusion, midbrain TCS is an effective diagnostic tool for detecting PD in the Korean population. However, it does not reflect the severity or phenotypes of parkinsonism.     

Predictive value of transcranial sonography in the diagnosis of Parkinson's disease.

Transcanial sonography (TCS) is increasingly applied in the diagnosis of Parkinson's disease (PD), but investigator bias may influence the results of examination. Blinding the sonographer to the clinical diagnosis of 42 PD patients and 35 controls, we obtained a positive predictive value of 85.7% and a negative predictive value of 82.9% in the diagnosis of PD solely by interpreting the results of TCS, indicating that TCS is a valuable additional tool in the diagnosis of PD.     

帕金森病患者经颅脑实质超声所见与临床评价

目的探讨经颅脑实质超声中发现的中脑黑质高回声与帕金森病(PD)的关系。方法连续入选2010~2013年中日友好医院门诊和住院诊断的123例PD患者及78例健康对照者,行经颅脑实质超声检查,测量黑质区域强度Ⅲ级的信号面积、第三脑室宽度及基底节区有无异常信号。并对123例PD患者进行统一帕金森病评定量表(UPDRS)评分、HoehnYahr分级。最后分析黑质高回声面积与UPDRS评分、HoehnYahr分级的相关性。结果最后入组89例PD患者及60例健康对照者。89例PD患者中,81例患者黑质高回声面积≥0.2 cm2;60例健康志愿者中,5例黑质高回声面积≥0.2 cm2。PD患者组的黑质高回声面积与健康对照组有明显差异。Pearson相关性分析发现黑质高回声面积的大小与患者发病年龄及病程长短无关系;较大侧黑质高回声与UPDRS评分的总分、第Ⅲ部分及HoehnYahr分级有明显相关性。黑质高回声面积在临床症状(UPDRSⅢ)较重的对侧较大。结论我国PD患者中脑黑质高回声是PD的一个特征性标记,其面积大小与PD患者运动症状的严重程度呈正相关,临床上可将经颅脑实质超声作为PD患者诊断的工具之一。     

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. © 2010 Movement Disorder Society     

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.     

Detection of presymptomatic Parkinson's disease: combining smell tests, transcranial sonography, and SPECT.

Olfactory loss is among the early signs of Parkinson's disease (PD). We investigated whether "idiopathic" olfactory dysfunction might relate to signs of nigral degeneration. Olfactory tests were combined with transcranial sonography of the substantia nigra and single photon emission computed tomography (SPECT) imaging. Thirty patients diagnosed with idiopathic olfactory loss participated. Eleven of these patients exhibited an increased echogenicity of the SN in the transcranial sonography. In 10 of these 11 patients, SPECT scans with (123)I-FP-CIT were performed. Median uptake ratios in the basal ganglia were pathological in 5 patients, 2 patients exhibited borderline findings, and 3 patients had normal results. Considering patients with idiopathic olfactory dysfunction, noninvasive transcranial sonography seems to be helpful in identifying patients potentially at risk to develop PD. Longitudinal follow-up studies are necessary to estimate the ratio of patients with dopaminergic cell loss in the basal ganglia who will develop PD in the future.     

Combination of transcranial sonography, olfactory testing, and MIBG myocardial scintigraphy as a diagnostic indicator for Parkinson's disease

Background: Appropriate diagnostic biomarkers are useful for improving speed and accuracy of a diagnosis. Substantia nigra (SN) hyperechogenicity visualized by transcranial sonography (TCS), olfactory dysfunction, and the reduced uptake of ¹²³I‐metaiodobenzylguanidine (MIBG) in myocardial scintigraphy have been suggested as potential biomarkers for the identification of Parkinson’s disease (PD). Objectives: To evaluate the diagnostic potential of these tests and to determine whether combining them increases their diagnostic power. Methods: Subjects were 44 patients with clinically diagnosed PD and 36 healthy controls. TCS of the SN, the odor stick identification test for Japanese (OSIT‐J), and MIBG myocardial scintigraphy were conducted. Results: Eleven patients with PD (25%) and four controls (11%) were excluded because of an insufficient acoustic temporal bone window in the TCS. Thus, 33 patients with PD and 32 healthy controls were finally included. The diagnostic sensitivity of TCS, OSIT‐J, and MIBG myocardial scintigraphy was 78.8%, 84.8%, and 60.6%, respectively. The specificity of TCS and OSIT‐J was 93.8% and 78.1%, respectively. The combination of TCS of the SN and OSIT‐J substantially increased the sensitivity to a sufficient level for discriminating patients with PD from controls. Conclusion: TCS of the SN and olfactory testing play complementary roles in increasing diagnostic power in PD. As both tests are easy to perform, noninvasive, and inexpensive, the combination of TCS of the SN and olfactory testing may contribute to early and accurate diagnosis of PD.     

Parkinson's disease and depression: evidence for an alteration of the basal limbic system detected by transcranial sonography

OBJECTIVES—Depression is a frequent symptom inParkinson's disease. Compelling evidence suggests a role of thebrainstem in the control of mood and cognition. In patients withunipolar depression transcranial sonography (TS) studies have shownstructural alteration of the mesencephalic brainstem raphe which couldsuggest an involvement of the basal limbic system in the pathogenesisof primary mood disorders. The objective of the present study was toevaluate whether a similar alteration could be found in depressedpatients with Parkinson's disease using TS.
METHODS—Thirty patients with Parkinson's diseaseand 30 age and sex adjusted controls were examined by TS. Rapheechogenicity was rated semiquantitatively. The severity of motorsymptoms and depression was rated using standard research instruments.
RESULTS—Raphe echogenicity was significantlyreduced in depressed patients with Parkinson's disease compared withnon-depressed patients with Parkinson's disease and control subjects.Raphe echogenicity correlated negatively with degree of motorimpairment, and differences in raphe echo between depressed andnon-depressed patients with Parkinson's disease were upheld when motorimpairment was controlled for.
CONCLUSION—These preliminary findings suggestthat, as in unipolar depression, a morphological alteration of thebrainstem raphe might be involved in the pathogenesis of depression inParkinson's disease. This raphe alteration may reflect involvement inthe basal limbic system in the pathogenesis of secondary depression.This concept is in line with current knowledge on the pathogenesis ofboth depression in Parkinson's disease and primary depressive disorders.

     

Effects of repetitive transcranial magnetic stimulation on voice and speech in Parkinson's disease

OBJECTIVE: To investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on vocal function in Parkinson's disease (PD). MATERIAL AND METHODS: Two different sets of rTMS parameters were investigated on 30 patients with PD: active or sham 15 Hz rTMS of the left dorsolateral prefrontal cortex (LDLPFC) (110% of motor threshold (MT), 3000 pulses per session) and active 5 Hz rTMS of the primary motor cortex (M1)-mouth area (90% MT, 2250 pulses per session). A blind rater evaluated speech characteristics (acoustic and perceptual analysis of voice) and voice-related quality of life (V-RQOL). RESULTS: rTMS of LDLPFC resulted in mood amelioration and subjective improvement of the V-RQOL only (71.9% improvement, P < 0.001), but not in objective measures such as fundamental frequency (P = 0.86) and voice intensity (P = 0.99). On the other hand, rTMS of M1-mouth induced a significant improvement of the fundamental frequency (12.9% for men and 7.6% for women, P < 0.0001) and voice intensity (20.6%, P < 0.0001). CONCLUSIONS: Our findings provide initial evidence that rTMS of the primary motor cortex might yield a beneficial effect on vocal function in PD.     

LRRK2 is a component of granular alpha-synuclein pathology in the brainstem of Parkinson's disease

Classical Parkinson's disease (PD) is characterized by the appearance of Lewy bodies (LBs) in affected brain regions, showing mostly compact alpha-synuclein deposition, in contrast with punctate or granular deposition, hypothesized to represent early stages of aggregation. Leucine-rich repeat kinase 2 (LRRK2) is the commonest mutated gene in inherited and idiopathic PD. LRRK2 mutation carriers display a diverse neuropathology, including alpha-synuclein and tau inclusions, suggesting an upstream role for LRRK2 in protein aggregation. We studied LRRK2 expression throughout the normal human brain with three different antibodies. We also examined the pattern of LRRK2 expression in relation to alpha-synuclein aggregation and LB formation in the brainstem of sporadic LB disease. Physiological LRRK2 expression was not restricted to regions preferentially affected in PD and LRRK2 often localized to the nuclear envelope in addition to the known cytoplasmic expression. In PD, we were able to consistently detect LRRK2 in the halo of a minority (approximately 10%) of nigral LBs using three different antibodies. Only one antibody detected LRRK2 in the core of approximately 80% of classic LBs. In the lower brainstem, most notably in the dorsal motor nucleus of the vagus, we found previously unrecognized LRRK2 labelling of complex globular lesions, filled with LB-like matter showing a punctate or granular staining for alpha-synuclein. This was often accompanied by strong LRRK2 expression within dystrophic neurites. Our findings confirm widespread physiological LRRK2 expression in the human brain and suggest an association of LRRK2 with possible early-stage alpha-synuclein pathology in the brainstem of PD.     

高频重复经颅磁刺激对帕金森合并抑郁患者的临床疗效分析

目的 研究探讨高频重复经颅磁刺激(rTMS)治疗帕金森合并抑郁患者的临床疗效及脑血流灌注参数变化情况.方法 选取我院2018年4月～2020年4月期间收治的88例帕金森病合并抑郁症患者,采用随机数字表法分为对照组和观察组,每组各44例.对照组患者采取常规治疗,观察组患者在对照组基础上接受高频rTMS治疗,疗程均为4w....     

Effects of inhibitory rTMS on bladder function in Parkinson's disease patients

Patients affected by Parkinson's disease (PD) may present with lower urinary tract (LUT) dysfunction characterized by involuntary detrusor overactivity. We evaluated possible impact of a 2‐week course of low frequency 1 Hz repetitive transcranial magnetic stimulation (rTMS) on LUT behavior in eight advanced PD patients complaining of urinary disturbances. We tested the effects of rTMS measuring urodynamic examination and the International Prostate Symptoms Score (IPSS) questionnaire, used for evaluation of subjective LUTS. rTMS was able to improve temporarily LUT behavior in PD patients, increasing bladder capacity and the first sensation of filling phase. Moreover, a reduction of IPSS score was noticed, due to an improvement on filling phase symptoms. The beneficial effects assessed with the IPSS lasted for up to 2 weeks after the end of the stimulation. rTMS seems to be an effective, noninvasive alternative treatment for PD patients with urinary disturbances. © 2009 Movement Disorder Society     

Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease

OBJECTIVES: Cognitive impairment is a common feature in Parkinson's disease (PD) and is an important predictor of quality of life. Past studies showed that some aspects of cognition, such as working memory, can be enhanced following dopaminergic therapy and transcranial magnetic stimulation. The aim of our study was to investigate whether another form of noninvasive brain stimulation, anodal transcranial direct current stimulation (tDCS), which increases cortical excitability, is associated with a change in a working memory task performance in PD patients. METHODS: We studied 18 patients (12 men and 6 women) with idiopathic PD. The patients performed a three-back working memory task during active anodal tDCS of the left dorsolateral prefrontal cortex (LDLPFC), anodal tDCS of the primary motor cortex (M1) or sham tDCS. In addition, patients underwent two different types of stimulation with different intensities: 1 and 2 mA. RESULTS: The results of this study show a significant improvement in working memory as indexed by task accuracy, after active anodal tDCS of the LDLPFC with 2 mA. The other conditions of stimulation: sham tDCS, anodal tDCS of LDLPFC with 1 mA or anodal tDCS of M1 did not result in a significant task performance change. CONCLUSION: tDCS may exert a beneficial effect on working memory in PD patients that depends on the intensity and site of stimulation. This effect might be explained by the local increase in the excitability of the dorsolateral prefrontal cortex.     

Determination of ventricular diameters in multiple sclerosis patients with transcranial sonography (TCS)

Abstract.Context: Brain atrophy is an indicator of diffuse brain pathology that appears even in the early stages of multiple sclerosis (MS). Magnetic resonance imaging (MRI) techniques used in clinical trials suggest a correlation between ventricular enlargement and axonal pathology and clinical disability in MS.Objective: To evaluate by transcranial sonography (TCS) and MRI ventricular diameters in order to assess prospectively the development of brain atrophy in MS.Setting: MS outpatient clinic of a university hospital.Patients and Methods: 38 MS patients (27 females, 11 males) were followed up for 2 years. Ventricular diameters (third ventricle, right and left lateral ventricle) were determined by TCS at baseline, 12 and 24 months and correlated with clinical disability (Expanded Disability Status Scale, EDSS), and the Multiple Sclerosis Functional Composite Score (MSFC). MRI was performed at study entry and after two years.Main outcome measure: Correlation of ventricular diameters measured by TCS and MRI with assessment of clinical disability in MS patients at baseline and after two years.Results: TCS and MRI measurements especially of third ventricle diameter matched closely at study entry and after two years (r = 0.9; p < 0.0001). At all time points the width of the third ventricle was significantly correlated with clinical disability (EDSS: r = 0.6, p < 0.01; MSFC: r = –0.6, p < 0.02). In the follow-up over 2 years there was an increase of the width of the third ventricle in comparison with study entry (p < 0.002). Increase of third ventricular width at study entry was associated with higher EDSS levels after 2 years (p = 0.01).Conclusion: Assessment of ventricular diameters by TCS is a reliable tool with which to monitor brain atrophy in the longitudinal follow-up of MS patients. Because TCS is a simple, inexpensive, non-invasive and generally available bedside-test it may be used in clinical practice as well as in therapeutic trials to assess brain atrophy.(died unexpectedly 05. 08. 2003)