Transcranial sonography and [18F]fluorodeoxyglucose positron emission tomography for the differential diagnosis of parkinsonism: a head-to-head comparison.

BACKGROUND AND PURPOSE: Brain imaging with positron emission tomography using [(18) F]fluorodeoxyglucose (FDG-PET) and transcranial B-mode sonography (TCS) improves the differential diagnosis of parkinsonism. The diagnostic merits of these approaches in identifying and differentiating atypical parkinsonian syndromes (APS) are compared. METHODS: Data were included from 36 patients with clinically suspected APS who underwent PET and TCS. FDG-PET scans were analyzed by visual assessment (including voxel-based statistical maps) of a priori defined disease-specific metabolic patterns. Sonographers achieved diagnoses according to pre-defined criteria for echogenicities of the substantia nigra and lenticular nucleus, and third ventricle diameter. Patients with APS were identified and allocated to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). RESULTS: After a median follow-up period of 9 months, the final clinical diagnoses (reference standard) were Parkinson's disease, n = 15; MSA, n = 9; PSP, n = 7; and CBD, n = 5 (n = 21 APS in total). Six patients (4 APS) showed an insufficient bone window for TCS. In the remaining 30 patients, sensitivity/specificity for diagnosing APS were 82%/100% and 82%/85% for FDG-PET and TCS, respectively. Diagnostic accuracies did not differ between FDG-PET (90%) and TCS (83%; P = 0.69). Likewise, overall accuracy of subgroup classification (non-APS, MSA, PSP and CBD) did not differ between modalities (FDG-PET 87% and TCS 83%; P = 1.00). CONCLUSIONS: FDG-PET and TCS show comparable accuracies for differential diagnosis of neurodegenerative parkinsonism. This preliminary study supports the use of TCS and warrants further prospective validation.

A longitudinal study of tremor frequencies in Parkinson's disease and essential tremor.

OBJECTIVE: There is evidence that the tremor frequency in essential tremor (ET) decreases with time. Longitudinal studies on the evolution of tremor frequencies in Parkinson's disease (PD) have so far not been published. Here, we present a longitudinal analysis of tremor frequencies in PD and ET. METHODS: We analyzed the standardized accelerometric and electromyographic tremor recordings of 53 patients with PD and 38 patients with ET who underwent repeated routine tremor recordings between 1991 and 2002. RESULTS: In an average follow-up period of 44.9 months in PD and 50.6 months in ET, the average number of tremor recordings was 3.3 in PD and 3.7 in ET. In both disorders, tremor frequencies tended to decrease with time. The average annual decrease of the tremor frequency was 0.09 Hz/year in Parkinsonian rest tremor, 0.08 Hz/year in Parkinsonian postural tremor and 0.12 Hz/year in ET. CONCLUSIONS: The tremor frequency decreases with time in both PD and ET. The similarity of this decrease in PD and ET may point to a common underlying pathophysiological mechanism. SIGNIFICANCE: Decreasing tremor frequencies with time may be functionally important by inducing larger tremor amplitudes due to the low-pass filtering properties of muscles and limbs.

Do stroke patients with normal carotid arteries require TEE for exclusion of relevant aortic plaques?

OBJECTIVES: This study investigated (a) the hypothesis that stroke patients with aortic atheroma would show comparable atherosclerotic changes in the carotid arteries, which are easily accessible for ultrasound evaluation and (b) the possibility of carotid duplex sonography as a replacement for transoesophageal echocardiography (TEE) for the exclusion or prediction of relevant aortic plaques. METHODS: In 301 consecutive patients (mean age 62 years) with acute cerebral ischaemia, two dimensional ultrasound measurements were taken of common carotid artery intima media thickness (IMT) and maximal plaque area (PA) and the local degree of internal carotid artery (ICA) stenosis were determined. Maximal aortic wall thickness (AWT) was assessed by TEE. RESULTS: An IMT < or =0.9 mm yielded a negative predictive value (NPV) of 95.8% for exclusion of aortic atheromas > or =4 mm and an NPV of 100% for the exclusion of aortic thrombi. However, positive predictive value of IMT >0.9 mm was low (29.6%), increasing only slightly in the presence of carotid plaques (33%). Incidence of aortic thrombi was significantly higher with > or =50% compared with <50% ICA stenosis (11.3% v 3.9%, respectively). IMT and PA correlated moderately with AWT (r = 0.47, r = 0.53, respectively; p<0.001). Systolic blood pressure, coronary heart disease and peripheral artery disease, increased IMT, and ICA stenosis > or =50% were independently related to AWT > or =4 mm. CONCLUSIONS: A high NPV of normal carotid ultrasound does not support routine TEE for the exclusion of complex aortic plaques as a high risk source of cerebral embolism. However, in patients with carotid atherosclerosis, particularly in those with ICA stenosis > or =50%, TEE should be performed to exclude an additional high risk source for stroke.

On studentising and blocklength selection for the bootstrap on time series.

For independent data, non-parametric bootstrap is realised by resampling the data with replacement. This approach fails for dependent data such as time series. If the data generating process is at least stationary and mixing, the blockwise bootstrap by drawing subsamples or blocks of the data saves the concept. For the blockwise bootstrap a blocklength has to be selected. We propose a method for selecting the optimal blocklength. To improve the finite size properties of the blockwise bootstrap, studentised statistics is considered. If the statistic can be represented as a smooth function model this studentisation can be approximated efficiently. The studentised blockwise bootstrap method is applied for testing hypotheses on medical time series.

Dynamic cerebral autoregulation in acute ischemic stroke assessed from spontaneous blood pressure fluctuations.

BACKGROUND AND PURPOSE: This study investigates dynamic cerebral autoregulation assessed from spontaneous blood pressure (ABP) and cerebral blood flow velocity (CBFV) fluctuations and its time course in acute ischemic stroke. METHODS: Forty patients admitted with acute ischemic stroke in the territory of the middle cerebral artery (MCA) were enrolled. Admission National Institutes of Health Stroke score was 6+/-4. Study 1 was performed within 22 (+/-11) hours and study 2 was performed within 134 (+/-25) hours of ictus. The final analysis comprised 33 and 29 patients for study 1 and study 2, respectively. Twenty-five age- and sex-matched controls were studied. ABP (Finapres method) and CBFV in both MCAs (transcranial Doppler) were recorded over 10 minutes. Correlations between diastolic and mean ABP and CBFV fluctuations were averaged, yielding the correlation coefficient indices (Dx, Mx). Transfer function analysis was applied to obtain phase shift and gain between ABP and CBFV oscillations. RESULTS: No disturbance of autoregulation was indicated by all parameters at study 1. Separate analyses for clinical severity, stroke side, and size did not reveal significant differences for the various autoregulatory indices at study 1 and 2. At study 2, MCA flow velocity was significantly increased on both sides, the autoregulation index Mx was slightly but significantly (P<0.05) worse on both sides in comparison to study 1, and phase showed a trend toward poorer values on affected sides. No significant differences to controls occurred. Clinical outcome in patients completing both studies was good in all but one patient. CONCLUSIONS: Dynamic cerebral autoregulation assessed from spontaneous blood pressure fluctuations does not seem to be relevantly disturbed in early minor MCA stroke. At the subacute stage, slight autoregulatory disturbance may be present.

Effect of carotid endarterectomy or stenting on impairment of dynamic cerebral autoregulation.

BACKGROUND AND PURPOSE: Analysis of dynamic cerebral autoregulation (DCA) from spontaneous blood pressure fluctuations might contribute to prognosis of severe internal carotid artery stenosis, but its response to carotid recanalization has not been investigated so far. This study investigates the effect of carotid endarterectomy or stenting on various DCA parameters. METHODS: In 58 patients with severe unilateral stenosis undergoing carotid endarterectomy (n=41) or stenting (n=17), cerebral blood flow velocity (CBFV, transcranial Doppler) and arterial blood pressure (ABP, Finapres method) were recorded over 10 minutes before and on average 3 days after carotid recanalization. Nineteen patients were additionally examined after 7 months. Correlations between diastolic and mean ABP and CBFV fluctuations were averaged to form the correlation coefficient indices (diastolic [Dx] and mean values [Mx]). Transfer function parameters (low-frequency phase and high-frequency gain between ABP and CBFV oscillations) were calculated over the same 10 minutes. CO2 reactivity was assessed via inhalation of 7% CO2. RESULTS: Before recanalization, all DCA parameters were clearly impaired ipsilaterally compared with contralateral sides. Phase, Dx, and Mx indicated early normalization of DCA after both endarterectomy and stenting. By multiple regression, the degree of DCA improvement was highly significantly related to the extent of impairment before recanalization. No significant change in DCA was found at follow-up. Ipsilateral gain and CO2 reactivity increased significantly less after endarterectomy than after stenting (P<0.05). CONCLUSIONS: Dynamic cerebral dysautoregulation in patients with severe carotid obstruction is readily and completely remedied by carotid recanalization.

Bilateral severe carotid artery stenosis or occlusion - cerebral autoregulation dynamics and collateral flow patterns.

BACKGROUND: Bilateral severe obstruction of the internal carotid artery is a hemodynamically critical state. We aimed to (1) analyze dynamic cerebral autoregulation (DCA) in affected patients, and (2) to correlate DCA data with different collateral flow patterns. METHODS: DCA was assessed noninvasively by transfer function analysis (phase shift) of respiratory-induced oscillations at 0.1 Hz of arterial blood pressure (Finapres method) and cerebral blood flow velocity (transcranial Doppler) in 30 patients with severe bilateral carotid stenosis (> or =75%) or occlusion. CO(2)-reactivity was measured via inhalation of 7% CO(2). 30 patients with unilateral stenosis were recruited as controls. RESULTS: Patients with bilateral 75-89% stenosis had a virtually preserved phase shift. A pronounced reduction was found in bilateral critical stenosis or obstruction (90-100%). Patients with ipsilateral 90-100% and contralateral 75-89% stenosis had a significantly less severe reduction of phase shift on the ipsilateral side. CO(2)-reactivity showed a less marked reduction in patients with bilateral critical stenosis or occlusion. Phase shift was best if "Willisian" collaterals were present. Significantly reduced values were found if only secondary collaterals (ophthalmic artery, leptomeningeal flow) were detected. Poorest values occurred with recruitment of functionally stenosed "Willisian" collaterals. CO(2)-reactivity showed poor values with sole recruitment of secondary collaterals, whereas functionally stenosed primary collaterals did not show values as poor as for phase shift. Clinically symptomatic patients had significantly lower phase shift and CO(2)-reactivity values. CONCLUSIONS: DCA is severely impaired in bilateral critical carotid stenosis or occlusion. Sole recruitment of secondary collaterals and signs of a functional stenosis in primary ("Willisian") collaterals reflect insufficient collateral supply with a poor hemodynamic status. CO(2)-reactivity assessing the vasodilatory reserve and DCA represent different information for characterizing cerebral hemodynamic impairment. Determining transfer function phase might be a physiologically well supported approach for analysis of cerebral hemodynamic compromise.

Dynamic cerebral autoregulation and collateral flow patterns in patients with severe carotid stenosis or occlusion.

The quality of collateral blood supply in carotid disease is pivotal for the resulting hemodynamic compromise. However, the interrelation between different patterns of collateral blood flow and actual impairment of cerebral autoregulation (CAR) has not been analyzed so far. Dynamic CAR was assessed noninvasively by the phase shift between respiratory-induced 0.1-Hz oscillations of arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) in 101 patients with severe unilateral carotid stenosis (> or = 75%) or occlusion. CO(2)-vasomotor reactivity was assessed via inhalation of 7% CO(2). Spontaneously activated collaterals via primary (anterior/posterior communicating artery, type I, n = 65) and secondary (ophthalmic artery / leptomeningeal with or without primary pathways, group II, n = 24) pathways were assessed by transcranial Doppler/duplex sonography. Signs of functional stenosis in the anterior collateral pathways were subsumed under type III (n = 12). Best dynamic CAR (phase shift) on affected sides was observed for type I (n = 65), in which values did not differ significantly from contralateral sides. Reduced phase shift values were present in type II; poorest values were observed for type III. CO(2)-reactivity differed mainly between type I and the other types. A less distinct differentiation of autoregulatory impairment was found when dividing patients into groups of different degrees of stenosis. Symptomatic patients (previous TIA/stroke) were significantly less frequent in the group with type I collateral flow and had significantly lower phase shift and CO(2)-reactivity values. In conclusion, we found that dynamic CAR is substantially impaired if secondary collateral pathways are activated or if functional stenosis in the activated anterior collateral pathway is present. These hemodynamic constellations are also associated with a higher proportion of clinically symptomatic patients. Determination of dynamic CAR by transfer function analysis represents a convenient, sensitive method for detection of cerebral hemodynamic compromise in obstructive carotid disease.

Dynamic synchronisation of central oscillators in essential tremor.

OBJECTIVE: Coherence analysis of electromyography (EMG) signals in essential tremor (ET) suggests that tremor in the right and left arm is induced by independent central oscillators. The sensorimotor cortex seems to be part of the tremor-generating neuronal network in ET. Here, we investigated using electroencephalography (EEG) whether the independence of central oscillators in ET is supported by the analysis of cortical activity. METHODS: In 8 patients with ET, bilateral hand tremor was activated by wrist extension. EMGs from the wrist flexors and extensors were recorded simultaneously with an EEG. EEG-EMG coherence was estimated for 74 epochs of 60 s duration. RESULTS: In 42.6% of the cases, EEG-EMG coherence at the tremor frequency existed only with the contralateral sensorimotor cortex. However, 21.6% of the tremor-EMGs were coherent with EEG activity over both the contralateral and ipsilateral sensorimotor cortex. Bilateral and exclusively contralateral EEG-EMG coherence could alternate within the same recording. Bilateral EEG-EMG coherence was associated with increased right-left EEG-EEG coherence, increased right-left EMG-EMG coherence as well as with increased tremor strength. CONCLUSIONS: In ET, central oscillators in the right and left brain are not entirely independent of each other. They may dynamically synchronise, presumably by interhemispheric coupling via the corpus callosum.

Time delay as a parameter for cerebrovascular reactivity in patients with severe carotid stenosis.

BACKGROUND: Amplitude responsiveness of cerebral blood flow velocity (CBFV) to CO(2) is an established test of cerebrovascular reserve capacity. We aimed to analyze the time course of CBFV during CO(2 )reactivity testing in patients with severe carotid stenosis. METHODS: 87 patients were assigned to three different groups according to the degree of stenosis (A 75-89%, B 90-94%, C 95-100%) and CBFV dynamics was assessed by transcranial Doppler sonography during hypercapnia induced by inhalation of 7% CO(2. )Time constants for the duration of CBFV and the end-tidal CO(2 )partial pressure (Pet(CO2)) increase and decrease were calculated. In addition, time delays between subsequent changes of Pet(CO2) and CBFV during on- and offset of hypercapnia were determined. RESULTS: There was a significant reduction of conventional CO(2) reactivity on the side ipsilateral to the stenosis in all groups. Time constants of CBFV showed no major differences between ipsi- and contralateral sides or between different groups. The off delay between the decrease in Pet(CO2) and the consequent decrease in CBFV was the only out of 6 different dynamic parameters which significantly differentiated critical stenosis and occlusion from severe stenosis. Retest variability showed a highly significant correlation. CONCLUSIONS: Analysis of the dynamic CBFV response during the applied CO(2) inhalation protocol revealed a significant and reproducible delay parameter which has power to detect cerebral hemodynamic compromise in patients with carotid artery stenosis similar to the conventional CO(2 )reactivity parameter.

Challenging cerebral autoregulation in patients with preganglionic autonomic failure.

Intact cerebral autoregulation is essential to prevent cerebral hypoperfusion during pronounced changes in arterial blood pressure (ABP) in patients with autonomic failure (AF). It is still a matter of debate whether and to what extent cerebral autoregulation is disturbed in these patients. This study evaluates the interaction between cerebral blood flow velocity (CBFV) and ABP during Valsalva maneuver (VM) and tilt-table testing in nine patients with multiple system atrophy including AF and in 14 age-matched controls. CBFV and ABP were recorded noninvasively using transcranial Doppler sonography and the Finapres device. Responses to VM were graded by the autoregulation slope index (ASI). Cerebrovascular resistance changes were estimated by the conventional ratio ABP/CBFV and by the dynamic pressure-velocity relationship. To challenge cerebral autoregulation further, tests were repeated under hypercapnic predilation of cerebral arterioles. During VM, CBFV reincreased in patients despite a pronounced ABP drop and showed an overshoot after the strain, thus, being similar to controls. The ASI was higher in patients than in controls ( p < 0.05). During 70 degrees head-up tilt, ABP dropped markedly, but the decrease in CBFV was small and did not differ significantly from controls. In patients, both tests were associated with a substantial decrease of the dynamic but not of the conventional pressure-velocity relationship. Under hypercapnia, the CBFV response in patients remained unchanged. We conclude that 1). cerebral arterioles have the capacity for adequate vasodilation during ABP drops in patients with AF and that this ability is still present under hypercapnic predilation. 2). The mechanism of cerebral autoregulation in itself does not seem to be affected by the AF but is rather well exercised. 3) The VM presents, in addition to tilt-table testing, a simple test for clinical evaluation of cerebral autoregulation in patients with AF.

Transfer function analysis for clinical evaluation of dynamic cerebral autoregulation--a comparison between spontaneous and respiratory-induced oscillations.

Oscillations of arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) can be used for non-invasive assessment of cerebral autoregulation using transfer function analysis. Either spontaneous oscillations (SPO) around 0.1 Hz or respiratory induced oscillations during deep breathing (DB) at a rate of 6/min have been used so far. We investigated 168 patients with severe carotid stenosis or occlusion to evaluate transfer function analysis and compare the SPO and DB approaches. ABP was assessed non-invasively (Finapres), CBFV was measured in the middle cerebral artery using transcranial Doppler sonography. Transfer function phase (P) and gain (G) were extracted from the respective spectra in a low (0.06-0.12 Hz) and high (0.20-0.30 Hz) frequency range (LF, HF) of SPO and from the 0.1 (LF) and 0.2 (HF) Hz peaks induced by DB. For SPO, significant side-to-side differences and differences between groups of severe and critical stenosis were found for P(LF), while P(HF) did not prove to be a significant parameter. G(LF) showed significant side-to-side differences, while G(HF) additionally differed significantly between severe and critical stenosis and occlusion, respectively. For DB, significant side-to-side differences were found for P(LF, HF). Mainly G(HF) differed significantly between the affected and contralateral sides, while both HF and LF gains showed lower values in groups with a higher degree of stenosis. Correlation between G and P values was generally poor. Using Bland-Altman plots a poor inter-method agreement was found mainly for P. Correlations between SPO and DB were higher for G than for P (LF r = 0.64 versus 0.44, HF 0.69 versus 0.28). Analysing reproducibility in 16 patients, only for P(LF, HF) of DB was a highly significant correlation found (Spearman's r up to 0.78). For G(LF, HF) correlations were significant for both SPO and DB with slightly higher r coefficients for SPO. In conclusion, the present study showed that (1) transfer functions P and G represent different information for characterization of dynamic cerebral autoregulation in the frequency domain. (2) Inter-method agreement between DB and SPO is poor for P and moderate for G values. (3) P extracted from DB has a higher reproducibility. (4) The extraction of P and G from the SPO phase spectra is critical and future work on standardizing this process is needed. (5) At present, the DB protocol might be slightly advantageous as a routine diagnostic tool.

Essential tremor and cerebellar dysfunction: abnormal ballistic movements.

BACKGROUND: Clinical characteristics reminiscent of cerebellar tremor occur in patients with advanced essential tremor. Ballistic movements are known to be abnormal in cerebellar disease. The hypothesis was proposed that ballistic movements are abnormal in essential tremor, reflecting cerebellar dysfunction. OBJECTIVE: To elucidate the role of the cerebellum in the pathophysiology of essential tremor. METHODS: Kinematic parameters and the triphasic electromyographic (EMG) components of ballistic flexion elbow movements were analysed in patients assigned to the following groups: healthy controls (n = 14), pure essential postural tremor (ET(PT); n = 17), and essential tremor with an additional intention tremor component (ET(IT); n = 15). RESULTS: The main findings were a delayed second agonist burst (AG(2)) and a relatively shortened deceleration phase compared with acceleration in both the essential tremor groups. These abnormalities were most pronounced in the ET(IT) group, which had additional prolongation of the first agonist burst (AG(1)) and a delayed antagonist burst (ANT). CONCLUSIONS: Abnormalities of the triphasic pattern and kinematic parameters are consistent with a disturbed cerebellar timing function in essential tremor. These abnormalities were most pronounced in the ET(IT) group. The cerebellar dysfunction in essential tremor could indicate a basic pathophysiological mechanism underlying this disorder. ET(PT) and ET(IT) may represent two expressions within a continuous spectrum of cerebellar dysfunction in relation to the timing of muscle activation during voluntary movements.

Variability of frequency and phase between antagonistic muscle pairs in pathological human tremors.

We investigated the electromyographic activity (EMG) of flexor and extensor muscles with different hand positions in patients with essential (ET) and parkinsonian (PD) tremor. Using a previously developed bootstrap method and standard cross-spectral analysis, we performed statistical tests to assess the effect of hand position on: (1) the frequency of the EMG; and (2) the phase between the EMGs recorded from antagonistic muscle pairs. Frequency as well as phases changed significantly with different positions of the hands but not during the recordings when the position was left unchanged. Besides confirmation that frequency and phase are stationary and reliable parameters during short-term recordings under controlled laboratory conditions, these results are of particular interest for ambulatory long-term tremor measurements. A higher variability of the estimated parameters reported in long-term recordings may perhaps reflect a patient's mobility only. Our study shows that long-term recording systems should have the means to monitor the patient's movements to provide reliable results.

Tremor-correlated cortical activity in essential tremor.

BACKGROUND: In patients with parkinsonian resting tremor, tremor-correlated activity in the contralateral sensorimotor cortex has been studied by both magnetoencephalography (MEG) and electroencephalography (EEG). In essential tremor, MEG failed to detect cortical involvement. The objective of this study was to investigate whether EEG recording can reveal tremor-correlated cortical activity in patients with essential tremor or enhanced physiological tremor. METHODS: Seven patients with essential tremor and three patients with enhanced physiological tremor participated in the study. Unilateral postural tremor was activated by wrist extension on the right or on the left side. Electromyography (EMG) signals arising from the wrist extensor and flexor muscles, and a high-resolution EEG were recorded simultaneously. Coherences between the time series of the rectified tremor EMG and the EEG were estimated. FINDINGS: In five of nine arms with essential tremor, we found highly significant coherences at the tremor frequency between the tremor EMG and the EEG. Isocoherence maps illustrating the topography of significant coherences over the scalp showed that the maximum coherences were located over the contralateral sensorimotor cortex. In the patients with enhanced physiological tremor, we were unable to detect consistent significant corticomuscular coherences at the tremor frequency. INTERPRETATION: Using simultaneous EEG-EMG recordings, we showed that significant corticomuscular coherences at the tremor frequency can be found in essential tremor. This finding contrasts with a recent study based on MEG recordings. The results suggest that the sensorimotor cortex is involved in the generation of essential tremor, in a similar way to that previously shown in parkinsonian resting tremor.

Tremor-correlated cortical activity detected by electroencephalography.

OBJECTIVE: In this study we investigated whether cortical activity related to Parkinsonian resting tremor can be detected by electroencephalography (EEG). METHODS: Seven patients with idiopathic Parkinson's disease suffering from unilateral tremor participated in the study. Electromyography (EMG) signals arising from the wrist extensor and flexor muscles as well as a high resolution EEG were recorded simultaneously. Coherencies between EEG and EMG were calculated. RESULTS: In all patients, we found highly significant coherencies at the tremor frequency or its first harmonic between the tremor EMG and contralateral EEG channels. There were no significant coherencies between the tremor EMG and ipsilateral EEG channels. Isocoherency maps illustrating the topography of the coherencies over the scalp showed that the maximum coherencies were situated over the cortical motor areas. In one case, a high coherency was also found over the parietal cortex. CONCLUSIONS: The results show for the first time that tremor-correlated cortical activity can be detected by electroencephalography. The findings underline that motor areas of the cerebral cortex are involved in the neuronal network generating resting tremor in Parkinson's disease.

Side-to-side correlation of muscle activity in physiological and pathological human tremors.

OBJECTIVE: Many tremors occur always or often bilaterally. The question arises whether this could be explained by a common source or commonly transmitting pathways or by bilaterally represented, independent structures with the same oscillatory properties. A similar tremor frequency does not provide sufficient information to clarify this question. METHODS: We analyze coherencies between surface electromyographies (EMG) to investigate if bilateral physiologic (PT), essential (ET), Parkinsonian (PD) and orthostatic (OT) tremors originate from a common source for both sides of the body. We show that commonly used techniques to test whether coherencies are significant could lead to false positive results for tremor EMGs. A new estimation procedure is proposed to test EMG tremor time series on their linear independence. We apply this test to bilateral tremors. RESULTS: All measured EMG-pairs in OT (n = 7) were highly coherent between both sides with reproducible coherency values of up to 0.99. All other investigated tremors, i.e. PT and enhanced physiological tremors (EPT, n = 117), ET (n = 76) and PD resting and postural tremors (n = 70) do not show a significant side-to-side correlation. CONCLUSIONS: This finding shows that the pathophysiologies of OT and other pathological tremors are definitely different. Either they have different origins or different kinds of transmitting pathways. The proposed method might also be used to investigate other electrophysiological data and is a helpful, easy to use investigation for a daily clinical routine.

Classical conditioning of the electrically elicited blink reflex in humans: a new method of data analysis.

The eyeblink conditioning paradigm is a well-established model to study learning processes in humans and animals. Especially results from animal studies have supplied new insight into physiological pathways and brain structures involved in associative motor learning and memory. An important role of the cerebellum and its afferent fiber systems could be shown. Recent studies in humans have given evidence that results of animal experiments can be applied directly to the human condition. A high variation of baseline EMG activity and/or spontaneous blinks may influence the analysis of classical conditioning of the electrically elicited blink reflex in humans. To optimize differentiation between real conditioned responses and stimulus-independent EMG activity, we developed an algorithm which is fully automated and independent of a possible bias of an examiner. In a first step the algorithm decides whether a subject fulfills the criteria of a successful learning process or not. The second step quantifies the learning process. For quantification of the learning process, the following parameters were calculated: number of conditioned responses, onset of conditioning, time and amount of maximal conditioning, speed of conditioning and speed of habituation. According to our criteria, 80% of the healthy volunteers acquired conditioned responses. There is an age-related decline in eyeblink classical conditioning. Analysis of patient groups with different types of lesions will further improve our knowledge and understanding of pathways involved in learning processes in humans. The proposed new algorithm of data analysis takes less than 10 s on a standard computer, is more sensitive and more specific in detecting conditioned responses and, therefore, may further improve the value and reliability of the eyeblink conditioning paradigm in clinical research.

Multimodality monitoring during passive tilt and Valsalva maneuver under hypercapnia.

In occlusive cerebrovascular disease cerebral blood flow (CBF) autoregulation can be impaired and constant CBF during fluctuations in blood pressure (BP) cannot be guaranteed. Therefore, an assessment of cerebral autoregulation should consider not only responsiveness to CO2 or Diamox. Passive tilting (PT) and Valsalva maneuver (VM) are established tests for cardiovascular autoregulatory function by provoking BP changes. To develop a comprehensive test for vasomotor reactivity with a potential increase of sensitivity and specificity, the authors combined these maneuvers. Blood pressure, corrected to represent arterial pressure at the level of the circle of Willis, middle cerebral artery Doppler frequencies (DF), heart rate (HR) and endtidal partial pressure of CO2 (PtCO2) were measured continuously and noninvasively in 81 healthy subjects (19-74 years). Passive tilt and Valsalva maneuver were performed under normocapnia (mean, 39 + 4 mmHg CO2) and under hypercapnia (mean, 51 + 5 mm Hg CO2). Resting BP, HR, and DF increased significantly under hypercapnia. Under normocapnia and hypercapnia, PT induced only minor, nonsignificant changes in mean BP at the level of the circle of Willis compared to baseline (normocapnia: + 2 + 15 mm Hg; hypercapnia: -3 +/- 13 mm Hg). This corresponded with a nonsignificant decrease of the mean of DF (normocapnia: -4 +/- 11%; hypercapnia -6 +/- 12%). Orthostasis reduced pulsatility of BP by a predominantly diastolic increase of BP without significant changes in pulsatility of DF. Valsalva maneuver, with its characteristic rapid changes of BP due to elevated intrathoracic pressure, showed no significant BP differences in changes to baseline between normocapnic and hypercapnic conditions. Under both conditions the decrease in BP in phase II was accompanied by significantly increased pulsatility index ratio (PIDF/PIBP). Valsalva maneuver and PT as established tests in autonomic control of circulation provoked not only changes in time-mean of BP but also in pulsatility of BP. The significant increase in pulsatility ratio and decrease of the DF/BP ratio during normocapnia and hypercapnia indicated preserved CBF autoregulation within a wide range of CO2 partial pressures. Hypercapnia did not significantly influence the autoregulatory indices during VM and PT. Physiologically submaximally dilated cerebral arterioles can guarantee unchanged dynamics of cerebral autoregulation. Combined BP and MCA-DF assessment under hypercapnia enables investigating the effect of rapid changes of blood pressure on CO2-induced predilated cerebral arterioles. Assuming no interference of hypercapnia-induced vasodilation, VM, with its rapid, distinct changes in BP, seems especially to be adequate provocation for CBF autoregulation. This combined vasomotor reactivity might provide a more sensitive diagnostic tool to detect impaired cerebral autoregulation very early.