Jaco W. Pasman

Predicting Hand Motor Recovery in Severe Stroke: The Role of Motor Evoked Potentials in Relation to Early Clinical Assessment

Objective. The primary aim of this study was to compare the predictive value of motor evoked potentials (MEPs) and early clinical assessment with regard to long-term hand motor recovery in patients with profound hemiplegia after stroke. Methods. The sample was an inception cohort of 39 stroke patients with an acute, ischemic, supratentorial stroke and an initial upper-extremity paralysis admitted to an academic hospital. Hand motor function recovery was defined at 26 weeks poststroke as a Fugl–Meyer Motor Assessment (FMA) hand score >3 points. The following prognostic factors were compared at week 1 and week 3 poststroke: motor functions as assessed by the FMA upper-extremity and lower-extremity subscores, and the presence of an MEP in the abductor digiti minimi and biceps brachii muscle. Results. Both the presence of an abductor digiti minimi–MEP and any motor recovery in the FMA upper-extremity subscore showed a positive predictive value of 1.00 at weeks 1 and 3. The FMA lower-extremity subscore showed the best negative predictive value (0.90; 95% CI 0.78-1.00 at week 1 and 0.95; 95% CI 0.87-1.00 at week 3). Conclusions. In stroke patients with an initial paralysis of the upper extremity the presence or absence of an MEP has similar predictive value compared with early clinical assessment with regard to long-term hand motor recovery.

Clinical and biochemical effects of zileuton in patients with the Sjögren-Larsson syndrome

Abstract. The Sjögren-Larsson syndrome (SLS) is an inborn error of lipid metabolism, characterised clinically by congenital ichthyosis, mental retardation and spasticity. Patients also suffer from severe pruritus. The degradation of leukotriene (LT) B4 is one of the defective metabolic routes in SLS. Zileuton inhibits the synthesis of LTB4 and the cysteinyl leukotrienes. Five SLS patients were treated with zileuton for 3 months. Favourable effects were found on pruritus score (P=0.006), general well-being, and background activity of electroencephalographic studies. Neuropsychological test results did not change significantly. There was, however, a clinically important trend towards improvement in the speed of information processing. Results of cerebral MRI and proton magnetic resonance spectroscopy did not change during therapy. Urinary concentrations of LTB4 and ω-OH-LTB4 decreased significantly (P=0.02 and P=0.003 respectively), while their concentrations in CSF were normal at baseline and remained so after therapy. Conclusion: patients with Sjögren-Larsson syndrome might benefit from treatment with zileuton, especially with respect to the agonising pruritus. The findings reported here, point to a crucial role for leukotriene B4 in the pathogenesis of pruritus.

Motor Evoked Potentials of the Lower Extremity in Predicting Motor Recovery and Ambulation After Stroke: A Cohort Study

OBJECTIVE To assess the prognostic value of motor evoked potentials (MEPs) in the lower extremity with respect to motor recovery and functional recovery in stroke patients. DESIGN Cohort study. SETTING The department of neurology at a university hospital. PARTICIPANTS Thirty-eight acute-stroke patients with complete paralysis (paralysis subgroup) or severe paresis (paresis subgroup) of the lower extremity. MEPs of the vastus medialis and the tibialis anterior muscles were recorded between days 3 and 10 after stroke onset. INTERVENTIONS Not applicable. Main outcome measures A separate proximal leg motor score (maximum, 16 points) and crural motor score (maximum, 2 points) were defined within the lower-limb subset of the original Fugl-Meyer Motor Assessment to evaluate the motor performance at regular intervals until 6 months after stroke. The transfer item of the Barthel Index and the Functional Ambulation Categories scores were used to assess transfer and walking ability. RESULTS For the paralysis subgroup (n=30), the follow-up was complete in 27 patients (2 patients died, 1 patient underwent above-knee amputation). At 26 weeks, 20 patients experienced proximal motor recovery (mean score +/- standard deviation, 11.70+/-4.48), and 12 of them also showed crural motor recovery (mean score, 1.40+/-.51). Nine patients (33%) could perform an independent transfer safely, and 7 (26%) had learned to walk independently. Analysis revealed significant relationships for tibialis anterior muscle MEPs and motor recovery of crural leg muscles (odds ratio [OR]=18.00; 95% confidence interval [CI], 1.31-894.40), but not for vastus medialis muscle MEPs and proximal motor recovery (OR=6.00; 95% CI,.53-303.00). We found no association between vastus medialis muscle MEPs and recovery of ambulation. However, tibialis anterior muscle MEPs seemed to provide a test with prognostic value for the ability to perform independent transfers (OR=17.50; 95% CI, 1.36-267.00), but not for walking (OR=5.25; 95% CI,.40-77.57). Patients in the paresis subgroup experienced more favorable motor and functional recovery than did those in the paralysis subgroup. CONCLUSIONS Tibialis anterior muscle MEPs registered in subacute phase after stroke may provide important prognostic information, both for motor recovery of the crural muscles and for the ability to perform independent transfers in patients with initial complete paralysis of the lower extremity. Vastus medialis muscle MEPs were not predictive for motor and functional recovery.

Motor evoked potentials in predicting recovery from upper extremity paralysis after acute stroke.

Objective: The use of motor evoked potentials (MEPs) in predicting recovery after stroke still appears to be somehow equivocal. We assessed the prognostic value of MEPs with respect to arm and hand motor recovery in acute stroke patients. Methods: This cohort study included 43 consecutive acute stroke patients with complete paralysis of the upper extremity. MEPs of the abductor digiti minimi muscle (ADM) and the biceps brachii muscle (BB) were obtained within 10 days after stroke onset. The upper limb subset of the Fugl-Meyer Motor Assessment was used to evaluate the motor performance at regular intervals until 6 months after stroke. Results: The follow-up was complete in 40 patients (2 patients died and 1 patient had a recurrent stroke); 14 patients showed motor recovery of the arm and their mean 26-week arm motor score was 17.93 (range 3–30, SD 11.68); hand motor recovery occurred in 11 patients and their mean 26-week hand motor score was 11.09 (range 4–14, SD 4.10). Stepwise logistic regression revealed prognostic models for both arm and hand motor recovery based on BB MEPs (odds ratio 7.69, confidence interval, CI, 1.16–50.95) and ADM MEPs (odds ratio 16.20, CI 2.51–104.40), respectively. Conclusions: The predictive significance of MEPs with respect to motor recovery of the upper extremity was obvious in our homogeneous sample of patients. This agrees with the paradigm that motor recovery after infarction is strongly dependent on a critical residual sparing of the corticospinal function. In this context, the test properties of MEPs in predicting motor recovery are discussed. The added value of MEPs with respect to motor recovery of the upper extremity should be regarded as established for patients with initial paralysis, especially since clinical examination alone lacks the possibility to detect the potential for motor recovery in these cases.

Maturational Changes in Automated EEG Spectral Power Analysis in Preterm Infants

Our study aimed at automated power spectral analysis of the EEG in preterm infants to identify changes of spectral measures with maturation. Weekly (10–20 montage) 4-h EEG recordings were performed in 18 preterm infants with GA <32 wk and normal neurological follow-up at 2 y, resulting in 79 recordings studied from 27+4 to 36+3 wk of postmenstrual age (PMA, GA + postnatal age). Automated spectral analysis was performed on 4-h EEG recordings. The frequency spectrum was divided in delta 1 (0.5–1 Hz), delta 2 (1–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), and beta (13–30 Hz) band. Absolute and relative power of each frequency band and spectral edge frequency were calculated. Maturational changes in spectral measures were observed most clearly in the centrotemporal channels. With advancing PMA, absolute powers of delta 1 to 2 and theta decreased. With advancing PMA, relative power of delta 1 decreased and relative powers of alpha and beta increased, respectively. In conclusion, with maturation, spectral analysis of the EEG showed a significant shift from the lower to the higher frequencies. Computer analysis of EEG will allow an objective and reproducible analysis for long-term prognosis and/or stratification of clinical treatment.

The effect of preterm birth on brainstem, middle latency and cortical auditory evoked responses (BMC AERs)

Recent studies on the maturation of auditory brainstem evoked responses (ABRs) present conflicting results, whereas only sparse reports exist with respect to the maturation of middle latency auditory evoked responses (MLRs) and auditory cortical evoked responses (ACRs). The present study reports the effect of preterm birth on the maturation of auditory evoked responses in low risk preterm infants (27-34 weeks conceptional age). The ABRs indicate a consistent trend towards longer latencies for all individual ABR components and towards longer interpeak latencies in preterm infants. The MLR shows longer latencies for early component P0 in preterm infants. The ACRs show a remarkable difference between preterm and term infants. At 40 weeks CA the latencies of ACR components Na and P2 are significantly longer in term infants, whereas at 52 weeks CA the latencies of the same ACR components are shorter in term infants. The results support the hypothesis that retarded myelination of the central auditory pathway is partially responsible for differences found between preterm infants and term infants with respect to late ABR components and early MLR component P0. Furthermore, mild conductive hearing loss in preterm infants may also play its role. A more complex mechanism is implicated to account for the findings noted with respect to MLR component Na and ACR components Na and P2.

Quantitative Analysis of Amplitude-Integrated Electroencephalogram Patterns in Stable Preterm Infants, with Normal Neurological Development at One Year

Background: The amplitude-integrated EEG (aEEG) is feasible for monitoring cerebral activity in preterm infants. However, quantitative data on normal patterns in these infants are limited. Objective: To study maturational aEEG changes in a cohort of stable preterm infants by automated quantification. Methods: In a cohort of stable preterm infants with gestational age (GA) <32 weeks and normal neurological follow-up at 1 year, weekly 4 h EEG recordings were performed. aEEG traces were obtained from channel C3-C4. The upper margin amplitude (UMA), lower margin amplitude (LMA) and bandwidth (BW) were quantitatively calculated using an expert software system. In addition, the relative duration of discontinuous background pattern (discontinuous background defined as activity with LMA <5 µV, expressed as DC-%) was calculated. Results: 79 aEEG recordings (4–6 recordings/infant) were obtained in 18 infants. Analysis of the first week recordings demonstrated a strong positive correlation between GA and LMA, while DC-% decreased significantly. Longitudinally, all infants showed increase of LMA. Multivariate analysis showed that GA and postnatal age (PA) both contributed independently and equally to LMA and DC-%. We found a strong correlation between postmenstrual age (GA + PA) and LMA and DC-%, respectively. Conclusion: To our knowledge, this is the first study where aEEG development was studied by automated quantification of aEEG characteristics in a cohort of stable preterm infants with a normal neurological development at 1 year of age. LMA and DC-% are simple quantitative measures of neurophysiologic development and may be used to evaluate neurodevelopment in infants.

Analysis of recovery processes after stroke by means of transcranial magnetic stimulation.

Summary: The objective of this study was to use motor evoked potentials (MEPs) to analyze the integrity of fast corticospinal functions as the neurophysiologic basis for motor recovery in stroke patients. This was a cohort study including 44 acute stroke patients with paralysis of the upper or the lower extremity. Motor evoked potentials of the abductor digiti minimi, the biceps brachii, the vastus medialis, and the tibialis anterior were performed within 10 days (mean, 6.9 days; range, 3 to 10 days) and 40 days (mean, 27.8 days; range, 14 to 40 days) after stroke onset. A separate score was defined for proximal and distal motor functions of the upper and lower extremity within the original Fugl‐Meyer motor assessment. Motor performance was evaluated simultaneously with the MEP assessments and 26 weeks after stroke. For all the muscles in which a response was present during the first investigation, obvious recovery of the fast corticospinal functions occurred. For the abductor digiti minimi amplitude ratio and the vastus medialis MEP amplitude the differences between the two investigations were significant. An MEP response could be elicited in more cases at the second than on the first MEP assessment. A present MEP response during the first registration indicated nearly always subsequent motor recovery, both for proximal and distal motor functions of the upper and lower extremity. However, motor recovery was also observed in some patients for whom no MEP response could be elicited. Regression analysis showed significant relationships between the abductor digiti minimi (P = 0.020/0.004 [t1/t2])and biceps brachii (P = 0.020/0.004 [t1/t2]) MEP amplitude parameters and the 26‐week hand and arm motor scores. No relationship existed between the tibialis anterior and the vastus medialis MEP parameters and the leg motor scores. Motor recovery manifests neurophysiologically often as the recovery of fast corticospinal functions. In many cases, assessment by MEPs is more sensitive than clinical examination to detect residual corticospinal functions, which forms the pathophysiologic basis for the predictive value of MEPs for motor recovery after stroke.

The maturation of auditory cortical evoked responses between (preterm) birth and 14 years of age

In this study we report on the maturation of the auditory cortical evoked response (ACR) waveform between (preterm) birth and 14 years of age. From the results it can be concluded that the ACR waveform morphology shows substantial age-dependent changes until the age of 14 years. Two transitional periods could be recognized. The first between 36 and 41 weeks conceptional age; the second between 4 and 6 years of age. The adult waveform complex is achieved between 14 and 16 years of age. Further research is needed to determine whether these transitional periods in the maturation of ACRs correspond with important functional changes of the central auditory system.

Quantitative analysis of maturational changes in EEG background activity in very preterm infants with a normal neurodevelopment at 1 year of age

BACKGROUND The electroencephalographic (EEG) background pattern of preterm infants changes with postmenstrual age (PMA) from discontinuous activity to continuous activity. However, changes in discontinuity have been investigated by visual analysis only. AIM To investigate the maturational changes in EEG discontinuity in healthy preterm infants using an automated EEG detection algorithm. STUDY DESIGN Weekly 4h EEG recordings were performed in preterm infants with a gestational age (GA)<32weeks and normal neurological follow-up at 1year. The channel C3-C4 was analyzed using an algorithm which automatically detects periods of EEG inactivity (interburst intervals). The interburst-burst ratio (IBR, percentage of EEG inactivity during a moving time window of 600s) and mean length of the interburst intervals were calculated. Using the IBR, discontinuous background activity (periods with high IBR) and continuous background activity (periods with low IBR) were automatically detected and their mean length during each recording was calculated. Data were analyzed with regression and multivariate analysis. RESULTS 79 recordings were performed in 18 infants. All recordings showed a cyclical pattern in EEG discontinuity. With advancing PMA, IBR (R(2)=0.64; p<0.001), interburst interval length (R(2)=0.43; p<0.001) and length of discontinuous activity (R(2)=0.38; p<0.001) decreased, while continuous activity increased (R(2)=0.50; p<0.001). Multivariate analysis showed that all EEG discontinuity parameters were equally influenced by GA and postnatal age. CONCLUSION Analyzing EEG background activity in preterm infants is feasible with an automated algorithm and shows maturational changes of several EEG derived parameters. The cyclical pattern in IBR suggests brain organisation in preterm infant.