Characterization of motor and somatosensory function for stroke patients.

In a pilot study, stroke patients with a lesion related to the motor system were studied using magnetoencephalography (MEG) and electromyography (EMG). The patients performed sustained finger movements for 30 s followed by 30 s of rest and 20 repetitions of this sequence in total. Task-related cortical signals derived from MEG were observed here at very different frequency scales. Slow signals below 0.1 Hz were extracted by independent component analysis and are associated with the sustained activation of the motor cortex, the dcMEG motor activation. MEG-EMG coupling phenomena in the 10-30 Hz range were analyzed using the imaginary part of coherency and are attributed to cortico-muscular coupling driving the muscles. Additionally a signal from the somatosensory cortex due to an electrical stimulation at the wrist, the N20m, was recorded as a physiological marker. Field maps and time series associated with the three types of signals are presented for one patient and one control subject as the signal quality of the patient data was not sufficient to achieve a group result. The feasibility of a comprehensive electrophysiological measuring and analysis procedure of the motor function for stroke research is demonstrated by the results.

A prospective polysomnographic study on the evolution of complex sleep apnoea.

Complex sleep apnoea (CompSA) may be observed following continuous positive airway pressure (CPAP) treatment. In a prospective study, 675 obstructive sleep apnoea patients (mean age 55.9 yrs; 13.9% female) participated. Full-night polysomnography was performed at diagnosis, during the first night with stable CPAP and after 3 months of CPAP. 12.2% (82 out of 675 patients) had initial CompSA. 28 of those were lost to follow-up. Only 14 out of the remaining 54 patients continued to satisfy criteria for CompSA at follow-up. 16 out of 382 patients not initially diagnosed with CompSA exhibited novel CompSA after 3 months. 30 (6.9%) out of 436 patients had follow-up CompSA. Individuals with CompSA were 5 yrs older and 40% had coronary artery disease. At diagnosis, they had similar sleep quality but more central and mixed apnoeas. On the first CPAP night and at follow-up, sleep quality was impaired (more wakefulness after sleep onset) for patients with CompSA. Sleepiness was improved with CPAP, and was similar for patients with or without CompSA at diagnosis and follow-up. CompSA is not stable over time and is mainly observed in predisposed patients on nights with impaired sleep quality. It remains unclear to what extent sleep impairment is cause or effect of CompSA.

Coherence and imaginary part of coherency identifies cortico-muscular and cortico-thalamic coupling.

The understanding of the interaction between muscle control and cortical areas and between subcortical and cortical areas is important for the effective treatment of patients with movement disorders. The combination of coherence (COH) and the imaginary part of coherency (iCOH) is applied here to electrophysiological data from patients with a movement disorder and to data from healthy subjects performing finger movements. The COH and iCOH between magnetoencephalographic (MEG) and electromyographic (EMG) signals of the healthy subjects yields the expected result for cortico-muscular coupling. Based on this the COH and iCOH between sub-thalamic nucleus local field potentials (STN-LFP) and MEG signals are assessed for deep brain stimulation patients with externalized LFP electrodes. The results suggest interactions in the 10 to 20 Hz range. Artificially mimicking volume conduction by re-referencing the STN electrodes to a surface EEG electrode leads to large changes in the COH and iCOH. This suggests that volume conduction is not important for the analysis of interactions between MEG and bipolar STN electrodes.

[An assessment tool for analysing the early vocal development of young children with cochlear implant]. / Ein Untersuchungsverfahren zur Analyse der vorsprachlichen Entwicklung bei Kleinkindern mit Cochlea-Implantat.

BACKGROUND: Early vocal development of German-speaking cochlear implant recipients has rarely been assessed so far. There-fore the purpose of this study was to describe the early vocal development following successful implantation. METHODS: A case study was designed to assess the temporal progression of early vocal development in a young cochlear implant recipient who was bilaterally implanted at the age of 8;3 months. Data were collected during one year by recording parent-child interactions on a monthly basis. The first recording was made before the onset of the signal-processors, the 12 following recordings were made during the first year of implant use. The child's vocalizations were classified according to the vocalization categories and developmental levels from the Stark Assessment of Early Vocal Development--Revised (SAEVD-R). This assessment tool was translated into German in this study and used with German-speaking children for the first time. It allows a coding of prelinguistic utterances via auditory perceptual analysis. RESULTS: The results show an overall decrease of early vocalizations and an increase of speech-like vowels and consonants. In the first six months no apparent progress took place; The child produced almost exclusively vocalizations from Levels 1-3. In the second half of the year an increase of canonical utterances (Level 4) and advanced forms (Level 5) was observed. However, vocalizations beyond the canonical babbling phase, especially vocants and closants as well as their combinations, continued to be dominant throughout the first year of implant use. The progress of development of the child investigated in this study is comparable to other children implanted at young age who had also been assessed with the SAEVD-R. In comparison to normal-hearing children, the implanted child's development seemed to progress slightly faster. Interrater- and intrarater-reliability using the SAEVD-R were measured for two independent observers and for a first and second coding procedure and revealed to be acceptable to good. CONCLUSION: The use of SAEVD-R for an implanted German-speaking child allowed the investigation of prelinguistic vocal development before the onset of words. The fact that early vocalizations remain the dominant form throughout the first year of hearing experience emphasizes the importance of documenting and analysing prelinguistic vocal development in order to monitor progression of speech acquisition.

DC-magnetoencephalography and time-resolved near-infrared spectroscopy combined to study neuronal and vascular brain responses.

The temporal relation between vascular and neuronal responses of the brain to external stimuli is not precisely known. For a better understanding of the neuro-vascular coupling changes in cerebral blood volume and oxygenation have to be measured simultaneously with neuronal currents. With this motivation modulation dc-magnetoencephalography was combined with multi-channel time-resolved near-infrared spectroscopy to simultaneously monitor neuronal and vascular parameters on a scale of seconds. Here, the technique is described, how magnetic and optical signals can be measured simultaneously. In a simple motor activation paradigm (alternating 30 s of finger movement with 30 s of rest for 40 min) both signals were recorded non-invasively over the motor cortex of eight subjects. The off-line averaged signals from both modalities showed distinct stimulation related changes. By plotting changes in oxy- or deoxyhaemoglobin as a function of magnetic field a characteristic trajectory was created, which was similar to a hysteresis loop. A parametric analysis allowed quantitative results regarding the timing of coupling: the vascular signal increased significantly slower than the neuronal signal.

Clinical and biochemical study of 28 patients with mucopolysaccharidosis type VI.

This paper presents data collected by a Brazilian center in a multinational multicenter observational study of patients with mucopolysaccharidosis type VI (MPS VI), aiming at determining the epidemiological, clinical, and biochemical profile of these patients. Twenty-eight south-American patients with MPS VI were evaluated through medical interview, physical exam, echocardiogram, electrocardiogram, ophthalmologic evaluation, quantification of glycosaminoglycans (GAGs) in urine, and measurement of the activity of N-acetylgalactosamine-4-sulfatase (ARSB) in leukocytes. 92.9% of patients were Brazilian. Mean age at diagnosis and at evaluation was 48.4 months and 97.1 months, respectively. 88% of patients had onset of symptomatology before the age of 36 months. Consanguinity was reported by 27% of the families. Mean weight and height at birth were 3.481 kg and 51.3 cm, respectively. The most frequently reported clinical manifestations were short stature, corneal clouding, coarse facial features, joint contractures, and claw hands. All patients presented with echocardiogram changes as well as corneal clouding. Mean ARSB activity in leukocytes was 5.4 nmoles/h/mg protein (reference values: 72-174), and urinary excretion of GAGs was on average 7.9 times higher than normal. The number of clinical manifestations did not show a significant correlation with the levels of urinary GAGs nor with the ARSB activity. Also, no significant correlation was found between the levels of urinary GAGs and the ARSB activity. It was concluded that MPS VI has high morbidity and that, when compared with data published in the literature, patients in our study were diagnosed later and presented with a higher frequency of cardiological findings.

Molecular analysis of the Pi*Z allele in patients with liver disease.

Alpha1-antitrypsin (AAT) is the main protease inhibitor in human plasma. There are more than 75 variants of this protein that differ from each other by their isoelectric point. Most of these alleles cause a reduction in AAT levels; the most common allele is Pi*Z. The main complications related to the Pi*Z allele are obstructive pulmonary disease and liver disease. Some Pi*Z allele carriers present cholestatic jaundice and cirrhosis. The Z type is associated with a secretion defect, which leads to deficiency of AAT and to the formation of intrahepatocytic inclusions in affected subjects. The diagnosis of AAT deficiency can be made by different techniques, including molecular analysis, although the final diagnosis should be done in conjunction with demonstration of the periodic acid-Schiff-positive globules on liver biopsy. In this study, specimens of 29 patients with cryptogenic cirrhosis between age 1 month and 18 years, and of 100 controls were submitted to polymerase chain reaction followed by digestion with TaqI enzyme. Five of the 29 patients had undergone liver transplantation. Three patients were heterozygous for the Pi*Z allele, and two were homozygous (allele frequency = 12.07%; 7/58). Among the controls, who represented the population of Porto Alegre, 1 in 100 individuals was heterozygous for the Pi*Z allele, resulting in an allele frequency of 0.5% (1/200). The high frequency of Pi*Z alleles among the patients indicates the usefulness of AAT molecular testing in children with cholestatic jaundice and cirrhosis.

[Prerequisites, indications and contraindications of IV-lysis of ischemic stroke with rt-PA]. / Voraussetzungen, Indikationen und Kontraindikationen der systemischen Lysebehandlung des akuten ischämischen Insultes mit rt-PA.

BACKGROUND AND PURPOSE: To evaluate prerequisites, safety, and efficacy of i.v.-thrombolysis of ischemic stroke with rtPA in an academic medical center. METHODS: Over a period of 2 years and 10 months all patients admitted with a diagnosis of stroke were recruited. Inclusion and exclusion criteria for i.v.-thrombolysis were combined from large scale randomized controlled trials, the time window, however, could be extended up to 4 hours in subjects with a negative CT-scan. Prespecified outcome parameters were the modified Rankin Scale (mRS) and the Barthel Index (BI) at 3 months, and symptomatic hemorrhagic complications. Additionally, time parameters, such as onset-admission-time, door-Ct-time, door-needle time, and onset-needle time were recorded. RESULTS: During the reported period 103 patients underwent i.v.-thrombolysis, corresponding to 14.9% of all patients with ischemic stroke, and 47% of patients with ischemic stroke arriving in < 3 hours after symptom onset. The mean baseline NIHSS was 14, the mean mRS 13 (3-34), the mean age 70 (+/- 12) years. The following time intervals were observed: Onset-admission-time 64 min., door-CT-time 27 min., admission-needle-time 80 min., and onset-needle-time 142 min. There were 4 symptomatic intracerebral hemorrhagic transformations, including 3 parenchymal hemorrhages, 2 of them lethal, and one with almost full recovery. According to the mRS, 39% of patients had a good (mRS 0-1), 72% a good to moderate recovery (mRS 0-2). The corresponding figures for the BI were 60% BI 95-100 and 72% BI > 90. The mortality was 15%. CONCLUSION: The i.v.-thrombolysis of ischemic stroke with rt-PA demands appropriate organisation of the pre- and in-hospital phase and can be performed safely and efficaciously in daily clinical routine if inclusion and exclusion criteria as well as all safety measures during the critical phase after therapy are strictly obeyed.

Intravenous tPA for ischemic stroke team performance over time, safety, and efficacy in a single-center, 2-year experience.

BACKGROUND AND PURPOSE: Safety and efficacy concerns toward thrombolysis for ischemic stroke prevail among many neurologists because of the risks of hemorrhage and the small proportion of suitable patients. We therefore prospectively assessed feasibility, safety, efficacy, and team performance in a single center to prove whether thrombolytic treatment is practical in daily clinical routine. METHODS: Patients were prospectively recruited over a 2-year period. Major inclusion and exclusion criteria from large, randomized controlled trials were combined. Prespecified outcome parameters were the modified Rankin scale (MRS) and the Barthel Index (BI) at 3 months and symptomatic hemorrhagic complications. In addition, certain time intervals during the diagnostic process preceding thrombolysis were prospectively recorded. RESULTS: Within 2 years a total of 75 patients underwent intravenous thrombolysis, corresponding to 9.4% of all admitted patients with stroke and 14.9% of patients with ischemic stroke. Mean+/-SD age was 68+/-13 (range 34 to 90) years; median baseline National Institutes of Health Stroke Scale score was 13+/-6 (range 2 to 34). Thrombolysis was started at an average time of 144 minutes after symptom onset, and 13 patients (17.3%) were treated beyond 3 hours. Two cerebral hemorrhages (2.7%) occurred. Outcome according to the MRS was good (MRS 0 to 1) in 40%, moderate (MRS 2 to 3) in 32%, and poor (MRS 4 to 5) in 13%; the corresponding results, as measured by the BI, were 61% (BI 95 to 100, good), 16% (BI 55 to 90, moderate), and 8% (BI 0 to 50, poor). The mortality rate was 15%. Over 2 years the median door-to-CT time decreased from 30 to 22 minutes (27%), and the door-to-needle time was shortened from 96 to 73 minutes (14%). The mean number of patients treated per month increased from 2 to 4. CONCLUSIONS: Thrombolytic therapy can be performed safely and efficaciously in daily clinical routine. More than a minority of acute stroke patients might be eligible for intravenous thrombolysis. The performance of a stroke team can be improved over time, subsequently increasing the proportion of eligible patients and thereby the efficiency of the method.

Non-invasive single-trial monitoring of human movement-related brain activation based on DC-magnetoencephalography.

Neuroimaging techniques, such as fMRI, PET and near-infrared spectroscopy, monitor task-related neuronal activations in the brain indirectly through the associated neurovascular/metabolic responses. To assess the primary neuronal activations directly, magnetoencephalography was combined here with a mechanical modulation of the head-to-sensor position and signal separation via independent component analysis. In all of five subjects this approach allowed to monitor the time evolution of DC fields (<0.1 Hz) over the left hemisphere related to complex finger movements of the right hand alternating with rest periods (30 s each). Throughout the recording period of 30 min, stable task-related DC fields were recordable in a single-trial mode, i.e. without any averaging. DC-MEG opens up the possibility of analysing non-invasively cortical DC-activity also in stroke, migraine or epilepsy patients.

Scattered brain infarct pattern on diffusion-weighted magnetic resonance imaging in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Infarct patterns on brain imaging contribute to the etiologic classification of ischemic stroke. However, the association of specific subtypes of infarcts and etiologic mechanisms is often weak, and acute lesions are frequently missed on initial computed tomography (CT). Diffusion-weighted imaging (DWI) is superior in visualizing acute ischemic lesions as compared to CT and conventional magnetic resonance imaging (MRI). In our prospective study, we addressed the question whether a distinct pattern of infarction on DWI is associated with infarct etiology and clinical outcome. METHODS: Sixty-two patients with clinical signs of acute ischemic stroke and negative acute CT upon admission underwent DWI within 10 days after the ictus. Neurological status was documented using the NIH stroke scale. A scattered lesion pattern was defined by at least 2 separate hyperintense DWI lesions within the territory of one of the major cerebral arteries. Ischemic lesions were defined as acute if the region was demarcated strongly hyperintense in all DW images, and if the apparent diffusion coefficient was below normal. RESULTS: In 32 patients, DWI revealed a scattered lesion pattern, while in 30 patients a single acute lesion was detected. In patients with scattered lesions, potential arterial or cardiac embolic sources were detected in 26 patients (81.3%), as compared to 5 patients (16.6%) in the group with single lesions (chi(2) test, p < 0.0001). The neurological status of patients with scattered lesions improved significantly more than among patients with single lesions (Mann-Whitney test, p < 0.0003). CONCLUSION: A scattered lesion pattern on DWI in patients with acute brain infarction and negative initial CT scan is associated with an embolic etiology and may indicate a favorable clinical outcome.

Transtentorial herniation after unilateral infarction of the anterior cerebral artery.

BACKGROUND: Fatal cerebral herniation is a common complication of large ("malignant") middle cerebral artery infarcts but has not been reported in unilateral anterior cerebral artery (ACA) infarction. CASE DESCRIPTION: We report a 47-year-old woman who developed an acute left hemiparesis during an attack of migraine. Cranial CT (CCT) was normal but demonstrated narrow external cerebrospinal fluid compartments. Transcranial Doppler sonography was compatible with occlusion of the right ACA. Systemic thrombolytic therapy with tissue plasminogen activator was initiated 105 minutes after symptom onset. Follow-up CCT 24 hours after treatment revealed subtotal ACA infarction with hemorrhagic conversion. Two days later, the patient suddenly deteriorated with clinical signs of cerebral herniation, as confirmed by CCT. An extended right hemicraniectomy was immediately performed. Within 6 months, the patient regained her ability to walk but remained moderately disabled. CONCLUSIONS: This is the first reported case of unilateral ACA infarct leading to almost fatal cerebral herniation. Narrow external cerebrospinal fluid compartments in combination with early reperfusion, hemorrhagic transformation, and additional dysfunction of the blood-brain barrier promoted by tissue plasminogen activator and migraine may have contributed to this unusual course.

Prophylactic antipyretic treatment with acetaminophen in acute ischemic stroke: a pilot study.

Fever is associated with poor outcome in acute stroke. Forty-two consecutive, normothermic patients with acute ischemic stroke were, within 24 hours from symptom onset, randomized to either receive 4 g acetaminophen daily (n = 20) or matched placebo (n = 22). Fever of greater than 37.5 degrees C occurred in 36.4% of patients in the placebo group, compared with 5.0% in the acetaminophen group (Fisher's exact test, p = 0.014). Prophylactic antipyretic treatment with acetaminophen may be effective in the prevention of fever after acute ischemic stroke.

Unique frequency of known mutations in Brazilian MPS I patients.

The frequency of 10 known mutations in the IDUA gene-Q70X, A75T, H82P, R89Q, 678-7 g-->a, L218P, A327P, R383H, W402X, and P533R-was estimated in a group of 24 index cases with mucopolysaccharidosis type I. Three affected relatives were also analysed. Six of the 10 mutations screened were present in our patients (Q70X, R89Q, A327P, R383H, W402X, and P533R). These mutations account for 54% of the alleles; 37% of the genotypes were defined. Frequencies of these mutations are markedly different from those in the literature. A novel combination Q70X/A327P is described. This was the first time Brazilian MPS I patients were analysed with molecular techniques. The low frequency of common mutations indicates that a more comprehensive analysis of the IDUA gene should be done to delineate the mutation profile of MPS I better in our population.

Clinical and laboratorial study of 19 cases of mucopolysaccharidoses.

UNLABELLED: The mucopolysaccharidoses (MPS) are a heterogeneous group of inborn errors of lysosomal glycosaminoglycan (GAG) metabolism. The importance of this group of disorders among the inborn errors of metabolism led us to report 19 cases. METHOD: We performed clinical, radiological, and biochemical evaluations of the suspected patients, which allowed us to establish a definite diagnosis in 19 cases. RESULTS: Not all patients showed increased GAG levels in urine; enzyme assays should be performed in all cases with strong clinical suspicion. The diagnosis was made on average at the age of 48 months, and the 19 MPS cases, after a full clinical, radiological, and biochemical study, were classified as follows: Hurler - MPS I (1 case); Hunter - MPS II (2 cases); Sanfilippo - MPS III (2 cases); Morquio - MPS IV (4 cases); Maroteaux-Lamy - MPS VI (9 cases); and Sly - MPS VII (1 case). DISCUSSION: The high relative frequency of Maroteaux-Lamy disease contrasts with most reports in the literature and could express a population variability.

Clinical and molecular studies in five Brazilian cases of Friedreich ataxia.

Friedreich ataxia (FRDA), the most common autosomal recessive ataxia, is caused in 94% of cases by homozygous expansions of an unstable GAA repeat localised in intron 1 of the X25 gene. We have investigated this mutation in five Brazilian patients: four with typical FRDA findings and one patient with atypical manifestations, who was considered to have some other form of cerebellar ataxia with retained reflexes. The GAA expansion was detected in all these patients. The confirmation of FRDA diagnosis in the atypical case may be pointing out, as in other reports, that clinical spectrum of Friedreich's ataxia is broader than previously recognised and includes cases with intact tendon reflexes.

A simplified procedure for the isolation of immunoglobulins from human serum using a novel type of thiophilic gel at low salt concentration.

By coupling 3-(2-mercaptoethyl)quinazoline-2,4(1H,3H)dione (MECH) to divinyl sulfone activated agarose, a novel thiophilic matrix was obtained which allows the binding of immunoglobulins from different sources. In contrast to other thiophilic gels, antibodies are bound at low ionic strength and can easily be desorbed in intact form by elution with dilute alkali. The potential of using the MECH-gel was demonstrated by the purification of antibodies from human and animal (goat, rabbit, mouse) sera. The functional integrity of the purified antibodies was established with cytoplasmic islet cell antibodies from the sera of patients with type I diabetes and autoantibodies against thyroid peroxidase from patients with Graves' and Hashimoto's disease.