A Myocardial Infarction During Intravenous Recombinant Tissue Plasminogen Activator Infusion for Evolving Ischemic Stroke.

INTRODUCTION: There are reports of an ischemic stroke during intravenous recombinant tissue-type plasminogen activator (rtPA) for evolving myocardial infarction (MI), and the risk of stroke shortly after an acute MI seems to be higher than in the control population, attributed to intracardiac thrombus formation. CASE REPORT: We report a case of fatal MI developing immediately after the start of rtPA infusion for middle cerebral artery stroke in an 88-year-old woman. We assume that the systemic thrombolysis with rtPA led to the fragmentation of an underlying cardiac thrombus, which embolized and occluded the coronary artery and caused MI. This hypothesis is discussed with respect to a short review of the related literature. CONCLUSIONS: An embolic MI seems to be a rare but serious complication in thrombolysis therapy with rtPA.

The Essen Stroke Risk Score in one-year follow-up acute ischemic stroke patients.

BACKGROUND AND PURPOSE: We aimed to validate the usefulness of the Essen Stroke Risk Score (ESRS) to predict stroke recurrence in a hospital-based follow-up study. METHODS: We followed up 730 consecutive patients admitted to a neurological stroke unit in Berlin, Germany, with ischemic stroke (IS) or transient ischemic attack (TIA). The mean follow-up time was 13.4 months (SD 5.9). We calculated the time of event-free survival by Kaplan-Meier estimates. RESULTS: The cumulative rate of a recurrent stroke was 10.4% (76 of 730). The risk of a recurrent stroke was significantly higher in patients with an ESRS >2 (p = 0.01; log rank). The area under the curve (AUC) was 0.59. The risk of a vascular event (VE), defined as a fatal or nonfatal IS or myocardial infarction, was significantly higher in patients with an ESRS >2 (p = 0.003; log rank). The AUC was 0.58. Stratifying the data at exact 1-year follow-up, 9 of 185 (10.3%) patients with an ESRS ≤2 suffered a recurrent stroke, while 56 of 311 (18%) patients with an ESRS >2 did so (p < 0.02; χ(2)). Thirty-six of 196 (18.4%) patients with an ESRS ≤2 suffered a VE, while 156 of 353 (35.7%) patients with an ESRS >2 did so (p < 0.001; χ(2)). CONCLUSIONS: The ESRS identifies groups of patients with TIA or IS who are at significantly increased risk for a recurrent stroke and cardiovascular event. Patients with a high ESRS require short-term follow-up and reevaluation of secondary prevention strategies.

Wallerian degeneration of pyramidal tract after paramedian pons infarct.

BACKGROUND: The intention of this study was the prospective analysis of Wallerian degeneration of the pyramidal tract after paramedian pons infarction. METHODS: Patients with paramedian pons infarct underwent MR imaging including diffusion tensor imaging at admission and got 1-3 MR scans up to 6 months of follow-up. Clinical scores and transcranial magnetic stimulation were acquired in the acute phase and 3-6 months later. The pyramidal tracts were manually segmented in fractional anisotropy (FA) color maps after coregistration of all MR datasets of each patient. FA as well as axial and radial diffusivity were measured in the volume of lesioned and contralateral pyramidal tracts distally to the ischemic lesion. RESULTS: From 11 patients studied, 7 developed Wallerian degeneration detected as statistically significant decrease in FA over time in the distal pyramidal tract. Wallerian degeneration could be detected at the earliest between the first and the third days after the onset of symptoms. A continuous decrease in FA and an increase in axial and radial diffusivity in degenerating pyramidal tracts over time were demonstrated. A significant correlation between NIHSS score on admission and the slope of relative axial diffusivity and a significant correlation between motor-evoked potential amplitudes of the arm on admission and the outcome relative FA was found. CONCLUSIONS: The initial MR image cannot predict the following Wallerian degeneration. However, the severity of motor disturbance and the motor-evoked potential of the arm on admission could be possible parameters to predict Wallerian degeneration. For estimation of Wallerian degeneration over time, at least 2 diffusion tensor imaging measurements have to be done at different time points.

Topodiagnostic implications of hemiataxia: an MRI-based brainstem mapping analysis.

The topodiagnostic implications of hemiataxia following lesions of the human brainstem are only incompletely understood. We performed a voxel-based statistical analysis of lesions documented on standardised MRI in 49 prospectively recruited patients with acute hemiataxia due to isolated unilateral brainstem infarction. For statistical analysis individual MRI lesions were normalised and imported in a three-dimensional voxel-based anatomical model of the human brainstem. Statistical analysis revealed hemiataxia to be associated with lesions of three distinct brainstem areas. The strongest correlation referred to ipsilateral rostral and dorsolateral medullary infarcts affecting the inferior cerebellar peduncle, and the dorsal and ventral spinocerebellar tracts. Secondly, lesions of the ventral pontine base resulted in contralateral limb ataxia, especially when ataxia was accompanied by motor hemiparesis. In patients with bilateral hemiataxia, lesions were located in a paramedian region between the upper pons and lower midbrain, involving the decussation of dentato-rubro-thalamic tracts. We conclude that ataxia following brainstem infarction may reflect three different pathophysiological mechanisms. (1) Ipsilateral hemiataxia following dorsolateral medullary infarctions results from a lesion of the dorsal spinocerebellar tract and the inferior cerebellar peduncle conveying afferent information from the ipsilateral arm and leg. (2) Pontine lesions cause contralateral and not bilateral ataxia presumably due to major damage to the descending corticopontine projections and pontine base nuclei, while already crossed pontocerebellar fibres are not completely interrupted. (3) Finally, bilateral ataxia probably reflects a lesion of cerebellar outflow on a central, rostral pontomesencephalic level.

Time course of diffusion imaging in acute brainstem infarcts.

PURPOSE: To study the time course of diffusion imaging at the lesion site in brainstem infarcts. MATERIALS AND METHODS: Sequential MR scans were acquired from 24 patients with brainstem infarcts. Diffusion-weighted images (DWI), T(2)-weighted images (T(2)w), maps of apparent diffusion coefficient, and maps of fractional anisotropy were generated from each MR scan. A trend function was fitted to these measurements to model an objective, general time course of the studied parameters. RESULTS: Apparent diffusion coefficient (ADC) continuously decreased over time until a transition time around 45 hours; afterwards a continuous increase took place. After the 14th day ADC reached values similar to the ADC of the intact contralateral side (pseudonormalization) and then further increased. Fractional anisotropy (FA) decreased continuously over 3 to 6 months. CONCLUSION: Times of transition and pseudonormalization of ADC were longer than described for territorial hemispheric infarcts and describe the acute to subacute phase of brainstem ischemia. In contrast, the continuous decline of FA over 3 to 6 months indicates a chronic process of change of histological structures in brainstem ischemia, and may be regarded as an indicator of the chronic phase.

Levetiracetam as a treatment option in non-convulsive status epilepticus.

Non-convulsive status epilepticus (NCSE) is characterized by continuous or recurrent, generalized or focal epileptiform activity on the electroencephalogram and diverse clinical symptoms with alterations of mental state and vigilance. NCSE is not rare but certainly under diagnosed. There is some debate about how aggressive NCSE should be treated, as high dose anticonvulsants maybe partially responsible for the morbidity and mortality of patients with NCSE. We hypothesized that levetiracetam (LEV) as a well tolerated, highly effective new anticonvulsant, may be a safe treatment option. We retrospectively analyzed all (8) patients with NCSE who received levetiracetam from our database, compared with 11 patients with NCSE treated with conventional intravenous status medication as controls. These eight patients showed a marked clinical improvement with final cessation of ictal EEG-activity and clinical symptoms of NCSE after initiation of LEV within 3 days (mean 1.5 days). The response to conventional treatment was similarly effective but there were severe side effects whereas no relevant side effects in the LEV-treated group were noticed. A long-term follow up (6-36 months from discharge) revealed six patients with a persisting reduction in seizure frequency on medication with LEV. One patient changed the anticonvulsive medication because of inefficacy and one died from other causes than epilepsy 2 months after discharge from hospital. We found no significant differences in hospitalisation time, time in intensive care unit and outcome between the LEV group and the control group. This retrospectively acquired data suggests that LEV may be a well tolerated, effective treatment option in NCSE. This highlights the need for a prospective controlled study to further elucidate the utility of LEV in the treatment of NCSE, particularly as an intravenous formulation is now available.

Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.

Valproic acid-induced hepatopathy: nine new fatalities in Germany from 1994 to 2003.

PURPOSE: Valproic acid (VPA) is an antiepileptic drug (AED) commonly used for generalized and focal epilepsies. We provide an update on hepatotoxic side effects in Germany between 1994 and 2003. METHODS: We mailed a questionnaire to all members of the German Section of the International League Against Epilepsy, asking for VPA-induced side effects, especially severe side effects such as hepatopathy. RESULTS: As a result of our questionnaire, we found 31 cases of reversible hepatotoxicity and nine cases of lethal hepatopathies in Germany from 1994 to 2003. CONCLUSIONS: The outcome of patients with severe hepatotoxicity is better than that in the past. The risk of a VPA-induced hepatopathy is not limited to patients younger than 2 years, receiving polytherapy, or patients with congenital or acquired metabolic diseases.

Somatotopic organization of the corticospinal tract in the human brainstem: a MRI-based mapping analysis.

To investigate the incompletely understood somatotopical organization of the corticospinal tract in the human brainstem, we performed a voxel-based statistical analysis of standardized magnetic resonance scans of 41 prospectively recruited patients with pyramidal tract dysfunction caused by acute brainstem infarction. Motor hemiparesis was rated clinically and by the investigation of motor evoked potentials to arms and legs. Infarction affected the pons in 85% of cases. We found the greatest level of significance of affected brainstem areas between the pontomesencephalic junction and the mid pons. Lesion location was significantly more dorsal in patients with hemiparesis affecting more proximal muscles and was significantly more ventral in patients with predominantly distal limb paresis. Comparison of magnetic resonance lesion from patients with paresis predominantly affecting arm or leg did not show significant topographical differences. We conclude that a topographical arm/leg distribution of corticospinal fibers is abruptly broken down as the descending corticospinal tract traverses the pons. Corticospinal fibers, however, follow a somatotopical order in the pons with fibers controlling proximal muscles being located close to the reticular formation in the dorsal pontine base, and thus more dorsal than the fibers controlling further distal muscle groups.

Anisotropy of human linea alba: a biomechanical study.

BACKGROUND: Recently, a new model of fiber architecture of the linea alba has been described consisting of an oblique fiber layer of intermingling oblique fibers, a transverse fiber layer containing mainly transverse fibril bundles, and a variable, small irregular fiber layer. In this study the morphological model was proven using direction-specific biomechanical measurements of the linea alba. MATERIAL AND METHODS: Thirty-one human abdominal walls were analyzed (16 male and 15 female). Six strips of collagen tissue with a width of 1 cm were exsected from each linea alba transversely, obliquely, and longitudinally according to the main fiber directions. An increasing force from 2 to 24 N was applied to these strips, and the corresponding strain represented by the relative elongation was measured, which allows the calculation of a direction-specific compliance of the tissue. RESULTS: The compliance is highest in longitudinal and smallest in transverse direction. In the infraumbilical part of the female linea alba the compliance was significantly smaller in the transverse direction than in the oblique direction. Moreover, the compliance in the transverse direction was significantly smaller in women than in men. CONCLUSIONS: A distinct anisotropy of morphological and biomechanical properties was demonstrated as well as sex-dependent differences. The compliance correlates with the distribution of fiber orientation in the linea alba. These biomechanical results constitute the functional correlation with the fiber morphology of the linea alba and correspond well to our earlier proposed model of fiber architecture.

Organic bipolar disorder occurring together with spontaneous intracranial hypotension.

Spontaneous intracranial hypotension (SIH) is known to cause postural headache, often combined with auditory, and vestibular symptoms, nausea, vomiting, and diplopia. We report a 63-year-old male patient who for the first time developed a depressive episode followed by acute manic symptoms during the course of SIH, both relieved after treatment of the underlying organic disturbance.

Cortical vestibular representation in the superior temporal gyrus.

We present the unique case of a patient with a circumscribed solitary cerebral metastasis of a malignant melanoma extending from the medial part of the superior temporal gyrus to the lower part of the 1st long insular gyrus causing gait and stance instability and an ipsiversive tilt of the subjective visual vertical. Oculomotor disorders could not be detected. We suggest that the superior temporal gyrus is likely to be involved in spatial orientation presumably using otolithic information.

Event-related fMRI with painful electrical stimulation of the trigeminal nerve.

Several functional brain imaging studies of pain using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have shown that painful stimulation causes activation of different brain areas. The aim of the present study was to develop and implement painful stimulation of the trigeminal nerve, which can be applied with event-related paradigms by using MRI. Twelve healthy, right-handed volunteers were examined. Painful electrical stimulation of the first trigeminal branch was performed. In an event-related setting with a 1.5 T clinical scanner with EPI capability, the following fMRI parameters were used: 20 slices, 3 mm thickness, isotropic voxel, 306 measurements with 54 randomized events. Statistical postprocessing was performed with SPM99. Activation of the ipsi- and contralateral secondary somatosensory cortex (SII), and the contralateral insular cortex was observed as well as a contralateral thalamic activation (T=4.45, extension 15 voxels). Six of the 12 volunteers revealed also activation of the cingulate cortex. The investigation demonstrates that painful stimulation of the trigeminal nerve activates the contralateral insular cortex, SII, and thalamus, as well as the ipsilateral SII. In contrast to other studies, the cingulate cortex was only activated inconsistently.

Bilateral Wallerian degeneration of the medial cerebellar peduncles after ponto-mesencephalic infarction.

Three patients with acute large paramedian ponto-mesencephalic infarctions developed a bilateral retrograde degeneration of the medial cerebellar peduncles within 4 months after the insult. In an initial magnetic resonance imaging (MRI) within the first 2 weeks, the medial cerebellar peduncles showed normal intensities, but a control MRI after 4 months showed bright hyperintensities in the T2-TSE weighted images, and moderately increased signal intensities in echo planar imaging-diffusion weighted imaging were seen, possibly representing bilateral Wallerian degeneration of the cerebellar-pontine fibers.

Electrophysiological brainstem testing in the diagnosis of reversible brainstem ischemia.

The aim of this study was to evaluate the sensitivity of multimodal electrophysiological brainstem testing in the diagnosis of clinically suspected reversible ischemic deficits of the brainstem compared with diffusion weighted MR imaging. We investigated 158 consecutive patients presenting with signs of acute brainstem dysfunction. Serial electrophysiological brainstem tests including masseter reflex, blink reflex, masseter inhibitory reflex, AEP, MEP, EOG and the oculoauricular phenomenon were applied. In 14 of the 158 patients neurological deficits resolved in less than 24 hours, which was suggestive of a transitory ischemic attack (TIA), 19 patients had brainstem signs for more than 24 hours but less than 1 week, suggestive of a reversible ischemic neurological deficit (RIND). Electrophysiological data indicated acute functional brainstem lesions in 54,5 % of patients with transient clinical brainstem impairment. Lesion detection rate was significantly higher when combining electrophysiological data and MRI (60,4 %) than using acute brainstem abnormalities in diffusion weighted MRI alone (39,4 %). We conclude that diffusion weighted MRI and electrophysiological brainstem testing are complimentary sensitive indicators of acute brainstem lesions in patients with reversible neurological deficits. Correct identification of brainstem ischemia influences the therapeutic regimen and may improve patient outcome.

Diffusion-weighted MRI of cholesteatomas of the petrous bone.

PURPOSE: To investigate if primary cholesteatomas of the petrous bone show high signal in diffusion-weighted imaging (DWI). MATERIALS AND METHODS: In this blinded study, we compared 15 patients with clinically certain cases and later surgically proven cholesteatomas vs. 12 patients with clinically acute otitis of the middle ear and 20 volunteers without petrous bone disease. Two blinded readers without knowledge of the clinical data decided in consensus agreement whether there was a pathologic signal increase in the petrous bone in an anisotropic single-shot echo-planar imaging (EPI) DWI sequence, an artifact, or no signal increase. RESULTS: Thirteen of 15 patients with cholesteatomas showed bright signal in EPI DWI, whereas 10 of 12 patients with acute otitis media and all volunteers presented the usual low signal of petrous bone. CONCLUSION: EPI DWI is a fast diagnostic method that may be an additional valuable tool in the workup of suspected cholesteatomas. The ability of this technique to differentiate between cholesteatomas and granulomas or chronic otitis is not yet available.