Subcortical reorganization in amyotrophic lateral sclerosis.

The cerebral cortex reorganizes in response to central or peripheral lesions. Although basal ganglia and cerebellum are key components of the network dedicated to movement control, their role in motor reorganization remains elusive. We therefore tested if slowly progressive neurodegenerative motor disease alters the subcortical functional anatomy of the basal ganglia-thalamo-cerebellar circuitry. Ten patients with amyotrophic lateral sclerosis (ALS) and ten healthy controls underwent functional magnetic resonance imaging (fMRI), while executing a simple finger flexion task. Cued by an acoustic trigger, they squeezed a handgrip force transducer with their right hand at 10% of their maximum voluntary contraction force. Movement frequency, amplitude, and force were controlled. Statistical parametric mapping of task-related BOLD-response revealed increased activation in ALS patients as compared to healthy controls. The main activation increases were found in the supplementary motor area, basal ganglia, brainstem, and cerebellum. These findings suggest that degeneration of cortical and spinal motor neurons in ALS leads to a recruitment of subcortical motor structures. These subcortical activation patterns strongly resemble functional activation in motor learning and might therefore represent adaptations of cortico-subcortical motor loops as a - albeit finally ineffective - mechanism to compensate for the ongoing loss of motor neurons in ALS.

Determinants of IV heparin treatment in patients with ischemic stroke.

Management of acute ischemic stroke with IV unfractionated heparin is subject to debate. The authors evaluated patient-related and institutional factors influencing its use in 42 hospitals. Cardioembolic stroke type, carotid stenosis, atrial fibrillation, and treatment in stroke units or intensive care units significantly increased the probability of use. However, there are large unexplained variations in IV heparin use among hospitals.

Neuroimaging evidence for cortical involvement in the preparation and in the act of swallowing.

This study employed whole head magnetoencephalography and synthetic aperture magnetometry to investigate the cortical topography of the preparation and the execution of volitional and reflexive water swallowing and of a simple tongue movement. Concerning movement execution, activation of the mid-lateral primary sensorimotor cortex was strongly lateralized to the left during volitional water swallowing, less strongly lateralized to the left during reflexive water swallowing, and not lateralized at all during tongue movement. In contrast, the preparation for both volitional water swallowing and tongue movement showed a bilateral activation of the primary sensorimotor cortex. No activation was seen prior to reflexive water swallowing. Activation of the left insula and frontal operculum was observed only during both the preparation and the execution of volitional water swallowing. These new findings suggest a left hemispheric dominance for the cortical control of swallowing in humans.

Spontaneous internal carotid artery dissection and alpha-1-antitrypsin deficiency.

Spontaneous cervical arterial dissection is an important cause of juvenile stroke. However, etiopathology and genetic background remain poorly understood. We report on a 45-year-old-male patient with homozygous alpha-1-antitrypsin (alpha-1-AT) deficiency in whom internal carotid artery dissection occurred in the absence of any other known risk factors. The relevance of alpha-1-AT deficiency for spontaneous cervical arterial dissections is discussed.

[The megadolichobasilar artery--a clinical chameleon]. / Die dolichoectatische Basilaris. Ein klinisches Chamäleon.

The megadolichobasilar artery is a rare vascular disease, which usually becomes apparent either due to cerebral ischemia or due to compression of the brainstem or the cranial nerves, thereby leading to a large variety of neurological symptoms. We report on a patient who suffered a sudden right-sided deafness accompanied by vertigo and vomiting. Initially, an idiopathic sensorineural hearing loss was diagnosed and later on, after no improvement took place in spite of conservative therapy, a rupture of the round window membrane was suspected. Two weeks after the first symptoms had occurred the patient developed a hemiparesis on the left side.Radiology disclosed a dilated and partially thrombosed basilar artery as well as a paramedian pontine infarction. We therefore assumed that the patient's symptoms had been caused by thrombotic occlusion of the labyrinthine artery and several rami ad pontem. The article reviews the great variety of clinical symptoms caused by megadolichobasilar artery and discusses important therapeutic options.

Degree of language lateralization determines susceptibility to unilateral brain lesions.

Language is considered a function of either the left or, in exceptional cases, the right side of the brain. Functional imaging studies show, however, that in the general population a graded continuum from left hemispheric to right hemispheric language lateralization exists. To determine the functional relevance of lateralization differences, we suppressed language regions using transcranial magnetic stimulation (TMS) in healthy human subjects who differed in lateralization of language-related brain activation. Language disruption correlated with both the degree and side of lateralization. Subjects with weak lateralization (more bilaterality) were less affected by either left- or right-side TMS than were subjects with strong lateralization to one hemisphere. Thus in some people, language processing seems to be distributed evenly between the hemispheres, allowing for ready compensation after a unilateral lesion.

Initiation and development of fingertip forces during whole-hand grasping.

The present study examined the initiation of digit contact and fingertip force development during whole-hand grasping. Sixteen healthy subjects grasped an object instrumented with force transducers at each digit and lifted it 10 cm. The grip (normal) and load (tangential) forces and the position of the object were recorded. Twenty-five lifts were performed with various object weights (300 g, 600 g, 900 g) and surface textures (sandpaper and rayon). Despite the large number of degrees of freedom, grip initiation with an object using the whole hand was characterized by stereotypical contact patterns, which are idiosyncratic to each subject across all object weights and textures. However, in spite of the initial asymmetric control, the forces were mainly synchronized by the occurrence of the peak grip and load force rates. The contribution of each digit to the total grip force decreased from radial to ulnar digits. The final force distribution was generally established already at the onset of load forces. Only subtle adjustments were seen thereafter, suggesting a fairly fixed force distribution pattern throughout the grasp. The findings suggest that, despite the large number of degrees of freedom in terms of contact initiation and force distribution in whole-hand grasping: (1) subjects employ preferred movement patterns to establish object contact with their digits, and (2) synchronize the subsequent force development and temporal coordination of the task. Thus while the complexity of the task requires control mechanisms beyond those seen in two-finger precision grasping, there are strategies to simplify the complex task of the initiation and development of fingertip forces in whole-hand grasping.

Language and spatial attention can lateralize to the same hemisphere in healthy humans.

BACKGROUND: Disorders of language classically occur after left brain lesions, and disorders of spatial attention after right brain lesions. It is unclear whether the hemispheric dissociation of functions is a fixed pattern of brain organization. OBJECTIVE: The authors determined whether lateralization of language and lateralization of spatial attention also dissociate in people with atypical (i.e., right hemispheric) language dominance. METHODS: The authors selected 10 subjects with typical, i.e., left hemispheric, and 10 with atypical, i.e., right hemispheric, language representation on a random basis from a sample of 326 healthy volunteers examined with functional transcranial Doppler sonography (fTCD) for language dominance. In these subjects, hemispheric lateralization of cerebral perfusion during a line bisection task was determined with fTCD. RESULTS: The authors found a dissociation between dominance for language and spatial attention in all but four subjects. In the latter subjects, there was a significant lateralization to the right hemisphere for both tasks. The four subjects showed normal intellectual, linguistic, and spatial performance, with normal EEG and MRI scans of the brain. CONCLUSION: Even in the absence of brain pathology, the same hemisphere can be dominant in control of both language and spatial attention.

Objective assessment of progression in Huntington's disease: a 3-year follow-up study.

Objective measures to assess progression of Huntington's disease (HD) are desirable. The authors have previously found that patients with HD with higher Unified Huntington's Disease Rating Scale (UHDRS) motor scores exhibited higher variability of isometric grip forces while grasping an object. Therefore, the authors assessed grip force variability during this task in 10 HD patients with a 3-year follow-up. Grip force variability increased in all patients at the follow-up. Thus, grip force variability during grasping might be an objective and quantitative measure to assess motor deficits associated with the progression of HD.

[Stroke patients in general practice. Preventing recurrent infarct]. / Schlaganfall-Patienten in der Hausarztpraxis. Dem Reinsult vorbeugen.

Stroke patients have a high recurrence risk of 4-14% per year--depending on individual etiology. The best way of preventing a repeat insult and protecting the patient's remaining quality of life is to rigorously apply all available secondary prophylactic possibilities. These include measures aimed at modifying a health-endangering lifestyle, as well as medical treatment of all risk-enhancing illnesses. The present article offers an overview of the major confirmed and modifiable risk factors for stroke (arterial hypertension, smoking, atrial fibrillation, diabetes mellitus, overweight, hyper-cholesterolemia, thrombophilia, immoderate use of alcohol, lack of exercise, use of contraceptives, migraine), and outlines therapeutic strategies for secondary prevention.

Behavioural relevance of atypical language lateralization in healthy subjects.

In most humans, language is lateralized to the left side of the brain. It has been speculated that this hemispheric specialization is a prerequisite for the full realization of linguistic potential. Using standardized questionnaires and performance measures, we attempted to determine if there are behavioural correlates of atypical, i.e. right-hemispheric and bilateral, language lateralization. The side and degree of language lateralization were determined by measuring the hemispheric perfusion differences by functional transcranial Doppler ultrasonography during a word generation task in healthy volunteers. Subjects with left (n = 264), bilateral (n = 31) or right (n = 31) hemisphere language representation did not differ significantly with respect to mastery of foreign languages, academic achievement, artistic talents, verbal fluency or (as assessed in a representative subgroup) in intelligence or speed of linguistic processing. These findings suggest that atypical hemispheric specialization for language, i.e. right-hemisphere or bilateral specialization, is not associated with major impairments of linguistic faculties in otherwise healthy subjects.

Functional reorganization of the human primary somatosensory cortex after acute pain demonstrated by magnetoencephalography.

The somatosensory system is capable of functional reorganization following peripheral denervation or training. Studies on human amputees with phantom limb pain provided evidence that these reorganizational changes are modulated through nociceptive input. In the present study we used magnetoencephalographic recordings of six healthy volunteers to assess whether acute pain by itself causes a reorganization of the primary somatosensory cortex. After the induction of an intense experimental pain at the thenar of the left hand by intradermal injection of capsaicin, the extent of the cortical hand representation and the distance between the hand representation and the localization of the lip decreased. A likely mechanism for this acute reorganization is that pain induced hyperresponsiveness of the left thenar to tactile input from neighboring body sites.

D-amphetamine does not improve outcome of somatosensory training.

BACKGROUND: D-amphetamine has been shown to affect early stages of stroke recovery, and may have a beneficial effect on functions when administered later after stroke. OBJECTIVE: To test D-amphetamine effects on skill acquisition after the acute or subacute stages of stroke, when lesion-related structural changes have consolidated. METHODS: Sixteen healthy subjects were treated with D-amphetamine during a 4-week training of tactile frequency discrimination in a placebo-controlled, double-blind design. RESULTS: All subjects improved significantly in tactile temporal acuity. However, improvement did not differ in subjects treated with or without D-amphetamine. CONCLUSION: No beneficial effect of D-amphetamine on somatosensory training improvements was found in healthy subjects.

Handedness and hemispheric language dominance in healthy humans.

In most people the left hemisphere of the brain is dominant for language. Because of the increased incidence of atypical right-hemispheric language in left-handed neurological patients, a systematic association between handedness and dominance has long been suspected. To clarify the relationship between handedness and language dominance in healthy subjects, we measured lateralization directly by functional transcranial Doppler sonography in 326 healthy individuals using a word-generation task. The incidence of right-hemisphere language dominance was found to increase linearly with the degree of left-handedness, from 4% in strong right-handers (handedness = 100) to 15% in ambidextrous individuals and 27% in strong left-handers (handedness = -100). The relationship could be approximated by the formula: f1.gif" BORDER="0">. These results clearly demonstrate that the relationship between handedness and language dominance is not an artefact of cerebral pathology but a natural phenomenon.

Assessment of hemispheric language lateralization: a comparison between fMRI and fTCD.

The cerebral blood flow velocity (CBFV) in the basal arteries during a word-generation task was assessed by functional transcranial Doppler ultrasonography (fTCD) and by functional magnetic resonance imaging (fMRI). The study investigates how event-related CBFV modulations in the middle cerebral artery (MCA) relate to regional cerebral blood flow (rCBF) changes. Both fMRI and fTCD were used in 13 subjects (7 men, 6 women, aged 21 to 44 years). The maximum difference of relative CBFV changes between the left and right MCA during the word-generation task was used as the language laterality index (LIfTCD). For the fMRI examination during the nearly identical language task, the corresponding index was defined by LIfMRI = 100(N(L) - N(R))/(N(L) + N(R)), where N(L) and N(R) refer to the numbers of voxels activated in the left and right hemisphere, respectively. The evoked CBFV changes expressed by LIfTCD and the corresponding laterality index, LIfMRI, estimated by fMRI showed a close linear relation (regression analysis: r = 0.95, p < 0.0001). The results of this study demonstrate that language-related velocity changes in the MCAs relate to rCBF increases in a linear fashion. Since the laterality indices assessed by fMRI and fTCD are in such close agreement both techniques can therefore be used in a complementary way.

Functional magnetic resonance imaging (fMRI) clinical studies in ALS--paradigms, problems and promises.

Functional magnetic resonance imaging (fMRI) provides high-resolution, non-invasive estimates of neural activity detected by a blood oxygen level dependent signal by assessing the increase in blood flow to the local vasculature that accompanies neural activity in the brain. fMRI studies with standard hand motor test (index-thumb opposition, ITO, or pinch) in ALS patients show good test-retest reliability and similar amplitude of signals in ALS patients compared with control subjects. Isometric force can be performed with careful control for the force exerted, recruitment of other muscles and motion artefact. The volume (number of voxels above threshold) of sensorimotor and cerebellar cortex activated by ITO is reproducibly larger in ALS patients compared with control subjects. Imagined movements in ALS have been studied, as in amputees, and larger volumes are activated in ALS patients with imagined movements as well, compared with control subjects. fMRI studies in ALS patients evaluating cortical activation during pure somatosensory stimulation cutaneous stimulation of the hand to elicit the palmomental response and cutaneous stimulation of the sole to elicit the plantar response - indicate that ALS patients activate a significantly smaller volume of the contralateral sensorimotor cortex compared to control subjects. No statistically significant difference was seen in other areas, including the ipsilateral cerebellum and the contralateral thalamus. An anterior shift in the volume of cortex activated by these paradigms occurs in ALS patients, with a volume of activation, anteriorly, not activated in control subjects. fMRI studies will complement other clinical neurophysiological and neuroimaging techniques in our future attempts to solve the riddle of ALS and other motor neuron diseases.

Language lateralization in healthy right-handers.

Our knowledge about the variability of cerebral language lateralization is derived from studies of patients with brain lesions and thus possible secondary reorganization of cerebral functions. In healthy right-handed subjects 'atypical', i.e. right hemisphere language dominance, has generally been assumed to be exceedingly rare. To test this assumption we measured language lateralization in 188 healthy subjects with moderate and strong right-handedness (59% females) by a new non-invasive, quantitative technique previously validated by direct comparison with the intracarotid amobarbital procedure. During a word generation task the averaged hemispheric perfusion differences within the territories of the middle cerebral arteries were determined. (i) The natural distribution of language lateralization was found to occur along a bimodal continuum. (ii) Lateralization was equivalent in men and women. (iii) Right hemisphere dominance was found in 7.5% of subjects. These findings indicate that atypical language dominance in healthy right-handed subjects of either sex is considerably more common than previously suspected.

Cortical asymmetries of the human somatosensory hand representation in right- and left-handers.

Hemispheric asymmetry is known for higher brain functions like language and attention. We tested whether such an asymmetry also exists in the representation of elementary sensory functions. Magnetic source imaging was used to compare the cortical somatosensory hand representation in seven right- and five left-handed individuals. In all right-handers the representation of the dominant hand was larger than the contralateral one in the corresponding hemispheres. In contrast, only two out of five left-handers revealed a larger representation of the dominant left hand compared to the right one. In agreement with previous findings on the lateralization of language and attention, there is a strong correlation between handedness and the extent of the cortical hand representation in right-, but not in left-handers. We conclude that a profound functional hemispheric asymmetry also exists in primary sensory cortices.

Cortical tuning: a function of anticipated stimulus intensity.

We investigated the activation of the brain during anticipation of tactile stimuli by continuous cerebral blood flow velocity (CBFV) monitoring with bilateral transcranial Doppler sonography. A forced choice paradigm was performed where a first group of subjects (n=16) was expecting suprathreshold and a second group (n=19) was anticipating threshold tactile stimuli to the index finger after a cueing tone. During the anticipation of suprathreshold stimuli the CBFV always exhibited a significantly stronger increase in the right hemisphere than in the left, even when stimuli were anticipated at the right index finger. Conversely when stimuli at perception threshold were expected, the respective contralateral hemisphere showed a significantly stronger perfusion increase. These data show that preparatory activation of the brain during stimulus anticipation is dependant on the expected stimulus intensity.