Functional recovery and rehabilitation of postural impairment and gait ataxia in patients with acute cerebellar stroke.

Studies about recovery from cerebellar stroke are rare. The present study assessed motor deficits in the acute phase after isolated cerebellar stroke focusing on postural impairment and gait ataxia and outlines the role of lesion site on motor outcome, the course of recovery and the effect of treadmill training. 23 patients with acute and isolated cerebellar infarction participated. Deficits were quantified by ataxia scores and dynamic posturography in the acute phase and in a follow up after 2 weeks and 3 months. MRI data were obtained to correlate lesion site with motor performance. Half of the patients that gave informed consent and walked independently underwent a 2-week treadmill training with increasing velocity. In the acute phase patients showed a mild to severe ataxia with a worse performance in patients with infarction of the superior in comparison to the posterior inferior cerebellar artery. However, after 3 months differences between vascular territories were no longer significant. MRI data showed that patients with larger infarct volumes had a significantly more severe ataxia. In patients with ataxia of stance, gait and lower limbs lesions were more common in cerebellar lobules IV to VI. After 3 months a mild ataxia in lower limbs and gait, especially in gait speed persisted. Because postural impairment had fully recovered, remaining gait ataxia was likely related to incoordination of lower limbs. Treadmill training did not show significant effects. Future studies are needed to investigate whether intensive coordinative training is of benefit in patients with cerebellar stroke.

Cerebellar regions involved in adaptation to force field and visuomotor perturbation.

Studies with patients and functional magnetic resonance imaging investigations have demonstrated that the cerebellum plays an essential role in adaptation to visuomotor rotation and force field perturbation. To identify cerebellar structures involved in the two tasks, we studied 19 patients with focal lesions after cerebellar infarction. Focal lesions were manually traced on magnetic resonance images and normalized using a new spatially unbiased template of the cerebellum. In addition, we reanalyzed data from 14 patients with cerebellar degeneration using voxel-based morphometry. We found that adjacent regions with only little overlap in the anterior arm area (lobules IV to VI) are important for adaptation in both tasks. Although adaptation to the force field task lay more anteriorly (lobules IV and V), lobule VI was more important for the visuomotor task. In addition, regions in the posterolateral cerebellum (Crus I and II) contributed to both tasks. No consistent involvement of the posterior arm region (lobule VIII) was found. Independence of the two kinds of adaptation is further supported by findings that performance in one task did not correlate to performance in the other task. Our results show that the anterior arm area of the cerebellum is functionally divided into a more posterior part of lobule VI, extending into lobule V, related to visuomotor adaption, and a more anterior part including lobules IV and V, related to force field adaption. The posterolateral cerebellum may process common aspects of both tasks.

Impaired prehension is associated with lesions of the superior and inferior hand representation within the human cerebellum.

Impairment of patients with cerebellar disease in prehension is well recognized. So far specific localizations within the human cerebellum associated with the impairment have rarely been assessed. To address this question we performed voxel-based lesion symptom mapping (VLSM) in patients with chronic focal cerebellar lesions in relation to specific deficits in prehensile movements. Patients with stroke within the posterior inferior cerebellar artery territory (n = 13) or the superior cerebellar artery (SCA) territory (n = 7) and corresponding control subjects were included in the study. Participants reached out, grasped, and lifted an object with either the left or right hand and with fast or normal movement speed. Both kinematic and grip-force parameters were recorded. Magnetic resonance imaging anatomical scans of the cerebellum were acquired, and lesions were marked as regions of interest. For VLSM analysis, a nonparametric test (Brunner-Munzel) was applied. Cerebellar patients showed clear abnormalities in hand transport (impaired movement speed and straightness) and, to a lesser degree, in hand shaping (increased finger touch latencies) while grip function was preserved. Deficits were most prominent in patients with SCA lesions and for ipsilesional, fast movements. Disorders in hand transport may be more difficult to compensate than deficits in hand shaping and grip-force control in chronic focal lesions of the cerebellum because of higher demands on predictive control of interaction torques. Lesions of the superior cerebellar cortex (lobules IV, V, VI) were associated with slower hand transport, whereas lesions of both superior (lobules VI, V, VI) and inferior cerebellar cortex (lobules VII, VIII) were associated with impaired movement straightness. These findings show that both the superior and inferior hand representations within the cerebellum contribute to hand transport during prehensile movements; however, they may have a different functional role.

Recovery of upper limb function after cerebellar stroke: lesion symptom mapping and arm kinematics.

BACKGROUND AND PURPOSE: Loss of movement coordination is the main postacute symptom after cerebellar infarction. Although the course of motor recovery has been described previously, detailed kinematic descriptions of acute stage ataxia are rare and no attempt has been made to link improvements in motor function to measures of neural recovery and lesion location. This study provides a comprehensive assessment of how lesion site and arm dysfunction are associated in the acute stage and outlines the course of upper limb motor recovery for the first 4 months after the infarction. METHODS: Sixteen adult patients with cerebellar stroke and 11 age-matched healthy controls participated. Kinematics of goal-directed and unconstrained finger-pointing movements were measured at the acute stage and in 2-week and 3-month follow-ups. MRI data were obtained for the acute and 3-month follow-up sessions. A voxel-based lesion map subtraction analysis was performed to examine the effect of ischemic lesion sites on kinematic performance. RESULTS: In the acute stage, nearly 70% of patients exhibited motor slowing with hand velocity and acceleration maxima below the range of the control group. MRI analysis revealed that in patients with impaired motor performance, lesions were more common in paravermal lobules IV/V and affected the deep cerebellar nuclei. Stroke affecting the superior cerebellar artery led to lower motor performance than infractions of the posterior cerebellar artery. By the 2-week-follow-up, hand kinematics had improved dramatically (gains in acceleration up to 86%). Improvements between the 2-week and the 3-month-follow-ups were less pronounced. CONCLUSIONS: In the acute stage, arm movements were mainly characterized by abnormal slowness (bradykinesia) and not dyscoordination (ataxia). The motor signs were associated with lesions in paravermal regions of lobules IV/V and the deep cerebellar nuclei. Motor recovery was fast, with the majority of gains in upper limb function occurring in the first 2 weeks after the acute phase.

Aphasia and neglect are uncommon in cerebellar disease: negative findings in a prospective study in acute cerebellar stroke.

The aim of the present study was to examine if the most frequent cognitive disorders after cortical damage with a well-known cerebral lateralization, namely aphasia, neglect and extinction, are present in an unselected series of continuously admitted patients with acute cerebellar stroke. Twenty-two adults with acute cerebellar stroke were compared with 22 age- and education-matched healthy control subjects. High-resolution magnetic resonance images showed infarctions of the left cerebellar hemisphere in 12 and of the right hemisphere in ten patients. Standard aphasia tests revealed no statistically significant difference comparing patients with right- and left-sided ischemia and controls, whereas patients with left-sided ischemia showed mild deficits in a verb generation task. Neglect and extinction tasks revealed no significant differences between groups. Our findings support previous observations in the literature that cerebellar patients frequently perform within the normal range in standard neuropsychological tests. This does not exclude, however, that abnormalities may be present in more sophisticated testing of language and visuospatial functions.

Megalographia in children with cerebellar lesions and in children with attention-deficit/hyperactivity disorder.

Structural changes of the cerebellum have been reported in attention-deficit/hyperactivity disorder (ADHD) in several studies. The cerebellum is a structure essential for motor coordination and motor learning. Beside behavioral deficits, children with ADHD often show slight motor abnormalities. In the present study, handwriting was examined in both children with ADHD and children with cerebellar lesions. By writing the same sentence several times, letter height increased in the ADHD and cerebellar groups but not in controls. Comparable disorders of handwriting in cerebellar and ADHD children support previous studies, which suggest a contribution of cerebellar dysfunction to motor abnormalities in ADHD. However, an involvement of non-cerebellar dysfunctions in ADHD cannot be excluded.

Evaluation of multiple-session delay eyeblink conditioning comparing patients with focal cerebellar lesions and cerebellar degeneration.

The acquisition and timing of delay-conditioned eyeblink responses (CRs) have been shown to be significantly impaired in patients with disorders restricted to the cortex of the superior cerebellum. We were interested if patients improve incidences and timing of CRs across three sessions on three consecutive days. A standard delay paradigm was used in 9 patients with diffuse cerebellar degeneration, 13 patients with ischemic cortical cerebellar lesions and in 13 controls. High-resolution magnetic resonance imaging (MR imaging) was used to ensure that hemispheral lobules VI and/ or Crus I were lesioned in all stroke patients with the interposed nuclei being preserved. On day 1 patients with stroke but not with degenerative disorders showed significant CR acquisition, although total CR incidences remained significantly lower than in controls. No further improvement was visible on days 2 and 3 neither in patients with focal lesions nor in patients with cerebellar degeneration. CRs occurred earlier in cerebellar patients, most pronounced in patients with degenerative disorders. In patients with stroke but not in the degenerative group timing had improved on the third day close to values of the control subjects. Findings show that lesions of the cerebellar cortex produce permanent deficits in the acquisition of delay-conditioned eyeblink responses. Overall, mean CR incidence was higher in focal compared to degenerative disorders, most likely because the critical lobules (VI and Crus I) were lesioned only in part. Intact anterior lobe, which it thought to contribute to CR timing, may explain recovery of disordered timing in focal cerebellar patients.

Genome-wide association study of intracranial aneurysm identifies three new risk loci.

Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with approximately 832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 x 10(-12)), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 x 10(-9)) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 x 10(-9)). We also confirmed prior associations near SOX17 (8q11.23-q12.1; OR = 1.28, P = 1.3 x 10(-12)) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 x 10(-22)). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.

Balance control in sitting and standing in children and young adults with benign cerebellar tumors.

Children and young adolescents with chronic surgical cerebellar lesions show persistent balance control problems during standing when lesions affect the deep cerebellar fastigial and adjacent interposed nuclei. The purpose of this study is to confirm that the same lesion sites are also associated with permanent signs of trunkal ataxia during sitting. A second aim is to demonstrate that examining the postural control of patients while sitting or standing on a foam cushion may constitute a simple clinical exam yielding results commensurate to a more involved dynamic posturography exam. Balance control was assessed in 16 patients after surgery of a benign cerebellar tumor in chronic state and healthy age- and gender-matched control subjects. Using an ultrasound-based kinematic recording system, trunkal and shoulder sway was measured during sitting and standing in different conditions. High-resolution MRI scans were acquired in the cerebellar patients. Voxel-wise statistical lesion symptom mapping was performed to compare lesioned areas between affected and unaffected patients in a given condition using χ² tests. During sitting, 56% of cerebellar patients exhibited trunkal sway outside the range of healthy controls, and 87.5% of cerebellar patients revealed abnormal sway patterns during standing. Abnormalities were most pronounced when visual information was absent, and somatosensory information became unreliable and/or when the base of support along the medio-lateral axis was minimized during tandem stance. Lesion symptom mapping revealed that pathological values in the behavior data were more likely in patients with surgical lesions involving the fastigial nuclei (NF) and adjacent interposed nuclei (NI). In patients with surgery <1-year lesions of the inferior cerebellar vermis also had an impact on balance function. Our results corroborate previous evidence that the extent of permanent damage to the deep cerebellar nuclei greatly impacts on the recovery on balance function.

Surgical treatment of primary intracranial myxoma in a child following radiotherapy: case report and review of the literature.

INTRODUCTION: Myxomas are benign tumors of the mesenchymal origin and account for about half of the benign cardiac tumors. Occasionally, they occur at other locations, but the intracranial manifestation of a myxoma is exceptionally rare. As a secondary neoplasia following radiotherapy, myxoma has only been reported once in the literature. MATERIAL AND METHODS: A 12-year-old girl, who was previously treated for a medulloblastoma, was diagnosed with a new lesion at the left transverse sinus in the follow-up magnetic resonance imaging (MRI). Indication for surgery was made and complete removal could be achieved. RESULTS AND DISCUSSION: Histological examination revealed a myxoma. Further staging showed no other manifestation of the myxoma. The close relation to the radiation field of the posterior fossa makes it highly suggestive that the myxoma developed as a secondary neoplasia induced by radiotherapy. Treatment philosophy for this benign tumor entity is a completed resection of the lesion with regular follow-up MRI.

Timing of conditioned eyeblink responses is impaired in children with attention-deficit/hyperactivity disorder.

Structural changes of the cerebellum have been reported in several psychiatric diseases like schizophrenia, autism and attention-deficit/hyperactivity disorder (ADHD). Beside behavioral deficits children with ADHD often show slight motor abnormalities. Cerebellar malfunction may contribute. The cerebellum is a structure essential for motor coordination, various forms of motor learning and timing of motor responses. In the present study, eyeblink conditioning was applied to investigate learning and timing of motor responses both in children with ADHD and children with cerebellar lesions. Acquisition, timing and extinction of conditioned eyeblink responses were investigated in children with ADHD, children with chronic surgical cerebellar lesions and controls using a standard delay paradigm with two different interstimulus intervals. Timing of conditioned eyeblink responses was significantly impaired in children with ADHD in the long interstimulus interval condition. Also in children with cerebellar lesions conditioned responses (CR) tended to occur earlier than in controls. Incidences of CRs were significantly reduced in children with cerebellar lesions and tended to be less in children with ADHD than in controls. Extinction of the CRs was impaired in children with cerebellar lesions in both interstimulus interval conditions and in children with ADHD in the long interstimulus interval condition. Cerebellar malfunction may contribute to disordered eyeblink conditioning in ADHD. However, because CR abnormalities differed between ADHD and cerebellar subjects, dysfunction of non-cerebellar structures cannot be excluded.

Visuomotor adaptive improvement and aftereffects are impaired differentially following cerebellar lesions in SCA and PICA territory.

The aim of the present study was to elucidate the contribution of the superior and posterior inferior cerebellum to adaptive improvement and aftereffects in a visuomotor adaptation task. Nine patients with ischemic lesions within the territory of the posterior inferior cerebellar artery (PICA), six patients with ischemic lesions within the territory of the superior cerebellar artery (SCA) and 17 age-matched controls participated. All subjects performed center-out reaching movements under 60 degrees rotation of visual feedback. For the assessment of aftereffects, we tested retention of adaptation and de-adaptation under 0 degrees visual rotation. From this data we also quantified five measures of motor performance. Cerebellar lesion-symptom mapping was performed using magnetic resonance imaging subtraction analysis. Adaptive improvement during 60 degrees rotation was significantly degraded in PICA patients and even more in SCA patients. Subtraction analysis revealed that posterior (Crus I) as well as anterior cerebellar regions (lobule V) showed a common overlap related to deficits in adaptive improvement. However, for aftereffect measures as well as for motor performance variables only SCA patients, but not PICA patients showed significant differences to control subjects. Subtraction analysis showed that affection of lobules V and VI were more common in patients with impaired retention and de-adaptation, respectively. Data shows that areas both within the superior and posterior inferior cerebellum are involved in adaptive improvement. However, only the superior cerebellum including lobules V and VI appears to be important for aftereffects and therefore true adaptive ability.

Postural and gait performance in children with attention deficit/hyperactivity disorder.

Up to 50% of children and adolescents with attention deficit/hyperactivity disorder (ADHD) exhibit motor abnormalities including altered balance. Results from brain imaging studies indicate that these balance deficits could be of cerebellar origin as ADHD children may show atrophy in those regions of the cerebellum associated with gait and balance control. To address this question, this study investigated postural and gait abilities in ADHD children and compared their static and dynamic balance with children with known lesions in the cerebellum. Children diagnosed with ADHD according to DSM IV-TR diagnostic criteria were compared with children with chronic surgical cerebellar lesions and age-matched controls. A movement coordination test was used to assess differences in motor development. Postural and gait abilities were assessed using posturography, treadmill walking and a paced stepping task. Volumes of the cerebellum and the cerebrum were assessed on the basis of 3D magnetic resonance images (MRI). Children with cerebellar lesions showed significant performance decrements in all tasks compared with the controls, particularly in the movement coordination test and paced stepping task. During dynamic posturography ADHD-participants showed mild balance problems which correlated with findings in cerebellar children. ADHD children showed abnormalities in a backward walking task and minor abnormalities in the paced stepping test. They did not differ in treadmill walking from the controls. These findings support the notion that cerebellar dysfunction may contribute to the postural deficits seen in ADHD children. However, the observed abnormalities were minor. It needs to be examined whether balance problems become more pronounced in ADHD children exhibiting more prominent signs of clumsiness.

Aphasia, neglect and extinction are no prominent clinical signs in children and adolescents with acute surgical cerebellar lesions.

The aim of the present study was to examine if clinically significant signs of aphasia, neglect or extinction, which have a well-known cerebral lateralization, are present in children and adolescents with acute focal lesions following tumour surgery in the cerebellum. Eight children and adolescents with cerebellar tumours were tested within days after tumour surgery. None of the children had received radiation or chemotherapy at the time of testing. Eleven age- and education-matched control subjects with major orthopedic surgery participated. High-resolution magnetic resonance images showed lesions of the right cerebellar hemisphere in three and of the left hemisphere in five children. Standard aphasia tests revealed no statistically significant difference comparing children with right- and left-sided lesions and controls. Mild signs of language disturbance, however, were present in single subjects with right-sided cerebellar lesions. Neglect and extinction tasks revealed minor abnormalities, which lacked consistent lateralization and were best explained by more unspecific attentional deficits and motor disorders in acute post-surgical stage. Acute right-sided cerebellar lesions can be followed by mild signs of language disturbances in single subjects. Clinically significant signs of neglect and extinction, however, are not observed in children and adolescents with acute surgical cerebellar lesions.

Cerebellar lesion studies of cognitive function in children and adolescents - limitations and negative findings.

An increasing number of human lesion and functional brain imaging studies appear to support the hypothesis that the cerebellum contributes to a wide range of non-motor functions, including attention, language and visuospatial functions. Various abnormalities have been reported in standard neuropsychological tests in children and adolescents who have been treated for cerebellar tumors. This review focuses on limitations of lesion studies and negative findings in children and adolescents with focal cerebellar lesions. Frequently cited early findings have not been replicated in later studies or have been explained by motor components of the tasks. Such discrepancies may relate to a number of methodological problems. In addition to impaired motor function, it is unclear to what extent deficits in neuropsychological tests are caused by unspecific effects such as increased intracranial pressure and depression. Effects of extracerebellar lesions are frequently not considered. Although a role of the cerebellum in specific aspects of non-motor functions seems obvious it is still an open question which cognitive functions are involved, why and to what extent. It is a matter of ongoing discussion whether or not cognitive dysfunction belongs to the symptoms of cerebellar disease. Overall, disorders appear to be mild and far less frequent than disorders observed following lesions of cerebral areas. The aim of the review is to demonstrate that many findings frequently cited to support cerebellar involvement in cognition are insufficient to prove the hypothesis. There is ongoing need of well-controlled lesion studies, which show that disorders are due to cerebellar lesions independent of motor dysfunction and other confounding factors.

Reliability and validity of ICARS in focal cerebellar lesions.

To evaluate the therapies for cerebellar diseases appropriate neurological assessment methods to measure severity of ataxia are required. Reliability and validity of the semiquantitative International Cooperative Ataxia Rating Scale (ICARS) has recently been examined in patients with degenerative ataxias. We evaluated reliability (internal consistency), criterion-related validity and internal construct validity of ICARS for the first time in patients with focal cerebellar lesions (68 patients with surgical lesions and 68 patients with ischemic lesions). For comparison 45 patients with degenerative cerebellar ataxia were included. We found an excellent Cronbach's alpha as a measurement for internal consistency which was independent from underlying disease. Criterion-related validity was high. Total ICARS score mirrored clearly the immediate postsurgical worsening and the improvement during the first 3 months after focal surgical and ischemic lesions, whereas in chronic state of focal and degenerative cerebellar disorders ICARS score remained nearly unchanged. Principal component analysis in patients with focal lesions revealed five distinct and clinically meaningful factors which corresponded to the four ICARS subscores and reflected the laterality of kinetic functions. In degenerative disorders, however, the items for the subscore "kinetic function" loaded to more than one factor. Total ICARS score seems to be a useful and valid measurement to describe the time course of ataxia in patients with focal and degenerative disorders affecting primarily the cerebellum. Validity of subscores however is good in focal, but not in degenerative disorders.

Reliability and validity of the scale for the assessment and rating of ataxia: a study in 64 ataxia patients.

The objective of this study was to test the reliability and validity of the Scale for the Assessment and Rating of Ataxia (SARA) in ataxia patients not suffering from autosomal dominant spinocerebellar ataxia (SCA). To this end, 64 patients with various ataxia disorders or stable cerebellar lesions were rated independently by two investigators. In addition to SARA, the following assessment instruments were applied: ataxia disease stage, Barthel index and part IV (functional assessment) of the Unified Huntington's Disease Rating scale (UHDRS-IV). Eighteen patients were rated twice. Inter-rater and intrarater reliability were very high with ICCs of 0.98 and 0.99. Internal consistency was high indicated by Cronbach's alpha of 0.97. Factorial analysis revealed that the rating results were mainly determined by one major factor with an eigenvalue of 6.34 which explained 52.8% of the variance. SARA score increased with disease stage (P<0.0001) and was closely correlated with Barthel index (r=-0.63, P<0.0001) and UHDRS-IV (r=-0.62, P<0.0001), but only weakly correlated with disease duration (r=0.44, P<0.001). The results suggest that SARA is a reliable and valid measure of ataxia in non-SCA ataxia patients.

Analysis of intrathecal interleukin-6 as a potential predictive factor for vasospasm in subarachnoid hemorrhage.

OBJECTIVE: Inflammatory response seems to be one of the relevant pathophysiological aspects for developing vasospasm in subarachnoid hemorrhage. The probable diagnostic value of intrathecal proinflammatory markers is still unclear and is assessed in this study. METHODS: We analyzed daily clinical data and laboratory tests of the cerebrospinal fluid (CSF) of 64 patients with mostly poor-grade subarachnoid hemorrhage during a period of 14 days. Special attention was given to the relationship between the development of vasospasm and the time course of the intrathecal interleukin (IL)-6 concentrations in CSF (IL-6CSF). The potential power of IL-6CSF for predicting vasospasm was studied. RESULTS: Vasospasm developed in 28.1% of the patients, with a mean onset of 6.4 days after bleeding, and was detected by conventional methods. Patients with vasospasm demonstrated statistically significant higher median values of IL-6CSF on Days 4 and 5 (P < 0.05). Most importantly, the increase of IL-6CSF preceded the conventional signs of vasospasm. A cut-off value of IL-6CSF of at least 2000 pg/ml on Day 4 yielded an 11.72-fold higher relative risk (95% confidence interval, 2.93-46.60) of developing vasospasm, predicting vasospasm with a sensitivity of 88.9% and a specificity of 78.3%. We found a statistically significant correlation between IL-6CSF and delayed cerebral ischemia for Day 7 (P = 0.03). However, there was no correlation with IL-6CSF on any other day and outcome. CONCLUSION: IL-6CSF seems to be a reliable early marker for predicting vasospasm after subarachnoid hemorrhage on Days 4 and 5 before clinical onset.

Patients with chronic focal cerebellar lesions show no cognitive abnormalities in a bedside test.

The aim of the present study was to show whether cognitive deficits are present in chronic cerebellar patients using a self-developed, validated bedside screening test. Twenty-one adults with a history of infarction within the territory of the posterior-inferior (PICA) or the superior cerebellar artery (SCA), and 25 age-, sex-, and education-matched healthy controls participated. Lesion localization was based on individual 3D MRI scans. The test took 10-12 min including subtests of naming, executive functions, attention, figural and verbal memory, reading, long-term memory, mental arithmetic, higher order motor control, and spatial functions. Though individual patients tended to make more errors than controls, neither total error score nor subscores revealed significant group differences. No obvious cognitive deficits appeared to be present in chronic cerebellar patients as assessed by a bedside screening test.