Mapping of long-term cognitive and motor deficits in pediatric cerebellar brain tumor survivors into a cerebellar white matter atlas.

PURPOSE: Diaschisis of cerebrocerebellar loops contributes to cognitive and motor deficits in pediatric cerebellar brain tumor survivors. We used a cerebellar white matter atlas and hypothesized that lesion symptom mapping may reveal the critical lesions of cerebellar tracts. METHODS: We examined 31 long-term survivors of pediatric posterior fossa tumors (13 pilocytic astrocytoma, 18 medulloblastoma). Patients underwent neuronal imaging, examination for ataxia, fine motor and cognitive function, planning abilities, and executive function. Individual consolidated cerebellar lesions were drawn manually onto patients' individual MRI and normalized into Montreal Neurologic Institute (MNI) space for further analysis with voxel-based lesion symptom mapping. RESULTS: Lesion symptom mapping linked deficits of motor function to the superior cerebellar peduncle (SCP), deep cerebellar nuclei (interposed nucleus (IN), fastigial nucleus (FN), ventromedial dentate nucleus (DN)), and inferior vermis (VIIIa, VIIIb, IX, X). Statistical maps of deficits of intelligence and executive function mapped with minor variations to the same cerebellar structures. CONCLUSION: We identified lesions to the SCP next to deep cerebellar nuclei as critical for limiting both motor and cognitive function in pediatric cerebellar tumor survivors. Future strategies safeguarding motor and cognitive function will have to identify patients preoperatively at risk for damage to these critical structures and adapt multimodal therapeutic options accordingly.

Cognitive and fine motor deficits in a pediatric sickle cell disease cohort of mixed ethnic origin.

Cerebrovascular disease is an important feature of pediatric sickle cell disease (SCD) and may lead to cognitive and motor impairment. Our cross-sectional study examined the incidence and severity of these impairments in a pediatric cohort without clinical cerebrovascular events from Berlin of mixed ethnic origin. Thirty-two SCD patients (mean age 11.14 years, range 7.0-17.25 years; males 14) were evaluated for full-scale intelligence (IQ) (German version WISC-III), fine motor function (digital writing tablet), and executive function (planning, attention, working memory, and visual-spatial abilities) with the Amsterdam Neuropsychological Tasks (ANT) program and the Tower of London (ToL). Data on clinical risk factors were retrieved from medical records. Full-scale IQ of patients was preserved, whereas performance IQ was significantly reduced (91.19 (SD 12.17) d = 0.7, p = 0.007). SCD patients scored significantly lower than healthy peers when tested for executive and fine motor functions, e.g., planning time in the ToL (6.73 s (SD 3.21) vs. 5.9 s in healthy peers (SD 2.33), d = 0.5, p = <0.001) and frequency on the writing tablet (mean z score -0.79, d = 0.7, p < 0.001). No clinical risk factors were significantly associated with incidence and severity of cognitive and motor deficits. Despite the preservation of full-scale IQ, our SCD cohort of mixed origin exhibited inferior executive abilities and reduced fine motor skills. Our study is limited by the small size of our cohort as well as the lack for control of sociodemographic and socioeconomic factors modulating higher functions but highlights the need for early screening, prevention, and specific interventions for these deficits.

DTI fiber tractography of cerebro-cerebellar pathways and clinical evaluation of ataxia in childhood posterior fossa tumor survivors.

Pediatric posterior fossa (PF) tumor survivors experience long-term motor deficits. Specific cerebrocerebellar connections may be involved in incidence and severity of motor dysfunction. We examined the relationship between long-term ataxia as well as fine motor function and alteration of differential cerebellar efferent and afferent pathways using diffusion tensor imaging (DTI) and tractography. DTI-based tractography was performed in 19 patients (10 pilocytic astrocytoma (PA) and 9 medulloblastoma patients (MB)) and 20 healthy peers. Efferent Cerebello-Thalamo-Cerebral (CTC) and afferent Cerebro-Ponto-Cerebellar (CPC) tracts were reconstructed and analyzed concerning fractional anisotropy (FA) and volumetric measurements. Clinical outcome was assessed with the International Cooperative Ataxia Rating Scale (ICARS). Kinematic parameters of fine motor function (speed, automation, variability, and pressure) were obtained by employing a digitizing graphic tablet. ICARS scores were significantly higher in MB patients than in PA patients. Poorer ICARS scores and impaired fine motor function correlated significantly with volume loss of CTC pathway in MB patients, but not in PA patients. Patients with pediatric post-operative cerebellar mutism syndrome showed higher loss of CTC pathway volume and were more atactic. CPC pathway volume was significantly reduced in PA patients, but not in MB patients. Neither relationship was observed between the CPC pathway and ICARS or fine motor function. There was no group difference of FA values between the patients and healthy peers. Reduced CTC pathway volumes in our cohorts were associated with severity of long-term ataxia and impaired fine motor function in survivors of MBs. We suggest that the CTC pathway seems to play a role in extent of ataxia and fine motor dysfunction after childhood cerebellar tumor treatment. DTI may be a useful tool to identify relevant structures of the CTC pathway and possibly avoid surgically induced long-term neurological sequelae.

Trauma- and distress-associated mental illness symptoms in close relatives of patients with severe traumatic brain injury and high-grade subarachnoid hemorrhage.

BACKGROUND: Close relatives (CR) of patients with severe traumatic brain injury (TBI) and high-grade subarachnoid hemorrhage (SAH) suffer extraordinary distress during the treatment: Distress may lead to persisting mental illness symptoms within the spectrum of post-traumatic stress disorder (PTSD), anxiety disorders, and depression. The primary goal of this study was to determine the prevalence and severity of these symptoms in CR. The secondary goal was identification of associated factors. METHOD: Standardized interviews were conducted with 53 CR (mean age of 57.7 ± 11.4 years) of patients with TBI °III (n = 27) and high-grade SAH H&H °III-V (n = 26) between 5 and 15 months after the event. The interviews contained a battery of surveys to quantify symptoms of PTSD, anxiety disorders, and depression, i.e., Impact of Event Scale (IES-R), 36-item Short-Form General Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HADS). Fixed and modifiable possibly influencing factors were correlated. RESULTS: Twenty-eight CR (53 %) showed IES-R scores indicating a probable diagnosis of PTSD. Twenty-five CR (47 %) showed an increased anxiety score and 18 (34 %) an increased depression score using HADS. Mean physical component summary of SF-36 was not abnormal (49.1 ± 9.1), whereas mean mental component summary was under average (41.0 ± 13.2), indicating a decreased quality of life caused by mental effects. Perception of the interaction quality with the medical staff and involvement into medical decisions correlated negatively with severity of mental illness symptoms. Evasive coping strategies were highly significantly associated with symptoms. CONCLUSIONS: This study quantifies an extraordinarily high prevalence of mental illness symptoms in CR of patients with critical acquired brain injury due to SAH and TBI. Modifiable factors were associated with severity of mental illness symptoms. Prospective studies testing efficiency of early psychotherapeutic interventions are needed.

Development of Laterality and Bimanual Interference of Fine Motor Movements in Childhood and Adolescence.

Drawing and handwriting are fine motor skills acquired during childhood. We analyzed the development of laterality by comparing the performance of the dominant with the nondominant hand and the effect of bimanual interference in kinematic hand movement parameters (speed, automation, variability, and pressure). Healthy subjects (n = 187, 6-18 years) performed drawing tasks with both hands on a digitizing tablet followed by performance in the presence of an interfering task of the nondominant hand. Age correlated positively with speed, automation, and pressure, and negatively with variability for both hands. As task complexity increased, differences between both hands were less pronounced. Playing an instrument had a positive effect on the nondominant hand. Speed and automation showed a strong association with lateralization. Bimanual interference was associated with an increase of speed and variability. Maturation of hand laterality and the extent of bimanual interference in fine motor tasks are age-dependent processes.

Loss of fine motor function correlates with ataxia and decline of cognition in cerebellar tumor survivors.

BACKGROUND: Motor and cognitive function losses resemble handicaps in pediatric posterior fossa tumor survivors. Several factors determine type and extent of impairment. We quantified loss of fine motor function and its association with ataxia and intelligence in patients with and without adjuvant treatment. PROCEDURE: Fine motor function, extent of ataxia and cognitive function were assessed in 25 medulloblastoma (MB) and 16 cerebellar pilocytic astrocytoma (PA) patients at least 1 year after completion of therapy. Kinematic parameters (speed, automation, variability, and pressure) of different movement complexity levels were investigated employing a digitizing graphic tablet. Degree of ataxia was quantified using the International Cooperative Ataxia Rating Scale and cognition was determined using the Wechsler Intelligence Scale. RESULTS: Kinematic parameters of low and high complexity tasks as well as ataxia of MB patients were strongly impaired. Fine motor impairment was weaker in PA patients, but still evident in the complex task of writing. Ataxia was significantly more pronounced in medulloblastoma patients. Young age and short recovery time correlated significantly with impaired kinematic parameters. Ataxia was strongly associated with inferior fine motor function. Cognition, especially performance IQ, was associated with dysfunctional kinematic parameters. CONCLUSION: The digitizing tablet detected extent of fine motor function loss at varying levels of complexity of pediatric cerebellar tumor survivors. This tool promises to be a potentially effective method for measuring fine motor function in clinical trials and may be helpful in studying mechanisms of neurotoxicity in posterior fossa tumor patients as well as success of rehabilitation.

Influence of age and movement complexity on kinematic hand movement parameters in childhood and adolescence.

Development of fine motor functions, especially drawing and handwriting, are crucial for performance in school, autonomy in everyday life and the general human development. A variety of neurological and psychiatric conditions in childhood and adolescence stunt the normal development of fine motor skills. We sought to define the normal development of the kinematic parameters of fine motor movement and determine the influence of gender, laterality of handedness and extracurricular training on fine motor skills. One hundred and eighty-seven children and adolescents (mean age: 11.6 years (+/-S.D.: 3.58), range: 6-18 years) were included in the study. Participants performed drawing and handwriting tasks on a digitizing graphic tablet. Movement and pressure data were transferred to a computer using a sensor-equipped pen and post-processed using CSWIN. Movements were segmented into strokes and several kinematic parameters were calculated. The kinematic parameters that were analyzed represented speed (frequency and stroke peak velocity), automation (number of direction changes of velocity per stroke), variability (variation coefficient of stroke peak velocity) and pressure. Progression of kinematic parameters for each movement domain of the handwriting and circle drawing tasks correlated significantly with age (Pearson's correlation, p<0.003). Speed, automation and pressure increased with age, whereas variability decreased. Nonlinear regressions revealed maturation of hand movements at a certain age. Age of completed maturation depended on the task complexity (drawing circles vs. handwriting) and kinematic parameters. In the speed and automation domains, handwriting movements finish maturing later than circle drawing. Male subjects drew circles at significantly higher speeds than female subjects. Fine motor practice and laterality of handedness did not influence kinematic parameters. A repeated measure ANOVA confirmed the significant interdependency between age and complexity level for speed and automation (p<0.001). The digitizing graphic tablet is an extremely valuable tool in determining the normal development of hand movement skills of children and adolescents by measuring relevant daily tasks like handwriting and drawing. In our study, we showed that future analyses of impaired movement in children and adolescents need to take age and gender into consideration. Furthermore, differences were observed in the maturation of different task complexities, the complex fine motor function reaching maturity later than basic and repetitive movement patterns.

Selective Brain Cooling after Traumatic Brain Injury: Effects of Three Different Cooling Methods-Case Report.

Background In experimental models of neuronal damage, therapeutic hypothermia proved to be a powerful neuroprotective method. In clinical studies of traumatic brain injury (TBI), this very distinct effect was not reproducible. Several meta-analyses draw different conclusions about whether therapeutic hypothermia can improve outcome after TBI. Adverse side effects of systemic hypothermia, such as severe pneumonia, have been held responsible by some authors to counteract the neuroprotective effect. Selective brain cooling (SBC) attempts to take advantage of the protective effects of therapeutic hypothermia without the adverse side effects of systemic hypothermia. Methods Three different methods of SBC were applied in a patient who had severe TBI with recurrent increases of intracranial pressure (ICP) refractory to conventional forms of treatment: (1) external cooling of the scalp and neck using ice packs prior to hemicraniectomy, (2) external cooling of the craniectomy defect using ice packs after hemicraniectomy, and (3) cooling by epidural irrigation with cold Ringer solution after hemicraniectomy. Results External scalp cooling before hemicraniectomy, external cooling of the craniectomy defect, and epidural irrigation with cold fluid resulted in temperature differences (brain temperature to body temperature) of - 0.2°, - 0.7°, and - 3.6°C, respectively. ICP declined with decreasing brain temperature. Conclusion Previous external cooling attempts for SBC faced the problem that brain temperature could not be lowered without a simultaneous decrease of systemic temperature. After hemicraniectomy, epidural irrigation with cold fluid may be a simple and effective way to lower ICP and apply one of the most powerful methods of cerebroprotection after severe TBI.

Autologous bone graft versus PEKK cage for vertebral replacement after 1- or 2-level anterior median corpectomy.

OBJECT Anterior cervical corpectomy with fusion has become the most widely used procedure for the treatment of multilevel cervical stenosis. Although an autologous bone graft is the gold standard for vertebral replacement after corpectomy, industrial implants have become popular because they result in no donor-site morbidity. In this study, the authors compared clinical and radiological results of autologous iliac grafts versus those of bone-filled polyetherketoneketone (PEKK) cage implants. METHODS The clinical and radiological data of 46 patients with degenerative multilevel cervical stenosis and who underwent 1- or 2-level anterior median corpectomy between 2004 and 2012 were analyzed. The patients in Group 1 were treated with vertebral replacement with an autologous iliac graft, and those in Group 2 were treated with a PEKK cage implant. Each patient also underwent osteosynthesis with an anterior plate-screw system. Visual analog scale (VAS) and European Myelopathy Scale scores, loss of height and regional cervical lordosis angle, and complication rates of the 2 groups were compared. RESULTS The mean follow-up time was 20 months. In both groups, the VAS and European Myelopathy Scale scores improved significantly. The loss of height was 3.7% in patients with iliac grafts and 5.3% in patients with PEKK implants. The rates of osseous fusion were similar in Groups 1 and 2 (94.7% and 91.3%, respectively). At the end of the follow-up period, none of the patients complained about donor-site pain. One patient in Group 1 suffered a fracture of the iliac bone that required osteosynthesis. Four patients in Group 2 had to receive revision surgery for cage and/or plate-screw dislocation and new neurological deficit or intractable pain. CONCLUSIONS Preoperative pain and radicularand myelopathic symptoms improve after decompression irrespective of the material used for vertebral replacement. The use of PEKK cages for vertebral replacement seems to result in a higher risk of implant-related complications. A prospective randomized study is necessary to supply evidence for the use of autografts and artificial implants after anterior cervical corpectomy with fusion.

Feasibility of the Combined Application of Navigated Probabilistic Fiber Tracking and Navigated Ultrasonography in Brain Tumor Surgery.

BACKGROUND: Surgical resection of intra-axial tumors is a challenging procedure because of indistinct tumor margins, infiltration, and displacement of white matter tracts surrounding the lesion. Hence, gross total tumor resection without causing new neurologic deficits is demanding, especially in tumor sites adjoining eloquent structures. Feasibility of the combination of navigated probabilistic fiber tracking to identify eloquent fiber pathways and navigated ultrasonography to control brain shift was tested. METHODS: Eleven patients with lesions adjacent to eloquent white matter structures (pyramidal tract, optic radiation and arcuate fascicle) were preoperatively subjected to magnetic resonance imaging including diffusion-weighted imaging on a 3-T magnetic resonance system (Trio [Siemens, Erlangen, Germany]). Probabilistic fiber tracking was performed using the tools of the FMRIB Software Library (FSL). Results of probabilistic fiber tracking and high-resolution anatomic images were integrated into the neuronavigation system Stealth Station (Medtronic, Minneapolis, Minnesota, USA) together with the navigated ultrasonography (SonoNav [Medtronic]). RESULTS: FSL-based probabilistic fiber tracking depicted the pyramidal tract, the optic radiation, and arcuate fascicle anatomically plausibly. Integration of the probabilistic fiber tracking into neuronavigation was technically feasible and allowed visualization of the reconstructed fiber pathways. Navigated ultrasonography controlled brain shift. CONCLUSIONS: Integration of probabilistic fiber tracking and navigated ultrasonography into intraoperative neuronavigation facilitated anatomic orientation during glioma resection. FSL-based probabilistic fiber tracking integrated sophisticated fiber tracking algorithms, including modeling of crossing fibers. Combination with navigated ultrasonography provided a three-dimensional estimation of intraoperative brain shift and, therefore, improved the reliability of neuronavigation.

Differences in supratentorial damage of white matter in pediatric survivors of posterior fossa tumors with and without adjuvant treatment as detected by magnetic resonance diffusion tensor imaging.

PURPOSE: To elucidate morphologic correlates of brain dysfunction in pediatric survivors of posterior fossa tumors by using magnetic resonance diffusion tensor imaging (DTI) to examine neuroaxonal integrity in white matter. PATIENTS AND METHODS: Seventeen medulloblastoma (MB) patients who had received surgery and adjuvant treatment, 13 pilocytic astrocytoma (PA) patients who had been treated only with surgery, and age-matched healthy control subjects underwent magnetic resonance imaging on a 3-Tesla system. High-resolution conventional T1- and T2-weighted magnetic resonance imaging and DTI data sets were obtained. Fractional anisotropy (FA) maps were analyzed using tract-based spatial statistics, a part of the Functional MRI of the Brain Software Library. RESULTS: Compared with control subjects, FA values of MB patients were significantly decreased in the cerebellar midline structures, in the frontal lobes, and in the callosal body. Fractional anisotropy values of the PA patients were not only decreased in cerebellar hemispheric structures as expected, but also in supratentorial parts of the brain, with a distribution similar to that in MB patients. However, the amount of significantly decreased FA was greater in MB than in PA patients, underscoring the aggravating neurotoxic effect of the adjuvant treatment. CONCLUSIONS: Neurotoxic mechanisms that are present in PA patients (e.g., internal hydrocephalus and damaged cerebellar structures affecting neuronal circuits) contribute significantly to the alteration of supratentorial white matter in pediatric posterior fossa tumor patients.