Paul Buderath

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.

Balance and motor speech impairment in essential tremor

The pathogenesis of essential tremor (ET) is still under debate. Several lines of evidence indicate that ET is associated with cerebellar dysfunction. The aim of the present study was to find corroborating evidence for this claim by investigating balance and speech impairments in patients with ET. In addition, the effect of deep brain stimulation (DBS) on balance and speech function was studied. A group of 25 ET patients including 18 with postural and/or simple kinetic tremor (ETpt) and seven ET patients with additional clinical signs of cerebellar dysfunction (ETc) was compared to 25 healthy controls. In addition, 12 ET patients with thalamic DBS participated in the study. Balance control was assessed during gait and stance including tandem gait performed on a treadmill as well as static and dynamic posturography. Motor speech control was analyzed through syllable repetition tasks. Signs of balance impairment were found in early stages and advanced stages of ET. During locomotion, ET patients exhibited an increased number of missteps and shortened stride length with tandem gait. ETc patients and, to a lesser extent, ETpt patients had increased postural instability in dynamic posturography conditions that are sensitive to vestibular or vestibulocerebellar dysfunction. ETc but not ETpt patients exhibited significantly increased syllable durations. DBS had no discernable effect on speech performance or balance control. We conclude that the deficits in balance as well as the subclinical signs of dysarthria in a subset of patients confirm and extend previous findings that ET is associated with an impairment of the cerebellum.

[ 18 F]FDG PET/MRI vs. PET/CT for whole-body staging in patients with recurrent malignancies of the female pelvis: initial results

PurposeTo evaluate the diagnostic potential of PET/MRI with [18F]FDG in recurrent ovarian and cervical cancer in comparison to PET/CT.MethodsA group of 19 patients with suspected recurrence of pelvic malignancies (ovarian cancer, 11 patients; cervical cancer, 8 patients) scheduled for an [18F]FDG PET/CT were subsequently enrolled for a PET/MRI. The scan protocol comprised: (1) a T1-W axial VIBE after contrast agent adminstration, (2) an axial T2-W HASTE, (3) a coronal TIRM, (4) an axial DWI, and dedicated MR sequences of the female pelvis including (5) a T1-W VIBE before contrast agent adminstration, (6) a sagittal T2-W TSE, and (7) a sagittal T1-W dynamic VIBE. The datasets (PET/CT, PET/MRI) were rated separately by two readers regarding lesion count, lesion localization, lesion conspicuity (four-point scale), lesion characterization (benign/malignant/indeterminate) and diagnostic confidence (three-point scale). All available data (histology, prior examinations, PET/CT, PET/MRI, follow-up examinations) served as standard of reference. Median values were compared using the Wilcoxon rank sum test.ResultsMetastatic lesions were present in 16 of the 19 patients. A total of 78 lesions (malignant, 58; benign, 20) were described. Both PET/CT and PET/MRI allowed correct identification of all malignant lesions and provided equivalent conspicuity (3.86 ± 0.35 for PET/CT, 3.91 ± 0.28 for PET/MRI; p > 0.05). Diagnostic confidence was significantly higher for PET/MRI in malignant (p < 0.01) and benign lesions (p < 0.05).ConclusionBoth PET/CT and PET/MRI offer an equivalently high diagnostic value for recurrent pelvic malignancies. PET/MRI offers higher diagnostic confidence in the discrimination of benign and malignant lesions. Considering the reduced radiation dose and superior lesion discrimination, PET/MRI may serve as a powerful alternative to PET/CT in the future.

Correlation of Standardized Uptake Value and Apparent Diffusion Coefficient in Integrated Whole-Body PET/MRI of Primary and Recurrent Cervical Cancer

Background To evaluate a potential correlation of the maximum standard uptake value (SUVmax) and the minimum apparent diffusion coefficient (ADCmin) in primary and recurrent cervical cancer based on integrated PET/MRI examinations. Methods 19 consecutive patients (mean age 51.6 years; range 30–72 years) with histopathologically confirmed primary cervical cancer (n = 9) or suspected tumor recurrence (n = 10) were prospectively enrolled for an integrated PET/MRI examination. Two radiologists performed a consensus reading in random order, using a dedicated post-processing software. Polygonal regions of interest (ROI) covering the entire tumor lesions were drawn into PET/MR images to assess SUVmax and into ADC parameter maps to determine ADCmin values. Pearson’s correlation coefficients were calculated to assess a potential correlation between the mean values of ADCmin and SUVmax. Results In 15 out of 19 patients cervical cancer lesions (n = 12) or lymph node metastases (n = 42) were detected. Mean SUVmax (12.5±6.5) and ADCmin (644.5±179.7×10−5 mm2/s) values for all assessed tumor lesions showed a significant but weak inverse correlation (R = −0.342, p<0.05). When subdivided in primary and recurrent tumors, primary tumors and associated primary lymph node metastases revealed a significant and strong inverse correlation between SUVmax and ADCmin (R = −0.692, p<0.001), whereas recurrent cancer lesions did not show a significant correlation. Conclusions These initial results of this emerging hybrid imaging technique demonstrate the high diagnostic potential of simultaneous PET/MR imaging for the assessment of functional biomarkers, revealing a significant and strong correlation of tumor metabolism and higher cellularity in cervical cancer lesions.

ERCC1-Positive Circulating Tumor Cells in the Blood of Ovarian Cancer Patients as a Predictive Biomarker for Platinum Resistance

BACKGROUND Platinum resistance constitutes one of the most recognized clinical challenges for ovarian cancer. Notably, the detection of the primary tumor-based excision repair cross-complementation group 1 (ERCC1) protein by immunohistochemistry was recently shown to be inaccurate for the prediction of platinum resistance. On the basis of the previous finding that circulating tumor cells (CTC) in the blood of ovarian cancer patients are prognostically significant, and given our hypothesis that the negative prognostic impact of CTC may arise from a cellular phenotype associated with platinum resistance, we asked whether expression of the excision repair cross-complementation group 1 (ERCC1) gene in the form of the ERCC1 transcript in CTC may be a suitable blood-based biomarker for platinum resistance. METHODS The presence of CTC was analyzed by immunomagnetic CTC enrichment (n = 143 patients) targeting the epithelial epitopes epithelial cell adhesion molecule (EPCAM) (also known as GA733-2) and mucin 1, cell surface associated (MUC1), followed by multiplex reverse-transcription PCR to detect the transcripts EPCAM, MUC1, and mucin 16, cell surface associated (MUC16) (also known as CA125), including ERCC1 transcripts in a separate approach. ERCC1 expression in primary tumors was comparatively assessed by immunohistochemistry, using the antibody 8F1. RESULTS At primary diagnosis, the presence of CTC was observed in 14% of patients and constituted an independent predictor of overall survival (OS) (P = 0.041). ERCC1-positive CTC (ERCC1(+)CTC) were observed in 8% of patients and constituted an independent predictor, not only for OS but also for progression-free survival (PFS) (P = 0.026 and P = 0.009, respectively). More interestingly, we discovered the presence of ERCC1(+)CTC at primary diagnosis to be likewise an independent predictor of platinum resistance (P = 0.010), whereas ERCC1 expression in corresponding primary tumor tissue predicted neither platinum resistance nor prognosis. CONCLUSIONS The presence of ERCC1(+)CTC can serve as a blood-based diagnostic biomarker for predicting platinum resistance at primary diagnosis of ovarian cancer.

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.

Definition of compartment-based radical surgery in uterine cancer: radical hysterectomy in cervical cancer as 'total mesometrial resection (TMMR)' by M Höckel translated to robotic surgery (rTMMR).

BackgroundRadical hysterectomy has been developed as a standard treatment in Stage I and II cervical cancers with and without adjuvant therapy. However, there have been several attempts to standardize the technique of radical hysterectomy required for different tumor extension with variable success. Total mesometrial resection as ontogenetic compartment-based oncologic surgery - developed by open surgery - can be standardized identically for all patients with locally defined tumors. It appears to be promising for patients in terms of radicalness as well as complication rates. Robotic surgery may additionally reduce morbidity compared to open surgery. We describe robotically assisted total mesometrial resection (rTMMR) step by step in cervical cancer and present feasibility data from 26 patients.MethodsPatients (n = 26) with the diagnosis of cervical cancer were included. Patients were treated by robotic total mesometrial resection (rTMMR) and pelvic or pelvic/periaortic robotic therapeutic lymphadenectomy (rtLNE) for FIGO stage IA-IIB cervical cancer.ResultsNo transition to open surgery was necessary. No intraoperative complications were noted. The postoperative complication rate was 23%. Within follow-up time (mean: 18 months) we noted one distant but no locoregional recurrence of cervical cancer. There were no deaths from cervical cancer during the observation period.ConclusionsWe conclude that rTMMR and rtLNE is a feasible and safe technique for the treatment of compartment-defined cervical cancer.

Definition of Compartment Based Radical Surgery in Uterine Cancer—Part I: Therapeutic Pelvic and Periaortic Lymphadenectomy by Michael Höckel Translated to Robotic Surgery

Objective. To define compartment based therapeutic pelvic and periaortic lymphadenectomy in cervical and endometrial cancer. Compartment based oncologic surgery appears to be favorable for patients in terms of radicality as well as complication rates, and the same appears to be true for robotic surgery. We describe a method of robotically assisted compartment based lymphadenectomy step by step in uterine cancer and demonstrate feasibility data from 35 patients. Methods. Patients with the diagnosis of endometrial (n = 16) or cervical (n = 19) cancer were included. Patients were treated by rTMMR (robotic total mesometrial resection) or rPMMR (robotic peritoneal mesometrial resection) and pelvic or pelvic/periaortic rtLNE (robotic therapeutic lymphadenectomy) with cervical cancer FIGO IB-IIA or endometrial cancer FIGO I-III. Results. No transition to open surgery was necessary. Complication rates were 13% for endometrial cancer and 21% for cervical cancer. Within follow-up time median (22/20) month we noted 1 recurrence of cervical cancer and 2 endometrial cancer recurrences. Conclusions. We conclude that compartment based rtLNE is a feasible and safe technique for the treatment of uterine cancers and is favorable in aspects of radicality and complication rates. It should be analyzed in multicenter studies with extended followup on the basis of the described technique.

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.

Intraoperative navigation in robotically assisted compartmental surgery of uterine cancer by visualisation of embryologically derived lymphatic networks with indocyanine-green (ICG)

To evaluate feasibility of intraoperative visualization of embryologically defined organ compartments and their drainage by ICG in uterine cancer.