Chen Hoffmann

Sheba Medical Center, Gan, Tel Aviv, Israel

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Publications (62)219.95 Total impact

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    ABSTRACT: Background and propose: Familial Creutzfeldt-Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. The typical presenting symptoms include cognitive decline, behavioral changes and gait disturbances; however, some patients may have an unusual presentation such as a stroke-like presentation, alien hand syndrome or visual disturbances. The aim of this paper is to describe uncommon presentations in our series of consecutive patients with E200K fCJD. Methods: The study group included consecutive fCJD patients followed up as part of a longitudinal prospective study ongoing since 2003 or hospitalized since 2005. The clinical diagnosis of probable CJD was based on accepted diagnostic criteria and supported by typical magnetic resonance imaging, electroencephalographic findings, elevated cerebrospinal fluid tau protein levels and by genetic testing for the E200K mutation. Disease symptoms and signs were retrieved from the medical files. Results: The study population included 77 patients (42 men) with a mean age of disease onset of 60.6 ± 7.2 years. The most prevalent presenting symptoms were cognitive decline followed by gait impairment and behavioral changes. However, six patients had an unusual presentation including auditory agnosia, monoparesis, stroke-like presentation, facial nerve palsy, pseudobulbar syndrome and alien hand syndrome. Conclusions: Our case series illustrates the wide phenotypic variability of the clinical presentation of patients with fCJD and widens the clinical spectrum of the disease. A high level of clinical suspicion may prove useful in obtaining early diagnosis and therefore avoiding costly and inefficient diagnostic and therapeutic strategies.
    No preview · Article · Jan 2016 · European Journal of Neurology

  • No preview · Article · Nov 2015 · International journal of radiation oncology, biology, physics
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    ABSTRACT: Background/Objectives: We have recently presented high resolution treatment response assessment maps (TRAMs) enabling efficient separation between tumor (contrast clearance >1 hr post injection, blue) and treatment-effects (TEs, contrast accumulation, red), validated histologically in 54 resected patients. Here we demonstrate potential advantages in delineating SRS dose-effects using the TRAMs. Methods: In a preliminary study on 7 brain metastases, T1-Gd and the TRAMs were co-registered to the SRS dose-plan and pixel-by-pixel analysis was performed comparing baseline T1-Gd/TRAMs and dose-plan to T1-Gd/TRAMs acquired 141±12 days (day140) post SRS. Results: T1-Gd showed that the percentage of enhancing pixels at baseline that turned non-enhancing at day140 increased moderately from 40.4% to 54.2% between 13-21.7Gy with a sharp rise to 98% above 21.7Gy. Similar analysis with the TRAMs showed linear increase in tumor-kill from 83% at 18Gy to 100% at 21.7Gy. T1-Gd also showed that the percentage of non-enhancing pixels at baseline (normal-appearing brain) that turned enhancing at day140 increased linearly to 20.2Gy, where it raised sharply to 48% followed by a sharp drop at 21.2Gy. The TRAMs showed that the linear increase to 20.2Gy may be explained by new tumor growth with a sharp drop at 20.2Gy, while the sharp rise at 20.2Gy may be explained by non-enhancing pixels that turned into red/TEs. Per-lesion analysis showed significant correlations between average treatment-dose and blue growth-rates (r2=0.78;p<0.01). Percentage of blue volumes exposed to >20Gy was found higher in solid (88%) versus cystic (54%) lesions. Conclusions: These preliminary results demonstrate the TRAMs potential advantages in delineating SRS dose effects. Efficacy at lower doses was higher when studied by the TRAMs versus T1-Gd, thresholds were depicted more sharply, and the TRAMs suggest induction of TEs in normal-appearing brain at >20Gy in agreement with significant drop in new tumor growth (may be explained by anti-tumor-infiltration effects) at this threshold.
    Full-text · Conference Paper · Oct 2015
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    ABSTRACT: Purpose: Talipes equinovarus (TEV) is a common birth defect. Differentiation between isolated and complex TEV is fundamental due to its effect on prognosis. Association between TEV and poor neurological outcome is more prominent in complex cases and highlights the significance of brain evaluation. The aim of the current study was to evaluate the contribution of fetal brain MRI to sonographic evaluation. Materials and Methods: In this retrospective study we evaluated charts of all pregnant patients referred for fetal brain MRI due to fetal TEV between 1/1/2011 and 12/31/14 in a single tertiary referral center. Isolated and complex TEV were differentiated according to associated anomalies. Brain US and MRI results were compared. Results: 28 pregnant patients were included with an average gestation and parity of 2.5 and 1.5, respectively. Both isolated and complicated TEV groups included 14 fetuses after initial TEV diagnosis on anatomical survey. Brain sonography and MRI were normal among 12/14 patients with isolated TEV while two patients were later diagnosed with mild ventriculomegaly. US brain evaluation has revealed pathologic findings in 4 (28.6 %) cases in the complicated TEV group, while MRI demonstrated abnormal findings in 8 (57.1 %) fetuses with notable severity diversity. In 6 cases, MRI diagnosed additional pathologies which were not demonstrated by US. Conclusion: Brain fetal MRI is an efficient tool during antenatal evaluation of complicated TEV with a high percentage of additional findings not demonstrated songraphically while its efficacy in isolated cases is in doubt. The current study expands the relevance of fetal brain MRI in cases of non-CNS anomalies.
    No preview · Article · Sep 2015 · Ultraschall in der Medizin
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    ABSTRACT: To evaluate the impact of symmetric and asymmetric isolated mild ventriculomegaly (IMVM, atrial width 10-15 mm) on apparent diffusion coefficient (ADC) values in fetal brain areas. Sixty-seven sequential fetal head magnetic resonance imaging scans (feMRI) of VM cases performed between 2009 and 2014 were compared to 38 normal feMRI scans matched for gestational age (controls). Ultrasound- and MRI-proven IMVM cases were divided into asymmetrical (AVM, ≥2 mm difference in atrial width), symmetrical (SVM, <2 mm difference in atrial width), and asymmetrical IMVM with one normal-sized ventricle (AV1norm). ADC values were significantly elevated in the basal ganglia (BG) of the SVM and AV1norm groups compared to controls (p < 0.004 and p < 0.013, respectively). High diffusivity was constantly detected in the BG ipsilateral to the enlarged atria relative to the normal-sized atria in the AV1norm group (p < 0.03). Frontal lobe ADC values were significantly reduced in the AVM and SVM groups (p < 0.003 and p < 0.003 vs. controls). Temporal lobe ADC values were significantly reduced in the AVM group (p < 0.001 vs. controls). Isolated mild ventriculomegaly is associated with distinct ADC value changes in different brain regions. This phenomenon could reflect the pathophysiology associated with different IMVM patterns. • Various ventriculomegaly patterns are associated with distinct diffusional changes • Frontal and temporal lobe ADC values are altered bilaterally, even in asymmetric ventriculomegaly • Basal ganglia ADC values are elevated ipsilateral to the enlarged ventricle.
    No preview · Article · Jul 2015 · European Radiology

  • No preview · Conference Paper · Jun 2015
  • R Ber · O Bar-Yosef · C Hoffmann · D Shashar · R Achiron · E Katorza
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    ABSTRACT: Posterior fossa malformations are a common finding in prenatal diagnosis. The objectives of this study are to re-evaluate existing normal MR imaging biometric data of the fetal posterior fossa, suggest and evaluate new parameters, and demonstrate the possible clinical applications of these data. This was a retrospective review of 215 fetal MR imaging examinations with normal findings and 5 examinations of fetuses with a suspected pathologic posterior fossa. Six previously reported parameters and 8 new parameters were measured. Three new parameter ratios were calculated. Interobserver agreement was calculated by using the intraclass correlation coefficient. For measuring each structure, 151-211 MR imaging examinations were selected, resulting in a normal biometry curve according to gestational age for each parameter. Analysis of the ratio parameters showed that vermian lobe ratio and cerebellar hemisphere ratio remain constant with gestational age and that the vermis-to-cisterna magna ratio varies with gestational age. Measurements of the 5 pathologic fetuses are presented on the normal curves. Interobserver agreement was excellent, with the intraclass correlation coefficients of most parameters above 0.9 and only 2 parameters below 0.8. The biometry curves derived from new and existing biometric data and presented in this study may expand and deepen the biometry we use today, while keeping it simple and repeatable. By applying these extensive biometric data on suspected abnormal cases, diagnoses may be confirmed, better classified, or completely altered. © 2015 American Society of Neuroradiology.
    No preview · Article · Feb 2015 · American Journal of Neuroradiology
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    ABSTRACT: Purpose: 1) To evaluate and classify the indications for fetal brain MRI in a tertiary referral center. 2) To assess the contribution of fetal brain MRI to fetal neurosonography. Materials and Methods: A retrospective study in a tertiary medical center during a two-year period (2011 - 2012) included pregnant women who underwent fetal brain MRI. MRI was implemented at 32 weeks of gestation unless a severe abnormality possibly requiring earlier medical intervention was suspected. Results: 633 patients were included, 40 (6.3 %) underwent repeated examinations with a total of 733 fetal MRI scans. Patients were classified to three main indication cohorts: Suspected primary brain anomaly (52.9 %), non-CNS disorders (32.5 %) and obstetrical complications (14.6 %). These cohorts were further divided into 16 separate groups with lateral ventricle abnormalities being the most common (23.7 %), followed by exposure to TORCH (17.5 %) and cerebral cortex abnormalities (13 %). 149 (19.3 %) fetal MRI scans demonstrated additional findings. Repeated examinations were commonly implemented in complicated monochorionic-biamniotic (MCBA) twin pregnancies (34.6 %) and in cases of supra-tentorial cysts (19 %). The average gestational age for MRI scan in the MCBA group was 26 ± 5 weeks in comparison to ≥ 31st weeks in all other groups (p < 0.001). Conclusion: The current study describes a detailed picture of fetal brain MRI indications. Most patients were referred because of CNS anomalies. The impressive diversity of 16 separate entities emphasizes the expanding use of fetal brain MRI. Complicated MCBA pregnancies, which may have dramatic events, constitute a unique challenge due to early and repetitive MRI examinations and may serve as a role model for the contribution of fetal MRI during antenatal evaluation. The contribution of MRI to prenatal evaluation in various indications is discussed. © Georg Thieme Verlag KG Stuttgart · New York.
    Full-text · Article · Dec 2014 · Ultraschall in der Medizin
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    ABSTRACT: Familial Creutzfeldt–Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. While carriers are born with this mutation, they usually remain asymptomatic until middle age. Early detection of conversion is crucial for understanding and eventually for the treatment of the disease. The aim of this study was to report longitudinal MRI data in E200K individuals who eventually converted from healthy mutation carriers to clinically symptomatic CJD. As a part of a prospective study, asymptomatic E200K mutation carriers were scanned annually until their conversion to symptomatic disease. Standardized diffusion and anatomical MR sequences were performed before and after clinical conversion in the subjects and those were compared to 15 non-carrier siblings (“healthy controls”). Blinded radiological readings and region of interest analyses were performed. Radiological readings of individual cases failed to detect characteristic changes in the scans taken before the conversion. Region of interest analysis of diffusion changes in pre-symptomatic stage was inconclusive; however, ADC reduction was found in early and late stages of the disease. Computerized volumetric analysis revealed monotonic volume reductions in thalamus, putamen and caudate following conversion, and the lateral ventricles showed dilatation of up to 62 % after clinical conversion. Although the clinical manifestations at disease onset are variable, the diffusion abnormalities and/or volume changes in the thalamus and basal ganglia during conversion may indicate early involvement of the thalamostriatal neuronal circuit.
    Full-text · Article · Dec 2014 · Journal of Neurology
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    ABSTRACT: Conventional magnetic resonance imaging (MRI) is unable to differentiate tumor/nontumor enhancing tissues. We have applied delayed-contrast MRI for calculating high resolution treatment response assessment maps (TRAMs) clearly differentiating tumor/nontumor tissues in brain tumor patients. One hundred and fifty patients with primary/metastatic tumors were recruited and scanned by delayed-contrast MRI and perfusion MRI. Of those, 47 patients underwent resection during their participation in the study. Region of interest/threshold analysis was performed on the TRAMs and on relative cerebral blood volume maps, and correlation with histology was studied. Relative cerebral blood volume was also assessed by the study neuroradiologist. Histological validation confirmed that regions of contrast agent clearance in the TRAMs >1 h post contrast injection represent active tumor, while regions of contrast accumulation represent nontumor tissues with 100% sensitivity and 92% positive predictive value to active tumor. Significant correlation was found between tumor burden in the TRAMs and histology in a subgroup of lesions resected en bloc (r(2) = 0.90, P < .0001). Relative cerebral blood volume yielded sensitivity/positive predictive values of 51%/96% and there was no correlation with tumor burden. The feasibility of applying the TRAMs for differentiating progression from treatment effects, depicting tumor within hemorrhages, and detecting residual tumor postsurgery is demonstrated. The TRAMs present a novel model-independent approach providing efficient separation between tumor/nontumor tissues by adding a short MRI scan >1 h post contrast injection. The methodology uses robust acquisition sequences, providing high resolution and easy to interpret maps with minimal sensitivity to susceptibility artifacts. The presented results provide histological validation of the TRAMs and demonstrate their potential contribution to the management of brain tumor patients. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    No preview · Article · Nov 2014 · Neuro-Oncology
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    ABSTRACT: BACKGROUND: Conventional MRI is unable to differentiate tumor/non-tumoral enhancing tissues on conventional T1-MRI (radionecrosis/pseudoprogression). We have applied delayed contrast MRI for calculating high resolution (1mm3) treatment response assessment maps (TRAMs) clearly differentiating tumor/non-tumoral tissues in brain tumor patients and validated the TRAMs histologically. We further assessed the sensitivity and positive predictive value (PPV) of rCBV/KTrans (DSC/DCE MRI) to tumor. METHODS: 162 patients with primary/metastatic tumors were recruited/followed on study. The maps were validated by comparing pre-surgical maps of 51 patients with histology. Histological evaluation consisted of blinded pathological reports and non-blinded evaluation of 62 biopsies and 8 en-block samples. The sensitivity/PPV of rCBV to tumor was studied for 46 resected patients, where rCBV was compared with histology. The sensitivity/PPV of rCBV/KTranse was studied separately for 49/42 non-resected patients where these parameters were compared with the TRAMs. RESULTS: Histological validation confirmed that regions of contrast agent-clearance > 1hr post contrast injection represent morphologically active tumor while regions of contrast accumulation represent non-tumor tissues. Based on the blinded histological reports, the TRAMs showed sensitivity/PPV to active tumor of 100%/92%. The addition of the non-blinded data resulted in sensitivity/PPV of 99%/95%. Significant correlation was found between tumor volumes in the TRAMs and in the en-block samples (r2 = 0.84, p < 0.0001). Comparison of rCBV with histology resulted in sensitivity/PPV of 51%/96%. When comparing rCBV/KTrans to the TRAMs we found a sensitivity of 23%/24% and PPV of 100%/90% to tumor regions in the TRAMs. The lower sensitivity of rCBV to tumor in the non-resected patients may be attributed to the larger percentage of smaller metastatic tumors that tend towards lower perfusion. CONCLUSIONS: Despite the high PPV of rCBV/KTrans to tumor, the low sensitivity suggests that 49%-76% of the tumors will remain undetected. Our data suggest that the TRAMs provide both high PPV and high sensitivity to tumor tissues.
    No preview · Conference Paper · Nov 2014
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    ABSTRACT: Objectives To evaluate effects of cytomegalovirus (CMV) infection on apparent diffusion coefficient (ADC) values of the fetal brain in utero.Methods Fifty-eight sequential fetal head magnetic resonance imaging (feMRI) scans of PCR-verified CMV-infected fetuses were retrospectively (2008–2012) analyzed and compared to a normal control group. Gestational age (GA) at infection ranged from 1–32 weeks, and feMRI scanning was performed at GA 24–38. The frontal, parietal, temporal and occipital lobes (mainly white matter), basal ganglia (BG), thalamus, pons and cerebellum were analyzed by assessing ADC values. Two pregnancies were terminated and PM correlation was available. Regional ADC measurements were similarly obtained from 36 GA-matched uninfected fetuses.ResultsADC values of the CMV-infected fetuses significantly and negatively correlated with GA in all brain regions except the basal ganglia. The cerebellum had the steepest decline (r =0.52, P < .0001). Maternal age correlated positively with ADC in the frontal lobe (P < .05). Age at infection and overt pathological changes did not significantly affect ADC. ADC values of affected fetuses were significantly reduced in the frontal (P < .0001), parietal (P < .0001), occipital (P = .0005), and temporal (P = .001) lobes and thalamus (P = .006) compared to non-infected fetuses.ConclusionsCMV infection of the fetal brain results in a highly significant, region-dependent reduction of ADC values in the frontal, parietal, occipital and temporal lobes and thalamus, probably reflecting hypercellularity and inclusion bodies in damaged areas. Further studies are needed to determine if reduction in ADC values may serve as a prognostic factor in CMV-infected fetuses.
    No preview · Article · Nov 2014 · Ultrasound in Obstetrics and Gynecology
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    ABSTRACT: Costeff syndrome (CS) is a rare autosomal-recessive neurological disorder, which is known almost exclusively in patients of Iraqi Jewish descent, manifesting in childhood with optic atrophy, ataxia, chorea and spastic paraparesis. Our aim was to study the clinical spectrum of CS and natural history using a cross-sectional study design. Consecutive patients with CS were recruited to the study. Patients were diagnosed based on clinical features, along with elevated urinary levels of methylglutaconic and methylglutaric acid, and by identification of the disease-causing mutation in the OPA3 gene in most. All patients were examined by a neurologist and signs and symptoms were rated. 28 patients with CS (16 males, 21 families, age at last observation 28.6 ± 16.1 years, range 0.5-68 years) were included. First signs of neurological deficit appeared in infancy or early childhood, with delayed motor milestones, choreiform movements, ataxia and visual disturbances. Ataxia and chorea were the dominant motor features in childhood, but varied in severity among patients and did not seem to worsen with age. Pyramidal dysfunction appeared later and progressed with age (r = 0.71, p < 0.001) leading to spastic paraparesis and marked gait impairment. The course of neurological deterioration was slow and the majority of patients could still walk beyond the fifth decade. While visual acuity seemed to deteriorate, it did not correlate with age. CS is a rare neurogenetic disorder that causes serious disability and worsens with age. Spasticity significantly increases over the years and is the most crucial determinant of neurological dysfunction.
    No preview · Article · Sep 2014 · Journal of Neurology
  • E. Katorza · G. Yaniv · E. Konen · C. Hoffmann

    No preview · Article · Sep 2014 · Ultrasound in Obstetrics and Gynecology

  • No preview · Article · Sep 2014 · Ultrasound in Obstetrics and Gynecology
  • B. Weisz · Y. Yinon · C. Hoffmann · S. Lipitz

    No preview · Article · Sep 2014 · Ultrasound in Obstetrics and Gynecology
  • E. Katorza · E. Bertucci · C. Hoffmann · R. Ber · Y. Gilboa · V. Mazza · R. Achiron

    No preview · Article · Sep 2014 · Ultrasound in Obstetrics and Gynecology
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    Full-text · Article · Sep 2014 · Ultrasound in Obstetrics and Gynecology
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    Anat Biegon · Chen Hoffmann
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    ABSTRACT: Application of modern magnetic resonance imaging (MRI) techniques to the live fetus in utero is a relatively recent endeavor. The relative advantages and disadvantages of clinical MRI relative to the widely used and accepted ultrasonographic approach are the subject of a continuing debate; however the focus of this review is on the even younger field of quantitative MRI as applied to non-invasive studies of fetal brain development. The techniques covered under this header include structural MRI when followed by quantitative (e.g., volumetric) analysis, as well as quantitative analyses of diffusion weighted imaging, diffusion tensor imaging, magnetic resonance spectroscopy and functional MRI. The majority of the published work reviewed here reflects information gathered from normal fetuses scanned during the 3(rd) trimester, with relatively smaller number of studies of pathological samples including common congenital pathologies such as ventriculomegaly and viral infection.
    Preview · Article · Aug 2014
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    ABSTRACT: Monochorionic twins, treated by laser due to twin-twin-transfusion syndrome (TTTS) are at increased risk of neurodevelopment impairment. Our aim was to evaluate the additional value of Diffusion Weighted Imaging (DWI) over fetal sonography and T2-MRI in detection of acute ischemic cerebral lesions shortly following fetoscopic laser coagulation (FLC). This is a prospective cohort study of patients with TTTS treated by FLC. All patients underwent fetal brain DWI and T2-MRI within 24-96 hours after the procedure and a follow-up MRI at 30-32 weeks of gestation. All patients also had frequent evaluation by fetal sonography until delivery. Thirty patients with TTTS were included in the study. Eight pregnancies (group A) resulted in survival of only one twin after the procedure, whereas the other 22 pregnancies resulted in dual twin survival (Group B). Two fetuses in group A and 4 fetuses in group B had evidence of transient bleeding in the germinal matrix. Three fetuses in group B while none in group A had diffused ischemic changes in the white matter. One fetus died in-utero 24 hours after the MRI. The other 2 fetuses in group B demonstrated an acute infarct 24-48 hours after the procedure. Subsequent scans at 28-29 and 32 weeks showed brain atrophy compatible with an old infarct. DWI can demonstrate cerebral damage immediately after FLC. Larger cohorts are needed to determine the role of fetal MRI in the prenatal assessment and follow-up of patients with TTTS.
    No preview · Article · Jul 2014 · Ultrasound in Obstetrics and Gynecology

Publication Stats

328 Citations
219.95 Total Impact Points

Institutions

  • 2006-2016
    • Sheba Medical Center
      • Department of Pathology
      Gan, Tel Aviv, Israel
  • 2007-2015
    • Tel Aviv University
      • • Department of Obstetrics and Gynecology
      • • Department of Neurology
      Tell Afif, Tel Aviv, Israel
  • 2014
    • Stony Brook University
      • Department of Medicine
      Stony Brook, New York, United States