Malformation of cortical development with abnormal cortex: early ultrasound diagnosis between 14 and 24 weeks of gestation.

OBJECTIVE: To describe neurosonographic findings diagnostic or highly suggestive of the presence of malformations of cortical development involving the cortex that may be identified before 24 weeks of gestation. METHODS: This was a retrospective single-center study of fetuses referred for neurosonography, during 2012-2019, with an abnormal cortical or sulcation pattern diagnosed early in the mid trimester. Stored files were analyzed for demographic data, abnormal brain findings, non-central nervous system abnormalities, final diagnosis and postnatal outcome. RESULTS: The study cohort included 20 fetuses, with a mean gestational age at diagnosis of 18.7 (range, 14.4-23.6) weeks, in 11 of which the diagnosis was made before 20 weeks of gestation. Reasons for referral were: midline anomaly (n = 7), ventriculomegaly (n = 4), infratentorial findings (n = 3), suspected malformation of cortical development (n = 3), 'abnormal brain' (n = 2) and skeletal dysplasia (n = 1). On neurosonography, both the sulcation pattern and the cortical layer were abnormal in four cases, only the sulcation pattern was considered abnormal in seven and only the cortical layer was abnormal in nine. Nineteen fetuses presented with associated central nervous system anomalies and six also had non-central nervous system malformations. One case was recurrent. Eighteen parents opted for termination of pregnancy, including one selective termination in a twin pregnancy, and two fetuses were liveborn. CONCLUSIONS: Familiarity with fetal brain anatomy and its early sonographic landmarks allowed early diagnosis of malformations involving cortical development. These patients are likely to represent the most severe cases and all had associated malformations. The presence of an abnormal cortical layer and/or abnormal overdeveloped sulci appear to be early signs of malformation of cortical development. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetal neurosonography as accurate tool for diagnosis of brain involvement in tuberous sclerosis.

OBJECTIVE: To demonstrate the potential utility of dedicated neurosonography for the diagnosis of fetal brain involvement in tuberous sclerosis complex. METHODS: This was a multicenter retrospective study of fetuses at high risk for tuberous sclerosis complex. Dedicated neurosonographic, fetal magnetic resonance imaging (MRI) and postnatal reports were reviewed. Data collected included reason for referral, gestational age at which cardiac rhabdomyoma was first suspected and final number of cardiac rhabdomyomas detected on dedicated imaging. We searched for tuberous sclerosis complex-related brain involvement, defined as the presence of one or more of the following findings: white-matter lesions; subependymal nodules; cortical/subcortical tubers; and subependymal giant-cell astrocytoma. RESULTS: We included 20 patients at high risk of tuberous sclerosis complex, of whom 19 were referred for the presence of cardiac rhabdomyomas and one for a deletion in chromosome 16 involving the tuberous sclerosis complex gene locus. Cardiac rhabdomyomas were diagnosed at a mean gestational age of 27 + 2 weeks (range, 16 + 0 to 36 + 3 weeks) and the mean number of cardiac rhabdomyomas per patient was 4 (range, 1-10). Brain involvement was present in 15 fetuses, in 13 of which the disease was confirmed in one or more of the following ways: chromosomal microarray analysis (n = 1), exome sequencing (n = 7), autopsy (n = 4), clinical tuberous sclerosis complex in the newborn (n = 4) and a sibling diagnosed with clinical tuberous sclerosis complex (n = 1). In two cases, the disease could not be confirmed: one was lost to follow-up and autopsy, following termination of pregnancy, was not performed in the other. Among the five cases without brain findings, tuberous sclerosis complex was confirmed in three by exome sequencing (n = 2) and/or autopsy findings (n = 2). The two remaining cases had normal exome sequencing; one case had five cardiac rhabdomyomas, which was a highly suggestive finding, while in the final case, the autopsy was considered normal, representing the only false-positive case in our cohort. CONCLUSIONS: Contrary to current literature, dedicated neurosonography appears to be effective in the diagnosis of brain involvement in fetuses at risk of tuberous sclerosis complex and should be used as the first-line approach. Although the number of cases in which MRI was performed was small, it seems that, in the presence of ultrasound findings, the added value of MRI is low. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal diagnosis of rhombencephalosynapsis: neuroimaging features and severity of vermian anomaly.

OBJECTIVES: To describe the prenatal neuroimaging spectrum of rhombencephalosynapsis (RES) and criteria for its classification according to the severity of vermian anomaly. METHODS: In this multicenter retrospective study of fetuses with RES between 2002 and 2020, the medical records and brain ultrasound and magnetic resonance images were evaluated comprehensively to determine the severity of the vermian anomaly and the presence of associated brain findings. RES was classified, according to the pattern of vermian agenesis and the extent of the fusion of the hemispheres, as complete RES (complete absence of the vermis) or partial RES (further classified according to the part of the vermis that was missing and, consequently, the region of hemispheric fusion, as anterior, posterior, severe or mixed RES). Findings were compared between cases with complete and those with partial RES. RESULTS: Included in the study were 62 fetuses with a gestational age ranging between 12 and 37 weeks. Most had complete absence of the vermis (complete RES, 77.4% of cases), a 'round-shaped' cerebellum on axial views (72.6%) and a transverse cerebellar diameter (TCD) < 3rd centile (87.1%). Among the 22.6% of cases with partial RES, 6.5% were classified as severe partial, 6.5% as partial anterior, 8.1% as partial mixed and 1.6% as partial posterior. Half of these cases presented with normal or nearly normal cerebellar morphology and 28.5% had a TCD within the normal limits. Infratentorially, the fourth ventricle was abnormal in 88.7% of cases overall, and anomalies of the midbrain and pons were frequent (93.5% and 77.4%, respectively). Ventriculomegaly was observed in 80.6% of all cases, being more severe in cases with complete RES than in those with partial RES, with high rates of parenchymal and septal disruption. CONCLUSIONS: This study provides prenatal neuroimaging criteria for the diagnosis and classification of RES, and identification of related features, using ultrasound and magnetic resonance imaging. According to our findings, a diagnosis of RES should be considered in fetuses with a small TCD (severe cerebellar hypoplasia) and/or a round-shaped cerebellum on axial views, during the second or third trimester, especially when associated with ventriculomegaly. Partial RES is more common than previously thought, but presents an extreme diagnostic challenge, especially in cases with normal or nearly-normal cerebellar morphobiometric features. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Bi-allelic IARS mutations in a child with intra-uterine growth retardation, neonatal cholestasis, and mild developmental delay.

Recently, bi-allelic mutations in cytosolic isoleucyl-tRNA synthetase (IARS) have been described in three individuals with growth delay, hepatic dysfunction, and neurodevelopmental disabilities. Here we report an additional subject with this condition identified by whole-exome sequencing. Our findings support the association between this disorder and neonatal cholestasis with distinct liver pathology. Furthermore, we provide functional data on two novel missense substitutions and expand the phenotype to include mild developmental delay, skin hyper-elasticity, and hypervitaminosis D.

Region-specific reductions in brain apparent diffusion coefficient in cytomegalovirus-infected fetuses.

OBJECTIVE: To evaluate the effects of cytomegalovirus (CMV) infection on apparent diffusion coefficient (ADC) values of the fetal brain in utero. METHODS: In this retrospective analysis we compared 58 fetal head magnetic resonance imaging (fhMRI) scans of PCR-verified CMV-infected fetuses, obtained in 2008-2012, with those of a normal control group of 36 gestational age (GA)-matched uninfected fetuses scanned between 2006 and 2012. Estimated GA at infection ranged from 1 to 32 weeks, and fhMRI was performed at 24 to 38 weeks. The frontal, parietal, temporal and occipital lobes (mainly white matter), basal ganglia, thalamus, pons and cerebellum were analyzed by assessing ADC values. Two pregnancies were terminated and postmortem confirmation was available in these cases. RESULTS: ADC values of CMV-infected fetuses correlated significantly and negatively with GA in all brain regions except the basal ganglia. The cerebellum had the greatest reduction (r = -0.52, P < 0.0001). Maternal age correlated positively with ADC in the frontal lobe (P < 0.05). GA at infection and overt pathological changes did not affect ADC significantly. Compared with non-infected fetuses, ADC values of affected fetuses were significantly reduced in the frontal (P < 0.0001), parietal (P < 0.0001), occipital (P = 0.0005) and temporal (P = 0.001) lobes and thalamus (P = 0.006). CONCLUSION: CMV 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. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of microcephaly at birth using three reference ranges for fetal head circumference: can we improve prenatal diagnosis?

OBJECTIVE: To evaluate the prediction of microcephaly at birth (micB) using established and two new reference ranges for fetal head circumference (HC) and to assess whether integrating additional parameters can improve prediction. METHODS: Microcephaly in utero was defined as a fetal HC 3SD below the mean for gestational age according to Jeanty et al.'s reference range. The records of cases with fetal microcephaly (Fmic) were evaluated for medical history, imaging findings, biometry and postnatal examination/autopsy findings. Microcephaly was confirmed at birth (micB) by an occipitofrontal circumference (OFC) or a brain weight at autopsy 2SD below the mean for gestational age. The new INTERGROWTH-21(st) Project and a recent Israeli reference for fetal growth were applied for evaluation of the Fmic positive predictive value (PPV) for diagnosis of micB cases. Optimal HC cut-offs were determined for each of the new references with the aim of detecting all micB cases whilst minimizing the number of false positives found to have a normal HC at birth. We also assessed the difference between the Z-scores of the prenatal HC and the corresponding OFC at birth, the frequency of small-for-gestational age (SGA), decreased HC/abdominal circumference (AC) and HC/femur length (FL) ratios, the prevalence of associated malformations and family history. RESULTS: Forty-two fetuses were diagnosed as having Fmic according to the Jeanty reference, but micB was confirmed in only 24 (PPV, 57.1%). The optimal INTERGROWTH and Israeli reference HC cut-offs for micB diagnosis were mean - 3SD and mean - 2.3SD, resulting in a statistically non-significant improvement in PPV to 61.5% and 66.7%, respectively. The presence of a family history of microcephaly, SGA, associated malformations and application of stricter HC cut-offs resulted in a higher PPV of micB, although not statistically significant and with a concurrent increase in the number of false-negative results. The deviation of the HC from the mean, by all references, was significantly larger compared with the actual deviation of the OFC at birth, with mean differences between the corresponding Z-scores of -1.15, -1.95 and -0.74 for the Jeanty, INTERGROWTH and Israeli references, respectively. CONCLUSIONS: The evaluated reference ranges all result in considerable over-diagnosis of fetal microcephaly. The use of the two new HC reference ranges did not significantly improve micB prediction compared with that of Jeanty et al., whilst use of additional characteristics and stricter HC cut-offs could improve the PPV with an increase in false negatives. The postnatal OFC deviates significantly less from the mean compared with the prenatal HC, and we propose that adjustment for this would enable better prediction of the actual OFC deviation at birth. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Application of a novel prenatal vertical cranial biometric measurement can improve accuracy of microcephaly diagnosis in utero.

OBJECTIVE: To construct a reference range for a new vertical measurement of the fetal head and to assess whether its combination with fetal head circumference (HC) can prevent the misdiagnosis of microcephaly in fetuses with an acrocephalic-like head deformation. METHODS: A new vertical cranial biometric measurement was defined: the foramen magnum-to-cranium distance (FCD), measured between the foramen magnum and the upper inner cranial border along the posterior wall of the brainstem. The measurement was performed in a precise mid-sagittal plane using a three-dimensional multiplanar display of a sagittally acquired sonographic volume of the fetal head. The normal reference range was developed by measuring 396 healthy fetuses of low-risk singleton pregnancies between 15 and 40 gestational weeks. This reference was applied to 25 fetuses with microcephaly diagnosed prenatally (Fmic) based on HC ≥ 3 SD below the mean for gestational age. We determined an optimal FCD cut-off for combination with HC to detect all cases found with microcephaly at birth (micB), while excluding the fetuses with normal head circumference at birth (NHCB), who were described postnatally as having an acrocephalic-like cranial deformation. RESULTS: In the healthy singleton fetuses, FCD increased with gestational age, with a quadratic equation providing an optimal fit to the data (adjusted R(2) = 0.934). The measurement could be assessed in 95.2% of cases. Of the 25 cases diagnosed with Fmic prenatally, on the basis of HC alone, 14 were micB and 11 were NHCB. We observed FCD below the mean - 2SD for gestational age in all 14 micB cases, but in only four of the 11 NHCB cases (P < 0.003). An acrocephalic-like cranial deformation was described at birth in five of the seven NHCB cases with normal FCD. The mean ± SD FCD Z-score of the micB cases was significantly lower (P < 0.001) than that of the false-positive ones: -3.85 ± 0.96 SD and -1.59 ± 1.45 SD, respectively. Based on HC measurement alone, the positive predictive value (PPV) was 56%. Combination of the HC and FCD criteria raised the PPV to 78%, decreasing the number of false positives from 11 to four, without missing any of the 14 micB cases. CONCLUSIONS: Fetal vertical cranial biometric assessment in the mid-sagittal plane is feasible and correlates well with gestational age. In our series, a vertical cranial deformation was a frequent cause of a false Fmic diagnosis made on the basis of HC alone. Combination of the new vertical cranial biometric measurement with HC measurement can exclude these cases and thus improve diagnostic accuracy for Fmic. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Medullary Tegmental Cap Dysplasia: Fetal and Postnatal Presentations of a Unique Brainstem Malformation.

BACKGROUND AND PURPOSE: Medullary tegmental cap dysplasia is a rare brainstem malformation, first described and defined by James Barkovich in his book Pediatric Neuroimaging from 2005 as an anomalous mass protruding from the posterior medullary surface. We describe the neuroimaging, clinical, postmortem, and genetic findings defining this unique malformation. MATERIALS AND METHODS: This is a multicenter, international, retrospective study. We assessed the patients' medical records, prenatal ultrasounds, MR images, genetic findings, and postmortem results. We reviewed the medical literature for all studies depicting medullary malformations and evaluated cases in which a dorsal medullary protuberance was described. RESULTS: We collected 13 patients: 3 fetuses and 10 children. The medullary caps had multiple characteristics. Associated brain findings were a rotated position of the medulla, a small and flat pons, cerebellar anomalies, a molar tooth sign, and agenesis of the corpus callosum. Systemic findings included the following: polydactyly, hallux valgus, large ears, and coarse facies. Postmortem analysis in 3 patients revealed that the cap contained either neurons or white matter tracts. We found 8 publications describing a dorsal medullary protuberance in 27 patients. The syndromic diagnosis was Joubert-Boltshauser syndrome in 11 and fibrodysplasia ossificans progressiva in 14 patients. CONCLUSIONS: This is the first study to describe a series of 13 patients with medullary tegmental cap dysplasia. The cap has different shapes: distinct in Joubert-Boltshauser syndrome and fibrodysplasia ossificans progressive. Due to the variations in the clinical, imaging, and postmortem findings, we conclude that there are multiple etiologies and pathophysiology. We suggest that in some patients, the pathophysiology might be abnormal axonal guidance.

Can syndromic macrocephaly be diagnosed in utero?

OBJECTIVES: To compare the outcomes of fetuses with apparently isolated macrocephaly and those with associated findings, and to compare prenatal findings with postnatal diagnoses in children with syndromic macrocephaly. METHODS: We reviewed the files of all patients referred for suspected fetal macrocephaly, during a 10-year period from 2000, to a large prenatal diagnosis unit with expertise in fetal neurology counseling. Macrocephaly was defined as head circumference (HC) > 2 SDs of the norm. Patients with confirmed HC > 2 SD were identified and contacted, and their development was evaluated. RESULTS: Adequate data for analysis were available for 98 patients, in 82 of whom the fetal macrocephaly was considered isolated (Group A), and in 16 of whom associated fetal anomalies were identified (Group B). Macrocephaly was diagnosed earlier in Group B patients (28.4 vs. 32.3 weeks, P = 0.069), and the HC in Group B patients was larger (Z-score 2.95 vs. 2.3, P < 0.001). From Group A there were 81 liveborn; one of whom was diagnosed as having infantile autism. From Group B, there were nine liveborn. The associated central nervous system findings, as demonstrated by ultrasound and magnetic resonance imaging, included mild ventriculomegaly, malformations of cortical development, callosal abnormalities, overdeveloped sulcation, large cavum septi pellucidi, large subarachnoid spaces, mega cisterna magna, periventricular pseudocyst, open operculum and vermian dysgenesis. Syndromic diagnosis was made in utero in five fetuses and after birth in three. In eight patients, associated malformations were confirmed after birth but a specific diagnosis was not reached. CONCLUSIONS: When fetal macrocephaly is associated with other brain or systemic anomalies, syndromic macrocephaly can be diagnosed in utero. Fetuses with syndromic macrocephaly have a significantly larger HC, usually > 2.5 SD above the mean. Isolated macrocephaly, particularly when the HC is < 2.5 SD above the norm, may be clinically benign.

Juvenile onset of primary low-grade cutaneous B-cell lymphoma.

BACKGROUND: Cutaneous lymphomas rarely occur in children and adolescents, and are mostly of the T-cell lineage. Low-grade primary cutaneous B-cell lymphoma (CBCL) is extremely rare in individuals under 18 years old. Only 11 patients under 20 years old have been reported in the literature. OBJECTIVES: To evaluate the number of patients younger than 18 years with primary CBCL diagnosed at our centre and to investigate its clinicopathological features, treatment and course in this age group. METHODS: We reviewed the files of all 90 patients with primary CBCL who attended the Department of Dermatology of our tertiary care university-affiliated centre from 1992 to 2007. RESULTS: Four patients who met study criteria were identified: three girls and one boy. Mean age at diagnosis was 16.6 years (range 16-17). Three patients had cutaneous marginal zone lymphoma (CMZL), and one had a spindle-cell (sarcomatoid) lymphoma, most probably follicular centre cell type. All were treated with the standard regimen used in adults. The mean duration of follow up was 45 months. No extracutaneous progression was noted. At present two of the four patients are in complete clinical remission. CONCLUSIONS: In Israel, primary CBCL apparently occurs more often in young patients than reported in the literature. CMZL is the most frequent type. Long follow up is mandatory to assess the biological behaviour of CBCL in the paediatric/adolescent age group.

Thick fetal corpus callosum: an ominous sign?

OBJECTIVE: Anomalies of the corpus callosum are frequently diagnosed during pregnancy, but a thick corpus callosum is a rare finding and its significance is not clear. We aimed to assess the significance of thick fetal corpus callosum by reviewing our experience of such cases. METHODS: The records of all fetuses with anomalies of the corpus callosum referred to the prenatal diagnosis units of two university hospitals from 2000 to 2007 were reviewed. Nine fetuses with a thick corpus callosum were identified. RESULTS: In all cases there were associated abnormalities: macrocephaly, ventriculomegaly, vermian agenesis, abnormal sulcation or encephalocele. Four pregnancies were terminated and in each of these cases the autopsy confirmed dysmorphic features and additional brain abnormalities. Five infants were delivered; two died shortly after birth, one suffers from mental retardation, one had neonatal convulsions and one is developing normally. CONCLUSIONS: A thick fetal corpus callosum is usually associated with other brain anomalies and is part of a neurogenetic syndrome in most cases.

Prenatal diagnosis of congenital agenesis of the fetal portal venous system.

OBJECTIVE: To describe the prenatal diagnosis and review our experience of fetal congenital agenesis of the portal venous system (CAPVS) and to review the current literature on this poorly documented vascular malformation. METHODS: This was a retrospective survey covering the 12-year period between 1996 and 2008. The database of a single, large, ultrasonographic tertiary academic referral center in Israel was analyzed and cases with a prenatal diagnosis of CAPVS were identified. All fetuses underwent detailed biometric and structural ultrasound examinations and a precise anatomical description of the fetal umbilical, portal and hepatic venous system was noted, as well as the presence of aberrant vessels, shunt location and the presence or absence of the DV. Results of fetal echocardiography, karyotyping and toxoplasma, rubella, cytomegalovirus and herpes evaluations were determined. Medical records were evaluated. Diagnosis was confirmed by pathology, postmortem venography or neonatal ultrasound or venography. Liveborns were examined by a certified neonatologist and long-term follow-up from pediatric gastroenterology units was determined. RESULTS: Nine cases with CAPVS were studied. In all cases an aberrant umbilical-portal vein was the primary indication for detailed portal system evaluation. Five fetuses demonstrated total CAPVS (Type I) and four showed partial agenesis of the portal vein (Type II). Among the five Type I fetuses, there was a shunt from the umbilical vein to the inferior vena cava in three (60%), to the right atrium in one and to the coronary sinus in one. In this group, in only one case could we delineate a common confluence between the splenic vein and the superior mesenteric vein shunting to the inferior vena cava. In four cases termination of pregnancy was performed due to additional findings: one case with hydrothorax, ascites and mitral atresia, one with cleft lip/palate and one with trisomy 21. One case had no additional anomalies, but the parents elected to terminate the pregnancy. All four of the Type II fetuses had a portosystemic shunt: in two cases to the right atrium, in one to the iliac vein and in one to the right hepatic vein. In three, the shunt resolved spontaneously. In only one case was abnormal liver function present over a follow-up period of 2-10 years. CONCLUSION: CAPVS can be detected prenatally. An abnormal course of the umbilical vein necessitates prompt sonographic evaluation of the umbilical-portal venous system and meticulous investigation for additional anomalies. Complete CAPVS may be associated with remote clinical consequences of which the parents should be informed. Partial CAPVS has a favorable prognosis.

Very Early In-Utero Diagnosis of Walker-Warburg Phenotype: The Cutting Edge of Technology.

BACKGROUND: Walker-Warburg phenotype is a severe and lethal autosomal recessive disorder, belonging to a group of congenital malformations defined as abnormal pial basement membrane formation. So far, prenatal diagnosis was considered possible only during late pregnancy. METHODS: First trimester assessment of a pregnancy suspected to be affected by Walker-Warburg phenotype, using a high-resolution transvaginal ultrasound probe (6-12 MHz), T2 MR imaging (1.5T), molecular genetics and histopathology. RESULTS: Very early diagnosis of the Walker-Warburg phenotype at 11 weeks of gestation proved possible by depicting the classic signs of this entity, confirmed by molecular genetics, post-abortion MR imaging and histopathology. CONCLUSION: Advancements in ultrasound equipment and technology, molecular genetics and histopathology have made very early detection of this syndrome possible, thus shedding new light on the natural history of this malformation.

Expression of AML1-d, a short human AML1 isoform, in embryonic stem cells suppresses in vivo tumor growth and differentiation.

The human AML1 gene encodes a heterodimeric transcription factor which plays an important role in mammalian hematopoiesis. Several alternatively spliced AML1 mRNA species were identified, some of which encode short protein products that lack the transactivation domain. When transfected into cells these short isoforms dominantly suppress transactivation mediated by the full length AML1 protein. However, their biological function remains obscure. To investigate the role of these short species in cell proliferation and differentiation we generated embryonic stem (ES) cells overexpressing one of the short isoforms, AML1-d, as well as cells expressing the full length isoforms AML1-b and AML2. The in vitro growth rate and differentiation of the transfected ES cells were unchanged. However, overexpression of AML1-d significantly affected the ES cells' ability to form teratocarcinomas in vivo in syngeneic mice, while a similar overexpression of AML1-b and AML2 had no effect on tumor formation. Histological analysis revealed that the AML1-d derived tumors were poorly differentiated and contained numerous apoptotic cells. These data highlight the pleiotropic effects of AML1 gene products and demonstrate for the first time an in vivo growth regulation function for the short isoform AML1-d.

Fulminant subacute sclerosing panencephalitis in association with pregnancy.

Subacute sclerosing panencephalitis developed during pregnancy in a 27-year-old woman and immediately after delivery in an 18-year-old woman. In both, disease took an acute and fulminant course culminating in a vegetative state within several weeks. It is suggested that the relative older age of disease presentation and the unusually rapid neurologic deterioration were partially due to immunologic and hormonal alterations of pregnancy.

Forms of dystonia in patients with Parkinson's disease.

We studied various forms of dystonia associated with Parkinson's disease (PD) in 207 patients who were on levodopa therapy for more than 1 year. Dystonia, sometimes more than one type, occurred in 63 (30%). In five patients, dystonia preceded initiation of treatment. Fifteen patients had peak-dose dystonia, 33 had early-morning dystonia, and 20 had "off-period" dystonia. The different clinical features of the dystonias are presented and compared. Findings indicate that dystonia is a frequent feature of levodopa-treated PD patients.

Quantitative MR volumetry in Alzheimer's disease. Topographic markers and the effects of sex and education.

We determined topographic selectivity and diagnostic utility of brain atrophy in probable Alzheimer's disease (AD) and correlations with demographic factors such as age, sex, and education. Computerized imaging analysis techniques were applied to MR images in 32 patients with probable AD and 20 age- and sex-matched normal control subjects using tissue segmentation and three-dimensional surface rendering to obtain individualized lobar volumes, corrected for head size by a residualization technique. Group differences emerged in gray and white matter compartments particularly in parietal and temporal lobes. Logistic regression demonstrated that larger parietal and temporal ventricular CSF compartments and smaller temporal gray matter predicted AD group membership with an area under the receiver operating characteristic curve of 0.92. On multiple regression analysis using age, sex, education, duration, and severity of cognitive decline to predict regional atrophy in the AD subjects, sex consistently entered the model for the frontal, temporal, and parietal ventricular compartments. In the parietal region, for example, sex accounted for 27% of the variance in the parietal CSF compartment and years of education accounted for an additional 15%, with women showing less ventricular enlargement and individuals with more years of education showing more ventricular enlargement in this region. Topographic selectivity of atrophic changes can be detected using quantitative volumetry and can differentiate AD from normal aging. Differential effects of sex and years of education can also be detected by these methods. Quantification of tissue volumes in vulnerable regions offers the potential for monitoring longitudinal change in response to treatment.

Memory impairments associated with hippocampal versus parahippocampal-gyrus atrophy: an MR volumetry study in Alzheimer's disease.

Delayed memory impairments and medial temporal-lobe atrophy are considered to be cardinal features of Alzheimer's disease (AD). The goal of the present magnetic resonance (MR) volumetry study was to investigate the relationship between both features. We determined MR-derived estimates of hippocampal and parahippocampal volume in a sample of 27 AD patients and in a group of 26 healthy control subjects (NCs) of comparable age and education. We examined the performance of the two groups on immediate and delayed recall trials of an auditory-verbal list-learning task (CVLT), a visual non-verbal memory task (Visual Reproduction of the WMS-R), and a screening procedure that provides an estimate of overall cognitive functioning (DRS). Volumes of the hippocampus and the parahippocampal gyrus were significantly smaller in AD patients than in NCs. AD patients were impaired in their overall level of cognitive functioning and showed memory deficits under immediate and delayed recall conditions. The association between medial temporal-lobe atrophy and cognitive impairments in AD was found to be highly specific: Hippocampal volume correlated positively with delayed but not immediate recall of the verbal auditory list learning task. In contrast, parahippocampal gyrus volume, specifically in the right hemisphere, was positively related to delayed but not immediate recall of the non-verbal visual memory task. In NCs, there was a trend towards a negative association between hippocampal volumes and delayed verbal recall. Our results suggest that hippocampal and parahippocampal gyrus atrophy in AD are related to distinct aspects of the patients' memory impairments. Our findings have implications for current discussions regarding contributions of the hippocampus and the parahippocampal gyrus to memory in the intact human brain.