Pallister-Hall syndrome (OMIM #146510) is a rare autosomal dominant condition caused by a mutation in the GLI3 gene. The cardinal feature of Pallister-Hall syndrome is the presence of hypothalamic ...hamartomas, which may manifest with seizures, panhypopituitarism and visual impairment. In Pallister-Hall syndrome, dysplastic histogenetic processes responsible for hypothalamic hamartomas are thought to disrupt early craniofacial development. The clinical presentation of Pallister-Hall syndrome may include: characteristic facies (low-set and posteriorly angulated ears, short nose with flat nasal bridge), cleft palate and uvula, bifid epiglottis and laryngotracheal cleft, limb anomalies (e.g., polysyndactyly, short limbs and nail dysplasia), anal atresia, genitourinary abnormalities and congenital heart defects.
We report the case of two monochorionic diamniotic twins diagnosed with Pallister-Hall syndrome during the neonatal period, after the identification of a hypothalamic hamartoma on day 1 by cerebral ultrasound scan, later confirmed by brain magnetic resonance imaging. Cerebral ultrasound and magnetic resonance imaging presentations were identical in both twins.
We review previously published cases (four reports) of hypothalamic hamartomas identified via cerebral ultrasound and compare reported ultrasonographic features. Main differential diagnoses based on cerebral ultrasound findings are discussed. Full description of typical magnetic resonance imaging appearance is also provided. This is the first case reported in the literature of monochorionic diamniotic twins affected by genetically confirmed Pallister-Hall syndrome with identical hypothalamic hamartomas at cerebral ultrasound and magnetic resonance imaging. Moreover, this paper adds to the existing literature on the sonographic appearance of hypothalamic hamartomas. Considering the consistency in hypothalamic hamartomas' sonographic appearance, we support the use of cerebral ultrasound as a first-line neuroimaging modality in case of clinical suspicion of Pallister-Hall syndrome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gillespie syndrome (GLSP) is a rare congenital disorder characterized by partial aniridia, hypotonia, progressive cerebellar hypoplasia, nonprogressive ataxia, and intellectual disability. All ...causative variants to date affect the central or the 3ʹ‐terminal domains of ITPR1 gene and exhibit autosomal recessive or dominant inheritance pattern. We investigated by exome sequencing the molecular cause of GLSP in a family composed by consanguineous healthy parents, two affected siblings and one healthy son. We found the novel splice site variant c.278_279 + 2delACGT located at the 5ʹ‐end of ITPR1. The affected siblings were homozygotes, their parents heterozygous carriers and the variant was absent in the healthy son, indicating a recessive inheritance pattern. The deletion abolished the splice‐donor site at exon 5/intron 5 junction, causing the skipping of exon 5 and the generation of a premature STOP codon. The mutation is predicted to result in the synthesis of a 64‐amino acids nonfunctional protein. The mutant transcript comprised >96% of ITPR1 mRNA in the affected siblings, indicating that a small amount of wild‐type transcript was still present. The novel autosomal recessive mutation here reported is the first variant affecting the ITPR1 N‐terminal suppressor domain, thus extending the spectrum of the pathogenetic variants in GLSP and the range of the associated clinical manifestations.
This study investigated for the first time brain ischemic involvement in 19 consecutive neurologically asymptomatic PNH patients by non-enhanced cerebral MRI, and by intracranial arterial and venous ...angio-MRI. Eleven cases (58%, 7 aged <65) showed pathological findings: 9 white matter (WM) abnormalities related to chronic ischemic small vessel disease, 2 a focal abnormality >5 mm, and 5 cases a score >4 by the age-related white matter changes (ARWMC) scale. Compared with age and sex-matched controls (1:2 ratio), patients showed an increased frequency of periventricular WM vascular degeneration (32% versus 5.2%, p = 0.04) and of severe lesions (ARWMC scale score >4) (26% versus 2.6%, p = 0.05), and a higher overall ARWMC scale score (3.5 ± 1.07 versus 2.0 ± 0.8, mean ± SD, p < 0.0001). Notably, vascular abnormalities suspected for prior partial venous thrombosis, were observed in PNH cases only. MRI lesions were not related to blood counts, hemolytic markers, clone size, disease duration, and therapy with eculizumab. Neurological examination was unremarkable in all patients but one (Parkinson disease). Psychiatric assessment revealed a case of generalized anxiety disorder, 1 bipolar disorder type 2, and 1 adjustment disorder. In conclusion, brain MRI may be useful at diagnosis and during the course of the disease to explore subclinical neurological involvement.
Objective
The study aims at comparing the diagnostic accuracy of qualitative and quantitative assessment of the susceptibility in the precentral gyrus in detecting amyotrophic lateral sclerosis (ALS) ...with predominance of upper motor neuron (UMN) impairment.
Methods
We retrospectively collected clinical and 3T MRI data of 47 ALS patients, of whom 12 with UMN predominance (UMN-ALS). We further enrolled 23 healthy controls (HC) and 15 ALS Mimics (ALS-Mim). The Motor Cortex Susceptibility (MCS) score was qualitatively assessed on the susceptibility-weighted images (SWI) and automatic metrics were extracted from the quantitative susceptibility mapping (QSM) in the precentral gyrus. MCS scores and QSM-based metrics were tested for correlation, and ROC analyses.
Results
The correlation of MCS score and susceptibility skewness was significant (Rho = 0.55,
p
< 0.001). The susceptibility SD showed an AUC of 0.809 with a specificity and positive predictive value of 100% in differentiating ALS and ALS Mim versus HC, significantly higher than MCS (Z = −3.384,
p
-value = 0.00071). The susceptibility skewness value of −0.017 showed specificity of 92.3% and predictive positive value of 91.7% in differentiating UMN-ALS versus ALS mimics, even if the performance was not significantly better than MCS (Z = 0.81,
p
= 0.21).
Conclusion
The MCS and susceptibility skewness of the precentral gyrus show high diagnostic accuracy in differentiating UMN-ALS from ALS-mimics subjects. The quantitative assessment might be preferred being an automatic measure unbiased by the reader.
Clinical relevance statement
The clinical diagnostic evaluation of ALS patients might benefit from the qualitative and/or quantitative assessment of the susceptibility in the precentral gyrus as imaging marker of upper motor neuron predominance.
Key Points
• Amyotrophic lateral sclerosis diagnostic work-up lacks biomarkers able to identify upper motor neuron involvement.
• Susceptibility-weighted imaging/quantitative susceptibility mapping–based measures showed good diagnostic accuracy in discriminating amyotrophic lateral sclerosis with predominant upper motor neuron impairment from patients with suspected motor neuron disorder.
• Susceptibility-weighted imaging/quantitative susceptibility mapping–based assessment of the magnetic susceptibility provides a diagnostic marker for amyotrophic lateral sclerosis with upper motor neuron predominance.
Objectives
The aim of our study was to investigate whether the magnetic susceptibility varies according to the amyotrophic lateral sclerosis (ALS) phenotypes based on the predominance of upper motor ...neuron (UMN)/lower motor neuron (LMN) impairment.
Methods
We retrospectively collected imaging and clinical data of 47 ALS patients (12 with UMN predominance (UMN-ALS), 16 with LMN predominance (LMN-ALS), and 19 with no clinically defined predominance (Np-ALS)). We further enrolled 23 healthy controls (HC) and 15 ALS mimics (ALS-Mim). These participants underwent brain 3-T magnetic resonance imaging (3-T MRI) with T1-weighted and gradient-echo multi-echo sequences. Automatic segmentation and quantitative susceptibility mapping (QSM) were performed. The skewness of the susceptibility values in the precentral cortex (SuscSKEW) was automatically computed, compared among the groups, and correlated to the clinical variables.
Results
The Kruskal-Wallis test showed significant differences in terms of SuscSKEW among groups (
χ
2
(3) = 24.2,
p
< 0.001), and pairwise tests showed that SuscSKEW was higher in UMN-ALS compared to those in LMN-ALS (
p
< 0.001), HC (
p
< 0.001), Np-ALS (
p
= 0.012), and ALS-Mim (
p
< 0.001). SuscSKEW was highly correlated with the Penn UMN score (Spearman’s rho 0.612,
p
< 0.001).
Conclusion
This study demonstrates that the clinical ALS phenotypes based on UMN/LMN sign predominance significantly differ in terms of magnetic susceptibility properties of the precentral cortex. Combined MRI-histopathology investigations are strongly encouraged to confirm whether this evidence is due to iron overload in UMN-ALS, unlike in LMN-ALS.
Key Points
• Magnetic susceptibility in the precentral cortex reflects the prevalence of UMN/LMN impairment in the clinical ALS phenotypes.
• The degree of UMN/LMN impairment might be well described by the automatically derived measure of SuscSKEW in the precentral cortex.
• Increased SuscSKEW in the precentral cortex is more relevant in UMN-ALS patients compared to those in Np-ALS and LMN-ALS patients.
Purpose
To describe normal foetal brain development with high resolution post-mortem MRI (PMMRI) of non-fixed foetal brains.
Methods
We retrospectively collected PMMRIs of foetuses without ...intracranial abnormalities and chromosomal aberrations studied after a termination of pregnancy due to extracranial abnormalities or after a spontaneous intrauterine death. PMMRIs were performed on a 3-T scanner without any fixation and without removing the brain from the skull. All PMMRIs were evaluated in consensus by two neuroradiologists.
Results
Our analysis included ten PMMRIs (median gestational age (GA): 21 weeks; range: 17–28 weeks). At 19 and 20 weeks of GA, the corticospinal tracts are recognisable in the medulla oblongata, becoming less visible from 21 weeks. Prior to 20 weeks the posterior limb of the internal capsule (PLIC) is more hypointense than surrounding deep grey nuclei; starting from 21 weeks the PLIC becomes isointense, and is hyperintense at 28 weeks. From 19–22 weeks, the cerebral hemispheres show transient layers: marginal zone, cortical plate, subplate, and intermediate, subventricular and germinal zones.
Conclusion
PMMRI of non-fixed
in situ
foetal brains preserves the natural tissue contrast and skull integrity. We assessed foetal brain development in a small cohort of foetuses, focusing on 19–22 weeks of gestation.
Key Points
•
Post-mortem magnetic resonance imaging (PMMRI) of non-fixed head is feasible.
•
PMMRI of unfixed in situ foetal brains preserves the natural tissue contrast.
•
PMMRI provide a good depiction of the normal foetal brain development.
•
PMMRI of unfixed in situ foetal brains preserves the skull integrity.
•
PMMRI pattern of foetal brain development at early gestational age is described.
Magnetic resonance imaging (MRI) is a well-established imaging modality which is used in all districts of the musculoskeletal and peripheral nerve systems. More recently, initial studies have applied ...multiparametric MRI to evaluate quantitatively different aspects of musculoskeletal and peripheral nerve diseases, thus providing not only images but also numbers and clinical data. Besides
1
H and
31
P magnetic resonance spectroscopy, diffusion-weighted imaging (DWI) and blood oxygenation level-dependent imaging, diffusion tensor imaging (DTI) is a relatively new MRI-based technique relying on principles of DWI, which has traditionally been used mainly for evaluating the central nervous system to track fibre course. In the musculoskeletal and peripheral nerve systems, DTI has been mostly used in experimental settings, with still few indications in clinical practice. In this review, we describe the potential use of DTI to evaluate different musculoskeletal and peripheral nerve conditions, emphasising the translational aspects of this technique from the experimental to the clinical setting.
RAB39B pathogenic variants cause X-linked Parkinsonism associated with Intellectual Disability, known as Waisman syndrome, a very rare disorder that has been mainly identified through exome ...sequencing in large Parkinson's disease cohorts.
In this study we searched for pathogenic variants in RAB39B in two Italian families affected by X-linked early-onset Parkinsonism and Intellectual Disability.
Three patients received neurological evaluation and underwent RAB39B sequencing.
Two novel RAB39B frameshift variants were found to result in the absence of RAB39B protein (family 1: c.137dupT; family 2: c.371delA). Patients showed unilateral rest tremor and bradykinesia; one of them also displayed an early-onset postural tremor. Paramagnetic substance deposition in the substantia nigra, globus pallidi, red nucleus, putamen and pulvinar was assessed by brain imaging. Two patients also showed moderate calcification of globus pallidi.
In this study we highlight the evidence that X-linked early-onset Parkinsonism associated with Intellectual Disability occurs as a pattern of clinical and neuroimaging features attributable to RAB39B pathogenic variants.
•Loss of RAB39B may lead to X-linked Parkinsonism with Intellectual Disability.•Two novel RAB39B frameshift variants result in the absence of RAB39B protein.•We discuss the syndromic Parkinsonism's variable expression that may affect women.•We support the evidence that neuroimaging adds specific features to the syndrome.•RAB39B somatic mosaicism may be important for unravelling Parkinson's disease.
Background:
Elderly bipolar disorder (BD) and behavioural variant of frontotemporal dementia (bvFTD) may exhibit similar symptoms and both disorders are characterized by selective abnormalities in ...cortical and subcortical regions that are associated with cognitive and emotional impairments. We aimed to investigate common and distinct neural substrates of BD and bvFTD by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques.
Methods:
3-Tesla MRI and 18 fluorodeoxyglucose–PET scans were acquired for 16 elderly BD patients, 23 bvFTD patients with mild cognitive impairments and 68 healthy controls (48 for PET and 20 for MRI analyses).
Results:
BD and bvFTD patients exhibit a different localization of grey matter reductions in the lateral prefrontal cortex, with the first group showing grey matter decrease in the ventrolateral prefrontal cortex and the latter group showing grey matter reductions in the dorsolateral prefrontal cortex as well as unique grey matter and metabolic alterations within the orbitofrontal cortex. The bvFTD group also displayed unique volumetric shrinkage in regions within the temporo-parietal network together with greater metabolic impairments within the temporal cortex and more extensive volumetric and metabolic abnormalities within the limbic lobe. Finally, while the BD group showed greater grey matter volumes in caudate nucleus, bvFTD subjects displayed lower metabolism.
Conclusion:
This MRI-PET study explored, for the first time to the best of our knowledge, structural and functional abnormalities in bvFTD and elderly BD patients, with the final aim of identifying the specific biological signature of these disorders, which might have important implications not only in prevention but also in differential diagnosis and treatment.
We describe a mother and son with focal epilepsy, mild cognitive impairment, and pachygyria, which was parieto‐occipital in the mother and with remarkable posterior greater than anterior severity in ...the son. Overall clinical manifestations, although overlapping in type, were likewise slightly more severe in the son. Using targeted resequencing through a gene panel for malformations of cortical development, we identified the c.655 T > A p.(Trp219Arg) novel missense variant in the LIS1 gene, segregating in the proband and in his mother. Western Blot analysis, qPCR gene expression and RT‐PCR disclosed no significant differences between proband, his parents, and controls. Epilepsy and mild cognitive impairment can be the only clinical presentation of constitutional LIS1 mutations, which can therefore be inherited if the associated phenotype implies limited or no reproductive disadvantage. Parents of patients harboring LIS1 mutations should be assessed for their mutation carrier status.
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