Genetic background of grey matter brain networks related to attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder and is associated with structural grey matter differences in the brain. We investigated the genetic background of some of these brain differences in a sample of 899 adults and adolescents consisting of individuals with ADHD and healthy controls. Previous work in an overlapping sample identified three ADHD-related grey matter brain networks located in areas of the superior, middle, and inferior frontal gyrus as well as the cerebellar tonsil and culmen. We associated these brain networks with protein coding genes using a statistical stability selection approach. We identified ten genes, the most promising of which were NR3C2, TRHDE, SCFD1, GNAO1, and UNC5D. These genes are expressed in brain and linked to neuropsychiatric disorders including ADHD. With our results we aid in the growing understanding of the aetiology of ADHD from genes to brain to behaviour.

Hypothesis on the pathophysiology of syringomyelia based on analysis of phase-contrast magnetic resonance imaging of Chiari-I malformation patients

Background: Despite a number of hypotheses, our understanding of the pathophysiology of syringomyelia is still limited. The current prevailing hypothesis assumes that the piston-like movement of the cerebellar tonsils drives the cerebrospinal fluid (CSF) into the syrinx through the spinal perivascular space. However, it still needs to be verified by further experimental data. A major unexplained problem is how CSF enters and remains in the syrinx that has a higher pressure than the subarachnoid space. Methods: I analyzed phase-contrast MRI scans of 18 patients with Chiari-I malformation with syringomyelia undergoing foramen magnum decompression and 21 healthy volunteers. I analyzed the velocity waveforms of the CSF and the brain in various locations. The obtained velocity waveforms were post-processed using a technique called synchronization in situ. I compared between the preoperative data and the control data (case-control study), as well as between the preoperative and postoperative data (cohort study). Results: The syrinx shrank in 17 (94%) patients with good clinical improvement. In Chiari-I patients, the velocity of the tonsil was significantly larger than controls, but was significantly smaller than that of the CSF in the subarachnoid space, suggesting passive rather than active movement. The abnormal tonsillar movement disappeared after surgery, but the velocity waveform of the spinal subarachnoid CSF did not change. These results, contradicting the above mentioned hypothesis, required an alternative explanation. I thus hypothesized that there is a CSF channel between the fourth ventricle and the syrinx. This channel assumes one-way valve function when mildly compressed by the cyclical movement of the cerebellar tonsil. The decompression of the tonsils switches off the one-way valve, collapsing the syrinx. Conclusions: My hypothesis reasonably explained my data that clearly contradicted the existing hypothesis, and successfully addressed the above-mentioned theoretical problem. It will serve as a working hypothesis for further study of syringomyelia pathophysiology.

Diagnostic utility of parasagittal measurements of tonsillar herniation in Chiari I malformation

Background and purpose Although the cerebellar tonsils are parasagittal structures, the extent of tonsillar herniation (ETH) in Chiari I malformation (CMI) is currently measured in the midsagittal plane. We measured the ETH of each cerebellar tonsil in the parasagittal plane and assessed their diagnostic utility by comparing them to the midsagittal ETH measurements in predicting cough-associated headache (CAH), an indicator of clinically significant disease in CMI. Methods Eighty-five CMI patients with 3D-MPRAGE images were included. Neurosurgeons determined the presence of CAH. Sagittal images were used to measure ETH in the midsagittal (MS_ETH) and parasagittal planes (by locating tonsillar tips on each side on reformatted coronal images). Given the parasagittal ETH (PS_ETH) asymmetry in the majority of cases, they were considered Smaller_PS_ETH or Larger_PS_ETH. The accuracy of ETH measurements was assessed by the receiver operating characteristic (ROC) curve. Results Of 85 patients, 46 reported CAH. ROC analysis showed an area under the curve (AUC) of 0.78 for Smaller_PS_ETH significantly better than 0.65 for MS-ETH in predicting CAH ( p = 0.001). An AUC of 0.68 for Larger_PS_ETH was not significantly different from MS_ETH. The sensitivity and specificity of predicting CAH were 87% and 28% for MS_ETH >6 mm versus 90% and 46% for Smaller_PS_ETH >6 mm, and 52% and 67% for MS_ETH >9 mm versus 48% and 87% for Smaller_PS_ETH >9 mm. At ETH >15 mm, no differences were seen between the measurements. Conclusions Diagnostic utility of ETH measurements in detecting clinically significant CMI can be improved by parasagittal measurements of the cerebellar tonsillar herniation.

Brain Activation of College Students in China With Premenstrual Syndrome Localized by BOLD-fMRI

Background: Most studies on the mechanism behind premenstrual syndrome (PMS) have focused on fluctuating hormones, but little evidence exists regarding functional abnormalities in the affected brain regions of college students. Thus, the aim of this study is to localize PMS's abnormal brain regions by BOLD-fMRI in college students.Methods: Thirteen PMS patients and fifteen healthy control (HC) subjects underwent a BOLD-fMRI scan during the luteal phase induced by depressive emotion pictures. The BOLD-fMRI data were processed by SPM 8 software and rest software based on MATLAB platform. Each cluster volume threshold (cluster) was greater than 389 continuous voxels, and the brain area with single voxel threshold P < 0.05 (after correction) was defined as the area with a significant difference. The emotion report form and the instruction implementation checklist were used to evaluate the emotion induced by picture.Results: Compared to the HC, right inferior occipital gyrus, right middle occipital gyrus, right lingual gyrus, right fusiform gyrus, right inferior temporal gyrus, cerebelum_crus1_R，cerebelum_6_R, culmen, the cerebellum anterior lobe, tuber, cerebellar tonsil of PMS patients were enhanced activation. Sub-lobar，sub-gyral，extra-nuclear，right orbit part of superior frontal gyrus, right middle temporal gyrus, right Orbit part of inferior frontal gyrus, limbic lobe, right insula, bilateral anterior and adjacent cingulate gyrus, bilateral caudate, caudate head, bilateral putamen, left globus pallidus were decreased activation.Conclusion: Our findings may improve our understanding of the neural mechanisms involved in PMS.

The Effects of rs405509 on APOEε4 Non-carriers in Non-demented Aging

BackgroundThere is evidence that the T allele of rs405509 located in the apolipoprotein E (APOE) promotor region is a risk factor for Alzheimer’s disease (AD). However, the effect of the T/T allele on brain function in non-demented aging is still unclear.MethodsWe analyzed the effects of the rs405509 T/T allele on cognitive performances using multiple neuropsychological tests and local brain function using resting-state functional magnetic resonance imaging (rs-fMRI).ResultsSignificant differences were found between T/T carriers and G allele carriers on general cognitive status, memory, and attention (p &lt; 0.05). Rs-fMRI analyses demonstrated decreased amplitude of low frequency fluctuation (ALFF) in the right middle frontal gyrus, decreased percent amplitude of fluctuation (PerAF) in the right middle frontal gyrus, increased regional homogeneity (ReHo) in the right cerebellar tonsil and decreased ReHo in the right putamen, and decreased degree centrality (DC) in the left middle frontal gyrus (p &lt; 0.05, corrected). Furthermore, significant correlations were found between cognitive performance and these neuroimaging changes (p &lt; 0.05).ConclusionThese findings suggest that T/T allele may serve as an independent risk factor that can influence brain function in different regions in non-demented aging.

Gray matter networks associated with attention and working memory deficit in ADHD across adolescence and adulthood

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neuropsychiatric disorder and may persist into adulthood. Working memory and attention deficits have been reported to persist from childhood to adulthood. How neuronal underpinnings of deficits differ across adolescence and adulthood is not clear. In this study, we investigated gray matter of two cohorts, 486 adults and 508 adolescents, each including participants from ADHD and healthy controls families. Two cohorts both presented significant attention and working memory deficits in individuals with ADHD. Independent component analysis was applied to the gray matter of each cohort, separately, to extract cohort-inherent networks. Then, we identified gray matter networks associated with inattention or working memory in each cohort, and projected them onto the other cohort for comparison. Two components in the inferior, middle/superior frontal regions identified in adults and one component in the insula and inferior frontal region identified in adolescents were significantly associated with working memory in both cohorts. One component in bilateral cerebellar tonsil and culmen identified in adults and one component in left cerebellar region identified in adolescents were significantly associated with inattention in both cohorts. All these components presented a significant or nominal level of gray matter reduction for ADHD participants in adolescents, but only one showed nominal reduction in adults. Our findings suggest although the gray matter reduction of these regions may not be indicative of persistency of ADHD, their persistent associations with inattention or working memory indicate an important role of these regions in the mechanism of persistence or remission of the disorder.

Posttraumatic Delayed Jugular Foramen Syndrome in a Toddler

Background Multiple lower cranial nerve palsies have been attributed to occipital condyle fractures in older children and adults, but no clinical details of other possible mechanisms have been described in infants. Case Report A 33-month-old boy suffered blunt head trauma. A bilateral skull base fracture was diagnosed, with favorable outcome during the first days after trauma. On the sixth day, the patient began to refuse drinking and developed hoarseness. Physical examination and additional investigations revealed paralysis of left VII, IX, X, and XI cranial nerves. A follow-up computed tomography (CT) scan disclosed a left petrous bone fracture involving the lateral margin of the jugular foramen, and a cranial magnetic resonance imaging (MRI) study showed a left cerebellar tonsil contusion. He improved after methylprednisolone was started. Three months later, he was asymptomatic, although mild weakness and atrophy of the left sternocleidomastoid and trapezius muscles remained 1 year later. Discussion A posttraumatic “jugular foramen syndrome” is rare in children, but it has been reported shortly after occipital condyle fracture, affecting mainly IX, X, and XI cranial nerves. In this toddler, delayed symptoms appeared with unilateral involvement. While an occipital fracture was ruled out, neuroimaging findings suggest the hypothesis of a focal contusion as a consequence of a coup-contrecoup injury. Conclusion This exceptional case highlights the importance of gathering physical examination, anatomical correlation, and neuroimaging to yield a diagnosis.

Acquired Chiari Type 1 Malformation Secondary to Paget’s Disease of the Bone: A Case Report

Chiari type 1 malformations are characterised by caudal descent of cerebellar tonsil into foramen magnum. Usually it is congenital. Paget’s disease causing acquired chiari type 1 malformation is rare with only five reported cases in the literature. The diagnosis is primarily by Magnetic Resonance Imaging (MRI). Authors reported a case of acquired chiari type 1 malformation due to paget’s disease in a 58-year-old male patient diagnosed by MRI and Computed Tomography (CT). The patient presented with complaints of headache, unsteady gait, slow movements with weakness in all the four limbs, difficulty in walking which aggravated since three days and stammering of speech. Initially a diagnosis of motor neuron disease was suspected and the patient was subjected for MRI examination of brain and spine. MRI revealed platybasia with cerebellar tonsillar herniation with calvarial thickening and multiple vertebral collapse. The CT of brain and spine was done to evaluate bones specifically in view of thickened cranial vault and multiple vertebral collapse on MRI which revealed features of paget’s disease in the form of widened sclerotic bone with lytic areas and thickened trabeculae. Hence, diagnosis of paget’s disease causing acquired chiari type 1 malformation was made which correlated with biochemical findings. The management is different in primary and acquired chiari type 1 malformation and hence it is important to diagnose this condition which is relatively rare.

Spontaneous cerebrospinal fluid leak via foramen rotundum in a non-obese male presented as pseudo-Chiari malformation type I: a case report and literature review

Spontaneous cerebrospinal fluid (sCSF) leak from the skull base has been previously reported, but there are few reports of sCSF leak from the foramen rotundum due to its rare occurrence. This case report describes a 15-year-old male patient that presented with left side watery rhinorrhoea that had been present since he was 4 years of age and a history of repeated bouts of meningitis of unknown cause. A discharge sample from the nose tested positive for beta-2 transferrin. Preoperative computed tomography (CT) revealed a fistula between the cerebellopontine angle and the left sphenoid sinus. There was also a pseudo-Chiari malformation type I with ectopia of the cerebellar tonsil. Endoscopic transnasal surgery identified a leak from the foramen rotundum that was repaired using autologous material and a contralateral pedicle nasoseptal flap. At 6 months after surgery, the patient reported no recurrence of the CSF leakage. Postoperative CT imaging revealed that the cerebellar tonsil was back in the normal position, indicating that the preoperative Chiari malformation was possibly due to decreased CSF volume. This current case shows that a rare case of sCSF leak from the foramen rotundum can be effectively repaired using the endoscopic transnasal approach.