Periventricular Region Research Articles

Lesion location across diagnostic regions in multiple sclerosis

BackgroundLesions in the periventricular, (juxta)cortical, and infratentorial region, as visible on brain MRI, are part of the diagnostic criteria for Multiple sclerosis (MS) whereas lesions in the subcortical region are currently only a marker of disease activity. It is unknown whether MS lesions follow individual spatial patterns or whether they occur in a random manner across diagnostic regions. AimFirst, to describe cross-sectionally the spatial lesion patterns in patients with MS. Second, to investigate the spatial association of new lesions and lesions at baseline across diagnostic regions. MethodsExperienced neuroradiologists analyzed brain MRI (3D, 3T) in a cohort of 330 early MS patients. Lesions at baseline and new solitary lesions after two years were segmented (manually and by consensus) and classified as periventricular, (juxta)cortical, or infratentorial (diagnostic regions) or subcortical—with or without Gadolinium-enhancement. Gadolinium enhancement of lesions in the different regions was compared by Chi square test. New lesions in the four regions served as dependent variable in four zero-inflated Poisson models each with the six independent variables of lesions in the four regions at baseline, age and gender. ResultsAt baseline, lesions were most often observed in the subcortical region (mean 13.0 lesions/patient), while lesion volume was highest in the periventricular region (mean 2287 µl/patient). Subcortical lesions were less likely to show gadolinium enhancement (3.1 %) than juxtacortical (4.3 %), periventricular (5.3 %) or infratentorial lesions (7.2 %). Age was inversely correlated with new periventricular, juxtacortical and subcortical lesions. New lesions in the periventricular, juxtacortical and infratentorial region showed a significant autocorrelative behavior being positively related to the number of lesions in the respective regions at baseline. New lesions in the subcortical region showed a different behavior with a positive association with baseline periventricular lesions and a negative association with baseline infratentorial lesions. ConclusionAcross regions, new lesions do not occur randomly; instead, new lesions in the periventricular, juxtacortical and infratentorial diagnostic region are associated with that at baseline. Lesions in the subcortical regions are more closely related to periventricular lesions. Moreover, subcortical lesions substantially contribute to lesion burden in MS but are less likely to show gadolinium enhancement (than lesions in the diagnostic regions).

White-matter abnormalities in presymptomatic GRN and C9orf72 mutation carriers.

A large proportion of familial frontotemporal dementia is caused by TAR DNA-binding protein 43 (transactive response DNA-binding protein 43 kDa) proteinopathies. Accordingly, carriers of autosomal dominant mutations in the genes associated with TAR DNA-binding protein 43 aggregation, such as Chromosome 9 open reading frame 72 (C9orf72) or progranulin (GRN), are at risk of later developing frontotemporal dementia. Brain imaging abnormalities that develop before dementia onset in mutation carriers may serve as proxies for the presymptomatic stages of familial frontotemporal dementia due to a genetic cause. Our study objective was to investigate brain MRI-based white-matter changes in predementia participants carrying mutations in C9orf72 or GRN genes. We analysed mutation carriers and their family member controls (noncarriers) from the University of British Columbia familial frontotemporal dementia study. First, a total of 42 participants (8 GRN carriers; 11 C9orf72 carriers; 23 noncarriers) had longitudinal T1-weighted MRI over ∼2 years. White-matter signal hypointensities were segmented and volumes were calculated for each participant. General linear models were applied to compare the baseline burden and the annualized rate of accumulation of signal abnormalities among mutation carriers and noncarriers. Second, a total of 60 participants (9 GRN carriers; 17 C9orf72 carriers; 34 noncarriers) had cross-sectional diffusion tensor MRI available. For each participant, we calculated the average fractional anisotropy and mean, radial and axial diffusivity parameter values within the normal-appearing white-matter tissues. General linear models were applied to compare whether mutation carriers and noncarriers had different trends in diffusion tensor imaging parameter values as they neared the expected age of onset. Baseline volumes of white-matter signal abnormalities were not significantly different among mutation carriers and noncarriers. Longitudinally, GRN carriers had significantly higher annualized rates of accumulation (estimated mean: 15.87%/year) compared with C9orf72 carriers (3.69%/year) or noncarriers (2.64%/year). A significant relationship between diffusion tensor imaging parameter values and increasing expected age of onset was found in the periventricular normal-appearing white-matter region. Specifically, GRN carriers had a tendency of a faster increase of mean and radial diffusivity values and C9orf72 carriers had a tendency of a faster decline of fractional anisotropy values as they reached closer to the expected age of dementia onset. These findings suggest that white-matter changes may represent early markers of familial frontotemporal dementia due to genetic causes. However, GRN and C9orf72 mutation carriers may have different mechanisms leading to tissue abnormalities.

Parietal and occipital leukoaraiosis due to cerebral ischaemic lesions decrease the driving safety performance of healthy older adults

Leukoaraiosis, a common ischaemic lesion diagnosed using magnetic resonance imaging (MRI), can influence driving safety performance (DSP). Most older drivers with leukoaraiosis are unaware of their affliction. Japan is a super-aged country, where preventing accidents caused by older drivers is an urgent national issue. We investigated the subcortical and periventricular leukoaraiosis regions that were most involved in DSP decline. The driving skills of 101 drivers (49 men, 52 women; mean age, 77.88 ± 3.77 years) without dementia were assessed by official driving instructors, using actual vehicles on a closed-circuit course. Parietal and occipital (but not frontal or temporal) leukoaraiosis volumes were significantly correlated with decreased DSP scores regardless of age, especially when turning right at intersections, which needs more attention than turning left because left-side driving is legally enforced in Japan. Occipital leukoaraiosis was also involved via a decline in dynamic visual cognitive function. MRI-based assessment of leukoaraiosis volume and localisation may enable the identification of older drivers prone to DSP deterioration. Risk factors for leukoaraiosis include smoking and lifestyle-related diseases such as hypertension. Thus, brain healthcare in patients with MRI-diagnosed leukoaraiosis may be particularly useful for the risk management of traffic accidents caused by the elderly in Japan.

White matter hyperintensities in Down syndrome: associations with demographic, genetic, fluid and imaging biomarkers of Alzheimer's disease

AbstractBackgroundStrong associations between age, Alzheimer’s disease (AD), and vascular risk factors create challenges to delineate the specific relationships between white matter hyperintensities (WMH) and AD pathophysiology. Down syndrome (DS), a genetically determined form of AD, is not typically complicated by systematic vascular risk factors like hypertension and atherosclerosis and can therefore provide critical information in this regard. We aim to further characterize topography of WMH in DS along the AD continuum and define associations with demographic, genetic, fluid and other imaging biomarkers.MethodIn this cross‐sectional study, adults with DS from Down‐Alzheimer Barcelona Neuroimaging Initiative (DABNI) underwent a 3T‐MRI protocol, including 3D‐T1 and 3D‐FLAIR acquisitions. Gray matter (GM) volumes were computed using the CAT12 Toolbox. WMH were segmented using the lesion prediction algorithm implemented in the Lesion Segmentation Toolbox for SPM12. Segmented maps were binarized (threshold of 0.5) and WMH volumes were extracted in each brain lobe, subregions of the corpus callosum, and periventricular versus deep regions (using the standard 10mm limit from the lateral ventricles). Non‐parametric statistical tests were used to assess effects of disease severity on WMH and define associations between WMH and demographic and genetic data, CSF AD biomarkers and GM volumes.ResultsWe included 116 individuals with DS (Table 1). WMH volume was higher in prodromal and demented groups for all brain regions (Fig 1). Moreover, WMH increased with disease severity such that the demented group demonstrated larger WMH volume than the prodromal group in periventricular regions, frontal and temporal lobes, and body and splenium subregions of the corpus callosum. Total WMH volume was associated with age but not sex, intellectual disability or APOE haplotype (Fig 2). Total WMH volume was negatively related to CSF Aβ42/40 ratio and positively related to CSF t‐tau and p‐tau‐181 concentrations (Fig 3). Associations with GM volumes were widespread, but strongest in parieto‐occipital‐temporal regions.ConclusionWMH increases with AD pathology and the emergence of clinical symptoms in DS, a population with lower vascular risk factors. It also relates to neurodegeneration in typical AD regions at both asymptomatic and symptomatic stages. Altogether, this suggests that WMH might be intrinsically related to AD pathophysiological processes.

Improvement of erectile dysfunction using endothelial progenitor cells from fetal cerebral vasculature in the cavernous nerve injury of rats

BackgroundBecause of limited differentiation to endothelium from mesenchymal stem cells, it has been strongly recommended to use endothelial progenitor cells for the regeneration of the damaged endothelium of corpora cavernosa. This study was performed to investigate the immortalized human cerebral endothelial cells and their capability for repairing erectile dysfunction in a rat model of cavernous nerve injury. Circulating endothelial progenitor cells were isolated from human fetal brain vasculature at the periventricular region of telencephalic tissues. Over 95% of CD 31-positive cells were sorted and cultured for 10 days. Human cerebral endothelial progenitor cells were injected into the cavernosa of rats with cavernous nerve injury. Erectile response was then assessed. In in vivo assays, rats were divided into three groups: group 1, sham operation: group 2, bilateral cavernous nerve injury: and group 3, treatment with human cerebral endothelial cells after cavernous nerve injury.ResultsEstablished immortalized circulating endothelial progenitor cells showed expression of human telomerase reverse transcriptase transcript by RT-PCR. They also showed the expression of vascular endothelial growth factor, von Willebrand factor, vascular endothelial growth factor receptor, and CD31, cell type-specific markers for endothelial cells by RT-PCR. In in vitro angiogenesis assays, they demonstrated tube formation that suggested morphological properties of endothelial progenitor cells. In in vivo assays, impaired erectile function of rat with cavernous nerve injury recovered at 2, 4, and 12 weeks after transplantation of human cerebral endothelial cells into the cavernosa.ConclusionsTelomerase reverse transcriptase-circulating endothelial progenitor cells from fetal brain vasculature could repair erectile dysfunction of rats with cavernous nerve injury.

Increased relative biological effectiveness and periventricular radiosensitivity in proton therapy of glioma patients

PurposeCurrently, there is an intense debate on variations in intra-cerebral radiosensitivity and relative biological effectiveness (RBE) in proton therapy of primary brain tumours. Here, both effects were retrospectively investigated using late radiation-induced brain injuries (RIBI) observed in follow-up after proton therapy of patients with diagnosed glioma. MethodsIn total, 42 WHO grade 2–3 glioma patients out of a consecutive patient cohort having received (adjuvant) proton radio(chemo)therapy between 2014 and 2017 were eligible for analysis. RIBI lesions (symptomatic or clinically asymptomatic) were diagnosed and delineated on contrast-enhanced T1-weighted magnetic resonance imaging scans obtained in the first two years of follow-up. Correlation of RIBI location and occurrence with dose (D), proton dose-averaged linear energy transfer (LET) and variable RBE dose parameters were tested in voxel- and in patient-wise logistic regression analyses. Additionally, anatomical and clinical parameters were considered. Model performance was estimated through cross-validated area-under-the-curve (AUC) values. ResultsIn total, 64 RIBI lesions were diagnosed in 21 patients. The median time between start of proton radio(chemo)therapy and RIBI appearance was 10.2 months. Median distances of the RIBI volume centres to the cerebral ventricles and to the clinical target volume border were 2.1 mm and 1.3 mm, respectively. In voxel-wise regression, the multivariable model with D, D × LET and periventricular region (PVR) revealed the highest AUC of 0.90 (95 % confidence interval: 0.89–0.91) while the corresponding model without D × LET revealed a value of 0.84 (0.83–0.86). In patient-level analysis, the equivalent uniform dose (EUD11, a = 11) in the PVR using a variable RBE was the most prominent predictor for RIBI with an AUC of 0.63 (0.32–0.90). ConclusionsIn this glioma cohort, an increased radiosensitivity within the PVR was observed as well as a spatial correlation of RIBI with an increased RBE. Both need to be considered when delivering radio(chemo)therapy using proton beams.

Stereology of gonadotropin-releasing hormone and kisspeptin neurons in PACAP gene-deficient female mice.

The hypothalamic gonadotropin-releasing hormone (GnRH)-kisspeptin neuronal network regulates fertility in all mammals. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide isolated from the hypothalamus that is involved in the regulation of several releasing hormones and trop hormones. It is well-known that PACAP influences fertility at central and peripheral levels. However, the effects of PACAP on GnRH and kisspeptin neurons are not well understood. The present study investigated the integrity of the estrous cycle in PACAP-knockout (KO) mice. The number and immunoreactivity of GnRH (GnRH-ir) neurons in wild-type (WT) and PACAP KO female mice were determined using immunohistochemistry. In addition, the number of kisspeptin neurons was measured by counting kisspeptin mRNA-positive cells in the rostral periventricular region of the third ventricle (RP3V) and arcuate nucleus (ARC) using the RNAscope technique. Finally, the mRNA and protein expression of estrogen receptor alpha (ERα) was also examined. Our data showed that the number of complete cycles decreased, and the length of each cycle was longer in PACAP KO mice. Furthermore, the PACAP KO mice experienced longer periods of diestrus and spent significantly less time in estrus. There was no difference in GnRH-ir or number of GnRH neurons. In contrast, the number of kisspeptin neurons was decreased in the ARC, but not in the R3PV, in PACAP KO mice compared to WT littermates. Furthermore, ERα mRNA and protein expression was decreased in the ARC, whereas in the R3PV region, ERα mRNA levels were elevated. Our results demonstrate that embryonic deletion of PACAP significantly changes the structure and presumably the function of the GnRH-kisspeptin neuronal network, influencing fertility.

Novel Insight into the Role of the Kiss1/GPR54 System in Energy Metabolism in Major Metabolic Organs.

The Kiss1/GPR54 system is a multifunctional genetic system with an essential role in regulating energy balance and metabolic homeostasis. In the mammalian hypothalamus, two major populations of neurons, the rostral periventricular region of the third ventricle (RP3V) and the arcuate nucleus (ARC), produced kisspeptin. Kiss1ARC neurons input kisspeptin and glutamate to feeding-associated neurons to regulate energy intake and expenditure balance. Kisspeptin in the peripheral circulation is involved in lipid accumulation in adipose tissue. In the hepatic and pancreatic circuits, kisspeptin signaling affects insulin secretion, suggesting the critical role of the Kiss1/GPR54 system in regulating glucose and lipid metabolism. In addition, this review also predicts the role of the Kiss1/GPRS4 system in skeletal muscle in association with exercise performance. Recent studies have focused on the link between kisspeptin signaling and energy homeostasis, further investigation of potential function is warranted. Therefore, this review summarizes the role of the Kiss1/GPRS4 system in the major metabolic organs in relation to energy metabolism homeostasis, aiming to endow the reader with a critical and updated view of the Kiss1/GPR54 system in energy metabolism.

Etiology- and region-specific characteristics of transependymal cerebrospinal fluid flow.

Transependymal flow (TEF) of CSF, often delineated as T2-weighted hyperintensity adjacent to the lateral ventricles on MRI, is a known imaging finding, usually in the setting of CSF flow disturbances. Specific radiological features of TEF and their relationships with clinical markers of hydrocephalus and underlying disease pathology are not known. Here, the authors describe the radiological features and clinical associations of TEF with implications for CSF circulation in the setting of intracranial pathology. After obtaining IRB review and approval, the authors reviewed the radiological records of all patients who underwent intracranial imaging with CT or MRI at St. Louis Children's Hospital, St. Louis, Missouri, between 2008 and 2019 to identify individuals with TEF. Then, under direct review of imaging, TEF pattern, degree, and location and underlying pathology and other radiological and clinical features pertaining to CSF circulation and CSF disturbances were noted. TEF of CSF was identified in 219 patients and was most prevalent in the setting of neoplasms (72%). In 69% of the overall cohort, TEF was seen adjacent to the anterior aspect of the frontal horns and the posterior aspect of the occipital horns of the lateral ventricles, and nearly half of these patients also had TEF dorsal to the third ventricle near the splenium of the corpus callosum. This pattern was independently associated with posterior fossa medulloblastoma when compared with pilocytic astrocytoma (OR 4.75, 95% CI 1.43-18.53, p = 0.0157). Patients with congenital or neonatal-onset hydrocephalus accounted for 13% of patients and were more likely to have TEF circumferentially around the ventricles without the fronto-occipital distribution. Patients who ultimately required permanent CSF diversion surgery were more likely to have the circumferential TEF pattern, a smaller degree of TEF, and a lack of papilledema at the time of CSF diversion surgery. CSF transmigration across the ependyma is usually restricted to specific periventricular regions and is etiology specific. Certain radiological TEF characteristics are associated with tumor pathology and may reflect impaired or preserved ependymal fluid handling and global CSF circulation. These findings have implications for TEF as a disease-specific marker and in understanding CSF handling within the brain.

Magnetic resonance imaging features of isolated periventricular heterotopia in pediatric epilepsy: a comparative study

Periventricular nodular heterotopia is a neurodevelopmental disorder in which neurons fail to migrate to the cortical surface, forming discrete areas of grey matter adjacent to the lateral ventricles. Given that periventricular nodular heterotopia is seen as an incidental finding in patients without epilepsy, causality between periventricular nodular heterotopia and epilepsy cannot be assumed. Furthermore, the structural characteristics of periventricular nodular heterotopia in patients with epilepsy are poorly defined and can be misleading. In this article, we investigate whether structural radiological characteristics of heterotopia can predict epileptogenicity in pediatric patients. Pediatric patients with periventricular nodular heterotopia, but no other epilepsy-associated cortical abnormalities on magnetic resonance imaging, were identified and divided into two groups: with epilepsy and without epilepsy. Radiological characteristics of laterality, regionalization, largest dimension and number of nodules were compared between the two groups. Only periventricular nodular heterotopia spreading across several regions was associated with a statistically higher chance of epilepsy. Other features including laterality, individual region, number and largest dimension did not reliably predict epileptogenicity. Most radiological characteristics of periventricular nodular heterotopia are similar in patients with and without epilepsy. The involvement of multiple periventricular regions with heterotopia was the only feature that inferred a higher risk of epilepsy. Periventricular nodular heterotopia requires a comprehensive work-up and should be interpreted in the context of each individual patient and not assumed to be directly causative of epilepsy, nor unrelated to it. Therefore, further studies using additional structural and functional imaging modalities are needed to determine the radiological features of epileptogenic periventricular nodular heterotopia.

Multiple Sclerosis – Challenges in Diagnosis

Multiple Sclerosis is an inflammatory demyelinating disease that affects the central nervous system, and is uncommon among the Asian population. It can present with a variety of symptoms, depending on the location of the demyelinating plaques, which could also potentially mimic a range of neurological and non-neurological disorders. We report a 24-year-old woman who presented with recurrent non-specific lower limb numbness, without any other neurological symptoms or signs. The symptoms were presumed to be nonspecific, but they re-occurred eight months later, leading to a more extensive investigation, including whole spine and brain MRI. The MRI showed multiple white matter lesions that are hyperintense on T2W/FLAIR, seen at the right corona radiata, bilateral parietal lobes, right periventricular region and spinal cord, with a simultaneous presence of gadolinium-enhancing and nonenhancing lesions, fulfilling 2017 Mc Donald’s diagnostic criteria for multiple sclerosis. After the careful exclusion of differential diagnoses, she was given pulsed IV methylprednisolone for 5 days, followed by oral teriflunomide. She improved partially, and at 2 months following discharge, she was tolerating the medication well with no further relapses.

Multiple Sclerosis – Challenges in Diagnosis

Multiple Sclerosis is an inflammatory demyelinating disease that affects the central nervous system, and is uncommon among the Asian population. It can present with a variety of symptoms, depending on the location of the demyelinating plaques, which could also potentially mimic a range of neurological and non-neurological disorders. We report a 24-year-old woman who presented with recurrent non-specific lower limb numbness, without any other neurological symptoms or signs. The symptoms were presumed to be nonspecific, but they re-occurred eight months later, leading to a more extensive investigation, including whole spine and brain MRI. The MRI showed multiple white matter lesions that are hyperintense on T2W/FLAIR, seen at the right corona radiata, bilateral parietal lobes, right periventricular region and spinal cord, with a simultaneous presence of gadolinium-enhancing and nonenhancing lesions, fulfilling 2017 Mc Donald’s diagnostic criteria for multiple sclerosis. After the careful exclusion of differential diagnoses, she was given pulsed IV methylprednisolone for 5 days, followed by oral teriflunomide. She improved partially, and at 2 months following discharge, she was tolerating the medication well with no further relapses.

Acute Cognitive Dysfunction in a Patient With Traumatic Brain Injury: A Clinical Vignette.

Acute Cognitive Dysfunction in a Patient With Traumatic Brain Injury: A Clinical Vignette.

Modeling Neonatal Intraventricular Hemorrhage through Intraventricular Injection of Hemoglobin.

Neonatal intraventricular hemorrhage (IVH) is a common consequence of premature birth and leads to brain injury, posthemorrhagic hydrocephalus (PHH), and lifelong neurological deficits. While PHH can be treated by temporary and permanent cerebrospinal fluid (CSF) diversion procedures (ventricular reservoir and ventriculoperitoneal shunt, respectively), there are no pharmacological strategies to prevent or treat IVH-induced brain injury and hydrocephalus. Animal models are needed to better understand the pathophysiology of IVH and test pharmacological treatments. While there are existing models of neonatal IVH, those that reliably result in hydrocephalus are often limited by the necessity for large-volume injections, which may complicate modeling of the pathology or introduce variability in the clinical phenotype observed. Recent clinical studies have implicated hemoglobin and ferritin in causing ventricular enlargement after IVH. Here, we develop a straightforward animal model that mimics the clinical phenotype of PHH utilizing small-volume intraventricular injections of the blood breakdown product hemoglobin. In addition to reliably inducing ventricular enlargement and hydrocephalus, this model results in white matter injury, inflammation, and immune cell infiltration in periventricular and white matter regions. This paper describes this clinically relevant, simple method for modeling IVH-PHH in neonatal rats using intraventricular injection and presents methods for quantifying ventricle size post injection.

Minimally Invasive Resection of Intraventricular Pilocytic Astrocytoma Using the Aurora Surgiscope in an Adult Patient: Technical Note

Pilocytic astrocytomas account for approximately 5%-6% of all gliomas and are most commonly diagnosed between the ages of 8 and 13 years. Although they may occur throughout the neuraxis, approximately two thirds arise from the cerebellum and optic pathway. Other locations of origin include midline structures such as thalamus, hypothalamus, and periventricular regions. Surgical approaches to lateral or third ventricular tumors include anterior transcallosal, subfrontal translamina terminalis, and anterior transcortical approaches. The Aurora Surgiscope is a single-use, disposable minimally invasive neurological endoscope designed for intraparenchymal hemorrhage evacuation. We present the successful use of this system to aid resection of a large intraventricular pilocytic astrocytoma. A 29-year-old man presented with signs of developing hydrocephalus and was found to have a large intraventricular tumor, which was later identified to be a rare intraventricular pilocytic astrocytoma. A ventriculostomy was performed as a temporizing measure, and he was transferred to our tertiary care facility for surgical management. Sulcal dissection was performed, and the endoscope was inserted to create a minimally invasive corridor to the lateral ventricle. Using the endoscope, bimanual surgery using multiple instruments simultaneously was possible and enabled gross total resection of the tumor. The patient tolerated the procedure well and was discharged at his neurological baseline level. Extensive sulcal dissection preceding placement of the endoscope allowed access to the intraventricular space with minimal passage of parenchymal tissue. High-definition visualization was provided and allowed the operating surgeon to freely use both hands during surgery.

Presentations and Treatment of Multiple Sclerosis in Pakistan: A Retrospective Review of 188 Cases.

Approximately 10 out of every 100,000 people in Pakistan have multiple sclerosis (MS), yet there is a dearth of research on MS in the country, with most prior studies limited by small sample sizes. We wish to report on the largest study of MS patients from Pakistan. The objectives of this study were to identify demographic characteristics, disease characteristics, hospitalization causes, and past and current treatments of patients with MS in Pakistan. A retrospective review of patient records of all patients diagnosed with MS was carried out at the Department of Medicine at the Aga Khan University Hospital in Karachi and the Pakistan Institute of Medical Sciences in Islamabad. Medical records were used to generate a list of patients who were admitted at participating centers with a diagnosis of MS between December 2019 and September 2020. The diagnosis of MS was based on McDonald criteria. The study was approved by the ethics review committees of both participating centers.The study included 188 patients (mean age, 31.1 ± 11.22 years), with 37.2% men and 62.8% women. Relapsing-remitting MS was the most common type (81%), followed by primary progressive (10%) and secondary progressive (9%). The most common finding on T2-weighted fluid-attenuated inversion recovery MRI sequences was the presence of multiple foci (69.2%), most seen in the periventricular region (52.1%), followed by the juxtacortical region (49.3%). A single focus of gadolinium enhancement was observed in 20% of patients, most seen in the spinal cord (23.9%), followed by the periventricular area (18.1%).Medication infusion was the most common reason for hospitalization, reported in 16% of cases, followed by exacerbation of MS in 13.8% cases, and infection in 4.3% cases. Ocrelizumab (5.3%), steroids (3.8%), and rituximab (3.2%) were the most common treatments prescribed. Patients had been treated previously with oral and intravenous steroids, azathioprine, and mitoxantrone, as shown in TABLE 1.A detailed study of MRI lesions found multiple foci to be the most prevalent (69.2%), with periventricular and juxtacortical lesions the most common sites (52.1% and 49.3%, respectively). Incidental MS was reported in less than 1% of MRI scans.1 Disease characteristics and MRI findings in our group of MS patients were consistent with publications from other parts of the world.2 We explored reasons for hospitalization, the most common of which were MS exacerbation and medication infusions. Most patients (83%) were not taking any medications at their most recent evaluation. A prior study stated that 95% of patients received pulse steroids.3,4 Other treatments mentioned in literature include interferon beta, methotrexate, mitoxantrone,4,5 ocrelizumab, teriflunomide, alemtuzumab, and, per informal reports from neurologists, rituximab and azathioprine.3 Wasay et al found that less than one-fourth of all patients received disease-modifying therapies, of which 11% received methotrexate, 10% received mitoxantrone, and 1% received interferon beta therapy.4 However, recent years have seen a rise in the use of disease-modifying therapies due to an aggressive disease course or secondary progressive MS.6

Intraventricular hemorrhage in extremely low birth weight infant: a case report

This article focuses on the problem of intraventricular hemorrhage in preterm infants with low and extremely low body weight. Premature newborns are most susceptible to this pathology due to the morpho-functional immaturity of brain tissues and blood vessels. Pathological factors lead to lesion of the vessel wall and a massive hemorrhage in the cavity of the ventricles, sometimes with a breakthrough into the white matter. The morphological findings of hemorrhage in the lateral ventricles of the brain in a child born with extremely low body weight are presented on an example of a clinical case. The article presents a description of the morphology of damage to the germinal matrix and choroid plexus as one of the most common sources of hemorrhage. The main attention is paid to the state of the blood vessels: arterioles, venules, capillaries. Possible causes and consequences of vascular injury in the periventricular region are indicated here. According to the recent studies, intraventricular hemorrhage appears more often due to damage to the choroid plexus in children born at 37 weeks of gestation and later. In this report we consider the problem of hemorrhage from the reducing germinal matrixs vessels into the subependymal region with spreading into the white matter and lateral ventricles.

A Complicated Case of Catatonia

IntroductionMany different causes of catatonia are well-documented in medicine. Modern understanding of catatonia has evolved in the last 100 years with the suggestion that there is a root cause in neuroinflammation. This is a case report of a young woman who presented to the emergency department with altered mental status, found to have catatonia responsive to lorazepam, with the underlying etiology being a diagnosis of multiple sclerosis.ObjectivesA case-based approach is used to support the following learning objectives: - Review the diagnostic criteria for catatonia - Distinguish between simple and malignant catatonia - Review the Bush-Francis Scale - Review available treatmentMethodsMother brings 24-year-old woman into the hospital for altered mental status and changes in behavior including staring spells, periods of withdrawal, refusal to eat, lack of purposeful movement, apraxia, and mutism that worsened 24 hours prior to presentation.ResultsThe patient was afebile with negative covid-19 test. Recent diagnosis of Bell’s palsy treated with antivirals and oral steroird, which terminated just prior to presentation. Additionally, patient had outpatient treatment for vertigo. Lumbar puncture was negative for an infectious process. MRI revealed multiple stable white matter lesions in the periventricular, pontine, and subcortical regions, some oriented perpendicular to the corpus callosum.ConclusionsThis case of a 24-year-old woman with catatonia brought an opportunity to retrospectively review a case in detail in order to feature learning objectives that review very important considerations in the evaluation, differential diagnosis, symptom tracking, and treatment of catatonia. The future of research in catatonia is bright and diverse.DisclosureNo significant relationships.

Neuromyelitis Optica and Differential Diagnosis (mimics)

Neuromyelitis Optica is an inflammatory neurodegenerative demyelinating autoimmune channelopathy affecting brain and spinal cord, for which Aquaporin-4(AQP4) water channels are the main target. Discovery of the AQP4 immunoglobulin (IGG) antibody in 2004 was a major step for understanding the disease which helped to distinguish from multiple sclerosis and other demyelinating diseases. Aquaporin -4 (AQP4) is a water channel protein expressed in two major isoforms which includes a short isoform M1 and a isoform M23 , AQP4 is expressed heavily on astrocyte endfeet end process at blood brain barrier, nodes of Ranvier and neuronal synapses processes in spinal cord, optic nerves , brain stem, thalamus ,hypothalamus, dorsal medulla at area postrema, diencephalon, subcortical white matter, gray and white matter in spinal cord, periaqueductal and periventricular region.

Chronic Stress and Ovulatory Dysfunction: Implications in Times of COVID-19

Stress is known to be associated with adverse health outcomes. The COVID-19 pandemic and its associated lockdowns are examples of chronic stressors. Lockdown measures inadvertently caused significant psychological distress and became a powerful source of anxiety/stress, sleep disturbances, nutritional changes and weight gain. Stress is known to impact women's health specifically, through hypothalamic-pituitary-gonadal (HPG) axis dysfunction and resultant ovulatory dysfunction. Such dysfunction may manifest in menstrual irregularities and/or infertility due to hypothalamic hypogonadism. Here, we review the key physiological mediators of stress and associated ovulatory dysfunction. The kisspeptinergic system is comprised of sets of neurons located in the hypothalamus, the rostral periventricular region of the third ventricle (RP3V) and the arcuate nucleus (ARC). This system links nutrition, reproductive signals and stress. It plays a key role in the function of the HPG axis. During chronic stress, the kisspeptinergic system affects the HPG axis, GnRH pulsatility, and, therefore, ovulation. Leptin, insulin and corticotrophin-releasing hormone (CRH) are thought to be additional key modulators in the behavioral responses to chronic stress and may contribute to stress-related ovulatory dysfunction. This mini-review also summarizes and appraises the available evidence on the negative impact of chronic stress as a result of the COVID-19 pandemic lockdowns. It proposes physiological mechanisms to explain the observed effects on women's reproductive health and well-being. The review suggests areas for future research.