Neurological Symptoms In Patients Research Articles

Update on neurological symptoms in patients infected with severe acute respiratory syndrome coronavirus-2.

Novel coronavirus 19 (COVID-19) is the latest and most intense epidemic, which is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In addition to causing respiratory symptoms, SARS-CoV-2 can have severe effects on the nervous system. Clinically, COVID-19 patients have been reported ranging from mild hypogeusia and hyposmia to severe neurological disorders, such as encephalopathy, encephalitis, strokes, and seizures syndrome. However, the pathological mechanisms of this SARS-CoV-2 neuro aggressiveness remain unclear, so it is of great significance to explore the neurological effects of SARS-CoV-2 infection. To facilitate clinicians to timely recognize the manifestations of COVID-19 patients with neurological injury and timely treatment, the author hereby reviews the latest research progress in the possible pathways, clinical manifestations, and pathogenesis of COVID-19 patients with nerve injury.

Clinical and morphological features of SARS-COV-2 associated acute hemorrhagic necrotizing encephalopathy: case report

BackgroundThe current case report presents acute hemorrhagic necrotizing encephalopathy (AHNE) as an example of a fatal complication, the etiology of which could be coronavirus disease 2019 (COVID-19) with multiple organ damage along with the existing respiratory tuberculosis.Case presentationA male in his 20s had severe symptoms of central nervous system lesion, which developed against the background of COVID-19 and respiratory tuberculosis, for which he was treated in the intensive care unit. Autopsy confirmed that he died from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated AHNE in adults with severe fatal endothelial dysfunction and respiratory tuberculosis. The main morphological signs of brain damage were desquamative endotheliitis, thrombosis, parenchymal hemorrhagic necrosis, encephalitis, severe necrobiotic neuronal damage.ConclusionThe defeat of endothelial cells with the development of generalized endotheliitis in COVID-19, especially in conjunction with comorbid pathology, in particular tuberculosis, can lead to a fatal complication that affects the nervous system—AHNE. Therefore, it is worth paying close attention to the appearance of neurological symptoms in patients with a similar combination of diseases.

A case report of Cryptococcus neoformans meningitis after recovery from COVID-19 infection in a kidney transplant recipient patient

Background: Fungal infections in transplant recipient patients are among the main causes of mortality and disability due to immunosuppression. Involvement of the central nervous system because of fungal infections is one of the important and treatable factors in such patients. This study investigated a case of a 58-year-old diabetic patient with a history of kidney transplantation infected by cryptococcal meningitis 3 months after recovery from coronavirus disease 2019 (COVID-19) infection. A 58-year-old diabetic patient with a history of kidney transplantation presented with a complaint of prolonged headache, fever, nausea, and vomiting. The patient was admitted to the same center 3 months before with a diagnosis of COVID-19 infection. The examinations performed after cerebrospinal fluid sampling showed a slight reduction in the patient's neurological symptoms, and the analysis of cerebrospinal fluid and the use of Indian culture and ink demonstrated evidence of fungal infection. After treatment with Amphotericin and Flowocytosine, the patient was discharged from the hospital in a good general condition.

Neurological and neurodevelopmental symptoms in children with familial Mediterranean fever and their siblings.

Familial Mediterranean fever is a common autoinflammatory disease characterized by periodic attacks of fever and serositis.There are few reports describing neurological symptoms in patients with FMF. The aim of this study was to systematically assess the neurologic and developmental involvement in pediatric patients with FMF. Between the years 2016 and 2019, parents of children with FMF were asked to complete a questionnaire regarding the presence of neurological and developmental symptoms in their children with and without FMF. Demographic data, clinical characteristics, and disease course of FMF patients were collected from the medical charts. Neurodevelopmental manifestations were compared between the children with FMF and their siblings. A total of 205 children were enrolled (11.6 ± 4.7years of age): 111 children with FMF and 94 healthy siblings in the control group. Neurological morbidity was frequently reported in children with FMF: 44 (40%) had recurrent headaches, 31 (28%) ADHD symptoms, 27 (24%) learning disabilities, and 10 (9%) febrile convulsions. Headaches and febrile convulsions were significantly more prevalent in children with FMF as compared to their siblings (ps < 0.05). ADHD and learning disabilities were associated with poor adherence to colchicine treatment.Conslusions: The present study found an increased prevalence of ADHD, learning disabilities, headaches, and febrile seizures in children with FMF. The findings underscore the importance of addressing the neurodevelopmental domain in children with FMF. In addition, detection and treatment of ADHD and learning disabilities could improve adherence with therapy and control of the underlying disease. What is Known: •Familial Mediterranean fever (FMF) is the most common inherited auto-inflammatory disease, characterized by recurrent attacks of fever, serositis, and arthritis. •Some previous case reports also described rare neurological manifestations in children with FMF. What is New: •The study found an increased prevalence of headaches, febrile seizures, ADHD, and learning disabilities, in children with FMF. •The findings underscore the importance of addressing the neurological domain in this population, which could potentially improve adherence with therapy and control of the underlying disease.

Neurologic Complications in Patients with Cancer.

Neurologic symptoms are commonly seen in patients with cancer and can be among the most challenging to diagnose and manage. It is often difficult to determine if new neurologic symptoms are secondary to direct effects of a malignant lesion, systemic complications of disease, paraneoplastic disorders, or side effects of cancer treatment itself. However, early diagnosis and treatment of each of these conditions can improve patients' quality of life and long-term functional outcomes. In this review, we describe a systematic approach to the diagnosis of new neurologic symptoms in patients with known malignancy. We have categorized the neurologic complications of cancer through a mechanistic approach, with an emphasis on ascertaining underlying pathophysiology to guide treatment choice. This review focuses on the acute neurologic complications of cancer that require hospital admission.

Editors' Note: CSF Biomarkers in Patients With COVID-19 and Neurologic Symptoms: A Case Series

In “CSF Biomarkers in Patients With COVID-19 and Neurologic Symptoms: A Case Series,” Edén et al. describe CSF results in 6 patients with neurologic symptoms in the setting of COVID-19 infection. Three patients had a positive CSF SARS-CoV-2 PCR initially, although the cycle threshold was elevated (>35), indicating a low viral load. It is important that SARS-CoV-2 RNA was undetectable in all 3 samples when reanalyzed. All patients had elevated CSF neopterin and β2-microglobulin. Kumar and Lall comment that these findings are consistent with nonspecific inflammation and emphasize the fact that neuropathogenesis in COVID-19 is multifactorial because of systemic inflammation, hypoxemia, hypercoagulability, and potentially unidentifiable mechanisms. Brenner agrees that these findings suggest COVID-19 does not directly invade the CNS, but that it can cause an autoimmune or immune-mediated meningoencephalitis. He proposes that treatment with steroids, IVIG, and/or plasmapheresis may be considered. Edén agrees that a number of different mechanisms may contribute to the development of neurologic symptoms in patients with COVID-19 and reinforces the need for ongoing research to evaluate potential interventions. In “CSF Biomarkers in Patients With COVID-19 and Neurologic Symptoms: A Case Series,” Edén et al. describe CSF results in 6 patients with neurologic symptoms in the setting of COVID-19 infection. Three patients had a positive CSF SARS-CoV-2 PCR initially, although the cycle threshold was elevated (>35), indicating a low viral load. It is important that SARS-CoV-2 RNA was undetectable in all 3 samples when reanalyzed. All patients had elevated CSF neopterin and β2-microglobulin. Kumar and Lall comment that these findings are consistent with nonspecific inflammation and emphasize the fact that neuropathogenesis in COVID-19 is multifactorial because of systemic inflammation, hypoxemia, hypercoagulability, and potentially unidentifiable mechanisms. Brenner agrees that these findings suggest COVID-19 does not directly invade the CNS, but that it can cause an autoimmune or immune-mediated meningoencephalitis. He proposes that treatment with steroids, IVIG, and/or plasmapheresis may be considered. Edén agrees that a number of different mechanisms may contribute to the development of neurologic symptoms in patients with COVID-19 and reinforces the need for ongoing research to evaluate potential interventions.

Characterization and management of neurological adverse events during immune-checkpoint inhibitors treatment: an Italian multicentric experience.

Neurological immune-related adverse events (nirAEs) are rare toxicities of immune-checkpoint inhibitors (ICI). With the increase of ICI oncological indications, their incidence is growing. Their recognition and management remain nevertheless challenging. A national, web-based database was built to collect cases of neurological symptoms in patients receiving ICI and not attributable to other causes after an adequate workup. We identified 27 patients who developed nirAEs (20 males, median age 69years). Patients received anti-PD1/PDL1 (78%), anti-CTLA4 (4%), or both (19%). Most common cancers were melanoma (30%) and non-small cell lung cancer (26%). Peripheral nervous system was mostly affected (78%). Median time to onset was 43.5days and was shorter for peripheral versus central nervous system toxicities (36 versus 144.5days, p = 0.045). Common manifestations were myositis (33%), inflammatory polyradiculoneuropathies (33%), and myasthenia gravis (19%), alone or in combination, but the spectrum of diagnoses was broad. Most patients received first-line glucocorticoids (85%) or IVIg (15%). Seven patients (26%) needed second-line treatments. At last follow-up, four (15%) patients were deceased (encephalitis, 1; myositis/myasthenia with concomitant myocarditis, 2; acute polyradiculoneuropathy, 1), while seven (26%) had a complete remission, eight (30%) partial improvement, and six (22%) stable/progressing symptoms. ICI treatment was discontinued in most patients (78%). Neurological irAEs are rare but potentially fatal. They primarily affect neuromuscular structures but encompass a broad range of presentations. A prompt recognition is mandatory to timely withheld immunotherapy and administrate glucocorticoids. In corticoresistant or severely affected patients, second-line treatments with IVIg or plasmapheresis may result in additional benefit.

Serum ammonia use: unnecessary, frequent and costly

Background/objectiveWhile ammonia plays a role in the complex pathophysiology of hepatic encephalopathy (HE), serum ammonia is unreliable for both diagnosis of, and correlation with, neurological symptoms in patients with cirrhosis....

Sex-Related Risk of Cardiac Involvement in Hereditary Transthyretin Amyloidosis: Insights From THAOS

ObjectivesBecause patients with ATTRv cardiomyopathy are more likely to be male, this analysis aimed to increase information on associations between sex and genotype, phenotype, and degree of myocardial involvement in ATTRv amyloidosis. BackgroundTransthyretin amyloid cardiomyopathy is a progressive, fatal disease that occurs due to accumulation of wild-type or variant (ATTRv) transthyretin amyloid fibrils in the myocardium. MethodsThe Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing global longitudinal observational survey of patients with ATTR amyloidosis and asymptomatic carriers with TTR mutations. Data from THAOS (data cutoff: January 6, 2020) were analyzed to determine any sex-based differences in genotype, phenotype, and presence of cardiac and neurological symptoms in patients with ATTRv amyloidosis and in patients with ATTRv amyloidosis and cardiomyopathy. ResultsThere were 2,790 patients with ATTRv amyloidosis enrolled in THAOS, with male patients more likely to have symptoms of cardiac involvement and a cardiac phenotype. Male prevalence was greater in patients with more severe cardiac manifestations of disease, as assessed with N-terminal pro–B-type natriuretic peptide, left-ventricular (LV) ejection fraction, mean LV wall thickness divided by height, and LV mass index divided by height. Sex, age at disease onset, and genotype category were identified by multivariate analyses as risk factors for the development of cardiomyopathy (defined as increased LV septum thickness divided by height). ConclusionsIn this analysis, myocardial involvement was more frequent and pronounced in male patients with ATTRv amyloidosis, suggesting that there may be biological characteristics that inhibit myocardial amyloid infiltration in females or facilitate it in males.

A patient with probable neuro‐Behçet's disease presenting a unique linear pontine trigeminal root lesion and a linear subcortical white matter lesion

AbstractBackgroundNeuro‐Behçet's disease (NBD) is typically characterized by inflammatory lesions with vasculitis in the brainstem and basal ganglia. Subcortical white matter lesions and linear lesions along the intramedullary trigeminal nerve are rare, and these lesions make NBD difficult to differentiate from other demyelinating diseases, such as multiple sclerosis.Case presentationA 48‐year‐old woman with an 11‐year history of intestinal Behçet's disease was referred to Department of Neurology, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Japan owing to numbness on the left side of her face and oral cavity for 12 days. Neurological examination revealed left facial hypoesthesia. Brain magnetic resonance imaging showed a linearly shaped T2/fluid‐attenuated inversion recovery hyperintense magnetic resonance imaging lesion in the left pons, which corresponded neuroanatomically with the intramedullary trigeminal root. Based on the presumptive diagnosis of NBD, a course of high‐dose intravenous methylprednisolone was administered on the 14th hospital day. Thereafter, the patient's neurological symptoms improved. However, on the 18th hospital day, the patient developed a linear subcortical white matter lesion with vasogenic edema in the right hemisphere that resolved after the re‐administration of high‐dose intravenous methylprednisolone.ConclusionThe case of a patient with NBD presenting with atypical brain lesions is reported. The NBD in this case might have a pathogenetic mechanism that is different from that of typical NBD.

Neurological symptoms in hospitalised patients with COVID-19 and their association with in-hospital mortality

To evaluate the spectrum of neurological symptoms in patients with COVID-19 during the first 14 days of hospitalisation and its association with in-hospital mortality. We included 200 patients with RT-PCR-confirmed COVID-19 admitted to University Hospital in Krakow, Poland. In 164 patients, a detailed questionnaire concerning neurological symptoms and signs was performed prospectively within 14 days of hospitalisation. In the remaining 36 patients, such questionnaires were completed retrospectively based on daily observations in the Department of Neurology. During hospitalisation, 169 patients (84.5%) experienced neurological symptoms; the most common were: fatigue (62.5%), decreased mood (45.5%), myalgia (43.5%), and muscle weakness (42.5%). Patients who died during hospitalisation compared to the remainder were older (79 [70.5-88.5] vs. 63.5 [51-77] years, p = 0.001), and more often had decreased level of consciousness (50.0% vs. 9.3%, p < 0.001), delirium (33.3% vs. 4.4%, p < 0.001), arterial hypotension (50.0% vs. 19.6%, p = 0.005) or stroke during (18.8% vs. 3.3%, p = 0.026) or before hospitalisation (50.0% vs. 7.1, p < 0.001), whereas those who survived more often suffered from headache (42.1% vs. 0%, p = 0.012) or decreased mood (51.7% vs. 0%, p = 0.003). Most hospitalised patients with COVID-19 experience neurological symptoms. Decreased level of consciousness, delirium, arterial hypotension, and stroke during or before hospitalisation increase the risk of in-hospital mortality.

Neurological Consequences of Cytokine Release Syndrome Following Subcutaneous Recombinant IL-15 and Haploidentical Donor Natural Killer Cell Therapy for Advanced Acute Myeloid Leukemia

Abstract Cytokine Release Syndrome (CRS) is associated with elevated cytokine levels, macrophage activation, and IL-6 production after antibody or cell-based immunotherapy. We have observed over 200 patients with no CRS following adoptively transferred haploidentical donor natural killer (haplo-NK) cell products after lymphodepleting chemotherapy plus IL-2; and achieved complete remission in 30-50% of patients with refractory AML. To promote NK cell expansion without stimulation of Treg that may compromise NK function, we tested the substitution of IL-2 with the NCI manufactured rIL-15. Using the same lymphodepleting preparative regimen (Fludarabine 25 mg/m2IV for 5 days and Cyclophosphamide 60 mg/kg IV for 2 days) we infused CD3- and CD19-depleted haplo-NK incubated overnight with rIL-15 (10 ng/mL) prior to infusion. Two cohorts received rIL-15; either intravenously x 12 daily doses (at the Phase I MTD of 0.75 mcg/kg) or subcutaneously x 10 doses (5 days on, 2 days off, 5 days on at 2 mcg/kg SQ, the MTD when used as monotherapy in solid tumor patients). CRS was defined by modified CRS grading criteria (Lee et al. Blood, 2014). Results: Forty patients with relapsed/refractory AML were treated with haplo-NK plus IV rIL-15 (n=24) or SQ rIL-15 (n=16). Patients received an average of 11.6 IV doses [9-12, 96% of planned doses] or 7.5 SQ doses [1-10, 75% of planned doses]. Dosing was stopped for toxicity. No CRS events were observed after IV dosing. However, after SQ dosing, 9 of 16 patients [56%] had grade 1-4 CRS; [4 (25%) with grade 3-4 CRS) (Table 1). The median time from NK infusion to onset of CRS was 8 days [2-44]. Six of the 9 CRS patients (66%) had neurological events. Neurological toxicities included grade 1-2 encephalopathy (n=2), intracranial hemorrhage (ICH) (n=2, grade 1 and grade 5), and grade 4 seizures (n=2). One additional event (a patient with a fall resulting in ICH due to pre-existing gait abnormality) without evidence of CRS was not considered as IL-15 associated neurotoxicity CRS. Symptoms resolved in 4 of 5 patients who received treatment for neurologic CRS (3 received both steroids and Tocilizumab, 1 received steroids only, 1 patient did not require treatment as symptoms resolved with stopping IL-15). Non-neurologic toxicity included hypoxia (n=2) and hypotension (n=3). No significant correlations were found between development of CRS and absolute lymphocyte or monocyte count, presence or absence of haplo-NK expansion at day 14, number of rIL-15 doses received, or disease burden at baseline as measured by blast percentage in bone marrow. In the IV rIL-15 cohort, only 2 of 14 patients at the MTD (14%) cleared leukemia and underwent transplantation. In contrast, 8 of 16 patients (50%, P=0.04) in the SQ rIL-15 cohort achieved CR (n=7) or CRp (n=1), with 6 patients proceeding to alloHCT consolidation. CRS did not limit the clinical benefit in the SQ cohort as 4 of 9 [44%] patients with CRS achieved CR/PR compared to 4 of 7 [57%] patients without CRS. Pharmacokinetic data showed slower clearance of rIL-15 in SQ compared to IV dosing, as shown by higher trough levels prior to dose 2 (501 vs. 233 pg/mL, p Download : Download high-res image (163KB) Download : Download full-size image Disclosures Bachanova: Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Seattle-Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Zymogen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oxis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Miller: Celegene: Consultancy; Oxis Biotech: Consultancy; Fate Therapeutics: Consultancy, Research Funding.

Three-dimensional analysis of the characteristics of joint motion and gait pattern in a rodent model following spinal nerve ligation

BackgroundThe spinal nerve ligation (SNL) rat is well known as the most common rodent model of neuropathic pain without motor deficit. Researchers have performed analyses using only the von Frey and thermal withdrawal tests to evaluate pain intensity in the rat experimental model. However, these test are completely different from the neurological examinations performed clinically. We think that several behavioral reactions must be observed following SNL because the patients with neuropathic pain usually have impaired coordination of the motions of the right–left limbs and right–left joint motion differences. In this study, we attempted to clarify the pain behavioral reactions in SNL rat model as in patients. We used the Kinema-Tracer system for 3D kinematics gait analysis to identify new characteristic parameters of each joint movement and gait pattern.ResultsThe effect of SNL on mechanical allodynia was a 47 ± 6.1% decrease in the withdrawal threshold during 1–8 weeks post-operation. Sagittal trajectories of the hip, knee and ankle markers in SNL rats showed a large sagittal fluctuation of each joint while walking. Top minus bottom height of the left hip and knee that represents instability during walking was significantly larger in the SNL than sham rats. Both-foot contact time, which is one of the gait characteristics, was significantly longer in the SNL versus sham rats: 1.9 ± 0.15 s vs. 1.03 ± 0.15 s at 4 weeks post-operation (p = 0.003). We also examined the circular phase time to evaluate coordination of the right and left hind-limbs. The ratio of the right/left circular time was 1.0 ± 0.08 in the sham rats and 0.62 ± 0.15 in the SNL rats at 4 weeks post-operation.ConclusionsWe revealed new quantitative parameters in an SNL rat model that are directly relevant to the neurological symptoms in patients with neuropathic pain, in whom the von Frey and thermal withdrawal tests are not used at all clinically. This new 3D analysis system can contribute to the analysis of pain intensity of SNL rats in detail similar to human patients’ reactions following neuropathic pain.

‘Long COVID’ needs to be addressed by multiple specialties

‘Long COVID’ needs to be addressed by multiple specialties

Ineffective Drugs: Cerebrolysin and Piracetam

The study of drug efficacy is greatly importance, since the data obtained can be used as a scientific tool for re-evaluating drugs. The aim of the study is to evaluate the efficacy of cerebrolysin and piracetam in patients with acute ischemic stroke. The study included 124 patients with moderate acute ischemic stroke (AIS). All patients were divided into two experimental groups and one control group. The control group included 40 people receiving standard therapy (acetylsalicylic acid, lisinopril, nebivolol, pentoxifylline, L-lysine escinate). The cerebrolysin group consisted of 42 patients who additionally received cerebrolysin (10ml) in a volume of 200ml (0.9% NaCl) once a day. The piracetam group included 42 patients who additionally received piracetam (10ml) in a volume of 200ml (0.9% NaCl) three times a day. The course of inpatient treatment lasted 3 weeks. At the end of treatment, there was a significant (p &lt;0.05) regression of neurological symptoms in patients with acute ischemic stroke in all comparison groups by 1.75 (p &lt;0.05) times in the control group, by 1.85 (p &lt; 0.05) in the cerebrolysin group and by 1.78 (p &lt;0.05) in the piracetam group. There was no statistically significant intergroup difference (p&gt; 0.05). The study results do not demonstrate clinical benefits of cerebrolysin and piracetam for treating acute ischemic stroke.

Investigating the effects of volar wrist cock-up splint and dorsal lock wrist hand orthosis in reducing signs of carpal tunnel syndrome.

Background: Carpal tunnel syndrome (CTS) is the most common compressive neuropathy presenting with sharp pain, parenthesis, dysfunction of the hand in coordination and gripping. Splinting is the most common conservative intervention to improve pain and enological symptom of this Syndrome (CTS). With regard to the importance of these interventions and controversies about different designs of splints, the aim of this study was to compare the therapeutic effects of volar wrist cock-up orthosis and dorsal lock wrist hand orthosis on pain, sensory and motor latency in carpal tunnel syndrome. Methods: In this Randomized controlled trial study, 30 patients diagnosed with mild to moderate CTS were recruited. The subjects were randomly divided into two equal groups. Both groups received one form of splints for three weeks. Before receiving the splints, Electromyography (EMG) and Visual analog scale (VAS) were performed. Then, two different designs of splints were used for a period of three weeks. After that, EMG and Numerical Rating Scale (NRS-11) were repeated to reveal the effects of splints on reducing pain, sensory and motor latency in CTS. Independent t and paired t-tests were done uding SPSS software version 19.0. P-value was set at 0.05. Results: All the variables in both groups showed significant improvement. The NRS-11 test was significantly improved in the dorsal lock wrist hand orthosis group (p<0.05). Conclusion: This study showed that the use of the dorsal lock wrist hand orthosis for about three weeks was significantly improved pain and neurological symptoms of patients with CTS because of maintaining the wrist in the neutral position. Knowing this fact helps us to design and make a less cumbersome and restrictive splint with an accurate position for the wrist and distal joints.

Back to the future: lessons from past viral infections and the link with Parkinson's disease.

During the current coronavirus disease 2019 (COVID-19) pandemic, there has been noticeable increase in the reporting of neurological symptoms in patients. There is still uncertainty around the significance and long-term consequence of these symptoms. There are also many outstanding questions on whether the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) can directly infect the central nervous system (CNS). Given the long association between viral infections with neurodegenerative conditions such as Parkinson’s disease (PD), it seems timely to review this literature again in the context of the COVID-19 pandemic and to glean some useful information from studies on similar viruses. In this commentary, we will consider the current knowledge on viral infections in the brain. In addition, we review the link between viral infection and neurodegeneration in PD, and review the recent literature on SARS infections, the potential link with PD and the potential areas of study in the future.

Slc20a2-Deficient Mice Exhibit Multisystem Abnormalities and Impaired Spatial Learning Memory and Sensorimotor Gating but Normal Motor Coordination Abilities.

BackgroundPrimary familial brain calcification (PFBC, OMIM#213600), also known as Fahr’s disease, is a rare autosomal dominant or recessive neurodegenerative disorder characterized by bilateral and symmetrical microvascular calcifications affecting multiple brain regions, particularly the basal ganglia (globus pallidus, caudate nucleus, and putamen) and thalamus. The most common clinical manifestations include cognitive impairment, neuropsychiatric signs, and movement disorders. Loss-of-function mutations in SLC20A2 are the major genetic causes of PFBC.ObjectiveThis study aimed to investigate whether Slc20a2 knockout mice could recapitulate the dynamic processes and patterns of brain calcification and neurological symptoms in patients with PFBC. We comprehensively evaluated brain calcifications and PFBC-related behavioral abnormalities in Slc20a2-deficient mice.MethodsBrain calcifications were analyzed using classic calcium-phosphate staining methods. The Morris water maze, Y-maze, and fear conditioning paradigms were used to evaluate long-term spatial learning memory, working memory, and episodic memory, respectively. Sensorimotor gating was mainly assessed using the prepulse inhibition of the startle reflex program. Spontaneous locomotor activity and motor coordination abilities were evaluated using the spontaneous activity chamber, cylinder test, accelerating rotor-rod, and narrowing balance beam tests.ResultsSlc20a2 homozygous knockout (Slc20a2-HO) mice showed congenital and global developmental delay, lean body mass, skeletal malformation, and a high proportion of unilateral or bilateral eye defects. Brain calcifications were detected in the hypothalamus, ventral thalamus, and midbrain early at postnatal day 80 in Slc20a2-HO mice, but were seldom found in Slc20a2 heterozygous knockout (Slc20a2-HE) mice, even at extremely old age. Slc20a2-HO mice exhibited spatial learning memory impairments and sensorimotor gating deficits while exhibiting normal working and episodic memories. The general locomotor activity, motor balance, and coordination abilities were not statistically different between Slc20a2-HO and wild-type mice after adjusting for body weight, which was a major confounding factor in our motor function evaluations.ConclusionThe human PFBC-related phenotypes were highly similar to those in Slc20a2-HO mice. Therefore, Slc20a2-HO mice might be suitable for the future evaluation of neuropharmacological intervention strategies targeting cognitive and neuropsychiatric impairments.

Comparison of outcomes of patients with COVID-19 with primary pulmonary, gastrointestinal, and neurological symptoms

Background: Coronavirus disease 2019 (COVID-19) is the largest and most severe epidemic since the 1918 flu, and its emergence has created unprecedented challenges to public health. Clinical manifestations in patients are very diverse, and can range from asymptomatic disease to severe illness with death. The main purpose of this study was to compare the outcomes of patients with Covid-19 with early pulmonary, gastrointestinal, and neurological symptoms in patients admitted to hospitals in Qazvin City, Iran. Methods: This was a retrospective study with 300 samples, performed after obtaining ethics license and obtaining patient consent. The samples were selected using purposive method. Confirmation of COVID-19 was done due to having a lung scan confirmed by an internal medicine or infectious disease specialist, as well as having a positive polymerase chain reaction (PCR) test. Exclusion criteria also included pregnancy. Findings: The group of patients presented with early pulmonary symptoms were significantly different from the other two groups in terms of mortality, intensive care unit, intubation and hospitalization (P < 0.050). Conclusion: Patients presenting with early pulmonary symptoms should be given priority in hospitalization. © 2021 Isfahan University of Medical Sciences(IUMS). All rights reserved.

Utility of Magnetic Resonance Spectroscopy for the Progression of Neurological Symptoms in Lenticulostriate Artery Territory Infarction

ObjectivesThe present study aimed to examine the effectiveness of proton magnetic resonance spectroscopy (1HMRS) in determining the progression of neurological symptoms resulting in acute ischemic stroke in patients with lenticulostriate artery (LSA) infarction. Materials and Methods1HMRS was performed within 72 h after neurological symptom onset. Voxel of interest was placed in tissue that included the pyramidal tract and identified diffusion weighted echo planar spin-echo sequence (DWI) coronal images. Infarct volume in DWI was calculated using the ABC/2 method. 1HMRS data (tNAA, tCr, Glx, tCho, and Ins) were analyzed using LCModel. Progressive neurological symptoms were defined as an increase of 1 or more in the NIHSS score. Patients who underwent 1HMRS after progressive neurological symptoms were excluded. ResultsIn total, 77 patients were enrolled. Of these, 19 patients had progressive neurological symptoms. The patients with progressive neurological symptoms were significantly more likely to be female and had higher tCho/tCr values, higher rates of axial slices ≥ 3 slices on DWI, higher infarct volume on DWI, higher maximum diameter of infarction of axial slice on DWI, and higher SBP on admission compared to those without. Multivariable logistic analysis revealed that higher tCho/tCr values were independently associated with progressive neurological symptoms after adjusting for age, sex, and initial DWI infarct volume (tCho/tCr per 0.01 increase, OR 1.26, 95% CI 1.03–1.52, P = 0.022). ConclusionsIncreased tCho/tCr score were associated with progressive neurological symptoms in patients with LSA ischemic stroke. Quantitative evaluation of 1HMRS parameters may be useful for predicting the progression of neurological symptoms.