Neurol. Int., Volume 13, Issue 2 (June 2021) – 15 articles

Cardio-cerebral infarction, which refers to an acute ischemic stroke (AIS) and acute myocardial infarction (AMI) that occur concurrently, is an uncommon phenomenon with a grave prognosis. Intraluminal carotid thrombus (ICT) is an infrequently encountered cause of ischemic stroke and can be associated with an underlying hypercoagulable state. One severe yet prevalent complication of infection with Coronavirus Disease 2019 (COVID-19) is thrombosis from multi-pathway inflammatory responses. Here, we present a unique case of cardio-cerebral infarction, with a free-floating intraluminal thrombus in the left internal carotid artery, in the setting of recent COVID-19 infection, and with the etiology of both events attributed to a COVID-19 hypercoagulable state. CT perfusion imaging also showed an interesting imaging finding of hyperperfusion, which is believed to be a form of dysfunctional cerebral autoregulation. Full article

Medical management of epilepsy seeks to eliminate or to reduce the frequency of seizures, help patients maintain a normal lifestyle, and maintain psychosocial and occupational activities, while avoiding the negative side effects of long-term treatment. Current FDA approved drugs have been shown to have similar efficacy; however, they all share a commonality of having side effects that have the potential to significantly reduce a patient’s quality of life. Cenobamate, a newly-FDA approved drug used to treat partial-onset seizures in adult patients, has demonstrated promise in that it works on two proposed mechanisms that are commonly associated with epilepsy. Cenobamate acts as a positive allosteric modulator of the GABA_A ion channels and is effective in reducing repetitive neuronal firing by inhibition of voltage-gated sodium channels, although the complete mechanism of action is currently unknown. The efficacy of Cenobamate with its low toxicity and adverse drug reaction profile emphasizes the need to further evaluate antiepileptic therapies containing sulfamoylphenyl and/or carbamate moieties in their chemical structure. Recent studies have found more patients to be seizure free during the maintenance period when compared to placebo. The most common side effects reported in with Cenobamate are somnolence, dizziness, headache, nausea, and fatigue. There are currently ongoing phase III studies looking to further evaluate the long-term benefits of Cenobamate and investigate adverse events. Full article

Distinguishing between tumefactive demyelinating lesions (TDLs) and brain tumors in multiple sclerosis (MS) can be challenging. A progressive course is highly common with brain tumors in MS and no single neuroimaging technique is foolproof when distinguishing between the two. We report a case of a 41-year-old female with relapsing–remitting multiple sclerosis, who had a suspicious lesion within the left frontal hemisphere, without a progressive course. The patient experienced paresthesias primarily to her right hand but remained stable without any functional decline and new neurological symptoms over the four years she was followed. The lesion was followed with brain magnetic resonance imaging (MRI) scans, positron emission tomography–computed tomography scans, and magnetic resonance spectroscopy. Together, these scans favored the diagnosis of a TDL, but a low-grade tumor was difficult to rule out. Examination of serial brain MRI scans showed an enlarging lesion in the left middle frontal gyrus involving the deep white matter. Neurosurgery was consulted and an elective left frontal awake craniotomy was performed. Histopathology revealed a grade II astrocytoma. This case emphasizes the importance of thorough and continuous evaluation of atypical MRI lesions in MS and contributes important features to the literature for timely diagnosis and treatment of similar cases. Full article

Brain tumors are primary or metastatic malignancies of the central nervous system (CNS) with significant morbidity and mortality. The overall prevalence of cancer including brain cancer has increased by more than 10% according to the National Institute of cancer statistics. The average percent increase in primary brain tumor incidence for ages 75–79, 80–84, and 85 and older were 7%, 20.4%, and 23.4%, respectively. This manuscript describes a retrospective study of geriatric cases admitted to the Neurosurgical Department in Khoula Hospital (KH) and diagnosed with brain cancer from 1 January 2016 to 31 December 2019. Of the study cohort, 58.5% were more than 75 years of age. The male-to-female ratio was (1:1.1). Meningiomas are found to be the commonest tumor (52.8%) followed by glioblastoma (GBM) (18.9%). Most of the patients had a Glasgow coma scale (GCS) score of 14–15 on admission (69.9%). Patients diagnosed with a non-meningioma tumor had lower GCS score on admission compared to meningioma patients with statistical significance (p = 0.04). Also, there was a significant difference between the length of stay (LOS) and the type of intervention (surgical vs. conservative), in which patients received a conservative type of management found to have a shorter length of stay (LOS) compared with the patients who underwent surgical intervention (p < 0.005). In Oman, the number of geriatric oncology cases remained stable over the 4 years. The incidence of geriatric neuro-oncology cases was higher in patients aged more than 75 years of age. Finally, the GCS score was affected by the type of tumor. The length of stay varies according to the treatment administered. Special care must be taken when dealing with geriatric neuro-oncological cases due to the high potential rate of mortality and morbidity among those group, and a more holistic approach is recommended as an essential need to evaluate the overall situation of those patients and manage them accordingly. Full article

The severity of Parkinson’s disease (PD) is developed by multifactorial factors. Falls can worsen disease severity. We previously found that frontal assessment battery (FAB) score was associated with a higher risk of future falls. This eight-year follow-up study aimed to verify whether factors including low FAB score can be the risk of PD progression based on the Hoehn and Yahr scale. In total, 95 patients were initially enrolled in this research and 45 were included in the final follow-up. Then, the cohort was classified into patients with and without disease progression, defined by upgrade of Hoehn-Yahr stage. Differences in clinical characteristics between patients with disease progression and those without were evaluated using the Mann–Whitney U test. Eighteen independent variables were evaluated via a univariate logistic regression analysis. Of the 45 patients enrolled, 32 had disease progression and 13 had no progression. Age (p = 0.033), BFI score (p = 0.003), Zung self-rating depression (p = 0.011), and anxiety scale (p = 0.026) were significantly increased in patients who had disease progression than those with no disease progression. On multivariate logistic regression analysis, brief fatigue inventory (BFI) score (OR = 1.048, p = 0.045, 95% CI = 1.001–1.098) was significantly related to disease progression. All BFI subscores related to general fatigue. Fatigue could predict the progression of motor dysfunction severity over a longitudinal duration in patients with PD with disease progression, having declining physical and mental fatigue. Full article

Multiple sclerosis (MS) is a prevalent neurologic autoimmune disorder affecting two million people worldwide. Symptoms include gait abnormalities, perception and sensory losses, cranial nerve pathologies, pain, cognitive dysfunction, and emotional aberrancies. Traditional therapy includes corticosteroids for the suppression of relapses and injectable interferons. Recently, several modern therapies—including antibody therapy and oral agents—were approved as disease-modifying agents. Monomethyl fumarate (MMF, Bafiertam) is a recent addition to the arsenal available in the fight against MS and appears to be well-tolerated, safe, and effective. In this paper, we review the evidence available regarding the use of monomethyl fumarate (Bafiertam) in the treatment of relapsing-remitting MS. Full article

Background: An outbreak of African swine fever (ASF) in China in 2020 has led to an unprecedented shortage of nadroparin. Most patients, especially those kept in hospital for surgery, are currently treated with prophylactic anticoagulation (AC). In search of alternatives for nadroparin (fraxiparine), we found no sufficient data on alternatives for neurosurgical patients, such as tinzaparin of European origin. We compared nadroparin and tinzaparin concerning adverse events (bleeding versus thromboembolic events) in neurosurgical patients. Methods: Between 2012 and 2018, 517 neurosurgical patients with benign and malignant brain tumors as well as 297 patients with subarachnoid hemorrhage (SAH) were treated in the Department of Neurosurgery, University Hospital Leipzig, receiving prophylactic anticoagulation within 48 h. In 2015, prophylactic anticoagulation was switched from nadroparin to tinzaparin throughout the university hospital. In a retrospective manner, the frequency and occurrence of adverse events (rebleeding and thromboembolic events) in connection with the substance used were analyzed. Statistical analysis was performed using Fisher’s exact test and the chi-squared test. Results: Rebleeding rates were similar in both nadroparin and tinzaparin cohorts in patients being treated for meningioma, glioma, and SAH combined (8.8% vs. 10.3%). Accordingly, the rates of overall thromboembolic events were not significantly different (5.5% vs. 4.3%). The severity of rebleeding did not vary. There was no significant difference among subgroups when compared for deep vein thrombosis (DVT) or pulmonary embolism (PE). Conclusion: In this retrospective study, tinzaparin seems to be a safe alternative to nadroparin for AC in patients undergoing brain tumor surgery or suffering from SAH. Full article

Introduction: Flow diverters such as the pipeline embolization device (PED) cause hemodynamic changes of the treated vessel segment. In posterior communicating artery (PcomA), aneurysms’ unique anatomic consideration have to be taken in account due to the connection between the anterior and posterior circulation. We hypothesize that in conjunction with PcomA remodeling, there will also be remodeling of the ipsilateral P1 segment of the posterior cerebral artery (PCA) after PED treatment for PcomA aneurysms. Methods: We retrospectively collected radiological as well as clinical data of PcomA aneurysm patients treated with PED including PcomA and P1 vessel diameters before and after treatment as well as patient and aneurysm characteristics. Results: Overall, 14 PcomA aneurysm patients were included for analysis and PED treatment was performed without complications in all patients. In 10 out of 14 patients (71%), a decrease in PcomA diameter was observed and there was a significant mean decrease of 0.78 mm in PcomA diameter on angiographic last follow-up (LFU) (p = 0.003). In the same patient population (10 out of 14 patients), there was meanwhile a significant mean increase of 0.43 mm in the ipsilateral P1 segment diameter observed (p = 0.015). These vessel remodeling effects were in direct correlation with aneurysm occlusion since all of these patients showed aneurysm occlusion at LFU while 29% showed only partial occlusion without vessel remodeling effects. A decrease in PcomA diameter was directly associated with aneurysm occlusion (p = 0.042). There were no neurologic complications on LFU. Conclusion: In the treatment of PcomA aneurysms with PED, the P1 segment of the PCA increases in diameter while the PcomA diameter decreases. Our results suggest that this remodeling effect is associated with aneurysm occlusion and decrease of PcomA is hemodynamically compensated for by an increase in the ipsilateral P1 diameter. Full article

Guillain–Barré syndrome (GBS) is an acute, immune-mediated inflammatory peripheral polyneuropathy characterized by ascending paralysis. Most GBS cases follow gastrointestinal or chest infections. Some patients have been reported either following or concomitant with head trauma, neurosurgical procedures, and rarely hemorrhagic stroke. The exact pathogenesis is not entirely understood. However, blood–brain barrier damage may play an essential role in triggering the autoimmune activation that leads to post-stroke GBS. Here, we present two cases of fulminant GBS following hemorrhagic stroke to remind clinicians to be aware of this rare treatable complication if a stroke patient develops unexplainable flaccid paralysis with or without respiratory distress. Full article

Glutamate, the major excitatory neurotransmitter, plays a ubiquitous role in most aspects of normal brain functioning. Its indispensable position is paradoxically doubled by a high excitotoxic potential following disruption of its dynamic equilibrium. Several lines of evidence have suggested the involvement of the glutamatergic N-methyl-D-aspartate receptor (NMDAR) in learning, memory formation, and human cognition. Furthermore, NMDARs play a pivotal role in various neuropsychiatric disorders, recently being identified as an important locus for disease-associated genomic variation. The GRIN2A gene encodes the NMDAR’s GluN2A subunit. Genetic alterations of GRIN2A result in phenotypic pleiotropy, predisposing to a broad range of epilepsy syndromes, with an elusive and unpredictable evolution and response to treatment. The archetypal GRIN2A-related phenotype comprises the idiopathic focal epilepsies (IFEs), with a higher incidence of GRIN2A mutants among entities at the more severe end of the spectrum. We report the case of a patient heterozygous for GRIN2A, c.1081C>T, presenting with febrile convulsions and later superimposed atonic seizures, expressive language delay, and macrocephaly. As the number of reported GRIN2A variants is continuously increasing, the phenotypic boundaries gradually grow faint. Therefore, it is fundamental to maintain an acute critical awareness of the possible genetic etiology of different epilepsy syndromes. So far, therapeutic strategies rely on empirical observations relating genotypes to specific drugs, but the overall success of treatment remains unpredictable. Deciphering the functional consequences of individual GRIN2A variants could lead to the development of precision therapeutic approaches for patients carrying NMDAR mutations. Full article

Li-Fraumeni syndrome (LFS) is a rare high-penetrance and autosomal-dominant pathological condition caused by the germline mutation of the TP53 gene, predisposing to the development of tumors from pediatric age. We conducted a qualitative systematic review following the ENTREQ (Enhancing Transparency in Reporting the Synthesis of Qualitative Research) framework. A search was made in MEDLINE/Pubmed and MeSH Database using the terms “Li-Fraumeni” AND “pediatric high-grade glioma (HGG)”, identifying six cases of HGGs in pediatric patients with LFS. We added a further case with peculiar features such as no familiar history of LFS, association of embryonal rhabdomyosarcoma and bithalamic HGG, whose immunohistochemical profile was accurately defined by Next Generation Sequencing. Knowledge synthesis and case analysis grounded the discussion about challenges in the management of this pathology in pediatric age. Full article

Background and Aims: Nerve conduction study (NCS) measures how fast an electrical impulse moves through the nerve and is a standard technique for diagnosing and assessing neurological diseases. Despite diabetes and obesity being a common accompaniment of peripheral neuropathy, their effects on NCS patterns have not been elucidated conclusively. Our study aimed to assess several anthropometric and metabolic factors with NCS outcomes to address this gap. Research Design and Methods: This retrospective chart analysis study was conducted on subjects who underwent NCS between 1 January 2009 and 31 December 2019 at a regional hospital. Metabolic, anthropometric, demographical and NCS data were collected from patients’ health records. Results: In total, 120 subjects presenting with sensorimotor peripheral neuropathy symptoms were included in the study. Age, HbA1c, urea and ESR variables were significantly negatively associated with nerve conduction outcomes (Spearman’s correlation rho between −0.210 and −0.456, p < 0.038). HbA1c and age consistently had the most substantial contribution to velocity and amplitude in all regression models (beta coefficients between −0.157 and 0.516, p < 0.001). Urea also significantly account for a large amount of variance in amplitude and velocity in the lower limbs. Conclusion: This study suggests that the severity of sensorimotor neuropathy is influenced by glycaemic control, age and uraemia. The interpretation of NCS results must consider these factors suggesting that improved glycaemic and uraemic control may improve nerve conduction outcomes. Full article

Tumor-treating fields (TTFields) are alternating electric fields applied continuously to the brain by attaching two-pair arrays on the scalp. Although TTFields therapy has demonstrated efficacy against supratentorial glioblastoma (GBM) in adults, its safety and efficacy in children have not been confirmed. Despite differences in the genetic etiology of the adult and pediatric forms of GBM, both have certain clinical behaviors in common, allowing us to test TTFields therapy in pediatric GBM. Recently, several, pediatric case-series using TTFields therapy have been published, and a few, prospective, pediatric studies are ongoing. Because GBMs are extremely rare in pediatric patients, where they comprise a wide variety of genetic subtypes, these pediatric studies are feasibility studies targeting various types of malignant brain tumor. Although they are important for confirming the safety and feasibility of TTFields therapy in the pediatric population, confirming its efficacy against each type of pediatric brain tumor, including the GBM, is difficult. Our clinical research team, therefore, planned an investigator-initiated clinical trial targeting pediatric supratentorial GBMs (as in adults) with the aim of expanding regulatory approval of TTFields therapy for pediatric GBM treatment based on safety and exploratory efficacy data in combination with the accumulated evidence on adult GBMs. Full article

Epileptic encephalopathy is a condition resulting from extreme forms of intractable childhood epilepsy. The disease can cause severe delays in cognitive, sensory, and motor function development, in addition to being fatal in some cases. Missense mutations of SCN8A, which encodes Nav1.6, one of the main voltage-gated sodium channel subunits in neurons and muscles, have been linked to early infantile SCN8A encephalopathy. Herein, we report the case of a 5-month-old girl with SCN8A encephalopathy with a novel missense mutation. Apart from intractable seizures and autistic phenotypes, the results of blood and biochemical tests, electroencephalogram (EEG) results, and brain magnetic resonance imaging (MRI) results were all normal. As the phenotypes caused by these mutations cannot be identified by any clinical, neuroimaging, or electrophysiological features, genetic sequencing should be considered to identify the underlying genetic causes. Although phenytoin is recommended as a last-resort treatment for SCN8A encephalopathy, the administration of the oxcarbazepine, instead of phenytoin, mitigated this patient’s intractable seizures. Full article

The involvement of the central nervous system in sarcoidosis can manifest with a variety of neurological symptoms, and most of them can be nonspecific. The diagnosis of neurosarcoidosis (NS) can therefore be very challenging without a tissue biopsy. Both computed tomography (CT) and magnetic resonance imaging (MRI) are important imaging modalities in the diagnosis of NS, and MRI is the modality of choice due to its superior soft-tissue contrast resolution. We present a case series of NS with interesting neuroimaging features, complex neurological presentations, and clinical courses. We identify five cases presenting with clinically isolated neurosarcoidosis (CINS) without any other signs or symptoms of systemic disease which were diagnosed as NS on biopsy. In the first case, we describe a patient with an intramedullary cervical spinal cord lesion. In the second case we describe a patient presenting with inflammatory changes and enhancement in the orbit. The third case demonstrates a lesion with calcification around the region of the foramen of Monro. The fourth case shows multiple ring-enhancing lesions. Lastly, the fifth case exhibits unusual findings with both optic neuritis and a cerebellar nodule. We aim to describe the complicated clinical course with neurological workup, neuro-imaging, and eventual diagnosis and treatment of these challenging cases to highlight the variable presentations of NS. This case series will remind clinicians that NS should always be in the differential diagnosis when a patient presents with nonspecific neurological symptoms with unusual neuroimaging findings. Full article