Central nervous system manifestations following vaccination against COVID-19.

Coronavirus disease 2019 (COVID-19) vaccination has become the most effective countermeasure in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, vaccination is associated with side effects. This narrative review focuses on central nervous system (CNS) manifestations following COVID-19 vaccination and provides a summary of the potential underlying mechanisms and methods of diagnosis and management of the vaccination-related CNS manifestations. Headache, myalgia, optic neuritis, seizure, multiple sclerosis, acute disseminated encephalomyelitis and encephalitis, delirium, acute transverse myelitis, and stroke have been reported after COVID-19 vaccination. Constant headache and myalgia are common manifestations that may necessitate further clinical investigation for stroke. To limit consequences, it is imperative to follow standard treatment protocols for each neurological disorder following COVID-19 vaccination. Immunosuppressive medication can be helpful in the treatment of seizures following vaccination since the immune response is involved in their etiology. Clinicians should be aware of the manifestations after COVID-19 vaccination to respond promptly and effectively. Clinical guidelines for the management of CNS manifestations following COVID-19 vaccination are in high demand and would be useful in each new SARS-CoV-2 variant pandemic.

Vagus Nerve Stimulation in Ischemic Stroke.

PURPOSE OF REVIEW: Vagus nerve stimulation (VNS) has emerged as a potential therapeutic approach for neurological and psychiatric disorders. In recent years, there has been increasing interest in VNS for treating ischemic stroke. This review discusses the evidence supporting VNS as a treatment option for ischemic stroke and elucidates its underlying mechanisms. RECENT FINDINGS: Preclinical studies investigating VNS in stroke models have shown reduced infarct volumes and improved neurological deficits. Additionally, VNS has been found to reduce reperfusion injury. VNS may promote neuroprotection by reducing inflammation, enhancing cerebral blood flow, and modulating the release of neurotransmitters. Additionally, VNS may stimulate neuroplasticity, thereby facilitating post-stroke recovery. The Food and Drug Administration has approved invasive VNS (iVNS) combined with rehabilitation for ischemic stroke patients with moderate to severe upper limb deficits. However, iVNS is not feasible in acute stroke due to its time-sensitive nature. Non-invasive VNS (nVNS) may be an alternative approach for treating ischemic stroke. While the evidence from preclinical studies and clinical trials of nVNS is promising, the mechanisms through which VNS exerts its beneficial effects on ischemic stroke are still being elucidated. Therefore, further research is needed to better understand the efficacy and underlying mechanisms of nVNS in ischemic stroke. Moreover, large-scale randomized clinical trials are necessary to determine the optimal nVNS protocols, assess its long-term effects on stroke recovery and outcomes, and identify the potential benefits of combining nVNS with other rehabilitation strategies.

Neuroinflammation in Acute Ischemic and Hemorrhagic Stroke.

PURPOSE OF REVIEW: This review aims to provide an overview of neuroinflammation in ischemic and hemorrhagic stroke, including recent findings on the mechanisms and cellular players involved in the inflammatory response to brain injury. RECENT FINDINGS: Neuroinflammation is a crucial process following acute ischemic stroke (AIS) and hemorrhagic stroke (HS). In AIS, neuroinflammation is initiated within minutes of the ischemia onset and continues for several days. In HS, neuroinflammation is initiated by blood byproducts in the subarachnoid space and/or brain parenchyma. In both cases, neuroinflammation is characterized by the activation of resident immune cells, such as microglia and astrocytes, and infiltration of peripheral immune cells, leading to the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species. These inflammatory mediators contribute to blood-brain barrier disruption, neuronal damage, and cerebral edema, promoting neuronal apoptosis and impairing neuroplasticity, ultimately exacerbating the neurologic deficit. However, neuroinflammation can also have beneficial effects by clearing cellular debris and promoting tissue repair. The role of neuroinflammation in AIS and ICH is complex and multifaceted, and further research is necessary to develop effective therapies that target this process. Intracerebral hemorrhage (ICH) will be the HS subtype addressed in this review. Neuroinflammation is a significant contributor to brain tissue damage following AIS and HS. Understanding the mechanisms and cellular players involved in neuroinflammation is essential for developing effective therapies to reduce secondary injury and improve stroke outcomes. Recent findings have provided new insights into the pathophysiology of neuroinflammation, highlighting the potential for targeting specific cytokines, chemokines, and glial cells as therapeutic strategies.

Saffron as a promising therapy for diabetes and Alzheimer's disease: mechanistic insights.

The prevalence of both Alzheimer's disease (AD) and diabetes mellitus is increasing with the societies' aging and has become an essential social concern worldwide. Accumulation of amyloid plaques and neurofibrillary tangles (NFTs) of tau proteins in the brain are hallmarks of AD. Diabetes is an underlying risk factor for AD. Insulin resistance has been proposed to be involved in amyloid-beta (Aß) aggregation in the brain. It seems that diabetic conditions can result in AD pathology by setting off a cascade of processes, including inflammation, mitochondrial dysfunction, and ROS and advanced glycation end products (AGEs) synthesis. Due to the several side effects of chemical drugs and their high cost, using herbal medicine has recently attracted attention for the treatment of diabetes and AD. Saffron and its active ingredients have been used for its anti-inflammatory, anti-oxidant, anti-diabetic, and anti-AD properties. Therefore, in the present review paper, we take account of the clinical, in vivo and in vitro evidence regarding the anti-diabetic and anti-AD effects of saffron and discuss the preventive or postponing properties of saffron or its components on AD development via its anti-diabetic effects.

Stroke Associated with COVID-19 Vaccines.

OBJECTIVES: Development of safe and effective vaccines against coronavirus disease 2019 (COVID-19) remains the cornerstone of controlling this pandemic. However, there are increasing reports of various types of stroke including ischemic stroke, and hemorrhagic stroke, as well as cerebral venous sinus thrombosis (CVST) after COVID-19 vaccination. This paper aims to review reports of stroke associated with COVID-19 vaccines and provide a coherent clinical picture of this condition. MATERIALS AND METHODS: A literature review was performed with a focus on data from recent studies. RESULTS: Most of such patients are women under 60 years of age and who had received ChAdOx1 nCoV-19 vaccine. Most studies reported CVST with or without secondary ischemic or hemorrhagic stroke, and some with Vaccine-induced Thrombotic Thrombocytopenia (VITT). The most common clinical symptom of CVST seen after COVID-19 vaccination was headache. The clinical course of CVST after COVID-19 vaccination may be more severe than CVST not associated with COVID vaccination. Management of CVST following COVID-19 vaccination is challenging and may differ from the standard treatment of CVST. Low molecular weight heparin is commonly used in the treatment of CVST; however, it may worsen outcomes in CVST associated with VITT. Furthermore, administration of intravenous immunoglobulin and high-dose glucocorticoids have been recommended with various success rates. CONCLUSION: These contradictory observations are a source of confusion in clinical decision-making and warrant further study and development of clinical guidelines. Clinicians should be aware of clinical presentation, diagnosis, and management of stroke associated with COVID-19 vaccination.

Peripheral Nervous System Manifestations Associated with COVID-19.

PURPOSE OF REVIEW: The present review discusses the peripheral nervous system (PNS) manifestations associated with coronavirus disease 2019 (COVID-19). RECENT FINDINGS: Nerve pain and skeletal muscle injury, Guillain-Barré syndrome, cranial polyneuritis, neuromuscular junction disorders, neuro-ophthalmological disorders, neurosensory hearing loss, and dysautonomia have been reported as PNS manifestations in patients with COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. COVID-19 has shown syndromic complexity. Not only does SARS-CoV-2 affect the central nervous system but also it involves the PNS. The PNS involvement may be due to dysregulation of the immune system attributable to COVID-19. Here we review the broad spectrum of PNS involvement of COVID-19.

Correction to: Central Nervous System Manifestations Associated with COVID-19.

The original version contained incorrect formatting of Dr. Napolis. His first name should be Mario and his last name should be Di Napoli.

Blood Pressure Variability: A New Predicting Factor for Clinical Outcomes of Intracerebral Hemorrhage.

Spontaneous primary intracerebral hemorrhage (ICH) is a stroke subtype associated with the highest mortality rate. High blood pressure (BP) is the most common cause of non-lobar ICH. Recent clinical trials have been inconclusive regarding the efficacy of aggressive BP lowering to improve ICH outcome. The association between high BP and ICH prognosis is rather complex and parameters other than absolute BP levels may be involved. In this regard, there is accruing evidence that BP variability (BPV) plays a major role in ICH outcome. Different BPV indices have been used to predict hematoma growth, neurological deterioration, and functional recovery. This review highlights the available evidence about the relationship between BPV and clinical outcomes among patients. We identified standard deviation (SD), residual SD, coefficient of variation, mean absolute change, average real variability, successive variation, spectral analysis using Fourier analysis, and functional successive variation (FSV) as indices to assess BPV. Most studies have demonstrated the association of BPV with ICH outcome, suggesting a need to monitor and control BP fluctuations in the routine clinical care of ICH patients. When large inter-subject variability exists, FSV is a viable alternative quantification of BPV as its computation is less sensitive to differences in the patient-specific observation schedules for BP than that of traditional indices.

Central Nervous System Manifestations Associated with COVID-19.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) has become a global health crisis of our time. The disease arises from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that binds to angiotensin-converting enzyme 2 (ACE2) receptors on host cells for its internalization. COVID-19 has a wide range of respiratory symptoms from mild to severe and affects several other organs, increasing the complexity of the treatment. There is accumulating evidence to suggest that SARS-CoV-2 can target the nervous system. In this review, we provide an account of the COVID-19 central nervous system (CNS) manifestations. RECENT FINDINGS: A broad spectrum of the CNS manifestations including headache, impaired consciousness, delirium, loss of smell and taste, encephalitis, seizures, strokes, myelitis, acute disseminated encephalomyelitis, neurogenic respiratory failure, encephalopathy, silent hypoxemia, generalized myoclonus, neuroleptic malignant syndrome and Kawasaki syndrome has been reported in patients with COVID-19. CNS manifestations associated with COVID-19 should be considered in clinical practice. There is a need for modification of current protocols and standing orders to provide better care for COVID-19 patients presenting with neurological symptoms.

Coronavirus Disease 2019 and Stroke: Clinical Manifestations and Pathophysiological Insights.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health threat. Some COVID-19 patients have exhibited widespread neurological manifestations including stroke. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been reported in patients with COVID-19. COVID-19-associated coagulopathy is increasingly recognized as a result of acute infection and is likely caused by inflammation, including inflammatory cytokine storm. Recent studies suggest that axonal transport of SARS-CoV-2 to the brain can occur via the cribriform plate adjacent to the olfactory bulb that may lead to symptomatic anosmia. The internalization of SARS-CoV-2 is mediated by the binding of the spike glycoprotein of the virus to the angiotensin-converting enzyme 2 (ACE2) on cellular membranes. ACE2 is expressed in several tissues including lung alveolar cells, gastrointestinal tissue, and brain. The aim of this review is to provide insights into the clinical manifestations and pathophysiological mechanisms of stroke in COVID-19 patients. SARS-CoV-2 can down-regulate ACE2 and, in turn, overactivate the classical renin-angiotensin system (RAS) axis and decrease the activation of the alternative RAS pathway in the brain. The consequent imbalance in vasodilation, neuroinflammation, oxidative stress, and thrombotic response may contribute to the pathophysiology of stroke during SARS-CoV-2 infection.

Reanimation of triceps muscle using ulnar nerve fascicle transfer to the nerve to long head of the triceps muscle.

BACKGROUND: Triceps muscle serves an important role in extension of the elbow. Its action is required for reaching out objects without using the trunk. Elbow extension is an important function for natural stabilization of the elbow. The aim of this study was to evaluate restoration of elbow extension in adults suffering triceps muscle palsy with various causes, by using transfer of a fascicle of ulnar nerve to the long head of triceps branch of the radial nerve. MATERIALS AND METHODS: In the present case series, 7 patients with partial brachial plexus injury or posterior cord injury, where triceps muscle was involved, were subjected to motor fascicle of ulnar nerve transfer to the nerve to long head of triceps for restoration of elbow extension. Follow-ups, including EMG-NCV (electromyography-nerve conduction velocity) 6 and 12 months after surgery and elbow extension muscle strength using MRC grading, were carried out. RESULTS: Six patients (85.71%) achieved a functional muscle strength of M4 for their elbow extension. In all of the patients, re-innervation was discovered using EMG-NCV. CONCLUSION: This surgical technique (ulnar nerve fascicle transfer to long head of the triceps) for improving elbow extension is promising in patients with brachial plexus injury.

Soleus nerve transfer to deep peroneal nerve for treatment of foot drop.

Different mechanisms including knee dislocation, replacement surgery, nerve tumor, lumbar disc herniation, sharp injury, and gunshot wound lead to foot drop. Several surgical techniques have been used for treatment of foot drop, however, they have had sub-optimal outcomes. Soleus branch of tibial nerve is a good donor for nerve transfer for treatment of foot drop. In this is retrospective study, we reviewed medical records of 6 consecutive patients with sustained foot drop following injury to lumbar root or peroneal nerve, who underwent transfer of the soleus branch of tibial nerve to deep peroneal nerve during 2014-2016. The mean age of the patients was 44.8 years and duration of injury to surgery and follow-up was 8.3 and 14.6 months, respectively. At the end of the follow-up, ankle dorsiflexion force was M4 in two patients (with traumatic peroneal nerve injury with M3 toe extension) and was M2 in one patient. There were three patients with lumbar degenerative disease. Of these patients, two showed M0 and one patient experienced M1 ankle dorsiflexion. We recommend that transfer of soleus nerve to deep peroneal nerve is used as an alternative technique for treatment of foot drop.

Lobectomy in traumatic brain injury patients with intracerebral hemorrhage and delayed contusion.

BACKGROUND: TBI, standing for Traumatic Brain Injury, is a leading cause of death worldwide; nonetheless, data on its management has hitherto been sparse. In view of the fact that brain lobectomy is a contentious issue in the management of TBI, we set out the current study to assess the mortality rate and outcomes of TBI with delayed contusion or Intracerebral Hemorrhage (ICH) undergoing lobectomy. METHODS: We evaluated 135 TBI patients with delayed contusion or ICH undergoing brain lobectomy from 2001 to 2013. Withal, the mortality and Glasgow Outcome Scale (GOS) and Glasgow Comma Scale (GCS) rates were assessed in these patients and the association in between was sought. RESULTS: The TBI patients undergoing brain lobectomy (77% male versus 23 % female) had a mean age of 43.4±20.3 years and experienced a survival rate of 62.2% (71% in females versus 60% in males). Favorable GOS was observed in 53% of male patients, compared with 27% in the females. Age was demonstrated to significantly affect the mortality rate (p=0.0001). Initial GCS score was associated with GOS as 79.1% of the survived patients with a GCS of higher than 9 on admission were discharged with favorable GOS. CONCLUSIONS: The evidence from the present study indicates that lobectomy can be an acceptable surgical procedure in management of TBI patients with delayed contusion or ICH.

Association of MS4A6A, CD33, and TREM2 gene polymorphisms with the late-onset Alzheimer's disease.

Introduction: Alzheimer's disease (AD), which is a progressive neurodegenerative disorder, causes structural and functional brain disruption. MS4A6A, TREM2, and CD33 gene polymorphisms loci have been found to be associated with the pathobiology of late-onset AD (LOAD). In the present study, we tested the hypothesis of association of LOAD with rs983392, rs75932628, and rs3865444 polymorphisms in MS4A6A, TREM2, CD33 genes, respectively. Methods: In the present study, 113 LOAD patients and 100 healthy unrelated age- and gender-matched controls were selected. DNA was extracted from blood samples by the salting-out method and the genotyping was performed by RFLP-PCR. Electrophoresis was carried out on agarose gel. Sequencing was thereafter utilized for the confirmation of the results. Results: Only CD33 rs3865444 polymorphism revealed a significant difference in the genotypic frequencies of GG (P = 0.001) and GT (P = 0.001), and allelic frequencies of G (P = 0.033) and T (P = 0.03) between LOAD patients and controls. Conclusion: The evidence from the present study suggests that T allele of CD33 rs3865444 polymorphism is associated with LOAD in the studied Iranian population.

Anti-inflammatory effects of alosetron mediated through 5-HT3 receptors on experimental colitis.

Development of new medicine with fewer deleterious effects and more efficacies for treatment of inflammatory bowel disease is needed. 5-Hydroxytryptamine 3 receptor (5-HT3R) antagonists have exhibited analgesic and anti-inflammatory features in vitro and in vivo. The present study was designed to evaluate the anti-inflammatory effect of alosetron, a 5-HT3R antagonist, on trinitrobenzenesulfonic acid (TNBS)-induced ulcerative colitis in rats. Two h subsequent to induce colitis (intracolonic instillation of TNBS, 50 mg/kg) in male Wistar rats, alosetron (1 mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide (mCPBG, a 5-HT3R agonist, 5 mg/kg), or alosetron + mCPBG were administrated intraperitoneally for 6 days. Animals were thereafter sacrificed and the efficacy of drugs was evaluated macroscopically, histologically, and biochemically (myeloperoxidase, tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta) on distal colon samples. Treatment with alosetron and dexamethasone improved macroscopic and microscopic colonic damages significantly and decreased myeloperoxidase activity and colonic levels of inflammatory cytokines. The profitable effects of alosetron were antagonized by concurrent administration of mCPBG. Our data provided evidence that the protective effects of alosetron on TNBS-induced colitis can be mediated by 5- HT3R.

Spontaneous Cervical Epidural Hematoma with Stroke Manifestations.

Spontaneous cervical epidural hematoma (SCEH), which is a rare disease, is manifested as by a sudden quadriplegia or paraplegia and other neurological deficits. SCEH can compress the spinal cord resulting in its clinical manifestations. The reported etiological risk factors are anticoagulants, coagulopathies, vascular malformations, infections, and herniated discs. Here, we report a 77-year-old woman with a presenting chief complaint of left hemiparesis and a history of hypertension. The medical drugs in use were aspirin and antihypertensives. The initiating presentations were hemiparesis, in favor of ischemic stroke, so the patient admitted to neurology ward and received anticoagulant therapy with the initial diagnosis of stroke. Although clinical manifestations and examinations are important in these patients due to mimicking stroke picture, imaging evaluation is paramount for a definite diagnosis, which in our case showed a SCEH, who was suspected to have an ischemic stroke during the initial assessment because its initial demonstration mimicked ischemic stroke. This patient underwent laminectomy after 3 days and showed a clinical recovery the day after. Her muscle strength improved gradually, and neurological symptoms were diminished after physiotherapy.

Mitochondrial DNA G15927A and G15928A variations in patients with multiple sclerosis.

BACKGROUND: Modern genetics has offered a fresh perspective on the pathology of Multiple Sclerosis (MS). As mitochondrial DNA (mtDNA) variations are held to be potential contributors to the complex pathobiology of MS, the present study tests the claim that mtDNA G15927A or G15928A variations, or both, are associated with MS in an Iranian population. MATERIALS AND METHODS: Following DNA extraction from blood samples of 100 subjects with relapsing-remitting MS, and 100 healthy unrelated control subjects, PCR-RFLP analyses was carried out by HpaII restriction enzyme reaction. Electrophoresis was then performed with 3% Agarose gel. As the restriction enzyme did not differentiate between two neighboring nucleotide positions (G15927A and G15928A), all PCR products with a variant allele were sequenced to determine the exact position of the variation. RESULTS: The MtDNA G15927A or G15928A variations were observed in 11 of all 100 cases of MS (11%) and in 7 of 100 healthy control subjects (7%) (P = 0.3, OR = 1.6, 95% CI = 0.5-5.2). Having sequenced all the PCR products with the variant allele (11 cases and 7 controls), the mtDNA G15927A variation was found in one of the 100 cases (1%) and 3 of 100 controls (3%) (P = 0.3, OR = 0.3, 95% CI = 0.0-4.1). Therefore, the mtDNA G15928A variation was present in 10 of the 100 cases (10%) and in 4 of 100 controls (4%) (P = 0.09, OR = 2.6, 95% CI = 0.7-12.0). CONCLUSION: Neither mtDNA variation, G15927A or G15928A, was associated with MS in the studied Iranian population. There was a non-significant association of the G15927A and the G15928A variations separately with MS.

Double nerve transfer for restoration of hand grasp and release in C7 tetraplegia following complete cervical spinal cord injury.

Cervical spinal cord injury (SCI) can cause tetraplegia. Nerve transfer has been routinely utilized for reconstruction of hand in brachial plexus injuries. Here, we report reconstruction of finger flexion (hand grasp) and extension (hand release) in a victim of cervical spinal cord injury with tetraplegia. We also focus on importance of extension phase in restoration of hand function in the tetraplegic case, in addition to provision of a detailed description of both operations including text, photographs, and a video. We used double nerve transfer, namely brachialis branches of musculocutaneous nerve to anterior interosseous nerve (AIN) and supinator branch of radial nerve to posterior interosseous nerve (PIN). We found that brachialis nerve transfer to AIN (for finger flexion) and supinator branch nerve transfer to PIN (for finger extension) can provide finger flexion and extension simultaneously. Brachialis nerve transfer to AIN and supinator branch nerve transfer to PIN may be an acceptable surgical technique to restore hand grasp and release in tetraplegia after SCI.

Successful recovery of sensation loss in upper brachial plexus injuries.

OBJECTIVE: Injuries of the upper trunk of the brachial plexus may trigger motor and sensory deficits. There exists a growing body of literature with respect to the reconstruction of motor deficits in upper trunk brachial plexus injuries by using nerve transfers; albeit to date, very few old reports have focused on the reconstruction of sensory loss resulting from upper trunk injuries. In this case series, we review six cases (five males and one female) with upper trunk brachial plexus injuries undergoing sensory nerve transfers. METHODS: Sensory reconstruction was carried out by using transfer of the ulnar to the median nerves, innervating adjacent aspects of the little and ring fingers (the fourth web space) and adjacent aspects of the thumb and the index finger (the first web space), respectively. RESULTS: The mean age of our six patients was 30.5 ± 9 years old (range 20-45). The mean time interval between the injury and subsequent surgery was 6.6 ± 1.8 months (range 5-10). Five patients achieved S3 or S3+ in both the thumb and the index finger while the sixth one regained S2+ in the index finger while also achieving S3 in the thumb according to the Highet-Zachary system scoring scale. CONCLUSION: These results suggest that nerve transfers can achieve satisfactory outcomes in patients having sensory reconstruction after upper brachial plexus injuries, and thus, we lay emphasis on reviving the use of sensory nerve transfer techniques in such patients.

The First Experience of Triple Nerve Transfer in Proximal Radial Nerve Palsy.

BACKGROUND: Injury to distal portion of posterior cord of brachial plexus leads to palsy of radial and axillary nerves. Symptoms are usually motor deficits of the deltoid muscle; triceps brachii muscle; and extensor muscles of the wrist, thumb, and fingers. Tendon transfers, nerve grafts, and nerve transfers are options for surgical treatment of proximal radial nerve palsy to restore some motor functions. Tendon transfer is painful, requires a long immobilization, and decreases donor muscle strength; nevertheless, nerve transfer produces promising outcomes. We present a patient with proximal radial nerve palsy following a blunt injury undergoing triple nerve transfer. CASE DESCRIPTION: The patient was involved in a motorcycle accident with complete palsy of the radial and axillary nerves. After 6 months, on admission, he showed spontaneous recovery of axillary nerve palsy, but radial nerve palsy remained. We performed triple nerve transfer, fascicle of ulnar nerve to long head of the triceps branch of radial nerve, flexor digitorum superficialis branch of median nerve to extensor carpi radialis brevis branch of radial nerve, and flexor carpi radialis branch of median nerve to posterior interosseous nerve, for restoration of elbow, wrist, and finger extensions, respectively. CONCLUSIONS: Our experience confirmed functional elbow, wrist, and finger extensions in the patient. Triple nerve transfer restores functions of the upper limb in patients with debilitating radial nerve palsy after blunt injuries.