High-Throughput Strategy for Profiling Sequential Section With Multiplex Staining of Mouse Brain

The brain modulates specific functions in its various regions. Understanding the organization of different cells in the whole brain is crucial for investigating brain functions. Previous studies have focused on several regions and have had difficulty analyzing serial tissue samples. In this study, we introduced a pipeline to acquire anatomical and histological information quickly and efficiently from serial sections. First, we developed a serial brain-slice-staining method to stain serial sections and obtained more than 98.5% of slices with high integrity. Subsequently, using the self-developed analysis software, we registered and quantified the signals of imaged sections to the Allen Mouse Brain Common Coordinate Framework, which is compatible with multimodal images and slant section planes. Finally, we validated the pipeline with immunostaining by analyzing the activity variance in the whole brain during acute stress in aging and young mice. By removing the problems resulting from repeated manual operations, this pipeline is widely applicable to serial brain slices from multiple samples in a rapid and convenient manner, which benefits to facilitate research in life sciences.

Recovery of Severe Dialysis Disequilibrium Syndrome with Uncal Herniation Following Therapy with Mannitol, Hyperventilation and Hypertonic Saline

Dialysis disequilibrium syndrome (DDS) is a rare complication of dialysis, especially with the general application of preventive strategies. Severe DDS with brain herniation is believed to be fatal. We present a patient presenting with bilateral uncal herniation after receiving two dialysis sessions with low-efficiency settings. The serial brain magnetic resonance imaging studies showed the temporal evolution of DDS-induced cerebral edema. With aggressive treatment of hypertonic saline and mannitol, the patient made a remarkable recovery. This case highlights that we should be cautious about this severe complication of dialysis even with preventive strategies, and recovery is possible with prompt recognition and treatment.

Complicated Pneumococcal Meningitis: A Diagnostic and Therapeutic Challenge

Meningitis is an uncommon complication of head trauma. Vasculitis in bacterial meningitis is seen in 9–25% of adults while neurological deficits in bacterial meningitis are seen in about one-third of children. We report a 5-year-old boy, previously healthy who was admitted in March 2019 to Latifa Women’s and Children’s Hospital, Dubai, UAE, with pneumococcal meningitis. One day before presentation, he had a history of fall with head trauma while running at school. Initial brain CT scan was normal. Few hours after admission, the child was noticed to be drowsy with cold extremities and mottled skin. He was shifted to PICU and, ultimately, he required intubation and mechanical ventilation. The child continued spiking high-grade fever with deterioration in the neurologic status. His GCS deteriorated to 4/15 with decerebrations posture. He underwent serial brain imaging which revealed multiple chronic infarcts with hydrocephalic changes due to ongoing cerebral vasculitis. The child was started on steroid therapy on 28 April 2019 after which his condition improved at an incredible pace.

Enlarged periventricular space and periventricular lesion extension on baseline brain MRI predicts poor neurological outcomes in cryptococcus meningoencephalitis

In Cryptococcus neoformans meningoencephalitis, brain MRI findings might reflect the phathomechanism of disease progression that is fungal accumulation in the peri-venular space and consequent invasion into the parenchyma. This study analyzed serial brain MRI findings of 76 patients with cryptococcus meningoencephalitis in association with the disease progression and outcomes. MRI parameters included the enlarged periventricular space (ePVS) score (range 0–8), periventricular lesion extension, cryptococcoma, and hydrocephalus. Clinical outcomes at 2-week, 10-week, and 6-month were evaluated using modified Rankin scale (mRS). At 6 months, 15 (19.7%) patients died and 34 (44.1%) had poor neurological outcomes (mRS scores > 2). At baseline, an ePVS score of ≥ 5 (Odds-ratio [OR]: 94.173, 95% confidence-interval [95%CI]: 7.507–1181.295, P < .001), periventricular lesion extension (OR: 51.965, 95%CI: 2.592–1041.673, P = .010), and presence of encephalitis feature (OR: 44.487, 95%CI: 1.689–1172.082, P = .023) were associated with 6-month poor outcomes. Presence of two or more risk factors among encephalitis feature, ePVS score ≥ 5, and periventricular lesion extension at baseline, was associated with 6-month poor outcomes (area under the curve [AUC]: 0.978, P < .001) and mortality (AUC: 0.836, P < .001). Disease progression was associated with interval development of cryptococcoma and hydrocephalus. Brain MRI findings might be useful in predicting outcomes and monitoring the progression of cryptococcus meningoencephalitis.

NeuroAid II (MLC901) in Haemorrhagic Stroke

Stroke is a leading cause of death and disability. NeuroAid (MLC601), which originates from Traditional Chinese Medicine, comprises herbal and animal components, and has been shown to improve the functional status of patients after ischaemic stroke. The use of NeuroAid II (MLC901), which comprises only the herbal components of MLC601, in haemorrhagic stroke has not been previously reported. Our patient is a 63-year-old male with a significant stroke risk factor of hypertension. He developed visual field defect, aphasia, unilateral weakness, and hemisensory loss. CT scan showed a left thalamic haemorrhage. In addition to anti-hypertensive therapy and intensive rehabilitation, he was prescribed MLC901. Over a period of 6 months, he had significant improvements in his motor, sensory, and speech function. There were no adverse events, serial brain CT scans showed resolution of the haemorrhage. MLC901 may have a role in post-stroke recovery after intracranial haemorrhage.

Outcomes of Cryptococcus meningoencephalitis and associated magnetic resonance imaging findings

In Cryptococcus Neoformans meningoencephalitis, brain MRI findings might reflect the phathomechanism of disease progression that is fungal accumulation in the peri-venular space and consequent invasion into the parenchyma. This study analyzed serial brain MRI findings of 76 patients with cryptococcus meningoencephalitis in association with the disease progression and outcomes. MRI parameters included the enlarged periventricular space (ePVS) score (range 0 − 8), periventricular lesion extension, cryptococcoma, and hydrocephalus. Clinical outcomes at 2-week, 10-week, and 6-month were evaluated using modified Rankin scale (mRS) scores. At 6 months, 15 (19.7%) patient died and 34 (44.1%) had poor neurological outcomes (mRS scores > 2). At baseline, an ePVS score of ≥ 5 (Odds-ratio [OR]: 94.173, 95% confidence-interval [95% CI]: 7.507 − 1181.295, P < 0.001), periventricular lesion extension (OR: 51.965, 95% CI: 2.592 − 1041.673, P = 0.010), and presence of encephalitis feature (OR: 44.487, 95% CI: 1.689 − 1172.082, P = 0.023) were associated with 6-month poor outcomes. Presence of two or more risk factors at baseline was highly associated with the 6-month poor outcomes (area under the curve [AUC]: 0.978, P < 0.001) and mortality (AUC: 0.836, P < 0.001). Disease progression was associated with interval development of cryptococcoma and hydrocephalus. In conclusion, brain MRI findings might be useful in predicting poor outcomes and monitoring the disease progression of cryptococcus meningoencephalitis.

Intranasally Administered Human MSC-Derived Extracellular Vesicles Pervasively Incorporate into Neurons and Microglia in both Intact and Status Epilepticus Injured Forebrain

Extracellular vesicles (EVs) derived from human bone marrow mesenchymal stem cells (hMSCs) have great promise as biologics to treat neurological and neurodegenerative conditions due to their robust antiinflammatory and neuroprotective properties. Besides, intranasal (IN) administration of EVs has caught much attention because the procedure is noninvasive, amenable for repetitive dispensation, and leads to a quick penetration of EVs into multiple regions of the forebrain. Nonetheless, it is unknown whether brain injury-induced signals are essential for the entry of IN-administered EVs into different brain regions. Therefore, in this study, we investigated the distribution of IN-administered hMSC-derived EVs into neurons and microglia in the intact and status epilepticus (SE) injured rat forebrain. Ten billion EVs labeled with PKH26 were dispensed unilaterally into the left nostril of naïve rats, and rats that experienced two hours of kainate-induced SE. Six hours later, PKH26 + EVs were quantified from multiple forebrain regions using serial brain sections processed for different neural cell markers and confocal microscopy. Remarkably, EVs were seen bilaterally in virtually all regions of intact and SE-injured forebrain. The percentage of neurons incorporating EVs were comparable for most forebrain regions. However, in animals that underwent SE, a higher percentage of neurons incorporated EVs in the hippocampal CA1 subfield and the entorhinal cortex, the regions that typically display neurodegeneration after SE. In contrast, the incorporation of EVs by microglia was highly comparable in every region of the forebrain measured. Thus, unilateral IN administration of EVs is efficient for delivering EVs bilaterally into neurons and microglia in multiple regions in the intact or injured forebrain. Furthermore, incorporation of EVs by neurons is higher in areas of brain injury, implying that injury-related signals likely play a role in targeting of EVs into neurons, which may be beneficial for EV therapy in various neurodegenerative conditions including traumatic brain injury, stroke, multiple sclerosis, and Alzheimer’s disease.

Autoimmune Encephalitis and CSF Anti-GluR3 Antibodies in an MS Patient after Alemtuzumab Treatment

A 45-year-old Italian woman, affected by relapsing–remitting multiple sclerosis (RR-MS) starting from 2011, started treatment with alemtuzumab in July 2016. Nine months after the second infusion, she had an immune thrombocytopenic purpura (ITP) with complete recovery after steroid treatment. Three months after the ITP, the patient presented with transient aphasia, cognitive deficits, and focal epilepsy. Serial brain magnetic resonance imaging showed a pattern compatible with encephalitis. Autoantibodies to glutamate receptor 3 peptide A and B were detected in cerebrospinal fluid and serum, in the absence of any other diagnostic cues. After three courses of intravenous immunoglobulin (0.4 mg/kg/day for 5 days, 1 month apart), followed by boosters (0.4 mg/kg/day) every 4–6 weeks, her neurological status improved and is currently comparable with that preceding the encephalitis. Autoimmune complications of the central nervous system during alemtuzumab therapy are relatively rare: only one previous case of autoimmune encephalitis following alemtuzumab treatment has been reported to date.