A Girl from Qatar with Post-Infantile Acquired Cerebral Palsy Caused By Submersion Injury: A Rare Etiology and a Therapeutic-Challenge.

Background: Cerebral palsy is a heterogeneous disorder that can cause a lifelong disability that is associated with a non-progressive damage in the brain. It is commonly caused by antenatal, perinatal, early postnatal and neonatal conditions. However, post-neonatal cases of acquired cerebral palsy have also been reported, and were commonly caused by infection. Patients and Methods: The family of a girl from Qatar, who developed severe cerebral palsy caused by submersion injury, consulted us about the possible therapies for her condition. Clinical picture and brain imaging abnormalities are described, and the relevant literatures were reviewed with the aim of suggesting possible evidence-based therapies. Results: At the age of 23 months, a previously healthy girl developed anoxic encephalopathy after experiencing submersion injury. MRI showed evidence of significant hypoxic ischemic injury primarily affecting the deep grey matter, hippocami, mid-brain and the posterior cortex. EEG showed diffuse slowness of cerebral activity and diffuse attenuation of the background without no epileptic abnormalities suggesting diffuse encephalopathy resulting from diffuse cortical injury. At the about age of three and half years, her family consulted us about her condition as she was still showing no awareness to the environment, showing no significant spontaneous movements. She had poor head control. Unable to sit or stand alone, and had a flexed posture. She was on levetiracetam (Keppra), diazepam, and baclofen 30 mg daily. She was still having tracheotomy, and was fed through gastrostomy tube. Conclusion: In this paper, the rare occurrence of severe post-infantile cerebral palsy is described. Emphasis is made on the possibility of using evidence-based multi-factorial therapies in cerebral palsy.

A Girl from Qatar with Post-Infantile Acquired Cerebral Palsy Caused By Submersion Injury: A Rare Etiology and a Therapeutic Challenge

Background: Cerebral palsy is a heterogeneous disorder that can cause a lifelong disability that is associated with a non-progressive damage in the brain. It is commonly caused by antenatal, perinatal, early postnatal and neonatal conditions. However, post-neonatal cases of acquired cerebral palsy have also been reported, and were commonly caused by infection. Patients and methods: The family of a girl from Qatar, who developed severe cerebral palsy caused by submersion injury, consulted us about the possible therapies for her condition. Clinical picture and brain imaging abnormalities are described, and the relevant literatures were reviewed with the aim of suggesting possible evidence-based therapies. Results: At the age of 23 months, a previously healthy girl developed anoxic encephalopathy after experiencing submersion injury. MRI showed evidence of significant hypoxic ischemic injury primarily affecting the deep grey matter, hippocami, mid-brain and the posterior cortex. EEG showed diffuse slowness of cerebral activity and diffuse attenuation of the background without no epileptic abnormalities suggesting diffuse encephalopathy resulting from diffuse cortical injury. At the about age of three and half years, her family consulted us about her condition as she was still showing no awareness to the environment, showing no significant spontaneous movements. She had poor head control. Unable to sit or stand alone, and had a flexed posture. She was on levetiracetam (Keppra), diazepam, and baclofen 30 mg daily. She was still having tracheotomy, and was fed through gastrostomy tube. Conclusion: In this paper, the rare occurrence of severe post-infantile cerebral palsy is described. Emphasis is made on the possibility of using evidence-based multi-factorial therapies in cerebral palsy.

Accumulation of meningeal lymphocytes, but not myeloid cells, correlates with subpial cortical demyelination and white matter lesion activity in progressive MS patients

Subpial cortical demyelination is an important component of multiple sclerosis (MS) pathology contributing to disease progression, yet mechanism(s) underlying its development remain unclear. Compartmentalized inflammation involving the meninges may drive this type of injury. Given recent findings identifying substantial white matter (WM) lesion activity in patients with progressive MS, elucidating whether and how WM lesional activity relates to meningeal inflammation and subpial cortical injury is of interest. Using post-mortem formalin-fixed paraffin-embedded tissue blocks (range, 5-72 blocks; median, 30 blocks) for each of 27 progressive MS patients, we assessed the relationship between meningeal inflammation, the extent of subpial cortical demyelination, and the state of subcortical WM lesional activity. Meningeal accumulations of T cells and B cells, but not myeloid cells, were spatially adjacent to subpial cortical lesions and greater immune-cell accumulation was associated with higher subpial lesion numbers. Patients with a higher extent of meningeal inflammation harboured a greater proportion of active and mixed (active-inactive) WM lesions, and an overall lower proportion of inactive and remyelinated WM lesions. Our findings support the involvement of meningeal lymphocytes in subpial cortical injury, and also point to a potential link between inflammatory subpial cortical demyelination and pathological mechanisms occurring in the subcortical white matter.

P75 neurotrophin receptor controls subventricular zone neural stem cell migration after stroke

Stroke is the leading cause of adult disability. Endogenous neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to the brain repair process. However, molecular mechanisms underlying CNS disease-induced SVZ NSPC-redirected migration to the lesion area are poorly understood. Here, we show that genetic depletion of the p75 neurotrophin receptor (p75NTR−/−) in mice reduced SVZ NSPC migration towards the lesion area after cortical injury and that p75NTR−/− NSPCs failed to migrate upon BDNF stimulation in vitro. Cortical injury rapidly increased p75NTR abundance in SVZ NSPCs via bone morphogenetic protein (BMP) receptor signaling. SVZ-derived p75NTR−/− NSPCs revealed an altered cytoskeletal network- and small GTPase family-related gene and protein expression. In accordance, BMP-treated non-migrating p75NTR−/− NSPCs revealed an altered morphology and α-tubulin expression compared to BMP-treated migrating wild-type NSPCs. We propose that BMP-induced p75NTR abundance in NSPCs is a regulator of SVZ NSPC migration to the lesion area via regulation of the cytoskeleton following cortical injury.

Sex differences in recovery of motor function in a rhesus monkey model of cortical injury

Background Stroke disproportionately affects men and women, with women over 65 years experiencing increased severity of impairment and higher mortality rates than men. Human studies have explored risk factors that contribute to these differences, but additional research is needed to investigate how sex differences affect functional recovery and hence the severity of impairment. In the present study, we used our rhesus monkey model of cortical injury and fine motor impairment to compare sex differences in the rate and degree of motor recovery following this injury. Methods Aged male and female rhesus monkeys were trained on a task of fine motor function of the hand before undergoing surgery to produce a cortical lesion limited to the hand area representation of the primary motor cortex. Post-operative testing began two weeks after the surgery and continued for 12 weeks. All trials were video recorded and latency to retrieve a reward was quantitatively measured to assess the trajectory of post-operative response latency and grasp pattern compared to pre-operative levels. Results Postmortem analysis showed no differences in lesion volume between male and female monkeys. However, female monkeys returned to their pre-operative latency and grasp patterns significantly faster than males. Conclusions These findings demonstrate the need for additional studies to further investigate the role of estrogens and other sex hormones that may differentially affect recovery outcomes in the primate brain.

Roles of Cytokines in the Temporal Changes of Microglial Membrane Currents and Neuronal Excitability and Synaptic Efficacy in ATP-Induced Cortical Injury Model

Cytokines are important neuroinflammatory modulators in neurodegenerative brain disorders including traumatic brain injury (TBI) and stroke. However, their temporal effects on the physiological properties of microglia and neurons during the recovery period have been unclear. Here, using an ATP-induced cortical injury model, we characterized selective effects of ATP injection compared to needle-control. In the damaged region, the fluorescent intensity of CX3CR1-GFP (+) cells, as well as the cell density, was increased and the maturation of newborn BrdU (+) cells continued until 28 day-post-injection (dpi) of ATP. The excitability and synaptic E/I balance of neurons and the inward and outward membrane currents of microglia were increased at 3 dpi, when expressions of tumor necrosis factor (TNF)-α/interleukin (IL)-1β and IL-10/IL-4 were also enhanced. These changes of both cells at 3 dpi were mostly decayed at 7 dpi and were suppressed by any of IL-10, IL-4, suramin (P2 receptor inhibitor) and 4-AP (K+ channel blocker). Acute ATP application alone induced only small effects from both naïve neurons and microglial cells in brain slice. However, TNF-α alone effectively increased the excitability of naïve neurons, which was blocked by suramin or 4-AP. TNF-α and IL-1β increased and decreased membrane currents of naïve microglia, respectively. Our results suggest that ATP and TNF-α dominantly induce the physiological activities of 3 dpi neurons and microglia, and IL-10 effectively suppresses such changes of both activated cells in K+ channel- and P2 receptor-dependent manner, while IL-4 suppresses neurons preferentially.

Mini-temporal approach as an alternative to the classical pterional approach for resective temporal region surgeries: Technical note

Background Classical pterional appoach for temporal surgeries may cause atrophy and dysfunction of temporalis, injury to the facial nerve, as well as unnecessary cortical exposure. As an alternative to the classical pterional approach for such surgeries, we hereby describe an mini-temporal approach which reduces these risks and proven to be practical in neurological surgeries. Methods In the mini-temporal incision design, the frontal end of the incision never surpassed the hairline at the level of temporal line, and a one-layer skin-galea-muscle flap was detached from the cranium, effectively avoiding the injuries of facial nerve. The surgical bone window was completely located underneath the temporalis muscle, allowing it to be completely repositioned postoperatively. Results We demonstrated the application of mini-temporal approach in a variety of temporal region tumors, which can be applied to complete successful resective surgeries while effectively reducing injuries to extra-temporal cortex, temporalis and facial nerve. There were no postoperative complications related to extra-temporal cortical damage, atrophy of temporalis or injury to the facial nerve. Conclusion The mini-temporal approach can effectively shorten the time of craniotomy and closure, decrease the size of bony removal, increase the restoration of temporalis during closure and lower the chance of facial nerve injury. Therefore, it improves cosmetic outcomes and reduces the risk of unintentional extra-temporal cortical injury, which fully embodies the minimally invasive principle in neurosurgery.