Testing the cognitive effects of tadalafil. Neuropsychological secondary outcomes from the PASTIS trial.

Cerebral small vessel disease (SVD) is a major cause of cognitive impairment in older people. As secondary endpoints in a phase-2 randomised clinical trial, we tested the effects of single administration of a widely-used PDE5 inhibitor, tadalafil, on cognitive performance in older people with SVD. In a double-blinded, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥ 7 days apart (randomised to order of treatment). The Montreal Cognitive Assessment (MOCA) was administered at baseline, alongside a measure to estimate optimal intellectual ability (Test of Premorbid Function). Then, before and after treatment, a battery of neuropsychological tests was administered, assessing aspects of attention, information processing speed, working memory and executive function. Sixty-five participants were recruited and 55 completed the protocol (N = 55, age: 66.8 (8.6) years, range 52-87; 15/40 female/male). Median MOCA score was 26 (IQR: 23, 27], range 15-30). No significant treatment effects were seen in any of the neuropsychological tests. There was a trend towards improved performance on Digit Span Forward (treatment effect 0.37, C.I. 0.01, 0.72; P = 0.0521). We did not identify significant treatment effects of single-administration tadalafil on neuropsychological performance in older people with SVD. The trend observed on Digit Span Forward may help to inform future studies. Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT00123456, https://eudract.ema.europa.eu. Unique identifier: 2015-001,235-20NCT00123456.

Transglabellar resection of frontal sinus cholesterol granuloma extending cranially through cecum foramina: Technical note.

Background: Cholesterol granuloma (CG) commonly occurs in the petrous apex; their occurrence in the anterior cranial fossa CGs is rare. Subfrontal approaches are the conventional surgical approaches for the resection of midline lesions of the anterior cranial fossa and frontal sinuses. In this article, we describe a successful minimally invasive approach for resection of a small midline anterior cranial fossa CG. Methods: We report a rare case of frontal air sinus CG extending intradurally through the foramen caecum. The surgical management of this patient involved the use of a minimally invasive transglabellar approach and a butterfly incision and the patient outcomes at 1 year after the surgery. Results: The lesion was totally resected with no complications and the patient was discharged on the 3rd postoperative day. A 1-year follow-up scan showed neither residual nor recurrence of the lesion. Conclusion: The transglabellar approach through a butterfly incision offers a safe approach for the resection of a lesion extending from the frontal air sinuses to the anterior cranial fossa with no complications, shorter hospital stay, and good cosmetic results.

Unilateral microscopic approach for lumbar spinal stenosis decompression: a scoping review.

BACKGROUND: Microscopic unilateral laminotomy for bilateral decompression (ULBD) is a minimally invasive technique used in the treatment of lumbar spinal stenosis and could limit spinal instability and be associated with better clinical outcomes. However, there is ongoing debate regarding its utility compared to conventional laminectomy (CL). The primary objective was to collate and describe the current evidence base for ULBD, including perioperative parameters, functional outcomes, and complications. The secondary objective was to identify operative techniques. METHODS: A scoping review was conducted between January 1990 and August 2022 according to the PRISMA extension for scoping reviews (PRISMA-ScR) guidelines. Major databases were searched for full text English articles reporting on outcomes following microscopic unilateral laminotomy in patients with lumbar spinal stenosis. RESULTS: Seventeen articles met the inclusion criteria. Two studies were randomised controlled trials. Two studies were prospective data collection and the rest were retrospective analysis. Three studies compared ULBD with CL. ULBD preserves the osteoligamentous complex and may be associated with shorter operative time, less blood loss, and similar clinical outcomes when compared to CL. CONCLUSION: This review highlights that ULBD aims to minimise disruption to the normal posterior spinal anatomy and may have acceptable clinical outcomes. It also highlights that it is difficult to draw valid conclusions given there are limited data available as most studies identified were retrospective or did not have a comparator group.

Carbon fibre instrumentation for scoliosis surgery in children with spinal cord intramedullary tumours: a novel technical note.

INTRODUCTION: Scoliosis in children is the most common spinal deformity seen by general practitioners, paediatricians and spinal surgeons. Progressive scoliosis can result in the development of a worsening deformity and cosmesis. Patients usually present with aesthetic concerns. Progressive scoliosis that fails conservative management may require or be offered surgical intervention. Intramedullary tumours may be associated with scoliosis. Management of patients with these dual pathologies can be challenging. Classical scoliosis instrumentation utilising titanium implants impairs post-operative MRI evaluation with metal artefacts. Carbon fibre instrumentations has the potential to reduce the imaging metal artefacts but has not been described in scoliosis correction. METHODS: Surgical technical note describing correction of scoliosis in two adolescents' with intradural tumours utilising carbon fibre implants. RESULTS: We developed a hybrid approach where we initially used titanium implants to manipulate the deformity then replaced the construct with carbon fibre implants in the same setting to maintain the deformity correction with good follow up outlook. CONCLUSION: Our technique is robust, safe and replicable. It enabled appropriate post-operative MRI evaluation of the neural structures with a reduced risk of metal artefacts.

Giant cell glioblastoma multiforme presents as acute pathological nontraumatic subdural haematoma.

We describe a case of giant cell glioblastoma multiforme (GBM) that presented with a non-traumatic acute subdural haematoma (NASDH). A 57-year-old male had a sudden onset headache and rapid deterioration in conscious level with Glasgow Coma Scale (GCS) of 5 and dilated unreactive left pupil. CT of the head revealed a left acute subdural haematoma with mass effect and a left parietal lesion. Our literature review revealed that glioblastoma presenting as an acute subdural haematoma is extremely unusual. To our knowledge, we report the second case. We propose an invasion of the arachnoid and cortical veins by the aggressive tumour as a possible underlying mechanism.

Dissection-related tandem occlusion may be different from atherothrombotic tandem occlusion.

OBJECTIVES: The optimal endovascular treatment for tandem occlusion in anterior circulation ischaemic stroke remains unknown. The aim of this study was to examine how the aetiology of carotid pathology, dissection versus atherothrombosis, affects clinical outcomes. MATERIALS AND METHODS: Data was obtained from prospectively collected registries from two stroke centres between April 2016 and December 2020. Tandem cases with complete cervical internal carotid artery (ICA) occlusion or near-total occlusion (≥90% stenosis) were included. Patients were divided into two groups based on carotid pathology: dissection versus atherothrombosis. RESULTS: A total of 134 patients were included: 36 were dissection and 98 were atherothrombosis. The dissection group had better clinical outcomes compared to the atherothrombosis group, although after adjusting for age and stroke risk factors differences were non-significant. In the non-stented cohort, the dissection patients achieved a better outcome (modified Rankin scale 0-2) than atherothrombotic patients (57% vs. 34%, p=0.04) at 90-days. CONCLUSION: Dissection-related tandem occlusions appear to have different clinical features from atherothrombotic tandem occlusions which suggests different management strategies are needed.

Resolving solitary osteolytic lumbar tuberculosis in young adult.

Lumbar vertebral tuberculosis presenting with a focal solitary osteolytic lesion is rare in spinal tuberculosis (TB) and the English literature describing this entity is scant. The differential diagnosis includes primary and secondary malignancies. In this report, we describe a case of 35-year-old woman who presented with low back pain and was found to have a focal L4 vertebral lytic lesion on MRI and CT. Whole body CT was carried out as a potential malignancy staging procedure and demonstrated lung lesions suggestive of TB. Her neurological and general examination were entirely normal. Her blood test was positive for QuantiFERON Gold. She was managed conservatively with anti-TB medications and serial imaging which showed evidence of resolution of the osteolytic lesion. Although it is unusual for TB to present as an isolated osteolytic vertebral body lesion, the possibility should always be considered in the differential diagnosis, along with neoplastic processes. Conservative medical management, in the absence of neurological deficits and deformity, is the main stay of management with a very good outlook.

Vascular Collagen Type-IV in Hypertension and Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease (SVD) is common in older people and causes lacunar stroke and vascular cognitive impairment. Risk factors include old age, hypertension and variants in the genes COL4A1/COL4A2 encoding collagen alpha-1(IV) and alpha-2(IV), here termed collagen-IV, which are core components of the basement membrane. We tested the hypothesis that increased vascular collagen-IV associates with clinical hypertension and with SVD in older persons and with chronic hypertension in young and aged primates and genetically hypertensive rats. METHODS: We quantified vascular collagen-IV immunolabeling in small arteries in a cohort of older persons with minimal Alzheimer pathology (N=52; 21F/31M, age 82.8±6.95 years). We also studied archive tissue from young (age range 6.2-8.3 years) and older (17.0-22.7 years) primates (M mulatta) and compared chronically hypertensive animals (18 months aortic stenosis) with normotensives. We also compared genetically hypertensive and normotensive rats (aged 10-12 months). RESULTS: Collagen-IV immunolabeling in cerebral small arteries of older persons was negatively associated with radiological SVD severity (ρ: -0.427, P=0.005) but was not related to history of hypertension. General linear models confirmed the negative association of lower collagen-IV with radiological SVD (P<0.017), including age as a covariate and either clinical hypertension (P<0.030) or neuropathological SVD diagnosis (P<0.022) as fixed factors. Reduced vascular collagen-IV was accompanied by accumulation of fibrillar collagens (types I and III) as indicated by immunogold electron microscopy. In young and aged primates, brain collagen-IV was elevated in older normotensive relative to young normotensive animals (P=0.029) but was not associated with hypertension. Genetically hypertensive rats did not differ from normotensive rats in terms of arterial collagen-IV. CONCLUSIONS: Our cross-species data provide novel insight into sporadic SVD pathogenesis, supporting insufficient (rather than excessive) arterial collagen-IV in SVD, accompanied by matrix remodeling with elevated fibrillar collagen deposition. They also indicate that hypertension, a major risk factor for SVD, does not act by causing accumulation of brain vascular collagen-IV.

The Effect of COVID-19 National Lockdown on the Time from Presentation to Surgery of Patients with Suspected Cauda Equina Syndrome: Two UK Tertiary Centers' Study.

OBJECTIVE: To investigate if COVID-19 UK lockdown measures resulted in a delay in the presentation and treatment of patients with cauda equina syndrome (CES). METHODS: This is a multicenter retrospective study of patients with surgically treated CES across 3 time periods: April-May 2020 (first lockdown), August-September 2020 (no-lockdown group), and January-February 2021 (second lockdown). Data regarding duration of symptoms, time from referral to admission, time from admission to surgery, and postoperative outcomes were collected. RESULTS: A total of 56 patients (male: 26, female: 30, mean age: 44.3 years) were included in the study (n = 14, n = 18, and n = 24 in the 3 time periods, respectively). There was no significant difference in duration of symptoms across the time periods (12.6 days vs. 8.2 days vs. 3.8 days) (P = 0.16). Nearly all the patients were admitted within 48 hours of referral (n = 55, 98.2%). The majority of patients were operated on within 48 hours: first lockdown (n = 12, 85.7%), no-lockdown (n = 16, 88.9%), and second lockdown (n = 21, 87.5%). The length of hospital stay was significantly shorter in the second lockdown (3.3 days) versus the other 2 time periods (4.4 days and 6.4 days) (P = 0.02). Thirteen complications were present, with dural tear being the most common (n = 6, 10.7%). Majority reported symptom improvement (n = 53, 94.6%), with a similar number discharged home (n = 54, 96.4%). CONCLUSION: Despite the pandemic, patients with CES were promptly admitted and operated on with good outcomes. Shorter duration of hospital stay could be attributed to adaptation of spinal services.

Presentation, Management, and Outcome of Primary Leiomyosarcoma of the Spine: A Systematic Review.

OBJECTIVE: Primary spinal leiomyosarcoma (PSL) is extremely rare. A case is presented, followed by a systematic review establishing the consensus on presentation, diagnosis, management, and outcomes. Comparison is made with metastatic spinal leiomyosarcoma (MSL). METHODS: A systematic review was conducted in line with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Eligibility criteria were decided before the literature search was conducted. Data were extracted and analyzed. RESULTS: A total of 397 articles were identified, 25 of which conformed to the eligibility criteria. Thirty-four cases were included in the analysis. PSL had a female preponderance (69.2%), with back pain being the most common presenting symptom (60.9%). Neurologic signs were present in most (69.6%), with tumors typically in the thoracic spine (46.9%). Diagnosis was primarily made using magnetic resonance imaging (64.7%) and computed tomography (55.9%), with a histologic sample being obtained in all cases. Most patients underwent operative management (91.2%), with variable use of neoadjuvant and adjuvant therapies. Operative approach differed greatly and outcome after surgical management was stated in 48.4% of patients, all noting an improvement from presentation. Patient follow-up was limited (median, 7 months), with most patients being free of disease (43.8%). CONCLUSIONS: PSL diagnosis is challenging, with positron emission tomography-computed tomography and histopathologic sampling playing an important role. There is a limited evidence base for the treatment strategies used but surgical management is key, with generally good outcomes. Prognosis for PSL seems to be better than for MSL. There is scope for more dedicated research in PSL and MSL.

The PASTIS trial: Testing tadalafil for possible use in vascular cognitive impairment.

INTRODUCTION: There are few randomized clinical trials in vascular cognitive impairment (VCI). This trial tested the hypothesis that the PDE5 inhibitor tadalafil, a widely used vasodilator, increases cerebral blood flow (CBF) in older people with symptomatic small vessel disease, the main cause of VCI. METHODS: In a double-blind, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥7 days apart (randomized to order of treatment). The primary endpoint, change in subcortical CBF, was measured by arterial spin labelling. RESULTS: Tadalafil increased CBF non-significantly in all subcortical areas (N = 55, age: 66.8 (8.6) years) with greatest treatment effect within white matter hyperintensities (+9.8%, P = .0960). There were incidental treatment effects on systolic and diastolic blood pressure (-7.8, -4.9 mmHg; P < .001). No serious adverse events were observed. DISCUSSION: This trial did not identify a significant treatment effect of single-administration tadalafil on subcortical CBF. To detect treatment effects may require different dosing regimens.

Test-retest reliability of arterial spin labelling for cerebral blood flow in older adults with small vessel disease.

Cerebral small vessel disease (SVD) is common in older people and is associated with lacunar stroke, white matter hyperintensities (WMH) and vascular cognitive impairment. Cerebral blood flow (CBF) is reduced in SVD, particularly within white matter.Here we quantified test-retest reliability in CBF measurements using pseudo-continuous arterial spin labelling (pCASL) in older adults with clinical and radiological evidence of SVD (N=54, mean (SD): 66.9 (8.7) years, 15 females/39 males). We generated whole-brain CBF maps on two visits at least 7 days apart (mean (SD): 20 (19), range 7-117 days).Test-retest reliability for CBF was high in all tissue types, with intra-class correlation coefficient [95%CI]: 0.758 [0.616, 0.852] for whole brain, 0.842 [0.743, 0.905] for total grey matter, 0.771 [0.636, 0.861] for deep grey matter (caudate-putamen and thalamus), 0.872 [0.790, 0.923] for normal-appearing white matter (NAWM) and 0.780 [0.650, 0.866] for WMH (all p<0.001). ANCOVA models indicated significant decline in CBF in total grey matter, deep grey matter and NAWM with increasing age and diastolic blood pressure (all p<0.001). CBF was lower in males relative to females (p=0.013 for total grey matter, p=0.004 for NAWM).We conclude that pCASL has high test-retest reliability as a quantitative measure of CBF in older adults with SVD. These findings support the use of pCASL in routine clinical imaging and as a clinical trial endpoint.All data come from the PASTIS trial, prospectively registered at: https://eudract.ema.europa.eu (2015-001235-20, registered 13/05/2015), http://www.clinicaltrials.gov (NCT02450253, registered 21/05/2015).

Acute foot drop secondary to lumbar disc prolapse after seizure.

Generalised tonic-clonic seizures have been reported to cause musculoskeletal injuries including vertebral fractures usually without resultant neurological deficit. Lumbar disc prolapse resulting in neurological deficits following seizures has not been reported. We report a 43-year-old man who presented after a generalised seizure at which point he developed worsening of low back pain and left sciatica followed by an acute foot drop. His lumbo-sacral MRI demonstrated a diffuse disc bulge at L4-5 level and a large, caudally migrated, free disc fragment with resulting severe canal stenosis at L4/5 and left lateral recess stenosis at L5/S1. He underwent urgent left L4/5 and L5/S1 micro-discectomies with resolution of his symptoms. We illustrate a rare but important treatable complication of seizures. Detailed history and clinical examination in patients with post-ictal neurological deficit should be conducted to identify the specific cause. Appropriate imaging should be performed if there remains any doubt regarding diagnosis.

Paraganglioma of the cauda equina: a tertiary centre experience and scoping review of the current literature.

Cauda equina paragangliomas are rare benign extra-adrenal neuroendocrine tumours arising from the neural crest cells associated with autonomic ganglia. These tumours are often mistaken preoperatively for ependymomas or schwannomas. Patients present with axial or radicular pain with or without neurological deficits. Recurrence, secretory features and length of follow-up are controversial. We conducted a retrospective cohort study of paraganglioma through searching a prospectively maintained histopathology database. Patient demographics, presentation, surgery, complications, recurrence, follow-up and outcome between 2004 and 2016 were studied. The primary aim was to collate and describe the current evidence base for recurrence and secretory features of the tumour. The secondary objective was to report outcome and follow-up strategy. A scoping review was performed in accordance with the PRISMA-ScR Checklist. Ten patients were diagnosed (M:F 7:3) with a mean age of 53.6 ± 5.1 (range 34-71 years). MRI scans revealed intradural lumbar enhancing lesions. All patients had complete microsurgical excisions without adjuvant therapy with no recurrence with a mean follow-up of 5.1 ± 1.4 years. Tumours were attached to the filum terminale. Electron microscopic images demonstrated abundant neurosecretory granules with no evidence of catecholamine production. A total of 620 articles were screened and 65 papers (including ours) combining 121 patients (mean age 48.8 and M:F 71:50) were included. The mean follow-up was 3.48 ± 0.46 (range 0.15-23 years). Back pain was the most common symptom (94%). Cure following surgery was achieved in 93% of the patients whilst 7% had recurrence. Total resection likely results in cure without the need for adjuvant therapy or prolonged follow-up. However, in certain situations, the length of follow-up should be determined by the treating surgeon.

Strokectomy for malignant middle cerebral artery infarction: experience and meta-analysis of current evidence.

Strokectomy means surgical excision of infarcted brain tissue post-stroke with preservation of skull integrity, distinguishing it from decompressive hemicraniectomy. Both can mitigate malignant middle cerebral artery (MCA) syndrome but evidence regarding strokectomy is sparse. Here, we report our data and meta-analysis of strokectomy compared to hemicraniectomy for malignant MCA infarction. All malignant MCA stroke cases requiring surgical intervention in a large tertiary centre (January 2012-December 2017, N = 24) were analysed for craniotomy diameter, complications, length of follow-up and outcome measured using the modified Rankin score (mRS). Good outcome was defined as mRS 0-3 at 12 months. In a meta-analysis, outcome from strokectomy (pooled from our cohort and published strokectomy studies) was compared with hemicraniectomy (our cohort pooled with published DECIMAL, DESTINY and HAMLET clinical trial data). In our series (N = 24, 12/12 F/M; mean age: 45.83 ± 8.91, range 29-63 years), 4 patients underwent strokectomy (SC) and 20 hemicraniectomy (HC). Among SC patients, craniotomy diameter was smaller, relative to HC patients (86 ± 13.10 mm, 120 ± 4.10 mm, respectively; p = 0.003), complications were less common (25%, 55%) and poor outcomes were less common (25%, 70%). In the pooled data (N = 41 SC, 71 HC), strokectomy tended towards good outcome more than hemicraniectomy (OR 2.2, 95% CI 0.99-4.7; p = 0.051). In conclusion, strokectomy may be non-inferior, lower risk and cost saving relative to hemicraniectomy sufficiently to be worthy of further investigation and maybe a randomised trial.

Aspergillus fumigatus causing vertebral osteomyelitis in an immunocompetent patient: a case report and literature review.

Aspergillus vertebral osteomyelitis causing deformity in immunocompetent patients is uncommon. We describe a previously healthy 68-year-old male who was referred after 2 years of lower thoracic back pain and gibbus. His inflammatory markers and HIV test were normal. Imaging demonstrated bony destruction of T12/L1 and L2 with vertebral collapse. Following inconclusive CT-guided biopsy, he underwent reconstructive spinal surgery. Histopathology showed fungi and Aspergillus fumigatus was cultured. He was treated with isavuconazole 200 mg once daily for 12 months with a satisfactory clinical outcome. We present a summary of recently published cases of atraumatic Aspergillus vertebral osteomyelitis in immunocompetent patients without risk factors. Fungal infection should be considered in culture-negative spondylodiscitis, even in the absence of risk factors.

Innate Immune Anti-Inflammatory Response in Human Spontaneous Intracerebral Hemorrhage.

Background and Purpose: Spontaneous intracerebral hemorrhage (sICH) is a common form of hemorrhagic stroke, with high mortality and morbidity. Pathophysiological mechanisms in sICH are poorly understood and treatments limited. Neuroinflammation driven by microglial-macrophage activation contributes to brain damage post-sICH. We aim to test the hypothesis that an anti-inflammatory (repair) process occurs in parallel with neuroinflammation in clinical sICH. Methods: We performed quantitative analysis of immunohistochemical markers for microglia and macrophages (Iba1, CD68, TMEM119, CD163, and CD206) in brain tissue biospecimens 1 to 12 days post-sICH and matched control cases. In a parallel, prospective group of patients, we assayed circulating inflammatory markers (CRP [C-reactive protein], total white cell, and monocyte count) over 1 to 12 days following sICH. Results: In 27 supratentorial sICH cases (n=27, median [interquartile range] age: 59 [52­80.5], 14F/13M) all microglia-macrophage markers increased post-sICH, relative to control brains. Anti-inflammatory markers (CD163 and CD206) were elevated alongside proinflammatory markers (CD68 and TMEM119). CD163 increased progressively post-sICH (15.0-fold increase at 7­12 days, P<0.001). CD206 increased at 3 to 5 days (5.2-fold, P<0.001) then returned to control levels at 7 to 12 days. The parenchymal immune response combined brain-derived microglia (TMEM119 positive) and invading monocyte-derived macrophages (CD206 positive). In a prospective sICH patient cohort (n=26, age 74 [66­79], National Institutes of Health Stroke Scale on admission: 8 [4­17]; 14F/12M) blood CRP concentration and monocyte density (but not white blood cell) increased post-sICH. CRP increased from 0 to 2 to 3 to 5 days (8.3-fold, P=0.020) then declined at 7 to 12 days. Monocytes increased from 0 to 2 to 3 to 5 days (1.8-fold, P<0.001) then declined at 7 to 12 days. Conclusions: An anti-inflammatory pathway, enlisting native microglia and blood monocytes, occurs alongside neuroinflammation post-sICH. This novel pathway offers therapeutic targets and a window of opportunity (3­5 days post-sICH) for delivery of therapeutics via invading monocytes.

Freehand external ventricular drain insertion - is there a learning curve?

BACKGROUND: Accuracy of freehand insertion of external ventricular drains (EVDs) is influenced by many factors including etiology and presence of midline shift. We sought to assess if junior neurosurgical trainees' performance in accurately inserting EVDs improves with experience, using a radiological grading system. METHODS: EVD insertion procedures from the first 3 years of training were identified from the operative logbooks of three trainees. Postoperative CT head scans were graded for accuracy of placement and intraventricular catheter length. RESULTS: 40 frontal EVDs performed primarily by the trainees were identified, after 34 assists, revision surgeries, parietal, or occipital insertions were excluded from the study. The mean number (±1 SD) of procedures was 7.7 ± 4.5 at ST3, 4.7 ± 2.5 at ST2, and 1 ± 1 at ST1. About 80% of EVDs were optimally inserted. There was no statistically significant difference in placement accuracy between the three training grades (P = 0.669), nor any difference in intraventricular catheter length (P = 0.697). There were no statistically significant differences between surgeons' accuracy at each grade. CONCLUSION: We report good accuracy of EVDs tip position inserted by junior neurosurgery trainees. Trainees perform more procedures independently as they progress in their career. Further studies including senior years of training performance, other procedure factors and outcome should be considered.

Malignant middle cerebral artery infarction following subacute subdural hematoma: A case report and literature review.

BACKGROUND: Subacute subdural hematomas (ASDH) are only treated surgically when they cause mass effect significant enough to give symptoms. Rarely, sub-ASDH may cause enough pressure to result in a malignant middle cerebral artery (MCA) territory infarction. Decompressive craniectomy (DC) is the last resort to reduce intracranial pressure following malignant MCA infarction. Herein, we review the literature and describe a case of MCA/posterior cerebral artery (PCA) territories infarction following drainage of a sub-ASDH that was treated with DC with good outcome. CASE DESCRIPTION: We report a case of malignant right-sided MCA/PCA infarction in a 62-year-old man who presented with progressive headache following a cycling incident leading to a head injury. Initial CT head demonstrated a small right ASDH. He had no neurological deficit, headache settled on analgesia, and there was no expansion of the SDH on the repeat CT; therefore, he was managed conservatively. He was admitted 6-days later with worsening headaches and hyponatremia. Repeat CT revealed an increase in size of the hematoma and mass effect leading to a mini-craniotomy and evacuation of hematoma. He developed left-sided hemiplegia, slurred speech and hyponatremia, and CT head demonstrated a right-sided MCA/PCA infarction with significant mass effect. He underwent emergent DC and subsequent cranioplasty and ultimately recovered to mRS of 2. CONCLUSION: SDH are frequent neurosurgical entities. Malignant MCA/PCA strokes following mini-craniotomies are rare but need to be considered especially during the consent process.

Sonic Hedgehog Signaling Promotes Peri-Lesion Cell Proliferation and Functional Improvement after Cortical Contusion Injury.

Traumatic brain injury (TBI) is a leading cause of death and disability globally. No drug treatments are available, so interest has turned to endogenous neural stem cells (NSCs) as alternative strategies for treatment. We hypothesized that regulation of cell proliferation through modulation of the sonic hedgehog pathway, a key NSC regulatory pathway, could lead to functional improvement. We assessed sonic hedgehog (Shh) protein levels in the cerebrospinal fluid (CSF) of patients with TBI. Using the cortical contusion injury (CCI) model in rodents, we used pharmacological modulators of Shh signaling to assess cell proliferation within the injured cortex using the marker 5-Ethynyl-2'-deoxyuridine (EdU); 50mg/mL. The phenotype of proliferating cells was determined and quantified. Motor function was assessed using the rotarod test. In patients with TBI there is a reduction of Shh protein in CSF compared with control patients. In rodents, following a severe CCI, quiescent cells become activated. Pharmacologically modulating the Shh signaling pathway leads to changes in the number of newly proliferating injury-induced cells. Upregulation of Shh signaling with Smoothened agonist (SAG) results in an increase of newly proliferating cells expressing glial fibrillary acidic protein (GFAP), whereas the Shh signaling inhibitor cyclopamine leads to a reduction. Some cells expressed doublecortin (DCX) but did not mature into neurons. The SAG-induced increase in proliferation is associated with improved recovery of motor function. Localized restoration of Shh in the injured rodent brain, via increased Shh signaling, has the potential to sustain endogenous cell proliferation and the mitigation of TBI-induced motor deficits albeit without the neuronal differentiation.