Selumetinib for plexiform neurofibromas in neurofibromatosis type 1: a single-institution experience.

BACKGROUND: Plexiform neurofibromas (PN) are the most frequent tumors associated with Neurofibromatosis type 1 (NF-1). PN can cause significant complications, including pain, functional impairment, and disfigurement. There is no efficient medical treatment and, surgical resection of large PN is frequently infeasible. Selumetinib (AZD6244/ARRY-142886) is a mitogen-activated protein kinase enzyme (MEK1/2) inhibitor and works by targeting the MAPK pathway. It is an investigational treatment option for inoperable symptomatic PN associated with NF-1. Herein, we describe a single institutional experience with selumetinib for inoperable PN in NF-1. METHODS: Case series study of demographics, clinical, baseline characteristics, treatment effect, and follow-up of consecutive genetically confirmed NF1 patients with inoperable PN associated with significant or potential significant morbidity treated with selumetinib (April 2018 to April 2019). RESULTS: Nineteen patients were treated with selumetinib. Predominant target locations were head and neck (31.6%, 6/19), chest (26.3%, 5/19) and pelvis (21%, 4/19) and the most important comorbidities were disfigurement (47.4%, 9/19) and pain (26.3%, 5/19). The mean follow-up time was 223 days (range 35-420 days). All but one had sustained clinical improvement, mainly in the first 60-90 days of treatment. In one patient, the treatment was suspended after 168 days (lack of clear benefit and left ventricular ejection fraction drop). There were no adverse effects leading to treatment suspension. CONCLUSIONS: In the first observational study of selumetinib for NF-1 associated PN we showed that the drug was associated with clinical and radiological improvement. Our study also confirms the safety described in the clinical trials.

Cortical deafness of following bilateral temporal lobe stroke.

Cortical deafness is an extremely rare clinical manifestation that originates mainly from bilateral cortical lesions in the primary auditory cortex. Its main clinical manifestation is the bilateral sudden loss of hearing. Diagnosis is difficulty due to its rarity and similarity with other language and communication disorders, such as Wernicke's aphasia, auditory agnosia or verbal deafness. Herein, we present a case report of a young woman with a sudden bilateral loss of auditory comprehension. Initially, a psychiatric nature of the disorder was considered, but the persistence of the symptoms, lead to the diagnosis of cortical deafness secondary to bilateral ischemic lesions in both temporal lobes. Progressive improvement occurred and three months after the initial manifestations she manifested pure verbal deafness. Cortical deafness usually has a poor functional prognosis, with limited therapeutic options. Rehabilitation and speech therapy is recommended to improve the chance of patients achieving communication skills.

p.G360R Is a Pathogenic GLA Gene Mutation Responsible for a Classic Phenotype of Fabry Disease.

The authors report the case of a classic phenotype of Fabry disease in a 60-year-old male patient presenting with left ventricular hypertrophy and stroke. Genetic analysis revealed 2 GLA-gene variants, i.e., p.R356Q and p.G360R. This clinical case highlights that the finding of 2 or more GLA gene variants in a Fabry patient should lead to a careful evaluation in order to determine their exact role in the condition. This case also provides the first clinical evidence that the p.G360R mutation is pathogenic and responsible for a classic phenotype of Fabry disease. The clinical improvement following the initiation of enzyme replacement therapy reinforces the importance of Fabry disease awareness and diagnosis in patients exhibiting red flags, such as left ventricular hypertrophy and stroke.

Late Hospital Arrival for Thrombolysis after Stroke in Southern Portugal: Who Is at Risk?

BACKGROUND: Delayed hospital arrival remains the main reason for the low rates of thrombolysis in eligible acute ischemic stroke (AIS) patients. The role of socioeconomic and clinical factors for the prehospital delay of AIS remains poor and has never been studied in Portugal. OBJECTIVES: Describe the socioeconomic and clinical factors leading to delayed hospital admission of AIS patients eligible to thrombolysis. METHODS: A case-control study with a consecutive thrombolyzed AIS patients from 2010 to 2015. Controls were patients who did not receive thrombolysis because of late hospital arrival. Logistic regression with stepwise forward regression analysis was used to identify independent predictors of delayed admission to receive thrombolysis with intravenous tissue-type plasminogen activator (rtPA). RESULTS: Of the 1247 patients admitted with AIS, 76 (6%) arrived on-time and received intravenous rtPA. Controls were 65.8% (146/222) of the total number of patients included in the study. Overall, the mean age was 73 years (±11, 61), a minority were below 60 years, and 43.7% were women. Being beneficiary of social insertion income (odds ratio [OR]: .286; .124-.662, P = .003), not having any telephone contact (OR: .145; .039-.536, .004) or having exclusive landline (.055; .014-.210, <.001) and posterior circulation stroke (OR: .266; .087-.811, P = .020) decreased the likelihood of hospital arrive on-time rtPA. The use of prehospital ambulance services increased (OR: 6.478; 2.751-15.254, P < .001) the odds of ER on-time arrival for thrombolysis. CONCLUSIONS: Poverty, lack of stroke awareness, or difficulties in requesting immediate medical help are the main factors implicated in late-hospital admission for thrombolysis in AIS. Stroke awareness campaigns, promotion of activation of national emergency number and stroke code can increase the rate of thrombolysis.

Short-Term Outcome of Spontaneous Intracerebral Hemorrhage in Algarve, Portugal: Retrospective Hospital-Based Study.

BACKGROUND: The short-term outcome from spontaneous intracerebral hemorrhage (SICH) is influenced by local quality of care and population specificities. There are no studies about the SICH mortality in southern Portugal. The objective of this study was to describe the predictors of 30-day in-hospital SICH mortality in Algarve, the southernmost region of Portugal. METHODS: Logistic regression was used to identify predictors of in-hospital death. Kaplan-Meier analysis was used to estimate survival over time based on SICH severity. RESULTS: Of the 549 cases, 349 (63.6%) were men; the mean age was 71.4 years. Two hundred seventeen patients (39.5%) did not receive stroke unit (SU) care. The 30-day mortality was 34.4%. Independent predictors of death were older age (odds ratio [OR] = 1.096, 95% confidence interval [CI] = 1.031-2.062, P = .022) per additional year, vitamin K antagonists use (OR = 5.464, 95% CI = 2.088-25.714, P = .043), admission Glasgow Coma Scale (GCS) score of 8 or lower (OR = 20.511, 95% CI = 7.862-62.168, P < .0001) or GCS score of 9-12 (OR = 12.709, 95% CI = 3.078-44.113, P < .0001), hematoma volume (OR = 1.037, 95% CI = 1.004-1.071, P = .028) per additional milliliter, intraventricular dissection (OR = 1.916, 95% CI = 1.105-4.566, P = .046), and pneumonia (OR 12.918, 95% CI = 4.603-24.683, P < .0001). SU care was independently associated with reduction of death (OR .395, 95% CI = .126-.635, P = .004). Severity correlated with short time to death (P < .0001). Sixty-five of the patients (39.2%) died after the seventh day of SICH ("non-neurological deaths"). CONCLUSIONS: The in-hospital 30-day mortality is high in the region. Admitting more patients to the SU and implementation of preventive strategies of complications can reduce mortality.

Intracerebral hemorrhage as a manifestation of cerebral hyperperfusion syndrome after carotid revascularization: systematic review and meta-analysis.

BACKGROUND: Intracerebral hemorrhage (ICH) in the context of cerebral hyperperfusion syndrome (CHS) is an uncommon but potentially lethal complication after carotid revascularization for carotid occlusive disease. Information about its incidence, risk factors and fatality is scarce. Therefore, we aimed to perform a systematic review and meta-analysis focusing on the incidence, risk factors and outcomes of ICH in the context of CHS after carotid revascularization. METHODS: We searched the PubMed and EBSCO hosts for all studies published in English about CHS in the context of carotid revascularization. Two reviewers independently assessed each study for eligibility based on predefined criteria. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the PROSPERO register was made (register no. CRD42016033190), including the pre-specified protocol. RESULTS: Forty-one studies involving 28,956 participants were deemed eligible and included in our analysis. The overall quality of the included studies was fair. The pooled frequency of ICH in the context of CHS was 38% (95% CI: 26% to 51%, I2 = 84%, 24 studies), and the pooled case fatality of ICH after CHS was 51% (95% CI: 32% to 71%, I2 = 77%, 17 studies). When comparing carotid angioplasty with stenting (CAS) with carotid endarterectomy (CEA), post-procedural ICH in the context of CHS was less frequent in CEA. ICH following CHS occurred less often in large series and was rare in asymptomatic patients. The most common risk factors were periprocedural hypertension and ipsilateral severe stenosis. CONCLUSIONS: ICH as a manifestation of CHS is rare, more frequent after CAS and associated with poor prognosis. Periprocedural control of hypertension can reduce its occurrence.

Clinical Course and Outcomes of Small Supratentorial Intracerebral Hematomas.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) volume, particularly if ≥30 mL, is a major determinant of poor outcome. We used a multinational ICH data registry to study the characteristics, course, and outcomes of supratentorial hematomas with volumes <30 mL. METHODS: Basic characteristics, clinical and radiological course, and 30-day outcomes of these patients were recorded. Outcomes were categorized as early neurological deterioration (END), hematoma expansion, Glasgow Outcome Scale (GOS), and in-hospital death. Poor outcome was defined as composite of in-hospital death and severe disability (GOS ≤ 3). Comparison was conducted based on hemorrhage location. Logistic regression using dichotomized outcome scales was applied to determine predictors of poor outcome. RESULTS: Among 375 cases of supratentorial ICH with volumes <30 mL, expansion and END rates were 19.2% and 7.5%, respectively. Hemorrhage growth was independently associated with END (odds ratio: 28.7, 95% confidence interval [CI]: 8.51-96.5; P < .0001). Expansion rates did not differ according to ICH location. Overall, 13.9% (exact binomial 95% CI: 10.5-17.8) died in the hospital and 29.1% (CI: 24.5-34.0) had severe disability at 30 days; there was a cumulative poor outcome rate of 42.9% (CI: 37.9-48.1). Age, admission Glasgow Coma Scale, intraventricular extension, and END were independently associated with poor outcome. There was no difference in poor outcome rates between lobar and deep locations (40.2% versus 43.8%, P = .56). CONCLUSION: Patients with supratentorial ICH <30 mL have high rates of poor outcome at 30 days, regardless of location. Nearly 1 in 5 hematomas <30 mL expands, leading to END or death.

24-hour rhythmicity of seizures in refractory focal epilepsy.

The occurrence of seizures in specific types of epilepsies can follow a 24-hour nonuniform or nonrandom pattern. We described the 24-hour pattern of clinical seizures in patients with focal refractory epilepsy who underwent video-electroencephalography monitoring. Only patients who were candidates for epilepsy surgery with an unequivocal seizure focus were included in the study. A total of 544 seizures from 123 consecutive patients were analyzed. Specific time of seizures were distributed along 3- or 4-hour time blocks or bins throughout the 24-hour period. The mean age of the subjects was 37.7 years, with standard deviation of 11.5 years, median of 37. The majority were females (70/56%). The majority of patients had a seizure focus located in the mesial temporal lobe (102/83%) and in the neocortical temporal lobe (13/11%). The remaining patients had a seizure focus located in the extratemporal lobe (8/6%). The most common etiology was mesial temporal sclerosis (86/69.9%). Nonuniform seizure distribution was observed in seizures arising from the temporal lobe (mesial temporal lobe and neocortical temporal lobe), with two peaks found in both 3- and 4-hour bins: 10:00-13:00/16:00-19:00 and 08:00-12:00/16:00-20:00 respectively (p=0.004). No specific 24-hour pattern was identified in seizures from extratemporal location. The 24-hour rhythmicity of seizure distribution is recognized in certain types of epilepsy, but studies on the topic are scarce. Their replication and validation is therefore needed. Our study confirms the bimodal pattern of temporal lobe epilepsy independently of the nature of the lesion. However, peak times differ between different studies, suggesting that the ambient, rhythmic exogenous factors or environmental/social zeitgebers, may modulate the 24-hour rhythmicity of seizures. Characterization of these 24-hour patterns of seizure occurrence can influence diagnosis and treatment in selected types of epilepsy, such as the case of temporal lobe epilepsy, the most common drug-resistant epilepsy.

Shifting the CARASIL paradigm: report of a non-Asian family and literature review.

BACKGROUND AND PURPOSE: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a rare form of nonhypertensive cerebral small-vessel disease caused by mutations in the HTRA1 gene. CARASIL is characterized by early adulthood onset of subcortical infarcts, cognitive impairment, alopecia, and spondylosis. Until recently, this disorder was almost exclusively reported in the Asian population. METHODS: Description of the clinical, imaging, and genetic study of 2 siblings with CARASIL, with a brief comparative review of published non-Asian cases of the disease. RESULTS: Both patients exhibited the typical phenotype: cerebral small-vessel disease, spondylosis, and abnormal hair lost. Mutation screening was performed for NOTCH3 and HTRA1 genes. No mutations were found in NOTCH3. The study revealed the presence of a homozygous c.496C>T substitution in HTRA1 in both siblings. CONCLUSION: This report highlights the need of considering this entity in the differential diagnosis of cerebral small-vessel disease in young patients, even in the non-Asian populations.

Good outcome after intravenous thrombolysis for acute stroke in a patient under treatment with dabigatran.

The novel oral anticoagulants (NOACs) are indicated for stroke and systemic embolism prophylaxis in patients with nonvalvular atrial fibrillation (AF). Very few cases of intravenous recombinant tissue plasminogen activator (IV rt-PA) in patients under treatment with NOACs have been described. The decision to thrombolyze patients under NOACs is complex and requires a balance between the benefits of treatment and the risk of symptomatic hemorrhagic complications.We describe an unusual case of treatment IV rt-PA for acute ischemic stroke in a patient receiving dabigatran for AF. The decision to treat the patient with IV rt-PA was based on the combination of normal coagulation times with the long time elapsed after the last dose of dabigatran, when the drug effect was predictably residual.

From Spinal Ependymoma to Superficial Siderosis: A Bottom to Top Cause of Progressive Neurological Deterioration.

Superficial siderosis (SS) is an infrequent condition characterized by hemosiderin deposition in the central nervous system, resulting from chronic subarachnoid hemorrhage, often linked to dural mater diseases. Through a case report of a 50-year-old male with severe sensorineural hearing loss and newly diagnosed epilepsy, we explore SS triggered by a spinal ependymoma, diagnosed via resonance magnetic imaging (MRI). This case highlights the necessity of comprehensive neuroaxis imaging to identify treatable etiologies. The complexity of SS, with its varied clinical presentations, necessitates early detection and a multidisciplinary treatment approach. Despite limited treatment options and the uncertain efficacy of therapies like deferiprone, early intervention is crucial for mitigating irreversible neurological damage and enhancing patient prognosis.

Establishment of an induced pluripotent cell line (ABCRIi001-A) from an elderly female for ageing research.

Human induced pluripotent stem cells (hiPSCs) hold promises to model and understand human diseases, including those associated with ageing. Here, we describe ABCRIi001-A, a hiPSC line generated from peripheral blood mononuclear cells (PBMCs) of a 79-year-old female enrolled in a study for development of an ageing score (ALFA Score). PBMCs were reprogrammed using three Sendai virus-based reprogramming vectors (hKOS, hc-Myc, and hKlf4). ABCRIi001-A showed normal morphology and karyotype, viral clearance, absence of genomic aberrations, and their pluripotency was confirmed by expression of pluripotency-related markers and their ability to differentiate into the three germ layers. ABCRIi001-A is valuable for ageing-related studies.

Prognostic factors associated with disability in a cohort of neuromyelitis optica spectrum disorder and MOG-associated disease from a nationwide Portuguese registry.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) and MOG-associated disease (MOGAD) are an increasingly recognized group of demyelinating disorders of the central nervous system. Previous studies suggest that prognosis is predicted by older age at onset, number of relapses, the severity of the first attack and autoantibody status. OBJECTIVE: To study prognostic factors associated with disability progression and additional relapses in the 3-year follow-up of a national NMOSD/MOGAD cohort. RESULTS: Out of 180 of the initial Portuguese cohort, data on 82 patients was available at the end of the follow-up period (2019-2022). Two patients died. Twenty (24.4%) patients had one or more attack in this period (25 attacks in total), mostly transverse myelitis (TM) (56.0%) or optic neuritis (32.0%). MOGAD was significantly associated with a monophasic disease course (p = 0.03), with milder attacks (p = 0.01), while AQP4 + NMOSD was associated with relapses (p = 0.03). The most common treatment modalities were azathioprine (38.8%) and rituximab (18.8%). AQP4 + NMOSD more frequently required chronic immunosuppressive treatment, particularly rituximab (p = 0.01). Eighteen (22.5%) had an EDSS ≥6 at the end of the follow-up. AQP4 + NMOSD (p < 0.01) and the occurrence of transverse myelitis (TM) during disease (p = 0.04) correlated with an EDSS≥6 at the end of the follow-up period. MOGAD was significantly associated with an EDSS<6 (p < 0.01), and MOG+ cases that reached an EDSS>6 were significantly older (64.0 ± 2.8 versus 31.0 ± 17.1, p = 0.017). A bivariate logistic regression model including the serostatus and TM attacks during disease history successfully predicted 72.2% of patients that progressed to an EDSS≥6. CONCLUSION: This study highlights that myelitis predict increased disability (EDSS≥6) in NMOSD/MOGAG and AQP4 positivity is associated with increased disability.

Valproic acid-induced hyperammonaemic coma and unrecognised portosystemic shunt.

Hyperammonaemic encephalopathy is a rare and potentially fatal complication of valproic acid treatment. The clinical presentation of hyperammonaemic encephalopathy is wide and includes seizures and coma. We present a case of hyperammonaemic coma precipitated by sodium valproate use for symptomatic epilepsy in a patient with unrecognised portosystemic shunt, secondary to earlier alcoholism. The absence of any stigmata of chronic liver disease and laboratory markers of liver dysfunction delayed the recognition of this alcohol-related complication. The portal vein bypass led to a refractory, valproic acid-induced hyperammonaemic coma. The patient fully recovered after dialysis treatment.

Neutrophil-to-leukocyte ratio and admission glycemia as predictors of short-term death in very old elderlies with lobar intracerebral hemorrhage.

BACKGROUND: The incidence of spontaneous intracerebral hemorrhage (SICH) is highest in very old elderlies (≥75 years). The increasing use of antithrombotic drugs is shifting the epidemiology of SICH towards predominance of lobar subtype, suggesting an incremented propensity of bleeding associated with underlying cerebral amyloid angiopathy. With population aging and antithrombotic use, a parallel raise of proportion of lobar SICH is occurring. Improvement of prognostication in this specific age group and SICH type is needed. Routine blood biomarkers can contribute to prediction of short-term mortality after SICH. OBJECTIVE: Our aim was to investigate the contribution of routine blood biomarkers for short-term mortality (30-days) in elderly patients with lobar SICH. METHODS: Retrospective analysis of consecutive 130 patients with ≥ 75 years and lobar SICH. The outcome was 30-day mortality. Logistic regression analysis was used to investigate whether admission routine biomarkers can be used as predictors. RESULTS: The case fatality was 40.8%. Admission glycaemia level, neutrophil to lymphocyte ratio and mean platelet volume were significantly different between groups (p = 0.001, p = 0.024, p = 0.038, respectively). There was no significant difference in all other routine biomarkers. On multivariate analysis, admission higher mean BG level (odds ratio [OR]: 1.010, 95% confidence interval [CI]: 1.001-1.019, p = 0.026) and neutrophil to lymphocyte ratio (OR: 1.070, 95% CI: 1.008-1.136, p = 0.027) emerged as predictors. CONCLUSION: In very old patients with lobar SICH, higher BG level and neutrophil to lymphocyte ratio are associated with increased risk of short-term death.

Severe neurocysticercosis in a quaternary hospital from Mozambique: Case series analysis.

BACKGROUND: Neurocysticercosis (NCC) is severe and leading global cause of morbidity and mortality. The disease presents with a variety of clinical presentations from focal to diffuse neurological symptoms. Despite being an endemic country, there are no studies describing the clinico-epidemiological characteristics of NCC in Mozambique. Herein, we describe a consecutive cases series of NCC from the national reference Hospital in Maputo, capital of Mozambique. METHODS: Consecutive cases of NCC diagnosed during a 3-year period (January/2020-December/2022) were retrieved from the institutional clinical files and imaging database. RESULTS: Six cases of NCC were identified, with mean age of 43.1 years (range 26-66). Four were males (66.6 %). The median time from the beginning of clinical manifestations to the diagnosis was 6 months (range 3-18 months). All patients presented with severe parenchymal NCC, with seizures (n = 5, 83 %) being the most common manifestation. Other clinical manifestations were dementia (n = 1) and hydrocephalus (n = 1). The imaging showed multiple lesions at different stages, with half (n = 3) of them showing the coexistence of nodular calcified lesions at earlier stages (vesicular, colloidal and granular stages). Patients were treated with anthelminthic drugs, corticosteroids and anticonvulsants and no deaths to report. The 3rd month modified Rankin scale was ≤ 2 in 83 % of patients. CONCLUSION: In our case series, patients with NCC presented very late, with severe advanced stage disease, with multiple coexistent short and long-term brain lesions. These findings can be explained eventually because of the Maputo Central Hospital being national referral center receiving commonly more severe cases. Studies aiming to clarify the diagnosis pathways/barriers and NCC awareness among medical doctors working at primary and secondary health care level is mandatory to assess the real burden of NCC and implement timely diagnosis and care of patients affected by this neglected disease.

Non-ketotic hyperglycaemia induced occipital reflex focal seizures.

A myriad of neurological manifestations can occur in association with ketotic and non ketotic hyperglycaemic states. Contrary to diabetic coma, which is a universal complication under relatively established metabolic circumstances, the pathophysiology beyond hyperglycaemic-associated positive neurological manifestations, including seizures, remains to be elucidated. The occurrence of symptomatic focal epilepsy as a manifestation of diabetes-related hyperglycaemia is seldom reported. Herein, we present a case of focal epilepsy with alternating positive and negative neurological manifestations as the initial manifestation of diabetes-related hyperglycaemia. The electroencephalogram confirmed the diagnosis of focal occipital seizures, and the brain magnetic resonance imaging depicted the associated typical transient imaging findings in the occipital lobe. Seizures were refractory to antiepileptics, and symptomatic control was achieved after achieving normoglycemia. On follow-up, complete clinical and imaging recovery occurred. Reflex focal epilepsy in the context of hyperglycaemic states is a rare condition, and the possibility of misdiagnosis is likely high. As reported in similar cases, seizures can be resistant to antiepileptics. An important message to highlight is that seizures associated with hyperglycaemic status can be resistant to antiepileptic treatment and only cease with glycaemic control.