Dimensions of Arachnoid Bulk Ratio: A Superior Optic Nerve Sheath Index for Intracranial Pressure.

Background Discrepancies in the literature regarding optimal optic nerve sheath diameter (ONSD) cutoffs for intracranial pressure (ICP) necessitate alternative neuroimaging parameters to improve clinical management. Purpose To evaluate the diagnostic accuracy of the dimensions of the perineural subarachnoid space to the optic nerve sheath ratio, measured using US, in predicting increased ICP. Materials and Methods In a prospective cohort study from April 2022 to December 2023, patients with suspected increased ICP underwent optic nerve US to determine the dimensions of arachnoid bulk (DAB) ratio and ONSD before invasive ICP measurement. Correlation between the parameters and ICP, as well as diagnostic accuracy, was assessed using area under the receiver operating characteristic curve (AUC) analysis. Results A total of 30 participants were included (mean age, 39 years ± 14 [SD]; 24 female). The DAB ratio and ONSD were significantly larger in participants with increased ICP (38% [0.16 of 0.42] and 14% [0.82 of 6.04 mm], respectively; P < .001). The DAB ratio showed a stronger correlation with ICP than ONSD (rs = 0.87 [P < .001] vs rs = 0.61 [P < .001]). The DAB ratio and ONSD optimal cutoffs for increased ICP were 0.5 and 6.5 mm, respectively, and the ratio had higher sensitivity (100% vs 92%) and specificity (94% vs 83%) compared with ONSD. Moreover, the DAB ratio better predicted increased ICP than ONSD, with a higher AUC (0.98 [95% CI: 0.95, 1.00] vs 0.86 [95% CI: 0.71, 0.95], P = .047). Conclusion An imaging ratio was proposed to predict ICP based on the relative anatomy of the cerebrospinal fluid space, demonstrating more accurate diagnosis of increased ICP and a strong correlation with ICP values, suggesting its potential utility as a neuroimaging marker in clinical settings. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Shepherd in this issue.

Early brain injury after aneurysmal subarachnoid hemorrhage: a multimodal neuromonitoring study.

INTRODUCTION: There is a substantial amount of evidence from animal models that early brain injury (EBI) may play an important role for secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Cerebral microdialysis (CMD) allows online measurement of brain metabolites, including the pro-inflammatory cytokine interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9), which is indicative for disruption of the blood-brain barrier. METHODS: Twenty-six consecutive poor-grade aSAH patients with multimodal neuromonitoring were analyzed for brain hemodynamic and metabolic changes, including CMD-IL-6 and CMD-MMP-9 levels. Statistical analysis was performed by using a generalized estimating equation with an autoregressive function. RESULTS: The baseline cerebral metabolic profile revealed brain metabolic distress and an excitatory response which improved over the following 5 days (P <0.001). Brain tissue hypoxia (brain tissue oxygen tension of less than 20 mm Hg) was common (more than 60% of patients) in the first 24 hours of neuromonitoring and improved thereafter (P <0.05). Baseline CMD-IL-6 and CMD-MMP-9 levels were elevated in all patients (median = 4,059 pg/mL, interquartile range (IQR) = 1,316 to 12,456 pg/mL and median = 851 pg/mL, IQR = 98 to 25,860 pg/mL) and significantly decreased over days (P <0.05). A higher pro-inflammatory response was associated with the development of delayed cerebral ischemia (P = 0.04), whereas admission disease severity and early brain tissue hypoxia were associated with higher CMD-MMP-9 levels (P <0.03). Brain metabolic distress and increased IL-6 levels were associated with poor functional outcome (modified Rankin Scale of more than 3, P ≤0.01). All models were adjusted for probe location, aneurysm securing procedure, and disease severity as appropriate. CONCLUSIONS: Multimodal neuromonitoring techniques allow insight into pathophysiologic changes in the early phase after aSAH. The results may be used as endpoints for future interventions targeting EBI in poor-grade aSAH patients.

Higher brain extracellular potassium is associated with brain metabolic distress and poor outcome after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Elevated brain potassium levels ([K+]) are associated with neuronal damage in experimental models. The role of brain extracellular [K+] in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) and its association with hemorrhage load, metabolic dysfunction and outcome has not been studied so far. METHODS: Cerebral microdialysis (CMD) samples from 28 poor grade aSAH patients were analyzed for CMD [K+] for 12 consecutive days after ictus, and time-matched to brain metabolic and hemodynamic parameters as well as corresponding plasma [K+]. Statistical analysis was performed using a generalized estimating equation with an autoregressive function to handle repeated observations of an individual patient. RESULTS: CMD [K+] did not correlate with plasma [K+] (Spearman's ρ = 0.114, P = 0.109). Higher CMD [K+] was associated with the presence of intracerebral hematoma on admission head computed tomography, CMD lactate/pyruvate ratio >40 and CMD lactate >4 mmol/L (P < 0.05). In vitro retrodialysis data suggest that high CMD [K+] was of brain cellular origin. Higher CMD [K+] was significantly associated with poor 3-month outcome, even after adjusting for age and disease severity (P < 0.01). CONCLUSIONS: The results of this pilot study suggest that brain extracellular [K+] may serve as a biomarker for brain tissue injury in poor-grade aSAH patients. Further studies are needed to elucidate the relevance of brain interstitial K+ levels in the pathophysiology of secondary brain injury after aSAH.

Pearls & Oy-sters: A Challenging Optic Neuropathy-What Not to Miss in Optic Nerve Sheath Enhancement.

Optic neuropathies include a wide range of disorders from ischemic, toxic, demyelinating, or inflammatory processes with acute/subacute onset to more gradual compressive or genetic etiologies. Accurate clinical history and multimodality optic nerve imaging including MRI and optical coherence tomography have greatly improved the diagnosis of patients with optic neuropathies. We report a case of a woman with severe monocular visual acuity deficit. Optic nerve sheath enhancement seen on MRI led to a broad differential diagnosis including demyelinating causes, optic nerve sheath meningioma (ONSM), tuberculosis, and sarcoid optic neuropathy. Lack of response to treatment with steroids or plasmapheresis led to biopsy, which confirmed the diagnosis of ONSM.

Handicap as a Measure of Perceived-Health Status in Parkinson's Disease.

Background: Handicap is a patient-centered measure of health status that encompasses the impact of social and physical environment on daily living, having been assessed in advanced and late-stage Parkinson's Disease (PD). Objective: To characterize the handicap of a broader sample of patients. Methods: A cross-sectional study of 405 PD patients during the MDS-UPDRS Portuguese validation study, using the MDS-UPDRS, Unified Dyskinesias Rating Scale, Nonmotor symptoms questionnaire, PDQ-8 and EQ-5D-3L. Handicap was measured using the London Handicap Scale (LHS). Results: Mean age was 64.42 (±10.3) years, mean disease duration 11.30 (±6.5) years and median HY 2 (IQR, 2-3). Mean LHS was 0.652 (±0.204); "Mobility," "Occupation" and "Physical Independence" were the most affected domains. LHS was significantly worse in patients with longer disease duration, older age and increased disability. In contrast, PDQ-8 did not differentiate age groups. Handicap was significantly correlated with disease duration (r = -0.35), nonmotor experiences of daily living (EDL) (MDS-UPDRS-I) (r = -0.51), motor EDL (MDS-UPDRS-II) (r = -0.69), motor disability (MDS-UPDRS-III) (r = -0.49), axial signs of MDS-UPDRS-III (r = -0.55), HY (r = -0.44), presence of nonmotor symptoms (r = -0.51) and PDQ-8 index (r = -0.64) (all P < 0.05). Motor EDL, MDS-UPDRS-III and PDQ-8 independently predicted Handicap (adjusted R 2 = 0.582; P = 0.007). Conclusions: The LHS was easily completed by patients and caregivers. Patients were mild-moderately handicapped, which was strongly determined by motor disability and its impact on EDL, and poor QoL. Despite correlated, handicap and QoL seem to differ in what they measure, and handicap may have an added value to QoL. Handicap seems to be a good measure of perceived-health status in a broad sample of PD.

Longitudinally extensive transverse myelitis with anti-myelin oligodendrocyte glycoprotein antibodies following SARS-CoV-2 infection.

We report the case of a patient with symptoms of myelopathy following acute SARS-CoV-2 infection. MRI documented a longitudinally extensive transverse myelitis and further investigation was unremarkable with the exception of positivity for MOG-IgG in serum. This report extends the spectrum of post-COVID-19 neurological syndromes, and documents a very significant improvement to long-term oral corticosteroid therapy in this setting. Further prospective studies are needed to establish the risk of recurrence in this subset of patients.

Total TauProtein as Investigated by Cerebral Microdialysis Increases in Hypothermic Cardiac Arrest: A Pig Study.

The understanding and neurological prognostication of hypoxic ischemic encephalopathy (HIE) after hypothermic cardiac arrest (CA) is limited. Recent data suggest that the protein tau (total tau) might be a useful marker for outcome in patients with HIE. This translational porcine study aimed to analyze brain physiology in relation to total tau protein release during hypothermic CA. Eight domestic pigs were studied as part of a prospective porcine study using cerebral microdialysis (CMD). CMD samples for tau analysis were collected at baseline, after reaching the targeted core temperature of 28°C (hypothermia), after hypoxic hypercapnia (partial asphyxia), and finally 20 minutes after cardiopulmonary resuscitation. CMD-total tau-protein was analyzed using enzyme-linked immunosorbent essay. Cerebral tau protein was slightly elevated at baseline most likely due to an insertion trauma, remained stable during hypercapnic hypoxia, and significantly (p = 0.009) increased in 8/8 pigs during resuscitation to 1335 pg/mL (interquartile range: 705-2100). CMD-tau release was associated with lower levels of brain tissue oxygen tension (p = 0.011), higher CMD-lactate/pyruvate ratio, higher CMD-lactate, CMD-glutamate, and CMD-glycerol levels (p < 0.001, respectively), but not with cerebral perfusion pressure, intracranial pressure, or CMD-glucose levels. This study demonstrates an immediate tau protein release accompanied by deranged cerebral metabolism and decreased brain tissue oxygen tension during mechanical resuscitation in hypothermic CA. Understanding tau physiology and release kinetics is important for the design and interpretation of studies investigating tau as a biomarker of HIE.

Consensus Protocol for the Treatment of Super-Refractory Status Epilepticus.

INTRODUCTION: Super-refractory status epilepticus is defined as status epilepticus that persists or recurs 24 hours after anaesthetic therapy onset or after its withdrawal. It is mostly found in intensive care units and carries high mortality but good long-term prognosis for those who survive. In contrast with the initial phases of status epilepticus, treatment lacks strong scientific evidence and is mostly derived from case reports or small case series. OBJECTIVE: To propose a protocol for the treatment of super-refractory status epilepticus in level III intensive care units, focusing on the treatment strategies to control clinical and/or electroencephalographic epileptic activity. MATERIAL AND METHODS: Narrative review of the literature by PubMed search. Available evidence was discussed in consensus meetings by intensive care and neurology experts' from a level III intensive care unit and one of the Portuguese reference centres for the treatment of refractory epilepsy, respectively. RESULTS: Anaesthetics with the highest level of evidence are propofol, midazolam, thiopental and ketamine. These represent the basis of the treatment of super-refractory status epilepticus and should be used in combination with antiepileptic drugs. The level of evidence for the latter is lower, however, levetiracetam, topiramate, pregabalin, lacosamide, valproic acid, phenytoin and perampanel may be recommended. Alternative therapeutic strategies with very low level of evidence are recommended in cases of total absence of clinical response, such as magnesium sulphate, pyridoxine, ketogenic diet, therapeutic hypothermia and immunosupression. CONCLUSION: We propose a treatment protocol based on a sequential combination of anaesthetics, anti-epileptic drugs and alternative therapies. Strategies to evaluate treatment response and to wean drugs based on clinical results are also proposed.

Introdução: O estado de mal epiléptico super-refractário define-se como um estado de mal epiléptico que persiste ou recorre 24 horas após o início da terapêutica anestésica ou após a sua suspensão. Encontra-se fundamentalmente em unidades de cuidados intensivos e está associado a uma elevada mortalidade apesar de ter um bom prognóstico a longo prazo nos doentes que sobrevivem. Ao contrário das fases iniciais do estado de mal epiléptico, o tratamento não é baseado numa forte evidência científica e deriva principalmente de relatos ou pequenas séries de casos. Objectivo: Propor um protocolo de tratamento do estado de mal epiléptico super-refractário em unidades de cuidados intensivos de nível III, focando-se nas estratégias de tratamento para controlar a actividade epiléptica clínica e/ou electroencefalográfica. Material e Métodos: Revisão narrativa da literatura no PubMed, seguida de discussão em reuniões de consenso de peritos de medicina intensiva e neurologia de uma unidade de cuidados intensivos de nível III e de um dos centros de referência para o tratamento da epilepsia refractária em Portugal, respectivamente. Resultados: Os fármacos anestésicos com maior nível de evidência são o propofol, midazolam, tiopental e ketamina. Estes representam a base do tratamento do estado de mal super-refractário e devem ser utilizados em combinação com fármacos antiepilépticos. O nível de evidência para estes últimos é menor, contudo, podem ser recomendados o levetiracetam, topiramato, pregabalina, lacosamida, perampanel, ácido valpróico, fenitoína e perampanel. São recomendadas estratégias terapêuticas alternativas com muito baixo nível de evidência, em casos de ausência total de resposta clínica, tais como o sulfato de magnésio, piridoxina, dieta cetogénica, hipotermia terapêutica e imunossupressão. Conclusão: Propomos um protocolo de tratamento baseado numa combinação sequencial de fármacos anestésicos, antiepilépticos e terapêuticas alternativas. São também propostas estratégias de avaliação da eficácia da terapêutica e de desmame farmacológico progressivo de acordo com a resposta clínica obtida.

Intermittent rhabdomyolysis with adult onset associated with a mutation in the ACADVL gene.

Deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD) is an autosomal recessive disease. Most common phenotypes occur in the neonatal period or in childhood with cardiomyopathy, hepatomegaly, and hypoketogenic hypoglycemia. Juvenile/adult-onset is characterized by exercise intolerance and recurrent rhabdomyolysis triggered by prolonged exercise or fasting. This article reports a patient with the homozygous mutation c.1097G>A (p.R366H) in the ACADVL gene. In Portugal, VLCAD deficiency became part of the neonatal screening plan in 2004, and as of 2012, 8 early-onset cases have been diagnosed, giving an incidence rate of 1:97.238 per 737.902 newborns. This patient was diagnosed outside of the neonatal screening plan. Beta-oxidation defects pose a diagnostic challenge because of their transient clinical and laboratorial manifestations and the absence of morphological changes in muscle biopsy further complicate matters, especially in the late-onset forms of the disease. The adult phenotype of VLCAD deficiency is highlighted, emphasizing the need for a high suspicion index and the value of tandem mass spectrometry for the diagnosis.