Multiple Ring-Enhancing Brain Lesions: Fulminant Diffuse Cerebral Toxoplasmosis or Cerebral Metastases?

ABSTRACT: In this case report, we describe a 76-year-old woman, presenting with dizziness for the past 2 months, without other focal neurological signs. A magnetic resonance imaging of the brain was ordered by her GP. The MRI demonstrated multiple ring-enhancing lesions, both supratentorial and infratentorial. Lumbar puncture showed normal findings, in particular a normal cell count and culture. Because of the radiologic appearance, initially thought to be suggestive of cerebral abscesses, antibiotics were started. However, further workup revealed a new diagnosis of a stage IV (metastatic) small cell lung carcinoma, making diffuse brain metastases more likely. The patient was transferred to oncology/pneumology, where she was started on whole-brain radiotherapy, after which systemic therapy would start. However, because of further clinical deterioration, she was admitted at the palliative ward, where she died only 3 months after the initial presentation. In this case report, we emphasize the importance of keeping a broad differential diagnosis and briefly review the various possible pathologies causing ring-enhancing lesions.

The effect of anesthesia on hemodynamics and outcome of patients undergoing thrombectomy after acute ischemic stroke: a retrospective analysis.

BACKGROUND: Anesthesia during thrombectomy remains a matter of debate. We retrospectively investigated the influence of intraprocedural blood pressure and type of anaesthetic agent on 3-month functional outcome and mortality in stroke patients undergoing mechanical thrombectomy under general anesthesia in a single center study. METHODS: All patients suffering from stroke who presented between January 2019 and July 2021 at Ziekenhuis Oost-Limburg Genk, Belgium and who received thrombectomy were included. Patient's characteristics and outcome data had been collected for benchmarking. Detailed perioperative data were exported from the electronic anesthesia records and clinically validated. Patients were stratified by peri-operative presence of hypotension (MAP < 65 mmHg at any time point) versus no-hypotension (MAP ≥ 65 mmHg). RESULTS: All 98 patients received mechanical thrombectomy under general anesthesia. Thirty-six percent (n = 35) was hypotensive peri-operatively at any time point. Proportion of sevoflurane use was higher in non-hypotensive patients compared to hypotensive patients (73% (n = 45) vs. 51% (n = 18), p = 0.04). Peri-operative use of vasopressors was higher in the hypotensive group compared to non-hypotensive (88% (n = 30) vs. 63% (n = 39), p = 0.008). Proportion of patients with good functional outcome at 3 months (mRS 0-2) was higher in non-hypotensive patients compared to hypotensive patients 44% (n = 27) vs. 24% (n = 8), p < 0.05. 90-day mortality was lower in non-hypotensive patients compared to hypotensive patients 21% (n = 13) vs. 43% (n = 15), (p = 0.02). CONCLUSION: Patients who are hypotensive at any given time during thrombectomy under general anesthesia may have worse neurological outcome compared to non-hypotensive patients. The best anaesthetic management for mechanical thrombectomy needs to be clarified prospectively in large multicenter studies.

Reduced Left Atrial Appendage Flow Is Associated With Future Atrial Fibrillation After Cryptogenic Stroke.

BACKGROUND: Hemostasis within the left atrial appendage (LAA) is a common cause of stroke, especially in patients with atrial fibrillation (AF). Although LAA flow provides insights into LAA function, its potential for predicting AF has yet to be established. The aim of this study was to explore whether LAA peak flow velocities early after cryptogenic stroke are associated with future AF on prolonged rhythm monitoring. METHODS: A total of 110 patients with cryptogenic stroke were consecutively enrolled and underwent LAA pulsed-wave Doppler flow assessment using transesophageal echocardiography within the early poststroke period. Velocity measurements were analyzed offline by an investigator blinded to the results. Prolonged rhythm monitoring was conducted on all participants via 7-day Holter and implantable cardiac monitoring devices, with follow-up conducted over a period of 1.5 years to determine the incidence of AF. The end point of AF was defined as irregular supraventricular rhythm with variable RR interval and no detectable P waves lasting ≥30 sec during rhythm monitoring. RESULTS: During a median follow-up period of 539 days (interquartile range, 169-857 days), 42 patients (38%) developed AF, with a median time to AF diagnosis of 94 days (interquartile range, 51-487 days). Both LAA filling velocity and LAA emptying velocity (LAAev) were lower in patients with AF (44.3 ± 14.2 and 50.7 ± 13.3 cm/s, respectively) compared with patients without AF (59.8 ± 14.0 and 76.8 ± 17.3 cm/sec, respectively; P < .001 for both). LAAev was most strongly associated with future AF, with an area under the receiver operating characteristic curve of 0.88 and an optimal cutoff value of 55 cm/sec. Age and mitral regurgitation were independent determinants of reduced LAAev. CONCLUSIONS: Impaired LAA peak flow velocities (LAAev < 55 cm/sec) in patients with cryptogenic stroke are associated with future AF. This may facilitate the selection of appropriate candidates for prolonged rhythm monitoring to improve its diagnostic accuracy and implementation.

From Mild Gait Difficulties to a Sudden Coma: A Rare Case of Marchiafava-Bignami Disease.

ABSTRACT: In this case report we describe the case of a 66-year old man with subacute gait difficulties, with a progression to confusion coma with multiple generalised epileptic seizures during the following days. Biochemical analysis showed hyperglycaemia, cerebrospinal fluid (CSF) testing showed a mild lymphocytic pleocytosis and an elevated protein and lactate. Broad-spectrum antibiotics and antiviral therapy where initiated. However, all other CSF testing remained negative. Magnetic resonance imaging of the brain showed remarkably symmetric hyperintense T2 white matter lesions most noticable in the corpus callosum. The lesion pattern was suggestive of a metabolic or toxic encephalopathy, the preponderance for the corpus callosum was furthermore suggestive for Marchiafava-Bignami disease (MDB), as was the clinical course since admission of the patient. A high dose IV substitution of vitamin B1, B6 and B12 was started and antibiotic and antiviral therapy was discontinued. After one day the patient showed progressive regaining of consciousness and he returned to premorbid functioning in a matter of 1-2 weeks. MRI of the brain after 1 week showed notable improvement of the white matter lesions. At routine follow-up two weeks later he presented with icterus and a diagnosis of Epstein-Barr virus (EBV) hepatitis was made, lymph node biopsies showed an EBV positive diffuse large cell B-cell lymphoma (DLCBL). MDB is mostly associated with severe alcoholism, with malnourishment being the second leading cause, however there are case reports describing MDB in patients with chronically poorly controlled diabetes mellitus. We hypothesize that his condition may have been precipitated by his poorly controlled diabetes mellitus. However it is also possible that weight loss (probably related to the DLCBL diagnosis) might have contributed to a state of malnourishment and therefore played a role in the aetiology as well.

Multicentric validation of a reduced features case-mix set for predicting functional outcome after ischemic stroke in Belgium.

INTRODUCTION: Ischemic stroke is the second cause of death and leading cause of severe disability worldwide. A reduced features set of CT-DRAGON (age, NIHSS on admission and pre-stroke mRS) predicts 90-day functional outcome after stroke in a single center. The current study was designed to validate this adapted CT-DRAGON score in three major Belgian hospitals, in the framework of future case-mix adjustment. METHODS: This retrospective study included stroke patients, treated by thrombolysis, thrombectomy, a combination of both or neither thrombolysis or thrombectomy (conservative treatment) in 2019. Patient characteristics and 90-day mRS were collected. Multivariable logistic regression analysis of 90-day mRS 0-2 vs. 3-6 and 0-5 vs. 6 with the reduced features set was performed. Discriminative performance was assessed by the area under the receiver operating characteristic curve (AUROC). RESULTS: Thirty-three percent of patients (413/1243) underwent treatment. Majority of strokes was treated conservatively (n = 830, 67%), 18% (n = 225) was treated by thrombolysis, 7% (n = 88) by thrombectomy and 8% (n = 100) by thrombolysis and thrombectomy. Age, NIHSS and pre-stroke mRS were independently associated with 90-day mRS 0-2 (all p ≤ 0.0001, AUROC 0.88). When treatment modality was added in the model, age, NIHSS, pre-stroke mRS and treatment modality were independently associated with 90-day mRS 0-2 (p < 0.0001, p < 0.0001, p < 0.0001 and p = 0.0001) AUROC 0.89). Age, NIHSS, pre-stroke mRS and treatment modality were independently associated with 90-day survival (p = 0.0001, p < 0.0001, p < 0.0001 and p = 0.008, AUROC 0.86). DISCUSSION: The reduced features set (age, NIHSS and pre-mRS) was independently associated with long-term functional outcome in a Belgian multicentric cohort, making it useful for case-mix adjustments in Belgian stroke centers. Treatment modality was associated with long-term outcome.

Interaction between stroke severity and quality indicators of acute stroke care: a single-center retrospective analysis.

Ischemic stroke leads to substantial mortality and morbidity worldwide. Door-to-CT time, door-to-needle time (DNT), and door-to-groin time (DGT) are important quality indicators of stroke care. However, patient characteristics remain important determinants of outcome as well. In this single-center study, we investigated the interaction between these quality indicators and stroke severity regarding long-term functional outcome. All consecutive stroke patients treated at the ZOL stroke center, Genk, Belgium, between 2017 and 2020 were included in this retrospective observational study. Stroke severity was graded as "mild" if National Institutes of Health Stroke Scale (NIHSS) was equal to or lower than 8, "moderate" if NIHSS was between 9 and 15, and "severe" if NIHSS was higher than 16. Modified Rankin Scale (mRS) scores were collected before and 3 months after stroke. Ordinal regression analysis with correction for patient characteristics of functional outcome was done. A total of 1255 patients were included, of which 84% suffered an ischemic CVA (n = 1052) and 16% a TIA (n = 203). The proportion of patients treated conservatively or with thrombolysis, thrombectomy, or the combination of both differed according to stroke severity (p < 0.0001). Door-to-CT time was longer in mild and moderate stroke (p < 0.0001). Median DNT also differed between stroke categories: 46 (IQR 31-70) min for mild vs. 36 (25-56) min for moderate vs. 30 (21-45) min for severe stroke (p = 0.0002). Median DGT did not differ between stroke severity categories (p = 0.15). NIHSS on admission and pre-stroke mRS were independently associated with mRS at 90 days. Operational performance, reflected in door-to-CT time and DNT, was worse in patients with mild and moderate stroke severity. DNT was also associated with functional outcome in our center, along with pre-stroke mRS, NIHSS on admission and age.

Transdural Thoracic Disk Herniation with Longitudinal Slitlike Dural Defect Causing Intracranial Hypotension: Report of 2 Cases.

BACKGROUND: Intracranial hypotension (IH) has a widely variable clinical and radiologic presentation. Secondary IH may be caused by degenerative spine disorders and in particular by thoracic disk herniations (TDHs). METHODS: We present 2 patients with a transdural TDH, a secondary IH, and superficial siderosis in 1. RESULTS: Case 1 presented with headache, cognitive decline, staggering gait, bilateral subdural effusions, cerebral sagging, an extradural spinal cerebrospinal fluid (CSF) collection suggesting secondary IH, and a calcified TDH at T9-T10. Case 2 presented with intermittent pain at the craniocervical junction provoked exclusively by specific physical activities, superficial siderosis mainly in the posterior fossa, an extradural spinal CSF collection, and a calcified TDH at T7-T8 yet no intracranial signs of IH. In both cases, using strict thoracoscopic technique, we removed a transdural TDH and reconstructed an underlying longitudinal slitlike dural defect with smooth lining. Follow-up magnetic resonance imaging scans confirmed a dramatically improved situation without residual extradural intraspinal CSF collection or signs of IH. CONCLUSIONS: This paper adds to the evidence that some cases of IH and even superficial siderosis are caused by transdural erosion of a TDH that may be otherwise asymptomatic. The dura may degenerate due to chronic compression, and a longitudinal slitlike dural defect with smooth lining may develop, causing continuous (Case 1) or intermittent (Case 2) intraspinal CSF leakage. To the best of our knowledge, such dural defects closely resembling the ones observed in idiopathic spinal cord herniation have never been demonstrated on intraoperative endoscopic video in IH patients.

Predicting Prognosis of Intracerebral Hemorrhage (ICH): Performance of ICH Score Is Not Improved by Adding Oral Anticoagulant Use.

BACKGROUND: The intracerebral hemorrhage (ICH) score is a commonly used prognostic model for 30-day mortality in ICH, based on five independent predictors (ICH volume, location, Glasgow Coma Scale, age, and intraventricular extension). Use of oral anticoagulants (OAC) is also associated with mortality but was not considered in the ICH score. We investigated (a) whether the predictive performance of ICH score is similar in OAC-ICH and non-OAC-ICH and (b) whether addition of OAC use to the ICH score increases the prognostic performance of the score. METHODS: We retrospectively selected all consecutive adult non-traumatic ICH cases (three hospitals, region South-Limburg, the Netherlands 2004-2009). Mortality at 30 days was recorded. Using univariable and multivariable logistic regression, association between OAC use and 30-day mortality was tested. Then (a) we computed receiver operating characteristic (ROC) curves for ICH score and determined the area under the curve (AUC) in OAC-ICH and non-OAC-ICH. Then (b) we created a New ICH score by adding OAC use to the ICH score. We calculated correlation between 30-day mortality and ICH score, respectively, New ICH score using Spearman correlation test. We computed ROC curves and calculated the AUC. RESULTS: We analyzed 1,232 cases, 282 (22.9%) were OAC related ICH. Overall, 30-day mortality was 39.3%. OAC use was independently associated with 30-day mortality (OR 2.09, 95% CI, 1.48-2.95; p < 0.001), corrected for the five predictors of the ICH score. The ICH score performed slightly better in non-OAC-ICH (AUC 0.840) than in OAC-ICH (AUC 0.816), but this difference was not significant (p = 0.39). The ICH score and the New ICH score were both significantly correlated with 30-day mortality (rho 0.58, p < 0.001 and 0.59, p < 0.001, respectively). The AUC for the ICH score was 0.837, for New ICH score 0.840. This difference was not significant. CONCLUSION: The ICH score is a useful tool for predicting 30-day mortality both in patient who use and patients who do not use OAC. Although OAC use is an independent predictor of 30-day mortality, addition of OAC use to the existing ICH score does not increase the prognostic performance of this score.

Mortality after primary intracerebral hemorrhage in relation to post-stroke seizures.

Seizures after intracerebral hemorrhage are repeatedly seen. Whether the development of seizures after intracerebral hemorrhage affects survival in the long term is unknown. This study aims to determine the relation between seizures (i.e., with and without anti-epileptic therapy) and long-term mortality risk in a large patient population with intracerebral hemorrhage. We retrospectively included patients with a non-traumatic ICH in all three hospitals in the South Limburg region in the Netherlands between January 1st 2004 and December 31st 2009, and we assessed all-cause mortality until March 14th 2016. Patient who did not survive the first seven days after intracerebral hemorrhage were excluded from analyses. We used Cox multivariate analyses to determine independent predictors of mortality. Of 1214 patients, 783 hemorrhagic stroke patients fulfilled the inclusion criteria, amongst whom 37 (4.7%) patients developed early seizures (within 7 days after hemorrhage) and 77 (9.8%) developed late seizures (more than 7 days after hemorrhage). Seizure development was not significantly related to mortality risk after correction for conventional vascular risk factors and hemorrhage severity. However, we found a small but independent relation between the use of anti-epileptic drugs and a lower long-term mortality (HR = 0.32, 95% CI 0.11-0.91). In our large population, seizures and epilepsy did not relate independently to an increased mortality risk after hemorrhage.

The G1662S NaV1.8 mutation in small fibre neuropathy: impaired inactivation underlying DRG neuron hyperexcitability.

OBJECTIVE: Painful small fibre neuropathy (SFN) represents a significant public health problem, with no cause apparent in one-half of cases (termed idiopathic, I-SFN). Gain-of-function mutations of sodium channel NaV1.7 have recently been identified in nearly 30% of patients with biopsy-confirmed I-SFN. More recently, gain-of-function mutations of NaV1.8 have been found in patients with I-SFN. These NaV1.8 mutations accelerate recovery from inactivation, enhance the response to slow depolarisations, and enhance activation at the channel level, thereby producing hyperexcitability of small dorsal root ganglion (DRG) neurons, which include nociceptors, at the cellular level. Identification and functional profiling of additional NaV1.8 variants are necessary to determine the spectrum of changes in channel properties that underlie DRG neuron hyperexcitability in these patients. METHODS: Two patients with painful SFN were evaluated by skin biopsy, quantitative sensory testing, nerve conduction studies, screening of genomic DNA for mutations in SCN9A and SCN10A and electrophysiological functional analysis. RESULTS: A novel sodium channel NaV1.8 mutation G1662S was identified in both patients. Voltage-clamp analysis revealed that the NaV1.8/G1662S substitution impairs fast-inactivation, depolarising the midpoint (V1/2) by approximately 7 mV. Expression of G1662S mutant channels within DRG neurons rendered these cells hyperexcitable. CONCLUSIONS: We report for the first time a mutation of NaV1.8 which impairs inactivation, in patients with painful I-SFN. Together with our earlier results, our observations indicate that an array of NaV1.8 mutations, which affect channel function in multiple ways, can contribute to the pathophysiology of painful peripheral neuropathy.

Small-fiber neuropathy Nav1.8 mutation shifts activation to hyperpolarized potentials and increases excitability of dorsal root ganglion neurons.

Idiopathic small-fiber neuropathy (I-SFN), clinically characterized by burning pain in distal extremities and autonomic dysfunction, is a disorder of small-caliber nerve fibers of unknown etiology with limited treatment options. Functional variants of voltage-gated sodium channel Nav1.7, encoded by SCN9A, have been identified in approximately one-third of I-SFN patients. These variants render dorsal root ganglion (DRG) neurons hyperexcitable. Sodium channel Nav1.8, encoded by SCN10A, is preferentially expressed in small-diameter DRG neurons, and produces most of the current underlying the upstroke of action potentials in these neurons. We previously demonstrated two functional variants of Nav1.8 that either enhance ramp current or shift activation in a hyperpolarizing direction, and render DRG neurons hyperexcitable, in I-SFN patients with no mutations of SCN9A. We have now evaluated additional I-SFN patients with no mutations in SCN9A, and report a novel I-SFN-related Nav1.8 mutation I1706V in a patient with painful I-SFN. Whole-cell voltage-clamp recordings in small DRG neurons demonstrate that the mutation hyperpolarizes activation and the response to slow ramp depolarizations. However, it decreases fractional channels resistant to fast inactivation and reduces persistent currents. Current-clamp studies reveal that mutant channels decrease current threshold and increase the firing frequency of evoked action potentials within small DRG neurons. These observations suggest that the effects of this mutation on activation and ramp current are dominant over the reduced persistent current, and show that these pro-excitatory gating changes confer hyperexcitability on peripheral sensory neurons, which may contribute to pain in this individual with I-SFN.

Prevalence and associated behavioral symptoms of depression in mild cognitive impairment and dementia due to Alzheimer's disease.

BACKGROUND: Mild cognitive impairment (MCI) is a clinical concept that categorizes subjects who are in an intermediate cognitive state between normal aging and dementia. The aims of this study are to determine the prevalence of significant depressive symptoms in MCI and Alzheimer's disease (AD) patients and to characterize the behavior associated with significant depressive symptoms in MCI and AD patients. METHODS: A cross-sectional analysis of baseline data from a prospective, longitudinal study on behavioral symptoms of dementia and MCI was performed. The study population consisted of 270 MCI and 402 AD patients. Behavioral assessment was performed by means of Middelheim Frontality Score, Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) and Cohen-Mansfield Agitation Inventory. The presence of significant depressive symptoms was defined as a Cornell Scale for Depression in Dementia total score >7. RESULTS: The prevalence of significant depressive symptoms in AD patients (25%) was higher compared with MCI patients (16%) (p = 0.005). Patients with significant depressive symptoms showed an increased severity of frontal lobe symptoms, behavioral symptoms and agitation (Middelheim Frontality Score, Behave-AD and Cohen-Mansfield Agitation Inventory total scores; p < 0.001). Also, most of the individual frontal lobe and behavioral symptoms were more prevalent and severe, resulting in higher Behave-AD global scores. Mild cognitive impairment patients with depressive symptoms showed more severe behavioral symptoms and more severe verbally agitated behavior than AD patients without depressive symptoms (p < 0.001). CONCLUSIONS: Frontal lobe and behavioral symptoms are more prevalent and severe in MCI and AD patients with significant depressive symptoms as compared with patients without depressive symptoms.