Imaging features and ultraearly hematoma growth in intracerebral hemorrhage associated with COVID-19.

PURPOSE: Intracerebral hemorrhage (ICH) is an uncommon but deadly event in patients with COVID-19 and its imaging features remain poorly characterized. We aimed to describe the clinical and imaging features of COVID-19-associated ICH. METHODS: Multicenter, retrospective, case-control analysis comparing ICH in COVID-19 patients (COV19 +) versus controls without COVID-19 (COV19 -). Clinical presentation, laboratory markers, and severity of COVID-19 disease were recorded. Non-contrast computed tomography (NCCT) markers (intrahematoma hypodensity, heterogeneous density, blend sign, irregular shape fluid level), ICH location, and hematoma volume (ABC/2 method) were analyzed. The outcome of interest was ultraearly hematoma growth (uHG) (defined as NCCT baseline ICH volume/onset-to-imaging time), whose predictors were explored with multivariable linear regression. RESULTS: A total of 33 COV19 + patients and 321 COV19 - controls with ICH were included. Demographic characteristics and vascular risk factors were similar in the two groups. Multifocal ICH and NCCT markers were significantly more common in the COV19 + population. uHG was significantly higher among COV19 + patients (median 6.2 mL/h vs 3.1 mL/h, p = 0.027), and this finding remained significant after adjustment for confounding factors (systolic blood pressure, antiplatelet and anticoagulant therapy), in linear regression (B(SE) = 0.31 (0.11), p = 0.005). This association remained consistent also after the exclusion of patients under anticoagulant treatment (B(SE) = 0.29 (0.13), p = 0.026). CONCLUSIONS: ICH in COV19 + patients has distinct NCCT imaging features and a higher speed of bleeding. This association is not mediated by antithrombotic therapy and deserves further research to characterize the underlying biological mechanisms.

New-onset myasthenia gravis after mRNA SARS-CoV-2 vaccination: a case series.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease that targets acetylcholine receptor (AChR) of the neuromuscular junction. New-onset MG after SARS-CoV-2 vaccination has rarely been reported. CASE PRESENTATION: We report about three patients who presented new-onset myasthenia gravis after receiving mRNA SARS-CoV-2 vaccination. The patients were all males and older than 55 years. All the patients presented with ocular and bulbar symptoms. The interval between vaccine administration and MG onset ranged from 3 days after the first dose to 10 days after the second dose. All the patients had elevated serum AChR antibodies and responded to pyridostigmine. Two out of three patients were successfully treated with IVIG or plasma exchange and with long-term immunosuppression. CONCLUSIONS: MG is a rare disease; clinicians should be aware of possible new-onset MG after SARS-CoV-2 vaccination, especially with the current recommendation of booster doses. The hyperstimulation of the innate immune system or the exacerbation of a subclinical pre-existing MG could be possible explanations.

CD163 as a Potential Biomarker of Monocyte Activation in Ischemic Stroke Patients.

In ischemic stroke patients, a higher monocyte count is associated with disease severity and worse prognosis. The complex correlation between subset phenotypes and functions underscores the importance of clarifying the role of monocyte subpopulations. We examined the subtype-specific distribution of the CD163+ and CD80+ circulating monocytes and evaluated their association with the inflammatory status in 26 ischemic stroke patients and 16 healthy controls. An increased percentage of CD163+/CD16+ and CD163+/CD14++ events occurred 24 and 48 h after a stroke compared to the controls. CD163+ expression was more pronounced in CD16+ non-classical and intermediate monocytes, as compared to CD14+ classical subtype, 24 h after stroke. Conversely, the percentage of CD80+/CD16+ events was unaffected in patients; meanwhile, the percentage of CD80+/CD14+ events significantly increased only 24 h after stroke. Interleukin (IL)-1beta, TNF-alpha, and IL-4 mRNA levels were higher, while IL-10 mRNA levels were reduced in total monocytes from patients versus controls, at either 24 h or 48 h after stroke. The percentage of CD163+/CD16+ events 24 h after stroke was positively associated with NIHSS score and mRS at admission, suggesting that stroke severity and disability are relevant triggers for CD163+ expression in circulating CD16+ monocytes.

Subarachnoid Extension Predicts Lobar Intracerebral Hemorrhage Expansion.

Background and Purpose- We investigated whether subarachnoid extension (SAHE) of intracerebral hemorrhage (ICH) is associated with hematoma expansion (HE). Methods- Retrospective analysis of patients with primary spontaneous ICH admitted at 3 academic hospitals in Italy. The study population was divided into a development and a replication cohort. SAHE was rated on baseline noncontrast computed tomography by investigators blinded to clinical data. The main outcome of interest was HE, defined as ICH growth >33% mL and/or >6 mL. Predictors of HE were explored with multivariable logistic regression stratified by ICH location (lobar versus nonlobar). Results- A total of 360 and 192 patients were included in the development and replication cohort, respectively. SAHE was identified with good interrater reliability (K=0.82), and its frequency was 27.8% in the development and 24.5% in the replication cohort. In univariate analysis, HE was more common in patients with SAHE (52.0% versus 27.3%; P<0.001). When controlling for confounders in logistic regression, SAHE was an independent predictor of lobar HE (odds ratio, 6.00 [95% CI, 2.16-16.64]; P=0.001) whereas there was no association with HE in nonlobar ICH (odds ratio, 0.55 [95% CI, 0.17-1.84]; P=0.334). The increased risk of HE in lobar ICH with SAHE was confirmed in the replication cohort (odds ratio, 3.46 [95% CI, 1.07-11.20]; P=0.038). Conclusions- SAHE predicts HE in lobar ICH. This may improve the stratification of HE risk in clinical practice or future trials targeting HE. Further research is needed to confirm our findings and characterize the underlying biological mechanisms.

Validation and Comparison of Noncontrast CT Scores to Predict Intracerebral Hemorrhage Expansion.

BACKGROUND AND PURPOSE: The BAT, BRAIN, and HEP scores have been proposed to predict hematoma expansion (HE) with noncontrast computed tomography (NCCT). We sought to validate these tools and compare their diagnostic performance. METHODS: We retrospectively analyzed two cohorts of patients with primary intracerebral hemorrhage. HE expansion was defined as volume growth > 33% or > 6 mL. Two raters analyzed NCCT scans and calculated the scores, blinded to clinical and imaging data. The inter-rater reliability was assessed with the interclass correlation statistic. Discrimination and calibration were calculated with area under the curve (AUC) and Hosmer-Lemeshow χ2 statistic, respectively. AUC comparison between different scores was explored with DeLong test. We also calculated the sensitivity, specificity, positive, and negative predictive values of the dichotomized scores with cutoffs identified with the Youden's index. RESULTS: A total of 230 subjects were included, of whom 86 (37.4%) experienced HE. The observed AUC for HE were 0.696 for BAT, 0.700 for BRAIN, and 0.648 for HEP. None of the scores had a significantly superior AUC compared with the others (all p > 0.4). All the scores had good calibration (all p > 0.3) and good-to-excellent inter-rater reliability (interclass correlation > 0.8). BAT ≥ 3 showed the highest specificity (0.81), whereas BRAIN ≥ 6 had the highest sensitivity (0.76). CONCLUSIONS: The BAT, BRAIN, and HEP scores can predict HE with acceptable discrimination and require just a baseline NCCT scan. These tools may be used to stratify the risk of HE in clinical practice or randomized controlled trials.

Carotid dissection mimicking a new attack of cluster headache.

BACKGROUND: Symptomatic cluster headache (CH) secondary to internal carotid artery dissection (ICAD) has been frequently reported, however, as far as we know, the coexistence of episodic CH and acute symptomatic CH secondary to ICAD has not. CASE REPORT: A 39 year-old man, affected by episodic CH since the age of 19, presented an atypical headache associated with his usual autonomic symptoms. After a series of negative tests, MRA eventually revealed dissection of the right distal internal carotid artery. DISCUSSION AND CONCLUSIONS: The coexistence of episodic CH and acute CH symptomatic of ICAD in our patient suggests that, at least in some cases, CH and ICAD may be different expressions of a common underlying cause: hidden vessel wall damage. When risk factors and the change - though partial - of clinical features suggest symptomatic cases, CH patients have to be strictly monitored over time. Given the lack of a gold standard investigation for dynamic diseases such as dissections, these patients require multimodal diagnostic investigation over time, even in cases where exams are normal at onset.

Caring for acute coronary syndrome and other time-sensitive medical emergencies during the coronavirus disease 2019 pandemic in Northern Italy: report from a hub center.

BACKGROUND: The Lombardy region, in Northern Italy, suffered a major outbreak of Coronavirus disease 2019 (COVID-19) at the end of February 2020. The health system was rapidly overwhelmed by the pandemic. It became evident that patients suffering from time-sensitive medical emergencies like stroke, cerebral hemorrhage, trauma and acute myocardial infarction required timely, effective and safe pathways to be treated. The problem was addressed by a regional decree that created a hub-and-spoke system for time-sensitive medical emergencies. METHODS: We report the re-organizational changes adopted at a hub hospital (despite having already destined to COVID-19 patients most resources), and the number of emergent procedures for medical emergencies on the first 30-day of activity. These data were compared with the hospital activity in the same period of the previous year. RESULTS: Organizational changes were implemented in few hours. Dedicated pathways for non-COVID-19 patients affected by a medical emergency were set up in the emergency department, in the labs and in the operating theater. Ten intensive beds were implemented from a high-dependency unit; two operating rooms were reserved 24 h/day to neurosurgical or trauma emergencies. The number of emergent procedures was not different from that of the previous year, no admission refusal, no treatment delay and no viral transmission to the treated patients were recorded. No viral transmission to health care workers was observed. CONCLUSIONS: Re-organization of a hospital in order to adopt a hub-and-spoke model resulted feasible and allowed to face acute coronary syndrome and other time-sensitive medical emergencies timely and safely.

Vitamin D, Chronic Migraine, and Extracranial Pain: Is There a Link? Data From an Observational Study.

Several studies focused on the role of vitamin D (vitD) in pain chronification. This study focused on vitD level and pain chronification and extension in headache disorders. Eighty patients with primary headache underwent neurological examination, laboratory exams, including serum calcifediol 25(OH)D, and headache features assessment along with three questionnaires investigating depression, anxiety, and allodynia. The 86.8% of the population had migraine (48% episodic and 52% chronic). The 44.1% of patients had extracranial pain, and 47.6% suffered from allodynia. A vitD deficit, namely a serum 25(OH)D level <20 ng/ml, was detectable in 46.1% of the patients, and it occurred more frequently (p = 0.009) in patients suffering from chronic migraine (CM)-medication overuse migraine (MOH) (62.9%) than in episodic migraine (EM, 25.7%) or tension-type headache (TTH, 11.4%). The occurrence of extracranial pain and allodynia was higher in the CM-MOH than in the EM and in the TTH groups but was not related to the co-occurrence of vitD deficiency (Fisher's exact test p = 0.11 and p = 0.32, respectively). Our findings show that 25(OH)D deficit is also related to chronic headache, probably because of vitD anti-inflammatory and tolerogenic properties, reinforcing the idea of a neuroinflammatory mechanism underpinning migraine chronification.

Hematoma Expansion in Intracerebral Hemorrhage With Unclear Onset.

OBJECTIVE: To investigate the prevalence, predictors, and prognostic effect of hematoma expansion (HE) in patients with intracerebral hemorrhage (ICH) with unclear symptom onset (USO). METHODS: We performed a retrospective analysis of patients with primary spontaneous ICH admitted at 5 academic medical centers in the United States and Italy. HE (volume increase >6 mL or >33% from baseline to follow-up noncontrast CT [NCCT]) and mortality at 30 days were the outcomes of interest. Baseline NCCT was also analyzed for presence of hypodensities (any hypodense region within the hematoma margins). Predictors of HE and mortality were explored with multivariable logistic regression. RESULTS: We enrolled 2,165 participants, 1,022 in the development cohort and 1,143 in the replication cohort, of whom 352 (34.4%) and 407 (35.6%) had ICH with USO, respectively. When compared with participants having a clear symptom onset, patients with USO had a similar frequency of HE (25.0% vs 21.9%, p = 0.269 and 29.9% vs 31.5%, p = 0.423). Among patients with USO, HE was independently associated with mortality after adjustment for confounders (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.43-4.89, p = 0.002). This finding was similar in the replication cohort (OR 3.46, 95% CI 1.86-6.44, p < 0.001). The presence of NCCT hypodensities in patients with USO was an independent predictor of HE in the development (OR 2.59, 95% CI 1.27-5.28, p = 0.009) and replication (OR 2.43, 95% CI 1.42-4.17, p = 0.001) population. CONCLUSION: HE is common in patients with USO and independently associated with worse outcome. These findings suggest that patients with USO may be enrolled in clinical trials of medical treatments targeting HE.

An Example of a Stroke Unit Reshaping in the Context of a Regional Hub and Spoke System in the COVID-19 Era.

During the COVID-19 outbreak, the Neurology and Stroke Unit (SU) of the hospital of Varese had to serve as a cerebrovascular hub, meaning that the referral area for the unit doubled. The number of beds in the SU was increased from 4 to 8. We took advantage of the temporary suspension of the out-patient clinic and reshaped our activity to guarantee the 24/7 availability of recombinant tissue Plasminogen Activator (rtPA) intravenous therapy (IVT) in the SU, and to ensure we were able to admit patients to the SU as soon as they completed endovascular treatment (EVT). In 42 days, 46 stroke patients were admitted to our hospital, and 34.7% of them underwent IVT and/or EVT, which means that we treated 0.38 patients per day; in the baseline period from 2016 to 2018, these same figures had been 23.5% and 0.23, respectively. The mean values of the door-to-first CT/MRI and the door-to-groin puncture, but not of the onset-to-door and the door-to-needle periods were slightly but significantly longer than those observed in the baseline period in 276 patients. On an individual basis, only one patient exceeded the door-to-groin puncture time limit computed from the baseline period by about 10 min. None of the patients had a major complication following the procedures. None of the patients was or became SARS-CoV2 positive. In conclusion, we were able to manage the new hub-and-spoke system safely and without significant delays. The reshaping of the SU was made possible by the significant reduction of out-patient activity. The consequences of this reduction are still unknown but eventually, this emergency will suggest ways to reconsider the management and the allocation of health system resources.

Brain white matter impairment in congenital adrenal hyperplasia.

BACKGROUND: Congenital adrenal hyperplasia (CAH) is an inherited recessive disorder of adrenal steroidogenesis. Past reports suggested that brain white matter could be involved in CAH. OBJECTIVE: To detect the presence, and possible changes over time, of brain white matter abnormalities in patients with CAH. DESIGN: Neurological examination and brain magnetic resonance imaging (MRI) that were repeated in 12 patients after a mean interval of 11 years. SETTING: Pavia, northern Italy. Patients Twenty-two patients with CAH. MAIN OUTCOME MEASURES: Evaluation of clinical neurological findings and brain MRI T2-weighted images. RESULTS: Ten (45%) of 22 patients with CAH had white matter abnormalities (diffuse in 4 cases, focal in 3 cases, and both diffuse and focal in 3 cases) on MRI. The MRI findings never changed over repeated assessments. CONCLUSIONS: Subclinical brain white matter involvement is frequent in CAH. This might be due to hormonal imbalance during brain development or corticosteroid treatments. Our study findings indicate that a relationship with demyelinating diseases can also be suggested. Diagnosis of CAH should be suspected in young subjects with brain MRI white matter abnormalities that are not otherwise explicable.

Acute oculomotor impairment with anti-GQ1b IgG due to central nervous system dysfunction.

We report the case of a patient with isolated central oculomotor impairment and anti-GQ1b antibody. The patient was referred to us with acute vertical diplopia. The neurological examination revealed right internuclear ophthalmoplegia (INO), skew deviation and mild gait ataxia. Extensive laboratory analyses, CSF study, multimodal evoked potentials and brain MRI were normal. Eye movement recording showed saccade dysmetria in addition to the INO. The subjective visual vertical was abnormally tilted to the left. The anti-GQ1b IgG antibody was detectable on serum DOT-BLOT. The brainstem and cerebellar features of the oculomotor impairment suggested that in our patient the anti-GQ1b IgG antibody showed a preferential cross-reaction with central nervous system epitopes. This finding is at variance with previous reports on anti-GQ1b syndrome with acute ophthalmoplegia, all of which argue for a localization of GQ1b epitopes within the peripheral nervous system, even though, in the light of the description of the ocular motor disorder, a central involvement might have co-occurred in this case.

Congenital adrenal hyperplasia and multiple sclerosis: is there an increased risk of multiple sclerosis in individuals with congenital adrenal hyperplasia?

BACKGROUND: Congenital adrenal hyperplasia (CAH) is an inherited recessive disorder of adrenal steroidogenesis, generally caused by a total or partial deficiency in 21-hydroxylase, due to a deletion of or mutations in the CYP21 gene (the gene that codes for 21-hydroxylase). Impaired cortisol biosynthesis results in corticotropin hypersecretion, which leads to overproduction of intermediate metabolites and androgens. OBJECTIVE: To describe for the first time, to our knowledge, a patient with CAH and multiple sclerosis (MS). DESIGN: Case report. PATIENT: A 22-year-old woman, diagnosed at birth as having a salt-losing 21-hydroxylase deficiency, had sudden visual loss in the right eye and pyramidal, sensory, and cerebellar signs. Repeated brain magnetic resonance images showed focal white matter lesions in periventricular areas, the corpus callosum, the cerebellum, and the brainstem. A cerebrospinal fluid examination revealed several oligoclonal bands. Thereafter, she had 2 relapses, characterized by ataxia and diplopia, and recovered after corticosteroid treatment. RESULTS: The reported case fulfills the diagnostic criteria for CAH and MS. CONCLUSIONS: Some clues suggest that the association between CAH and MS could be nonincidental: a possible MS susceptibility locus is on chromosome 6p21, on which the CYP21 gene is located; the CYP21 gene and the CYP21P pseudogene alternate in tandem with the C4 genes (the genes that code for the homonym complement protein) (C4AQ0 is particularly frequent in patients with relapsing-remitting MS); and, in previous studies, brain magnetic resonance imaging showed T2-hyperintense focal areas in the white matter of CAH patients. Our observation should alert neurologists to the presence of signs and symptoms suggestive of late-onset CAH in MS patients and, in turn, endocrinologists to the appearance of neurological signs and symptoms in CAH patients.

The H reflex from the abductor brevis hallucis muscle in healthy subjects.

In order to evaluate the clinical applicability of a neurophysiological technique, information is required about the effect of technical and subjective factors on the measured parameters, and whether these measures are reliable. The reliability of measurement of a given parameter is inversely related to the variability shown by a set of measurements of that parameter made on the same subject under similar conditions. Reliable measures are fundamental to the clinical utility of any technique. We evaluated the reliability using the intraclass correlation coefficient (ICC), and assessed both single-point and test-retest normal limits for H-reflex parameters of abductor brevis hallucis (ABH). The H reflex from the ABH muscle was recorded in 36 of 43 subjects, but could not be elicited in 7 of 11 subjects who were >60 years of age. The Hmax latency increased as height increased, whereas Hmax amplitude and Hmax/Mmax amplitude ratio decreased as age and height increased. The Hmax latency and Hmax/Mmax amplitude ratio, but not Hmax amplitude, proved to be reliable. The usefulness of the H reflex from ABH in the evaluation of S2 radiculopathies is described.

Cerebral venous thrombosis and demyelinating diseases: report of a case in a clinically isolated syndrome suggestive of multiple sclerosis onset and review of the literature.

Cerebral venous thrombosis (CVT) has been described in several cases of clinically definite multiple sclerosis (MS). In the majority of these, lumbar puncture followed by intravenous corticosteroid treatment was suspected as the cause. We report what is, to our knowledge, the first case of a patient with a multifocal clinically isolated syndrome suggestive of MS onset, who developed multiple CVT after lumbar puncture and during high-dose i.v. corticosteroid treatment We conclude that the sequence 'lumbar puncture followed by corticosteroid treatment' may be a contributory risk factor for the development of CVT when associated with other risk factors.

Disability and mortality in a cohort of multiple sclerosis patients: a reappraisal.

The aim of the study was to evaluate how the natural history of multiple sclerosis (MS) had changed over a 15-year period. We compared disability and mortality in a cohort of 83 MS patients hospitalised in the Neurological Institute of Pavia, northern Italy, from January 1, 1990, to December 31, 1991, with a similar cohort of 52 patients analysed in the past. After the follow-up, an unfavourable course (death or relevant disability) was observed in 41% of the patients in the new cohort, compared to 63.5% of the patients in the old one. The percentage of deceased patients was reduced from 25 to 6%. The analysis of the pooled data of the two cohorts indicates a recent tendency of firstly hospitalised patients having a shorter disease duration and a lower disability level, which could explain the relevant decrease both in mortality and disability. Finally, our findings confirmed that age at onset, early disability and a short interval between onset and secondary progression increase the risk of an unfavourable course.

Fatigue in multiple sclerosis: multidimensional assessment and response to symptomatic treatment.

Sixty relapsing remitting multiple sclerosis (MS) patients were selected on the basis of their score on the Fatigue Severity Scale (FSS) and formed two groups: 40 patients (fatigued MS; MSf) scored above the 75th percentile of a previously assessed representative MS sample (100 patients), and 20 age- and sex-matched patients (nonfatigued MS patients; MSnf) scored below the 25th percentile. The patients underwent clinical evaluation (Expanded Disability Status Scale (EDSS)), further assessment of fatigue (Fatigue Impact Scale), scales evaluating depression (Hamilton Depression Rating Scale (HDRS) and Beck's Depression Inventory (BDI)) and neuropsychological tests. All patients were evaluated for muscle fatigability and central activation by means of a biomechanical test of sustained contraction; they also underwent somatosensory evoked potentials (SSEPs) and transcranial magnetic stimulation (TMS). The patients of the MSf subgroup were then randomized to one of the following two treatments: 4-aminopyridine (4-AP) 24 mg/day and fluoxetine (FLX) 20 mg/day. After a one-week titration this treatment proceeded for 8 weeks. At the end of the treatment, EDSS, fatigue and depression scores were further evaluated. At baseline, fatigue test scores consistently correlated with depression and cognitive test scores, but not with the fatigability test. Fatigue scores decreased in both treatment groups in a similar way. Due to the design of the study, this cannot be disjoined from a placebo effect. The changes of fatigue scores could not be predicted in the FLX group, whereas in the 4-AP group higher basal fatigability test scores were associated with greater reduction in fatigue scores.