Can sPD-1 and sPD-L1 Plasma Concentrations Predict Treatment Response among Patients with Extraparenchymal Neurocysticercosis?

Extraparenchymal neurocysticercosis (EP-NC) is a chronic, potentially life-threatening disease that responds poorly to initial anthelmintic drug therapy. A depressed specific reactivity of peripheral lymphocytes and an increased level of specific Tregs accompanies EP-NC. The immune checkpoint pathway PD-1 and its ligand PD-L1 downregulates effector T cells, causing specific immune suppression in chronic diseases. This study explored whether their soluble forms, sPD-1/sPD-L1, are present in plasma among patients with EP-NC and if their levels could be associated with treatment response. A total of 21 patients with vesicular EP-NC and 22 healthy controls were included. Patients received standard treatment and were followed for six months to assess treatment response by assessing changes in cyst volume determined with 3D MRI. The presence of both sPD-1 and sPD-L1 was more frequently detected among patients with EP-NC than in healthy controls and had higher concentrations. Among patients, higher pre-treatment levels of both markers were associated with a poor treatment response, and the sensitivity and specificity of the sPD-1/sPD-L1 ratio for predicting any response to treatment were high. Our results are consistent with the presence of lymphocyte exhaustion and open new research perspectives to improve the prognosis of patients with this severe disease.

Seizures following COVID-19 vaccination in Mexico: A nationwide observational study.

The COVID-19 pandemic led to the development and emergency approval of an array of effective vaccines against SARS-CoV-2. Given the relatively small number of patients included in vaccine trials, postapproval epidemiological surveillance is crucial to detect infrequent vaccine-related adverse events. We conducted a nationwide retrospective descriptive study evaluating the incidence of seizures among recipients of SARS-CoV-2 vaccines in Mexico from December 24, 2020 (date of administration of first doses nationwide) to October 29, 2021. Among 81 916 351 doses of any vaccine that were administered, we documented seizures in 53 patients, of which 31 (60%) were new onset seizures. The incidence rate of seizures per million doses was highest for mRNA-1273 (Moderna) with 2.73 per million, followed by BNT162b2 (Pfizer-BioNTech) with 1.02 per million, and Ad5-nCoV (CanSino) with 1.01 per million. Thus, we found that seizures following SARS-CoV-2 vaccination are exceedingly rare events.

Incidence of Guillain-Barré syndrome following SARS-CoV-2 immunization: Analysis of a nationwide registry of recipients of 81 million doses of seven vaccines.

BACKGROUND AND PURPOSE: Information on Guillain-Barré syndrome (GBS) as an adverse event following immunization (AEFI) against SARS-CoV-2 remains scarce. We aimed to report GBS incidence as an AEFI among adult (≥18 years) recipients of 81,842,426 doses of seven anti-SARS-CoV-2 vaccines between December 24, 2020, and October 29, 2021, in Mexico. METHODS: Cases were retrospectively collected through passive epidemiological surveillance. The overall observed incidence was calculated according to the total number of administered doses. Vaccines were analyzed individually and by vector as mRNA-based (mRNA-1273 and BNT162b2), adenovirus-vectored (ChAdOx1 nCov-19, rAd26-rAd5, Ad5-nCoV, and Ad26.COV2-S), and inactivated whole-virion-vectored (CoronaVac) vaccines. RESULTS: We identified 97 patients (52 males [53.6%]; median [interquartile range] age 44 [33-60] years), for an overall observed incidence of 1.19/1,000,000 doses (95% confidence interval [CI] 0.97-1.45), with incidence higher among Ad26.COV2-S (3.86/1,000,000 doses, 95% CI 1.50-9.93) and BNT162b2 recipients (1.92/1,00,000 doses, 95% CI 1.36-2.71). The interval (interquartile range) from vaccination to GBS symptom onset was 10 (3-17) days. Preceding diarrhea was reported in 21 patients (21.6%) and mild COVID-19 in four more (4.1%). Only 18 patients were tested for Campylobacter jejuni (positive in 16 [88.9%]). Electrophysiological examinations were performed in 76 patients (78.4%; axonal in 46 [60.5%] and demyelinating in 25 [32.8%]); variants were similar across the platforms. On admission, 91.8% had a GBS disability score ≥3. Seventy-five patients (77.3%) received intravenous immunoglobulin, received seven plasma exchange (7.2%), and 15 (15.5%) were treated conservatively. Ten patients (10.3%) died, and 79.1% of survivors were unable to walk independently. CONCLUSIONS: Guillain-Barré syndrome was an extremely infrequent AEFI against SARS-CoV-2. The protection provided by these vaccines outweighs the risk of developing GBS.

Stroke Among SARS-CoV-2 Vaccine Recipients in Mexico: A Nationwide Descriptive Study.

BACKGROUND AND OBJECTIVES: Information on stroke among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines remains scarce. We report stroke incidence as an adverse event following immunization (AEFI) among recipients of 79,399,446 doses of 6 different SARS-CoV-2 vaccines (BNT162b2, ChAdOx1 nCov-19, Gam-COVID-Vac, CoronaVac, Ad5-nCoV, and Ad26.COV2-S) between December 24, 2020, and August 31, 2021, in Mexico. METHODS: This retrospective descriptive study analyzed stroke incidence per million doses among hospitalized adult patients (≥18 years) during an 8-month interval. According to the World Health Organization, AEFIs were defined as clinical events occurring within 30 days after immunization and categorized as either nonserious or serious, depending on severity, treatment, and hospital admission requirements. Acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and cerebral venous thrombosis (CVT) cases were collected through a passive epidemiologic surveillance system in which local health providers report potential AEFI to the Mexican General Board of Epidemiology. Data were captured with standardized case report formats by an ad hoc committee appointed by the Mexican Ministry of Health to evaluate potential neurologic AEFI against SARS-COV-2. RESULTS: We included 56 patients (31 female patients [55.5%]) for an overall incidence of 0.71 cases per 1,000,000 administered doses (95% CI 0.54-0.92). Median age was 65 years (interquartile range [IQR] 55-76 years); median time from vaccination to stroke (of any subtype) was 2 days (IQR 1-5 days). In 27 (48.2%) patients, the event was diagnosed within the first 24 hours after immunization. The most frequent subtype was AIS in 43 patients (75%; 0.54 per 1,000,000 doses, 95% CI 0.40-0.73), followed by ICH in 9 (16.1%; 0.11 per 1,000,000 doses, 95% CI 0.06-0.22) and SAH and CVT, each with 2 cases (3.6%; 0.03 per 1,000,000 doses, 95% CI 0.01-0.09). Overall, the most common risk factors were hypertension in 33 (58.9%) patients and diabetes in 22 (39.3%). Median hospital length of stay was 6 days (IQR 4-13 days). At discharge, functional outcome was good (modified Rankin Scale score 0-2) in 41.1% of patients; in-hospital mortality rate was 21.4%. DISCUSSION: Stroke is an exceedingly rare AEFI against SARS-CoV-2. Preexisting stroke risk factors were identified in most patients. Further research is needed to evaluate causal associations between SARS-COV-2 vaccines and stroke.

Neurologic adverse events among 704,003 first-dose recipients of the BNT162b2 mRNA COVID-19 vaccine in Mexico: A nationwide descriptive study.

mRNA vaccines against SARS-CoV-2 are remarkably effective. Limited information exists about the incidence of adverse events following immunization (AEFI) with their use. We conducted a prospective observational study including data from 704,003 first-doses recipients; 6536 AEFI were reported, of whom 65.1% had at least one neurologic AEFI (non-serious 99.6%). Thirty-three serious events were reported; 17 (51.5%) were neurologic (observed frequency, 2.4/100,000 doses). At the time of writing this report, 16/17 cases had been discharged without deaths. Our data suggest that the BNT162b2 mRNA COVID-19 vaccine is safe; its individual and societal benefits outweigh the low percentage of serious neurologic AEFI. This information should help to dissipate hesitancy towards this new vaccine platform.

Diffuse cerebral angiomatosis: a case report with fatal outcome.

Diffuse cerebral angiomatosis is a rare disorder of the brain and only 5 cases have been reported to date. We report a 16-year-old female patient who presented to the emergency department with seizures. The patient had no hereditary syndromes, no epistaxis, no skin lesions and no telangiectasia. There was no livedo reticularis. The ophthalmologic examination was within normal limits. Magnetic resonance angiography (MRA) showed multiple diffuse tortuous vessels all around the brain tissue and ventricular system. Brain CT showed multiple calcifications. Digital subtraction angiography (DSA) demonstrated multiple arteriovenous shunts and diffuse arteriovenous malformations (AVM) without a typical nidus, draining into dilated cerebral veins. Multimodal ultrasound showed increased flow velocities in all cerebral arteries. We report the case of a patient with diffuse cerebral angiomatosis. This is the third study in which hemodynamic indices were evaluated through transcranial Doppler. Unlike all other case reports our patient had a bad outcome with important disability, dementia and drug resistant epilepsy that lead to the patient's death.HighlightsDiffuse cerebral angiomatosis is a rare disorder of the brain and only 5 cases have been reported to date.Unlike all other case reports our patient had a bad outcome with disability, dementia and drug resistant epilepsy that lead to the patient's death.

Dopaminergic Hyperactivity in Neurological Patients with Delirium.

BACKGROUND: Delirium has important etiological, prognostic, and therapeutic implications. The study of neurochemical markers in this condition is relevant to the understanding of its pathophysiology. The assessment of the dopamine system is particularly relevant, as dopamine antagonists are the most used drugs in delirium. AIM: To analyze neurotransmission markers in patients with delirium, focusing in the dopamine metabolite, homovanillic acid. METHODS: A case-control study was performed at the National Institute of Neurology and Neurosurgery, Mexico, including hospitalized patients in which lumbar puncture was obtained for diagnostic purposes. Cases were selected if they fulfilled DSM-5 criteria for delirium. Age-paired controls were patients in which delirium was ruled out, selected at the same clinical scenario, during the same period. Neurological and systemic diagnoses were registered. Delirium was assessed using the DRS-98-R instrument. The dopamine metabolite, homovanillic acid (HVA), was measured by means of high-performance liquid chromatography. Other neurotransmission markers were also measured (5-hydroxyindoleacetic acid, glutamate, aspartate, GABA, glycine, arginine, citrulline, nitrites, and nitrates). A logistic regression model was used to determine pathogenic factors associated with the presence of delirium. RESULTS: 68 neurological patients with delirium and 68 patients without delirium were included. Higher homovanillic acid levels in cerebrospinal fluid were significantly associated with delirium. This result was significant after a subanalysis in patients without exposure to antipsychotics. Male gender and autoimmune limbic encephalitis were also associated with the presence of delirium. CONCLUSIONS: In hospitalized neurological patients, dopaminergic hyperactivity and autoimmune limbic encephalitis are pathogenic factors associated with the presence of delirium.

[White matter hyperintensities and cognitive function in patients with late onset mania]. / Lesiones hiperintensas de la sustancia blanca y función cognoscitiva en pacientes con manía de inicio tardío.

Bipolar disorder is characterized by affective episodes in the mania-depression spectrum. Ninety per cent of the cases have an onset before age 50. In the patients with late onset mania, white matter hyperintensities (WMH) may be seen in the MRI FLAIR sequence, although these are of uncertain significance. A case-control study was done, including patients with late onset mania attended at the National Institute of Neurology and Neurosurgery, as well as healthy controls which were paired by age, sex, and academic level. Sagital FLAIR CUBE volumetric images were obtained, and later on assessed by an expert neuroradiologist, blinded to the diagnostic category. Neuropsychological measures were obtained. The patients with late onset mania showed statistically significant deficiencies (p < 0.05) in motor programming tasks, and inhibitory control tasks, according to the Frontal Assessment Battery, as well as a significant increase in the number of WMH in the right third frontal gyrus, the left first temporal gyrus, and the left second temporal gyrus. The total number of WMH and the Frontal Assessment Battery total score showed a significant inverse correlation.

Relevance of 3D magnetic resonance imaging sequences in diagnosing basal subarachnoid neurocysticercosis.

Imagenological diagnosis of subarachnoid neurocysticercosis is usually difficult when classical magnetic resonance imaging (MRI) sequences are used. The purpose of this study was to evaluate the advantages of 3D MRI sequences (Fast Imaging Employing Steady-state Acquisition (FIESTA) and Spoiled Gradient Recalled Echo (SPGR)) with respect to classical sequences (Fluid Attenuation Inversion Recovery (FLAIR) and T1) in visualizing Taenia solium cyst in these locations. Forty-seven T. solium cysts located in the basal cisterns of the subarachnoid space were diagnosed in eighteen Mexican patients. A pre-treatment MRI was performed on all patients, and all four sequences (FIESTA, FLAIR, T1 SPGR, and T2) were evaluated independently by two neuroradiologists. The sensitivity of each sequence to detect the parasite membrane and scolex was evaluated, along with its capacity to detect differences in signal intensity between cerebrospinal fluid (CSF) and cysts. FIESTA sequences allowed the visualization of cyst membrane in 87.2% of the parasites evaluated, FLAIR in 38.3%, SPGR in 23.4%, and T2 in 17.0%. The superiority of FIESTA sequences over the other three imaging methods was statistically significant (P<0.001). Scolices were detected by FIESTA twice as much as the other sequences did, although this difference was not significant (P>0.05). Differences in signal intensity between CSF and parasite cysts were significant in FIESTA (P<0.0001), SPGR (P<0.0001), and FLAIR (P=0.005) sequences. For the first time, the usefulness of 3D MRI sequences to diagnose T. solium cysts located in the basal cisterns of the subarachnoid space was demonstrated. The routine use of these sequences could favor an earlier diagnosis and greatly improve the prognosis of patients affected by this severe form of the disease.

Subarachnoid basal neurocysticercosis: a focus on the most severe form of the disease.

Neurocysticercosis is an endemic disease in Latin America, Asia and Africa with growing occurrence in industrialized countries due to the increase in migration from low- and middle-income to high-income countries. The most severe clinical presentation is when the parasite is located in the subarachnoid space at the base of the brain (NCSAB). Aside from its clinical presentation, the severity of this form of the disease is due to the difficulties in diagnosis and treatment. Although NCSAB frequency is lower than that reported for the parenchymal location of the parasite, its clinical relevance must be emphasized. We provide a critical review of the central epidemiological, clinical, diagnostic and therapeutic features of this particular form of the disease, which is still associated with unacceptably high rates of morbidity and mortality.

Subarachnoidal Neurocysticercosis non-responsive to cysticidal drugs: a case series.

BACKGROUND: Neurocysticercosis (NC) is one of the most frequent parasitic diseases of the central nervous system. Cysticidal drugs, albendazole and praziquantel, are generally effective when parasites localize in the parenchyma. In contrast, parasites lodged in the subarachnoid basal cisterns are less responsive to treatment. CASE PRESENTATION: The clinical and radiological pictures of six Mexican patients non-respondent to cysticidal treatment are presented. CONCLUSIONS: The possible factors involved in the cysticidal non-response are discussed and hints are provided of potentially useful changes to therapeutic protocols.