Cancer immunotherapy represents a novel anticancer strategy that acts directly on the immune system, promoting its activation toward cancer cells to enhance its natural ability to fight cancer. Among ...various treatments currently used or investigated, chimeric antigen receptors (CAR) T-cell therapy and immune checkpoint inhibitors (ICIs) have consistently proven their efficacy. These innovations are progressively improving the standard of care in cancer treatment, yet they are hampered by novel neurological adverse events, attributing to neurologists a key role in the multidisciplinary oncological team. Indeed, neurotoxicity may develop in up to 77% of patients who received CAR T-cell therapy and usually presents with encephalopathy characterized by a predominant frontal lobe dysfunction. This neurotoxicity is related to cytokine release syndrome, a systemic hyperinflammatory condition triggered by CAR T-cells. On the other hand, following treatment with ICIs, unrestrained T-cells may lead to central and peripheral neurological disorders by antigen-directed autoimmunity. Notably, biological and clinical similarities have been underlined between neurotoxicity related to CAR T-cell therapy and neurological manifestations of cytokine storms (e.g. COVID-19-related encephalopathy), as well as between a subgroup of ICI-related neurological adverse events and paraneoplastic neurological syndromes. Therefore, these cancer immunotherapy-related neurological syndromes may provide an unprecedented, perhaps transitory, opportunity to shed light on the underlying pathogenic mechanisms of a wide spectrum of neurological syndromes and to push forward our knowledge in neuroimmunology.
Objective
To determine whether erenumab is effective and safe in refractory chronic migraine with medication overuse headache.
Methods
In this prospective, multicentric, real-life study, chronic ...migraine with medication overuse headache patients who received erenumab were recruited. Study inclusion was limited to patients who previously failed onabotulinumtoxinA in addition to at least three other pharmacological commonly used migraine preventive medication classes.
Results
Of 396 patients who received erenumab, 38% (
n
= 149) met inclusion criteria. After 3 months, 51% (
n
= 76) and 20% (
n
= 30) patients achieved ≥ 50% and ≥ 75% reduction in monthly headache days, respectively. Monthly pain medications intake decreased from 46.1 ± 35.3 to 16.8 ± 13.9 (
p
< 0.001), while monthly headache days decreased from 25.4 ± 5.4 to 14.1 ± 8.6 (
p
< 0.001). Increasing efficacy of erenumab over the study period was observed. Allodynia was a negative predictive factor of erenumab response (odds ratio = 0.47;
p
= 0.03). Clinical conversion to episodic migraine with no medication overuse was observed in 64% (
n
= 96) patients. No serious adverse events were observed.
Conclusions
Erenumab reduced significantly migraine frequency and pain medication intake in refractory chronic migraine with MOH patients.
Objective
To report on efficacy and safety of intravenous immunoglobulin (IVIg) therapy in a case series of patients with COVID-19-related encephalopathy.
Methods
We retrospectively collected data on ...all patients with COVID-19 hospitalized at two Italian hospitals who developed encephalopathy during disease course and were treated with IVIg.
Results
Five patients (two females, mean age 66.8 years) developed encephalopathy after a mean of 12.6 days, since the onset of respiratory/constitutional symptoms related to COVID-19. Four patients suffered severe respiratory distress, three of which required invasive mechanical ventilation. Neurological manifestations included impaired consciousness, agitation, delirium, pyramidal and extrapyramidal signs. EEG demonstrated diffuse slowing in all patients. Brain MRI showed non-specific findings. CSF analysis revealed normal cell count and protein levels. In all subjects, RT-PCR for SARS-CoV-2 in CSF tested negative. IVIg at 0.4 g/kg/die was commenced 29.8 days (mean, range: 19–55 days) after encephalopathy onset, leading to complete electroclinical recovery in all patients, with an initial improvement of neuropsychiatric symptoms observed in 3.4 days (mean, range: 1–10 days). No adverse events related to IVIg were observed.
Conclusions
Our preliminary findings suggest that IVIg may represent a safe and effective treatment for COVID-19-associated encephalopathy. Clinical efficacy may be driven by the anti-inflammatory action of IVIg, associated with its anti-cytokine qualities.
Introduction
Headache is the most prevalent neurological manifestation in adults and one of the leading causes of disability worldwide. In children and adolescents, headaches are arguably responsible ...for a remarkable impact on physical and psychological issues, yet high-quality evidence is scarce.
Material and methods
We searched cross-sectional and cohort studies in Embase, Medline, Web of Science, and Cochrane databases from January 1988 to June 2022 to identify the prevalence of headaches in 8–18 years old individuals. The risk of bias was examined with the Joanna Briggs Institute (JBI) scale. A random-effects model was used to estimate the pooled prevalence of pediatric headache. Subgroup analyses based on headache subtypes were also conducted.
Results
Out of 5,486 papers retrieved electronically, we identified 48 studies that fulfilled our inclusion criteria. The pooled prevalence of primary headaches was 11% for migraine overall 95%CI: 9–14%, 8% for migraine without aura (MwoA) 95%CI: 5–12%, 3% for migraine with aura (MwA) 95%CI:2–4% and 17% for tension-type headache (TTH) 95% CI: 12–23%. The pooled prevalence of overall primary headache in children and adolescents was 62% 95% CI: 53–70%, with prevalence in females and males of 38% 95% CI: 16–66% and 27% 95% CI: 11–53% respectively. After the removal of studies ranked as low-quality according to the JBI scale, prevalence rates were not substantially different. Epidemiological data on less common primary headaches, such as trigeminal autonomic cephalalgias, were lacking.
Conclusion
We found an overall remarkably high prevalence of primary headaches in children and adolescents, even if flawed by a high degree of heterogeneity. Further up-to-date studies are warranted to complete the picture of pediatric headache-related burden to enhance specific public interventions.
Objective
Many neurological manifestations are associated with COVID‐19, including a distinct form of encephalopathy related to cytokine storm, the acute systemic inflammatory syndrome present in a ...subgroup of COVID‐19 patients. Cytokine storm is also associated with immune effector cell‐associated neurotoxicity syndrome (ICANS), a complication of chimeric antigen receptor T‐cell (CAR‐T) therapy, a highly effective treatment for refractory hematological malignancies. We investigated whether COVID‐19‐related encephalopathy, ICANS, and other encephalopathies associated with cytokine storm, share clinical and investigative findings.
Methods
Narrative literature review.
Results
Comparisons between COVID‐19‐related encephalopathy and ICANS revealed several overlapping features. Clinically, these included dysexecutive syndrome, language disturbances, akinetic mutism and delirium. EEG showed a prevalence of frontal abnormalities. Brain MRI was often unrevealing. CSF elevated cytokine levels have been reported. A direct correlation between cytokine storm intensity and severity of neurological manifestations has been shown for both conditions. Clinical recovery occurred spontaneously or following immunotherapies in most of the patients. Similar clinical and investigative features were also reported in other encephalopathies associated with cytokine storm, such as hemophagocytic lymphohistiocytosis, sepsis, and febrile infection‐associated encephalopathies.
Interpretation
COVID‐19‐related encephalopathy and ICANS are characterized by a predominant electro‐clinical frontal lobe dysfunction and share several features with other encephalopathies associated with cytokine storm, which may represent the common denominator of a clinical spectrum of neurological disorders. Therefore, we propose a unifying definition of cytokine storm‐associated encephalopathy (CySE), and its diagnostic criteria.
Background
Erenumab is a monoclonal antibody acting against calcitonin gene-related peptide receptor which has been found effective even for the treatment of chronic migraine (CM) complicated with ...medication overuse headache (MOH). According to the present guidelines, the treatment with erenumab should continue for up to 1 year. The aim of the present study is to explore the evolution of patients affected by CM and MOH at the baseline, after erenumab discontinuation.
Methods
One hundred and eighty-five patients affected by CM and MOH were recruited and followed up after erenumab discontinuation. The number of migraine days per month, the number of painkillers taken per month, the number of days in which one medication was used for a month were collected every 30 days for the 3 months following erenumab suspension.
Results
At the 3rd month after suspension, patients displayed a significantly higher number of migraine days per month, a significantly higher painkiller consumption, and a significantly higher migraine-related disability. A high body mass index and the presence of aura were positively correlated with the relapse of CM and MOH.
Conclusion
Patients affected by CM and MOH at the baseline displayed a significant worsening of their headaches after erenumab discontinuation.
Chimeric antigen receptor (CAR) T-cell therapy is an emerging highly effective treatment for refractory haematological malignancies. Unfortunately, its therapeutic benefit may be hampered by ...treatment-related toxicities, including neurotoxicity. Early aggressive treatment is paramount to prevent neurological sequelae, yet it potentially interferes with the anti-cancer action of CAR T-cells. We describe four CAR T-cells infused patients who presented with reiterative writing behaviours, namely paligraphia, as an early manifestation of neurotoxicity, and eventually developed frontal predominant encephalopathy (one mild, three severe). Paligraphia may represent an early, specific, and easily detectable clinical finding of CAR T-cell therapy-related neurotoxicity, potentially informing its management.
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