Over the past decade, cancer immunotherapy with immune checkpoint inhibitors (ICIs) has significantly improved the outcome of many malignancies. However, with the broad use of ICIs, neurological ...immune related adverse events (irAE) are increasingly recognized. ICI-induced encephalitis (ICI-iE) is a particularly severe irAE, often leading to treatment termination, long-term sequalae or death. Despite its high morbidity and mortality, data on clinical features and diagnostic criteria are limited.
We aimed to define clinical, radiologic and laboratory characteristics of ICI-iE and identify factors that discriminate it from anti-leucine-rich glioma-inactivated (anti-LGI)-1 encephalitis and herpes simplex virus (HSV)-1 encephalitis – two alternative causes of encephalitis – to increase the awareness of ICI-iE and improve its diagnosis and management.
To that end, we retrospectively collected 30 cases of ICI-iE that were reported to the Side Effect Registry Immuno-Oncology (SERIO) and 46 cases of anti-LGI1 encephalitis or herpes simplex virus (HSV)-1 encephalitis that presented to a large German neurological referral center (Charité Universitätsmedizin Berlin) between January 2015 and September 2021. Signs and symptoms, imaging and electroencephalogram features, laboratory findings and outcome measures were assessed using standardized case report forms as well as patients’ medical records and compared between the groups.
The data reported here represents the largest primary cohort of patients with ICI-iE to date and the first comparison with other types of encephalitis. As all three disorders – ICI-iE, HSV-1 encephalitis and anti-LGI1 encephalitis – are rare neurological entities, this dataset can be used as a reference in future clinical studies on ICI-induced neurotoxicity, neurological autoimmune disorders, and central nervous system infections.
Purpose of review This review highlights recent knowledge on the diagnosis and treatment of immune checkpoint inhibitor-induced neurological side effects (irNAE) focussing on the neuromuscular ...system. Recent findings irNAEs mainly resemble sporadic neuromuscular autoimmune diseases and paraneoplastic neurological syndromes. However, neurological symptoms may be unspecific (muscle weakness, fatigue) in the oncological setting and carry the risk of misdiagnosis and delayed therapeutic intervention. The role of disease-specific neuromuscular autoantibodies in the diagnosis is controversial as preexisting autoantibodies may otherwise be present before immune checkpoint inhibitor (ICI) treatment without clinical symptoms and may not develop in case of irNAE manifestation. A new necrotising form of myositis (irMyositis) has been described presenting with facial weakness and ptosis mimicking myasthenia gravis. It comes along with a high rate of severe myocarditis accounting for a triad overlap syndrome (myasthenia/myositis/myocarditis). The role of modern biologicals in the treatment of irNAEs has to be determined. Summary irNAEs are rare but carry the risk of permanent morbidity and mortality. Early suspicion and diagnosis are key to prevent neurological sequelae. Beyond interruption of ICI administration, treatment corresponds to sporadic autoimmune diseases. The myasthenia/myositis/myocarditis overlap syndrome deserves special attention as it carries the highest risk of mortality. The role of neurotoxic pretreatment regimens, preexisting subclinical neurological autoimmune diseases and the risk of ICI-re-challenge after irNAEs has to be further investigated.
Palliative Care in der Neurologie Hertler, Caroline; Hundsberger, Thomas
Praxis (Bern. 1994),
11/2021, Letnik:
110, Številka:
15
Journal Article
Recenzirano
Zusammenfassung. In der Neurologie als Disziplin finden sich klare Überschneidungen mit der Palliative Care. Dennoch findet eine frühe Integration von palliativer Versorgung begleitend zur ...neurologischen Behandlung eher selten statt, und weiterhin bestehen Missverständnisse in Bezug auf den Zeitpunkt des Einbezugs von Palliative Care und deren Rolle jenseits der oft verwechselten reinen «End-of-Life Care» und Hospizpflege. Ein weiterer Ausbau und die Nutzung der Synergien sollte in den kommenden Jahren integraler Bestandteil beider Disziplinen werden und eine entsprechende Schulung insbesondere junger ärztlicher Kolleginnen und Kollegen im Fokus der Ausbildung stehen.
We determined the nucleotide sequence 3.8 kb upstream and 5.2 kb downstream of the toxin genes A and B of
Clostridium difficile. Nine ORFs were discovered. Based on PCR-directed approaches, two were ...attributed to the pathogenicity locus (PaLoc). The other seven were found in every
C. difficile isolate obtained from the human gastrointestinal tract, respectless of their toxinogenicity. The ORFs
cdul and
cdu2/2′ upstream of the PaLoc displayed similarity to repressors of Gram-positive bacteria (
cdul), and to an Na
+/H
+ antiporter described for
Enterococcus hirae (cdu2/2'). Downstream of the locus a putative ABC transporter (
cdd2–4) was identified. With a set of three paired primers used in polymerase chain reactions we succeeded in delineating the PaLoc. Sequencing of the appropriate stretch of DNA in
C. difficile VPI10463 and four additional toxinogenic strains proved a high conservation of the borders of the PaLoc in all these strains. Our data define the locus as a distinct genetic element. Comparing the sequences of five toxinogenic and five non-toxinogenic strains the integration site of the PaLoc was defined. This showed that a stretch of 115 bp found in non-toxinogenic strains is replaced by the 19-kb locus in toxinogenic strains. Analysis of the boundary sequences showed that the locus is obviously not a mobile genetic element by itself. Instead we propose that it is the independent pathogenic part of a more extended genetic element associated with virulence. The 115 bp of nontoxinogenic strains replaced by the locus in toxinogenic strains carry the putative transcription terminator of the
cdul, a predicted repressor protein. A possible polar effect of the loss of this terminator on transcription of the
TcdABCDE genes is discussed. Such an effect would explain the unidirectional insertion of the PaLoc at a single site of the
C. difficile genome and might give a rationale for the development of the disease which is induced after antibiotical treatment.
There is only limited data on improvements of critical medical care is resulting in a better outcome of comatose survivors of cardiopulmonary resuscitation (CPR) with generalized myoclonus. There is ...also a paucity of data on the temporal dynamics of electroenephalographic (EEG) abnormalities in these patients.
Serial EEG examinations were done in 50 comatose survivors of CPR with generalized myoclonus seen over an 8 years period.
Generalized myoclonus occurred within 24 hours after CPR. It was associated with burst-suppression EEG (n = 42), continuous generalized epileptiform discharges (n = 5), alpha-coma-EEG (n = 52), and low amplitude (10 microV <) recording (n = 1). Except in 3 patients, these EEG-patterns were followed by another of these always nonreactive patterns within one day, mainly alpha-coma-EEG (n = 10) and continuous generalized epileptiform discharges (n = 9). Serial recordings disclosed a variety of EEG-sequences composed of these EEG-patterns, finally leading to isoelectric or flat recordings. Forty-five patients died within 2 weeks, 5 patients survived and remained in a permanent vegetative state.
Generalized myoclonus in comatose survivors of CPR still implies a poor outcome despite advances in critical care medicine. Anticonvulsive drugs are usually ineffective. All postanoxic EEG-patterns are transient and followed by a variety of EEG sequences composed of different EEG patterns, each of which is recognized as an unfavourable sign. Different EEG-patterns in anoxic encephalopathy may reflect different forms of neocortical dysfunction, which occur at different stages of a dynamic process finally leading to severe neuronal loss.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cerebral cavernomas are thin-walled vascular lesions composed of dilated capillary spaces. De novo formation of cavernomas after cerebral radiotherapy has been suspected since 1994. They are mostly ...seen in children after irradiation of brain tumours. Radiation dose and the developing juvenile brain are predisposing factors causing cavernomas. However, the underlying mechanisms are still far from being understood. In adults, radiation-induced cavernomas (RICs) usually occur 10 years after a high cumulative radiation dosage of >30 Gy. Here, we report a 45-year-old man with new-onset focal epileptic seizures caused by a haemorrhagic lesion noted on cerebral computed tomography scan. Brain MRI showed the typical appearance of a ruptured cavernoma. Of note, a cerebral MRI scan 5 years earlier showed no corresponding lesion. The patient had been treated with haematopoietic stem cell transplantation for acute myeloid leukaemia (AML) 16 years before. As part of this procedure, total body irradiation (TBI) consisting of 12 Gy was administered. According to the data from the literature, the typical delay from irradiation and a former normal brain MRI scan, we assume that our patient suffers from a RIC. To our knowledge, this is the first documented adult AML patient with a RIC treated with TBI. We aim to increase awareness among neurologists for the association of cranial irradiation or TBI and de novo cavernomas in patients suffering from malignant diseases.
Purpose of Review
Immune checkpoint inhibitors represent a major step forward in the field of oncologic immunotherapy these last years and have significantly increased survival of cancer patients in ...an ever-growing number of indications. These agents block specific immune checkpoint molecules (programmed cell death protein 1 and its ligand as well as cytotoxic T-lymphocyte-associated antigen 4) that normally downregulate the immune response. These new agents show a specific range of adverse effects induced by abnormal immunologic activation.
Recent Findings
Many different neurologic adverse events have been described, including encephalitis, myelopathy, aseptic meningitis, meningoradiculitis, Guillain-Barré-like syndrome, peripheral neuropathy (including mononeuropathy, mononeuritis multiplex, and polyneuropathy) as well as myasthenic syndrome.
Summary
Immune checkpoint inhibitors have shown promising results in cancer but can possibly induce autoimmune disorders. Although rare, neurological adverse events require prompt recognition and treatment to avoid substantial morbidity.
Radiotherapy is widely used for brain tumors but can cause radiation necrosis (RN). Laser interstitial thermal therapy (LITT) is a relatively new therapeutic modality for RN and its impact on patient ...outcome is still not well understood. Based on a systematic literature search (n=33), the authors discuss the available evidence. Most studies found a positive safety/efficacy profile, as LITT may help to lengthen survival, prevent progression, taper steroids, and improve neurological symptoms while remaining safe. Prospective studies on this subject are needed and may result in LITT becoming an essential therapeutic option for the treatment of RN.
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