Epidemiological evidence suggests that the incidence of ischaemic stroke in young adults (18-50 years) has increased substantially. These patients have a long life expectancy after stroke, and the costs of long-term care pose huge challenges to health-care systems. Although the current recommendations for treatment of young and old (>50 years) patients with stroke are similar, the optimal management of young adult patients with stroke is unknown. They are usually not included in trials, and specific subanalyses limited to young adult patients with stroke are usually not done, owing to lower incidence of stroke and lower prevalence of vascular risk factors in young adults. Progress has been made in identifying patients with a considerable risk of stroke occurrence, such as those with patent foramen ovale. Future prevention studies might result in a decrease in the incidence of stroke and its sequelae in young adults. The development of guidelines specifically devoted to the management of stroke in young adults will be an important step in achieving this aim.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(18)30233-3.pdf

Epidemiology, aetiology, and management of ischaemic stroke in young adults

Neuromuscular adverse events following cancer treatment with anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are relatively rare, yet potentially fatal. We performed a systematic review to characterize the clinical presentation, diagnostic workup, and management of neuromuscular disorders (NMDs) in patients treated with nivolumab or pembrolizumab monotherapy or concurrent with other immunologic agents, such as ipilimumab. Sixty-one publications on 85 patients (mean age 66.9 years [range 34–86]; male/female 2.6:1; 59% metastatic melanoma) were identified from selected indexing databases until June 2018. Forty-eight patients had received nivolumab and 39 pembrolizumab. The mean number of PD-1 inhibitor treatment cycles prior to onset of symptoms was 3.6 (range 1–28). Symptoms included oculomotor (47%), respiratory (43%), bulbar (35%), and proximal weakness (35%), as well as muscle pain (28%). Diagnoses were categorized as myasthenia gravis (27%), neuropathy (23%), myopathy (34%), or a combination of these (16%). After a critical review of the data, however, evidence did not support the stated NMD diagnosis in 13% of cases, while up to 25% of patients had signs of additional NMDs. Cardiac complications occurred in more than 30% of patients diagnosed with myasthenia gravis or myositis. Mortality was high in these patients, despite adequate treatment strategies including corticosteroid, IV immunoglobulins, and plasma exchange. The clinical presentation of NMDs associated with PD-1 inhibitors is often atypical, with considerable overlap between myasthenia gravis and myopathy, and cardiac/respiratory complications are common.

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Neuromuscular adverse events associated with anti-PD-1 monoclonal antibodies: Systematic review.

Immune checkpoint inhibitor (ICI) therapy has revolutionized the management of various cancers with previously poor prognosis. Despite its great efficacy, the therapy is associated with a wide spectrum of immune-related adverse events (irAE) including neurological symptoms which can affect all parts of the central and peripheral nervous system. Even though these events are rare, they are of high relevance as the rate of residual symptoms or even fatal outcomes is remarkable. To provide a detailed overview of neurological adverse events associated with immune checkpoint-inhibitor therapy we conducted a literature search. While focusing on ipilimumab, nivolumab, and pembrolizumab therapy, all available case reports as well as larger case series and clinical trials have been considered. Eighty-two case reports about checkpoint-inhibitor therapy induced symptoms of the peripheral nervous system have been published, while only 43 case reports addressed central nervous system abnormalities. The frequency of immune checkpoint-inhibitor therapy inducing neurological adverse events is about 1% in larger studies. Especially neuromuscular adverse events exhibit distinct clinical and diagnostic characteristics. Additionally, several affected patients presented with overlap-syndromes, which means that symptoms and diagnostic findings indicating myositis, myasthenia gravis, and neuropathy were present in one individual patient at the same time. Thus, neurological and particularly neuromuscular adverse events of immune checkpoint-inhibitor therapy may constitute a new disease entity.

Neurological Immune Related Adverse Events Associated with Nivolumab, Ipilimumab, and Pembrolizumab Therapy—Review of the Literature and Future Outlook

In recent years, immune checkpoint inhibitors have been increasingly used in patients with metastatic cancers with favorable oncological outcomes; however, there have also been increasing number of cancer survivors who have developed immune-related adverse events. Little is known about PD-1 inhibitor-associated neuromuscular complications. Neuromuscular disorders are the most common neurological complication reported in PD-1 inhibitor-treated patients. Myasthenia gravis, immune-mediated myopathies, and Guillain-Barre syndrome are among commonly reported immune-related neuromuscular complications. HyperCKemia occurs frequently in patients with PD-1 inhibitor-associated myasthenia gravis, indicating coexisting myopathies or myocarditis. Oculobulbar weakness is a unique and common presentation of PD-1 inhibitor-associated immune-mediated myopathies with or without concomitant myasthenia gravis. High-dose steroid monotherapy may be associated with clinical deterioration in some patients with PD-1 inhibitor-associated myasthenia gravis, immune-mediated myopathies, or Guillain-Barre syndrome. PD-1 inhibitor-associated neuromuscular complications have some characteristic features compared to their idiopathic counterparts. Although steroid monotherapy is commonly used in non-neuromuscular autoimmune disorders triggered by anti-PD-1 therapy, this may lead to unfavorable outcomes in some patients with PD-1 inhibitor-associated neuromuscular complications.

Neuromuscular Complications of Programmed Cell Death-1 (PD-1) Inhibitors.

The "diabetic foot attack" is one of the most devastating presentations of diabetic foot disease, typically presenting as an acutely inflamed foot with rapidly progressive skin and tissue necrosis, at times associated with significant systemic symptoms Without intervention, it may escalate over hours to limb-threatening proportions and poses a high amputation risk There are only best practice approaches but no international protocols to guide management Immediate recognition of a typical infected diabetic foot attack, predominated by severe infection, with prompt surgical intervention to debride all infected tissue alongside broad-spectrum antibiotic therapy is vital to ensure both limb and patient survival Postoperative access to multidisciplinary and advanced wound care therapies is also necessary More subtle forms exist: these include the ischemic diabetic foot attack and, possibly, in a contemporary categorization, acute Charcot neuroarthropathy To emphasize the importance of timely action especially in the infected and ischemic diabetic foot attack, we revisit the concept of "time is tissue" and draw parallels with advances in acute myocardial infarction and stroke care At the moment, international protocols to guide management of severe diabetic foot presentations do not specifically use the term However, we believe that it may help increase awareness of the urgent actions required in some situations

The Diabetic Foot Attack: "'Tis Too Late to Retreat!"

The Intercollegiate Stroke Working Party (ICSWP) published the 5th edition of the National clinical guideline for stroke in October 2016.[1][1] It provides the most up to date and comprehensive overview of the management of stroke available, covering the whole of the pathway from acute care to

https://www.rcpjournals.org/content/clinmedicine/17/2/154.full.pdf

The latest national clinical guideline for stroke

HH. Phenotypic variability of a distinct deletion in McLeod syndrome. Mov Disord 2007;22:1358–1361. 7. Dotti MT, Battisti C, Malandrini A, Federico A, Rubio JP, Circiarello G, et al. McLeod syndrome and neuroacanthocytosis with a novel mutation in the XK gene. Mov Disord 2000;15:1282–1284. 8. Witting N, Andersen LK, Vissing J. Axial myopathy: an overlooked feature of muscle diseases. Brain 2016;139(Pt 1):13–22. 9. Diaz-Manera J, Llauger J, Gallardo E, Illa I. Muscle MRI in muscular dystrophies. Acta Myol 2015;34:95–108. 10. Barnett MH, Yang F, Iland H, Pollard JD. Unusual muscle pathology in McLeod syndrome. J Neurol Neurosurg Psychiatry 2000;69:655– 657.

Gavin R Young

Papers

The latest national clinical guideline for stroke

Guillain-Barré-like syndrome during pembrolizumab treatment.