Saša A. Živković

Neurologic complications after liver transplantation.

Neurologic complications are relatively common after solid organ transplantation and affect 15%-30% of liver transplant recipients. Etiology is often related to immunosuppressant neurotoxicity and opportunistic infections. Most common complications include seizures and encephalopathy, and occurrence of central pontine myelinolysis is relatively specific for liver transplant recipients. Delayed allograft function may precipitate hepatic encephalopathy and neurotoxicity of calcineurin inhibitors typically manifests with tremor, headaches and encephalopathy. Reduction of neurotoxic immunosuppressants or conversion to an alternative medication usually result in clinical improvement. Standard preventive and diagnostic protocols have helped to reduce the prevalence of opportunistic central nervous system (CNS) infections, but viral and fungal CNS infections still affect 1% of liver transplant recipients, and the morbidity and mortality in the affected patients remain fairly high. Critical illness myopathy may also affect up to 7% of liver transplant recipients. Liver insufficiency is also associated with various neurologic disorders which may improve or resolve after successful liver transplantation. Accurate diagnosis and timely intervention are essential to improve outcomes, while advances in clinical management and extended post-transplant survival are increasingly shifting the focus to chronic post-transplant complications which are often encountered in a community hospital and an outpatient setting.

Neuroimaging and Neurologic Complications after Organ Transplantation

Neurologic complications are common after transplantation and affect 30‐60% of transplant recipients. The etiology of most of the posttransplant neurologic disorders is related to the opportunistic infections, both systemic and involving central nervous system (CNS), toxicity of immunosuppressive medications, and the metabolic insult created by the underlying primary disease and the transplant procedure. Neuroimaging studies are one of the key tools in the evaluation and enable early diagnosis of neurologic complications in transplant patients, especially posterior reversible leukoencephalopathy syndrome, central pontine myelinolysis, intracerebral hemorrhage, and fungal and bacterial abscesses. Magnetic resonance imaging (MRI) is the preferred technique, but each of the available neuroimaging techniques offers a unique insight into the pathophysiologic mechanisms underlying neurologic complications of transplantation. The role of neuroimaging in this population includes early detection of calcineurin inhibitor neurotoxicity, opportunistic infections, neoplasia, metabolic disorders, or cerebrovascular diseases. In addition, we can monitor longitudinal progression of disease and treatment response.

Neurologic Manifestations of Transplant Complications

Neurologic complications affect posttransplant recovery of more than 20% of transplant recipients. Etiology is usually related to surgical procedure of transplantation, primary disorders causing failure of transplanted organ, opportunistic infections, and neurotoxicity of immunosuppressive medications. Risk of opportunistic infections and immunosuppressant neurotoxicity is greatest within the first six months, but it persists along with long-term maintenance immunosuppression required to prevent graft rejection. Neurotoxicity may require alteration of immunosuppressive regimen, and prompt therapy of opportunistic infections improves outcomes.

Myasthenia triggered by immune checkpoint inhibitors: New case and literature review

Immune checkpoint molecules are potent regulators of immunologic homeostasis that prevent the development of autoimmunity while maintaining self-tolerance. Inhibitors of immune checkpoint molecules are used as immunotherapy in the treatment of melanoma and different types of refractory cancer, and can trigger various autoimmune complications including myositis and myasthenia gravis. We describe a case of generalized myasthenia gravis induced by pembrolizumab and review 11 other cases. Five patients also had elevated serum CK levels ranging from 1200 to 8729 IU/L, and biopsy showed myositis in one. Severity was highly variable as symptoms normalized spontaneously in one patient, but three others developed myasthenic crisis (including two with fatal outcomes). Steroids have been recommended as a preferred treatment of autoimmune complications of immune-checkpoint inhibitors. Myasthenia gravis should be considered when weakness, diplopia or bulbar symptoms are seen after treatment with immune checkpoint inhibitors, and additional studies are needed to characterize association with hyperCKemia.

The clinical spectrum of neurologic disorders after intestinal and multivisceral transplantation

Živković SA, Eidelman BH, Bond G, Costa G, Abu‐Elmagd KM. The clinical spectrum of neurologic disorders after intestinal and multivisceral transplantation.
Clin Transplant 2009: DOI: 10.1111/j.1399‐0012.2009.01065.x
© 2009 John Wiley & Sons A/S.

Vasculitis as an adverse event following immunization - Systematic literature review.

BACKGROUND Several types of vasculitis have been observed and reported in temporal association with the administration of various vaccines. A systematic review of current evidence is lacking. OBJECTIVE This systematic literature review aimed to assess available evidence and current reporting practice of vasculitides as adverse events following immunization (AEFI). METHODS We reviewed the literature from 1st January 1994 to 30th June 2014. This review comprises randomized controlled trials, observational studies, case series, case reports, reviews and comments regardless of vaccine and target population. RESULTS The initial search resulted in the identification of 6656 articles. Of these, 157 articles were assessed for eligibility and 75 studies were considered for analysis, including 6 retrospective/observational studies, 2 randomized controlled trials, 7 reviews, 11 case series, 46 case reports and 3 comments. Most of the larger, higher quality studies found no causal association between vaccination and subsequent development of vasculitis, including several studies on Kawasaki disease and Henoch-Schönlein purpura (IgA vasculitis). Smaller case series reported a few cases of vasculitis following BCG and vaccines against influenza and hepatitis. Only 24% of the articles reported using a case definition of vasculitis. CONCLUSIONS Existing literature does not allow establishing a causative link between vaccination and vasculitides. Further investigations were strengthened by the use of standardized case definitions and methods for data collection, analysis and presentation to improve data comparability and interpretation of vasculitis cases following immunization.

Approach to vasculitic neuropathies.

Since vasculitic neuropathy is treatable and potentially debilitating, clinicians should develop an approach to neuropathy that increases the likelihood of uncovering existing systemic or nonsystemic vasculitis. The presence of a connective tissue disease, systemic vasculitis, asymmetric or non-length-dependent axonal polyneuropathy, or multiple axonal mononeuropathies should heighten suspicion, but vasculitic neuropathy can also present as a distal symmetric polyneuropathy with or without other organ involvement. Electrodiagnostic testing utilizing extensive nerve conductions may be helpful in identifying features suggestive of vasculitic neuropathy and in selecting an abnormal nerve and muscle for biopsy confirmation. An array of laboratory tests may lead to identification of a systemic disorder that is either characterized by or predisposes to vasculitic neuropathy. The mainstays of treatment are corticosteroids and cyclophosphamide, but other drugs are used in specific conditions. With early diagnosis and careful monitoring of treatment regimens, the prognosis is usually good.

Neurologic complications following lung transplantation.

BACKGROUND Neurologic complications are frequent after solid organ transplantation, but their spectrum in lung transplant recipients has not been characterized. METHODS Retrospective analysis of medical records of 132 consecutive adult lung allograft recipients transplanted at the University of Pittsburgh Medical Center between 2001 and 2003 with a follow-up until December 31, 2005. RESULT Neurologic complications were reported in 68% of lung transplant recipients. Most common complications were impairment of consciousness (25%), neuromuscular complications (21%) and headaches (20%). The presence of neurologic complications did not affect posttransplant survival. Neurologic complications were commonly related to immunosuppressant neurotoxicity (17%) and opportunistic infections (11%). There was a trend for an increased frequency of seizures and headaches in recipients with cystic fibrosis (p>0.05). CONCLUSIONS Neurologic complications are a significant source of morbidity in lung transplant recipients. High prevalence of immunosuppressant toxicity is attributable to higher immunosuppression needs for effective prevention of allograft rejection. Frequent opportunistic infections are associated with complications related to systemic and CNS infections and toxicity of antibiotics. Patients with cystic fibrosis may be at higher risk of neurologic complications, but larger studies are needed to corroborate this finding and fully characterize the spectrum of neurologic complications following lung transplantation.

Treatment of tardive dyskinesia with levetiracetam in a transplant patient

Objective –  To describe successful treatment of tardive dyskinesia with levetiracetam.

Myasthenia gravis and scleroderma: Two cases and a review of the literature

Myasthenia gravis is uncommon in patients with scleroderma, and when diagnosed is usually associated with previous use of d-penicillamine. Clinically, both myasthenia and scleroderma may present with fatigue, weakness and bulbar symptoms, so one of diagnoses may be delayed. We report two new cases and review clinical features of 12 other reported cases of co-existing scleroderma and myasthenia gravis, unrelated to previous d-penicillamine therapy. Co-occurrence of myasthenia and scleroderma was reported almost exclusively (13/14) in women with a mean latency of 7.03 years. Most patients (10/11) had seropositive generalized myasthenia, and there were no cases with exclusively ocular symptoms. Three patients with pre-existing myasthenia were safely treated with d-penicillamine. Myasthenia and scleroderma occur in the context of an underlying autoimmune diathesis, but their co-occurrence could be underreported as the recognition of either disorder may be delayed by overlapping clinical symptoms. Our findings also suggest that d-penicillamine may be cautiously used in selected patients with pre-existing scleroderma and myasthenia, when potential benefits outweigh the risk of possible myasthenia exacerbation.