The spectrum of Epstein-Barr virus infections of the central nervous system after organ transplantation.

BACKGROUND: Epstein-Barr virus (EBV)-related neurologic complications have a diverse presentation in transplant recipients, creating diagnostic and therapeutic challenges for clinicians. In this case series, we report unique manifestations of EBV related neurologic complications following solid organ transplant and highlight pitfalls in management. CASE PRESENTATIONS: A retrospective search of the electronic medical record of all patients from January 2015 to December 2020 who underwent solid organ transplantation and had central nervous system complications as determined by ICD-10 codes were included. Three patients with unique manifestation of EBV-related neurologic complications after liver transplantation were identified. The first was a 52-year-old man with a live-donor liver transplant 11 years prior for Budd-Chiari syndrome presented with several weeks of headache and several lesions on brain MRI; he was diagnosed with primary central nervous system post-transplant lymphoproliferative disorder. The second patient was a 63-year-old man with a deceased-donor liver transplant 16 years prior for alpha-1-antitrypsin deficiency and was found to have a stroke; he was diagnosed with EBV encephalitis. The final patient was a 75-year-old woman with a deceased-donor liver transplant six years prior for primary biliary cirrhosis who presented with four months of gait instability; she was diagnosed with EBV myelitis. A review of the literature was performed to supplement description of the different diseases. CONCLUSIONS: EBV-related central nervous infection in post-transplant patients can manifest in a variety of neurologic syndromes, which can be challenging to diagnose. Careful correlation of clinical, pathologic, and radiologic findings and a high index of suspicion are crucial in identification and appropriate management.

Movement Disorder Emergencies.

Acute presentation of new movement disorders and acute decompensation of chronic movement disorders are uncommon but potentially life-threatening. Inadvertent or purposeful overdose of many psychiatric medications can result in acute life-threatening movement disorders including serotonin syndrome, neuroleptic malignant syndrome, and malignant catatonia. Early withdrawal of potentiating medications, treatment with benzodiazepines and other diagnosis-specific drugs, and providing appropriate supportive care including airway and breathing management, hemodynamic stabilization, fluid resuscitation, and renal support including possible hemodialysis are the mainstays of acute management. Many of these conditions require admission to the neurologic intensive care unit.

Toxin-Induced Subacute Encephalopathy.

Subacute toxic encephalopathies are challenging to identify due to their often insidious tempo of evolution, nonspecific manifestations, relative infrequency as individual entities, and frequent lack of specific diagnostic testing. Yet they are crucial to recognize-in aggregate, subacute toxic encephalopathies are a common problem that can lead to severe, irreversible harm if not diagnosed and treated efficiently. This article reviews the clinically relevant aspects of some of the more important subacute toxic encephalopathy syndromes caused by inorganic toxins, carbon monoxide, antibiotics, antineoplastic agents, and psychiatric medications.

Severe cerebral involvement in adult-onset hemophagocytic lymphohistiocytosis.

The diagnosis of hemophagocytic lymphohistiocytosis (HLH) with cerebral involvement is challenging given the rarity of HLH and its resemblance to the much more common severe sepsis. Timely diagnosis and treatment may be lifesaving. We report two cases demonstrating different and rare forms of severe brain involvement in adult patients with HLH: acute necrotizing encephalopathy, and diffuse hemorrhagic disease due to disseminated intravascular coagulation. Severe HLH with brain involvement in adults is rare. HLH with cerebral involvement should be considered in patients presenting with severe systemic inflammatory response syndrome (SIRS) but negative cultures and unusual or unexpectedly severe clinical and/or radiologic signs of cerebral dysfunction. Similar brain injury may occur in patients with cytokine storm syndrome due to COVID-19. BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) presents with fevers, rash, organomegaly, cytopenia, and increased triglycerides and ferritin (Ramos-Casals et al., 2014) [1]. Neurologic abnormalities are reported in about one-third of patients (Cai et al., 2017), including a few cases of acute necrotizing encephalopathy (ANE) (Xiujuan et al., 2015). Coagulation abnormalities are frequent in HLH patients (Valade et al., 2015). OBJECTIVE: To raise awareness about the importance of early diagnosis and treatment of HLH with neurological involvement to prevent serious complications and demise.

Recent Advances in the Acute Management of Intracerebral Hemorrhage.

Primary intracerebral hemorrhage (ICH) is a common, devastating disease that lacks an effective specific treatment. Mortality is high, functional outcomes are poor, and these have not substantially changed for decades. There is, therefore, considerable opportunity for advancement in the management of ICH. In recent years, a significant amount of research has begun to address this gap. This article is aimed at updating neurologists on the most clinically relevant contemporary research.

Recent Advances in the Acute Management of Intracerebral Hemorrhage.

Primary intracerebral hemorrhage (ICH) is a common, devastating disease that lacks an effective specific treatment. Mortality is high, functional outcomes are poor, and these have not substantially changed for decades. There is, therefore, considerable opportunity for advancement in the management of ICH. In recent years, a significant amount of research has begun to address this gap. This article is aimed at updating neurologists on the most clinically relevant contemporary research.

ICU management of aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) has very high morbidity and mortality rates. Optimal intensive care unit (ICU) management requires knowledge of the potential complications that occur in this patient population. METHODS: Review of the ICU management of SAH. Level of evidence for specific recommendations is provided. RESULTS: Grading scales utilizing clinical factors and brain imaging studies can help in determining prognosis and are reviewed. Misdiagnosis of SAH is fairly common so the clinical symptoms and signs of SAH are summarized. The ICU management of SAH is discussed beginning with a focus on avoiding aneurysm re-rupture and securing the aneurysm, followed by a review of the neurologic and medical complications that may occur after the aneurysm is secured. Detailed treatment strategies and areas of current and future research are reviewed. CONCLUSIONS: The ICU management of the patient with SAH can be particularly challenging and requires an awareness of all potential neurologic and medical complications and their urgent treatments.

Treatment of unruptured intracranial aneurysms: surgery, coiling, or nothing?

The decision of whether and how to treat an unruptured intracranial aneurysm (UIA) is complex. The goal in caring for patients with UIAs is to maximize their duration of high-quality life by optimally balancing the risks of aneurysm rupture--the "natural history" of the aneurysm--with those of treatment-related adverse outcomes. In this article, we review the literature concerning the natural history of UIAs and summarize the procedure-associated morbidity and mortality and efficacy of surgical clipping and endovascular coiling. Using this information, we make recommendations regarding the optimal management of patients with UIAs.

Evaluation of brain biopsy in the diagnosis of severe neurologic disease of unknown etiology.

OBJECTIVE: To determine the value of non-stereotactic brain biopsies in patients with severe neurologic disease of unknown etiology and indeterminate brain imaging. METHODS: We reviewed 42 consecutive patients who underwent non-stereotactic brain biopsy at a single institution for evaluation of severe neurologic disease of unknown etiology. All patients had indeterminate or normal imaging results. Seventy-nine percent had been symptomatic for less than a year. Exclusion criteria were immunocompromise or a preoperative diagnosis of intracranial neoplasm. Diagnostic yield and surgical complication rate were calculated. We performed exploratory univariate analysis aimed at identifying clinical features possibly predictive of diagnostic biopsies. RESULTS: A histologic diagnosis was achieved in 12 of 42 biopsies (29%). Three patients experienced minor transient complications from the procedure (7%). There were no permanent deficits or deaths. Treatment was altered based on biopsy result in five patients (12%). A more precise prognosis was obtained in eight patients (19%). In total, 11 different patients (26%) benefited from biopsy. Exploratory univariate analysis showed a possible inverse relationship between age and the likelihood of a diagnostic biopsy (OR=0.929; 95% CI=0.864-0.998). CONCLUSIONS: Our data suggest that the value of non-stereotactic brain biopsy is sufficiently high and the morbidity sufficiently low to justify its use in carefully selected patients with severe neurologic disease that remains undiagnosed despite thorough less invasive evaluation.

An unusual cause of fixed dilated pupils after cardiac surgery.

BACKGROUND: The presence of fixed, dilated pupils after cardiac surgery is an ominous sign, typically indicating severe diffuse hypoxic-ischemic brain injury. Rarely, however, this finding can be seen as a result of focal midbrain ischemia. It is important to differentiate between these syndromes, as the latter might be amenable to acute stroke treatments, and because they affect consciousness very differently. CASE: A 46-year-old man with diffuse atherosclerosis underwent coronary artery bypass grafting and closure of an incidentally discovered patent foramen ovale. He underwent neurologic evaluation on post-operative day 6 because he was not speaking and appeared to have a new right hemiparesis. Eye movements, pupillary, and lid function were all normal at this time. MRI showed multiple posterior circulation infarcts, involving both cerebral peduncles. On post-operative day 12, he became unresponsive, quadriplegic, and had bilaterally fixed, dilated pupils. CT showed low attenuation in nearly the entirety of both cerebral peduncles. DISCUSSION: Midbrain infarction is rare. Bilateral midbrain infarction is even rarer and typically presents as locked-in syndrome with preservation of pupillary function and at least vertical eye movements. In our review of the literature, we found only three other cases of midbrain infarction associated with bilateral mydriasis. As in our case, these characteristically involved the anteromedial midbrain bilaterally. CONCLUSIONS: Fixed, dilated pupils after cardiac surgery can rarely be caused by bilateral anteromedial midbrain infarctions. It is important to differentiate this from the much more common diffuse hypoxic-ischemic injury.