Cortical and Subcortical Dysmetabolism Are Dynamic Markers of Clinical Disability and Course in Anti-LGI1 Encephalitis.

BACKGROUND AND OBJECTIVES: This [18F]fluorodeoxyglucose (FDG) PET study evaluates the accuracy of semiquantitative measurement of putaminal hypermetabolism in identifying anti-leucine-rich, glioma-inactivated-1 (LGI1) protein autoimmune encephalitis (AE). In addition, the extent of brain dysmetabolism, their association with clinical outcomes, and longitudinal metabolic changes after immunotherapy in LGI1-AE are examined. METHODS: FDG-PET scans from 49 age-matched and sex-matched subjects (13 in LGI1-AE group, 15 in non-LGI1-AE group, 11 with Alzheimer disease [AD], and 10 negative controls [NCs]) and follow-up scans from 8 patients with LGI1 AE on a median 6 months after immunotherapy were analyzed. Putaminal standardized uptake value ratios (SUVRs) normalized to global brain (P-SUVRg), thalamus (P/Th), and midbrain (P/Mi) were evaluated for diagnostic accuracy. SUVRg was applied for all other analyses. RESULTS: P-SUVRg, P/Th, and P/Mi were higher in LGI1-AE group than in non-LGI1-AE group, AD group, and NCs (all p < 0.05). P/Mi and P-SUVRg differentiated LGI1-AE group robustly from other groups (areas under the curve 0.84-0.99). Mediotemporal lobe (MTL) SUVRg was increased in both LGI1-AE and non-LGI1-AE groups when compared with NCs (both p < 0.05). SUVRg was decreased in several frontoparietal regions and increased in pallidum, caudate, pons, olfactory, and inferior occipital gyrus in LGI1-AE group when compared with that in NCs (all p < 0.05). In LGI1-AE group, both MTL and putaminal hypermetabolism were reduced after immunotherapy. Normalization of regional cortical dysmetabolism associated with clinical improvement at the 6- and 20-month follow-up. DISCUSSION: Semiquantitative measurement of putaminal hypermetabolism with FDG-PET may be used to distinguish LGI1-AE from other pathologies. Metabolic abnormalities in LGI1-AE extend beyond putamen and MTL into other subcortical and cortical regions. FDG-PET may be used in evaluating disease evolution in LGI1-AE. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that semiquantitative measures of putaminal metabolism on PET can differentiate patients with LGI1-AE from patients without LGI1-AE, patients with AD, or NCs.

Neurologic Complications of Surgery and Anesthesia.

Surgery and anesthesia carry risks of ischemic, hemorrhagic, hypoxic, and metabolic complications, all of which can result in neurologic symptoms and deficits. Patients with underlying cardiovascular and cerebrovascular risk factors are particularly vulnerable. In this article the authors review the neurologic complications of surgery and anesthesia, with a focus on the role of the neurologic consultant in preoperative evaluation and risk stratification and diagnosis and management of postoperative complications.

Influence of Autoimmune Antibody Testing on the Use of Immunotherapy on an Inpatient Neurology Service.

OBJECTIVE: To determine the frequency of autoimmune antibody testing in an inpatient neurology setting and its influence on immunotherapy use on an inpatient neurology service. METHODS: A retrospective descriptive cohort study of patients admitted to the neurology inpatient service at a large tertiary academic medical center who had autoimmune and/or paraneoplastic antibody testing performed between 10/1/2017 and 10/1/2018. Characteristics of patients' initial clinical presentation, antibody testing results, test timing in relation to initiating immunotherapy, and final diagnosis using consensus criteria were extracted and analyzed. Case reports of patients with positive antibody panels are presented. RESULTS: Of 1,604 patients, 50 patients (3.1%) had an antibody panel sent. Tests resulted after an average of 17 days (range 7-27). The most common clinical presenting symptom in those with a panel sent was encephalopathy. There were 5 (10%) positive serum panels and no positive CSF panels. Only one of these 5 patients had autoimmune encephalitis and was treated with immunotherapy. Of those with negative serum and CSF panels, 15 were treated acutely with empiric immunotherapy and the remainder with supportive care. Of those treated with immunotherapy, 14/15 (93%) were treated before the panel tests resulted. Four patients who had negative panels but were empirically treated met consensus criteria for an autoimmune-mediated neurologic process. CONCLUSION: Our study suggests that the results of antibody testing did not influence inpatient neurologists' decision to treat with immunotherapy as most treatments began prior to final results being available.

Neuroradiologic Pearls for Neuro-oncology.

PURPOSE OF REVIEW: This article reviews key principles in the identification of tumors of the central nervous system (CNS) using standard and advanced imaging modalities. This article highlights the pitfalls and pearls of the imaging evaluation of patients with cancer at time of diagnosis and during cancer therapy and discusses the challenges of the imaging evaluation of treatment-related toxicities. RECENT FINDINGS: Treatment of CNS tumors with surgery, chemotherapy, or radiation alters the imaging appearance of the tumor and can be associated with a variety of treatment-related toxicities. The clinician must be familiar with how to assess response to treatment and how to differentiate tumor progression from treatment-related effects. SUMMARY: Management and follow-up of neuro-oncology patients is optimized by a comprehensive radiologic approach to CNS tumors and recognition of the challenges in the assessment of response to treatments.

Yield of Brain MRI in Clinically Diagnosed Epilepsy in the Kingdom of Bhutan: A Prospective Study.

BACKGROUND: People with epilepsy (PWE) in low- and middle-income countries may not access the health resources that are considered optimal for epilepsy diagnosis. The diagnostic yield of magnetic resonance imaging (MRI) has not been well studied in these settings. OBJECTIVES: To report the diagnostic yield of brain MRI and identify clinical associations of abnormal MRI findings among PWE in a neurocysticercosis-endemic, resource-limited setting and to identify the proportion and putative structural brain causes of drug-resistant epilepsy. METHODS: PWE were prospectively enrolled at the Jigme Dorji Wangchuck National Referral Hospital in Bhutan (2014-2015). Each participant completed clinical questionnaires and a 1.5-Tesla brain MRI. Each MRI was reviewed by at least 1 radiologist and neurologist in Bhutan and the United States. A working definition of drug-resistant epilepsy for resource-limited settings was given as (a) seizures for >1 year, (b) at least 1 seizure in the prior year, and (c) presently taking 2 or more antiepileptic drugs (AEDs). Logistic regression models were constructed to test the cross-sectional association of an abnormal brain MRI with clinical variables. FINDINGS: A total of 217 participants (125 [57%] female; 54 [25%] < 18 years old; 199 [92%] taking AEDs; 154 [71%] with a seizure in the prior year) were enrolled. There was a high prevalence of abnormal brain MRIs (176/217, 81%). Mesial temporal sclerosis was the most common finding (n = 115, 53%, including 24 children), exceeding the number of PWE with neurocysticercosis (n = 26, 12%, including 1 child) and congenital/perinatal abnormalities (n = 29, 14%, including 14 children). The number of AEDs (odds ratio = .59, P = .03) and duration of epilepsy (odds ratio = 1.11, P = .02) were significantly associated with an abnormal MRI. Seizure in the prior month was associated with the presence of mesial temporal sclerosis (odds ratio = .47, P = .01). A total of 25 (12%) participants met our definition of drug-resistant epilepsy, with mesial temporal sclerosis (n = 10), congenital malformations (n = 5), and neurocysticercosis (n = 4) being the more common findings. CONCLUSIONS: The prevalence of abnormalities on brain MRI for PWE in resource-limited settings is high as a result of a diffuse range of etiologies, most commonly mesial temporal sclerosis. Drug-resistant epilepsy accounted for 12% of the referral population in a conservative estimation.

Neurocysticercosis in Bhutan: a cross-sectional study in people with epilepsy.

BACKGROUND: We sought to provide an assessment of the burden of neurocysticercosis among people with epilepsy (PWE) in Bhutan and evaluate the yield of various tests for Taenia solium. METHODS: PWE were enrolled at the National Referral Hospital in Thimphu (2014-2015). Serum was tested for anti-Taenia solium IgG using ELISA (Ab-ELISA), enzyme-linked immunoelectrotransfer blot (EITB), and parasite antigen. Results were compared to brain MRI. Participants were categorized as definite neurocysticercosis (MRI and EITB positive), probable neurocysticercosis (MRI or EITB positive), or without neurocysticercosis. Logistic regression models were constructed to explore clinicodemographic associations. RESULTS: There were 12/205 (6%, 95% CI 2%, 9%) definite and 40/205 (20%, 95% CI 14%, 25%) probable neurocysticercosis cases. 25/205 (12%) with positive EITB did not have neurocysticercosis on MRI, and 15/205 (7%) participants with positive MRI had negative EITB. Participants with neurocysticercosis-suggestive lesions on MRI had an average of 1.2 cysts (parenchymal 26/27; nodular/calcified stage 21/27). In a multivariable analysis, present age (OR 1.05, 95% CI 1.01,1.09, p=0.025) was positively associated with (combined probable or definite) neurocysticercosis while mesial temporal sclerosis on MRI (OR 0.294, 95% CI 0.144, 0.598, p=0.001) was negatively associated. CONCLUSIONS: Neurocysticercosis was associated with 6-25% of epilepsy in a Bhutanese cohort. Combining EITB and MRI would aid the diagnosis of neurocysticercosis among PWE since no test identified all cases.

Imaging of Brain Tumors.

PURPOSE OF REVIEW: Neuroimaging is an essential tool for the diagnosis and management of brain tumors. RECENT FINDINGS: Advances in neuroimaging have allowed for noninvasive visualization of tumors and have changed how brain tumors are diagnosed and treated. Presurgical planning with the use of functional MRI (fMRI) and diffusion tensor MRI helps to preserve eloquent regions of the brain and fiber tracts, thereby decreasing patients' postsurgical morbidity. With the use of susceptibility-weighted imaging (SWI) filtered phase images, diffusion-weighted studies, and perfusion imaging techniques, deciphering posttreatment effects versus tumor progression can be facilitated. SUMMARY: With recent advancements and novel approaches, various MRI techniques can be used to help diagnose and assist in presurgical planning and posttreatment management of brain tumors.

Imaging of noninfectious inflammatory disorders of the spinal cord.

Myelitis, or inflammation of the spinal cord, produces a characteristic clinical syndrome. Among the many causes of myelitis are the prototypical demyelinating diseases multiple sclerosis and neuromyelitis optica, each of which has distinct clinical, pathologic, and radiographic features. Less distinct are the myelitides associated with systemic autoimmune conditions like sarcoidosis and lupus. Nondemyelinating conditions such as arachnoiditis, dural arteriovenous fistula, and tumor infiltration may also produce inflammation of the spinal cord. The objective of this review is to aid the clinician in the radiographic diagnosis of noninfectious inflammatory diseases of the spinal cord.

A practical approach to spine imaging.

PURPOSE OF REVIEW: The spine is a complex mechanical structure that surrounds and protects the spinal cord and nerve roots. It is capable of multidirectional movement and is susceptible to a large variety of pathologies that can affect spinal cord and nerve root function. Detection of spinal pathology is aided by a familiarity with normal spinal anatomy and its appearance on CT and MRI studies. Imaging of the spine is performed frequently, and a systematic approach toward image interpretation can prevent overlooking or incompletely assessing a lesion. RECENT FINDINGS: CT and MRI of the spine provide detailed views of normal and abnormal structures and allow for differentiation of vascular, inflammatory, infectious, neoplastic, traumatic, and degenerative etiologies of spine disease. SUMMARY: This article provides a strategy for interpreting CT and MRI studies of the spine and can be used as a primer for the other articles that follow in this issue of CONTINUUM, in which specific etiologies of spine and spinal cord pathology are considered in detail.

Reversible palinacousis from intracranial metastases.

Palinacousis is an auditory illusion consisting of perseveration or echoing of an external auditory stimulus after it has ceased. This rare clinical symptom has been reported in ictal (seizure), postictal, and nonictal states, and causative lesions have been most consistently found in or near the temporal lobes. It is distinct from the auditory hallucinations seen in psychiatric illness. We report the case of a 61-year-old man who experienced several days of palinacousis while undergoing treatment for newly diagnosed metastatic lung adenocarcinoma. Palinacousis was presumed to be triggered by intracranial metastases near the auditory cortex. An electroencephalogram showed bilateral theta slowing over the left greater than right temporal lobes without epileptiform activity. Palinacousis remitted with corticosteroid and whole brain radiation therapy.

Imaging of cancer therapy-induced central nervous system toxicity.

Cancer therapy, including radiation and chemotherapy, can be associated with harmful effects to the central nervous system. Recognition of classical neurotoxic syndromes is critical to appropriately guide and optimize patient management. As a result of cancer therapy-induced toxicity, patients may present with acute, subacute, and chronic neurologic symptoms that can be misinterpreted as tumor recurrence, infection, or paraneoplastic syndromes. In this review the advantages and limitations of various neuroimaging modalities such as computed tomography, magnetic resonance imaging, and positron emission tomography, frequently used in patients with cancer who present with diverse neurotoxic syndromes, are highlighted.

Diffusion tensor imaging in brainstem tuberculoma.

Integrity of descending white matter tracts can be evaluated by diffusion tensor imaging. In rim-enhancing intraparenchymal lesions, this technique can assist in the differentiation of demyelinating disease from tumor or abscess. Diffusion tensor imaging characteristics of tuberculoma have not been previously reported to our knowledge. A patient with headaches, dizziness, and mild left-sided weakness underwent MRI with diffusion tensor imaging. A large, rim-enhancing lesion within the pons was discovered, which subsequently was diagnosed as tuberculoma. Tractography maps prepared from diffusion tensor imaging data revealed predominantly displaced descending fiber tracts in the region of the rim-enhancing lesion. A few tracts adjacent to the lesion appeared truncated, and this abnormal finding correlated to the patient's clinical deficit. The tractography characteristics of diffusion tensor imaging in this patient potentially are distinct from those seen with demyelinating lesions, which may show more extensive tract truncation. Together with the consonance of exam findings and tract truncation seen in this patient, tractography may prove useful in the diagnosis of suspected tuberculoma.

HIV-2 encephalitis: case report and literature review.

We report the case of a 59-year-old man who moved from Cape Verde to Massachusetts at the age of 29. He had multiple sexual contacts with female partners in Cape Verde and with West African women in Massachusetts, as well as multiple past indeterminate HIV-1 antibody tests. He presented to our facility with 2-3 months of inappropriate behaviors, memory impairment, weight loss, and night sweats, at which time he was found to have an abnormal enhancing lesion of the corpus collosum on brain magnetic resonance imaging (MRI). Laboratory testing revealed a CD4 count of 63 cells/mm(3), positive HIV-2 Western blot, serum HIV-2 RNA polymerase chain reaction (PCR) of 1160 copies per milliliter and cerebrospinal fluid (CSF) HIV-2 RNA PCR of 2730 copies per milliliter. Brain biopsy demonstrated syncytial giant cells centered around small blood vessels and accompanied by microglia, which correlated with prior pathologic descriptions of HIV-2 encephalitis and with well-described findings of HIV-1 encephalitis. Based on genotype resistance assay results, treatment guidelines, and prior studies validating success with lopinavir-ritonavir, he was treated with tenofovir-emtricitabine and lopinavir-ritonavir, which has led to virologic suppression along with steady neurologic and radiologic improvement, although he continues to have deficits.