Acute Disseminated Encephalomyelitis (ADEM) and Increased Intracranial Pressure Associated With Anti-Myelin Oligodendrocyte Glycoprotein Antibodies.

BACKGROUND: Antibodies to the myelin oligodendrocyte glycoprotein (MOG) have been identified in about 40% of children with acute disseminated encephalomyelitis (ADEM). The objective of this report is to describe three individuals with fulminant ADEM complicated by increased intracranial pressure associated with the presence of the anti-MOG antibodies. METHODS: This is a retrospective case series. Informed consent was obtained from the concerned patients or caregivers. RESULTS: High intracranial pressure associated with ADEM in the presence of MOG antibodies can result in cerebral edema, herniation, prolonged hospital stay (average intensive care unit stay: 22 days, average hospital stay: 50.6 days), and long-term disability. CONCLUSION: Increased intracranial pressure complicating MOG antibody-related ADEM is a unique finding in our cases. This can complicate the clinical picture of ADEM and confers high morbidity. Long-term immunosuppression is warranted in selected cases with persistent seropositivity.

Increased intracranial pressure in Guillain-Barré syndrome: A case report.

RATIONALE: Guillain-Barré syndrome (GBS) is an inflammatory autoimmune demyelinating polyneuropathy that affects most of the peripheral nervous system. Papilledema and raised intracranial pressure (ICP) are seen in some patients, and are thought to be associated with elevated cerebrospinal fluid (CSF) protein-though CSF protein levels are normal in some patients, thus the specific mechanisms remain unclear. Interleukin (IL)-17 levels are elevated in the CSF and plasma in GBS patients, and elevated IL-17 in the CSF of patients with idiopathic intracranial hypertension has been reported. Intravenous immunoglobulin (IVIG) exerts therapeutic effects by downregulating IL-17 in GBS patients. PATIENT CONCERNS: Herein we describe a case of a 14-year-old girl who initially presented with relapsing limb weakness. DIAGNOSES: Magnetic resonance imaging revealed an enlarged ventricle, electromyography, and nerve conduction studies were suggestive of polyradiculopathy, and lumbar puncture revealed elevated ICP with normal cells and elevated protein values. INTERVENTIONS: She was treated with IVIG 0.4 g/kg per day for 5 days. OUTCOMES: At a 6-month follow-up there had been no recurrence. LESSONS SUBSECTIONS: In GBS patients who have a relapsing course and develop papilledema with possible immunological disturbance, an accurate early diagnosis in conjunction with the prompt initiation of immunotherapy may improve clinical symptoms and the prognosis.

IgG4-related disease: a rare but treatable cause of refractory intracranial hypertension.

Hypertrophic pachymeningitis secondary to IgG4-related disease is a rare but sometimes devastating cause of intracranial hypertension. It has the potential for an excellent response to corticosteroids or rituximab. We discuss the clinical presentation, imaging, histology (with its difficult distinction from lymphoma), management and follow-up of a case, including relapse and re-treatment following an initial response to rituximab.

Headache in systemic lupus erythematosus: results from a prospective, international inception cohort study.

OBJECTIVE: To examine the frequency and characteristics of headaches and their association with global disease activity and health-related quality of life (HRQOL) in patients with systemic lupus erythematosus (SLE). METHODS: A disease inception cohort was assessed annually for headache (5 types) and 18 other neuropsychiatric (NP) events. Global disease activity scores (SLE Disease Activity Index 2000 [SLEDAI-2K]), damage scores (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and Short Form 36 (SF-36) mental and physical component summary scores were collected. Time to first headache and associations with SF-36 scores were analyzed using Cox proportional hazards and linear regression models with generalized estimating equations. RESULTS: Among the 1,732 SLE patients enrolled, 89.3% were female and 48.3% were white. The mean ± SD age was 34.6 ± 13.4 years, duration of disease was 5.6 ± 5.2 months, and length of followup was 3.8 ± 3.1 years. At enrollment, 17.8% of patients had headache (migraine [60.7%], tension [38.6%], intractable nonspecific [7.1%], cluster [2.6%], and intracranial hypertension [1.0%]). The prevalence of headache increased to 58% after 10 years. Only 1.5% of patients had lupus headache, as identified in the SLEDAI-2K. In addition, headache was associated with other NP events attributed to either SLE or non-SLE causes. There was no association of headache with SLEDAI-2K scores (without the lupus headache variable), SDI scores, use of corticosteroids, use of antimalarials, use of immunosuppressive medications, or specific autoantibodies. SF-36 mental component scores were lower in patients with headache compared with those without headache (mean ± SD 42.5 ± 12.2 versus 47.8 ± 11.3; P < 0.001), and similar differences in physical component scores were seen (38.0 ± 11.0 in those with headache versus 42.6 ± 11.4 in those without headache; P < 0.001). In 56.1% of patients, the headaches resolved over followup. CONCLUSION: Headache is frequent in SLE, but overall, it is not associated with global disease activity or specific autoantibodies. Although headaches are associated with a lower HRQOL, the majority of headaches resolve over time, independent of lupus-specific therapies.

Anti-N-methyl-D-aspartate receptor encephalitis.

A case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis with an atypical finding of transient increased intracranial pressure is reported. Anti-NMDAR encephalitis is an underrecognized, novel and treatable form of encephalitis being increasingly identified as an explanation of encephalitis in young adults. Management of these patients requires a multidisciplinary approach involving neurologists, internists, nursing and rehabilitation staff. It is important for internists to recognize this condition and consider it in the differential diagnosis of encephalopathy. Internists also need to be familiar with the clinical manifestations and the treatment of the disease as they have an important role in the care of these patients during their prolonged stay in the hospital. Increased intracranial pressure is an atypical and underrecognized finding that has been only noted in a previous review on this disorder. It may present a diagnostic or management challenge in patients with anti-NMDAR encephalitis.

New insights in the prevention, diagnosis, and treatment of cryptococcal meningitis.

Cryptococcal meningitis (CM) remains a major cause of morbidity and mortality among immunocompromised patients, especially in areas of high HIV prevalence, although it can also cause disease in the apparently immunocompetent. Improving the management of HIV-associated CM is important to ensure that patients can survive to benefit from increasing access to ART. In this review we focus on recent advances in prevention, diagnosis, and treatment of CM.

The effects of brain injury on heart rate variability and the innate immune response in critically ill patients.

Brain injury and its related increased intracranial pressure (ICP) may lead to increased vagus nerve activity and the subsequent suppression of innate immunity via the cholinergic anti-inflammatory pathway. This may explain the observed increased susceptibility to infection in these patients. In the present study, we investigated the association between brain injury, vagus nerve activity, and innate immunity. We determined heart rate variability (HRV) as a measure of vagus nerve activity, plasma cytokines, and cytokine production of ex vivo lipopolysaccharide-stimulated whole blood in the first 4 days of admission to the neurological intensive care unit (ICU) in 34 patients with various forms of brain damage. HRV, immune parameters, and the correlations between these measures were analyzed in the entire group of patients and in subgroups of patients with conditions associated with high (intracranial hemorrhage [ICH]) and normal ICP (subarachnoid hemorrhage [SAH] with an extraventricular drain alleviating ICP). Healthy volunteers were used for comparison. HRV total spectral power and ex vivo-stimulated cytokine production were severely depressed in patients compared with healthy volunteers (p<0.05). Furthermore, HRV analysis showed that normalized units of high-frequency power (HFnu, corresponding with vagus nerve activity) was higher, and the low-frequency:high-frequency ratio (LF:HF, corresponding with sympathovagal balance) was lower in patients compared to healthy volunteers (p<0.05). HFnu correlated inversely with ex vivo-stimulated tumor necrosis factor-α (TNF-α) production (r=-0.22, p=0.025). The most pronounced suppression of ex vivo-stimulated cytokine production was observed in the ICH group. Furthermore, in ICH patients, HFnu correlated strongly with lower plasma TNF-α levels (r=-0.73, p=0.002). Our data suggest that brain injury, and especially conditions associated with increased ICP, is associated with vagus nerve-mediated immune suppression.

Liver derived pro-inflammatory cytokines may be important in producing intracranial hypertension in acute liver failure.

We describe a patient with paracetamol induced acute liver failure (ALF) who fulfilled criteria for poor prognosis and was waiting for a liver to become available for transplantation. Because of severe uncontrolled intracranial hypertension she underwent a hepatectomy that resulted in stabilization of her systemic and cerebral hemodynamics. She remained anhepatic for 14 h and was successfully bridged to liver transplantation. The removal of the liver was associated with a sharp and sustained reduction in the circulating pro-inflammatory cytokine concentration suggesting that liver derived pro-inflammatory cytokines may be important in the pathogenesis of intracranial hypertension in patients with ALF.

Idiopathic intracranial hypertension and anticardiolipin antibodies.

The association of idiopathic intracranial hypertension (IIH) or pseudotumour cerebri (PTC) with anticardiolipin antibodies (aCL-Abs) has been only acknowledged recently. However, its true incidence is as yet unknown. In this retrospective study, the co-occurrence of IIH and aCL-Abs was looked for among a relatively large group of patients diagnosed with IIH or PTC in the neuro-ophthalmology clinic during the years of 1992-8. All patients underwent routine blood tests and the presence of activated protein C resistance and protein S and protein C deficiency were recorded. ACL-Abs were determined in all patients. The co-occurrence of IIH and aCL-Abs was found in three out of 37 patients (8.1%), which is higher than the incidence of aCL-Abs in the general population but considerably lower than that reported in two previously published studies. The aCL-Ab positive patients in our series were significantly older and thinner than those in whom antibodies were undetected. In conclusion, it seems that patients with this association should be considered as a unique subgroup of IIH.

Delayed intracranial hypertension: relationship to leukocyte count.

OBJECTIVE: Secondary intracranial hypertension has been linked to leukocytosis. We examined our data bank containing physiologic recordings and outcome data of severely head injured patients to investigate the relationship between delayed increases in intracranial pressure (ICP), defined as occurring after a 12-hr period of normal ICP values, and leukocytosis. DESIGN: A retrospective study of observational data. SETTING: Regional neurosurgical unit and intensive care unit. PATIENTS: Sixty-four patients suffered increased ICP >20 mm Hg. Thirty-five patients fulfilled selection criteria for delayed increases in ICP (group 1). Twenty-nine patients with increased ICP with no preceding or intervening periods of normal ICP were selected as a comparison group (group 2). MEASUREMENTS AND MAIN RESULTS: Comparison of 12-month outcome revealed that 11% of group 1 patients died, with 49% remaining severely disabled, in contrast to group 2, where 35% of patients died and 14% were left severely disabled (p = .021). The pattern of outcome was independent of monitoring time, or injury severity. Regression modeling was performed for prediction of delayed increase in ICP. Of 46 patients with an initial increase then decrease in leukocyte count in the first 48 hrs, 65% experienced delayed increases in ICP, as compared with 18% of the 11 patients without this pattern p = .01 1). CONCLUSIONS: Patients with delayed increases have a significantly different pattern of outcome. Change in leukocyte count from admission to day 2 is a significant predictor of such a delayed increase.

Anticardiolipin antibodies are frequently present in patients with idiopathic intracranial hypertension.

BACKGROUND: Anticardiolipin antibodies (ACL-Ab) are associated with various neurologic syndromes, but idiopathic intracranial hypertension (IIH) has only rarely been reported in this context. OBJECTIVES: To delineate the frequency and clinical and radiological features of, as well as the cause-and-effect relationship between, ACL-Ab and IIH. METHODS: We analyzed the medical records of patients with IIH hospitalized between January 1989 and September 1995. All patients underwent magnetic resonance imaging or magnetic resonance venography or angiography. Excluded were patients with intracranial hypertension due to dural sinus thrombosis or traumatic, structural, neoplastic, or infectious disorders. Patients who were found on at least 2 separate occasions to have increased IgG titers of ACL-Ab were identified and compared with patients without ACL-Ab. RESULTS: Six (43%) of 14 patients with IIH had ACL-Ab. No differences in clinical, laboratory, or radiological variables could be found between patients with and without ACL-Ab. Only 3 of the 11 ACL-Ab-positive patients had previous systemic or neurologic abnormalities associated with ACL-Ab. CONCLUSIONS: Anticardiolipin antibodies may cause IIH through mechanisms unrelated to major venous thrombosis. Idiopathic intracranial hypertension is frequently associated with ACL-Ab and can be the presenting symptom of the antiphospholipid syndrome. There are no major clinical, laboratory, or radiological features that distinguish between patients with IIH with and without ACL-Ab.