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Multiple sclerosis (MS) is an autoimmune, inflammatory demyelinating disease of the central nervous system (CNS) and the most common disabling neurological disease in young adults.1,2 Pediatric MS with a clinical onset before the age of 18 years occurs in about 3–10% of MS patients.3 More than 90% of pediatric MS patients have a relapsing–remitting disease course.3,4 The clinical course differs between pediatric and adult MS patients. First, children more often present with an acute disease onset associated with disabling clinical symptoms.3–8 A polyfocal presentation at disease onset is more common in children (48.9%) than in adults (12%).5 Second, children show a significantly higher relapse rate early in the disease.4,9–12 Third, the remission after a severe relapse is better in children than in adults,4,5,7,8 with 62 to 66% of pediatric patients13,14 recovering completely from initial relapses compared to 46% of adult patients.14 Furthermore, the mean time of recovery after a relapse is shorter in pediatric MS (4.3 weeks) than in adult MS (6–8 weeks).11 Finally, children show a slower rate of disease progression7,15 and take approximately 10 years longer to reach the secondary progressive disease phase compared to adults. However, given their younger age at disease onset, they are approximately 10 years younger when they enter this phase of the disease.16 Overall, children develop irreversible physical disability more slowly than adults.9,13 Defining the factors that are associated with the clinical differences between pediatric and adult MS is of special interest. Pathological studies in particular represent a promising way of gaining more insight. To date, there has been no comprehensive histological study of pediatric MS available in the literature. This study investigates axonal pathology in pediatric inflammatory demyelinating lesions consistent with MS. Axonal loss, one of the hallmarks of MS lesions, is an important pathological correlate of nonremitting clinical disability and disease progression.17–19 Hence, there may be differences in axonal damage between pediatric and adult MS patients. Various histological and immunohistochemical staining methods are available to assess axonal damage. The classical methods for visualizing the axonal network are silver impregnation20 and immunohistochemistry for neurofilaments.21 Irreversible loss of axons may be determined by analyzing the reduction in axonal density, whereas the presence of axonal spheroids is a reflection of impaired axonal transport associated with acute and possibly reversible axonal injury. Immunostaining with the precursor of the beta-amyloid protein (amyloid precursor protein [APP]) or other anterogradely transported proteins, such as synuclein, are good markers to evaluate the extent of acute axonal damage, because anterograde transport is interrupted and APP and/or synuclein accumulate focally as spheroids.22–24 These APP-positive spheroids may persist for up to 30 days.22 The accumulation of APP may be reversible24 and in part account for the improvement of neurological symptoms observed after a relapse. In the present study, we analyzed axonal pathology in pediatric MS lesions and compared the findings with data from adult MS patients to determine whether differences contribute to different clinical outcomes.

Objective Intraoperative ultrasound displays dynamic processes intraoperatively. Performing burr-hole biopsies under a real-time visual control is an interesting option for the neurosurgeon. However, the percentage of conclusive diagnoses obtained by this technique and the rate of complications must be evaluated in a larger series. Methods One hundred consecutive intracranial biopsies were analyzed. Through a burr hole, the lesion was localized by ultrasonography, and the planned needle trajectory was superimposed onto the image. Intracranial vessels were imaged by Doppler flow signals. Biopsies were taken in a mean depth of 41 mm (maximal 65 mm) from different parts of each tumor. Results Thirty-six lesions involved the corpus callosum, 16 lesions were located deeply within the white matter, five in the internal capsule, and one in the upper brainstem. There were three cerebellar and 17 temporal lesions. Ten tumors did not exceed a diameter of 15 mm in any plane. The mean time interval from skin incision to the end of suturing was 45 minutes, and the mean time from the surgeons entering the operating theater to leaving the theater was 63 minutes. In 95% of the lesions, a diagnosis could be established. Transient neurologic deficits occurred in five patients, which were permanent in three. In 42 patients without postoperative neurological symptoms, postoperative computed tomography scans were obtained within 24 hours; a visible hemorrhage occurred in eight (19%), six of which were seen intraoperatively. Conclusion When intraoperative ultrasound−navigated biopsies were used they obtained a similar percentage of conclusive diagnoses as stereotactic biopsies. The complication rate is comparable as well. Emerging intracranial complications such as hemorrhages can be observed. However, their incidence cannot be decreased.

We report the clinical course and pathological features of a 52-year-old woman with fulminant acute disseminated encephalomyelitis (ADEM). She presented with subacute tetraparesis, which developed over 2 days, and progressive loss of consciousness. CCT showed pronounced bihemispherical and periventricular edema. Multifocal glioma was suspected, and the patient was referred for brain biopsy to the neurosurgery department at our hospital. On admission, the patient presented with progressive tetraparesis and aphasia. Subsequently, she developed epileptic seizures. Cranial magnetic resonance imaging (MRI) revealed confluent bihemispherical and periventricular white matter edema (Fig. 1a) with abnormal patchy gadolinium enhancement, compatible with progressive multifocal leukoencephalopathy (PML), multifocal brain tumor or ADEM. Cerebrospinal fluid (CSF) analysis revealed mild pleocytosis (11 cells/ll) with increased protein levels, and normal glucose and lactate levels. No intrathecal IgG and IgM synthesis or oligoclonal bands (OCB) were observed in CSF. Antiviral and antibiotic treatment was initiated. Stereotactic brain biopsy from right frontal periventricular white matter (Fig. 1b) was performed 5 days after disease onset. Histopathology ruled out malignant brain tumor but showed acute perivascular inflammation.

Background: Because of the emergence of novel therapies for multiple sclerosis (MS) and the associated increased risk of progressive multifocal leukoencephalopathy, John Cunningham (JC) virus infection has become a focus of interest for neurologists. However, little is known about JC virus infection in pediatric MS to date. Objective: We aimed to analyze the prevalence of anti-JC virus antibodies, the conversion rate and the influence of the anti-JC virus antibody status on the clinical course in a large pediatric MS cohort. Methods: Anti-JC virus antibodies were analyzed in serum samples within six months of disease onset and during the course of the disease. Clinical data were extracted from a pediatric MS databank. Results: A total of 51.6% of 256 patients were found to be positive for anti-JC virus antibodies at onset of disease. No correlation between antibody status and clinical course was seen. Analyzing 693 follow-up serum samples revealed high titer stability, and an annual conversion rate of 4.37% was seen. Conclusion: No evidence was found that seropositivity for anti-JC virus antibodies influences the clinical course. Surprisingly, seroprevalence for anti-JC virus antibodies was more than twice as high as anticipated in this age group, raising the question of whether the infection increases the risk of MS development.

Pediatric MS tends to present more often with an acute onset and a polysymptomatic form of the disease, possibly with encephalopathy and large tumefactive lesions similar to those observed in some cases of acute disseminated encephalomyelitis (ADEM), which makes it more difficult to differentiate between an explosive and severe onset of MS vs. ADEM. An ADEM-like first demyelinating event can be the first attack of pediatric MS, but international consensus definitions require two or more non-ADEM demyelinating events for diagnosis of MS. In our patient KIDMUS MRI criteria for MS (Mikaeloff et al. J Pediatr 144:246–252, 2004a; Mikaeloff et al. Brain 127:1942–1947, 2004b) were negative at first attack, but Barkhof criteria for lesion dissemination in space in adults (Barkhof et al. 120:2059–2069, 1997), Callen modified MS-criteria and Callen MS-ADEM criteria for children (Callen et al. Neurology 72:961–967, 2009a; Callen et al. Neurology 72:968–973, 2009b) were positive suggesting pediatric MS. As the clinical course was devastating with non-responsiveness upon high-dose immune modulatory therapy and due to the absence of an alternative diagnosis other than demyelinating disease brain biopsy was performed. Brain biopsy studies or autopsy case reports of fulminant pediatric MS patients are extremely rare. Histopathology revealed an inflammatory demyelinating CNS process with confluent demyelination, indicating the likelihood of a relapsing disease course compatible with an acute to subacute demyelinating inflammatory disease. This pattern was corresponding to the early active multiple sclerosis subtype I of Lucchinetti et al. (Ann Neurol 47(6):707–717, 2000). peerReviewed

e13016 Background: Ets-1 regulates migration & angiogenesis and is active in malignomas. Methods: We investigated Ets-1 in 60 glioblastomas WHO IV° & 40 astrocytomas WHO II° and evaluated its progn...