Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibodies have been recently described in children with acute disseminating encephalomyelitis (ADEM), but the clinical and neuroradiological characterisation of this subgroup is lacking. OBJECTIVE: To compare the clinical and neuroradiological features of paediatric ADEM with and without MOG antibodies. METHODS: Clinical course, cerebrospinal fluid (CSF)-, MRI studies, outcome and MOG status of 33 paediatric ADEM prospectively studied were reviewed. RESULTS: MOG antibodies (median 1:2560; range 1:160-1:20 480) were detected in 19 children with ADEM. The majority of children showed a decline of serum MOG-IgG titres over time. Children with MOG antibodies did not differ in their age at presentation, sex ratio, the presence of oligoclonal bands, clinical symptoms or initial severity, apart from a higher CSF cell count (p=0.038), compared with children without MOG antibodies. In addition, further relapsing demyelinating episodes associated with MOG antibodies were observed only in children with MOG antibodies. All 19 children with MOG antibodies had a uniform MRI pattern, characterised by large, hazy and bilateral lesions and the absence of atypical MRI features (eg, mainly small lesions, well-defined lesions), which was significantly different compared to that of children without MOG antibodies (p=0.003; and p=0.032, respectively). In addition, children with MOG antibodies had involvement of more anatomical areas (p=0.035) including the myelon characterised by a longitudinally extensive transverse myelitis (p=0.003), more often a complete resolution of lesions (p=0.036) and a better outcome (p=0.038). CONCLUSIONS: Patients with ADEM with MOG antibodies in our cohort had a uniform MRI characterised by large, bilateral and widespread lesions with an increased frequency of longitudinal extensive transverse myelitis and a favourable clinical outcome in contrast to children lacking MOG antibodies.

MRI findings in people with epilepsy and nodding syndrome in an area endemic for onchocerciasis: an observational study.

BACKGROUND: Onchocerciasis has been implicated in the pathogenesis of epilepsy. The debate on a potential causal relationship between Onchocerca volvulus and epilepsy has taken a new direction in the light of the most recent epidemic of nodding syndrome. OBJECTIVE: To document MRI changes in people with different types of epilepsy and investigate whether there is an association with O. volvulus infection. METHODS: In a prospective study in southern Tanzania, an area endemic for O. volvulus with a high prevalence of epilepsy and nodding syndrome, we performed MRI on 32 people with epilepsy, 12 of which suffered from nodding syndrome. Polymerase chain reaction (PCR) of O. volvulus was performed in skin and CSF. RESULTS: The most frequent abnormalities seen on MRI was atrophy (twelve patients (37.5%)) followed by intraparenchymal pathologies such as changes in the hippocampus (nine patients (28.1%)), gliotic lesions (six patients (18.8%)) and subcortical signal abnormalities (three patients (9.4%)). There was an overall trend towards an association of intraparenchymal cerebral pathologies and infection with O. volvulus based on skin PCR (Fisher's Exact Test p=0.067) which was most pronounced in children and adolescents with nodding syndrome compared to those with other types of epilepsy (Fisher's Exact Test, p=0.083). Contrary to skin PCR results, PCR of CSF was negative in all patients. CONCLUSION: The observed trend towards an association of intraparenchymal cerebral pathological results on MRI and a positive skin PCR for O. volvulus despite negative PCR of CSF is intriguing and deserves further attention.

Long-term outcome of children with acute cerebellitis.

BACKGROUND: Acute cerebellitis (AC) is characterized by cerebellar symptoms and magnetic resonance imaging (MRI) changes primarily confined to the cerebellum. OBJECTIVE: To analyze the neurological and cognitive long-term outcome of children with AC. METHODS: Children with AC diagnosed by typical clinical features and MRI findings were included in this retrospective study. Medical charts were reviewed and neurological deficits were assessed by neurological examination or by the expanded disability status scale telephone interview. Cognitive outcome was evaluated with a parental questionnaire (Kognitive Probleme bei Kindern und Jugendlichen). RESULTS: A total of 11 children (6 boys, 5 girls; age range: 3 years to 14 years and 10 months) were included. Of them, six children had a severe disease manifestation including mental status changes and neurological symptoms. Of the rest, two children had a moderate and three children had a mild form of AC. MRI of the cerebellum was obtained in the acute phase revealing signal alterations with different patterns. The average follow-up period was 4 years and 4 months. A complete recovery was observed in five children. Neurological sequelae were reported in five children ranging from ataxia to mild tremor. Cognitive deficits were found in six patients. The affected areas of cognition did include spatial visualization ability, language skills, and concentration. CONCLUSION: Neurological and cognitive sequelae are common in children with AC and underline the role of the cerebellum in cognition.

Basilar artery dissection: series of 12 consecutive cases and review of the literature.

BACKGROUND: Current knowledge on primary or isolated basilar artery dissection (IBAD) is limited to case vignettes and small patient series. OBJECTIVE: To delineate the frequency and clinical presentations of IBAD along with short-term outcome, specific prognosis and targeted management. METHODS: Data were derived from a series of 12 consecutive patients and a review of 88 cases reported in the literature. In all the cases, the dissection was confined to the basilar artery. RESULTS: Disease incidence was estimated at 0.25 per 100,000 person-years. IBAD accounted for roughly 1.0% of all subarachnoid hemorrhage events and for no less than 10.5 and 4.5% of posterior circulation and brain-supplying artery dissections, respectively. The main clinical presentations were subarachnoid hemorrhage (46%) and posterior circulation brain ischemia (42%). Subarachnoid hemorrhage typically manifested at a higher age than brain ischemia (mean age, 48.9 vs. 41.4 years) and was more prevalent among women. Rebleedings related to pseudoaneurysm formation in patients with subarachnoid hemorrhage and recurrent ischemia in stroke patients were common in the acute phase (26.1 and 33.3%, respectively) but were rare in the long term. The outcome was generally favorable in stroke patients but variable in subarachnoid hemorrhage (case fatality rate, 21.7%). The mainstay of therapy for subarachnoid hemorrhage related to IBAD was endovascular occlusion of the aneurysm pouch whereas stroke patients were usually put on anticoagulants. CONCLUSIONS: IBAD is probably an underrecognized disease with heterogeneous clinical presentation and prognosis. It should be considered as a differential diagnosis in peritruncal subarachnoid hemorrhage, classic subarachnoid hemorrhage and posterior circulation stroke, especially in young individuals. Case management is challenging and has to be tailored to each patient.

Hippocampal abnormalities in malformations of cortical development: MRI study.

OBJECTIVES: Hippocampal abnormalities may coexist with malformations of cortical development (MCD). This cross-sectional MRI study aimed at categorizing hippocampal abnormalities in a large group of MCD and comparing MCD patients with (group W) and without (group W/O) hippocampal abnormalities. METHODS: Hippocampal anatomy, rotation, size, internal structure, and MRI signal alterations were assessed visually by 3 independent raters in patients with MCD and epilepsy. Four types of hippocampal abnormalities were examined in 220 patients (116 women, mean age 31 +/- 16.6, range 2-76 years): partially infolded/hypoplastic hippocampus (HH), hippocampal sclerosis (HS), malrotated hippocampus (MH), and enlarged hippocampus (EH). The commonest MCD in the cohort were focal cortical dysplasia (27%), polymicrogyria (PMG) (21%), developmental tumors (15%), and periventricular nodular heterotopia (PNH) (14%). RESULTS: Hippocampal abnormalities were seen in 69/220 (31%) patients: HH in 34/69 (49%); HS in 18/69 (26%); MH in 15/69 (22%); and EH in 2/69 (3%). PNH (21/30 [70%]) and PMG (22/47 [47%]) were most commonly associated with hippocampal abnormalities. Compared to the W/O group, patients in the W group had a higher rate of learning disability (W 41/69 [59%] vs W/O 56/151 [37%]; p = 0.003) and delayed developmental milestones (W 36/69 [52%] vs W/O 53/151 [35%]; p = 0.025); groups did not differ otherwise with regard to clinical presentation. HH was associated with symptomatic generalized epilepsies (11/34 [32%]) and high rate of learning disability (27/34 [79%]), neurologic deficits (25/34 [73%]), and delayed developmental milestones (23/34 [68%]). CONCLUSIONS: About a third of patients with malformations of cortical development had hippocampal abnormalities. Patients with hypoplastic hippocampus had the most severe clinical phenotype.

Integration of multimodality imaging and surgical navigation in the management of patients with refractory epilepsy. A pilot study using a new minimally invasive reference and head-fixation system.

OBJECTIVE: To review the experience with a new system (VBH system) for minimally invasive frameless stereotactic guidance, acting as a common platform to provide multimodal image integration and surgical navigation in a consecutive series of 25 patients who underwent surgery for drug-resistant seizures. METHODS: The usefulness of the VBH system for integrating all images to produce one dataset and for intraoperative instrument guidance and navigation was judged semiquantitatively in a three-tiered scale (+, ++, +++). Seizure outcome was classified according to Engel. RESULTS: The presurgical evaluation extended over 21.2 months (mean). A total of 141 registrations of images were performed (mean 5.6 per patient, range: 2 to 16). In 19 (76%) of 25 patients structural data fused with functional data were used for the presurgical workup. Six patients proceeded directly to navigated resection. Nineteen patients (76%) underwent invasive recording, of whom 13 underwent resective surgery. In seven patients (28%) the combination of multimodal image fusion and intra-operative stereotactic guidance was judged "essential" (+++) to remove the epileptogenic zone. Integration of all images to form one dataset was "essential" (+++) for decision making in 15 and "helpful" (++) in 4 patients (overall 76% of patients). Intraoperative use of frameless neuronavigation was "essential" (+++) in ten and "helpful" (++) in all remaining patients. Eighty percent of the patients achieved satisfactory seizure outcome after 1 year. CONCLUSION: The VBH system is a safe and effective non-invasive tool for repetitive imaging, multimodal image fusion and frameless stereotactic surgical navigation in candidates for epilepsy surgery.

Stroke-like episodes in propionic acidemia caused by central focal metabolic decompensation.

Propionic acidemia caused by propionyl-CoA carboxylase deficiency frequently leads to neurologic complications. Herein we report an eleven-year-old patient with propionic acidemia having three stroke-like episodes during a period of 13 months characterized by acute reversible hemiplegia and vegetative symptoms like bradycardia or drowsiness. No biochemical signs of severe metabolic decompensation were detectable in plasma. At all three episodes, EEG was not indicative for status epilepticus, but in the acute episode it showed slowing of background activity emphasized on one side. MRI revealed reversible hyperintensities in cortical grey matter and basal ganglia. During the third episode a lumbar puncture was done in parallel with venous puncture. Concentrations of glutamine (902 micromol/L), glycine (24 micromol/L) and alanine (78 micromol/L) were elevated in CSF. In plasma glycine (1 859 micromol/L) and alanine (608 micromol/L) concentrations were also elevated, whereas the glutamine (458 micromol/L) concentration was normal. CSF/plasma ratios were elevated for glutamine (1.97) and alanine (0.13) and normal for glycine (0.01). We assume that the stroke-like episodes in our patient may be caused by an acute focal cerebral metabolic decompensation, which is detectable by unspecific changes in MRI and by measuring amino acids and lactate in CSF versus plasma.

Peripheral neuropathy as the sole initial finding in three children with infantile metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is a progressive white matter disease caused by arylsulfatase A deficiency. Demyelination in the nervous system is detected by cerebral magnetic resonance imaging (MRI) and neurophysiological studies. We present three children with infantile MLD, who had difficulties in standing and walking with absent reflexes. Protein levels in cerebral spinal fluid (CSF) were elevated and nerve conduction studies revealed slowing down of motor nerve conduction velocity. Initial cerebral MRIs showed no white matter changes. Consecutively, all three children developed clinical symptoms of neurodegenerative disease. Follow-up MRI and arylsulfatase A testing led to diagnosis of MLD. We conclude, that in young children who present with an acute/subacute demyelinating polyneuropathy, MLD is a differential diagnosis.

Clinical outcome of children presenting with a severe manifestation of acute disseminated encephalomyelitis.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is an acute, inflammatory-demyelinating disorder of the CNS with a favourable outcome in the majority of cases. OBJECTIVE: The aim of this study was to examine the long-term outcome of children with an initially severe form of ADEM. METHODS: Children with ADEM according to the criteria of the International Pediatric MS Study Group (IPMSSG) referred to the rehabilitation centre Vogtareuth were included. Neurological impairment was evaluated with a standardized telephone-based interview assessing the EDSS score. Neuropsychological outcome was assessed with review of the medical records and a standardized parental questionnaire (KOPKIJ). RESULTS: Twelve children (1 year 9 months to 13 years of age) were included. All children had focal-neurological signs and changes in mental status at presentation and an MRI of the brain showing a range of white and gray matter lesions. 11/12 patients with a mean follow-up of 6.2 years (2-13.6 years) had a monophasic course of the disease. One child had a multiphasic ADEM. Two children had an EDSS score of 0, three an EDSS of 2, five an EDSS between 3 and 5 and two children had an EDSS score of 6 and 9. Results of a standardized parental questionnaire (KOPKIJ) revealed that 7 children had deficits in the categories alertness, memory, school performance, visual-spatial skills and/or impulse control. CONCLUSION: The results of our study indicate that children with an initially severe manifestation of ADEM continue to have in the majority of cases neurological and neuropsychological handicaps.

Does caffeine modulate verbal working memory processes? An fMRI study.

To assess the effect of caffeine on the functional MRI signal during a 2-back verbal working memory task, we examined blood oxygenation level-dependent regional brain activity in 15 healthy right-handed males. The subjects, all moderate caffeine consumers, underwent two scanning sessions on a 1.5-T MR-Scanner separated by a 24- to 48-h interval. Each participant received either placebo or 100 mg caffeine 20 min prior to the performance of the working memory task in blinded crossover fashion. The study was implemented as a blocked-design. Analysis was performed using SPM2. In both conditions, the characteristic working memory network of frontoparietal cortical activation including the precuneus and the anterior cingulate could be shown. In comparison to placebo, caffeine caused an increased response in the bilateral medial frontopolar cortex (BA 10), extending to the right anterior cingulate cortex (BA 32). These results suggest that caffeine modulates neuronal activity as evidenced by fMRI signal changes in a network of brain areas associated with executive and attentional functions during working memory processes.

Electroclinical and imaging findings in ulegyria and epilepsy: a study on 25 patients.

PURPOSE: Ulegyria refers to cerebral cortex scarring, which results from a perinatal ischaemic brain injury. It presents with a characteristic gyral pattern: small circumvolutions with atrophy at sulci bottom and spared apex. Ulegyria is frequently associated with epilepsy, cerebral palsy and mental disability. We analysed electroclinical and MRI features in patients with ulegyria and epilepsy. PATIENTS AND METHODS: We reviewed 25 patients (14 males/11 females) with ulegyria and epilepsy from the database (about 5000 patients with epilepsy) of our unit. Patients were examined clinically, underwent high resolution MRI, EEG recordings, positron emission tomography, single photon emission computed tomography and neuropsychological testing. Two patients with refractory seizures underwent epilepsy surgery. RESULTS: Mean age of patients was 34 years (5-66) at the reassessment time. The majority (16/25, 64%) had a history of perinatal asphyxia. 15 patients had delayed developmental milestones; 20 had learning disabilities and five patients were severely disabled. Mean age at seizure onset was 4.2 years (1-18). 17 patients (68%) had medically intractable epilepsy. 11 patients (44%) had occipital lobe seizures. The majority (n = 24, 96%) had parieto-occipital lesions on MRI. In 13 patients (52%), ulegyria was bilateral. 12 patients (48%) had hippocampal sclerosis. Two patients underwent epilepsy surgery with an excellent postoperative outcome (Engel class IA and IC). CONCLUSION: Patients with ulegyria often have a history of perinatal asphyxia and present with pharmacoresistant seizures. Their presurgical assessment is complicated because of frequent dual pathology (hippocampal sclerosis) and bilateral lesions.

Recanalization after thrombolysis in stroke patients: predictors and prognostic implications.

OBJECTIVE: To estimate rates, predictors, and prognostic importance of recanalization in an unselected series of patients with stroke treated with IV thrombolysis. METHODS: We performed a CT angiography or transcranial Doppler (TCD) follow-up examination 24 hours after IV thrombolysis in 64 patients with documented occlusion of the intracranial internal carotid or middle cerebral artery (MCA). Complete recanalization was defined by a rating of 3 on the Thrombolysis in Myocardial Infarction or 4/5 on the Thrombolysis in Brain Ischemia grading scales. Information about risk factors, clinical features, and outcome was prospectively collected by standardized procedures. RESULTS: Complete recanalization was achieved in 36 of the 64 patients (56.3%). There was a nonsignificant trend of recanalization rates to decline with a more proximal site of occlusion: 68.4% (M2 segment of MCA), 53.1% (M1 segment), and 46.2% (carotid T) (p for trend = 0.28). Frequencies of vessel reopening were markedly reduced in subjects with diabetes (9.1% vs 66.0% in nondiabetics, p < 0.001) and less so in subjects with additional extracranial carotid occlusion (p = 0.03). Finally, complete recanalization predicted a favorable stroke outcome at day 90 independently of the information provided by age, NIH Stroke Scale, and onset-to-needle time. CONCLUSIONS: We found a high rate of vessel recanalization after IV thrombolysis occlusion. However, recanalization was infrequent in patients with diabetes and extracranial carotid occlusion. Information on recanalization was a powerful, early predictor for clinical outcome.

Intravascular pressure measurements in feeding pedicles of brain arteriovenous malformations.

Pressure measurements in arterial feeders of arteriovenous malformations (AVMs) can be easily acquired during endovascular treatment procedures. In this study, mean arterial pressure values in arterial feeders (Pfed) of brain AVMs were determined using a pressure measuring system connected to a standard microcatheter. A total of 148 measurements were performed in 139 patients. Mean systemic arterial pressure values were subtracted for correction. The levels of correlation between the pressure values and various clinical parameters (i.e., AVM location, size, previous hemorrhage) and pathoanatomical features of the AVM (e.g., nidus structure, number of draining veins) were determined. Pfed values were 54.5 mmHg on average. Pfed was lower in more distally located AVMs, in larger lesions and in AVMs with multiple drainage veins. Pressure values were significantly higher in patients with previous hemorrhage and in smaller AVMs. Our results support the importance of hemodynamic parameters in determining the presentation of AVMs. More extensive studies using this simple technique may further elucidate these mechanisms and may result in improved criteria for patient selection and reduction of complications.

Acute pulmonary edema, capillaritis and alveolar hemorrhage: pulmonary manifestations coexistent in antiphospholipid syndrome and systemic lupus erythematosus?

Pulmonary capillaritis and alveolar hemorrhage are rare yet serious and life threatening complications of systemic lupus erythematosus (SLE). Pulmonary manifestations of antiphospholipid syndrome (APS) are similar and include, apart from pulmonary embolism and pulmonary hypertension, pulmonary capillaritis, diffuse alveolar hemorrhage and respiratory insufficiency in patients with catastrophic APS. Herein, we described the radiological features of three patients with pulmonary and SLE-associated APS, manifested with pulmonary edema, capillaritis and alveolar hemorrhage. We observed that the radiological features of pulmonary APS shared close resemblance to those of pulmonary SLE. Based on these findings, we conclude that both entities are not only histologically, but also radiologically indistinguishable from each other, suggesting a mutual pathogenetic mechanism. This raises the question of whether some of the reported lupus pneumonitis cases in the past might be manifestations of APS rather than of SLE.

Large-vessel arteritis and myelodysplastic syndrome: report of two cases.

Myelodysplastic syndrome (MDS) is frequently associated with autoimmune diseases such as polymyalgia, arthritis, and rarely, with systemic vasculitis. The pathogenesis of these autoimmune complications remains unknown, but there is increasing evidence of profound immune dysregulation in MDS. In the few cases reported so far, vasculitides associated with MDS affected mainly cutaneous vessels. Here we describe two cases of acute large-vessel vasculitis in association with MDS. The first patient is a 67-yr-old male presenting with a massive large-vessel arteritis as primary manifestation of refractory anemia with excess of blasts type 1 (RAEB-1). The second patient is a 60-yr-old male, who presented with acute thoracic aortitis after a 2-yr history of refractory anemia with ringed sideroblasts (RARS). Both patients received immunosuppressive treatment with steroids, leading to rapid improvement of systemic inflammatory symptoms, vessel wall injury and peripheral blood counts. Whereas the first patient displayed sustained favorable hematologic responses under long-term steroid therapy, there was a rapid transformation into secondary acute myeloid leukemia in the second patient. We conclude that large-vessel vasculitis should be added to the list of potential autoimmune complications in MDS. In this clinical setting, steroid therapy may alleviate inflammatory symptoms and result in beneficial hematologic responses.

Pressure measurements in arterial feeders of brain arteriovenous malformations before and after endovascular embolization.

Arteriovenous malformations (AVMs) are composed of abnormal arterial and venous vessels in the brain causing arteriovenous shunts of arterialized blood directly from pial arteries to draining veins. The hemodynamics of these lesions is not well-understood. Changes in blood flow and pressure are probably related to the natural history of AVMs and may also play a major role in AVM treatment. In this study intra-arterial pressure was measured in feeding arteries of AVMs using a microcatheter that had been placed for subsequent embolization treatment (201 measurements were performed in 95 patients before and after the embolization procedure). Results show a direct relationship between pressure changes and degree of embolization. Since pressure changes during the embolization procedure are relatively small, it seems unlikely that these changes are the direct cause of rupture and periprocedural bleedings.