Mary Kurian

EEG source imaging in pediatric epilepsy surgery: a new perspective in presurgical workup.

Summary:  Purpose: Epilepsy is a relatively frequent disease in children, with considerable impact on cognitive and social life. Successful epilepsy surgery depends on unambiguous focus identification and requires a comprehensive presurgical workup, including several neuroimaging techniques [magnetic resonance imaging, positron emission tomography (PET), and single‐photon emission computed tomography (SPECT)]. These may be difficult to apply in younger or developmentally delayed children or both, requiring sedation, and hence, a significant workforce. Modern electric source imaging (ESI) provides accurate epileptic source‐localization information in most patients, with minimal patient discomfort or need for cooperation. The purpose of the present study was to determine the usefulness of ESI in pediatric EEG recordings performed with routine electrode arrays.

Opsoclonus-Myoclonus Syndrome in Anti–N-Methyl-D-Aspartate Receptor Encephalitis

BACKGROUND Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis has been recently reported as autoimmune/paraneoplastic encephalitis, affecting mostly young females. OBJECTIVE To describe opsoclonus-myoclonus syndrome in association with anti-NMDAR antibodies. DESIGN Case report. SETTING Geneva University Hospital. Patient A 23-year-old woman with opsoclonus-myoclonus syndrome. RESULTS Two weeks after an episode of gastroenteritis, the patient developed symptoms of depression associated with psychomotor slowing, progressive gait instability, and opsoclonus-myoclonus. Cerebrospinal fluid examination showed mild lymphocytic pleocytosis and intrathecal IgG synthesis with oligoclonal bands. The patients condition worsened rapidly to an akinetic mutism, followed by a period of agitation, delirium, and hallucinations. These gradually subsided; however, a frontal behavior and executive dysfunction persisted 5 months after symptom presentation. No tumor was found. Anti-NMDAR antibodies were found in the cerebrospinal fluid. CONCLUSIONS Opsoclonus-myoclonus may occur in patients with anti-NMDAR encephalitis. Prompt diagnosis of this disorder is important because after tumor removal and immunomodulatory therapies it has a relatively good prognosis.

Amyloid plaques and intraneuronal tau inclusions in A-beta-related angiitis (ABRA)

Idiopathic or primary angiitis of the central nervous system (PACNS) is a rare vasculitic disorder confined to the brain. The inflammatory process is segmental with a predilection for small arteries, particularly in the leptomeninges. Cerebral amyloid angiopathy (CAA) is characterized by deposition of amyloid in blood vessels within the cerebrum and overlying leptomeninges and encompasses a heterogeneous group of hereditary and sporadic diseases. CAA and PACNS have been described to occur together in some patients, hence the name A-betaamyloid (Ab)-related angiitis (ABRA) [1]. It is not known whether vascular Ab promotes inflammation or inflammatory changes induce b amyloid deposition. We describe the neuropathological features of a 67-year-old female patient in which the brain biopsy revealed ABRA, associated with some neuritic plaques and neuronal tau deposits, without any clinical evidence of CAA or Alzheimer’s disease (AD). A 67-year-old right-handed female patient, with no antecedent medical or surgical history, presented with progressive loss of memory and behavioural changes over a period of 5–6 months. On admission, her vital signs as well as general physical and neurological examinations were normal. Mini-Mental State Examination (MMSE) was 23/30 and neuropsychological testing showed marked attentional and frontal/dysexecutive deficits. Cerebrospinal fluid analysis (CSF) analysis showed slight lymphomonocytic pleiocytosis (eight leucocytes/mm, 0.5 g/l protein, and oligoclonal bands from intrathecal IgG synthesis). CSF tau and Ab 42 levels were within the normal range. Brain magnetic resonance imaging revealed a leptomeningeal contrast enhancement in both frontal regions and multiple subcortical white matter hyperintensities corresponding to ‘U’ fibres. A diagnostic brain biopsy in the right frontal region was performed and pathological analysis of the leptomeninges and the adjacent cortex revealed lymphoplasmacytic meningitis with giant cell arteritis (Figure 1). The affected vessels showed perivascular lymphoid cuffing, and destruction of the internal elastic lamina and other wall elements by the multinucleate giant cell infiltrate (Figure 1c,d). In addition to vasculitis, many leptomeningeal arteries and parenchymal arterioles contained a moderate to severe degree of amyloid deposits, confirmed by Congo red staining and birefringence under polarized light (Figure 1a,b) [2,3]. Amyloid-beta (Ab) peptide immunostain revealed reactivity both in microvessels and in microglia and giant cells indicating phagocytosis of amyloid deposits (Figure 1c,e). The same antibody marked numerous cortical plaques at various stages of maturity (Figure 1b), some of the neuritic type. Anti-tau immunohistochemistry showed occasional intraneuronal inclusions, mainly corresponding to pretangles (Figure 1f). Traces of prior bleeding were seen with Prussian blue iron stain, as well as signs of ischaemia in the form of scattered hypereosinophilic neurones and subcortical lacunar infarcts. Staining for fungi was negative. PCR analysis of the biopsied tissue was negative for tuberculosis. The patient was treated with high doses of intravenous methylprednisolone followed by daily oral prednisone and intravenous cyclophosphamide for 6 months followed by oral azathioprine. Her mental status rapidly improved under treatment, whereas she scored 29/30 on the MMSE and the extensive neuropsychological examination found only slight executive deficits. Moreover, she resumed all her daily activities and has been completely independent at a 1-year follow-up. The cerebromeningeal biopsy along with exclusion of an infectious or systemic vasculitic aetiology confirmed the diagnosis of PACNS associated with CAA, as described in ABRA. Several authors consider ABRA a distinct clinicopathological entity from PACNS, characterized by autoreactive Ab antibodies [4]. Besides lymphocytic histopathological patterns, granulomas and multinucleated giant cells have been reported in PACNS/CAA. Amyloid deposits may trigger an inflammatory process in susceptible individuals, as shown in Alzheimer immunization studies [5], but most Alzheimer and CAA patients do not develop vasculitic reactions. DiFrancesco et al.

Stroke-like Phenomena Revealing Multifocal Cerebral Vasculitis in Pediatric Lyme Neuroborreliosis

Stroke-like presentation in Lyme neuroborreliosis is rare in the pediatric age group. We report a previously healthy 12-year-old boy who presented with acute left hemiparesis and meningeal signs. Neuroimaging failed to reveal any cerebral infarction but demonstrated a multifocal cerebral vasculitis involving small, medium and large-sized vessels affecting both the anterior and posterior circulation. Concentric contrast enhancement of the basilar artery was also observed. Further investigations and laboratory findings were consistent with Lyme neuroborreliosis. A rapidly favorable clinical outcome was obtained with appropriate antibiotic treatment along with antiaggregants and steroids. Lyme neuroborreliosis should be considered in the diagnostic differential, not only in adults but also among children, especially in the context of an unexplained cerebral vasculitis.

Anti-NMDA receptor encephalitis: the importance of early diagnosis and aggressive immunotherapy in tumor negative pediatric patients

We read with interest the recent article by Kashyape et al. on the successful use of Cyclophosphamide in Anti-NMDA receptor encephalitis and the related editorial in the same issue. The authors of the article describe the clinical course and treatment of three female pediatric patients who had minimal response to first-line immunotherapy, including plasma exchanges for two of them, but dramatic clinical response after intravenous cyclophosphamide. They propose an early and aggressive approach when first-line immunotherapy, including steroids, immunoglobulins and plasma exchanges, fails. We report another interesting observation of a young girl, who showed an unexpectedly rapid clinical response and a complete recovery with a combination of plasma exchanges and rituximab started only three weeks after the onset of symptoms. Our patient was a 7-year-old female childwho presented to the emergency room with a history of behavioral changes (delirium, incoherent speech, auditory and visual hallucinations) and sleep disturbances since 10 days. On initial examination, choreiform movements of the upper and lower limbs, orofacial dyskinesia, and autonomic instability were observed. She also presented with a few self-limited seizures shortly after admission. Anti-NMDA receptor encephalitis was immediately suspected and rapidly confirmed with positive antibodies in both serum and cerebrospinal fluid. Cerebral MRI showed multiple patchy hyperintense T2 and FLAIR lesions. Tumor screening was negative. She was treated with a 5-day course of intravenous methylprednisolone from day 1 of her hospital admission (10 days after onset of symptoms) followed by oral prednisolone and intravenous immunoglobulins without any clinical response. Plasma exchanges were therefore started (at the beginning of the third week of symptoms), immediately followed by two doses of rituximab. Clinical improvement was observed 3 days after starting the plasma exchanges, with a rapid and progressive decrease in abnormal movements and agitation. She made continuous progress until she completely recovered, 8 weeks after her admission and a total of 10 cycles of Plasma exchanges. Repeat serum anti-NMDA receptor titers at 8 weeks were remarkably low (one tenth of the initial value), and her neurological examination was normal. On follow-up, 4 months after the onset of symptoms, she has resumed all her normal daily activities. Anti-NMDA receptor encephalitis is a severe disorder with a dramatic clinical presentation, with often a purely initial neuropsychiatric phase, evolving into a severe encephalopathy accompanied by involuntary movements, seizures and autonomic instability; the disease course is typically prolonged and needs intensive care treatment. Despite being highly suggestive on clinical grounds, the rarity of this entity makes it a diagnostic challenge, and a delay in the initiation of treatment may occur. An early diagnosis permits a rapid introduction of immunomodulatory therapy, and therefore, an early recovery. There is no established treatment protocol for the management of anti-NMDA receptor encephalitis. Similar to the patients reported in the paper by Kashyape et al., our patient did not show any response to steroids and immunoglobulins used as first-line options; however, the aggressive initiation of plasma exchange and rituximab from the third week of symptoms were rapidly followed by favorable effects, and the recovery phase was considerably shorter than previously reported. These observations underline the importance of an early recognition, likely to be crucial in the management of these patients. They also speak in favor of an aggressive therapeutic approach in these patients, including early plasma exchanges, as described also by other authors. The optimal type and mode of immunotherapy remain uncertain. Whether first-line steroids and immunoglobulin could even be avoided in favor of other therapeutic options needs further evaluation. Yours sincerely

Late onset of leucoencephalopathy with cerebral calcifications and cysts

Journal of Neuroradiology - In Press.Proof corrected by the author Available online since jeudi 20 janvier 2011

Focal cortical malformations in children with early infantile epilepsy and PCDH19 mutations: case report

In this case report we assess the occurrence of cortical malformations in children with early infantile epilepsy associated with variants of the gene protocadherin 19 (PCDH19). We describe the clinical course, and electrographic, imaging, genetic, and neuropathological features in a cohort of female children with pharmacoresistant epilepsy. All five children (mean age 10y) had an early onset of epilepsy during infancy and a predominance of fever sensitive seizures occurring in clusters. Cognitive impairment was noted in four out of five patients. Radiological evidence of cortical malformations was present in all cases and, in two patients, validated by histology. Sanger sequencing and Multiplex Ligation‐dependent Probe Amplification analysis of PCDH19 revealed pathogenic variants in four patients. In one patient, array comparative genomic hybridization showed a microdeletion encompassing PCDH19. We propose molecular testing and analysis of PCDH19 in patients with pharmacoresistant epilepsy, with onset in early infancy, seizures in clusters, and fever sensitivity. Structural lesions are to be searched in patients with PCDH19 pathogenic variants. Further, PCDH19 analysis should be considered in epilepsy surgery evaluation even in the presence of cerebral structural lesions.

“Gourmand syndrome” in a child with pharmacoresistant epilepsy

We report the case of a 10-year-old boy with pharmacoresistant epilepsy, symptomatic of a right temporoparietal hemorrhagic lesion, who displayed an eating passion as described for the gourmand syndrome (GS) in adults and discuss the role of epilepsy in GS. This patient presented with a significant change in his eating habits (abnormal preoccupation with the preparation and eating of fine-quality food) concordant with the onset of his seizure disorder, without any previous history of eating disorders or psychiatric illness. This observation corroborates the important role of the right cerebral hemisphere in disturbed eating habits, including the relatively benign GS, and, possibly rarely, in less benign eating disorders such as anorexia and obesity.

Early-onset or rapidly progressive scoliosis in children: Check the eyes!

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare autosomal recessive disorder characterized by the absence of conjugate horizontal eye movements, and progressive scoliosis developing in childhood and adolescence, caused by mutations in the ROBO3 gene which has an important role in axonal guidance and neuronal migration. We describe two female children aged 12 years and 18 months, with progressive scoliosis, in whom the neurological examination showed absent conjugate horizontal eye movements, but preserved vertical gaze and convergence. Cerebral Magnetic resonance imaging findings included pontine hypoplasia, absent facial colliculi, butterfly configuration of the medulla and a deep midline pontine cleft, while Diffusion tensor imaging (DTI) maps showed the absence of decussating ponto-cerebellar fibers and superior cerebellar peduncles. Somatosensory and motor evoked potential studies demonstrated ipsilateral sensory and motor responses. The diagnosis was confirmed by the identification of bi-allelic mutations in the ROBO3 gene.

Multifocal motor neuropathy with high titers of anti‐MAG antibodies

Multifocal motor neuropathy (MMN) and anti‐myelin‐associated glycoprotein (anti‐MAG)‐associated neuropathy are clinically and electrophysiologically distinct entities. We describe a patient with characteristic features of both neuropathies, raising the possibility of an overlap syndrome. A 49‐year‐old patient reported a history of slowly progressive predominantly distal tetraparesis, with mild sensory deficits. Nerve conduction studies demonstrated persistent motor conduction blocks outside compression sites, typical of MMN. Laboratory findings revealed persistently high titers of anti‐MAG immunoglobulin Mλ (IgMλ) paraprotein in the context of a monoclonal gammapathy of unknown significance. Skin biopsy of distal lower limb revealed IgM positive terminal nerve perineurium deposits. This case suggests that the distinction between subtypes of chronic inflammatory neuropathies may not be as clear as initially thought, and that the pattern of pathogenicity of anti‐MAG antibodies may vary.