Ata Siddiqui

N-Methyl-D-Aspartate Receptor Antibodies in Post-Herpes Simplex Virus Encephalitis Neurological Relapse

Herpes simplex virus encephalitis (HSVE) is a devastating condition that relapses, often with a chorea in children, despite adequate antiviral treatment. At relapse, evidence of viral replication is frequently absent, suggesting that the relapse may be immune‐mediated. Seven children who had a neurological relapse following their initial encephalitis, identified from 20 cases of pediatric HSVE, were studied. Serum and/or cerebrospinal fluid (CSF) were tested for N‐methyl‐D‐aspartate receptor (NMDAR) and other antibodies previously reported in central nervous system autoimmunity. Five of the 7 relapsing children had choreoathetosis; 2 of these were NMDAR antibody–positive, 2 were negative (1 with HSV‐positive CSF), and 1 was not available for testing. An additional patient, who relapsed with cognitive regression but with no movement disorder, was also NMDAR antibody–positive. In 2 of the NMDAR antibody–positive patients who were treated at relapse and in 1 who was treated only after 10 years of having a relapsing encephalopathy, a beneficial response was observed. Neurological relapses after HSVE may frequently be immune‐mediated, particularly in children with chorea. NMDAR antibodies are common, and immunotherapy may be beneficial.

NMDA receptor antibodies associated with distinct white matter syndromes

Objective: To report the clinical and radiologic findings of children with NMDA receptor (NMDAR) antibodies and white matter disorders. Method: Ten children with significant white matter involvement, with or without anti-NMDAR encephalitis, were identified from 46 consecutive NMDAR antibody–positive pediatric patients. Clinical and neuroimaging features were reviewed and the treatment and outcomes of the neurologic syndromes evaluated. Results: Three distinct clinicoradiologic phenotypes were recognized: brainstem encephalitis (n = 3), leukoencephalopathy following herpes simplex virus encephalitis (HSVE) (n = 2), and acquired demyelination syndromes (ADS) (n = 5); 3 of the 5 with ADS had myelin oligodendrocyte glycoprotein as well as NMDAR antibodies. Typical NMDAR antibody encephalitis was seen in 3 patients remote from the first neurologic syndrome (2 brainstem, 1 post-HSVE). Six of the 7 patients (85%) who were treated acutely, during the original presentation with white matter involvement, improved following immunotherapy with steroids, IV immunoglobulin, and plasma exchange, either individually or in combination. Two patients had escalation of immunotherapy at relapse resulting in clinical improvement. The time course of clinical features, treatments, and recoveries correlated broadly with available serum antibody titers. Conclusion: Clinicoradiologic evidence of white matter involvement, often distinct, was identified in 22% of children with NMDAR antibodies and appears immunotherapy responsive, particularly when treated in the acute phase of neurologic presentation. When observed, this clinical improvement is often mirrored by reduction in NMDAR antibody levels, suggesting that these antibodies may mediate the white matter disease.

Distinguishing optic neuritis in neuromyelitis optica spectrum disease from multiple sclerosis: a novel magnetic resonance imaging scoring system.

Background: The management of acute optic neuritis differs according to the underlying etiology and techniques which may help with early differential diagnosis are therefore of considerable value. Objective: We wanted to determine if multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) could be differentiated on the basis of neuroimaging abnormalities of the anterior visual pathways following an episode of optic neuritis. Methods: Magnetic resonance imaging (MRI) findings of 27 patients diagnosed with MS (n = 15) or NMOSD (n = 12), who presented with acute isolated optic neuritis over a 3-year period, were reviewed retrospectively. The extent and location of inflammation along the anterior visual pathways were analyzed. A novel scoring system was devised, based upon the number of anatomical segments involved. Results: Patients with NMOSD had a relative risk of 7.5 (confidence interval: 0.3–17.3) of having a score of 4 or more. Only NMOSD patients were found to have a score of 6 or higher. A trend for more posterior involvement of the anterior visual pathways was noted in the NMOSD group. Conclusion: This pilot study suggests that the MRI-based scoring system described here may aid in distinguishing patients with optic neuritis who have MS vs NMOSD. Visual pathway inflammation in NMOSD patients appears to be more extensive than in MS, mirroring the longitudinally extensive spinal cord lesions found in neuromyelitis optica.

White matter abnormalities and dystonic motor disorder associated with mutations in the SLC16A2 gene

Aim  Mutations in the SLC16A2 gene have been implicated in Allan–Herndon–Dudley syndrome (AHDS), an X‐linked learning disability * syndrome associated with thyroid function test (TFT) abnormalities. Delayed myelination is a non‐specific finding in individuals with learning disability whose genetic basis is often uncertain. The aim of this study was to describe neuroimaging findings and neurological features in males with SLC16A2 gene mutations.

Extensive white matter abnormalities associated with neonatal Parechovirus (HPeV) infection

White matter changes in the neonatal period are commonly associated with hypoxic-ischaemic injuries and, less frequently, infections. Enteroviral (EV) meningoencephalitis as a cause of extensive white matter changes in newborns is well documented but Human Parechovirus (HPeV) associated with a similar picture has only been recently recognized. We report a case of HPeV-related neonatal meningoencephalitis associated with extensive white matter abnormalities, giving rise to a wide differential diagnosis including consequences of hypoxic-ischaemic encephalopathy (HIE) and periventricular leucomalacia (PVL). This case highlights the importance of excluding both EV and HPeV infection in neonates presenting with signs and symptoms of encephalitis. Moreover, HPeV infection ought to be considered in infants with white matter changes suggestive of HIE but no convincing history of a perinatal hypoxic-ischaemic insult.

EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy

Vici syndrome is a progressive neurodevelopmental multisystem disorder caused by mutations in the autophagy gene EPG5. Byrne et al. characterise the phenotype of 50 affected children, revealing callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, immune dysfunction, developmental delay and microcephaly. Downregulation of epg5 in Drosophila results in autophagic abnormalities and progressive neurodegeneration.

Central motor conduction studies and diagnostic magnetic resonance imaging in children with severe primary and secondary dystonia

Aim  Dystonia in childhood has many causes. Imaging may suggest corticospinal tract dysfunction with or without coexistent basal ganglia damage. There are very few published neurophysiological studies on children with dystonia; one previous study has focused on primary dystonia. We investigated central motor conduction in 62 children (34 males, 28 females; age range 3–19y, mean age 10y 8mo, SD 4y 8mo) with severe dystonia to evaluate corticospinal tract integrity before consideration for deep brain stimulation.

Role of thyroidectomy in advanced laryngeal and pharyngolaryngeal carcinoma

Objective: Total thyroidectomy (TThy) or hemithyroidectomy (HThy) in conjunction with a total laryngectomy (TL) or pharyngolaryngectomy (PL) for laryngeal carcinoma often results in hypothyroidism requiring life-long thyroid hormone replacement. The aims were to determine the incidence of thyroid gland (TG) invasion in patients undergoing TL or TPL with TThy or HThy for laryngeal or hypopharyngeal carcinoma and to assess predicative factors. Study Design: Case series with chart review. Setting: Guys Hospital, London, UK. Subjects and Methods: Thirty-five patients from 2004 to 2008 were reviewed. Specimens were examined to determine the incidence of TG invasion and predicative factors. Preoperative imaging was reviewed to assess the radiological evidence of TG invasion. Results: TL and TThy were performed in 19 patients, TL and HThy in three patients, and PL and TThy in 13 patients. Surgery was performed for primary and recurrent carcinoma in 28 and eight patients, respectively. Histological evidence of invasion of the TG was found in three patients (8.5%). No significant relationship was found between TG invasion and patients sex, subsite of primary carcinoma, stage of primary disease at surgery, degree of differentiation, or the presence of subglottic extension. In addition, no significant relationship was found between the presence of TG invasion and recurrent disease. Definite evidence of radiological invasion of the TG was seen in only one patient. Conclusions: Invasion of the TG in patients undergoing TL or TPL is a rare event and limits the need for TThy in most cases.

Generalized arterial calcification of infancy: Phenotypic spectrum among three siblings including one case without obvious arterial calcifications†‡

Generalized arterial calcification of infancy (GACI) (OMIM no. 208000) is characterized by calcification of the major arteries and soft tissues and associated with mutations in the ENPP1 gene. Most affected patients die within the first 6 months of life although prolonged survival is increasingly recognized. We report on three siblings with GACI and striking phenotypic variability. Two siblings (including the sibling survivor) were compound heterozygotes for mutations in exon 7 (c.783C>G (p.Y261X)) and exon 8 (c. 878_879delAA (p.K293fsX5)) of the ENPP1 gene confirming the diagnosis of GACI. The sibling survivor did not have calcification on X‐ray studies or evidence of hypophosphatemic rickets. GACI may be under recognized and we emphasize consideration of this condition in patients with multiple arterial stenosis even in the absence of radiographic calcification. This adds to the expanding phenotype of GACI and supports a potential role for modifying genes.

Osmotic demyelination syndrome associated with hypophosphataemia: 2 cases and a review of literature

Central and extrapontine myelinolysis are collectively known as osmotic demyelination syndrome. This encephalopathic illness has been well documented in the adult literature, occurring most commonly in the context of chronic alcoholism, correction of hyponatraemia and liver transplantation. Aetiology and outcome in the paediatric population are less well understood.