Jay Desai

Acute Cerebellar Ataxia, Acute Cerebellitis, and Opsoclonus-Myoclonus Syndrome

Acute cerebellar ataxia and acute cerebellitis represent a process characterized by parainfectious, postinfectious, or postvaccination cerebellar inflammation. There is considerable overlap between these entities. The mildest cases of acute cerebellar ataxia represent a benign condition that is characterized by acute truncal and gait ataxia, variably with appendicular ataxia, nystagmus, dysarthria, and hypotonia. It occurs mostly in young children, presents abruptly, and recovers over weeks. Neuroimaging is normal. Severe cases of cerebellitis represent the other end of the spectrum, presenting with acute cerebellar signs often overshadowed by alteration of consciousness, focal neurological deficits, raised intracranial pressure, hydrocephalus, and even herniation. Neuroimaging is abnormal and the prognosis is less favorable than in acute cerebellar ataxia. Acute disseminated encephalomyelitis may be confused with acute cerebellitis when the clinical findings are predominantly cerebellar, but lesions on neuroimaging are usually widespread. Paraneoplastic opsoclonus-myoclonus syndrome is often initially misdiagnosed as acute cerebellar ataxia, but has very specific features, course, and etiopathogensis.

Reduced perfusion in Broca's area in developmental stuttering

To study resting cerebral blood flow in children and adults with developmental stuttering.

Wernicke encephalopathy in children and adolescents

BackgroundWernicke encephalopathy is caused by thiamine (vitamin B1) deficiency. It is generally considered to be a disease of adult alcoholics. However, it is known to occur in the pediatric population and in non-alcoholic conditions.Data sourcesWe searched PubMed with the key words Wernicke, thiamine, pediatric, children and adolescents and selected publications that were deemed appropriate.ResultsThe global prevalence rates of hunger, poverty and resultant nutrient deprivation have decreased in the 21st century. However, several scenarios which may predispose to Wernicke encephalopathy may be increasingly prevalent in children and adolescents such as malignancies, intensive care unit stays and surgical procedures for the treatment of obesity. Other predisposing conditions include magnesium deficiency and defects in the SLC19A3 gene causing thiamine transporter-2 deficiency. The classic triad consists of encephalopathy, oculomotor dysfunction and gait ataxia but is not seen in a majority of patients. Treatment should be instituted immediately when the diagnosis is suspected clinically without waiting for laboratory confirmation. Common magnetic resonance findings include symmetric T2 hyperintensities in dorsal medial thalamus, mammillary bodies, periaqueductal gray matter, and tectal plate.ConclusionsWernicke encephalopathy is a medical emergency. Delay in its recognition and treatment may lead to significant morbidity, irreversible neurological damage or even death. This article aims to raise the awareness of this condition among pediatricians.

Treatment of pediatric chronic inflammatory demyelinating polyneuropathy: Challenges, controversies, and questions

Pediatric chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon acquired disorder of unknown cause, presumed to have an immunological basis. We report 20 patients seen at Children′s Hospital Los Angeles over a period of 10 years. The outcome of our patients was favorable in a vast majority with good response to various treatments instituted. However, residual neurologic deficit was common. The choice of treatment modality was empirical and selected by the treating neurologist. Intravenous immunoglobulin (IVIG) and corticosteroids were most commonly utilized for treatment. Plasmapheresis, mycophenolate mofetil, rituximab, cyclophosphamide, azathioprine, and abatacept were added if the patients were refractory to IVIG or became corticosteroid dependent. The spectrum of disease severity ranged from a single monophasic episode, to multiphasic with infrequent relapses with good response to IVIG, to progressive disease refractory to multiple therapies.

Does one more medication help? Effect of adding another anticonvulsant in childhood epilepsy.

Objectives: To study adding an anticonvulsant in children with uncontrolled epilepsy on ≥1 appropriate anticonvulsants. Methods: Chart review, patients with intractable epilepsy in a neurology clinic July 1, 2004 to December 31, 2007. Inclusion: Children on ≥1 stable anticonvulsant who had a second, third, or fourth anticonvulsant added. Exclusions: Noncompliance, subtherapeutic doses, and/or serum anticonvulsant levels, inappropriate anticonvulsant for seizure type, inadequate documentation, infantile spasms, or significant dosage changes in the baseline anticonvulsant(s) over the follow-up period. Patients were followed until further therapeutic changes occurred or September 30, 2008, whichever came first. Outcome: ≥50% decrease in seizure frequency. Results: Charts reviewed: 1886. Patients who met criteria: 84. Time to assessment: 4 weeks to 42 months (median = 7 months). ≥50% reduction in seizure frequency: 35 of 52 patients with second agent added; 5 of 30 patients with third agent added (P = .0001). Conclusions: Worthwhile seizure reduction is reasonably likely with the addition of a second anticonvulsant, but much less likely with the addition of third anticonvulsant.

Multisystem involvement in neuromyelitis optica

We describe a case of pediatric neuromyelitis optica (NMO) with muscle and lung involvement in addition to central nervous system disease. Our patient initially presented with features of area postrema syndrome, then subsequently with optic neuritis. The patient also had recurrent hyperCKemia that responded to corticosteroids. Finally, axillary and hilar adenopathy with pulmonary consolidation were noted as well and responded to immunomodulation. Our case highlights multisystem involvement in NMO including non-infectious pulmonary findings which have not been described in the pediatric population previously.

Proton Chemical Shift Imaging of the Brain in Pediatric and Adult Developmental Stuttering

Importance Developmental stuttering is a neuropsychiatric condition of incompletely understood brain origin. Our recent functional magnetic resonance imaging study indicates a possible partial basis of stuttering in circuits enacting self-regulation of motor activity, attention, and emotion. Objective To further characterize the neurophysiology of stuttering through in vivo assay of neurometabolites in suspect brain regions. Design, Setting, and Participants Proton chemical shift imaging of the brain was performed in a case-control study of children and adults with and without stuttering. Recruitment, assessment, and magnetic resonance imaging were performed in an academic research setting. Main Outcomes and Measures Ratios of N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (NAA) to creatine (Cr) and choline compounds (Cho) to Cr in widespread cerebral cortical, white matter, and subcortical regions were analyzed using region of interest and data-driven voxel-based approaches. Results Forty-seven children and adolescents aged 5 to 17 years (22 with stuttering and 25 without) and 47 adults aged 21 to 51 years (20 with stuttering and 27 without) were recruited between June 2008 and March 2013. The mean (SD) ages of those in the stuttering and control groups were 12.2 (4.2) years and 13.4 (3.2) years, respectively, for the pediatric cohort and 31.4 (7.5) years and 30.5 (9.9) years, respectively, for the adult cohort. Region of interest–based findings included lower group mean NAA:Cr ratio in stuttering than nonstuttering participants in the right inferior frontal cortex (−7.3%; P = .02), inferior frontal white matter (−11.4%; P < .001), and caudate (−10.6%; P = .04), while the Cho:Cr ratio was higher in the bilateral superior temporal cortex (left: +10.0%; P = .03 and right: +10.8%; P = .01), superior temporal white matter (left: +14.6%; P = .003 and right: +9.5%; P = .02), and thalamus (left: +11.6%; P = .002 and right: +11.1%; P = .001). False discovery rate–corrected voxel-based findings were highly consistent with region of interest findings. Additional voxel-based findings in the stuttering sample included higher NAA:Cr and Cho:Cr ratios (regression coefficient, 197.4-275; P < .001) in the posterior cingulate, lateral parietal, hippocampal, and parahippocampal cortices and amygdala, as well as lower NAA:Cr and Cho:Cr ratios (regression coefficient, 119.8-275; P < .001) in the superior frontal and frontal polar cortices. Affected regions comprised nodes of the Bohland speech-production (motor activity regulation), default-mode (attention regulation), and emotional-memory (emotion regulation) networks. Regional correlations were also observed between local metabolites and stuttering severity (r = 0.40-0.52; P = .001-.02). Conclusions and Relevance This spectroscopy study of stuttering demonstrates brainwide neurometabolite alterations, including several regions implicated by other neuroimaging modalities. Prior ascription of a role in stuttering to inferior frontal and superior temporal gyri, caudate, and other structures is affirmed. Consistent with prior functional magnetic resonance imaging findings, these results further intimate neurometabolic aberrations in stuttering in brain circuits subserving self-regulation of speech production, attention, and emotion.

Encephalitis due to antibodies to voltage gated potassium channel (VGKC) with cerebellar involvement in a teenager

Encephalitis due to antibodies to voltage gated potassium channel (VGKC) typically presents with limbic encephalitis and medial temporal lobe involvement on neuroimaging. We describe a case of 13 year girl female with encephalitis due to antibodies to VGKC with signal changes in the cerebellar dentate nuclei bilaterally and clinical features that suggested predominant cerebellar involvement. These have never been reported previously in the literature. Our case expands the phenotypic spectrum of this rare condition.

Clinical Associations of Occipital Intermittent Rhythmic Delta Activity

Association of occipital intermittent rhythmic delta activity with absence seizures has been well documented in the published literature. Two recent studies have also described an association with focal seizures. After obtaining approval from our Institutional Review Board, all electroencephalograms with occipital intermittent rhythmic delta activity at our institution between July 1, 2006 and December 31, 2009 were identified. Charts of these patients were reviewed to collect clinical data. A matched comparison group was assembled. Thirty-one of the patients who met criteria had evaluable clinical data. Fifteen had generalized seizures (9 absence; 2 tonic-clonic; 3 absence and tonic-clonic; 1 absence, tonic-clonic, myoclonic, and atonic). Eleven had focal seizures. One had both generalized tonic-clonic and focal seizures. Events in 1 were nonepileptic in nature. Documentation was inadequate for seizure classification in 3. There was a statistically significant difference between the study and comparison groups for absence seizures, but not for focal seizures.

Acute Flaccid Myelitis Cases Presenting During a Spike in Respiratory Enterovirus D68 Circulation: Case Series From a Single Pediatric Referral Center.

Abstract Background In 2014, a global outbreak of Enterovirus D68 (EV-D68) caused severe respiratory disease and was associated with an increase in acute flaccid myelitis (AFM) cases. Despite heightened surveillance, both EV-D68 detection and AFM reporting dropped in 2015. As AFM reporting increased in 2016, we sought to better understand AFM and EV-D68 epidemiology at our institution. Methods Chart review of clinical presentation and workup was conducted on patients meeting the case definition for AFM for 2015-16. To determine EV-D68 prevalence at CHLA, samples positive for Rhinovirus/Enterovirus (RV/EV) by FilmArray® Respiratory Panel (FA-RP) in September 2016 were screened for EV-D68 by RT-PCR. Results were compared with a research algorithm developed within the FilmArray®Trend epidemiology software. After establishing accurate EV-D68 prediction, the algorithm was used on historic FA-RP assays to measure EV-D68 prevalence at CHLA in 2015 and 2016. Results 7 patients with a median age of 3.3 years and no significant past medical history presented with AFM between July 15 - October 15, 2016, while none were identified in 2015. All had acute onset patchy weakness involving mostly the upper limbs and grey matter involvement on MRI. 6/7 reported fever/upper respiratory infection prior to AFM onset. CSF from 7/7 was negative by FilmArray®meningitis/encephalitis Panel and 2/7 were positive for EBV DNA. Further work up on CSF and blood were negative. 4/7 (57.1%) patients were RV/EV positive from respiratory samples and 3 were confirmed as EV-D68 by RT-PCR. IVIG was given in 7/7 cases. Patients were discharged after an average of 8.8 (4.8-13.6) days. The FilmArray Trend monitoring revealed that during the time of AFM presentation in 2016, 226/778 patients tested for respiratory viruses by the FA-RP were positive for RV/EV. Of those, 29.2% (66/226) were positive for EV-D68 compared with 0.02% (2/224) over the same period in 2015. Conclusion As shown by CDC surveillance data, we saw a resurgence of AFM cases in 2016 compared with 2015. All 7 patients identified were previously healthy and had persistent weakness at discharge. Cases were accompanied by increases in circulating respiratory EV-D68. Further investigation of the correlation between EV-D68 resurgence and AFM is warranted. Disclosures L. Meyers, BioFire Diagnostics: Employee, Salary. J. Jones, Biofire Diagnostics LLC: Employee, Salary. J. Dien Bard, BioFire: Consultant and Investigator, Research grant and Speaker honorarium.