Lalitha Sivaswamy

Alterations in Frontal Lobe Tracts and Corpus Callosum in Young Children with Autism Spectrum Disorder

Major frontal lobe tracts and corpus callosum (CC) were investigated in 32 children with autism spectrum disorder (ASD, mean age: 5 years), 12 nonautistic developmentally impaired children (DI, mean age: 4.6 years), and 16 typically developing children (TD, mean age: 5.5 years) using diffusion tensor imaging tractography and tract-based spatial statistics. Various diffusion and geometric properties were calculated for uncinate fasciculus (UF), inferior fronto-occipital fasciculus (IFO), arcuate fasciculus (AF), cingulum (Cg), CC, and corticospinal tract. Fractional anisotropy was lower in the right UF, right Cg and CC in ASD and DI children; in right AF in ASD children; and in bilateral IFO in DI children, compared with TD children. Apparent diffusion coefficient was increased in right AF in both ASD and DI children. The ASD group showed shorter length of left UF and increased length, volume, and density of right UF; increased length and density of CC; and higher density of left Cg, compared with the TD group. Compared with DI group, ASD group had increased length, volume, and density of right UF; higher volume of left UF; and increased length of right AF and CC. Volume of bilateral UF and right AF and fiber density of left UF were positively associated with autistic features.

A diffusion tensor imaging study of the cerebellar pathways in children with autism spectrum disorder

Children with autistic spectrum disorder are known to have histopathological abnormalities in the cerebellum. Diffusion tensor imaging has been utilized to study abnormalities in connectivity and microintegrity in brains of such children. A region of interest approach was adopted to study cerebellar outflow and inflow pathways in 27 children (24 males; mean age, 5.0 years) with autism, and comparison was made with 16 normally developing controls. An increase in the mean diffusivity of bilateral superior cerebellar peduncles in those with autistic spectrum disorder was noted, as was a reversal of the asymmetry pattern in fractional anisotropy of the middle cerebellar peduncle and the inferior cerebellar peduncle in the autistic spectrum disorder group, compared with controls. This study reiterates the underconnectivity between the cerebellum and neocortex, using diffusion tensor imaging.

Absence of Arcuate Fasciculus in Children with Global Developmental Delay of Unknown Etiology: A Diffusion Tensor Imaging Study

OBJECTIVE To investigate cortical association tracts using diffusion tensor imaging (DTI) in children with global developmental delay of unknown etiology. STUDY DESIGN We performed DTI in 20 patients (age range: 18-83 months, mean: 45 +/- 16 months, 12 males) with a history of global developmental delay and 10 typically developing children (age range: 26-99 months, mean: 54 +/- 24 months, 5 males). DTI tractography was performed to isolate major cortical association tracts. RESULTS In 9 out of 20 patients, arcuate fasciculus (AF) was absent bilaterally and in another 2 patients, it was absent in left hemisphere. In contrast, AF was present bilaterally in all typically developing children. Fractional Anisotropy (FA) of inferior longitudinal fasciculus (ILF) was asymmetric in the control group but not in the developmental delay group (P = .04). FA was significantly reduced in right ILF in developmentally delayed children compared with controls (P = .03). FA of other association tracts was not different between patients and controls (P = NS). The apparent diffusion coefficient (ADC) showed no asymmetry for these tracts in controls or developmentally delayed children (P = NS). CONCLUSIONS DTI can be used to identify absence of AF and inadequate maturation of ILF in children with global developmental delay of unknown etiology.

Active Comparator-Controlled, Rater-Blinded Study of Corticotropin-Based Immunotherapies for Opsoclonus-Myoclonus Syndrome

To test the efficacy and safety of corticotropin-based immunotherapies in pediatric opsoclonus-myoclonus syndrome, 74 children received corticotropin alone or with intravenous immunoglobulin (groups 1 and 2, active controls); or both with rituximab (group 3) or cyclophosphamide (group 4); or with rituximab plus chemotherapy (group 5) or steroid sparers (group 6). There was 65% improvement in motor severity score across groups (P < .0001), but treatment combinations were more effective than corticotropin alone (P = .0009). Groups 3, 4, and 5 responded better than group 1; groups 3 and 5 responded better than group 2. The response frequency to corticotropin was higher than to prior corticosteroids (P < .0001). Fifty-five percent had adverse events (corticosteroid excess), more so with multiagents (P = .03); and 10% had serious adverse events. This study demonstrates greater efficacy of corticotropin-based multimodal therapy compared with conventional therapy, greater response to corticotropin than corticosteroid-based therapy, and overall tolerability.

The corticospinal tract in Sturge-Weber syndrome: a diffusion tensor tractography study.

OBJECTIVE To utilize diffusion tensor tractography and evaluate the integrity of the corticospinal tract in children with unilateral Sturge-Weber syndrome (SWS). METHODS Sixteen children (age: 1.5-12.3 years) with SWS involving one hemisphere and varying degrees of motor deficit, underwent magnetic resonance imaging (MRI) as part of a prospective clinical research study. Diffusion tensor imaging (DTI) was obtained and fiber tracking of the corticospinal tract was performed yielding average FA and ADC values along the pathway. These values were compared between the two hemispheres (affected vs. unaffected) and also correlated with the degree of motor deficits, after correction for age. RESULTS Corticospinal tract FA values on the side of the affected hemisphere were lower (p=0.008) and ADC values were higher (p=0.011) compared to the normal side. Furthermore, FA and ADC values on the side of the angioma did not show the normal age-related variations, which the contralateral corticospinal pathway values did demonstrate. Although none of the patients had severe hemiparesis, those with moderate motor deficit had increased ADC values, as compared to those with mild (p=0.009) or no motor deficit (p=0.045). CONCLUSION MRI with DTI shows abnormalities of the corticospinal tract in children with SWS even before severe motor impairment develops. Thus, DTI can be a clinically useful method to evaluate the integrity of the corticospinal tract in young children who are at risk for progressive motor dysfunction.

Seizure control following palliative resective surgery for intractable epilepsy-a pilot study.

BACKGROUND Patients with intractable epilepsy who have bilateral epileptic foci may not qualify for curative epilepsy surgery. In some cases palliative resection may be undertaken with a goal to decrease seizure frequency and improve quality of life. Here we present data on the outcome of palliative epilepsy surgery in children. METHODS We reviewed medical charts of children who underwent palliative resection for intractable epilepsy during the years 1999-2013 at Childrens Hospital of Michigan. The palliative intent of resection was declared preoperatively. Outcome was assessed in terms of seizure reduction. RESULTS There were 18 patients (11 males, median age of surgery was 3.5 years [range 0.5-16 years]). The median duration of follow-up after surgery was 12.5 months (range 6-60 months). Hemispherectomy was the most commonly performed palliative resection (nine patients), followed by lobectomy (six patients), multilobar resection (one patient), and tuberectomy (two patients). Reduction in seizure frequency was observed in 11 patients, with eight patients achieving seizure freedom on antiepileptic drugs and three with >50% reduction in seizure frequency. Transient improvement in seizure frequency occurred in two patients, whereas there was no benefit in five patients. CONCLUSIONS Beneficial effects of epilepsy surgery may be realized in carefully selected situations wherein the most epileptogenic focus is resected to reduce seizure burden and improve quality of life.

Management of Pediatric Migraine in a Tertiary Care Versus Community Based Emergency Department: An Observational Pilot Study

BACKGROUND Because of a lack of guidelines for the management of pediatric migraine in the emergency department setting, marked variations in treatment protocols exist between institutions. We aimed to characterize differences in management strategies for pediatric migraine treatment between a community-based and a tertiary care emergency department. METHODS A retrospective cohort study was performed to include pediatric patients presenting with headache fulfilling the International Classification of Headache Disorders-2 migraine criteria in a tertiary care (site 1) and a community based (site 2) emergency department. The two sites were compared with respect to patient demographics and approach to treatment. RESULTS A total of 158 patients at site 1 (mean age 13.6 years, 70% female, 68% African-American) and 63 patients at site 2 (mean age 16.7 years, 71% female, 100% Caucasian) were analyzed. Opiate use (7.6% vs. 33%), imaging (6.3% vs. 20.6%), use of nonsteroidal anti-inflammatory drugs/serotonin agonists at discharge (72.7% vs. 22.2%), and admission rates to hospital (22% vs. 0%) were significantly different. Logistic regression analysis indicated that the main predictors of hospital admission were use of opiates and intravenous combination abortive therapy. CONCLUSION Low rates of intravenous combination therapy, antidopaminergic agent, and serotonin agonist use were noted across both hospital settings. Community-based physicians used opiates and obtained neuro-imaging more than those in the academic setting. Standardization of care in the emergency setting coupled with reliable acute care plans that are based on evidenced-based guidelines can allow for better control of episodic migraine and reduce emergency department visits.

Approach to Neonatal Seizures

Neonatal seizures can be difficult to recognize given the variation in their presentation. Hence, diagnosis and appropriate treatment may be delayed. Morphology of seizures in this age group is discussed, followed by common etiological entities. Special emphasis is laid on treatable disease states such as vitamin responsive seizure disorders and benign conditions that may not warrant aggressive treatment. Conditions that may have devastating neurological consequences are discussed in some detail so that the treating pediatrician can provide realistic information to the parents of such newborns. Imaging and laboratory workup is outlined, followed by guidelines for ordering and interpreting an electroencephalogram in this age group. Finally, treatment options in the form of antiepileptics are discussed with mention of new avenues for diagnosis and treatment that may become commonly employed in the future.

Approach to Acute Ataxia in Childhood: Diagnosis and Evaluation

Ataxia refers to motor incoordination that is usually most prominent during movement or when a child is attempting to maintain a sitting posture. The first part of the review focuses on the anatomic localization of ataxia--both within the nervous system and without--using a combination of historical features and physical findings. The remainder of the review discusses etiological considerations that vary depending on the age group under consideration. In infancy, certain specific diseases, such as opsoclonus myoclonus ataxia syndrome, must receive special mention because the underlying disease process may be amenable to surgical intervention. In the toddler- and school-age groups, certain conditions (such as stroke and acute cerebellitis) require immediate recognition and imaging, whereas others (such as post-infectious ataxia and concussion) require close follow-up. Finally, mention must be made of diseases outside of the central nervous system that can present with ataxia, such as Guillain-Barré syndrome.

Adherence to Quality Measures in a Pediatric Epilepsy Center: A Pilot Study

A retrospective study was conducted to determine compliance with the American Academy of Neurology quality measures for epilepsy care in a single tertiary care pediatric epilepsy clinic. Paper and electronic charts of children 0 to 20 years of age, with an established diagnosis of epilepsy, who receive their medical care at the Childrens Hospital of Michigan in Detroit, were reviewed. Of the eight quality measures suggested for surveillance, the least compliant measures were counseling for young adults of childbearing age and recommendations regarding epilepsy specific safety issues. The quality measures where greatest adherence was demonstrated were ordering and review of electroencephalogram results at clinic visits and documentation of frequency of seizures. Practitioner education, use of electronic checklists, and an automated tracking system may enhance compliance and ultimately lead to superior patient care.