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Background Patients with autism spectrum disorder and developmental delay or encephalopathy rarely demonstrate no or negligible hair and nail growth, suggesting a biotin-responsive clinical disorder. Methods A ten-year-old girl presented with features of autism spectrum disorder, isolated headaches, and episodes of headaches and limb shaking. Her medical history revealed that her hair and nails did not grow. Administration of biotin restored her nail and hair growth and improved intellectual ability and school performance. Her episodes of headaches, single limb shaking, and loss of consciousness responded to administration of acetazolamide, and her school performance and social skills further improved. Results A de novo c.1091 C > T, p.T364M pathogenic variant was found in the ATP1A2 gene by whole-exome sequencing, but a genetic etiology in the biotin-responsive metabolic pathways was not identified. Conclusions The combination of biotin and acetazolamide treatment was successful in restoring normal mental function and school performance. Poor or no clinical nail and hair growth in any child with a developmental delay-autism spectrum disorder presentation should be considered as evidence for a biotin-responsive genetic disorder even when exome testing is negative.

Localization of the epileptogenic zone (EZ) is challenging in children with tuberous sclerosis complex (TSC). We sought to ascertain whether brain MRI could identify the EZ in TSC patients independent of the clinical and diagnostic data.Presurgical MRI's of 34 children with TSC who underwent epilepsy surgery at Miami Children's Hospital were retrospectively reevaluated by experts blinded to all other data. Changes typical of TSC (tubers, calcifications, cystic changes) and abnormalities of the perituberal cortex typical of focal cortical dysplasia (FCD) (increased cortical thickness, abnormal gyration, transmantle change, gray/white matter junction blurring) were identified and their localization was compared with the resection site. Sensitivity, specificity and accuracy of individual MRI features to localize the EZ were determined and statistically compared between postoperatively seizure-free and non-seizure-free patients as well as clusters of features typical of FCD and TSC.MRI alone correctly localized the resection cavity in all 19 postoperatively seizure-free patients and 12 of 15 non-seizure-free subjects. Sensitivity, specificity and accuracy of MRI features typical of FCD to localize EZ (90%, 96% and 96%, respectively) were superior to those typical of TCS (79%, 75% and 75%, p0.0001). Increased cortical thickness and abnormal gyral formation outside tubers occurred only in the resection site. Resection sites were better predicted by MRI in seizure-free than in non-seizure-free patients.Thorough MRI evaluation identifies the EZ in a significant proportion of TSC patients. Epileptogenic regions were mostly characterized by "FCD-like" changes outside cortical tubers. The findings may have important practical consequences for surgical planning in TSC.

The preoperative evaluation of patients with suspected cortical dysplasia involves detailed neurologic and neuropsychologic evaluations, electroencephalography, and comprehensive neuroimaging and functional studies. The goal is to identify a focal region of seizure onset and to assess for motor impairments, speech and language difficulties, or developmental delay. Although the electroencephalogram abnormalities in cortical dysplasia are nonspecific, they typically include unusual high-amplitude (slowing and focal) activity. The association of cortical dysplasia with cardiovascular, dermatologic, and other systemic disorders is discussed.

Many patients who were once considered inoperable are candidates for a wide variety of surgical procedures. This trend is particularly striking at pediatric centers that serve patients with diverse forms of epilepsy that compromise development. Newer diagnostic techniques, including structural and functional imaging, EEG monitoring, and surgical technology, can provide a complete representation of the etiology and expression of the epileptic focus, including accurate cortical localization. This review focuses on several forms of epilepsy that, until recently, were not regarded to be surgically amenable. The adverse seizure and neurobehavioral prognosis in patients with these disorders provides the justification to search for innovative treatments. With more sophisticated tools for preoperative evaluation and an expanding knowledge base, it is likely that the number of surgical candidates will continue to increase in the future.

To define the contribution of the EEG evaluation in children with seizures and Sturge-Weber syndrome, we reviewed EEG data in 14 radiologically confirmed cases. Thirteen exhibited marked voltage attenuation that was localized to the region of the cerebral angiomatosis. Polymorphic slowing occurred ipsilateral to the lesion in six patients and was bilateral in six. By contrast, interictal spikes were evident in only two patients and did not always correlate with the angiomatosis. Seizures were captured in four patients and consistently revealed ictal discharges only at the periphery of the lesion. These findings indicate that abnormalities of EEG background rather than interictal spikes are consistently present early in the course of Sturge-Weber syndrome and correlate with the region of angiomatosis.

There are no reports of an association between obsessive-compulsive disorder and cingulate epilepsy in childhood. We report the behavioral, cognitive, and EEG findings in a young girl with medically resistant seizures and severe obsessive-compulsive symptomatology. Her Scalp EEG and neuropsychological test scores suggested right frontal lobe dysfunction. The intractability of her seizures and progressive intellectual and psychosocial deterioration prompted evaluation for excisional surgery. Intracranial EEG recording demonstrated a focal seizure origin in the right anterior cingulate gyrus. Cingulotomy resulted in freedom from seizures and significant improvement in her obsessive-compulsive symptoms.

We studied the clinical efficacy of 4-channel cassette recording of the EEG for 105 children being evaluated for possible seizures or further clarification of a known seizure disorder. Compared to the conventional EEG, 24 hour cassette EEG (C-EEG) studies yielded new diagnostic electroclinical information for 21 percent of the children (22 patients). For 41 percent of cases, the C-EEG findings considerably broadened the clinical knowledge of the disorder and provided a basis for therapy modification. In the remaining 38 percent, no significant electrical or clinical events occurred so that C-EEG studies yielded no new important information. The utility of C-EEG was greatest for younger patients with generalized epilepsies whereas older children with partial epilepsies constituted the majority of diagnostic failures. These findings demonstrate that C-EEG recording may contribute useful information concerning childhood paroxysmal disorders, and underscore the importance of careful patient selection.

Differentiating seizures from pseudoseizures frequently is challenging in very young children manifesting repetitive, stereotypic behavior. Using video electroencephalographic recording, we evaluated 60 patients, younger than 10 years of age, with episodic signs and symptoms believed to be seizures despite repeatedly normal routine electroencephalograms. Nine patients (15%) had simple partial and atypical absence seizures. Twenty-four patients (40%) had pseudoseizures presenting as rhythmic movements or staring. Pseudoseizure frequency was greater than the frequency of true seizures; brief staring episodes were common. Motor pseudoseizures usually were of longer duration than true seizures and could be brought on with verbal encouragement. Furthermore, the stereotypic motor presentations were quite different from those of true motor seizures but were difficult to recognize from historic, clinical, and routine electroencephalographic data. Symptomatic patients can be clinically diagnosed by analyzing confirmed episodes with video electroencephalography.