SUMMARYObjective: Seizures constitute a frequent yet under-described manifestation of mitochondrial disorders (MDs). The aim of this study was to describe electroencephalography (EEG) findings and clinical seizure types in a population of children and adults with mitochondrial disease. Methods: Retrospective chart review of 165 records of children and adults with mitochondrial disease seen in the University of Texas Houston Mitochondrial Center between 2007 and 2012 was performed; all subjects were diagnosed with confirmed mitochondrial disease. EEG findings and clinical data, including seizure semiology and response to antiepileptic drugs (AEDs), were analyzed and categorized. Results: Sixty-six percent (109/165) of subjects had a routine EEG performed. Sixtyone percent (67/109) of EEG studies were abnormal and 85% (56/67) had epileptiform discharges. The most common EEG finding was generalized slowing (40/67, 60%). The most frequent category of epileptiform activity seen was multifocal discharges (41%), followed by focal (39%) and generalized (39%) discharges. Clinical seizures were seen in 55% of subjects and the most common types of seizures observed were complex partial (37%) and generalized tonic-clonic (GTC; 37%). The most common seizure type in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) was GTC (33%), with generalized or focal discharges seen on EEG. In Leigh syndrome GTC (11%) and complex partial (11%) seizures were the most frequent types. Of 60 subjects with clinical seizures, 28% were intractable to medical treatment. Significance: Mitochondrial disorder should be included in the list of differential diagnosis in any child that presents with encephalopathy, seizures, and a fluctuating clinical course. Given the relatively high prevalence of EEG abnormalities in patients with MD, EEG should be performed during initial evaluation in all patients with MD, not only upon clinical suspicion of epilepsy.

PFT in childhood PBO was characterized by significant airway obstruction. Over time, FVC (lung parenchyma) increased and FEV1 (airway) remained stable, but FEV1/FVC ratio declined more than expected, suggesting a mismatch in the growth of the airway and lung parenchyma (dysanaptic growth). Further studies in larger populations are needed to validate these observations.

A retrospective chart review study was performed to determine the presence of sleep disordered breathing (SDB) in children with primary mitochondrial disease (MD). The symptoms, sleep-related breathing, and movement abnormalities are described for 18 subjects (ages 1.5 to 18 years, 61% male) with MD who underwent polysomnography in our pediatric sleep center from 2007 to 2012. Of the 18 subjects with MD, the common indications for polysomnography were excessive somnolence or fatigue (61%, N = 11), snoring (44%, N = 8), and sleep movement complaints (17%, N = 3). Polysomnographic measurements showed SDB in 56% (N = 10) (obstructive sleep apnea in 60% (N = 6), hypoxemia in 40% (N = 4), and sleep hypoventilation in 20% (N = 2)). There was a significant association between decreased muscle tone and SDB (P: 0.043) as well as obese and overweight status with SDB (P = 0.036). SDB is common in subjects with MD. Early detection of SDB, utilizing polysomnography, should be considered to assist in identification of MD patients who may benefit from sleep-related interventions.

No abstract

A previously healthy 10-year-old girl presented with subacute onset of ataxia and acute-onset cardiac and pulmonary failure. Magnetic resonance imaging (MRI) of the brain showed symmetric T2 fluid-attenuated inversion recovery hyperintensities in the dorsal pons, medulla, and inferior cerebellar peduncles; nerve conduction velocities and electromyography demonstrated a sensorimotor axonal neuropathy consistent with Friedreich ataxia. Within 12 months, the patient fully recovered and molecular testing of the frataxin gene was unremarkable. Two years later, the patient returned with acute neurologic decompensation and died one month later from progressive demyelination of the brainstem. Mitochondrial DNA sequencing revealed a mutation at 8344A>G in transfer RNA lysine with heteroplasmy at 98% consistent with a diagnosis of a primary mitochondrial disorder.