Delineation of the movement disorders associated with FOXG1 mutations.

OBJECTIVE: The primary objective of this research was to characterize the movement disorders associated with FOXG1 mutations. METHODS: We identified patients with FOXG1 mutations who were referred to either a tertiary movement disorder clinic or tertiary epilepsy service and retrospectively reviewed medical records, clinical investigations, neuroimaging, and available video footage. We administered a telephone-based questionnaire regarding the functional impact of the movement disorders and perceived efficacy of treatment to the caregivers of one cohort of participants. RESULTS: We identified 28 patients with FOXG1 mutations, of whom 6 had previously unreported mutations. A wide variety of movement disorders were identified, with dystonia, choreoathetosis, and orolingual/facial dyskinesias most commonly present. Ninety-three percent of patients had a mixed movement disorder phenotype. In contrast to the phenotype classically described with FOXG1 mutations, 4 patients with missense mutations had a milder phenotype, with independent ambulation, spoken language, and normocephaly. Hyperkinetic involuntary movements were a major clinical feature in these patients. Of the symptomatic treatments targeted to control abnormal involuntary movements, most did not emerge as clearly beneficial, although 4 patients had a caregiver-reported response to levodopa. CONCLUSIONS: Abnormal involuntary movements are a major feature of FOXG1 mutations. Our study delineates the spectrum of movement disorders and confirms an expanding clinical phenotype. Symptomatic treatment may be considered for severe or disabling cases, although further research regarding potential treatment strategies is necessary.

The role of hypoxia-ischemia in term newborns with arterial stroke.

The role of generalized hypoxia-ischemia in the genesis of perinatal focal arterial stroke remains puzzling. Animal studies have demonstrated that hypoxia-ischemia may alter blood flow through the ductus venosus, thereby increasing the risk for placental emboli entering the cerebral circulation. A retrospective review was performed of clinical records of all term newborns admitted to a tertiary perinatal center between January 1995 and May 2007 with acute arterial stroke on neuroimaging during the first week of life. Newborns were classified into 2 groups on the basis of neuroimaging abnormalities: stroke alone, or stroke and nonfocal hypoxic-ischemic brain injury. A total of 62 newborns had focal or multifocal stroke, 36 with stroke alone and 26 with stroke with nonfocal hypoxia-ischemia. Multiple risk factors for hypoxia-ischemia occurred in most newborns in both groups. These data indicate that hypoxia-ischemia may play a role in the genesis of stroke in the term newborn with or without evidence of nonfocal hypoxic-ischemic brain injury on neuroimaging.