A De Novo Dominant Negative Mutation in DNM1L Causes Sudden Onset Status Epilepticus with Subsequent Epileptic Encephalopathy.

Mitochondrial dynamics such as fission and fusion play a vital role in normal brain development and neuronal activity. DNM1L encodes a dynamin-related protein 1 (Drp1), which is a GTPase essential for proper mitochondrial fission. The clinical phenotype of DNM1L mutations depends on the degree of mitochondrial fission deficiency, ranging from severe encephalopathy and death shortly after birth to initially normal development and then sudden onset of refractory status epilepticus with very poor neurologic outcome. We describe a case of a previously healthy 3-year-old boy with a mild delay in speech development until the acute onset of a refractory status epilepticus with subsequent epileptic encephalopathy and very poor neurologic outcome. The de novo missense mutation in DNM1L (c.1207C > T, p.R403C), which we identified in this case, seems to determine a unique clinical course, strikingly similar to four previously described patients in literature with the identical de novo heterozygous missense mutation in DNM1L.

Successful treatment of a newborn with acute myocardial infarction on the first day of life.

Cardiogenic shock occurring after acute neonatal myocardial infarction (MI) due to coronary artery thrombosis is very rarely encountered. Acute neonatal MI typically presents suddenly with usually a fatal outcome. Treatment options in patients with this condition are limited. There are previous case reports in the literature advocating the use of extracorporeal membrane oxygenation for hemodynamic support. In this report, we present a newborn with severe MI secondary to thrombus formation within the left anterior descending coronary artery. There also proved to be a Factor V Leiden heterozygotic mutation. The patient initially presented with cardiogenic shock. After resuscitation and thrombolytic therapy were administered, coronary artery patency was restored resulting in myocardial revitalization and recovery of left-ventricular function within 4 weeks.

Do patients with congenital hemiparesis and ipsilateral corticospinal projections respond differently to constraint-induced movement therapy?

This study investigates whether the type of corticospinal reorganization (identified by transcranial magnetic stimulation) influences the efficacy of constraint-induced movement therapy (CIMT). Nine patients (five males, four females; mean age 16y [SD 6y 5mo], range 11-30y) controlling their paretic hand via ipsilateral corticospinal projections from the contralesional hemisphere and seven patients (three males, four females; mean age 17y [SD 7y], range 10-30y) with preserved crossed corticospinal projections from the affected hemisphere to the paretic hand underwent 12 consecutive days of CIMT. A Wolf motor function test applied before and after CIMT revealed a significant improvement in the quality of upper extremity movements in both groups. Only in patients with preserved crossed projections, however, was this amelioration accompanied by a significant gain in speed, whereas patients with ipsilateral projections tended to show speed reduction. These data, although preliminary, suggest that patients with congenital hemiparesis and ipsilateral corticospinal projections respond differently to CIMT.

(Re-)organization of basal ganglia in congenital hemiparesis with ipsilateral cortico-spinal projections.

In congenital hemiparesis after pre- or perinatally acquired unilateral brain lesions, many patients control their paretic hand via ipsilateral cortico-spinal projections from the contralesional hemisphere. In order to clarify the pattern of basal ganglia activation in case of such a shift of the primary motor cortical representation (M1) of the paretic hand to the contralesional hemisphere, fMRI was performed in eight patients with congenital hemiparesis due to unilateral periventricular white matter lesions and ipsilateral corticospinal projections to the paretic hand (as determined by focal transcranial magnetic stimulation). FMRI during active movements of the paretic hand yielded basal ganglia activation in the ipsilateral (=contralesional) hemisphere, but not in the contralateral (lesioned) hemisphere. Thus, (re-)organization in congenital hemiparesis with ipsilateral cortico-spinal projections includes, in addition to the ipsilateral primary motor cortex (M1), also the ipsilateral basal ganglia - in contrast to the primary somatosensory cortex (S1), which is typically preserved in the affected hemisphere.

Cortical neuromodulation by constraint-induced movement therapy in congenital hemiparesis: an FMRI study.

OBJECTIVE: The aim of this study was to assess neuromodulative effects of CIMT in congenital hemiparesis. PATIENTS AND METHODS: Ten patients (age range: 10-30 years) with congenital hemiparesis due to unilateral cortico-subcortical infarctions in the middle cerebral artery territory, and with preserved cortico-spinal projections from the affected hemisphere to the paretic hand, were included. After a twelve-day period of constraint-induced movement therapy (CIMT), all showed a significant improvement of paretic hand function. Immediately before and after therapy, functional MRI during active and passive hand movements was performed to monitor cortical activation. RESULTS: Four patients showed consistent increases in cortical activation during movements of the paretic hand in the primary sensorimotor cortex of the affected hemisphere. Of the remaining six patients, three showed similar changes, but these results were potentially contaminated by an improved task performance after therapy. No significant alteration in activation was observed in two patients, and one showed movement artifacts. CONCLUSIONS: Even a short period of CIMT can induce changes of cortical activation in congenital hemiparesis. In our sample, increases in fMRI activation were consistently observed in the primary sensorimotor cortex of the affected hemisphere. Thus, the potential for neuromodulation is preserved in the affected hemisphere after early brain lesions.