Objective and Clinically Feasible Analysis of Diffusion MRI Data can Help Predict Dystonia After Neonatal Brain Injury.

BACKGROUND: Dystonia in cerebral palsy is debilitating but underdiagnosed precluding targeted treatment that is most effective if instituted early. Deep gray matter injury is associated with dystonic cerebral palsy but is difficult to quantify. Objective and clinically feasible identification of injury preceding dystonia could help determine the children at the highest risk for developing dystonia and thus facilitate early dystonia detection. METHODS: We examined brain magnetic resonance images from four- to five-day-old neonates after therapeutic hypothermia for hypoxic-ischemic encephalopathy at a tertiary care center. Apparent diffusion coefficient values in the striatum and thalamus were determined using a web-based viewer integrated with the electronic medical record (IBM iConnect Access). The notes of specialists in neonatal neurology, pediatric movement disorders, and pediatric cerebral palsy (physicians most familiar with motor phenotyping after neonatal brain injury) were screened for all subjects through age of five years for motor phenotype documentation. RESULTS: Striatal and thalamic apparent diffusion coefficient values significantly predicted dystonia with receiver operator characteristic areas under the curve of 0.862 (P = 0.0004) and 0.838 (P = 0.001), respectively (n = 50 subjects). Striatal apparent diffusion coefficient values less than 1.014 × 10-3 mm2/s provided 100% specificity and 70% sensitivity for dystonia. Thalamic apparent diffusion coefficient values less than 0.973 × 10-3 mm2/s provided 100% specificity and 80% sensitivity for dystonia. CONCLUSIONS: Lower striatal and thalamic apparent diffusion coefficient values predicted dystonia in four- to five-day-old neonates who underwent therapeutic hypothermia for hypoxic ischemic encephalopathy. Objective and clinically feasible neonatal brain imaging assessment could help increase vigilance for dystonia in cerebral palsy.

Localization of Basal Ganglia and Thalamic Damage in Dyskinetic Cerebral Palsy.

BACKGROUND: Dyskinetic cerebral palsy affects 15%-20% of patients with cerebral palsy. Basal ganglia injury is associated with dyskinetic cerebral palsy, but the patterns of injury within the basal ganglia predisposing to dyskinetic cerebral palsy are unknown, making treatment difficult. For example, deep brain stimulation of the globus pallidus interna improves dystonia in only 40% of patients with dyskinetic cerebral palsy. Basal ganglia injury heterogeneity may explain this variability. METHODS: To investigate this, we conducted a qualitative systematic review of basal ganglia and thalamic damage in dyskinetic cerebral palsy. Reviews and articles primarily addressing genetic or toxic causes of cerebral palsy were excluded yielding 22 studies (304 subjects). RESULTS: Thirteen studies specified the involved basal ganglia nuclei (subthalamic nucleus, caudate, putamen, globus pallidus, or lentiform nuclei, comprised by the putamen and globus pallidus). Studies investigating the lentiform nuclei (without distinguishing between the putamen and globus pallidus) showed that all subjects (19 of 19) had lentiform nuclei damage. Studies simultaneously but independently investigating the putamen and globus pallidus also showed that all subjects (35 of 35) had lentiform nuclei damage (i.e., putamen or globus pallidus damage); this was followed in frequency by damage to the putamen alone (70 of 101, 69%), the subthalamic nucleus (17 of 25, 68%), the thalamus (88 of 142, 62%), the globus pallidus (7/35, 20%), and the caudate (6 of 47, 13%). Globus pallidus damage was almost always coincident with putaminal damage. CONCLUSIONS: Noting consistent involvement of the lentiform nuclei in dyskinetic cerebral palsy, these results could suggest two groups of patients with dyskinetic cerebral palsy: those with putamen-predominant damage and those with panlenticular damage involving both the putamen and the globus pallidus. Differentiating between these groups could help predict response to therapies such as deep brain stimulation.

Connectivity of the human pedunculopontine nucleus region and diffusion tensor imaging in surgical targeting.

OBJECT: The pedunculopontine nucleus (PPN) region of the brainstem has become a new stimulation target for the treatment of gait freezing, akinesia, and postural instability in advanced Parkinson disease (PD). Because PD locomotor symptoms are probably caused by excessive gamma-aminobutyric acidergic inhibition of the PPN, low-frequency stimulation of the PPN may overcome this inhibition and improve the symptoms. However, the anatomical connections of this region in humans are not known in any detail. METHODS: Diffusion weighted magnetic resonance (MR) images were acquired at 1.5 teslas, and probabilistic tractography was used to trace the connections of the PPN region in eight healthy volunteers. A single seed voxel (2 x 2 x 2 mm) was chosen in the PPN just lateral to the decussation of the superior cerebellar peduncle, and the Diffusion Toolbox of the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain was used to process the acquired MR images. The connections of each volunteer's PPN region were analyzed using a human brain MR imaging atlas. RESULTS: The PPN region was connected with the cerebellum and spinal cord below and to the thalamus, pallidum, subthalamic nucleus, and motor cortex above. The regions of the primary motor cortex that control the trunk and upper and lower extremities had the highest connectivity compared with other parts of motor cortex. CONCLUSIONS: These findings suggest that connections of the PPN region with the primary motor cortex, basal ganglia, thalamus, cerebellum, and spinal cord may play important roles in the regulation of movement by the PPN region. Diffusion tensor imaging tractography of the PPN region may be used preoperatively to optimize placement of stimulation electrodes and postoperatively it may also be useful to reassess electrode positions.