Julie A. Matsumoto

Brain imaging as a predictor of early functional outcome following traumatic brain injury in children, adolescents, and young adults.

Objectives:A depth of lesion (DOL) model using brain imaging has been proposed to aid in medical decision-making and planning for rehabilitation resource needs. The purpose of this study was to determine the early prognostic value of a DOL classification system for children and young adults following severe traumatic brain injury. Methods and Outcome measures:CT/MRI brain imaging studies on 92 patients, aged 3 to 21, admitted to the Kluge Childrens Rehabilitation Center, University of Virginia, were evaluated to determine DOL. Images were classified according to 5 DOL levels (cortical to brainstem). Functional outcomes in mobility, self-care, and cognition, as rated on the WeeFIM instrument, were compared by DOL levels. Results:Admission WeeFIM scores were significantly different for the DOL levels with the highest score for frontal and/or temporal lesions and the lowest for lesions including the brainstem or cerebellum (P < .001). However, the deeper the lesion, the greater the functional gains (P = .05), resulting in discharge WeeFIM scores that were not significantly different across DOL levels. Patients with deeper lesions tended to have longer lengths of stay in rehabilitation but were able to “catch up” with patients who had more superficial lesions. Conclusions:While relatively simple and convenient, the DOL classification system is limited in its usefulness as an early prognostic tool. It may not be possible to predict outcome in the early acute phase in the intensive care unit on the basis of standard brain imaging alone. Patients with deeper lesions may enter rehabilitation at a more impaired level but can make remarkable progress, though it may take longer than for less severely injured individuals.

Abnormal head MRI in a neurologically normal boy with hypomelanosis of Ito

We report on an 8.5-year-old boy with hypomelanosis of Ito (HI) who has an abnormal MRI of the brain but is neurologically normal. There have been many reports of abnormal brain imaging studies in patients with HI, but all reported patients have had abnormal neurologic findings or symptoms. Our patient has had serial, stable head MRI white matter changes and has remained neurologically normal without any neurologic sequelae.

The apolipoprotein gene and recovery from brain injury among extremely preterm infants.

Background: Extremely preterm infants have an increased risk of brain injury and, consequently, are more likely to exhibit signs of motor, cognitive or behavioral impairment. Various factors, including genetic, may influence how the brain responds to an injury, ranging from no to complete recovery. The apolipoprotein E (APOE) gene codes for a protein in the brain involved in maintenance and repair of neurons. Objective: To determine whether any of the three APOE alleles are related to improved outcome. Methods: A total of 87 preterm infants with birth weights less than 1,000 g and no obvious preexisting brain abnormalities were genotyped for the APOE gene; 71 of these were assessed with the Bayley III Scales at a corrected age of 12-15 months. Brain MRI was obtained on a subgroup of 52 infants at term equivalent. Results: No significant relationship was found between the three APOE alleles and developmental outcomes or brain MRI findings. Conclusion: APOE does not appear to be related in a direct way to the developmental sequelae of white or gray matter injury in extremely preterm infants.

Enhancement of multiple cranial and spinal nerves in vanishing white matter: expanding the differential diagnosis

Abnormal cranial or spinal nerve contrast enhancement on MRI in cases of suspected pediatric leukodystrophy is recognized as an important clue to the diagnosis of either metachromatic leukodystrophy or globoid cell leukodystrophy (Krabbe disease). We report a case of genetically confirmed childhood vanishing white matter with enhancement of multiple cranial and spinal nerves in addition to the more typical intracranial findings. This case expands the limited differential diagnosis of cranial nerve or spinal nerve enhancement in cases of suspected leukodystrophy and may aid in more efficient work-up and earlier diagnosis of vanishing white matter.

Teaching NeuroImages: Intracranial hypotension in a patient with Marfan syndrome

An 18-year-old man with Marfan syndrome and migraine headaches presented with acute worsening of headaches with postural changes following spinal fusion surgery for scoliosis. Lumbar spine MRI done before surgery showed diffuse dural ectasia (figure 1). Brain MRI after surgery showed distended transverse and sagittal dural venous sinuses1 and an enlarged pituitary gland suggesting intracranial hypotension (figure 2). He was treated conservatively with rest, fluids, and caffeine. Patients with Marfan syndrome frequently have dural ectasia2 and are at risk of CSF leaks after spinal surgery leading to intracranial hypotension. Our case highlights subtle changes on brain MRI suggesting intracranial hypotension.

White Matter Changes in an Untreated, Newly Diagnosed Case of Classical Homocystinuria:

The authors report the case of a 4-year-old boy who developed progressive unilateral weakness and developmental delays prior to his diagnosis of classical homocystinuria. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse white matter changes, raising the concern for a secondary diagnosis causing leukoencephalopathy, since classical homocystinuria is not typically associated with these changes. Other inborn errors of the transsulfuration pathway have been reported as causing these changes. Once begun on therapy for his homocystinuria, his neurologic deficits resolved and his delays rapidly improved. Repeat MRI performed one year after instating therapy showed resolution of his white matter abnormalities. This case illustrates the need to consider homocystinuria and other amino acidopathies in the differential diagnosis of childhood white matter diseases and lends weight to the hypothesis that hypermethioninemia may induce white matter changes.

Foveal hypoplasia in autosomal recessive spastic ataxia of Charlevoix-Saguenay

A 14-year-old boy presented with a presumed diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The neurological examination, nerve conduction study, and brain imaging results were all consistent with the diagnosis. The ophthalmologic examination was notable for a prominent myelinated nerve fiber layer extending from the disk along the major temporal arcades in both eyes. Loss of foveal depression was noted clinically and on spectral domain optical coherence tomography. This case highlights a novel finding that may aid in the diagnosis of ARSACS.

Teaching NeuroImages: Resolution of MRI abnormalities in megalencephalic leukoencephalopathy with subcortical cysts

A boy was diagnosed at age 10 months with megalencephalic leukoencephalopathy with subcortical cysts (MLC) based on progressive macrocephaly and characteristic MRI findings (figure, A–C).1 Over subsequent years, initial motor delays resolved and neurobehavioral difficulties were mild. On repeat MRI at 6 years (figure, D–F), only small areas of frontal and temporal white matter signal alteration remained, consistent with remitting MLC (MLC2b). MLC2b is associated with heterozygous mutations in HEPACAM with autosomal dominant inheritance. Often, one parent has macrocephaly.1 Unlike the more common phenotype seen with MLC1 mutations, MLC2b patients demonstrate remarkable MRI improvement and have a better clinical prognosis.2

CENTRAL NERVOUS SYSTEM INVOLVEMENT IN AXONAL CHARCOT-MARIE-TOOTH DISEASE

Charcot–Marie–Tooth (CMT) disease is the most common inherited peripheral neuropathy, with an estimated prevalence of 1 in 2,500. The disease is phenotypically and genetically heterogeneous, and various classification schemes have focused on clinical presentation, inheritance pattern, and specific genetic mutations. The pathophysiology of peripheral nerve dysfunction in CMT has been extensively characterized by electrophysiological and pathological studies. Central nervous system involvement is considered unusual and has been occasionally reported in X-linked CMT and postmortem studies. We report a patient with CMT II in whom spinal cord atrophy was observed in vivo by means of magnetic resonance imaging (MRI). The patient is a 67-year-old man with a long history of CMT. He first noticed symptoms including bilateral foot drop, frequent ankle sprains, and falls in his early teens. Gradually he developed symmetric progressive distal numbness, weakness, and muscle atrophy in both legs. The upper extremities were involved in a similar pattern but at a later time. Electrodiagnostic tests (EDX) done when he was in his early 30s were said to be consistent with CMT disease. His symptoms progressed slowly over the next 30 years, but there was relatively rapid functional decompensation within the past year. There is a strong family history. His son has similar symptoms and has electrophysiological features of CMT. His father and grandfather both had high arches and ‘‘leg weakness,’’ but they were not evaluated by physicians. On examination, he had high arches, striking distal muscle atrophy especially in the lower extremities, profound distal muscle weakness, length-dependent sensory loss, and absent deep tendon reflexes throughout. No palpable nerve hypertrophy was found. Cranial nerves were intact. He had diminished muscle tone. His plantar reflexes were mute, however upon plantar stimulation, triple flexion was observed bilaterally. He otherwise had no clinical symptoms or findings suggesting central involvement. MRI of the spine performed to evaluate the cause for the triple flexion reflex revealed diffuse, severe spinal cord atrophy without signal abnormality (Fig. 1). Axial images suggested uniform involvement of the spinal cord. Postcontrast imaging was only done of the lower thoracic cord and lumbar spine and showed no abnormal enhancement. A repeat EDX revealed absent sensory nerve action potentials, absent right peroneal compound muscle action potential (CMAP), and low CMAP amplitudes and slow conduction velocities in other motor nerves (right ulnar 0.2 mV and 42 m/s, right median 0.2 mV and 54 m/s, right tibial 0.1 mV and 33 m/s); concentric needle examination demonstrated enlarged motor unit potentials and reduced recruitment. These findings suggest a chronic, severe, widespread sensorimotor peripheral polyneuropathy, with prominent features of axonal involvement. We consider the clinical features of our patient to be most consistent with CMT II given the prominent axonal loss. Hereditary motor and sensory neuropathy type V (HMSN V) can have similar electrophysiological findings but is associated with prominent spasticity, which was not present in our patient. Genetic testing was not performed due to the patient’s preference. We failed to find any reports of radiographic studies of spinal cord pathology in patients with CMT. We report here in vivo evidence of central nervous system involvement in a patient with CMT II disease. The MRI findings in our patient are consistent with several autopsy observations of CMT patients. Postmortem study of a 73-year-old with CMT II reported anterior horn cell and dendritic degeneration at the cervical and lumbar levels. Yoshimura et al. reported severe posterior column degeneration and atrophy of anterior horn cells in a 41-year-old with CMT II. A similar finding was observed in an autopsy of a 92-year-old with CMT 1B. CMT is primarily a peripheral nerve disease; however, our observations complement postmortem studies that suggest the pathology may extend to involve the central nervous system at least to the level of the spinal cord affecting both the anterior and posterior portions. It is unclear whether this is a primary process or VC 2009 Wiley Periodicals, Inc.