Case reportEarly infantile Krabbe disease: deceptively normal magnetic resonance imaging and serial neurophysiological studies
Introduction
Globoid cell leukodystrophy (GLD; Krabbe disease), is a progressive neurodegenerative disease caused by deficient activity of galactosylceramidase (galactocerebroside β-galactosidase) and transmitted by autosomal recessive inheritance [1]. Neuroimaging studies, delay in nerve conduction velocities and elevated cerebrospinal fluid protein are suggestive of extensive myelin breakdown. An infantile form with onset before 6 months, a late infantile form with onset between 6 and 36 months, a juvenile form with onset between 3 and 7 years, and an adult one with onset after 7 years have been recognized according to differences in the age of onset and in the clinical manifestations 1, 2. Usually, patients with GLD manifest stagnation in psychomotor development and irritability between 4 and 6 months of age, while spasticity and peripheral neuropathy develop subsequently [1]. However, early infantile cases with onset immediately after birth are on record [1].
We report serial clinical, magnetic resonance imaging (MRI) and neurophysiological findings of a Greek patient with early onset GLD, who had a deceptively normal initial MRI examination.
Section snippets
Case report
The patient was a female born to healthy, non-consanguineous parents without a familial history of neurodegenerative disorders, delivered at term after cesarean section. At the third day of life, she was admitted to the hospital because of pronounced irritability and myoclonic jerks of the right arm (and occasionally of the right leg). Head circumference was above the 97th percentile, while the neurological examination demonstrated decreased muscle tone, brisk deep tendon reflexes and
Neuroradiological and neurophysiological studies
Cranial computed tomography (CT) at the third day disclosed no abnormality, while an electroencephalogram (EEG) showed generalised slow wave activity, predominately over the left parieto-occipital region.
A repeated EEG performed at 3 months of age, prior to antiepileptic drugs withdrawal, revealed mild generalised slowing with no paroxysmal or focal abnormalities, while magnetic resonance imaging (MRI) of the brain at the same age demonstrated normal findings, showing normal myelination of the
Discussion
Although there are numerous case descriptions of MRI findings in infantile GLD [1], only occasionally are serial MRI findings documented in early infantile 4, 5, 6or late infantile forms [7]. Finelli et al. [6], reported a patient with early infantile Krabbe disease who had a deceptively normal initial MRI examination. However, their patient had already an abnormal CT appearance prior to the MRI, with hyperdensities of the thalami, thus suggesting the disorder, since early CT changes in early
References (10)
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2018, Volpe's Neurology of the NewbornHigh-throughput screening of stem cell therapy for globoid cell leukodystrophy using automated neurophenotyping of twitcher mice
2013, Behavioural Brain ResearchCitation Excerpt :The majority of late-infantile GLD patients (7–36 months) initially presents with gait abnormalities, such as clumsiness, inability to maintain sitting or standing positions, and increased muscle tone, before progressing to cerebellar ataxia and possible spastic quadriplegia [49,50,53]. The development and worsening of these symptoms are highly monitored in these patients, especially because the early stages of GLD can appear normal using computed tomography and magnetic resonance imaging [49,51]. Although the twitcher mouse model differs from the human patient in many aspects (e.g., lifespan), the presentation of motor symptoms in the twitcher mouse is similarly progressive and debilitating.
Normal neuroimaging in early-onset Krabbe disease
2011, Pediatric NeurologyCitation Excerpt :Although it is recognized that MRI abnormalities may be difficult to identify early in the course of the disease, MRI-negative Krabbe disease has not been reported before in early-onset Krabbe disease cases. MRI may be deceptively normal in early infantile Krabbe disease at the onset of the disease, but as the disease progresses, characteristic MRI features of Krabbe disease do appear [5,6]. This pattern is probably largely related to the still immature myelination preventing recognition of the presence and extent of white matter abnormalities.
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2011, Magnetic Resonance ImagingCitation Excerpt :Several neurological, neuropsychological, and neuropsychiatric conditions are associated with brain changes in pediatric subjects [1–4], other than those accompanying normal aging [5].
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