Clinical History
Four year old boy presented with history of regression of milestones and startle response along with rhythmic repetitive movement of upper limb since 15th month of age. EEG was normal with generalised spike at the time of sound-induced startle. Biochemical examination revealed increased serum lactate.
Imaging Findings
Symmetrical bilateral T2/FLAIR caudate and putamina nucleus hyperintensity with restriction on DWI images. MRS showing inverted lactate peak at 1.33ppm. Hyperintensity also noted in periaqueductal grey matter and brain stem.
Discussion
Subacute necrotizing encephalomyelopathy, or Leigh syndrome (LS), is a progressive neurodegenerative disorder characterized by clinical features of psychomotor retardation, feeding difficulties, intermittent abnormalities of the respiratory rhythm, cranial palsies, and ataxia, with onset usually in infancy or early childhood. Symmetrical spongiform lesions, a characteristic neuropathologic finding, first described by Leigh in 1951. This is because of vacuolation of the neuropil with preservation of the neurons and capillary proliferation. [1]
LS is the result of heterogeneous biochemical or molecular abnormalities in the mitochondria, although 40% to 65% of patients have no definite metabolic derangement. [2]
Age of presentation is usually less than 2 years (infantile form), however, presentation in adolescence and adulthood has also been reported. The child usually presents with psychomotor regression, abnormal muscle tone, weakness, dystonia, brainstem and cerebellar dysfunction (ataxia), visual loss, missed milestones or regression of the achieved milestones, tachypnoea, and seizures. Death usually occurs within few years after onset of symptoms, typically from progressive respiratory failure. [1]
Laboratory analysis shows metabolic acidosis with elevated blood, CSF lactate, and pyruvate concentrations. [1]
It is usually inherited as an autosomal recessive trait. The underlying defect can be at any of the sites in the enzyme pathway for respiratory metabolism. [4]
The diagnostic criteria are:
(1) Progressive neurological disease with motor and intellectual developmental delay.
(2) Signs and symptoms of brain-stem and/or basal ganglia disease.
(3) Raised lactate levels in blood and/or cerebrospinal fluid.
(4) Characteristic symmetric necrotic lesions in the basal ganglia and/or brainstem.
The most characteristic neuroradiological findings are bilateral, symmetric focal hyperintensities in the basal ganglia, thalamus, substantia nigra, and brainstem nuclei. Proton spectroscopy demonstrates elevated brain lactate levels in the basal ganglia, occipital cortex, and brainstem. [5]
Specific therapy for mitochondrial disorders in children is not available. These patients are usually treated symptomatically with multivitamin therapy and other supportive treatment.
Differential Diagnosis List
Leigh's disease (Mitochondrial disorder)
Profound perinatal asphyxia
Mitochondrial encephalopathy lactic acidosis stroke-like episodes (MELAS)
Glutaric aciduria type I (GA-1)
Final Diagnosis
Leigh's disease (Mitochondrial disorder)
