A 4 months old male infant was transferred from Tunisia to our hospital by ambulance. His consanguinous parents had sought medical advice in our hospital previously due to their child’s abnormal fixed gaze that lasted for 30 minutes and stopped spontaneously. They discharged their child against medical advice to go to Tunisia where the child’s condition deteriorated as he got admitted to the PICU of a private hospital there. After a brain MRI done in Tunisia, the child was transferred by ambulance on nasal cannulae back to Libya. He was immediately intubated upon admission due to severe respiratory acidosis. Upon admission, findings were the following: The child was gasping & cyanotic. Vitals: SpO2= 60%, HR=98, RR=10, BP=87/530 ABG: pH=6.99, pCO2=123 pO2=19, sO2=12, HCO3=28, BE= -8, Lactate=32 Chest: absent air entry bilaterally CVS: S1+S2+ bradycardia, palpable femoral and peripheral pulses. Abdomen: soft lax, liver edge palpable. Genitalia: bilateral hydroceles. CNS: AF at level, round regular and reacting pupils, hypertonia and exaggerated reflexes, GCS 9. The management was to intubate the child, sedate him and connect him initially to P-SIMV mode. After 2 weeks of admission and 1 failed trial at extubation, the child was discharged back home with a number of oral medications necessary to his condition. The report of the brain MRI done in Tunisia revealed the following: Bilateral symmetrical signal anomalies touching the Niger locus, the anterior aspects of the 2 thalamic nuclei as well as the posterior aspect of the cerebral trunc, suggesting more likely a metabolic insult in particular a mitochondrial cytopathy of Leigh’s disease that is to be related to the clinical and biological findings. Leigh’s disease is associated with mt-DNA. It is a progressive neurodegenerative disorder. Nonspecific initial features include FTT & persistent vomiting. Decompensation with lactic acidosis during an intercurrent illness is typically associated with psychomotor retardation or regression. A period of recovery may follow initial decompensation but the individual rarely returns to prior developmental status before the illness. Neurologic features include hypotonia, spasticity, dystonia, muscle weakness, hypo/hyperreflexia, seizures (myoclonic or GTC), infantile spasms, movement disorders (chorea), cerebellar ataxia, peripheral neuropathy. Brainstem lesions may cause respiratory difficulty, swallowing difficulty, persistent vomiting, hypo/hyperthermia. Ophthalmological findings include optic atrophy, retinitis pigmentosa, eye movement disorders. Extraneurologic features include: cardiac HCM, hepatic (hepatomegaly or liver failure), renal (renal tubulopathy or diffuse glomerulocystic kidney damage). Most affected have episodic deterioration interspaced with “plateaus” during which development may be quite stable or even show some progress of variable duration. Death is typical by 2-3 yrs, mostly due to respiratory or cardiac failures. In undiagnosed patients, death may appear sudden and unexpected. To make a diagnosis of Leigh’s disease, clinical criteria and molecular genetic testing are necessary. Clinical criteria include: 1- progressive neurological disease with motor and intellectual developmental delay 2- signs and symptoms of brainstem and basal ganglia disease 3- raised lactate in blood &/or CSF 4- 1 or more of the following: a. Characteristic radio-imaging b. Typical neuropathology: multiple focal symmetric necrotic lesions in basal ganglia, thalamus, brainstem, dentate nuclei & optic nerves. Histologically spongiform lesions with demyelination gliosis and vascular proliferation. Neuronal loss can occur. c. Typical neuropathology in a similarly affected sibling. Molecular genetic testing included a number of mitochondrial genes, of which MT-ATP6 (T8993G and T8993C) was present in 10-20% of cases of Leigh’s disease. In our PICU, management focused on post-diagnosis evaluation and treatment. This included: 1- Developmental assessment 2- Neurologic evaluation, MRI, MRS & EEG is seizures suspected 3- Metabolic evaluation, plasma & CSF lactate & pyruvate concentrations, urine organic acids to exclude organic acidemias 4- Ophthalmologic evaluation 5- Cardiac evaluation The child indeed had an abnormal MRI consistent with the diagnosis, plasma lactate that was consistently high (above 20 mg/dL), as well as HCM by echocardiography with a pansystolic murmur and pedal edema. Moreover, the child had an elder sister who died at 6 months of age in our PICU due to an undiagnosed neurodegenerative illness. After 2 weeks of admission and 1 failed trial at extubation due to aspiration pneumonitis, the child was discharged back home with a number of oral medications necessary to his condition. These included folic acid, thiamine, L-carnitine, biotin, propanolol, Keppra syrup, Co-enzyme Q10, and sucralfate. After 20 days from his discharge, the child presented again in the same picture with a deteriorating level of consciousness. He remained intubated on the APRV mode until his sudden death after 17 days from his 2nd admission. انا لله وانا اليه راجعون Dr. Manal Badi Maging wise diagnostic Clues: Bilateral symmetrical involvement of Basal ganglia ( Putamen > Caudate > Globus pallidi), thalami, Brain stem (substantia nigra of mid brain > Pons > Medulla), Dentate nuclei of cerebellum, Periventricular white matter. Hypodense on CT and T2 hyperintense on MR with restricted diffusion in acute stages.
Posted on: Thu, 02 Oct 2014 20:12:27 +0000
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