An 8-year-old girl was admitted to Rasool Akram hospital with bilateral horizontal gaze palsy, ataxia and drowsiness. The gaze palsy was initiated in the right eye during the last year and then gradually affected the left eye during the previous month. She developed unsteady gait, drowsiness, progressive ataxia, intention tremor and seizure during the admission time. The past medical history of the patient revealed that she was the first child of the family, from a consanguineous marriage. She had also developmental milestone delay. She had the history of seizure around 4 years ago, without current medication therapy.
The vital signs were stable during her admission time. She was confused; however, she responded to verbal stimulations. Horizontal gaze palsy was detected in both eyes under ocular examinations, without any vertical gaze palsy. Nystagmus was not observed during the examination .The normal light reflection was detected in her pupils. Ocular examination revealed retinal atrophy and pale disk in both sides. Cranial nerve examination was normal. Deep tendon reflexes (DTR) were Brisk. Cerebellar examination revealed positive tandem gait, intention tremor, ataxic and wide based gait. The results of finger-to-nose and heel to shin tests were detected normal. The biochemical test results, complete blood count (CBC) and electrolytes were reported within the normal ranges. Dorsal midbrain involvement were reported in brain Magnetic resonance imaging (MRI) (Figure 1), which was provided one month ago out of our center. Total abdominal and pelvic ultrasounds were performed in order to rule out the possibility of organomegaly and malignancy. Electroencephalography (EEG) was performed showing slowing background activity prominent in posterior area without epileptiform discharges.
On the 5th day of admission, the patient presented a generalized tonic-clonic (GTC) seizure lasted for one minute. Cerebrospinal fluid (CSF) was analyzed for cells, biochemical tests, lactated dehydrogenase (LDH), and lactate contents that the results were reported acceptable. Anti- Neuromyelitis optica antibody (NMO), IgG index and oligoclonal bands (OCB) tests were performed for the possibility of autoimmune diseases. A basic metabolic panel test was performed for the assessment of serum ammoniac, lactate, pyruvate, and amino acids content with high performance liquid chromatography (HPLC) method. The possibility of specific metabolic syndromes was ruled out with all normal metabolic results. The patient received biotin, Vitamin B1, B12 and Vitamin E to evaluate the possibility of Wernicke-Korsakoff syndrome. However, no change in signs and symptoms was observed following these treatments. Serum immunoglobulins were evaluated in order to rule out the possibility of ataxia telangiectasia and other immune deficiencies. The laboratory test results including ANA; Anti-ds-DNA; serum complements (C3, C4, C5), SSA-Ro, SSA-LA; RPR; AFP; Anti-GM Ab (IgM and IgA); β2 glycoproteins; Anti-phospholipids; Anti- cardiolipin (IgM and IgG); HLA (B5 and B51); and serum ACE were within normal values. Therefore, the possibility of neuro-Behcet disease, lupus erythematous, neuro-brucellosis, and neuro-sarcoidosis was declined by detecting laboratory results. The infectious diseases biomarkers were performed to rule out the possibility of infectious diseases including HIV Ab, VDRL, Anti-toxoplasma Ab (IgM and IgG), wright and 2ME. Wilson's disease was evaluated by 24-hour urine copper test. Serum levels of vitamin B12 and folic acid were normal. Listeria infection was a recommended diagnosis due to midbrain involvement. So, Ampicillin and Gentamycin was then started empirically.
On the 10th day of admission, the second brain MRI was performed with and without contrast for the second time (Figure 2). Abnormal high signal flair and T2 lesions were detected in medulla, Midbrain, bilateral putamen nuclei and cerebellar dentate nucleus. Corticosteroid pulse therapy was started to resolve involved areas, increased signal in midbrain, progressive ophthalmoplegia and consequently the possibility of inflammatory lesions.
On the 15th day of admission, Magnetic Resonance Spectroscopy (MRS) demonstrated an elevated lactate peak in involved areas which could indicate the possibility of mitochondrial disease (Figure 3). Mitochondrial treatment cocktail (including Vitamin B2, Vitamin B6, folic acid, L-carnitine and coenzyme Q) was prescribed for the patient. Gaze palsy of the eyes, ataxia, tremor and ophthalmoplegia were improved relatively. The patient was discharged with mitochondrial treatment cocktail and oral prednisolone (1mg/kg/day). The patient was examined again two weeks after discharge. The complete improvement was observed in eye movements and gaze palsy; however, a mild intention tremor and ataxia were detected during the examination time. Whole exome sequencing was done to evaluate any genetic disorder. Finally, the molecular genetic test result showed mutation in NDUFS4 gene, confirming the diagnosis of Leigh syndrome.