Abstracts

Rationale: Patients with chronic lactic acidosis may have a subyacent mitochondrial disorder involving the respiratory enzimatic chain, Krebs cycle or the pyruvate dehydrogense complex ( PDH). The risk of neurological complications could be tailored by looking at the areas of the brain affected .Methods: We have retrospectively reviewed the brain magnetic resonance images ( T2 and T1 gadolinium enhancement signals) of 43 patients followed in our institution with chronic lactic acidosis using the software available in our institution(stentor). 13 patients had a PDH disorder, 23 patients had a cytochrome oxidase disorder ( COX), and 7 patients had a different abnormality of the respiratory chain (e.g.MELAS, MERFF, Oxidation/Phosphorilation disorder). The data was analyzed for the presence of lessions in the brain parenchyma. Areas of focal versus diffuse atrophy were also included. The data was contrasted among the three groups by comparing ATP zones, atrophy and other abnormal findings. Then, a correlation with clinical findings was stablished by reviewing the available data in our electronic medical records (Net/access). Results: Patients with COX dysfunction had a higher risk of developing a mesial globus pallidus lession ( 42 %)and a very low risk of developing a caudate /thalamic lession. The risk of periaqueductal gray matter disease was 30 %, dorsal pons/dentate was 28 % and medullary nuclei was 21 %. Patients in this group were also more prone to develop a high demand ATP zone and less likely an ischemic change. In contrast, patients with a PDH complex disorder had a higher risk of developing generalized atrophy and an almost non existent risk of ischemic change. In the group of patients with MELAS/MERFF/Oxphos dysfunction, there was a higher incidence of focal atrophy and stroke and no risk of developing high ATP demand zones . The comparison between the three mitochondrial disorders groups in regard of ATP zone, atrophy and other abnormal findings showed an statistically significant difference ( p <0.05) in ATP zones between patiens with COX disorders and MELAS. There was almost universal developmental delay present in our studied population ( 95 %).The next most common abnormality was hypotonia ( 46 %). Seizures were seen in 27 % of the cases. Other potential complications seen included faillure to thrive ( 11 %) , perypheral neuropathy ( 2.3%) and hypertonia ( 7%)Conclusions: Our study demonstrate the presence of high ATP demand lessions in patients with chronic lactic acidemia, which likely represent areas of higher metabolic turnout and therefore more metabolically active and prone to ischemia. The patients with such disorder had a higher risk of developing neurological complications, including developemental delay and epilepsy. Our research was limited due to the lack of long term follow up studies. Further investigations are needed to beter understand the implications of this findings. (There were no sources of fundings for this study)