Eight carriers of the A3243G mutation of mitochondrial DNA without stroke-like episodes were monitored for up to 7 years in clinical and metabolic studies, by magnetic resonance imaging (MRI) and positron emission tomography (PET). None developed mitochondrial encephalopathy (MELAS), but 2 developed diabetes mellitus, 1 terminal kidney failure and 2 cardiomyopathy. One patient improved markedly under ubiquinone. Electroencephalography showed progressive slowing in 2 cases, but electrophysiological tests and MRI were otherwise noncontributary. PET showed widespread cortical and basal ganglion metabolic deficits in 6 cases. We conclude that internal medical complications are more common than MELAS in adult carriers of the mutation. PET findings, firstly reported in such patients, suggest that chronic subclinical encephalopathy is very frequent, and PET may play a role in monitoring in the future.
Cardiac transplantation entails surgical disruption of the sympathetic nerve fibres from their somata, resulting in sympathetic denervation. In order to investigate the occurrence of sympathetic re-innervation, neurotransmitter scintigraphy using the norepinephrine analogue iodine-123 metaiodobenzylguanidine (MIBG) was performed in 15 patients 2-69 months after transplantation. In addition, norepinephrine content and immunohistochemical reactions of antibodies to Schwann cell-associated S100 protein, to neuron-specific enolase (NSE) and to norepinephrine were examined in 34 endomyocardial biopsies of 29 patients 1-88 months after transplantation. Anterobasal 123I-MIBG uptake indicating partial sympathetic re-innervation could be shown in 40% of the scintigraphically investigated patients 37-69 months after transplantation. In immunohistochemical studies 83% of the patients investigated 1-72 months after transplantation showed nerve fibres in their biopsies but not positive reaction to norepinephrine. Significant norepinephrine content indicating re-innervation could not be detected in any biopsy. It was concluded that in spite of the lack of norepinephrine content there seemed to be immunohistological and scintigraphic evidence of sympathetic re-innervation. An explanation for this contradictory finding may be the reduced or missing norepinephrine storage ability compared to the restored uptake ability of regenerated sympathetic nerve fibres.
Iodine-123 metaiodobenzylguanidine (MIBG) is a noradrenaline analogue which can be used as a tracer to investigate the cardiac sympathetic nervous system. Regional ischaemia leads to noradrenaline depletion with functional denervation which can be demonstrated by reduced MIBG uptake. In order to evaluate the reversibility of ischaemia-associated damage to the sympathetic nervous system, neuronal scintigraphy with 123I-MIBG and myocardial rest and stress perfusion scintigraphy with technetium-99m sestamibi was performed in 16 patients with coronary artery disease before and 3-4 months after percutaneous transluminal coronary angioplasty (PTCA). Partial re-innervation occurred in five patients, the degree of stenosis of remaining lesions being estimated by repeat angiography to be below 40%. Unchanged MIBG defects could be confirmed in four patients with residual lesions of between 40% and 50%. Increased MIBG defects were shown in three patients with significant restenoses of more than 70%. In all patients the neuronal defects exceeded the ischaemia-induced or scar-associated perfusion defects. Three patients dropped out of this study: one for technical reasons, one due to emergency aortocoronary bypass surgery and one due to diabetic polyneuropathy. This investigation shows that the sympathetic nervous system is highly sensitive to ischaemia. Further studies need to be done to assess the conditions allowing re-innervation after PTCA.
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