Do Pregnant Women and Those at Risk of Developing Post- Natal Depression Consume Lower Amounts of Long Chain Omega-3 Polyunsaturated Fatty Acids?
2010

Victoria F Cosatto email@example.com
Now at Centre for Vision Research
Westmead Millennium Institute
University of Sydney Westmead Hospital
Hawkesbury Rd, Westmead NSW 2145Australia

Paul L Else email@example.com
School of Health Sciences and Metabolic Research Centre
University of Wollongong
2522NSW

Barbara J Meyer
School of Health Sciences and Metabolic Research Centre
University of Wollongong
2522NSW

Do Pregnant Women and Those at Risk of Developing Post- Natal Depression Consume Lower Amounts of Long Chain Omega-3 Polyunsaturated Fatty Acids?

Nutrients
2201010.3390/nu2020198Received: 28 January 2010 / Accepted: 11 February 2010 /nutrients * Author to whom correspondence should be addressed; E-Mail: firstname.lastname@example.com; 199long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA)pregnant womenpostnatal depression OPEN ACCESS
The aims were to compare intakes of long chain omega-3 polyunsaturated fatty acid (LC n-3 PUFA) in pregnant and non-pregnant women in Australia and to compare these intakes to the Australian National Nutrition Survey of 1995 (NNS95)[1]and to determine if the LC n-3 PUFA intakes differed in women who may be 'at risk' compared with women 'not at risk' of developing post-natal depression (PND). A validated LC n-3 PUFA food frequency questionnaire and pregnant women's Edinburgh Postnatal Depression Scale (EPDS) scores were used. LC n-3 PUFA intakes were comparable to the NNS95 but did not differ due to pregnancy or whether or not a woman is at risk of developing PND. Keywords: long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA); pregnant women; postnatal depression OPEN ACCESS Nutrients 2010, 2 199 1. IntroductionThe health benefits of consuming long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA), particularly eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), are numerous and include cardiovascular, immune and putative mental health benefits[2][3][4][5][6][7]. EPA and DHA can reduce the risk of coronary heart disease by up to 25% and sudden cardiac death by approximately 45%[8,9]. LC n-3 PUFA are also essential for proper growth and development of the foetus. During pregnancy the circulating levels of maternal EPA and DHA are upregulated[10,11]and selectively transferred to the developing foetus via the placenta [12] to be incorporated into tissues such as the photoreceptors of the retina [13] and membranes of the central nervous system[14]. LC n-3 PUFA supplementation studies during pregnancy have shown prolonged gestation [15], increased birth weight and length[15]and improved visual acuity of the newborn[16].Both EPA and DHA can be desaturated and elongated from shorter chain n-3 PUFA precursor known as α-linolenic acid (ALA, 18:3n-3)[17][18][19], although the physiological relevance of this conversion is questionable. Studies by  show that in men less than 6% of ALA is converted to EPA and only 0.05% converted to DHA, although in women the conversion rate is much higher at 21% and 9% respectively. Therefore to obtain the potential health benefits from LC n-3 PUFA, consumption of preformed EPA and DHA is better than relying on the conversion of ALA to LC n-3 PUFA.During pregnancy, women may need to supplement their diet with extra LC n-3 PUFA in order to cater for the extra demand of the foetus in addition to their own physiological needs[10]. Fish and seafood is the best source of the LC n-3 PUFA, followed by meat and eggs[20]. A recent study by Hibbeln et al. [21]  showed that women who consumed more than 340g of fish/seafood per week (equivalent to two fish meals a week) during their pregnancy, had offspring with higher IQ at age 8 compared with the offspring whose mothers consumed less than 340g per week of fish/seafood.Observational studies have shown that LC n-3 PUFA serum and phospholipid levels are lower in people who suffer from depression compared to healthy control subjects[22]. It is possible that during pregnancy women with lower tissue levels of LC n-3 PUFA are more at risk of developing postnatal depression (PND). Certainly DHA is mobilised in the maternal circulation during pregnancy [12] and if DHA is being released from the maternal brain to meet the demand of the foetus this could contribute to the development of PND, but more research is warranted. Investigators believe that supplementing the diet with LC n-3 PUFA enriched foods may prevent this[23].The consensus statement for dietary fat intakes for pregnant and lactating women suggests an intake of DHA of at least 200mg/day[24]. Recently in Australia there has been some acknowledgement of the health benefits of the consumption of DHA and other LC n-3 PUFA during pregnancy [25], yet documented evidence regarding pregnant women and their consumption of LC n-3 PUFA is lacking. Currently, there does not appear to be a link between LC n-3 PUFA intakes and postnatal depression[26], however this is based on a very limited number of studies.Therefore the aims of this study were (1) to determine the intakes of LC n-3 PUFA in pregnant and non-pregnant women in Australia; (2) to compare these intakes to those of Australian females assessed in the Australian National Nutrition Survey of 1995 (NNS95) [1] and (3) to determine if the LC n-3

PUFA intakes differed in women diagnosed 'at risk' of developing PND compared with women 'not at risk' of PND.

Methods

Subject Recruitment

Pregnant women were recruited from the South-West Sydney Area Health Service in Australia whilst attending their first antenatal doctor's visit at the outpatients' clinic. All women booked in for their initial doctor's visit were given an information sheet, by antenatal clinic reception staff, outlining the background to the study. A researcher then approached the women to ask if they would like to participate in the study by completing a food frequency questionnaire (FFQ).

Non-pregnant women were recruited through both an e-mail and poster advertisement campaign both at the University of Wollongong and local community. Subjects were required to have maintained a constant diet over the previous 3 months; apart from this there were no other exclusion criteria. Ethics approval for this study was granted both from the University of Wollongong and South-West Sydney Area Health Service.

Administration of the Demographic and LC n-3 PUFA Food Frequency Questionnaire (FFQ) to Pregnant and Non-Pregnant Women

LC n-3 PUFA intakes in women were determined using a newly validated FFQ [27,28]. Volunteers were asked to complete the tailored FFQ during their antenatal clinic visit, or during arranged visits to the University of Wollongong. Other information supplied by the women included age (years), height (cm), weight (kg) and for pregnant women gestation stage (weeks). Digital scales and a wall-mounted stadiometer were used by a researcher to measure weights and heights, respectively, for the nonpregnant women. However, equipment to measure weight and height was not available at the antenatal clinic on the day so measurements were self-reported by the pregnant women.

Analysis of Daily LC n-3 PUFA Intakes

The Foodworks Fatty Acid Database [29] was used to analyse each subject's FFQ. To determine the daily consumption rate of each type of food (in grams per day), from the previous 3 months, the portion amount (in grams) was multiplied and/or divided by the frequency of each type of food consumed. The daily consumption intake for EPA, docosapentaenoic acid (DPA, 22:5n-3), DHA and total LC n-3 PUFA were then calculated by multiplying individual fatty acid content, per 100g of food, by the daily food intake per gram. The amount of LC n-3 PUFA was then further divided by 1000 to ascertain the fatty acid content in mg/day.

The Australian National Nutrition Survey 1995 (NNS95)

The Australian NNS95 [30] measured the energy and nutrition intakes of all food and beverages reported by 13, 858 men and women (19 years and over) using a 24-hour recall method. For validation reasons, a sub-sample of participates (n = 8,321) also completed a FFQ reporting consumption for over 100 different food types, as well as vitamins and supplements, proceeding 12 months prior to the study [30]. Howe et al. [1] later re-assessed the LC n-3 PUFA content from foods recorded by subjects in both NNS95 24-hour recall and FFQ using a more accurate fatty acid compositional database [1]. Previously, the database used to analysis the NNS95 did not have the fatty acid content for certain foods sources such as meat products [1]. For this reason the LC n-3 intakes of the pregnant and nonpregnant women in this study will be compared to the re-assessed LC n-3 PUFA intakes by Howe et al. [1].

The Edinburgh Postnatal Depression Scale (EPDS)

The EPDS is a simple 10 item self-report scale specifically developed to detect the severity and extent of depression during the postnatal period [31]. The EPDS has also been validated for use during the antenatal period [32], as women diagnosed with postnatal depression may have already been depressed during pregnancy [33]. Although the EPDS is not intended to substitute for a full psychiatric assessment, it is used as a tool to assist primary health care workers, without psychiatric experience, to define a population, which needs further evaluation [34]. For this study all pregnant women at the hospital first attend the antenatal clinic to record their medical history and to complete the EPDS. To identify all possible cases of depression, during the antenatal period, the hospital selected a cut-off score of ≥10. Therefore, women who scored 10 or greater on the EPDS were regarded as 'at risk' of developing postnatal depression and were immediately referred for counselling. Women, who scored nine or less, on the EPDS, were considered as 'not at risk' of developing PND. At the time of subject recruitment the researcher was blind to the patient's EPDS score, so the patient's medical record number (MRN) was recorded, to assist a second researcher in obtaining EPDS score and/or identifying the number of subjects recruited in each group. The study was unblinded after the FFQs were analysed for the LC n-3 PUFA intakes.

Statistical Analysis

A power calculation using the mean difference of 200mg DHA and a power of 80% at a significance level of 0.05 was completed and 75 women from each group were deemed to be adequate for the study. The data for subject characteristics is presented as mean and standard deviation (SD). The data for EPA, DPA, DHA and total LC n-3 PUFA intakes are presented as mean and standard error of the mean (SEM) as well and the median and the range. Since the data distribution for EPA, DPA, DHA and total LC n-3 PUFA was not normally distributed a Wilcoxon nonparametric test was used to compare the fatty acid data between the pregnant group and the non-pregnant group as well as the LC n-3 PUFA intakes in women 'at risk' (EPDS score ≥ 10) and 'not at risk' (EPDS score < 10) of developing post-natal depression. All p values < 0.05 were considered significantly different. All statistical analysis was performed using JMP statistical software package version 4.0 (SAS institute, Cary, NC, USA).

Results and Discussion

Study Participants

During subject recruitment, 133 pregnant women were approached and asked to participate in the study by completing the questionnaires and 115 (86%) agreed to participate. A further, 21 subjects were excluded from the study because they either did not fully complete their questionnaire (n 15) or they did not return the questionnaire (n 6). The total number of women who completed the FFQ and hence were eligible for the study was 94 (82%). For the non-pregnant women, 33 volunteers were recruited for this study.

The characteristics of the study participants showed no significant differences in age and height in the pregnant and non-pregnant women, but the pregnant women obviously weighed heavier than the non-pregnant women. Characteristics of the study participants are shown in Table 1.

LC n-3 Intakes for Pregnant Women, and Non-Pregnant Women and Women from the NNS95

The comparison of the LC n-3 PUFA intakes for the pregnant women, non-pregnant women and women aged 19 years and over from the Australian NNS95 [1] was inclusive of all meat, fish and egg products but excluded all enriched foods and fish oil supplements, as such foods were not available in the NNS95. The mean and median intakes of LC n-3 PUFA (mg/day) consumed by the pregnant women group, are comparable to the average intakes of women aged 19 years and over in the NNS95.

The average EPA, DHA and total LC n-3 PUFA intake of the pregnant compared to the non-pregnant women was not significantly different. However, pregnant women's intakes of DPA were higher (P < 0.05) than the non-pregnant women. A multiple regression analysis did not show any variables such as age, height or weight influencing the DPA intake of the non-pregnant group. This difference in DPA intake could be explained by the amount of meat and seafood products consumed by each group. On average the pregnant women consumed more meat products per day than the non-pregnant women and women from the NNS (174 grams versus 109 grams versus 158 grams, respectively). However, the pregnant women consumed less fish/seafood products per day than the non-pregnant women (35 grams versus 51 grams) and slightly more than the women from the NNS (35 grams versus 26 grams). The comparisons of the mean, median and range of intakes (mg/day) of LC n-3 PUFA for the pregnant women, non-pregnant women and women aged 19 years and over from the Australian NNS95 [1] is shown in Table 2.

Contribution of LC n-3 PUFA Foods

The relative contribution of LC n-3 PUFA intakes was mainly from foods i.e., meat, fish and eggs, followed by enriched foods and the least amount from fish oil supplements in pregnant women. The main contributor was the natural food sources followed by enriched foods consumed by 48% (n = 45) of the women. Enriched food supplements (Blackmores Ltd. (20 Jubilee Ave, Warriewood, NSW 2102, Australia) pregnancy and lactation formula) were consumed by 5% (n = 5) of the women. The consumption of enriched foods and supplements by these pregnant women provided an additional 8, 1, 29 and 33 mg/day of EPA, DPA, DHA and total LC n-3 PUFA, respectively, to the daily intake (comparison of intakes between tables 2 and 3). The pregnant women all consumed at least some type of meat product (100%; n 94), most consumed some type of seafood (88%; n 83) and most consumed eggs (72%; n 68) Table 3.

Differences in Food Intakes for Women 'at risk' and 'not at risk' of Developing post Natal Depression

There were no differences in the LC n-3 PUFA intakes for women 'at risk' and 'not at risk' of developing PND. There were no differences in grams per day for intakes for eggs, fish/seafood, meat and enriched food consumption between women 'at risk' and women 'not at risk' of PND (results not shown). There were no significant differences in intakes for EPA, DPA, DHA or total LC n-3 PUFA between the 'at risk' and the 'not at risk' groups. Even though this table suggests 'at risk' women had 20% higher DHA intakes than 'not at risk' women, this is due to one outlier in each of the two groups. These outliers consumed 588mg DHA (from 'not at risk' group) and 632mg DHA (from 'at risk' group). When these two outliers were deleted from the analysis, the mean DHA intakes in the 'not at risk' group and the 'at risk' group became 119mg and 118mg, respectively. The differences in LC n-3 PUFA intakes for women 'at risk' and 'not at risk' of developing postnatal depression is shown in Table 4. There were no differences in EPA, DHA and LC n-3 PUFA intakes as assessed by the LC n-3 PUFA questionnaire between pregnant and non-pregnant women, however DPA intakes were significantly higher in pregnant women (Table 2). Oily fleshed fish and seafood generally, particularly when harvested from cold-water regions, are a rich source of EPA and DHA [35], whereas meat products, such as beef and lamb, contain a much higher DPA content [1]. As the pregnant women consumed more meat than the non-pregnant women this would explain the differences in DPA intake between the two groups. In addition 5 of the 33 non-pregnant women in the study were vegetarians, which would contribute to the lower DPA intakes, whereas there were no vegetarians in the pregnant women group. However, the majority of the vegetarians (4 out of 5) still ate fish and eggs and a further analysis excluding the vegetarians still resulted in lower DPA intakes in the non-pregnant group (data not shown). Nevertheless, the overall intake of total LC n-3 PUFA was not significantly different between the pregnant and non-pregnant women groups.

The non-pregnant women group included eight women up to 14 years older than the pregnant women, therefore an analysis excluding all women aged > 41, was conducted. These results were the same as those found including the older women (data not shown). Furthermore, estimates of the LC n-3 PUFA dietary intakes in both the pregnant and non-pregnant women compared favourably with the results of the NNS95 (Table 2). However, given that LC n-3 PUFA consumption is skewed to the right, comparisons of median intakes from both the pregnant and non-pregnant groups to the mean intakes in the NNS95 were not significantly different. Hence our results indicate that pregnant women in this study do not necessarily consume a higher intake of LC n-3 PUFA compared to non-pregnant women.

To our knowledge there are no other studies that have compared individual LC n-3 PUFA intake between pregnant and non-pregnant women. However, two previous longitudinal Dutch studies that reported the total n-3 PUFA (including ALA) of women during pregnancy found no significant changes in their dietary intakes pre and post-pregnancy [36,37]. The Otto et al. [36] study measured the amount of n-3 PUFA from a group of women pre-conception and then later at 10 weeks of pregnancy. While the Al et al. [37] study (1996) measured intakes in women within the first 13 weeks, at 22 weeks and again at 32 weeks of pregnancy and found no differences in LC n-3 PUFA intakes.

Our results also show that there were no differences between the amount of daily LC n-3 PUFA consumed between women 'at risk' and 'not at risk' of developing PND groups (Table 4). To date there are no other studies that have used a validated FFQ to compare the LC n-3 PUFA intakes from foods such as meat, seafood, eggs, n-3 PUFA enriched foods and fish oil supplements in women 'at risk' and 'not at risk' of developing PND. Even so these findings are consistent with a previous study between non-pregnant women aged 23-97 years categorised as depressed or non-depressed [38] where they found no difference in LC n-3 PUFA intakes. However, one limitation of this study is the limited number of women at risk of developing PND available in the study. It is likely that women with depression may have been less likely to participate in a study or that some of the women screened as 'not at risk of developing depression' at the time of the study recruitment, later developed depression [33]. Unfortunately, data on the women who later developed postnatal depression was not collected, as a second EPDS is not routinely administered, at the hospital, to women after they have given birth. Therefore it is important for hospital staff to screen all pregnant women during an antenatal visit to identify possible cases that maybe 'at risk' of developing PND. A lower EPDS cut-off score (≥10) was used by the hospital to identify all possible cases of depression. Using a cut-off score ≥10 as opposed to ≥13 or ≥15 will increase the sensitivity of the EPDS to reduce the number of false negatives but may increase the number of false positives [31]. A validation study of the EPDS during pregnancy reported that a 14/15 cut-off score correctly identified all women with major depression (sensitivity 100%). Whereas using a lower 12/13 cut-off score identified the women with major depression and minor depression but also included some false positives [32]. The hospital, in this study, intentionally used a lower EPDS cut-off score (≥10) as a safety net to ensure that no women with antenatal depression would be missed. Therefore, women who scores 10 or greater on the EPDS were regarded as 'at risk' of developing PND and were referred to a local community centre for counselling. Changing the cut-off scores to ≥13 and ≥15 to minimize false positives still did not produce any differences in LC n-3 PUFA intakes between the groups 'at risk' or 'not at risk' of developing PND (results not shown).

In this sample, the % rate of women 'at risk' of developing PND, using an EPDS cut-off score of ≥10, ≥13 and ≥15 were 19%, 13% and 12%, respectively, with a mean EPDS score 6.2 (SD 5.2). In comparison the Australian beyondblue Postnatal Depression program [39] where 40,333 pregnant women were screened for depression using the same EPDS cut-off scores was 20%, 9% and 5%, respectively, with a mean EPDS score 6.6 (SD 4.4). However, the pregnant women from our study deemed 'at risk' was screened at an average of 20 weeks gestation compared to the beyondblue PND program where women were screened at an average of 26 weeks gestation [39]. However, 52% of women in the beyondblue PND program were recruited from the state of New South Wales. They were screened at an average of 16 weeks and % rates of antenatal depression, using a EPDS cut-off score of ≥10, ≥13 and ≥15, were 17%, 6% and 4%, respectively, mean score 7.5 (SD 3.9) [39]. Our results show that our pregnant women screened for antenatal depression, had a similar prevalence rate to the beyondblue PND program when using the EPDS cut-off score of ≥10 [39]. Therefore our small study sample is a representative sample as the EPDS cut-off score of >10 was used.

For this study, a difference of 200mg/day of LC n-3 PUFA was used in a power calculation to detect a significant difference between the women 'at risk' and 'not at risk' of developing PND. Therefore a sample size of 75 women was required for each group. While this was achieved for the 'not at risk' of developing PND group (n = 76) the 'at risk' of developing PND group contained only 18 women. A further power calculation for DHA alone (with a mean of 200mg/day and a standard deviation of 95 as found in our data results) showed that if the 'at risk' of developing PND group did contain 75 women the intakes would still not be significant. To detect a significant difference the sample size required would require at least 710 women total. Furthermore, Table 4 suggests that intakes of DHA in women 'at risk' of developing PND is higher than women 'not at risk' of developing PND. Therefore if this study had the statistical power, the results would not support our hypothesis.

Whether or not a difference of 200mg/day of DHA would have any clinical affect between women 'at risk' for depression or 'not at risk' for depression is still unclear. For this study, although not significantly different, the 'not at risk' women consumed 10 mg less DHA (96mg DHA) compared with the 'at risk' women who consumed 106mg DHA (Table 4). Whereas, Koletzko et al. [24] and The International Society for the Study of Fatty Acids and Lipids (ISSFAL) [40,41] recommend during pregnancy at least 200mg/day of DHA alone, the median DHA intake found in our study and the NNS95 (83 mg/day) are much lower than this.

If DHA intakes are no different in women 'at risk' versus 'not at risk' of developing PND, then other factors may be considered. This includes metabolic abnormality in lipid metabolism or oxidative damage caused by smoking [42]. Furthermore, social and economic factors may also contribute to the risk of developing depression [43].

There are various recommendations for consumption of LC n-3 PUFA and they range from 135 to 1600mg [20]. In Australia the National Health and Medical Research Council (NHMRC) Nutrient Reference Values, and recommend an adequate intake (AI) for LC n-3 PUFA at 160mg/day for adult men and 90mg/day for adult women [44] but these recommendations are based on median/mean intakes of the Australian population [1,20]. In pregnancy these AI recommendations are higher at 110mg/day for 14-18 year olds and 115mg/day for 19-50 year olds [44]. The NHMRC also have Suggested Dietary Target (SDT) intakes for optimal health and the SDT for LC n-3 PUFA is 610mg/day for men and 430mg/day for women [44] and these are based on 90 th percentile of Australian population intakes [1,20]. Whilst it is difficult to establish an exact amount of DHA needed to supply the needs of the growing and developing foetus and replenish the mother's maternal stores [10], there are recommendations specifically for DHA. The ISSFAL proposed an adequate intake for pregnant women to consume > 200mg/day [40,41] and the European consensus statement proposed at least 200mg/day of DHA alone [24].

In this study the median intake shows that 50% of the women consumed an LC n-3 PUFA and DHA intake less than 268mg/day and 96mg/day, respectively. Furthermore, only 9% of the women consumed the proposed ideal recommended intake of > 200mg/day of DHA during pregnancy and lactation [40,41]. If the foetus accumulates on average ≈ 67 mg DHA/day from the maternal supply during the last trimester of pregnancy [45], as predicted from post-mortem studies [46], then the mother will have very little or no DHA left over to provide for her own physiological needs [10]. Maternal plasma concentrations of a range of fatty acids are increased during pregnancy [12,47] among these are the LC n-3 PUFA. There is no evidence of increased maternal LC n-3 PUFA intake during pregnancy [36,37] so it is likely that the majority of these LC n-3 PUFA are mobilised from maternal stores with some contribution from oestrogen stimulated conversion of ALA to DHA [18]. Interestingly the growing foetus preferentially takes up DHA and the omega-6 PUFA called arachidonic acid (AA, 20:4n-6) and these two fatty acids become important building blocks for the foetal brain [12]. There is some evidence that women during pregnancy become deficient in DHA and as pregnancy continues their DHA deficiency index (as defined by the 22:5n-6/22:4n-6 ratio) increases during pregnancy [12]. This DHA deficiency returns to normal 6 months post-partum [47]. However this is not observed in all populations [47]. It should be noted that it is difficult to deduce net transfer of fatty acids from mother to foetus from random measurement of maternal steady state plasma concentrations. Nonetheless, the high foetal demand and absolute requirement for DHA would suggest that pregnant women are under stress in terms of providing enough DHA to her growing foetus. A recent study reported that pregnant women lack the knowledge of the importance of LC n-3 PUFA consumption during pregnancy [48]. Therefore, there is obviously a need to educate women of childbearing age about the benefits of increasing their LC n-3 PUFA intakes [48] and the best alternatives are by consuming more fish products [20].

There are various reports on actual intakes for women of reproductive age as outlined by Sioen et al. [49]. The actual intakes of EPA range from 46 to 278mg/day, DPA intakes range from 10 to 75mg/day, DHA intakes range from 67 to 497mg/day and LC n-3 PUFA intakes range from 156-775mg/day [49]. For our study, both pregnant and non-pregnant women, the average total LC n-3 PUFA intake of 263mg/day and 241mg/day, respectively, meets the AI recommendations of the NHMRC but falls short of the NHMRC SDT recommendations and the recently released National Heart Foundation of Australia's recommended EPA and DHA intake of 500mg/day for healthy adults including pregnant women [50] as well as the recommendations by ISSFAL [40,41] and the European consensus [24].

The results of our study showed no difference between the average amount of seafood, meat, eggs and enriched foods (grams per day) consumed between pregnant women 'at risk' of developing PND and those 'not at risk' of developing PND. In contrast to our study, a cross-sectional national New Zealand study of 4644 adult men and women (15+ years) reported that non-fish eaters scored significantly lower on a mental health test (poorer mental health) compared to the fish eaters' on the same mental health test (better mental health) [51]. Unlike our study, fish consumption was categorised into those who consumed no fish of any kind and those who consumed some kind of fish (ranging from ≥1 fish serving per month to ≥ 2 per day) [51]. However, the National New Zealand study did not include and compare other foods that contain LC n-3 PUFA such as meat or enriched foods.

From the current study, 51% of the pregnant women were supplementing their diet with LC n-3 PUFA enriched foods such as milk, bread, eggs and fat spreads and/or fish oil supplements (Table 3). This contributed to a total of 12% of their daily LC n-3 PUFA intakes; 5% EPA, 1% DPA, 22% DHA. Enriched foods can be very useful to top-up daily levels of LC n-3 PUFA when other enriched foods like fish and meat have already been incorporated into the diet [52]. A recent study [53] found that a group of overweight subjects with a habitual low fish intake could significantly increase their daily LC n-3 PUFA intake from 258mg to 1195 mg/day by incorporating up to eight various LC n-3 PUFA enriched foods into their diet. This same study showed that consumption of these enriched foods resulted in increased erythrocyte LC n-3 PUFA levels to a similar extent than if the subjects consumed fish/seafood [54].

A limitation of this study was the lack of blood biomarkers from the women, such as erythrocyte LC n-3 PUFA levels which are indicative of tissue LC n-3 PUFA levels. However, a previous study found using the same FFQ that 53 healthy adults reported LC n-3 PUFA intakes parallel levels analysed in erythrocytes and plasma and these intakes [27,28] were also comparable to those reported in the NNS95. Another limitation of our current study is the comparability of the pregnant and non-pregnant women. Pregnant women were recruited from a hospital, whilst the non-pregnant women were recruited from the University of Wollongong and the wider Wollongong community. Whilst it is recognised that women with a higher level of education or income were more aware of issues related to LC n-3 PUFA [48], however, the results of our current study compare favourably to the intakes of women assessed in the NNS95, which covers a wide range of education and income levels. It must also be noted there was a difference in methodologies used between this study (FFQ including enriched foods) and the NNS95 (24 hr food recall and FFQ) [30]. As well a difference of 9 years between this study (data collected 2004) and the NNS95 and within that time frame the availability of LC n-3 PUFA foods and the dietary habits of individuals have changed, especially with the introduction of LC n-3 PUFA enriched foods. For that reason we compared the LC n-3 PUFA intakes of pregnant and non-pregnant women, excluding the enriched foods, and their intakes compared favourably to those intakes of women reported in the NNS95. Furthermore due to limited time for subject recruitment 75 women for each of the groups was not achieved as only 18 women 'at risk' of developing PND and 33 non-pregnant women, compared to 76 women 'not at risk' of developing PND were recruited for this study. However, the data were also compared to that of the NNS95 which contained 5770 women.

In summary the LC n-3 PUFA intakes did not differ between pregnant women and non-pregnant women and were comparable to the intakes as recorded by the Australian NNS95. In our study, the average total LC n-3 PUFA intake for both pregnant and non-pregnant women meet the recommendations of some but not all recommended ranges for healthy adults. The LC n-3 PUFA intakes did not differ between the pregnant women 'at risk' of developing PND and 'not at risk' of developing PND. Although there is an impression that inadequate LC n-3 PUFA intakes in pregnant women may predispose them to developing postnatal depression due to growing foetal organ systems (particularly the nervous systems) requiring increased amounts of LC n-3 PUFA [23], the results of this study do not currently support this deficiency concept.

Conclusion

Dietary LC n-3 PUFA intakes did not differ between pregnant and non-pregnant women nor did they differ between women 'at risk' and 'not at risk' of developing PND. Furthermore, the average total LC n-3 PUFA intakes for both pregnant and non-pregnant women are low compared to recommendations from various organisations.

Table 1 .
1Characteristics of pregnant and non-pregnant women study participants 1,2 .Pregnant women
Non-Pregnant Women
(n 33)
Characteristics
(n) Mean ± SD Range Mean ± SD Range
Age (years)
94
28
± 5
18-41 33
± 11
21-55

Height (cm)
78 164 ± 8
146-180 162
± 8 145-176

Weight (kg)
86
79
± 20 45-144 61
± 11
43-90

Body mass index (kg/m 2 ) 75
29
± 7
20-54 23
± 3
19-31

Pregnancy Stage (weeks) 94
20
± 5
10-34 N/A 3

1 Values are mean ± SD
2 Note from the pregnant women, 16 women did not report their height, 8 did not report their
weight.
3 N/A Not applicable

Table 2 .
2Comparison of LC n-3 PUFA intakes (mg/day) without the inclusion of enriched foods and fish oil supplements for pregnant women with non-pregnant women and the NNS 95 (Howe et al., 2006) 1 .Pregnant women (n 94)
Non-pregnant women (n 33)
NNS 95
(n 5770)
Fatty
Acid

Mean SEM Median Range Mean SEM Median Range Mean
SEM

EPA
mg/day

79
6
72
4-321
69
10
53
0-294
60
2

DPA
mg/day

85 *
6
75
3-422
49 *
7
35
0-146
52
1

DHA
mg/day

99
9
75
6-579
124
21
106
0-673
83
3

LC n-3
PUFA
mg/day

263
19
235
16-
1080

241
36
189
0-1110 195
5

1 Abbreviations: LC n-3 PUFA -Long Chain Omega-3 Polyunsaturated Fatty Acid; NNS 95 -
National Nutrition Survey 1995 [1] ; SEM-Standard Error of the Mean; EPA -Eicosapentaenoic
acid; DPA-docosapentaenoic acid; DHA-docosahexaenoic acid; LC n-3 PUFA-sum of
EPA+DPA+DHA
 *  P < 0.05 comparison of pregnant and non-pregnant women (Wilcoxon non-parametric test)

Table 3 .
3Contribution of enriched foods and fish oil supplements in pregnant women to the total LC n-3 PUFA intakes (mg/day) from all sources. 1 LC n-3 PUFA -Long Chain Omega-3 Polyunsaturated Fatty Acid; SEM -Standard Error of the Mean; EPA -eicosapentaenoic acid; DPA -docosapentaenoic acid; DHA -docosahexaenoic acidFatty Acid for food group
Mean SEM Median Range
Meat, fish and eggs (n 94)
EPA
79
6
72
4-321
DPA
85
6
75
3-422
DHA
99
9
75
6-579
Total LC n-3 PUFA
263
19
235
16-1080
Enriched Foods (n 45)
EPA
11
2
6
0.22-40
DPA
3
0.5
1
0-16
DHA
38
5
27
0.9-181
Total LC n-3 PUFA
51
7
33
1-234
Fish oil supplements (n 5)
EPA
54
10
64
16-64
DPA
0
0
0
0
DHA
213
38
250
63-250
Total LC n-3 PUFA
267
47
314
79-314
Meat, fish, eggs, enriched foods
and fish oil supplements (n 94)
EPA
87
6
75
5-321
DPA
86
6
76
4-422
DHA
128
11
96
8-632
Total LC n-3 PUFA
302
20
268
17-1145

1

Table 4 .
4Comparison of LC n-3 PUFA intakes between pregnant women 'not at risk' and 'at risk' of developing PND as assessed by the Edinburgh Postnatal Depression Scale 1 .Fatty acid

Women 'not at risk' of developing
PND (n 76)

Women 'at risk' of developing
PND (n 18)

P
value *
Mean
SEM
Median
Mean
SEM
Median
EPA mg/day
87
7
78
91
14
70
0.90
DPA mg/day
84
7
77
94
12
76
0.55
DHA mg/day
123
11
96
150
37
106
0.92
LC n-3 PUFA
mg/day

294
21
270
344
60
253
0.77

1 PND -Postnatal Depression; SEM -Standard Error of the Mean;
EPA -Eicosapentaenoic acid; DPA-docosapentaenoic acid; DHA -docosahexaenoic acid;
LC n-3 PUFA -Long Chain Omega-3 Polyunsaturated Fatty Acid
* P < 0.05 (Wilcoxon Nonparametric test)

© 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
AcknowledgmentsThe authors would like to acknowledge the University of Wollongong for funding the study, the hospital staff for their assistance and the study volunteers for their participation in the study and Pam Davy, and Ken Russell, for their assistance with statistical analysis.
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When battery exhaustion lets the lame walk: a case report on the importance of long-term stimulator monitoring in deep brain stimulation

Martin Sommer
Elisabeth Mirjam Stiksrud
Kajetan Von Eckardstein
Veit Rohde
Walter Paulus
When battery exhaustion lets the lame walk: a case report on the importance of long-term stimulator monitoring in deep brain stimulation
C A S E R E P O R T Open Access
Background: Deep brain stimulation is increasingly used in the treatment of advanced Parkinson's disease. While its short-term effectiveness is well documented, there are only few reports on long-term outcomes, and the need to repeatedly reprogram the stimulator is seldom reported. Case presentation: We present a 74-year-old man with gait impairment, which had been mistaken for worsening of the disease and only remitted when the stimulator battery was exhausted indicating that the stimulator itself had been the cause. Conclusion: This case highlights the need to repeatedly monitor not only battery capacity, but also stimulator-related side-effects for an extended period after implantation and, if necessary, to refer to centres capable of systematically reprogramming the device.

Background

Deep brain stimulation is an effective method for reducing off times and hyperkinesia in advanced stages of idiopathic Parkinson's disease [1,2]. While there are controlled long-term outcome studies that confirm the on-going effectiveness of the treatment [3], the clinical results outside of controlled trials are less well documented, and subjective outcome reports are occasionally disappointing [4][5][6]. We present a striking example of a patient who had been wheelchair-bound for years due to stimulator-related side-effects. Once this was detected by chance because of battery exhaustion, we were able to partially improve his gait and speech clarity by reprogramming the stimulator.

Case presentation

A 74-year-old, retired teacher with a 20-year history of idiopathic Parkinson's disease had undergone bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in a centre with experience in the method. We first saw him seven years after the implantation when he presented in our clinic to have the device transiently switched off for scheduled dental surgery. He was wheelchair-bound outside his home and used a walking frame at home. His caregiver reported that he fell frequently, and he was dysarthric to an extent that almost completely hindered oral communication. The UPDRS III score was 32 of a possible 108 points; the DBS settings were 130 Hz with 60 microseconds pulse width and monopolar setting with the second deepest electrode contact on each side acting as cathode and the case acting as anode with an amplitude of 2.5 V in the right and 3.0 V in the left hemisphere. He was on medication with levodopa, entacapone, and pramipexole divided into seven daily doses, with a total levodopa equivalent dose of 998 mg [7], oral quetiapine 25 mg at night-time for his visual hallucinations, as well as oral rivastigmine 3 mg in the morning for dementia. The Kinetra® battery capacity was indicated as "OK" with a voltage of 2,56 V and 40-90 % of the capacity used.

Five months after our first contact, the patient's caregiver contacted the first author and reported that the patient was surprisingly able to walk independently, and that the clarity of this speech had improved markedly. She also reported that the deep brain stimulator no longer responded to the patient's controlling device.

We confirmed that the battery was exhausted. He was able to speak intelligibly with mild hypophonia. Rising from chair was fast, but postural responses were markedly reduced, resulting in a very unsteady, albeit independent gait over a distance of several meters. The UPDRS part III score was 24. He was now on medication with levodopa, entacapone and pramipexole every four hours, with a total levodopa equivalent dose of 1182 mg, oral quetiapine 25 mg at night-time and a rivastigmine patch 9 mg in the morning.

Expecting a relapse and worsening of the parkinsonian symptoms in the foreseeable future, we implanted an Activa PC ® device and left the stimulator off until his clinical condition should worsen. To avoid falls, we recommended that he walk only with assistance and with a walking frame.

After a further four months the patient presented with increasingly incapacitating fluctuations of motor function that made walking with the frame more and more difficult, indicating further disease progression. The other motor symptoms were stable except for a slight worsening of his hypophonia and very poor postural stability, resulting in a UPDRS part III score of 27. We carefully retested the electrodes and opted for a bipolar setting in the left hemisphere with contact 3 negative and contact 2 positive at 3.5 V, and a monopolar setting in the right hemisphere with the deepest contact 7 as cathode and the case as anode at 2.0 V, with 130 Hz frequency and 60 microseconds pulse width bilaterally. We discharged the patient with less pronounced dyskinesias, and medication with levodopa, entacapone and pramipexole in eight doses over the day, with a total levodopa equivalent dose of 1182 mg, oral quetiapine 25 mg at night-time, and oral rivastigmine 3 mg three times daily.

Conclusion

We report on a patient with an obvious post-operative over-stimulation, which made him wheelchair-bound, which was mistaken for disease progression and undetected for years, also by ourselves at the initial presentation. An incorrectly programmed stimulator was only recognized as the cause when he was able to walk after the stimulator battery had been exhausted.

We assume that internal capsule stimulation impaired his walking. Over-stimulation causing internal capsule stimulation was a frequent finding in a recent retrospective study on causes for dissatisfaction with STN deep brain stimulation [6]. Slowly decreasing postoperative microlesional effects [8], impedances changing over months [9] or years [10] after surgery all evolve on prolonged time scales that are difficult to predict, and influence the effects and side-effects of DBS. Disease progression and the occurrence of axial and nondopamine-responsive symptoms further complicate the clinical picture [11][12][13][14]. This extends the postoperative stimulator optimization phase to 12 months [6]. Some DBS centres advocate routinely rescheduling the patients six or twelve months after surgery [8] in order to detect secondary postoperative worsening of symptoms. Strategies to reduce axial side effects include smaller stimulation fields by bipolar settings [8], reduced stimulation frequencies reported to be effective in some patients [15][16][17], or interleaved stimulation of deeper electrode contacts [18].

In summary, this case exemplifies the importance of long-term postoperative stimulator programming to make the full long-term potential of deep brain stimulation available to the patient.

Consent

Written informed consent was obtained from the patient for publication of the case report. A copy of the written consent is available for review by the Editor of this journal.

Competing interests MS., EMS. and KvE. have participated in deep brain stimulation teaching courses financed by Medtronic, Inc.

Authors' contributions MS and EMS had the neurological patient contacts and acquired the data and drafted the manuscript. MS and WP conceived the case report. All authors critically discussed the indication for battery replacement and therapeutic steps. KvE and VR had the neurosurgical patient contact and performed the battery replacement. All authors read and approved the final manuscript.
 AcknowledgementsWe thank the dental surgery team for close cooperation.Submit your next manuscript to BioMed Central and take full advantage of:
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International Journal of Neurology & Brain Disorders
2016

Yong Seon Choi
Department of Neurology
Bundang Jesaeng General Hospital
20Seohy

Ji Yeong Chae
Department of Neurology
Bundang Jesaeng General Hospital
20Seohy

Hyung Woo
Department of Neurology
Bundang Jesaeng General Hospital
20Seohy

Kim
Department of Neurology
Bundang Jesaeng General Hospital
20Seohy

Jae Min Lee
Department of Neurology
Bundang Jesaeng General Hospital
20Seohy

Jung Ho Won
Department of Neurology
Bundang Jesaeng General Hospital
20Seohy

Sun Hong You
Department of Neurology
Bundang Jesaeng General Hospital
20Seohy

Hyun-Jeung Yu
Department of Neurology
Bundang Jesaeng General Hospital
20Seohy

Eun Hye Jeong
Department of Neurology
Bundang Jesaeng General Hospital
20Seohy

M.DEun Hye Jeong
Department of Neurology
Bundang Jesaeng General Hospital
20Seohy

International Journal of Neurology & Brain Disorders

Int J Neurol Brain Disord |
34201610.15436/2377-1348.16.1117Received Date: September 14, 2016 Accepted Date: October 24, 2016*Corresponding author: Citation: Jeong, E.H. et al. Isolated Mi-tochondrial Myopathy Misdiagnosed as
Mitochondrial myopathies are caused by dysfunction of the mitochondria and are systemic disorders that present with diverse clinical manifestations. They have been found to be especially prevalent in children. In this report, we present the case of a 55-year-old male patient who developed progressive symmetric proximal muscle weakness in both upper and lower extremities. Although the elevated levels of muscle enzymes and the findings of magnetic resonance imaging of lower extremities were suggestive of polymyositis, we made a final diagnosis of isolated mitochondrial myopathy based on the result of the biopsy of the thigh muscle. In this report, we emphasize the importance of performing a correct differential diagnosis of myopathies, particularly in the cases without evidence of involvement of other organs.Citation:Jeong, E.H. et al. Isolated Mitochondrial Myopathy Misdiagnosed as Polymyositis. (2016) Int J Neuro Brain Dis 3(4): 1-4. Int J Neurol Brain Disord | Volume 3: Issue 4www.ommegaonline.org encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); myoclonus, epilepsy, and ragged red fibers (MER-RF); ataxia-neuropathy syndromes, and isolated myopathy. Since mitochondrial myopathies comprise such a heterogeneous Copyrights:

Introduction

Mitochondria are intracellular organelles that host the components of the respiratory chain and produce adenosine triphosphate. They play an integral part of the metabolism in the body, and contain maternally-inherited mitochondrial DNA (mtDNA). Mutations in these genes and in nuclear DNA impair the function of nerves, muscles, the brain, the liver, and the endocrine system, which are heavily reliant on aerobic metabolism. Mutations in mtDNA and nuclear DNA lead to mitochondrial disorders with heterogeneous and polymorphic pathological manifestations [1] . The clinical expression of mitochondrial myopathy in the affected skeletal muscle may vary in terms of severity from mild exercise intolerance to fatal infantile encephalomyopathy or multisystemic dysfunction.

Mitochondrial myopathies include progressive external ophthalmoplegia; Kearns-Sayre syndrome; mitochondrial group of disorders, each with its own distinctive symptoms and clinical characters, diagnosing these disorders accurately and promptly is difficult [2] . Moreover, in case of isolated myopathy, differential diagnosis with other causes of myopathies is sometimes challenging because of absence of other systemic manifestations. We report a case of isolated mitochondrial myopathy confirmed by muscle biopsy, initially misdiagnosed as polymyositis.

Case Report

55-year-old male patient was admitted to the hospital with progressive general weakness and fatigue 3 months before. The patient had a medical history of pulmonary tuberculosis 25 years ago and had remained remission-free ever since. There were no other notable medical histories including seizure or stroke, and the patient was not on any medication. He was a florist and reported neither a personal history of smoking or drinking nor a family history of neuromuscular disorders or he-reditary diseases. The patient complained of general weakness and early fatigue while walking, especially with difficulty in ascending stairs, rising from supine or sitting position, and raising his arms above his head. Physical examination showed a blood pressure of 98/65 mmHg, a heart rate of 92 beats per minute, a respiration rate of 18 breaths per minute, and a body temperature of 36.5°C. His height was 167 cm, and weight was 56.7 kg. A clinical assessment of the head, neck, chest, abdomen, and skin did not reveal any particular signs. Neurological examination demonstrated that the cranial nerve functions were normal with no ptosis or ophthalmoparesis, but the muscle strength of both shoulders and hips was weakened to Medical Research Council grade IV. Although his toe and heel gait motions were normal, squatting was impaired. No sensory abnormalities were noted, and also there were no abnormalities in the deep tendon reflex and cerebellar function.

Peripheral blood tests showed that white blood cell count was 11.8 × 10 3 /L, the hemoglobin level was 10.4 g/dL, and the platelet count was 508 × 10 3 /L. The erythrocyte sedimentation rate was 120 mm/hr, the blood urea nitrogen level was 14 mg/dL, and the creatinine level was 0.76 mg/dL. Liver function tests found a level of aspartate transaminase of 267 IU/L, an alanine aminotransferase level of 143 IU/L, a total bilirubin level of 0.40 mg/dL, an alkaline phosphatase level of 256 IU/L, and a gamma glutamic transpeptidase level of 23 IU/L. Viral hepatitis markers were within the normal range. The level of creatine phosphokinase was elevated to 6,531 IU/L and the level of creatine kinase isoenzyme elevated to 67.49 ng/mL, but otherwise the results of blood coagulation tests and urinalysis were normal. Arterial blood gas analysis under subatmospheric pressure results were: pH, 7.456; pO 2 , 73.8 mmHg; pCO 2 , 39.6 mmHg; and HCO 3 -, 27.3 mmol/L. When screened for autoimmune antibodies, the patient was positive for anti-nuclear antibodies and anti-SSA antibodies. Negative results were found for anti-ribonucleo protein antibodies, anti-Smith antibodies, anti-Jo-1 antibodies, anti-Scl 70 antibodies, and anti-neutrophil cytoplasmic antibodies. The result of electrocardiography was normal and plain chest radiography did not show any abnormal signs.

The patient showed progressive symmetric proximal muscle weakness in both extremities, so we suspected myopathy and performed nerve conduction study and electromyography (EMG). The result of nerve conduction study was normal and the EMG on the right upper and lower extremities revealed denervation potentials in the biceps brachii, triceps brachii, flexor carpi ulnaris, vastus lateralis, tibialis anterior and paralumbosacral (L4-5, S1) muscles, suggestive of active-stage myopathy. The results of magnetic resonance imaging (MRI) of lower extremities showed diffuse symmetric signal changes and mild edema with enhancement of bilateral thighs and pelvic muscles [ Figure 1]. Depending on the clinical presentation of progressive symmetric proximal muscle weakness, laboratory findings including elevated muscle enzymes and erythrocyte sedimentation rate, the results of EMG and MRI, we initially diagnosed as polymyositis. For confirmation of the diagnosis, we performed muscle biopsy of the right rectus femoris muscle. Due to the time period before biopsy results, the patient received corticosteroid and showed some improvement of the symptoms. However, the result of the biopsy showed ragged red fibers in modified Gomori trichrome stain and abnormal mitochondria with parking lot inclusions on electron microscopy (EM), suggestive of mitochondrial myopathy [ Figure 2]. In order to assess the possibility of other organ involvement and to evaluate possible complications, we performed a biopsy of the liver, but found normal findings. Likewise, ophthalmologic examination, echocardiogram, electroencephalography (EEG) and brain MRI all returned normal findings. In order to evaluate the possibility of other mitochondrial disorders, we tested the patient's blood for the MT-TL1 and MT-TK genes, which are known to be related with MELAS and MERRF, and found that the results were negative. Therefore, we finally diagnosed as isolated mitochondrial myopathy, and administered coenzyme Q10 and carnitine to the patient.

Discussion

A notable feature of muscular disorders is that they present with common clinical presentations, symptoms, and laboratory findings, which makes it important to differentiate mitochondrial myopathy, inflammatory diseases, and degenerative diseases when diagnosing and treating muscular disorders. With myopathy, physical and laboratory investigations by themselves cannot be used to diagnose the condition conclusively. A muscle biopsy must be carried out in order to obtain a definitive diagnosis. Although the primary dysfunction in mitochondrial myopathy is at the level of the mitochondria, it presents as a systemic disease with clinical symptoms involving a broad range of systems, usually affecting the nervous system and muscles, both of which include components that consume a large amount of energy.

The causes of mitochondrial myopathies include mutations in mtDNA, defects in nuclear DNA sequences that encode proteins that are translated in the mitochondria, dysregulated interaction between mtDNA and nuclear DNA, and the direct effects of drugs such as zidovudine and clevudine. Mitochondrial disorders can be classified by genotype. The heterogeneity of genetic defects leads to variation in clinical symptoms among individuals. The genetic defects of mitochondrial myopathies can be classified according to the type of DNA mutation: deletions in mtDNA, duplication of mtDNA, point mutations in mtDNA, or other mutations in nuclear DNA. Mutations in genes relating to the replication of mtDNA or to respiratory chain reactions, such as the DNA polymerase gamma catalytic subunit and mtD-NA genes encoding cytochrome b (MTCYB), thymidine kinase 2 (TK2), and cytochrome oxidase (COX), have been implicated in mitochondrial myopathy [3,4] .

Mitochondrial myopathies are clinically and genetically diverse. This diversity is attributed to the range of mitochondria that can elicit the symptoms of these disorders. Within mitochondrial mutations, duplication and point mutations of mtDNA are inheritable, but deletion mutations are not. This is the reason for which a high level of genetic heterogeneity, which refers to the mixture of mutated and non-mutated genes, is seen among individuals [5] . Since hundreds to thousands of mitochondria exist in a cell and, within a single mitochondrion, only a subset of the several mtDNA that exist experience mutations, upon the somatic division of cells, the degree of mutation in the mtDNA differs substantially among cells: This concept is described as heteroplasmy.

Therefore, the differences in the mutational load of the mtDNA at the cellular level that occur as a result of heteroplasmy account for the differences in the severity of the symptoms among individuals. In general, it has been shown that the symptoms of mitochondrial myopathy manifest when the proportion of mutated mtDNA is over 85%. Interestingly, it has been shown that the effect of the same mutational load may differ among organs and tissues within a patient. Not only can the same mutational load lead to differences in the symptoms that are experienced, it can also lead to differences among patients that explain the variability in clinical presentation. Studies have attempted to identify a relationship between the heteroplasmy of mtDNA in the blood and the severity of symptoms, but no conclusive correlation has yet been found [6] .

According to a previous case report, a case of mitochondrial myopathy mimicking polymyositis with increased level of muscle enzymes was finally diagnosed with Kearns-Sayre syndrome confirmed by muscle biopsy and genetic analysis [7] . In our patient, the results of the study including the elevated level of muscle enzymes and the erythrocyte sedimentation rate, positive antinuclear antibodies, and the MRI suggestive of myositis were indicative of inflammatory myopathy such as polymyositis. However, the result of muscle biopsy performed to confirm our diagnosis showed ragged red fibers in modified Gomori trichrome stain and swollen mitochondria with parking lot inclusions on EM, suggestive of mitochondrial myopathy.

In general, a conclusive diagnosis of mitochondrial myopathy can be made if a biopsy shows ragged red fibers in Gomori trichrome stain or if EM shows an abnormal proliferation of mitochondria, enlarged mitochondria, or the presence of parking-lot inclusion bodies. Furthermore, when muscle biopsy results are inconclusive for diagnosis, biochemical approaches can help to detect defects in the components of the mitochondrial respiratory chain, such as complex I deficiency, complex II deficiency, or complex IV deficiency, and molecular genetic approaches such as sequencing of the genome to detect genetic defects or mutations can make a valuable contribution [1,2] . In the present case, unfortunately we could not corroborate our diagnosis through additional biochemical or genetic tests providing a more detailed assessment of the pathogenesis of the condition, but we thought that the histological findings with special staining and EM were sufficient to drive the correct diagnosis. In general, mitochondrial myopathy patients present with clinical features of multi-organ dysfunction, and rarely present with isolated symptoms. In our case, bilateral symmetric proximal muscle weakness of the extremities was the only symptom. We excluded the possibility of coexisting dysfunction of other organs by several special studies such as EEG, brain MRI, cardiac evaluation, and liver biopsy, so we could make a final diagnosis of isolated mitochondrial myopathy.

Unfortunately, no available treatments target the fundamental cause of mitochondrial myopathy, and no consensus exists for the gold standard of treatment. Studies have shown that the supplementation of respiratory chain components such as coenzyme Q10 and L-carnitine is beneficial, which has led to their use in treatment. In recent years, since dichloroacetate has been shown to reduce toxic metabolites, such as lactic acid, it has been used as an experimental agent. Similarly, antioxidants such as vitamin K3, vitamin C, riboflavin, and thiamine have been tested, but yet have not shown significant clinical value [8,9] . In addition, several international and national level reports have shown that patients with mitochondrial disorders, specifically MELAS, have responded to corticosteroid treatment, as described in our case. However, the exact mechanism by which steroids act on patients with mitochondrial disorders is unknown. According to some reports, steroids have been shown not only to exert their effect in the nucleus but also in the mitochondria, because glucocorticoid receptors have been found in the mitochondria. This means that steroids may exert their effect on the pathogenesis of disease by acting on the receptor, on the nuclear DNA, or even cooperatively. Furthermore, steroids have been shown to directly stimulate mitochondrial transcription, thereby exerting a beneficial effect by influencing the biosynthesis of the respiratory chain [10,11] .

Mitochondrial myopathies are commonly associated with other neurological symptoms, and in most patients, other organs are already affected by the time of diagnosis. However, for cases of isolated myopathy such as described in our case, since the isolation of the condition within a single organ must be verified through a process of elimination, a more discriminatory approach is required, which explains the need of performing a muscle biopsy.

In this case report, the authors initially misdiagnosed a patient's illness at the time of admission as polymyositis, however, finally diagnosed as isolated mitochondrial myopathy after muscle biopsy. Thus, a postulated diagnosis of myopathy must be confirmed through a biopsy of the tissue of concern.

Figure 1 :Figure 2 :
12Gadolinium-enhanced T1-weighted axial (A) and coronal (B) images of magnetic resonance imaging of lower extremities reveal diffuse symmetric signal changes and mild edema with enhancement in muscles of bilateral thighs (quadriceps femoris group, semitendinosus, sartorius, gracillis muscles) and pelvis (obturator internus and externus muscles) (arrows). Electron microscopy of muscle biopsy shows swollen mitochondria with parking lot inclusions(arrows).

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