How Much Vitamin D is Too Much? A Case Report and Review of the Literature.

BACKGROUND: The beneficial effects of vitamin D, together with the high prevalence of vitamin D deficiency, have led to an expanding use of vitamin D analogues. While inappropriate consumption is a recognized cause of harm, the determination of doses at which vitamin D becomes toxic remains elusive. CASE PRESENTATION: A 56-year woman was admitted to our Hospital following a 3-week history of nausea, vomiting, and muscle weakness. The patient had been assuming a very high dose of cholecalciferol for 20 months (cumulative 78,000,000UI, mean daily 130,000UI), as indicated by a non-- conventional protocol for multiple sclerosis. Before starting vitamin D integration, serum calcium and phosphorus levels were normal, while 25OH-vitamin D levels were very low (12.25 nmol/L). On admission, hypercalcemia (3.23 mmol/L) and acute kidney injury (eGFR 20 mL/min) were detected, associated with high concentrations of 25OH-vitamin D (920 nmol/L), confirming the suspicion of vitamin D intoxication. Vitamin D integration was stopped, and in a week, hypercalcemia normalized. It took about 6 months for renal function and 18 months for vitamin D values to go back to normal. CONCLUSION: This case confirms that vitamin D intoxication is possible, albeit with a high dose. The doses used in clinical practice are far lower than these and, therefore, intoxication rarely occurs even in those individuals whose baseline vitamin D serum levels have never been assessed. Repeated measurements of vitamin D are not necessary for patients under standard integrative therapy. However, patients and clinicians should be aware of the potential dangers of vitamin D overdose.

Thyrotoxic Hypokalemic Periodic Paralysis Triggered by Dexamethasone Administration.

Thyrotoxic hypokalemic periodic paralysis (THPP) is a disease characterized by recurrent episodes of muscle weakness due to intracellular potassium shifting in the presence of high levels of thyroid hormone. It occurs more commonly amongst young Asian men with underlying Graves' disease. Attacks are commonly precipitated by ingestion of carbohydrate-rich meals or alcohols, stress or strenuous exercise. Herein, we describe an adult Thai man suffering from a hypokalemic periodic paralysis attack after receiving a dexamethasone injection. The diagnosis of Graves' disease was confirmed by his thyroid function test and a presence of thyrotropin-receptor antibody. His weakness and hypokalemia responded well to potassium supplement and a non-selective beta blocker, while his thyrotoxicosis was initially controlled by an anti-thyroid medication and subsequently with a subtotal thyroidectomy. Clinicians should beware of this manifestation when administering steroids in the thyrotoxic patients, especially of Asian male descent.

Anti-HMGCR myopathy presenting with acute systolic heart failure.

Necrotising autoimmune myopathy (NAM) is an immune-mediated myopathy that may be associated with statin use, malignancy or an autoimmune connective tissue disease, but it can also be idiopathic. Anti-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy is an extremely rare side effect of statin use, occurring in approximately 2-3 out of every 100 000 patients who use statins. Patients typically present with subacute proximal muscle weakness and creatine kinase levels >10 times the upper limit of normal. The diagnosis is suggested by muscle biopsy showing necrotic fibres with minimal inflammation along with positive anti-HMGCR antibodies. Treatment nearly always requires multiple immunosuppressive agents, the earlier use of which is associated with improved outcomes. Reports of statin-induced NAM leading to heart failure are limited. We present the case of a 69-year-old woman with statin-induced NAM who presented with acute systolic heart failure. Early initiation of high-dose corticosteroids and IVIG resulted in significant improvement in her symptoms.

Decreased bone mineral density in experimental myasthenia gravis in C57BL/6 mice.

Experimental autoimmune myasthenia gravis (EAMG), an animal model of myasthenia gravis (MG), can be induced in C57BL/6 (B6, H-2 b) mice by 2-3 injections with Torpedo californica AChR (tAChR) in complete Freund's adjuvant. Some EAMG mice exhibit weight loss with muscle weakness. The loss in body weight, which is closely associated with bone structure, is particularly evident in EAMG mice with severe muscle weakness. However, the relationship between muscle weakness and bone loss in EAMG has not been studied before. Recent investigations on bone have shed light on association of bone health and immunological states. It is possible that muscle weakness in EAMG developed by anti-tAChR immune responses might accompany bone loss. We determined whether reduced muscle strength associates with decreased bone mineral density (BMD) in EAMG mice. EAMG was induced by two injections at 4-week interval of tAChR and adjuvants in two different age groups. The first tAChR injection was either at age 8 weeks or at 15 weeks. We measured BMD at three skeletal sites, including femur, tibia, and lumbar vertebrae, using dual energy X-ray absorptiometry. Among these bone areas, femur of EAMG mice in both age groups showed a significant decrease in BMD compared to control adjuvant-injected and to non-immunized mice. Reduction in BMD in induced EAMG at a later-age appears to parallel the severity of the disease. The results indicate that anti-tAChR autoimmune response alone can reduce bone density in EAMG mice. BMD reduction was also observed in adjuvant-injected mice in comparison to normal un-injected mice, suggesting that BMD decrease can occur even when muscle activity is normal. Decreased BMD observed in both tAChR-injected and adjuvant-injected mice groups were discussed in relation to innate immunity and bone-related immunology involving activated T cells and tumour necrosis factor-related cytokines that trigger osteoclastogenesis and bone loss.

Diospyros rhodocalyx (Tako-Na), a Thai folk medicine, associated with hypokalemia and generalized muscle weakness: a case series.

INTRODUCTION: Diospyros rhodocalyx (Tako-Na) is a Thai folk medicine purported to promote longevity, treat impotence, etc. We present patients with hypokalemia, weakness and hypertension after consuming Tako-Na tea. CASE SERIES: Case 1: A 61-year-old man was brought in nine hours after drinking 400-500 mL of Tako-Na tea. One handful of Tako-Na bark was boiled in water to make tea. He had vomiting and watery diarrhea six hours after drinking it. He took no medications and had no history of hypertension. The only remarkable vital sign was BP 167/90 mmHg. Physical examination revealed generalized muscle weakness. Laboratory findings were potassium 2.7 mmol/L, bicarbonate 24 mmol/L, and transtubular potassium gradient (TTKG) 5.6. He was discharged the next day with a BP 140/90 mmHg and potassium 4.2 mmol/L. Case 2: A 78-year-old man, a friend of case 1, also drank Tako-Na tea from the same pot at the same time as case 1. He also had vomiting and diarrhea six hours later. He took no medications despite past history of hypertension (baseline SBP 140-160). Initial BP was 230/70 mmHg. He also had muscle weakness. Laboratory findings were potassium 3.3 mmol/L, bicarbonate 24 mmol/L, TTKG 7.37 and normal thyroid function. He was also discharged the next day with a BP 148/70 mmHg and potassium 4.2 mmol/L. Case 3-7: These were patients reported to a poison center and their potassium concentrations were 1.4, 1.4, 3.3, 1.3 and 1.2 mmol/L, respectively. Three of them were intubated and case 3 died. CONCLUSIONS: Tako-Na contains betulin, betulinic acid, taraxerone, lupeol, and lupenone. Their structures are similar to glycyrrhetic acid, the active metabolite of glycyrrhizic acid found in licorice which is well known to cause pseudoaldosteronism. Glycyrrhetic acid is potent in inhibiting 11-beta-hydroxysteroid dehydrogenase, and causes pseudoaldosteronism. We hypothesize that the compounds in Tako-Na act in the same way as glycyrrhetic acid in producing pseudoaldosteronism.

Pilot study of safety and efficacy of polyprenols in combination with coenzyme Q10 in patients with statin-induced myopathy.

BACKGROUND AND OBJECTIVE: Statin-induced myopathy (SIM) has been partially attributed to deficiency of dolichol and coenzyme Q10 (CoQ10). We aimed to test the safety and efficacy of plant polyprenols in combination with CoQ10 for alleviation of SIM. MATERIALS AND METHODS: In an open-label, one-center prospective pilot study patients with SIM received conifer-tree needle polyprenols (4mg/day) and CoQ10 (100mg/day) for 8 weeks. Symptoms and safety were evaluated according to symptom severity score (0-10), creatine kinase (CK) levels, exercise test, dynamometry, complete blood count, clinical biochemistry and electrocardiography. RESULTS: Of the 14 patients, 11 completed the study per protocol. Two patients withdrew consent due to travels abroad, and it was discontinued for one patient with stage 3 chronic kidney disease due to asymptomatic elevations of liver enzymes at week 4. No safety parameters changed significantly in per protocol group. Non-significant increase of CK levels was observed (P=0.231). Muscle pain (n=10) and weakness (n=7) scores improved significantly (P<0.001 and P=0.018, respectively). Muscle pain completely disappeared in 2 patients, weakness resolved in 3 patients and cramps disappeared in two patients. Four patients assessed improvement strong enough to consider increase of statin dose. No changes were observed in exercise test or dynamometry. CONCLUSIONS: Conifer-tree polyprenols in combination with CoQ10 may be generally safe in patients with SIM, but caution should be exercised in patients with glomerular filtration rate <60mL/min and routine monitoring of the liver enzymes and CK is advocated in all patients. The observed efficacy provides the rationale for a larger, double-blind controlled study with polyprenols.

Proximal muscular atrophy and weakness: An unusual adverse effect of deferasirox iron chelation therapy.

Deferasirox is a standard treatment for chronic transfusional iron overload. Adverse effects of deferasirox have been reported in large prospective studies. We report two cases of monozygotic twins manifesting with proximal muscular atrophy and weakness under deferasirox. Discontinuation of deferasirox resulted in symptom improvement and ultimately in complete remission five months after successful haematopoietic stem cell transplantation. Broad diagnostic work-up could not bring evidence of another aetiology of muscular weakness. Iron overload or beta thalassemia itself as a cause is considered unlikely in our patients because the chronological coincidence of muscular symptoms was contra-directional to serum ferritin levels and significant clinical improvement was observed promptly after cessation of deferasirox even before transplantation. These observations suggest that the development of muscular weakness in patients on deferasirox should be recognised as a possible adverse effect of the drug.

Isoniazid induced motor-dominant neuropathy.

Isoniazid though a very effective treatment for tuberculosis can cause severe motor-dominant neuropathy which can be reversible with pyridoxine supplementation. A 45-year-old female diagnosed with psoas abscess, culture positive for mycobacterium tuberculosis, was started on anti- tuberculous treatment with four drugs, including isoniazid at a dose of 5 mg/kg/day. Three months later she developed severe motor weakness of lower limbs with loss of ankle and knee reflexes. She was treated with vitamin B6 injections and isoniazid treatment was continued. Her motor weakness gradually improved in a few months, but mild sensory impairment persisted even after two years. There is need for vigilance regarding neurological effects of isoniazid in seemingly low-risk individuals in whom development of symptoms should raise the suspicion about slow acetylator status. Timely therapeutic intervention with high-dose vitamin B6 can reduce the long-term morbidity associated with this easily reversible condition.

Reversible weakness and encephalopathy while on long-term valproate treatment due to carnitine deficiency.

We describe a case of a 35-year-old woman who presented with bilateral leg weakness and encephalopathy while on long-term valproate therapy. She was diagnosed with valproate-induced encephalopathy due to carnitine deficiency. Clinical improvement occurred with oral carnitine supplementation. Our case report highlights the importance of considering carnitine deficiency in patients presenting with unexplained neurological signs while on long-term valproate treatment.

Prospective induction of peripheral neuropathy by the use of Tartarian Buckwheat.

Tartarian Buckwheat is an effective hypoglycemic medicinal herb. Its main active ingredients are flavonoids. We report here 5 cases of new onset polyneuropathy with dyskinesia prospectively induced by tartarian buckwheat products. Clinical and electrophysiological evidence along with laboratory tests were reviewed and analyzed. All patients were male, with an average age of 52.2 ± 10.9 years old (range: 40-66 years) and had a recent history of using tartarian buckwheat for diabetes therapy. The average time of use was 2.5 ± 1.0 months (range: 1.5-4 months). The average duration of the clinical course was 0.9 ± 0.2 months (range: 0.5-1 months). Symptoms included numbness and weakness of the limbs (5/5, 100%), hoarseness (4/5, 80%), dysphagia (1/5, 20%), bilateral facial paralysis (1/5, 20%), urinary disorders (3/5, 60%) and gonadal abnormality (4/4, 100%). Nerve conduction studies suggested more severe damages in motor nerves than sensory nerves. All the patients showed abnormality on Von Frey filaments determination. Hence, tartarian buckwheat products may cause toxic peripheral nerve lesion and the use of herbal medication needs to be better regulated and closely monitored.

[Levator muscle gravis following injection of lidocaine: a case report].

An allergic reaction was occurred in a 17-years old girl who was undergoing local anesthesia before tonsillectomy. Ptosis was observed in right side of patient shortly after injection of lidocaine to right palate. Then the patient feel grasp and cough, accompanied by nausea and vomiting. The patient was placed in supine position. Dexamethasone and epinephrine was administrated intramuscularly, symptoms were relieved 10 minutes later.

Nitrogen-bisphosphonate therapy is linked to compromised coenzyme Q10 and vitamin E status in postmenopausal women.

BACKGROUND: Nitrogen-bisphosphonates (N-BPs) are the most widely used drugs for bone fragility disorders. Long-term or high-dose N-BP use is associated with unusual serious side effects such as osteonecrosis of the jaw, musculoskeletal pain, and atypical fractures of long bones. It has escaped notice that the pathway N-BPs block is central for the endogenous synthesis of coenzyme Q10, an integral enzyme of the mitochondrial respiratory chain and an important lipid-soluble antioxidant. Our objective was to assess the coenzyme Q10 and antioxidant status in relation to N-BP exposure in women with postmenopausal osteoporosis. METHODS: Seventy-one postmenopausal women (age, 73.5 ± 5.5 y) with osteoporosis and no other malignancy were included in this cross-sectional study. Seventeen were treatment naive, 27 were on oral N-BP, and 27 were on i.v. N-BP. RESULTS: Vitamin E γ-tocopherol levels (µmol/mL) were significantly reduced in N-BP users [oral, H(2) = 18.5, P = .02; i.v., H(2) = 25.2, P < .001; mean rank comparisons after Kruskal-Wallis test). Length of time (days) of N-BP exposure, but not age, was inversely associated with the coenzyme Q10/cholesterol ratio (µmol/mol) (ß = -0.27; P = .025), which was particularly low for those on i.v. N-BP (mean difference = -35.0 ± 16.9; 95% confidence interval, -65.2 to -4.9; P = .02). CONCLUSION: The degree of N-BP exposure appears related to compromised coenzyme Q10 status and vitamin E γ-tocopherol levels in postmenopausal women with osteoporosis. This phenomenon may link to certain adverse N-BP-associated effects. Confirmation of this would suggest that therapeutic supplementation could prevent or reverse certain complications of long-term N-BP therapy for at-risk individuals.

Vitamin D deficiency: a forgotten treatable cause of motor delay and proximal myopathy.

We report a four-year-old African boy referred for proximal muscle weakness, fatigability and episodic limb pain. Classical causes of structural and metabolic myopathy were initially considered before clinical and biological features of vitamin D deficiency rickets were identified. Prompt treatment with vitamin D and calcium supplementation led to a complete reversal of the muscle symptoms. Rickets-associated myopathy should be included in the differential diagnosis of proximal myopathy, especially in at-risk individuals. Vitamin D deficiency and its prevention remain important health issues in industrialized countries.

Botulinum injection for the management of myofascial pain in the masticatory muscles. A prospective outcome study.

We prospectively analysed the outcome after botulinum injection in patients who did not recover after conservative measures to manage masticatory myofascial pain, and who were not willing to take low dose tricyclic antidepressants as a muscle relaxant. We prospectively 62 patients were assessed with visual analogue scores (VAS) for pain on the affected side before, and 6 weeks after botulinum injection(s) (50 units Dysport in up to 3 sites), and measured mouth opening in mm. Of those treated 49 (79%) showed at least some improvement (pain reduced by more than 25%). Patients reported more than a 90% reduction in the VAS for 25 (30%) of the 84 sides of the face treated. Only 22 of the 62 patients had more than one course of treatment to the same side. Interincisal distance improved by a mean/median of 0.9 mm (p<0.03) after treatment. Side effects included 3 cases of temporary weakness of a facial muscle. Ranking the VAS pain scores using the Wilcoxon test before and after injection showed a significant reduction in pain (median change -29.5, interquartile range -53 to -16, p<0.0001). The treatment significantly improved patients' pain scores and the overall mean/median reduction in pain was 57%. Botulinum injection does not guarantee complete resolution of myofascial pain, but it usually has some beneficial effect in improving the symptoms, and should be considered as an alternate treatment for masticatory myofascial pain if conservative methods have failed.

Monocrotophos toxicity and bioenergetics of muscle weakness in the rat.

Acute organophosphate pesticide poisoning is a common medical emergency with high fatality in agricultural communities of Asia. Organophosphate compounds inhibit acetylcholinesterase and prolonged neuromuscular weakness is a major cause of morbidity and mortality of poisoning. Organophosphate pesticide induced muscle weakness may not only arise from inhibition of acetylcholinesterase but also from non-cholinergic pathomechanisms, particularly mitochondrial dysfunction, affecting the production of sufficient ATP for muscle function. This study examined whether muscle weakness in rats subject to monocrotophos toxicity (0.8LD50) was caused by inhibition of ATP synthesis, by oxidative phosphorylation and glycolysis, in addition to inhibition of muscle acetylcholinesterase. Severe muscle weakness in rats following monocrotophos administration was associated with inhibition of muscle acetylcholinesterase (30-60%) but not with reduced ATP production. The rats rapidly recovered muscle strength with no treatment. The ability of rats to spontaneously reactivate dimethoxy phosphorylated acetylcholinesterase and efficiently detoxify organophosphates may prevent severe inhibition of muscle acetylcholinesterase following acute severe monocrotophos poisoning. This may protect rodents against the development of prolonged muscle weakness induced by organophosphates.

What stands in the way of treating palmar hyperhidrosis as effectively as axillary hyperhidrosis with botulinum toxin type A.

Botulinum Toxin type A (BTX-A) has revolutionized the treatment of focal hyperhidrosis (HH) in recent years and has dramatically reduced the invasive surgical techniques that have been performed in the past to control severe focal HH unresponsive to topical therapies. Whereas BTX-A injections are easily performed to control axillary HH with little or no analgesia, pain management is a must during the injection of palmar and plantar HH with BTX-A because of the intense pain generated with the 30 to 40 needle punctures needed on each hand or foot through the densely innervated skin present in those areas. For that reason, many physicians who contentedly treat axillary HH with BTX-A injections, refuse to do so for palmar and plantar HH. Although pain is the major stumbling block deterring patients and physicians from choosing this treatment option, it is not the only one. Many other factors may play a role in deciding whether or not to treat palmar and plantar HH with BTX-A injections. This article reviews these factors and presents some personal data from patients who have already been treated with BTX-A injections on the palms and soles and who came back once or more for repeat treatments when the effect of BTX-A started to fade away. "Jet Anesthesia" was the pain management method used in this group.