Myopathy associated with type 3 glycogenosis

A patient who developed osteomalacia while receiving phenytoin sodium 200–300 mg daily for 8 years for treatment of a seizure disorder is reported. In addition, this patient had folic acid deficiency. Throughout the patient received only phenytoin sodium. Recent reports of abnormalities of calcium metabolism due to anticonvulsant drugs are reviewed.     

Gelastic seizures in tuberous sclerosis complex: case report and literature review

Gelastic seizures are typically associated with hypothalamic hamartoma. Given the rarity of gelastic seizures, pathways for the motor and emotional aspects of laughter have been hypothesized but remain unclear. The authors perform a literature review to discuss what is known about these pathways. They also report a child who presented with tuberous sclerosis complex initially without cutaneous stigmata, who later developed gelastic seizures. Only 2 case reports of patients with tuberous sclerosis complex who subsequently developed gelastic epilepsy have previously been reported. In discussing his case, the authors postulate additional etiologies for gelastic seizures.     

Cutaneous Side-effects of Immunomodulators in MS

Local skin reactions to subcutaneous injections of interferon beta (IFNB) or glatiramer acetate (GA) in multiple sclerosis (MS) are frequent, while severe cutaneous toxicity is rare. Both IFNB and GA are immunomodulatory drugs that have excellent safety profiles and are currently used for treatment of MS. They are administered by SC injection every other day for IFNB-1b, three times a week for IFNB-1a or daily for 20 mg for GA. The most common adverse effects, which occur in approximately 20-60% of patients, include pain, inflammation and induration at the injection sites. Another adverse effect is frank panniculitis followed by localized lipoatrophy at the injection sites, which has been described in half of the patients receiving GA injections but is also described with Subcutaneous IFNB-1b. No guidelines have yet been established for the treatment of skin reactions, which is a frequent point for discussion between neurologists and dermatologists. In addition, no treatment has been found for established lipoatrophy. The prevention and management of cutaneous side-effects include patient education, regular examination and manual palpation of all injection sites. Non-steroid antiinflammatory gels, local corticosteroids or endermology can help patients to resolve side-effects and to continue immunomodulatory treatment.     

Diabetic ketoacidosis associated with lithium: case report

Diabetic ketoacidosis developed in a 41-year-old man who had been receiving lithium for 4 months. The patient required daily insulin administration following the discontinuation of lithium.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Hemichorea: a rare presentation of tuberculoma

Hemichorea due to tuberculoma has not been reported. We managed a 16-year-old girl who developed transient left hemichorea due to right sided striatal tuberculoma. Chorea regressed following 1 week of antitubercular treatment with corticosteroid therapy and disappeared at 3 months. In a patient presenting with chorea, striatal tuberculoma should also be considered especially in the area where tuberculosis is prevalent.     

Carbamazepine-induced drug-induced hypersensitivity syndrome in a 14-year-old Japanese boy

Drug-induced hypersensitivity syndrome (DIHS) is a life-threatening idiosyncratic drug reaction, and an early accurate diagnosis is essential for its treatment. We describe a 14-year-old boy with localization-related epilepsy, who developed severe adverse cutaneous and systemic reactions after 3 weeks of carbamazepine administration. During the course of the clinical symptoms, reactivation of human herpesvirus 6 (HHV-6) was proven by detection of the HHV-6 genome in serum and elevation of HHV-6 immunoglobulin G (IgG). He fulfilled the newly established criteria for DIHS. Among eight identified medications that can precipitate DIHS, four are antiepileptic drugs. Establishing a treatment strategy for DIHS is warranted to improve its outcome. Therefore, it is important to raise awareness of DIHS among epileptologists.     

Suspected lamotrigine-induced toxic epidermal necrolysis

Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare, life treating cutaneous reactions. Most cases of toxic epidermal necrolysis are drug induced. The drugs with the highest estimated incidence include co-trimoxazloe (trimethoprim-sulfamethoxazole), sulfadoxine-pyrethamine, and carbamazepine. Among other drugs, the reported reaction rates are relatively low for lamotrigine and sulbactam-ampicillin. We describe a patient who developed toxic epidermal necrolysis after either administration of lamotrigine or of ampicillin.     

Neuroleptic malignant syndrome induced by ziprasidone on the second day of treatment.

Neuroleptic malignant syndrome (NMS) is the rarest and most serious of the neuroleptic-induced movement disorders. We describe a case of neuroleptic malignant syndrome (NMS) associated with the use of ziprasidone. Although conventional neuroleptics are more frequently associated with NMS, atypical antipsychotic drugs like ziprasidone may also be a cause. The patient is a 24-year-old male with a history of schizophrenia who developed signs and symptoms of NMS after 2 days of treatment with an 80-mg/day dose of orally administrated ziprasidone. This case is the earliest (second day of treatment) NMS due to ziprasidone reported in the literature.     

Refractory epilepsy: treatment with new antiepileptic drugs.

Five antiepileptic drugs have been marketed in the last decade. We report here a retrospective study of patients attending our unit who were prescribed one of the new antiepileptic drugs. All these patients had refractory localization related epilepsy and had failed to respond to a first-line drug. The drugs had a different profile of side-effects but topiramate (42%) was the most common drug to be withdrawn due to side-effects as compared with tiagabine (26%), vigabatrin (16%), gabapentin (16%), and lamotrigine (15%). With regard to efficacy, 31% of the patients receiving gabapentin had a greater than 50% reduction in seizures compared with lamotrigine (25%), topiramate (20%), vigabatrin (19%) and tiagabine (11%). The number of patients remaining seizure free with gabapentin was 8% whilst for lamotrigine this was 5%, vigabatrin 5%, topiramate 1% and tiagabine 4%. In conclusion, all these five antiepileptic drugs are useful in treating refractory localization related epilepsy.     

Phenytoin Induced Erythema Multiforme after Cranial Radiation Therapy

The prophylactic use of phenytoin during and after brain surgery and cranial irradiation is a common measure in brain tumor therapy. Phenytoin has been associated with variety of adverse skin reactions including urticaria, erythroderma, erythema multiforme (EM), Stevens-Johnson syndrome, and toxic epidermal necrolysis. EM associated with phenytoin and cranial radiation therapy (EMPACT) is a rare specific entity among patients with brain tumors receiving radiation therapy while on prophylactic anti-convulsive therapy. Herein we report a 41-year-old female patient with left temporal glial tumor who underwent surgery and then received whole brain radiation therapy and chemotherapy. After 24 days of continous prophylactic phenytoin therapy the patient developed minor skin reactions and 2 days later the patient returned with generalized erythamatous and itchy maculopapuler rash involving neck, chest, face, trunk, extremities. There was significant periorbital and perioral edema. Painful mucosal lesions consisting of oral and platal erosions also occurred and prevented oral intake significantly. Phenytoin was discontinued gradually. Systemic admistration of corticosteroids combined with topical usage of steroids for oral lesions resulted in complete resolution of eruptions in 3 weeks. All cutaneous lesions in patients with phenytoin usage with the radiotherapy must be evoluated with suspicion for EM.     

Intracranial Hemorrhage Sparing Meningioma in an Anticoagulated Patient

BACKGROUND AND PURPOSE: The risk of intracerebral hemorrhage (ICH) in patients receiving antithrombotic therapy is well known. However, there is sparse literature regarding the risk of intracerebral hemorrhage in patients receiving warfarin, who have an intracranial meningioma. METHODS AND RESULTS: We report a case of a 66-year-old man who developed multifocal ICHs in the context of supratherapeutic anticoagulation. There was sparing of the intracranial meningioma despite the development and growth of multiple intraparenchymal hemorrhages that resulted in death. We also review the literature evaluating the risk of ICH in anticoagulated patients with an intracranial meningioma. CONCLUSIONS: The findings of this case lend further support to the gradually developing notion of relative safety of anticoagulation in patients with meningioma. They also underscore the importance of close monitoring of the INR.     

Problems in the use of long-acting hypnotics in older patients

Insomnia and the use of long-acting hypnotic drugs are prevalent in geriatric populations. These drugs have been shown in the laboratory to adversely affect motor performance in the elderly. To examine the clinical significance of these findings, comparisons were made between patients who experienced a fall during their hospital stay and those who did not fall. It was found that patients over 70 years of age who experienced a fall in the hospital were more likely to be receiving flurazepam than the patients who did not fall.     

Allergy to tartrazine in psychotropic drugs

BACKGROUND: High psychiatric morbidity has been reported among those who complain of food intolerance or allergy. Many cases of food allergy or intolerance to drugs are not due to allergy to the food or drugs themselves, but to the additives used for coloring, flavoring, preserving, thickening, emulsifying, or stabilizing the product. Of various coloring dyes used, tartrazine (FD & C yellow no. 5) is the color most frequently incriminated in producing allergic reactions. The exact epidemiology and pattern of allergic reactions to tartrazine in psychotropic drugs have not been frequently studied and reported. METHOD: The present study included consecutive outpatients (May 1996 to April 1998) who developed allergic reactions or intolerance to tartrazine in psychotropic drugs. Total patients exposed to tartrazine-containing drugs were also recorded. The subjects showing allergic reactions to tartrazine were then exposed to non-tartrazine-containing brands. RESULTS: Of 2210 patients exposed to tartrazine-containing drugs, 83 (3.8%) developed allergic reactions. The symptoms subsided within 24 to 48 hours of stopping the drug. None of the patients showed allergy to non-tartrazine-containing brands. History of allergy to tartrazine was present in 13.2%, and 15.7% of patients had a history of aspirin sensitivity. CONCLUSION: Tartrazine allergy should be considered in patients developing drug allergy, because it would require changing the brand rather than stopping treatment with that drug.     

Acute encephalopathy with hyperammonemia and dicarboxylic aciduria during calcium hopantenate therapy: a patient report

We report a 3-year-old Japanese girl who developed acute encephalopathy while receiving calcium hopantenate (Calcium D-(+)-4-(2, 4-dihydroxy-3,3-dimethylbutyramido) butyrate hemihydrate). She had hyperammonemia, elevated CPK, lactic acidemia and pyruvic acidemia, however, she did not show elevated SGOT or SGPT. Calcium hopantenate has been used in Japan for the treatment of mental retardation with behavior abnormalities. Recently there have been three reports on the occurrence of Reye-like syndrome in patients receiving this drug. Clinical signs and laboratory data of these patients are similar to those of Reye syndrome. Calcium hopantenate causes pantothenic acid deficiency in the young rat, which may reduce the content of coenzyme A. If this drug decreases coenzyme A biosynthesis, it may reduce beta-oxidation of fatty acids and levels of dicarboxylic acids would increase because of increasing omega-oxidation. We suspect that there is a possible relationship between the occurrence of acute encephalopathy and calcium hopantenate therapy.     

Cutaneous reactions in patients with solitary cysticercus granuloma on phenytoin sodium

Several medical conditions are believed to be associated with an increased risk of cutaneous adverse reactions to anti-epileptic drugs. The aim of this study was to study the frequency and nature of cutaneous reactions in a cohort of patients being treated with phenytoin sodium for seizures, who were divided into those with a solitary cysticercus granuloma (SCG) and those with a condition other than SCG, to determine if the presence of SCG increases the risk of cutaneous adverse reaction to phenytoin. A cohort of 117, consecutively begun on treatment with phenytoin for seizure control, were followed up prospectively for the development of cutaneous reactions. There were 63 patients with SCG upon imaging and 54 patients to whom phenytoin was administered for seizures due to causes other than SCG or multiple neurocysticercosis. Cutaneous reactions were significantly more common (p = 0.02) in patients with SCG (9/63 patients; 14.3%) than in controls (2/54 patients; 3.7%). The spectrum of skin reactions in patients with SCG included benign skin rash (n = 3), anticonvulsant hypersensitivity syndrome (n = 4), Stevens-Johnson syndrome (n = 1), and urticaria (n = 1). Individuals with seizures due to SCG have a high incidence of cutaneous adverse reactions to phenytoin. This fact should be kept in mind when initiating them on treatment with this anti-epileptic drug.     

Are prophylactic antiparkinson drugs necessary? A controlled study of procyclidine withdrawal.

Of 55 aftercare patients receiving long-term treatment with antipsychotic and antiparkinson (AP) drugs, 37 were switched to being given placebo, and 18 remained on a regimen of procyclidine hydrochloride. The dose of antipsychotic was kept constant. After three weeks extrapyramidal side effects (EPS) developed in 54% of those patients receiving placebo and in none of those receiving procyclidine (P less than .002): Twenty-seven percent of the placebo group had EPS without akinesia, and in the same percentage akinesia developed (P = .003). We believe the risk-benefit ratio favors the routine use of AP drugs for prophylaxis and maintenance so as to avoid misdiagnosing as psychopathology, unspontaneity due to akinesia, and to reduce unreliable pill-taking due to EPS.     

Urinary retention in the course of neuroleptic therapy with haloperidol

A case history was presented of a 49-year-old female patient, who had developed paranoid-hallucinatory schizophrenia for the first time and suffered from an acute functional bladder obstruction while receiving haloperidol. Thorough urological examination showed no pathologic findings except for a medium-grade urinary tract infection. No beneficial effects were obtained after application of parasympathicomimetic substances (carbachol, distigminebromide). After discontinuation of haloperidol therapy normal bladder function returned. The question as to the basic causative pharmacologic mechanism remains unanswered but the hypothesis that bladder dysfunction is due solely to the anticholinergic side-effects of haloperidol merits further critical elucidation and research.     

Polymyositis and cutaneous vasculitis in a patient with myelodysplastic syndrome]

We report a 60-year-old man with myelodysplastic syndrome (MDS) who developed polymyositis and cutaneous vasculitis. He noticed difficulty in climbing up stairs 4 months before admission. On admission, he showed brownish skin pigmentation in the distal positions of the four extremities. Neurological examination revealed muscle weakness of the neck flexor and proximal muscles of four extremities. Serum myogenic enzymes including creatine kinase increased, and electromyography showed denervation potentials and MUPs were myogenic, which was compatible with polymyositis. Muscle biopsy indicated perivascular mononuclear cell infiltration and muscle fiber necrosis with cytoplasmic bodies and rimmed vacuoles in the muscle fibers. Complete blood cell counts revealed macrocytic normochromic anemia and bone marrow puncture disclosed marked hyperplasia of megakaryocytes, erythroblasts and myeloblasts, suggesting a refractory anemia type of MDS. In addition, skin biopsy showed chronic cutaneous vasculitis. Serum protein electrophoresis and immunoelectrophoresis revealed the presence of IgM gamma type monoclonal gammopathy. With immunosuppressive therapy, serum creatine kinase level was decreased. Since immunological abnormalities and the presence of autoimmune diseases have been reported in patients with MDS, both polymyositis and chronic cutaneous vasculitis in the present patient may be caused by the similar autoimmune mechanisms related to MDS.