Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149958 (complex partial seizures)
 2,563 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seizures are extremely common in the elderly, with an annual incidence reaching 100 per 100000 people aged over 60 years. Most are precipitated by acute symptomatic illnesses such as stroke or systemic disease. Chronic neurological diseases such as Alzheimer's disease may also cause seizures. The aetiology of seizures in many patients is unknown. Seizures may be situational and subside quickly, but the prevalence of chronic seizures--epilepsy--is as high as 1% in the elderly. The majority of seizures are of partial onset, especially complex partial. Complex partial seizures at this age may be very subtle and hard to diagnose. Generalised-onset seizures also occur, perhaps as a result of diffuse changes with aging or degenerative disease or to a combination of genetic and environmental factors. The prognosis for complete seizure control in this population is relatively favourable. Physiological and disease-related changes with aging result in complex pharmacokinetics. Most changes lead to a need for gentler drug treatment with cautious initiation of drugs at lower dosages. Consideration must be given to renal and hepatic function, protein binding and drug interactions. Determinations of free (unbound) drug concentrations are helpful for highly protein bound drugs. The dosages of newer drugs excreted renally must be adjusted based on creatinine clearance. The dosage of most drugs is determined empirically by careful observation of seizure control and adverse effects. Carbamazepine, valproic acid (sodium valproate), gabapentin and lamotrigine have certain theoretical advantages, but comparative trials of anticonvulsants in the elderly are needed. The ideal drug for older patients would be effective, without neurological toxicity, with low protein binding, a nonparticipant in drug interactions and amenable to once daily administration.
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PMID:Epidemiology and drug treatment of epilepsy in elderly people. 1058 73

Guanidinoacetate methyltransferase (GAMT) deficiency is a rare disorder of creatine synthesis resulting in cerebral creatine depletion. We present a 38-year-old patient, the first Japanese case of GAMT deficiency. Developmental delay started after a few months of age with a marked delay in language, which resulted in severe intellectual deficit. She showed hyperactivity and trichotillomania from childhood. Epileptic seizures appeared at 18 months and she had multiple types of seizures including epileptic spasms, brief tonic seizures, atypical absences, complex partial seizures with secondary generalization, and "drop" seizures. They have been refractory to multiple antiepileptic drugs. Although there have been no involuntary movements, magnetic resonance imaging revealed T2 hyperintense lesions in bilateral globus pallidi. Motor regression started around 30 years of age and the patient is now able to walk for only short periods. Very low serum creatinine levels measured by enzymatic method raised a suspicion of GAMT deficiency, which was confirmed by proton magnetic resonance spectroscopy and urinary guanidinoacetate assay. GAMT gene analysis revealed that the patient is a compound heterozygote of c.578A>G, p.Gln193Arg and splice site mutation, c.391G>C, p.Gly131Arg, neither of which have been reported in the literature. We also identified two aberrant splice products from the patient's cDNA analysis. The patient was recently started on supplementation of high-dose creatine and ornithine, the effects of which are currently under evaluation. Although rare, patients with developmental delay, epilepsy, behavioral problems, and movement disorders should be vigorously screened for GAMT deficiency, as it is a treatable disorder.
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PMID:A Japanese adult case of guanidinoacetate methyltransferase deficiency. 2384 10

Dietary protein restriction may improve determinants of CKD progression. However, the extent of improvement and effect of ketoanalogue supplementation are unclear. We conducted a prospective, randomized, controlled trial of safety and efficacy of ketoanalogue-supplemented vegetarian very low-protein diet (KD) compared with conventional low-protein diet (LPD). Primary end point was RRT initiation or >50% reduction in initial eGFR. Nondiabetic adults with stable eGFR<30 ml/min per 1.73 m(2), proteinuria <1 g/g urinary creatinine, good nutritional status, and good diet compliance entered a run-in phase on LPD. After 3 months, compliant patients were randomized to KD (0.3 g/kg vegetable proteins and 1 cps/5 kg ketoanalogues per day) or continue LPD (0.6 g/kg per day) for 15 months. Only 14% of screened patients patients were randomized, with no differences between groups. Adjusted numbers needed to treat (NNTs; 95% confidence interval) to avoid composite primary end point in intention to treat and per-protocol analyses in one patient were 4.4 (4.2 to 5.1) and 4.0 (3.9 to 4.4), respectively, for patients with eGFR<30 ml/min per 1.73 m(2) Adjusted NNT (95% confidence interval) to avoid dialysis was 22.4 (21.5 to 25.1) for patients with eGFR<30 ml/min per 1.73 m(2) but decreased to 2.7 (2.6 to 3.1) for patients with eGFR<20 ml/min per 1.73 m(2) in intention to treat analysis. Correction of metabolic abnormalities occurred only with KD. Compliance to diet was good, with no changes in nutritional parameters and no adverse reactions. Thus, this KD seems nutritionally safe and could defer dialysis initiation in some patients with CKD.
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PMID:Ketoanalogue-Supplemented Vegetarian Very Low-Protein Diet and CKD Progression. 2682 49

Cefepime is a 4th generation cephalosporin often used for its ability to cover gram-positives, gram negatives, anaerobic bacteria, and, most importantly, pseudomonas. Prior to initiation of cefepime, the medication is dosed based on the renal function to avoid a multitude of its toxicity profiles, including encephalopathy, aphasia, myoclonus, seizures, and nonconvulsive status epilepticus. These risks are increased in the presence of renal impairment. We present a case of a 65-year-old woman who had presented to the emergency department (ED) two weeks after initiation of outpatient IV cefepime therapy with concerns of altered mentation and decreased oral intake. In the ED, the patient was noted to have a creatinine: 5.77 (baseline of 0.76) and urea: 94. During evaluation by the ED provider, the patient was noted to have transient slurring of speech, speech arrest, and tonic-clonic movements on the right. CT of the head, followed by CT angiography of the head and neck, demonstrated no acute intracranial pathology. Spot EEG revealed generalized slowing with unclear left-sided epileptiform discharges. There was a concern for complex partial seizures. Neurology and nephrology were consulted. The patient was given 1 g of levetiracetam, and emergent dialysis was performed. After dialysis, no other epileptiform activity was noted with the improvement of her encephalopathy. The patient returned to her baseline mentation. Here we emphasize the importance of recognizing cefepime's toxicity profile while triaging patients. In the rare event of toxicity, immediate treatment is discontinuing the offending agent and initiation of emergent hemodialysis.
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PMID:Cefepime-Induced Seizures: The Overlooked Outpatient Adverse Reaction. 3269 29