Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients presenting with subacute amnesia are frequently seen in acute neurological practice. Amongst the differential diagnoses, herpes simplex encephalitis, Korsakoff's syndrome and limbic encephalitis should be considered. Limbic encephalitis is typically a paraneoplastic syndrome with a poor prognosis; thus, identifying those patients with potentially reversible symptoms is important. Voltage-gated potassium channel antibodies (VGKC-Ab) have recently been reported in three cases of reversible limbic encephalitis. Here we review the clinical, immunological and neuropsychological features of 10 patients (nine male, one female; age range 44-79 years), eight of whom were identified in two centres over a period of 15 months. The patients presented with 1-52 week histories of memory loss, confusion and seizures. Low plasma sodium concentrations, initially resistant to treatment, were present in eight out of 10. Brain MRI at onset showed signal change in the medial temporal lobes in eight out of 10 cases. Paraneoplastic antibodies were negative, but VGKC-Ab ranged from 450 to 5128 pM (neurological and healthy controls <100 pM). CSF oligoclonal bands were found in only one, but bands matched with those in the serum were found in six other patients. VGKC-Abs in the CSF, tested in five individuals, varied between <1 and 10% of serum values. Only one patient had neuromyotonia, which was excluded by electromyography in seven of the others. Formal neuropsychology testing showed severe and global impairment of memory, with sparing of general intellect in all but two patients, and of nominal functions in all but one. Variable regimes of steroids, plasma exchange and intravenous immunoglobulin were associated with variable falls in serum VGKC-Abs, to values between 2 and 88% of the initial values, together with marked improvement of neuropsychological functioning in six patients, slight improvement in three and none in one. The improvement in neuropsychological functioning in seven patients correlated broadly with the fall in antibodies. However, varying degrees of cerebral atrophy and residual cognitive impairment were common. Over the same period, only one paraneoplastic case of limbic encephalitis was identified between the two main centres. Thus, VGKC-Ab-associated encephalopathy is a relatively common form of autoimmune, non-paraneoplastic, potentially treatable encephalitis that can be diagnosed by a serological test. Establishing the frequency of this new syndrome, the full range of clinical presentations and means of early recognition, and optimal immunotherapy, should now be the aim.
 ...
PMID:Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. 1496 Apr 97

Recent findings raised evidence that in early-onset left temporal lobe epilepsy, women show greater functional plasticity for verbal memory than men. In particular, women with lesion- or epilepsy-driven atypical language dominance show an advantage over men. The question asked in this study was whether there is evidence of sex- and language dominance-dependent late, i.e. adult age, plasticity for verbal memory when epilepsy surgery is performed in these patients. Pre- and 1-year postoperative memory performance was evaluated in 169 patients (94 males and 75 females) who underwent left temporal lobe surgery and who had WADA testing of hemispheric language dominance prior to surgery. Verbal memory and figural memory were assessed by list-learning paradigms. According to the Bonn intracarotid amobarbital test (IAT) protocol, patients were categorized into left dominant or atypically dominant (right, incomplete left or right, and bilateral dominant) groups. Results were controlled for the hypothesized sex differences. Thirty-four percent of men and 47% of women displayed patterns of atypical language dominance. Atypical dominance was related to an early onset of epilepsy. Men showed a larger time window for development of atypical dominance but, differently from women, the pattern of atypical dominance was more strictly determined by the age at onset of epilepsy. Atypically dominant women showed better verbal memory than typically dominant women or men. After surgery, right dominant patients had better verbal memory outcome than patients with bilateral or left language dominance who showed significant memory loss. No effect of sex on verbal memory change was found. Figural memory deteriorated in men and improved in women, when they were not left dominant. Seizure outcome had no effect on performance changes. It was concluded that better preserved verbal memory in atypically dominant women before surgery indicates greater benefit from atypical dominance in women than men with regard to the initial damage associated with left hemisphere epilepsy. Later in life, when epilepsy surgery causes additional damage, no such sex difference is observed, indicating that the women's advantage over men is fixed to an early time window in life. Postoperative changes in figural memory suggest dynamics in crowding and suppression patterns. Whether this reflects late plasticity and compensation needs further demonstration. For clinical practice, it is important to note that incomplete right hemisphere and bilateral language dominance do not protect against verbal memory loss after left-sided temporal lobe surgery.
 ...
PMID:The impact of sex and language dominance on material-specific memory before and after left temporal lobe surgery. 1512 17

In a retrospective chart review, we identified 35 patients with medically refractory epilepsy (MRE) who had been converted from polypharmacy to monotherapy and maintained on monotherapy for at least 12 months. None of the 35 patients had worsening of their seizure frequency after the conversion to monotherapy. Fourteen of the 35 patients (40%) became seizure-free. Nine of 35 patients (26%) had a 50% reduction in seizure frequency. Five of 35 patients (14%) had a 75% reduction in seizure frequency. Twenty-eight (80%) of 35 patients participated in a quality-of-life questionnaire. Quality of life was rated as better on monotherapy as compared with polypharmacy in a number of domains: memory loss, concern over medication long-term effects, difficulty in taking the medications, trouble with leisure time activities, and overall state of health. This improvement reached statistical significance. Conversion to monotherapy in patients with MRE may be successful in achieving a reduction in seizure frequency and an improvement in quality-of-life parameters. A prospective, randomized trial is necessary to validate these findings.
 ...
PMID:Improvement in seizure control and quality of life in medically refractory epilepsy patients converted from polypharmacy to monotherapy. 1514 4

Juhn Wada developed a test while in Montreal designed to definitively confirm hemispheric lateralization of speech in candidates for surgical treatment of epilepsy. By unilateral intra-carotid administration of a bolus of a general anesthetic, classically sodium amobarbital, function can be tested in the non-injected hemisphere, while the injected side is dysfunctional. The test has been expanded to test memory functions in the hemisphere (temporal lobe) contralateral to expected surgery (memory reserve) in the hope of contra-indicating surgery that may result in global amnestic syndromes (patient HM). Conversely, risk of material-specific memory loss following surgery can be assessed by testing memory in the hemisphere/temporal lobe to be operated ("functional adequacy"). Memory dysfunction, when concordant with EEG seizure onset and chosen side of temporal lobe surgery has also been shown to correlate with favourable post-operative seizure outcome. Nevertheless, the test remains invasive, requiring an angiogramme. Non-invasive alternatives such as fMRI and PET and their reported reliability compared to a Wada test are discussed. A world-wide shortage of amobarbital has led to the use of some other anesthetic agents. Overall, the indications for the test and the manner in which it is performed vary greatly from one institution to the next. It is used almost systematically in some institutions and very rarely in others. Future perspectives are discussed.
 ...
PMID:[What is the current role of a Wada test in the pre-surgical work-up of pharmacologically intractable epilepsy in adults?]. 1533 62

Craniopharyngiomas are rare brain tumors of the hypothalamo-pituitary region, developing from embryonic remnants of Rathke's pouch and sac. Their overall incidence is 0.13 per 100,000 person years. Most frequently, they are suprasellar, start growing in childhood and originate neurological and hormonal symptoms. We retrospectively studied patients treated in our institution for craniopharyngioma in the last 10 years, in order to evaluate their clinical, imaging and pathological characteristics. Of the 32 patients analysed, 18 were females and 14 males with ages ranging between 6 and 81 years (early onset group--EOG aged 5-14 years: 7 patients; middle age onset group--MAOG aged 15-49 years: 15 patients; late age onset group--LOG aged > or = 50 years: 10 patients). Visual impairment was the most frequent presenting clinical feature in EOG (71.4%) and MAOG (86.6%), while in the LOG personality and cognitive changes including memory loss predominated (60%). Headaches were very frequent in all groups (EOG 42.8%, MAOG 60%, LOG 40%). Meningitis and seizures were presenting features, each in one patient. Regarding endocrine symptoms and signs, growth failure was present in 57.2% of the EOG. Amenorrhea was present in 5 of 10 female patients of the MAOG. Preoperatively, TSH was deficient in 25%, ACTH in 15.6% and gonadotropin in 25% of the patients. There were no cases of diabetes insipidus. Preoperative CT and MR revealed a calcified mass in 12 (37.5%), a partially cystic mass in 20 (62.5%) and a lesion involving or extending into the third ventricle in 7 (21.9%) patients. Twenty seven (84.4%) patients were treated primarily by surgery. In 4 (12.5%) cases the tumour was considered inoperable and 1 (3.1%) patient refused surgery; all were in the LOG. Surgical approach was transsphenoidal in 2/27 (7.4%) (all of them in the LAOG) and by craniotomy in the others. The tumour removable was considered complete in 10 (37%--EOG 2/7, MAOG 6/15, LOG 2/5) and subtotal in 17 (62.9%) patients. Eight (29.6%) patients were reoperated for recurrent tumour. Postoperative radiotherapy was administered in 12 cases with residual tumor, and 3 inoperable tumors were treated primarily by conventional external radiotherapy. Pathological study revealed the adamantinomatous type in 25 (92.6%) and the papillary type in 2 (7.4%--all men in the MAOG) tumors. The average follow-up was longer in the EOG (82.6 +/- 40.7 months) than in MAOG (57.2 +/- 48.5 months) and in LOG (48 +/- 92 months). Four (12.5%) patients died, 1 during the follow-up period due to a radiation-induced astrocytoma and 3 in the postoperative period because of cerebral hemorrhage and hydrocephalus (1 in the EOG and 2 in the LOG). In summary, we found the clinical presentation to be different in the 3 age groups, with a large number of patients in the MAOG. In this group were the only examples of the papillary form. Better prognosis was associated with a total resection at initial surgery.
 ...
PMID:[Craniopharyngiomas. Clinicopathological aspects in different age groups]. 1552 57

Limbic encephalitis was identified as a clinicopathological entity in 1968. Up to a few years ago, 200 cases were described, most associated with lung cancer and more infrequently with other tumors. The recent identification of patients with this syndrome, idiopathic limbic encephalitis, who never develop cancer and have high titers of antibodies to voltage-gated potassium channels (VGKC) and an excellent response to immunosuppressive therapy, has extended the etiological spectrum and suggests that the syndrome may be under-recognized. The disorder, which develops in a few days or weeks, is characterized by the development of short-term memory loss, seizures, confusion and psychiatric features. The presence of symptoms beyond the limbic system is highly suggestive of a paraneoplastic origin. When limbic encephalitis is suspected, the following tests should be performed in order to demonstrate: a) involvement of the temporal lobes (EEG and brain MRI); b) presence of inflammatory abnormalities in the CSF, and c) the presence of onconeural antibodies or anti-VGKC. Once the diagnosis is confirmed by the clinical picture and MRI findings, treatment must be initiated without waiting for the antibody results because its negativity does not exclude the diagnosis. Detection of an onconeural antibody will confirm that the limbic syndrome is paraneoplastic and will help us to search for an underlying tumor and to predict possible response to the treatment. The recommended treatment is cycles of methylprednisolone (1 g/day for 3 to 5 days). Therapeutic response in the idiopathic limbic encephalitis is excellent and may be good in limbic encephalitis with anti-Ma2 or without onconeural antibodies. On the contrary, immunosuppressant treatment is not usually effective in limbic encephalitis associated to anti-Hu antibodies.
 ...
PMID:[Limbic encephalitis: a probably under-recognized syndrome]. 1570 18

We describe the clinical phenotype and pathology of a new autosomal dominant late-onset familial form of Alzheimer's disease in four extensive kindred originated in a genetically isolated population. Twelve affected and 16 unaffected members of these kindred were examined clinically, and a brain post-mortem study was carried out in one case. The preliminary genetic assessment included complex segregation analysis, evaluation of the power to detect linkage, and exclusion of candidate genes. Dementia has been recorded for six generations in ancestors of examined cases. Review of death certificates allowed linking of all subjects in four extensive pedigrees. Affected individuals examined had progressive memory loss with onset between 57 and 74 years of age, along with seizures, myoclonus and parkinsonism in advanced stages. The brain of the case examined post-mortem showed widespread neocortical neuritic plaques and neurofibrillary tangles (stage VI of Braak), amyloid angiopathy, and Lewy bodies restricted to limbic areas. Sequencing exons 16 and 17 of amyloid precursor protein, and exons 4-12 of presenilin 1 and presenilin 2 genes did not disclose any mutations. Genotyping with markers D21S265, D14S71, D14S77, D1S2850 and D1S479 located 1-3 cM from the previously reported genes further excluded linkage to these genes. Seven out of 12 cases were apolipoprotein E (APOE) epsilon3/3, although the presence of an APOE epsilon4 allele was associated with an increased risk of dementia (odd ratio 6.17; 95% confidence interval: 1.15-33.15), but not to an earlier age of onset. Complex segregation analysis showed that the best model fitting the data was that of a major gene (dominant) with a gene frequency close to 3% in this population. Simulation analysis predicted an average logarithm of odds (LOD) of 2.2 at = 0.05. These four families, which seem to be part of a common extended pedigree originated by a founder arriving in this region in the 18th century, represent an autosomal dominant late-onset familial Alzheimer's disease not linked to previously known genetic loci. The simulation analysis suggests that it will be feasible to locate a novel responsible gene in these kindred.
 ...
PMID:A multigenerational pedigree of late-onset Alzheimer's disease implies new genetic causes. 1584 24

We report seven patients, six from a single institution, who developed subacute limbic encephalitis initially considered of uncertain aetiology. Four patients presented with symptoms of hippocampal dysfunction (i.e. severe short-term memory loss) and three with extensive limbic dysfunction (i.e. confusion, seizures and suspected psychosis). Brain MRI and [(18)F]fluorodeoxyglucose (FDG)-PET complemented each other but did not overlap in 50% of the patients. Combining both tests, all patients had temporal lobe abnormalities, five with additional areas involved. In one patient, FDG hyperactivity in the brainstem that was normal on MRI correlated with central hypoventilation; in another case, hyperactivity in the cerebellum anticipated ataxia. All patients had abnormal CSF: six pleocytosis, six had increased protein concentration, and three of five examined had oligoclonal bands. A tumour was identified and removed in four patients (mediastinal teratoma, thymoma, thymic carcinoma and thyroid cancer) and not treated in one (ovarian teratoma). An immunohistochemical technique that facilitates the detection of antibodies to cell surface or synaptic proteins demonstrated that six patients had antibodies to the neuropil of hippocampus or cerebellum, and one to intraneuronal antigens. Only one of the neuropil antibodies corresponded to voltage-gated potassium channel (VGKC) antibodies; the other five (two with identical specificity) reacted with antigens concentrated in areas of high dendritic density or synaptic-enriched regions of the hippocampus or cerebellum. Preliminary characterization of these antigens indicates that they are diverse and expressed on the neuronal cell membrane and dendrites; they do not co-localize with VGKCs, but partially co-localize with spinophilin. A target autoantigen in one of the patients co-localizes with a cell surface protein involved in hippocampal dendritic development. All patients except the one with antibodies to intracellular antigens had dramatic clinical and neuroimaging responses to immunotherapy or tumour resection; two patients had neurological relapse and improved with immunotherapy. Overall, the phenotype associated with the novel neuropil antibodies includes dominant behavioural and psychiatric symptoms and seizures that often interfere with the evaluation of cognition and memory, and brain MRI or FDG-PET abnormalities less frequently restricted to the medial temporal lobes than in patients with classical paraneoplastic or VGKC antibodies. When compared with patients with VGKC antibodies, patients with these novel antibodies are more likely to have CSF inflammatory abnormalities and systemic tumours (teratoma and thymoma), and they do not develop SIADH-like hyponatraemia. Although most autoantigens await characterization, all share intense expression by the neuropil of hippocampus, with patterns of immunolabelling characteristic enough to suggest the diagnosis of these disorders and predict response to treatment.
 ...
PMID:Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. 1603 Jan 81

Alzheimer disease (AD) is the most common neurodegenerative disease presenting with relentless memory loss. A number of factors contribute to comorbidity and mortality and seizures are among the most common ones. Seizures worsen existing demantia, and by causing falls lead to serious complications like fractures and intracranial hemorrhage. Hippocampus is one of the earliest affected structures in brain in AD. It undergoes atrophy followed by progressive neuron loss. Atrophy appears much before the clinical manifestations of AD develop. Hence, there is a potential for its prevention or reversal. Neuron loss in brains of AD have two important consequences: these include development of AD and seizures. Patients of AD have unusually high incidence of seizures and the first seizure episode in this population is considered to be an indication of treatment with anti-seizure drugs. Among many drugs that have been shown to prevent hippocampal atrophy is phenytoin. It is time tested and proven anticonvulsant that can be used to prevent the development of atrophy and consequent development of AD. Phenytoin can thus be exploited for its dual effects i.e. reversal of hippocampal atrophy and anti-seizure effects. Selection of patients, appropriate dose, duration, monitoring and drug safety are important issues to be addressed before the testing of this hypothesis can be considered. Ideal candidates will be those who are at risk of development of AD or those with milder symptoms.
 ...
PMID:Can phenytoin prevent Alzheimer's disease? 1701 26

The most common medical problems in brain tumor patients include the management of seizures, peritumoral edema, medication side effects, venous thromboembolism (VTE), fatigue and cognitive dysfunction. Despite their importance, there are relatively few studies specifically addressing these issues. There is increasing evidence that brain tumor patients who have not had a seizure do not benefit from prophylactic antiepileptic medications. Patients on corticosteroids are at greater risk of Pneumocystis jerovecii pneumonia and may benefit from prophylactic therapy. There is also growing evidence suggesting that anticoagulation may be more effective than inferior vena cava IVC) filtration devices for treating VTE in brain tumor patients and the risk of hemorrhage with anticoagulation is relatively small. Low-molecular weight heparin may be more effective than coumadin. Medications such as modafinil and methylphenidate have assumed an increasing role in the treatment of fatigue, while donepezil and memantine may be helpful with memory loss.
 ...
PMID:Medical management of patients with brain tumors. 1680 80


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>