levetiracetam and Brain-Diseases

The case report aims to discuss the clinical symptoms and treatment of encephalopathy caused by a novel syntaxin- binding protein 1 (STXBP1) genetic mutation.. The patient, a girl, was born at 38+4 weeks of gestation. She had frequent spasm attacks accompanied by obvious psychomotor development retardation since the neonatal period. Genetic screening identified a novel STXBP1 genetic mutation.. Early-onset epileptic encephalopathy with STXBP1 mutation.. We adjusted the antiepileptic strategy to oral levetiracetam and topiramate, and intravenous administration of adrenocorticotropic hormone(ACTH) for 2 weeks. Subsequently, prednisone was continued, and gradually reduced and withdrawn over 3 months.. The treatment was effective with complete control of the epileptic seizures and improvements in the electroencephalogram readings. However, the effects on psychomotor ability were slow and limited. A literature review of STXBP1 mutation cases in which ACTH was administered showed that complete seizure control is observed in 60% of cases, 20% are partially affected, and the remaining 20% show no effect.. ACTH and levetiracetam had good therapeutic effects in epilepsy control in this case of de novo STXBP1 mutation. ACTH is an effective drug for early-onset epileptic encephalopathy caused by STXBP1 mutation. However, controlling epilepsy using this therapy does not alter the psychomotor development retardation caused by the STXBP1 mutation.

Topics: Adrenocorticotropic Hormone; Anticonvulsants; Brain Diseases; Electroencephalography; Epilepsy; Female; Hormones; Humans; Infant; Levetiracetam; Munc18 Proteins; Mutation; Piracetam; Prednisone; Psychomotor Performance; Treatment Outcome

The aim of this paper was to summarize of current knowledge about neuronal injuries during epileptogenesis process and possibilities of neuroprotection.. Many of agents from a wide range of classes have been proposed to possess neuroprotective potential, but especially in experimental and preclinical conditions. Among the antiepileptic drugs topiramate (TPM) and levetiracetam (LEV) possess neuroprotective effects in experimental models of brain damage. Promising protection against cell loss display antioxidants and neurotrophins.. Important and difficult problem of neuroprotective therapy in childhood epilepsy require further experimental and clinical investigations.

Topics: Anticonvulsants; Brain Diseases; Child; Epilepsy; Fructose; Humans; Levetiracetam; Neuroprotective Agents; Piracetam; Topiramate

Syntaxin binding protein 1 (STXBP1) plays an important role in the release of synaptic vesicles. STXBP1-related encephalopathy is a brain dysfunction caused by STXBP1 variation. Levetiracetam (LEV) exerts antiepileptic effects by binding to synaptic vesicle protein 2A (SV2A). This study aimed to analyze the prognosis of LEV treatment of STXBP1 encephalopathy (STXBP1-E) and the correlation among genotype, phenotype, and LEV efficacy.. Patients with pathogenic STXBP1 variants were collected from multiple centers, and their clinical history, video electroencephalogram (vEEG) characteristics, imaging examination data, and anti-seizure medication (ASM) history were systematically analyzed. The ASMs related to the prognosis were explored.. Forty patients with STXBP1-E were enrolled in this study. The detailed ASM usage of 37 patients was recorded without intervening in ASM selection. At the endpoint of six months treatment, the results of Fisher's exact test showed that in all ASMs, LEV affected the prognosis of patients with STXBP1-E. LEV was effective in improving the partial remission rate but did not achieve seizure freedom. However, LEV monotherapy could achieve seizure freedom in patients with other early-onset epileptic and encephalopathy. For refractory West syndrome (WS) or Ohtahara syndrome (OS), LEV combined with other ASMs could improve the seizure remission rate.. LEV increased the seizure reduction rate and improved the vEEG characteristics in patients with STXBP1-E, but not seizure freedom. LEV combined with other ASMs could increase the seizure reduction rate, especially for refractory WS or OS. Thus, LEV could be considered after identifying the pathogenicity of STXBP1 variants.

Topics: Anticonvulsants; Brain Diseases; Humans; Levetiracetam; Munc18 Proteins; Phenotype; Piracetam

Symptoms of COVID-19, as reported during the SARS-CoV-2 pandemic in 2019-2020, are primarily respiratory and gastrointestinal, with sparse reports on neurological manifestations. We describe the case of a 17-year old female with Cornelia de Lange syndrome and well controlled epilepsy, who sustained significant cortical injury during a COVID-19 associated multi-inflammatory syndrome.

Topics: Acute Kidney Injury; Adolescent; Airway Extubation; Anticonvulsants; Blood Coagulation Disorders; Bone Marrow Failure Disorders; Brain Diseases; Brain Edema; C-Reactive Protein; COVID-19; De Lange Syndrome; Disease Progression; Electroencephalography; Epilepsy; Female; Ferritins; Humans; Influenza B virus; Influenza, Human; Levetiracetam; Magnetic Resonance Imaging; Midazolam; Necrosis; Phenobarbital; Pseudomonas Infections; Respiration, Artificial; Rhabdomyolysis; SARS-CoV-2; Seizures; Sepsis; Systemic Inflammatory Response Syndrome; Tachycardia, Ventricular

BACKGROUND Cefepime-induced neurotoxicity has been described in intensive care units (ICUs) and neuro ICU settings, occurring in patients started on cefepime for management of severe infections and sepsis. Most cases occur within 1 to 10 days after starting the drug. We publish a case that occurred on the general medical ward of a patient who had been on cefepime therapy for 4 weeks prior to admission. The aim of this study was to improve the knowledge of this serious condition to general internists as our patient was being managed on the general medical ward. CASE REPORT A 72-year-old female on prolonged intravenous antibiotics for sacral and pelvic osteomyelitis presented with acute encephalopathy and aphasia in the setting of an acute kidney injury. Due to the acute focal neurologic deficit, she was initially admitted as a stroke alert. After a negative magnetic resonance imaging (MRI) of the brain, an electroencephalogram (EEG) was pursued and showed nonconvulsive status epilepticus (NCSE). NCSE was likely a result of cefepime therapy in the setting of an acute kidney injury. CONCLUSIONS Cefepime-induced neurotoxicity should be suspected in any patient on cefepime therapy who develops acute changes in mental status, myoclonus, or evidence of seizures. Risk factors for the disease include older age, renal dysfunction, critical illness, and inappropriate dosing based upon renal function. A high index of suspicion is required and delays in diagnosis are common as there are frequently multiple possible causes for altered mental status in systemically ill patients requiring treatment with broad-spectrum antibiotics.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Anticonvulsants; Aphasia; Brain Diseases; Cefepime; Female; Humans; Levetiracetam; Lorazepam; Osteomyelitis; Status Epilepticus

Objective Reversible splenial lesion syndrome (RESLES) is a clinical radiological syndrome characterized by a reversible lesion of the splenium of the corpus callosum with a decreased apparent diffusion coefficient (ADC) value. The clinical manifestations of RESLES are diverse. Methods Fifteen cases of adult RESLES patients (10 males and 5 females) were retrospectively selected from the radiology system using the key word "corpus callosum" at a university-affiliated tertiary care hospital between May 1, 2015 and December 31, 2019. The possible precipitating factors, clinicoradiological findings and modified Rankin Scale (mRS) on follow-up were then analyzed. Results The patient ages ranged from 22 to 53 years old. The mean age was 34 years old. The most common neurological symptoms included headache (3/15), dizziness (3/15), first onset of seizure (3/15), paroxysmal blurred vision (2/15), vertigo (2/15), amnesia (2/15), and confused consciousness without seizure (2/15), followed by drowsiness (1/15), paresthesia (1/15), dysmetria (1/15) and dysarthria (1/15). The precipitating factors included infection, seizure, anti-epileptic treatment with levetiracetam, carbamazepine, valproate, hyperglycemia, hypoglycemia, cerebral venous sinus thrombosis, and rabies vaccine injection prior to the onset of RESLES. All cases were carefully followed up and had excellent prognoses. Conclusion RESLES manifests as variety of symptoms with less specificity and precipitating factors. Paroxysmal blurred vision may be a relatively specific symptom of RESLES. Levetiracetam, carbamazepine or valproate could be the cause of RESLES, exposure to the rabies vaccine could be another predisposing factors for RESLES as well. RESLES type 1 was therefore found to be highly "reversible" with an excellent prognosis.

Topics: Adult; Anticonvulsants; Brain Diseases; Carbamazepine; Causality; Corpus Callosum; Female; Headache; Humans; Levetiracetam; Male; Middle Aged; Paraspinal Muscles; Prognosis; Retrospective Studies; Seizures; Valproic Acid; Vertigo; Young Adult

Topics: Adult; Anti-Inflammatory Agents; Anticonvulsants; Brain Diseases; Carotid Artery, Internal; Computed Tomography Angiography; Dexamethasone; Embolization, Therapeutic; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Spain

Topics: Adolescent; Albendazole; Anthelmintics; Anticonvulsants; Brain; Brain Diseases; Emigrants and Immigrants; Epilepsy; Hispanic or Latino; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Mutism; Neurocysticercosis

De novo heterozygous mutations in STXBP1/Munc18-1 cause early infantile epileptic encephalopathies (EIEE4, OMIM #612164) characterized by infantile epilepsy, developmental delay, intellectual disability, and can include autistic features. We characterized the cellular deficits for an allelic series of seven STXBP1 mutations and developed four mouse models that recapitulate the abnormal EEG activity and cognitive aspects of human STXBP1-encephalopathy. Disease-causing STXBP1 variants supported synaptic transmission to a variable extent on a null background, but had no effect when overexpressed on a heterozygous background. All disease variants had severely decreased protein levels. Together, these cellular studies suggest that impaired protein stability and STXBP1 haploinsufficiency explain STXBP1-encephalopathy and that, therefore, Stxbp1+/- mice provide a valid mouse model. Simultaneous video and EEG recordings revealed that Stxbp1+/- mice with different genomic backgrounds recapitulate the seizure/spasm phenotype observed in humans, characterized by myoclonic jerks and spike-wave discharges that were suppressed by the antiepileptic drug levetiracetam. Mice heterozygous for Stxbp1 in GABAergic neurons only, showed impaired viability, 50% died within 2-3 weeks, and the rest showed stronger epileptic activity. c-Fos staining implicated neocortical areas, but not other brain regions, as the seizure foci. Stxbp1+/- mice showed impaired cognitive performance, hyperactivity and anxiety-like behaviour, without altered social behaviour. Taken together, these data demonstrate the construct, face and predictive validity of Stxbp1+/- mice and point to protein instability, haploinsufficiency and imbalanced excitation in neocortex, as the underlying mechanism of STXBP1-encephalopathy. The mouse models reported here are valid models for development of therapeutic interventions targeting STXBP1-encephalopathy.

Topics: Animals; Anticonvulsants; Brain Diseases; Cells, Cultured; Cerebral Cortex; Embryo, Mammalian; Epilepsy; Exploratory Behavior; Gene Expression Regulation; Haploinsufficiency; HEK293 Cells; Humans; Intellectual Disability; Levetiracetam; Mice; Mice, Inbred C57BL; Mice, Transgenic; Munc18 Proteins; Nerve Tissue Proteins; Synapsins; Synaptic Transmission

We report the case of an aborted awake craniotomy for a left frontotemporoinsular glioma due to ammonia encephalopathy on a patient taking Levetiracetam, valproic acid and clobazam. This awake mapping surgery was scheduled as a second-stage procedure following partial resection eight days earlier under general anesthesia. We planned to perform the surgery with local anesthesia and sedation with remifentanil and propofol. After removal of the bone flap all sedation was stopped and we noticed slow mentation and excessive drowsiness prompting us to stop and control the airway and proceed with general anesthesia. There were no post-operative complications but the patient continued to exhibit bradypsychia and hand tremor. His ammonia level was found to be elevated and was treated with an infusion of l-carnitine after discontinuation of the valproic acid with vast improvement. Ammonia encephalopathy should be considered in patients treated with valproic acid and mental status changes who require an awake craniotomy with patient collaboration.

Topics: Anesthesia, General; Anesthesia, Local; Anticonvulsants; Aphasia; Benzodiazepines; Brain Diseases; Brain Mapping; Brain Neoplasms; Carnitine; Clobazam; Conscious Sedation; Consciousness Disorders; Craniotomy; Dominance, Cerebral; Frontal Lobe; Glioma; Humans; Hyperammonemia; Hypnotics and Sedatives; Intraoperative Complications; Language; Levetiracetam; Male; Middle Aged; Piperidines; Piracetam; Propofol; Remifentanil; Seizures; Temporal Lobe; Valproic Acid

A 37-year-old man with a known history of neurofibromatosis 1 (NF1) presented within 2 days of diarrhoeal illness followed by encephalopathy, facial twitching, hypoglycaemia, hypotension, tachycardia and low-grade fever. Examination showed multiple café-au-lait spots and neurofibromas over the trunk, arms and legs and receptive aphasia with right homonymous hemianopia, which resolved. Workup for cardiac, inflammatory and infectious aetiologies was unrevealing. A brain MRI showed gyral swelling with increased T2 fluid-attenuated inversion recovery signal and diffusion restriction in the left cerebral cortex. Neuroendocrine findings suggested panhypopituitarism with centrally derived adrenal insufficiency. Supportive treatment, hormone supplementation, antibiotics, antivirals and levetiracetam yielded clinical improvement. A follow-up brain MRI showed focal left parieto-occipital atrophy with findings of cortical laminar necrosis. In conclusion, we describe a case of NF1-associated panhypopituitarism presenting as hypoglycaemic seizures and stroke-like findings, hitherto unreported manifestations of NF1. Prompt recognition and treatment of these associated conditions can prevent devastating complications.

Topics: Adult; Anti-Bacterial Agents; Anticonvulsants; Antiviral Agents; Brain Diseases; Cafe-au-Lait Spots; Diarrhea; Fluid Therapy; Functional Neuroimaging; Hormone Replacement Therapy; Humans; Hypopituitarism; Levetiracetam; Magnetic Resonance Imaging; Male; Nerve Sheath Neoplasms; Neurofibromatosis 1; Piracetam; Seizures; Stroke; Testosterone; Treatment Outcome

Topics: Anticonvulsants; Benzodiazepines; Bradycardia; Brain Diseases; Cerebral Cortex; Clobazam; Drug Resistance; Electroencephalography; Heart Arrest; Humans; Lamotrigine; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Piracetam; Seizures; Triazines

We describe the case of a 22-year-old male affected by NFLE reporting paroxysmal RLS-like symptoms. The patient was referred to our Sleep Center due to nocturnal paresthesias and cramps involving the left leg and leading to sleep fragmentation. At age 4, the patient presented with secondary generalized seizures preceded by left leg discomfort, controlled on CBZ. After successive therapy discontinuation, leg symptoms built up in frequency and duration until a secondary generalized seizure re-occurred. On CBZ prompt resumption no further GM seizures occurred albeit persistence of night-time frequent cramps and paraesthesia. Sleep EEG demonstrated asymmetric interictal sharp theta on the right posterior frontal areas, whereas brain MRI results were consistent with a Taylor type right frontal cortical dysplasia. CBZ augmentation and add on therapy with LEV led to further frequency reduction of sensory symptoms.

Topics: Anticonvulsants; Brain Diseases; Carbamazepine; Electroencephalography; Epilepsy; Epilepsy, Frontal Lobe; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Malformations of Cortical Development; Malformations of Cortical Development, Group I; Piracetam; Restless Legs Syndrome; Young Adult

We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy.. A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges.. Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.

Topics: Adult; Anticonvulsants; Brain Diseases; Electroencephalography; Epilepsy; Humans; Levetiracetam; Male; Piracetam; Valproic Acid

Levetiracetam (LEV) is used in the setting of acute brain injury for seizure treatment or prophylaxis but its safety and efficacy in this setting is unknown.. We retrospectively analyzed the patterns of use and safety/efficacy of LEV in 379 patients treated in the neuroscience intensive care unit (NSICU). We extracted from the charts clinical data including diagnosis, AED therapy before and during stay in the NSICU, complications of treatment, length of stay, and clinical outcomes (improvement, Glasgow Coma Scale, and death). We analyzed the data using binary and ordered (multi-category) logistic regression.. Overall, our findings are that phenytoin used prior to the NSICU admission was frequently replaced with LEV monotherapy (P < 0.001). Patients treated with LEV monotherapy when compared to other AEDs had lower complication rates and shorter NSICU stays. Older patients and patients with brain tumors or strokes were preferentially treated with LEV for prevention and/or management of seizures (all P < or = 0.014).. The results of this study suggest that LEV is a frequently used AED in the setting of acute brain injury and that it may be a desirable alternative to phenytoin. Prospective studies evaluating the long-term safety, efficacy and outcomes of LEV in this setting are indicated.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Diseases; Brain Neoplasms; Cerebral Hemorrhage; Comorbidity; Critical Illness; Epilepsy; Humans; Intensive Care Units; Length of Stay; Levetiracetam; Middle Aged; Piracetam; Retrospective Studies; Stroke; Treatment Outcome

Cortical laminar necrosis (CLN) is radiologically defined as high intensity cortical lesions on T1 weighted MRI images following a gyral distribution. Histopathologically, CLN is characterised by pannecrosis of the cortex involving neurones, glial cells, and blood vessels. It has been reported to be associated with hypoxia, metabolic disturbances, drugs, and infections. We present two patients who developed CLN and permanent neurological deficits after prolonged and repeated focal status epilepticus. The possible mechanisms leading to CLN in these patients are discussed, together with the implications of prompt and aggressive treatment in similar cases.

Topics: Adult; Anticonvulsants; Aphasia, Wernicke; Brain Diseases; Cerebral Cortex; Functional Laterality; Hemianopsia; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Necrosis; Paresis; Phenytoin; Piracetam; Status Epilepticus; Tomography, Emission-Computed, Single-Photon