Effects of metformin on glucose metabolism and mitochondrial function in patients with obstructive sleep apnea: A pilot randomized trial.

Obstructive sleep apnea (OSA) is associated with increased risk for diabetes, and standard treatment with positive airway pressure (PAP) device shows inconsistent effects on glucose metabolism. Metformin is known to treat and prevent diabetes, but its effects on skeletal muscle mitochondrial function are not completely understood. Here, we evaluate the effects of metformin on glucose metabolism and skeletal muscle mitochondrial function in patients with OSA. Sixteen adults with obesity (50.9 ± 6.7 years, BMI: 36.5 ± 2.9 kg/m2 ) and moderate-to-severe OSA were provided with PAP treatment and randomized to 3 months of placebo (n = 8) or metformin (n = 8) treatment in a double-blind parallel-group design. Whole body glucose metabolism was determined by oral glucose tolerance test. A skeletal muscle biopsy was obtained to evaluate mitochondrial respiratory capacity and expression of proteins related to mitochondrial dynamics and energy metabolism. Whole body insulin-sensitivity (Matsuda index) did not change in metformin or placebo treated groups. However, metformin treatment prevented increases in insulin release relative to placebo during follow-up. Insulin area under the curve (AUC) and insulin to glucose AUC ratio increased in placebo but remained unchanged with metformin. Furthermore, metformin treatment improved skeletal muscle mitochondrial respiratory capacity and dynamics relative to placebo. Metformin treatment prevented the decline in whole body glucose homeostasis and skeletal muscle mitochondrial function in patients with moderate to severe OSA. Patients with OSA may benefit from the addition of metformin to prevent diabetes.

Nonconvulsive Status Epilepticus With Generalized Spike-and-Wave Discharges: Pathophysiological and Nosological Considerations.

Absence status epilepticus (ASE) is the most common type of status epilepticus in patients with idiopathic generalized epilepsy (IGE). Like absence seizure, ASE is characterized by generalized spike-and-wave discharges (GSWDs) on the electroencephalogram (EEG). Once considered specific for IGE, GSWDs have increasingly been observed in other forms of epilepsy, as well as in patients with no prior epilepsy. Here, we report three patients with different types of nonconvulsive status epilepticus (NCSE) in which the EEG correlate was GSWDs: a 44-year-old woman with juvenile absence epilepsy who manifested ASE, a 73-year-old woman with anoxic brain injury complicated by NCSE with well-formed GSWDs (as seen in IGE and de novo ASE), and a 41-year-old woman with frontal lobe epilepsy who developed focal NCSE with impaired consciousness. Evidently, patients with generalized epilepsy, focal epilepsy, and no prior epilepsy can all manifest NCSE with similar electroclinical characteristics, i.e., GSWDs and impaired consciousness. This observation adds to the existing evidence that seizures, whether classified as focal or generalized, often involve focal and generalized elements in their pathophysiology. To fully understand seizure pathophysiology, we must steer away from the focal-versus-generalized paradigm that has dominated the nosology of seizures and epilepsy for a very long time.

Autoimmune Myelitis and Myocarditis in a Patient With Anti-Aquaporin-4, Antinuclear, and Antiphospholipid Autoantibodies: The Neuromyelitis Optica-Systemic Lupus Erythematosus (NMO-SLE) Overlap Syndrome.

The coexistence of two or more autoimmune diseases is well-known, e.g., a person can have neuromyelitis optica (NMO) and systemic lupus erythematosus (SLE) at the same time. We report a case of NMO-SLE overlap syndrome with myelitis and myocarditis as the initial manifestations. The patient, a 64-year-old man, presented with a 15-day history of ascending sensory loss and a 10-day history of exertional dyspnea. Magnetic resonance imaging (MRI) revealed longitudinally extensive transverse myelitis (LETM) from C7 to T6. Serology showed a high anti-aquaporin-4 antibody level. We diagnosed NMO based on these findings. Echocardiography showed a hypokinetic left ventricle with a severely reduced ejection fraction. Cardiac MRI demonstrated delayed gadolinium enhancement in the myocardium consistent with active inflammation. Because the cardiac findings could not be explained on the basis of NMO, we started searching for another autoimmune disease. Serology came back positive for a variety of autoantibodies, including antinuclear, anti-dsDNA, anti-chromatin, anti-cardiolipin, anti-ß2-glycoprotein-1, and lupus anticoagulant. These findings, along with leukopenia and low serum complement C4, prompted us to diagnose SLE, in addition to NMO. He was initially treated with plasmapheresis and methylprednisolone. Maintenance therapy consisted of rituximab, hydroxychloroquine, and aspirin. One year later, he only complained of mild paresthesia in the feet. Patients with NMO should always be screened for SLE especially if they have signs and symptoms that cannot be accounted for by NMO alone, e.g., our patient had myocarditis. Conversely, patients with SLE and evidence of transverse myelitis should be screened for anti-AQP4 antibodies.

Insufficient Sleep Syndrome: A Blind Spot in Our Vision of Healthy Sleep.

Chronic sleep deficiency (CSD) poses a threat to physical health, mental well-being, and social functioning. The concept of behaviorally induced CSD has not changed much since it was first introduced four decades ago. Behaviorally induced CSD is currently referred to as insufficient sleep syndrome (ISS). In the latest edition of the International Classification of Sleep Disorders (ICSD-3, 2014), ISS is considered a disorder of central hypersomnolence with diagnostic codes ICD-9-CM 307.44 and ICD-10-CM F51.12. In this review, we will describe the biological importance of sleep, the ramifications of CSD on the individual and society, the nosological status and diagnostic features of ISS, and the apparent lack of attention to ISS in contemporary medical practice and public health programs. The last three decades have seen a global rise in voluntary sleep curtailment such that ISS may already be the leading cause of CSD, not only in adults but also in school-aged children and adolescents. Acknowledging ISS as a public health priority is a necessary first step in our response to the global threat of CSD and CSD-related health consequences. It is only by confronting ISS directly that we can hope to develop and implement effective educational and advocacy programs, along with more responsible public health policies and regulations.

Electroclinical Mismatch During EEG Acquisition: What It Might Mean, What We Might Need to Do.

An electroclinical mismatch is present if the electroencephalogram (EEG) shows evidence of moderate to severe diffuse encephalopathy but the patient's mental status is only mildly altered. We describe five cases in which seizure or status epilepticus was suspected due to electroclinical mismatch. In all five cases, EEG was ordered to rule out nonconvulsive status epilepticus as the cause of the altered mental status. EEG initially showed generalized delta activity (GDA), with variable degrees of rhythmicity, with or without superimposed theta activity, with or without sporadic epileptiform discharges. During EEG acquisition, all patients followed commands and answered questions. The mental status change was limited to mild inattention and temporal disorientation. Benzodiazepine challenge was performed by administering lorazepam 2-mg IV. Within 10 minutes of injection, GDA started to break up and subsequently disappeared. EEG showed prominent sleep spindles in three patients and background changes, indicating drowsiness in two patients. The assessment of clinical response to lorazepam was confounded by sleepiness in all patients. Serial EEG recording or continuous EEG monitoring revealed reemergence of GDA, at times appearing more rhythmic than the GDA in the baseline study. All patients received nonsedating antiseizure drugs. GDA completely resolved and mental status normalized two to five days after starting antiseizure medication. In cases of electroclinical mismatch, the absence of clear-cut epileptiform discharges does not exclude the possibility that cortical hyperexcitability is contributing to the encephalopathic process. A positive response to benzodiazepine challenge suggests the presence of cortical hyperexcitability and the need to start, or increase the dosage of, antiseizure drugs.

Ictal Hypersalivation and Salivary Gland Enlargement in a Patient With Acquired Frontal Lobe Epilepsy.

Hypersalivation is a well-known ictal semiology of benign Rolandic epilepsy and other childhood epilepsy syndromes. There are also occasional reports of adults with temporal, parietal, or frontal lobe epilepsy in which hypersalivation is a prominent seizure manifestation. Notably lacking are reports linking salivary gland enlargement to ictal hypersalivation. A 33-year-old man with frontal lobe epilepsy due to a ruptured aneurysm presented with focal seizures and facial swelling. The only seizures he had in the past were generalized tonic-clonic seizures. Eight days prior to admission, he started having focal seizures characterized by pronounced hypersalivation, speech arrest, impaired awareness, and left upper extremity posturing or automatism. Seizure frequency increased from five to 30 per day. Four days prior to admission, his face started to swell up, and his family thought he had mumps. Computed tomography (CT) of the head showed encephalomalacia in the inferomedial cortex of the right frontal lobe, the same lesion seen in his old CT images. Maxillofacial CT revealed enlargement of the parotid and submandibular glands. Although electroencephalography (EEG) showed seizure onset in the right frontal region, the initial ictal discharge on the scalp may represent seizure propagation from a focus near the zone of encephalomalacia. After seizure freedom was achieved with antiepileptic drugs, the patient's salivary glands decreased in size and returned to normal.

Delayed Toxic-Hypoxic Leukoencephalopathy As Sequela of Opioid Overdose and Cerebral Hypoxia-Ischemia.

Delayed leukoencephalopathy in the aftermath of toxic exposure and cerebral hypoxia-ischemia is known as "delayed post-hypoxic leukoencephalopathy" (DPHL) but the name "delayed toxic-hypoxic leukoencephalopathy" (DTHL) may be more accurate if toxic and hypoxic mechanisms are both involved in the pathogenesis of delayed leukoencephalopathy. DTHL is characterized by initial recovery from toxic exposure and cerebral hypoxia-ischemia, clinical stability over a few weeks, and subsequent neurological deterioration with the sudden emergence of diffuse white matter disease. A 46-year-old man suffered respiratory failure and hypotension as a result of opioid overdose. Brain MRI showed watershed infarcts and EEG showed diffuse theta-delta slowing consistent with global cerebral hypoperfusion. He recovered fully and was discharged with intact cognitive function. Three weeks later, he presented with abulia and psychomotor retardation. MRI revealed extensive white matter hyperintensity and EEG showed diffuse polymorphic delta activity. DTHL was diagnosed based on classic MRI features, history of opioid overdose and hypoxic brain injury, and negative test results for etiology of white matter disease. He developed akinetic mutism prompting administration of methylprednisolone 1000-mg IV q24h for five days. He also received amantadine 100-mg PO q12h. His cognition, motivation, and psychomotor function slowly improved and returned to baseline about two months after the overdose. Clinic reassessment two and a half months after the overdose revealed normal cognitive function, slight residual MRI hyperintensity, and mild EEG slowing anteriorly. Toxic-metabolic myelinopathy causing diffuse demyelination in the deep white matter is a perfect explanation for the patient's neurological symptoms, MRI changes, EEG findings, and time course of recovery.

Benzodiazepine Withdrawal Catatonia, Delirium, and Seizures in a Patient With Schizoaffective Disorder.

Benzodiazepine withdrawal symptoms vary from mild anxiety to life-threatening delirium or seizures. In susceptible individuals, such as those with mood disorders, benzodiazepine withdrawal may also precipitate catatonia. A 26-year-old man with schizoaffective disorder (depressed type with catatonia) ran out of lorazepam and presented with catatonia, delirium, and seizures. He was taking olanzapine, venlafaxine, and trazodone for schizoaffective disorder. Lorazepam 2 mg twice daily kept him free of catatonia for 6 months. Besides catatonia and delirium, lorazepam withdrawal also triggered convulsive seizures and nonconvulsive status epilepticus. He was admitted to the intensive care unit where he underwent continuous video-EEG monitoring. Catatonia resolved with lorazepam on day 2. Seizures stopped with levetiracetam, lacosamide, and propofol on day 4. His mental status was normal when he was discharged on day 6. If not immediately recognized and treated, catatonia and delirium can lead to significant morbidity or mortality. Unfortunately, physicians tend to overlook catatonia and delirium, especially if both syndromes are present. At first, we suspected that our patient had ictal catatonia, but video-EEG showed no clear-cut correlation between catatonia, seizures, and epileptiform activity. As with prior observations, the patient's catatonia was more sensitive to benzodiazepine withdrawal and treatment than his seizures. The efficacy of benzodiazepines in aborting catatonia, seizures, and mixed delirium-catatonia syndromes suggests a key pathogenetic role of abnormal GABA neurotransmission in these brain disorders.

Stroke-Onset Seizures During Midbrain Infarction in a Patient With Top of the Basilar Syndrome.

Risk factors for early-onset seizures in acute ischemic stroke include anterior circulation stroke, infarction of the cerebral cortex, large infarct size, and ischemic-to-hemorrhagic transformation. We define stroke-onset seizures as seizures occurring within 2 hours of stroke onset. A 64-year-old woman presented with top of the basilar artery syndrome-thalamic infarction occurred first and midbrain infarction 12 days later. She manifested stroke-onset seizures during midbrain infarction, which was heralded by stupor. Within 2 hours of the onset of stupor, she had a clonic seizure of the lower extremities, electroencephalography (EEG) revealed nonconvulsive status epilepticus, and an episode of convulsive movements of all extremities was recorded on video and on EEG. Continuous EEG recording showed epileptiform discharges that would appear, disappear, and reappear over a 3-week period. It took 3 weeks and 4 antiepileptic drugs to fully suppress cortical hyperexcitability, perhaps because injury to some midbrain structures resulted in global lowering of the seizure threshold. The most important risk factor for stroke-onset seizures appears to be posterior circulation stroke, particularly brainstem infarction. The difference in risk profile between stroke-onset seizures and other forms of early-onset seizures suggest that their pathophysiology is not exactly the same. Focusing some of the research spotlight on stroke-onset seizures can help us better understand their unique clinical, electrographic, radiologic, and pathophysiologic features.

Full Recovery From Cocaine-Induced Toxic Leukoencephalopathy: Emphasizing the Role of Neuroinflammation and Brain Edema.

Toxic leukoencephalopathy (TL) is characterized by white matter disease on magnetic resonance imaging (MRI) and evidence of exposure to a neurotoxic agent. We describe a case of cocaine-induced TL in which extensive white matter disease did not preclude full recovery. A 57-year-old man with substance abuse disorder presented with a 5-day history of strange behavior. On admission, he was alert but had difficulty concentrating, psychomotor retardation, and diffuse hyperreflexia. Brain MRI revealed confluent subcortical white matter hyperintensities with restricted diffusion in some but not in other areas. Electroencephalography (EEG) showed mild diffuse slowing. Blood tests were normal except for mild hyperammonemia. Urine screen was positive for cocaine and benzodiazepine but quantitative analysis was significant only for cocaine. Prednisone 60-mg qd was initiated on day 4, tapered over a 5-day period, and discontinued on day 9. He was discharged after 3 weeks. Cognitive function returned to normal 2 weeks after discharge. Five months later, neurologic exam and EEG were normal and MRI showed near-100% resolution of white matter lesions. TL has been attributed to white matter ischemia/hypoxia resulting in demyelination/axonal injury. The clinical, EEG, and MRI findings and time course of recovery of our patient suggest that cocaine-induced inflammation/edema resulted in TL but not in ischemic/hypoxic injury. While inflammation/edema may have regressed when cocaine was discontinued, we cannot exclude a role for prednisone in protecting the patient from the ischemic/hypoxic sequelae of inflammation/edema. MRI is indispensable for diagnosing TL but EEG may provide additional useful diagnostic and prognostic information.

Dexamethasone as Abortive Treatment for Refractory Seizures or Status Epilepticus in the Inpatient Setting.

Refractory seizures or status epilepticus (RS/SE) continues to be a challenge in the inpatient setting. Failure to abort a seizure with antiepileptic drugs (AEDs) may lead to intubation and treatment with general anesthesia exposing patients to complications, extending hospitalization, and increasing the cost of care. Studies have shown a key role of inflammatory mediators in seizure generation and termination. We describe 4 patients with RS/SE that was aborted when dexamethasone was added to conventional AEDs: a 61-year-old female with temporal lobe epilepsy who presented with delirium, nonconvulsive status epilepticus, and oculomyoclonic status; a 56-year-old female with history of traumatic left frontal lobe hemorrhage who developed right face and hand epilepsia partialis continua followed by refractory focal clonic seizures; a 51-year-old male with history of traumatic intracranial hemorrhage who exhibited left-sided epilepsia partialis continua; and a 75-year-old female with history of breast cancer who manifested nonconvulsive status epilepticus and refractory focal clonic seizures. All patients continued experiencing RS/SE despite first- and second-line therapy, and one patient continued to experience RS/SE despite third-line therapy. Failure to abort RS/SE with conventional therapy motivated us to administer intravenous dexamethasone. A 10-mg load was given (except in one patient) followed by 4.0- 5.2 mg q6h. All clinical and electrographic seizures stopped 3-4 days after starting dexamethasone. When dexamethasone was discontinued 1-3 days after seizures stopped, all patients remained seizure-free on 2-3 AEDs. The cessation of RS/SE when dexamethasone was added to conventional antiseizure therapy suggests that inflammatory processes are involved in the pathogenesis of RS/SE.

Focal Epileptiform Discharges Can Mimic Electrode Artifacts When Recorded on the Scalp Near a Skull Defect.

Breach rhythm, the hallmark of skull defect, is a familiar finding in the electroencephalogram (EEG). A hole in the skull can also give rise to unfamiliar EEG findings. We present 3 patients with a skull defect whose scalp EEG showed focal epileptiform discharges that resembled F4 electrode artifacts-a 23-year-old man with a right-sided craniectomy for traumatic brain injury, a 63-year-old woman with a history of bifrontal craniectomy and meningioma resection, and a 77-year-old woman who had a right hemicraniectomy for a life-threatening subdural hematoma. In all 3 patients, the F4 electrode was directly above or near a skull defect, and scalp EEG showed phase-reversing waves in FP2-F4 and F4-C4 with no clear-cut "physiological field" (even when the EEG was displayed at a higher sensitivity). In the first 2 patients, the technologist tried to eliminate the "electrode artifacts" by cleaning the scalp thoroughly, replacing the F4 electrode, and maintaining electrode impedance between 2 and 5 kΩ. These measures failed to eliminate the "electrode artifacts" so the EEG was recorded from four 10-10 electrode sites around F4. Extending the montage made it clear that what appeared as F4 electrode artifacts were actually focal epileptiform discharges. Correlation with other electroclinical and neuroimaging data was enough to resolve this issue in the third patient, obviating the need to extend the montage. When recording and interpreting the EEG of patients with a craniotomy or craniectomy, EEG professionals should be aware that focal epileptiform discharges can masquerade as electrode artifacts.

Periodic Lateralized Epileptiform Discharges can Survive Anesthesia and Result in Asymmetric Drug-induced Burst Suppression.

Drug-induced burst suppression (DIBS) is bihemispheric and bisymmetric in adults and older children. However, asymmetric DIBS may occur if a pathological process is affecting one hemisphere only or both hemispheres disproportionately. The usual suspect is a destructive lesion; an irritative or epileptogenic lesion is usually not invoked to explain DIBS asymmetry. We report the case of a 66-year-old woman with new-onset seizures who was found to have a hemorrhagic cavernoma and periodic lateralized epileptiform discharges (PLEDs) in the right temporal region. After levetiracetam and before anesthetic antiepileptic drugs (AEDs) were administered, the electroencephalogram (EEG) showed continuous PLEDs over the right hemisphere with maximum voltage in the posterior temporal region. Focal electrographic seizures also occurred occasionally in the same location. Propofol resulted in bihemispheric, but not in bisymmetric, DIBS. Remnants or fragments of PLEDs that survived anesthesia increased the amplitude and complexity of the bursts in the right hemisphere leading to asymmetric DIBS. Phenytoin, lacosamide, ketamine, midazolam, and topiramate were administered at various times in the course of EEG monitoring, resulting in suppression of seizures but not of PLEDs. Ketamine and midazolam reduced the rate, amplitude, and complexity of PLEDs but only after producing substantial attenuation of all burst components. When all anesthetics were discontinued, the EEG reverted to the original preanesthesia pattern with continuous non-fragmented PLEDs. The fact that PLEDs can survive anesthesia and affect DIBS symmetry is a testament to the robustness of the neurodynamic processes underlying PLEDs.

Fetal-Type Variants of the Posterior Cerebral Artery and Concurrent Infarction in the Major Arterial Territories of the Cerebral Hemisphere.

Fetal-type or fetal posterior cerebral artery (FPCA) is a variant of cerebrovascular anatomy in which the distal posterior cerebral artery (PCA) territory is perfused by a branch of the internal carotid artery (ICA). In the presence of FPCA, thromboembolism in the anterior circulation may result in paradoxical PCA territory infarction with or without concomitant infarction in the territories of the middle (MCA) or the anterior (ACA) cerebral artery. We describe 2 cases of FPCA and concurrent acute infarction in the PCA and ICA territories-right PCA and MCA in Patient 1 and left PCA, MCA, and ACA in Patient 2. Noninvasive angiography detected a left FPCA in both patients. While FPCA was clearly the mechanism of paradoxical infarction in Patient 2, it turned out to be an incidental finding in Patient 1 when evidence of a classic right PCA was uncovered from an old computed tomography scan image. Differences in anatomical details of the FPCA in each patient suggest that the 2 FPCAs are developmentally different. The FPCA of Patient 1 appeared to be an extension of the embryonic left posterior communicating artery (PcomA). Patient 2 had 2 PCAs on the left (PCA duplication), classic bilateral PCAs, and PcomAs, and absent left anterior choroidal artery (AchoA), suggesting developmental AchoA-to-FPCA transformation on the left. These 2 cases underscore the variable anatomy, clinical significance, and embryological origins of FPCA variants.

Tumefactive multiple sclerosis and hepatitis C virus 2a/2C infection: Dual benefit of long-term interferon beta-1a therapy?

Hepatitis C virus (HCV) infection has been implicated in triggering acute disseminated encephalomyelitis but not tumefactive multiple sclerosis. We report the case of a 17-year-old female who presented with a 5-day history of left hemiparesis and hemisensory loss followed by a right third nerve palsy. Tumefactive multiple sclerosis was diagnosed based on the absence of encephalopathic signs, the presence of tumefactive brain lesions, the exclusion of neoplastic and infectious causes of the lesions by biopsy, and the occurrence of relapse after a period of remission. The patient was at risk for HCV infection due to parenteral drug abuse and multiple sexual partners. Serial HCV antibody tests and RNA polymerase chain reaction assays revealed acute HCV infection and genotyping showed HCV genotype 2a/2c. She was treated with high-dose methylprednisolone and discharged with only mild left hand weakness. Interferon beta-1a 30mcg was administered intramuscularly once a week. Remission from HCV infection was achieved in three years without standard anti-HCV therapy. This case suggests that CNS myelin is a potential target of the immune response to HCV 2a/2c infection, the HCV 2a/2c virus may be involved in triggering autoimmune tumefactive brain lesions, and interferon beta-1a is effective against HCV 2a/2c infection. We recommend serial HCV antibody testing and HCV RNA PCR assay, preferably with HCV genotyping, in all patients with acute inflammatory demyelinating diseases of the CNS.

Unihemispheric burst suppression.

Burst suppression (BS) consists of bursts of high-voltage slow and sharp wave activity alternating with periods of background suppression in the electroencephalogram (EEG). When induced by deep anesthesia or encephalopathy, BS is bihemispheric and is often viewed as a non-epileptic phenomenon. In contrast, unihemispheric BS is rare and its clinical significance is poorly understood. We describe here two cases of unihemispheric BS. The first patient is a 56-year-old woman with a left temporoparietal tumor who presented in convulsive status epilepticus. EEG showed left hemispheric BS after clinical seizure termination with lorazepam and propofol. The second patient is a 39-year-old woman with multiple medical problems and a vague history of seizures. After abdominal surgery, she experienced a convulsive seizure prompting treatment with propofol. Her EEG also showed left hemispheric BS. In both cases, increasing the propofol infusion rate resulted in disappearance of unihemispheric BS and clinical improvement. The prevailing view that typical bihemispheric BS is non-epileptic should not be extrapolated automatically to unihemispheric BS. The fact that unihemispheric BS was associated with clinical seizure and resolved with propofol suggests that, in both cases, an epileptic mechanism was responsible for unihemispheric BS.

Sporadic Creutzfeldt-Jakob disease with focal findings: caveats to current diagnostic criteria.

The clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is largely based on the 1998 World Health Organization diagnostic criteria. Unfortunately, rigid compliance with these criteria may result in failure to recognize sporadic CJD (sCJD), especially early in its course when focal findings predominate and traditional red flags are not yet present. A 61-year-old man presented with a 3-week history of epilepsia partialis continua (jerking of the left upper extremity) and a 2-week history of forgetfulness and left hemiparesis; left hemisensory neglect was also detected on admission. Repeated brain magnetic resonance imaging (MRI) showed areas of restricted diffusion in the cerebral cortex, initially on the right but later spreading to the left. Electroence-phalography (EEG) on hospital days 7, 10, and 14 showed right-sided periodic lateralized epileptiform discharges. On day 20, the EEG showed periodic sharp wave complexes leading to a diagnosis of probable sCJD and subsequently to definite sCJD with brain biopsy. Neurological decline was relatively fast with generalized myoclonus and akinetic mutism developing within 7 weeks from the onset of illness. CJD was not immediately recognized because of the patient's focal/lateralized manifestations. Focal/lateralized clinical, EEG, and MRI findings are not uncommon in sCJD and EEG/MRI results may not be diagnostic in the early stages of sCJD. Familiarity with these caveats and with the most current criteria for diagnosing probable sCJD (University of California San Francisco 2007, MRI-CJD Consortium 2009) will enhance the ability to recognize sCJD and implement early safety measures.

Typical Spike-and-Wave Activity in Hypoxic-Ischemic Brain Injury and its Implications for Classifying Nonconvulsive Status Epilepticus.

INTRODUCTION: Typical spike-and-wave activity (TSWA) in the electroencephalogram (EEG) indicates idiopathic generalized epilepsy (IGE). IGE-related nonconvulsive status epilepticus (NCSE) is typically an absence status epilepticus (ASE). ASE and TSWA respond dramatically to benzodiazepines. Patients with no history of seizure/epilepsy may develop ASE "de novo" in the context of an acute brain disorder. However, we are aware of only one previous case of de novo ASE with TSWA in hypoxic-ischemic brain injury. CASE PRESENTATION: A 65-year-old man, with congestive heart failure and history of substance abuse, survived cardiorespiratory arrest after 18 minutes of cardiopulmonary resuscitation. Post-resuscitation, the patient was in coma with intact brainstem function. Toxicology was positive for cocaine and marijuana. Eyelid myoclonus suggested NCSE, which was initially treated with lorazepam and fosphenytoin. EEG monitoring showed sustained TSWA confirming NCSE and demonstrating de novo ASE (the patient and his family never had seizure/epilepsy). The TSWA was resistant to lorazepam, levetiracetam, and low-dose midazolam; it was eliminated only with midazolam at a dose that resulted in burst-suppression (≥1.2 mg/kg/hour). CONCLUSION: This is an unusual case of TSWA and hypoxic-ischemic brain injury in a patient with no history of seizure/epilepsy. The TSWA was relatively resistant to benzodiazepines suggesting that cerebral hypoxia-ischemia spared the thalamocortical apparatus generating TSWA but impaired the cortical/thalamic inhibitory circuits where benzodiazepines act to suppress TSWA. Albeit rare, 'post-hypoxic' TSWA offers us some valuable insights for classifying and managing nonconvulsive status epilepticus.

Botulinum toxin injections for simple partial motor seizures associated with pain.

Intractable epilepsy with painful partial motor seizures is a relatively rare and difficult disorder to treat. We evaluated the usefulness of botulinum toxin to reduce ictal pain. Two patients received two or four botulinum toxin (BTX) injections at one-to-two-month intervals. Patient 1 had painful seizures of the right arm and hand. Patient 2 had painful seizures involving the left foot and leg. Injections were discontinued after improved seizure control following resective surgery. Both patients received significant pain relief from the injections with analgesia lasting at least two months. Seizure severity was reduced, but seizure frequency and duration were unaffected. For these patients, BTX was effective in temporarily relieving pain associated with muscle contraction in simple partial motor seizures. Our findings do not support the hypothesis that modulation of motor end-organ feedback affects focal seizure generation. BTX is a safe and reversible treatment that should be considered as part of adjunctive therapy after failure to achieve control of painful partial motor seizures.

Human Rabies with Initial Manifestations that Mimic Acute Brachial Neuritis and Guillain-Barré Syndrome.

INTRODUCTION: Human rabies can be overlooked in places where this disease is now rare. Its diagnosis is further confused by a negative history of exposure (cryptogenic rabies), by a Guillain-Barré syndrome (GBS) type of presentation, or by symptoms indicating another diagnosis, eg, acute brachial neuritis (ABN). CASE PRESENTATION: A 19-year-old Mexican, with no past health problems, presented with a two-day history of left shoulder, arm, and chest pain. He arrived in Louisiana from Mexico five days prior to admission. Of particular importance is the absence of a history of rabies exposure and immunization. On admission, the patient had quadriparesis, areflexia, and elevated protein in the cerebrospinal fluid, prompting a diagnosis of GBS. However, emerging neurological deficits pointed towards acute encephalitis. Rabies was suspected on hospital day 11 after common causes of encephalitis (eg, arboviruses) have been excluded. The patient tested positive for rabies IgM and IgG. He died 17 days after admission. Negri bodies were detected in the patient's brain and rabies virus antigen typing identified the vampire bat as the source of infection. CONCLUSION: Rabies should be suspected in every patient with a rapidly evolving GBS-like illness-even if there is no history of exposure and no evidence of encephalitis on presentation. The patient's ABN-like symptoms may be equivalent to the pain experienced by rabies victims near the inoculation site.