Incidence of acute ischemic cerebrovascular events in a cohort of HIV-infected patients.

The prevalence of vascular diseases in HIV (human immunodeficiency virus)-infected individuals has been comprehensively investigated. However, their incidence of ischemic cerebrovascular events has not been thoroughly examined. Our aim was to examine the rate of ischemic stroke or TIA (transient ischemic attack) in a defined HIV population and to find the risk factors that are characteristic in this population. A case-controlled retrospective cohort study of HIV patients followed up at Kaplan Medical Center between 2009 and 2017 was performed. The study included 300 patients who had been compared to a matched age and gender group. The data were collected by reviewing patients' files and imaging studies. The first goal was to compare the incidence of ischemic cerebrovascular events in both groups. Secondary endpoints were to characterize the types of cerebrovascular events and risk factors in the study group versus the general population. There were more ischemic stroke cases in the study group vs. the control group. After adjusting for vascular risk factors in a multivariate analysis, the odds ratio for a cerebrovascular accident in the HIV patient group was 2.29 (p = 0.057). Notably, in the comparative group, the vascular risk factors' rate (hyperlipidemia, IHD and smoking) was higher than in the HIV group. In this study, ischemic cerebrovascular events were more common in HIV-infected patients than in the control group, in spite of the fact that they had fewer vascular risk factors.

Intravenous Lacosamide in Seizure Clusters: Dose and Efficacy.

PURPOSE: The objective of our study was to evaluate the relationship between the loading dose and efficacy of lacosamide (LCM), when used in seizure clusters (SCs). METHODS: A cohort of patients with SC treated with intravenous (IV)-LCM between September 2017 and September 2019 was retrospectively examined. Demographic data, type of seizure emergency, etiology, response rate, previous oral antiepileptic drugs used, total LCM loading dose, and side effects were reviewed. RESULTS: Thirty-nine cases of epileptic emergencies treated with IV LCM were collected. The mean age was 59.25 years (18-88 years), and the median loading dose was 136.5 mg (100-300 mg) with a response rate in the whole population of 29.2%. Nine patients received a loading dose of 200 to 300 mg, and their response rate was 89%. Common side effects (drowsiness and dizziness) were mild. No electrocardiogram changes or other cardiovascular side effects, or unexpected side effects were seen. CONCLUSIONS: In adults with SC, a loading dose of IV LCM of 200 mg or more achieved 89% response rate in this cohort. Loading doses of less than 300 mg caused mild side effects only.

Creutzfeldt-Jakob and Vascular Brain Diseases: Their Overlap and Relationships.

Only a few case reports of stroke-like onset of Creutzfeldt-Jakob disease (CJD) have previously been published. We aimed to analyze the neurological, imaging, electroencephalographic (EEG), and laboratory features of patients with this very rare phenomenon. Here, we review the clinical characteristics, onset features, and clinical course variants of stroke-like CJD in 23 such patients. The median age of the patients was 71 years (range: 56-84 years); 12 were women. In 20 patients, CJD was sporadic. Thirteen patients developed apoplexy-like onset of symptoms, whereas the others had prodromal non-specific complaints. Most often the patients manifested with pyramidal signs (n = 13), ataxia (n = 9), and aphasia (n = 8). On MRI DWI sequence, all subjects had abnormal hyperintensities in various parts of the cerebral cortex, striatum, or thalamus, while EEG detected periodic triphasic waves only in 11. CSF 14-3-3 protein and total τ-protein were abnormal in 17 of 23 cases. All patients died, median lifespan being 2 months (range: 19 days-14 months). In conclusion, a complex of clinical, radiological, and laboratory manifestations of stroke-like onset of CJD is outlined. The clinical relationships between CJD and stroke are considered, in an attempt to highlight this rare presentation of an uncommon disease.

Case report: Isolated muscle neuromyotonia, as presenting feature of Isaacs' syndrome.

An autoimmune form of Isaacs' syndrome is commonly associated with VGKC complex antibodies and characterized by continuous muscle activity of extremity muscles. Here, we describe a CASPR2 and LGI1 positive patient with neuromyotonia clinically and electrophysiologically isolated to gastrocnemius muscles only. IVIG course and plasma exchange were ineffective, but symptoms significantly improved after a course of high-dose steroids. This case demonstrates that focal hyperexcitability should raise suspicion for autoimmunity. LGI1 antibody can be positive in patients with only peripheral nerve system involvement and if one treatment fails, other should be tried.

Estimation of seizures prevalence in ischemic strokes after thrombolytic therapy.

PURPOSE: Post stroke seizures are a complication that occur in 5-20% of acute ischemic stroke (AIS) patients, cause a reduction in quality of life and a greater burden on the health system. There is not enough data regarding an association between today's standard of care treatment in AIS: recombinant tissue plasminogen activator (r-tPA) and the risk for post stroke seizures. Our aim in this work is to reveal such a connection. METHOD: A non-randomized retrospective cohort-controlled study of 234 patients, who were hospitalized with acute ischemic stroke at Kaplan Medical Center in the years 2009-2015 and were divided into two different treatment groups: r-tPA and antiaggregant therapy(n = 141) and antiaggregant therapy only (n = 95) was conducted by us. Information regarding demographics, medical history, nature of the event, including NIHSS values on admission, discharge, and post stroke seizures, were obtained for each group. Follow-up was done for one year. RESULTS: During the year of follow-up, 19 patients (8.1%) of the overall cohort, developed seizures: 12 of them (12.6%) belonged to the control group and 7 (5%) to the study group p < 0.05). Results showed a decrease in the risk for developing seizure when treated with r-tpA, comparing to antiaggregants (odds ratio = 0.64). CONCLUSION: This study suggests there is an association between r-tPA treatment and reduction of the risk for post stroke seizures.

Occurrence of overt seizures in comatose survivor patients treated with targeted temperature.

Background: Unconscious patients after out-of-hospital cardiac arrest have a high risk of death. Therapeutic hypothermia is recommended by international resuscitation guidelines in order to attenuate secondary destructive physiological processes such as reperfusion injury, apoptosis, and cerebral edema. The target temperature to reach ranges between 32 and 34°C for at least 24 hr. Hypothermia can induce metabolic disturbances. There are some reports in the literature indicating the presence of seizures during targeted temperature management. On the other hand, postanoxic seizures are a sign of unfavorable neurological outcome. The purpose of this study was to evaluate the occurrence of overt seizures in comatose survivor patients treated with targeted temperature in respect to overt seizures in a normal temperature group of comatose patients. Methods: This was a retrospective study of unconscious adults post cardiopulmonary resuscitation, hospitalized in the intensive care unit during the years 2008-2015. The patients were divided into two groups: those treated with hypothermia and those with normal body temperature. Both groups were evaluated for the appearance of overt seizures during their hospitalization which was the primary outcome of the study. Results: The data of 88 consecutive unconscious patients after out-of-hospital cardiac arrest were collected. Twenty-six patients were treated with targeted temperature (32-34°C) and 62 patients with normal temperature. In the hypothermic group, 6 (23%) patients developed overt seizures during hospitalization compared to 11 (17%) in the normothermic group. The mortality rate was similar in both groups, 16 (61%) in the hypothermic group and 38 (61%) in the conservative group. According to the present study, overt seizures were more common in the group treated with hypothermia.

The phenotypic spectrum of ARHGEF9 includes intellectual disability, focal epilepsy and febrile seizures.

Mutations or structural genomic alterations of the X-chromosomal gene ARHGEF9 have been described in male and female patients with intellectual disability. Hyperekplexia and epilepsy were observed to a variable degree, but incompletely described. Here, we expand the phenotypic spectrum of ARHGEF9 by describing a large Ethiopian-Jewish family with epilepsy and intellectual disability. The four affected male siblings, their unaffected parents and two unaffected female siblings were recruited and phenotyped. Parametric linkage analysis was performed using SNP microarrays. Variants from exome sequencing in two affected individuals were confirmed by Sanger sequencing. All affected male siblings had febrile seizures from age 2-3 years and intellectual disability. Three developed afebrile seizures between age 7-17 years. Three showed focal seizure semiology. None had hyperekplexia. A novel ARHGEF9 variant (c.967G>A, p.G323R, NM_015185.2) was hemizygous in all affected male siblings and heterozygous in the mother. This family reveals that the phenotypic spectrum of ARHGEF9 is broader than commonly assumed and includes febrile seizures and focal epilepsy with intellectual disability in the absence of hyperekplexia or other clinically distinguishing features. Our findings suggest that pathogenic variants in ARHGEF9 may be more common than previously assumed in patients with intellectual disability and mild epilepsy.

Lamotrigine as monotherapy in clinical practice: efficacy of various dosages in epilepsy.

OBJECTIVES/AIMS: The study was designed to evaluate the optimal dosage of lamotrigine, as monotherapy, in the treatment of adults suffering from complex partial seizures with or without secondary generalization in everyday clinical practice. MATERIALS AND METHODS: The ones used in this study was the collection of the data of all adult patients treated with lamotrigine, retrospectively. The dosage and efficacy of treatment were evaluated along with side effects and retention rate. RESULTS: They showed that, out of 188 patients, 77% continued lamotrigine treatment; the mean effective dose was 250 mg or higher of lamotrigine, and the results more pronounced in older patients (age above 30 years) and those with a longer disease duration (5 years and more). CONCLUSION: It may be appropriate to reach a daily lamotrigine dose above 250 mg in adult patients suffering from epilepsy for more than 5 years using lamotrigine as monotherapy.

Burden and outcome of prevalent ischemic brain disease in a national acute stroke registry.

BACKGROUND AND PURPOSE: Previous overt stroke and subclinical stroke are frequent in patients with stroke; yet, their clinical significance and effects on stroke outcome are not clear. We studied the burden and outcome after acute ischemic stroke by prevalent ischemic brain disease in a national registry of hospitalized patients with acute stroke. METHODS: Patients with ischemic stroke in the National Acute Stroke Israeli prospective hospital-based registry (February to March 2004, March to April 2007, and April to May 2010) with information on previous overt stroke and subclinical stroke per computed tomography/MRI (n=3757) were included. Of them, a subsample (n=787) was followed up at 3 months. Logistic regression models were computed for outcomes in patients with prior overt stroke or subclinical stroke, compared with patients with first stroke, adjusting for age, sex, vascular risk factors, stroke severity, and clinical classification. RESULTS: Two-thirds of patients had a prior overt stroke or subclinical stroke. Death rates were similar for patients with and without prior stroke. Adjusted odds ratios (OR; 95% confidence interval [CI]) for disability were increased for patients with prior overt stroke (OR, 1.31; 95% CI, 1.03-1.66) and subclinical stroke (OR, 1.45; 95% CI, 1.16-1.82). Relative odds of Barthel Index≤60 for patients with prior overt stroke (OR, 2.04; 95% CI, 1.14-3.68) and with prior subclinical stroke (OR, 2.04; 95% CI, 1.15-3.64) were twice higher than for patients with a first stroke. ORs for dependency were significantly increased for patients with prior overt stroke (OR, 1.95; 95% CI, 1.19-3.20) but not for those with subclinical stroke (OR, 1.36; 95% CI, 0.84-2.19). CONCLUSIONS: In our national cohort of patients with acute ischemic stroke, nearly two thirds had a prior overt stroke or subclinical stroke. Risk of poor functional outcomes was increased for patients with prior stroke, both overt and subclinical.

Seizures after very mild head or spine trauma.

Traumatic brain injury (TBI) is a major cause of seizures in the general population. Several studies have shown an increased risk of epilepsy after traumatic brain injury, depending on risk factors, such as severity and time post trauma. The aim of our study was to evaluate the appearance of late seizures after a very mild head trauma or whiplash injury. All patients admitted to the emergency room after a very mild head trauma or whiplash injury during 2008-2010 were evaluated prospectively within 24 hours of the event and followed up 1 year later for evaluation of seizure appearance. The appearance of seizures in the head trauma or whiplash injury group was compared to a control group of orthopedic injury patients. A total of 2999 patients were included in the study--2005 patients with involvement of head and spine trauma and 994 in an orthopedic control group. Three patients (0.1%) out of the whole study group developed seizures: 2 (0.18%) in the head trauma group and 1 (0.1%) in the control group. The conclusion of the study was that post trauma seizure incidence is not significantly different in patients with very mild head or spine trauma and is similar respective to subjects with no non-head or cervical spine injury. This may have medico-legal repercussions.

SPECT-DTPA as a tool for evaluating the blood-brain barrier in post-stroke seizures.

Stroke is a well-known cause for seizures in the adult population. Research in animal models indicates that abnormalities in the blood-brain barrier (BBB) permeability can play a role in the development of spontaneous seizures or status epilepticus. The integrity of the BBB was investigated in patients with late post-stroke seizures by performing DTPA-SPECT studies to evaluate the correlation of BBB dysfunction in late post-stroke seizures. All patients with late-onset post-cortical stroke seizures hospitalized during 2009-2010 underwent a brain DTPA-SPECT within 72 h of the first seizure and were compared to a control group of stroke patients without seizures. Twenty-eight patients were included in the study. Twelve out of 14 (85.7%) in the group of seizure post-stroke patients had a positive brain DTPA-SPECT showing disruption of the BBB in the region of the stroke respective to four patients out of 14 (28.6%) in the control group of stroke patients without seizures (p = 0.001). The results of this study suggest that there is a correlation between late post-stroke seizures and BBB disruption, as revealed by DTPA-SPECT examination. Perhaps, this finding could lead to the hypothesis that the BBB disruption can predict developing seizures in patients with cortical stroke.

Low-level laser therapy applied transcranially to rats after induction of stroke significantly reduces long-term neurological deficits.

BACKGROUND AND PURPOSE: Low-level laser therapy (LLLT) modulates various biological processes. In the present study, we assessed the hypothesis that LLLT after induction of stroke may have a beneficial effect on ischemic brain tissue. METHODS: Two sets of experiments were performed. Stroke was induced in rats by (1) permanent occlusion of the middle cerebral artery through a craniotomy or (2) insertion of a filament. After induction of stroke, a battery of neurological and functional tests (neurological score, adhesive removal) was performed. Four and 24 hours poststroke, a Ga-As diode laser was used transcranially to illuminate the hemisphere contralateral to the stroke at a power density of 7.5 mW/cm2. RESULTS: In both models of stroke, LLLT significantly reduced neurological deficits when applied 24 hours poststroke. Application of the laser at 4 hours poststroke did not affect the neurological outcome of the stroke-induced rats as compared with controls. There was no statistically significant difference in the stroke lesion area between control and laser-irradiated rats. The number of newly formed neuronal cells, assessed by double immunoreactivity to bromodeoxyuridine and tubulin isotype III as well as migrating cells (doublecortin immunoactivity), was significantly elevated in the subventricular zone of the hemisphere ipsilateral to the induction of stroke when treated by LLLT. CONCLUSIONS: Our data suggest that a noninvasive intervention of LLLT issued 24 hours after acute stroke may provide a significant functional benefit with an underlying mechanism possibly being induction of neurogenesis.

Pathological laughter as a symptom of midbrain infarction.

Pathological laughter is an uncommon symptom usually caused by bilateral, diffuse cerebral lesions. It has rarely been reported in association with isolated cerebral lesions. Midbrain involvement causing pathological laughter is extremely unusual. We describe three patients who developed pathological laughter after midbrain and pontine-midbrain infarction. In two patients a small infarction in the left paramedian midbrain was detected, whereas the third one sustained a massive bilateral pontine infarction extending to the midbrain. Laughter heralded stroke by one day in one patient and occurred as a delayed phenomenon three months after stroke in another. Pathological laughter ceased within a few days in two patients and was still present at a two year follow-up in the patient with delayed-onset laughter. Pathological laughter can herald midbrain infarction or follow stroke either shortly after onset of symptoms or as a delayed phenomenon. Furthermore, small unilateral midbrain infarctions can cause this rare complication.