Acute Onset Of Neurological Symptoms Research Articles

Clinical and radiological description of 120 pediatric stroke-like episodes.

Stroke-like episodes (SLEs) are defined as acute onset of neurological symptoms mimicking a stroke and radiological lesions non-congruent to vascular territory. We aimed to analyze the acute clinical and radiological features of SLEs to determine their pathophysiology. We performed a monocenter retrospective analysis of 120 SLEs in 60 children over a 20-year period. Inclusion criteria were compatible clinical symptoms and stroke-like lesions on brain magnetic resonance imaging (MRI; performed for all 120 events) with focal hyperintensity on diffusion-weighted imaging in a non-vascular territory. Three groups were identified: children with mitochondrial diseases (n = 22) involving mitochondrial DNA mutations (55%) or nuclear DNA mutations (45%); those with other metabolic diseases or epilepsy disorders (n = 22); and those in whom no etiology was found despite extensive investigations (n = 16). Age at first SLE was younger in the group with metabolic or epilepsy disorders (18 months vs. 128 months; p < 0.0001) and an infectious trigger was more frequent (69% vs. 20%; p = 0.0001). Seizures occurred in 75% of episodes, revealing 50% episodes of SLEs and mainly leading to status epilepticus (90%). Of the 120 MRI scans confirming the diagnosis, 28 were performed within a short and strict 48-h period and were further analyzed to better understand the underlying mechanisms. The scans showed primary cortical hyperintensity (n = 28/28) with decreased apparent diffusion coefficient in 52% of cases. Systematic hyperperfusion was found on spin labeling sequences when available (n = 18/18). Clinical and radiological results support the existence of a vicious circle based on two main mechanisms: energy deficit and neuronal hyperexcitability at the origin of SLE.

Gastrointestinal carcinoma first presenting as pituitary mass: recognition of a rare case and multidisciplinary approach for the management of pituitary metastases

Abstract Introduction PMs (pituitary metastases) are rare and only a few cases are reported in the literature. In half of the documented cases, PMs originate from breast and lung cancers, rarely from other sites. They can grow rapidly and present local invasiveness, leading to acute onset of neurological symptoms, such as headache, visual and oculomotor disturbances, or endocrinological signs, such as diabetes insipidus and hypopituitarism. Their rarity and the lack of specific clinical and radiological features often impede their differentiation from other more common sellar area lesions, particularly when history of malignancy is absent. As PMs can be life-threatening, they must be recognized and treated promptly. Management of PMs may also be difficult because the prognosis depends on the course of the primary neoplasm. The case presented below is one of the few documented cases in the world of a pituitary metastasis from a primary gastrointestinal carcinoma. Clinical Case A 76-year-old woman, with no history of malignancy, presented with headache, dizziness and diplopia. Neurologic examination was remarkable for complete left ophthalmoplegia associated with sensitivity deficit in the left half face. Radiologic investigations documented a voluminous sellar and suprasellar formation, with extension in the ipsilateral cavernous sinus, compressing the optic chiasm and ipsilateral temporal lobe. The mass appeared heterogeneous as component of apoplectic infarction. Left cavernous sinus syndrome in apoplectic macroadenoma was diagnosed. Surgical removal of the lesion was performed through a transsphenoidal endoscopic endonasal approach. The histological exam disclosed a metastasis of adenocarcinoma with widespread necrotic-haemorrhagic elements. The immunohistochemical profile suggested an origin from a primary gastrointestinal carcinoma. Hormone replacement therapy and adjuvant therapy were instituted, although radiological investigations failed to identify the site of the primary gastrointestinal carcinoma. Postoperative MRI showed a parasellar residual tumor, which was radiologically stable at 6-month follow-up. The patient will undergo a radiotherapy and neurosurgical evaluation. Conclusions Clinicians should consider the possibility of PMs in patients with symptoms and signs that may suggest the presence of a pituitary mass. Since PMs can be cancer first manifestation, the recognition of PMs determines the referral to adequate oncological therapy. Prognosis is usually poor and it's difficult to estimate as it varies significantly depending on the systemic disease and the primary histology. Recognition and management of PMs remain complex and require a multidisciplinary team of endocrinologists, oncologists, neurosurgeons and neuroradiologists.

PRES and RCVS: Two Distinct Entities or a Spectrum of the Same Disease?

ObjectivesTo report a case of a patient with overlapping posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), and review the existing literature emphasizing the pathophysiological overlap of these two entities. Materials and MethodsWe conducted a literature search in electronic database PubMed identifying studies reporting the overlap of PRES and RCVS. ResultsPRES and RCVS are two increasingly recognized entities that share similar clinical and imaging features. PRES is characterized by vasogenic edema predominantly in the parieto-occipital regions, associated with acute onset of neurological symptoms including encephalopathy, seizures, headaches, and visual disturbances. RCVS is characterized by reversible segmental and multifocal vasoconstriction of the cerebral arteries and classically presents with thunderclap headache, with or without associated focal neurological deficits and seizures. PRES is frequently associated with uncontrolled hypertension but can also be seen in the setting of renal failure, exposure to cytotoxic agents, or pre-eclampsia. RCVS is often triggered by exposure to vasoactive agents, postpartum state, or immunosuppression. We report a case of a patient presenting with vision changes and hemiparesis, and found to have extensive cytotoxic and vasogenic edema involving the cortex and subcortical white matter on brain imaging. These changes were primarily noted in the parieto-occipital and brainstem regions, along with features of reversible vasculopathy on vascular imaging suggestive of coexisting PRES and RCVS. ConclusionsPRES and RCVS share precipitating factors, clinical and radiological features, and frequently co-exist, suggesting a common pathophysiological mechanism related to reversible dysregulation of cerebral vasculature, endothelial dysfunction, and breakdown of the blood-brain barrier.

Statins in patients with acute ischemic stroke: when we should start therapy?

Lipid-lowering therapy is known to be an important part of ischemic stroke secondary prevention, however, the exact timing of its initiation or re-starting in the patients with ischemic stroke is not yet defined strictly. Accumulating evidence of pleiotropic (i. e. non-lipid-lowering) effects of statins in various conditions, including ischemia, urges their implementation in the clinical practice. In this review, we discuss the evidence on the effectiveness of early statin introduction in different populations of patients with ischemic stroke. We also attempt to define our original position on the optimal time after the acute onset of neurological symptoms to introduce lipid-lowering therapy.

Delineating the phenotypic spectrum of sulfite oxidase and molybdenum cofactor deficiency.

ObjectiveTo define the phenotypic spectrum of isolated sulfite oxidase (ISOD) and molybdenum cofactor deficiency (MoCD), aiming to promote timely diagnosis and assist in future clinical trial design.MethodsWe analyzed clinical, radiographic, biochemical, and genetic data from 146 patients reported in the literature.ResultsWe stratified patients into 2 phenotypic subgroups based on clinical and radiographic characteristics. In the first (Class I), patients presented early in life (age 1–50 days) with acute onset of neurologic symptoms and development of diffuse brain injury with cystic leukomalacia. Patients in the second subgroup (Class II) presented later in life (age 30 days–23 years) with prominent movement abnormalities and selective injury of the basal ganglia and cerebellum. A significant difference in survival estimates correlated with milder disease severity among Class II patients. Substantial overlap in sulfur-containing metabolite levels prevented discrimination of subgroups based on diagnostic biomarkers, but genotype-phenotype correlations suggested that residual SUOX activity may contribute to milder phenotypes.ConclusionsPatients with SUOX and MoCD gravitate toward 1 of 2 distinct clinicoradiographic profiles. Patient stratification may help promote accurate diagnosis, prognostication, and aid in the design of future clinical trials.

Complex partial seizures as sole presentation of acute stroke - Rare learning case

68 years old gentleman presented to ER with three days history of sudden onset of frequent spells of confusion and memory disturbance. These last for thirty to forty seconds at a time leaving him feeling very tired. His wife noted that he becomes unresponsive and stares in vague without jerks. He also described feeling as if he goes in a short dream repeatedly. He is diabetic, hypertensive and had CABG previously. Also suffered with long standing depression using SSRI’s on and off. No past history of similar symptoms, TIA or stroke. He admitted to have low mood. Clinically was fully alert, orientated but was unable to read or write nor to perform simple calculation without other focal signs. HisECG and basic blood tests were within normal limits. An MRI scan of the brain revealed a subacute infarction in the left medial temporal lobe with spots of minor bleeds. An EEG showed active seizure discharges from the same area. He was managed as inpatient with Aspirin and clopidogrel, atorvastatin and levetiracetam. He did well and all his symptoms resolved. He remained stable on follow up in the out patient three weeks later. Although it is well known, but very rare for a stroke to present with complex partial seizures without classical focal neurological signs, presenting with only seizures is even rarer. The back ground of depressive illness and vagueness of symptoms delayed his reporting to emergency department. Acute onset of neurological symptoms in a patient of such age with vascular risks should lead to imaging early.

Surgical outcomes in patients with anti-N-methyl D-aspartate receptor encephalitis with ovarian teratoma

Anti-N-methyl-D-aspartate receptor encephalitis is an autoimmune encephalitis mediated by anti-N-methyl-D-aspartate receptor antibodies. Ovarian teratoma is closely related to anti-N-methyl-D-aspartate receptor encephalitis. However, the optimal treatment remains unknown, and strategies used for the diagnosis and therapy, including surgical intervention of ovarian teratoma, are debatable. The objective of the study was to study the clinical features of anti-N-methyl-D-aspartate receptor encephalitis with ovarian teratoma to further understand the disease. This single-center prospective study included patients with anti-NMDAR encephalitis with ovarian teratoma from 2011 to 2016 who were admitted to Peking Union Medical College Hospital, Beijing, and discussed the clinical characteristics, treatment, and prognosis of the disease. The diagnosis of anti-N-methyl-D-aspartate receptor encephalitis was established preoperatively by identifying anti-N-methyl-D-aspartate receptor antibodies in the cerebrospinal fluid. Ovarian teratomas were suspected preoperatively by pelvic ultrasound and were diagnosed pathologically after laparoscopic detection and ovarian tumor resection. All patients were treated with first-line immunotherapy (steroids, intravenous immunoglobulin, and plasmapheresis), and when the therapy failed, they were treated with second-line immunotherapy (cyclophosphamide and rituximab). All patients were followed up regularly, and N-methyl-D-aspartate receptor antibodies, pelvic ultrasound, and neurological condition were monitored. Neurological symptoms were assessed using the modified Rankin Scale. A total of 108 female patients with anti-N-methyl-D-aspartate receptor encephalitis were screened, of whom, 29 patients (26.9% of 108; mean age ± SD, 23.14 ± 6.59 years) had pathologically confirmed ovarian teratoma. The incidence of fever, decreased consciousness, arrhythmia, central hypoventilation, ventilator-assisted respiration, and intensive unit care (75.9%, 65.5%, 27.6%, 55.2%, 55.2%, and 58.6%, respectively) were significantly higher in patients with ovarian teratoma than in those without ovarian teratoma. The modified Rankin Scale at the acute onset in those 29 patients was 4.11 ± 1.20, which was also much higher than that in patients without ovarian teratoma (3.58 ± 1.08). Of the 29 patients with ovarian teratoma, 22 (75.9%) underwent laparoscopy during the acute onset of neurological symptoms. The mean diameter of the tumor was 4.61 ± 3.41 cm (SD), and the smallest tumor was only 1 cm in the unilateral ovary. All other cysts, except 4 bilateral cysts (13.8%), were unilateral. Only 1 patient was diagnosed pathologically with immature ovarian teratoma, while others had benign ovarian teratomas. In all, 28 patients (96.5%) had a good outcome (modified Rankin Scale ≤2) and 1 died. In the follow-up visit (mean duration, 37.69 months), the relapse rate of encephalitis in patients with ovarian teratoma undergoing laparoscopic cystectomy was 14.6%, whereas for those without ovarian teratoma, the relapse rate was 33.3%. The removal of ovarian teratoma was associated with reduced risk of relapse. Patients having anti-N-methyl-D-aspartate receptor encephalitis with ovarian teratomas tend to present more severe neurological conditions. The diameter of the tumor in these patients is not very large and could be as small as 1 cm, and thus, careful exploration should be considered during surgery. Most of the ovarian teratomas in patients with anti-N-methyl-D-aspartate receptor encephalitis are mature. Early operative treatment is safe and effective because it is associated with reduced risk of relapse and complete recovery.

Brain Aneurysms in the Pediatric Population of Slovenia: A Case Series.

Brain aneurysms are rare in the pediatric population. The diagnosis of a brain aneurysm in a child may be difficult because of its infrequency and often subtle or nonspecific clinical presentation. Endovascular therapy and microsurgical treatment are increasingly used approaches in treating children, possibly contributing to favorable outcomes if patients are treated in a timely manner. We were interested in the clinical presentation, symptoms, diagnostics, treatment, and follow-up of pediatric patients with brain aneurysms in Slovenia. This was a retrospective review of medical documentation of children with intracranial aneurysms treated at the University Children's Hospital in Ljubljana, Slovenia, from January 1998 to December 2017. We identified a cohort of eight children (median age: 14.9 years; range: 2.8-17.7). The estimated incidence of pediatric brain aneurysms in Slovenia is 0.12/100,000 children per year. We observed a male predominance (1.7:1). Half of the patients presented with acute onset of neurologic symptoms and three with subarachnoid hemorrhage. One of the patients had a related stroke. The presenting symptoms were tonic-clonic seizures, hemiparesis, paresthesias, speech disturbance, and cranial nerve palsy. The other half of aneurysms were identified incidentally. Five patients had anterior circulation aneurysms; the most prevalent location was the internal carotid artery. One patient was treated with surgical procedures, four patients were treated with endovascular procedures, and three patients were treated conservatively. Outcome was excellent in all patients. Endovascular interventions and microsurgical procedures appear to be safe and effective in the treatment of brain aneurysms in the pediatric population. Asymptomatic patients with brain aneurysms need close follow-up.

'Stroke chameleons'

The diagnosis of acute stroke should be correct and early that allows physician planning the most effective treatment strategies (reperfusion therapy, undifferentiated (basic) treatment, early secondary prevention). However, stroke symptoms can be atypical and similar to some other (non-vascular) event. It can significantly complicate the clinical diagnosis of stroke and decrease the patient's chances for effective treatment. A stroke should be suspected in every patient with acute onset of neurological symptoms, especially when the patient has the 'vascular' risk factors. Furthermore it is important to remember that negative CT-scan data and/or MRI data do not exclude the presence of not only ischemic stroke but also hemorrhagic stroke. The article describes the main variants of strokes with atypical symptoms (strokes-chameleons), emphasizes the importance of careful clinical examination, provides supportive differential diagnostic criteria and discusses limitations of neuroimaging methods.

Computed Tomography Angiography in Head and Neck Emergencies

Computed tomography angiography (CTA) offers a rapid means of evaluating the vasculature of the head and neck in patients presenting with acute onset of neurologic symptoms and blunt trauma to the head and neck. CTA is noninvasive, easy to acquire, and offers excellent detail in identifying site and nature of the lesion. The learning objectives of this article are to review normal anatomy and variants, recognize CTA appearance of vascular pathologies, describe typical parameters used for acquiring the study, and recognize common pitfalls.

Chapter 26 - Posterior reversible encephalopathy in the intensive care unit

Posterior reversible encephalopathy syndrome (PRES) is increasingly diagnosed in the emergency department, and medical and surgical intensive care units. PRES is characterized by acute onset of neurologic symptoms in the setting of blood pressure fluctuations, eclampsia, autoimmune disease, transplantation, renal failure, or exposure to immunosuppressive or cytotoxic drugs, triggers known to admit patients to the intensive care unit (ICU). Although the exact pathophysiology remains unknown, there is growing consensus that PRES results from endothelial dysfunction. Because of the heterogeneous nature of the disorder, it is probable that different mechanisms of endothelial injury are etiologically important in different clinical situations. The presence of bilateral vasogenic edema on brain imaging, particularly in parieto-occipital regions, is of great diagnostic utility but PRES remains a clinical diagnosis. Although largely reversible, PRES can result in irreversible neurologic injury and even death. The range of clinical and radiographic manifestations of the syndrome is probably broader than previously thought, and it is imperative that clinicians become familiar with the full spectrum of the disorder, as prompt recognition and elimination of an inciting factor improve outcome. PRES may be the most frequent toxic-metabolic encephalopathy seen in the ICU.

Mimics of Acute Stroke

Stroke affects approximately 800,000 people in the United States each year and is the fourth major leading cause of adult mortality.1 Rapid diagnostic evaluation and prompt treatment are important to prevent death and disability from a stroke. The literature suggests that up to 30% of patients who present with acute onset of neurologic symptoms were found to have a stroke misdiagnosis. In addition, the safety of thrombolytic therapy for stroke mimics has not been fully studied. Although patients with acute stroke can benefit substantially from thrombolytic therapy, misdiagnosis of acute stroke can carry serious implications, and it is imperative that radiologists make a prompt and accurate diagnosis. Combining various imaging techniques and interpreting imaging findings in appropriate clinical contexts will help with selection of appropriate therapy.

Insights into the Pathology of the α3 Na(+)/K(+)-ATPase Ion Pump in Neurological Disorders; Lessons from Animal Models.

The transmembrane Na+-/K+ ATPase is located at the plasma membrane of all mammalian cells. The Na+-/K+ ATPase utilizes energy from ATP hydrolysis to extrude three Na+ cations and import two K+ cations into the cell. The minimum constellation for an active Na+-/K+ ATPase is one alpha (α) and one beta (β) subunit. Mammals express four α isoforms (α1−4), encoded by the ATP1A1-4 genes, respectively. The α1 isoform is ubiquitously expressed in the adult central nervous system (CNS) whereas α2 primarily is expressed in astrocytes and α3 in neurons. Na+ and K+ are the principal ions involved in action potential propagation during neuronal depolarization. The α1 and α3 Na+-/K+ ATPases are therefore prime candidates for restoring neuronal membrane potential after depolarization and for maintaining neuronal excitability. The α3 isoform has approximately four-fold lower Na+ affinity compared to α1 and is specifically required for rapid restoration of large transient increases in [Na+]i. Conditions associated with α3 deficiency are therefore likely aggravated by suprathreshold neuronal activity. The α3 isoform been suggested to support re-uptake of neurotransmitters. These processes are required for normal brain activity, and in fact autosomal dominant de novo mutations in ATP1A3 encoding the α3 isoform has been found to cause the three neurological diseases Rapid Onset Dystonia Parkinsonism (RDP), Alternating Hemiplegia of Childhood (AHC), and Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS). All three diseases cause acute onset of neurological symptoms, but the predominant neurological manifestations differ with particularly early onset of hemiplegic/dystonic episodes and mental decline in AHC, ataxic encephalopathy and impairment of vision and hearing in CAPOS syndrome and late onset of dystonia/parkinsonism in RDP. Several mouse models have been generated to study the in vivo consequences of Atp1a3 modulation. The different mice show varying degrees of hyperactivity, gait problems, and learning disability as well as stress-induced seizures. With the advent of several Atp1a3-gene or chemically modified animal models that closely phenocopy many aspects of the human disorders, we will be able to reach a much better understanding of the etiology of RDP, AHC, and CAPOS syndrome.

Acute Paraplegia due to Thoracic Hematomyelia.

Spontaneous intraspinal intramedullary hemorrhage is a rare entity with the acute onset of neurologic symptoms. The etiology of idiopathic spontaneous hematomyelia (ISH) is unknown, and there are few published case reports. Hematomyelia is mostly associated with trauma, but the other nontraumatic etiologies are vascular malformations, tumors, bleeding disorders, syphilis, syrinx, and myelitis. MRI is a good choice for early diagnosis. Hematomyelia usually causes acute spinal cord syndrome due to the compression and destruction of the spinal cord. A high-dose steroid treatment and surgical decompression and evacuation of hematoma are the urgent solution methods. We present idiopathic spontaneous hematomyelia of a previously healthy 80-year-old male with a sudden onset of back pain and paraplegia.

Ventriculitis due to infection with Rhizopus arrhizus

A 52-year-old heart–lung transplant patient presented to the emergency department with acute onset of neurologic symptoms. MRI showed ballooning of the left ventricle, midline shift and contrast enhancement in the anterior horn of the left ventricle. Ventricle neuroendoscopy revealed whitish, floccose aerial structures within the left ventricle. Brain biopsy cultures grew Rhizopus arrhizus. Therapy with liposomale amphotericin B and posaconazole was performed. Except for hemianopsia and deficits in minute motor activity, the patient completely recovered.

A Survey about the Temporal Pattern of Stroke Occurrence

Article type: Original Article Background: Temporal variation of stroke onset is suggested in some studies contained somewhat varieties. It is proposed that some predisposing changes occur in some ascertained times consequently resulted in stroke occurrence in some special times. Objective: To determine the circadian and circaseptan variation of stroke onset. Materials and Methods: This cross sectional study was conducted from March 2012 to February 2013 in an academic hospital in the North of Iran. All patients with acute onset of neurological symptoms were enrolled in the study after being diagnosed as a stroke patient. The diagnosis was made by a neurologist using brain imaging. Age, gender, history of diabetes and hypertension, time and date of stroke onset were recorded for all patients. The data were analysed using Chi-square test in SPSS software version19. Results: A total of eight hundred sixty-nine patients with mean age of 67.5±12.4 years (55.6% women 44.4% men) were admitted during one year study. Eighty-five percent of stroke cases were ischemic in nature and the others were hemorrhagic type. Distribution of cases during a day was not uniform (p < 0.0001). The peak of stroke onset occurred in the mornings (7-9 a.m.) followed by a second peak in the evenings (7-9 p.m.). In addition, the distribution of cases during the week was also not uniform (p < 0.016). Conclusion: Stroke occurrence has a diurnal variation probably resulted from circadian physiologic changes. Although there is a circaseptan variation in the times of stroke record, it seemingly isn’t related to physiologic changes.

Abstract T P47: Feasibility of Rapid Short Sequence Magnetic Resonance Imaging for Screening Stroke Mimics within the IV-tPA Treatment Window - A Pilot Study

Background &amp; Purposes: Up to 30 percent of patients presenting with acute onset of neurological symptoms may suffer from stroke mimics (SMs). MRI is highly sensitive for detection of acute ischemia; however, its clinical utility in the acute stage is limited secondary to the complexity, availability, and time required for a comprehensive brain MRI. In this pilot study, we investigated the feasibility of rapid short sequence (RSS) MRI to screen possible SMs while keeping the door-to-needle (DTN) time below one hour. Subjects &amp; Methods: We developed clinical criteria to clinically suspect possible SMs and deployed RSS MRI in those patients presenting with acute stroke like-symptoms. Our RSS MRI protocol takes 5-6 minutes and includes DWI, ADC, and FLAIR sequences. The patients also received a non-contrast CT head at the time of ER presentation as standard of care. The new processes to our code stroke protocol included adding MRI technicians to the code stroke, the stroke nurse or physician filling out the MRI screening sheet and transporting the patient to the MRI suite. The stroke physicians were also available at the MRI console to read the MRI and the stroke team was on standby to initiate IV tPA infusion in the MR suite, if it was indicated. Results: In a 9-month period, we evaluated 35 patients, who met our criteria for possible SMs, using RSS MRI (mean age 49, 78% women, median NIHSS 4). Three patients had diagnosis of an acute ischemic stroke on RSS MRI and received IV TPA while still in the MR suite. The DTN time ranged from 48 to 58 minutes. The median door-to-imaging time was 43 minutes (range 38-49). All of our patients with a RSS MRI negative for acute stroke had a final diagnosis other than stroke. Conclusions: Our preliminary results show that RSS MRI can be rapidly obtained in selected patients without delaying the DTN time. This screening method avoids unnecessary IV-tPA administration to SMs.

Accidental Substance Abuse Poisoning In Children: Experience of the Dammam Poison Control Center

Abstract Introduction: Cannabis and amphetamines are the most commonly used illegal drugs in adults in Saudi Arabia. Accidental Substance Abuse poisoning is an uncommon form of poisoning in children, but potentially serious. Objective: To describe the clinical presentation, diagnosis and treatment of children with accidental poisoning from various forms of substances of abuse in a pediatric secondary hospital. Material and Methods: We report on14 patients with accidental intoxication by amphetamines, cannabis and opiates. Results: The clinical presentation was variable deterioration in level of consciousness, somnolence, ataxia, tremor, apnea, hypotonia and seizure. The investigation of toxic urine detected benzphetamine, tetrahydrocannabinol (THC) and morphine in all cases of amphetamine, cannabis and heroine intoxication respectively. In all patients with amphetamine and cannabis intoxication supportive measures were established. In only one case of acute heroine intoxication was naloxone therapy given. All cases recovered well and were discharged within 24-48 hours of admission. Conclusion: A high index with early priority of suspicion should be maintained for substances of abuse involving “amphetamines, cannabis or morphine” intoxication in previously healthy children with acute onset of neurological symptoms of unknown etiology. Accidental poisoning by various substances of abuse is, in itself, an alarm signal on the attitude of parents in caring for their children. These families deserve special monitoring by social services, since such accidents may be covering up child abuse.

Glucose intolerance and insulin resistance as predictors of low platelet response to clopidogrel in patients with minor ischemic stroke or TIA

The relation between high on-treatment platelet reactivity (HPR), and the level of glucose intolerance and insulin resistance (IR) was studied in clopidogrel-treated patients with minor ischemic stroke or TIA. The cohort consisted of 66 patients, 11 of which had known type 2 diabetes mellitus (DM). Platelet aggregation in whole blood (Multiplate™) and metabolic variables were measured 1 month after acute onset of neurological symptoms. Glucose tolerance was measured by Oral Glucose Tolerance Test (OGTT). IR was estimated by homeostasis model assessment HOMA-IR. Patients were categorized as “responders” (R) or “non-responders” (NR) to clopidogrel according to an established cut-off in platelet aggregation induced by adenosine diphosphate (ADP). In total, 14/66 (21%) patients were NR. Impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or DM was seen in 13/14 NR (93%), while for R this was the case in 25/52 (48%), p = 0.001. The percentage of NR was 33% in patients with DM and 35% in patients with IGT or IFG. In the group with normal glucose tolerance (NGT) the percentage of NR was low, 4% (1/28). Fasting plasma glucose (f-PG) was higher for NR than for R, 6.0 (5.5–6.7) mM vs. 5.3 (5.0–6.0) mM, p = 0.023. Glycated hemoglobin (HbA1c) did not differ between NR and R. NR also had higher arachidonic acid-induced platelet aggregation than R, and a tendency towards higher aggregation induced by thrombin receptor agonist peptide (TRAP), indicating that HPR reflects a global platelet hyper-reactivity. HOMA-IR was calculated for 52 of the patients above without known diabetes, 9 of which were NR (17%). NR were significantly more insulin resistant than R, with median HOMA-IR 4.5 (3.0–7.4) compared to 2.1 (1.5–3.2) for R, p = 0.001. HOMA-IR and fasting plasma insulin were the only metabolic variables with significant relationships to ADP-induced platelet aggregation. The results suggest that HPR develops in the pre-diabetic phase. A metabolic disturbance with glucose intolerance and/or high level of IR was a pre-requisite for HPR in the tested cohort. Conversely, normal glucose tolerance combined with normal or mildly elevated HOMA-IR excluded HPR. NR are likely to constitute a high-risk group among patients with ischemic cerebrovascular disease. Measurement of f-PG or HbA1c is insufficient to identify NR, while OGTT and HOMA-IR are more predictive.

Tau protein concentrations in the cerebrospinal fluid of children with acute disseminated encephalomyelitis

Background: Acute disseminated encephalomyelitis (ADEM) is clinically characterized by the acute onset of neurological symptoms after a viral infection or immunization, and is thought to represent an autoimmune disease directed against myelin. Tau protein is a phosphorylated microtubule-associated protein, primarily located in neuronal axons. Increased levels of tau protein in cerebrospinal fluid (CSF) are found in various pathological conditions. Methods: We used tau protein as a marker of axonal damage and examined its concentration in the CSF of 27 children with ADEM. Results: CSF tau protein concentration in children with ADEM was significantly higher than that in the CSF of control subjects (P=0.008). There were no significant differences in CSF tau protein concentrations in the ADEM patients with and without encephalopathy. The CSF tau protein concentration in patients with partial lesion resolution in follow-up brain MRI was significantly higher than in patients with complete lesion resolution (P=0.014). Conclusions: In conclusion, we demonstrated that CSF tau protein concentration was significantly increased in ADEM patients. Our findings suggest that axonal damage may occur in addition to demyelination in children with ADEM.