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Treatment of experimental stroke with opiate antagonists. Effects on neurological function, infarct size, and survival.

The effects are reported of acute and long-term continuous administration of three opiate antagonists--naloxone, naltrexone, and diprenorphine--on neurological function, survival, and infarct size in a feline model of acute focal cerebral ischemia. All three drugs produced statistically significant improvement in motor function following acute administration without concomitant changes in level of consciousness; saline had no effect. Naloxone and naltrexone significantly prolonged survival (p less than 0.01); diprenorphine did not. Infarct size was not altered by any treatment administered. These findings confirm previous work suggesting that, with the appropriate methodology, treatment with opiate antagonists partially reverses neurological deficits. They also show that opiate antagonists prolong survival in certain conditions of acute and subacute focal cerebral ischemia without altering the area of infarcted tissue.

Animals↗

Early rehabilitation for stroke patients: a new look.

Many investigators have argued that early rehabilitation is important to maximize recovery from stroke and have documented a correlation between better outcomes and earlier admission to rehabilitation. But is this correlation good evidence for causation? In a sample of 94 stroke patients admitted to a comprehensive rehabilitation hospital, shorter onset-admission intervals definitely correlated with functional status outcomes (r = 0.27, p less than or equal to 0.006). However, when functional status upon admission, prior acute care improvement, level of consciousness shortly after the stroke, and other patient characteristics were partialled out, the correlation disappeared (partial r = -0.03, ns). The putative effect of early rehabilitation was attributable to the better health of stroke patients who could be admitted earlier to rehabilitation. Indications were that optimal timing for rehabilitation may differ depending upon side of paralysis. Rather than assuming that earlier is always better, future research and practice should concentrate on grading rehabilitative efforts to the capacities and needs of patients.

Adult↗

Can a clinical score aid in early diagnosis and treatment of various stroke syndromes?

BACKGROUND: Accurate and timely diagnosis of hemorrhagic and nonhemorrhagic strokes helps in patient management. Neuroimaging studies are useful in diagnosis and distinction of hemorrhagic (HS) and nonhemorrhagic (NHS) strokes. The use of clinical variables, such as Siriraj stroke scores (SSS), has shown good sensitivity, specificity and predictive values (distinguishing stroke types). The aim of our study was to evaluate the use of SSS in a U.S. population and assess whether it could aid to expedite treatment decisions. METHODS: Levels of consciousness, vomiting, headache and atheroma markers used in SSS were applied to patients who met the criteria for stroke. RESULTS: Of the 302 patients identified, the SSS classified 254 with sensitivity of 36% (HS) and 90% (NHS) and positive predictive values of 77% and 61%, respectively. CONCLUSION: Our results suggest that SSS is not reliable in distinguishing stroke types (in a US population). Definite neuroimaging studies are needed prior to thrombolytic therapy.

Aged↗

Panic disorder in African-Americans: symptomatology and isolated sleep paralysis.

While attention has been paid to the study of panic disorder (PD) with or without agoraphobia among Caucasians, surprisingly little empirical research within the United States has looked at the phenomenology of PD among minority groups. In this paper we present data we have collected and review other research on the phenomenology, social supports, and coping behavior among African-Americans with panic disorder. Our studies indicate that, in comparison to Caucasians, African-Americans with PD reported more intense fears of dying or going crazy, as well as higher levels of numbing and tingling in their extremities. African-Americans reported higher rates of comorbid post traumatic disorder and more depression. African-Americans also used somewhat different coping strategies (such as religiosity and counting one's blessings), less self-blame, and were somewhat more dissatisfied with social supports. The incidence of isolated sleep paralysis was, as per previous reports, higher in African-Americans. These findings, results of other research, and the implications for assessment and treatment are discussed within a semantic network analysis of panic (Hinton and Hinton 2002, this issue).

Adaptation, Psychological↗

[Neurological form of onset in haemophagocytic lymphohistiocytosis].

INTRODUCTION: Haemophagocyte lymphohistiocytosis (HLH) is a hematological disorder, autosomal recessive and in which there is benign proliferation of histiocytes with intense phagocytic activity of hematopoietic cells. The clinical features include fever, pancytopenia, coagulation disorders, liver dysfunction, the presence of histiocytes and haemophagocytes in the bone marrow, lymph nodes, spleen and liver. The nervous system is always involved and sooner or later patients develop a nervous system disorder with variable symptoms which may include irritability, disorders of consciousness, convulsions, ataxia, nystagmus or signs of intracranial hypertension. CLINICAL CASE: Onset of the disease showing purely neurological features is rare. We therefore describe the case of an 8 month old baby with HLH with a purely neurological condition involving irritability, horizontal rapid eye movements and vertical saccadic movements of both eyes and focal convulsive seizures. Initial complementary examinations were normal, except for study of the CSF with a lowered protein level and cells (monocytes). Finding hepatosplenomegaly and pallor, together with the laboratory investigations, made it advisable to do a bone marrow punch biopsy to detect haemophagocytes which would be diagnostic of HLH. In spite of chemotherapy there was rapid neurological deterioration, with alterations of the white matter and hydrocephaly which required insertion of a ventriculo-peritoneal shunt. The patient died when he was 10 months old. CONCLUSIONS: The cases of HLH in which cerebromeningeal disorders alone precede systemic symptoms are extremely rare. Hence the interest in reporting this case, so that it may be borne in mind in other cases of acute neurological onset. In this case initially there was encephalitis alone, but this was rapidly followed by systemic complications.

Anticonvulsants↗

Neural response to emotional faces with and without awareness: event-related fMRI in a parietal patient with visual extinction and spatial neglect.

This study examined whether differential neural responses are evoked by emotional stimuli with and without conscious perception, in a patient with visual neglect and extinction. Stimuli were briefly shown in either right, left, or both fields during event-related fMRI. On bilateral trials, either a fearful or neutral left face appeared with a right house, and it could either be extinguished from awareness or perceived. Seen faces in left visual field (LVF) activated primary visual cortex in the damaged right-hemisphere and bilateral fusiform gyri. Extinguished left faces increased activity in striate and extrastriate cortex, compared with right houses only. Critically, fearful faces activated the left amygdala and extrastriate cortex both when seen and when extinguished; as well as bilateral orbitofrontal and intact right superior parietal areas. Comparison of perceived versus extinguished faces revealed no difference in amygdala for fearful faces. Conscious perception increased activity in fusiform, parietal and prefrontal areas of the left-hemisphere, irrespective of emotional expression; while a differential emotional response to fearful faces occurring specifically with awareness was found in bilateral parietal, temporal, and frontal areas. These results demonstrate that amygdala and orbitofrontal cortex can be activated by emotional stimuli even without awareness after parietal damage; and that substantial unconscious residual processing can occur within spared brain areas well beyond visual cortex, despite neglect and extinction.

Aged↗

Valproic acid-induced hyperammonemia: a case report.

The authors present a case of a patient treated with valproic acid for seizure disorder who presented with acute mental status changes consistent with encephalopathy. Notably, her serum ammonia level was 3 times the upper limit of normal, despite an only mildly elevated aspartate aminotransferase and normal bilirubin. Her serum valproic acid level was in the therapeutic range. Her symptoms resolved with discontinuation of valproic acid and supportive care. The authors review the possible mechanisms of valproic acid-associated hyperammonemia with encephalopathy and propose clinical practice modifications to minimize the incidence of this adverse reaction to this generally well-tolerated and clinically important psychotropic medication.

Ammonia↗

[Neurologic complications of pagetic basilar impressions and their surgical treatment].

Paget's disease of the skull is the main cause of basilar artery syndromes in the adult. They may cause various neurological symptoms, including signs of ischemia of the spinal cord or medulla, or involvement of the cranial nerves and brain stem and, also, distant symptoms due to hydrocephalus, with various mental disorders including transient, recurrent, coma. The authors discuss 30 cases found in the world literature and 6 unreported personal cases, study the clinical symptoms of these cases of basilar artery compression due to Paget's disease, and the methods of neuro-radiological investigation, and emphasize the interest, in severe forms, of early surgical decompression before the stage of severe neurological complications. Regular supervision of patients with Pagets disease is thus essential to detect at an early stage, decompensation of basilar artery insufficiency in Paget's disease. In late forms, calcitonin may be indicated.

Aged↗

Dreamy states and psychoses in temporal lobe epilepsy: mediating role of affect.

Among 104 patients with temporal lobe epilepsy treated in our clinic between 1992-1995, thirteen patients with repeated dreamy states were evaluated for affective manifestations of dreamy states and their relationship with psychotic states. The types of dreamy states were classified as déjà vu, jamais vu and reminiscence. The affective experiences during dreamy states were evaluated as positive, negative or neutral. As a result, seven patients had déjà vu and/or reminiscence: seizure manifestations in four of these patients were affectively evaluated as positive (familiar and/or pleasurable), and three as neutral. Six cases had experience of jamais vu: five of them were affectively evaluated as negative (mostly fear), and one as neutral. Psychiatrically, only four patients with jamias vu accompanied by feelings of fear had mental disorders: a chronic paranoid-hallucinatory state in two cases, a chronic paranoid state in one case, and obsessive-compulsive symptoms in one case. Other patients who had positive or neutral affect did not demonstrate psychiatric disturbances. Thus, most patients with jamais vu were accompanied by negative affect of fear, and those patients with jamais vu tended to show more psychotic symptoms than those with reminiscence or déjà vu, which were associated with positive or neutral affects. Based on these results, we discuss the possibility that repeated negative feelings associated with jamais vu are one of the causes for developing epileptic psychoses.

Adult↗

Clinical and biological abnormalities in patients after fasciolosis treatment.

OBJECTIVE: The aim of this communication was to report clinical disorders and biological abnormalities in patients followed over a 3- to 18-year period after the last date of fasciolosis treatment. These observations were noted in 87 individuals (out of 711) during a 30-year epidemiological survey. RESULTS: We noted diffuse pain in the right hypochondrium, persisting 2 to 6 years after treatment (3.7% of persons), and weight loss appearing during treatment and persisting afterwards (2.1%). CONCLUSIONS: Our current state of knowledge leads us to asking whether pain in the right hypochondrium and weight loss would not be due to the presence of persistent hepatic lesions following fasciolosis treatment. Other investigations in patients after treated fasciolosis are necessary to confirm these abnormalities and determine their frequency.

Animals↗

Clinically significant drug interactions with cholinesterase inhibitors: a guide for neurologists.

Cholinesterase inhibitors are the only pharmacological class indicated for the treatment of mild to moderate Alzheimer's disease. These drugs are also being used off label to treat severe cases of Alzheimer's disease or vascular dementia and other disorders. The widespread use of cholinesterase inhibitors raises the possibility of their use in combination regimens, with the subsequent risk of deleterious drug-drug interactions in high-risk populations. The purpose of this review is to present the possible sources of pharmacokinetic or pharmacodynamic drug-drug interactions involving cholinesterase inhibitors. The four cholinesterase inhibitors (tacrine, donepezil, rivastigmine and galantamine) that are currently available have different pharmacological properties that expose patients to the risk of several types of drug interactions of nonequivalent clinical relevance. The principal proven clinically relevant drug interactions involve tacrine and drugs metabolised by the cytochrome P450 (CYP) 1A2 enzyme, as well as tacrine or donepezil and antipsychotics (which results in the appearance of parkinsonian symptoms). The bioavailability of galantamine is increased by coadministration with paroxetine, ketoconazole and erythromycin. It is of interest to note that because rivastigmine is metabolised by esterases rather than CYP enzymes, unlike the other cholinesterase inhibitors, it is unlikely to be involved in pharmacokinetic drug-drug interactions. Care must be taken to reduce the risk of inducing central (excitation, agitation) or peripheral (e.g. bradycardia, loss of consciousness, digestive disorders) hypercholinergic effects via drug interactions with cholinesterase inhibitors. A review of the literature does not reveal any alarming data but does highlight the need for prudent prescription, particularly when cholinesterase inhibitors are given in combination with psychotropics or antiarrhythmics. Possible interactions involving other often coprescribed antidementia agents (e.g. memantine, antioxidants, cognitive enhancers) remain an open area requiring particularly prudent use.

Cholinesterase Inhibitors↗

[Post-anoxic myoclonic encephalopathy (Lance-Adams syndrome): report of 6 cases].

Six patients are studied (five females and one male) in which disorders of consciousness varying from stupor to coma have occurred following variable periods of cerebral hypoxia caused either by cardiorespiratory standstill (five cases) or acute pulmonary injury. After a few hours they had generalized convulsive crisis of tonic-clonic type. As consciousness was regained they developed generalized myoclonic trembling of great intensity. Hence post-anoxic myoclonic encephalopathy is characterized. It is also called the Lance-Adams syndrome, in honor of the authors that described it in 1963. Five patients underwent electroencephalographic examination; the tracing showed typical myoclonus potentials in some, and characteristic diffuse brain injury in others. Electromyography was carried out in one patient, and cerebral computerized tomography in two others. The latter revealed an accentuated widening of sylvian cleft at the base in one them, specially on the right side, which explain his dementia-like picture. The biochemical analysis of the spinal fluid was normal in five cases.

Adult↗

Siriraj stroke score and validation study to distinguish supratentorial intracerebral haemorrhage from infarction.

OBJECTIVES: To develop a simple, reliable, and safe diagnostic tool for acute stroke syndromes in a setting where computerised brain scanning was not readily available and to validate its accuracy with regard to pathological types of stroke. DESIGN: 13 clinical variables that potentially might differentiate supratentorial cerebral haemorrhage from infarction were recorded and tested by multivariate analysis in a prospective study of 174 patients with acute stroke. In developing the Siriraj stroke score stepwise discriminant analysis of the variables was followed by a linear discriminant equation to differentiate between supratentorial haemorrhage and infarction. The score obtained was validated against scores in 206 other patients with stroke, computerised brain scans being used for definitive diagnosis. SETTING: Siriraj Hospital Medical School, Mahidol University, Bangkok. SUBJECTS: Prospective study: 174 consecutive patients with acute supratentorial stroke syndrome (not subarachnoid haemorrhage) admitted to Siriraj Hospital during 1984-5; validation study: 206 patients admitted to Siriraj Hospital or another hospital for supratentorial intracerebral haemorrhage or infarction. RESULTS: The Siriraj stroke score was developed and calculated as (2.5 x level of consciousness) + (2 x vomiting) + (2 x headache) + (0.1 x diastolic blood pressure) - (3 x atheroma markers) - 12. A score above 1 indicates supratentorial intracerebral haemorrhage, while a score below -1 indicates infarction. The score between 1 and -1 represents an equivocal result needing a computerised brain scan or probability curve to verify the diagnosis. In the validation study of the Siriraj stroke score the diagnostic sensitivities of the score for cerebral haemorrhage and cerebral infarction were 89.3% and 93.2% respectively, with an overall predictive accuracy of 90.3%. CONCLUSION: The Siriraj stroke score is widely accepted and applied in hospitals throughout Thailand as a simple and reliable bedside method for diagnosing acute stroke.

Acute Disease↗

[Clinico-pathogenetic features of cerebral cysticercosis accompanied by mental disorders].

On the basis of a study of 32 cases of brain cysticerrcosis with mental disturbances the author proposes a classification of these disorders. The classification provides an assessment of the stages in the development of the disease, the localization of the morbid process, the type ot development and the symptomatology of the disease. The authors distinguish the following stages of the morbid process: the penetration of the parasite (lasting 3-4 months); an exotoxicosis (excretion into the brain products of metabolism, lasting for 5-10 years); an exotoxicosis (excretion into the brain products of desintegration of the dying parasite, ensues after 5-10 years); residual. The clinical types of development according to the author are the following: primary-hypertoxic rapidly leading to a lethal outcome; progressive-remittent; chronic-progressive. The highest lethality falls on the 1st decade of the diseases.

Adolescent↗

The prognostic value of blood glucose in patients with acute stroke.

We prospectively studied levels of blood glucose and glycohemoglobin, and their correlations with types, severity, and prognosis of stroke in 37 patients with brain infarction (BI) and 35 patients with brain hemorrhage (BH). We found that in the BH group, patients with an elevated glucose level due to stress, diabetes, or both, had a lower consciousness level on admission, larger hematoma size, higher incidence of rupture into the ventricles, and a worse 1-month outcome than patients with a normal glucose level (p less than 0.05). In patients with BI, however, no significant difference was found as related to levels of glucose, though a difference in 6-month mortality between stress hyperglycemic and normoglycemic patients (p less than 0.05) was found. We conclude that an elevated glucose level is associated with a worse clinical condition, larger hematoma size, higher incidence of rupture into the ventricles, and worse outcome in patients with BH. However, it seems to be the severity of the stroke, not the hyperglycemia, that causes the poor outcome. Hyperglycemia may be an epiphenomenon of stroke severity.

Aged↗

Two aspects of impaired consciousness in Alzheimer's disease.

Alzheimer's disease (AD) is a degenerative dementia characterized by different aspects of impaired consciousness. For example, there is a deficit of controlled processes that require conscious processing of information. Such an impairment is indexed by decreased performances at controlled cognitive tasks, and it is related to reduced brain metabolic activity in a network of frontal, posterior associative, and limbic regions. Another aspect of impaired consciousness is that AD patients show variable levels of anosognosia concerning their cognitive deficits. A discrepancy score between patient's and caregiver's assessment of cognitive functions is one of the most frequently used measures of anosognosia. A high discrepancy score has been related to impaired activity in the superior frontal sulcus and the parietal cortex in AD. Anosognosia for cognitive deficits in AD could be partly explained by impaired metabolism in parts of networks subserving self-referential processes (e.g., the superior frontal sulcus) and perspective-taking (e.g., the temporoparietal junction). We hypothesize that these patients are impaired in the ability to see themselves with a third-person perspective (i.e., being able to see themselves as other people see them).

Agnosia↗

[Analysis of specificity of resected esophageal cancer patients with a history of apoplexy].

We studied 15 resected cases with a history of apoplexy (2.5%) among 599 cases of esophageal cancer admitted between 1972 and 1993. Fourteen were male, and female, aged 48 to 77 years. Twelve had suffered from cerebral infarction, 2 intracerebral hemorrhage, and one subarachnoid hemorrhage. Duration from apoplexy to operation was between 2 months and 19 years in the cerebral infarction cases, between 8 and 10 years in the intracerebral hemorrhage cases and 4 years in the subarachnoid hemorrhage case. Preoperative neurological disturbance was found in 7 of the 12 cerebral infarction cases, and in both intracerebral hemorrhage cases. Four cases showed hemiplegia, and the other 5 cases showed partial paralysis of limbs. Preoperative complications were found in 7 of the 15 cases, and consisted of diabetes mellitus in 5, hypertension in 4, bronchial asthma in one, and renal dysfunction in one case. Intra- and postoperative complications were found in 11 of the 15 cases, and consisted of anastomotic leakage in 5, delirium in 3, apoplexy in 2, peritonitis in one, ARDS in one, intraoperative cardiac arrest in one, and wound infection in one. Postoperative disorders of consciousness were found in 5 cases, consisting of delirium in 3, and excitation at awakening of anethesia in 2 cases. Rate of direct operative death was 6.7% in preoperative apoplectic patients, and 8.5% in non-apoplectic patients, and there was no significant difference between the 2 groups. On the other hand, rate of postoperative apoplexy was 13.3% in the preoperative apoplectic patients, and 0.4% in non-apoplectic patients. There was a significant difference between them (p < 0.01). But they were cured of it, and left our hospital. It is concluded that active surgical treatment can be indicated for esophageal cancer patients with a history of apoplexy, if more attention is given to the management of diabetes mellitus or hypertension.

Aged↗

Response of idiopathic hypereosinophilic syndrome to treatment with imatinib mesylate.

Idiopathic hypereosinophilic syndrome (HES) is a rare hematologic disorder characterized by persistent eosinophilia with organ involvement. Patients with HES have a poor prognosis, but the disease course can be heterogeneous. Treatment of HES has included corticosteroids, chemotherapeutic agents such as cyclophosphamide, vincristine, hydroxyrea, and most recently interferon-alpha (IFN-alpha) which has shown long-term beneficial effects. We herein report on a patient with HES who had disease resistant to steroids, and chemotherapy with 2-chlorodeoxyadenosine and cytarabine, but who had a significant response after only 8 days of treatment with imatinib mesylate 100mg daily. The possible mechanism of response is discussed. This observation may lead to a better understanding of the pathophysiology of HES, and may provide a new form of effective therapy for the disease.

Alkylating Agents↗