Antidepressant withdrawal syndromes: phenomenology and pathophysiology

The literature reporting signs and symptoms produced by the abrupt or gradual withdrawal of antidepressants is reviewed. Patients with antidepressant withdrawal syndromes are presented and principles governing their care are highlighted. Finally, the author summarizes evidence that antidepressant-induced supersensitivity of central and peripheral muscarinic cholinergic mechanisms may account for commonly observed antidepressant withdrawal phenomena.     

Acute coronary syndromes. The diagnostic role of troponins

Acute coronary syndromes (ACSs) represent the acute life-threatening phases of coronary heart disease. Clinical symptoms, EKG, and CK-MB measurements are frequently insufficient to evaluate patients without persisting ST elevations. Serial determinations of troponin T or troponin I after arrival in hospital disclose minor myocardial injury in patients presenting as unstable angina. This finding allows the currently best risk stratification and may contribute to cost-effectiveness. Without elevated troponins the risk for death or myocardial infarction during 30 days follow-up is not more than 1%. The lack of elevated troponins does not implicate that these patients do not have coronary artery disease. Patients with positive evidence of troponins represent a high-risk group who should be hospitalized and further evaluated, because the risk for myocardial infarction and death in 30 days is approximately 20%. Current studies indicate that early revascularization under glycoprotein IIb/IIIa antagonists represent the optimal treatment.     

Complex regional pain syndromes: new aspects on pathophysiology and therapy

Complex-regional pain syndromes (CRPS), formerly known as Sudeck's dystrophy and causalgia, belong to the neuropathic pain syndromes. CRPS may develop following fractures, limb trauma or lesions of the peripheral or central (CNS) nervous system. Occasionally, CRPS may also develop spontaneously. The clinical picture comprises a characteristic clinical triade of symptoms including autonomic (disturbances of skin temperature, colour, presence of sweating abnormalities), sensory (pain and hyperalgesia) and motor (paresis, tremor, dystonia) disturbances. Diagnosis is mainly based on clinical signs. However, additional laboratory, neurophysiological and radiological examinations may help to corroborate correct diagnosis. Several pathophysiological concepts have been proposed to explain the complex symptoms of CRPS: 1, facilitated neurogenic inflammation; 2, pathological sympatho-afferent coupling; 3, neuroplastic changes within the CNS. Furthermore, there is accumulating evidence that genetic factors may predispose for CRPS. Therapy is based on a multidisciplinary approach. Non-pharmacological approaches include physiotherapy and occupational therapy. Pharmacotherapy is based on individual symptoms and includes steroids, free radical scavengers, treatment of neuropathic pain, and finally agents interfering with bone metabolism (calcitonin, biphosphonates). Sympathetic blocks are useful for the treatment of sympathetically maintained pain. Invasive therapeutic concepts include implantation of spinal cord stimulators. This review covers new aspects of pathophysiology and therapy of CRPS.     

Acute depressed mood as a trigger of acute coronary syndromes.

BACKGROUND: Some cases of acute coronary syndrome (ACS) may be triggered by emotional states such as anger, but it is not known if acute depressed mood can act as a trigger. METHODS: 295 men and women with a verified ACS were studied. Depressed mood in the two hours before ACS symptom onset was compared with the same period 24 hours earlier (pair-matched analysis), and with usual levels of depressed mood, using case-crossover methods. RESULTS: 46 (18.2%) patients experienced depressed mood in the two hours before ACS onset. The odds of ACS following depressed mood were 2.50 (95% confidence intervals 1.05 to 6.56) in the pair-matched analysis, while the relative risk of ACS onset following depressed mood was 4.33 (95% confidence intervals 3.39 to 6.11) compared with usual levels of depressed mood. Depressed mood preceding ACS onset was more common in lower income patients (p = .032), and was associated with recent life stress, but was not related to psychiatric status. CONCLUSIONS: Acute depressed mood may elicit biological responses that contribute to ACS, including vascular endothelial dysfunction, inflammatory cytokine release and platelet activation. Acute depressed mood may trigger potentially life-threatening cardiac events.     

Acute hypertension in intracerebral hemorrhage: pathophysiology and treatment

Non-traumatic or spontaneous intracerebral hemorrhage (ICH) is defined as intra-parenchymal bleeding with or without extension into the ventricles and rarely into the subarachoid space. Primary ICH in most cases is associated with chronic hypertension. Acute hypertension is associated with hematoma expansion, and poor neurological outcome. The treatment of hypertension in acute ICH is a topic of controversy. Experiments have shown an area of ischemia around the hematoma, with the reduction of regional cerebral blood flow (CBF) secondary to compression of microvasculature. Not all scientific results agree with the above findings. Recent studies have shown that CBF decreases in the perihematoma region but with concomitant reduction of cerebral metabolism, which would argue against an area of ischemia in the perihematoma region. Based on the above result, there have been several clinical trials looking at clinical outcome and decrease in hematoma expansion rates with reduction of blood pressure acutely after ICH. The parameters for the blood pressure control are still under investigation. The American Heart Association has put forward guidelines for blood pressure control which have been adopted in the centers around the country. We have described the protocol we use at our center for the blood pressure control in patients with acute ICH.     

Acute coronary syndromes do not promote prolonged in vivo FXII-dependent prothrombotic activity

BACKGROUND: Coagulation FXII is activated on contact with lipoprotein particles. It has been suggested that contact with subendothelial tissue provides an alternative biological surface for FXII activation. Our aim was to investigate whether activated FXII (FXIIa) is elevated in patients with coronary atherosclerosis, and whether disease status (acute phase or stable state) affects circulating levels of FXIIa. METHODS: Circulating FXIIa levels were measured in the peripheral blood of 122 patients with coronary atherosclerosis (32, stable angina; 54, unstable angina; 36, nQ myocardial infarction) and in 45 age-matched subjects (Contr). RESULTS: FXIIa levels (median, first and third quartiles; ng/ml) were higher in patients than in Contr: 1.61 (1.26-2.02) vs. 1.34 (1.13-1.81) (p<0.01). FXIIa levels were similar among patients with stable angina [1.66 (1.23-1.91)], unstable angina [1.53 (1.21-2.04)], and nQ myocardial infarction [1.75 (1.34-2.03)]. The three groups of patients had similar prevalence for most atherothrombotic risk factors; patients with stable angina had an increased severity of coronary disease, which did not explain the different levels of FXIIa. Fasting levels of triglycerides were the best predictor of FXIIa levels in our patients. CONCLUSIONS: The finding of similar FXIIa levels among patients in either acute or chronic phases of coronary atherosclerosis suggests that the initial arterial denudation and the acute-phase response associated to acute coronary syndromes are not major determinants for prolonged FXII activation.     

Molecular pathophysiology of schizophrenia and preventive strategy in pubertal period

A novel frameshift mutation in glyoxalase 1 (GLO1) gene was detected in a patient with schizophrenia of a pedigree with multiple affected individuals. The patient carrying the mutation showed decreased enzymatic activity by 50%, 3.7 times high level of advanced glycation end products (AGEs) that is substrate of GLO1 and 20% of serum vitamin B6 compared to controls. Case-control study of GLO1 gene suggested that Ala allele of Glu111Ala was associated with schizophrenia. In vitro study using COS-7 cells transfected with cDNA of GLO1 yielded that enzymatic activity is lower in GLO1 with Ala111 than that of Glu111. The homozygotes of Ala111 showed 16% decreased GLO1 activities in RBC as compared with that of Glu111/Ala111 and Glu111/Glu111. Plasma AGEs levels were significantly high and serum vitamin B6 was significantly low in 45 schizophrenics than that of 61 control subjects. Supplementation of vitamin B6 to cases with the genetic defect of GLO1 before onset of psychosis is suggested to be possible strategy for prevention of schizophrenia until pubertal stage since such mutation carriers could have been exposed by high level of AGEs for a long time before disease onset.     

Acute brain syndromes.

Four hundred and nine cases of acute brain syndrome, encountered in psychiatric consultations among 54,942 general hospital patients over a 5 year period, fell into 4 groups according to symptom picture: lethargic, bewildered, agitated and psychotic. Treatment included reality orientation, protection and pharamacologic measures.     

Acute intraoperative brain herniation during elective neurosurgery: pathophysiology and management considerations.

OBJECTIVES: To describe operative procedures, pathophysiological events, management strategies, and clinical outcomes after acute intraoperative brain herniation during elective neurosurgery. METHODS: Review of clinical diagnoses, operative events, postoperative CT findings, intracranial pressure, and arterial blood pressure changes and outcomes in a series of patients in whom elective neurosurgery had to be abandoned because of severe brain herniation. RESULTS: Acute intraoperative brain herniation occurred in seven patients. In each patient subarachnoid or intraventricular haemorrhage preceded the brain herniation. The haemorrhage occurred after intraoperative aneurysm rupture either before arachnoidal dissection (three) or during clip placement (one); after resection of 70% of a recurrent hemispheric astroblastoma; after resection of a pineal tumour; and after a stereotactic biopsy of an AIDS lesion. In all patients the procedure was abandoned because of loss of access to the intracranial operating site, medical measures to control intracranial pressure undertaken (intravenous thiopentone), an intraventricular catheter or Camino intracranial pressure monitor inserted, and CT performed immediately after scalp closure. The patients were transferred to an intensive care unit for elective ventilation and multimodality physiological monitoring. Using this strategy all patients recovered from the acute ictus and no patient had intracranial pressure > 35 mm Hg. Although one patient with an aneurysm rebled and died three days later the other six patients did well considering the dramatic and apparently catastrophic nature of the open brain herniation. CONCLUSIONS: There are fundamental differences in the pathophysiological mechanisms, neuroradiological findings, and outcomes between open brain herniation occurring in post-traumatic and elective neurosurgical patients. The surprisingly good outcomes in this series may have occurred because the intraoperative brain herniation was secondary to extra-axial subarachnoid or intraventricular haemorrhage rather than intraparenchymal haemorrhage or acute brain oedema. Expeditious abandonment of the procedure and closure of the cranium may also have contributed to the often very satisfactory clinical outcome.     

Acute and chronic pain syndromes in multiple sclerosis

A representative sample of 117 patients with definite multiple sclerosis (MS) was interviewed on pain syndromes. Chronic syndromes lasting more than one month included dysaestesthesia, low back pain, spasms, tonic seizures, tightening and painful sensations in the extremities. Acute syndromes included neuralgia, L'Hermitte's sign and pain associated with optic neuritis. Thirty-five per cent were pain-free. Of the remaining patients had 45% pain at the time of the examination, 32% indicated pain among the most severe symptoms of MS and 23% had pain at the onset of MS. The number of patients with pain at the time of the examination increased with age and duration of disease. Patients with pain were significantly more often spastic and significantly more often sought alternative treatment forms. No difference was found for mean age, sex, physical impairment, duration of disease from onset of MS, depressive score and score of delayed verbal memory.     

Lobar cerebral hemorrhages: Acute clinical syndromes in 26 cases

The acute syndromes and CT findings are described in 26 cases of spontaneous cerebral hemorrhage. Occipital hemorrhage (11 cases) caused severe pain around the ipsilateral eye and dense hemianopia. Left temporal hemorrhage (7 cases) began with mild pain in or just anterior to the ear, fluent dysphasia with poor auditory comprehension but relatively good repetition, and a visual deficit subtending less than a hemianopia. Frontal hemorrhage (4 cases) caused a distinctive syndrome beginning with severe contralateral arm weakness, minimal leg and face weakness, and frontal headache. Parietal hemorrhage (3 cases) began with anterior temporal (“temple”) headache and hemisensory deficit, sometimes involving the trunk to the midline. One patient had a right temporal hemorrhage. Spontaneous lobar hemorrhage and branch artery embolism in the same region produce similar clinical syndromes. Headache is a first and prominent symptom. A rapid but not instantaneous onset over several minutes, when combined with one of the typical syndromes, suggests lobar hemorrhage rather than other types of stroke. Ancillary investigations (including CT scanning, angiography in 11 patients, and autopsy in 4) disclosed 2 patients with bleeding diatheses due to warfarin, 2 with arteriovenous malformations, and 1 with metastatic tumor. Only 8 of the 26 patients had chronic hypertension (blood pressure greater than 130/85 mm Hg), suggesting that hypertension is not an etiological factor in most lobar hemorrhages.     

Insights into the pathophysiology of psychomotor regression in CSWS syndromes from FDG-PET and EEG-fMRI

Epilepsy syndromes with continuous spikes-and-waves during slow sleep (CSWS) are age-related epileptic encephalopathies characterized by the development of various types of psychomotor regression in close temporal concordance with the appearance of the electroencephalography (EEG) pattern of CSWS. Functional cerebral imaging studies performed in children with CSWS have shown evidence for the existence of increase in metabolism or perfusion at the site of the epileptic focus, associated with decrease in metabolism or perfusion in distant and connected brain areas. Longitudinal [18F]-fluorodeoxyglucose–positron emission tomography (FDG-PET) studies and effective connectivity analyses have suggested the existence of a pathophysiologic link between increases and decreases in metabolism/perfusion that could be explained by the theory of remote inhibition. These findings highlight that the psychomotor regression observed in CSWS syndromes is not only related to the neurophysiologic impairment at the site of the epileptic foci but also to epilepsy-induced neurophysiologic changes in distant connected brain areas.     

Acute extrapyramidal syndromes in neuroleptic-treated elders: a pilot study.

The incidence, morbidity, and risk factors for acute extrapyramidal syndromes (EPS) such as akathisia and drug-induced parkinsonism (DIP) in neuroleptic-treated elders have not been systematically explored. This study presents data on 17 elderly patients who were prospectively examined for up to 4 weeks for acute EPS, functional and cognitive status, and behavioral disturbances. Seventy-one percent of subjects developed DIP, and 18% developed akathisia. Predictors of DIP included pre-neuroleptic treatment parkinsonian signs and neuroleptic dose, despite use of low doses of neuroleptics. Development of acute EPS was associated with failure to improve behaviorally. New-onset urinary incontinence was the most common functional abnormality.     

Sleep patterns in patients with acute coronary syndromes

BackgroundLittle is known about sleep quality in patients with acute coronary syndromes (ACS) admitted to the coronary care unit (CCU). The aim of this study was to assess nocturnal sleep in these patients, away from the CCU environment, and to evaluate potential connections with the disease process.MethodsTwenty-two patients with first ever ACS, who were not on sedation or inotropes, underwent a full-night polysomnography (PSG) in our sleep disorders unit within 3 days of the ACS and follow-up PSGs 1 and 6 months later.ResultsPSG parameters showed a progressive improvement over the study period. There was a statistically significant increase in total sleep time (TST), sleep efficiency, slow wave sleep (SWS), and rapid eye movement (REM) sleep, while arousal index, wake after sleep onset (WASO) and sleep latency decreased. Six months after the acute event, sleep architecture was within the normal range.ConclusionsPatients with ACS have marked alterations in sleep macro- and micro-architecture, which have a negative influence on sleep quality. The changes tend to disappear over time, suggesting a relationship with the acute phase of the underlying disease.