The "Sisi syndrome": a new form of depression?

A new depressive entity called the "Sisi syndrome," named in reference to the former empress of Austria, was introduced by a drug company in 1998. Their advertising campaign presents information about nosology, symptoms, and recommended therapy. We review the relevant literature about this syndrome and are not able to confirm the statements about it. The lack of scientific proof of it as an independent entity of depression stands in contrast to the widespread media coverage in Germany, which was organized by a public relations company. Therefore, we discuss new kinds of marketing strategies ("disease mongering") by drug companies and conclude with some preventive recommendations.     

The first assessment of soluble CD146 in women with unexplained pregnancy loss. A new insight?

The mechanisms responsible for pregnancy loss have not all been elucidated. CD146 is a cell adhesion molecule involved in the control of both endothelium integrity and intermediate trophoblast invasiveness, two potential key features in the pathogenesis of pregnancy loss. As CD146 is detectable as a soluble form in the plasma (sCD146), we investigated sCD146 plasma levels in women with a history of pregnancy loss. We conducted a paired case-control study to compare sCD146 plasma levels in 100 women with unexplained pregnancy losses (2 or more consecutive losses at or before 21 weeks of gestation, or at least one later loss) and in 100 age-matched control women (no pregnancy loss and at least one living child). The sCD146 concentrations were determined at least 2 months after the last obstetrical event. Patients and controls were comparable regarding thrombophilia. Among the patients, 83 women experienced early pregnancy losses (average of 3 losses, mean gestation of 6.6 weeks) and 22 women suffered at least one late pregnancy loss. We found significantly higher sCD146 plasma levels in the 100 patients compared to age matched control women (p < 0.001). The sCD146 plasma levels did not correlate with the number of pregnancy losses nor with the mean gestation time. Alterations in sCD 146 plasma levels could be related to endothelial dysfunction associated to defective endovascular trophoblast invasiveness. Additional studies should explore whether sCD146 assessment could provide diagnostic and prognostic information with a view to screening and thus managing women with unexplained pregnancy loss.     

Autism with facial port-wine stain: a new syndrome?

The hallmark of Sturge-Weber syndrome is leptomeningeal angiomatosis. Over 15 years, four children were identified (2 boys, age 2.9-6 years) with unilateral facial port-wine stain, referred for presumable Sturge-Weber syndrome but who were also autistic. Computed tomography and magnetic resonance imaging scans failed to show evidence of leptomeningeal angioma in all four children. Three of the children had a history of seizures. Detailed neuropsychologic testing of three children revealed a similar presentation, characterized by developmental disturbance, particularly involving delayed onset of language, and early-emerging social atypicality. Positron emission tomography scanning of cerebral glucose metabolism revealed hypometabolism in the bilateral medial temporal regions, anterior cingulate gyrus, frontal cortex, right temporal cortex, and cerebellum. The pattern of glucose hypometabolism differed from that of 12 children with infantile autism (age 2.7-7.9 years) who had mild left medial temporal but more severe right temporal cortical hypometabolism and showed a reversal of normal frontotemporal asymmetry of glucose metabolism. Unilateral facial port-wine stain and autism with no intracranial angioma on conventional imaging may represent a rare clinical entity distinct from both infantile autism and previously described variants of Sturge-Weber syndrome.     

Living with dementia from the perspective of older people: Is it a positive story?

Dementia, even at an early stage, may pose problems and challenge one's quality of life. Having accurate knowledge of what one experiences when living with dementia is important for developing proactive care for individuals with dementia and their families. The aim of our Grounded Theory study was to explore what it means for elderly people to live with early-stage dementia. We interviewed 20 elderly people with probable mild dementia and their family members. Living with dementia was often presented as a positive narrative, one that told of only minor problems and which stressed abilities and contentment with life. Being valued, rather than losing one's cognition or identity was central in their experience. More in-depth analyses of participants' narratives revealed, however, that they were constantly balancing their feelings of value and worthlessness, struggling to remain someone of value. This struggle was prompted by threats posed by dementia and by the persons' interactions with others. Superficially, a positive narrative may be understood as a lack of awareness or as denial due to cognitive loss. Our findings suggest, however, that we should look beyond this superficial view and seek to understand the narrative as an expression of one's attempt to counterbalance devaluation.     

The first line of therapy in a girl with juvenile myoclonic epilepsy: Should it be valproate or a new agent?

Juvenile myoclonic epilepsy is a common idiopathic generalized epileptic syndrome that includes generalized myoclonic seizures and commonly generalized tonic–clonic and generalized absence seizures. Before the emergence of the newer antiepileptic drugs (AEDs) in the 1990s, valproate was the usual first-line treatment in both men and women. However, the frequent adverse effect of weight gain and the risk of teratogenicity have resulted in a search for alternative first-line therapies in women. Four new AEDs— lamotrigine, topiramate, levetiracetam, and zonisamide—have been used as monotherapy or adjunctive therapy for juvenile myoclonic epilepsy in small patient series. Because they are not associated with weight gain and because they may have less risk of teratogenicity than valproate, they have been proposed as alternative first-line agents in women who have childbearing potential. However, the new AEDs may not be effective for all the seizure types of juvenile myoclonic epilepsy, and valproate appeared overall more effective in a large comparative trial in idiopathic generalized epilepsy. In addition, valproate is often effective at lower doses that have less teratogenicity, and an extended-release preparation may be less likely to produce weight gain. The current review presents evidence and arguments supporting the use of a new AED and those supporting the use of valproate as the first-line treatment in a girl with newly diagnosed juvenile myoclonic epilepsy. The review then concludes with a compromise approach.     

The benzodiazepine site of the GABAA receptor: an old target with new potential?

The gamma-aminobutyric acid-A (GABA(A)) receptors is the target for the most widely prescribed sleep medicines. It is a ligand-gated ion channel, activated by the amino acid neurotransmitter GABA, which normally results in hyperpolarization of neurons leading to reduced action potential firing, and thereby a reduction in neuronal activity. It has a rich pharmacology with a number of separate modulator binding sites. The best studied of these is the benzodiazepine site. Modulation of GABA(A) receptor activity by benzodiazepines produces sedative, hypnotic, anxiolytic and anticonvulsant activities. Short half-life benzodiazepines such as triazolam have been particularly useful in treating insomnia, but concerns have been raised regarding tolerance potential and dependence liability of classical benzodiazepines, which has led to reduced prescribing of these agents. In recent years, the treatment of sleep disorders has moved towards the use of non-benzodiazepine sedative hypnotics. These agents act at the same site on the GABA(A) receptor, but feature less of the problems associated with classical benzodiazepines. Recent progress in our understanding of the diversity and pharmacology of GABA(A) receptor subtypes has provided a rational explanation for the efficacy of these compounds. Findings from preclinical studies reveal promising avenues for the design of better therapeutics in the near future.     

Diffuse pachygyria with cerebellar hypoplasia: a milder form of microlissencephaly or a new genetic syndrome?

We report on 2 families with diffuse pachygyria and cerebellar hypoplasia, who presented hypotonia, ataxia, seizures, and developmental delay since infancy. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed decreased gyral formation in the cerebral cortex and marked hypoplasia in the cerebellum. Cerebellar hypoplasia is often associated with type 2 lissencephaly; however, our cases showed no polymicrogyria, and their clinical findings were quite mild compared with those of microlissencephaly. Their characteristic phenotype suggested a new genetic syndrome, which was possibly inherited as an autosomal recessive trait.     

Afebrile benign convulsions with mild gastroenteritis: a new entity?

Afebrile seizures in children usually necessitate investigations in order to determine the etiology and estimate the prognosis. Recently, convulsions that are described as benign but afebrile have been documented in children, in association with diarrhea, and are now recognized as a distinct entity. Benign afebrile seizures with mild gastroenteritis are defined as convulsions accompanying symptoms of mild diarrhea without dehydration or electrolyte derangement and without fever before and after the seizures in healthy children without meningitis, encephalitis or encephalopathy. The convulsions are short, symmetrical, generalized tonic–clonic seizures, occurring in clusters. Laboratory studies (full blood count, blood glucose, creatinine, serum electrolytes, cerebrospinal fluid, bacterial and viral cultures) are usually normal, and other investigations (neuroimaging and electroencephalogram) are not necessary. Prognosis is always favorable (normal psychomotor development, no recurrences of seizures), and anticonvulsant therapy is not warranted. Recognition of this benign infantile convulsion avoids extensive evaluation and long‐term anticonvulsant therapy; physicians may reassure the parents regarding the lack of long‐term sequelae. In conclusion, this type of seizure seems to be a new entity, but it awaits a correct place in the large group of infantile convulsion disorders.     

Novel anticonvulsants: a new generation of mood stabilizers?

Accumulating evidence suggests that at least some novel anticonvulsants may have mood-stabilizing properties. This paper reviews the literature for empirical studies of this topic. Lamotrigine has the most evidence in favor of its efficacy, with two double-blind studies in which it was more efficacious than placebo in the treatment of bipolar depression. However, it is associated with a 1/1000 risk of potentially fatal Stevens-Johnson syndrome. Gabapentin, although safe and well-tolerated, has been found in two double-blind studies not to be efficacious in treatment-refractory mania or refractory bipolar depression. Topiramate is currently supported only by naturalistic evidence of mild to moderate mood-stabilizing efficacy, but it has the advantage of often producing weight loss. Based on these data, lamotrigine may be effective, in monotherapy or as an adjunct, for treating depression in type I bipolar disorder, but suggestions regarding gabapentin and topiramate await further efficacy data. Most of the current findings derive from small, non-double-blind studies, and further research is required before clinicians can consider any of these agents to be mood stabilizers.     

Recurrent optic neuromyelitis with endocrinopathies: a new syndrome or just a coincidence?

The spectrum of optic neuromyelitis (ONM) ranges from monophasic or recurrent idiopathic forms of the disease, to ONM associated with autoimmune disorders. A distinct form of the disease, called recurrent ONM with endocrinopathies, characterized by spinal cord involvement (cavitations with syringomyeloid sensory disturbance), rapid evolution to blindness and paraplegia, characteristic cerebrospinal fluid (CSF) findings, and association with hypothalamus-pituitary dysfunction, has recently been described. The first case of ONM with endocrinopathies in a female Caucasian from Europe is presented, supporting the existence of this syndrome as a separate entity.     

The role of alpha-synuclein in neurodegenerative diseases: a potential target for new treatment strategies?

Alpha-synuclein (AS) is the main constituent of Lewy bodies. There is an ongoing discussion if overexpression is already dangerous, or if toxicity is subjected to oligomers, protofibrils or mature aggregates. The facts that the central hydrophobic part of AS is also a constituent of amyloid plaques in Alzheimer's disease (AD) and that a majority of patients have Lewy bodies and Lewy neurites in specific brain areas raised our interest in the contribution of AS to AD pathogenesis. The N-terminal amino acid sequence 1-15 of beta-synuclein (BS) seems to be a natural antiaggregation factor for AS. We synthesized a library with different sequence variations. Several of these peptides displayed neuroprotective activity in tissue culture models of neurodegeneration induced by oxidative stress or beta-amyloid 1-42. In spite of the fact that these peptides have a short half-life, a significant in vivo reduction in brain plaque load and improvement of behavior was demonstrated in amyloid precursor protein transgenic mice after intranasal treatment for 2 months. KEGV, the shortest sequence, was also active after intraperitoneal application. The in vitro effects cannot be explained by the antiaggregatory potential, but most likely by interaction of BS derivates with antiapoptotic PI3/Akt or antioxidative pathways. The possibility that BS-derived peptidomimetics act as neuroprotectants and prevent protein misfolding suggests therapeutic usefulness.     

Enhancing recovery after stroke with noradrenergic pharmacotherapy: a new frontier?

Despite much progress in stroke prevention and acute intervention, recovery and rehabilitation have traditionally received relatively little scientific attention. There is now increasing interest in the development of stroke recovery drugs and innovative rehabilitation techniques to promote functional recovery after completed stroke. Experimental work over the past two decades indicates that pharmacologic intervention to enhance recovery may be possible in the subacute stage, days to weeks poststroke, after irreversible injury has occurred. This paper discusses the concept of "rehabilitation pharmacology" and reviews the growing literature from animal studies and pilot clinical trials on noradrenergic pharmacotherapy, a new experimental strategy in stroke rehabilitation. Amphetamine, a monoamine agonist that increases brain norepinephrine levels, is the most extensively studied drug shown to promote recovery of function in animal models of focal brain injury. Further research is needed to investigate the mechanisms and clinical efficacy of amphetamine and other novel therapeutic interventions on the recovery process.