Metabolic risks in older adults receiving second-generation antipsychotic medication

Metabolic syndrome is prevalent in older adults and increases the risk of cardiovascular disease. Second-generation antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone) increase the risk of metabolic syndrome and present many challenges for psychiatrists. In this article, we review the relationships between second-generation antipsychotics and metabolic syndrome with a focus on older adults. Because few studies focus exclusively on older adults, we augment this review with relevant findings from younger adults. The differential risk factors of each medication are reviewed, as are recent findings in monitoring and treating metabolic syndrome. Olanzapine and clozapine are more strongly associated with metabolic risks, whereas aripiprazole and ziprasidone are less associated. Although lifestyle modifications can help to reduce some aspects of metabolic syndrome, lifestyle modifications in conjunction with metformin therapy appear to be most effective.     

Orbitofrontal syndrome in psychiatry

Orbitofrontal syndrome is a variant of frontal lobe syndrome in which behavioural disturbances are prevailing. It results from bilateral lesions of the orbitofrontal cortex and the medial face of frontal lobe. Patients present disorganized hyperactivity. They are distractable, impulsive, euphoric and unable to abide by social rules. They often have instinctive disinhibition (hypersexuality, hyperphagia and urinary behaviour disorders). In spite of severe behavioural disturbances cognitive functions are often intact so that orbitofrontal syndrome may be confounded with two psychiatric disorders: mania (or hypomania) and antisocial personality disorder. In this article we present a case report of orbitofrontal syndrome which was initially misdiagnosed as mania. Clinical features and possible modes of presentation of this syndrome are discussed. It is suggested that serotonin reuptake inhibitors may be of some use in this disorder.     

Thyroid function in Down syndrome.

The thyroid function of 181 patients with Down syndrome was investigated. When compared with a control group of 163 children we found T4 and FT4 levels to be significantly lower and T3 and TSH levels to be significantly higher in the Down syndrome population. Of the 181 patients with Down syndrome, 29 (16%) showed evidence of either uncompensated or compensated hypothyroidism: 11 (6%) had both low T4 and high TSH levels, 14 (8%) had only high TSH values, and 4 (2%) had only low T4 values. One of the patients with Down syndrome had a significantly elevated T4 level. Studying different age groups, we observed a decline of the mean T4, FT4, T3, FT3, and TBG values with advancing age. T4, T3, and TSH blood levels obtained in 1988 were slightly but not significantly lower when compared with values from 1985. Because thyroid dysfunctions in patients with Down syndrome are more common than in the general population, periodic thyroid hormone function tests should be performed in persons with Down syndrome in particular as they advance in age. Thus, individuals with significantly abnormal results can be identified early before clinical symptoms become manifest. If patients with Down syndrome are found to have a thyroid hormone disorder, appropriate treatment should be forthcoming, which in turn will enhance their quality of life.     

Tigroid pattern on magnetic resonance imaging in Lowe syndrome

Lowe (oculocerebrorenal) syndrome is an X-linked recessive disorder characterised by congenital cataract, glaucoma, cognitive developmental delay and renal tubular Fanconi syndrome. In this report we present a patient with Lowe syndrome with a tigroid pattern on cranial MRI, which has not been previously reported as an imaging feature of this syndrome.     

Sympathetic skin response in premenstrual syndrome

Abstract Premenstrual syndrome is a term which includes a broad group of emotional, behavioral and physical symptoms that occur for several days before menses and subside following the menstrual period. Many women experience premenstrual syndrome symptoms, particularly physical ones such as breast tenderness and swelling. Approximately 5–10% women suffer from severe premenstrual syndrome and another 30–40% have moderate symptoms. Premenstrual syndrome continues to be an unsolved problem.In this study, we evaluated 24 premenstrual syndrome patients and 20 healthy women in the control group. The ages of the women were 22–34 years (mean ± SD: 25±3) for the premenstrual syndrome group and 23–34 (25±3) for the control group. The sympathetic skin response was recorded from the palms, soles and genital regions by using electrical stimuli to the median nerve at the wrist.The sympathetic skin response was recorded twice, in the follicular and late luteal phases of menstruation.The follicular and late luteal phase sympathetic skin response of the two groups were compared. The amplitudes and latency values of the late luteal and follicular phase sympathetic skin response from the premenstrual syndrome group and control group women were statistically similar. We also did not find any latency or amplitude difference in the sympathetic skin response obtained from the three regions of the premenstrual syndrome patients and the control group.We checked sympathetic skin response in the symptomatic (late luteal phase) and asymptomatic (follicular phase) periods of patients with premenstrual syndrome, a disorder known to have many autonomic symptoms, to determine whether there was sudomotor sympathetic involvement.The results of our PMS patients indicate at the very least that there is no difference with the control subjects as regards peripheral sudomotor functions.     

Association of NOS3 gene with metabolic syndrome in hypertensive patients

Recent data from animal models indicate that the eNOS null mice present a phenotype that resemble the human metabolic syndrome (hypertension, insulin resistance and hypertriglyceridemia). In this work, we have studied whether NOS3 gene, previously related to endothelial dysfunction, might have a role in metabolic syndrome susceptibility in hypertensive patients. To carry out the study, we genotyped 105 hypertensive patients < or = 60 years old with two polymorphisms of NOS3 gene: 1132 T>C and 7164 G>T (GeneBank:AF519768.1). To check the allelic frequency of these polymorphisms in our geographical area, we also genotyped 94 unselected healthy controls (control group). To perform sample genotyping, we designed a novel FRET system coupled to real time PCR. There were no differences in genotypic distribution or allelic frequency between hypertensive patients and the control group. However, we observed that 786CC genotype was significantly more frequent in hypertensive patients with metabolic syndrome than in those without the syndrome (p=0.0022). When both polymorphisms were analyzed, we identified the 786C894G as the risk haplotype for metabolic syndrome susceptibility (p=0.011). These data suggest a role of the NOS3 gene in the pathogenesis of metabolic syndrome in hypertensive patients.     

Oxidative stress in Rett syndrome

The investigation of parameters that might influence the neurological evolution of Rett syndrome might also yield new information about its pathogenic mechanisms. Oxidative stress caused by oxygen free radicals is involved in the neuropathology of several neurodegenerative disorders, as well as in stroke and seizures. To evaluate the free radical metabolism in Rett syndrome, we measured red blood cell antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase) and plasma malondialdehyde, as lipid peroxidation marker in a group of patients with Rett syndrome. No significant differences were observed in erythrocyte glutathione peroxidase, glutathione reductase and catalase activities, between the Rett syndrome patients and the control group. Erythrocyte superoxide dismutase activities were significantly decreased in Rett syndrome patients (P<0.001) compared with the control group. Plasma malondialdehyde concentrations were significantly increased in Rett syndrome patients (P<0.001). An unbalanced nutritional status in Rett syndrome might explain the reduced enzyme activity found in these patients. Our results suggest that free radicals generated from oxidation reactions might contribute to the pathogenesis of Rett syndrome. The high levels of malondialdehyde reflect peroxidative damage of biomembranes that may contribute to progressive dementia, impaired motor function, behavioural changes, and seizures, in Rett syndrome. We found a probable relationship between the degree of oxidative stress and the severity of symptoms, which should be further investigated with a larger number of patients in different disease stages.     

Resistance to rocuronium in a child with Schwartz-Jampel syndrome type 1 B

In Schwartz-Jampel syndrome micrognathia and jaw muscle rigidity may result in difficult or impossible tracheal intubation. Since the dose-response relationship to muscle relaxants is unknown in this rare disease we assessed by mechanomyography the neuromuscular response to the rocuronium in a two-year-old child with Schwartz-Jampel syndrome (SJS) Type 1 B. Rocuronium's dose-response curve was markedly shifted (3.5-fold dose) to the right when compared to healthy children and intubation conditions were improved. This resistance to NDMR may result from a lower acetylcholine degradation rate suggested as being the consequence of mutation of the gene encoding perlecan (HSPG2) in SJS. Thus, considerably higher doses of NDMR than usual may be required for facilitation of tracheal intubation in patients with SJS. Since evidence for genetic heterogeneity of SJS exists we also recommend incremental doses of a rapidly acting NDMR with continuous monitoring of neuromuscular function so as to assess the optimum relaxant dose.     

Cavanagh's syndrome (congenital thenar hypoplasia)

Thenar hypoplasia can be an isolated defect, as in Cavanagh's syndrome, can be present with cardiac (Holt-Oram syndrome) or eye (Okihiro's syndrome) disorders, or can be associated with hand anomaly, as in Haas's malformation. Vascular abnormality may be associated with thenar hypoplasia, which has been demonstrated in Okihiro's syndrome. Cavanagh's syndrome is a rare anomaly of the upper extremities that presents with unilateral or bilateral hypoplasia of the thenar eminence. Typical clinical, radiographic, and electrophysiologic findings emphasize the diagnosis. Differentiation from carpal tunnel syndrome is important to prevent unnecessary intervention. Electrophysiologic and radiographic findings are necessary tools for the physician to establish a correct diagnosis and make an appropriate referral. Because of its rarity, we present the case of an 8-year-old girl with this syndrome.     

A case of myasthenia gravis accompanied by steroid-resistant nephritic syndrome and CD57+ lymphocytes expansion in peripheral blood]

A 38-year-old woman showed symptoms of myasthenia gravis (MG) three months after receiving thymectomy for malignant thymoma. She was treated with anti-acetylcholine esterase drugs and azathioprine over 10 years with two exacerbations, which were controlled by plasmapheresis and large amounts of steroid. Nephrotic syndrome developed suddenly at the age of 48, was progressive even after azathioprine withdrawal, and resistant to several immunosuppressive therapies such as steroids and cyclosporine A, and plasmapheresis. She died of systemic infection one-and-a-half years after the onset of nephrotic syndrome. Immunological studies revealed several abnormalities of cellular immunity. The expansion of gamma-delta T cells and CD57+ lymphocytes in peripheral blood was characteristic findings. These cells are thought to originate from the extrathymic process. Nephrotic syndrome has been thought to be sometimes complicated with thymoma. Although some pathogenetic possibilities about combination of nephrotic syndrome and thymoma were supposed, none has yet been clarified. As we noticed the remarkable increase in the number of CD57+ cells, we examined its proportion in the peripheral blood of patients with MG and/or thymoma, as well as in individuals without sickness. The study revealed the expansion of CD57+ cells in MG thymoma patients (32.3 +/- 15.9%), compared with healthy controls (15.2 +/- 5.4%), MG non-thymoma patients (20.3 +/- 11.5%), and thymoma non-MG patients (15.2 +/- 12.0%) statistically (Mann-Whitney's U test). Therefore, we supposed that the peripheral CD57+ cell expansion was associated with parathymic immunological abnormalities, such as MG, thymoma, and nephrotic syndrome.     

Therapeutic effect of inosine in Tourette syndrome and its possible mechanism of action

We found incidentally 3 years ago that inosine relieved the symptoms in a patient with Tourette syndrome. Since then, 36 patients suffered from Tourette syndrome were exclusively treated with inosine, 50-90 mg/kg daily in divided doses. The vocal and non-vocal tic attacks were counted either by the observation of an examiner or with a video-tape record. The clinical status was scored as the sum of the number of various tic attacks recorded during a period of 60 minutes (video-tape record) or 20 minutes (direct observation). According to the scores obtained from double blind cross-over trial (11 cases) and open trial (25 cases), the tic attacks were well controlled in 75% of patients treated. A follow-up study by the end of one year medication the efficacy of inosine was still impressive in 50% of patients. Since we have observed that inosine potentiated the release of dopamine from rat striatal synaptosomes, mimicked the action of some dopamine antagonists, it is suggested that inosine might behave as a dopamine antagonist and exerts its effect on Tourette syndrome as haloperidol does.     

Biological nature of depressive symptoms in borderline personality disorder: endocrine comparison to recurrent brief and major depression

Borderline personality disorder (BPD) often shows depressive symptoms and their biological nature albeit extensively discussed remains controversial. The knowledge of this nature seems essential as it could imply key therapeutic strategies. We have found BPD and major depression (MD) not to share biological abnormalities. We have proposed BPD to frequently display an affective syndrome distinct from the nonborderline MD both in terms of quality and duration of symptoms and of biological substrate. A substantial number of BPD patients can be diagnosed as having clinical Recurrent Brief Depression (RBD) which has been proposed to overlap with BPD. RBD has been found to share perturbed biological substrate with MD but we have previously not found this abnormal substrate in BPD. Our aim was to study the possibility that BPD patients with depressive symptoms and even clinically diagnosed with RBD have a biological substrate distinct from RBD without BPD and from MD, and therefore an specific affective syndrome. We compared 20 BPD in-patients without co-existing MD to 20 sex- and age-matched non-BPD recurrent brief depressives and to 20 sex- and age-matched non-BPD major depressives on the thyrotropin-releasing hormone stimulation test (TRH-ST) and the dexamethasone suppression test (DST). Twelve BPD patients were diagnosed as having also RBD. BPD had less TRH-ST blunting than MD. TRH-ST did not differentiate BPD from RBD. RBD and MD patients shared equivalent TRH-ST values but BPD patients with clinically diagnosed RBD did not. BPD and RBD showed less perturbed DST than MD. DST did not differentiate BPD from RBD. BPD and RBD share most of the endocrinological normal substrate already described in BPD but RBD also share abnormalities with MD. Whereas we can conceptualize RBD as being an endocrinologically perturbed depressive syndrome, this may not be the case for the possible specific affective syndrome of BPD even if it can be for now diagnosed as being RBD.     

Recurrent alien hand syndrome in a multiple sclerosis case

Alien hand syndrome is the strange feeling of one's hand behaving independently. This syndrome has rarely been reported in multiple sclerosis (MS) patients. Herein, we present a 34-year-old female MS patient who had recurrent symptoms of alien hand syndrome that were evaluated as MS attacks based on cranial magnetic resonance imaging that showed demyelinating lesions in the corpus callosum. Alien hand syndrome is classified according to the location of the lesion and the presenting symptoms. As such, our patient can best be classified as a callosal alien hand case.     

A case of the corpus callosum and alien hand syndrome from a discrete paracallosal lesion

Here we present a patient with an isolated paracallosal brain lesion who exhibited behavioral changes associated with the corpus callosum syndrome (CCS) including features of the alien hand syndrome (AHS). The CCS is also known as the split-brain syndrome, the syndrome of hemisphere disconnection, the syndrome of brain bisection and the syndrome of the cerebral commissures. Because most reported cases of CCS were caused by tumors which extended beyond the corpus callosum (CC) and did not always induce a complete disconnection, there was much controversy about the role of the CC and the existence of a specific CCS. Aside from surgically based cases, the full complement of the CCS is infrequently clinically encountered. The patient described has a classic CCS from natural causes. This case report is unique in exhibiting a complete CCS with AHS secondary to an ischemic event affecting the left pericallosal region. To our knowledge this is the first case report of such a combination.     

Chronic fatigue syndrome in patients with Lyme borreliosis

Several authors have reported a chronic fatigue-like syndrome in patients that have suffered from Lyme borreliosis in the past. To further investigate this suspicion of an association without sample bias, we carried out a prospective, double-blind study and tested 1, 156 healthy young males for Borrelia antibodies. Seropositive subjects who had never suffered from clinically manifest Lyme borreliosis or neuroborreliosis showed significantly more often chronic fatigue (p = 0.02) and malaise (p = 0.01) than seronegative recruits. Therefore we believe it is worth examining whether an antibiotic therapy should be considered in patients with chronic fatigue syndrome and positive Borrelia serology.     

Incongruent cerebral growth in sudden infant death syndrome

Sudden infant death syndrome remains a leading cause of post-neonatal mortality in developed countries. Its etiopathogenic mechanisms are unknown. In this neuropathologic study, we noticed that the weights of the brains of infants who died from sudden infant death syndrome (n = 97) were invariably heavier in comparison with those of a group of age-matched controls (n = 23) issuing from the same local population. Brain edema was not a major element, and there were no significant microscopic or macroscopic cerebral anomalies in the brains from either of the study groups. Head circumference did not show a parallel increase in infants with sudden infant death syndrome. The excessive brain weight might reflect abnormal cerebral development and could be detrimental to vital neural control. In a previous study, we disclosed cytokine overexpression in the brains of these victims. Whether increased brain weight is linked to cytokine up-regulation remains, however, a moot case and merits further exploration.     

Cognitive and social factors in the development of infants with Down syndrome

Infants and young children with Down syndrome can be engaging and affectionate. It seems that in the early months of life their personal relations may be relatively 'spared' the effects of limitations in their capacities for information-processing. Yet how far is this the case as development proceeds? In this paper we discuss some ways in which social and cognitive development interact and mutually influence one another over the first year or so of life, and present preliminary findings from a longitudinal study of infants with and without Down syndrome. The evidence suggests that the development of 'triadic' (person-person-world) social interactions may be affected by limited information-processing capacities in infants with Down syndrome, through a complex socially-mediated developmental trajectory.     

Substance P immunoreactivity in the enteric nervous system in Rett syndrome

Rett syndrome is associated with profound mental retardation and motor disability in girls. It has a characteristic clinical phenotype which includes abnormalities of the autonomic nervous system. Feeding impairment and severe constipation are two symptoms of this autonomic dysfunction. Substance P, an important peptide in the autonomic nervous system, is decreased in the cerebrospinal fluid of Rett syndrome. We have demonstrated that substance P immunoreactivity is significantly decreased in Rett syndrome brain-stem and may be related to the autonomic dysfunction. In this study, we have continued the investigation of substance P in the enteric nervous system. We immunohistochemically examined the normal developing bowel in 22 controls (ages, 14 gestational weeks to 31 years) using formalin fixed tissue, with antibodies to substance P, tyrosine hydroxylase and vasoactive intestinal peptide. We compared the immunoreactivity of normal controls with 14 cases of Rett syndrome (ages, 5–41 years) and observed that the expression of substance P, tyrosine hydroxylase and vasoactive intestinal peptide immunoreactivity in the bowel in Rett syndrome was not significantly different from that of controls. This suggests that the feeding impairment and constipation in Rett syndrome relate to dysfunction of the autonomic nervous system originating outside of the bowel, in the brain-stem, as suggested by our previous study.     

Contributing to the early detection of Rett syndrome: the potential role of auditory Gestalt perception

To assess whether there are qualitatively deviant characteristics in the early vocalizations of children with Rett syndrome, we had 400 native Austrian-German speakers listen to audio recordings of vocalizations from typically developing girls and girls with Rett syndrome. The audio recordings were rated as (a) inconspicuous, (b) conspicuous or (c) not able to decide between (a) and (b). The results showed that participants were accurate in differentiating the vocalizations of typically developing children compared to children with Rett syndrome. However, the accuracy for rating verbal behaviors was dependent on the type of vocalization with greater accuracy for canonical babbling compared to cooing vocalizations. The results suggest a potential role for the use of rating child vocalizations for early detection of Rett syndrome. This is important because clinical criteria related to speech and language development remain important for early identification of Rett syndrome.