Poor stimulus discriminability as a common neuropsychological deficit between ADHD and reading ability in young children: a moderated mediation model.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is frequently associated with poorer reading ability; however, the specific neuropsychological domains linking this co-occurrence remain unclear. This study evaluates information-processing characteristics as possible neuropsychological links between ADHD symptoms and RA in a community-based sample of children and early adolescents with normal IQ (⩾70). METHOD: The participants (n = 1857, aged 6-15 years, 47% female) were evaluated for reading ability (reading single words aloud) and information processing [stimulus discriminability in the two-choice reaction-time task estimated using diffusion models]. ADHD symptoms were ascertained through informant (parent) report using the Development and Well-Being Assessment (DAWBA). Verbal working memory (VWM; digit span backwards), visuospatial working memory (VSWM, Corsi Blocks backwards), sex, socioeconomic status, and IQ were included as covariates. RESULTS: In a moderated mediation model, stimulus discriminability mediated the effect of ADHD on reading ability. This indirect effect was moderated by age such that a larger effect was seen among younger children. CONCLUSION: The findings support the hypothesis that ADHD and reading ability are linked among young children via a neuropsychological deficit related to stimulus discriminability. Early interventions targeting stimulus discriminability might improve symptoms of inattention/hyperactivity and reading ability.

High CSF transforming growth factor beta levels after subarachnoid haemorrhage: association with chronic communicating hydrocephalus.

BACKGROUND: Chronic communicating hydrocephalus is a common sequela of subarachnoid haemorrhage and develops when the flow and drainage of CSF are impaired after fibrosis in the subarachnoid space. Released by platelets into the CSF after subarachnoid haemorrhage, transforming growth factor (TGF)beta1/beta2 are potent fibrogenic agents that may promote post-haemorrhagic fibrosis and chronic communicating hydrocephalus. METHODS: Temporal changes in total (latent plus active) TGFbeta1/beta2 CSF levels of post-haemorrhage patients developing acute hydrocephalus were measured using ELISA to discover if titres were higher in patients that subsequently developed chronic communicating hydrocephalus, compared with those that did not. RESULTS: Mean (SD) CSF levels of total TGFbeta1 were 97 (42) pg/ml and total TGFbeta2 were 395 (39) pg/ml in control patients with (non-haemorrhagic) hydrocephalus. For days 1-5 post-subarachnoid haemorrhage (dph), levels of 1427 (242) pg/ml and 976 (191) pg/ml were seen for total TGFbeta1 and TGFbeta2, respectively. Beyond 5 dph, total TGFbeta1/beta2 levels declined but remained significantly elevated (p<0.01) above control patient values for at least 19 dph. Haemorrhagic patients that went on to develop chronic communicating hydrocephalus had significantly higher levels of total TGFbeta1 (p<0.01) and TGFbeta2 (p<0.05) between 1 and 9 dph, compared with those of haemorrhagic patients that did not. CONCLUSIONS: Acutely measured levels of TGFbeta1/beta2 in the CSF of patients with subarachnoid haemorrhage are thus potential prognostic biomarkers for the subsequent development of chronic communicating hydrocephalus, indicating likely dependency on CSF shunting.

Coordinated brain development: exploring the synchrony between changes in grey and white matter during childhood maturation.

Brain development during childhood and early adolescence is characterized by global changes in brain architecture. Neuroimaging studies have revealed overall decreases in cortical thickness (CT) and increases in fractional anisotropy (FA). Furthermore, previous studies have shown that certain cortical regions display coordinated growth during development. However, there is significant heterogeneity in the timing and speed of these developmental transformations, and it is still unclear whether white and grey matter changes are co-localized. In this multimodal neuroimaging study, we investigated the relationship between grey and white matter developmental changes and asynchronous maturation within brain regions in 249 normally developing children between the ages 7-14. We used structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to analyze CT and FA, respectively, as well as their covariance across development. Consistent with previous studies, we observed overall cortical thinning with age, which was accompanied by increased FA. We then compared the coordinated development of grey and white matter as indexed by covariance measures. Covariance between grey matter regions and the microstructure of white matter tracts connecting those regions were highly similar, suggesting that coordinated changes in the cortex were mirrored by coordinated changes in their respective tracts. Examining within-brain divergent trajectories, we found significant structural decoupling (decreased covariance) between several brain regions and tracts in the 9- to 11-year-old group, particularly involving the forceps minor and the regions that it connects to. We argue that this decoupling could reflect a developmental pattern within the prefrontal region in 9- and 11-year-old children, possibly related to the significant changes in cognitive control observed at this age.

Alterations in serotonin and neuropeptide Y content of cerebrovascular sympathetic nerves following experimental subarachnoid hemorrhage.

The effect of an experimental subarachnoid hemorrhage (SAH) upon neurotransmitter content in sympathetic nerves supplying the major cerebral arteries of the rat has been examined by immunohistochemical analysis and high performance liquid chromatography with electrochemical detection (HPLC-ECD). In particular, changes that occur in sympathetic nerve content of the vasoconstrictor agents serotonin (5-HT) and neuropeptide Y (NPY), which are colocalized with noradrenaline, were assessed. Subarachnoid hemorrhage was induced by a single injection of autologous arterial blood into the cerebrospinal fluid (CSF) space of the cisterna magna. The density of 5-HT-containing and NPY-containing perivascular nerve fibers per unit area of vessels was measured at defined intervals from 15 min to 5 days post-SAH. In addition, an HPLC study was performed to quantify the actual amounts of 5-HT and noradrenaline present in circle of Willis vessels at 3 h post-SAH. Comparison was made with sham-operated animals and animals that received a cisternal injection of buffered saline in place of blood. Our results reveal a major increase in cerebrovascular sympathetic nerve content of serotonin, arising by uptake, presumably from subarachnoid blood clot, within the first 3 h post-SAH. Neuropeptide Y content, however, decreased from 3 up to 48 h posthemorrhage. By 3 days post-SAH, when the majority of subarachnoid clot had resorbed, the sympathetic nerve content of both NPY and 5-HT was restored to normal. This pattern of change was not observed in either sham-operated or saline-injected controls.

The time course of intracranial pathophysiological changes following experimental subarachnoid haemorrhage in the rat.

The rat subarachnoid haemorrhage (SAH) model was further studied to establish the precise time course of the globally reduced CBF that follows and to ascertain whether temporally related changes in cerebral perfusion pressure (CPP) and intracranial pressure (ICP) take place. Parallel ultrastructural studies were performed upon cerebral arteries and their adjacent perivascular subarachnoid spaces. SAH was induced by a single intracisternal injection of autologous arterial blood. Serial measurements of regional cortical CBF by hydrogen clearance revealed that experimental SAH resulted in an immediate 50% global reduction in cortical flows that persisted for up to 3 h post SAH. At 24 h, flows were still significantly reduced at 85% of control values (p less than 0.05), but by 48 h had regained normal values and were maintained up to 5 days post SAH. ICP rose acutely after haemorrhage to nearly 50 mm Hg with C-type pressure waves being present. ICP then fell slowly, only fully returning to control levels at 72 h. Acute hydrocephalus was observed on autopsy examination of SAH animals but not in controls. Reductions in CPP occurred post SAH, but only in the order of 15%, which could not alone account for the fall in CBF that took place. At 48 and, to a lesser extent, 24 h post SAH, myonecrosis confined largely to smooth muscle cells of the immediately subintimal media was observed. No significant changes in the intima or perivascular nerve plexus were seen. Within 24 h of haemorrhage, a limited degree of phagocytosis of erythrocytes by pial lining cells took place. However, early on the second day post SAH, a dramatic increase in the numbers of subarachnoid macrophages arose from a transformation of cells of the pia-arachnoid. This period was characterised by intense phagocytic activity, erythrocytes, fibrin, and other debris being largely cleared over the next 24 h. At 5 days post SAH the subarachnoid macrophage population declined, cells losing their mobile active features to assume a more typical pia-arachnoid cell appearance once more. Our studies indicate that this increasingly utilised small animal model of SAH develops global cortical flow changes only acutely, and it is likely that early vasospasm, secondary to released blood products rather than pressure changes per se, is responsible for the initial cerebral ischaemia that develops. Interestingly, both cerebral arterial vasculopathy and perivascular macrophage phagocytic activity are most marked at approximately 48 h following SAH in the rat, a time at which a phase of delayed cerebral arterial narrowing has previously been documented.

Transforming growth factor-beta1 in the cerebrospinal fluid of patients with subarachnoid hemorrhage: titers derived from exogenous and endogenous sources.

Transforming growth factor-beta1 (TGF-beta1) is a fibrogenic cytokine that is involved in postinjury repair and is implicated in the etiology of postsubarachnoid hemorrhage (SAH) chronic communicating hydrocephalus. TGF-beta1 was measured by enzyme-linked immunosorbant assay (ELISA) in sequential samples of cerebrospinal fluid (CSF) in 11 patients with hydrocephalus after SAH; levels were seen to be biphasically elevated and sources were investigated. TGF-beta1 levels were compared with albumin levels that estimated CSF blood content. Control samples from nonhemorrhagic hydrocephalics were tested similarly. Mean total TGF-beta1 levels were elevated to 4400+/-3435 (+/-SD) pg/mL greater than control levels of 97+/-42 at 1 to 2 days posthemorrhage. Thereafter, levels fell to 714+/-401 by 5 to 6 days posthemorrhage, then rose to a second peak of 1667+/-774 at 9 to 10 days posthemorrhage, remaining significantly increased until 19 days posthemorrhage (P = 0.007). The first peak probably derived from extravasated platelets and correlated with increased albumin levels in the CSF. The second TGF-beta1 peak rose greater than CSF albumin levels that had stabilized at this time, and thus was attributed to a tissue-specific response rather than a re-bleed. TGF-beta1 was detected in the choroid secretory epithelium from controls, but levels were greater in SAH patients at 10 to 12 days posthemorrhage. The authors conclude that the elevated levels of TGF-beta1 in CSF after SAH are derived initially from blood and later from endogenous sources such as the choroid plexus.

Epidural haematoma requiring surgical decompression following repeated cervical epidural steroid injections for chronic pain.

We report a case of epidural haematoma following a steroid injection into the cervical epidural space. The complication occurred on the seventh such injection over a 2 year period for chronic spinal pain. Surgical decompression over the seventh cervical and the upper 3 thoracic vertebrae was required to alleviate the symptoms of paralysis and anaesthesia. The patient subsequently required skin grafting to the surgical site and two trans-urethral resections of the prostate gland during his 6 week hospital admission. He made a full recovery.

5-Hydroxytryptamine demonstrated immunohistochemically in rat cerebrovascular nerves largely represents 5-hydroxytryptamine uptake into sympathetic nerve fibres.

This study has re-examined, by immunohistochemistry, a proposed serotonergic innervation of major cerebral vessels in the rat. Previous studies had demonstrated a dense perivascular plexus of 5-hydroxytryptamine immunoreactive nerve fibres upon major cerebral vessels in this and many other species. The present work has shown, however, that 5-hydroxytryptamine immunoreactive nerve fibres are rarely observed in cerebral vessels prepared by perfusion-fixation in situ, and only form a well-developed plexus in vessels prepared, as in previous studies, by immersion-fixation. Prior treatment with a predominantly noradrenergic uptake inhibitor desmethylimipramine but not the serotonergic uptake inhibitor fluoxetine produced a major diminution in the 5-hydroxytryptamine immunoreactive plexus visualized in these immersion-fixed vessels. In addition, 5-hydroxytryptamine immunoreactive nerves were only occasionally observed in immersion-fixed vessels from animals that had been pretreated with 6-hydroxydopamine to produce adrenergic denervation. The removal, firstly, of vessel-contained blood, by left ventricular perfusion with Krebs' solution, prior to vessel dissection and immersion-fixation, resulted in an absence of 5-hydroxytryptamine immunoreactivity in perivascular nerves. Immunoreactivity could then be restored by briefly incubating vessels in Krebs' solution containing either blood or 5-hydroxytryptamine before fixation. It would appear therefore that 5-hydroxytryptamine is rarely present under normal circumstances in the perivascular nerves of major cerebral vessels, and that previous descriptions of a dense serotonergic nerve plexus represent 5-hydroxytryptamine in blood released during vessel dissection being taken up via the noradrenaline-uptake system into perivascular sympathetic nerves. The possibility is thus raised that 5-hydroxytryptamine uptake and interaction within perivascular adrenergic nerves could occur in those cerebrovascular disorders where blood is released.

Serial determinations of regional cerebral blood flow in the rat using simple chronically implanted platinum wire microelectrodes.

The ability to reliably obtain serial determinations of regional cerebral blood flow (rCBF) over time in small animals using simple and inexpensively constructed platinum-wire microelectrodes has been investigated. Repeated measurements of local cortical flow were obtained on a daily basis using the hydrogen clearance technique in a group of 18 animals, in each of which, 6 electrodes were chronically implanted. Our studies have shown the simple microelectrodes utilised to give a low variability of results, as well as being well tolerated and provoking minimal tissue reaction even over prolonged periods of time. Under identical steady-state conditions, serial determinations of rCBF were obtained for up to one week, with a maximum variation in mean values of only 12%, a result that compares favourably with the known serial determination error for the technique in the shorter term.

Ultrastructure of serotonin-containing nerve fibres in the middle cerebral artery of the rat and evidence for its localization within catecholamine-containing nerve fibres by immunoelectron microscopy.

This study has examined the ultrastructural characteristics of serotonin (5-HT)-like immunoreactive (5-HT-I) nerves in the perivascular plexus of a major cerebral blood vessel and their relationship with catecholaminergic (CA) nerves. This was achieved by immunohistochemistry for 5-HT used alone and in combination with simultaneous 5-hydroxydopamine (5-OHDA) false transmitter preloading to demonstrate catecholaminergic nerves examined by electron microscopy. About 15% of perivascular nerves showed some 5-HT-like immunoreactivity. These nerves were characterised by a predominance of small pleomorphic vesicles with a diameter of 40-50 nm and a few large granular vesicles about 100-150 nm diameter. 5-HT-I nerves were found at all levels of the perivascular plexus, from the outer adventitia where they were formed together with non-reactive nerves into bundles by Schwann cells and their processes, to more singly at the adventitia-media border, sometimes in close apposition to smooth muscle cells, separated by some 125 nm. Examination of animals treated by 5-OHDA preloading revealed that 5-HT-I nerves were almost invariably identified as catecholaminergic. However, CA nerves did not always show 5-HT-like immunoreactivity, some 25% only being doubly labelled in this study. Treatment of animals with the catecholaminergic nerve uptake blocker desmethylimipramine resulted in abolition of 5-HT-like immunoreactivity. These results provide direct ultrastructural evidence for the localisation of 5-HT within the perivascular catecholaminergic nerves of a major cerebral vessel and suggest that the contained 5-HT is mainly derived by uptake rather than synthesis within them.

The reciprocal synapse in the external plexiform layer of the mammalian olfactory bulb.

It has recently been claimed by Ramon-Moliner29, that reciprocal synapses between mitral (and tufted) cell dendrites and granule cell gemmules, which for more than 10 years have been thought to represent a major feature of the structural and functional organization of the olfactory bulb28, are non-existent or, at best, extremely rare. The challenge is based on the contention that there is little, if any, morphological evidence to substantiate the existence of the gemmulofugal component of the reciprocal synapse. We have re-examined by electron microscopy the external plexiform layer (EPL) of the olfactory bulb of adult rabbits and rats. The study was carried out in conventionally prepared material, using individual and serial sections, goniometry, and quantitative analysis of montages, and also in material stained by the E-PTA and BIUL methods. According to currently accepted morphological criteria, gemmulofugal synapses can be identified consistently and with confidence at all levels in the EPL: they are particularly clearly and unambiguously resolved in E-PTA and BIUL preparations. At least the majority of gemmulofugal and mitrofugal synapses are closely associated in reciprocal pairs, as many previous authors have reported. Furthermore, there are approximately as many gemmulofugal as mitrofugal synapses in the EPL, which supports the long-standing proposal that the overall synaptic relationship between granule cells and mitral cells is a reciprocal one. We conclude that the challenge of Ramon-Moliner to the reality and significance of the reciprocal synapse is not well-founded.

Case report: ossification of the thoracic ligamenta flava in a Caucasian: a rare cause of myelopathy.

Ossification of the ligamenta flava is rare and has been described almost exclusively in Japanese people. We present a case in which ossification of the thoracic ligamenta flava caused compressive myelopathy in a Caucasian.

Cage versus tricortical graft for cervical interbody fusion. A prospective randomised study.

We conducted a prospective, randomised study of 42 cervical interbody fusions undertaken with either an autologous tricortical graft or a cage. The factors assessed in the two groups were: (1) time taken to achieve fusion; (2) neck disability index; (3) pain score; (4) interbody height ratio; (5) interbody angle and (6) the influence of smoking on fusion. No statistical difference was seen in the time taken to achieve fusion, neck disability index, interbody height ratio, or interbody angles. Smoking did not have any effect on the fusion process. The pain score was significantly lower in the tricortical graft group at six months. We conclude that both methods of fusion give similar results, although tricortical graft fusion is cheaper than cage fusion, and is more effective in reducing the pain score.

Central neurocytoma without intraventricular extension.

A case of central neurocytoma is reported, presenting as a tumor of the occipital lobe, closely related to the ependyma of the occipital horn of the lateral ventricle but not actually invading it. This is a distinctly uncommon location, and only four tumors have been reported so far in a lobar position, without an intraventricular component. The case broadens our knowledge of this recently described tumor and gives an opportunity for discussion of the role of radiotherapy in its management, which currently remains controversial.

Central neurocytoma: a correlative clinicopathologic and radiologic analysis.

BACKGROUND: Central neurocytoma was described as a well differentiated tumor of neuronal origin, distinct from ganglion cell tumors and neuroblastoma. An initially perceived benign biologic behavior has been questioned by subsequent reports of anaplastic and recurrent tumors. We report six cases of central neurocytoma, with variable clinical and pathologic features that stimulate discussion on the management of these tumors. METHODS: Of the 95 oligodendrogliomas treated in our institution in the last 40 years, three tumors were reclassified as central neurocytomas on histologic reappraisal. Three additional cases prospectively diagnosed as central neurocytomas are reported. The clinical, pathologic, and radiologic features are reviewed. RESULTS: Early recurrence, not related to malignant histologic features, was noted in two patients who had not received postoperative radiotherapy. Anaplastic histologic changes were not accompanied by malignant biologic behavior in another patient. Neither patient with recurrent tumor was controlled by radiotherapy alone. Chemotherapy with carboplatin reduced tumor size temporarily in one of these patients. CONCLUSION: An entirely benign nature for this tumor is questioned and it appears that there may be malignant variants. Surgery should aim for maximum possible excision, as the location of the tumor allows. The role of postoperative radiotherapy remains controversial and may be considered in cases of subtotal excision of tumors with anaplastic histologic features. Chemotherapy may be of benefit in cases recurring despite surgery and radiotherapy.

Middle cerebral artery revascularization. Anatomical studies and considerations on the anastomosis site.

In the surgical management of skull base lesions and vascular diseases such as giant aneurysms, involvement of the internal carotid artery may require the resection or the occlusion of the vessel. The anastomosis of the external carotid artery and the middle cerebral artery with venous graft may be indicated to re-establish the blood flow. To determine the best suture site in the middle cerebral artery, an anatomical study was carried out. Fourteen cerebral hemispheres were analysed after the injection of red latex into the internal carotid artery. The superior and inferior trunk of the main division of the middle cerebral artery have more than 2 mm of diameter. They are superficial allowing an anastomosis using a venous graft. The superior trunk has a disadvantage, it gives rise to branches for the precentral and post-central giri. The anastomosis with the inferior trunk presents lower risk of neurological deficit even though the angular artery originates from it.

Cortical thinning of the right anterior cingulate cortex in spider phobia: a magnetic resonance imaging and spectroscopy study.

There a lack of consistent neuroimaging data on specific phobia (SP) and a need to assess volumetric and metabolic differences in structures implicated in this condition. The aim of this study is investigate possible metabolic (via (1)H MRS) and cortical thickness abnormalities in spider-phobic patients compared to healthy volunteers. Participants were recruited via public advertisement and underwent clinical evaluations and MRI scans. The study started in 2010 and the investigators involved were not blind in respect to patient groupings. The study was conducted at the Ribeirão Preto Medical School University Hospital of the University of São Paulo, Brazil. Patients with spider phobia (n=19) were matched to 17 healthy volunteers with respect to age, education and socio-economic status. The spider SP group fulfilled the diagnostic criteria for spider phobia according to the Structured Clinical Interview for DSM-IV. None of the participants had a history of neurological, psychiatric or other relevant organic diseases, use of prescribed psychotropic medication or substance abuse. All imaging and spectroscopy data were collected with a 3 T MRI scanner equipped with 25 mT gradient coils in 30-minute scans. The Freesurfer image analysis package and LC Model software were used to analyze data. The hypothesis being tested was formulated before the data collection (neural correlates of SP would include the amygdala, insula, anterior cingulate gyrus and others). The results indicated the absence of metabolic alterations, but thinning of the right anterior cingulate cortex (ACC) in the SP group when compared to the healthy control group (mean cortical thickness±SD: SP=2.11±0.45 mm; HC=2.16±0.42 mm; t (34)=3.19, p=0.001 [-35.45, 71.00, -23.82]). In spectroscopy, the ratios between N-acetylaspartate and creatine and choline levels were measured. No significant effect or correlation was found between MRS metabolites and scores in the Spider Phobia Questionnaire and Beck Anxiety Inventory (p>0.05). The ACC is known to be related to the cognitive processing of fear and anxiety and to be linked with the conditioning circuit. The MRS findings are preliminary and need more studies. The finding of reduced ACC thickness in SP is in agreement with evidence from previous functional neuroimaging studies and highlights the importance of this brain area in the pathophysiology of SP.

Is cerebellar volume related to bipolar disorder?

BACKGROUND: Recent data suggest that cerebellum influences emotion modulation in humans. The findings of cerebellar abnormalities in bipolar disorder (BD) are especially intriguing given the link between the cerebellum emotional and behavioral regulation. The purpose of this study was to evaluate cerebellar volume in patients with euthymic BD type I compared to controls. Moreover, we investigated the possible relationship between cerebellar volume and suicidal behavior. METHODS: Forty-patients with euthymic BD type I, 20 with and 20 without history of suicide attempt, and 22 healthy controls underwent an MRI scan. The participants were interviewed using the Structured Clinical Interview with the DSM-IV axis I (SCID-I), the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS) and the Barratt Impulsiveness Scale (BIS-11). RESULTS: Groups were age, gender and years of schooling-matched. The left cerebellum (p=0.02), right cerebellum (p=0.02) and vermis (p<0.01) were significantly smaller in the BD group; however, there were no volumetric differences between the BD subjects with and without suicidal attempt. There was no correlation between cerebellar measurements and clinical variables. LIMITATIONS: The main strength is that our sample consisted of patients with euthymic BD type I without any comorbidities, however, these results cannot establish causality as the cross-sectional nature of the study. CONCLUSIONS: Our findings suggest that the reduction in cerebellar volumes observed in BD type I might be a trait-related characteristic of this disorder. Additional studies with larger samples and subtypes of this heterogeneous disorder are warranted to determine the possible specificity of this cerebellar finding.

Neural injury repair: hope for the future as barriers to effective CNS regeneration become clearer.

In this review the author outlines the early history of clinical and scientific research upon the inability of the CNS in man to successfully regenerate following injury. As we proceed into the 21st Century we have gained a far greater understanding of the molecular biology, pathology and other factors that lead to the adult CNS being non-supportive and indeed actively inhibitory to axonal regrowth. On the basis of these recent advances in knowledge, the author outlines possible therapeutic approaches that may enable more effective CNS regeneration to be accomplished in the future.

Hyponatraemia in neurosurgical patients: diagnosis using derived parameters of sodium and water homeostasis.

Seventeen unselected, consecutive patients with intracranial disease and accompanying hyponatraemia were studied. All would previously have been diagnosed as having the syndrome of inappropriate antidiuretic hormone (ADH) secretion on the basis of spot plasma/urinary electrolyte testing with the application to them of existing standard laboratory criteria. Timed urinary collections and matching plasma samples were available in all but three cases for the derivation of creatinine, osmotic and free-water clearances, tubular reabsorbed water, and fractional water and sodium excretions. In a number of patients the plasma renin, aldosterone and ADH levels were also assayed. On the basis of the overall findings, 13 patients were diagnosed as in fact having a salt-wasting state whilst in only four patients was the diagnosis of inappropriate ADH secretion (SIADH) substantiated. It is suggested that obtaining simple derived parameters of sodium and water homeostasis can add significantly in differentiating between these quite opposite syndromes.